Magnetic Resonance Angiography (MRA) and Magnetic Resonance Venography (MRV)

Number: 0094

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References


Policy

Scope of Policy

This Clinical Policy Bulletin addresses magnetic resonance angiography (MRA) and magnetic resonance venography (MRV).

  1. Medical Necessity

    Aetna considers the following medically necessary when criteria are met:

    1. Magnetic Resonance Angiography (MRA)

      1. MRA is considered appropriate when it can replace a more invasive test (e.g., contrast angiography) and reduce risk for members. While MRA is a rapidly evolving technology, its clinical safety and effectiveness for all anatomical regions have not been established by the peer- reviewed medical literature. The following indications are considered medically necessary according to the selection criteria outlined below:

        1. Head and neck for any of the following conditions:

          1. As a follow-up study for a known arterio-venous malformation (AVM), and for a known non-ruptured intra-cranial aneurysm (ICA) that is greater than 3 mm in size; or
          2. As a follow-up of ICA after coiling; or
          3. To definitively establish presence of stenoses or other abnormalities of the vertebrobasilar system in members with symptoms highly suggestive of vertebrobasilar syndrome (binocular vision loss, diplopia, dysarthria, dysphagia, positional vertigo); or
          4. To evaluate members with signs/symptoms highly suggestive of leaking/ruptured ICA or AVM (i.e., blood in the cerebral spinal fluid, stiff neck, sudden explosive headache); or
          5. To evaluate pulsatile tinnitus in members with signs or symptoms suggestive of a vascular lesion; or
          6. To rule out ICA, including aneurysms of the circle of Willis, in members who are thought to be at higher risk (e.g., history of ICA in a first-degree relative or presence of polycystic kidney disease); or
          7. To evaluate conditions of the carotid arteries such as:

            1. Aneurysm tumor;
            2. Cervicocranial arterial dissection in members with suggestive signs or symptoms (e.g., amaurosis fugax, oculo-sympathetic palsy, symptoms of focal brain ischemia, and unilateral headache);
            3. Injury to the carotid artery;
            4. Stenotic/occlusive disease in asymptomatic members who are candidates for carotid endarterectomy surgery (CEA) when a Duplex Doppler scan is abnormal;
            5. Stenotic/occlusive disease in symptomatic members (e.g., cerebro-vascular disease or transient ischemic attack);

            Note: As MRA is considered an alternative to angiography for evaluation of the carotids, a subsequent angiography would only be considered medically necessary if there was a significant discrepancy between the findings of Duplex ultrasonography and MRA that would impact on surgical planning.

        2. Chest for any of the following indications:

          1. For diagnosis, treatment planning, and post-operative follow-up for conditions of the thoracic aorta such as aneurysm (true or pseudoaneurysm), dissection, or stenotic/occlusive vascular disease; or
          2. For diagnosis, treatment planning, and post-operative surgical shunt evaluation in members with congenital heart disease (CHD) or developmental anomalies of the thoracic vasculature (e.g., atresia or hypoplasia of the pulmonary arteries, coarctation of the aorta, double aortic arch, interrupted inferior vena cava, partial anomalous venous connection, persistent left superior vena cava, right-sided aortic arch, total anomalous pulmonary venous connection, and truncus arteriosus); or
          3. For diagnosing a suspected pulmonary embolism when the use of intravascular iodinated contrast material is contraindicated, or as a substitute for pulmonary angiography when a ventilation/perfusion (V/Q) scan does not provide sufficient information for treatment decisions; or
          4. For pulmonary venous and left atrial evaluation, pre- and post-radiofrequency ablation for atrial fibrillation;
        3. Spine for individuals with known cases of spinal cord arterio-venous fistula and arterio-venous malformation. MRA of the spinal canal is considered experimental and investigational for all other indications;
        4. Abdomen/pelvis for any of the following indications:

          1. To assess of the main renal arteries for the evaluation of renal artery stenosis in persons with refractory uncontrolled hypertensionFootnote1* not due to pheochromocytoma; or
          2. To assess persons with sickle cell disease; or
          3. To assess pelvic (e.g., aorto-iliac) arteries for stenoses in members with peripheral vascular disease; or
          4. To evaluate endoleaks following endovascular repair of abdominal aortic aneurysm; or
          5. To evaluate hepatic vasculature prior to transjugular intrahepatic portosystemic shunt (TIPS); or
          6. To determine the extent of an abdominal aortic aneurysm and associated occlusive disease in members undergoing elective repair; or
          7. Evaluation of the body part from which the free tissue transfer flap is being taken for breast reconstruction preoperative planning (e.g., MRA of the abdomen and pelvis for DIEP flap); or
          8. To evaluate for chronic mesenteric ischemia;

          Footnote1*Refractory hypertension is defined as diastolic blood pressure consistently greater than 100 mm Hg on 3 or more blood pressure medications.

        5. Lower extremity as an initial test for diagnosis and surgical planning in the treatment of peripheral arterial disease of the lower extremity. A subsequent angiography study is only required if the inflow vessel is not identified on the MRA. If conventional catheter angiography is performed first, doing a subsequent MRA may be indicated if a distal run-off vessel is not identified. Both tests should not be routinely performed;
        6. Allergy, etc. in members with documented allergy to iodinated contrast material, and in members who have accelerating hypertension and/or accelerating renal insufficiency;
      2. Use of gadofosveset trisodium (Ablavar, previously marketed as Vasovist injection) is considered an appropriate agent for medically necessary contrast-enhanced MRA of blood vessels in the abdomen and lower extremities in adults.

    2. Magnetic Resonance Venography (MRV)

      For any of the following indications:

      1. For evaluation of thrombosis or compression by tumor of the cerebral venous sinus in members who are at risk (e.g., hyper-coagulable disorders, meningitis, oral contraceptive use, otitis media, sinusitis, underlying malignant process) or have signs or symptoms (e.g., drowsiness and confusion accompanying a headache, focal motor or sensory deficits, papilledema, or seizures); or
      2. For evaluation of cerebral venous infarction identified on CT or MRI of the head; or
      3. For evaluation of venous thrombosis or occlusion in the large systemic veins (e.g., superior vena cava, subclavian, or other deep veins in the chest); or
      4. For evaluation of venous thrombosis or occlusion in the portal and/or hepatic venous system (e.g., Budd-Chiari syndrome); or
      5. For chronic pelvic pain, when pelvic congestion syndrome is suspected and ultrasound findings are equivocal.
  2. Experimental and Investigational

    The following indications are considered experimental and investigational because the effectiveness of these approaches has not been established (not an all inclusive list):

    1. Magnetic Resonance Angiography (MRA)

      1. Cardiac MRI for velocity flow mapping; or
      2. Diagnosing cerebral arteriovenous malformations; or
      3. Evaluating accessory renal arteries in prospective renal donors, including potential living kidney donors; or
      4. Evaluating members with symptoms suggestive of dural, sagittal or cavernous sinus thrombosis/occlusion; or
      5. Evaluating microvascular compression associated with trigeminal neuralgia; or
      6. Evaluating premature ventricular contraction; or
      7. Evaluating recurrent cystic hygroma of the axilla; or
      8. Evaluating varices at hepatico-jejunostomy after liver transplantation; or
      9. Evaluating vasa previa; or
      10. Management of Chiari malformation type I; or
      11. Predicting pulmonary hypertension; or
      12. Ruling out ICA in members who have vague central nervous system symptoms (e.g., dizziness, headache, non-specific sensory loss, or vertigo); or
      13. Screening for renovascular hypertension; or
      14. Screening of the general population for ICAs; or
      15. Surveillance of individuals with brain cancer following radiotherapy;
    2. Ferumoxytol-enhanced MRA for evaluation of transplant renal artery stenosis;
    3. Combined unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (MRA) for vascular mapping in renal impairment;
    4. Magnetic Resonance Venography (MRV)

      1. MRV for diagnosis of deep vein thrombosis (DVT) in the arms or legs because the peer-reviewed medical literature has not established MRV to be superior to Duplex ultrasonography for this purpose. MRV is considered experimental and investigational for all other indications (e.g., diagnosis of chronic cerebrospinal venous insufficiency, and nutcracker syndrome, and prediction of outcome in tuberculous meningitis);
      2. Pelvic MRV for diagnostic evaluation of cryptogenic stroke;
      3. Quantitative MRV for measurement of venous flow after cerebral venous sinus stenting;
      4. Ferumoxytol-enhanced MRV for the diagnosis of chronic kidney disease.

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

Magnetic Resonance Angiography (MRA) & Venography (MRV):

Head and neck:

CPT codes covered if selection criteria are met:

70544 Magnetic resonance angiography, head; without contrast material(s)
70545      with contrast material(s)
70546      without contrast material(s), followed by contrast material(s) and further sequences
70547 Magnetic resonance angiography, neck; without contrast material(s)
70548      with contrast material(s)
70549      without contrast material(s), followed by contrast material(s) and further sequences

ICD-10 codes covered if selection criteria are met for MRA:

A52.05 Other cerebrovascular syphilis [intracranial aneurysm]
D43.0 - D43.9 Neoplasm of uncertain behavior of brain and central nervous system
G08 Intracranial and intraspinal phlebitis and thrombophelbitis [intracranial aneurysm]
G44.1 Vascular headache, not elsewhere classified [sudden explosive headache, unilateral headache]
G45.0 - G45.9 Transient cerebral ischemic attacks and related syndromes
H34.00 - H34.03 Transient retinal artery occlusion
H49.00 - H49.03 Third [oculomotor] nerve palsy
H53.2 Diplopia
H54.3 Unqualified visual loss, both eyes
H81.10 - H81.13 Benign paroxysmal vertigo
H81.41 - H81.49 Vertigo of central origin
H93.11 - H93.19 Tinnitus
H93.A1 - H93.A9 Pulsatile tinnitus
I60.00 - I60.9 Nontraumatic subarachnoid hemorrhage
I67.0 - I67.9 Other cerebrovascular diseases
I71.02 - I71.03 Dissection of abdominal or thoracoabdominal aorta
I71.3 - I71.4 Abdominal aortic aneurysm, ruptured or without rupture
I71.5 - I71.6 Thoracoabdominal aneurysm, ruptured or without mention of rupture
I77.71 Dissection of carotid artery
I77.74 Dissection of vertebral artery
M43.6 Torticollis
Q28.2 Arteriovenous malformation of cerebral vessels [not covered for magnetic resonance angiography for diagnosis]
R13.10 - R13.19 Dysphagia
R42 Dizziness and giddiness
R43.0 - R43.9 Disturbances of smell and taste
R47.02 - R47.9 Speech disturbances, not elsewhere classified
R51 Headache [sudden explosive headache, unilateral headache]
R55 Syncope and collapse
R83.9 Unspecified abnormal findings in cerebrospinal fluid [blood in CSF]
S15.001+ - S15.099+ Injury of carotid artery of neck
Z82.3 Family history of stroke

ICD-10 codes not covered for indications listed in the CPB for MRA:

C71.0 - C71.9 Malignant neoplasm of brain
C76.0 Malignant neoplasm of head, face and neck
C79.31 Secondary malignant neoplasm of brain
D33.0 - D33.2 Benign neoplasm of brain
G50.0 Trigeminal neuralgia [not covered for the evaluation of microvascular compression]
T86.49 Other complications of liver transplant [varices at hepatico-jejunostomy]

ICD-10 codes covered if selection criteria are met for MRV:

C71.0 - C71.9 Malignant neoplasm of brain
C76.0 Malignant neoplasm of head and neck
D33.0 - D33.2 Benign neoplasm of brain
D43.0 - D43.9 Neoplasm of uncertain behavior of brain and central nervous system
G00.0 - G03.9 Meningitis
G44.1 Vascular headache, not elsewhere classified
H47.10 - H47.13 Papilledema
H65.00 - H67.9 Otitis media
I63.6 Cerebral infarction due to cerebral venous thrombosis, nonpyogenic [identified by CT or MRI of the head]
J01.00 - J01.91 Acute sinusitis
J32.0 - J32.9 Chronic sinusitis
R29.810 - R29.91 Other symptoms involving nervous and musculoskeletal systems [focal or sensory deficits]
R51 Headache
R56.00 - R56.9 Convulsions, not elsewhere classified [seizures]
Z79.3 Long-term (current) use of hormonal contraceptives

ICD-10 codes not covered for indications listed in the CPB for MRV:

G45.0 - G45.9 Transient cerebral ischemic attacks and related syndromes [diagnosis of chronic cerebro-spinal venous insufficiency]
I67.0 - I67.9 Other cerebrovascular diseases [diagnosis of chronic cerebro-spinal venous insufficiency]

Chest:

CPT codes covered if selection criteria are met:

71555 Magnetic resonance angiography, chest (excluding myocardium), with or without contrast material(s)

Other CPT codes related to the CPB:

75557-75564 Cardiac magnetic resonance imaging for velocity flow mapping

HCPCS codes covered if selection criteria are met:

C8909 Magnetic resonance angiography with contrast, chest (excluding myocardium)
C8910 Magnetic resonance angiography without contrast, chest (excluding myocardium)
C8911 Magnetic resonance angiography without contrast followed by with contrast, chest (excluding myocardium)

ICD-10 codes covered if selection criteria are met for MRA:

I26.01 - I26.99 Pulmonary embolism
I48.0 - I48.2, I48.91 Atrial fibrillation
I71.010, I71.011, I71.012, I71.019 Dissection of thoracic aorta
I71.10 - I71.13 Thoracic aortic aneurysm, ruptured
I71.20 - I71.23 Thoracic aortic aneurysm, without rupture
Q20.0 - Q28.9 Congenital malformations of the circulatory system

ICD-10 codes not covered for indications listed in the CPB for MRA:

I49.3 Ventricular premature depolarization

ICD-10 codes covered if selection criteria are met for MRV:

I82.B11 - I82.B29 Embolism and thrombosis of subclavian vein
I82.210 - I82.211 Embolism and thrombosis of superior vena cava
I82.290 Acute venous embolism and thrombosis of other thoracic veins

Spine:

CPT codes covered if selection criteria are met:

72159 Magnetic resonance angiography, spinal canal and contents, with or without contrast materials(s)
C8931 Magnetic resonance angiography with contrast, spinal canal and contents
C8932 Magnetic resonance angiography without contrast, spinal canal and contents
C8933 Magnetic resonance angiography without contrast followed by with contrast, spinal canal and contents

ICD-10 codes covered if selection criteria are met for MRA:

I77.0 Arteriovenous fistula, acquired [spinal cord]
Q27.9 Congenital malformation of peripheral vascular system, unspecified [spinal cord]

Abdomen/Pelvis:

CPT codes covered if selection criteria are met:

72198 Magnetic resonance angiography, pelvis, with or without contrast material(s)
74185 Magnetic resonance angiography, abdomen, with or without contrast material(s)

Other CPT codes related to the CPB:

37182 Insertion of transvenous intrahepatic portosystemic shunt(s) (TIPS) (includes venous access, hepatic and portal vein catheterization, portography with hemodynamic evaluation, intrahepatic tract formation/dilatation, stent placement and all associated imaging guidance and documentation)

HCPCS codes covered if selection criteria are met:

A9583 Injection, Gadofosveset Trisodium, 1 ml [Ablavar, Vasovist]
C8900 Magnetic resonance angiography with contrast, abdomen
C8901 Magnetic resonance angiography without contrast, abdomen
C8902 Magnetic resonance angiography without contrast followed by with contrast, abdomen

ICD-10 codes covered if selection criteria are met for MRA:

D57.00 - D57.819 Sickle-cell disorders
I10 - I16.2 Hypertensive diseases
I70.1 Atherosclerosis of renal artery
I71.02 Dissection of abdominal aorta
I71.03 Dissection of thoracoabdominal aorta
I74.01 - I74.09 Embolism and thrombosis of abdominal aorta
I77.3 - I77.6 Other disorders of arteries and arterioles [aortoiliac stenosis]
K55.011 - K55.9 Vascular disorders of intestine [chronic mesenteric ischemia]
K76.6 Portal hypertension
Z91.041 Radiographic dye allergy status [contrast allergy, renal insufficiency]

ICD-10 codes not covered for indications listed in the CPB for MRA:

D35.00 - D35.02 Benign neoplasm of adrenal gland
O69.4xx0 - O69.4xx9 Labor and delivery complicated by vasa previa
Z13.6 Encounter for screening for cardiovascular disorders
Z52.4 Kidney donor

ICD-10 codes covered if selection criteria are met for MRV:

D68.00 - D68.9 Other coagulation defects
I82.0 Budd-Chiari syndrome
I82.1 Thrombophlebitis migrans
I82.220 - I82.221 Embolism and thrombosis of inferior vena cava
I82.3 Embolism and thrombosis of renal vein
K75.1 Phelbitis of portal vein
R10.2 Pelvic and perineal pain [pelvic pain when pelvic congestion syndrome is suspected and pelvic ultrasound findings are equivocal]

ICD-10 codes not covered for indications listed in the CPB for MRV:

I63.0 - I63.9 Cerebral infarction

Ferumoxytol-enhanced MRA and MRV - no specific code:

ICD-10 codes not covered for indications listed in the CPB for MRA:

I70.1 Atherosclerosis of renal artery
N18.1 - N18.9 Chronic kidney disease (CKD)

Lower extremity:

CPT codes covered if selection criteria are met:

73725 Magnetic resonance angiography, lower extremity, with or without contrast material(s)

HCPCS codes covered if selection criteria are met:

A9583 Injection, Gadofosveset Trisodium, 1 ml [Ablavar, Vasovist]
C8912 Magnetic resonance angiography with contrast, lower extremity
C8913 Magnetic resonance angiography without contrast, lower extremity
C8914 Magnetic resonance angiography without contrast, followed by with contrast, lower extremity

ICD-10 codes covered if selection criteria are met for MRA:

I74.3 Embolism and thrombosis of arteries of the lower extremities
I79.8 Disorders of arteries, arterioles and capillaries in diseases classified elsewhere

ICD-10 codes not covered for indications listed in the CPB for MRV:

A17.0 Tuberculous meningitis
I80.10 - I80.299 Phlebitis and thrombophlebitis of other and unspecified deep vessels of lower extremities
I82.401 - I82.5z9 Acute and chronic embolism and thrombosis of deep veins of lower extremities
I87.1 Compression of vein [nutcracker syndrome]

Upper extremity:

Other CPT codes related to the CPB:

72159 Magnetic resonance angiography, spinal canal and contents, with or without contrast material(s)
73225 Magnetic resonance angiography, upper extremity, with or without contrast material(s)

ICD-10 codes not covered for indications listed in the CPB for MRV:

A17.0 Tuberculous meningitis
I80.8 Phlebitis and thrombophlebitis of other sites
I82.a11 - I82.a19 Acute embolism and thrombosis of axillary veins
I82.601 - I82.729 Acute and chronic embolism and thrombosis of superficial and deep veins of upper extremity

Combined unenhanced computed tomography and ferumoxytol-enhanced magnetic resonance angiography:

CPT codes not covered for indications listed in the CPB:

Combined unenhanced computed tomography and ferumoxytol-enhanced magnetic resonance angiography, Ferumoxytol-enhanced MRA - no specific code:

Other HCPCS codes related to the CPB:

Q0138 Injection, ferumoxytol, for treatment of iron deficiency anemia, 1 mg (non-esrd use)
Q0139 Injection, ferumoxytol, for treatment of iron deficiency anemia, 1 mg (for esrd on dialysis)

ICD-10 codes not covered for indications listed in the CPB for combined CT and Ferumoxytol -enhanced MRA:

N00.0 - N29 Renal diseases

Background

Magnetic resonance angiography (MRA) is an application of magnetic resonance imaging (MRI) that provides visualization of blood flow, as well as images of normal and diseased blood vessels.  While MRA appears to be a rapidly developing technology, the clinical safety and effectiveness of this procedure for all anatomical regions has not been proven.

The use of MRA in evaluating flow in the carotid arteries, the circle of Willis, the anterior, middle or posterior cerebral arteries, the vertebral or basilar arteries, or the venous sinuses have been the most well researched applications.  Numerous articles have demonstrated that MRA can image the vessels with a high degree of sensitivity and specificity.  However, the appropriate use of MRA in this setting must be coordinated with the use of the competing technologies, Duplex ultrasonography and angiography.  There is no mention in the literature that all 3 technologies should be used routinely in the work-up of carotid artery disease.  In terms of screening patients with symptoms suggestive of disease, duplex ultrasonography has been shown to be equivalent to MRA, and thus this test is recommended as the initial diagnostic test.  In terms of surgical planning, MRA has been shown to be competitive with angiography, therefore this test can be the second definitive test used for surgical planning.  In this scenario, an angiography would only be considered medically necessary if the ultrasonography and MRA showed major discrepancies.  Finally, in a more limited role, MRA has been suggested as an alternative to angiography in those patients unable to undergo an angiogram due to allergy to contrast material.

Patients with transient ischemic attacks or strokes typically undergo MRI as part of the initial work-up to identify infarcted areas in the brain.  An intra-cranial MRA can be easily appended to the MRI and for that reason has been frequently ordered.  However, an intra-cranial MRA is considered not medically necessary.  MRI can adequately image any infarcted areas, and in the case of transient ischemic attacks, by definition, one would not expect to see any vascular abnormalities.  The use of MRA in the work-up of patients with the vertebrobasilar syndrome must be considered on a case-by-case basis.  The MRA may be appropriate in patients when other sources of emboli have been ruled out, and the MRA is considered as an alternative to an angiogram in order to establish the diagnosis of vertebral artery disease.

Although MRA provides additional imaging capabilities for intra-cranial aneurysms (ICAs) and vascular lesions, it is not clear from the literature how this information will impact on patient management.  In particular, patients who present subacutely with symptoms consistent with aneurysm or vascular malformations will probably undergo a conventional spin-echo MRI followed by angiography, if indicated.  It is unclear from the literature how MRA would alter this imaging hierarchy.  Several authors commented that the anatomic detail provided by MRA is not sufficient to replace an angiogram.  Magnetic resonance angiography has also been suggested as a novel screening technique for patients at high risk for aneurysm; however, its clinical relevance is unknown because of a lack of understanding of the natural history of aneurysms and which aneurysms represent a high risk of rupture.  Due to its low diagnostic yield, MRA is considered not medically necessary for the routine work-up of patients with non-specific, non-focal symptoms, such as headache or dizziness.

Magnetic resonance angiography is an effective non-invasive technique for establishing a diagnosis and evaluating the extent and severity of nearly all diseases of the thoracic aorta.  Studies have shown that MRA of the chest has a high level of diagnostic accuracy for pre-operative and post-operative evaluation of aortic dissection of aneurysm.  Depending on the clinical presentation, MRA may be used as an alternative to other non-invasive imaging technologies (e.g.,  trans-esophageal echocardiography and CT).

Saremi and Tafti (2009) noted that cardiac ablation procedures have become the standard of therapy for various arrhythmias including atrial fibrillation (AF).  Understanding the morphological characteristics of the left atrium (LA) and pulmonary vein (PV) in detail and identification of its anatomic variants is crucial to perform a successful ablation procedure and minimize complications.  The current techniques for radiofrequency ablation of AF include targeting the PVs or the tissue in the antrum of the LA.  Localization of the anatomic structures within the LA is performed by using fluoroscopy, electro-anatomic mapping, and intra-cardiac echocardiography. Multi-dimensional CT and MRA are invaluable techniques for better visualization of the anatomic landmarks that are essential for cardiac ablation procedures as well as prompt diagnosis and, in selected cases, prevention of procedure-related complications.  Some of the complications of ablation procedures may include cardiac tamponade, PV stenosis, as well as esophageal and phrenic nerve injuries.

Holmes et al (2009) stated that ablation procedures for AF are being performed with increasing frequency.  One of the most serious complications is the development of pulmonary vein stenosis, which occurs in 1 % to 3 % of current series.  The presentation of pulmonary vein stenosis varies widely.  The majority of patients are symptomatic although specific referral bias patterns can affect this.  Symptoms may include dyspnea or hemoptysis or may be consistent with bronchitis.  These symptoms are affected by the number of stenotic veins as well as the severity of the stenosis.  The more severe the stenosis and the greater number of stenosed veins result in more symptoms.  Because of the variability in symptoms, clinicians must have heightened sensitivity to the presence of the condition.  Diagnostic tests of value include MRA and computed tomography.  Although echocardiography has been used, it does not usually provide adequate assessment.  Progression of stenosis is unpredictable and may be rapid.  The specific anatomy of the stenosis varies widely and affects management.  Because of the presence of antral fusion of the origin of the left superior and left inferior pulmonary vein, a stenosis involving 1 or the other can impinge and affect outcome.  In this setting, bifurcation techniques familiar to interventional cardiology are very helpful.  Controversy currently exists about the optimal treatment approach.  The use of balloons and larger stents (approximately 10 mm) results in more optimal results than just balloon angioplasty alone; however, even with stent implantation, recurrent re-stenosis may occur in 30 % to 50 % of patients.  Follow-up of these patients typically involves computed tomography imaging to document re-stenosis.  If significant re-stenosis is identified, it should be treated promptly because of the potential for progression to total occlusion.

Furthermore, a CMS decision memo (2010) noted that it has received a position statement in the form of a combined comment from the American College of Cardiology (ACC), American College of Radiology (ACR), American Society of Neuroradiology (ASNR), North American Society for Cardiovascular Imaging (NASCI), and the Society for Cardiovascular Magnetic Resonance (SCMR).  They were in favor of combining the currently separate NCDs, allowing local Medicare contractor discretion to cover use of MRA for additional indications which are currently non-covered, and they recommended national coverage for MRA of the pulmonary veins before and after radiofrequency ablation for AF.

Current scientific data shows that diagnostic pulmonary MRAs are improving due to recent developments such as faster imaging capabilities and gadolinium-enhancement.  However, these advances in MRA are not significant enough to warrant replacement of pulmonary angiography in the diagnosis of pulmonary embolism for patients who have no contraindication to receiving intravenous iodinated contrast material.  The tortuous pulsatile nature of the coronary arteries presents an imposing technical challenge to MRA.  The application of MRA for this purpose is still in its infancy.

Studies have proven that MRA is considered a reliable diagnostic tool for the pre-operative evaluation of patients who will undergo elective abdominal aortic aneurysm (AAA) repair.  In addition, scientific data has revealed that MRA is considered comparable to conventional angiography in determining the extent of the AAA, as well as evaluation of aorto-illiac occlusion disease and renal artery pathology that may be necessary in the surgical planning for AAA repair.  If pre-operative angiography is not necessary, then patients are not exposed to the risks associated with invasive contrast procedures, namely allergic reactions, end-organ damage or arterial injury.  Magnetic resonance angiography has also become accepted as a method to detect suspected stenosis in the main renal arteries; its inability to image distal lesions and accessory arteries limits its diagnostic abilities.

Although MRA assessment for the evaluation of renal artery stenosis is acceptable, the accuracy of MRA as a screening method for renovascular hypertension is unproven, and MRA is inadequate in the identification of accessory renal arteries because it has not achieved the level of accuracy needed to replace conventional angiography in the evaluation of potential living renal donors.

Surgical planning for peripheral arterial occlusive disease in the lower extremities depends on identification of adequate inflow and distal run off vessels.  Magnetic resonance angiography has been shown to be a superior technique in identifying distal run-off vessels and is competitive with angiography in identifying appropriate inflow vessels.  Therefore, MRA can be used as an initial test for surgical planning, with a subsequent angiography only if the inflow vessel is not identified.  If angiography is performed first, an MRA may be appropriate if a distal run-off vessel is not identified because MRA is capable of detecting a viable run-off vessel for bypass not seen on traditional angiography, especially when exploratory surgery is not believed to be a reasonable medical course of action for the patient.

On December 24, 2008, the United States Food and Drug Administration (FDA) approved Vasovist injection (gadofosveset trisodium, now marketed as Ablavar), the first contrast imaging agent for use in patients undergoing MRA.  Gadofosveset reversibly binds to albumin providing extended intravascular enhancement compared with existing extracellular magnetic resonance contrast agents.  Administration of gadofosveset provides a clearer image in patients who are suspected of having blockages or other problems with the blood vessels in their abdomen or extremities.  The safety and effectiveness of Vasovist was established in 2 clinical trials of patients with known or suspected aorto-iliac disease.  In the studies, patients underwent MRA with and without Vasovist and their scans were compared to standard X-ray pictures using contrast.  Magnetic resonance angiography with Vasovist detected more arterial disease than MRA performed without Vasovist and the pictures were of improved technical quality.

Bosch et al (2008) evaluated the safety and effectiveness of gadofosveset in patients with pedal arterial disease.  A total of 185 adult patients with known or suspected pedal arterial disease were randomized in a group receiving 0.03 mmol/kg and a group receiving 0.05 mmol/kg of gadofosveset for MRA of the pedal arteries.  Gadofosveset-enhanced and unenhanced time-of-flight MR angiograms were compared with conventional angiograms for the presence of vascular stenosis.  All patients underwent drug safety analysis.  For each of 3 blinded readers, the specificity (21 to 35 %) of gadofosveset-enhanced MRA was a statistically significant (p < 0.010) improvement over that of unenhanced MRA in the detection of clinically significant (greater than 50 %) stenosis.  The sensitivities of the 2 techniques were similar.  For all blinded readers of MR angiograms, sensitivity, specificity, and accuracy were higher with use of the 0.03-mmol/kg dose of gadofosveset than with the 0.05-mmol/kg dose.  In the 0.03-mmol/kg group, 28 % of patients reported a total of 50 adverse events, 96 % of which were reported as mild or moderate.  In the 0.05-mmol/kg group, 28 % of patients reported a total of 55 adverse events, 98 % of which were reported as mild or moderate.  No patients died; 1 patient left the study because of myocardial infarction considered unrelated to the study drug.  The authors concluded that because of markedly better efficacy than no contrast agent and a minimal and transient side-effect profile, 0.03 mmol/kg of gadofosveset was found safe and effective for MRA of patients with pedal arterial disease.

In a multi-center, comparative, phase III single-dose clinical study, McGregor et al (2008) examined the effectiveness of gadofosveset-enhanced MRA for evaluation of renal artery disease.  Gadofosveset (0.03 mmol/kg) was administered to adult patients with known or suspected renal arterial disease; the drug allows collection of images in the first-pass and steady-state phases.  The combination of these images was compared to non-contrast MRA, using catheter X-ray angiography (XRA) as the standard of reference.  All MRA images were collected at 1.5 T in 1 imaging session for direct comparison, and XRA within 30 days.  Sensitivity, specificity, and accuracy for diagnosing significant disease (stenosis greater than or equal to 50 %) were calculated for MRA using 3 independent blinded readers.  Patient safety was monitored for 72 to 96 hours.  A total of 145 patients were enrolled and received gadofosveset; the 127 with complete efficacy data entered the primary efficacy analysis.  Gadofosveset-enhanced MRA led to significant improvement (p < 0.01) in sensitivity (+25 %, +26 %, +42 %), specificity (+23 %, +25 %, +29 %), and accuracy (+23 %, +28 %, +29 %) over non-enhanced MRA for the 3 readers.  The rate of uninterpretable examinations decreased from 30 % to less than 2 %.  There were no serious adverse events, and the most common adverse events were nausea, pruritis, and headache (8 % each).  No significant trends in clinical chemistry parameters, nor significant changes in serum creatinine, were found following administration of gadofosveset.  The authors concluded that in patients with known or suspected renal arterial disease, gadofosveset-enhanced MRA significantly improves sensitivity, specificity, and accuracy versus non-enhanced MRA.  Gadofosveset was safe and well-tolerated in this patient population.

There is evidence that MRA, as an adjunct to conventional MRI, is useful in the evaluation of the of spinal cord.  Farb et al (2002) described the cases of 9 patients with initial MRI and clinical findings suggestive of spinal dural arterio-venous fistula (AVF) who underwent spinal MRA with an auto-triggered elliptic centric ordered three-dimensional (3-D) gadolinium-enhanced technique (hereafter, this MRA technique) before conventional intra-arterial angiography.  In all 9 patients, findings with this MRA technique correctly and precisely localized the spinal dural AVF.  Observer error resulted in 1 case in which the site of the fistula was not prospectively reported, but was easily identified retrospectively on the spinal MR angiogram.

Saraf-Lavi E et al (2002) studied the sensitivity, specificity, and accuracy of MRI alone compared with MRI plus MRA in determining whether dural AVF are present and established the accuracy of MRA in predicting fistula level.  A total of 20 patients with surgically proven dural AVF (diagnosed with radiographic digital subtraction angiography) and 11 control patients who had normal digital subtraction angiography findings underwent routine MRI plus 3-D contrast-enhanced MRA of the spine.  Images were reviewed in 2 stages (stage I, MRI only; stage II, MRI plus MRA) by 3 neuroradiologists who were blinded to the final diagnoses.  The sensitivity, specificity, and accuracy of the 3 reviewers in detecting the presence of fistulae ranged from 85 % to 90 %, from 82 % to 100 %, and from 87 % to 90 %, respectively, for stage I, compared with values of 80 % to 100 %, 82 %, and 81 % to 94 %, respectively, for stage II.  For each reviewer, there were no significant differences between the values for stage I and stage II; however, among the reviewers, one of the more experienced neuroradiologists had significantly greater sensitivity than a less experienced neuroradiologist for stage II.  On average, the percentage of true positive results for which the correct fistula level was predicted increased from 15 % for stage I to 50 % for stage II, and the correct level +/- one level was predicted in 73 % for stage II.  MR evidence of increased intra-dural vascularity was significantly greater in patients with dural AVF.  The authors concluded that the addition of MRA to standard MRI of the spine may improve sensitivity in the detection of spinal dural fistulae.  The principal benefit of MRA is in the improved localization of the vertebral level of the fistula, which potentially expedites the subsequent digital subtraction angiography study.

Luetmer et al (2005) tested the hypothesis that elliptic centric contrast-enhanced MRA can be used to detect spinal dural AVFs, predict the level of fistulas, and reduce the radiation dose and volume of iodinated contrast material associated with conventional angiography.  These researchers examined 31 patients who presented with suspected spinal dural AVF.  All patients underwent MRA and conventional angiography.  The effect of MRA on subsequent conventional angiography was assessed by analyzing total fluoroscopy time and volume of iodinated contrast material used.  At angiography, spinal dural AVFs were diagnosed in 22 of 31 patients, and MRA depicted an AVF in 20 of the 22 patients.  Magnectic resonance angiographic findings correctly predicted a negative angiogram in 7 of 9 cases.  Of the 20 true-positive MRA results, the level of the fistula was included in the imaging volume in 14.  In 13 of these 14 cases, MRA results correctly predicted the side and the level of the fistula to within 1 vertebral level.  Fluoroscopy time and the volume of contrast agent was reduced by more than 50 % in the 13 patients with a spinal dural AVF in whom MRA prospectively indicated the correct level.  The authors concluded that contrast-enhanced MRA can be used to detect spinal dural AVFs, predict the level of fistulas, and substantially reduce the radiation dose and volume of contrast agent associated with catheter spinal angiography.

Meckel et al (2007) stated that digital subtraction angiography (DSA) is the method of reference for imaging of dural AVF (DAVF).  The goal of this study was to analyze the value of different MR images including 3-D contrast-enhanced MRA with a high temporal resolution in diagnostic and follow-up imaging of DAVFs.  A total of 18 MR/MRA examinations from 14 patients with untreated (n = 9) and/or treated (n = 9) DAVFs were evaluated.  Two observers assessed all MR and MRA investigations for signs indicating the presence of a DAVF, for fistula characteristics such as fistula grading, location of fistulous point, and fistula obliteration after treatment.  All results were compared with DSA findings.  On time-resolved 3-D contrast-enhanced (TR 3-D) MRA, the side and presence of all patent fistulas (n = 13) were correctly indicated, and no false-positive findings were observed in occluded DAVFs (n = 5).  Grading of fistulas with this imaging technique was correct in 77 % and 85 % of patent fistulas for both readers, respectively.  On T2-weighted images, signs indicative of a DAVF were encountered only in fistulas with cortical venous reflux (56 %), whereas on 3-D time-of-flight (TOF) MRA, most fistulas (88 %) were correctly detected.  In complete fistula occlusion, false-positive findings were encountered on both T2-weighted images and on TOF MRA images.  The authors concluded that TR 3-D MRA proved reliable in detecting DAVFs and suitable for follow-up imaging.  The technique allowed -- within limitations -- to grade DAVFs.  Although 3-D TOF MRA can depict signs of DAVFs, its value for follow-up imaging is limited.

Mull et al (2007) examined the validity of MRA for identification of spinal arterio-venous (AV) abnormalities.  A total of 34 consecutive patients with suspicion of spinal vascular abnormalities underwent digital subtraction angiography (DSA) after MRA.  The level and side of the suspected spinal DAVF (SDAVF) and the feeding arteries in spinal AV malformations (SAVMs) were determined from MRA and compared with DSA.  DSA revealed SDAVF in 20 abnormalities of which 19 were spinal and 1 was tentorial with spinal drainage, as well as SAVM in 11 patients.  In 3 patients, MRA and DSA were both normal.  For detection of spinal AV abnormalities, neither false-positive nor false-negative MRA result was obtained.  The MRA-derived level of the feeding artery in SDAVF agreed with DSA in 14 of 19 cases.  In 5 cases, a mis-match of 1 vertebral level (not side) was noted for the feeding artery.  For the tentorial AVF, only the spinal drainage was depicted; the feeding artery was outside the MRA field of view.  In intra-dural SAVM, the main feeding artery was identified by MRA in 10 of 11 patients.  Magnetic resonance angiography could differentiate between glomerular and fistulous SAVM in 4 of 6 cases and between sacral SDAVF and filum terminale SAVM in 2 of 5 cases.  The authors concluded that MRA reliably detects or excludes various types of spinal AV abnormalities and localizes the (predominant) arterial feeder of most spinal AV shunts.  Although classification of the subtype of SAVMs remains difficult, with MRA it greatly helps to focus subsequent DSA.

Sharma and Westesson (2008) noted that contrast-enhanced MRA has been increasingly used in the evaluation of spinal vascular malformations.  Furthermore, in a review on advances in spinal cord MRA, Backes and Nijenhuis (2008) noted that current fast contrast-enhanced MR techniques are able to
  1. visualize vessels supplying or draining the spinal cord and
  2. differentiate spinal cord arteries from veins. 

The localization of the Adamkiewicz artery, the largest artery supplying the thoraco-lumbar spinal cord, has become possible in a reproducible and reliable manner.  Knowledge of the anatomic location of this artery and its arterial supplier may be of benefit in the work-up for aortic aneurysm surgery to reduce incidences of ischemic injury.  Spinal cord MRA is ready to become a diagnostic tool that can compete with catheter angiography for detecting and localizing arterial feeders of vascular lesions and is strongly advised for use prior to invasive catheter angiography.

An UpToDate review on "Prevalence and evaluation of ventricular premature beats" (Podrid, 2012) does not mention the use of magnetic resonance angiography.

Lookstein et al (2004) compared the findings of time resolved-MRA (TR-MRA) with conventional angiography for the characterization of endoleaks.  Between June 2002 and June 2003, 12 patients with documented endoleaks following endovascular repair of aortic aneurysms (10 abdominal and 2 thoracic) underwent TR-MRA to identify and characterize the endoleak.  All patients had nitinol-based aortic stent grafts.  MRA was performed on a 1.5-Tesla magnet (Sonata class; Siemens Medical Systems, Iselin, NJ).  The TR-MRA studies were reviewed under continuous observation as a "cine MR angiogram".  These MRA data sets were used to classify the endoleaks into types 1 through 3.  The patients underwent conventional angiography following the MRA to confirm the findings and to plan treatment.  The MRA findings were compared with the findings made at conventional arteriography.  TR-MRA identified 7 patients with type 1 leaks, including 4 proximal and 3 distal.  Four patients had type 2 leaks, including 2 arising from the inferior mesenteric artery and 2 from an ilio-lumbar artery.  One patient had a type 3 leak.  Conventional angiography confirmed the type of endoleak in all 12 patients.  The authors concluded that these initial results demonstrated TR-MRA to be an effective non-invasive method for classifying endoleaks.  This technique may allow for screening of patients with endoleaks to identify those requiring urgent repair.

The American College of Radiology (ACR)/North American Society for Cardiovascular Imaging (NASCI)/Society for Pediatric Radiology (SPR)’s practice guideline on “The performance of pediatric and adult body magnetic resonance angiography (MRA)” (ACR-NASCI-SPR, 2010) stated that abdominal and pelvic MRA can be used for post-procedure assessment for detection of suspected leak following aortic aneurysm surgery or MR-compatible aortic stent graft placement”.  Moreover, the ACR’s Appropriateness Criteria on “Abdominal Aortic Aneurysm: Interventional Planning and Follow-up” (2012) stated that “For detection and sizing of endoleak, MRA is at least as sensitive as, and probably better than CTA …. 3D contrast-enhanced MRA and time resolved MRA are highly sensitive to endoleaks”.  The ACR’s recommendation was given a “7” rating; and 7, 8, and 9 “ratings” denote “Usually appropriate”.

Furthermore, an UpToDate review on “Endovascular repair of abdominal aortic aneurysm” (Chaer, 2014) states that “CT angiography with delayed images is the most widely used modality for follow-up after endovascular aneurysm repair (EVAR).  It is accurate for maximal diameter measurement, and for the detection of endoleak and other device-related complications.  However, CT angiography is costly and repeated radiation exposure is associated with an increased lifetime cancer risk.  Repeated administration of intravenous contrast may also contribute to a progressive decline in renal function that has been observed following EVAR.  The guidelines for the management of abdominal aortic aneurysm (AAA) from the Society for Vascular Surgery advocate CT angiography at 1 and 12 months during the first year after EVAR.  Imaging at six months is no longer routinely recommended unless an endoleak or other device-related abnormality is identified at the one-month imaging study after EVAR.  If an endoleak or aneurysm enlargement is not documented during the first year after EVAR, DU [duplex ultrasonography] is an alternative to CT angiography for ongoing postoperative surveillance …. MR imaging is not a standard modality for EVAR surveillance, but can be used in specific situations where CT angiography is contraindicated.  The advantage of MR imaging is the lack of exposure to ionizing radiation.  Disadvantages are its lack of wide availability and difficulty evaluating device integrity due to artifact.  The placement of stent-grafts made of nitinol does not preclude MR imaging, though MR imaging is contraindicated for stainless-steel-based grafts (e.g., Cook, Zenith)”.

Miller et al (2009) stated that neuro-vascular compression (NVC) of the trigeminal nerve is associated with trigeminal neuralgia (TN), but also occurs in many patients without facial pain.  These researchers identified anatomical characteristics of NVC associated with TN.  A total of 30 patients with type 1 TN (intermittent shock-like pain) and 15 patients without facial pain underwent imaging for analysis of 30 trigeminal nerves ipsilateral to TN symptoms, 30 contralateral to TN symptoms, and 30 in asymptomatic patients were include in this study.  Patients underwent 3-T MRI including balanced fast-field echo and MRA.  Images were fused and reconstructed into virtual cisternoscopy images that were evaluated to determine the presence and degree of NVC.  Reconstructed coronal images were used to measure nerve diameter and cross-sectional area.  The incidence of arterial NVC in asymptomatic nerves, nerves contralateral to TN symptoms, and nerves ipsilateral to TN symptoms was 17 %, 43 %, and 57 %, respectively.  The difference between symptomatic and asymptomatic nerves was significant regarding the presence of NVC, nerve distortion, and the site of compression (p < 0.001, Fisher exact test).  The most significant predictors of TN were compression of the proximal nerve (odds ratio 10.4) and nerve indentation or displacement (odds ratio 4.3).  There was a tendency for the development of increasingly severe nerve compression with more advanced patient age across all groups.  Decreased nerve size was observed in patients with TN but did not correlate with the presence or extent of NVC.  The authors concluded that trigeminal NVC occurs in asymptomatic patients but is more severe and more proximal in patients with TN.  Moreover, they stated that this information may help identify patients who are likely to benefit from micro-vascular decompression (MVD).

Zacest et al (2010) stated that TN is a neuropathic pain syndrome that is often associated with NVC of the TN and may be effectively treated with MVD.  The authors used high-resolution MRI with 3D reconstruction in patients with constant facial pain (type 2 TN) to determine the presence/absence of NVC and thus a potential MVD benefit.  They retrospectively contacted patients to evaluate outcome.  All patients who reported spontaneous onset of constant facial pain (type 2 TN), which occurred at least 50 % of the time, who had undergone high-resolution 3-T MRI with 3D reconstruction were retrospectively selected for this study.  Clinical history, facial pain questionnaire data, physical examination findings, and results from 3-T 3D MRI reconstruction were recorded for all patients.  Intra-operative findings and clinical pain outcome were recorded for all patients who underwent MVD.  Data obtained in 27 patients were assessed.  On the basis of history and 3D MRI reconstruction findings, 13 patients were selected for MVD (Group A) and 14 underwent conservative treatment (Group B).  Typical or suspected artery- or vein-induced NVC was predicted pre-operatively in 100 % of Group A patients and in 0 % of Group B patients.  At the time of MVD, definitive NVC was confirmed in 11 (84.6 %) of 13 Group A patients.  Following MVD, facial pain was completely relieved in 3 (23 %), improved in 7 (53.8 %), and no better in 3 (23 %) of 13 Group A patients.  A history of episodic (type 1 TN) pain at any time was reported in 100 % and 50 % of Group A and Group B patients, respectively.  A type 1 TN pain component was reportedly improved/relieved in all Group A patients, but the type 2 TN pain component was improved in only 7 (53.8 %) of 13 patients.  The mean post-operative follow-up duration was 13 months.  The authors concluded that high-resolution 3D MRI reconstruction in patients with constant facial pain (type 2 TN) can help determine the presence/absence of NVC.  They stated that surgical selection based on both clinical and radiological criteria has the potential to improve surgical outcome in patients with type 2 TN who may potentially benefit from MVD.  However, even in such selected patients, pain relief is likely to be incomplete.

Leal et al (2014) prospectively evaluated atrophic changes in trigeminal nerves (TGNs) using measurements of volume (V) and cross-sectional area (CSA) from high-resolution 3-T MR images obtained in patients with unilateral TN, and correlated these data with patient and NVC characteristics and with clinical outcomes.  Anatomical TGN parameters (V and CSA) were obtained in 50 patients (30 women and 20 men; mean age of 56.42 years, range of 22 to 79 years) with classic TN before treatment with MVD.  Parameters were compared between the symptomatic (ipsilateralTN) and asymptomatic (contralateralTN) sides of the face; 20 normal control subjects were also included.  Two independent observers blinded to the side of pain separately analyzed the images.  Measurements of V (from the pons to the entrance of the nerve into Meckel's cave) and CSA (at 5 mm from the entry of the TGN into the pons) for each TGN were performed using imaging software and axial and coronal projections, respectively.  These data were correlated with patient characteristics (age, duration of symptoms before MVD, side of pain, sex, and area of pain distribution), NVC characteristics (type of vessel involved in NVC, location of compression along the nerve, site of compression around the circumference of the root, and degree of compression), and clinical outcomes at the 2-year follow-up after surgery.  Comparisons were made using Bonferroni's test.  Inter-observer variability was assessed using the Pearson correlation coefficient.  The mean V of the TGN on the ipsilateralTN (60.35 ± 21.74 mm(3)) was significantly smaller (p < 0.05) than those for the contralateralTN and controls (78.62 ± 24.62 mm(3) and 89.09 ± 14.72 mm(3), respectively).  The mean CSA of the TGN on the ipsilateralTN (4.17 ± 1.74 mm(2)) was significantly smaller than those for the contralateralTN and controls (5.41 ± 1.89 mm(2) and 5.64 ± 0.85 mm(2), respectively).  The ipsilateralTN with NVC Grade III (marked indentation) had a significantly smaller mean V than the ipsilateralTN with NVC Grade I (mere contact), although it was not significantly smaller than that of the ipsilateralTN with NVC Grade II (displacement or distortion of root).  The ipsilateralTN with NVC Grade III had a significantly smaller mean CSA than the ipsilateralTN with NVC Grades I and II (p < 0.05).  The TGN on the ipsilateralTN in cured patients had a smaller mean CSA than that on the ipsilateralTN of patients with partial pain relief or treatment failure (p < 0.05).  The same finding was almost found in relation to measurements of V, but the p value was slightly higher at 0.05.  The authors concluded that the findings of this study showed that TGN atrophy in patients with TN can be demonstrated by high-resolution imaging.  Moreover, they stated that these data suggested that atrophic changes in TGNs, which significantly correlated with the severity of compression and clinical outcomes, may help to predict long-term prognosis after vascular decompression.

An UpToDate review on “Trigeminal neuralgia” (Bajwa et al, 2014) states that “Neuroimaging with head CT or MRI is useful for identifying the small proportion of patients who have a structural lesion (e.g., tumor in the cerebellopontine angle, demyelinating lesions including multiple sclerosis) as the cause of painful trigeminal neuropathy.  In addition, high resolution MRI and magnetic resonance angiography (MRA) may be useful for identifying vascular compression as the etiology of classic TN, but the utility of these studies has not been established …. The 2008 AAN/EFNS practice parameter identified seven studies that performed high-resolution brain MRI and/or magnetic resonance angiography (MRA) to demonstrate neurovascular compression in patients with TN.  The following observations were made:

  • There was wide variation among the included studies for both sensitivity (range 52 to 100 %) and specificity (29 to 93 %).
  • In 3 of the 5 highest-quality MRI studies (cohort surveys with prospective data collection), the difference in rate of neurovascular trigeminal nerve compression on the symptomatic side compared with asymptomatic side was statistically non-significant.

Given these inconsistent results, the AAN/EFNS concluded that there is insufficient evidence to support or refute the utility of MRI to identify neurovascular compression in classic TN, or to indicate the most reliable MRI technique”.

Magnetic Resonance Angiography (MRA) for the Diagnosis of Cerebral Arteriovenous Malformation

In a retrospective, observational study, Chowdhury et al (2015) compared MRA and DSA in diagnosis of cerebral arterio-venous malformation (AVM).  A total of 30 patients with hemorrhagic stroke age ranging from 13 to 65 years were selected on the basis of inclusion and exclusion criteria as the study sample.  MRA and DSA were done in all the selected patients.  The mean age of the patients of hemorrhagic stroke was 30.3 ± 14.3 years and male to female ratio was 2.7:1.  Regarding the venous drainage of AVM 13 and 12 were superficial and deep, respectively, and evaluated 100 % by MRA.  In the diagnosis of cerebral AVM nidus size S1: less than 3 and S2: 3 to 6 cm sensitivity was 100 % but accuracy was 100 % and 73.3 %, respectively.  DSA was 100 % sensitive in the diagnosis of superficial and deep venous drainage AVM.  Regarding the eloquence of brain area 15 had no eloquence by both MRA and DSA and identification of eloquence of brain area sensitivity was 73.3 % and accuracy was 86.7 %.  The main feeding vessels were found (22, 73.3 %) in both DSA and MRA findings.  Distal vessels was seen (8, 26.7 %) in DSA but not seen in MRA findings.  Intra-nidal aneurysm and angiopathic AVM were seen in 3 (10.0 %) and 4 (13.3 %), respectively in DSA.  This study was carried out to diagnose the patients presented with cerebral AVM by MRA and DSA.  The authors concluded that MRA could not be evaluated flow status of AVM, distal feeding arteries, intra-nidal aneurysm and angiopathic AVM, which could be detected by DSA.  So, DSA is superior to MRA in diagnosis of cerebral AVM.

MRA for the Diagnosis and Treatment Response in Individuals with Moyamoya Disease

Uchino et al (2015) stated that noncontrast-enhanced time-resolved 4-dimensional MRA using an arterial spin labeling technique (ASL-4D MRA) is emerging as a next generation angiography for the management of neurovascular diseases.  This study evaluated the feasibility of ASL-4D MRA for the diagnosis of Moyamoya disease (MMD) and MMD staging by using DSA and TOF MRA as current standards.  A total of 11 consecutive non-operated patients who underwent DSA for the diagnosis of MMD were recruited.  Two independent observers evaluated the 3 tests.  The data were analyzed for inter-observer and inter-modality agreements on MMD stage; 9 of 22 hemispheres underwent surgical re-vascularization and ASL-4D MRA was repeated post-operatively.  Time-resolved inflow of blood through the cerebral vessels, including moyamoya vessels, was visualized in all the 22 non-operated hemispheres.  MMD stages assessed by DSA and ASL-4D MRA were completely matched in 18 hemispheres, with a significant positive correlation between these modalities (r = 0.93, p < 0.001).  Inter-observer agreement with ASL-4D MRA (κ = 0.91 ± 0.04, p < 0.001) and inter-modality agreement between ASL-4D MRA and DSA (κ = 0.93 ± 0.04, p < 0.001) were both excellent.  MMD stages assessed by ASL-4D MRA have also a significant positive correlation with those assessed by TOF MRA (r = 0.68, p = 0.004).  Repeated ASL-4D MRA clearly demonstrated the bypassed arteries and changes in the dynamic flow patterns of cerebral arteries in all the 9 hemispheres after surgical re-vascularization.  Of these, post-operative focal hyper-perfusion was detected by single photon emission tomography in 7 hemispheres.  In 5 of the 7 hemispheres (71 %) with post-operative hyper-perfusion, ASL-4D MRA demonstrated focal hyper-intense signals in the bypassed arteries, although TOF MRA did not.  The authors concluded that noninvasive ASL-4D MRA is feasible for the diagnosis of MMD staging.  This next generation angiography may be useful for monitoring disease evolution and treatment response in cerebral arteries after revascularization surgery in MMD.  These preliminary findings need to be validated by well-designed studies.

MRA for the Evaluation of Aneurysm Coiling

In a systematic review and meta-analysis, Ernst et al (2015) examined the inter-rater reliability of visual rating of aneurysm occlusion as study end-point.  Electronic databases (MEDLINE, EMBASE, PubMed, and the Cochrane Library) were searched up to June 2014.  Assessment of risk for bias was based on the Quality Appraisal Tool for Studies of Diagnostic Reliability and the Guidelines for Reporting Reliability and Agreement studies.  Inter-rater reliability estimates were pooled across studies using meta-analysis, and the influence of several factors (e.g., imaging methods, grading scales, and occlusion rate) was tested with meta-regression.  From 1,193 titles, 644 abstracts and 87 full-text versions were reviewed.  A total of 26 articles met the inclusion criteria and provided 77 reliability estimates; 21 different rating scales were used, and statistical analysis varied.  Mean inter-rater agreement of the pooled studies was substantial (κ = 0.65; 95 % confidence interval [CI]: 0.60 to 0.69).  Reliability varied significantly as a function of imaging methods, grading scales, occlusion rates, and their interaction.  Observer agreement substantially increased with increasing occlusion rate in digital subtraction angiography but not in MA.  Reliability was higher in studies using 2- or 3-value grading scales than in studies with 4-value grading scales.  The authors concluded that there was significant heterogeneity between studies evaluating the reliability of visual evaluation of aneurysm coiling.  On the basis of this analysis, these researchers found that the combination of MRA, 3-value grading scale, and 2 trained raters appeared most promising for usage as surrogate study end-points.

Marciano and colleagues (2017) noted that data about non-invasive follow-up of aneurysm after stent-assisted coiling is scarce.  In a retrospective, single-center study, these investigators compared TOF MRA (3D-TOF-MRA) and contrast-enhanced MRA (CE-MRA) at 3-Tesla, with DSA for evaluating aneurysm occlusion and parent artery patency after stent-assisted coiling.  Patients were included if they had an intracranial aneurysm treated by stent-assisted coiling between March 2008 and June 2015, followed with both MRA sequences (3D-TOF-MRA and CE-MRA) at 3-Tesla and DSA, performed in an interval of less than 48 hours.  A total of 35 aneurysms were included.  Regarding aneurysm occlusion evaluation, agreement with DSA was better for CE-MRA (K = 0.53) than 3D-TOF-MRA (K = 0.28).  Diagnostic accuracies for aneurysm remnant depiction were similar for 3D-TOF-MRA and CE-MRA (p = 1).  Both 3D-TOF-MRA (K = 0.05) and CE-MRA (K = -0.04) were unable to detect pathological vessel compared to DSA, without difference in accuracy (p = 0.68).  For parent artery occlusion detection, agreement with DSA was substantial for 3D-TOF-MRA (K = 0.64) and moderate for CE-MRA (K = 0.45), with similar good diagnostic accuracies (p = 1).  The authors concluded that after stent-assisted coiling treatment, 3D-TOF-MRA and CE-MRA demonstrated good accuracy to detect aneurysm remnant (but tended to over-estimation).  They stated that although CE-MRA agreement with DSA was better, there was no statistical difference between 3D-TOF-MRA and CE-MRA accuracies.  Both MRAs were unable to provide a precise evaluation of in-stent status; but could detect parent vessel occlusion.

Ernst and associates (2018) stated that understanding aneurysm growth is critical for the appropriate follow-up of patients after coil embolization and the need for re-treatment.  These researchers stratified the growth dynamics of aneurysm recurrences after coiling by volumetric analysis and determined predictive factors for aneurysm recurrences.  Source images of follow-up 3D-TOF-MRA scans were compared with the first post-interventional TOF-MRA scan and analyzed for residual flow after co-registration using ANALYZE-software.  In the event of incomplete occlusion, the residual volume was segmented and calculated.  Growth dynamic was determined for each aneurysm after embolization.  These researchers analyzed 326 patients with 345 aneurysms from 2 centers. Each case had at least 2 TOF-MRA examinations after endovascular therapy.  The mean observation interval was 59 months.  Volumetric analysis of 1,139 follow-up MRAs revealed that 218/345 aneurysms (63.2 %) showed complete occlusion on initial follow-up imaging, and of these 95.0 % remained stable.  A steady increase in intra-aneurysmal flow was observed in 83/345 (24.1 %).  Less frequent observations were a steep increase (21/345; 6.1 %) and a decrease (27/345; 7.8 %).  Independent predictors of increasing residual flow were greatest aneurysm diameter, total coil length, and incomplete occlusion.  The authors concluded that volumetric analysis of registered 3D-TOF-MRA follow-up datasets allowed the detection of different growth patterns with high precision, avoided the low inter-rater reliability, and represented a promising approach for future studies that include analysis of more complex predictors of residual flow.  In cases of aneurysm recurrence after coiling, the major pattern appeared to be a steady increase in intra-aneurysmal flow over several months.

MRA for the Evaluation of Varices at Hepatico-Jejunostomy after Liver Transplantation

Jimbo et al (20150 reported the case of a 7-year old Japanese girl who had undergone living-donor liver transplantation (LT) at the age of 10 months for decompensated liver cirrhosis caused by biliary atresia presented with recurrent episodes of obscure gastrointestinal bleeding (GIB) with anemia.  Over the following 6 years, she experienced 5 episodes of GIB requiring hospitalization.  Subsequent evaluations including repeat esophagogastroduodenoscopy (EGD), colonoscopy (CS), contrast-enhanced computed tomography (CT), and Meckel's scan all failed to reveal a bleeding source.  However, varices at the site of hepatico-jejunostomy were detected on abdominal ultrasonography and MRA at the age of 7 years.  The authors concluded that MRA might be more helpful than contrast-enhanced CT for identifying such bleeding.  These preliminary findings need to be validated by well-designed studies.

MRA for Management of Chiari Malformation Type I

In a retrospective study, Ohtonari et al (2018) examined CSF) dynamics at the cranio-cervical junction (CCJ) using Time-SLIP MRI to demonstrate the significance of ventral and dorsal combined CSF dynamics in assessing CSF flow disturbance in patients with Chiari malformation type I (CM-I).  A total of 15 examinations were carried out in 9 cases of CM-I (3 female patients; mean age of 24.7 years; range of 11 to 46 years) before or after cranio-cervical decompression.  The longitudinal maximum movement of the caudal edge of tagged midsagittal CSF at the CCJ was measured as length of motion (LOM), and total on the ventral and dorsal sides was defined as total LOM.  In 8 conditions, where it was concluded that no cranio-cervical decompression was necessary or where symptoms improved following cranio-cervical decompression based on the clinical symptoms, total LOM was 49.8 ± 13.1 mm.  In contrast, in the 7 cases where cranio-cervical decompression was mandatory, total LOM was 23.2 ± 9.2 mm.  Significant differences were identified between the 2 groups.  Total LOM of less than 35.0 mm resulted to indicate the insufficiency of CSF dynamics, because it corresponded to the necessity of cranio-cervical decompression based on patients' symptoms.  The authors concluded that Time-SLIP MRI enabled clinicians to use novel dynamic indices, such as CSF motions, in addition to the conventional findings acquired by MRI.  In particular, it was essential to examine combined ventral and dorsal CSF dynamics in assessing CSF patency at the CCJ in patients with CM-I.

The authors stated that this study had several drawbacks.  Because this study had a retrospective design and the sample size was small (9 cases), further prospective studies are needed in a larger population in the future.  The CSF flow imaging using Time-SLIP MRI started to be applied clinically only since 2012 by Toshiba Corporation, Japan.  However, even in Japan in which this equipment has been developed, the possession rate of Time-SLIP technique remains limited; thus, all 15 examinations in this series were carried out in a satellite clinic, in which Time-SLIP MRI was only available in the authors’ group.  Because of such circumstance, the timing of examinations ranged widely between pre-operative stage and revision stage of former surgery and was limited to only pre-operative or post-operative stage in some cases.  Because these researchers have not yet compared the LOM assessment factor in their series to control groups, their analysis of LOM regarding the difference between ventral and dorsal subarachnoid spaces has just begun in normal volunteers.  It also remains unclear if similar results are brought in symptomatic cases without syrinx, or in the degree of tonsillar ectopia in incidentally diagnosed CM-I.  The suffering rate of cervical cord syrinx in this trial, 8 of 9 patients, might be also biased, because it could be an independent indicator of surgery.  However, in the daily clinical field, these investigators usually treat more symptomatic patients compared with incidentally diagnosed or asymptomatic cases.  In this series, the suffering rate of syrinx in symptomatic patients reached almost 85 %.  Under such circumstances, these investigators hoped that LOM will be a beneficial assessment factor in the comparison between normal volunteers and patients with CM-I in future investigations.

Furthermore, an UpToDate review on “Chiari malformations” (Khoury, 2022) does not mention magnetic resonance angiography / MRA as a management option.

MRA for the Surveillance of Individuals with Brain Cancer Following Radiotherapy

In a feasibility study, Bullitt et al (2007) examined if MRA can depict intracranial vascular morphologic changes during treatment of brain metastases from breast cancer and if serial quantitative vessel tortuosity measurements can be used to predict tumor treatment response sooner than traditional methods.  Institutional review board approval and informed consent were obtained for this HIPAA-compliant study.  A total of 22 women aged 31 to 61 years underwent brain MRA prior to and 2 months after initiation of lapatinib therapy for brain metastases from breast cancer.  Vessels were extracted from MR angiograms with a computer program.  Changes in vessel number, radius, and tortuosity were calculated mathematically, normalized with values obtained in 34 healthy control subjects (19 women, 15 men; age range of 19 to 72 years), and compared with subsequent assessments of tumor volume and clinical course.  All patients exhibited abnormal vessel tortuosity at baseline.  Nineteen (86 %) patients did not exhibit improvement in vessel tortuosity at 2-month follow-up, and all patients demonstrated tumor growth at 4-month follow-up.  Vessel tortuosity measurements enabled these researchers to correctly predict treatment failure 1 to 2 months earlier than did traditional methods.  Three (14 %) patients had quantitative improvement in vessel tortuosity at 2-month follow-up, with drop-out of small abnormal vessels and straightening of large vessels.  Each of the 2 patients for whom further follow-up data were available responded to treatment for more than 6 months.  The authors concluded that these findings established the feasibility of using MRA to quantify vessel shape changes during therapy.  Moreover, they stated that although further research is required, results suggested that changes in vessel tortuosity might enable early prediction of tumor treatment response.

An Information Sheet on “Further tests for brain tumours” from Cancer Research UK (Last updated November 25, 2013) did not mention annual MRA as a surveillance tool for patients with brain cancer.

A “Brain Tumor Glossary of Terms” from the Brain Tumor Trial Collaborative (2015) states that “MRA does not have significant application for the detection or definition of cancer of the brain”.

Also, an UpToDate review on “Assessment of disease status and surveillance after treatment in patients with brain tumors” (Wen, 2015) does not mention MRA as a management tool.

Furthermore, National Comprehensive Cancer Network (NCCN)’s clinical practice guideline on “Central nervous system cancers” (Version 1.2015) states that “Cerebral angiography is occasionally performed, often for surgical planning ….”; it does not mention MRA as a management tool.

The use of an MRA/MRV as part of the work-up of a patient with suspected cerebral thrombosis (i.e., dural sagittal or cavernous sinus thrombosis) must be considered on a case by case basis.  Magnetic resonance imaging is considered the imaging method of choice for establishing the diagnosis, but MRA/MRV may be useful in following the course of the disease.

Magnetic resonance venography (MRV) is now very effective for the evaluation of diseases of larger veins.  The specific indications for using MRV for evaluating the vena cavae are diagnosis of vena caval thrombus, differentiation of tumor thrombus and blood clot of the vena cava, diagnosis of superior vena caval syndrome, identification of superior vena caval invasion or encasement by lung or mediastinal tumors, diagnosis of the Budd-Chiari syndrome, diagnosis of caval anomalies such as persistent left superior vena cava and interrupted inferior vena cava, and identification of the presence and cause of obstruction or occlusion of the brachiocephalic, subclavian, and jugular veins.

Duplex ultrasonography is the typical initial diagnostic test for deep vein thrombosis (DVT).  Magnetic resonance venography has not been shown to be superior to ultrasonography, except in imaging the deep femoral and hypogastric vessels.  However, information about these vessels is frequently not needed to make patient management decisions, except perhaps in patients with pulmonary emboli where the source of the emboli has not been identified by ultrasonography.  McRae and Ginsberg (2004) MRV has the potential to be used as a stand-alone test for DVT but requires further evaluation.  Moreover, in a retrospective study (n = 973), Borer et al (2005) found that discontinuation of screening by means of ultrasound and MRV for the diagnosis of DVT did not change the rate of pulmonary embolism in patients with closed fractures of the pelvis or acetabulum.

Bates et al (2012) stated that objective testing for DVT is crucial because clinical assessment alone is unreliable and the consequences of misdiagnosis are serious.  This guideline focused on the identification of optimal strategies for the diagnosis of DVT in ambulatory adults.  The methods of this guideline followed those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.  These investigators suggested that clinical assessment of pre-test probability of DVT, rather than performing the same tests in all patients, should guide the diagnostic process for a first lower extremity DVT (Grade 2B).  In patients with a low pre-test probability of first lower extremity DVT, these researchers recommended initial testing with D-dimer or ultrasound (US) of the proximal veins over no diagnostic testing (Grade 1B), venography (Grade 1B), or whole-leg US (Grade 2B).  In patients with moderate pre-test probability, they recommended initial testing with a highly sensitive D-dimer, proximal compression US, or whole-leg US rather than no testing (Grade 1B) or venography (Grade 1B).  In patients with a high pre-test probability, they recommended proximal compression or whole-leg US over no testing (Grade 1B) or venography (Grade 1B).  The authors concluded that favored strategies for diagnosis of first DVT combined use of pre-test probability assessment, D-dimer, and US.  There is lower-quality evidence available to guide diagnosis of recurrent DVT, upper extremity DVT, and DVT during pregnancy.

The role of chronic cerebrospinal venous insufficiency (CCSVI) in the pathogenesis of multiple sclerosis (MS) is a matter of debate.  Chronic cerebrospinal venous insufficiency was first diagnosed using specialized trans-cranial and extra-cranial Doppler ultrasonography.  Some have advocated the use of MRV in place of trans-cranial Doppler because the results of MRV are less operator dependent.  However, there are limited data to support the use of MRV in diagnosis of CCSVI. I n a pilot study, Hojnacki et al (2010) the value of neck MRV for the diagnosis of CCSVI compared to Doppler sonography (DS) and selective venography (SV) in patients with MS and in healthy controls (HC).  A total of 10 MS patients and 7 HC underwent DS, 2D-Time-Of-Flight (TOF) venography and 3D-Time Resolved Imaging of Contrast Kinetics angiography (TRICKS). Patients with MS also underwent SV.  The internal jugular veins (IJVs) and the vertebral veins (VVs) were assessed by both MRV sequences, and the findings were validated against SV and DS; SV has been considered the diagnostic gold standard for MS patients.  All MS patients and none of the HC presented CCSVI, according to the DS criteria.  This was confirmed by SV.  For CCSVI diagnosis, DS showed sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) of 100 %, whereas the figures were 40 %, 85 %, 58 %, 80 % and 50 % for 3D-TRICKS, and 30 %, 85 %, 52 %, 75 % and 46 % for 2D-TOF in the IJVs.  In MS patients, compared to SV, DS showed sensitivity, specificity, accuracy, PPV and NPV of 100 %, 75 %, 95 %, 94 % and 100 %, whereas the figures were 31 %, 100 %, 45 %, 100 % and 26 % for 3D-TRICKS and 25 %, 100 %, 40 %, 100 % and 25 % for 2D-TOF in the IJVs.  The authors concluded that the use of MRV for diagnosis of CCSVI in MS patients has limited value, and the findings should be interpreted with caution and confirmed by other imaging techniques such as DS and SV.

Abdalla et al (2015) searched the literature for further evidence for the use of MRV in the detection of suspected DVT and re-evaluated the accuracy of MRV in the detection of suspected DVT.  PubMed, EMBASE, Scopus, Cochrane, and Web of Science were searched.  Study quality and the risk of bias were evaluated using the QUADAS 2.  A random effects meta-analysis including subgroup and sensitivity analyses were performed.  The search resulted in 23 observational studies all from academic centers; 16 articles were included in the meta-analysis.  The summary estimates for MRV as a diagnostic non-invasive tool revealed a sensitivity of 93 % (95 % CI: 89 % to 95 %) and specificity of 96 % (95 % CI: 94 % to 97 %).  The heterogeneity of the studies was high.  Inconsistency (I2) for sensitivity and specificity was 80.7 % and 77.9 %, respectively.  The authors concluded that further studies investigating the use of MRV in the detection of suspected DVT did not offer further evidence to support the replacement of US with MRV as the first-line investigation.  However, they stated that MRV may offer an alternative tool in the detection/diagnosis of DVT for whom US is inadequate or not feasible (such as in the obese patient).

MRA for Evaluation of Vasa Previa

Iwahashi and associates (2016) noted that vasa previa is a rare complication, and rupture of vasa previa during pregnancy may lead to significant perinatal mortality.  These investigators reported a case of vasa previa evaluated prenatally using non-contrast time-of-flight MRA (TOF-MRA).  A 22-year old primiparous woman was referred to the authors’ hospital due to suspicion of vasa previa.  Trans-vaginal US showed 2 vessels running over the internal os.  To obtain further information, MRI and TOF-MRA were performed.  Caesarean section was performed, and macroscopic findings of the vascular distribution on the fetal membrane were consistent with those identified by TOF-MRA.  The authors concluded that TOF-MRA in addition to MRI may be an option for prenatal identification of the precise 3D vascular distribution in patients with vasa previa.  The role of MRA for evaluation of patients with vasa previa needs to be further investigated.

Ferumoxytol-Enhanced MRA for Evaluation of Transplant Renal Artery Stenosis

Fananapazir and co-workers (2017) determined the accuracy of ferumoxytol-enhanced MRA in assessing the severity of transplant renal artery stenosis (TRAS), using digital subtraction angiography (DSA) as the reference standard.  The authors’ Institutional Review Board approved this retrospective, Health Insurance Portability and Accountability Act-compliant study.  A total of 33 patients with documented clinical suspicion for TRAS (elevated serum creatinine, refractory hypertension, edema, and/or audible bruit) and/or concerning sonographic findings (elevated renal artery velocity and/or intra-parenchymal parvus tardus waveforms) underwent a 1.5T MRA with ferumoxytol prior to DSA.  All DSAs were independently reviewed by an interventional radiologist and served as the reference standard.  The MRAs were reviewed by 3 readers who were blinded to the US and DSA findings for the presence and severity of TRAS.  Sensitivity, specificity, and accuracy for identifying substantial stenoses (greater than 50 %) were determined.  Intra-class correlation coefficients (ICCs) were calculated among readers.  Mean differences between the percent stenosis from each MRA reader and DSA were calculated.  On DSA, a total of 42 stenoses were identified in the 33 patients.  The sensitivity, specificity, and accuracy of MRA in detecting substantial stenoses were 100 %, 75 to 87.5 %, and 95.2 to 97.6 %, respectively, among the readers.  There was excellent agreement among readers as to the percent stenosis (ICC = 0.82); MRA over-estimated the degree of stenosis by 3.9 to 9.6 % compared to DSA.  The authors concluded that ferumoxytol-enhanced MRA provided high sensitivity, specificity, and accuracy for determining the severity of TRAS.  They stated that these findings suggested that ferumoxytol-enhanced MRA can potentially be used as a non-invasive examination following US to reduce the number of unnecessary conventional angiograms.  These preliminary findings need to be validated by well-designed studies.

Ferumoxytol-Enhanced MRA for Evaluation of Potential Kidney Transplant Recipients

Stoumpos and associates (2018) stated that traditional contrast-enhanced methods for scanning blood vessels using MRI or CT carry potential risks for patients with advanced kidney disease.  Ferumoxytol is a super-paramagnetic iron oxide nanoparticle preparation that has potential as an MRI contrast agent in assessing the vasculature.  A total of 20 patients with advanced kidney disease requiring aorto-iliac vascular imaging as part of pre-operative kidney transplant candidacy assessment underwent ferumoxytol-enhanced MRA (FeMRA) between December 2015 and August 2016.  All scans were performed for clinical indications where standard imaging techniques were deemed potentially harmful or inconclusive.  Image quality was evaluated for both arterial and venous compartments.  First-pass and steady-state FeMRA using incremental doses of up to 4 mg/kg body weight of ferumoxytol as intravenous contrast agent for vascular enhancement was performed.  Good arterial and venous enhancements were achieved, and FeMRA was not limited by calcification in assessing the arterial lumen.  The scans were diagnostic and all patients completed their studies without adverse events (AEs).  The authors concluded that their preliminary experience supported the feasibility and utility of FeMRA for vascular imaging in patients with advanced kidney disease due for transplant listing, which has the advantages of obtaining both arteriography and venography using a single test without nephrotoxicity.  These preliminary findings need to be validated by well-designed studies.

Ferumoxytol-Enhanced MRV for Diagnosis of Chronic Kidney Disease

Luhar and associates (2016) noted that ferumoxytol is an ultra-small superparamagnetic iron oxide (USPIO) particle that is FDA-approved for parenteral treatment of iron deficiency anemia in adults with chronic kidney disease (CKD).  Because of the association between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with severe CKD, these researchers evaluated the diagnostic role of ferumoxytol-enhanced MRV in children with CKD.  A total of 20 children underwent 22 high-resolution ferumoxytol-enhanced MRV examinations at 3.0 T.  High-resolution 3D contrast-enhanced imaging was performed at a minimum of 3 time-points following injection of ferumoxytol at a total dose of 4 mg/kg of body weight.  Two blinded pediatric radiologists independently scored 6 named veins on ferumoxytol-enhanced MRV examinations according to a 3-point subjective score, where a score greater than or equal to 2 was considered diagnostic.  Additionally, all relevant venous structures in the included field of view were analyzed for occlusive or non-occlusive thrombosis, compression and presence of collaterals.  All patients underwent ferumoxytol-enhanced MRV successfully and without adverse event (AE).  The overall scores of the reviewing radiologists for all venous structures were 2.7 to 2.9.  In all cases, the reviewers were confident basing their diagnoses on the ferumoxytol-enhanced MRV findings.  In 12 of 22 examinations, findings on follow-up imaging or invasive procedures were available to correlate with the findings on ferumoxytol-enhanced MV.  There was complete concordance between the findings from follow-up imaging and invasive procedures with findings from ferumoxytol-enhanced MV.  The authors concluded that ferumoxytol holds promise as a powerful alternative to gadolinium-based contrast agents for reliable, high-resolution MRV in children with CKD.

MRA for Prediction of Pulmonary Hypertension

Rengier and colleagues (2016) demonstrated the feasibility of automated 3D volumetry of central pulmonary arteries based on MRA to evaluate pulmonary artery volumes in patients with pulmonary hypertension compared to healthy controls, and examined the potential of the technique for predicting pulmonary hypertension.  Magnetic resonance angiography of pulmonary arteries was acquired at 1.5T in 20 patients with pulmonary arterial hypertension and 21 healthy normotensive controls; 3D model-based image analysis software was used for automated segmentation of main, right and left pulmonary arteries (MPA, RPA and LPA).  Volumes indexed to vessel length and mean, minimum and maximum diameters along the entire vessel course were assessed and corrected for body surface area (BSA).  For comparison, diameters were also manually measured on axial reconstructions and double oblique multi-planar reformations.  Analyses were performed by 2 cardiovascular radiologists, and by 1 radiologist again after 6 months.  Mean volumes of MPA, RPA and LPA for patients/controls were 5,508 ± 1,236/3,438 ± 749, 3,522 ± 934/1,664 ± 468 and 3,093 ± 692/1,812 ± 474 μl/(cm length x m2 BSA) (all p < 0.001).  Mean, minimum and maximum diameters along the entire vessel course were also significantly increased in patients compared to controls (all p < 0.001).  Intra- and inter-observer agreement were excellent for both volume and diameter measurements using 3D segmentation (ICCs 0.971 to 0.999, p < 0.001).  Area under the curve for predicting pulmonary hypertension using volume was 0.998 (95 % CI: 0.990 to 1.0, p < 0.001), compared to 0.967 using manually measured MPA diameter (95 % CI: 0.910 to 1.0, p < 0.001).  The authors concluded that automated MRA-based 3D volumetry of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters in patients with pulmonary arterial hypertension compared to healthy controls.  They stated that pulmonary artery volume may serve as a superior predictor for pulmonary hypertension compared to manual measurements on axial images; but verification in a larger study population is needed.

MRA for Evaluation of Individuals with Blunt Vertebral Artery

Karagiorgas and colleagues (2017) noted that the role of MRA in the evaluation of patients with blunt vertebral artery has not been fully established.  These researchers examined the diagnostic accuracy of MRA in comparison to DSA for the detection of blunt vertebral artery injury in trauma patients.  A computer-assisted literature search of the PubMed, Scopus, Highwire, Web of Science, and LILACS was conducted, in order to identify studies reporting on the sensitivity and specificity of MRA in comparison to DSA for the detection of blunt vertebral artery injury in trauma patients.  The Database search retrieved 91 studies; 5 studies fulfilled the eligibility criteria; 2 authors assessed the risk of bias and applicability concerns using QUADAS-2.  Two-by-two contingency tables were constructed on a per-vessel level.  Heterogeneity was tested by the statistical significance of Cochran's Q, and was quantified by the Higgins's I2 metric.  The pooled estimates of sensitivity and specificity for blunt vertebral artery injury detection with MRA in comparison to DSA were calculated based on the bi-variate model.  The meta-analysis was supplemented by subgroup and sensitivity analysis, as well as analysis for publication bias.  There was significant clinical heterogeneity in the targeted population, inclusion criteria, and MRA related parameters.  The reporting bias and applicability concerns were moderate and low, respectively.  In the overall analysis, the sensitivity ranged from 25 % to 85 %, while the specificity varied from 65 % to 99 %, across studies.  According to the bi-variate model, the pooled sensitivity and specificity of MRA in the evaluation of patients with blunt vertebral artery was as high as 55 % (95 % CI: 32.1 % to 76.7 %), and 91 % (95 % CI: 66.3 % to 98.2 %), respectively.  Subgroup analysis in terms of MRA sequence sensitivity of phase, the contrasted MRA (75 % [95 % CI: 43 % to 92 %]) appeared to be superior to the time-of-flight (TOF) MRA (46 % [95 % CI: 20 % to 74 %]).  The addition of contrast enhancement did not appear to improve the diagnostic yield of MRA.  The Egger's test did not identify any significant publication bias (p = 0.2).  The authors concluded that MRA had a moderate diagnostic accuracy in the diagnosis of blunt vertebral artery injuries.  They stated that further studies on high-field magnetic resonance scanners are recommended.  The current meta-analysis had 2 major drawbacks:
  1. the small number of eligible studies, and
  2. the lack of studies on newer, high-field MR scanners.

MRA for Mapping of Perforators Prior to DIEP Flap Breast Reconstruction

Wade and colleagues (2018) stated that prior to DIEP flap breast reconstruction, mapping the perforators of the lower abdominal wall US, computed tomography angiography (CTA) or MRA reduces the risk of flap failure.  These investigators examined the additional potential benefit of a reduction in operating time.  They systematically searched the literature for studies concerning adult women undergoing DIEP flap breast reconstruction, which directly compared the operating times and adverse outcomes for those with and without pre-operative perforator mapping by US, CTA or MRA.  Outcomes were extracted, data meta-analyzed and the quality of the evidence appraised.  A total of 14 articles were included.  Pre-operative perforator mapping by CTA or MRA significantly reduced operating time (mean reduction of 54 mins [95 % CI: 3 to 105], p = 0.04), when directly compared to DIEP flap breast reconstruction with no perforator mapping.  Further, perforator mapping by CTA was superior to US, as CTA saved more time in theater (mean reduction of 58 mins [95 % CI: 25 to 91], p < 0.001) and was associated with a lower risk of partial flap failure (relative risk [RR] 0.15 [95 % CI: 0.04 to 0.6], p = 0.007).  All studies were at risk of methodological bias and the quality of the evidence was very low.  The authors concluded that the quality of research regarding perforator mapping prior to DIEP flap breast reconstruction was poor and although pre-operative angiography appeared to save operative time, reduce morbidity and confer cost savings, higher quality research is needed.

MRA for Detection of Jugular Venous Reflux and Non-Pulsatile Subjective Tinnitus

Yildirim and colleagues (2019) examined if there is an association between jugular venous reflux and non-pulsatile subjective tinnitus (NPST) using real-time four-dimensional (4D) MRA.  Patients with unilateral NPST who underwent contrast-enhanced MRI with a special protocol were included in the study.  Thick slab dynamic maximum intensity projection images were obtained including interleaved stochastic trajectories (TWIST)-MRI examination.  All patients were requested to perform Valsalva maneuver during the sequence . Jugular venous reflux grading was performed as follows: absence of reflux or if reflux did not reach the base of the skull: Grade 0; if reflux reached the jugular bulb, but no intra-cranial contrast was observed: Grade 1; and if reflux extended into the intra-cranial cortical veins and/or the cavernous sinus above the jugular bulb: Grade 2.  This trial included a total of 30 patients, 23 male and 7 female; mean age of 49 years (range of 17 to 74 years).  Jugular venous reflux was not identified (Grade 0) in 20 patients; Grade 1 reflux was determined in 7 cases and Grade 2 reflux was observed in 3 cases.  Notably, only patients with Grade 2 reflux described worsening of their tinnitus symptoms during the examination and their daily activities as well.  The authors concluded that NST might also be associated with hemodynamic problems of the venous system and the MRI protocol starting with TWIST accompanied with Valsalva maneuver is not well-known, yet appeared to be a feasible and beneficial method to detect potential jugular venous reflux in NPST patients.

The authors stated that this study had several drawbacks.  First, and most important according  this trial consisted of relatively small numbers of patients (n = 30).  Thus, these researchers considered this trial as a preliminary study.  Selection of patients who had only unilateral and reflux disease caused this limitation.  These investigators noted that that they would work in a wider group as the series expands.  Second, MRI artifacts occurred secondary to movements of the patients during Valsalva maneuver; however, the authors substantially surpassed these artifacts with the high temporal resolution of the MRI sequence that they used.  These preliminary findings need to be validated by well-designed studies.

MRA for Diagnosis of Intra-Cranial Artery Stenosis

Jaiswal and colleagues (2019) stated that one of the most common causes of acute cerebral infarction (ACI) is intra-cranial artery stenosis (ICAS).  These researchers examined the accuracy of trans-cranial Doppler (TCD) compared with MRA for diagnosing ICAS in patients with ACI.  Consecutive patients presenting with ACI to the neurology department underwent both MRA and TCD examination within 6 hours of difference.  To calculate the agreement between the results of MRA and TCD, kappa coefficient test was used.  Sensitivity, specificity, PPV and NPV for TCD were calculated in comparison with MRA.  A total of 115 patients were included in this trial.  There were 77 men (66.95 %) and 38 women (33.04 %).  The mean age of patients was 68.32 ± 10.66 years (range of 29 to 80).  The agreement between TCD and MRA in detecting stenosis was 0.56 for anterior circulation artery (ACA), and 0.40 for posterior circulation artery (PCA).  For the detection of ICAS, sensitivity, specificity, PPV, and NPV were 85.9, 90.0, 98.2, and 50.0 % for ACA and 73.5, 86.7, 96.2, and 40.0 % for PCA, respectively.  The authors concluded that moderate agreement of ACA stenosis and fair agreement for PCA stenosis was found between TCD and MRA in the evaluation of ICAS.  In anterior circulation, the diagnostic accuracy of TCD was higher compared with the posterior circulation.

The authors stated that this study has several drawbacks.  First, this was a single-center study.  Second, the sample size was very small (n = 115).  Third, some patients were excluded because they did not have an acoustic bone window and others had contraindications for MRA.  Fourth, TCD is an operator-dependent technique that requires considerable experience in intra-cranial arterial anatomy and understanding.

MRA for Evaluation of Thoracic Outlet Syndrome

Zhang and colleagues (2019) introduced a novel method combining contrast-enhanced MRA (CE-MRA), short inversion time inversion recovery sampling perfection with application-optimized contrasts using different flip angle evolutions (T2-STIR-SPACE) and volumetric interpolated breath-hold examination (VIBE) sequences in the assessment of thoracic outlet syndrome (TOS).  CE-MRA, T2-STIR-SPACE, and VIBE techniques were employed to evaluate neurovascular bundles in 27 patients clinically suspected of TOS.  Images were evaluated to determine the cause of neurovascular bundle compression.  Surgical exploration was performed in patients with abnormal MRI results.  A total of 20 patients were found to be abnormal: 6 cases showed only neurogenic TOS and the correlates included infra-clavicular hemangiomas (n = 1) and transverse cervical artery (n = 5).  Arterial-neurogenic TOS was found in 4 cases, including subclavian lymph node metastasis from breast cancer (n = 3) and schwannoma (n = 1).  Arterial-venous-neurogenic TOS was found in 1 subject, and the correlates included a fibrous band from the cervical rib and elongated C7 transverse process.  In this case, the subclavian artery/vein was compressed dynamically.  Venous-neurogenic TOS was noted in 1 subject; 9 patients were considered as post-traumatic TOS, including brachial plexus edema (n = 3), the brachial plexus rupture (n = 2), peri-brachial plexus effusion (n = 3), and stenosis of the SCA (n = 1).  In the remaining 7 patients, MRI did not detect abnormalities.  The authors concluded that TOS could be evaluated by CE-MRA, T2-STIR-SPACE, and VIBE during a single examination, with a reduced contrast material dose.  This imaging modality performed well in showing the anatomical structure of the neurovascular bundle and the cause of the compression.

The authors stated that this study had several drawbacks.  First, bone abnormalities could be difficult to identify at MR imaging but are best identified on plain radiograph.  Second, gadolinium is a contrast agent that is toxic to people with kidney and liver disease; MRA cannot be performed in patients with low glomerular filtration rate.  Third, these researchers did not examine the differences in findings of MRI at neutral and provocative locations.  Lastly, these subjects had various causes of brachial plexus diseases.  The authors stated that further prospective studies are recommended in future work to focus on certain types of brachial plexus neuropathy.

Magnetic Resonance Venography (MRV) for Diagnosis of Pelvic Congestion Syndrome

Champaneria and colleagues (2016) stated that pelvic congestion syndrome (PCS) is described as chronic pelvic pain (CPP) arising from dilated and refluxing pelvic veins, although the causal relationship between pelvic vein incompetence (PVI) and CPP is not established.  Non-invasive screening methods such as Doppler US and MRV are used before confirmation by venography.  Percutaneous embolization has become the principal treatment for PCS, with high success rates often cited.  These researchers systematically reviewed the definitions and diagnostic criteria of PCS, the association between PVI and CPP, the accuracy of various non-invasive imaging techniques and the effectiveness of embolization for PVI; and identified factors associated with successful outcome.  They also surveyed clinicians and patients to assess awareness and management of PCS and gauge the enthusiasm for further research.  A comprehensive search strategy encompassing various terms for pelvic congestion, pain, imaging techniques and embolization was deployed in 17 bibliographic databases, including Medline, Embase and Web of Science.  There was no restriction on study design.  Methodological quality was assessed using appropriate tools.  Online surveys were sent to clinicians and patients.  The quality and heterogeneity generally precluded meta-analysis and so results were tabulated and described narratively.  These investigators identified 6 association studies, 10 studies involving US, 2 studies involving MRV, 21 case series and 1 poor-quality randomized trial of embolization.  There were no consistent diagnostic criteria for PCS.  These researchers found that the associations between CPP and PVI were generally fairly similar, with 3 of 5 studies with sufficient data showing statistically significant associations (OR of between 31 and 117).  The prevalence of PVI ranged widely, although the majority of women with PVI had CPP.  Trans-vaginal Doppler US and MRV are both useful screening methods, although the data on accuracy were limited.  Early substantial relief from pain symptoms was observed in approximately 75 % of women undergoing embolization, a figure which generally increased over time and was sustained.  Re-intervention rates were generally low.  Transient pain was a common occurrence following foam embolization, while there was a less than 2 % risk of coil migration.  Confidence in the embolization technique was reasonably high, although there was a desire to strengthen the evidence base.  Even among women with CPP, fewer than 50 % had any knowledge about PCS.  The authors concluded that the data supporting the diagnosis and treatment of PCS were limited and of variable methodological quality.  There is some evidence to tentatively support a causative association, but it cannot be categorically stated that PVI is the cause of CPP in women with no other pathology, as the 6 most pertinent studies drew on clinically disparate populations and defined PVI inconsistently.  Embolization appeared to provide symptomatic relief in the majority of women and is safe.  However, the majority of included studies of embolization were relatively small case series and only the randomized controlled trial (RCT) was considered at risk of potential biases.  The authors concluded that there is scope and demand for considerable further research.  They stated that the question of the association of PVI and CPP requires a well-designed and well-powered case-control study, which will also provide data to derive a diagnostic standard.  An adequately powered randomized trial is essential to provide evidence on the effectiveness of embolization, but this faces methodological challenges.

Steenbeek and colleagues (2018) stated that in the work-up of patients with suspected pelvic congestion syndrome (PCS), venography is currently the gold standard.  Yet if non-invasive diagnostic tools are found to be accurate, invasive venography might no longer be indicated as necessary.  These investigators carried out a literature search in PubMed and Embase from inception until May 6, 2017.  Studies comparing non-invasive diagnostic tools to a reference standard in the work-up of patients with (suspected) PCS were included.  Relevant data were extracted and methodological quality of individual included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.  A total of 9 studies matched the inclusion criteria; 6 studies compared US to venography and 3 studies described a MRI technique.  In using transvaginal US (TVUS), the occurrence of a vein greater than 5 mm crossing the uterine body had a specificity of 91 % (95 % CI: 77 to 98 %) and occurrence of pelvic varicoceles a sensitivity and specificity of 100 % (95 % CI: 89 to 100 %) and 83 % (95 % CI: 66 to 93 %), respectively.  In transabdominal US, reversed caudal flow in the ovarian vein accounted for a sensitivity of 100 % (95 % CI: 84 to 100 %).  Detection of PCS with MRI techniques resulted in a sensitivity varying from 88 to 100 %.  The authors concluded that the sensitivity of US and MRI appeared to be adequate, which indicated a role for both tests in an early stage of the diagnostic work-up.  However, these researchers stated that due to methodological flaws and diversity in outcome parameters, more high standard research is needed to establish a clear advice for clinical practice.  These investigators discussed the study by Asciutto et al (2008), which examined the application of MRV in the assessment of women with PCS. They stated that MRV seemed to be highly sensitive for insufficiency in pelvic plexus, ovarian or hypogastric veins; especially hypogastric vein insufficiency accounted for a high sensitivity (100 %), but the specificity was low, which resulted in a high prevalence of false‐positive results.

Combined Unenhanced Computed Tomography and Ferumoxytol-Enhanced Magnetic Resonance Angiography for Vascular Mapping in Renal Impairment

In an IRB-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant study, Yosida and colleagues (2020) examined the feasibility of fusing complementary, high-contrast features from unenhanced CT and ferumoxytol-enhanced MRA (FE-MRA) for pre-procedural vascular mapping in patients with renal impairment.  This trial included 15 consecutive patients who underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multi-feature image.  Source images from CT and MRA were segmented and registered.  To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on 3D models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment.  These researchers then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points).  Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal).  The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets.  The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent non-concordance between the source FE-MRA and fused images.  The offsets were compared using concordance correlation coefficients.  Inter-observer agreement was assessed using intra-class correlation coefficients and Bland-Altman analyses.  A total of 13 patients (aged 76 ± 12 years; 7 women) with aortic valve stenosis and chronic kidney disease and 2 patients with thoraco-abdominal vascular aneurysms and chronic kidney disease underwent FE-MRA for pre-procedural vascular assessment, and unenhanced CT examinations were available in all patients; no ferumoxytol-related AEs occurred.  There were 247 matched POIs evaluated on the source FE-MRA and fused images.  In patients with implantable medical devices, the mean offsets in spatial position were 0.31 ± 0.51 mm (ρ = 0.99; Cb = 1; 95 % CI: 0.99 to 0.99) for Δx, 0.27 ± 0.69 mm (ρ = 0.99; Cb = 0.99; 95 % CI: 0.99 to 0.99) for Δy, and 0.20 ± 0.59 mm (ρ = 1; Cb = 1; 95 % CI: 0.99 to 1.00) for Δz.  Inter-observer agreement was excellent (intra-class correlation coefficient, > 0.99).   The mean difference in offset between readers was 1.5 mm.  The authors concluded that accurate 3D feature fusion was feasible, combining luminal information from FE-MRA with vessel wall information on unenhanced CT.  These researchers stated that this frame-work holds promise for combining the complementary strengths of MRI and CT to generate information-rich, multi-feature composite vascular images.

MRV for the Diagnostic Evaluation of Cryptogenic Stroke

Liberman et al (2014) stated that paradoxical embolization is frequently posited as a mechanism of ischemic stroke in patients with patent foramen ovale (PFO).  Several studies have suggested that the deep lower extremity (LE) and pelvic veins might be an embolic source in cryptogenic stroke (CS) patients with PFO.  In this single-center, retrospective, observational study, consecutive adult patients with ischemic stroke or transient ischemic attack (TIA) and a PFO who underwent pelvic MRV as part of an inpatient diagnostic evaluation were included in this study to determine pelvic and LE DVT prevalence in CS versus non-CS stroke subtypes.  Among the 131 patients who met inclusion criteria, 126 (96.2 %) also had LE duplex US data.  DVT prevalence overall was 7.6 % (95 % CI: 4.1 to 13.6), pelvic DVT 1.5 % (95 % CI: 0.1 to 5.8), and LE DVT 7.1 % (95 % CI: 3.6 to 13.2).  One patient with a pelvic DVT also had a LE DVT.  Comparing patients with CS (n = 98) with non-CS subtypes (n = 33), there was no significant difference in the prevalence of pelvic DVT (2.1 % versus 0 %, p = 1), LE DVT (6.2 % versus 10.3 %, p = 0.43), or any DVT (7.2 % versus 9.1 %, p = 0.71).  The authors concluded that among patients with ischemic stroke/TIA and PFO, the majority of detected DVTs were in LE veins rather than the pelvic veins and did not differ by stroke subtype.  They stated that the routine inclusion of pelvic MRV in the diagnostic evaluation of CS warrants further prospective investigation.

Osgood et al (2015) noted that substantial proportion of ischemic strokes has no identified underlying cause.  Notably, the prevalence of a PFO is increased in CS populations, which may serve as a conduit for paradoxical emboli originating from DVT including the pelvic veins.  Yet, there are no published guidelines for the assessment of pelvic veins as part of the stroke work-up and few studies have systematically investigated pelvic veins as a potential source for paradoxical emboli in CS patients.  Further, there is a relative paucity of data regarding pelvic DVT in CS and results have been conflicting.  These investigators determined the prevalence of pelvic DVT in select CS patients with PFO who underwent MRV.  They retrospectively identified patients (n = 50) who underwent contrast-enhanced pelvic MRV at the discretion of the treating physician for the evaluation of CS in the presence of a PFO during hospitalization at a single academic stroke center between January 2011 through December 2013.  Multivariable logistic regression analyses were used to assess for factors independently associated with the presence of an abnormal MRV pelvis.  Patients (47 ± 13 years of age) had MRV performed 4 ± 3 days after their incident stroke; 9 patients had an abnormal MRV (18 %).  Of these, 4 (8 %) had pelvic vein thrombosis and 5 (10 %) a May-Thurner anatomic variant.  All patients with pelvic DVT were subsequently anti-coagulated with warfarin (none had abnormal hypercoagulability testing).  Clinical clues suggesting paradoxical embolism were present in as many as 40 % of patients.  On multivariable logistic regression, a history of any risk factors predisposing to DVT (odds ratios [OR] 6.7; coefficient 1.9; BCa 95 % CI: 0.08 to 20.2; p = 0.014) as well as the number of predisposing risk factors (OR 3.9; coefficient 1.4; BCa 95 % CI: 0.25-4.2; p = 0.005) predicted the presence of pelvic vein pathology on MRV.  The authors demonstrated a relatively high prevalence of pelvic DVT among select CS patients emphasizing the importance of considering the pelvic veins as a potential source for emboli particularly in the presence of risk factors known to predispose DVT.  Because patients were included at the treating physician's discretion, these findings reflected “real-life” practice.  They stated that the results may be of clinical importance as inclusion of pelvic vein imaging in CS patients with PFO had impactful therapeutic and nosologic implications.  These researchers noted that further study is needed to define patients most likely to benefit from pelvic vein imaging.

MRV for Screening Venous Thromboembolism Following Musculoskeletal Trauma

On behalf of the Orthopaedic Trauma Association Evidence Based Quality Value and Safety Committee, Sagi and colleagues (2015) (i) provided a summation of the current practice patterns of North American orthopedic surgeons for venous thrombo-embolism (VTE) prophylaxis after musculoskeletal trauma, and (ii) established a set of guidelines and recommendations based on the most current and best available evidence for VTE prophylaxis after musculoskeletal trauma.  A 24 item questionnaire titled "OTA VTE Prophylaxis Survey" was sent to active members of the Orthopedic Trauma Association.  PubMed and OVID/MEDLINE were used to search the current published literature regarding VTE prophylaxis in trauma patients using the following search terms: deep venous thrombosis, DVT, pulmonary embolism, PE, venous thromboembolism, VTE, prophylaxis, trauma, fracture, pneumatic compression device, PCD, sequential compression device, SCD, screening, ultrasound, duplex, ultrasonography, DUS, venography, magnetic resonance venography, MRV, inferior vena cava, IVC, filter, and IVCF.  Each recommendation was graded using articles that were considered by the subcommittee as "the best available evidence" using the grading system adopted and endorsed by the American Academy of Orthopedic Surgeons' Evidenced Based Quality and Value committee.  Overall, 185 of 1,545 members completed the online survey.  The range and variety of prophylaxis and screening methods used among orthopedic trauma surgeons in North America is large, with a number of agents or methods for which no literature exists to support their use in musculoskeletal trauma.  A set of recommendations and guidelines were constructed based on the results of the literature analysis and graded according to guidelines mentioned above.  The authors concluded that due to the wide variability in practice patterns, poor scientific support for various therapeutic regimens and important medical-legal implications highlighted by the survey, a standardized set of guidelines and recommendations for VTE prophylaxis after musculoskeletal trauma will be critical in helping to improve patient care and minimize surgeons' exposure to potentially litigious activity.

Quantitative MRV for Measurement of Venous Flow after Cerebral Venous Sinus Stenting

Esfahani et al (2015) stated that endovascular stenting is an effective treatment for patients with clinically significant cerebral venous sinus stenosis.  Traditionally, stenting is indicated in elevated intravenous pressures on conventional venography; however, non-invasive monitoring is more desirable.  Quantitative MRV (qMRV) is an imaging modality that measures blood flow non-invasively.  Established in the arterial system, applications to the venous sinuses have been limited.  These researchers examined qMRV in the measurement of venous sinus flow in patients undergoing endovascular stenting and identified a relationship with intravenous pressures.  A total of 5 patients with intra-cranial hypertension secondary to venous sinus stenosis underwent cerebral venous stenting between 2009 and 2013 at a single institution.  Pre-operatively, venous sinus flow was determined by using qMRV, and intravenous pressure was measured during venography.  After stenting, intravenous pressure, qMRV flow, and clinical outcomes were assessed and compared.  A mean pre-stenotic intravenous pressure of 45.2 mm Hg was recorded before stenting, which decreased to 27.4 mm Hg afterward (Wilcoxon signed rank test p = 0.04).  Total jugular outflow on qMRV increased by 260.2 ml/min.  Analysis of the change in intravenous pressure and qMRV flow identified a linear relationship (Pearson correlation r = 0.926).  All patients displayed visual improvement at 6 weeks.  The authors concluded that venous outflow by qMRV increased after endovascular stenting and correlated with significantly improved intravenous pressures.  They stated that these findings introduced qMRV as a potential adjunct to measure venous flow after stenting, and as a plausible tool in the selection and post-operative surveillance of the patient who has cerebral venous sinus stenosis.

Non-Contrast-Enhanced MRV Using Magnetization-Prepared Rapid Gradient-Echo in the Pre-Operative Evaluation of Living Liver Donor Candidates

Yamashita and co-workers (2017) compared the diagnostic performance of non-contrast-enhanced magnetic resonance venography using magnetization-prepared rapid gradient-echo (MPRAGE-MRV) and conventional CT venography (CTV) in pre-operative evaluation of venous tributaries for living donor liver transplantation.  Institutional review board approval and written informed consent were obtained for this prospective study of 73 donor candidates.  Of these, 23 underwent right-sided graft hepatectomy without middle hepatic vein.  One or more tributaries, other than the right hepatic vein, were reconstructed for 20 of the 23 grafts.  For these 20 grafts, the number and location of the tributaries requiring reconstruction were evaluated based on venography, and diagnostic performance was analyzed using surgical records as a reference standard.  For each candidate, the number of small tributaries directly joining the inferior vena cava was counted in each venographic image; a paired-sample t-test was used to assess differences.  The severity of respiratory artifacts in MPRAGE-MRV was qualitatively evaluated, and compared using Wilcoxon's rank-sum test.  All reconstructed venous tributaries were prospectively identified using both methods.  MPRAGE-MRV tended to provide a greater number of small tributaries than conventional CTV (mean of 2; 95 % CI: [1.66 to 2.34], and 1.74; [1.44 to 2.04], respectively), although the difference was not significant (p = 0.10); MPRAGE-MRV was superior or equal to CTV in 52 subjects (71.2 %), and inferior in 21 subjects (28.8 %).  Respiratory artifacts were significantly less severe in the former subjects (p < 0.0001).  The authors concluded that MPRAGE-MRV has the potential to replace conventional CTV in the pre-operative evaluation of living liver donor candidates.

MRV for Prediction of Outcome in Tuberculous Meningitis

Bansod and colleagues (2018) evaluated the prevalence and predictors of venographic abnormalities in tuberculous meningitis.  Consecutive patients of tuberculous meningitis were included in the study.  Clinical evaluation, cerebro-spinal fluid (CSF) examination and contrast-enhanced MRI of brain were carried out.  Every participant was subjected to time of flight MRV.  Presence of filling defects at superior sagittal sinus, dominant transverse or sigmoid sinus, and non-visualization of deep venous system was considered suggestive of thrombosis.  The presence of filling defects at non-dominant transverse or sigmoid sinus was considered suggestive of thrombosis only in the presence of corresponding changes in T1, T2, and GRE sequences, parenchymal changes or presence of collaterals.  Patients were followed-up for 6 months.  A modified Barthel index of less than or equal to 12 at 6 months was taken as poor outcome.  Of the 107 patients, MRV was found to be abnormal in 12 patients (11.2 %).  The superior sagittal sinus was the most commonly involved sinus.  On uni-variate analysis, the presence of vomiting (p = 0.004), altered sensorium (p = 0.004), seizures (p < 0.001), vision impairment (p = 0.038), papilledema (p < 0.001), diplopia, oculomotor palsies, basal exudates (p = 0.004) and modified Barthel index (MBI) of less than or equal to 12 at baseline (p = 0.004) were significantly associated with an abnormal MRV.  On multi-variate analysis, none of the above factors was found to be significant.  No association was found between an abnormal MRV and poor outcome.  The authors concluded that MRV abnormalities suggestive of venous sinus thrombosis could occur in approximately 11 % patients; superior sagittal sinus is the most commonly involved sinus.  Moreover, they stated that an abnormal MRV may not predict a poor outcome in patients with tuberculous meningitis.

MRV for Diagnosis of Central Venous Occlusion

Shahrouki and colleagues (2019) noted that although cardiovascular MRV (CMRV) is generally regarded as the technique of choice for imaging the central veins, conventional CMRV is not ideal.  Gadolinium-based contrast agents (GBCA) are less suited to steady-state venous imaging than to first-pass arterial imaging and they may be contraindicated in patients with renal impairment where evaluation of venous anatomy is frequently required.  These researchers examined the diagnostic performance of 3-dimensional (3D) ferumoxytol-enhanced CMRV (FE-CMRV) for suspected central venous occlusion (CVO) in patients with renal failure and to evaluate its clinical impact on patient management.  In this institutional review board (IRB)-approved and HIPAA-compliant study, a total of 52 consecutive adult patients (47 years, inter-quartile range [IQR] 32 to 61; 29 men) with renal impairment and suspected venous occlusion underwent FE-CMRV, following infusion of ferumoxytol.  Breath-held, high resolution, 3D steady-state FE-CMRV was performed through the chest, abdomen and pelvis.  Two blinded reviewers independently scored 21 named venous segments for quality and patency.  Correlative catheter venography in 14 patients was used as the reference standard for diagnostic accuracy.  Retrospective chart review was conducted to determine clinical impact of FE-CMRV.  Inter-observer agreement was determined using Gwet's AC1 statistic.  All patients underwent technically successful FE-CMRV without any AEs; 99.5 % (1,033/1,038) of venous segments were of diagnostic quality (score greater than or equal to 2/4) with very good inter-observer agreement (AC1 = 0.91).  Inter-observer agreement for venous occlusion was also very good (AC1 = 0.93).  The overall accuracy of FE-CMRV compared to catheter venography was perfect (100.0 %).  No additional imaging was needed before a clinical management decision in any of the 52 patients; 24 successful and uncomplicated venous interventions were performed following pre-procedural vascular mapping with FE-CMRV.  The authors concluded that 3D FE-CMRV was a practical, accurate and robust technique for high-resolution mapping of central thoracic, abdominal and pelvic veins, and could be used to inform image-guided therapy.  It may play a pivotal role in the care of patients in whom conventional contrast agents may be contraindicated or ineffective.

The authors stated that this study had several drawbacks.  First, the number of vessels used for the diagnostic accuracy assessment was relatively low.  The limiting factor was the number of catheter images because these were available only for vessels that were injected and relevant to the clinical procedure.  Nonetheless, the analysis spanned the majority of venous segments and thus decreased the risk of a potential selection bias.  The long interval between the FE-CMRV and some catheter studies (up to 98 days) could cause a length time bias.  Despite this, the agreement between both modalities was very high.  FE-CMRV of the central veins has already shown promising results in small pediatric cohorts and in patients with pelvic vein thrombosis, but this study addressed a large adult cohort and established diagnostic accuracy and value added to patient care and management.

MRV for Evaluation of Chronic Occlusive Ilio-Femoral Venous Disease

Saleem and Raju (2021) noted that techniques to diagnose and treat chronic iliofemoral venous obstruction (CIVO) have continued to evolve.  Intra-vascular US (IVUS) displays real-time cross-sectional venous anatomy and could be used to guide venous interventions; however, being invasive, it is not a suitable initial screening tool.  The comparison of IVUS with other 3D contrast imaging modalities is less well documented.  In a systematic analysis, these researchers examined the performance of IVUS and other 3D contrast imaging modalities for the evaluation of CIVO.  They carried out a search of various databases, including Medline, Embase, EBSCOhost, Cochrane Library, CINAHL PLUS, and Web of Science to identify studies that had compared IVUS and at least 1 other multi-dimensional contrast imaging modality, including multi-planar venography, CTV, CTA, or MRV in the evaluation of CIVO.  A total of 2,117 articles were screened; of these, 8 met the inclusion criteria.  Furthermore, 12 other studies were identified that had compared IVUS and single plane venography.  A meaningful meta-analysis could not be conducted owing to data heterogeneity.  The quality of evidence varied from very low to low.  IVUS identified stenotic lesions in 0 % to 30 % more patients compared with multi-planar venography.  The CTV and IVUS measurements correlated well with each other.  The sensitivity of the 2-segment CTV technique approached 97 %.  The specificity of CTV was 57 % to 86 % and varied with the venous segment.  The sensitivity and specificity of MRV compared with IVUS was 100 % and 22.7 %, respectively.  The authors concluded that given that IVUS is considered the reference standard used to guide venous interventions in patients with CIVO, the use of venography, despite using multiple projection views, under-estimated the severity and presence of venous stenosis and should not be used as the only diagnostic modality.  These researchers stated that 3D-CTV is non-invasive with a high sensitivity.  It can be used to screen patients who might benefit from a more invasive investigation with IVUS.  CTV can also be considered for the pre-operative planning of venous interventions in patients with CIVO.

MRV for Diagnosis of Nutcracker Syndrome

Nastasi et al (2022) stated that nutcracker syndrome (NCS) is an increasingly recognized venous compressive disease.  Although individuals with NCS can experience debilitating symptoms, making an accurate diagnosis can often be challenging owing to the broad spectrum of clinical presentations and radiologic findings.  In a systematic review, these investigators examined the most frequent clinical and radiologic criteria used in establishing a diagnosis of NCS and have proposed a comprehensive framework for clinical decision-making.  They identified all observational studies or case-series studies performed within the past 10 years that had examined patients with a clinical and radiologic diagnosis of NCS.  The extracted data included details related to the study design, subject demographics, presenting clinical features, and radiologic criteria.  These details were compared between studies and synthesized to establish a comprehensive diagnostic framework that would be applicable to clinical practice.  These researchers included 14 studies with a total of 384 patients with NCS.  The most common clinical features of NCS were hematuria (69.5 %), left flank or abdominal pain (48.4 %), pelvic pain (23.1 %), and varicocele (15.8 %); CT and US were the most commonly used imaging modalities, with a threshold for left renal vein stenosis of greater than 80 % the most frequently used diagnostic parameter.  A total of 8 studies had used venography, with the reno-caval pressure gradient the most commonly measured parameter; 2 studies had reported using intra-vascular US.  The findings from the authors’ review have shown that a thorough clinical work-up of NCS should include critical evaluation of the presenting clinical features and exclusion of alternative diagnoses.  All patients should undergo Duplex US with or without the addition of CT or MRI.  Any patient considered for therapeutic intervention should also undergo diagnostic venography with measurement of the reno-caval pressure gradient and, if available, intra-vascular US with measurement of the left renal vein diameters.  The authors concluded that NCS is a challenging condition in terms of the diagnosis and management both.  These investigators have proposed a comprehensive diagnostic framework based on the currently available literature to aid in clinical decision-making.

An UpToDate review on “Etiology and evaluation of hematuria in adults” (Perazella and O'Leary, 2022) states that “Nutcracker syndrome is usually suspected when CT or MRI shows intrarenal and perirenal varices, and early enhancement of the left gonadal vein collateral.  The diagnosis is confirmed on Doppler ultrasound demonstrating left renal vein compression with elevated velocities”.  Magnetic resonance venography is not mentioned as a diagnostic tool.

Furthermore, an UpToDate review on “Evaluation of microscopic hematuria in children” (Boyer, 2022) states that “The frequency of nutcracker syndrome as a cause of hematuria in children appears to be highest in Asia … Doppler ultrasonographic findings were consistent with nutcracker syndrome in 21 of 23 with gross hematuria and 17 of 52 with microscopic hematuria”.  Magnetic resonance venography is not mentioned as a diagnostic tool.


References

The above policy is based on the following references:

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