Improving Interpretation of MRA and CTA in Patients with Suspected Renal Artery Stenosis
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ABSTRACT:Contrast-enhanced computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) are widely used in patients with suspected renal artery stenosis as screening techniques. Both are accurate in depicting anatomical changes of renal vasculature. However, when interpreting MRA/CTA, additional functional information including asymmetrical size, post-stenotic dilatation and asymmetric enhancement may help determine the hemodynamic significance of renal artery stenoses, thus improving the interpretation and accuracy of renal MRA/CTA. Exciting advances in MR including new contrast agents and techniques to characterize borderline lesions are now becoming available.
VASCULAR DISEASE MANAGEMENT 2011;8:E34–E37
Key words: renal artery stenosis; MRA; CT
Renal artery stenosis causes renal ischemia and hypertension. When bilateral, progressive ischemic nephropathy may lead to renal failure and dialysis.1 Angioplasty and stent therapy for renal artery stenosis is controversial since several trials have shown similar benefits with medical therapy alone. The CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study is a prospective, multicenter study randomizing patients with systolic hypertension and severe renal artery stenosis to either medical therapy or medical therapy with renal artery stenting. Patients with atherosclerotic renal artery stenosis are randomized into either medical therapy or balloon angioplasty/stent and are followed for up to 10 years to determine which therapy has the best outcomes.
To avoid the devastating consequences of uncontrolled renovascular hypertension and renal failure, it is critical to diagnose renal artery stenosis as early as possible. Renal artery stenosis may be identified on a variety of imaging modalities even when it is unrelated to the patient’s hypertension. As a result, there is an emerging trend toward using advanced imaging techniques to evaluate not just the renal artery caliber, but to also look for signs indicating that the stenosis is hemodynamically significant and thus likely to be the cause of hypertension.
Conventional angiography with measurement of pressures proximal and distal to the stenosis is the gold standard for diagnosing hemodynamically significant renal artery stenosis,2 but it is not an ideal screening examination due to the invasiveness, radiation exposure and nephrotoxic iodinated contrast media. Less invasive techniques have been developed to detect and assess renal arterial disease.3–5 Doppler ultrasonography and captopril renography have focused on detecting the hemodynamic effects of a functionally significant renal artery stenosis, whereas computed tomography (CT) and magnetic resonance (MR) angiography are more effective in detecting renal artery morphological changes using a subjective impression of stenosis severity to predict functional significance. In the CORAL study, several noninvasive imaging techniques are utilized as randomization pathways which include duplex ultrasound, CTA and MRA. Here we review the utility and technical aspects of renal artery CTA and MRA.
Advances in CT technology that allow spiral multidetector acquisitions with slice thickness typically 1.5 mm or thinner can provide accurate anatomic images of even small renal arteries during the arterial phase of a fast iodinated contrast agent bolus. The sensitivity and specificity for diagnosing renal artery stenosis range from 67–100% and 77–98%, respectively.6
Compared to conventional catheter angiography, CTA is less invasive with faster acquisition, better soft tissue visualization, and it allows multiplanar imaging of the renal arteries in any obliquity. CTA has the advantage over MRA of being technically easier to perform with accuracy comparable to MRA.7–9 However, CTA has the risks of ionizing radiation and nephrotoxicity from iodinated contrast agents. Currently, CTA is not utilized in patients with azotemia or kidney transplant unless alternative techniques that do not use iodinated contrast have been inadequate or are not available. When there is severe calcification in the renal arteries, the luminal narrowing may be obscured and/or overestimated.
A major limitation of CTA is that the technique is only capable of providing an anatomic assessment with minimal physiological information about the stenosis. This emphasizes the shortcoming of using the widely accepted anatomic criterion of a 75% decrease in cross-sectional area for diagnosing severe and significant stenosis to predict the functional significance of the stenosis without considering the influence of renal blood flow. A morphologically severe stenosis might not induce a pressure gradient if the artery has slow flow due to renal parenchymal damage. There is no benefit from dilating a severe renal artery stenosis when the ischemic nephropathy is already end-stage.
MRA with gadolinium enhancement for diagnosing renal artery stenosis has sensitivities and specificities of 88–100% and 70–100%, respectively, with low interobserver variability,10 especially for severe stenoses > 70%. Thus, the use of MRA may avoid invasive diagnostic procedures.11 In addition, renal MRA eliminates the need for aortography at the time of subsequent angioplasty,12 thereby reducing iodinated contrast load and radiation exposure during renal revascularization. By showing the precise location of each renal artery and the angle arising from the aorta, catheter manipulation is also decreased, thereby potentially reducing the risk of cholesterol emboli. Interpreting renal MRA images includes analyzing for both luminal anatomy and evidence of diminished or asymmetrical renal function, which occurs in the setting of hemodynamically significant renal artery stenosis.
Post-stenotic dilatation. Post-stenotic dilatation of greater than 20% is commonly seen with moderate-to-severe renal artery stenosis. When the renal artery lumen narrows, blood flow accelerates to maintain the same volume across a narrower cross-sectional area. Accelerated jet flow tends to impact the artery wall distal to the stenosis, eventually producing post-stenotic dilatation. Note, however, that post-stenotic dilatation is greatest with moderate stenoses and diminishes in the most severe stenoses that are nearly occlusive and do not allow enough jet-flow through the lumen. For this reason, post-stenotic dilatation should not be relied upon as a primary indicator of hemodynamic significance.
Corticomedullary differentiation. On T1-weighted images, the renal cortex is brighter than the medulla. Loss of this corticomedullary differentiation (CMD) on unenhanced T1-weighted images is a nonspecific marker of renal dysfunction. Although this can occur with any renal disease, it is expected in ischemic nephropathy. Following gadolinium injection, a reduction of CMD also results from the decreased blood flow that is more pronounced in the cortex than in the medulla.
Symmetry of kidney size and parenchymal thickness. Normal kidneys typically measure 11–13 cm in length, with a tendency for the right kidney to be slightly smaller (up to 1 cm); typical parenchymal thickness is 1.7 + 0.3 cm.13 Hemodynamically significant RAS reduces the perfusion pressure within the ischemic kidney, causing it to shrink. In addition, long-term ischemia destroys nephrons, resulting in gradual renal atrophy and further reducing the parenchymal volume. Whenever an ischemic kidney is > 1 cm smaller than the contralateral kidney, the possibility of hemodynamic significance should be considered. A difference in kidney volume may be a more reliable index than kidney length. However, when there are bilateral renal artery stenoses, both kidneys shrink, making this criterion less useful.
Symmetry of gadolinium (Gd) enhancement and excretion. An ischemic kidney will enhance more slowly compared to a normally perfused contralateral kidney. In addition, a delayed scan (~10 minutes after contrast administration) can help assess renal excretory function. On state-of-the-art MR scanners with TE
Functional MR Sequences
3-D phase contrast MRA. Three-dimensional (3-D) phase contrast (PC) MRA has the potential for assessing pressure gradients by identifying spin dephasing at stenoses. With flow encoding in all three axes on 3-D PC, image intensity corresponds to speed. Flowing blood is bright, while stationary tissues are dark. Mild stenoses appear less severe because accelerated flow creates a blooming effect. When a stenosis reaches critical severity (> 75% narrowing) to cause a pressure gradient, flow accelerated through a tight stenosis becomes disorganized, separated, swirling and turbulent. Flow jets dephase and destroy MR phase coherence, causing dephasing of the MR signal, which is especially prominent on 3-D PC MRA due to the relatively long echo time and the motion of protons during application of flow-encoding gradients.
Underestimation of mild stenoses and overestimation of severe stenoses used to be considered a disadvantage of flow-sensitive MRA, but it can also be useful for distinguishing between unimportant and hemodynamically significant stenoses.
2-D Cine Phase Contrast MR. Two-dimensional (2-D) cine PC is a fast, noninvasive way to measure the temporal pattern of renal artery blood flow at a single location. It can be performed after gadolinium-enhanced MRA to take advantage of increased signal-to-noise ratio. Using cardiac gating and breath holding, cine PC measures flow volume as well as velocity-time curves for a single renal artery cross-section. On PC flow curves, significant renal artery stenosis is characterized by delay or loss of the early systolic peak, reduction in renal capillary resistance and decreased total flow. A renal flow index 3 reportedly predicts if the patient is likely to benefit from revascularization.14 Combining cine PC data with Gd-enhanced MRA reduces the interobserver variability on stenosis grading.15 Recently, refinements to phase contrast imaging using radial acquisitions have allowed better depiction of renal stenoses with calculation of absolute pressure gradients.16
Time-resolved sequences. Contrast arrival time at the cortex may be similar for normal and ischemic kidneys, while the transit time from cortex to medulla is much longer (15 sec vs. 40 sec) for kidneys with renal artery stenosis and decreased function. Thus, medullary enhancement in ischemic kidneys is characterized by delayed and decreased enhancement. Lee et al reported using MR renography with low-dose Gd contrast (2 mL) to assess contrast enhancement of the renal cortex and medulla. After initial medullary enhancement (the first 20 seconds), dysfunctional kidneys demonstrated delayed medullary enhancement during the tubular phase (1 to 4 minutes), reflecting diminished glomerular filtration.17
Assessment of glomerular filtration rate (GFR) via Gd clearance rate. Gd extraction decreases in kidneys with severe renal artery stenosis. Combining renal artery flow measurements with an additional pulse sequence to measure Gd concentration in the renal artery (input) and renal vein (output) permits calculation of the Gd clearance rate for each kidney.18 Since Gd is filtered but not excreted or reabsorbed, this corresponds directly with creatinine clearance, i.e., GFR.
Diffusion-weighted MR imaging. Diffusion-weighted imaging is feasible for vascular-related renal dysfunction assessment by using larger B factors (requiring a strong gradient) to eliminate the confounding influences of glomerular filtration, tubular reabsorption, tubular secretion and urine flow on the apparent diffusion coefficient (ADC).19 The cortex of ischemic kidneys shows lower ADC values than that of the contralateral ones because reduced blood flow may have more physiological impact on the cortex than the medulla. In acute or chronic renal failure caused by other factors, both the cortex and medulla may show reduced ADC values.
Quantitative perfusion imaging. Quantitative perfusion measurement of the kidney has been introduced, which offers an independent measure of parenchymal blood flow in the renal cortex as well as the medulla that can be performed in patients with renal artery stenosis.20 Improvements in perfusion quantification may be possible with the recent FDA approval of ferumoxytol, and gadofosveset trisodium, which are iron and Gd-based blood pool contrast agents, respectively.21,22
Both MR spectroscopy and oxygen saturation may add information to help answer the question of which patients with renal artery stenosis will benefit from renal revascularization. MR spectroscopy takes advantage of the unique spin resonance of common organic molecules to determine their relative concentration in tissue. It can be applied to hydrogen protons as well as to isotopes of sodium, phosphorus, carbon and a host of other atoms. Another interesting MR capability is the measurement of blood oxygen saturation based upon the T2 shift in whole blood corresponding to the hemoglobin oxidation status.23 Ischemic organs tend to extract more oxygen, which results in decreased oxygen saturation in the venous blood coming from the organ. However, these and all of the other functional methods require further study to determine their relative importance for predicting hemodynamically significant stenosis and the potential for benefit from revascularization.
Many pathophysiological aspects of kidney function can be studied by MR. Combining evaluation of the renal artery stenosis with a functional assessment of the kidneys will allow renal MR angiography to become increasingly accurate, comprehensive and useful for clinical decision-making. This will be achievable especially if and when any of the MRA-based indices mentioned above can be shown to correspond to the activity of the renin-angiotensin system, both intrarenally and/or peripherally. Only then can the true clinical relevance to systemic hypertension of any observed localized renal structural or functional details be established, and clinically meaningful decisions be formulated.
Magnetic resonance angiography (MRA) of an anonymous patient with refractory hypertension randomized to medical therapy in the CORAL study showed a 90% right renal artery stenosis with post-stenotic dilatation (Figure 1), a small right kidney with decreased enhancement (Figure 2) and delayed gadolinium (Gd) excretion (Figure 4) and spin-dephasing on 3-D phase contrast imaging (Figure 3), indicating that this right renal artery stenosis is hemodynamically significant. There was only mild left renal artery stenosis with normal size, enhancement and Gd excretion by the left kidney and no spin dephasing in the left renal artery at the site of the stenosis.
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