Tim Leiner

Accuracy of Computed Tomographic Angiography and Magnetic Resonance Angiography for Diagnosing Renal Artery Stenosis

Context Physicians sometimes use computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) to diagnose renal artery stenosis. Contribution This prospective multicenter study compared CTA and MRA with digital subtraction angiography (the reference standard) in 402 hypertensive patients with suspected renal artery stenosis. Multiple experienced physicians sometimes disagreed about whether the CTA and MRA tests showed renal artery stenosis. The sensitivity estimates of CTA and MRA for detecting renal artery stenosis were 64% and 62%. Implications In this study, even trained physicians had difficulty interpreting some CTA and MRA tests, and neither test was sensitive enough to rule out renal artery stenosis. Renal artery stenosis may cause renovascular hypertension and renal impairment. Accurate detection and treatment of clinically relevant stenoses may cure or improve hypertension and preserve renal function. Current treatment options include surgery, percutaneous transluminal renal angioplasty with or without stent placement, and medical therapy. Despite the availability of several other diagnostic tests, intra-arterial digital subtraction angiography (DSA) remains the reference standard for anatomic diagnosis of renal artery stenosis. This test, however, is an invasive procedure that carries a risk for serious complications and is burdensome for patients (1, 2). For this reason, less invasive diagnostic alternatives, such as computed tomographic angiography (CTA) and 3-dimensional contrast-enhanced magnetic resonance angiography (MRA), are widely used for diagnostic work-up in patients with suspected renal artery stenosis. A recent meta-analysis (3) found that CTA and MRA were significantly better than non-contrast-enhanced magnetic resonance angiographic techniques, ultrasonography, captopril renal scintigraphy, and the captopril test at identifying renal artery stenosis when DSA was used as the reference standard. To date, however, only a limited number of small, well-designed studies have been published on the diagnostic accuracy of either CTA or MRA for detection of renal artery stenosis in patients with suspected renovascular hypertension (4-14). Because CTA and MRA seemed to be promising techniques with the potential to reduce the number of patients requiring conventional angiography, we set up a large-scale multicenter study to investigate the diagnostic performance of these tests, using DSA as reference standard, in hypertensive patients clinically deemed at risk for renal artery stenosis. The purpose of our study was to determine the interobserver agreement and diagnostic accuracy of CTA and MRA in comparison with DSA and to examine whether CTA or MRA can be used as an initial test for detection of renal artery stenosis. Methods We performed a prospective comparative study among CTA, MRA, and the reference standard, DSA, for the detection of renal artery stenosis. Each included patient underwent all 3 diagnostic tests. Participants Over a 3-year period, patients were prospectively recruited from the internal medicine outpatient clinics of 3 large teaching hospitals and 3 university hospitals in the Netherlands. The ethical review board of each hospital approved the study, and written informed consent was obtained from all participants. At the 2 hospitals that recruited most of the participating patients, enrollment was consecutive; the other participating hospitals included patients by using nonsystematic convenience samples. At the 6 participating centers, all hypertensive patients between 18 and 75 years of age with a diastolic blood pressure greater than 95 mm Hg were routinely screened for predefined clinical clues indicating renal artery stenosis, as described by the Working Group on Renovascular Hypertension (15) and others (16, 17). Patients were eligible for participation in the study if they exhibited at least 1 clinical clue. Exclusion criteria were known allergy to iodinated contrast agents; pregnancy; contraindications to MRA, CTA, or DSA (18, 19); contraindications to intervention; or previous participation in the study. All included patients were scheduled to have CTA, MRA, and DSA within a 3-month window. At the coordinating center (Maastricht University Hospital), included patients were scheduled to undergo CTA and MRA on the same day, followed by DSA the next day. At the other centers, the tests were performed on the basis of availability. No treatments that could affect the test results were allowed before all tests were completed. The case record forms for all patients were collected at the coordinating center, and the information was entered into a database. Imaging Techniques Each participating hospital was equipped with state-of-the art magnetic resonance scanners (1.0 or 1.5 Tesla), helical computed tomography scanners (single- or multi-detector row systems), and DSA equipment. In addition, hospitals were allowed to optimize scan protocols during the study when new insights emerged or when equipment was upgraded, an approach that conforms to usual clinical practice. Changes in scan protocols occurred twice (Appendix Table 1). To ensure state-of-the art magnetic resonance imaging, all scan protocols had to meet minimal quality standards in terms of spatial resolution and scan duration. The quality standards were defined by the coordinating center and were based on the protocols that were published at the start of the study. During the entire study, the coordinating center continuously monitored the quality of all images. Information about manufacturers, scan protocols, and contrast agents is shown in Appendix Table 1. All imaging was performed or supervised by experienced radiologists and radiologic technologists. Renal CTA, MRA, and DSA had already been part of clinical routine before the start of the study. Image Evaluation At the conclusion of study enrollment, 2 panels of 3 observers evaluated the CTA and MRA image data at the coordinating center. All observers had more than 3 years of experience evaluating such data on a regular basis, and for each method 1 observer had more than 6 years of experience. Each observer independently performed the evaluations and was blinded to all other results, including clinical information and DSA results. Digital image data for all CTA and MRA examinations were evaluated by using a work station equipped with all commonly used image-processing tools (EasyVision, release 4.2.1, Philips Medical Systems, Best, the Netherlands). Source images had to be examined in all cases before a final diagnosis could be made. The DSA images were evaluated by 4 vascular radiologists, all with more than 10 years of experience in this particular field. The first observer was the radiologist who actually performed the test; the evaluation took place during the DSA procedure. The second and third observers who judged each DSA examination knew the first observers judgment. If discrepancies existed among the first 3 observers with respect to the number of renal arteries involved or the nature, location, or severity of disease (differences of >10% in the degree of stenosis), a fourth radiologist, who had access to the diagnoses of the other observers, made the final diagnosis. This consensus approach has been used in several other CTA and MRA studies (6, 7, 12-14). All DSA observers were blinded to the results of CTA and MRA. To determine the degree of stenosis, the diameter of the most severely affected part of a renal artery was measured and related to the reference diameter, which was defined as the diameter of a representative nonaffected portion of the artery, preferably immediately distal to the stenosis (that is, beyond the site of poststenotic dilatation, if present). Fibromuscular dysplasia was diagnosed when multiple aneurysms separated by focal narrowing (string-of-beads sign) were observed. For CTA, MRA, and DSA, luminal narrowing of at least 50%, as well as all cases of fibromuscular dysplasia, was defined as clinically relevant renal artery stenosis (3). For each patient, the observers first recorded the number of renal arteries. Subsequently, these arteries were judged with respect to the presence or absence of stenosis (expressed as percentage of luminal narrowing), the nature of the stenosis (atherosclerotic or fibromuscular dysplasia), the location of the stenosis (ostial or truncal), and the level of confidence in the diagnosis (high, moderate, or poor) (6). Inconclusive examination results were noted on the standardized form used to collect all relevant data. Statistical Analysis The severity of the stenoses as seen on CTA and MRA was categorized on a 5-point scale (grade 1, 0% to 19%; grade 2, 20% to 49%; grade 3, 50% to 74% or fibromuscular dysplasia; grade 4, 75% to 99%; and grade 5, total occlusion [100% stenosis]). The Cohen weighted analysis was used to test for agreement beyond that of chance among the 3 observers of MRA and among the 3 observers of CTA (20). Unless stated otherwise, all analyses on the diagnostic accuracy of CTA and MRA (sensitivity, specificity, and receiver-operating curve [ROC] analysis) compared with DSA are based on patients as the unit of analysis. In the by-patient analysis, a patient was classified as having positive results if 1 or more renal arteries were found to be stenotic ( 50%) on DSA. The most severe stenosis per patient was used for analysis. Inconclusive CTA and MRA results were considered as positive test results because further diagnostic work-up would be required in clinical practice and these patients would be referred for DSA. Exact 2-sided 95% CIs for proportions were calculated by using a binomial distribution. Overall estimates of sensitivity, specificity, positive predictive value, and negative predictive value for all observers per method, including 95% CIs, were calculated by using the cluster option of Stata, version 8.2 (Stata Corp., College Station, Texas) (21). This

Diagnostic Performance of Noninvasive Myocardial Perfusion Imaging Using Single-Photon Emission Computed Tomography, Cardiac Magnetic Resonance, and Positron Emission Tomography Imaging for the Detection of Obstructive Coronary Artery Disease: A Meta-Analysis

OBJECTIVESnThis study aimed to determine the diagnostic accuracy of the 3 most commonly used noninvasive myocardial perfusion imaging modalities, single-photon emission computed tomography (SPECT), cardiac magnetic resonance (CMR), and positron emission tomography (PET) perfusion imaging for the diagnosis of obstructive coronary artery disease (CAD). Additionally, the effect of test and study characteristics was explored.nnnBACKGROUNDnAccurate detection of obstructive CAD is important for effective therapy. Noninvasive myocardial perfusion imaging is increasingly being applied to gauge the severity of CAD.nnnMETHODSnStudies published between 1990 and 2010 identified by PubMed search and citation tracking were examined. A study was included if a perfusion imaging modality was used as a diagnostic test for the detection of obstructive CAD and coronary angiography as the reference standard (≥50% diameter stenosis).nnnRESULTSnOf the 3,635 citations, 166 articles (n = 17,901) met the inclusion criteria: 114 SPECT, 37 CMR, and 15 PET articles. There were not enough publications on other perfusion techniques such as perfusion echocardiography and computed tomography to include these modalities into the study. The patient-based analysis per imaging modality demonstrated a pooled sensitivity of 88% (95% confidence interval [CI]: 88% to 89%), 89% (95% CI: 88% to 91%), and 84% (95% CI: 81% to 87%) for SPECT, CMR, and PET, respectively; with a pooled specificity of 61% (95% CI: 59% to 62%), 76% (95% CI: 73% to 78%), and 81% (95% CI: 74% to 87%). This resulted in a pooled diagnostic odds ratio (DOR) of 15.31 (95% CI: 12.66 to 18.52; I(2) 63.6%), 26.42 (95% CI: 17.69 to 39.47; I(2) 58.3%), and 36.47 (95% CI: 21.48 to 61.92; I(2) 0%). Most of the evaluated test and study characteristics did not affect the ranking of diagnostic performances.nnnCONCLUSIONSnSPECT, CMR, and PET all yielded a high sensitivity, while a broad range of specificity was observed. SPECT is widely available and most extensively validated; PET achieved the highest diagnostic performance; CMR may provide an alternative without ionizing radiation and a similar diagnostic accuracy as PET. We suggest that referring physicians consider these findings in the context of local expertise and infrastructure.

Risk factors for NSF: a literature review.

Emerging evidence linking gadolinium‐based contrast agents (GBCAs) to nephrogenic systemic fibrosis (NSF) has changed medical practice patterns toward forgoing GBCA‐enhanced magnetic resonance imaging (MRI) or substituting other imaging methods, which are potentially less accurate and often radiation‐based. This shift has been based on reports of high NSF incidence at sites where a confluence of risk factors occurred in patients with severe renal dysfunction. This review article explores the factors that affect NSF risk, compares risks of alternative imaging procedures, and demonstrates how risk can be managed by careful selection of GBCA dose, timing of injection with respect to dialysis, and other factors. Nearly half of NSF cases are a milder form that does not cause contractures or reduce mobility. It appears that eliminating even a single risk factor can reduce NSF incidence/risk at least 10‐fold. Elimination of multiple risk factors by using single‐dose GBCA, dialyzing dialysis patients quickly following GBCA administration, avoiding GBCA in acute renal failure while serum creatinine is rising, and avoiding nonionic linear GBCA in renal failure patients may reduce NSF risk more than a thousand‐fold, thereby allowing safe GBCA‐enhanced MRI in virtually all patients. J. Magn. Reson. Imaging 2009;30:1298–1308.

Three‐dimensional contrast‐enhanced moving‐bed infusion‐tracking (MoBI‐track) peripheral MR angiography with flexible choice of imaging parameters for each field of view

A technique to image peripheral arteries with flexible choice of scan parameters for separate stations was developed based on moving‐bed single‐bolus three‐dimensional gradient‐recalled echo magnetic resonance angiography. A volunteer study yielded higher signal‐ and contrast‐to‐noise ratios, less venous enhancement, and better subjective interpretability compared with imaging with fixed parameters for each station. Additionally, six patients were imaged to test the feasibility of the new method in a clinical setting. Imaging peripheral arteries with the new technique in volunteers yielded better image quality and is feasible for patients. J. Magn. Reson. Imaging 2000;11:368–377.

Motion of the distal renal artery during three-dimensional contrast-enhanced breath-hold MRA.

To study the potential detrimental effects of renal motion on breath‐hold three‐dimensional contrast‐enhanced (CE) magnetic resonance angiography (MRA).

Contemporary imaging techniques for the diagnosis of renal artery stenosis

Renal artery stenosis (RAS) is a potentially curable cause of renovascular hypertension (RVH) and is caused by either atherosclerosis or fibromuscular dysplasia (FMD) in the vast majority of patients. Although intra-arterial digital subtraction angiography (IA-DSA) is still considered the standard of reference test for the anatomical diagnosis of RAS, noninvasive techniques such as MR angiography, CT angiography, and color-aided duplex ultrasonography are promising alternatives that also allow functional characterization of RAS. We provide an overview of these techniques and discuss their relative merits and shortcomings. Analysis of high-quality studies shows that both MR and CT angiography are significantly more accurate for the diagnosis of at least 50% atherosclerotic RAS than ultrasonographic techniques. The primary strength of ultrasonography at present is its suggested ability to predict functional recovery based on preinterventional resistance index measurements. A still unresolved issue is the detection of FMD. Because missing RVH may have serious consequences the most important requirement for a screening test is that it has high sensitivity.

Gadobutrol-enhanced moving-table magnetic resonance angiography in patients with peripheral vascular disease: a prospective, multi-centre blinded comparison with digital subtraction angiography

Abstract.The purpose of this study was to compare moving-table three-dimensional contrast-enhanced magnetic resonance angiography (CE MRA), using 1.0-mol gadobutrol, with intra-arterial digital subtraction angiography (i.a. DSA) for evaluation of pelvic and peripheral arteries in patients with peripheral arterial occlusive disease. A total of 203 patients were examined in a prospective, multi-centre study at 1.0/1.5xa0T. Ten vessel segments of one leg were evaluated on-site and by three independent blinded reviewers off-site. One hundred eighty-two patients were evaluable in blinded reading. For pelvis and thigh, there was statistically significant diagnostic agreement between CE MRA and i.a. DSA on-site (94%) and off-site (86–88%). Overall, for detection of clinically significant stenoses, 93% sensitivity and 90% specificity were achieved in on-site evaluation, with 71–76 and 87–93% off-site; for detection of occlusion, sensitivity and specificity on-site were 91 and 97%, with 75–82 and 94–98% off-site. Evaluation was more sensitive on-site than off-site for detection of stenoses and occlusion, whereas specificity was similar. The CE MRA with 1.0-mol gadobutrol gave results comparable to those of i.a. DSA for the larger arteries of pelvis and thigh. Results for calf arteries were compromised by spatial resolution and technical limitations.

Contrast‐enhanced peripheral MR angiography using SENSE in multiple stations: Feasibility study

To investigate if the use of parallel imaging is feasible and beneficial for peripheral contrast‐enhanced magnetic resonance angiography (CE‐MRA).

Contrast‐enhanced peripheral MR angiography at 3.0 Tesla: Initial experience with a whole‐body scanner in healthy volunteers

To report preliminary experience with contrast‐enhanced magnetic resonance angiography (CE‐MRA) of the peripheral arteries on a 3.0 T whole‐body scanner equipped with a prototype body coil.

Replacement and reactive myocardial fibrosis in idiopathic dilated cardiomyopathy: comparison of magnetic resonance imaging with right ventricular biopsy

Background The presence of focal myocardial fibrosis, also called scar or replacement fibrosis, detected with late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) is a predictor of adverse outcome in patients with idiopathic dilated cardiomyopathy (DCM). 1,2 Increased interstitial (reactive) fibrosis determined with histological staining from endomyocardial biopsy (EMB) specimens has been described in DCM and associated with an adverse prognosis and impaired response to therapeutic interventions in selected groups of patients with DCM. 3―6 Aims We sought to describe the patterns of focal fibrosis in a group of patients with DCM and correlate focal fibrosis with interstitial fibrosis, myocardial viral load, and inflammation. A pilot study in 10 autopsies was performed to compare interstitial fibrosis from right ventricular (RV) with left ventricular (LV) EMB. Methods Study subjects were 60 consecutive patients with DCM (globally impaired systolic LV function not due to myocardial infarction, significant coronary artery disease, hypertension, valvular disease, or other known causes) referred to our hospital for EMB and CMR. Patients (n = 1) with infarct-like subendocardial or transmural LGE within the territory of a coronary artery and corresponding regional wall motion abnormalities only were not included to avoid the inclusion of patients with an embolic event. Three patients did not agree to participate resulting in a study population of 56. The study was approved.