J.M.A. van Engelshoven

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

Vascular calcifications as a marker of increased cardiovascular risk: A meta-analysis

Background: Several imaging techniques may reveal calcification of the arterial wall or cardiac valves. Many studies indicate that the risk for cardiovascular disease is increased when calcification is present. Recent meta-analyses on coronary calcification and cardiovascular risk may be confounded by indication. Therefore, this meta-analysis was performed with extensive subgroup analysis to assess the overall cardiovascular risk of finding calcification in any arterial wall or cardiac valve when using different imaging techniques. Methods and results: A meta-analysis of prospective studies reporting calcifications and cardiovascular end-points was performed. Thirty articles were selected. The overall odds ratios (95% confidence interval [CI]) for calcifications versus no calcifications in 218,080 subjects after a mean follow-up of 10.1 years amounted to 4.62 (CI 2.24 to 9.53) for all cause mortality, 3.94 (CI 2.39 to 6.50) for cardiovascular mortality, 3.74 (CI 2.56 to 5.45) for coronary events, 2.21 (CI 1.81 to 2.69) for stroke, and 3.41 (CI 2.71 to 4.30) for any cardiovascular event. Heterogeneity was largely explained by length of follow up and sort of imaging technique. Subgroup analysis of patients with end stage renal disease revealed a much higher odds ratio for any event of 6.22 (CI 2.73 to 14.14). Conclusion: The presence of calcification in any arterial wall is associated with a 3–4-fold higher risk for mortality and cardiovascular events. Interpretation of the pooled estimates has to be done with caution because of heterogeneity across studies.

Detection of lymph node metastases in head and neck cancer: a meta-analysis comparing US, USgFNAC, CT, and MR imaging

Purpose: To perform a meta-analysis comparing ultrasonography (US), US guided fine needle aspiration cytology (USgFNAC), computed tomography (CT), and magnetic resonance imaging (MRI) in the detection of lymph node metastases in head and neck cancer. Methods: MEDLINE, EMBASE and Cochrane databases were searched (January 1990–January 2006) for studies reporting diagnostic performances of US, USgFNAC, CT, and MRI to detect cervical lymph node metastases. Two reviewers screened text and reference lists of potentially eligible articles. Criteria for study inclusion: (1) histopathology was the reference standard, (2) primary tumors and metastases were squamous cell carcinoma and (3) data were available to construct 2 × 2 contingency tables. Meta-analysis of pairs of sensitivity and specificity was performed using bivariate analysis. Summary estimates for diagnostic performance used were sensitivity, specificity, diagnostic odds ratios (DOR) (95% confidence intervals) and summary receiver operating characteristics (SROC) curves. Results: From seventeen articles, 25 data sets could be retrieved. Eleven articles studied one modality: US (n = 4); USgFNAC (n = 1); CT (n = 3); MRI (n = 3). Six articles studied two or more modalities: US and CT (n = 2); USgFNAC and CT (n = 1); CT and MRI (n = 1); MRI and MRI-USPIO (Sinerem ® )( n = 2); US, USgFNAC, CT and MRI (n = 1). USgFNAC (AUC = 0.98) and US (AUC = 0.95) showed the highest areas under the curve (AUC). MRI-USPIO (AUC = 0.89) and CT (AUC = 0.88) had similar results. MRI showed an AUC = 0.79. USgFNAC showed the highest DOR (DOR = 260) compared to US (DOR = 40), MRI-USPIO (DOR = 21), CT (DOR = 14) and MRI (DOR = 7). Conclusion USgFNAC showed to be the most accurate imaging modality to detect cervical lymph node metastases.

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.

The role of ultrasonography as an adjunct to mammography in the detection of breast cancer. a systematic review.

The aim of this review was to summarise the diagnostic performance of ultrasonography as an adjunct to mammography in the detection of breast cancer and to identify clinical indications. A systematic review was performed of all publications in MEDLINE and EMBASE between 1990 and 2000 on the role of ultrasonography as an adjunct to mammography. 22 studies were included, showing a large variety of indications for ultrasonography and variations in the diagnostic performance of mammography and ultrasonography. There were six studies comparing a combined diagnosis of mammography and ultrasonography together with mammography alone, of which three studies had an increased sensitivity at the cost of a lower specificity. The methods of selecting the study population and interpretation of ultrasonography significantly influenced the diagnostic performance of mammography and ultrasonography relative to each other (P=0.003, P=0.03, respectively). Based on the studies reviewed, little evidence-based support was found to confirm the well recognised value of ultrasonography as an adjunct to mammography in the detection of breast cancer in clinical practice. Furthermore, no clinical indications for additional ultrasonography could be defined. The heterogeneity in the diagnostic performance in these studies may be explained by the methods of patient selection and ultrasonography interpretation, as well as by their poor quality.

Magnetic resonance imaging of atherosclerosis

Abundant data now link composition of the vascular wall, rather than the degree of luminal narrowing, with the risk for acute ischemic syndromes in the coronary, central nervous system, and peripheral arterial beds. Over the past few years, magnetic resonance angiography has evolved as a well-established method to determine the location and severity of advanced, lumen-encroaching atherosclerotic lesions. In addition, more recent studies have shown that high spatial resolution, multisequence MRI is also a promising tool for noninvasive, serial imaging of the aortic and carotid vessel wall, which potentially can be applied in the clinical setting. Because of the limited spatial resolution of current MRI techniques, characterization of coronary vessel wall atherosclerosis, however, is not yet possible and remains the holy grail of plaque imaging. Recent technical developments in MRI technology such as dedicated surface coils, the introduction of 3.0-T high-field systems and parallel imaging, as well as developments in the field of molecular imaging such as contrast agents targeted to specific plaque constituents, are likely to lead to the necessary improvements in signal to noise ratio, imaging speed, and specificity. These improvements will ultimately lead to more widespread application of this technology in clinical practice. In the present review, the current status and future role of MRI for plaque detection and characterization are summarized.

MR angiography of run-off vessels

Abstract. Magnetic resonance angiography has taken a huge step forward since the introduction of contrast-enhanced MR angiography using gadolinium chelates. The more conventional MR angiographic techniques, such as time-of-flight and phase-contrast MR angiography, have been ousted by contrast-enhanced MR angiography in most vascular areas. However, in imaging the lower extremities, the major obstacle is the length of the vascular tree. In order to cover the entire peripheral vasculature, at least two to three fields of view are required. Using contrast-enhanced MR angiography, the best results are obtained if the vessels of interest are imaged during passage of a bolus of contrast material. Vessel-to-background contrast in subsequent acquisitions using subsequent injections of contrast material is hampered by recirculation and leakage of previously injected gadolinium, enhancing both the venous system and surrounding tissue. To overcome this problem several research groups have come up with various solutions. The three main strategies employed can be classified as either bolus catch, bolus chase, or bolus track techniques. The purpose of this article is to explain working mechanisms of the three bolus imaging strategies for imaging both inflow and outflow vessels of the lower extremities, to show their advantages and disadvantages, and to review results described in the literature in imaging patients using these techniques.

Renovascular disease in patients with hypertension: detection with duplex ultrasound.

The aim of this study was to evaluate the accuracy of duplex ultrasound for the diagnosis of renovascular disease in a cohort of hypertensive patients. In 78 patients suspected of renovascular hypertension on clinical grounds duplex ultrasound examination of the renal arteries was performed. Renal angiography was used as the standard of reference. Duplex ultrasound was inconclusive in 11 kidneys (7%). None of the supernumerary renal arteries was detected with duplex ultrasound. The overall prevalence of significant renovascular disease (⩾50% stenosis) was 20%. Based on the combination of parameters at thresholds commonly applied in current literature: ie PSVmax >180 cm/sec and RAR >3.5 the overall sensitivity of duplex ultrasound for detection of haemodynamically significant renovascular disease was 50.0% with a specificity of 91.3% (PPV: 87.9%; NPV: 59.1). Lowering the thresholds for both parameters improved the test results at the cost of a significant increase of false positive examinations. In a population of hypertensive patients clinically suspected of renovascular hypertension, only limited results for duplex ultrasound could be acquired in the detection of renovascular disease. This result, in combination with the wide range of sensitivities and specificities published in international literature and the relatively large number of incomplete examinations does not support the general application of duplex ultrasound as a screening procedure for detection and assessment of renovascular disease.

Renal artery blood flow: quantification with breath-hold or respiratory triggered phase-contrast MR imaging

Abstract. The aim of this study was to evaluate the validity and reproducibility of breath-hold and respiratory triggered phase-contrast (PC) MR imaging techniques in the measurement of renal artery blood flow. In 12 healthy subjects cardiac-gated PC flow measurements were obtained in the renal arteries using a breath-hold and a respiratory-triggered technique. The flow measurements were repeated in each renal artery separately. Comparison between the sum of flow measurements in the renal arteries and the difference in aortic flow measurements above and below the renal arteries served as an internal control. The flow measurements showed a good reproducibility both with the breath-hold (r = 0.92, p < 0.0001) and with the respiratory-triggered (r = 0.91, p < 0.0001) technique. The validity of both methods was good and there was no statistically significant difference. Reproducible quantitative measurements of renal artery blood flow are possible with respiratory controlled, cardiac-gated, PC MR imaging.

The prevalence of gallstone disease in a dutch population

The prevalence of gallstone disease was studied by ultrasound screening of a hospital population of 424 men and 631 women, admitted to the University Hospital Maastricht (The Netherlands) for elective surgery unrelated to gallstone disease. The prevalence increased with age. In the oldest age category (70 to 79 years) 16% of the men and 40% of the women had gallstone disease. The proportion of subjects with gallstone disease who had undergone cholecystectomy was 39% in men and 50% in women. The prevalence of gallstone disease in Maastricht lies on the lower side within the range of prevalences found in other West European countries.