Peter M. T. Pattynama

Reliable Noninvasive Coronary Angiography With Fast Submillimeter Multislice Spiral Computed Tomography

Background—Multislice spiral computed tomography (MSCT) is a promising technique for noninvasive coronary angiography, although clinical application has remained limited because of frequently incomplete interpretability, caused by motion artifacts and calcifications. Methods and Results—In 59 patients (53 male, aged 58±12 years) with suspected obstructive coronary artery disease, ECG-gated MSCT angiography was performed with a 16-slice MSCT scanner (0.42-s rotation time, 12×0.75-mm detector collimation). Thirty-four patients were given additional &bgr;-blockers (average heart rate: 56±6 min−1). After contrast injection, all data were acquired during an approximately 20-s breath hold. The left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA), including ≥2.0-mm side branches, were independently evaluated by two blinded observers and screened for ≥50% stenoses. The consensus reading was compared with quantitative coronary angiography. MSCT was successful in 58 patients. Eighty-six of the 231 evaluated branches were significantly diseased. Without exclusion of branches, the sensitivity, specificity and positive and negative predictive value to identify ≥50% obstructed branches was 95% (82/86), 86% (125/145), 80% (82/102), and 97% (125/129), respectively. The overall accuracy for the LM, LAD, RCA, and LCX was 100%, 91%, 86%, and 81%, respectively. No obstructed LM, LAD, or RCA branches remained undetected. Classification of patients as having no, single, or multivessel disease was accurate in 78% (45/58) of patients and no patients with significant obstructions were incorrectly excluded. Conclusions—Improvements in MSCT technology, combined with heart rate control, allow reliable noninvasive detection of obstructive coronary artery disease.

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2–24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.

Non-invasive coronary angiography with multislice spiral computed tomography: impact of heart rate

Objective: To evaluate the impact of heart rate on the diagnostic accuracy of coronary angiography by multislice spiral computed tomography (MSCT). Design: Prospective observational study. Patients: 78 patients who underwent both conventional and MSCT coronary angiography for suspicion of de novo coronary artery disease (n=53) or recurrent coronary artery disease after percutaneous intervention (n=25). Setting: Tertiary referral centre. Methods: Intravenously contrast enhanced MSCT coronary angiography was done during a single breath hold, and ECG synchronised images were reconstructed retrospectively. All coronary segments of ≥ 2.0 mm without stents were evaluated by two investigators and compared with quantitative coronary angiography. Patients were classified according to the average heart rate (mean (SD)) into three equally sized groups: group 1, 55.8 (4.1) beats/min; group 2, 66.6 (2.8) beats/min; group 3, 81.7 (8.8) beats/min. Results: Image quality was sufficient for analysis in 78% of the coronary segments in patients in group 1, 73% in group 2, and 54% in group 3 (p < 0.01). The sensitivity and specificity for detecting significant stenoses (≥ 50% lumen reduction) in these assessable segments were: 97% (95% confidence interval (CI) 84% to 100%) and 96% in group 1; 74% (52% to 89%) and 94% in group 2; and 67% (33% to 90%) and 94% in group 3 (p < 0.05). Accounting for all segments of ≥ 2.0 mm, including lesions in non-assessable segments as false negatives, the sensitivity decreased to 82% (28/34 lesions, 95% CI 69% to 91%), 61% (14/23 lesions, 42% to 77%), and 32% (6/19 lesions, 15% to 50%), respectively (p < 0.01). Conclusions: MSCT allows reliable coronary angiography in patients with low heart rates.

Receiver operating characteristic (ROC) analysis: Basic principles and applications in radiology

Receiver operating characteristic (ROC) analysis is a widely accepted method for analyzing and comparing the diagnostic accuracy of radiological tests. In this paper we will explain the basic principles underlying ROC analysis and provide practical information on the use and interpretation of ROC curves. The major applications of ROC analysis will be discussed and their limitations will be addressed.

Single-Detector Helical Computed Tomography as the Primary Diagnostic Test in Suspected Pulmonary Embolism: A Multicenter Clinical Management Study of 510 Patients

Context One strategy for diagnosing pulmonary embolism is helical computed tomography (CT) of the pulmonary arteries followed by compression ultrasonography of the leg veins if the CT scan shows no embolism and no clear alternative diagnosis. Contribution This prospective study of 510 patients with clinically suspected pulmonary embolism found that one third of the CT scans that were negative for emboli identified alternative diagnoses. Only 2 of the 248 patients with negative CT scans and no alternative diagnoses had positive results on venous compression ultrasonography. 376 patients had no evidence of emboli on CT scans and did not receive anticoagulant therapy; 2 had documented thromboembolism during 3 months of follow-up. Implications Helical CT alone misses few clinically important pulmonary embolisms. The Editors The clinical diagnosis of pulmonary embolism is difficult because the symptoms are nonspecific. Therefore, objective diagnostic imaging is needed in all patients. Helical computed tomography (CT) of the pulmonary arteries is rapidly gaining acceptance as a diagnostic test for suspected pulmonary embolism. Helical CT is a relatively noninvasive procedure that can be used to diagnose pulmonary embolism by directly imaging the intravascular clot. Since the initial report on helical CT in suspected pulmonary embolism almost a decade ago (1), numerous validation studies have evaluated the accuracy of helical CT; overall sensitivities range from 64% to 100% and specificities range from 89% to 100% (2-4). It has become evident that helical CT cannot identify all patients with pulmonary embolism because it may miss clots confined to the subsegmental pulmonary artery branches. An advantage of helical CT is that it can provide an alternative diagnosis to explain the patients signs and symptoms. This is relevant because pulmonary embolism is not confirmed in two thirds of the patients in whom it was clinically suspected. From theoretical cost-effectiveness analyses, an optimal diagnostic strategy would combine helical CT with compression ultrasonography to detect venous thromboembolism (5). However, these analyses have not been validated by prospective clinical management studies in consecutive patients with suspected pulmonary embolism (5, 6). We performed a prospective outcome study in consecutive patients with suspected pulmonary embolism to evaluate a simple, relatively noninvasive diagnostic algorithm consisting of single-detector helical CT followed by serial venous compression ultrasonography of the veins in the lower limbs. Methods Study Design Three institutions in the Netherlands (Leiden University Medical Center, Leiden; Utrecht Medical Center, Utrecht; and Leyenburg Hospital, The Hague) participated in this clinical management study, which was part of the Advances in New Technologies Evaluating the Localisation of Pulmonary Embolism (ANTELOPE) multicenter initiative. The Ethics Committees of the participating centers approved the study protocol. The Figure shows the diagnostic strategy of the study. All included patients underwent helical CT of the pulmonary arteries within 24 hours after they presented with signs and symptoms of pulmonary embolism. Anticoagulant therapy was started when the CT scan showed pulmonary embolism. When results of CT were negative for pulmonary embolism but identified a clear alternative diagnosis that explained the patients clinical signs and symptoms, pulmonary embolism was considered absent and anticoagulant treatment was not started. A normal or inconclusive CT scan that did not show an alternative diagnosis was followed by compression ultrasonography on day 1. If findings on this first compression ultrasonography examination were normal, the study was repeated on days 4 and 7. The finding of deep venous thrombosis (DVT) on serial compression ultrasonography established a classifying diagnosis of pulmonary embolism, and anticoagulant treatment was started. In patients with normal results on serial compression ultrasonography, pulmonary embolism was considered absent and anticoagulant treatment was not started. No anticoagulant treatment was given during the diagnostic work-up. To assess the safety of the diagnostic strategy, patients were followed for 3 months. Figure. Outcomes at initial presentation and at 12 weeks in 512 patients with clinically suspected pulmonary embolism. CT = computed tomography; DVT = deep venous thrombosis. Patients All consecutive inpatients and outpatients who presented with clinically suspected pulmonary embolism in one of the three participating centers between April 1999 and May 2000 were eligible for study enrollment (Table 1). All patients were seen by the physician on call either at the emergency or outpatient department (approximately half were seen by pulmonary physicians and half by internists). Pulmonary embolism was suspected in patients with sudden onset of unexplained dyspnea; sudden deterioration of chronic obstructive lung disease; pleuritic chest pain exaggerated by breathing; and, occasionally, hemoptysis. The preceding signs and symptoms were sometimes seen in combination with known risk factors for venous thromboembolism. We excluded patients from the study if they had undergone objective diagnostic testing for pulmonary embolism or DVT during the week preceding screening for inclusion in the study or if they had received anticoagulant therapy or heparin for more than 24 hours before being evaluated for inclusion in the study. Additional exclusion criteria were age younger than 18 years, pregnancy, or failure to obtain written informed consent. Table 1. Patients Screened for the Advances in New Technologies Evaluating the Localisation of Pulmonary Embolism (ANTELOPE) Study (Part II) Three-Month Follow-up During follow-up, all patients received routine clinical care from their physicians. We instructed patients to report to the physician or to the local study coordinator immediately if they experienced signs or symptoms that suggested pulmonary embolism (dyspnea or pain on respiration) or DVT (swelling or pain in the legs). When in doubt, the study coordinator was always available for consultation. If venous thromboembolism was suspected, we used compression ultrasonography or phlebography in patients with suspected DVT and used pulmonary angiography in patients with suspected pulmonary embolism. These diagnostic tests have negative predictive values for excluding DVT and pulmonary embolism of greater than 98% (7-10). After 6 weeks and at the end of the 3-month follow-up period, the study coordinator saw all patients to assess the incidence of venous thromboembolism by completing standardized checklists. All relevant data were recorded on six separate forms that were part of the case record form; the forms provided information on contacts, diagnosis, admission, hemorrhage, mortality, and follow-up. Adjudication Recurring symptoms, deaths during the study, and deaths during follow-up were recorded and adjudicated by an independent adjudication committee, which was unaware of the diagnostic test outcomes and patient status. On the basis of the diagnostic and laboratory tests that were performed, the committee decided whether recurring symptoms were caused by venous thromboembolism or whether death could be attributed to venous thromboembolism, hemorrhage, or an unrelated cause. Hemorrhage was defined as major when bleeding required transfusion or the source of bleeding was located retroperitoneally or intracranially. Imaging Studies We used only single-detector helical CT scanners in this study. A 5-mm-per-second table feed was used to scan a 16-cm volume in the caudocranial direction from the top of the diaphragm to a level slightly above the aortic arch; a 5-mm collimation and a pitch of 1 (120 kV, 210 mA) was used. Imaging was delayed for 15 to 20 seconds after the start of the intravenous injection of contrast medium. The dose rate and total iodine dose were standardized. High creatinine serum values were not a contraindication for administering contrast medium. We took special measures, such as hydration and dialysis, to ensure patient safety. Imaging was done during a 32-second single breath hold. In patients who could not suspend respiration (very dyspneic patients), scanning was done during shallow, gentle respiration. Images were reconstructed at 2-mm intervals. We performed gray-scale compression ultrasonography by using a 7.5- to 10-MHz, phased-array linear probe at the level of the common femoral and popliteal veins (11). Deep venous thrombosis was diagnosed when the vein could not be compressed or a clear thrombus mass could be seen in the vein. No attempts were made to image the venous trajectory between these two levels or the calf veins; a two-point compression ultrasonography examination (venous compression examined at the groin and knee level) is similar in accuracy to more extensive examination of venous compressibility along the entire length of the common femoral vein until the trifurcation of the deep calf veins (12). CT Image Analysis Experienced CT radiologists read the scans on a monitor that allowed cine mode viewing (scrolling) at a standard mediastinal window (window width, 350 HU; window level, 50 HU) and lung window (window width, 1500 HU; window level, 500 HU) setting. Previous study results show no difference in the reliability of experienced CT radiologists (13). Overlapping images (now reconstructed every 3 mm) were also printed on hard-copy film at the two standard settings. Dual readings were not routinely performed because of the study design (a clinical management study). We used previously described criteria (1) to detect pulmonary embolism by CT. The quality of the CT scans was recorded in the case record form (filling of the pulmonary vessels, contrast enhancement, motion artifacts, and general readability). A CT scan was considered to be inconclusive if opacification of vess

Reproducibility of MRI-derived measurements of right ventricular volumes and myocardial mass

Magnetic resonance (MR) imaging has been shown to provide accurate measurements of right ventricular (RV) volumes and myocardial mass. The purpose of this study was to evaluate the reproducibility of MR imaging, which in clinical practice may be as important as its absolute accuracy. The reproducibility of MR imaging measurements of the right ventricle was assessed by analyzing 40 serial functional MR imaging examinations of the right ventricle with variance component analysis. Standard deviations and 95% ranges for change were: for RV myocardial mass, 5.9 and 16 g; and for RV ejection fraction, 6.0% and 16%, respectively. Reproducibility was similar for cine and spin-echo MR imaging. The intraobserver and interobserver errors were especially large, indicating that observer subjectivity is the limiting factor in the interpretation of the MR images. This study suggests that the reproducibility of RV measurements is adequate to detect RV hypertrophy and a low ejection fraction in the individual patient. For accurate follow-up examinations, whereby smaller changes are to be detected, the reproducibility of MR imaging measurements may not be sufficient. More effort is needed to improve the reproducibility of MR imaging measurements.

Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: Clinical outcome

PURPOSE To report the clinical outcome of treatment using real-time tumor tracking for 70 patients with inoperable stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Seventy inoperable patients with peripherally located early-stage NSCLC were treated with 45 or 60 Gy in three fractions using CyberKnife. Pathology was available in 51% of patients. Thirty-nine patients had a T1-tumor and 31 had a T2-tumor. Markers were placed using the vascular, percutaneous intra-, or extra-pulmonary approach, depending on the risk of pneumothorax. RESULTS The actuarial 2-year local control rate for patients treated with 60 Gy was 96%, compared to 78% for patients treated with a total dose of 45 Gy (p=0.197). All local recurrences (n=4) occurred in patients with T2-tumors. Overall survival for the whole group at two years was 62% and the cause specific survival was 85%. The median follow-up was 15 months. Grade 3 toxicity occurred in two patients (3%) after marker placement. Treatment-related late grade 3 toxicity occurred in 7 patients (10%). No grade > or = 4 toxicity occurred. CONCLUSION Excellent local control of 96% at 1- and 2-years was achieved using 60 Gy in three fractions for NSCLC patients treated with the real-time tumor tracking. Toxicity was low.

Evaluation of cardiac function with magnetic resonance imaging

A large body of evidence has accumulated to substantiate the accuracy of functional MR measurements of both ventricles. Because of good accuracy and superior reproducibility, MR imaging may be considered the gold standard for in vivo quantification of left and right ventricular ejection fraction, myocardial mass, and wall stress. New prospects for functional MR imaging include determination of the end-systolic volume-pressure relation as an index of myocardial contractility. The ability of MR imaging to detect wall motion disturbances may be enhanced further by combining myocardial tagging techniques with finite element analysis. Conventional MR imaging is limited by long examination times, but recent ultrafast modifications of echo-planar imaging allow completion of a functional heart study within seconds. Implementation of ultrafast MR imaging will greatly increase the usefulness of MR imaging for routine evaluation of cardiac function.

Can helical CT replace scintigraphy in the diagnostic process in suspected pulmonary embolism? A retrolective-prolective cohort study focusing on total diagnostic yield

Abstract. The aim of our study was to compare the diagnostic value of helical CT vs that of ventilation–perfusion (V/Q) scintigraphy as a first-line test in a diagnostic strategy in patients suspected of pulmonary embolism (PE). In a retrolective–prolective cohort study we tested the accuracy of helical CT vs V/Q scintigraphy in 123 patients suspected of PE. A diagnostic panel was asked to formulate the presumptive diagnosis on the presence or absence of PE, or of alternative disease by using two competing diagnostic strategies. These consisted of the patient history, laboratory tests and chest X-ray (together baseline tests) in combination with either helical CT or V/Q scintigraphy (CT strategy and V/Q strategy, respectively). The results were compared with the final diagnosis in each patient that was established from various reference tests (which included V/Q scintigraphy, pulmonary angiography and clinical follow-up). The CT and V/Q strategies were compared with regard to the accuracy for PE, for alternative diseases and with regard to the proportion of conclusive diagnoses that were made. The CT strategy was more accurate than the V/Q strategy for detecting or excluding PE. Sensitivity and specificity were 49 and 74 % for the V/Q strategy and 75 and 90 % for the CT strategy, respectively (P = 0.01). The CT strategy provided a conclusive diagnosis in a significantly larger proportion of patients than the V/Q strategy, 92 vs 72 % (P < 0.001). The CT strategy detected more alternative diagnosis than the V/Q strategy, 93 vs 51 %, respectively (P < 0.001). Helical CT seems more useful than V/Q scintigraphy as a first-line test in patients suspected of PE.

Intermittent Claudication: Clinical Effectiveness of Endovascular Revascularization versus Supervised Hospital-based Exercise Training—Randomized Controlled Trial

PURPOSE To compare clinical success, functional capacity, and quality of life during 12 months after revascularization or supervised exercise training in patients with intermittent claudication. MATERIALS AND METHODS This study had institutional review board approval, and all patients gave written informed consent. Between September 2002 and September 2005, 151 consecutive patients who presented with symptoms of intermittent claudication were randomly assigned to undergo either endovascular revascularization (angioplasty-first approach) (n = 76) or hospital-based supervised exercise (n = 75). The outcome measures were clinical success, functional capacity, and quality of life after 6 and 12 months. Clinical success was defined as improvement in at least one category in the Rutherford scale above the pretreatment level. Significance of differences between the groups was assessed with the unpaired t test, chi(2) test, or Mann-Whitney U test. To adjust outcomes for imbalances of baseline values, multivariable regression analysis was performed. RESULTS Immediately after the start of treatment, patients who underwent revascularization improved more than patients who performed exercise in terms of clinical success (adjusted odds ratio [OR], 39; 99% confidence interval [CI]: 11, 131; P < .001), but this advantage was lost after 6 (adjusted OR, 0.9; 99% CI: 0.3, 2.3; P = .70) and 12 (adjusted OR, 1.1; 99% CI: 0.5, 2.8; P = .73) months. After revascularization, fewer patients showed signs of ipsilateral symptoms at 6 months compared with patients in the exercise group (adjusted OR, 0.4; 99% CI: 0.2, 0.9; P < .001), but no significant differences were demonstrated at 12 months. After both treatments, functional capacity and quality of life scores increased after 6 and 12 months, but no significant differences between the groups were demonstrated. CONCLUSION After 6 and 12 months, patients with intermittent claudication benefited equally from either endovascular revascularization or supervised exercise. Improvement was, however, more immediate after revascularization.