Narinder Paul

Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study

AIMSnTo evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT).nnnMETHODS AND RESULTSnWe conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels.nnnCONCLUSIONSnThe combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

The Absence of Coronary Calcification Does Not Exclude Obstructive Coronary Artery Disease or the Need for Revascularization in Patients Referred for Conventional Coronary Angiography

OBJECTIVESnThis study was designed to evaluate whether the absence of coronary calcium could rule out >or=50% coronary stenosis or the need for revascularization.nnnBACKGROUNDnThe latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients.nnnMETHODSnA substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before.nnnRESULTSnIn all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 +/- 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of >or=50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 >or=50% stenosis. The overall sensitivity for CS = 0 to predict the absence of >or=50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with >or=50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium.nnnCONCLUSIONSnThe absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification. (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors [CORE-64]; NCT00738218).

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective “CORE-64” trial (“Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors”). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Prevalence of “silent” pulmonary emboli in adults after the Fontan operation ☆

OBJECTIVESnThe study was done to determine the prevalence of pulmonary emboli (PE) in asymptomatic adult Fontan patients and to identify the risk factors associated with PE.nnnBACKGROUNDnRight atrial thrombi and systemic thromboembolic complications have been reported after the Fontan procedure. However, the frequency of silent PE in this patient population is not known.nnnMETHODSnAll consecutive adult Fontan patients attending the adult congenital clinic over a six-month period underwent ventilation-perfusion (VQ) scanning and blood testing for thrombophilia tendency. If the VQ scan showed an intermediate or high probability for PE, a computerized tomography (CT) pulmonary angiogram was performed to confirm the presence of PE.nnnRESULTSnThirty patients (mean age 26 +/- 7 years, 57% men) were included in this study. Five (17%) adult Fontan patients had an intermediate or high probability for PE on VQ scan, all of which were confirmed on CT pulmonary angiography. No patient had a thrombophilia tendency. Pulmonary emboli were not present in any patients (30%) taking warfarin. Late age at time of Fontan operation (19 +/- 6 years vs. 11 +/- 6 years, p = 0.012) and type of Fontan anatomy (p = 0.001) were associated with increased risk of silent PE.nnnCONCLUSIONSnSeventeen percent of adult patients with Fontan procedure have clinically silent PE. The long-term hemodynamic implications of this with respect to Fontan attrition over time are unknown. Large randomized prospective studies looking at anticoagulation therapy in all Fontan patients are urgently needed.

Diagnostic accuracy of computed tomography coronary angiography according to pre-test probability of coronary artery disease and severity of coronary arterial calcification: The CORE-64 (Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography) international multicenter study

OBJECTIVESnThe purpose of this study was to assess the impact of patient population characteristics on accuracy by computed tomography angiography (CTA) to detect obstructive coronary artery disease (CAD).nnnBACKGROUNDnThe ability of CTA to exclude obstructive CAD in patients of different pre-test probabilities and in presence of coronary calcification remains uncertain.nnnMETHODSnFor the CORE-64 (Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography) study, 371 patients underwent CTA and cardiac catheterization for the detection of obstructive CAD, defined as ≥50% luminal stenosis by quantitative coronary angiography (QCA). This analysis includes 80 initially excluded patients with a calcium score ≥600. Area under the receiver-operating characteristic curve (AUC) was used to evaluate CTA diagnostic accuracy compared to QCA in patients according to calcium score and pre-test probability of CAD.nnnRESULTSnAnalysis of patient-based quantitative CTA accuracy revealed an AUC of 0.93 (95% confidence interval [CI]: 0.90 to 0.95). The AUC remained 0.93 (95% CI: 0.90 to 0.96) after excluding patients with known CAD but decreased to 0.81 (95% CI: 0.71 to 0.89) in patients with calcium score ≥600 (p = 0.077). While AUCs were similar (0.93, 0.92, and 0.93, respectively) for patients with intermediate, high pre-test probability for CAD, and known CAD, negative predictive values were different: 0.90, 0.83, and 0.50, respectively. Negative predictive values decreased from 0.93 to 0.75 for patients with calcium score <100 or ≥100, respectively (p = 0.053).nnnCONCLUSIONSnBoth pre-test probability for CAD and coronary calcium scoring should be considered before using CTA for excluding obstructive CAD. For that purpose, CTA is less effective in patients with calcium score ≥600 and in patients with a high pre-test probability for obstructive CAD.

Diagnostic performance of combined noninvasive coronary angiography and myocardial perfusion imaging using 320 row detector computed tomography: design and implementation of the CORE320 multicenter, multinational diagnostic study

Multidetector coronary computed tomography angiography (CTA) is a promising modality for widespread clinical application because of its noninvasive nature and high diagnostic accuracy as found in previous studies using 64 to 320 simultaneous detector rows. It is, however, limited in its ability to detect myocardial ischemia. In this article, we describe the design of the CORE320 study (Combined coronary atherosclerosis and myocardial perfusion evaluation using 320 detector row computed tomography). This prospective, multicenter, multinational study is unique in that it is designed to assess the diagnostic performance of combined 320-row CTA and myocardial CT perfusion imaging (CTP) in comparison with the combination of invasive coronary angiography and single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The trial is being performed at 16 medical centers located in 8 countries worldwide. CT has the potential to assess both anatomy and physiology in a single imaging session. The co-primary aim of the CORE320 study is to define the per-patient diagnostic accuracy of the combination of coronary CTA and myocardial CTP to detect physiologically significant coronary artery disease compared with (1) the combination of conventional coronary angiography and SPECT-MPI and (2) conventional coronary angiography alone. If successful, the technology could revolutionize the management of patients with symptomatic CAD.

Optimization of image acquisition techniques for dual-energy imaging of the chest

Experimental and theoretical studies were conducted to determine optimal acquisition techniques for a prototype dual-energy (DE) chest imaging system. Technique factors investigated included the selection of added x-ray filtration, kVp pair, and the allocation of dose between low- and high-energy projections, with total dose equal to or less than that of a conventional chest radiograph. Optima were computed to maximize lung nodule detectability as characterized by the signal-difference-to-noise ratio (SDNR) in DE chest images. Optimal beam filtration was determined by cascaded systems analysis of DE image SDNR for filter selections across the periodic table (Z(filter) = 1-92), demonstrating the importance of differential filtration between low- and high-kVp projections and suggesting optimal high-kVp filters in the range Z(filter) = 25-50. For example, added filtration of approximately 2.1 mm Cu, approximately 1.2 mm Zr, approximately 0.7 mm Mo, and approximately 0.6 mm Ag to the high-kVp beam provided optimal (and nearly equivalent) soft-tissue SDNR. Optimal kVp pair and dose allocation were investigated using a chest phantom presenting simulated lung nodules and ribs for thin, average, and thick body habitus. Low- and high-energy techniques ranged from 60-90 kVp and 120-150 kVp, respectively, with peak soft-tissue SDNR achieved at [60/120] kVp for all patient thicknesses and all levels of imaging dose. A strong dependence on the kVp of the low-energy projection was observed. Optimal allocation of dose between low- and high-energy projections was such that approximately 30% of the total dose was delivered by the low-kVp projection, exhibiting a fairly weak dependence on kVp pair and dose. The results have guided the implementation of a prototype DE imaging system for imaging trials in early-stage lung nodule detection and diagnosis.

Investigation of lung nodule detectability in low-dose 320-slice computed tomography.

Low-dose imaging protocols in chest CT are important in the screening and surveillance of suspicious and indeterminate lung nodules. Techniques that maintain nodule detectability yet permit dose reduction, particularly for large body habitus, were investigated. The objective of this study was to determine the extent to which radiation dose can be minimized while maintaining diagnostic performance through knowledgeable selection of reconstruction techniques. A 320-slice volumetric CT scanner (Aquilion ONE, Toshiba Medical Systems) was used to scan an anthropomorphic phantom at doses ranging from approximately 0.1 mGy up to that typical of low-dose CT (LDCT, approximately 5 mGy) and diagnostic CT (approximately 10 mGy). Radiation dose was measured via Farmer chamber and MOSFET dosimetry. The phantom presented simulated nodules of varying size and contrast within a heterogeneous background, and chest thickness was varied through addition of tissue-equivalent bolus about the chest. Detectability of a small solid lung nodule (3.2 mm diameter, -37 HU, typically the smallest nodule of clinical significance in screening and surveillance) was evaluated as a function of dose, patient size, reconstruction filter, and slice thickness by means of nine-alternative forced-choice (9AFC) observer tests to quantify nodule detectability. For a given reconstruction filter, nodule detectability decreased sharply below a threshold dose level due to increased image noise, especially for large body size. However, nodule detectability could be maintained at lower doses through knowledgeable selection of (smoother) reconstruction filters. For large body habitus, optimal filter selection reduced the dose required for nodule detection by up to a factor of approximately 3 (from approximately 3.3 mGy for sharp filters to approximately 1.0 mGy for the optimal filter). The results indicate that radiation dose can be reduced below the current low-dose (5 mGy) and ultralow-dose (1 mGy) levels with knowledgeable selection of reconstruction parameters. Image noise, not spatial resolution, was found to be the limiting factor in detection of small lung nodules. Therefore, the use of smoother reconstruction filters may permit lower-dose protocols without trade-off in diagnostic performance.

The reduction of image noise and streak artifact in the thoracic inlet during low dose and ultra-low dose thoracic CT.

Increased pixel noise and streak artifact reduce CT image quality and limit the potential for radiation dose reduction during CT of the thoracic inlet. We propose to quantify the pixel noise of mediastinal structures in the thoracic inlet, during low-dose (LDCT) and ultralow-dose (uLDCT) thoracic CT, and assess the utility of new software (quantum denoising system and BOOST3D) in addressing these limitations. Twelve patients had LDCT (120 kV, 25 mAs) and uLDCT (120 kV, 10 mAs) images reconstructed initially using standard mediastinal and lung filters followed by the quantum denoising system (QDS) to reduce pixel noise and BOOST3D (B3D) software to correct photon starvation noise as follows: group 1 no QDS, no B3D; group 2 B3D alone; group 3 QDS alone and group 4 both QDS and B3D. Nine regions of interest (ROIs) were replicated on mediastinal anatomy in the thoracic inlet, for each patient resulting in 3456 data points to calculate pixel noise and attenuation. QDS reduced pixel noise by 18.4% (lung images) and 15.8% (mediastinal images) at 25 mAs. B3D reduced pixel noise by approximately 8% in the posterior thorax and in combination there was a 35.5% reduction in effective radiation dose (E) for LDCT (1.63-1.05 mSv) in lung images and 32.2% (1.55-1.05 mSv) in mediastinal images. The same combination produced 20.7% reduction (0.53-0.42 mSv) in E for uLDCT, for lung images and 17.3% (0.51-0.42) for mediastinal images. This quantitative analysis of image quality confirms the utility of dedicated processing software in targeting image noise and streak artifact in thoracic LDCT and uLDCT images taken in the thoracic inlet. This processing software potentiates substantial reductions in radiation dose during thoracic LDCT and uLDCT.

Accuracy of Right and Left Ventricular Functional Assessment by Short-Axis vs Axial Cine Steady-State Free-Precession Magnetic Resonance Imaging: Intrapatient Correlation With Main Pulmonary Artery and Ascending Aorta Phase-Contrast Flow Measurements

Objective The left ventricle (LV) is routinely assessed with cardiac magnetic resonance imaging (MRI) by using short-axis orientation; it remains unclear whether the right ventricle (RV) can also be adequately assessed in this orientation or whether dedicated axial orientation is required. We used phase-contrast (PC) flow measurements in the main pulmonary artery (MPA) and the ascending aorta (Aorta) as nonvolumetric standard of reference and compared RV and LV volumes in short-axis and axial orientations. Methods A retrospective analysis identified 30 patients with cardiac MRI data sets. Patients underwent MRI (1.5 T or 3 T), with retrospectively gated cine steady-state free-precession in axial and short-axis orientations. PC flow analyses of MPA and Aorta were used as the reference measure of RV and LV output. Results There was a high linear correlation between MPA-PC flow and RV–stroke volume (SV) short axis (r = 0.9) and RV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 1.4 mL for RV axial and −2.3 mL for RV–short-axis vs MPA-PC flow. There was a high linear correlation between Aorta-PC flow and LV-SV short-axis (r = 0.9) and LV-SV axial (r = 0.9). Bland-Altman analysis revealed a mean offset of 4.8 m for LV short axis and 7.0 mL for LV axial vs Aorta-PC flow. There was no significant difference (P = .6) between short-axis–LV SV and short-axis–RV SV. Conclusion No significant impact of the slice acquisition orientation for determination of RV and LV stroke volumes was found. Therefore, cardiac magnetic resonance workflow does not need to be extended by an axial data set for patients without complex cardiac disease for assessment of biventricular function and volumes.