Ibrahim Danad

Hybrid Imaging Using Quantitative H215O PET and CT-Based Coronary Angiography for the Detection of Coronary Artery Disease

Hybrid imaging using PET in conjunction with CT-based coronary angiography (PET/CTCA) enables near-simultaneous quantification of myocardial blood flow (MBF) and anatomical evaluation of coronary arteries. CTCA is an excellent imaging modality to rule out obstructive coronary artery disease (CAD), but functional assessment is warranted in the presence of a CTCA-observed stenosis because the specificity of CTCA is relatively low. Quantitative H215O PET/CTCA may yield complementary information and enhance diagnostic accuracy. The purpose of this study was to evaluate the diagnostic accuracy of quantitative H215O PET/CTCA in a clinical cohort of patients with suspected CAD who underwent both cardiac H215O PET/CTCA and invasive coronary angiography (ICA). In addition, this study aimed to evaluate and compare the accuracy of hyperemic MBF versus coronary flow reserve (CFR). Methods: Patients (n = 120; mean age ± SD, 61 ± 10 y; 77 men and 43 women) with a predominantly intermediate pretest likelihood for CAD underwent both quantitative H215O PET/CTCA and ICA. A ≥50% stenosis at ICA or a fractional flow reserve ≤ 0.80 was considered significant. Results: Obstructive CAD was diagnosed in 49 of 120 patients (41%). The diagnostic accuracy of hyperemic MBF was significantly higher than CFR (80% vs. 68%, respectively, P = 0.02), with optimal cutoff values of 1.86 mL/min/g and 2.30, respectively. On a per-patient basis, the sensitivity, specificity, negative predictive value, and positive predictive value of CTCA were 100%, 34%, 100%, and 51%, respectively, as compared with 76%, 83%, 83%, and 76%, respectively, for quantitative hyperemic MBF PET. Quantitative H215O PET/CTCA reduced the number of false-positive CTCA studies from 47 to 6, although 12 of 49 true-positive CTCAs were incorrectly reclassified as false-negative hybrid scans on the basis of (presumably) sufficient hyperemic MBF. Compared with CTCA (61%) or H215O PET (80%) alone (both P < 0.05), the hybrid approach significantly improved diagnostic accuracy (85%). Conclusion: The diagnostic accuracy of quantitative H215O PET/CTCA is superior to either H215O PET or CTCA alone for the detection of clinically significant CAD. Hyperemic MBF was more accurate than CFR, implying that a single measurement of MBF in diagnostic protocols may suffice.

Diagnostic accuracy of quantitative H215O PET measurements of hyperemic myocardial blood flow versus coronary flow reserve for the detection of obstructive coronary artery disease

Triple-negative breast cancer, an aggressive subtype, represents 15% of invasive breast tumors. This prospective study investigated whether early changes in 18F-FDG tumor uptake during neoadjuvant chemotherapy (NAC) can predict outcomes. Methods: Twenty (M0) patients underwent 18F-FDG PET/CT at baseline and after the second cycle. NAC was continued irrespective of PET results. Results: At surgery, 6 patients had a pathologic complete response, whereas 14 had residual tumor. Four patients showed early relapse (in the 2 y after surgery). There were 11 metabolic responders and 9 nonresponders using a 42% decrease in maximum standardized uptake value as a cutoff. In nonresponding patients, the risk of residual tumor at surgery was 100% (vs. 45% in responders; P = 0.014), and the risk of early relapse was 44% (vs. 0%; P = 0.024). Conclusion: A less than 42% decrease in 18F-FDG uptake at 2 cycles means residual tumor at the end of NAC and a high risk of early relapse.

New Applications of Cardiac Computed Tomography: Dual-Energy, Spectral, and Molecular CT Imaging.

Computed tomography (CT) has evolved into a powerful diagnostic tool, and it is impossible to imagine current clinical practice without CT imaging. Because of its widespread availability, ease of clinical application, superb sensitivity for the detection of coronary artery disease, and noninvasive nature, CT has become a valuable tool within the armamentarium of cardiologists. In the past few years, numerous technological advances in CT have occurred, including dual-energy CT, spectral CT, and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging tool that permits accurate plaque characterization, assessment of myocardial perfusion, and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging.

Coronary pressure and flow relationships in humans: phasic analysis of normal and pathological vessels and the implications for stenosis assessment: a report from the Iberian-Dutch-English (IDEAL) collaborators

Abstract Background Our understanding of human coronary physiological behaviour is derived from animal models. We sought to describe physiological behaviour across a large collection of invasive pressure and flow velocity measurements, to provide a better understanding of the relationships between these physiological parameters and to evaluate the rationale for resting stenosis assessment. Methods and results Five hundred and sixty-seven simultaneous intracoronary pressure and flow velocity assessments from 301 patients were analysed for coronary flow velocity, trans-stenotic pressure gradient (TG), and microvascular resistance (MVR). Measurements were made during baseline and hyperaemic conditions. The whole cardiac cycle and the diastolic wave-free period were assessed. Stenoses were assessed according to fractional flow reserve (FFR) and quantitative coronary angiography DS%. With progressive worsening of stenoses, from unobstructed angiographic normal vessels to those with FFR ≤ 0.50, hyperaemic flow falls significantly from 45 to 19 cm/s, Ptrend < 0.001 in a curvilinear pattern. Resting flow was unaffected by stenosis severity and was consistent across all strata of stenosis ( Ptrend > 0.05 for all). Trans-stenotic pressure gradient rose with stenosis severity for both rest and hyperaemic measures ( Ptrend < 0.001 for both). Microvascular resistance declines with stenosis severity under resting conditions ( Ptrend < 0.001), but was unchanged at hyperaemia (2.3 ± 1.1 mmHg/cm/s; Ptrend = 0.19). Conclusions With progressive stenosis severity, TG rises. However, while hyperaemic flow falls significantly, resting coronary flow is maintained by compensatory reduction of MVR, demonstrating coronary auto-regulation. These data support the translation of coronary physiological concepts derived from animals to patients with coronary artery disease and furthermore, suggest that resting pressure indices can be used to detect the haemodynamic significance of coronary artery stenoses.

Impact of anatomical and functional severity of coronary atherosclerotic plaques on the transmural perfusion gradient: a [15O]H2O PET study.

BACKGROUND Myocardial ischaemia occurs principally in the subendocardial layer, whereas conventional myocardial perfusion imaging provides no information on the transmural myocardial blood flow (MBF) distribution. Subendocardial perfusion measurements and quantification of the transmural perfusion gradient (TPG) could be more sensitive and specific for the detection of coronary artery disease (CAD). The current study aimed to determine the impact of lesion severity as assessed by the fractional flow reserve (FFR) on subendocardial perfusion and the TPG using [(15)O]H2O positron emission tomography (PET) imaging in patients evaluated for CAD. METHODS AND RESULTS Sixty-six patients with anginal chest pain were prospectively enrolled and underwent [(15)O]H2O myocardial perfusion PET imaging. Subsequently, invasive coronary angiography was performed and FFR obtained in all coronary arteries irrespective of the PET imaging results. Thirty (45%) patients were diagnosed with significant CAD (i.e. FFR ≤0.80), whereas on a per vessel analysis (n = 198), 53 (27%) displayed a positive FFR. Transmural hyperaemic MBF decreased significantly from 3.09 ± 1.16 to 1.67 ± 0.57 mL min(-1) g(-1) (P < 0.001) in non-ischaemic and ischaemic myocardium, respectively. The TPG decreased during hyperaemia when compared with baseline (1.20 ± 0.14 vs. 0.94 ± 0.17, P < 0.001), and was lower in arteries with a positive FFR (0.97 ± 0.16 vs. 0.88 ± 0.18, P < 0.01). A TPG threshold of 0.94 yielded an accuracy to detect CAD of 59%, which was inferior to transmural MBF with an optimal cutoff of 2.20 mL min(-1) g(-1) and an accuracy of 85% (P < 0.001). Diagnostic accuracy of subendocardial perfusion measurements was comparable with transmural MBF (83 vs. 85%, respectively, P = NS). CONCLUSION Cardiac [(15)O]H2O PET imaging is able to distinguish subendocardial from subepicardial perfusion in the myocardium of normal dimensions. Hyperaemic TPG is significantly lower in ischaemic myocardium. This technique can potentially be employed to study subendocardial perfusion impairment in more detail. However, the diagnostic accuracy of subendocardial hyperaemic perfusion and TPG appears to be limited compared with quantitative transmural MBF, warranting further study.

Diagnosing coronary artery disease with hybrid PET/CT: It takes two to tango

The noninvasive diagnosis of coronary artery disease (CAD) is a challenging task. Although a large armamentarium of imaging modalities is available to evaluate the functional consequences of the extent and severity of CAD, cardiac perfusion positron emission tomography (PET) is considered the gold standard for this purpose. Alternatively, noninvasive anatomical imaging of coronary atherosclerosis with coronary computed tomography angiography (CCTA) has recently been successfully implemented in clinical practice. Although each of these diagnostic approaches has its own merits and caveats, functional and morphological imaging techniques provide fundamentally different insights into the disease process and should be considered to be complementary rather than overlapping. Hybrid imaging with PET/CT offers the possibility to evaluate both aspects nearly simultaneously, and studies have demonstrated that such a comprehensive assessment results in superior diagnostic accuracy, better prognostication, and helps in guiding clinical patient management. The aim of this review is to discuss the value of stand-alone CCTA and PET in CAD, and to summarize the available data on the surplus value of hybrid PET/CT including its strengths and limitations.

Cardiac filling volumes versus pressures for predicting fluid responsiveness after cardiovascular surgery: the role of systolic cardiac function

IntroductionStatic cardiac filling volumes have been suggested to better predict fluid responsiveness than filling pressures, but this may not apply to hearts with systolic dysfunction and dilatation. We evaluated the relative value of cardiac filling volume and pressures for predicting and monitoring fluid responsiveness, according to systolic cardiac function, estimated by global ejection fraction (GEF, normal 25 to 35%) from transpulmonary thermodilution.MethodsWe studied hypovolemic, mechanically ventilated patients after coronary (n = 18) or major vascular (n = 14) surgery in the intensive care unit. We evaluated 96 colloid fluid loading events (200 to 600 mL given in three consecutive 30-minute intervals, guided by increases in filling pressures), divided into groups of responding events (fluid responsiveness) and non-responding events, in patients with low GEF (<20%) or near-normal GEF (≥20%). Patients were monitored by transpulmonary dilution and central venous (n = 9)/pulmonary artery (n = 23) catheters to obtain cardiac index (CI), global end-diastolic volume index (GEDVI), central venous (CVP) and pulmonary artery occlusion pressure (PAOP).ResultsFluid responsiveness occurred in 8 (≥15% increase in CI) and 17 (≥10% increase in CI) of 36 fluid loading events when GEF was <20%, and 7 (≥15% increase in CI) and 17 (≥10% increase in CI) of 60 fluid loading events when GEF was ≥20%. Whereas a low baseline GEDVI predicted fluid responsiveness particularly when GEF was ≥20% (P = 0.002 or lower), a low PAOP was of predictive value particularly when GEF was <20% (P = 0.004 or lower). The baseline CVP was lower in responding events regardless of GEF. Changes in CVP and PAOP paralleled changes in CI particularly when GEF was <20%, whereas changes in GEDVI paralleled CI regardless of GEF.ConclusionsRegardless of GEF, CVP may be useful for predicting fluid responsiveness in patients after coronary and major vascular surgery provided that positive end-expiratory pressure is low. When GEF is low (<20%), PAOP is more useful than GEDVI for predicting fluid responsiveness, but when GEF is near-normal (≥20%) GEDVI is more useful than PAOP. This favors predicting and monitoring fluid responsiveness by pulmonary artery catheter-derived filling pressures in surgical patients with systolic left ventricular dysfunction and by transpulmonary thermodilution-derived GEDVI when systolic left ventricular function is relatively normal.

Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve

Importance At present, the choice of noninvasive testing for a diagnosis of significant coronary artery disease (CAD) is ambiguous, but nuclear myocardial perfusion imaging with single-photon emission tomography (SPECT) or positron emission tomography (PET) and coronary computed tomography angiography (CCTA) is predominantly used for this purpose. However, to date, prospective head-to-head studies are lacking regarding the diagnostic accuracy of these imaging modalities. Furthermore, the combination of anatomical and functional assessments configuring a hybrid approach may yield improved accuracy. Objectives To establish the diagnostic accuracy of CCTA, SPECT, and PET and explore the incremental value of hybrid imaging compared with fractional flow reserve. Design, Setting, and Participants A prospective clinical study involving 208 patients with suspected CAD who underwent CCTA, technetium 99m/tetrofosmin–labeled SPECT, and [15O]H2O PET with examination of all coronary arteries by fractional flow reserve was performed from January 23, 2012, to October 25, 2014. Scans were interpreted by core laboratories on an intention-to-diagnose basis. Hybrid images were generated in case of abnormal noninvasive anatomical or functional test results. Main Outcomes and Measures Hemodynamically significant stenosis in at least 1 coronary artery as indicated by a fractional flow reserve of 0.80 or less and relative diagnostic accuracy of SPECT, PET, and CCTA in detecting hemodynamically significant CAD. Results Of the 208 patients in the study (76 women and 132 men; mean [SD] age, 58 [9] years), 92 (44.2%) had significant CAD (fractional flow reserve ⩽0.80). Sensitivity was 90% (95% CI, 82%-95%) for CCTA, 57% (95% CI, 46%-67%) for SPECT, and 87% (95% CI, 78%-93%) for PET, whereas specificity was 60% (95% CI, 51%-69%) for CCTA, 94% (95% CI, 88%-98%) for SPECT, and 84% (95% CI, 75%-89%) for PET. Single-photon emission tomography was found to be noninferior to PET in terms of specificity (P < .001) but not in terms of sensitivity (P > .99) using the predefined absolute margin of 10%. Diagnostic accuracy was highest for PET (85%; 95% CI, 80%-90%) compared with that of CCTA (74%; 95% CI, 67%-79%; P = .003) and SPECT (77%; 95% CI, 71%-83%; P = .02). Diagnostic accuracy was not enhanced by either hybrid SPECT and CCTA (76%; 95% CI, 70%-82%; P = .75) or by PET and CCTA (84%; 95% CI, 79%-89%; P = .82), but resulted in an increase in specificity (P = .004) at the cost of a decrease in sensitivity (P = .001). Conclusions and Relevance This controlled clinical head-to-head comparative study revealed PET to exhibit the highest accuracy for diagnosis of myocardial ischemia. Furthermore, a combined anatomical and functional assessment does not add incremental diagnostic value but guides clinical decision-making in an unsalutary fashion.

Doppler-Derived Intracoronary Physiology Indices Predict the Occurrence of Microvascular Injury and Microvascular Perfusion Deficits After Angiographically Successful Primary Percutaneous Coronary Intervention

Background—A total of 40% to 50% of patients with ST-segment–elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Methods and Results—Sixty patients with ST-segment–elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure–flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure–velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H215O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H215O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure–velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). Conclusions—Doppler-flow–derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. Clinical Trial Registration—URL: http://www.trialregister.nl. Unique identifier: NTR3164.

Static and dynamic assessment of myocardial perfusion by computed tomography

Recent developments in computed tomography (CT) technology have fulfilled the prerequisites for the clinical application of myocardial CT perfusion (CTP) imaging. The evaluation of myocardial perfusion by CT can be achieved by static or dynamic scan acquisitions. Although both approaches have proved clinically feasible, substantial barriers need to be overcome before its routine clinical application. The current review provides an outline of the current status of CTP imaging and also focuses on disparities between static and dynamic CTPs for the evaluation of myocardial blood flow.