Time and event-specific deep learning for personalized risk assessment after cardiac perfusion imaging.

Standard clinical interpretation of myocardial perfusion imaging (MPI) has proven prognostic value for predicting major adverse cardiovascular events (MACE). However, personalizing predictions to a specific event type and time interval is more challenging. We demonstrate an explainable deep learning model that predicts the time-specific risk separately for all-cause death, acute coronary syndrome (ACS), and revascularization directly from MPI and 15 clinical features. We train and test the model internally using 10-fold hold-out cross-validation (n = 20,418) and externally validate it in three separate sites (n = 13,988) with MACE follow-ups for a median of 3.1 years (interquartile range [IQR]: 1.6, 3.6). We evaluate the model using the cumulative dynamic area under receiver operating curve (cAUC). The best model performance in the external cohort is observed for short-term prediction - in the first six months after the scan, mean cAUC for ACS and all-cause death reaches 0.76 (95% confidence interval [CI]: 0.75, 0.77) and 0.78 (95% CI: 0.78, 0.79), respectively. The model outperforms conventional perfusion abnormality measures at all time points for the prediction of death in both internal and external validations, with improvement increasing gradually over time. Individualized patient explanations are visualized using waterfall plots, which highlight the contribution degree and direction for each feature. This approach allows the derivation of individual event probability as a function of time as well as patient- and event-specific risk explanations that may help draw attention to modifiable risk factors. Such a method could help present post-scan risk assessments to the patient and foster shared decision-making.

Direct Risk Assessment From Myocardial Perfusion Imaging Using Explainable Deep Learning.

BACKGROUND: Myocardial perfusion imaging (MPI) is frequently used to provide risk stratification, but methods to improve the accuracy of these predictions are needed. OBJECTIVES: The authors developed an explainable deep learning (DL) model (HARD MACE [major adverse cardiac events]-DL) for the prediction of death or nonfatal myocardial infarction (MI) and validated its performance in large internal and external testing groups. METHODS: Patients undergoing single-photon emission computed tomography MPI were included, with 20,401 patients in the training and internal testing group (5 sites) and 9,019 in the external testing group (2 different sites). HARD MACE-DL uses myocardial perfusion, motion, thickening, and phase polar maps combined with age, sex, and cardiac volumes. The primary outcome was all-cause mortality or nonfatal MI. Prognostic accuracy was evaluated using area under the receiver-operating characteristic curve (AUC). RESULTS: During internal testing, patients with normal perfusion and elevated HARD MACE-DL risk were at higher risk than patients with abnormal perfusion and low HARD MACE-DL risk (annualized event rate, 2.9% vs 1.2%; P < 0.001). Patients in the highest quartile of HARD MACE-DL score had an annual rate of death or MI (4.8%) 10-fold higher than patients in the lowest quartile (0.48% per year). In external testing, the AUC for HARD MACE-DL (0.73; 95% CI: 0.71-0.75) was higher than a logistic regression model (AUC: 0.70), stress total perfusion deficit (TPD) (AUC: 0.65), and ischemic TPD (AUC: 0.63; all P < 0.01). Calibration, a measure of how well predicted risk matches actual risk, was excellent in both groups (Brier score, 0.079 for internal and 0.070 for external). CONCLUSIONS: The DL model predicts death or MI directly from MPI, by estimating patient-level risk with good calibration and improved accuracy compared with traditional quantitative approaches. The model incorporates mechanisms to explain to the physician which image regions contribute to the adverse event prediction.

Quantitative Assessment of Cardiac Hypermetabolism and Perfusion for Diagnosis of Cardiac Sarcoidosis.

BACKGROUND: Quantitative assessment of cardiac hypermetabolism from 18Flourodeoxy glucose (FDG) positron emission tomography (PET) may improve diagnosis of cardiac sarcoidosis (CS). We assessed different approaches for quantification of cardiac hypermetabolism and perfusion in patients with suspected CS. METHODS AND RESULTS: Consecutive patients undergoing 18FDG PET assessment for possible CS between January 2014 and March 2019 were included. Cardiac hypermetabolism was quantified using maximal standardized uptake value (SUVMAX), cardiometabolic activity (CMA) and volume of inflammation, using relative thresholds (1.3× and 1.5× left ventricular blood pool [LVBP] activity), and absolute thresholds (SUVMAX > 2.7 and 4.1). Diagnosis of CS was established using the Japanese Ministry of Health and Wellness criteria. In total, 69 patients were studied, with definite or possible CS in 29(42.0%) patients. CMA above 1.5× LVBP SUVMAX had the highest area under the receiver operating characteristic curve (AUC 0.92). Quantitative parameters using relative thresholds had higher AUC compared to absolute thresholds (p < 0.01). Interobserver variability was low for CMA, with excellent agreement regarding absence of activity (Kappa 0.970). CONCLUSIONS: Quantitation with scan-specific thresholds has superior diagnostic accuracy compared to absolute thresholds. Based on the potential clinical benefit, programs should consider quantification of cardiac hypermetabolism when interpreting 18F-FDG PET studies for CS.

Value of semiquantitative assessment of high-risk plaque features on coronary CT angiography over stenosis in selection of studies for FFRct.

INTRODUCTION: The degree of stenosis on coronary CT angiography (CCTA) guides referral for CT-derived flow reserve (FFRct). We sought to assess whether semiquantitative assessment of high-risk plaque (HRP) features on CCTA improves selection of studies for FFRct over stenosis assessment alone. METHODS: Per-vessel FFRct was computed in 1,395 vessels of 836 patients undergoing CCTA with 25-99% maximal stenosis. By consensus analysis, stenosis severity was graded as 25-49%, 50-69%, 70-89%, and 90-99%. HRPs including low attenuation plaque (LAP), positive remodeling (PR), and spotty calcification (SC) were assessed in lesions with maximal stenosis. Lesion FFRct was measured distal to the lesion with maximal stenosis, and FFRct<0.80 was defined as abnormal. Association of HRP and abnormal lesion FFRct was evaluated by univariable and multivariable logistic regression models. RESULTS: The frequency of abnormal lesion FFRct increased with increase of stenosis severity across each stenosis category (25-49%:6%; 50-69%:30%; 70-89%:54%; 90-99%:91%, p â€‹< â€‹0.001). Univariable analysis demonstrated that stenosis severity, LAP, and PR were predictive of abnormal lesion FFRct, while SC was not. In multivariable analyses considering stenosis severity, presence of PR, LAP, and PR and/or LAP were independently associated with abnormal FFRct: Odds ratio 1.58, 1.68, and 1.53, respectively (p â€‹< â€‹0.02 for all). The presence of PR and/or LAP increased the frequency of abnormal FFRct with mild stenosis (p â€‹< â€‹0.05) with a similar trend with 70-89% stenosis. The combination of 2 HRP (LAP and PR) identified more lesions with FFR < 0.80 than only 1 HRP. CONCLUSIONS: Semiquantitative visual assessment of high-risk plaque features may improve the selection of studies for FFRct.

Epicardial adipose tissue is associated with extent of pneumonia and adverse outcomes in patients with COVID-19.

AIM: We sought to examine the association of epicardial adipose tissue (EAT) quantified on chest computed tomography (CT) with the extent of pneumonia and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a post-hoc analysis of a prospective international registry comprising 109 consecutive patients (age 64 ±â€¯16 years; 62% male) with laboratory-confirmed COVID-19 and noncontrast chest CT imaging. Using semi-automated software, we quantified the burden (%) of lung abnormalities associated with COVID-19 pneumonia. EAT volume (mL) and attenuation (Hounsfield units) were measured using deep learning software. The primary outcome was clinical deterioration (intensive care unit admission, invasive mechanical ventilation, or vasopressor therapy) or in-hospital death. RESULTS: In multivariable linear regression analysis adjusted for patient comorbidities, the total burden of COVID-19 pneumonia was associated with EAT volume (ß = 10.6, p = 0.005) and EAT attenuation (ß = 5.2, p = 0.004). EAT volume correlated with serum levels of lactate dehydrogenase (r = 0.361, p = 0.001) and C-reactive protein (r = 0.450, p < 0.001). Clinical deterioration or death occurred in 23 (21.1%) patients at a median of 3 days (IQR 1-13 days) following the chest CT. In multivariable logistic regression analysis, EAT volume (OR 5.1 [95% CI 1.8-14.1] per doubling p = 0.011) and EAT attenuation (OR 3.4 [95% CI 1.5-7.5] per 5 Hounsfield unit increase, p = 0.003) were independent predictors of clinical deterioration or death, as was total pneumonia burden (OR 2.5, 95% CI 1.4-4.6, p = 0.002), chronic lung disease (OR 1.3 [95% CI 1.1-1.7], p = 0.011), and history of heart failure (OR 3.5 [95% 1.1-8.2], p = 0.037). CONCLUSIONS: EAT measures quantified from chest CT are independently associated with extent of pneumonia and adverse outcomes in patients with COVID-19, lending support to their use in clinical risk stratification.

Whole-vessel coronary 18F-sodium fluoride PET for assessment of the global coronary microcalcification burden.

PURPOSE: 18F-sodium fluoride (18F-NaF) has shown promise in assessing disease activity in coronary arteries, but currently used measures of activity - such as maximum target to background ratio (TBRmax) - are defined by single pixel count values. We aimed to develop a novel coronary-specific measure of 18F-NaF PET reflecting activity throughout the entire coronary vasculature (coronary microcalcification activity [CMA]). METHODS: Patients with recent myocardial infarction and multi-vessel coronary artery disease underwent 18F-NaF PET and coronary CT angiography. We assessed the association between coronary 18F-NaF uptake (both TBRmax and CMA) and coronary artery calcium scores (CACS) as well as low attenuation plaque (LAP, attenuation < 30 Hounsfield units) volume. RESULTS: In 50 patients (64% males, 63 ± 7 years), CMA and TBRmax were higher in vessels with LAP compared to those without LAP (1.09 [0.02, 2.34] versus 0.0 [0.0, 0.0], p < 0.001 and 1.23 [1.16, 1.37] versus 1.04 [0.93, 1.11], p < 0.001). Compared to a TBRmax threshold of 1.25, CMA > 0 had a higher diagnostic accuracy for detection of LAP: sensitivity of 93.1 (83.3-98.1)% versus 58.6 (44.9-71.4)% and a specificity of 95.7 (88.0-99.1)% versus 80.0 (68.7-88.6)% (both p < 0.001). 18F-NaF uptake assessed by CMA correlated more closely with LAP (r = 0.86, p < 0.001) than the CT calcium score (r = 0.39, p < 0.001), with these associations outperforming those observed for TBRmax values (LAP r = 0.63, p < 0.001; CT calcium score r = 0.30, p < 0.001). CONCLUSIONS: Automated assessment of disease activity across the entire coronary vasculature is feasible using 18F-NaF CMA, providing a single measurement that has closer agreement with CT markers of plaque vulnerability than more traditional measures of plaque activity.

Evaluation of the effect of reducing administered activity on assessment of function in cardiac gated SPECT.

BACKGROUND: We previously optimized several reconstruction strategies in SPECT myocardial perfusion imaging (MPI) with low dose for perfusion-defect detection. Here we investigate whether reducing the administered activity can also maintain the diagnostic accuracy in evaluating cardiac function. METHODS: We quantified the myocardial motion in cardiac-gated stress 99m-Tc-sestamibi SPECT studies from 163 subjects acquired with full dose (29.8 ± 3.6 mCi), and evaluated the agreement of the obtained motion/thickening and ejection fraction (EF) measures at various reduced dose levels (uniform reduction or personalized dose) with that at full dose. We also quantified the detectability of abnormal motion via a receiver-operating characteristics (ROC) study. For reconstruction we considered both filtered backprojection (FBP) without correction for degradations, and iterative ordered-subsets expectation-maximization (OS-EM) with resolution, attenuation and scatter corrections. RESULTS: With dose level lowered to 25% of full dose, the obtained results on motion/thickening, EF and abnormal motion detection were statistically comparable to full dose in both reconstruction strategies, with Pearson's r > 0.9 for global motion measures between low dose and full dose. CONCLUSIONS: The administered activity could be reduced to 25% of full dose without degrading the function assessment performance. Low dose reconstruction optimized for perfusion-defect detection can be reasonable for function assessment in gated SPECT.

Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging.

Myocardial oxygenation-the ability of blood vessels to supply the heart muscle (myocardium) with oxygen-is a critical determinant of cardiac function. Impairment of myocardial oxygenation is a defining feature of ischemic heart disease (IHD), which is caused by pathological conditions that affect the blood vessels supplying oxygen to the heart muscle. Detecting altered myocardial oxygenation can help guide interventions and prevent acute life-threatening events such as heart attacks (myocardial infarction); however, current diagnosis of IHD relies on surrogate metrics and exogenous contrast agents for which many patients are contraindicated. An oxygenation-sensitive cardiac magnetic resonance imaging (CMR) approach used previously to demonstrate that CMR signals can be sensitized to changes in myocardial oxygenation showed limited ability to detect small changes in signals in the heart because of physiologic and imaging noise during data acquisition. Here, we demonstrate a CMR-based approach termed cfMRI [cardiac functional magnetic resonance imaging (MRI)] that detects myocardial oxygenation. cfMRI uses carbon dioxide for repeat interrogation of the functional capacity of the heart's blood vessels via a fast MRI approach suitable for clinical adoption without limitations of key confounders (cardiac/respiratory motion and heart rate changes). This method integrates multiple whole-heart images within a computational framework to reduce noise, producing confidence maps of alterations in myocardial oxygenation. cfMRI permits noninvasive monitoring of myocardial oxygenation without requiring ionizing radiation, contrast agents, or needles. This has the potential to broaden our ability to noninvasively identify IHD and a diverse spectrum of heart diseases related to myocardial ischemia.

Three-Hour Delayed Imaging Improves Assessment of Coronary 18F-Sodium Fluoride PET.

Coronary 18F-sodium fluoride (18F-NaF) PET identifies ruptured plaques in patients with recent myocardial infarction and localizes to atherosclerotic lesions with active calcification. Most studies to date have performed the PET acquisition 1 h after injection. Although qualitative and semiquantitative analysis is feasible with 1-h images, residual blood-pool activity often makes it difficult to discriminate plaques with 18F-NaF uptake from noise. We aimed to assess whether delayed PET performed 3 h after injection improves image quality and uptake measurements. Methods: Twenty patients (67 ± 7 y old, 55% male) with stable coronary artery disease underwent coronary CT angiography (CTA) and PET/CT both 1 h and 3 h after the injection of 266.2 ± 13.3 MBq of 18F-NaF. We compared the visual pattern of coronary uptake, maximal background (blood pool) activity, noise, SUVmax, corrected SUVmax (cSUVmax), and target-to-background (TBR) ratio in lesions defined by CTA on 1-h versus 3-h 18F-NaF PET. Results: On 1-h PET, 26 CTA lesions with 18F-NaF PET uptake were identified in 12 (60%) patients. On 3-h PET, we detected 18F-NaF PET uptake in 7 lesions that were not identified on 1-h PET. The median cSUVmax and TBRs of these lesions were 0.48 (interquartile range [IQR], 0.44-0.51) and 1.45 (IQR, 1.39-1.52), respectively, compared with -0.01 (IQR, -0.03-0.001) and 0.95 (IQR, 0.90-0.98), respectively, on 1-h PET (both P < 0.001). Across the entire cohort, 3-h PET SUVmax was similar to 1-h PET measurements (1.63 [IQR, 1.37-1.98] vs. 1.55 [IQR, 1.43-1.89], P = 0.30), and the background activity was lower (0.71 [IQR, 0.65-0.81] vs. 1.24 [IQR, 1.05-1.31], P < 0.001). On 3-h PET, TBR, cSUVmax, and noise were significantly higher (respectively: 2.30 [IQR, 1.70-2.68] vs. 1.28 [IQR, 0.98-1.56], P < 0.001; 0.38 [IQR, 0.27-0.70] vs. 0.90 [IQR, 0.64-1.17], P < 0.001; and 0.10 [IQR, 0.09-0.12] vs. 0.07 [IQR, 0.06-0.09], P = 0.02). Median cSUVmax and TBR increased by 92% (range, 33%-225%) and 80% (range, 20%-177%), respectively. Conclusion: Blood-pool activity decreases on delayed imaging, facilitating the assessment of 18F-NaF uptake in coronary plaques. Median TBR increases by 80%, leading to the detection of more plaques with significant uptake than are detected using the standard 1-h protocol. A greater than 1-h delay may improve the detection of 18F-NaF uptake in coronary artery plaques.

Feasibility of Coronary 18F-Sodium Fluoride Positron-Emission Tomography Assessment With the Utilization of Previously Acquired Computed Tomography Angiography.

BACKGROUND: We assessed the feasibility of utilizing previously acquired computed tomography angiography (CTA) with subsequent positron-emission tomography (PET)-only scan for the quantitative evaluation of 18F-NaF PET coronary uptake. METHODS AND RESULTS: Forty-five patients (age 67.1±6.9 years; 76% males) underwent CTA (CTA1) and combined 18F-NaF PET/CTA (CTA2) imaging within 14 [10, 21] days. We fused CTA1 from visit 1 with 18F-NaF PET (PET) from visit 2 and compared visual pattern of activity, maximal standard uptake (SUVmax) values, and target to background ratio (TBR) measurements on (PET/CTA1) fused versus hybrid (PET/CTA2). On PET/CTA2, 226 coronary plaques were identified. Fifty-eight coronary segments from 28 (62%) patients had high 18F-NaF uptake (TBR >1.25), whereas 168 segments had lesions with 18F-NaF TBR ≤1.25. Uptake in all lesions was categorized identically on coregistered PET/CTA1. There was no significant difference in 18F-NaF uptake values between PET/CTA1 and PET/CTA2 (SUVmax, 1.16±0.40 versus 1.15±0.39; P=0.53; TBR, 1.10±0.45 versus 1.09±0.46; P=0.55). The intraclass correlation coefficient for SUVmax and TBR was 0.987 (95% CI, 0.983-0.991) and 0.986 (95% CI, 0.981-0.992). There was no fixed or proportional bias between PET/CTA1 and PET/CTA2 for SUVmax and TBR. Cardiac motion correction of PET scans improved reproducibility with tighter 95% limits of agreement (±0.14 for SUVmax and ±0.15 for TBR versus ±0.20 and ±0.20 on diastolic imaging; P<0.001). CONCLUSIONS: Coronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of 18F-NaF coronary uptake. This approach may facilitate selection of high-risk patients for PET-only imaging based on results from prior CTA, providing a practical workflow for clinical application.

Combined Quantitative Assessment of Myocardial Perfusion and Coronary Artery Calcium Score by Hybrid 82Rb PET/CT Improves Detection of Coronary Artery Disease.

UNLABELLED: Hybrid PET myocardial perfusion imaging (MPI) with CT allows the incorporation of coronary artery calcium (CAC) into the clinical protocol. We aimed to determine whether the combined analysis of MPI and CAC could improve the diagnostic accuracy of PET MPI in detection of obstructive coronary artery disease (CAD). METHODS: Consecutive patients (n = 152; mean age ± SD, 69 ± 12 y) without prior CAD, referred to (82)Rb PET MPI followed by invasive coronary angiography performed within 14 days, were studied. Myocardial perfusion was quantified automatically for left anterior descending, left circumflex, and right coronary artery territories as an ischemic total perfusion deficit (ITPD) for 456 vessels. Global and per-vessel CAC Agatston scores were calculated. Obstructive CAD was defined as 50% or greater stenosis of the left main and 70% or greater stenosis in the left anterior descending, left circumflex, and right coronary arteries. Logistic regression and 10-fold cross validation were used to derive and validate the combined ITPD/logCAC (logarithm of coronary calcium) scores. RESULTS: In the prediction of per-vessel obstructive CAD, the receiver-operating-characteristic area under the curve for combined per-vessel ITPD/logCAC score was higher, 0.85 (95% confidence interval [CI], 0.81-0.89), than standalone ITPD area under the curve, 0.81 (95% CI: 0.76-0.85), and logCAC score, 0.73 (95% CI, 0.68-0.78; P < 0.05). The integrated discrimination improvement of combined per-vessel ITPD/logCAC analysis was 0.07 (95% CI, 0.04-0.09; P < 0.0001), as compared with ITPD alone. CONCLUSION: Combined automatically derived per-vessel ITPD and logCAC score improves accuracy of (82)Rb PET MPI for detection of obstructive CAD.

Assessment of the relationship between stenosis severity and distribution of coronary artery stenoses on multislice computed tomographic angiography and myocardial ischemia detected by single photon emission computed tomography.

BACKGROUND: The relationship between luminal stenosis measured by coronary CT angiography (CCTA) and severity of stress-induced ischemia seen on single photon emission computed tomographic myocardial perfusion imaging (SPECT-MPI) is not clearly defined. We sought to evaluate the relationship between stenosis severity assessed by CCTA and ischemia on SPECT-MPI. METHODS AND RESULTS: ECG-gated CCTA (64 slice dual source CT) and SPECT-MPI were performed within 6 months in 292 patients (ages 26-91, 73% male) with no prior history of coronary artery disease. Maximal coronary luminal narrowing, graded as 0, ≥25%, 50%, 70%, or 90% visual diameter reduction, was consensually assessed by two expert readers. Perfusion defect on SPECT-MPI was assessed by computer-assisted visual interpretation by an expert reader using the standard 17 segment, 5 point-scoring model (stress perfusion defect of ≥5% = abnormal). By SPECT-MPI, abnormal perfusion was seen in 46/292 patients. With increasing stenosis severity, positive predictive value (PPV) increased (42%, 51%, and 74%, P = .01) and negative predictive value was relatively unchanged (97%, 95%, and 91%) in detecting perfusion abnormalities on SPECT-MPI. In a receiver operator curve analysis, stenosis of 50% and 70% were equally effective in differentiating between the presence and absence of ischemia. In a multivariate analysis that included stenosis severity, multivessel disease, plaque composition, and presence of serial stenoses in a coronary artery, the strongest predictors of ischemia were stenosis of 50-89%, odds ratio (OR) 7.31, P = .001, stenosis ≥90%, OR 34.05, P = .0001, and serial stenosis ≥50% OR of 3.55, P = .006. CONCLUSIONS: The PPV of CCTA for ischemia by SPECT-MPI rises as stenosis severity increases. Luminal stenosis ≥90% on CCTA strongly predicts ischemia, while <50% stenosis strongly predicts the absence of ischemia. Serial stenosis of ≥50% in a vessel may offer incremental value in addition to stenosis severity in predicting ischemia.

Nonlinear registration of serial coronary CT angiography (CCTA) for assessment of changes in atherosclerotic plaque.

PURPOSE: Coronary CT angiography (CCTA) is a high-resolution three-dimensional imaging technique for the evaluation of coronary arteries in suspected or confirmed coronary artery disease (CAD). Coregistration of serial CCTA scans would allow precise superimposition of images obtained at two different points in time, which could aid in recognition of subtle changes and precise monitoring of coronary plaque progression or regression. To this end, the authors aimed at developing a fully automatic nonlinear volume coregistration for longitudinal CCTA scan pairs. METHODS: The algorithm combines global displacement and local deformation using nonlinear volume coregistration with a volume-preserving constraint. Histogram matching of intensities between two serial scans is performed prior to nonlinear coregistration with dense nonparametric local deformation in which sum of squared differences is used as a similarity measure. The approximate segmentation of coronary arteries obtained from commercially available software provides initial anatomical landmarks for the coregistration algorithm that help localize and emphasize the structure of interest. To avoid possible bias caused by incorrect segmentation, the authors convolve the Gaussian kernel with the segmented binary coronary tree mask and define an extended weighted region of interest. A multiresolution approach is employed to represent coarse-to-fine details of both volumes and the energy function is optimized using a gradient descent method. The authors applied the algorithm in ten paired CCTA datasets (20 scans in total) obtained within 10.7 +/- 5.7 months from each other on a dual source CT scanner to monitor progression of CAD. RESULTS: Serial CCTA coregistration was successful in 9/10 cases as visually confirmed. The global displacement and local deformation of target registration error obtained from four anatomical landmarks were 2.22 +/- 1.15 and 1.56 +/- 0.74 mm, respectively, and the inverse consistency error of local deformation was 0.14 +/- 0.06 mm. The observer variability between two expert observers was 1.31 +/- 0.91 mm. CONCLUSIONS: The proposed coregistration algorithm demonstrates potential to accurately register serial CCTA scans, which may allow direct comparison of calcified and noncalcified atherosclerotic plaque changes between the two scans.

Quantitative assessment of myocardial perfusion abnormality on SPECT myocardial perfusion imaging is more reproducible than expert visual analysis.

BACKGROUND: Current guidelines of Food and Drug Administration for the evaluation of SPECT myocardial perfusion imaging (MPI) in clinical trials recommend independent visual interpretation by multiple experts. Few studies have addressed whether quantitative SPECT MPI assessment would be more reproducible for this application. METHODS AND RESULTS: We studied 31 patients (age 68 +/- 13, 25 male) with abnormal stress MPI who underwent repeat exercise (n = 11) or adenosine (n = 20) MPI within 9-22 months (mean 14.9 +/- 3.8 months) and had no interval revascularization or myocardial infarction and no change in symptoms, stress type, rest or stress ECG, or clinical response to stress on the second study. Visual interpretation per FDA Guidance used 17-segment, 5-point scoring by two independent expert readers with overread of discordance by a third expert, and percent myocardium abnormal was derived from normalized summed scores. The quantitative magnitude of perfusion abnormality was assessed by the total perfusion deficit (TPD), expressing stress, rest, and ischemic perfusion abnormality. High linear correlations were observed between visual and quantitative size of stress, rest, and ischemic defects (R = 0.94, 0.92, 0.84). Correlations of two tests were higher by quantitative than by visual methods for stress (R = 0.97 vs R = 0.91, P = 0.03) and rest defects (R = 0.94 vs R = 0.82, P = 0.03), respectively, and statistically similar for ischemic defects (R = 0.84 vs R = 0.70, P = ns). CONCLUSIONS: In stable patients having serial SPECT MPI, quantification is more reproducible than visual for magnitude of perfusion abnormality, suggesting its superiority for use in randomized clinical trials and monitoring the effects of therapy in an individual patient.

Aortic size assessment by noncontrast cardiac computed tomography: normal limits by age, gender, and body surface area.

OBJECTIVES: To determine normal limits for ascending and descending thoracic aorta diameters in a large population of asymptomatic, low-risk adult subjects. BACKGROUND: Assessment of aortic size is possible from gated noncontrast computed tomography (CT) scans obtained for coronary calcium measurements. However, normal limits for aortic size by these studies have yet to be defined. METHODS: In 4,039 adult patients undergoing coronary artery calcium (CAC) scanning, systematic measurements of the ascending and descending thoracic aorta diameters were made at the level of the pulmonary artery bifurcation. Multiple linear regression analysis was used to detect risk factors independently associated with ascending and descending thoracic aorta diameter and exclude subjects with these parameters from the final analysis. The final analysis groups for ascending and descending thoracic aorta included 2,952 and 1,931 subjects, respectively. Subjects were then regrouped by gender, age, and body surface area (BSA) for ascending and descending aorta, separately, and for each group, the mean, standard deviation, and upper normal limit were calculated for aortic diameter as well as for the calculated cross-sectional aortic area. Also, linear regression models were used to create BSA versus aortic diameter nomograms by age groups, and a formula for calculating predicted aortic size by age, gender, and BSA was created. RESULTS: Age, BSA, gender, and hypertension were directly associated with thoracic aorta dimensions. Additionally, diabetes was associated with ascending aorta diameter, and smoking was associated with descending aorta diameter. The mean diameters for the final analysis group were 33 +/- 4 mm for the ascending and 24 +/- 3 mm for the descending thoracic aorta, respectively. The corresponding upper limits of normal diameters were 41 and 30 mm, respectively. CONCLUSIONS: Normal limits of ascending and descending aortic dimensions by noncontrast gated cardiac CT have been defined by age, gender, and BSA in a large, low-risk population of subjects undergoing CAC scanning.

Simplified normal limits and automated quantitative assessment for attenuation-corrected myocardial perfusion SPECT.

BACKGROUND: We aimed to compare normal limits and the detection of coronary artery disease (CAD) with attenuation-corrected (AC) and non-attenuation-corrected (NC) myocardial perfusion single photon emission computed tomography (MPS) by use of a recently improved automated quantification technique. METHODS AND RESULTS: We acquired 415 rest/stress technetium 99m MPS studies on a Vertex dual-detector camera with a gadolinium 153 line source (Vantage Pro). Gender-specific NC, AC, and gender-combined AC normal limits were created from rest/stress images of 50 women and 50 men with a low likelihood of CAD (< 5%) and a median body mass index (BMI) of 30 kg/m2 in each gender group. BMI-specific normal limits (< 30 kg/m2 and > or = 30 kg/m2) were also compared. Total perfusion deficit and 17-segment summed scores in 174 patients were compared with angiography, and normalcy rates were established from 141 studies of low-likelihood patients. There were no differences between low-BMI and high-BMI normal limits for AC or NC studies. Male and female normal limits differed in 12 of 17 segments for NC stress studies and in 3 of 17 segments for AC stress studies (P < .01). The sensitivity, specificity, and normalcy rates for stenoses with 70% narrowing or greater were 89%, 73%, and 91%, respectively, for NC studies and 87%, 80%, and 95%, respectively, for AC studies (P = not significant). CONCLUSION: Automated detection of CAD by AC and NC MPS demonstrated similar sensitivity, specificity, and normalcy rates. Some gender differences were noted for AC normal limits.

Rapid assessment of left ventricular segmental wall motion, ejection fraction, and volumes with single breath-hold, multi-slice TrueFISP MR imaging.

BACKGROUND AND OBJECTIVE: To reduce imaging time and complexity, we sought to determine whether single breath-hold, multi-slice TrueFISP (SB-MST) magnetic resonance imaging (MRI) method is comparable to standard multi-breath-hold, multi-slice TrueFISP (MB-MST) for assessment of left ventricular (LV) wall motion abnormality (WMA), volumes, and ejection fraction (EF). METHODS AND RESULTS: We studied 62 patients having cardiac MRI at 1.5-Tesla. After acquiring standard MB-MST (one slice per breath-hold), SB-MST was performed, acquiring 3 short- and 2 long-axis views over only 20 heartbeats. Using both techniques, wall motion was scored using a 6-point, 17-segment LV model for all scans (62 patients x 2 techniques/patient = 124 scans) on two separate occasions. Separately, EF and ventricular volumes were evaluated using both MB-MST and SB-MST. For all analyses, MB-MST was considered the standard against which SB-MST was compared. Twenty-six of 62 patients exhibited at least one segmental WMA by MB-MST. Exact agreement for wall motion was found in 965/1054 segments (92%, kappa = 0.74, p < 0.001), and agreement was within 1 score point in 1010/1054 segments (96%). Considering a score >1 abnormal, exact agreement for presence of WMA was found in 131/193 segments (68%) abnormal by MB-MST and for absence of WMA in 838/861 segments (97%) normal by MB-MST. Agreement within 1 score point occurred in 167/193 abnormal (87%) and in 843/861 normal segments (98%). There were no significant differences in agreement between first and second read of the data. Variability of SB-MST on read one versus read two was small (5%, 996/1054 segments read identically, p = ns) and statistically identical to variability of MB-MST on read one versus read two (4%, 1007/1054 segments read identically, p = ns). For end-diastolic volumes, end-systolic volumes, and EF using SB-MST compared to MB-MST, mean differences were 9 +/- 15 ml, 6 +/- 12 ml, and 2 +/- 5%, and correlations were r = 0.97, 0.98 and 0.95, respectively. CONCLUSION: SB-MST accurately assesses wall motion, volumes and EF. This approach may serve as a screening exam for assessment of WMA and, under select circumstances, may substitute for standard multi-breath-hold method in situations requiring rapid accurate assessments of LV function.

Assessment of diastolic function using 16-frame 99mTc-sestamibi gated myocardial perfusion SPECT: normal values.

UNLABELLED: The purposes of this study were (a) to assess the feasibility of diastolic function (DFx) evaluation using standard 16-frame postexercise gated (99m)Tc-sestamibi myocardial perfusion SPECT (MPS), (b) to determine the relationship of the 2 common DFx parameters, peak filling rate (PFR) and time to peak filling (TTPF), to clinical and systolic function (SFx) variables in patients with normal myocardial perfusion and SFx, and (c) to derive and validate normal limits. METHODS: Ninety patients (71 men; age, 30-79 y) with normal exercise gated MPS were studied. None had hypertension, diabetes, rest electrocardiogram abnormality, or known cardiac disease. All patients reached > or = 85% of maximum predicted heart rate (HR). The population was randomized into derivation (n = 50) and validation (n = 40) groups. Univariable and multivariable approaches were deployed to assess the influence of clinical and functional variables on DFx parameters. RESULTS: PFR and TTPF were assessed in all patients. Mean values of PFR and TTPF in the whole study population were 2.62 +/- 0.46 end-diastolic volumes per second (EDV/s) and 164.6 +/- 21.7 ms, respectively. By applying a 2-SD cutoff to the mean values in the derivation group, the threshold for abnormal PFR and the threshold for abnormal TTPF were < 1.71 EDV/s and > 216.7 ms, respectively. The normalcy rates in the validation group for PFR and TTPF were both 100%. The PFR showed weak but significant correlations with age, EDV, end-systolic volume, left ventricular ejection fraction (LVEF), and poststress HR. However, TTPF did not correlate with these parameters. Final normal thresholds determined from the combined populations were PFR = 1.70 EDV/s and TTPF = 208 ms. Multivariable analysis showed that age, sex, LVEF, and HR are strong predictors for PFR, whereas TTPF was not influenced by any clinical or SFx variable. CONCLUSION: With a new algorithm in QGS, assessment of LV DFx is feasible using 16-frame gated MPS even without bad-beat rejection, resulting in normal limits similar to those reported with gated blood-pool studies. However, due to the dependency of PFR on SFx parameters, sex, HR, and age, TTPF appears to be a stable and more useful parameter with this approach. The clinical usefulness of these findings requires further study.