Comparing various AI approaches to traditional quantitative assessment of the myocardial perfusion in [82Rb] PET for MACE prediction.

Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [ 82 Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model ( p < 0.001 ), where the best AUC of 73.9% (CI 72.5-75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3-74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE.

Pulmonary blood volume assessment from a standard cardiac rubidium-82 imaging protocol: impact of adenosine-induced hyperemia.

BACKGROUND: This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia. METHODS: This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent serial rest/adenosine stress Rubidium-82 MPI sessions. Mean bolus transit times (MBTT) were obtained by calculating the time delay from the Rubidium-82 bolus arrival in the pulmonary trunk to the arrival in the left myocardial atrium. Using the MBTT, in combination with stroke volume (SV) and heart rate (HR), we estimated pulmonary blood volume (PBV = (SV × HR) × MBTT). We report the empirically measured MBTT, HR, SV, and PBV, all stratified by sex [male (M) vs female (F)] as mean (SD). In addition, we report grouped repeatability measures using the within-subject repeatability coefficient. RESULTS: Mean bolus transit times was shortened during adenosine stressing with sex-specific differences [(seconds); Rest: Female (F) = 12.4 (1.5), Male (M) = 14.8 (2.8); stress: F = 8.8 (1.7), M = 11.2 (3.0), all P ≤ 0.01]. HR and SV increased during stress MPI, with a concomitant increase in the PBV [mL]; Rest: F = 544 (98), M = 926 (105); Stress: F = 914 (182), M = 1458 (338), all P < 0.001. The following test-retest repeatability measures were observed for MBTT (Rest = 17.2%, Stress = 17.9%), HR (Rest = 9.1%, Stress = 7.5%), SV (Rest = 8.9%, Stress = 5.6%), and for PBV measures (Rest = 20.7%, Stress = 19.5%) CONCLUSION: Pulmonary blood volume can be extracted by cardiac rubidium-82 MPI with excellent test-retest reliability, both at rest and during adenosine-induced hyperemia.

Patient-tailored risk assessment of obstructive coronary artery disease using Rubidium-82 PET-based myocardial flow quantification with visual interpretation.

INTRODUCTION: Our aim was to estimate the probability of obstructive CAD (oCAD) for an individual patient as a function of the myocardial flow reserve (MFR) measured with Rubidium-82 (Rb-82) PET in patients with a visually normal or abnormal scan. MATERIALS AND METHODS: We included 1519 consecutive patients without a prior history of CAD referred for rest-stress Rb-82 PET/CT. All images were visually assessed by two experts and classified as normal or abnormal. We estimated the probability of oCAD for visually normal scans and scans with small (5%-10%) or larger defects (> 10%) as function of MFR. The primary endpoint was oCAD on invasive coronary angiography, when available. RESULTS: 1259 scans were classified as normal, 136 with a small defect and 136 with a larger defect. For the normal scans, the probability of oCAD increased exponentially from 1% to 10% when segmental MFR decreased from 2.1 to 1.3. For scans with small defects, the probability increased from 13% to 40% and for larger defects from 45% to > 70% when segmental MFR decreased from 2.1 to 0.7. CONCLUSION: Patients with > 10% risk of oCAD can be distinguished from patients with < 10% risk based on visual PET interpretation only. However, there is a strong dependence of MFR on patient's individual risk of oCAD. Hence, combining both visual interpretation and MFR results in a better individual risk assessment which may impact treatment strategy.

Splenic switch-off in regadenoson 82Rb-PET myocardial perfusion imaging: assessment of clinical utility.

BACKGROUND: Splenic switch-off (SSO) is a phenomenon describing a decrease in splenic radiotracer uptake after vasodilatory stress. We aimed to assess the diagnostic utility of regadenoson-induced SSO. METHODS: We included consecutive patients who had clinically indicated Regadenoson Rb-82 PET-MPI for suspected CAD. This derivation cohort (no perfusion defects and myocardial flow reserves (MFR) ≥ 2) was used to calculate the splenic response ratio (SRR). The validation cohort was defined as patients who underwent both PET-MPI studies and invasive coronary angiography (ICA). RESULTS: The derivation cohort (n = 100, 57.4 ± 11.6 years, 77% female) showed a decrease in splenic uptake from rest to stress (79.9 ± 16.8 kBq⋅mL vs 69.1 ± 16.2 kBq⋅mL, P < .001). From the validation cohort (n = 315, 66.3 ± 10.4 years, 67% male), 28% (via SRR = 0.88) and 15% (visually) were classified as splenic non-responders. MFR was lower in non-responders (SRR; 1.55 ± 0.65 vs 1.76 ± 0.78, P = .02 and visually; 1.18 ± 0.33 vs 1.79 ± 0.77, P < .001). Based on ICA, non-responders were more likely to note obstructive epicardial disease with normal PET scans especially in patients with MFR < 1.5 (SRR; 61% vs 34% P = .05 and visually; 68% vs 33%, P = .01). CONCLUSION: Lack of splenic response based on visual or quantitative assessment of SSO may be used to identify an inadequate vasodilatory response.

Semi-quantitative assessment of ischemia with rubidium-82 PET myocardial perfusion imaging.

PURPOSE: Semi-quantitative scores can be used as an adjunct to visual assessment in rubidium-82 positron emission tomography (82Rb PET). The semi-quantitative cut-off values used in 82Rb PET are derived from single-photon emission computed tomography (SPECT). It is unknown whether these cut-off values can be extrapolated to 82Rb PET. We compared the semi-quantitative with the visual assessment of ischemia and determined which summed difference score (SDS) score predicts ischemia best. METHODS: We included 108 patients who underwent 82Rb PET imaging and performed visual and semi-quantitative assessment. A scan with a SDS ≥ 2 and a summed stress score (SSS) ≥ 4 was considered to demonstrate ischemia. We compared the semi-quantitative with the visual assessment. RESULTS: 41 (38%) Normal scans, and 67 (62%) scans with ischemia and/or an irreversible defect were included. The semi-quantitative assessment showed ischemia more often than the visual assessment (51% vs 29%, P < .001). Patients with a low or intermediate pre-test probability of coronary artery disease (CAD) and a SDS < 4 did not demonstrate ischemia by visual assessment. CONCLUSION: Semi-quantitative assessment in 82Rb PET imaging clearly demonstrates the presence of ischemia. Ischemia is unlikely in patients with low and intermediate pre-test probability of CAD and a SDS < 4.

Assessment of late-term progression of cardiac allograft vasculopathy in patients with orthotopic heart transplantation using quantitative cardiac 82Rb PET.

The risk stratification and long-term survival of patients with orthotopic heart transplantation (OHT) is impacted by the complication of cardiac allograft vasculopathy (CAV). This study evaluates changes in myocardial blood flow (MBF) and myocardial coronary flow reserve (CFR) in a group of long-term OHT patients using quantitative cardiac 82Rb-positron emission tomography (PET). Twenty patients (7 females and 13 males, mean age = 72.7 ± 12.2 years with CAV and 62.9 ± 7.2 years without CAV and post-OHT mean time = 13.9 years), were evaluated retrospectively using dynamic cardiac 82Rb-PET at rest and regadenoson-induced stress. The patients also underwent selective coronary angiography (SCA) for diagnosis and risk stratification. CAV was diagnosed based on SCA findings and maximal intimal thickness greater than 0.5 mm, as defined by International Society of Heart and Lung Transplantation (ISHLT). Global and regional MBFs were estimated in three vascular territories using the standard 1-tissue compartment model for dynamic 82Rb-PET. The myocardial CFR was also calculated as the ratio of peak stress MBF to rest MBF. Among twenty patients, seven had CAV in, at least, one major coronary artery (ISHLT CAV grade 1 or higher) while 13 patients did not have CAV (NonCAV). Mean rate-pressure products (RPP) at rest were significantly elevated in CAV patients compared to those without CAV (P = 0.002) but it was insignificant at stress (P = NS). There was no significant difference in the stress MBFs between CAV and NonCAV patients (P = NS). However, the difference in RPP-normalized stress MBFs was significant (P = 0.045), while RPP-normalized MBFs at rest was not significant (P = NS). Both CFR and RPP-normalized CFR were significantly lower in CAV compared to NonCAV patients (P < 0.001). There were significant correlations between MBFs and RPPs at rest for both CAV (ρ = 0.764, P = 0.047) and NonCAV patients (ρ = 0.641, P = 0.017), while there were no correlations at stress for CAV (ρ = 0.232, P = NS) and NonCAV patients (ρ = 0.068, P = NS). This study indicates that the resting MBF is higher in late-term post-OHT patients. The high resting MBF and reduced CFR suggest an unprecedented demand of blood flow and blunted response to stress due to impaired vasodilatory capacity that is exacerbated by the presence of CAV.

Assessment of motion correction in dynamic rubidium-82 cardiac PET with and without frame-by-frame adjustment of attenuation maps for calculation of myocardial blood flow.

BACKGROUND: Patient motion during pharmacological stressing can have substantial impact on myocardial blood flow (MBF) estimated from dynamic PET. This work evaluated a motion correction algorithm with and without adjustment of the PET attenuation map. METHODS: Frame-by-frame motion correction was performed by three users on 30 rubidium-82 studies. Data were divided equally into three groups of motion severity [mild (M1), moderate (M2) and severe (M3)]. MBF data were compared for non-motion corrected (NC), motion-corrected-only (MC) and with adjustment of the attenuation map (MCAC). Percentage differences of MBF were calculated in the coronary territories and 17-segment polar plots. Polar plots of spill-over were also generated from the data. RESULTS: Median differences of 23% were seen in the RCA and 18% for the LAD in the M3 category for MC vs NC images. Differences for MCAC vs MC images were considerably smaller and typically < 10%. Spill-over plots for MC and MCAC were notably more uniform compared with NC images. CONCLUSION: Motion correction for dynamic rubidium data is desirable for future MBF software updates. Adjustment of the PET attenuation map results in only marginal differences and therefore is unlikely to be an essential requirement. Assessing the uniformity of spill-over plots is a useful visual aid for verifying motion correction techniques.

Serial Assessment of Coronary Flow Reserve by Rubidium-82 Positron Emission Tomography Predicts Mortality in Heart Transplant Recipients.

OBJECTIVES: This study aimed to evaluate the long-term prognostic value of serial assessment of coronary flow reserve (CFR) by rubidium Rb 82 (82Rb) positron emission tomography (PET) in heart transplantation (HT) patients. BACKGROUND: Cardiac allograft vasculopathy is a major determinant of late mortality in HT recipients. The long-term prognostic value of serial CFR quantification by PET imaging in HT patients is unknown. METHODS: A total of 89 patients with history of HT (71% men, 7.0 ± 5.7 years post-HT, age 57 ± 11 years) scheduled for dynamic rest and stress (dipyridamole) 82Rb PET between March 1, 2008 and July 31, 2009 (PET-1) were prospectively enrolled in a single-center study. PET myocardial perfusion studies were reprocessed using U.S. Food and Drug Administration-approved software (Corridor 4DM, version 2017) for calculation of CFR. Follow-up PET (PET-2) imaging was performed in 69 patients at 1.9 ± 0.3 years following PET-1. Patients were categorized based on CFR values considering CFR ≤1.5 as low and CFR >1.5 as high CFR. RESULTS: Forty deaths occurred during the median follow-up time of 8.6 years. Low CFR at PET-1 was associated with a 2.77-fold increase in all-cause mortality (95% confidence interval [CI]: 1.34 to 5.74; p = 0.004). CFR decreased over time in patients with follow-up imaging (PET-1: 2.11 ± 0.74 vs. PET-2: 1.81 ± 0.61; p = 0.003). Twenty-five patients were reclassified based on PET-1 and PET-2 (high to low CFR: n = 18, low to high CFR: n = 7). Overall survival was similar in patients reclassified from high to low as patients with low to low CFR, whereas patients reclassified from low to high had similar survival as patients with high to high CFR. In multivariate Cox regression of patients with PET-2, higher baseline CFR (hazard ratio [HR] for a 0.73 unit (one SD) increase: 0.36, 95% CI: 0.16 to 0.82) and reduction in CFR from PET-1 to PET-2 (HR for a 0.79 unit (one SD) decrease: 1.50 to 7.84) were independent predictors of all-cause mortality. CONCLUSIONS: Serial assessment of CFR by 82Rb PET independently predicts long-term mortality in HT patients.

The utility of 82Rb PET for myocardial viability assessment: Comparison with perfusion-metabolism 82Rb-18F-FDG PET.

BACKGROUND: 82Rb kinetics may distinguish scar from viable but dysfunctional (hibernating) myocardium. We sought to define the relationship between 82Rb kinetics and myocardial viability compared with conventional 82Rb and 18F-fluorodeoxyglucose (FDG) perfusion-metabolism PET imaging. METHODS: Consecutive patients (N = 120) referred for evaluation of myocardial viability prior to revascularization and normal volunteers (N = 37) were reviewed. Dynamic 82Rb 3D PET data were acquired at rest. 18F-FDG 3D PET data were acquired after metabolic preparation using a standardized hyperinsulinemic-euglycemic clamp. 82Rb kinetic parameters K1, k2, and partition coefficient (KP) were estimated by compartmental modeling RESULTS: Segmental 82Rb k2 and KP differed significantly between scarred and hibernating segments identified by Rb-FDG perfusion-metabolism (k2, 0.42 ± 0.25 vs. 0.22 ± 0.09 min-1; P < .0001; KP, 1.33 ± 0.62 vs. 2.25 ± 0.98 ml/g; P < .0001). As compared to Rb-FDG analysis, segmental Rb KP had a c-index, sensitivity and specificity of 0.809, 76% and 84%, respectively, for distinguishing hibernating and scarred segments. Segmental k2 performed similarly, but with lower specificity (75%, P < .001) CONCLUSIONS: In this pilot study, 82Rb kinetic parameters k2 and KP, which are readily estimated using a compartmental model commonly used for myocardial blood flow, reliably differentiated hibernating myocardium and scar. Further study is necessary to evaluate their clinical utility for predicting benefit after revascularization.

Cardiac (82)Rb PET/CT for fast and non-invasive assessment of microvascular function and structure in asymptomatic patients with type 2 diabetes.

AIMS/HYPOTHESIS: Coronary flow reserve (CFR) and coronary artery calcium (CAC) represent functional and structural aspects of atherosclerosis. We examined the prevalence of reduced CFR and high CAC scores in three predefined groups of participants without known cardiovascular disease: (1) patients with type 2 diabetes and albuminuria; (2) patients with type 2 diabetes and normoalbuminuria; and (3) non-diabetic controls. METHODS: In a cross-sectional design, cardiac (82)Rb positron emission tomography/computed tomography was conducted in 60 patients with type 2 diabetes who were free of overt cardiovascular disease and who were stratified by normoalbuminuria (<30 mg/24 h) (n = 30; age [mean ± SD] 60.9 ± 10.1 years) and albuminuria (≥ 30 mg/24 h) (n = 30; age 65.6 ± 4.8 years), and in 30 healthy, non-diabetic controls (age 59.8 ± 9.9 years). RESULTS: In controls, normoalbuminuric and albuminuric patients, CFR was 3.0 ± 0.8, 2.6 ± 0.8 and 2.0 ± 0.5, respectively. Reduced CFR (<2.5) was observed in 16.7%, 40.0% and 83.3% of participants, respectively, and median (interquartile range) CAC scores were 0 (0-81), 36 (1-325) and 370 (152-1,025), respectively (p for trend <0.01). After adjustment, the difference in CFR and CAC between albuminuric patients and controls remained significant (p ≤ 0.001). There were trends towards lower CFR and higher CAC scores in normoalbuminuric patients vs controls (p ≤ 0.023) and towards higher CAC scores in albuminuric vs normoalbuminuric patients (p = 0.026). In multivariate regression analysis, a higher urinary albumin excretion rate (UAER) tended to predict reduced CFR in the total population (p = 0.045). When the CAC score was added, there was also a trend (p = 0.032) towards an inverse association with reduced CFR. CONCLUSIONS/INTERPRETATION: Type 2 diabetic patients who were free of overt cardiovascular disease had a high prevalence of coronary microvascular dysfunction, especially with concomitant albuminuria, suggesting a common microvascular impairment occurring in multiple microvascular beds. Prospective studies are needed to show the prognostic significance of this finding.

Myocardial blood flow assessment with 82rubidium-PET imaging in patients with left bundle branch block.

OBJECTIVES: Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease. OBJECTIVE: We sought to investigate rubidium-82 (82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block. METHODS: Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress 82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII). RESULTS: Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001). CONCLUSION: The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by 82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.

Myocardial blood flow assessment with 82rubidium-PET imaging in patients with left bundle branch block

OBJECTIVES: Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease. OBJECTIVE: We sought to investigate rubidium-82 (82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block. METHODS: Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress 82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII). RESULTS: Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001). CONCLUSION: The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by 82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.

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.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

UNLABELLED: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. METHODS: Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences greater than 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. RESULTS: Qualifying scores of SSS = 2, SDS = 2, were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). CONCLUSION: (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.

Accurate estimation of dose distributions inside an eye irradiated with 106Ru plaques.

BACKGROUND: Irradiation of intraocular tumors requires dedicated techniques, such as brachytherapy with (106)Ru plaques. The currently available treatment planning system relies on the assumption that the eye is a homogeneous water sphere and on simplified radiation transport physics. However, accurate dose distributions and their assessment demand better models for both the eye and the physics. METHODS: The Monte Carlo code PENELOPE, conveniently adapted to simulate the beta decay of (106)Ru over (106)Rh into (106)Pd, was used to simulate radiation transport based on a computerized tomography scan of a patient's eye. A detailed geometrical description of two plaques (models CCA and CCB) from the manufacturer BEBIG was embedded in the computerized tomography scan. RESULTS: The simulations were firstly validated by comparison with experimental results in a water phantom. Dose maps were computed for three plaque locations on the eyeball. From these maps, isodose curves and cumulative dose-volume histograms in the eye and for the structures at risk were assessed. For example, it was observed that a 4-mm anterior displacement with respect to a posterior placement of a CCA plaque for treating a posterior tumor would reduce from 40 to 0% the volume of the optic disc receiving more than 80 Gy. Such a small difference in anatomical position leads to a change in the dose that is crucial for side effects, especially with respect to visual acuity. The radiation oncologist has to bring these large changes in absorbed dose in the structures at risk to the attention of the surgeon, especially when the plaque has to be positioned close to relevant tissues. CONCLUSION: The detailed geometry of an eye plaque in computerized and segmented tomography of a realistic patient phantom was simulated accurately. Dose-volume histograms for relevant anatomical structures of the eye and the orbit were obtained with unprecedented accuracy. This represents an important step toward an optimized brachytherapy treatment of ocular tumors.

Assessment of a protocol for routine simultaneous myocardial blood flow measurement and standard myocardial perfusion imaging with rubidium-82 on a high count rate positron emission tomography system.

OBJECTIVES: High count rate positron emission tomography (PET) systems offer the potential for accurate myocardial blood flow (MBF) quantification during first-pass dynamic imaging in conjunction with standard rubidium-82 (Rb-82) PET myocardial perfusion imaging (MPI). We investigate the feasibility of this using a Siemens Biograph mCT. MATERIALS AND METHODS: Current routine clinical PET MPI is performed with 1480 MBq (40 mCi) Rb-82. Dynamic first-pass images from 217 consecutive patients were reviewed for evidence of detector saturation, indicating that count rate limits had been exceeded. Phantom acquisitions in the presence of high count rates were performed to assess the effect of detector saturation on quantitative accuracy. RESULTS: Accurate MBF quantification and perfusion imaging using current protocols was successful in 85% of clinical cases. Detector block saturation was observed in 15% of cases, and phantom acquisitions indicate that saturation may have an adverse effect on quantitative accuracy. Visualization of transit or pooling of Rb-82 in the vessels in the axilla was the most consistent feature when saturation occurred. Reduction of administered activity to 1110 MBq (30 mCi) and subsequent evaluation of 159 patients ensured successful MBF quantification while maintaining good diagnostic quality perfusion imaging in 99% of cases. CONCLUSION: MBF quantification and good-quality standard perfusion imaging can be performed on a high count rate PET system using a single-acquisition protocol. The administered activity requires optimization and we recommend 1110 MBq for PET MPI with a Biograph mCT.

Transient ischemic dilation ratio in 82Rb PET myocardial perfusion imaging: normal values and significance as a diagnostic and prognostic marker.

UNLABELLED: In myocardial perfusion SPECT, transient ischemic dilation ratio (TID) is a well-established marker of severe ischemia and adverse outcome. However, its role in the setting of (82)Rb PET is less well defined. METHODS: We analyzed 265 subjects who underwent clinical rest-dipyridamole (82)Rb PET/CT. Sixty-two subjects without a prior history of cardiac disease and with a normal myocardial perfusion study had either a low or a very low pretest likelihood of coronary artery disease or negative CT angiography. These subjects were used to establish a reference range of TID. In the remaining 203 patients with an intermediate or high pretest likelihood, subgroups with normal and abnormal TID were established and compared with respect to clinical variables, perfusion defect scores, left ventricular function, and absolute myocardial flow reserve. Follow-up was obtained for 969 ± 328 d to determine mortality by review of the social security death index. RESULTS: In the reference group, TID ratio was 0.98 ± 0.06. Accordingly, a threshold for abnormal TID was set at greater than 1.13 (0.98 + 2.5 SDs). In the study group, 19 of 203 patients (9%) had an elevated TID ratio. Significant differences between subgroups with normal and abnormal TID ratio were observed for ejection fraction reserve (5.0 ± 6.4 vs. 1.8 ± 7.9; P < 0.05), difference between end-systolic volume (ESV) at rest and stress (ΔESV[stress-rest]; 1.8 ± 7.4 vs. 12.3 ± 13.0 mL; P < 0.0001), difference between end-diastolic volume (EDV) at rest and stress (ΔEDV[stress-rest]; 10.8 ± 11.5 vs. 23.8 ± 14.6 mL; P < 0.0001), summed rest score (1.8 ± 3.8 vs. 3.8 ± 7.6; P < 0.05), summed stress score (3.0 ± 5.4 vs. 7.5 ± 9.8; P < 0.002), summed difference score (1.3 ± 2.6 vs. 3.7 ± 5.3; P < 0.02), and global myocardial flow reserve (2.1 ± 0.8 vs. 1.7 ± 0.6; P < 0.02). Additionally, TID-positive patients had a significantly lower overall survival probability (P < 0.05). In a subgroup analysis of patients without regional perfusion abnormalities, TID-positive patients' overall survival probability was significantly smaller (P < 0.03), and TID was an independent predictor (exponentiation of the B coefficients [Exp(b)] = 6.22; P < 0.009) together with an ejection fraction below 45% (Exp[b] = 6.16; P < 0.002). CONCLUSION: The present study suggests a reference range of TID for (82)Rb PET myocardial perfusion imaging that is in the range of previously established values for SPECT. Abnormal TID in (82)Rb PET is associated with more extensive left ventricular dysfunction, ischemic compromise, and reduced global flow reserve. Preliminary outcome analysis suggests that TID-positive subjects have a lower overall survival probability.

Assessment of coronary vasoreactivity by multidetector computed tomography: feasibility study with rubidium-82 cardiac positron emission tomography.

BACKGROUND: Positron emission tomography (PET) during the cold pressor test (CPT) has been used to assess endothelium-dependent coronary vasoreactivity, a surrogate marker of cardiovascular events. However, its use remains limited by cardiac PET availability. As multidetector computed tomography (MDCT) is more widely available, we aimed to develop a measurement of endothelium-dependent coronary vasoreactivity with MDCT and similar radiation burden as with PET. METHODS AND RESULTS: A study group of 18 participants without known cardiovascular risk factor (9F/9M; age 60±6 years) underwent cardiac PET with (82)Rb and unenhanced ECG-gated MDCT within 4h, each time at rest and during CPT. The relation between absolute myocardial blood flow (MBF) response to CPT by PET (ml·min(-1)·g(1)) and relative changes in MDCT-measured coronary artery surface were assessed using linear regression analysis and Spearman's correlation. MDCT and PET/CT were analyzed in all participants. Hemodynamic conditions during CPT at MDCT and PET were similar (P>0.3). Relative changes in coronary artery surface because of CPT (2.0-21.2%) correlated to changes in MBF (-0.10-0.52ml·min(-1)·g(1)) (ρ=0.68, P=0.02). Effective dose was 1.3±0.2mSv for MDCT and 3.1mSv for PET/CT. CONCLUSIONS: Assessment of endothelium-dependent coronary vasoreactivity using MDCT CPT appears feasible. Because of its wider availability, shorter examination time and similar radiation burden, MDCT could be attractive in clinical research for coronary status assessment.

In vivo assessment of myocardial glucose uptake by positron emission tomography in adults with the PRKAG2 cardiac syndrome.

BACKGROUND: The PRKAG2 cardiac syndrome is an inherited metabolic disease of the heart characterized by excessive myocardial glycogen deposition. The biochemical alterations associated with this condition remain controversial and have not previously been studied in affected humans. METHODS AND RESULTS: Positron emission tomography (PET) imaging was used to quantitatively assess myocardial glucose uptake (MGU) in 6 adult subjects with the PRKAG2 cardiac syndrome and 6 healthy, matched control subjects using the glucose analogue (18)F-Fluoro-2-deoxyglucose (FDG). Studies were performed under a euglycemic hyperinsulinemic clamp to ensure stable blood glucose levels. Rubidium-82 perfusion scans were performed to ensure that myocardial differences in myocardial glucose uptake were not the result of significant myocardial scar. In adult patients with phenotypic expression of disease, the median myocardial glucose uptake of the left ventricle was 0.18 mumol/min/g (interquartile range, 0.14, 0.24), compared with 0.40 mumol/min/g (interquartile range, 0.30 to 0.45) in the control group (P=0.01). The median blood glucose during FDG-PET imaging was 4.72 mmol/L (interquartile range, 4.32 to 4.97) in the PRKAG2 group and 4.38 mmol/L (interquartile range, 3.90, 4.79) in the control group (P=NS). The significant decrease observed in myocardial glucose uptake in affected patients occurred in the absence of significant myocardial scar. CONCLUSIONS: The PRKAG2 cardiac syndrome is associated with a reduction of glucose uptake in adult patients affected with this genetic condition. In this pilot study, (18)F-FDG-PET imaging is a useful tool to assess alterations in myocardial glucose transport in this inherited metabolic disease and provide insight into the biochemical pathophysiology of the diseased state.