Phase I, first-in-human study of XTR004, a novel 18F-labeled tracer for myocardial perfusion PET: Biodistribution, radiation dosimetry, pharmacokinetics, and safety after a single injection at rest.

OBJECTIVES: This study assessed the imaging characteristics, pharmacokinetics and safety of XTR004, a novel 18F-labeled Positron Emission Tomography (PET) myocardial perfusion imaging tracer, after a single injection at rest in humans. METHODS: Eleven healthy subjects (eight men and three women) received intravenous XTR004 (239-290 megabecquerel [MBq]). Safety profiles were monitored on the dosing day and three follow-up visits. Multiple whole-body PET scans were conducted over 4.7 h to evaluate biodistribution and radiation dosimetry. Blood and urine samples collected for 7.25 h were metabolically corrected to characterize pharmacokinetics. RESULTS: In the first 0-12 min PET images of ten subjects, liver (26.81 ± 4.01), kidney (11.43 ± 2.49), lung (6.75 ± 1.76), myocardium (4.72 ± 0.67) and spleen (3.1 ± 0.84) exhibited the highest percentage of the injected dose (%ID). Myocardial uptake of XTR004 in the myocardium initially reached 4.72 %ID and 7.06 g/mL, and negligibly changed within an hour (Δ: 7.20%, 5.95%). The metabolically corrected plasma peaked at 2.5 min (0.0013896 %ID/g) and halved at 45.2 min. Whole-body effective dose was 0.0165 millisievert (mSv)/MBq. Cumulative urine excretion was 8.18%. Treatment-related adverse events occurred in seven out of eleven subjects (63.6%), but no severe adverse event was reported. CONCLUSIONS: XTR004 demonstrated a favorable safety profile, rapid, high, and stable myocardial uptake and excellent potential for PET myocardial perfusion imaging (MPI). Further exploration of XTR004 PET MPI for detecting myocardial ischemia is warranted.

Feasibility of myocardial blood flow quantification to detect flow-limited coronary artery disease with a one-day rest/stress continuous rapid imaging protocol on cardiac-dedicated cadmium zinc telluride single photon emission computed tomography.

BACKGROUND: It is clinically needed to explore a more efficient imaging protocol for single photon emission computed tomography (SPECT) myocardial blood flow (MBF) quantitation derived from cadmium zinc telluride (CZT) SPECT camera for the routine clinical utilization. METHODS: One hundred and twenty patients with matched clinical characteristics and angiographic findings who completed one-day rest/stress SPECT imaging with either the intermittently sequential imaging (ISI) protocol (two dynamic and two electrocardiography (ECG)-gated scans) or the continuous rapid imaging (CRI) protocol (two dynamic/ECG-gated scans) were included. MBF quantitation adopted residual activity correction (RAC) to correct for rest residual activity (RRA) in the stress dynamic SPECT scan for the detection of flow-limited coronary artery disease. RESULTS: The CRI protocol reduced about 6.2 times shorter than the ISI protocol (25.5 min vs 157.6 min), but slightly higher than the RRA (26.7% ± 3.6% vs 22.3% ± 4.9%). With RAC, both protocols demonstrated close stress MBF (2.18 ± 1.13 vs 2.05 ± 1.10, P > 0.05) and myocardial flow reserve (MFR) (2.42 ± 1.05 vs 2.48 ± 1.11, P > 0.05) to deliver comparable diagnostic performance (sensitivity = 82.1%-92.3%, specificity = 81.2%-91.2%). Myocardial perfusion and left ventricular function overall showed no significant difference (all P > 0.26). CONCLUSION: One-day rest/stress SPECT with the CRI protocol and rest RAC is feasible to warrant the diagnostic performance of MBF quantitation with a shortened examination time and enhanced patient comfort. Further evaluation on the impact of extracardiac activity to regional MBF and perfusion pattern is required. Additional evaluation is needed in a patient population that is typical of those referred for SPECT MPI, including those with known or suspected coronary microvascular disease.

SPECT myocardial blood flow quantitation for the detection of angiographic stenoses with cardiac-dedicated CZT SPECT.

PURPOSE: CZT SPECT with the enhanced imaging characteristic facilitates SPECT myocardial blood flow (MBF) quantitation moving toward a clinical utility to uncover myocardial ischemia. The purpose of this study was to investigate the diagnostic performance of stress MBF, myocardial flow reserve (MFR) and myocardial flow capacity (MFC) derived from CZT SPECT in the detection of coronary artery disease (CAD). METHODS: One-hundred and eighty patients underwent two-day rest/adenosine-stress scans for SPECT MBF quantitation. All dynamic SPECT images were reconstructed and corrected with necessary corrections. The one-tissue two-compartment kinetic model was utilized to fit kinetic parameters (K1, k2 and FBV) by numeric optimization and converted to MBF from K1. Rest MBF, stress MBF and MFR in left ventricle and coronary territories were calculated from flow polar maps. MFC was assessed by extents of moderately and severely abnormal flow statuses using an integrated flow diagram. Per-patient and per-vessel analyses were performed to determine cutoff values for the detection of angiographically obstructive and flow-limited CAD. RESULTS: Using the threshold of ≥ 50% stenosis, 149 patients (82.78%) were classified to have obstructive lesions in 355 vessels (65.74%). Using the threshold of ≥ 70% stenosis, 113 patients (62.78%) were classified to have flow-limited lesions in 282 vessels (52.22%). On per-patient analysis, the optimal cutoff values of stress MBF and MFR to detect ≥ 50% stenosis were (1.44 ml/min/g, 1.96) and (1.34 ml/min/g and 1.75) to detect ≥ 70% stenosis. The optimal cutoff values for severely and combined moderately severely abnormal MFC extents were (2.3-2.5%, 23.1%) and (7.5%, 29.4%), respectively. The overall sensitivity of MFC (0.84-0.86, 0.86-0.90) to detect ≥ 50% and ≥ 70% lesions surpassed those of stress MBF (0.78. 0.78) and MFR (0.80, 0.75) (all p < 0.05) with similar specificity (MFC = 0.84-0.90, 0.87-0.91; stress MBF = 0.87, 0.91; MFR = 0.84, 0.89) (all p≥ 0.05). CONCLUSION: The non-invasive SPECT MBF quantitation using CZT SPECT is a reliable method to detect angiographically obstructive and flow-limited CAD. Myocardial flow capacity can outperform with higher diagnostic sensitivity than stress MBF or MFR alone.

Diagnostic value of quantitative myocardial blood flow assessment by NaI(Tl) SPECT in detecting significant stenosis: a prospective, multi-center study.

OBJECTIVES: The aim of this prospective multi-center study was to investigate the diagnostic value of myocardial blood flow (MBF) quantification using NaI(Tl)-based single-photon emission computed tomography (SPECT) for determining coronary artery disease (CAD) defined by quantitative coronary angiography (QCA). BACKGROUND: Absolute quantitation of MBF and myocardial flow reserve (MFR) using SPECT is clinically feasible; however, whether flow quantification using NaI(Tl) SPECT is superior to commonly performed SPECT myocardial perfusion imaging (MPI) in determining CAD has not been evaluated. METHODS: Patients with suspected or known CAD underwent pharmacological stress/rest dynamic SPECT imaging and routine SPECT MPI followed by QCA. Obstructive disease was defined as ≥ 50% reduction in luminal diameter on QCA. RESULTS: One hundred fifty-four patients (462 vessels) were included in the analysis. Obstructive CAD was detected in 76/154 patients (49.4%) and 112/462 vessels (24.2%). Optimal cut-off values were 1.86 mL/min/g for stress MBF and 1.95 for MFR, respectively. Stress MBF and MFR were more sensitive than MPI in both individual patients (stress MBF vs MPI: 81.6% vs 51.3%; MFR vs MPI: 72.4% vs 51.3%) and in coronary vascular regions (stress MBF vs MPI: 78.6% vs 31.3%; MFR vs MPI: 75.9% vs 31.3%; all P < .01). In receiver operating characteristic curve analysis, quantification revealed a significantly greater area under the curve than MPI at the patient (stress MBF vs MPI: 0.761 vs 0.641; MFR vs MPI: 0.770 vs 0.641) and the vessel (stress MBF vs MPI: 0.745 vs 0.613; MFR vs MPI: 0.756 vs 0.613; all P < .05) levels. Integrating quantitative SPECT measures with MPI significantly increased the area under the curve and improved the discriminatory and reclassification capacity. CONCLUSION: Flow quantification using NaI(Tl) SPECT provides superior sensitivity and discriminatory capacity to MPI in detecting significant stenosis. Clinical trial registration NCT03637725.

Absolute Resting 13N-Ammonia PET Myocardial Blood Flow for Predicting Myocardial Viability and Recovery of Ventricular Function after Coronary Artery Bypass Grafting.

OBJECTIVE: We aimed to evaluate the feasibility of resting myocardial blood flow (rMBF), quantified with dynamic 13 N-Ammonia (NH3) PET, for identifying myocardial viability and predicting improvement of left ventricular ejection fraction (LVEF) after coronary artery bypass grafting (CABG). METHODS: Ninety-three patients with coronary artery disease (CAD) and chronic LVEF < 45%, scheduled for CABG, had dynamic 13NH3 PET and 18F-FDG PET imaging. The perfusion/metabolism polar maps were categorized in four patterns: normal (N), mismatch (M1), match (M2) and reverse mismatch (RM). The value of rMBF for identifying viable myocardium (M1, RM) and post CABG improvement of LVEF≥8% was analyzed by receiver operating characteristic (ROC) curves. Correlations of rMBF in segments to ΔLVEF post CABG were verified. RESULTS: Mean rMBFs were significantly different (N=0.60±0.14; M1=0.44±0.07, M2=0.34±0.08, RM=0.53±0.09 ml/min/g, P<0.001). The optimal rMBF cutoff to identify viable myocardium was 0.42 ml/min/g (sensitivity=88.3%, specificity=82.0%) and 0.43 ml/min/g for predicting improvement of LVEF ≥8% (74.6%, 80.0%). The extent and rMBF of combined M1/RM demonstrated a moderate to high correlation to improved LVEF (r=0.78, 0.71, P<0.001). CONCLUSION: Resting MBF, derived by dynamic 13NH3 PET, may be positioned as a supplement to 18F-FDG PET imaging for assessing the presence of viable myocardium and predicting potential improvement of LVEF after CABG.

Characterization of myocardial oxidative metabolism and myocardial external efficiency in high-risk alcohol cardiotoxicity and alcoholic cardiomyopathy via dynamic 11C-Acetate positron emission tomography.

INTRODUCTION: The purpose of this study was to evaluate subjects with high-risk alcohol cardiotoxicity and patients with alcoholic cardiomyopathy (ACM) via dynamic 11C-Acetate positron emission tomography (PET) imaging as a myocardial oxidative metabolic probe. METHODS AND RESULTS: We recruited 37 subjects with chronic alcohol consumption [18 with moderate consumption (MC), 19 with heavy consumption (HC)], 5 ACM patients, and 12 healthy controls to receive dynamic 11C-Acetate PET scans. PET imaging data were analyzed to calculate kinetic parameters (e.g., Kmono, K1 and k2) based on the mono-exponential and one-tissue compartmental models. Myocardial oxygen consumption (MVO2) and myocardial external efficiency (MEE) were then derived from these kinetic parameters. MVO2 was significantly lowered in the HC group and in ACM patients (0.121± 0.018 and 0.111 ± 0.017 mL·g-1·min-1, respectively) compared with those in healthy controls and MC subjects (0.144 ± 0.023 and 0.146 ± 0.027 mL·g-1·min-1, respectively; P < .01). MEE was significantly reduced in ACM patients (13.0% ± 4.3%) compared with those of healthy controls (22.4% ± 4.6%, P < .01), MC subjects (20.1% ± 4.5%, P < .05), and HC subjects (22.3% ± 4.5%, P < .001). CONCLUSION: Functional assessment via dynamic 11C-Acetate PET imaging may represent a clinically feasible probe for identifying cohorts with high-risk cardiotoxicity due to addictive alcohol consumption and ACM.

Assessment of cardiac amyloidosis with 99mTc-pyrophosphate (PYP) quantitative SPECT.

BACKGROUND: 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT. METHOD: Thirty-seven consecutive patients who underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in the myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis, and other pathogens (others) and among categories of Perugini visual scores (grades 0-3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated. RESULTS: The ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in the myocardium and blood-pool was [y = 1.424 × (1 - exp(- 0.759 × x)) + 0.104]. SUVmax of ATTR-CM (7.50 ± 2.68) was significantly higher than those of AL (1.96 ± 0.35) and others (2.00 ± 0.74) (all p < 0.05). SUVmax of grade 3 (8.95 ± 1.89) and grade 2 (4.71 ± 0.23) were also significantly higher than those of grade 1 (1.92 ± 0.31) and grade 0 (1.59 ± 0.39) (all p < 0.05). Correlation coefficient (R2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra = - 0.14; inter = - 0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877. CONCLUSIONS: 99mTc-PYP quantitative SPECT integrated with adjustable PVC factors is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

99mTc-3SPboroxime: A neutral 99mTc(III) radiotracer with high heart uptake and long myocardial retention.

BACKGROUND: 99mTc-3SPboroxime is a 99mTc(III) complex with high initial heart uptake comparable to that of 99mTc-Teboroxime, but with significantly longer myocardial retention in Sprague-Dawley rats. This study was performed to demonstrate its feasibility on myocardial perfusion imaging and myocardial blood flow quantification in swine models. METHODS: Dynamic single-photon emission computed tomography (SPECT) studies with 99mTc-3SPboroxime were performed in normal (with/without dipyridamole, n = 9) and acute myocardial infarction (AMI) swine (n = 3) in comparison with 99mTc-Teboroxime and 99mTc-Sestamibi. List-mode acquisitions were immediately started after injection and continued for 15 minutes. Regions of interest were drawn on heart (infarct and remote areas of AMI swine) and liver to generate time activity curves. Heart/liver and infarct/remote radioactivity ratios were calculated. One-tissue compartment model was implemented to obtain K1 and K2 values. RESULTS: The initial heart uptake of 99mTc-3SPboroxime was close to that of 99mTc-Teboroxime, but higher than that of 99mTc-Sestamibi. 99mTc-3SPboroxime had a myocardial retention longer than that of 99mTc-Teboroxime. The heart/liver ratio of 99mTc-3SPboroxime was higher than that of 99mTc-Teboroxime at later stage (13-15 minutes post-injection). The K1 value of 99mTc-3SPboroxime was much higher than that of 99mTc-Sestamibi, and the K2 value was significantly lower than that of 99mTc-Teboroxime both at rest and dipyridamole stress (rest K1: 0.63 ± 0.11 vs 0.40 ± 0.04 mL·min-1·g-1, P = 0.027; stress K1: 0.89 ± 0.05 vs 0.54 ± 0.08 mL·min-1·g-1, P = 0.031; rest K2: 0.22 ± 0.04 vs 0.33 ± 0.11 mL·min-1·g-1, P = 0.003; stress K2: 0.31 ± 0.03 vs 0.60 ± 0.30 mL·min-1·g-1, P = 0.047). High quality SPECT images could be obtained in any of the 5 minutes windows over the first 15 minutes after injection of 99mTc-3SPboroxime in normal and AMI swine models. Apical and anterior perfusion defects were clearly visualized in AMI swine. CONCLUSION: 99mTc-3SPboroxime is a promising radiotracer for future clinical translation considering its heart uptake, heart/liver ratio and SPECT image quality, as well as the advantage over 99mTc-Sestamibi in the definition of stress flow.

A method to measure the extent of myocardial ischemia and steal with SPECT myocardial blood flow quantitation.

OBJECTIVE: We introduced a method to measure the extent of myocardial ischemia and steal with SPECT MBF quantitation. METHODS: Eighty-seven patients who received rest/Dipyridamole-stress 99mTc-Sestamibi (MIBI) dynamic SPECT scans and coronary angiography were included. Dynamic SPECT images were reconstructed with full physical corrections. The one-tissue kinetic model was utilized to quantify K1 and further converted to MBF with required corrections. Rest MBF, stress MBF and myocardial flow reserve (MFR) were converted to a flow status polar map by a flow diagram. Extents of 7 flow statuses were verified their cutoff points for detecting stenoses. The diagnostic performance (DP) was compared to that of MFR. RESULTS: Cutoff point of the extent to detect ≥ 50% stenosis was 3.01% for ischemia-steal status and 20.3% for the combined status of ischemia-steal and moderate. Using these criteria, sensitivity, specificity and accuracy to detect ≥ 50% stenosis were (80%, 75%, 79%) and (86%, 68%, 80%) for ≥ 70% stenosis. The DP was superior to that of MFR < 2.0 criterion (≥ 50%: 70%, 63%, 69%; ≥ 70%: 73%, 61%, 69%) (all p < 0.015). CONCLUSION: SPECT MBF quantitation integrated with the flow diagram can measure the extent of myocardial ischemia and steal which appeared more accurate to detect angiographic stenoses than the single MFR parameter.

Simplified quantification of 13N-ammonia PET myocardial blood flow: A comparative study with the standard compartment model to facilitate clinical use.

BACKGROUND: Short imaging protocol to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) may enhance the clinical application of 13N-ammonia cardiac PET. We assessed the flow quantitation of 13N-ammonia PET implementing simple retention model and two-compartment model. METHODS: Fourteen healthy volunteers (HVT) and twenty-three clinical patients received 13N-ammonia PET/CT. The simple retention model used the first 7-minute image to quantify MBF. Global and regional MBF and MFR of the two models were compared. RESULTS: Global and regional MBF and MFR of these two models were highly correlated with mildly inferior correlation in RCA territory (global R2: rest MBF = 0.79, stress MBF = 0.65, MFR = 0.77; regional R2: rest MBF ≥ 0.72, stress MBF ≥ 0.52, MFR ≥ 0.68). There were significant differences for MFR (4.04 ± 0.72, 3.66 ± 0.48, p = .02) and rest MBF (0.69 ± 0.12, 0.78 ± 0.12, p = .02) between the two models in the HVT group. CONCLUSIONS: 13N-ammonia global and regional MBF and MFR from the simple retention model demonstrate strong correlations with that from the two-compartment model. Significant differences of MFR and rest MBF are noted in the HVT group, with a proposed normal reference value for the 13N-ammonia short simple retention protocol.

Myocardial blood flow quantitation in patients with congestive heart failure: head-to-head comparison between rapid-rotating gantry SPECT and CZT SPECT.

PURPOSE: Recently, the feasibility of myocardial blood flow (MBF) quantitation using rapid-rotating gantry (RRG) and cadmium-zinc-telluride (CZT) SPECT cameras has been demonstrated. We compared MBF quantitation using these two camera systems. METHODS: Twenty patients with congestive heart failure (CHF) and 20 patients without CHF (non-CHF) were included. On two consecutive days, dynamic SPECT imaging was performed after a bolus injection of 20 mCi of 99mTc-Sestamibi (MIBI) with RRG-SPECT and list-mode acquisition with CZT-SPECT. All dynamic SPECT images were reconstructed with full physical corrections, corrections for ventricular spillover and partial volume effect, using one-tissue kinetic modeling. Resting MBF converted from K1 was then corrected for MIBI extraction fraction and adjusted for rate-pressure product. RESULTS: In both patient groups, there was no significant difference between resting MBF values measured with RRG-SPECT and CZT-SPECT systems (P = 0.06, P = 0.2 respectively). For CHF patients, linear regression (LR) was y(RRG) = 1.0412x (CZT) (r = 0.97) with a small systemic difference (Δ = 0.03 mL·min-1·g-1, 95% CI - 0.11 to 0.20) by Bland-Altman analysis. For non-CHF patients, LR was y(RRG) = 1.025x (CZT) (r = 0.89) with also small systemic difference (ΔT= 0.02 mL·min-1·g-1, 95% CI - 0.14 to 0.19) in BA analysis. CONCLUSION: Physical corrections along with other image corrections can provide comparable MBF quantitations in both CHF and non-CHF patients, regardless of the type of SPECT systems used.

Improved image resolution on thoracic carcinomas by quantitative 18F-FDG coincidence SPECT/CT in comparison to 18F-FDG PET/CT.

Currently, 18F-FDG coincidence SPECT (Co-SPECT)/CT scan still serves as an important tool for diagnosis, staging, and evaluation of cancer treatment in developing countries. We implemented full physical corrections (FPC) to Co-SPECT (quantitative Co-SPECT) to improve the image resolution and contrast along with the capability for image quantitation. FPC included attenuation, scatter, resolution recovery, and noise reduction. A standard NEMA phantom filled with 10:1 F-18 activity concentration ratio in spheres and background was utilized to evaluate image performance. Subsequently, 15 patients with histologically confirmed thoracic carcinomas were included to undergo a 18F-FDG Co-SPECT/CT scan followed by a 18F-FDG PET/CT scan. Functional parameters as SUVmax, SUVmean, SULpeak, and MTV from both quantitative Co-SPECT and PET were analyzed. Image resolution of Co-SPECT for NEMA phantom was improved to reveal the smallest sphere from a diameter of 28 mm to 22 mm (17 mm for PET). The image contrast was enhanced from 1.7 to 6.32 (6.69 for PET) with slightly degraded uniformity in background (3.1% vs. 6.7%) (5.6% for PET). Patients' SUVmax, SUVmean, SULpeak, and MTV measured from quantitative Co-SPECT were overall highly correlated with those from PET ( r=0.82-0.88). Adjustment of the threshold of SUVmax and SUV to determine SUVmean and MTV did not further change the correlations with PET ( r=0.81-0.88). Adding full physical corrections to Co-SPECT images can significantly improve image resolution and contrast to reveal smaller tumor lesions along with the capability to quantify functional parameters like PET/CT.

Noninvasive Nuclear SPECT Myocardial Blood Flow Quantitation to Guide Management for Coronary Artery Disease.

Recently, myocardial blood flow quantitation with dynamic SPECT has been validated to enhance the detection of multivessel coronary artery disease (CAD) and conclude equivocal SPECT myocardial perfusion study. This advance opened an important clinical application to utilize the tool in guiding CAD management for area where myocardial perfusion tracers for PET are unavailable or unaffordable. We present a clinical patient with ongoing recursive angina who underwent multiple nuclear stress tests for a sequence of CAD evaluation in 26 months and demonstrated that SPECT myocardial blood flow quantitation properly guided CAD management to warrant patient outcome.

Avoiding full corrections in dynamic SPECT images impacts the performance of SPECT myocardial blood flow quantitation.

INTRODUCTION: This study investigated the performance of SPECT myocardial blood flow (MBF) quantitation lacking full physical corrections (All Corr) in dynamic SPECT (DySPECT) images. METHODS: Eleven healthy normal volunteers (HVT) and twenty-four patients with angiography-documented CAD were assessed. All Corr in 99mTc-sestamibi DySPECT encompassed noise reduction (NR), resolution recovery (RR), and corrections for scatter (SC) and attenuation (AC), otherwise no correction (NC) or only partial corrections. The performance was evaluated by quality index (R 2) and blood-pool spillover index (FBV) in kinetic modeling, and by rest flow (RMBF) and stress flow (SMBF) compared with those of All Corr. RESULTS: In HVT group, NC diminished 2-fold flow uniformity with the most degraded quality (15%-18% reduced R 2) and elevated spillover effect (45%-50% increased FBV). Consistently higher RMBF and SMBF were discovered in both groups (HVT 1.54/2.31 higher; CAD 1.60/1.72; all P < .0001). Bland-Altman analysis revealed positive flow bias (HVT 0.9-2.6 mL/min/g; CAD 0.7-1.3) with wide ranges of 95% CI of agreement (HVT NC -1.9-7.1; NR -0.4-4.4; NR + SC -1.1-4.3; NR + SC + RR -0.7-2.5) (CAD NC -1.2-3.8; NR -1.0-2.8; NR + SC -1.0-2.5; NR + SC + RR -1.1-2.6). CONCLUSIONS: Uncorrected physical interference in DySPECT images can extensively impact the performance of MBF quantitation. Full physical corrections should be considered to warrant this tool for clinical utilization.

SPECT myocardial blood flow quantitation toward clinical use: a comparative study with 13N-Ammonia PET myocardial blood flow quantitation.

OBJECTIVES: The aim of this study was to evaluate the accuracy of myocardial blood flow (MBF) quantitation of 99mTc-Sestamibi (MIBI) single photon emission computed tomography (SPECT) compared with 13N-Ammonia (NH3) position emission tomography (PET) on the same cohorts. BACKGROUND: Recent advances of SPECT technologies have been applied to develop MBF quantitation as a promising tool to diagnose coronary artery disease (CAD) for areas where PET MBF quantitation is not available. However, whether the SPECT approach can achieve the same level of accuracy as the PET approach for clinical use still needs further investigations. METHODS: Twelve healthy volunteers (HVT) and 16 clinical patients with CAD received both MIBI SPECT and NH3 PET flow scans. Dynamic SPECT images acquired with high temporary resolution were fully corrected for physical factors and processed to quantify K1 using the standard compartmental modeling. Human MIBI tracer extraction fraction (EF) was determined by comparing MIBI K1 and NH3 flow on the HVT group and then used to convert flow values from K1 for all subjects. MIBI and NH3 flow values were systematically compared to validate the SPECT approach. RESULTS: The human MIBI EF was determined as [1.0-0.816*exp(-0.267/MBF)]. Global and regional MBF and myocardial flow reserve (MFR) of MIBI SPECT and NH3 PET were highly correlated for all subjects (global R2: MBF = 0.92, MFR = 0.78; regional R2: MBF ≥ 0.88, MFR ≥ 0.71). No significant differences for rest flow, stress flow, and MFR between these two approaches were observed (All p ≥ 0.088). Bland-Altman plots overall revealed small bias between MIBI SPECT and NH3 PET (global: ΔMBF = -0.03Lml/min/g, ΔMFR = 0.07; regional: ΔMBF = -0.07 - 0.06 , ΔMFR = -0.02 - 0.22). CONCLUSIONS: Quantitation with SPECT technologies can be accurate to measure myocardial blood flow as PET quantitation while comprehensive imaging factors of SPECT to derive the variability between these two approaches were fully addressed and corrected.

SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

Feasibility and operator variability of myocardial blood flow and reserve measurements with 99mTc-sestamibi quantitative dynamic SPECT/CT imaging.

PURPOSE: Myocardial blood flow (MBF) quantification with dynamic SPECT could lead to widespread utilization of MBF imaging in clinical practice with little cost increase over current standard SPECT myocardial perfusion imaging. This work evaluates the feasibility and operator-dependent variability of MBF and flow reserve measurements with (99m)Tc-sestamibi (MIBI) dynamic SPECT imaging using a standard dual-head SPECT camera. METHODS: Twenty-eight patients underwent dipyridamole-stress and rest imaging with dynamic SPECT/CT acquisition. Quantitative images were iteratively reconstructed with all physical corrections and then myocardial and arterial blood regions of interest (ROI) were defined semi-automatically. A compartmental model was fitted to these ROI-sampled time-activity-curves, and flow-dependent MIBI extraction correction was applied to derive regional MBF values. Myocardial flow reserve (MFR) was estimated as stress/rest MBF ratio. MBF and MFR in low and high risk populations were evaluated for ability to detect disease. Images were each processed twice (≥7 days apart) by one expert and one novice operator to evaluate intra- and inter-operator variability of MBF and MFR measurement in the three coronary artery vascular territories. RESULTS: Mean rest flow, stress flow, and MFR values were 0.83, 1.82 mL·minute(-1)·g(-1), and 2.45, respectively. For stress/rest MFR, the inter-operator reproducibility was r(2) = 0.86 with RPC = 1.1. Stress MBF and MFR were significantly reduced (P < .05) in high risk (n = 9) vs low risk populations (n = 19), indicating ability to detect disease. For expert and novice operators very good intra-operator correlations of r(2) = 0.98 and 0.95 (n = 168, P < .001) were observed for combined rest and stress regional flow values. Bland-Altman reproducibility coefficients (RPC) were 0.25 and 0.47 mL·minute(-1)·g(-1) for the expert and novice operators, respectively (P < .001). Inter-operator correlation was r(2) = 0.91 and Bland-Altman RPC = 0.58 mL·minute(-1)·g(-1) (n = 336). CONCLUSIONS: MBF and reserve measurements using (99m)Tc-sestamibi on a traditional, two-headed camera with fast rotation and with quantitative dynamic SPECT appears to be feasible, warranting further investigation.