Gated SPECT-Derived Myocardial Strain Estimated From Deep-Learning Image Translation Validated From N-13 Ammonia PET.

RATIONALE AND OBJECTIVES: This study investigated the use of deep learning-generated virtual positron emission tomography (PET)-like gated single-photon emission tomography (SPECTVP) for assessing myocardial strain, overcoming limitations of conventional SPECT. MATERIALS AND METHODS: SPECT-to-PET translation models for short-axis, horizontal, and vertical long-axis planes were trained using image pairs from the same patients in stress (720 image pairs from 18 patients) and resting states (920 image pairs from 23 patients). Patients without ejection-fraction changes during SPECT and PET were selected for training. We independently analyzed circumferential strains from short-axis-gated SPECT, PET, and model-generated SPECTVP images using a feature-tracking algorithm. Longitudinal strains were similarly measured from horizontal and vertical long-axis images. Intraclass correlation coefficients (ICCs) were calculated with two-way random single-measure SPECT and SPECTVP (PET). ICCs (95% confidence intervals) were defined as excellent (≥0.75), good (0.60-0.74), moderate (0.40-0.59), or poor (≤0.39). RESULTS: Moderate ICCs were observed for SPECT-derived stressed circumferential strains (0.56 [0.41-0.69]). Excellent ICCs were observed for SPECTVP-derived stressed circumferential strains (0.78 [0.68-0.85]). Excellent ICCs of stressed longitudinal strains from horizontal and vertical long axes, derived from SPECT and SPECTVP, were observed (0.83 [0.73-0.90], 0.91 [0.85-0.94]). CONCLUSION: Deep-learning SPECT-to-PET transformation improves circumferential strain measurement accuracy using standard-gated SPECT. Furthermore, the possibility of applying longitudinal strain measurements via both PET and SPECTVP was demonstrated. This study provides preliminary evidence that SPECTVP obtained from standard-gated SPECT with postprocessing potentially adds clinical value through PET-equivalent myocardial strain analysis without increasing the patient burden.

Prediction of cardiac allograft vasculopathy using splenic switch-off on myocardial PET.

BACKGROUND: Heart transplantation (HTx) is a definitive therapy for refractory heart failure. Cardiac allograft vasculopathy (CAV), characterized by diffuse arteriopathy involving the epicardial coronary arteries and microvasculature, is the major cause of death for patients with HTx. 13N-ammonia positron emission tomography (NH3-PET) can offer diagnostic and prognostic utility for CAV. The splenic switch-off (SSO) detected in NH3-PET is a hemodynamic indicator of favorable response to adenosine. We hypothesized that both CAV and SSO reflected a pathology that progresses in parallel with systemic vascular endothelial dysfunction. Therefore, we quantitatively evaluated splenic adenosine reactivity measured using NH3-PET as an index of endothelial function, and examined its predictability for CAV. METHODS: Forty-eight patients who underwent NH3-PET after HTx were analyzed. The spleen ratio was calculated as the mean standardized uptake value, measured by placing an ROI on the spleen, at stress divided by that at rest. SSO was defined by a cutoff determined using receiver operating characteristic (ROC) analysis for the spleen ratio. The endpoint was appearance or progression of CAV. Predictability of SSO was analyzed using Kaplan-Meier analysis. RESULTS: The endpoint occurred in 9 patients during a mean follow-up of 45 ±â€¯17 months. ROC curve analysis demonstrated a cutoff of 0.94 for spleen ratio. Patients without SSO displayed a significantly higher CAV rate than those with SSO (p = 0.022). CONCLUSIONS: SSO reflects the endothelial function of systemic blood vessels and was a predictor of CAV in patients with HTx.

Risk Stratification Using Right Ventricular Longitudinal Strain Ratio Derived from 13N-Ammonia PET in Patients with Ischemic Heart Disease.

Purpose To investigate whether right ventricular (RV) myocardial strain ratio (RVMSR) assessed using nitrogen 13 ammonia (13N-NH3) PET can predict cardiovascular events in patients with ischemic heart disease (IHD). Materials and Methods This retrospective study included 480 consecutive patients (mean age, 66 years ± 12 [SD]; 334 males and 146 females) with IHD who underwent 13N-NH3 PET. RVMSR was defined as the ratio of RV strain during stress to that at rest. The primary end point was major adverse cardiac events (MACEs), defined as cardiac death or heart failure hospitalization. The ability of RVMSR to predict MACE was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) with 95% CIs. Results ROC curve analysis identified a sensitivity and specificity of 84% and 82%, respectively, for predicting MACE from RVMSR. Patients with reduced RVMSR (<110.2) displayed a significantly higher rate of MACE than those with a preserved RVMSR (34 of 240 vs four of 240; P < .001). Cox proportional hazards regression analysis of imaging parameters, including myocardial flow reserve, indicated that RVMSR was an independent predictor of MACE (HR, 0.94 [95% CI: 0.92, 0.97]; P < .001). Conclusion RVMSR was an independent predictor of MACE and has potential to aid in the risk stratification of patients with IHD. Keywords: Right Ventricular Myocardial Strain Ratio, Myocardial Flow Reserve, Ischemic Heart Disease, 13N-Ammonia Positron Emission Tomography Supplemental material is available for this article. © RSNA, 2024.

Prognostic value of right atrial strain in systemic sclerosis based on tissue tracking analysis using cine cardiac magnetic resonance imaging: a retrospective observational study.

Interstitial lung disease and cardiac involvement are common manifestations and prognostic factors of systemic sclerosis. However, it is unclear whether impaired right atrial function associated with interstitial lung disease in systemic sclerosis can be used as a prognostic factor in this patient population. Therefore, this study aimed to investigate the relationship between right atrial function, interstitial lung disease, and prognosis in patients with systemic sclerosis using tissue tracking analysis with cine cardiac magnetic resonance imaging. In this retrospective observational study, a total of 40 patients with systemic sclerosis were enrolled. Tissue tracking analysis was used to obtain time curves of right atrial strain. Reservoir (total strain), conduit (passive strain), and booster (active strain) pump function were calculated, and right atrial strain, interstitial lung disease, and clinical outcomes were examined. An adverse clinical event was defined as all-cause death. Overall, 23 patients had interstitial lung disease (58%). Six patients died during the follow-up (median, 44 months). The total skin score and right ventricular systolic pressure on echocardiography were higher in patients with an event than in those without an event (28 ± 16% vs. 13 ± 13%, P = 0.02; 46.3 ± 10.7 mmHg vs. 36.0 ± 8.5 mmHg, P = 0.01, respectively). Further, right atrial total strain and active strain were significantly lower in patients with an event than in those without an event (14.3 ± 11.3% vs. 25.8 ± 11.4%, P = 0.03; 3.48 ± 2.37 vs. 11.7 ± 6.78, P = 0.007, respectively). Multivariate analysis revealed that active strain was an independent predictor of all-cause death (hazard ratio 0.76, P = 0.029). Kaplan-Meier analysis revealed that the survival rate was significantly higher in patients with right atrial active strain levels above the cutoff 7.4 (P < 0.05). In systemic sclerosis, right atrial booster function was predictive of mortality. Hence, right atrial functional assessment may have incremental prognostic value for patients with systemic sclerosis, leading to better risk stratification.

13N-ammonia positron emission tomography for diagnosis and monitoring of ischemia without obstructive coronary artery disease.

BACKGROUND: Ischemia with no obstructive coronary arteries (INOCA), a chronic disorder with a poor prognosis, remains challenging to diagnose. 13N-ammonia positron emission tomography (13NH3 PET), which can quantify microcirculation, is its most reliable detection method. We aimed to investigate the differences in 13NH3 PET findings between INOCA and coronary artery disease (CAD). METHODS: Overall, consecutive 433 patients with known or suspected CAD underwent adenosine-stress 13NH3 PET. Based on the European Society of Cardiology guidelines, INOCA was defined as typical angina without coronary stenosis (INOCA n = 45, CAD n = 293, no CAD n = 95). Papillary muscle ischemia (PMI) and global myocardial flow reserve (MFR) were examined as microvascular injuries using 13NH3 PET. RESULTS: PMI was observed significantly more frequently in patients with INOCA than in those with CAD (40.0% vs. 11.6%, respectively; p = 0.02). Global MFR (1.84 ± 0.54 vs. 2.08 ± 0.66, respectively; p < 0.0001) and reactive hyperemia index were significantly lower in patients with INOCA than in those with CAD. Forty-five major adverse cardiac events (MACE) were recorded in a median follow-up time of 827 days. Kaplan-Meier analysis revealed that the survival rate worsened in patients with INOCA and PMI (log-rank test, p = 0.001). In the Cox proportional hazards model, PMI was an independent predictive factor for MACE (odds ratio, 4.16; 95% confidence interval, 2.13-8.15; p < 0.0001). CONCLUSIONS: PMI presence and decreased MFR were 13NH3 PET findings characteristic of INOCA. 13NH3 PET can be used to monitor the treatment course.

Deep learning approach using SPECT-to-PET translation for attenuation correction in CT-less myocardial perfusion SPECT imaging.

OBJECTIVE: Deep learning approaches have attracted attention for improving the scoring accuracy in computed tomography-less single photon emission computed tomography (SPECT). In this study, we proposed a novel deep learning approach referring to positron emission tomography (PET). The aims of this study were to analyze the agreement of representative voxel values and perfusion scores of SPECT-to-PET translation model-generated SPECT (SPECTSPT) against PET in 17 segments according to the American Heart Association (AHA). METHODS: This retrospective study evaluated the patient-to-patient stress, resting SPECT, and PET datasets of 71 patients. The SPECTSPT generation model was trained (stress: 979 image pairs, rest: 987 image pairs) and validated (stress: 421 image pairs, rest: 425 image pairs) using 31 cases of SPECT and PET image pairs using an image-to-image translation network. Forty of 71 cases of left ventricular base-to-apex short-axis images were translated to SPECTSPT in the stress and resting state (stress: 1830 images, rest: 1856 images). Representative voxel values of SPECT and SPECTSPT in the 17 AHA segments against PET were compared. The stress, resting, and difference scores of 40 cases of SPECT and SPECTSPT were also compared in each of the 17 segments. RESULTS: For AHA 17-segment-wise analysis, stressed SPECT but not SPECTSPT voxel values showed significant error from PET at basal anterior regions (segments #1, #6), and at mid inferoseptal regions (segments #8, #9, and #10). SPECT, but not SPECTSPT, voxel values at resting state showed significant error at basal anterior regions (segments #1, #2, and #6), and at mid inferior regions (segments #8, #9, and #11). Significant SPECT overscoring was observed against PET in basal-to-apical inferior regions (segments #4, #10, and #15) during stress. No significant overscoring was observed in SPECTSPT at stress, and only moderate over and underscoring in the basal inferior region (segment #4) was found in the resting and difference states. CONCLUSIONS: Our PET-supervised deep learning model is a new approach to correct well-known inferior wall attenuation in SPECT myocardial perfusion imaging. As standalone SPECT systems are used worldwide, the SPECTSPT generation model may be applied as a low-cost and practical clinical tool that provides powerful auxiliary information for the diagnosis of myocardial blood flow.

Optimization of Intraventricular Radioactive Concentration for 13N ammonia PET with Time-of-Flight Scanner: Simplified Phantom Study with Noise Equivalent Count Rate Analysis.

Background: Myocardial blood flow quantification (MBF) is one of the distinctive features for cardiac positron emission tomography. The MBF calculation is mostly obtained by estimating the input function from the time activity curve in dynamic scan. However, there is a substantial risk of count-loss because the high radioactivity pass through the left ventricular (LV) cavity within a short period. We aimed to determine the optimal intraventricular activity using the noise equivalent count rate (NECR) analysis with simplified phantom model. Methods: Positron emission tomography computed tomography scanner with LYSO crystal and time of flight was used for phantom study. 150 MBq/mL of 13N was filled in 10 mL of syringe, placed in neck phantom to imitate end-systolic small LV. 3D list-mode acquisition was repeatedly performed along radioactive decay. Net true and random count rate were calculated and compared to the theoretical activity in the syringe. NECR curve analysis was used to determine the optimal radioactive concentration. Result: The attenuation curves showed good correlation to the theoretical activity between 20 to 370, and 370 to 740 MBq (r2=1.0 ± 0.0001, p<0.0001; r2=0.99 ± 0.0001, p<0.0001 for 20 to 370, and 370 to 740, respectively), while did not over 740 MBq (p=0.62). NECR analysis revealed that the peak rate was at 2.9 Mcps, there at the true counts were significantly suppressed. The optimal radioactive concentration was determined as 36 MBq/mL. Conclusion: Simulative analysis for high-dose of 13N using the phantom imitating small LV confirmed that the risk of count-loss was increased. The result can be useful information in assessing the feasibility of MBF quantification in clinical routine.

Myocardial Strain Derived from 13N-ammonia Positron Emission Tomography: Detection of Ischemia-Related Wall Motion Abnormality.

Background: Due to the limitation of spatial resolution, cardiac nuclear medicine images have not been applied to feature-tracking method to automatic extraction of myocardial contours. We have successfully applied the feature-tracking method to high-resolution cine 13N-ammonia positron emission tomography (PET) images to calculate the regional myocardial strains. Here, we investigate the potential of 13N-ammonia PET-derived strain to detect ischemia-related wall motion abnormality. Methods: Data of adenosine-stress/rest 13N-ammonia PET for 95 coronary artery disease patients was retrospectively analyzed. Using an original algorithm dedicated to 13N-ammonia PET, the longitudinal strain (LS) corresponding to the three main coronary artery territories [right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex coronary artery (LCX)] was calculated from semi-automatic endocardial contours extraction on cine 13N-ammonia PET images of the left ventricular long-axis. The presence of ischemia in three main territories was determined from rest and stress-perfusion images. Results: In all three coronary territories, LS at stress was significantly smaller at rest in the ischemic region RCA: -19.2±8.0% vs. -22.7±6.1%, LAD: -19.0±6.9% vs. -24.4±6.4%, LCX: -20.5%±7.6% vs. -22.6±6.9%). In contrast, in the non-ischemic region, there was no significant difference between the LS at stress and at rest. Receiver-operating-characteristic analysis revealed that using the optimal cutoff of the LS ratio of stress to rest, ischemia could be diagnosed with area under the curve of 0.82 in the RCA, 0.86 in the LAD, and 0.69 in the LCX. Conclusions: Myocardial strain derived from endocardial feature-tracking of 13N-ammonia PET cine imaging is reduced in the ischemia induced by adenosine-stress. The LS ratio of stress to rest may detect wall motion abnormality related to ischemia.

Cardiac magnetic resonance imaging T1 mapping and late gadolinium enhancement entropy: Prognostic value in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) affects the myocardium, thereby resulting in a poor prognosis. Late gadolinium enhancement (LGE) entropy, derived from routine cardiac magnetic resonance (CMR) LGE images, is an index that reflects the complexity of the left ventricular myocardium. The aim of this study was to investigate whether LGE entropy can serve as a prognostic factor in patients with SSc. METHODS: Twenty-four patients with SSc, who underwent CMR-T1 mapping and LGE to identify myocardial damage, were enrolled, and LGE entropy was measured. Extracellular volume (ECV) values were calculated using the same CMR-LGE images. The endpoint was major adverse cardiac events (MACEs), comprising all-cause death, hospitalization due to heart failure, and the onset of sustained ventricular tachycardia and ventricular fibrillation. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of LGE entropy was analyzed using Kaplan-Meier analysis. RESULTS: The ROC curve analysis demonstrated a cut-off value of 7.39 for MACE with LGE entropy and had a sensitivity and specificity of 80 % and 79 %, respectively. Patients with LGE entropy ≥7.39 had a significantly higher MACE rate than those with LGE entropy <7.39 (p = 0.010). Moreover, LGE entropy ≥7.39 was a poor prognostic factor in patients without elevated ECV values. CONCLUSIONS: LGE entropy can be used to predict MACE and allows for further risk stratification in addition to ECV determination.

Prediction of cardiovascular events using myocardial strain ratio derived from 13N-ammonia positron emission tomography.

OBJECTIVES: Myocardial flow reserve (MFR), derived from ammonia N-13 positron emission tomography (NH3-PET), can predict the prognosis of patients with various heart diseases. We aimed to investigate whether myocardial strain ratio (MSR) was useful in predicting MACE and allowed for further risk stratification of cardiovascular events in patients with ischemic heart disease (IHD) in addition to MFR. METHODS: Ninety-five patients underwent NH3-PET because of IHD. MFR was determined as the ratio of hyperemic to resting myocardial blood flow (MBF). MSR was defined as the ratio of strains at stress and rest. The endpoint was major adverse cardiac events (MACE), including all-cause death, acute coronary syndrome, heart failure hospitalization, and revascularization. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of ME was analyzed using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to calculate the hazard ratio (HR) with 95% confidence interval (CI). RESULTS: The ROC curve analysis demonstrated a cutoff of 0.93 for MACE with MSR (sensitivity and specificity of 77% and 71%, respectively). Patients with MSR < 0.93 displayed a significantly higher MACE rate than those with MSR ≥ 0.93 (p = 0.0036). The Cox proportional hazards regression analysis indicated that MSR was an independent marker that could predict MACE in imaging and clinical parameters (HR, 7.32; 95% CI: 1.59-33.7, p = 0.011). CONCLUSIONS: MSR was an independent predictor of MACE and was useful for further risk stratification in IHD. MSR has the potential for a new indicator of revascularization in patients with IHD. KEY POINTS: • We hypothesized that combining myocardial flow reserve (MFR) with the myocardial strain ratio (MSR) obtained by applying the feature-tracking technique to ammonia N-13 PET would make it predictive of major adverse cardiac events (MACE) compared to MFR alone. • MSR was an independent predictor of MACE, allowing for further risk stratification in addition to MFR in patients with ischemic heart disease. • MSR is a potential new indicator of revascularization.

Imaging of Heart Type Fatty Acid Binding Protein Under Acute Reperfusion Ischemia Using Radio-labeled Antibody in Rat Heart Model.

Purpose: Heart-type fatty acid binding protein (H-FABP) is primary transporter of free fatty acid and plays an important role in myocardial metabolism, which is characterized by high specificity and rapid appearance under ischemic condition. The objective of this study was to clarify the usefulness of imaging study of targeting H-FABP appearance using radio-labeled antibody, and correlation with myocardial fatty acid metabolism and perfusion in acute reperfusion ischemia. Method: Wistar rats were allotted to sham-operated control group (sham; n=4), ischemia non-reperfused group (IG; n=5), and ischemia-reperfusion group (RG; n=5). Ligation of left coronary artery (LCA) was performed for IG and RG. 20 min of ischemia was followed by 60min of reperfusion for RG. 125I labeled anti H-FABP antibody (anti H-FABP), BMIPP and 99mTc-sestamibi (MIBI) was injected intravenously. Multi-tracer digital autoradiogram was performed using µ-imager®. The ratio of radioactivity in LCA related (culprit) area to the inferior (remote) area (target uptake ratio=TUR) was generated. Results: In sham group, no visually detectable accumulation was observed for the anti H-FABP image, and TURMIBI and TURBMIPP were equivalent to 1. In IG, TURMIBI and TURBMIPP were remarkably low (0.12±0.01, 0.24±0.07). In RG, TURMIBI was significantly lower (0.20±0.03, p<0.05 vs. other groups). However, TURBMIPP was significantly higher (2.78±1.28, p<0.05) compared to the sham and IG, whereas anti H-FABP showed markedly higher ratio in the reperfused area compared to the sham and IG (3.43±0.73 vs. 0.31±0.13 and 1.09±0.07 for IG and sham; p<0.05, and <0.01, respectively). Conclusion: Anti H-FABP accumulated specifically in reperfused area under acute ischemia, and it accorded to the area where fatty acid metabolism was activated. This study has shown the future potential for clinical application in vivo imaging of acute coronary syndrome.

Adverse Cardiac Events in Cardiac Sarcoidosis Prediction by 123I-betamethyl-p-iodophenyl-pentadecanoic Acid Single-Photon Emission Computed Tomography and Cardiac Magnetic Resonance Late Gadolinium Enhancement.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging can help detect myocardial damage. 123I-betamethyl-p-iodophenyl-pentadecanoic acid single-photon emission computed tomography (BMIPP-SPECT) was developed to evaluate fatty acid metabolism and has been reported to help detect myocardial damage in cardiac sarcoidosis (CS). We analyzed data from CMR-LGE and performed BMIPP-SPECT in patients with CS taking prednisolone and investigated the association of BMIPP-SPECT with LGE as a prognostic factor in CS. Patients with CS who underwent BMIPP-SPECT and CMR-LGE at the time of diagnosis within 2 months were classified into those with and without a major adverse cardiac event (MACE). Total BMIPP-SPECT defect score (BDS) and LGE extent score (LES) were used to estimate myocardial damage. The relation between BDS and LES was explored using Pearson's correlation coefficient. Their ability to predict MACEs was analyzed using Kaplan-Meier analysis. Medical data of 45 patients were analyzed retrospectively (mean follow-up, 4.5 years). BDS and LES were significantly correlated (p <0.0001). BDS was significantly greater for the group with MACE than that without MACE (p = 0.0008). LES of patients with MACE was significantly greater than those without MACE (p = 0.0045). Patients with BDS ≥16 had a significantly higher MACE rate than those with BDS <16 (p = 0.0029). The group with LES ≥9 was significantly associated with MACE (p = 0.0098). In conclusion, BDS reflected myocardial damage similar to that detected by CMR-LGE and was a predictive marker of MACE in patients with CS. BMIPP-SPECT may help predict the prognosis of patients with CS who cannot undergo CMR-LGE.

First Validation of Myocardial Flow Reserve Derived from Dynamic 99mTc-Sestamibi CZT-SPECT Camera Compared with 13N-Ammonia PET.

13N-ammonia positron emission tomography (NH3-PET) can evaluate myocardial blood flow (MBF) at rest, stress, and myocardial flow reserve (MFR) as well as the ratio of MBF at stress to that at rest. MFR is useful in predicting the prognoses of patients with various heart diseases. Cadmium-zinc-telluride single photon emission computed tomography (CZT-SPECT) enables us to acquire dynamic images of radiotracer kinetics and measure original MBF and MFR using 99mTc-sestamibi. This study aimed to investigate the utility of CZT-SPECT for quantitative assessment of MBF compared to NH3-PET. We validated the correlation of MBF and MFR between CZT-SPECT and NH3-PET. Fourteen patients using one-day rest/stress CZT-SPECT, D-SPECT followed by NH3-PET within 1 month were enrolled and analyzed prospectively. The reproducibility of the MBF and MFR obtained with these two methods was examined using Spearman's correlation coefficient and Bland-Altman plot analysis. The diagnostic value of D-SPECT for abnormal MFR defined using NH3-PET results as MFR < 2.0 was assessed using receiver-operating characteristic (ROC) analysis. The median duration between D-SPECT and NH3-PET was 20 days. Although MBF was overestimated by D-SPECT compared to NH3-PET at high value (mean difference, 0.43 [0.34-0.53]), MBF and MFR were correlated with the two modalities (MBF: r = 0.71, P < 0.0001, MFR: r = 0.60, P < 0.0001). The ROC curve analysis demonstrated a cutoff of 1.6 for detecting abnormal MFR with D-SPECT (sensitivity, 68%; specificity, 91%; AUC, 0.75). MBF and MFR obtained using D-SPECT and NH3-PET had a good correlation, suggesting that the quantitative MFR evaluation by CZT-SPECT may help understand the trend of NH3-PET MFR.

13 N-ammonia PET-derived right ventricular longitudinal strain and myocardial flow reserve in right coronary artery disease.

PURPOSE: We developed a feature-tracking algorithm for use with electrocardiography-gated high-resolution 13 N-ammonia positron emission tomography (PET) imaging, and we hypothesized it could be used to clarify the association between right ventricular (RV) longitudinal strain (LS) and right coronary artery (RCA) ischemia. The aim of this study was to investigate the association between the reduction of regional myocardial flow reserve (MFR) in RCA territories and PET-derived LS of the RV free wall. METHODS: Ninety-three patients with coronary artery stenosis > 50%, diagnosed by coronary computed tomography angiography, and 10 controls were retrospectively analyzed. RV-LS in the free wall was measured by a feature-tracking technique on the resting and stressed 13 N-ammonia PET images of horizontal long axis slices. The patients were sub-grouped according to regional MFR values at the territories of RCA, left anterior descending artery (LAD), and left circumflex coronary artery (LCx): RCA-MFR < 2.0 [n = 34], RCA-MFR ≥ 2.0 but MFR < 2.0 at LAD or LCx territories [n = 11], and MFR ≥ 2.0 for all territories [n = 48]. Stress and resting RV-LS were compared in each of the four groups. Multiple comparisons of RV-LS among the four groups were performed in the stress and resting state. RESULTS: Decreased stress RV-LS in patients with an RCA-MFR < 2.0 was observed. In the patients with MFR ≥ 2.0 for all territories, the stressed RV-LS was significantly increased compared to that in the resting state. Significantly decreased RV free wall LS during adenosine stress in patients with RCA-MFR < 2.0 was observed in the other three groups. CONCLUSIONS: We measured RV myocardial LS using feature tracking in cine imaging of 13 N-ammonia PET. The results of this study suggest that PET-derived stressed RV-LS is useful for detecting reduced RV myocardial motion due to ischemia in the RCA territory.

Relation of Left Atrial Flow, Volume, and Strain to Paroxysmal Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy.

This study aims to characterize flow, volume, and strain of the left atrium in hypertrophic cardiomyopathy (HC) with atrial fibrillation (AF) using cine cardiovascular magnetic resonance (CMR) imaging. Cine CMR data for 144 patients with HC, including 29 patients with episodes of paroxysmal AF and 13 patients with persistent AF, were retrospectively analyzed. The vortex flow of the left atrial (LA, %) was measured using a vortex flow map and was used as an estimate of flow. The LA end-systolic volume index (ml/m2), LA ejection fraction (%) and global peak longitudinal LA strain (%) derived from a feature-tracking method were used as estimates of volume and strain. Vortex flow of the LA in patients with paroxysmal AF was significantly smaller than in patients without AF (vertical long-axis view; 26.7 ± 10.8% vs 33.2 ± 12.2%, p <0.005). The patients with paroxysmal AF had greater LA end-systolic volume index and global peak longitudinal LA strain and lower LA ejection fraction compared with those without AF. In conclusion, patients with HC with paroxysmal AF are characterized by small vortex flow, large volume, and decreased strain of LA on cine CMR.

13N-ammonia positron emission tomography-derived endocardial strain for the assessment of ischemia using feature-tracking in high-resolution cine imaging.

BACKGROUND: Assessing endocardial strain using a single 13N-ammonia positron emission tomography (PET) scan would be clinically useful, given the association between ischemia and myocardial deformation. However, no software has been developed for strain analysis using PET. We evaluated the clinical potential of feature tracking-derived strain values measured using PET, based on associations with the myocardial flow reserve (MFR). METHODS AND RESULTS: This retrospective study included 95 coronary artery disease patients who underwent myocardial 13N-ammonia PET. Semi-automatic measurements were made using a feature-tracking technique during myocardial cine imaging, and values were calculated using a 16-segment model. Adenosine-stressed global circumferential strain (CS) and global longitudinal strain (LS) values were compared with global MFR values. Stressed and resting global strain values were also compared. Global strain values were significantly lower in 39 patients with abnormal MFRs [< 2.0] than in 56 patients with normal MFRs [≥ 2.0]. The global CS values in the stressed state were significantly decreased than the resting state values in patients with abnormal MFRs. CONCLUSIONS: This study applied endocardial feature-tracking to 13N-ammonia PET, and the results suggested that blood flow and myocardial motility could be clinically assessed in ischemic patients using a single PET scan.

13N-ammonia positron emission tomography-derived left-ventricular strain in patients after heart transplantation validated using cardiovascular magnetic resonance feature tracking as reference.

OBJECTIVE: Heart transplant rejection leads to cardiac allograft vasculopathy (CAV). 13N-ammonia positron emission tomography (PET) can be useful in detecting CAV, as it can evaluate both epicardial vessels and microvasculature. In this study, we evaluated the regional wall motion in heart transplant patients using our PET-specific feature-tracking (FT) algorithm for myocardial strain calculation and validated it using a cardiovascular magnetic resonance (CMR) FT strain as a reference. METHODS: A total of 15 heart transplant patients who underwent both 13N-ammonia PET and CMR within 3 months were retrospectively enrolled. The same slice position of short-axis cine images of the middle slice of left ventricle (LV) and the same slice position of horizontal long-axis cine images were selected for the two modalities to measure the circumferential strain (CS) and longitudinal strain (LS), respectively. Based on the FT technique, time-strain curves were calculated by semi-automatic tracking of the endocardial contour on cine images throughout a cardiac cycle. The peak value in the time-strain curve was defined as the representative value. Correlations of CS and LS between PET and CMR were analyzed using Pearson correlation coefficients. The inter-modality error of strain measurements was evaluated using intraclass correlation coefficients (ICCs) with two-way random single measures. RESULTS: Excellent correlations of CS and LS between PET and CMR were observed (CS: r = 0.80; p < 0.01; LS: r = 0.87; p < 0.01). Excellent ICCs were observed (0.89 and 0.85) in CS and LS derived from PET. CONCLUSIONS: We propose the first PET strain showing an excellent agreement with the CMR strain and high reproducibility in measurement.

Papillary muscle ischemia on high-resolution cine imaging of nitrogen-13 ammonia positron emission tomography: Association with myocardial flow reserve and prognosis in coronary artery disease.

BACKGROUND: The evaluation of papillary muscle (PM) perfusion through existing perfusion imaging, including single-photon emission computed tomography and magnetic resonance imaging, is not possible. Therefore, this study sought to investigate the detection of PM ischemia in coronary artery disease (CAD) using nitrogen-13 (N-13) ammonia positron emission tomography (NH3 PET) and its association with global myocardial flow reserve (MFR) and major adverse cardiac events (MACE). METHODS: Data of adenosine-stress NH3 PET for 263 consecutive patients with known or suspected CAD were retrospectively analyzed. PM ischemia was defined as the absence of PM accumulation under stress conditions and PM presence at rest on high-resolution cine imaging derived from PET-computed tomography scanner with time-of-flight technology. The primary outcome was MACE. RESULTS: Of 263 patients, 30 experienced mean follow-up period of 910 days (MACE), while 31 (11.8%) presented PM ischemia. Compared to patients without PM ischemia, those with PM ischemia reported a significantly lower global MFR and a significantly higher rate of MACE (P < .0001). CONCLUSION: NH3 PET enables the detection of PM ischemia in approximately 10% of patients with known or suspected CAD. PM ischemia is associated with reduced global MFR and is an important sign in predicting prognosis.

Myocardial Flow Reserve in Coronary Artery Disease with Low Attenuation Plaque: Coronary CTA and 13N-ammonia PET Assessments.

RATIONALE AND OBJECTIVES: Physiological measurements from coronary angiography show that coronary stenosis with necrotic core plaque reduces coronary flow reserve (CFR). Myocardial flow reserve (MFR) estimated by 13N-ammonia PET (NH3-PET) is a different index from CFR. Low attenuation plaque (LAP) on coronary CTA (CCTA) contains necrotic core, but the link between LAP and MFR has not been elucidated. We aimed to investigate the influence of LAP on MFR in coronary artery disease (CAD). MATERIALS AND METHODS: The study included 105 consecutive patients who underwent NH3-PET and CCTA within 3 months. Nonevaluable coronary arteries due to severe calcification and stent implants were excluded. Finally, 290 major vessels were retrospectively analyzed. Coronary arteries were divided into mild (1%-49%), moderate (50%-69% stenosis), and severe (≥70% stenosis) groups. Coronary plaques were classified either LAP (including soft tissue CT value <30 HU) or completely classified plaques. MFR for the major vessels were calculated and MFR <2.0 was considered a significant decrease. Comparison of MFR between territories with and without LAP, and the effect of plaque characteristics on MFR was analyzed. RESULTS: MFR was significantly lower for territories with LAP than with calcified plaques or no plaque (2.1 ± 0.7, 2.4 ± 0.7, and 2.3 ± 0.7; p < 0.05). There was no difference between calcified plaque and no plaque territories (p = 0.79). Multivariate logistic analysis for plaque characteristics and stenosis severity revealed that LAP and severe stenosis were independent predictors for territories with MFR <2.0 with odds ratios of 3.1 (95% confidence interval, 1.2-8.1) and 3.0 (95% confidence interval, 1.7-5.3). CONCLUSION: LAP reduced MFR compared with calcified plaque or no plaque in CAD. LAP is an independent predictor of the territory with MFR <2.0.

Coronary flow quantification estimated by dynamic 320-detector CT angiography: validation by 13N ammonia PET myocardial flow reserve.

OBJECTIVES: Resting coronary flow index (rCFI) estimated by 320-detector low-dose dynamic coronary CT angiography (CCTA) is a direct flow quantification using intracoronary attenuation. We propose modified-rCFI from new protocol combining dynamic scan and standard CCTA using dose-modulation, and validate its consistency with quantitative values and ischemia depicted by 13N-ammonia PET (NH3-PET). METHODS: 46 patients who underwent dynamic CCTA and NH3-PET for coronary artery disease were evaluated using original rCFI in 21 patients and modified-rCFI in 25 patients. Two types of rCFI were calculated for three major coronary arteries. Myocardial blood flow (MBF) at rest and stress, myocardial flow reserve (MFR), and the presence or absence of ischemia for three major territories were depicted by NH3-PET. Coronary territories were categorized as territories with MFR <2.0, ≥2.0, or with and without ischemia. Receiver operating characteristic analysis was performed to determine the optimal cut-off of rCFI to distinguish territories with MFR <2.0 or the presence of ischemia. RESULTS: rCFI and modified-rCFI had significant positive correlations with stress MBF and MFR. The optical cut-offs of rCFI and modified-rCFI of 0.39 and 0.61 could detect territories with MFR <2.0, with AUCs of 0.75 and 0.73, sensitivities of 48 and 34%, and specificities of 97 and 98%. Optimal cut-offs of rCFI and modified-rCFI distinguished ischemic segments from non-ischemic segments, with AUCs of 0.75 and 0.91, sensitivities of 53 and 50%, and specificities of 93 and 95%. CONCLUSION: Two types of rCFI correlated with quantitative values from NH3-PET, and were consistent with a high specificity in detecting functional ischemia. ADVANCES IN KNOWLEDGE: rCFI can contribute as additional functional test over standard CCTA in clinical work-up.