Evaluation of Coronary Circulation by 13N-Ammonia Myocardial Perfusion Positron Emission Tomography in Patients with Right Coronary Artery Occlusion Due to Kawasaki Disease.

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.

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.

Effect of Luseogliflozin on Myocardial Flow Reserve in Patients with Type 2 Diabetes Mellitus (LUCENT-J Study).

INTRODUCTION: In patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors has been shown to reduce hospital admission rates for heart failure (HF). However, the multiple mechanisms hypothesized and investigated to explain the cardioprotection of SGLT2 inhibitors are not fully understood. OBJECTIVES: The effect of luseogliflozin on myocardial flow reserve (MFR) in patients with T2D (LUCENT-J) study aims to examine the effects of SGLT2 inhibitors on myocardial perfusion. METHODS: The LUCENT-J study is a prospective, single-center, randomized, two-arm, parallel-group, open-label (i.e., the radiology readers are blinded), active-controlled study. A cohort of 40 patients with T2D with no or stable (with no history of myocardial infarction and with or without previous percutaneous coronary intervention) coronary artery disease will be included. Patients will be randomized in a 1:1 ratio to luseogliflozin or control and treated for 24 weeks. The primary outcome is the change in MFR, as measured by 13N-ammonia positron emission tomography/computed tomography, from baseline to 24 weeks after treatment initiation. PLANNED OUTCOMES: The LUCENT-J study will elucidate the mechanisms of cardioprotection by SGLT2 inhibitors in patients with T2D. TRIAL REGISTRATION: Japan Registry of Clinical Trials (JRCTs051220016).

Caloric restriction reduces proteinuria in male rats with established nephropathy.

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on established proteinuria. Rats, aged 12 ± 2 weeks, were administered 2.1 mg/kg of Adriamycin. Six weeks after injection, protein excretion was measured, and a [13 N]ammonia positron emission tomography (PET) scan was conducted to assess kidney perfusion. After 7 weeks rats were divided into four groups: ad libitum (AL) and CR groups fed either a 12% or a 20% protein diet. All groups were treated for 12 weeks. Blood pressure was measured and a second PET scan was acquired at the end of the study. The animals subjected to CR exhibited a 20.3% decrease in protein excretion (p = 0.003) compared to those in the AL groups. Additionally, blood pressure in the CR group was 21.2% lower (p < 0.001) than in the AL groups. While kidney function declined over time in all groups, the 20% CR group demonstrated the smallest decline. Thus CR effectively reduces urinary protein excretion and lowers blood pressure in rats with established proteinuria.

Clinical application of combination [11C]C-methionine and [13N]N-ammonia PET/CT in recurrent functional pituitary adenomas with negative MRI or [18F]F-FDG PET/CT.

BACKGROUND: We assessed the value of positron emission tomography/computed tomography (PET/CT) with [13N]N-ammonia ([13N]N-NH3) and [11C]C-methionine ([11C]C-MET) for the evaluation and management of recurrent secreting pituitary adenoma, which could not be detected by magnetic resonance imaging (MRI) or fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET. METHODS: Nine consecutive patients with biochemical and clinical evidence of active recurrent tumor not detected by MRI and [18F]F-FDG PET were enrolled in this study. All of the patients underwent [13N]N-NH3 and [11C]C-MET PET/CT, after which the pattern of tracer uptake was studied, the tumor position was located, and a clinical decision was made. RESULTS: In general, [11C]C-MET had a higher uptake in pituitary adenomas (PAs) than that in pituitary tissues, while [13N]N-NH3 had a higher uptake in pituitary tissue than in pituitary adenomas. Increased [11C]C-MET uptake was observed in all nine PAs and three pituitary tissues, while all pituitary tissues and only one pituitary adenoma showed increased [13N]N-NH3 uptake. Four patients had concordant imaging and surgical findings indicative of biochemical remission without hypopituitarism after treatment. Radiotherapy was adopted in two patients, medication in another two, and follow-up observation in one case. CONCLUSION: Combined [11C]C-MET and [13N]N-NH3 PET/CT is effective in the differentiation of PAs from pituitary tissue in recurrent functional PAs with negative MRI or [18F]F-FDG PET. These results provide a valuable reference for further disease management.

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.

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.

A Reliable Production System of Large Quantities of [13N]Ammonia for Multiple Human Injections.

[13N]Ammonia is one of the most commonly used Positron Emission Tomography (PET) radiotracers in humans to assess myocardial perfusion and measure myocardial blood flow. Here, we report a reliable semi-automated process to manufacture large quantities of [13N]ammonia in high purity by proton-irradiation of a 10 mM aqueous ethanol solution using an in-target process under aseptic conditions. Our simplified production system is based on two syringe driver units and an in-line anion-exchange purification for up to three consecutive productions of ~30 GBq (~800 mCi) (radiochemical yield = 69 ± 3% n.d.c) per day. The total manufacturing time, including purification, sterile filtration, reformulation, and quality control (QC) analyses performed before batch release, is approximately 11 min from the End of Bombardment (EOB). The drug product complies with FDA/USP specifications and is supplied in a multidose vial allowing for two doses per patient, two patients per batch (4 doses/batch) on two separate PET scanners simultaneously. After four years of use, this production system has proved to be easy to operate and maintain at low costs. Over the last four years, more than 1000 patients have been imaged using this simplified procedure, demonstrating its reliability for the routine production of large quantities of current Good Manufacturing Practices (cGMP)-compliant [13N]ammonia for human use.

Improved accuracy of the biodistribution and internal radiation dosimetry of 13 N-ammonia using a total-body PET/CT scanner.

BACKGROUND: Conventional short-axis PET typically utilizes multi-bed multi-pass acquisition to produce quantitative whole-body dynamic images and cannot record all the uptake information simultaneously, resulting in errors when fitting the time-activity curves (TACs) and calculating radiation doses. PURPOSE: The aim of this study is to evaluate the 13 N-ammonia biodistribution and the internal radiation doses using a 194 cm long total-body PET/CT scanner (uEXPLORER), and make a comparison with the previous short-axis PET results. METHODS: Ten subjects (age 40-74 years) received 13 N-NH3 injection (418.1-670.81 MBq) and were under a dynamic scan for about 60 min with using a 3-dimensional whole-body protocol. ROIs were drawn visually on 11 major organs (brain, thyroid, gallbladder, heart wall, kidneys, liver, pancreas, spleen, lungs, bone marrow, and urinary bladder content) for each subject. TACs were generated using Pmod and the absorbed radiation doses were calculated using Olinda 2.2. To compare with the conventional PET/CT, five points were sampled on uEXPLORER's TACs to mimic the result of a short-axis PET/CT (15 cm axial FOV, consisted of 9 or 10 bed positions). Then the TACs were obtained using the multi-exponential fitting method, and the residence time and radiation dose were also calculated and compared with uEXPLORER. RESULTS: The highest absorbed organ doses were the pancreas, thyroid, spleen, heart wall, and kidneys for the male. For the female, the first five highest absorbed organ dose coefficients were the pancreas, heart wall, spleen, lungs, and kidneys. The lowest absorbed dose was found in red marrow both for male and female. The simulated short-axis PET can fit TACs well for the gradually-changed uptake organs but typically underestimated for the rapid-uptake organs during the first-10 min, resulting in errors in the calculated radiation dose. CONCLUSION: uEXPLORER PET/CT can measure 13 N-ammonia's TACs simultaneously in all organs of the whole body, which can provide more accurate biodistribution and radiation dose estimation compared with the conventional short-axis scanners.

Meta-analysis of Saccharomyces cerevisiae on enhancement of growth performance, rumen fermentation and haemato-biochemical characteristics of growing goats.

The use of Saccharomyces cerevisiae (SC) feed additives to improve animal performance are on the increase; however, the results of the action of SC supplementation on goats performance indices are conflicting. Thus, the thrust of this meta-analysis was to examine the influence of dietary SC intervention on the growth performance, haemato-biochemical indices and ruminal fermentation characteristics of growing goats fed total mixed ration (TMR). The search conducted in Google Scholar, PubMed and Scopus databases using several keywords yielded 500 studies of which 16 full-text articles were utilised for study. Response variables were aggregated via a random-effects model. The results showed that goats fed SC experienced higher average daily gain (ADG) than the controls (as standardized mean difference, SMD = 2.14; 95% confidence interval, CI: 1.40 to 2.89). In converse, dietary SC intervention had a small impact on dry matter intake (DMI) and feed conversion ratio (FCR). Subgroup analysis demonstrated that SC type (active vs inactive) improved FCR and ADG in growing goats. Results suggested that SC preparation increased blood glucose, white blood cell (WBC), ruminal propionate and total volatile fatty acid levels. There is heterogeneity among the articles used in the study, and aspects of studied covariates explained the variation. In conclusion, this study indicated that dietary yeast can positively influence growth performance, haemato-biochemical indices, and rumen fermentation parameters of growing goats.

Left ventricular function and volumes from gated [13N]-ammonia positron emission tomography myocardial perfusion imaging: A prospective head-to-head comparison against CMR using a hybrid PET/MR device.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can be used to evaluate left ventricular (LV) volumes and function. We performed a head-to-head comparison of LV function and volumes obtained simultaneously using [13N]-ammonia-PET and cardiac magnetic resonance (CMR), with the latter serving as the reference standard. METHODS AND RESULTS: In this prospective study, 51 patients underwent [13N]-ammonia-PET MPI and CMR using a hybrid PET/MR device. Left ventricular end-systolic volumes (LVESV), end-diastolic volumes (LVEDV), stroke volumes (LVSV), ejection fractions (LVEF), and segmental wall motion were analyzed for both methods and were compared using correlational and Bland-Altman (BA) analysis; segmental wall motion was compared using ANOVA. The agreement between [13N]-ammonia-PET and CMR for LVEF was good, with minimal bias (- .6%) and narrow BA limits of agreement (- 7.9% to 6.8%), but [13N]-ammonia-PET systematically underestimated LV volumes, with high bias in LVESV (- 11.2 ml), LVEDV (- 28.9 ml), and LVSV (- 17.5 ml). Mean segmental wall motion in [13N]-ammonia-PET differed significantly among the corresponding normokinetic (6.6 ± 2 mm), hypokinetic (5.1 ± 2 mm), and akinetic (3.3 ± 2 mm) segments in CMR (P < .01). CONCLUSION: LVEF and LV wall motion can be accurately assessed using [13N]-ammonia-PET MPI, although LV volumes are significantly underestimated compared to CMR.

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.

Radiation Exposure to the Personnel Performing Myocardial Blood Flow Quantification Study Using 13N-ammonia Positron Emission Tomography/Computed Tomography.

Purpose: The present study aimed to evaluate radiation exposure to staff performing coronary flow reserve (CFR) measurement using 13N-ammonia. Materials and Methods: The radiation exposure rate during the administration of 13N-ammonia for the rest and stress part of the study was noted using an ionization chamber-based calibrated survey monitor. The radiation exposure to persons involved in dispensing radioactivity (D1), administering radioactivity (D2) and monitoring the patient during pharmacological stress (D3) were measured using an energy compensated Si-diode personal pocket dosimeter. Results: The average dose received by individuals with dosimeters D1, D2, and D3 was 1.28 ± 0.79 µSv, 1.56 ± 0.51 µSv, and 0.88 ± 0.97 µSv per injection, respectively, during the rest of study and 1.56 ± 0.96 µSv, 2.64 ± 1.22 µSv, and 2.2 ± 1.7 µSv per injection, respectively, during stress study. The average exposure rate during the administration of 13N-ammonia at 0.5 m and 1.5 m from the injection site was found to be 259 µSv/h and 53.4 µSv/h, respectively, during the rest study and 301 µSv/h and 67.25 µSv/h, respectively, during stress study. Conclusion: The exposure to the staff performing CFR study with 13N-ammonia was well within prescribed limits by the International Commission on Radiological Protection 103. The CFR measurement with 13N-ammonia positron emission tomography/computed tomography can be included in routine workups of cardiac patients without the fear of radiation exposure.

Development and evaluation of a radiomics model of resting 13N-ammonia positron emission tomography myocardial perfusion imaging to predict coronary artery stenosis in patients with suspected coronary heart disease.

Background: Coronary angiography (CAG) is usually performed in patients with coronary heart disease (CHD) to evaluate the coronary artery stenosis. However, patients with iodine allergy and renal dysfunction are not suitable for CAG. We try to develop a radiomics machine learning model based on rest 13N-ammonia (13N-NH3) positron emission tomography (PET) myocardial perfusion imaging (MPI) to predict coronary stenosis. Methods: Eighty-four patients were included with the inclusion criteria: adult patients; suspected CHD; resting MPI and CAG were performed; and complete data. Coronary artery stenosis >75% were considered to be significant stenosis. Patients were randomly divided into a training group and a testing group with a ratio of 1:1. Myocardial blood flow (MBF), perfusion defect extent (EXT), total perfusion deficit (TPD), and summed rest score (SRS) were obtained. Myocardial static images of the left ventricular (LV) coronary segments were segmented, and radiomics features were extracted. In the training set, the conventional parameter (MPI model) and radiomics (Rad model) models were constructed using the machine learning method and were combined to construct a nomogram. The models' performance was evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, decision analysis curve (DCA), and calibration curves. Testing and subgroup analysis were performed. Results: MPI model was composed of MBF and EXT, and Rad model was composed of 12 radiomics features. In the training set, the AUC/accuracy/sensitivity/specificity of the MPI model, Rad model, and the nomogram were 0.795/0.778/0.937/0.511, 0.912/0.825/0.760/0.936 and 0.911/0.865/0.924/0.766 respectively. In the testing set, the AUC/accuracy/sensitivity/specificity of the MPI model, Rad model, and the nomogram were 0.798/0.722/0.659/0.841, 0.887/0.810/0.744/0.932 and 0.900/0.849/0.854/0.841 respectively. The AUC of Rad model and nomogram were significantly higher than that of MPI model. The DCA curve also showed that the clinical net benefit of the Rad model and nomogram was similar but greater than that of MPI model. The calibration curve showed good agreement between the observed and predicted values of the Rad model. In the subgroup analysis of Rad model, there was no significant difference in AUC between subgroups. Conclusions: The Rad model is more accurate than the MPI model in predicting coronary stenosis. This noninvasive technique could help improve risk stratification and had good generalization ability.

Impaired coronary flow reserve in patients with supra-normal left ventricular ejection fraction at rest.

PURPOSE: Recently, a "U" hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar "U" curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%). METHODS: Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated 13 N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose-response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan-Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome. RESULTS: An inverted "U" curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF < 55%) (n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF < 65%) (n = 106) (57.9% vs 54.5% vs 34.3%, p < 0.01, respectively). Both snLVEF (p < 0.01) and rLVEF (p < 0.05) remained independent predictors for reduced cCFR after multivariable adjustment. Patients with snLVEF encountered more MACE than those with nLVEF (10.5% vs 0.9%, log-rank p = 0.01). CONCLUSIONS: Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.

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.

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.

Feasibility of exercise treadmill 13N-ammonia positron emission tomography myocardial perfusion imaging using an off-site cyclotron.

BACKGROUND: Myocardial perfusion imaging with treadmill exercise nitrogen-13 (13N)-ammonia positron emission tomography (PET) presents a logistical challenge. We investigated the feasibility of exercise treadmill (GXT) 13N-ammonia PET MPI using an off-site cyclotron for production of 13N-ammonia. METHODS: Thirty-three patients underwent GXT 13N-ammonia PET MPI over 23 months. 13N-ammonia doses were prepared at an off-site cyclotron. Patients underwent 13N-ammonia resting and 13N-ammonia GXT emission and transmission scans at our facility. Image quality, perfusion data, and clinical variables were evaluated. RESULTS: We analyzed 33 patients (7/26 female/male). Mean age was 63 ± 12 years and mean BMI was 33.7 ± 6.9. GXT PET was feasible in all patients. Image quality was good in 29 patients, adequate in 3, and severely compromised in 1 patient. Summed stress score was 4.5 ± 5.7. Resting and GXT left ventricular ejection fractions were 63.7 ± 10.9% and 66.3 ± 13.1%. TID ratio was 1.0 ± 0.1. CONCLUSIONS: Treadmill exercise 13N-ammonia PET is feasible in a large medical center without access to an on-site cyclotron. This technique requires close coordination with an off-site cyclotron but expands the role of PET to patients for whom exercise is more appropriate than pharmacologic stress imaging.

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.

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.