Background: Resting myocardial blood flow (rMBF) within regions of myocardial scar as measured by positron emission tomography (PET) has not yet been assessed with the radiotracer Rubidium⁸² (Rb⁸²) or correlated with scar thickness. Cardiac magnetic resonance imaging (cMRI) offers high spatial resolution and identifies myocardial scar with late gadolinium enhancement (LGE). Using Rb⁸² PET, we sought to characterize rMBF in regions of myocardial scar of varying thicknesses determined by cMRI.
Methods/Results: Patients with a history of myocardial infarction, a resting Rb⁸² PET study and a cMRI were identified. On cMRI, regions of infarction, defined as >50% LGE with akinesis, were sub-categorized as 50–75% LGE or >75% LGE, corresponding with increasing transmural scar thickness. PET zones of infarct based on size and %LGE by cMRI were quantified for mean and minimum rMBF. Mean rMBF (cc/min/g) in infarct zones with >75% LGE was 0.32±0.07 with a minimum rMBF of 0.19±0.03. In infarct zones with 50–75% LGE, rMBF was 0.45±0.14 (50–75% vs. >75%, p=0.002).
Conclusions: We identified rMBF within cMRI confirmed regions of myocardial scar of varying thicknesses. rMBF has an inverse relationship with the extent of LGE on cMRI, with the most severe regions (>75% LGE) having mean and minimal rMBF (cc/min/g) of 0.32±0.07 and 0.19±0.03, respectively.

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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 60 min 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 TUR_MIBI and TUR_BMIPP were equivalent to 1. In IG, TUR_MIBI and TUR_BMIPP were remarkably low (0.12±0.01, 0.24±0.07). In RG, TUR_MIBI was significantly lower (0.20±0.03, p<0.05 vs. other groups). However, TUR_BMIPP 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.

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Aim: Previous studies have demonstrated increased glucose uptake by ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in lung parenchyma in animal models or small pulmonary arterial hypertension (PAH) cohorts. However, it is not well known whether increased FDG uptake in the lung is a unique phenomenon in PAH or whether elevated pulmonary artery pressure (PAP) induces FDG uptake.
Methods and results: Nineteen patients with PAH, 8 patients with pulmonary hypertension due to left heart disease (PH-LHD), and 14 age matched control subjects were included. All PH patients underwent right heart catheterization and FDG-PET. The mean standard uptake value (SUV g/mL) of FDG in each lung was obtained and average values of both lungs were calculated as mean lung FDG SUV. The correlation between hemodynamics and mean lung FDG SUV was also analyzed in PH patients. Mean PAP (mPAP) was not significantly different between PAH and PH-LHD (45 ± 11 vs 43 ± 5 mmHg, p=0.51). PAH patients demonstrated significantly increased mean lung FDG SUV compared with PH-LHD and controls (PAH: 0.76 ± 0.26 vs PH-LHD: 0.51 ± 0.12 vs controls: 0.53 ± 0.16, p=0.0025). The mean lung FDG SUV did not correlate with mPAP either in PAH or PH-LHD.
Conclusion: PAH is associated with increased lung FDG uptake indicating increased glucose utilization in the lung. This may represent metabolic shift to glycolysis and/or active inflammation in the remodeled pulmonary vasculature, and is observed to a greater extent in PAH than in patients with PH secondary to LHD and control subjects without PH.

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Background: Smoothing in ^99mTc myocardial perfusion single-photon emission computed tomography (SPECT) often increases myocardial artifacts due to subdiaphragmatic activity near the heart. To reduce these artifacts, we developed a new process flow, masking on unsmoothed images (MUS), that includes the extraction of the myocardium by masking before smoothing.
Methods: This study evaluated the relationships between matrix sizes and distances to the subdiaphragmatic activity using the MUS method compared to conventional methods using a combination of image reconstruction methods (filtered back-projection [FBP] and ordered subset expectation maximization [OSEM]) with or without corrections (attenuation [AC], scatter [SC], and resolution recovery [RR]) using a myocardial phantom. The results were compared for two matrix sizes (pixel sizes) (128 × 128 [3.3 mm] and 64 × 64 [6.6 mm]); four subdiaphragmatic activity distances (5, 10, 15, and 20 mm); and three reconstruction methods (FBP without correction; OSEM with RR; and OSEM with AC, SC, and RR).
Results: In the conventional method, increasing distance resulted in interference with myocardial perfusion SPECT evaluation however, the artifacts were less apparent when the MUS method was applied. The images converted to 64 × 64 did not show the same effect as the 128 × 128 images, even when RR was used. The MUS method was useful for acquisition at 128 × 128, along with the use of RR in the reconstruction process.
Conclusion: MUS mitigated the effects of subdiaphragmatic activity on myocardial perfusion SPECT, particularly combined with 128 × 128 acquisitions and iterative reconstruction with RR.

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Objective: A working group (WG) of the Japanese Society of Nuclear Cardiology (JSNC) determined Japanese normal databases of myocardial perfusion single-photon emission computed tomography (SPECT) on semi-conductor gamma camera (D-SPECT), and the aim of this study was to validate its clinical utility.
Materials and methods: The normal myocardial perfusion SPECT (MPS) databases of Japanese patients in the ²⁰¹Tl stress/redistribution protocol (²⁰¹Tl protocol), ^99mTc stress/rest or rest/stress protocol (^99mTc protocol), and rest ^99mTc/stress ²⁰¹Tl simultaneous acquisition dual-isotope protocol (SDI protocol) were created by JSNC WG. The WG collected clinical cases for the ²⁰¹Tl protocol (male/female [m/f], 8/8), ^99mTc protocol (m/f, 9/7), and SDI protocol (m/f, 10/10) from WG participating hospitals. Four WG members read those clinical cases on a 17-segment and 5-point scale (0–4). Using the most frequent values as the score for each segment, weighted κ values were calculated with the scores obtained from quantitative perfusion software (QPS).
Results: Weighted κ values were as follows; ²⁰¹Tl stress/female, 0.77; ²⁰¹Tl rest/female, 0.74; ²⁰¹Tl stress/male, 0.81; ²⁰¹Tl rest/male, 0.68; ^99mTc stress/female, 0.77; ^99mTc rest/female, 0.62; ^99mTc stress/male, 0.77; ^99mTc rest/male, 0.75; SDI stress/female, 0.87; SDI rest/female, 0.82; SDI stress/male, 0.87; SDI rest/male, 0.85.
Conclusions: The diagnostic accuracy of Japanese MPS normal databases on D-SPECT were comparable with nuclear cardiology expert reading and further clinical applications are expected.

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Background: Recent advances in cardiac modalities contribute to the guidelines on the diagnosis of cardiac sarcoidosis (CS) updated by the Japanese Circulation Society. The multicenter registry, Japanese Cardiac Sarcoidosis Prognostic (J-CASP) study tried to reveal recent trends of diagnosis and outcomes in CS patients and to validate the non-invasive diagnostic approach, including cardiac ¹⁸F-fluorodeoxyglucose (FDG) study.
Methods/results: Databases from 12 hospitals consisting of 231 CS patients (mean age, 64 years; female, 65%; LV ejection fraction, 47%) diagnosed by the guidelines with FDG positron emission tomography (PET) study were integrated to compile clinical information on the diagnostic criteria and outcomes. Cardiac ¹⁸F-FDG uptake and magnetic resonance imaging (CMR) was positive identically in the histology-proven and clinically-diagnosed groups. The histology-proven group more frequently had reduce LV ejection fraction, myocardial perfusion abnormality and low-grade electrocardiogram (ECG) abnormality (P = 0.003 to 0.016) than did the clinical group. During a 45-month period, the histology-proven group more frequently underwent appropriate implantable cardioverter-defibrillator (ICD) treatment (14% versus 4%, P = 0.013) and new electronic device implantation (30% versus 12%, P = 0.007) than did clinical group, respectively. There, however, was no difference in all-cause or cardiac mortality or in new hospitalization due to heart failure progression between them.
Conclusion: The J-CASP registry demonstrated the rationale and clinical efficacies of non-invasive approach using advanced cardiac imaging modalities in the diagnosis of CS even when histological data were available.

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Background: Gated myocardial perfusion single-photon emission computed tomography (SPECT) has been used to non-invasively evaluate the left ventricular (LV) volume and function. This study aimed to measure the normal and range values for heart risk view-function (HRV-F) software using the Japanese Society of Nuclear Medicine Working Group (JSNM-WG) normal database and clarify the characteristics of the normal database.
Methods: We used 206 myocardial perfusion short-axis images from the normal database. Ejection fraction (EF), end-systolic volume (ESV), end-diastolic volume (EDV), peak filling rate (PFR), 1/3 mean filling rate (MFR), time to PFR (TTPF), and TTPF divided by RR interval (TPFR/RR) were calculated. Phase parameters of 95% histogram bandwidth and standard deviation were also computed using the phase analysis. The relationships among phase parameters, LV volumes, and body surface area (BSA) were evaluated in the age group of ≤65 years.
Results: Higher EF was observed in females than in males (p<0.0001). EDV and ESV were significantly higher in males than in females (p<0.0001). Additionally, PFR and 1/3 MFR significantly differed between sexes (p≤0.075). Phase parameters were higher in males than in females, and higher at stress than at rest. All diastolic parameters showed no significant differences between sexes in any age group, whereas differences have remained in phase values. Phase parameters were weakly correlated with EDV (r=0.31), ESV (r=0.43), and BSA (r=0.27), respectively.
Conclusions: Mean normal and range values of the normal database were determined using the HRV-F software. The normal and range values can help diagnose gated SPECT data in patients with cardiac diseases.

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Introduction: Although ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been widely utilized to assess the extent of inflammation, the association between the extent and severity of atherosclerosis and ¹⁸F-FDG uptake on PET remains unexamined. The current study aimed to investigate whether aortic calcium (AC) scores were associated with increased aortic uptake of ¹⁸F-FDG on PET.
Methods: A total of 167 consecutive patients with suspected lung cancer but unproven malignancy who underwent non-contrast-enhanced computed tomography (CT) and ¹⁸F-FDG PET/CT were enrolled. The average standardized uptake values in the ascending aorta were used to calculate the target-to-background ratio (Mean TBR). The total (thoracic and abdominal) AC scores were measured on non-contrast-enhanced chest and abdominal CT using the Agatston method, and were categorized into three groups (0, 1–399, and ≥400). The relationship between total AC scores and ¹⁸F-FDG uptake in the ascending aorta was assessed using multivariate linear regression analysis.
Results: In total, 68.26% were male, and a mean age was 67.10±14.70 years. Mean TBR values increased progressively with total AC score 0, 1–399, and ≥400 (1.01±0.07, 1.08±0.09, and 1.11±0.11, respectively; p<0.00001). Multivariate linear regression analysis revealed that increased total AC scores of 1–399 (β=0.06, 95% CI: 0.01–0.11, p=0.02) and ≥400 (β=0.11, 95% CI: 0.06–0.16, p<0.001) were significantly associated with higher Mean TBR.
Conclusions: The current study demonstrated that total AC scores were associated with Mean TBR. Patients with a greater extent and severity of aortic calcifications may possess increased atherosclerotic inflammatory activity as measured by ¹⁸F-FDG PET/CT.

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Background: Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHA code: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with ¹²³I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is useful to evaluate myocardial TG metabolism; its washout rate (WR) reflects myocardial lipolysis. This study reports the effects of CNT-01 (tricaprin), a developing orphan drug to facilitate lipolysis, on BMIPP-WR in patients with TGCV.
Methods: An investigator-initiated, multicenter, randomized, double-blind exploratory, trial (Phase IIa) was conducted (UMIN000035403). Seventeen patients with idiopathic TGCV were orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. Endpoints included delta BMIPP-WR and clinical parameters such as 6-min-walk distance and TGCV severity score.
Results: During the protocol, delta BMIPP-WRs were -0.26±3.28 and 7.08±3.28% (95% confidence intervals, -7.36 to 6.84 and -0.01 to 14.18) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference of delta BMIPP-WR between the two groups was significant (p=0.035) after one patient was excluded from the placebo group because of pseudonormalization of BMIPP-WR related to coronary bypass graft stenosis. Clinical parameters did not show significant changes.
Conclusions: This study proved the mechanism of CNT-01 to improve myocardial lipolysis in TGCV, as demonstrated by BMIPP scintigraphy.

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The Japanese Society of Nuclear Cardiology (JSNC) and the American Society of Nuclear Cardiology (ASNC) has a relationship through a memorandum of understanding (MOU). This April, the MOU was extended for two more years. Based on this MOU, we hold a joint symposium at the JSNC annual meeting early in the summer each year. The theme of the joint symposium this year was “Inflammatory diseases of heart and large vessels”. We consider the success of the joint symposium to be the fruit of the close relationship between JSNC and ASNC.

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Machine learning has become popular in clinical practice, and the amount of research that uses artificial intelligence is rapidly increasing. In contrast to conventional statistical and rule-based methods, machine learning creates algorithms based only on combinations of input and output databases. Basic understanding of the internal workings of artificial intelligence, its structures and need for appropriate databases, as well as its strengths and weaknesses is important for efficient machine learning application. The cardiological applications of machine learning include diagnosing coronary artery diseases and heart failure, and examples are addressed herein. A preliminary application of machine learning to a ¹²³I-metaiodobenzylguanidine-based risk model appears promising, and further studies using similar approaches are anticipated. Nuclear medicine physicians and cardiologists should play key roles in developing machine learning-based methods to ensure practical and reliable decisions.

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The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial has had a great impact on the management of chronic coronary artery disease (CAD). One of the implications of this trial is the importance of close patient follow-up. To improve patient prognosis, evaluation of the residual extent of ischemia after treatment may be important because several studies have shown a close relationship between residual ischemia and cardiac events. For this assessment, myocardial perfusion single-photon emission computed tomography (MPS) has been utilized and is almost the only modality.
Among the participants in the ISCHEMIA trial, more than 10% were excluded due to the absence of obstructive CAD. The pathophysiology of ischemia without non-obstructive coronary artery disease (INOCA) is gaining recognition; however, diagnosis is difficult, except for the assessment of myocardial flow reserve (MFR). Myocardial perfusion positron emission tomography (PET) is the most common modality for noninvasive evaluation of MFR; however, its availability in Japan is limited. For a breakthrough in this situation, a novel gamma camera with a cadmium zinc telluride (CZT) semiconductor might be one of the solutions that enables the evaluation of MFR with a commercially available perfusion tracer, similar to PET. Another solution is a novel PET tracer with a longer half-life. Clinical trials with ¹⁸F labeled perfusion agents have been initiated in Japan, and in a few years, delivery of this perfusion tracer will result in more frequent and easier assessment of MFR.

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Background: There is no phantom for image quality test in magnetic resonance imaging combined with positron emission tomography systems (PET/MRI systems). In MRI, radioactive water phantom containing 2-deoxy-2-[F-18] fluoro-D-glucose (¹⁸F-FDG) cannot be used due to the dielectric effect. Even for phantoms filled with MR-available solutions, the source current of the RF coil is strongly disturbed as the diameter of the phantom increases. Stable MR images require proper phantom size and solution selection. Previous reports have not provided these details. Other than that, few existing phantoms evaluate negative signals such as N-13 ammonia (¹³N-NH₃). We created a phantom for PET/MRI system for image quality test.
Methods: The phantom for the PET/MRI system was assembled in two portions. One portion is a signal part containing ¹⁸F-FDG radioactive water. The other portion is filled with polyvinyl alcohol glue to construct MRI image to generate μ-map. The glue part is allowed to rewrite the table position overlaps with the first layer, and attenuation correction is performed. Signals are set as positive (4 times and twice higher than background radioactivity) and negative (no radioactivity) columns with different sizes (15 mm φ and 7 mm φ). The PET images with X-ray computed tomography-based attenuation correction (CT-AC) and MRI-AC were evaluated by %-contrasts, variation and uniformity.
Results: The %-contrasts of the positive shallow signals with PET/magnetic resonance (MR) and PET/CT were 41.8% and 45.4%, respectively. And it of the positive deep signals with PET/MR and PET/CT were 40.7% and 44.9%. On the other hand, the %-contrasts of the negative shallow signals with PET/MR and PET/CT were 62.3% and 65.6%, respectively. And it of the negative deep signals with PET/MR and PET/CT were 60.7% and 63.7%. Moreover, the% Nj index of uniformity was 2.0% on PET / MRI images and 0.34% on PET / CT images. For negative signals that assume a decrease in myocardial blood flow, The image quality of MR-AC was almost the same as that of CT-AC. Consistency between the images after CT-AC and MR-AC correction were confirmed, and in particular, a stable MR-AC μ-map was obtained in the phantom study.
Conclusion: The suggested prototype phantom for generating μ-map is reasonable and useful for evaluating PET/MRI image quality, based on the present standard.

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The Japanese Circulation Society (JCS) 2021 guideline on radiation safety in cardiology was updated based on the eight best practices for myocardial perfusion single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI), which was determined by panels of international atomic energy agency (IAEA) nuclear cardiology protocols cross-sectional study (INCAPS). Although the guideline recommends to avoid too much ²⁰¹Tl or ²⁰¹Tl/^99mTc dual-isotope protocol, the utilization rate of ²⁰¹Tl for SPECT-MPI in Japan is considerably high compared to other countries. In Japan, protocols using ^99mTc should be appropriately promoted based on the guideline to reduce radiation exposure in SPECT-MPI. Among the eight practices, stress-only imaging is considered to be a useful strategy that contributes to a significant reduction in radiation exposure, and hybrid assessment in combination with rest computed tomography (CT)-MPI is one of the practical application methods.

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Since Agatston et al. first reported quantification of the coronary artery calcification score (CACS) in 1990, discussion of its clinical significance and use in diagnostic management has continued. Recent papers have reported the relationship between CACS and myocardial perfusion single photon emission computed tomography (SPECT: MPS) and its combined diagnostic value. When interpreting CACS results, it should be noted that the frequency of significant ischemia detected by MPS, likelihood of coronary artery disease (CAD), and event rate gradually increased from mild to moderate CACS (1-400). At present, high CACS is considered to be moderately consistent with abnormal MPS, and abnormal CACS in normal MPS may contribute to CAD risk stratification. However, it should be noted that CACS = 0 does not completely exclude CAD, which is particularly important when using CACS as a gatekeeper for MPS. Both stand-alone computed tomography (CT) scanner and hybrid SPECT-CT scanner are available for combined risk stratification of CACS and MPS in addition to improvement of image quality with attenuation correction.

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