The purpose of this practice recommendation is to specifically identify the critical steps involved in performing and interpreting ¹²³I-β-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and measurement of washout rate (WR) from the heart. This document will cover backgrounds, patient preparation, testing procedure, visual image interpretation, quantitation methods using planar and SPECT studies, and reporting of WR. The pitfall and some tips for the calculation of ¹²³I-BMIPP WR are also included. The targets of global and regional WR calculation include ischemic heart disease, cardiomyopathy, heart failure, and triglyceride deposit cardiomyovasculopathy, an emerging rare heart disease.

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Background: Single-photon emission computed tomography (SPECT) encounters difficulties in diagnosing severe multi-vessel coronary artery disease (svMVD) because of balanced ischemia. We estimated the predictive value of electrocardiogram-gated SPECT for svMVD and improved it using machine learning (ML).
Methods and results: We enrolled consecutive 335 patients (median age, 74 years; 255 men) who underwent adenosine stress-gated SPECT (^99mTechnesium) and coronary angiography. svMVD was defined as three-vessel disease or left main tract stenosis. Predictive models were constructed using statistical and ML methods. Eighteen cases (5%) showed svMVD, and diabetes, summed stress score (SSS), and the max difference among segmental time of stroke volume per cardiac cycle (MDSV: a parameter of left ventricular (LV) end-systolic dyssynchrony) on adenosine stress were independent significant predictors. The area under the receiver operating characteristic curve (AUC) of SSS and MDSV on stress were 0.759 and 0.763, respectively. Conversely, the extra trees classifier and light gradient boosting machine had improved AUC values of 0.826 and 0.870, respectively, and the MDSV on stress and diabetes showed high feature values in the ML models.
Conclusion: ML on SPECT helped to improve the diagnostic performance of svMVD and diabetes, and the parameters of LV dyssynchrony played essential roles in the ML predictive models.

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Background: The arithmetic mean of washout rate (WR) (namely, AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computerized tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. To solve this possible issue, we formulated a modified algorithm for calculating WR based on the total count (namely, TCWR).
Methods: The WR of iodine-123-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. Participants included those without cardiovascular diseases (normal), those with CD36 deficiency, triglyceride deposit cardiomyovasculopathy (TGCV), TGCV with old myocardial infarction (OMI), and non-TGCV with OMI.
Results: WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4 ± 8.5 and 27.3 ± 8.5% (p = 0.97); CD36 deficiency, -3.2 ± 6.5 and -4.1 ± 7.4% (p = 0.81); TGCV, 2.4 ± 6.3 and 2.2 ± 6.3% (p = 0.93); and TGCV with OMI, -0.9 ± 7.6 and -3.7 ± 8.4% (p = 0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8 ± 8.7 and 18.9 ± 6.7%, p = 0.0008).
Conclusions: TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.

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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.

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Background: Myocardial blood flow quantification (MBF) is one of the distinctive features for cardiac PET. 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: PETCT 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.

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Background: ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy evaluates the severity and prognosis of patients with heart failure. A prognostic model has been proposed using a multicenter study data of ¹²³I-MIBG scintigraphy. We evaluated the usefulness of the model using a database.
Methods: The study included 208 patients with noncompensated heart failure requiring hospitalization. ¹²³I-MIBG scintigraphy and echocardiography were performed predischarge and 6 months postdischarge. The 5-year mortality rate was calculated by the model and classified into tertiles.
Results: In 208 patients, 56 cardiac deaths occurred within the observation period (median, 4.83 years). In the evaluation of predischarge parameters, the predicted 5-year mortality was 15.5% ± 5.0%, 33.5% ± 3.9%, and 51.2% ± 8.2%, and 11 (16.2%), 18 (27.3%), and 27 (36.5%) cardiac deaths occurred in groups 1, 2, and 3, respectively. At the 6-month postdischarge evaluation, the estimated mortality was 8.2% ± 2.2%, 18.5% ± 4.8%, and 43.0% ± 12.1%, and 6 (9.4%), 21 (29.2%), and 29 (40.3%) cardiac deaths occurred, respectively. The predischarge Kaplan–Meier survival analysis showed significant difference between groups 1 and 3 (P value 0.014). Moreover, the 6-month postdischarge evaluation showed significant difference between group 1 and 2, and between groups 1 and 3 (P value 0.016, <0.001, respectively). For groups 1 and 3, the 6-month postdischarge difference was more significant than the predischarge difference (Chi-square 16.7 and 8.1, respectively).
Conclusions: The prognostic model using ¹²³I-MIBG scintigraphy was useful in predicting mortality risk in patients with heart failure. The estimated mortality at 6 months postdischarge was more useful than the predischarge estimation for heart failure hospitalization.

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Background: Technetium-99m pyrophosphate single photon emission computed tomography (^99mTc-PYP SPECT) imaging is widely used to diagnose cardiac amyloidosis, a disease characterized by amyloid protein deposits in the myocardium. The effects of viewing perspectives on interobserver agreement in the interpretation of ^99mTc-PYP SPECT images for the diagnosis of cardiac amyloidosis remain unclear.
Methods: A retrospective analysis of 32 consecutive patients who underwent ^99mTc-PYP imaging for the diagnosis of cardiac amyloidosis at Nagasaki University Hospital between October 2017 and February 2020 was performed. Four evaluators independently reviewed coronal, sagittal, and transaxial images and then all images together and made a categorical diagnosis based on predefined criteria. Interobserver agreement was analyzed using Cohen's Kappa analysis.
Results: Kappa coefficient values in the four-grade grading system (grades 0–3) ranged between 0.31 and 0.95, while those in the binary grading system (positive/negative) ranged between 0.88 and 1. The sagittal view showed the highest value in the four-grade grading system (0.95) and the lowest in the binary grading system (0.88). The transaxial view was more likely to show a consistently high kappa value in both the four-grade and binary grading systems. The use of the multiplanar view reduced the number of subjects classified as grade 1.
Conclusion: Our study demonstrates that the transaxial view provides the most consistent interpretation of ^99mTc-PYP SPECT images for the diagnosis of cardiac amyloidosis. The use of the multiplanar view may also reduce equivocal interpretations, which are graded as grade 1. Further studies with larger sample sizes and a quantitative analysis are needed to confirm the present results.

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Background: Cross-calibration of ¹²³I-labeled meta-iodobenzylguanidine (mIBG) myocardial-derived indices is essential to extrapolate findings from several clinical centers. Here, we conducted a phantom study to generate conversion coefficients for the calibration of heart-to-mediastinum ratios and compare them between Taiwan and Europe.
Methods: We used an acrylic phantom dedicated to ¹²³I-mIBG planar imaging to calculate the conversion coefficients of 136 phantom images derived from 36 Taiwanese institutions. A European phantom image database including 191 images from 27 institutions was used. Conversion coefficients were categorized into five collimator types: low-energy (LE) high-resolution (LEHR), LE general-purpose (LEGP), extended LEGP (ELEGP), medium-energy (ME) GP (MEGP), and ME low-penetration (MELP) collimators.
Results: The conversion coefficients were 0.53 ± 0.039, 0.59 ± 0.032, 0.79 ± 0.032, 0.96 ± 0.038, and 0.99 ± 0.050 for LEHR, LEGP, ELEGP, MEGP, and MELP collimators, respectively. The Taiwanese and European conversion coefficients for the LEHR, LEGP, and MELP collimators did not significantly differ. The coefficient of variation was slightly higher for the Taiwanese than the European conversion coefficients (3.7%–7.5% vs. 2.3%–5.6%).
Conclusions: We calculated conversion coefficients for various types of collimators used in Taiwan using a ¹²³I-mIBG phantom. In general, the Taiwanese and European conversion coefficients were comparable. These findings further corroborated and highlighted the need for ¹²³I-mIBG standardization using the phantom-determined conversion coefficients.

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Background: A three-dimensional (3D) approach to absolute quantitation of ¹²³I-metaiodobenzylguanidine (MIBG) sympathetic nerve imaging using single-photon emission tomography (SPECT) / computed tomography (CT) is not available. Therefore, we calculated absolute cardiac counts and standardized uptake values (SUVs) from images of 72 consecutive patients with cardiac and neurological diseases using ¹²³I-MIBG SPECT/CT and compared them with conventional planar quantitation. We aimed to develop new methods for 3D heart segmentation and the quantitation of these diseases.
Methods: We manually segmented early and late SPECT/CT images of the heart in 3D, then calculated mean (SUV_mean) and maximum (SUV_max) SUVs. We analyzed correlations between SUVs and planar heart-to-mediastinum ratios (HMRs), and between washout rates (WRs) derived from the SUVs and planar data. We also categorized WRs as normal or abnormal using linear regression lines determined by the relationship between SPECT/CT and planar WRs, and assessed agreement between them.
Results: We calculated SUV_mean and SUV_max from all early and late ¹²³I-MIBG SPECT/CT images. Planar HMRs correlated with early and late SUV_mean (R² = 0.59 and 0.73, respectively) and SUV_max (R² = 0.46 and 0.60, respectively; both p < 0.0001). The SPECT/CT WRs determined based on SUV_mean and SUV_max (R² = 0.79 and 0.45, p < 0.0001) closely correlated with planar WRs. Agreement of high and low WRs between planar WRs and SPECT/CT WRs calculated using SUV_max and SUV_mean reached 88.1% and 94.4% respectively.
Conclusions: We found that sympathetic nervous activity could be absolutely quantified in 3D from ¹²³I-MIBG SPECT/CT images. Therefore, we propose a new method for quantifying sympathetic innervation on SPECT/CT images.

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Background: The use of ²⁰¹Tl in myocardial perfusion single-photon emission computed tomography (SPECT) is predominantly not recommended because of the higher radiation exposure of ²⁰¹Tl compared to ^99mTc agent. However, the advent of new gamma cameras with semiconductor detectors has made it possible to reduce the ²⁰¹Tl dose and lower radiation exposure. In our hospital, the dose of ²⁰¹Tl is adjusted according to the patient's body mass index (BMI), with 50 MBq for BMI<25 and 74 MBq for BMI≥25. The dose of ²⁰¹Tl during simultaneous acquisition dual-isotope myocardial perfusion SPECT (MPS; stress ²⁰¹Tl and rest ^99mTc agent) exceeds 9 mSv/examination when 74 MBq of ²⁰¹Tl is administered. In order to further reduce the radiation dose, optimization of the ²⁰¹Tl dose was investigated.
Methods: Two hundred and eighty consecutive patients who underwent stress MPS using simultaneous acquisition dual-isotope protocol (SDI protocol) for the estimation of ischemic heart disease were included. Patients with prior myocardial infarction were excluded. Correlations between BMI and acquisition time were determined in patients receiving 50 MBq (n=154) or 74 MBq (n=126) of ²⁰¹Tl. In addition, linear regression analysis was used to determine the slope and intercept to derive a linear functional equation, and the theoretically optimal ²⁰¹Tl dose was evaluated.
Results: The correlation coefficient between BMI and acquisition time in the ²⁰¹Tl 50 MBq group was 0.532 (P < 0.00001) and in the ²⁰¹Tl 74 MBq group was 0.478 (P < 0.00001), both showing a positive correlation. Linear regression analysis yielded two equations: y=0.52x-0.32 (²⁰¹Tl 50 MBq group) and y=0.41x-0.69 (²⁰¹Tl 74 MBq group). Linear function equation results indicated that patients with BMI between 25 and 30 could be examined within approximately 15 minutes with 50 MBq of ²⁰¹Tl.
Conclusion: Considering examination efficiency, a single acquisition time of less than 15 minutes is ideal. Theoretically, patients with BMI less than 30 could be examined within approximately 15 minutes with 50 MBq of ²⁰¹Tl.

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The JSNC-ASNC joint symposium in the 33^rd JSNC annual meeting was held on Jun. 24^th, and we invited Prof. Mouaz H. Al-Mallah, who was the president of ASNC and requested the lecture entitled “Comparison of MPI and FFR_CT”. He introduced several cases and evidences reported previously, and summarized the current status of FFR_CT, especially about the diagnostic performance, prognostic value, and proper use, compared to MPI.

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Since 2007, The Japanese Society of Nuclear Cardiology (JSNC) has been conducting regional training workshops on film reading for physicians and technologists who are just beginning their career in cardiac nuclear medicine examinations. JSNC will continue this workshop to expand the fields of cardiac nuclear medicine examinations.

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Both exercise single photon emission computed tomography (SPECT) imaging and myocardial perfusion imaging with positron emission tomography produce multiple outcome variables. These include the stress electrocardiogram (ECG), visual perfusion assessment and quantitative myocardial blood flow. Bayes’ analysis using conditional probability allows the distillation of multiple test results into a single probability of disease for individual patients. This paper examines the application of conditional probability analysis to two noninvasive modalities that generate multiple outcome results: exercise ECG combined with SPECT imaging and vasodilator RB-82 positron emission tomography perfusion imaging combined with quantitative measure of absolute myocardial blood flow. In this manner, a single probability of disease incorporating all the available data is generated for an individual patient.

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Background: The ¹²³I-metaiodobenzylguanidine heart-to-mediastinum ratios (HMRs) have been standardized between D-SPECT and Anger cameras in a small patient cohort using a phantom-based conversion method. This study aimed to determine the validity of this method and compare the diagnostic performance of the two cameras in a larger patient cohort.
Methods: We retrospectively calculated HMRs from early and late anterior-planar equivalent and planar images acquired from 173 patients in 177 studies using D-SPECT and Anger cameras, respectively. The D-SPECT HMRs were cross-calibrated to an Anger camera using conversion coefficients based on previous phantom findings, then standardized to medium-energy general-purpose collimator conditions. Relationships between HMRs before and after corrections were investigated. Late HMRs were classified into four cardiac mortality risk groups and divided into two groups using a threshold of 2.2 to verify diagnostic performance concordance.
Results: Correction improved linear regression lines and differences in HMRs among the groups. The overall ratios of perfect concordance were (134 [75.7%] of 177), and higher in groups with very low (49 [80.3%] of 61) and high (51 [86.4%] of 59) HMRs when the standardized HMR was classified according to cardiac mortality risk. That between the systems was the highest (164 [92.7%] of 177) when the HMR was divided by a threshold value of 2.2.
Conclusions: Phantom-based conversion can standardize HMRs between D-SPECT and Anger cameras because the standardized HMR provided comparable diagnostic performance. Our findings indicated that this conversion could be applied to multicenter studies that include both D-SPECT and Anger cameras.

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¹⁸F-flurpiridaz is a novel positron emission computed tomography (PET) tracer in ongoing clinical trials in United States and Japan. A phase III prospective, open-label, multi-center study to assess the feasibility of ¹⁸F-flurpiridaz was reported by Maddahi et al. in patients with known or suspected coronary artery disease (CAD) in 2020 in United States (1). ¹⁸F-flurpiridaz binds to mitochondrial complex 1 and would distribute to the myocardium with its higher extraction fraction than those in single-photon emission computed tomography (SPECT) tracers (2). In that phase III trial, 795 participants with known or suspected CAD showed that sensitivity of ¹⁸F-flurpiridaz PET (for detection of ≥50% stenosis by invasive coronary angiography) was 71.9%, significantly (p < 0.001) higher than ^99mTc labeled SPECT agent (53.7%), while specificity did not meet the prespecified noninferiority criterion (76.2% vs. 86.6%, p=NS) (1). Therefore, a second phase III Food and Drug Administration trial was planned and completed by GE Healthcare. Late phase II open-label multicenter study of PET scan using ¹⁸F-flurpiridaz (named NMB58 in Japan) to assess myocardial blood flow and diagnostic feasibility in patients with known or suspected CAD started in Japan of 2023.

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