Value of PET ECG gating in a cross-validation study of cardiac function assessment by PET/MR imaging.

Villagran Asiares A, Vitadello T, Bogdanovic B, Solari EL, ... Ibrahim T, Nekolla SG
Background
This work investigated the impact of different cardiac gating methods on the assessment of cardiac function by FDG-PET in a cross-validation PET/MR study.
Methods and results
MR- and PET-based left ventricular end-diastolic, end-systolic volumes, and ejection fraction (EDV, ESV, and EF) were delineated in 30 patients with a PET/MR examination. Cardiac PET imaging was performed using three ECG gating methods: fixed number of gates per beat (STD), STD with a beat acceptance window (STD-BR), and fixed gate duration (FW). High MR-PET correlations were found in all the values. ESVs correlated better than EDVs and EFs: Pearson\'s r coefficient [0.92, 0.92, 0.92] in ESV vs [0.75, 0.81, 0.80] in EDV and [0.79, 0.91, 0.87] in EF, for each method [STD, STD-BR, FW]. Biases with respect to MRI for all the evaluated PET methods were less than 13% in EDV, 5% in ESV, and 14% in EF, but with wide limits of agreements, in the range (59-68)% in EDV, (65-70)% in ESV, and (49-71)% in EF. STD showed the strongest disagreement, while there were no marked differences between STD-BR and FW.
Conclusion
Based on these findings, PET- and MR-based cardiac function parameters were highly correlated but in substantial disagreement with variabilities introduced by the selected PET ECG gating method. The most significant differences were associated with the ECG gating method susceptible to highly irregular beats, while similar performance was observed in the methods using uniform adjustment of gates width per beat with the beat acceptance window, and fixed gate width along all the beats. Thus, strict quality controls of R peak detection are needed to minimize its impact on the function assessment.

© 2022. The Author(s).

J Nucl Cardiol: 30 Sep 2022; epub ahead of print

Detection of acute myocarditis by ECG-triggered PET imaging of somatostatin receptors compared to cardiac magnetic resonance: preliminary results.

Boursier C, Chevalier E, Varlot J, Filippetti L, ... Mandry D, Marie PY
Somatostatin receptors are overexpressed by inflammatory cells but not by cardiac cells, under normal conditions. This study assesses the detection of acute myocarditis by the ECG-triggered digital-PET imaging of somatostatin receptors (⁶⁸Ga-DOTATOC-PET), as compared to Cardiac Magnetic Resonance (CMR) imaging, which is the reference diagnostic method in this setting.
Methods
Fourteen CMR-defined acute myocarditis patients had a first 15-minutes ECG-triggered ⁶⁸Ga-DOTATOC PET recording, 4.4 ± 3.0 days from peak troponin, and 10 had a second 4.3 ± 0.3 months later. Myocardial/blood SUVmax ratio was analyzed relative to the normal upper limit of 2.18, which had been previously determined from oncology ⁶⁸Ga-DOTATOC-PET recordings of patients with a similar age range as the myocarditis patients.
Results
An increased myocardial ⁶⁸Ga-DOTATOC uptake relative to blood activity was invariably observed during the acute phase. SUVmax ratio exceeded 2.18 in all patients during the acute phase but also in 3/10 patients at 4-months, at a time when there were no more signs of active inflammation on CMR. A residual myocardial ⁶⁸Ga-DOTATOC uptake was still observed on all gated-PET cine loops at 4-months.
Conclusion
These preliminary results suggest that ⁶⁸Ga-DOTATOC ECG-triggered digital-PET may be as sensitive as CMR at detecting myocarditis during the acute phase and more sensitive at later stages.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 19 Sep 2022; epub ahead of print

A quick glance at selected topics in this issue.

Bhambhvani P, Hage FG, Iskandrian AE
\"A quick glance at selected topics in this issue\" aims to highlight contents of the Journal and provide a quick review to the readers.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 14 Sep 2022; epub ahead of print

The impact of coronary calcium score as an addition to myocardial perfusion imaging in altering clinical management (ICCAMPA trial).

Jayadeva PS, Stowers S, Tang EW, Vitola J, ... Elison B, Better N
Introduction
AIM: Myocardial perfusion imaging (MPI) is a key tool for the identification and risk stratification of patients with coronary artery disease. The use of a coronary calcium score further adds to prognostic data above MPI alone. In this study, our aim was to evaluate the extent to which the use of a coronary artery calcium (CAC) score, when co-reported with MPI, impacts changes in clinical management in patients without a history of coronary artery disease (CAD) undergoing functional imaging.
Methods
This is a multicenter international study which incorporated a standardized questionnaire to evaluate changes in clinician management after MPI results were given with and without the additional information of a CAC score. Calcium scoring on a SPECT-CT system was performed via a semiquantitative Shemesh score (0-12) with a 0-3 score from the left main, left anterior descending, left circumflex, and right coronary arteries. CT of the chest was read independently, and non-coronary findings were reported alongside the CAC score.
Results
A total of 281 patients were enrolled across 3 international centers (Brazil, Australia, New Zealand). Of the 281 patients, 133 (47%) had management altered after the clinician was made aware of the CAC score. The impact of the CAC in changing clinical management was significant, particularly in patients with a negative MPI (P < 0.0001), but also in MPI-positive patients (P = 0.0021). The most common management change was the addition or intensification of statin therapy.
Conclusion
The addition of the CAC component to MPI yielded significant management changes in nearly half of all patients undergoing MPI for suspected CAD. This trend was observed across all centers in the three countries involved and was particularly evident in patient with a negative MPI.

© 2022. Crown.

J Nucl Cardiol: 12 Sep 2022; epub ahead of print

Deep-learning-based estimation of attenuation map improves attenuation correction performance over direct attenuation estimation for myocardial perfusion SPECT.

Du Y, Shang J, Sun J, Wang L, ... Xu H, Mok GSP
Background
Deep learning (DL)-based attenuation correction (AC) is promising to improve myocardial perfusion (MP) SPECT. We aimed to optimize and compare the DL-based direct and indirect AC methods, with and without SPECT and CT mismatch.
Methods
One hundred patients with different ^99mTc-sestamibi activity distributions and anatomical variations were simulated by a population of XCAT phantoms. Additionally, 34 patients ^99mTc-sestamibi stress/rest SPECT/CT scans were retrospectively recruited. Projections were reconstructed by OS-EM method with or without AC. Mismatch between SPECT and CT images was modeled. A 3D conditional generative adversarial network (cGAN) was optimized for two DL-based AC methods: (i) indirect approach, i.e., non-attenuation corrected (NAC) SPECT paired with the corresponding attenuation map for training. The projections were reconstructed with the DL-generated attenuation map for AC; (ii) direct approach, i.e., NAC SPECT paired with the corresponding AC SPECT for training to perform direct AC.
Results
Mismatch between SPECT and CT degraded DL-based AC performance. The indirect approach is superior to direct approach for various physical and clinical indices, even with mismatch modeled.
Conclusion
DL-based estimation of attenuation map for AC is superior and more robust to direct generation of AC SPECT.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 12 Sep 2022; epub ahead of print

[Cu]Cu-DOTATATE PET metrics in the investigation of atherosclerotic inflammation in humans.

Jensen JK, Madsen JS, Jensen MEK, Kjaer A, Ripa RS
Purpose
The aim of this study was to assess and compare the arterial uptake of the inflammatory macrophage targeting PET tracer [⁶⁴Cu]Cu-DOTATATE in patients with no or known cardiovascular disease (CVD) to investigate potential differences in uptake.
Methods
Seventy-nine patients who had undergone [⁶⁴Cu]Cu-DOTATATE PET/CT imaging for neuroendocrine neoplasm disease were retrospectively allocated to three groups: controls with no known CVD risk factors (n = 22), patients with CVD risk factors (n = 24), or patients with known ischemic CVD (n = 33). Both maximum, mean of max and most-diseased segment (mds) standardized uptake value (SUV) and target-to-background ratio (TBR) uptake metrics were measured and reported for the carotid arteries and the aorta. To assess reproducibility between different reviewers, Bland-Altman plots were made.
Results
For the carotid arteries, SUV_max (P = .03), SUV_mds (0.05), TBR_max (P < .01), TBR_mds (P < .01), and mean-of-max TBR (P = .01) were overall shown to provide a group-wise difference in uptake. When measuring uptake values in the aorta, a group-wise difference was only observed with TBR_mds (P = .04). Overall, reproducibility of the reported uptake metrics was excellent for SUVs and good to excellent for TBRs for both the carotid arteries and the aorta.
Conclusion
Using [⁶⁴Cu]Cu-DOTATATE PET imaging as a marker of atherosclerotic inflammation, we were able to demonstrate differences in some of the most frequently reported uptake metrics in patients with different degrees of CVD. Measurements of the carotid artery as either maximum uptake values or most-diseased segment analysis showed the best ability to discriminate between the groups.

© 2022. The Author(s).

J Nucl Cardiol: 31 Aug 2022; epub ahead of print

Utility of 68Ga-DOTANOC PET/CT in therapeutic monitoring of cardiac sarcoidosis.

Jaleel J, Patel C, Khangembam B, Kumar S, Babu AS, Seth S
Cardiac sarcoidosis usually occurs as a manifestation of systemic sarcoidosis, even though isolated cardiac involvement is not uncommon. The usefulness of 68Ga-DOTANOC PET/CT in the diagnosis of CS has been previously documented in the literature. We present a case of cardiac sarcoidosis, where 68Ga-DOTANOC PET/CT was used for monitoring response to therapy.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 31 Aug 2022; epub ahead of print

Deep learning-based denoising in projection-domain and reconstruction-domain for low-dose myocardial perfusion SPECT.

Sun J, Jiang H, Du Y, Li CY, ... Yang BH, Mok GSP
Background
Low-dose (LD) myocardial perfusion (MP) SPECT suffers from high noise level, leading to compromised diagnostic accuracy. Here we investigated the denoising performance for MP-SPECT using a conditional generative adversarial network (cGAN) in projection-domain (cGAN-prj) and reconstruction-domain (cGAN-recon).
Methods
Sixty-four noisy SPECT projections were simulated for a population of 100 XCAT phantoms with different anatomical variations and ^99mTc-sestamibi distributions. Series of LD projections were obtained by scaling the full dose (FD) count rate to be 1/20 to 1/2 of the original. Twenty patients with ^99mTc-sestamibi stress SPECT/CT scans were retrospectively analyzed. For each patient, LD SPECT images (7/10 to 1/10 of FD) were generated from the FD list mode data. All projections were reconstructed by the quantitative OS-EM method. A 3D cGAN was implemented to predict FD images from their corresponding LD images in the projection- and reconstruction-domain. The denoised projections were reconstructed for analysis in various quantitative indices along with cGAN-recon, Gaussian, and Butterworth-filtered images.
Results
cGAN denoising improves image quality as compared to LD and conventional post-reconstruction filtering. cGAN-prj can further reduce the dose level as compared to cGAN-recon without compromising the image quality.
Conclusions
Denoising based on cGAN-prj is superior to cGAN-recon for MP-SPECT.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 18 Aug 2022; epub ahead of print

Utility of positron emission tomography myocardial perfusion imaging for identifying ischemia and guiding treatment in patients with anomalous coronary arteries.

Wang TKM, Dong T, Cremer PC, Najm H, Pettersson G, Jaber WA
Background
The assessment of anomalous coronary arteries (AAOCA) remains controversial without an optimal stress modality for ischemia. We evaluated the value of PET-CT myocardial perfusion imaging in these patients and subsequent management.
Methods and results
AAOCA patients (n = 82) undergoing PET-CT from 2015 to 2021 were retrospectively chart reviewed. Multivariable analyses performed to assess relevant clinical and imaging factors associated with ischemia on PET and AAOCA surgery. Key characteristics include mean age 45 ± 20 years, 30 (37%) female, 45 (55%) with chest pain, 19 (23%) anomalous left main coronary artery, 58 (71%) anomalous right coronary artery, 26 (32%) with objective ischemia on PET-CT, and 37 (45%) who underwent AAOCA surgery. Adverse outcomes over mean follow-up of 2.2 ± 1.8 years included one death and two myocardial infarctions. Anomalous left main was independently associated with ischemia on PET-CT, odds ratio (95% confidence intervals) 4.15 (1.31-13.1), P = .006. Chest pain and ischemia on PET-CT were independently associated with and provided incremental prognostic value for surgery, odds ratio 9.73 (2.78-34.0), P < .001 and 6.79 (1.99-23.2), P = .002, respectively.
Conclusion
Ischemia on PET-CT occurred in a third of our cohort, identifying patients who may benefit from surgery. Larger studies are needed to evaluate the interplay between AAOCA, ischemia by PET and surgery.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 17 Aug 2022; epub ahead of print

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

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

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 15 Aug 2022; epub ahead of print

Prognostic impact of patients\' management based on anatomic/functional phenotype: a study in patients with chronic coronary syndromes.

Liga R, Neglia D, Cavaleri S, Grasso E, Giorgetti A, Gimelli A
Background
In stable coronary artery disease (CAD), the prognostic interaction between clinical variables and treatment appropriateness based on anatomic/functional phenotype needs to be evaluated.
Methods
1585 consecutive patients underwent myocardial perfusion scintigraphy and coronary angiography within 90 days. Obstructive CAD (> 70% stenosis) with downstream moderate-to-severe ischemia (> 10%) was considered significant. Coronary revascularization was considered appropriate if all hemodynamically significant lesions were revascularized, while medical therapy only was deemed appropriate in the absence of hemodynamically significant CAD.
Results
Obstructive CAD and moderate-to-severe ischemia were documented in 1184 (75%) and 466 (29%) patients, respectively. Over mean follow-up of 4.7 ± 2.5 years, the primary endpoint (cardiac death and non-fatal myocardial infarction) occurred in 132 (8.2%) patients. Of patients with obstructive CAD, 797 (67%) were managed appropriately. Patients\' management was inappropriate in 389 patients, because either non-hemodynamically significant lesions were revascularized (50%, including 2 patients with non-obstructive lesions being inappropriately revascularized) or ischemia-causing CAD was left untreated (50%). At multivariate analysis, an inappropriate management (P < .001) was correlated with the primary endpoint, together with previous myocardial infarction (P = .009), lower ejection fraction (P < .001) and higher glucose levels (P < .001).
Conclusions
In stable CAD patients, management based on anatomic/functional phenotyping was correlated with a prognostic advantage at long-term follow-up. Correlation between treatment categories and patients\' prognosis. A significantly higher event-rate was observed in patients where hemodynamically significant coronary lesions were left untreated-either because MT was not-adherently chosen or in the case of incomplete revascularization-than in those that were revascularized completely (17.6% vs 5.1%; P < .001). Conversely, the revascularization of non-hemodynamically significant CAD correlated with a higher event-rate than that of similar patients managed medically (13.8% vs 8.3%, P = .04). The event-rate of patients in whom coronary revascularization was performed in the presence of hemodynamically significant CAD (\'appropriate revascularization\') was similar to those with \"No CAD/non-obstructive CAD\" (5.1% vs 3.5%; P = NS).

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 08 Aug 2022; epub ahead of print

Usefulness of the Vall d\'Hebron Risk Score to stratify the risk of patients with ischemic cardiomyopathy.

Romero-Farina G, Aguadé-Bruix S, Ródenas-Alesina E, Herrador L, Jordán P, Ferreira-González I
Background
To evaluate the Vall d\'Hebron-Risk-Score (VH-RS) to stratify the risk of patients with stable ischemic cardiomyopathy (ICM), and assess whether hemoglobin (Hb) and estimated glomerular filtration rate (eGFR) provide additional information to the VH-RS.
Methods and results
We analysed 673 consecutive patients with ICM who underwent gated SPECT. According to VH-RS, we stratified patients into 4-risk-levels: very-low-risk (VLR), low-risk (LR), moderate-risk (MR), and high-risk (HRi). We considered as MACEs: non-fatal myocardial infarction (MI), heart failure hospitalization (HF), coronary revascularization (CR), and cardiac death (CD). Also the cardiac-resynchronization-therapy (CRT), and the implantable-cardioverter-defibrillator (ICD) were investigated. During the follow-up (4.8 ± 2.7 years), 379 patients had MACEs (0.18/patient/year). There were no patients in VLR and LR. All patients were reclassified in 3-risk-levels (MRi = 48; HRi = 121; VHRi[very high risk] = 504). Most patients with MACEs were in VHRi level (test-for-trend: MACEs ≥ 1 without CRT/ICD, P < .001; combined non-fatal MI, CD and CR, P < .001; MACEs ≥ 1 with CRT/ICD, P < .001). The Hb and eGFR values do not properly improve the risk stratification obtained by the VH-RS (global-NRI[net-reclassification-improvement] was: (MACEs ≥ 1 without CRT/ICD: - 10.6%; non-fatal MI, CD and CR: - 9.08%; and MACEs ≥ 1 with CRT/ICD: - 8.85%).
Conclusion
VH-RS is effective in evaluating risk of patients with stable ICM. In our population, adding Hb and eGFR variables do not improve the performance of the VH-RS.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 08 Aug 2022; epub ahead of print

Pulmonary artery imaging with  Ga-FAPI-04 in patients with chronic thromboembolic pulmonary hypertension.

Gong JN, Chen BX, Xing HQ, Huo L, Yang YH, Yang MF
Background
The feasibility and significance of imaging pulmonary artery (PA) remodeling with ⁶⁸ Ga-fibroblast activating protein inhibitor (FAPI) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have not yet been addressed.
Methods
⁶⁸ Ga-FAPI uptake in the PA and ascending artery was evaluated in 13 patients with CTEPH and 13 matched non-CTEPH controls. The correlations of PA ⁶⁸ Ga-FAPI uptake and remodeling parameters derived from right heart catheterization (RHC) were analyzed.
Results
Of the 13 patients with CTEPH, nine (69%) showed visually enhanced ⁶⁸ Ga-FAPI-04 uptake, whereas none of the control subjects had increased ⁶⁸ Ga-FAPI-04 uptake in the PA. The prevalence of enhanced uptake in the main, lobar, and segmental PAs was 45% (17/38), 33% (16/48), and 28% (44/159), respectively. ⁶⁸ Ga-FAPI-04 activity in the PA was positively correlated with pulmonary arterial diastolic pressure (r = 0.571, P = 0.041).
Conclusion
⁶⁸ Ga-FAPI-04 has the potential for imaging fibroblast activation in the PA wall, and ⁶⁸ Ga-FAPI-04 activity in PA is positively correlated with pulmonary arterial diastolic pressure.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 04 Aug 2022; epub ahead of print

Influence of image reconstruction on quantitative cardiac O-water positron emission tomography.

Nordström J, Lindström E, Kero T, Sörensen J, Lubberink M
Background
The impact on quantitative ¹⁵O-water PET/CT of a wide range of different reconstruction settings, including regularized reconstruction by block-sequential regularized expectation maximization (BSREM), was investigated.
Methods
Twenty clinical stress scans from patients referred for assessment of myocardial ischemia were included. Patients underwent a 4-min dynamic stress PET scan with ¹⁵O-water on a digital PET/CT scanner. Twenty-two reconstructions were generated from each scan and a clinical reconstruction was used as reference. Varied parameters were number of iterations, filter, exclusion of time-of-flight and point-spread function, and regularization parameter with BSREM. Analyses were performed in aQuant utilizing two different methods and resulting regional myocardial blood flow (MBF), perfusable tissue fraction (PTF), and transmural MBF (MBFt) values were evaluated.
Results
Across the two analyses, correlations toward the reference reconstruction were strong for all parameters (ρ ≥ 0.83). Using automated analysis and the diagnostic threshold of hyperemic MBF at 2.3 mL⋅g^-1⋅min^-1, diagnosis was unchanged irrespective of reconstruction method in all patients except for one, where only four of the most extreme reconstruction methods resulted in a change of diagnosis.
Conclusion
The low sensitivity of MBF values to reconstruction method and, as previously shown, scanner type and PET/CT misalignment, confirms that diagnostic hyperemic MBF cutoff values can be consistently used for ¹⁵O-water.

© 2022. The Author(s).

J Nucl Cardiol: 04 Aug 2022; epub ahead of print

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

Liu L, Dai N, Yin G, Zhang W, ... Yu F, Che W
Background
A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients.
Methods
Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke).
Results
Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030).
Conclusion
caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 02 Aug 2022; epub ahead of print

Strengths and weaknesses of alternative noninvasive imaging approaches for microvascular ischemia.

Leo I, Nakou E, Artico J, Androulakis E, ... Indolfi C, Bucciarelli-Ducci C
Structural and functional abnormalities of coronary microvasculature are highly prevalent in several clinical settings and often associated with worse clinical outcomes. Therefore, there is a growing interest in the detection and treatment of this, often overlooked, disease. Coronary angiography allows the assessment of the Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). However, the measurement of these parameters is not always feasible because of limited technical availability and the need for a cardiac catheterization with a small but real risk of potential complications. Recent advances in non-invasive imaging techniques allow the assessment of coronary microvascular function with good accuracy and reproducibility. The objective of this review is to discuss the strengths and weaknesses of alternative non-invasive approaches used in the diagnosis of coronary microvascular dysfunction (CMD), highlighting the most recent advances for each imaging modality.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 02 Aug 2022; epub ahead of print

Effective suppression of myocardial glucose uptake using predesigned low-carbohydrate boxed meals.

Huang CK, Hou PN, Luzhbin D, Yang CW, Chang YT, Wu J
Background
Dietary preparation protocols are an effective means to suppress physiological myocardial ¹⁸F-fluorodeoxyglucose (FDG) uptake. This study aimed to investigate the efficacy of various carbohydrate-restricted diets using predesigned boxed meals.
Methods
The patients were divided into four groups to undergo different preparatory protocols as follows: a minimum 15-hours fast alone, two meals of high-fat, low-carbohydrate diet (HFLCD), two meals of high-animal-protein, low-carbohydrate diet (HAPLCD), and two meals of high-plant-based-protein, low-carbohydrate diet (HPPLCD). Boxed meals were prepared to meet the required carbohydrate restrictions. Myocardial SUV_max and SUV_mean were measured and the suppression rate was analyzed.
Results
The average myocardial SUV_max of fast alone, HFLCD, HAPLCD, and HPPLCD was 8.26 ± 5.85, 2.21 ± 1.50, 2.34 ± 1.88, and 4.10 ± 3.61, respectively, and the suppression rate was 36.6%, 93.3%, 93.3%, and 70%, respectively. The effectiveness of HFLCD, HAPLCD, and HPPLCD was all statistically superior to that of a 15-hours fast alone. SUV_max of HFLCD and HAPLCD showed no significant differences (p = 1), whereas HFLCD and HPPLCD had significant differences (p = .046).
Conclusions
Using the predesigned boxed meals based on carbohydrate restriction, HFLCD, HAPLCD, and HPPLCD can be administered to patients with different dietary needs, while providing a substantial reduction in physiological myocardial FDG uptake.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 02 Aug 2022; epub ahead of print

Coronary microvascular disease in hypertrophic and infiltrative cardiomyopathies.

Giannopoulos AA, Buechel RR, Kaufmann PA
Pathologic hypertrophy of the cardiac muscle is a commonly encountered phenotype in clinical practice, associated with a variety of structural and non-structural diseases. Coronary microvascular disease is considered to play an important role in the natural history of this pathological phenotype. Non-invasive imaging modalities, most prominently positron emission tomography and cardiac magnetic resonance, have provided insights into the pathophysiological mechanisms of the interplay between hypertrophy and the coronary microvasculature. This article summarizes the current knowledge on coronary microvascular dysfunction in the most frequently encountered forms of pathologic hypertrophy.

© 2022. The Author(s).

J Nucl Cardiol: 01 Aug 2022; epub ahead of print

The combined effect of air and transportation noise pollution on atherosclerotic inflammation and risk of cardiovascular disease events.

Osborne MT, Abohashem S, Naddaf N, Abbasi T, ... Fayad ZA, Tawakol A
Background
Air pollution and noise exposures individually associate with major adverse cardiovascular events (MACE) via a mechanism involving arterial inflammation (ArtI); however, their combined impact on ArtI and MACE remains unknown. We tested whether dual (vs. one or neither) exposure associates with greater ArtI and MACE risk and whether MACE risk is mediated via ArtI.
Methods
Individuals (N = 474) without active cancer or known cardiovascular disease with clinical ¹⁸F-FDG-PET/CT imaging were followed for 5 years for MACE. ArtI was measured. Average air pollution (particulate matter ≤ 2.5 μm, PM_2.5) and transportation noise exposure were determined at individual residences. Higher exposures were defined as noise > 55 dBA (World Health Organization cutoff) and PM_2.5 ≥ sample median.
Results
At baseline, 46%, 46%, and 8% were exposed to high levels of neither, one, or both pollutants; 39 experienced MACE over a median 4.1 years. Exposure to an increasing number of pollutants associated with higher ArtI (standardized β [95% CI: .195 [.052, .339], P = .008) and MACE (HR [95% CI]: 2.897 [1.818-4.615], P < .001). In path analysis, ArtI partially mediated the relationship between pollutant exposures and MACE (P < .05).
Conclusion
Air pollution and transportation noise exposures contribute incrementally to ArtI and MACE. The mechanism linking dual exposure to MACE involves ArtI.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Aug 2022; epub ahead of print

I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (I-OI5V) imaging visualized augmented sigma-1 receptor expression according to the severity of myocardial ischemia.

Wakabayashi H, Mori H, Hiromasa T, Akatani N, ... Kinuya S, Taki J
Background
We aimed to explore how the severity of myocardial ischemia affects myocardial sigma-1 receptor (Sig-1R) expression using ¹²⁵I-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (¹²⁵I-OI5V) imaging.
Methods and results
The left coronary artery was occluded for 30, 20, and 10 minute, to vary the severity of myocardial ischemia, followed by reperfusion. Dual-tracer autoradiography of the left ventricular short-axis slices was performed 3 and 7 days after reperfusion. ¹²⁵I-OI5V was injected 30 minute before sacrifice and the area at risk (AAR) was evaluated by ^99mTc-MIBI. Intense ¹²⁵I-OI5V uptake was observed in the AAR and was significantly increased with increasing ischemia duration. To evaluate salvaged and nonsalvaged areas (preserved and decreased perfusion areas), triple-tracer autoradiography was performed 3 days after reperfusion. After dual-tracer autoradiography, ²⁰¹Tl was injected 20 minute post ¹²⁵I-OI5V injection. On triple-tracer autoradiography, the AAR/normally perfused area ¹²⁵I-OI5V uptake ratio was positively correlated with the nonsalvaged area/whole left ventricular (LV) area ratio (P < .05). The AAR/normally perfused area ¹²⁵I-OI5V uptake ratio was negatively correlated with the ²⁰¹Tl uptake ratio of the AAR to normally perfused areas (P < .05). The comparison of the immunostaining distribution of ¹²⁵I-OI5V and the macrophage marker CD68 revealed that ¹²⁵I-OI5V was present mainly in, and immediately adjacent to the macrophage infiltration area.
Conclusions
Significant ¹²⁵I-OI5V uptake in the AAR depends on the duration of ischemia and reduced ²⁰¹Tl uptake; furthermore, ¹²⁵I-OI5V was found in and around the macrophage infiltrate area. These results indicate that iodine-labeled OI5V is a promising tool for visualizing Sig-1R expression according to the ischemic burden.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Aug 2022; epub ahead of print

A method using deep learning to discover new predictors from left-ventricular mechanical dyssynchrony for CRT response.

He Z, Zhang X, Zhao C, Ling X, ... Zou J, Zhou W
Background
Studies have shown that the conventional parameters characterizing left ventricular mechanical dyssynchrony (LVMD) measured on gated SPECT myocardial perfusion imaging (MPI) have their own statistical limitations in predicting cardiac resynchronization therapy (CRT) response. The purpose of this study is to discover new predictors from the polarmaps of LVMD by deep learning to help select heart failure patients with a high likelihood of response to CRT.
Methods
One hundred and fifty-seven patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at 6 [Formula: see text] 1 month follow up. The autoencoder (AE) technique, an unsupervised deep learning method, was applied to the polarmaps of LVMD to extract new predictors characterizing LVMD. Pearson correlation analysis was used to explain the relationships between new predictors and existing clinical parameters. Patients from the IAEA VISION-CRT trial were used for an external validation. Heatmaps were used to interpret the AE-extracted feature.
Results
Complete data were obtained in 130 patients, and 68.5% of them were classified as CRT responders. After variable selection by feature importance ranking and correlation analysis, one AE-extracted LVMD predictor was included in the statistical analysis. This new AE-extracted LVMD predictor showed statistical significance in the univariate (OR 2.00, P = .026) and multivariate (OR 1.11, P = .021) analyses, respectively. Moreover, the new AE-extracted LVMD predictor not only had incremental value over PBW and significant clinical variables, including QRS duration and left ventricular end-systolic volume (AUC 0.74 vs 0.72, LH 7.33, P = .007), but also showed encouraging predictive value in the 165 patients from the IAEA VISION-CRT trial (P < .1). The heatmaps for calculation of the AE-extracted predictor showed higher weights on the anterior, lateral, and inferior myocardial walls, which are recommended as LV pacing sites in clinical practice.
Conclusions
AE techniques have significant value in the discovery of new clinical predictors. The new AE-extracted LVMD predictor extracted from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Aug 2022; epub ahead of print

Value of rest F-FDG myocardial imaging in the diagnosis of obstructive coronary artery disease in Chinese patients with suspected unstable angina: A prospective real-world clinical study.

Yang X, Zhang F, Chen Y, Shao X, ... Li S, Wang Y
Background
This study aimed to determine the clinical value of rest ¹⁸F-FDG imaging in Chinese patients with non-acute chest pain, normal ECG, negative troponin, and suspected UA.
Methods
136 patients were prospectively included and underwent rest ¹⁸F-FDG PET imaging and coronary arteriography within 1 week.
Results
Obstructive CAD was diagnosed in 71 patients, and stenosis ≥ 70% was confirmed in 130 vascular territories. At patients and vascular level, rest ¹⁸F-FDG imaging showed sensitivity of 62.0%, 47.7%, specificity of 92.3%, 94.2%, accuracy of 76.5%, 79.4%, PPV of 89.8% and 79.5%, and NPV of 69.0% and 79.4%. The AUCs were 0.771 and 0.710. Of 71 patients with obstructive CAD, rest ¹⁸F-FDG imaging showed sensitivity of 47.7% and 58.8%, specificity of 91.6% and 91.2%, accuracy of 64.8% and 80.4%, PPV of 89.9% and 76.9% and NPV of 52.8% and 81.6% in all vascular level and single-vessel disease. In patients with two- or three-vessel disease, rest ¹⁸F-FDG imaging had a diagnostic sensitivity, specificity, accuracy, PPV, and NPV of 43.8%, 93.3%, 50.5%, 97.7%, and 20.6%. The AUCs were 0.696, 0.750, and 0.685.
Conclusion
Rest ¹⁸F-FDG imaging performed certain overall diagnostic efficiency for obstructive CAD in Chinese patients with suspected UA, especially the excellent high PPV in identifying culprit ischemic territory in patients with multivessel disease.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Aug 2022; epub ahead of print

Diagnostic accuracy of dynamic CZT-SPECT in coronary artery disease. A systematic review and meta-analysis.

Panjer M, Dobrolinska M, Wagenaar NRL, Slart RHJA
Background
With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities, such as quantitative coronary angiography (CAG) with fractional flow reserve (FFR) and positron emission tomography (PET), are lacking. This study aimed to evaluate the diagnostic accuracy of dynamic CZT single-photon emission tomography (SPECT) in coronary artery disease compared to quantitative CAG, FFR, and PET as reference.
Materials and methods
Different databases were screened for eligible citations performing dynamic CZT-SPECT against CAG, FFR, or PET. PubMed, OvidSP (Medline), Web of Science, the Cochrane Library, and EMBASE were searched on the 5th of July 2020. Studies had to meet the following pre-established inclusion criteria: randomized controlled trials, retrospective trails or observational studies relevant for the diagnosis of coronary artery disease, and performing CZT-SPECT and within half a year the methodological references. Studies which considered coronary stenosis between 50% and 70% as significant based only on CAG were excluded. Data extracted were sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Quality was assessed with QUADAS-2 and statistical analysis was performed using a bivariate model.
Results
Based on our criteria, a total of 9 studies containing 421 patients were included. For the assessment of CZT-SPECT, the diagnostic value pooled analysis with a bivariate model was calculated and yielded a sensitivity of 0.79 (% CI 0.73 to 0.85) and a specificity of 0.85 (95% CI 0.74 to 0.92). Diagnostic odds ratio (DOR) was 17.82 (95% CI 8.80 to 36.08, P < 0.001). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.86 (95% CI 2.76 to 5.38, P < 0.001) and 0.21 (95% CI 0.13 to 0.33, P < 0.001), respectively.
Conclusion
Based on the results of the current systematic review and meta-analysis, dynamic CZT-SPECT MPI demonstrated a good sensitivity and specificity to diagnose CAD as compared to the gold standards. However, due to the heterogeneity of the methodologies between the CZT-SPECT MPI studies and the relatively small number of included studies, it warrants further well-defined study protocols.

© 2021. The Author(s).

J Nucl Cardiol: 01 Aug 2022; 29:1686-1697

Hot spot imaging in cardiovascular diseases: an information statement from SNMMI, ASNC, and EANM.

Sperry BW, Bateman TM, Akin EA, Bravo PE, ... Miller EJ, Liu C
This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

© 2022. American Society of Nuclear Cardiology and Society of Nuclear Medicine and Molecular Imaging.

J Nucl Cardiol: 21 Jul 2022; epub ahead of print

2022 Artificial intelligence primer for the nuclear cardiologist.

Motwani M
Driven by advances in computing power, the past decade has seen rapid developments in artificial intelligence (AI) which now offers potential enhancements to every aspect of nuclear cardiology workflow including acquisition, reconstruction, segmentation, direct image analysis, and interpretation; as well as facilitating clinical and imaging big-data integration for superior personalized risk stratification. To understand the relevance and potential of AI in their field, this review provides a primer for nuclear cardiologists in 2022. The aim is to explain terminology and provide a summary of key current implementations, challenges, and future aspirations of AI-based enhancements to nuclear cardiology.

© 2022. Crown.

J Nucl Cardiol: 19 Jul 2022; epub ahead of print

Automated cardiovascular risk categorization through AI-driven coronary calcium quantification in cardiac PET acquired attenuation correction CT.

van Velzen SGM, Dobrolinska MM, Knaapen P, van Herten RLM, ... Greuter MJW, Išgum I
Background
We present an automatic method for coronary artery calcium (CAC) quantification and cardiovascular risk categorization in CT attenuation correction (CTAC) scans acquired at rest and stress during cardiac PET/CT. The method segments CAC according to visual assessment rather than the commonly used CT-number threshold.
Methods
The method decomposes an image containing CAC into a synthetic image without CAC and an image showing only CAC. Extensive evaluation was performed in a set of 98 patients, each having rest and stress CTAC scans and a dedicated calcium scoring CT (CSCT). Standard manual calcium scoring in CSCT provided the reference standard.
Results
The interscan reproducibility of CAC quantification computed as average absolute relative differences between CTAC and CSCT scan pairs was 75% and 85% at rest and stress using the automatic method compared to 121% and 114% using clinical calcium scoring. Agreement between automatic risk assessment in CTAC and clinical risk categorization in CSCT resulted in linearly weighted kappa of 0.65 compared to 0.40 between CTAC and CSCT using clinically used calcium scoring.
Conclusion
The increased interscan reproducibility achieved by our method may allow routine cardiovascular risk assessment in CTAC, potentially relieving the need for dedicated CSCT.

© 2022. The Author(s).

J Nucl Cardiol: 18 Jul 2022; epub ahead of print

Role of nuclear cardiology in diagnosis and risk stratification of coronary microvascular disease.

Ruddy TD, Tavoosi A, Taqueti VR
Coronary flow reserve (CFR) with positron emission tomography/computed tomography (PET/CT) has an important role in the diagnosis of coronary microvascular disease (CMD), aids risk stratification and may be useful in monitoring therapy. CMD contributes to symptoms and a worse prognosis in patients with coronary artery disease (CAD), nonischemic cardiomyopathies, and heart failure. CFR measurements may improve our understanding of the role of CMD in symptoms and prognosis in CAD and other cardiovascular diseases. The clinical presentation of CAD has changed. The prevalence of nonobstructive CAD has increased to about 50% of patients with angina undergoing angiography. Ischemia with nonobstructive arteries (INOCA) is recognized as an important cause of symptoms and has an adverse prognosis. Patients with INOCA may have ischemia due to CMD, epicardial vasospasm or diffuse nonobstructive CAD. Reduced CFR in patients with INOCA identifies a high-risk group that may benefit from management strategies specific for CMD. Although measurement of CFR by PET/CT has excellent accuracy and repeatability, use is limited by cost and availability. CFR measurement with single-photon emission tomography (SPECT) is feasible, validated, and would increase availability and use of CFR. Patients with CMD can be identified by reduced CFR and selected for specific therapies.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 18 Jul 2022; epub ahead of print

The value of cardiac sympathetic activity and mechanical dyssynchrony as cardiac resynchronization therapy response predictors: comparison between patients with ischemic and non-ischemic heart failure.

Mishkina AI, Saushkin VV, Atabekov TA, Sazonova SI, ... Popov SV, Zavadovsky KV
Background
Impaired cardiac sympathetic activity and mechanical dyssynchrony (MD) are associated with poor prognosis in patients with heart failure (HF) after cardiac resynchronization therapy (CRT). The study aims to assess the significance of scintigraphic evaluation of cardiac sympathetic innervation and contractility in predicting response to CRT in patients with ischemic and non-ischemic chronic HF.
Methods and results
The study includes 58 HF patients, who were referred for CRT. Prior to CRT all patients underwent ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) imaging and gated myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) SPECT/CT device. At a one-year follow-up post-CRT, the delayed heart-to-mediastinum ¹²³I-MIBG uptake ratio was an independent predictor of CRT response in non-ischemic HF patients (OR 1.469; 95% CI 1.076-2.007, p = .003). In ischemic HF patients the MD index histogram bandwidth (HBW) obtained by CZT-gated MPI had a predictive value (OR 1.06, 95% CI 1.001-1.112, p = .005) to CRT response.
Conclusion
CRT response can be predicted by cardiac ¹²³I-MIBG scintigraphy, specifically by the heart-to-mediastinum ratio in non-ischemic HF and by the MD index HBW in ischemic HF. These results suggest the value of a potentially useful algorithm to improve outcomes in HF patients who are candidates for CRT.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 14 Jul 2022; epub ahead of print

Association between myocardial ischemia and plaque characteristics in chronic total occlusion.

Cho SG, Lee JE, Kim HY, Song HC, Kim YH
Background
Myocardial ischemia varies in chronic total occlusion (CTO) despite the occluded artery. We analyzed whether it is associated with the plaque characteristics of the occluded segment.
Methods
We retrospectively enrolled 100 patients with CTO who underwent myocardial perfusion single-photon emission computed tomography (SPECT) and coronary computed tomography angiography (CCTA) within 2 months. CTO-related ischemia was classified as moderate to severe (summed difference score [SDS] of the CTO territory ≥ 5) or mild or none (SDS < 5) on SPECT. Using CCTA, the atherosclerotic plaques of the occluded segment were subdivided into low-density (- 100-30 HU), intermediate-density (31-350 HU), and high-density (351-1000 HU) plaques. The plaque composition was compared according to the severity of CTO-related ischemia.
Results
Moderate-to-severe CTO-related ischemia (n = 23) showed significantly higher proportion of intermediate-density plaques (72.4% vs. 64.0%), intermediate/low-density (7.10 vs. 3.65) and intermediate-to-high/low-density (7.78 vs. 3.80) plaque ratios, frequent shorter occlusion (30% vs. 6%), and lower volume (26.5 mm³ vs. 58.8 mm³) and proportion (11.4% vs. 20.8%) of low-density plaques. Multivariable analysis revealed significant associations between higher proportion of intermediate-density plaques and moderate-to-severe CTO-related ischemia, independent of occlusion length.
Conclusion
Higher proportion of intermediate-density plaques in the occluded segment was associated with the moderate-to-severe CTO-related ischemia.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 14 Jul 2022; epub ahead of print

A quick glance at selected topics in this issue.

Bhambhvani P, Hage FG, Iskandrian AE
\"A quick glance at selected topics in this issue\" aims to highlight contents of the Journal and provide a quick review to the readers.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 11 Jul 2022; epub ahead of print

To what extent does prior antimicrobial therapy affect the diagnostic performance of radiolabeled leukocyte scintigraphy in infective endocarditis?

Holcman K, Rubiś P, Ćmiel B, Ząbek A, ... Podolec P, Kostkiewicz M
Aims
This prospective, single-center study sought to assess to what extent there is interference between the hybrid technique of single-photon emission tomography-computed tomography with technetium99m-hexamethylpropyleneamine oxime-labeled leukocytes (99mTc-HMPAO-SPECT/CT) and antimicrobial therapy in patients with infective endocarditis (IE).
Methods and results
During the years 2015-2019, we enrolled 205 consecutive adults with suspected IE, all underwent 99mTc-HMPAO-SPECT/CT. The study population was divided into those who had received antimicrobial therapy up to 30 days prior to 99mTc-HMPAO-SPECT/CT (group 1, n = 96) and those who had not (group 2, n = 109). Patients were prospectively observed for 12 ± 10 months. Group 1 presented higher positive predictive values (91.89% vs. 60.00%, = 0.001), and decreased negative predictive values (77.97% vs. 90.54%, P = 0.04). Patients treated with antimicrobial therapy displayed false-negative 99mTc-HMPAO-SPECT/CT results more often [odds ratio (OR), 4.63; 95% confidence interval (CI), 1.41-15.23, P = .01], particularly when intravenous (OR 5.37; 95% CI 1.73-16.62, P = .004), definite (OR 9.43; 95% CI 2.65-33.51, P = .001), and combination antibiotic regimens (OR 8.1; 95% CI 2.57-25.64, P = .001) had been administered.
Conclusion
Prior antibiotic therapy affects 99mTc-HMPAO-SPECT/CT diagnostic properties. Patients treated with antimicrobial therapy display false-negative 99mTc-HMPAO-SPECT/CT results more often, especially if intravenous, definite, or combination regimens are administered.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 11 Jul 2022; epub ahead of print

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

Maurer A, Sustar A, Giannopoulos AA, Grünig H, ... Buechel RR, Fuchs TA
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.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 11 Jul 2022; epub ahead of print

Does [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) soft tissue uptake allow the identification of patients with the diagnosis of cardiac transthyretin-related (ATTR) amyloidosis with higher risk for polyneuropathy?

Wollenweber T, Kretschmer-Chott E, Wurm R, Rasul S, ... Hacker M, Traub-Weidinger T
Background
With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can possibly make an important contribution in the identification of patients at risk for PNP.
Methods
Fifty patients with cATTR, who underwent both planar whole-body DPD scintigraphy and nerve conduction studies (NCS) were retrospectively evaluated. A subgroup of 22 patients also underwent quantitative SPECT/CT of the thorax from which Standardized Uptake Values (SUVpeak) in the subcutaneous fat tissue of the left axillar region were evaluated.
Results
The Perugini score was significantly increased in patients with cATTR and additional diagnosis of PNP compared to patients without (2.51 ± 0.51 vs 2.13 ± 0.52; P = 0.03). Quantitative SPECT/CT revealed that DPD uptake in the subcutaneous fat of the left axillar region was significantly increased in cATTR patients with compared to patients without (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04).
Conclusion
This study suggests that DPD bone scintigraphy is a useful tool for identification of patients with cATTR and a risk for PNP due to increased DPD soft tissue uptake.

© 2022. The Author(s).

J Nucl Cardiol: 11 Jul 2022; epub ahead of print

Clinical features and prognosis of isolated cardiac sarcoidosis diagnosed using new guidelines with dedicated FDG PET/CT.

Okada T, Kawaguchi N, Miyagawa M, Matsuoka M, ... Yamaguchi O, Kido T
Background
Diagnostic guidelines for isolated cardiac sarcoidosis (iCS) were first proposed in 2016, but there are few reports on the imaging and prognosis of iCS. This study aimed to evaluate the use of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in predicting iCS prognosis.
Methods and results
We retrospectively reviewed the clinical and imaging data of 306 consecutive patients with suspected CS who underwent FDG PET/CT with a dedicated preparation protocol and included 82 patients (55 with systemic sarcoidosis including cardiac involvement [sCS], 27 with iCS) in the study. We compared the FDG PET/CT findings between the two groups. We examined the relationship between the CS type and the rate of adverse cardiac events. The iCS group had a significantly lower target-to-background ratio than the sCS group (P = 0.0010). The event-free survival rate was significantly lower in the iCS group than the sCS group (log-rank test, P < 0.0001). iCS was identified as an independent prognostic factor for adverse events (hazard ratio 3.82, P = 0.0059).
Conclusion
iCS was an independent prognostic factor for adverse cardiac events in patients with CS. The clinical diagnosis of iCS based on FDG PET/CT and new guidelines may be important.

© 2022. The Author(s).

J Nucl Cardiol: 08 Jul 2022; epub ahead of print

Content-based image retrieval for the diagnosis of myocardial perfusion imaging using a deep convolutional autoencoder.

Higaki A, Kawaguchi N, Kurokawa T, Okabe H, ... Yamada T, Okayama H
Background
Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) plays a crucial role in the optimal treatment strategy for patients with coronary heart disease. We tested the feasibility of feature extraction from MPI using a deep convolutional autoencoder (CAE) model.
Methods
Eight hundred and forty-three pairs of stress and rest myocardial perfusion images were collected from consecutive patients who underwent cardiac scintigraphy in our hospital between December 2019 and February 2022. We trained a CAE model to reproduce the input paired image data, so as the encoder to output a 256-dimensional feature vector. The extracted feature vectors were further dimensionally reduced via principal component analysis (PCA) for data visualization. Content-based image retrieval (CBIR) was performed based on the cosine similarity of the feature vectors between the query and reference images. The agreement of the radiologist\'s finding between the query and retrieved MPI was evaluated using binary accuracy, precision, recall, and F1-score.
Results
A three-dimensional scatter plot with PCA revealed that feature vectors retained clinical information such as percent summed difference score, presence of ischemia, and the location of scar reported by radiologists. When CBIR was used as a similarity-based diagnostic tool, the binary accuracy was 81.0%.
Conclusion
The results indicated the utility of unsupervised feature learning for CBIR in MPI.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 08 Jul 2022; epub ahead of print

Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

Shakowski C, Pham VA, Raines J, Quaife RA, Page RL
Background
Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking.
Methods
Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated.
Results
Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported.
Conclusion
Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 07 Jul 2022; epub ahead of print

Ongoing vascular inflammation evaluated by F-fluorodeoxyglucose positron emission tomography in patients long after Kawasaki disease.

Suda K, Tahara N, Bekki M, Nakamura T, ... Abe T, Fukumoto Y
Background
This study aimed to determine whether ongoing vascular inflammation presents in patients who had coronary artery aneurysms (CAAs) caused by Kawasaki disease (KD).
Methods
Subjects were 26 patients with a history of KD; 15 had giant CAA (gCAA) ≥ 8.0 mm and 11 had smaller CAA (smCAA) < 8 mm in the acute phase. They underwent X-ray computed tomography and ¹⁸F-fluorodeoxyglucose positron emission tomography. We determined the maximum coronary target-to-background ratio (CaTBR) and the mean thoracic aorta TBR (TaTBR) in each patient. They were compared between groups, and their correlation with various variables was determined.
Results
CaTBR and TaTBR were significantly higher in gCAA than in smCAA (P < .005 for both values) and were significantly higher even in patients without any metabolic risk factor (P < .05 for both values). The CAA size in acute phase significantly positively correlated with CaTBR (R² = 0.32) as well as TaTBR (R² = 0.28). Also, TaTBR significantly positively correlated with CaTBR (R² = 0.32) as well as cumulative number of metabolic risk factors (trend, P = .03).
Conclusions
Ongoing vascular inflammation may present long after KD, especially in patients with severe inflammation expressed as gCAA in the acute phase.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 07 Jul 2022; epub ahead of print

Multi-center study of inter-rater reproducibility, image quality, and diagnostic accuracy of CZT versus conventional SPECT myocardial perfusion imaging.

Mansour N, Nekolla SG, Reyes E, Angelidis G, ... Soman P, Rischpler C
Background
Cadmium-zinc-telluride (CZT)-based detectors exhibit higher diagnostic sensitivity in myocardial perfusion imaging (MPI) than conventional Anger-MPI for detection of coronary artery disease (CAD); however, reduced specificity and diagnostic accuracy of CZT-MPI were observed. This study aims to compare these different camera systems and to examine the degree of inter-rater reproducibility among readers with varying experience in MPI.
Methods
83 patients who underwent double stress/rest examinations using both a CZT and conventional SPECT cameras within one visit were included. Anonymized and randomized MPI-images were distributed to 15 international readers using a standardized questionnaire. Subsequent coronary angiography findings of ten patients served as a reference for analysis of sensitivity and specificity.
Results
Image quality was significantly better in CZT-MPI with significantly lower breast attenuation (P < 0.05). CZT-MPI exhibited higher sensitivity than Anger-MPI (87.5% vs. 62.5%) and significantly reduced specificity (40% vs. 100%). Readers experienced with both camera systems had the highest inter-rater agreement indicating higher reproducibility (CZT 0.54 vs. conv. 0.49, P < 0.05).
Conclusions
Higher diagnostic sensitivity of CZT-MPI offers advantages in detection of CAD yet potentially of at the cost of reduced specificity, therefore it requires special training and a differentiated evaluation approach, especially for non-experienced readers with such camera systems.

© 2022. The Author(s).

J Nucl Cardiol: 07 Jul 2022; epub ahead of print

Buccal caffeine strips for reversal of adverse symptoms of vasodilator stress.

Elsadany M, Stringer B, Bote J, Abdulla KH, ... Schwartz RG, Duvall WL
Background
Due to recurrent shortages of aminophylline, intravenous caffeine has emerged as a commonly used, safe and reliable method to treat adverse effects of vasodilator stress agents. We sought to evaluate the safety and effectiveness of buccal caffeine strips which are rapidly absorbed, inexpensive, readily available, and simplify caffeine administration.
Methods
Consecutive patients undergoing regadenoson stress SPECT MPI were assessed for the occurrence of symptoms during testing over an 11-week period at a single metropolitan hospital. Adverse symptoms, including their severity and duration, were recorded at the time of testing. Patient satisfaction was rated on a scale of 1 to 5 (5 being the most satisfied). Patients received reversal with caffeine if symptoms were felt to be significant enough by the patient and physician performing the test. The treatment received alternated week to week between IV caffeine (60 mg) or 100 mg buccal caffeine strips. Caffeine was given at least 3 minutes after tracer injection. A rescue dose of IV caffeine was offered 10 minutes later if indicated.
Results
Of the 122 patients enrolled in the study, 70 (57%) were included during buccal caffeine weeks and 52 (43%) during IV caffeine weeks, and only 28 (24%) received reversal with a caffeine agent. Seven (6%) received IV caffeine and 21 (17%) received buccal caffeine. There was no significant difference in symptom duration between IV and buccal caffeine after treatment (152.8 vs 163.4 seconds, P = 0.87). There was no significant difference in initial and final symptom severity between groups. Only 2 patients in the buccal group required rescue IV caffeine for ongoing symptoms and emesis. None of the IV group required a rescue dose. There was no significant difference in patient satisfaction between the groups (2.8 vs 3.2, P = 0.38).
Conclusion
Buccal caffeine strips are a safe, well tolerated, and effective initial strategy to reverse adverse effects of vasodilator stress in the minority of patients who request it. Buccal caffeine alone or with IV rescue caffeine was highly effective in reversing adverse effects and was free of major adverse clinical events.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 06 Jul 2022; epub ahead of print

Incremental prognostic value of positron emission tomography derived left ventricular mass.

Ahmed AI, Saad JM, Han Y, Malahfji M, Al-Mallah MH
Background
Left ventricular hypertrophy has been shown to be an independent predictor of outcomes in patients with coronary artery disease (CAD). We aimed to determine the incremental prognostic value of positron emission tomography (PET) derived left ventricular mass (LVM) to clinical variables and myocardial flow reserve (MFR).
Methods
We included consecutive patients who had clinically indicated PET myocardial perfusion imaging for suspected or established CAD. Patients were followed from the date of PET imaging for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention/coronary artery bypass grafting 90 days after imaging).
Results
A total of 2357 patients underwent PET MPI during the study period (47% female, mean age 66 ± 12 years, 87% hypertensive, 47% diabetic, 79% dyslipidemia). After a mean follow-up of 11.6 ± 6.6 months, 141 patients (6.0%, 5.1 per 1000 person-year) experienced MACE (86 D/24 MI/39 PCI/9 CABG). In nested multivariable Cox models, LVM was not independently associated with outcomes (HR 1.00, P = .157) and had no incremental prognostic value (C index: 0.75, P = .571) over MFR and clinical variables.
Conclusion
Our analysis shows that LVM provides no independent and incremental prognostic value over MFR and clinical variables.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 06 Jul 2022; epub ahead of print

PET/CT morphology and cardiac conduction disorders help discriminate primary cardiac lymphoma from primary cardiac sarcoma.

Yuan H, Qiu J, Chiu KWH, Chan LWC, ... Wei X, Jiang L
Background
Primary cardiac lymphoma (PCL) and primary cardiac sarcoma (PCS) are similar in clinical presentation but differ in management and outcomes. We aim to explore the role of PET morphology and clinical characteristics in distinguishing PCL from PCS.
Methods
Pretreatment ¹⁸F-FDG PET/CT and contrast-enhanced CT were performed in PCL (n = 14) and PCS (n = 15) patients. Patient demographics, overall survival, and progression-free survival were reviewed. PET/CT morphological and metabolic features were extracted. Specifically, R_Kurtosis, a PET-morphology parameter reflecting the tumor expansion within the heart, was calculated.
Results
Compared with PCS, PCL occurred at an older age, resulted in more cardiac dysfunctions and arrhythmias, and showed higher glucometabolism (SUV_max, SUV_peak, SUV_mean, MTV, and TLG). Curative treatments improved survival for PCL but not for PCS. Multivariable logistic regression identified R_Kurtosis (OR = 27.025, P = .007) and cardiac conduction disorders (OR = 37.732, P = .016) independently predictive of PCL, and classification and regression tree analysis stratified patients into three subgroups: R_Kurtosis ≥ 0.044 (probability of PCL 88.9%), R_Kurtosis < 0.044 with conduction disorders (80.0%), and R_Kurtosis < 0.044 without conduction disorders (13.3%).
Conclusion
PET-derived tumor expansion pattern (R_Kurtosis) and cardiac conduction disorders were helpful in distinguishing PCL from PCS, which might assist the clinical management.

© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.

J Nucl Cardiol: 05 Jul 2022; epub ahead of print