Amyloid myopathy: expanding the clinical spectrum of transthyretin amyloidosis-case report and literature review.

Ungericht M, Wanschitz J, Kroiss AS, Röcken C, ... Loescher WN, Poelzl G
We identified two patients with transthyretin (ATTR) amyloid myopathy (one ATTR variant amyloidosis, ATTRv; one wild-type ATTR amyloidosis, ATTRwt). Myopathy was the initial manifestation in ATTRwt, whereas it followed neuropathy and cardiomyopathy in ATTRv. The ATTRwt patient showed muscular tracer uptake on ^99mTc-DPD planar scintigraphy at the time of initial diagnosis, consistent with ATTR amyloid myopathy. The ATTRv patient underwent heart transplantation because of progressive heart failure. Within the next two years, progressive myopathic symptoms and extracardiac tracer uptake on ^99mTc-DPD planar scintigraphy were documented, attributable to ATTR amyloid myopathy. Interstitial amyloid deposits were confirmed by muscle biopsy in both patients, with a particularly high amyloid burden in the adipose tissue. This case report highlights the frequent concomitant presence of cardiac ATTR amyloidosis and ATTR amyloid myopathy. ATTR amyloid myopathy may precede cardiac manifestation in ATTRwt or occur after heart transplantation in ATTRv. Due to the high diagnostic accuracy of ^99mTc-DPD scintigraphy for detecting ATTR amyloid myopathy and the emergence of novel therapeutics, it is important to increase the awareness of its presence.

© 2022. The Author(s).

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

Echocardiographic indices of left ventricular function and filling pressure are not related to blood pool activity on pyrophosphate scintigraphy.

Asif T, Gupta A, Murthi M, Soman P, Singh V, Malhotra S
Background
Pyrophosphate (PYP) imaging has a high diagnostic accuracy for transthyretin cardiac amyloidosis (ATTR-CA). Indeterminate findings are often reported due to persistent blood pool activity, presumed to be from low cardiac output. We evaluated the relationship between blood pool activity on PYP imaging and echocardiographic indices of cardiac function.
Methods
Clinical and imaging data of 189 patients referred for PYP scintigraphy were evaluated. All patients underwent planar imaging and SPECT (diagnostic standard). Among those with a negative PYP SPECT, persistent left ventricular blood pool activity on planar images was inferred by a visual score ≥2 or a heart-to-contralateral (HCL) ratio ≥ 1.5. Absence of blood pool activity was inferred when both visual score was < 2 and HCL was < 1.5. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), stroke volume index (SVi), and left atrial pressure (LAP) were calculated from standard transthoracic echocardiograms.
Results
ATTR-CA was present in 43 (23%) patients. Among those with a negative PYP SPECT, 11 patients had significant blood pool activity. Patients with ATTR-CA had a lower LVEF, SVi, and GLS, with a higher LAP, compared to those without ATTR-CA. Among those without ATTR-CA, there were no significant differences in these parameters.
Conclusion
Approximately 8% of patients with a negative PYP SPECT have significant blood pool activity. Measures of cardiac function are not different among those with and without blood pool activity. PYP SPECT should be routinely performed in all patients to avoid false image interpretation.

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

J Nucl Cardiol: 16 May 2022; epub ahead of print

Quantitative Tc-DPD-SPECT/CT assessment of cardiac amyloidosis.

Kessler L, Fragoso Costa P, Kersting D, Jentzen W, ... Papathanasiou M, Rischpler C
Introduction
Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring.
Methods and materials
136 patients received ^99mTc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest.
Results
Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%.
Conclusion
We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.

© 2022. The Author(s).

J Nucl Cardiol: 13 May 2022; epub ahead of print

Definition and epidemiology of coronary microvascular disease.

Bradley C, Berry C
Ischemic heart disease remains one of the leading causes of death and disability worldwide. However, most patients referred for a noninvasive computed tomography coronary angiogram (CTA) or invasive coronary angiogram for the investigation of angina do not have obstructive coronary artery disease (CAD). Approximately two in five referred patients have coronary microvascular disease (CMD) as a primary diagnosis and, in addition, CMD also associates with CAD and myocardial disease (dual pathology). CMD underpins excess morbidity, impaired quality of life, significant health resource utilization, and adverse cardiovascular events. However, CMD often passes undiagnosed and the onward management of these patients is uncertain and heterogeneous. International standardized diagnostic criteria allow for the accurate diagnosis of CMD, ensuring an often overlooked patient population can be diagnosed and stratified for targeted medical therapy. Key to this is assessing coronary microvascular function-including coronary flow reserve, coronary microvascular resistance, and coronary microvascular spasm. This can be done by invasive methods (intracoronary temperature-pressure wire, intracoronary Doppler flow-pressure wire, intracoronary provocation testing) and non-invasive methods [positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), transthoracic Doppler echocardiography (TTDE), cardiac computed tomography (CT)]. Coronary CTA is insensitive for CMD. Functional coronary angiography represents the combination of CAD imaging and invasive diagnostic procedures.

© 2022. The Author(s).

J Nucl Cardiol: 09 May 2022; epub ahead of print

Artificial intelligence for disease diagnosis and risk prediction in nuclear cardiology.

Miller RJH, Huang C, Liang JX, Slomka PJ
Artificial intelligence (AI) techniques have emerged as a highly efficient approach to accurately and rapidly interpret diagnostic imaging and may play a vital role in nuclear cardiology. In nuclear cardiology, there are many clinical, stress, and imaging variables potentially available, which need to be optimally integrated to predict the presence of obstructive coronary artery disease (CAD) or predict the risk of cardiovascular events. In spite of clinical awareness of a large number of potential variables, it is difficult for physicians to integrate multiple features consistently and objectively. Machine learning (ML) is particularly well suited to integrating this vast array of information to provide patient-specific predictions. Deep learning (DL), a branch of ML characterized by a multi-layered convolutional model architecture, can extract information directly from images and identify latent image features associated with a specific prediction. This review will discuss the latest AI applications to disease diagnosis and risk prediction in nuclear cardiology with a focus on potential clinical applications.

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

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

Increasing angular sampling through deep learning for stationary cardiac SPECT image reconstruction.

Xie H, Thorn S, Chen X, Zhou B, ... Sinusas AJ, Liu C
Background
The GE Discovery NM (DNM) 530c/570c are dedicated cardiac SPECT scanners with 19 detector modules designed for stationary imaging. This study aims to incorporate additional projection angular sampling to improve reconstruction quality. A deep learning method is also proposed to generate synthetic dense-view image volumes from few-view counterparts.
Methods
By moving the detector array, a total of four projection angle sets were acquired and combined for image reconstructions. A deep neural network is proposed to generate synthetic four-angle images with 76 ([Formula: see text]) projections from corresponding one-angle images with 19 projections. Simulated data, pig, physical phantom, and human studies were used for network training and evaluation. Reconstruction results were quantitatively evaluated using representative image metrics. The myocardial perfusion defect size of different subjects was quantified using an FDA-cleared clinical software.
Results
Multi-angle reconstructions and network results have higher image resolution, improved uniformity on normal myocardium, more accurate defect quantification, and superior quantitative values on all the testing data. As validated against cardiac catheterization and diagnostic results, deep learning results showed improved image quality with better defect contrast on human studies.
Conclusion
Increasing angular sampling can substantially improve image quality on DNM, and deep learning can be implemented to improve reconstruction quality in case of stationary imaging.

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

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

Time-related aortic inflammatory response, as assessed with F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19: the COVAIR study.

Vlachopoulos C, Terentes-Printzios D, Katsaounou P, Solomou E, ... Tsioufis K, Anagnostopoulos C
Aim
Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19.
Methods
Between November 2020 and May 2021, in this pilot, case-control study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59 ± 12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring ¹⁸F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR.
Results
There was no significant difference in aortic ¹⁸F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, P = 0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, P = 0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to ¹⁸F-FDG PET-CT scan (Spearman\'s rho = - 0.528, P = 0.017 and Spearman\'s rho = - 0.480, p = 0.032, respectively). Patients who were scanned less than or equal to 60 days from admission (n = 11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, P = 0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, P = 0.038). There was a significant difference in IAS- TBR between patients scanned ≤ 60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], P = 0.036).
Conclusion
This is the first study suggesting that aortic inflammation, as assessed by ¹⁸F-FDG PET/CT imaging, is increased in the early post COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

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

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

A longitudinal pilot study to assess temporal changes in coronary arterial F-sodium fluoride uptake.

Kitagawa T, Sasaki K, Fujii Y, Tatsugami F, ... Hirokawa Y, Nakano Y
Purpose
How coronary arterial ¹⁸F-sodium fluoride (¹⁸F-NaF) uptake on positron emission tomography changes over the long term and what clinical factors impact the changes remain unclear. We sought to investigate the topics in this study.
Methods
We retrospectively studied 15 patients with ≥1 coronary atherosclerotic lesion/s detected on cardiac computed tomography who underwent baseline and follow-up (interval of >3 years) ¹⁸F-NaF positron emission tomography/computed tomography scans. Focal ¹⁸F-NaF uptake in each lesion was quantified using maximum tissue-to-background ratio (TBR_max). The temporal change in TBR_max was assessed using a ratio of follow-up to baseline TBR_max (R-TBR_max).
Results
A total of 51 lesions were analyzed. Mean R-TBR_max was 0.96 ± 0.21. CT-based lesion features (location, obstructive stenosis, plaque types, features of high-risk plaque) did not correlate with an increase in R-TBR_max. In multivariate analysis, baseline TBR_max significantly correlated with higher follow-up TBR_max (β = 0.57, P < 0.0001), and the presence of diabetes mellitus significantly correlated with both higher follow-up TBR_max (β = 0.34, P = 0.001) and elevated R-TBR_max (β = 0.40, P = 0.003).
Conclusion
Higher coronary arterial ¹⁸F-NaF uptake is likely to remain continuously high. Diabetes mellitus affects the long-term increase in coronary arterial ¹⁸F-NaF uptake.

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

J Nucl Cardiol: 29 Apr 2022; epub ahead of print

Rest/stress myocardial perfusion imaging by positron emission tomography with F-Flurpiridaz: A feasibility study in mice.

Bengs S, Warnock GI, Portmann A, Mikail N, ... Gebhard C, Haider A
Background
Myocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. ¹⁸F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with ¹⁸F-flurpiridaz is feasible in mice.
Methods
Rest/stress PET-MPI was performed with ¹⁸F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7-8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial ¹⁸F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium.
Results
Tracer kinetics were best described by a two-tissue compartment model. K₁ ranged from 6.7 to 20.0 mL·cm^-3·min^-1, while myocardial volumes of distribution (V_T) were between 34.6 and 83.6 mL·cm^-3. Of note, myocardial ¹⁸F-flurpiridaz uptake (%ID/g) was significantly correlated with K₁ at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman\'s coefficients (r_s) ranged between 0.478 and 0.681, R² values were generally low. In contrast, an excellent correlation of myocardial ¹⁸F-flurpiridaz uptake with V_T was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R² ≥ 0.98). Notably, K₁ and V_T were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K₁, V_T, and %ID/g ¹⁸F-flurpiridaz were virtually identical, suggesting that %ID/g ¹⁸F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice.
Conclusion
Our findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with ¹⁸F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

© 2022. The Author(s).

J Nucl Cardiol: 28 Apr 2022; epub ahead of print

Development and validation of ischemia risk scores.

Miller RJH, Rozanski A, Slomka PJ, Han D, ... Thomson LEJ, Berman DS
Background
The likelihood of ischemia on myocardial perfusion imaging is central to physician decisions regarding test selection, but dedicated risk scores are lacking. We derived and validated two novel ischemia risk scores to support physician decision making.
Methods
Risk scores were derived using 15,186 patients and validated with 2,995 patients from a different center. Logistic regression was used to assess associations with ischemia to derive point-based and calculated ischemia scores. Predictive performance for ischemia was assessed using area under the receiver operating characteristic curve (AUC) and compared with the CAD consortium basic and clinical models.
Results
During derivation, the calculated ischemia risk score (0.801) had higher AUC compared to the point-based score (0.786, p < 0.001). During validation, the calculated ischemia score (0.716, 95% CI 0.684- 0.748) had higher AUC compared to the point-based ischemia score (0.699, 95% CI 0.666- 0.732, p = 0.016) and the clinical CAD model (AUC 0.667, 95% CI 0.633- 0.701, p = 0.002). Calibration for both ischemia scores was good in both populations (Brier score  < 0.100).
Conclusions
We developed two novel risk scores for predicting probability of ischemia on MPI which demonstrated high accuracy during model derivation and in external testing. These scores could support physician decisions regarding diagnostic testing strategies.

© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

J Nucl Cardiol: 28 Apr 2022; epub ahead of print

Evaluation of balloon pulmonary angioplasty using lung perfusion SPECT in patients with chronic thromboembolic pulmonary hypertension.

Hashimoto H, Oka T, Nakanishi R, Mizumura S, ... Ota K, Ikeda T
Background
The aim of this study was to evaluate the effect of balloon pulmonary angioplasty (BPA) using lung perfusion single-photon emission computed tomography (SPECT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Methods and results
20 consecutive patients (64 ± 15 years) who were diagnosed with CTEPH and underwent BPA were included in this study. All patients underwent lung perfusion SPECT before and after BPA. The relationship between functional %volume of the lung calculated from the lung perfusion SPECT (FVL-LPSPECT), and other clinical parameters before and after BPA was assessed using the Wilcoxon signed-rank test. The correlation between each parameter and mean pulmonary artery pressure (mPAP) using the Spearman\'s correlation was performed. To determine predictors of mPAP for evaluating treatment effectiveness, significant parameters were included in multiple regression analysis. After BPA, world health organization functional classification, six-minute walk distance (6MWD), mPAP, and FVL-LPSPECT significantly improved. FVL-LPSPECT (r = - 0.728, P < 0.001) and 6MWD (r = - 0.571, P = 0.009) were significant correlation of mPAP. In the multiple regression analysis, FVL-LPSPECT was the most significant predictor of improvement in mPAP after BPA (P < 0.001).
Conclusions
This study demonstrated that the lung perfusion SPECT could be a potential measurement of the effectiveness of BPA in patients with CTEPH.

© 2022. The Author(s).

J Nucl Cardiol: 26 Apr 2022; epub ahead of print

Cross-vender, cross-tracer, and cross-protocol deep transfer learning for attenuation map generation of cardiac SPECT.

Chen X, Hendrik Pretorius P, Zhou B, Liu H, ... King MA, Liu C
It has been proved feasible to generate attenuation maps (μ-maps) from cardiac SPECT using deep learning. However, this assumed that the training and testing datasets were acquired using the same scanner, tracer, and protocol. We investigated a robust generation of CT-derived μ-maps from cardiac SPECT acquired by different scanners, tracers, and protocols from the training data. We first pre-trained a network using 120 studies injected with ^99mTc-tetrofosmin acquired from a GE 850 SPECT/CT with 360-degree gantry rotation, which was then fine-tuned and tested using 80 studies injected with ^99mTc-sestamibi acquired from a Philips BrightView SPECT/CT with 180-degree gantry rotation. The error between ground-truth and predicted μ-maps by transfer learning was 5.13 ± 7.02%, as compared to 8.24 ± 5.01% by direct transition without fine-tuning and 6.45 ± 5.75% by limited-sample training. The error between ground-truth and reconstructed images with predicted μ-maps by transfer learning was 1.11 ± 1.57%, as compared to 1.72 ± 1.63% by direct transition and 1.68 ± 1.21% by limited-sample training. It is feasible to apply a network pre-trained by a large amount of data from one scanner to data acquired by another scanner using different tracers and protocols, with proper transfer learning.

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

J Nucl Cardiol: 26 Apr 2022; epub ahead of print

Incidental cardiac uptake of Tc-diphosphonates is predictive of poor outcome: data from 9616 bone scintigraphies.

Salvalaggio A, Cipriani A, Righetto S, Artioli P, ... Cecchin D, Briani C
Background
Bone scintigraphy (BS) is highly diagnostic for amyloid transthyretin (ATTR) cardiomyopathy. Prevalence and prognostic value of BS cardiac uptake is not well established. Our aim was to assess the prevalence of subclinical cardiac ATTR amyloidosis in patients undergoing [^99mTc]MDP/DPD scintigraphy and to define their phenotype and prognosis.
Methods and results
BS scans performed for any clinical indications from 2009 to 2020 were reviewed. Patients were stratified according to Perugini visual score of cardiac uptake. Follow-up data were collected. Among 9616 BS scans, 0.7% (n = 67) showed cardiac uptake. In 47 (70%) patients, Perugini score was 1 and in 20 (30%) patients uptake was ≥ 2, suggesting cardiac ATTR amyloidosis. Forty subjects (61%) died during the follow-up (mean 47 ± 30 months). Compared with patients with Perugini score 1, those Perugini score ≥ 2 showed increased death rate (P = .018). Two (2/67) subjects were investigated for TTR gene mutations resulting negative.
Conclusions
In patients undergoing BS for different clinical indications, cardiac uptake suggesting cardiac ATTR amyloidosis is a rare, but still neglected finding, thus preventing possible diagnosis of ATTR cardiomyopathy. Importantly, cardiac uptake negatively affects the survival. Physicians should be aware of this rare, but crucial finding for timely diagnosis and treatment.

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

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

External validation of the CRAX2MACE model.

Hijazi W, Leslie W, Filipchuk N, Choo R, ... Slomka PJ, Miller RJH
Background
Single-photon emission computed tomography (SPECT) myocardial perfusion is frequently used to predict risk of major adverse cardiovascular events (MACE). We performed an external validation of the CRAX2MACE score, developed to estimate 2-year risk of MACE in patients with suspected coronary artery disease (CAD).
Methods
Patients who underwent clinically indicated SPECT with available follow-up for MACE were included (N = 2,985). The prediction performance for MACE (revascularization, myocardial infarction, or death) within 2 years for CRAX2MACE was compared with stress and ischemic total perfusion deficit (TPD) using area under the receiver operating characteristic curve (AUC). Calibration was assessed with calibration plots, Brier score, and the Hosmer-Lemeshow test.
Results
MACE occurred within 2 years in 243 (8.1%) patients. The AUC for CRAX2MACE (0.710, 95% CI 0.677-0.743) was significantly higher compared to stress TPD (AUC 0.669, 95% CI 0.632-0.706, P = .010) and ischemic TPD (AUC 0.664, 95% CI 0.627-0.700, P < .001). The model had acceptable goodness-of-fit (P = .103) and was well-calibrated with Brier score of 0.071.
Conclusion
CRAX2MACE had higher predictive performance for 2-year MACE than quantitative perfusion in an external population. The current model is simple to use and could be implemented to assist physicians when estimating patient risk.

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

J Nucl Cardiol: 13 Apr 2022; epub ahead of print

Optimization of the left ventricle ejection fraction estimate obtained during cardiac adenosine stress Rubidium-PET scanning: impact of different reconstruction protocols.

Lassen ML, Wissenberg M, Byrne C, Kjaer A, Hasbak P
Background
Left ventricular ejection fraction (LVEF) estimation using adenosine stress myocardial perfusion imaging (MPI) can be challenging. The short half-life of adenosine and the guideline-recommended adenosine infusion stop during Rubidium-82 acquisition protocol may affect the accuracy and repeatability of the LVEF measures.
Methods
This study comprised 25 healthy volunteers (median age 23 years) who underwent repeat myocardial perfusion imaging (MPI) sessions employing Rubidium-82 PET/CT. A guideline-recommended reconstruction protocol was used for both rest and adenosine stress MPI (150-360 s post-radiotracer injection, standard_recon). For the stress MPI protocol, two additional reconstruction protocols were considered; one was employing 60 seconds data (150-210 seconds, short_fixed) and the other a dynamic frame window based on the bolus arrival of Rubidium-82 in the heart until 210 seconds (x-210 seconds, short_individual). We report rest and stress LVEF, the LVEF reserve, and the LVEF reserve repeatability.
Results
Differences in the LVEF assessments were observed between the guideline recommended and alternative reconstruction protocol (LVEF stress MPI: standard_recon = 68 ± 7%, short_fixed = 71 ± 7% (P = .08), short_individual = 72 ± 7% (P = .04)), and the LVEF reserve was reduced for the guideline-recommended protocol (standard_recon = 7.8 ± 3.5, short_fixed = 10.1 ± 3.7, short_individual = 10.5 ± 3.6, all P < .001). The best repeatability measures were obtained for the short_individual protocol (repeatability: standard_recon = 45.3%, short_fixed = 41.2%, short_individual = 31.7%).
Conclusion
We recommend using the short_individual reconstruction protocol for improved LVEF repeatability and reserve assessment. Alternatively, in centers with limited technical support we recommend the use of the short_fixed protocol.

© 2022. The Author(s).

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

Associations between coronary/aortic F-sodium fluoride uptake and pro-atherosclerosis factors in patients with multivessel coronary artery disease.

Wen W, Gao M, Yun M, Meng J, ... Zhang X, Li X
Background
¹⁸F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD).
Methods
Patients with multivessel CAD prospectively underwent ¹⁸F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of ¹⁸F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the ¹⁸F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries.
Results
100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors.
Conclusions
Coronary ¹⁸F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic ¹⁸F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.

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

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

Diagnostic performance of IQ·SPECT with high-speed scanning: A preliminary quality control study in obese patients.

Werner RA, Martinez RB, Marcus C, Kruse MJ, ... Javadi MS, Rowe SP
Background
IQ·SPECT is a recently introduced collimator design for myocardial perfusion imaging (MPI). Little data exist on use of this collimator type in obese patients, particularly Class 2 or 3 [body mass index (BMI) > 35 kg/m²].
Methods
Two consecutive rest-stress MPI scans were prospectively acquired using a conventional collimator and IQ·SPECT (acquisition times of 20 and 7 minutes, respectively) in 20 patients with a BMI of >30 kg/m². Assigned by two blinded, independent readers, image quality (on a 5-point scale) and metrics of myocardial perfusion [summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS)] were compared. Software-based left ventricular ejection fraction (EF) was also correlated.
Results
Mean BMI was 39.6 ± 7.6 kg/m². Class 2 or 3 obesity was present in 12 patients (BMI, 44.1 ± 6.8 kg/m²). Gated/non-gated images from IQ·SPECT revealed fair to good quality scores (median ≥ 3.25), which were inferior to the conventional collimator (median ≥ 4.0; P ≤ 0.01). Significant correlative indices were achieved when comparing IQ·SPECT and conventional collimators for EF values (r = 0.86, P < 0.01), SSS (r = 0.75, P < 0.0001) and SRS (r = 0.60, P < 0.005), but not for SDS (r = 0.15).
Conclusion
IQ·SPECT was comparable to conventional SPECT in obese patients. The reduced acquisition time of IQ·SPECT may allow for improved throughput with no loss in diagnostic accuracy.

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

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

Simultaneous assessment of myocardial perfusion and adrenergic innervation in patients with heart failure by low-dose dual-isotope CZT SPECT imaging.

Assante R, D\'Antonio A, Mannarino T, Nappi C, ... Cuocolo A, Acampa W
Background
In patients with heart failure (HF) sequential imaging studies have demonstrated a relationship between myocardial perfusion and adrenergic innervation. We evaluated the feasibility of a simultaneous low-dose dual-isotope ¹²³I/^99mTc-acquisition protocol using a cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera.
Methods and results
Thirty-six patients with HF underwent simultaneous low-dose ¹²³I-metaiodobenzylguanidine (MIBG)/^99mTc-sestamibi gated CZT-SPECT cardiac imaging. Perfusion and innervation total defect sizes and perfusion/innervation mismatch size (defined by ¹²³I-MIBG defect size minus ^99mTc-sestamibi defect size) were expressed as percentages of the total left ventricular (LV) surface area. LV ejection fraction (EF) significantly correlated with perfusion defect size (P < .005), innervation defect size (P < .005), and early (P < .05) and late (P < .01) ¹²³I-MIBG heart-to-mediastinum (H/M) ratio. In addition, late H/M ratio was independently associated with reduced LVEF (P < .05). Although there was a significant relationship (P < .001) between perfusion and innervation defect size, innervation defect size was larger than perfusion defect size (P < .001). At multivariable linear regression analysis, ¹²³I-MIBG washout rate (WR) correlated with perfusion/innervation mismatch (P < .05).
Conclusions
In patients with HF, a simultaneous low-dose dual-isotope ¹²³I/^99mTc-acquisition protocol is feasible and could have important clinical implications.

© 2022. The Author(s).

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

Cardiac imaging for the assessment of patients being evaluated for kidney transplantation.

Kassab K, Doukky R
Cardiac risk assessment before kidney transplantation has become widely accepted. However, the optimal patient selection and screening tool for cardiac assessment remain controversial. Clinicians face several challenges in this process, including the ever-growing pre-transplant population, aging transplant candidates, increasing prevalence of coronary artery disease, and scarcity of donor organs. Optimizing the cardiovascular risk profile in kidney transplant candidates is necessary to better appropriate limited donor organs and improve patient outcomes. Increasing waiting times from the initial evaluation for transplant candidacy to the actual transplant raises questions regarding re-testing and re-stratification of risk. In this review, we summarize and discuss the current literature on cardiac evaluation prior to kidney transplantation. We also propose simple evidence-based evaluation algorithms for initial and follow-up CAD surveillance in patients being wait-listed for kidney transplantation.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 31 Mar 2022; 29:543-557

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: 31 Mar 2022; 29:392-394

Non-invasive diagnosis of vasospastic angina.

Ngo V, Tavoosi A, Natalis A, Harel F, ... Beanlands RSB, Pelletier-Galarneau M
Vasospastic angina (VSA), or variant angina, is an under-recognized cause of chest pain and myocardial infarction, especially in Western countries. VSA leads to a declined quality of life and is associated with increased morbidity and mortality. Currently, the diagnosis of VSA relies on invasive testing that requires the direct intracoronary administration of ergonovine or acetylcholine. However, invasive vasoreactivity testing is underutilized. Several non-invasive imaging alternatives have been proposed to screen for VSA. This review aims to discuss the strengths and limitations of available non-invasive imaging tests for vasospastic angina.

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

J Nucl Cardiol: 23 Mar 2022; epub ahead of print

A methodological framework for AI-assisted diagnosis of active aortitis using radiomic analysis of FDG PET-CT images: Initial analysis.

Duff L, Scarsbrook AF, Mackie SL, Frood R, ... Morgan AW, Tsoumpas C
Background
The aim of this study was to explore the feasibility of assisted diagnosis of active (peri-)aortitis using radiomic imaging biomarkers derived from [¹⁸F]-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET-CT) images.
Methods
The aorta was manually segmented on FDG PET-CT in 50 patients with aortitis and 25 controls. Radiomic features (RF) (n = 107), including SUV (Standardized Uptake Value) metrics, were extracted from the segmented data and harmonized using the ComBat technique. Individual RFs and groups of RFs (i.e., signatures) were used as input in Machine Learning classifiers. The diagnostic utility of these classifiers was evaluated with area under the receiver operating characteristic curve (AUC) and accuracy using the clinical diagnosis as the ground truth.
Results
Several RFs had high accuracy, 84% to 86%, and AUC scores 0.83 to 0.97 when used individually. Radiomic signatures performed similarly, AUC 0.80 to 1.00.
Conclusion
A methodological framework for a radiomic-based approach to support diagnosis of aortitis was outlined. Selected RFs, individually or in combination, showed similar performance to the current standard of qualitative assessment in terms of AUC for identifying active aortitis. This framework could support development of a clinical decision-making tool for a more objective and standardized assessment of aortitis.

© 2022. The Author(s).

J Nucl Cardiol: 23 Mar 2022; epub ahead of print

Ga-FAPI PET/CT for molecular assessment of fibroblast activation in right heart in pulmonary arterial hypertension: a single-center, pilot study.

Gu Y, Han K, Zhang Z, Zhao Z, ... Wang L, Fang W
Background
Positron emission tomography (PET) imaging with radiolabeled fibroblasts activation protein inhibitor (FAPI) provides the opportunity to directly visualize fibrosis. This study aimed to investigate the feasibility of ⁶⁸Ga-FAPI PET imaging in assessing right ventricular (RV) fibrotic remodeling and the relationship between FAPI uptake with parameters of pulmonary hemodynamics and cardiac function in pulmonary arterial hypertension (PAH) patients.
Methods
In this pilot study, sixteen PAH patients were enrolled to participate in cardiac ⁶⁸Ga-FAPI PET/CT imaging. All patients underwent right heart catheterization and echocardiography for assessment of pulmonary hemodynamics and cardiac function within seven days. Cardiac FAPI uptake was visually assessed and quantified as maximum standardized uptake value (SUVmax).
Results
Twelve PAH patients exhibited FAPI uptake in RV free wall and insertion point. The overall activity of FAPI accumulated in the RV free wall (SUVmax: 2.5 ± 1.8, P < 0.001) and insertion point (SUVmax:2.5 ± 1.7, P < 0.001) was significantly upregulated compared to left ventricle (SUVmax:1.5 ± 0.5). Patients with tricuspid annular plane systolic excursion (TAPSE) < 17 mm presented significantly higher uptake than those with TAPSE ≥ 17 mm in both RV free wall (SUVmax: 3.4 ± 1.9 vs 1.7 ± 1.1, P = 0.010) and insertion point (SUVmax: 3.4 ± 1.9 vs 1.6 ± 0.7, P = 0.028), indicating RV uptake of FAPI was associated with RV dysfunction. There was significant positive correlation between cardiac FAPI uptake and total pulmonary resistance and the level of N-terminal pro b-type natriuretic peptide.
Conclusions
⁶⁸Ga-FAPI PET/CT imaging is feasible to directly visualize fibrotic remodeling of RV in patients with PAH.

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

J Nucl Cardiol: 23 Mar 2022; epub ahead of print

Fully automated deep learning powered calcium scoring in patients undergoing myocardial perfusion imaging.

Sartoretti T, Gennari AG, Sartoretti E, Skawran S, ... Buechel RR, Messerli M
Background
To assess the accuracy of fully automated deep learning (DL) based coronary artery calcium scoring (CACS) from non-contrast computed tomography (CT) as acquired for attenuation correction (AC) of cardiac single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI).
Methods and results
Patients were enrolled in this study as part of a larger prospective study (NCT03637231). In this study, 56 Patients who underwent cardiac SPECT-MPI due to suspected coronary artery disease (CAD) were prospectively enrolled. All patients underwent non-contrast CT for AC of SPECT-MPI twice. CACS was manually assessed (serving as standard of reference) on both CT datasets (n = 112) and by a cloud-based DL tool. The agreement in CAC scores and CAC score risk categories was quantified. For the 112 scans included in the analysis, interscore agreement between the CAC scores of the standard of reference and the DL tool was 0.986. The agreement in risk categories was 0.977 with a reclassification rate of 3.6%. Heart rate, image noise, body mass index (BMI), and scan did not significantly impact (p=0.09 - p=0.76) absolute percentage difference in CAC scores.
Conclusion
A DL tool enables a fully automated and accurate estimation of CAC scores in patients undergoing non-contrast CT for AC of SPECT-MPI.

© 2022. The Author(s).

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

Radioiodinated hypericin as a tracer for detection of acute myocardial infarction: SPECT-CT imaging in a swine model.

Yang S, Ma J, Li T, Wang P, ... Ni Y, Shao H
Purpose
Hypericin (Hyp) is a natural compound with a newly discovered necrosis-avidity, which can be exploited as a necrosis-avid tracer once labeled with radioactive iodine as has been tested in rodent models. This study was to evaluate the effect of radioiodinated Hyp (¹³¹I-Hyp) for imaging detection of acute myocardial infarction (AMI) in conditions closer to clinical scenarios.
Methods
We established swine AMI models (n = 6) which were intravenously given ¹³¹I-Hyp and ^99mTc-sestamibi and underwent SPECT-CT imaging with high- and low-energy collimators. The acquired SPECT images were fused with cardiac CT images and correlated with postmortem autoradiography and macro- and microscopic pathology. Tissue γ counting was performed to determine biodistribution of ¹³¹I-Hyp.
Results
¹³¹I-Hyp based SPECT indicated clearly hot regions on ventricular walls which were all histologically proved as AMI. Complementally, the hot AMI regions on ¹³¹I-Hyp SPECT (infarct/myoc ratio of 15.3 ± 7.7) were inversely cold regions on ^99mTc-sestamibi SPECT (infarct/myoc ratio of 0.029 ± 0.021). Autoradiography of heart slices showed 9.8 times higher ¹³¹I-Hyp uptake in infarcted over normal myocardium. With γ counting, the mean ¹³¹I-Hyp uptake in infarcts was 10.69 ID%/g, 12.05 times of that in viable myocardium.
Conclusion
¹³¹I-Hyp shows a potential for clinical detection of AMI once I-131 is substituted by its isotope like I-124 or I-123 for PET or SPECT, respectively.

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

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

Change in positron emission tomography perfusion imaging quality with a data-driven motion correction algorithm.

Han Y, Ahmed AI, Hayden C, Jung AK, ... Nabi F, Al-Mallah MH
Introduction
Cardiac motion frequently reduces the interpretability of PET images. This study utilized a prototype data-driven motion correction (DDMC) algorithm to generate corrected images and compare DDMC images with non-corrected images (NMC) to evaluate image quality and change of perfusion defect size and severity.
Methods
Rest and stress images with NMC and DDMC from 40 consecutive patients with motion were rated by 2 blinded investigators on a 4-point visual ordinal scale (0: minimal motion; 1: mild motion; 2: moderate motion; 3: severe motion/uninterpretable). Motion was also quantified using Dwell Fraction, which is the fraction of time the motion vector shows the heart to be within 6 mm of the corrected position and was derived from listmode data of NMC images.
Results
Minimal motion was seen in 15% of patients, while 40%, 30%, and 15% of patients had mild moderate and severe motion, respectively. All corrected images showed an improvement in quality and were interpretable after processing. This was confirmed by a significant correlation (Spearman\'s correlation coefficient 0.626, P < .001) between machine measurement of motion quantification and physician interpretation.
Conclusion
The novel DDMC algorithm improved quality of cardiac PET images with motion. Correlation between machine measurement of motion quantification and physician interpretation was significant.

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

J Nucl Cardiol: 10 Mar 2022; epub ahead of print

Multi-task Deep Learning of Myocardial Blood Flow and Cardiovascular Risk Traits from PET Myocardial Perfusion Imaging.

Yeung MW, Benjamins JW, Knol RJJ, van der Zant FM, ... van der Harst P, Juarez-Orozco LE
Background
Advanced cardiac imaging with positron emission tomography (PET) is a powerful tool for the evaluation of known or suspected cardiovascular disease. Deep learning (DL) offers the possibility to abstract highly complex patterns to optimize classification and prediction tasks.
Methods and results
We utilized DL models with a multi-task learning approach to identify an impaired myocardial flow reserve (MFR <2.0 ml/g/min) as well as to classify cardiovascular risk traits (factors), namely sex, diabetes, arterial hypertension, dyslipidemia and smoking at the individual-patient level from PET myocardial perfusion polar maps using transfer learning. Performance was assessed on a hold-out test set through the area under receiver operating curve (AUC). DL achieved the highest AUC of 0.94 [0.87-0.98] in classifying an impaired MFR in reserve perfusion polar maps. Fine-tuned DL for the classification of cardiovascular risk factors yielded the highest performance in the identification of sex from stress polar maps (AUC = 0.81 [0.73, 0.88]). Identification of smoking achieved an AUC = 0.71 [0.58, 0.85] from the analysis of rest polar maps. The identification of dyslipidemia and arterial hypertension showed poor performance and was not statistically significant.
Conclusion
Multi-task DL for the evaluation of quantitative PET myocardial perfusion polar maps is able to identify an impaired MFR as well as cardiovascular risk traits such as sex, smoking and possibly diabetes at the individual-patient level.

© 2022. The Author(s).

J Nucl Cardiol: 09 Mar 2022; epub ahead of print

DSPECT-specific normative limits for left ventricular size and function.

Ibrahim J, Nieves RA, Barakat AF, Hynal K, Shpilsky D, Soman P
Background
Differences in spatial resolution and image filtering between the solid-state DSPECT and traditional Anger SPECT (ASPECT) cameras are likely to result in differences in LV measurements. However, DSPECT-specific normal values are not available. The traditional approach of using patients deemed to have a low (< 5%) probability of coronary artery disease for the derivation of normative values has a number of limitations. We used healthy organ-donor subjects without known disease or medication use for derivation of normal values.
Methods
Subjects were 92 consecutive kidney or liver donors who underwent single-day rest (5 mCi)-stress (15 mCi) Tc-99m sestamibi-gated SPECT myocardial perfusion imaging (MPI) on the DSPECT camera for pre-operative evaluation and had normal perfusion and LV function. Exclusion criteria included any known cardiac disease or medications. LV measurements were made on the post-stress supine stress images using QGS®.
Results
Of 92 subjects (mean age 54.4 ± 15.0 and 39% men), mean EF ± 2SD for women and men was 77.2% ± 14.1% and 70.0 % ± 14.7%, respectively. Mean end-diastolic volume ± 2SD for women and men was 67.0 ± 32.2 mL and 99.6 ± 51.6 mL (indexed 38.3 ± 17.2 mL/m² and 48.1 ± 25.9 mL/m²), respectively. Mean end-systolic volume ± 2SD for women and men was 16.1 ± 15.7 mL and 31.2 ± 29.2 mL (indexed 9.2 ± 8.8 mL/m² and 15.0 ± 14.2 mL/m²), respectively. Mean LV wall volume ± 2SD for women and men was 95.9 ± 26.0 mL and 112.0 ± 48.8 mL (indexed 55.0 ± 13.8 mL/m² and 54.1 ± 24.6 mL/m²), respectively.
Conclusion
We report DSPECT-specific LV measurements from normal subjects from which limits of normality can be derived for clinic use. Organ donors who undergo pre-operative MPI are a suitable cohort for the derivation of normal values.

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

J Nucl Cardiol: 09 Mar 2022; epub ahead of print

Impact of rubidium imaging availability on management of patients with acute chest pain.

Shaukat Ali A, Finnerty V, Harel F, Marquis-Gravel G, Vadeboncoeur A, Pelletier-Galarneau M
Objective
Evaluate the impact of 82-Rubidium positron emission tomography (PET) myocardial perfusion imaging (MPI) availability on patient management presenting at the emergency department (ED) with chest pain (CP).
Methods
This is a single-center retrospective study of clinical databases. Patients presenting with CP with a non-definitive suspicion of acute coronary syndrome (ACS) at the ED between April 2016 and February 2020 were divided into 2 groups based on PET availability. The proportion of invasive coronary angiography (ICA) without significant coronary artery disease (CAD), length of stay (LoS), and additional downstream testing were evaluated.
Results
There were 21,242 ED visits for CP without definitive ACS: 5,492 when PET is not available and 15,750 when PET is available. When PET is available, proportion of patients undergoing a MPI study was greater (20.7% vs 17.6%, P<0.0001), proportion of ICA without significant CAD was similar (18.5% vs 21.4%, P=0.24), and median ED LoS was shorter (16.6 vs 18.1 hours, P=0.03). Patients undergoing SPECT MPI had significantly more downstream testing (8.9% vs 6.4%, P=0.003) and a higher rate of coronary angiogram without significant CAD (21.2% vs 14.2%, P=0.09) compared to those who underwent PET MPI.
Conclusion
Availability of PET MPI was associated with an increased number of MPI referral from the ED, similar rates of ICA without significant CAD, decreased LoS, and fewer downstream testing.

© 2022. The Author(s).

J Nucl Cardiol: 22 Feb 2022; epub ahead of print