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