Diagnosis of left ventricular hypertrophy using non-ECG-gated O-water PET.

Sörensen J, Nordström J, Baron T, Mörner S, ... Magnusson P, Harms HJ
Aim
To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion ¹⁵O-water positron emission tomography (PET).
Methods
We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. ¹⁵O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland-Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients.
Results
High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001).
Conclusion
¹⁵O-water PET might detect LV hypertrophy with high accuracy and precision.

© 2021. The Author(s).

J Nucl Cardiol: 19 Jul 2021; epub ahead of print

Improving detection accuracy of perfusion defect in standard dose SPECT-myocardial perfusion imaging by deep-learning denoising.

Liu J, Yang Y, Wernick MN, Pretorius PH, Slomka PJ, King MA
Background
We previously developed a deep-learning (DL) network for image denoising in SPECT-myocardial perfusion imaging (MPI). Here we investigate whether this DL network can be utilized for improving detection of perfusion defects in standard-dose clinical acquisitions.
Methods
To quantify perfusion-defect detection accuracy, we conducted a receiver-operating characteristic (ROC) analysis on reconstructed images with and without processing by the DL network using a set of clinical SPECT-MPI data from 190 subjects. For perfusion-defect detection hybrid studies were used as ground truth, which were created from clinically normal studies with simulated realistic lesions inserted. We considered ordered-subset expectation-maximization (OSEM) reconstruction with corrections for attenuation, resolution, and scatter and with 3D Gaussian post-filtering. Total perfusion deficit (TPD) scores, computed by Quantitative Perfusion SPECT (QPS) software, were used to evaluate the reconstructed images.
Results
Compared to reconstruction with optimal Gaussian post-filtering (sigma = 1.2 voxels), further DL denoising increased the area under the ROC curve (AUC) from 0.80 to 0.88 (P-value < 10^-4). For reconstruction with less Gaussian post-filtering (sigma = 0.8 voxels), thus better spatial resolution, DL denoising increased the AUC value from 0.78 to 0.86 (P-value < 10^-4) and achieved better spatial resolution in reconstruction.
Conclusions
DL denoising can effectively improve the detection of abnormal defects in standard-dose SPECT-MPI images over conventional reconstruction.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 18 Jul 2021; epub ahead of print

The assessment of left ventricular mechanical dyssynchrony from gated Tc-tetrofosmin SPECT and gated F-FDG PET by QGS: a comparative study.

Lehner S, Graner FP, Fischer M, Ilhan H, Bartenstein P, Todica A
Background
Due to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the establishment of possible cut-off values for FDG PET to define dyssynchrony.
Methods
Gated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values.
Results
BW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods. There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%.
Conclusion
Gated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary.

© 2021. The Author(s).

J Nucl Cardiol: 18 Jul 2021; epub ahead of print

Effects of mineralocorticoid receptor antagonist eplerenone on cardiac sympathetic nerve activity and left ventricular remodeling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction.

Toda K, Kasama S, Toyama T, Kasahara M, Kurabayashi M
Purpose
The activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine and promotes structural remodeling of the heart. The mineralocorticoid receptor antagonist (MRA) eplerenone prevents left ventricular (LV) remodeling in patients with acute myocardial infarction, but its influence on cardiac sympathetic nerve activity (CSNA) has not been determined.
Methods
We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients in our database who underwent ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Eighty-four STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients who treated with MRA (N = 42), and those who did not (N = 42). The LV end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography, and plasma procollagen type III amino terminal peptide (PIIINP) was measured before and 3 weeks after treatment. The delayed total defect score (TDS), delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined using ¹²³I-MIBG scintigraphy after 3 weeks.
Results
Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the MRA group showed significantly lower TDS and WR values (TDS: 22.8 ± 8.1 vs 32.2 ± 11.5, P < 0.005; WR: 31.1 ± 9.0% vs 42.7 ± 9.9%, P < 0.001) and a significantly higher H/M ratio (2.23 ± 0.41 vs 2.03 ± 0.36, P < 0.05) than the non-MRA group. The degree of change in LV parameters, and PIIINP were more favorable in the MRA group than in the non-MRA group. Moreover, multiple linear regression analyses revealed that both WR and not MRA treatment were significant predictor for LV remodeling, along with PIIINP concentrations.
Conclusion
Administration of eplerenone improves CSNA and prevents LV remodeling in patients with a first STEMI.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 15 Jul 2021; epub ahead of print

Integration of quantitative absolute myocardial blood flow estimates from dynamic CZT-SPECT improves the detection of coronary artery disease.

Liu FS, Wang SY, Shiau YC, Wu YW
Background
Balanced ischemia with multi-vessel coronary artery disease (CAD) is difficult to diagnose with semiquantitative single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Dynamic cardiac SPECT provides quantitative estimations of stenosis severity and ischemic burden by assessing myocardial flow reserve (MFR) and myocardial blood flow (MBF). The aim of this study was to evaluate the incremental value of dynamic SPECT in multi-vessel coronary artery disease (CAD).
Methods
Patients with suspected CAD who underwent dynamic ECG-gated dipyridamole MPI and coronary angiography within 6 months were retrospectively reviewed. The performance of summed stress, rest and difference scores (SSS, SRS, SDS), post-stress and resting MBF (MBF_s, MBF_r) and MFR were compared at both patient level and vessel level.
Results
In 32 patients with 39 stenotic vessels, 12 had three-vessel disease (38%). Globally increased SSS and impaired MBF values were significantly associated with significant CAD at the patient level, but SDS and MFR were not. Regional increases in SSS and reductions in both MBF_s and MBF_r were significantly associated with stenotic vessels. The best cutoff value of global MBF_s to predict CAD was 3.5 ml·g^-1·min^-1 (area under the curve, AUC = .84, P = .002). The best cutoff value of regional MBF_s to detect significant stenosis was 3.6 ml·g^-1·min^-1 (AUC = .74, P < .001). However, the best possible cut-off values of MFR were not found. Sex-difference in both global and regional MBF_r but MBF_s was found, which might result in the non-significance in MFR.
Conclusions
This study validated a clinically available method to quantify MFR using dynamic CZT-SPECT. This method improved the detectability of multi-vessel CAD, and absolute MBF_s was superior to MFR and other semiquantitative MPI parameters.



J Nucl Cardiol: 07 Jul 2021; epub ahead of print

Diagnostic safety of a machine learning-based automatic patient selection algorithm for stress-only myocardial perfusion SPECT.

Eisenberg E, Miller RJH, Hu LH, Rios R, ... Berman DS, Slomka PJ
Background
Stress-only myocardial perfusion imaging (MPI) markedly reduces radiation dose, scanning time, and cost. We developed an automated clinical algorithm to safely cancel unnecessary rest imaging with high sensitivity for obstructive coronary artery disease (CAD).
Methods and results
Patients without known CAD undergoing both MPI and invasive coronary angiography from REFINE SPECT were studied. A machine learning score (MLS) for prediction of obstructive CAD was generated using stress-only MPI and pre-test clinical variables. An MLS threshold with a pre-defined sensitivity of 95% was applied to the automated patient selection algorithm. Obstructive CAD was present in 1309/2079 (63%) patients. MLS had higher area under the receiver operator characteristic curve (AUC) for prediction of CAD than reader diagnosis and TPD (0.84 vs 0.70 vs 0.78, P < .01). An MLS threshold of 0.29 had superior sensitivity than reader diagnosis and TPD for obstructive CAD (95% vs 87% vs 87%, P < .01) and high-risk CAD, defined as stenosis of the left main, proximal left anterior descending, or triple-vessel CAD (sensitivity 96% vs 89% vs 90%, P < .01).
Conclusions
The MLS is highly sensitive for prediction of both obstructive and high-risk CAD from stress-only MPI and can be applied to a stress-first protocol for automatic cancellation of unnecessary rest imaging.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print

Localization of myocardial FDG uptake for prognostic risk stratification in corticosteroid-naïve cardiac sarcoidosis.

Bekk M, Tahara N, Tahara A, Sugiyama Y, ... Abe T, Fukumoto Y
Background
The localization of myocardial 18F-fluorodeoxyglucose (FDG) uptake affecting long-term clinical outcomes has not been elucidated in patients with corticosteroid-naïve cardiac sarcoidosis (CS).
Objectives
This study sought to investigate the localization of myocardial FDG uptake on positron emission tomography (PET) and myocardial perfusion abnormality to predict adverse events (AEs) for a long-term follow-up in patients with corticosteroid-naïve CS.
Methods
Consecutive 90 patients with clinical suspicion of CS who underwent FDG-PET imaging to assess for inflammation were enrolled. AEs were defined as a composite of sustained ventricular tachycardia (VT), heart transplantation, and all-cause death, which were ascertained by medical records, defibrillator interrogation, and telephone interviews.
Results
Of 90 patients, 42 patients (mean age 62.9 ± 12.0 years; 76.2% females) were confirmed active cardiac involvement. Over a median follow-up of 4.9 years, 15 patients with CS experienced AEs including 6 sustained ventricular tachycardias (VT) and 9 deaths. Cox proportional-hazards model after adjustment for left ventricular systolic dysfunction revealed that FDG uptake in the right ventricle (RV) or basal anterolateral area of the left ventricle (LV) with myocardial perfusion abnormality was predictive of AEs.
Conclusions
FDG uptake in the RV or basal anterolateral area of the LV with myocardial perfusion abnormality provides long-term prognostic risk stratification in patients with corticosteroid-naïve CS.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print

The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: A systematic review.

Ahmed AI, Abebe AT, Han Y, Alnabelsi T, ... Tleyjeh IM, Al-Mallah MH
Purpose
Sarcoidosis is a multi-systemic inflammatory disease of unknown etiology. Cardiac sarcoidosis (CS) has been reported in as much as 25% of patients with systemic involvement. ¹⁸Fluorodeoxyglucose (FDG) positron emission tomography (PET) has a high diagnostic sensitivity/specificity in the diagnosis of CS. The aim of this review is to summarize evidence on the prognostic role of FDG PET.
Methods
Studies were identified by searching MEDLINE from inception to October 2020. Medical subject headings (MeSH) terms for sarcoidosis; cardiac and FDG PET imaging were used. Studies of any design assessing the prognostic role of FDG PET in patients with either suspected or confirmed cardiac sarcoidosis imaging done at baseline were included. Abnormal PET was defined as abnormal metabolism (presence of focal or focal-on-diffuse uptake of FDG) OR abnormal metabolism and a perfusion defect. Studies reporting any outcome measure were included. Pooled risk ratio for the composite outcome of MACE was done.
Results
A total of 6 studies were selected for final inclusion (515 patients, 53.4% women, 19.8% racial minorities.) Studies were institution based, retrospective in design and enrolled consecutive patients. All were observational in nature and published in English. All studies used a qualitative assessment of PET scans (abnormal FDG uptake with or without abnormal perfusion). Two studies assessed quantitative metrics (summed stress score in segments with abnormal FDG uptake, standardized uptake value and cardiac metabolic activity.) All studies reported major adverse cardiovascular events (MACE) as a composite outcome. After a mean follow up ranging from 1.4 to 4.1 years, there were a total of 105 MACE. All studies included death (either all-cause death or sudden cardiac death) and ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) as a component of MACE. Four of the six studies adjusted for several characteristics in their analysis. All four studies used left ventricular ejection fraction (LVEF). However, other adjustment variables were not consistent across studies. Five studies found a positive prognostic association with the primary outcome, two of which assessing right ventricular uptake.
Conclusion
Although available evidence indicates FDG PET can be used in the risk stratification of patients with CS, our findings show further studies are needed to quantify the effect in this patient group.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print

Transient ischemic dilation or transient RV visualization in patients with normal SPECT stress myocardial perfusion imaging: Correlation with CT coronary artery calcium scoring and coronary angiography.

Naghshtabrizi B, Alvandi M, Shaghaghi Z, Hadei SK, ... Moradi M, Rabie MAS
Background
Ancillary findings on MPI, such as transient ischemic dilation (TID) and transient right ventricular visualization (TRV), are recognized as markers of extensive CAD and predictive of adverse outcomes. They usually occur in association with stress-induced regional MPI abnormalities. However, the clinical significance of these ancillary markers in the presence of normal stress MPI is incompletely understood.
Methods
From a cohort of 564 consecutive patients referred for clinical SPECT stress MPI, 44 patients had normal stress SPECT MPI and either TID (n = 28) or TRV (n = 16). These imaging findings were correlated with CT coronary calcium (CAC), CT coronary angiography (CTA), and invasive coronary angiography (ICA) in patients with severe CAC ≥ 1000 HU. TID and TRV were quantified as stress/rest ratios. Severe CAD was defined as > 70% luminal stenosis on CTA or ICA.
Results
The median TID ratio was 1.23, with a range of 1.13-1.48; the median TRV ratio was 1.30, with a range of 1.20-1.48. Of 44 patients with TID or TRV, only 9 patients (20.5%) had severe obstructive > 70% CAD by angiography (6 of 28 patients (21.5%) with TID and 3 of 16 patients (19%) with TRV). Severe multi-vessel CAD occurred in only 2 of 44 patients (4.5%). In contrast, of 9 patients with CAC > 1000 HU, 6 (67%) had severe obstructive CAD.
Conclusion
In patients with normal stress SPECT MPI and TID or TRV, the incidence of severe obstructive CAD was relatively low and predominantly single-vessel CAD. These findings do not support the concept that TID or TRV with normal stress MPI is predictive of high-risk CAD.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print

MIBG cardiac imaging compared to ejection fraction in evaluation of cardiotoxicity: a systematic review.

Arrais TR, Cavalli GD, Dos Santos BT, Pereira GB, ... Grossman GB, Biolo A
Background
Advances in diagnosis and treatment of cancer has improved survival but resulted in increased cardiotoxic effects. The decrease in left ventricular ejection fraction (EF), one of the pillars of diagnosis of cardiotoxicity, seems to be a late process in the evolution of the disease, so ^123I-metaiodobenzylguanidine (MIBG) cardiac imaging has been proposed to detect early cardiac impairment. The aim of this systematic review was to evaluate the performance of MIBG cardiac scan in this scenario.
Methods and results
A systematic search was conducted in five international databases comparing MIBG parameters with EF for evaluation of cardiotoxicity. Twelve studies were included and separated in three groups. First, studies evaluating patients with established cardiotoxicity, in which EF was reduced and MIBG parameters were abnormal. Second, studies analyzing patients during or after treatment compared to controls, with MIBG parameters significantly different between groups in most studies, even when EF remained normal. Finally, studies analyzing anthracycline (ATC) dose-related changes, with alteration in MIBG parameters occurring even when EF was preserved.
Conclusion
Although studies had high methodological variability, cardiac sympathetic innervation imaging seems to be a promising tool for assessing early cardiotoxicity. Further studies are needed to analyze its diagnostic value in this scenario.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print

Reasons for discordance between positron emission tomography (PET) myocardial perfusion imaging (MPI) results and subsequent management.

Thomas M, Spertus JA, Kennedy KF, Thompson RC, ... Bateman TM, Patel KK
Background
Referral patterns to coronary angiography following positron emission tomography (PET) myocardial perfusion imaging (MPI) and reasons for non-referral following abnormal PET MPI are largely unknown.
Methods
Referral rates to coronary angiography within 90 days post PET MPI were determined. A random subset of 100 patients with severe (≥ 10%) ischemia on MPI between 2014-16 who were not referred for angiography were examined to better understand reasons as to why patients with high-risk MPI findings did not undergo coronary angiography.
Results
Among 19,282 unique patients, overall rate of 90-day coronary angiography was 18.5% (3574/19282). Among patients with severe ischemia, 64.1% (1930/3011) underwent angiography within 90 days; the rate was lower in those with mild-moderate (20.6% [1010/4898]) and no ischemia (5.6% [634/11373]). In the random sample of 100 patients, the most common physician reasons for non-referral were uncertainty regarding whether the test results were responsible for the patient\'s presenting symptoms, renal failure, and patient age, frailty, or cognitive status, while patient preference for medical management was by far the most common patient reason.
Conclusion
Referral rates for coronary angiography after PET correlate with severity of ischemia. However, there appear to be opportunities to reconsider testing for instances when results will not change clinical management.



J Nucl Cardiol: 23 Jun 2021; epub ahead of print

F-FDG PET/CT improves diagnostic certainty in native and prosthetic valve Infective Endocarditis over the modified Duke Criteria.

Primus CP, Clay TA, McCue MS, Wong K, ... Woldman S, Menezes LJ
Background
International guidance recognizes the shortcomings of the modified Duke Criteria (mDC) in diagnosing infective endocarditis (IE) when transoesophageal echocardiography (TOE) is equivocal. ¹⁸F-FDG PET/CT (PET) has proven benefit in prosthetic valve endocarditis (PVE), but is restricted to extracardiac manifestations in native disease (NVE). We investigated the incremental benefit of PET over the mDC in NVE.
Methods
Dual-center retrospective study (2010-2018) of patients undergoing myocardial suppression PET for NVE and PVE. Cases were classified by mDC pre- and post-PET, and evaluated against discharge diagnosis. Receiver Operating Characteristic (ROC) analysis and net reclassification index (NRI) assessed diagnostic performance. Valve standardized uptake value (SUV) was recorded.
Results
69/88 PET studies were evaluated across 668 patients. At discharge, 20/32 had confirmed NVE, 22/37 PVE, and 19/69 patients required surgery. PET accurately re-classified patients from possible, to definite or rejected (NRI: NVE 0.89; PVE 0.90), with significant incremental benefit in both NVE (AUC 0.883 vs 0.750) and PVE (0.877 vs 0.633). Sensitivity and specificity were 75% and 92% in NVE; 87% and 86% in PVE. Duration of antibiotics and C-reactive Protein level did not impact performance. No diagnostic SUV cut-off was identified.
Conclusion
PET improves diagnostic certainty when combined with mDC in NVE and PVE.



J Nucl Cardiol: 23 Jun 2021; epub ahead of print

N-ammonia positron emission tomography-derived endocardial strain for the assessment of ischemia using feature-tracking in high-resolution cine imaging.

Kawakubo M, Nagao M, Yamamoto A, Nakao R, ... Sasaki M, Sakai S
Background
Assessing endocardial strain using a single ¹³N-ammonia positron emission tomography (PET) scan would be clinically useful, given the association between ischemia and myocardial deformation. However, no software has been developed for strain analysis using PET. We evaluated the clinical potential of feature tracking-derived strain values measured using PET, based on associations with the myocardial flow reserve (MFR).
Methods and results
This retrospective study included 95 coronary artery disease patients who underwent myocardial ¹³N-ammonia PET. Semi-automatic measurements were made using a feature-tracking technique during myocardial cine imaging, and values were calculated using a 16-segment model. Adenosine-stressed global circumferential strain (CS) and global longitudinal strain (LS) values were compared with global MFR values. Stressed and resting global strain values were also compared. Global strain values were significantly lower in 39 patients with abnormal MFRs [< 2.0] than in 56 patients with normal MFRs [≥ 2.0]. The global CS values in the stressed state were significantly decreased than the resting state values in patients with abnormal MFRs.
Conclusions
This study applied endocardial feature-tracking to ¹³N-ammonia PET, and the results suggested that blood flow and myocardial motility could be clinically assessed in ischemic patients using a single PET scan.



J Nucl Cardiol: 10 Jun 2021; epub ahead of print

Myocardial perfusion recovery induced by an α-calcitonin gene-related peptide analogue.

Bentsen S, Sams A, Hasbak P, Edvinsson L, Kjaer A, Ripa RS
Background
Endogenous calcitonin gene-related peptide (CGRP) induces cardioprotective effects through coronary vasodilation. However, the systemic administration of CGRP induces peripheral vasodilation and positive chronotropic and inotropic effects. This study aims to examine the net effect on coronary perfusion of the systemically administered α-calcitonin gene-related peptide analogue, SAX, in rats during myocardial infarction.
Methods
Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [^99mTc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [^99mTc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [^99mTc]Tc-sestamibi SPECT/CT scan.
Results
Thirty-one rats survived the surgery and 20 completed the follow-up SPECT/CT scan (SAX n = 12; Placebo n = 8). At baseline, there was no difference in size of perfusion defect between the groups (P = .88), but at follow-up the SAX group had improved myocardial recovery compared to the placebo group (P = .04), corresponding to a relative perfusion recovery of 55% in SAX-treated rats.
Conclusion
The CGRP analogue, SAX, has a cardioprotective effect in this rat model of myocardial infarction, improving myocardial perfusion recovery after chronic occlusion of the coronary artery.



J Nucl Cardiol: 03 Jun 2021; epub ahead of print

CT-free attenuation correction for dedicated cardiac SPECT using a 3D dual squeeze-and-excitation residual dense network.

Chen X, Zhou B, Shi L, Liu H, ... Sinusas AJ, Liu C
Background
Attenuation correction (AC) using CT transmission scanning enables the accurate quantitative analysis of dedicated cardiac SPECT. However, AC is challenging for SPECT-only scanners. We developed a deep learning-based approach to generate synthetic AC images from SPECT images without AC.
Methods
CT-free AC was implemented using our customized Dual Squeeze-and-Excitation Residual Dense Network (DuRDN). 172 anonymized clinical hybrid SPECT/CT stress/rest myocardial perfusion studies were used in training, validation, and testing. Additional body mass index (BMI), gender, and scatter-window information were encoded as channel-wise input to further improve the network performance.
Results
Quantitative and qualitative analysis based on image voxels and 17-segment polar map showed the potential of our approach to generate consistent SPECT AC images. Our customized DuRDN showed superior performance to conventional network design such as U-Net. The averaged voxel-wise normalized mean square error (NMSE) between the predicted AC images by DuRDN and the ground-truth AC images was 2.01 ± 1.01%, as compared to 2.23 ± 1.20% by U-Net.
Conclusions
Our customized DuRDN facilitates dedicated cardiac SPECT AC without CT scanning. DuRDN can efficiently incorporate additional patient information and may achieve better performance compared to conventional U-Net.



J Nucl Cardiol: 02 Jun 2021; epub ahead of print

Diagnostic performance of White Blood Cell SPECT imaging against intra-operative findings in patients with a suspicion of prosthetic valve endocarditis.

Kooshki N, Grambow-Velilla J, Mahida B, Benali K, ... Rouzet F, Hyafil F
Aim
The objective of this study was to evaluate the diagnostic performance of white blood cells (WBC)-SPECT imaging in patients with suspicion of prosthetic valve endocarditis (PVE) against intra-operative findings.
Methods
36 consecutive patients who underwent cardiac surgery 30 days after WBC-SPECT imaging were identified retrospectively. Clinical, imaging, and biological results were collected from reports. WBC-SPECT results were classified as positive or negative and, if positive, the intensity of signal graded as intense or mild. Lesions observed during cardiac surgery were collected from surgeons\' reports.
Results
The 20 patients with positive WBC-SPECT study had confirmed PVE intra-operatively. Patients with intense signal on WBC-SPECT had high prevalence of abscesses (83%) compared to patients with only mild signal (12%). The three patients with negative WBC-SPECT but confirmed PVE had longer duration of antibiotic treatment before imaging and had no perivalvular abscess. Sensitivity, specificity, positive predictive and negative values, and accuracy of WBC-SPECT were measured at 87%, 100%, 100%, 81%, and 92%, respectively. Addition of WBC-SPECT results to the modified Duke score helped re-classify correctly 25% of patients from possible to definite PVE.
Conclusion
In patients with suspicion of PVE, WBC-SPECT imaging provides excellent diagnostic performance against intra-operative findings.



J Nucl Cardiol: 02 Jun 2021; epub ahead of print

Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling.

Siebermair J, Köhler MI, Kupusovic J, Nekolla SG, ... Rassaf T, Rischpler C
Background
Fibroblast activation protein (FAP) as a specific marker of activated fibroblasts can be visualized by positron emission tomography (PET) using Ga-68-FAP inhibitors (FAPI). Gallium-68-labeled FAPI is increasingly used in the staging of various cancers. In addition, the first cases of theranostic approaches have been reported. In this work, we describe the phenomenon of myocardial FAPI uptake in patients who received a Ga-68 FAPI PET for tumor staging.
Method and results
Ga-68 FAPI PET examinations for cancer staging were retrospectively analyzed with respect to cardiac tracer uptake. Standardized uptake values (SUV) were correlated to clinical covariates in a univariate regression model. From 09/2018 to 11/2019 N = 32 patients underwent FAPI PET at our institution. Six out of 32 patients (18.8%) demonstrated increased localized myocardial tracer accumulation, with remote FAPI uptake being significantly higher in patients with vs without localized focal myocardial uptake (SUV_max 2.2 ± .6 vs 1.5 ± .4, P < .05 and SUV_mean 1.6 ± .4 vs 1.2 ± .3, P < .05, respectively). Univariate regression demonstrated a significant correlation of coronary artery disease (CAD), age and left ventricular ejection fraction (LVEF) with remote SUV_mean uptake, the latter with a very strong correlation with remote uptake (R² = .74, P < .01).
Conclusion
Our study indicates an association of CAD, age, and LVEF with FAPI uptake. Further studies are warranted to assess if fibroblast activation can be reliably measured and may be used for risk stratification regarding early detection or progression of CAD and left ventricular remodeling.



J Nucl Cardiol: 30 May 2021; 28:812-821

Diagnostic accuracy of SPECT and PET myocardial perfusion imaging in patients with left bundle branch block or ventricular-paced rhythm.

Vidula MK, Wiener P, Selvaraj S, Khan MS, ... Julien H, Bravo PE
Background
The difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown.
Methods
We identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery.
Results
Of the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02).
Conclusions
PET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.



J Nucl Cardiol: 30 May 2021; 28:981-988

Internal validation of myocardial flow reserve PET imaging using stress/rest myocardial activity ratios with Rb-82 and N-13-ammonia.

Juneau D, Wu KY, Kaps N, Yao J, ... Ruddy TD, deKemp RA
Background
Myocardial flow reserve (MFR) measurement provides incremental diagnostic and prognostic information. The objective of the current study was to investigate the application of a simplified model for the estimation of MFR using only the stress/rest myocardial activity ratio (MAR) in patients undergoing rest-stress cardiac PET MPI.
Methods and results
Rest and dipyridamole stress dynamic PET imaging was performed in consecutive patients using ⁸²Rb or ¹³NH₃ (n = 250 each). Reference standard MFR was quantified using a standard one-tissue compartment model. Stress/rest myocardial activity ratio (MAR) was calculated using the LV-mean activity from 2 to 6 minutes post-injection. Simplified estimates of MFR (MFR_EST) were then calculated using an inverse power function. For ¹³NH₃, there was good correlation between MFR and MFR_EST values (R = 0.63), with similar results for ⁸²Rb (R = 0.73). There was no bias in the MFR_EST values with either tracer. The overall diagnostic performance of MFR_EST for detection of MFR < 2 was good with ROC area under the curve (AUC) = 83.2 ± 1.2% for ¹³NH₃ and AUC = 90.4 ± 0.7% for ⁸²Rb.
Conclusion
MFR was estimated with good accuracy using ⁸²Rb and ¹³NH₃ with a simplified method that relies only on stress/rest activity ratios. This novel approach does not require dynamic imaging or tracer kinetic modeling. It may be useful for routine quality assurance of PET MFR measurements, or in scanners where full dynamic imaging and tracer kinetic modeling is not feasible for technical or logistical reasons.



J Nucl Cardiol: 30 May 2021; 28:835-850

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging.

Bourque JM, Hanson CA, Agostini D, Bateman TM, ... Udelson JE, Maddahi J
Background
Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI.
Methods
The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m²; and (3) diabetic patients. This trial\'s design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA.
Conclusions
This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD.
Trial registration number
NCT03354273.



J Nucl Cardiol: 30 May 2021; 28:1105-1116

The prevalence of TTR cardiac amyloidosis among patients undergoing bone scintigraphy.

Bianco M, Parente A, Biolè C, Righetti C, ... Anselmino M, Montagna L
Background
Radiolabeled bisphosphonates bone scintigraphy is highly sensitive in detecting transthyretin (TTR) cardiac amyloidosis; data on the true prevalence of cardiac involvement in TTR amyloidosis are lacking.
Methods and results
This retrospective observational, monocentric study aims to estimate the prevalence of positive bone scan suspect for TTR cardiac amyloidosis among an all-comers population who underwent a bone scintigraphy. ECG, echocardiography and clinical status of patients with unexpected cardiac uptake (Perugini score 2-3) who underwent bone scintigraphy with [^99mTc]-HDP or [^99mTc]-DPD at San Luigi Gonzaga University Hospital between January 2015 and May 2020 have been collected. The prevalence of bone scintigraphy suspect for cardiac involvement was 0.54% (23/4,228). The bone scintigraphy was mainly performed using [^99mTc]-HDP (82.9%) and the dominant indication for the test was oncology in the 47.9% of cases. 8 Subjects had a history of neuropathy (34.8%) and 5 of carpal tunnel syndrome (21.7%). 11 Patients suffered a previous episode of heart failure (48%) while 5 patients (21.7%) were totally asymptomatic, without any sign or symptom before the bone scintigraphy making the nuclear examination crucial for an early diagnosis of TTR amyloidosis.
Conclusion
Bone scintigraphy allows suspecting TTR amyloidosis in a pre-clinical stage of the disease in an all-comers population of patients undergoing bone scintigraphy mainly for oncology reasons.



J Nucl Cardiol: 30 May 2021; 28:825-830

Prognosis and recurrence in cardiac sarcoidosis: Serial assessment of BMIPP SPECT and FDG-PET.

Yamamoto A, Nagao M, Watanabe E, Imamura Y, ... Sakai S, Hagiwara N
Background
We analyzed ¹⁸F-Fludeoxyglucose positron emission tomography (FDG-PET) and ¹²³I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) performed for cardiac sarcoidosis (CS) patients taking prednisolone, identified recurrence by FDG-PET, and investigated BMIPP as a recurrence and prognostic factor in CS.
Methods and results
CS patients who underwent BMIPP and FDG-PET within 2 months were enrolled. The recurrence-free group included patients with standardized uptake value (SUVmax) < 4 in the myocardium consecutively for ≥ 2 years. The total BMIPP SPECT defect score (BDS) was used to estimate myocardial damage. The predictability of the initial BDS and SUVmax for major adverse cardiac events (MACE) was analyzed using Kaplan-Meier analysis. Overall, 73 patients and 250 BMIPP and FDG-PET sets were analyzed retrospectively (mean follow-up, 3.5 years). The BDS was significantly greater for the recurrence group (N = 21) vs recurrence-free group (20 ± 13 vs 14 ± 12, P = 0.041). Patients with BDS ≥16 had a significantly higher MACE rate than patients with BDS < 16 (log-rank test, P = 0.016). However, MACE occurrence was comparable between patients with SUVmax ≥ 4 and < 4.
Conclusions
BDS is a predictive marker of recurrence and MACE. SUV is not related to MACE. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients.



J Nucl Cardiol: 30 May 2021; 28:919-929

Cardiac I-mIBG scintigraphy for prediction of catheter ablation outcome in patients with atrial fibrillation.

Sazonova SI, Varlamova JV, Nikitin NA, Minin SM, ... Popov SV, Romanov AB
Background
Previous studies show inconsistent results on the role of innervation imaging (with ¹²³I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post-CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF.
Methods
¹²³I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patient was followed for 12 months.
Results
Multivariable analysis demonstrated that late heart-to-mediastinum ratio (H/M_late) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/M_late <1.6 (sensitivity 73.53%, specificity 81.3%, AUC 0.792, P < .001) and WR > 25.11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0.712, P < .001) indicate high probability of AF relapses during 12 months after CA.
Conclusion
Pre-CA parameters of global cardiac sympathetic activity estimated by ¹²³I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients with normal LVEF and absence of significant CAD.



J Nucl Cardiol: 26 May 2021; epub ahead of print

Polarity status of trigger signal during ECG-gating affects parameters of LV function in gated myocardial perfusion SPECT.

Qutbi M, Soltanshahi M, FarokhiMoghadam F, Ramandi FL, Kaghazchi F, Ahmadi R
Introduction:
and background
The polarity status is one of the important items of specifications of trigger signal from cardiac trigger monitors with two options, either positive or negative. Some systems allow the user to set the polarity of trigger signal before imaging. Efforts should be made to set the polarity status according to the recommendations provided by the manufacturers. In case of inappropriate selection, changes in computation of end-systolic and end-diastolic volumes as well as ejection fraction may occur.
Objective
To investigate the effect of the polarity status of trigger signals in synchronization process during 8- and 16-frame gated SPECT imaging on the systolic and diastolic parameters of LV function.
Methods
Thirty-four patients referred for a myocardial perfusion SPECT were consecutively included in the study. The rest scan for each patient was performed with 8- and 16-frame gating simultaneously with positive trigger signal set by the operator in a cardiac trigger monitor and then repeated after manual selection of negative polarity. In total, the 4 imaging modes acquired were 8-frame/positive-trigger, 16-frame/positive-trigger, 8-frame/negative-trigger, and 16-frame/negative-trigger. All SPECT images were reconstructed and processed with the same values of parameters. Systolic and diastolic indices of LV function were derived in QGS of the Cedars-Sinai software and then were compared using various statistical tests, and a reliability analysis was also performed.
Results
The age of patients recruited in the study was 58.41 ± 8.94, and 16 (47.1%) males and 18 (52.9%) females. All the correlation coefficients between corresponding parameters in positive and negative trigger signals were statistically significant. The difference between the parameters of systolic function including EF, EDV, and ESV in positive and negative trigger signals was statistically significant in paired sample t test. Likewise, a statistically significant difference was also found between mean phase angle in scans with positive and negative trigger signals by a phase difference of 147.91 (41.0% of an average cardiac cycle) and 149 (41.3% of an average cardiac cycle) degrees in 8- and 16-frame gating modes, respectively. Strong agreement (according to high values of intra-class correlation coefficient) was found for all four pairs. According to Bland-Altman results, an offset of about 3 percentage units was found, both between imaging in 8-frame gating compared to 16-frame gating, higher value in favor of 16-frame gating, and also between imaging with positive polarity trigger compared to negative-polarity trigger, again higher value in favor of positive-polarity triggering.
Conclusion
The status of the polarity of trigger signals or similar CTM-camera delays in synchronization process during 8- and 16-frame gated SPECT imaging can be considered as one of the factors that may influence systolic and diastolic indices of LV function.



J Nucl Cardiol: 24 May 2021; epub ahead of print

Myocardial blood flows and reserves on solid state camera: Correlations with coronary history and cardiovascular risk factors.

Ferenczi P, Couffinhal T, Mamou A, Mamou Y, ... Coste P, Pinaquy JB
Objectives
Study designed to test association between stress-induced myocardial blood flow (sMBF), resting MBF (rMBF), and MBF reserve (MFR) and coronary artery disease (CAD) in a population of CAD and non-coronary patients. Secondary objectives were to confront visual analysis and dynamic analysis and to explore potential association between MBF and several cardiovascular risk factors
Methods:
A total of 155 patients who underwent dynamic myocardial perfusion imaging on a CZT camera were included. sMBF, rMBF, and MFR were evaluated, and cardiovascular risk was assessed.
Results
Significantly lower total sMBF and MFR were observed in CAD patient vs non-CAD patient. In comparison with visual analysis, lower sMBF were found in pathologic territory, lower rMBF in necrotic territory and lower MFR in necrotic ones. A significant correlation between total sMBF, rMBF and diabetes was found.
Conclusion
sMBF and MFR as assessed on CZT gamma-cameras can be used to determine the coronary state. Low total sMBF might be an independent risk factor of coronaropathy. An inverse correlation was suggested between total sMBF and rMBF with diabetes.



J Nucl Cardiol: 24 May 2021; epub ahead of print

New criteria for the diagnosis of infective endocarditis using 18F-FDG PET/CT imaging.

Gazzilli M, Albano D, Lucchini S, Peli A, ... Bertagna F, Giubbini R
Objectives
The purpose of this study was to examine a qualitative scoring system and a semi-quantitative method of FDG-PET/CT imaging in the diagnosis of infective endocarditis (IE).
Methods
We retrospectively included 108 patients who underwent 18F-FDG-PET/CT for suspected IE. PET/CT scans were interpreted using a 4-point score (0 = no uptake; 1 = cardiac uptake < blood-pool activity; 2 = blood-pool < uptake < liver activity; 3 = uptake > liver) and semi-quantitatively using SUVmax and SUVmean of the suspected valve lesion, liver, spleen, and of the bone marrow (BM). BM and spleen SUVmean were normalized to the liver, and hypermetabolism (HSBM) was defined as a BM or spleen-to-liver ratio > 1.
Results
Comparing the score criteria results with the clinical final diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of qualitative criteria were 93%, 81%, 84%, 91%, and 87%, respectively. A definite IE was documented in 83% of patients showing HSBM and abnormal cardiac uptake, 44% with abnormal cardiac uptake, 28% with HSBM, and 10% with neither one.
Conclusion
The qualitative scoring system is helpful in the diagnosis of IE. The HSBM is an additional, reliable indirect sign of IE.



J Nucl Cardiol: 24 May 2021; epub ahead of print

Determination of [N-13]-ammonia extraction fraction in patients with coronary artery disease by calibration to invasive coronary and fractional flow reserve.

Nye JA, Piccinelli M, Hwang D, Cooke CD, ... Koo BK, Garcia EV
Background
This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs.
Methods
39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures. [N-13]-ammonia dynamic rest/adenosine-stress PET imaging was conducted in all patients and absolute myocardial flow was estimated using four published compartmental models. The extraction fraction during hyperemic flow was iteratively estimated by maximizing the agreement between invasive CFR and FFR with the non-invasive analogs myocardial flow reserve (MFR) and relative flow reserve (RFR) at similar physiological states, respectively.
Results
Using the new patient-determined EFs, agreement between CFR vs MFR for Model 1 and 2 was moderate and poor for Model 3 and 4. All models showed moderate agreement for FFR vs RFR. When using published models of animal-determined EFs, agreement between CFR vs MFR remained moderate for Model 1 and 2, and poor for Model 3 and 4. Similarly, all models showed moderate agreement for FFR vs RFR using animal-determined EF values. None of the observed differences were statistically significant.
Conclusions
Flow measurements using extraction fraction correction for [N-13]-ammonia based on calibration to invasive intracoronary angiography physiological measures in patients with CAD were not discordant from those reported in the literature. Either patient-determined or traditional animal-determined EF correction, when used with the appropriate flow model, yields moderate agreement with invasive measurements of coronary flow reserve and fractional flow reserve.



J Nucl Cardiol: 24 May 2021; epub ahead of print

Comparison of Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography to magnetic resonance imaging to measure right ventricular volumes and ejection fraction in patients with cardiomyopathy.

Apert A, Canu M, Jankowski A, Riou L, ... Djaileb L, Barone-Rochette G
Aims
The objective of this study was to determine the accuracy of right ventricular function (RVF) assessed by Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography (CZT-ERNA).
Methods and results
Twenty-one consecutive patients with cardiomyopathy (aged 54 ± 19 years; 62% male) were included. RV ejection fraction (EF) and volumes were analyzed by CZT-ERNA and compared with values obtained by cardiac magnetic resonance imaging (CMR). Mean values were not different between CZT-ERNA and MRI for RVEF (48.1 ± 10.4% vs 50.8 ± 10.0%; P = .23). Significant correlations (P < .0001) were observed between CZT-ERNA and MRI for RVEF, RV end-diastolic volume, and end-systolic volume (r = 0.81, r = 0.93, and r = 0.96, respectively). Bland-Altman analysis showed a mean difference (bias) between CZT-ERNA and MRI for RVEF of -2.69% (95% CI - 5.35 to - 0.42) with good agreement between the 2 techniques (limits of agreement, -14.3 to 8.99). Intraobserver and interobserver reproducibility of RVF measured by CZT-ERNA was high.
Conclusion
CZT-ERNA provides accurate, reproducible assessment of RVF and appears as a good alternative to cardiac magnetic resonance for the evaluation of the magnitude of RVF in patients with cardiomyopathy.



J Nucl Cardiol: 13 May 2021; epub ahead of print

Aortic wall segmentation in F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based versus manual segmentation.

Piri R, Edenbrandt L, Larsson M, Enqvist O, ... Gerke O, Høilund-Carlsen PF
Background
We aimed to establish and test an automated AI-based method for rapid segmentation of the aortic wall in positron emission tomography/computed tomography (PET/CT) scans.
Methods
For segmentation of the wall in three sections: the arch, thoracic, and abdominal aorta, we developed a tool based on a convolutional neural network (CNN), available on the Research Consortium for Medical Image Analysis (RECOMIA) platform, capable of segmenting 100 different labels in CT images. It was tested on ¹⁸F-sodium fluoride PET/CT scans of 49 subjects (29 healthy controls and 20 angina pectoris patients) and compared to data obtained by manual segmentation. The following derived parameters were compared using Bland-Altman Limits of Agreement: segmented volume, and maximal, mean, and total standardized uptake values (SUVmax, SUVmean, SUVtotal). The repeatability of the manual method was examined in 25 randomly selected scans.
Results
CNN-derived values for volume, SUVmax, and SUVtotal were all slightly, i.e., 13-17%, lower than the corresponding manually obtained ones, whereas SUVmean values for the three aortic sections were virtually identical for the two methods. Manual segmentation lasted typically 1-2 hours per scan compared to about one minute with the CNN-based approach. The maximal deviation at repeat manual segmentation was 6%.
Conclusions
The automated CNN-based approach was much faster and provided parameters that were about 15% lower than the manually obtained values, except for SUVmean values, which were comparable. AI-based segmentation of the aorta already now appears as a trustworthy and fast alternative to slow and cumbersome manual segmentation.



J Nucl Cardiol: 11 May 2021; epub ahead of print

Transthyretin Cardiac Amyloidosis Scintigraphy Using Planar D-SPECT on Dedicated Cardiac CZT Camera.

Tshori S, Livschitz S, Volodarsky I, Goland S, ... Fabrikant J, George J
Background
Bone scintigraphy is a main diagnostic tool in suspected ATTR patients. Almost all literature is based on conventional whole body gamma cameras, and there is very sparse data evaluating the use of dedicated cardiac CZT cameras. The aim of this study was to evaluate the utility of bone scintigraphy in suspected transthyretin cardiac amyloidosis (ATTR-CA) patients on a dedicated cardiac CZT camera.
Methods
Seventy-three patients with suspected ATTR-CA underwent planar and SPECT Tc-99 m pyrophosphate scintigraphy using dedicated cardiac CZT camera between May and August 2019.
Results
Planar D-SPECT image quality was mostly good. Six patients were identified as ATTR-CA positive. Inter-observer agreement based on both Perugini score and on planar D-SPECT H/CL ratio was excellent.
Conclusions
ATTR-CA scintigraphy using dedicated cardiac CZT camera was feasible, and yielded planar D-SPECT images with excellent inter-observer agreement.



J Nucl Cardiol: 10 May 2021; epub ahead of print

Intravenous insulin injection supplemented with subsequent milk consumption is a safer formulation for cardiac viability F-FDG imaging.

Chen YC, Pan MJ, Wang QQ, Wang YH, Zhuo HL, Dai RZ
Background
The safety and efficacy of intravenous insulin injection coupled with subsequent milk consumption was evaluated for high-quality cardiac viability F-18-fluorodeoxyglucose (¹⁸F-FDG) images.
Methods and results
A total of 328 patients with known/suspected coronary artery disease received intravenous insulin injection with or without subsequent milk consumption for cardiac ¹⁸F-FDG imaging. When blood glucose levels had decreased by ≥ 20%, ¹⁸F-FDG was injected. Patients were scored for hypoglycemic symptoms using a 10-point scale (discomfort: 0, none; 1 to 3, mild; 4 to 6, moderate; 7 to 9, severe). An insulin-related hypoglycemic event was defined as an increased symptomatic score following insulin injection. The number of hypoglycemic events was significantly lower in the milk consumption group than in the group that did not (24/164 vs. 51/164, P < .01). Maximal and averaged standardized uptake value of the left ventricular myocardium (MyoSUVmax and MyoSUVmean) were also measured. The milk and control groups had similar mean hypoglycemic symptom scores (4.2 ± 4.0 vs. 3.3 ± 3.1, respectively), MyoSUVmax, and MyoSUVmean (11.1 ± 4.8, 7.3 ± 3.2 vs. 11.4 ± 4.5, 7.4 ± 3.2, respectively).
Conclusion
Intravenous insulin injection supplemented with subsequent milk consumption is a safer formulation for cardiac viability ¹⁸F-FDG imaging without impairing image quality.



J Nucl Cardiol: 04 May 2021; epub ahead of print

Assessment of a digital and an analog PET/CT system for accurate myocardial perfusion imaging with a flow phantom.

Siekkinen R, Kirjavainen AK, Koskensalo K, Smith NAS, ... Teräs M, Teuho J
In Myocardial Perfusion Imaging (MPI) with Positron Emission Tomography/Computed Tomography (PET/CT) systems, accurate quantification is essential. We assessed flow quantification accuracy over various injected activities using a flow phantom.
Methods
The study was performed on the digital 4-ring Discovery MI (DMI-20) and analog Discovery 690 (D690) PET/CT systems, using 325-1257 MBq of [¹⁵O]H₂O. PET performance and flow quantification accuracy were assessed in terms of count-rates, dead-time factors (DTF), scatter fractions (SF), time-activity curves (TACs), areas-under-the-curves (AUCs) and flow values.
Results
On DMI-20, prompts of 12.8 Mcps, DTF of 2.06 and SF of 46.1% were measured with 1257 MBq of activity. On the D690, prompts of 6.85 Mcps, DTF of 1.57 and SF of 32.5% were measured with 1230 MBq of activity. AUC values were linear over all activities. Mean wash-in flow error was - 9% for both systems whereas wash-out flow error was - 5% and - 6% for DMI-20 and D690. With the highest activity, wash-out flow error was - 12% and - 7% for the DMI-20 and D690.
Conclusion
DMI-20 and D690 preserved accurate flow quantification over all injected activities, with maximum error of - 12%. In the future, flow quantification accuracy over the activities and count-rates evaluated in this study should be assessed.



J Nucl Cardiol: 03 May 2021; epub ahead of print

Diagnostic accuracy of myocardial perfusion imaging in patients evaluated for kidney transplantation: A systematic review and meta-analysis.

Kelderman JR, Jolink FEJ, Benjamens S, Monroy-Gonzalez AG, Pol RA, Slart RHJA
Background
Cardiovascular disease is the most common cause of death after kidney transplantation. Coronary artery disease (CAD) assessment is therefore mandatory in patients evaluated for transplantation. We aimed to assess the diagnostic accuracy for CAD of single-photon emission computed tomography (SPECT) compared to the standards invasive coronary angiography (ICA) and coronary computed tomography angiography (CCTA) in patients evaluated for kidney transplantation.
Methods
We performed a systematic literature search in PubMed, EMBASE, Web of Science, OvidSP (Medline), The Cochrane Library and Google Scholar. Studies investigating the diagnostic accuracy of myocardial perfusion imaging (MPI) SPECT in patients evaluated for kidney transplantation were retrieved. After a risk of bias assessment using QUADAS-2, a meta-analysis was conducted.
Results
Out of 1459 records, 13 MPI SPECT studies were included in the meta-analysis with a total of 1245 MPI SPECT scans. There were no studies available with CCTA as reference. Pooled sensitivity of MPI SPECT for CAD was 0.66 (95% CI 0.53 to 0.77), pooled specificity was 0.75 (95% CI 0.63 to 0.84) and the area under the curve (AUC) was 0.76. Positive likelihood ratio was 2.50 (95% CI 1.78 to 3.51) and negative likelihood ratio was 0.41 (95% CI 0.28 to 0.61). Pooled positive predictive value was 64.9% and pooled negative predictive value was 74.1%. Significant heterogeneity existed across the included studies.
Conclusions
MPI SPECT had a moderate diagnostic accuracy in patients evaluated for kidney transplantation, with a high rate of false-negative findings. The use of an anatomical gold standard against a functional imaging test in the included studies is however suboptimal.



J Nucl Cardiol: 03 May 2021; epub ahead of print

Visual patterns of breast attenuation artifacts in women and men with an upright and supine cadmiun-zinc-telluride camera.

Waqar F, Athar MW, Dwivedi AK, Ahmad S, ... Khan N, Gerson MC
Background
Breast attenuation artifacts occurring with upright cadmium-zinc-telluride (CZT) cardiac imaging systems have not been well characterized.
Methods
216 consecutive patients with Single Photon Emission Computerized Tomography myocardial perfusion imaging and no angiographically significant obstructive coronary artery disease were identified. All upright and supine SPECT images as well as coronary angiograms were reviewed and analyzed in blinded fashion.
Results
In women imaged upright, more visual false positive defects were noted in the inferior wall compared to the anterior wall (26 vs. 10 at rest, p = 0.006, and 33 vs. 13 at stress, p < 0.001). Visual inferior wall defects were more common in the upright than supine position at stress (33 vs. 23, p = 0.018) and rest (26 vs. 14, p = 0.011), and most apparent in non-obese women (13 vs. 8, at stress, p = 0.059 and 11 vs. 5, at rest, p = 0.014).
Conclusions
With upright CZT myocardial perfusion imaging, women often have visible inferior wall attenuation artifact defects, likely from pendant breast tissue. These inferior wall attenuation artifacts may be seen in non-obese female patients.



J Nucl Cardiol: 03 May 2021; epub ahead of print

Prediction of 2-year major adverse cardiac events from myocardial perfusion scintigraphy and clinical risk factors.

Leslie WD, Bryanton M, Goertzen A, Slomka P
Background
We developed CRAX2MACE, a new tool derived from clinical and SPECT myocardial perfusion imaging (MPI) variables, to predict 2-year probability of major adverse cardiac event (MACE) comprising death, hospitalized acute myocardial infarction or coronary revascularization.
Methods
Consecutive individuals with SPECT MPI 2001-2008 had two-year MACE determined from population-based health services data. CRAX2MACE included age, sex, diabetes, recent cardiac hospitalization, pharmacologic stress, stress total perfusion deficit (TPD), ischemic (stress-rest) TPD, left ventricular ejection fraction and transient ischemic dilation ratio. Two-year event rates were classified as low (< 5%), moderate (5.0-9.9%), high (10-19.9%) and very high (20% or greater).
Results
The study population comprised 3896 individuals for the development and 1946 for the validation subgroups with subsequent MACE in 589 (15.1%) and 272 (14.0%), respectively. CRAX2MACE, derived from the development subgroups, accurately stratified MACE risk in the validation subgroup (area under the receiver operating characteristics curve 0.79) with stepwise increase in the observed event rate with increasing predicted risk category (low, 2.3%; moderate, 5.5%; high, 18.8%; very high 33.2%; P-trend < 0.001).
Conclusions
A simple tool based upon clinical risk factors and MPI variables predicts 2-year cardiac events. Risk stratification between the low and very high groups was greater than tenfold.



J Nucl Cardiol: 27 Apr 2021; epub ahead of print

Stress testing and myocardial perfusion imaging for patients after recovery from severe COVID-19 infection requiring hospitalization: A single-center experience.

Hasnie UA, Hawi R, Andrikopoulou E, Iskandrian AE, Hage FG
Background
As the coronavirus pandemic progresses, patients that have recovered from COVID-19-related hospitalization require resumption of care for other medical issues. Thus far, the literature has not detailed the experience of stress testing in this patient population.
Methods
We retrospectively reviewed patients that recovered from COVID-19-related hospitalizations and underwent SPECT MPI studies at the University of Alabama at Birmingham Medical Center.
Results
15 patients (median age 60 years, 67% male) were identified with COVID-19-related hospitalization and then underwent SPECT MPI imaging after recovery. During COVID-19-related hospitalization (median length of stay 8 days), patients received various COVID-19 therapies; 3 required mechanical ventilation. Stress tests (4 Exercise, 11 Pharmacologic) were performed 65 days (interquartile range 31-94 days) after the diagnosis of COVID-19. None of the patients experienced serious adverse events during or after stress testing. One patient required regadenoson reversal using aminophylline due to chest pain.
Conclusion
Over time, more patients that recover from COVID-19 infection will require MPI testing for myocardial ischemia evaluation. Our study provides some information regarding performing stress testing in patients who have recently recovered from COVID-19 infections requiring hospitalization. Further studies are recommended to establish formal protocols for testing in this cohort.



J Nucl Cardiol: 25 Apr 2021; epub ahead of print