Cardiac amyloidosis characterization by kinetic model fitting on [18F]florbetaben PET images.

Santarelli MF, Genovesi D, Scipioni M, Positano V, ... Emdin M, Marzullo P
Objective
To evaluate the feasibility of kinetic modeling-based approaches from [18F]-Flobetaben dynamic PET images as a non-invasive diagnostic method for cardiac amyloidosis (CA) and to identify the two AL- and ATTR-subtypes.
Methods and results
Twenty-one patients with diagnoses of CA (11 patients with AL-subtype and 10 patients with ATTR-subtype of CA) and 15 Control patients with no-CA conditions underwent PET/CT imaging after [18F]Florbetaben bolus injection. A two-tissue-compartment (2TC) kinetic model was fitted to time-activity curves (TAC) obtained from left ventricle wall and left atrium cavity ROIs to estimate kinetic micro- and macro-parameters. Combinations of kinetic parameters were evaluated with the purpose of distinguishing Control subjects and CA patients, and to correctly label the last ones as AL- or ATTR-subtype. Resulting sensitivity, specificity, and accuracy for Control subjects were: 0.87, 0.9, 0.89; as far as CA patients, the sensitivity, specificity, and accuracy were respectively 0.9, 1, and 0.97 for AL-CA patients and 0.9, 0.92, 0.97 for ATTR-CA patients.
Conclusion
Pharmacokinetic analysis based on a 2TC model allows cardiac amyloidosis characterization from dynamic [18F]Florbetaben PET images. Estimated model parameters allows to not only distinguish between Control subjects and patients, but also between AL- and ATTR-amyloid patients.



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

Predictive value of incidental right ventricular abnormalities identified on SPECT for mortality and pulmonary hypertension.

Jose A, Zhou C, Baker R, Walker J, ... Elwing JM, Gerson M
Background
The clinical significance of incidentally found RV abnormalities on low-risk SPECT studies is not well-defined. The objective of this study was to determine the predictive value of incidental right ventricular (RV) abnormalities identified on single photon emission computed tomography (SPECT) scans for mortality and pulmonary hypertension (PH).
Methods
We retrospectively analyzed all low-risk SPECT studies in patients without known coronary artery or pulmonary vascular disease, performed at our institution, from 2007-2020. Adjusted Cox proportional hazards models were used to evaluate the association between incidental RV abnormalities on low-risk SPECT studies and outcomes.
Results
Of the 4761 patients included in the analysis, mortality events were present in 494, and echocardiographic PH was present in 619. Incidental RV abnormalities on low-risk SPECT studies were significantly and independently associated with all-cause mortality (HR = 1.41, CI [1.07-1.86], P = 0.0152) and echocardiographic PH (HR = 2.06, CI [1.64-2.60], P < 0.0001).
Conclusions
These data suggest incidental RV abnormalities found on low-risk SPECT imaging studies are significantly and independently associated with increased mortality and risk of developing echocardiographic PH, and could identify high-risk patients for closer monitoring and additional diagnostic testing.



J Nucl Cardiol: 12 Apr 2021; epub ahead of print

Clinical impact of quantitative [O] HO PET/CT myocardial perfusion imaging on decision-making regarding invasive management of coronary artery disease.

Promteangtrong C, Jantarato A, Kunawudhi A, Kiatkittikul P, ... Boonkawin N, Chotipanich C
Background
This study was performed to determine the impact of oxygen-15-labeled water ([¹⁵O] H₂O) positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging (MPI) on referral for invasive coronary angiography (ICA) and revascularization.
Methods
This study involved 57 patients who underwent [¹⁵O] H₂O PET/CT MPI for evaluation of coronary artery disease (CAD). Data of referral for ICA and revascularization, clinical symptoms, and cardiac events within 6 months after MPI were assessed. Logistic regression was used to determine the predictors for referral and revascularization. The diagnostic values of hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) were calculated.
Results
Normal and abnormal MPI findings were observed in 18 (32%) and 39 (68%) patients, respectively. The referral rate was significantly different between the normal and abnormal MPI groups (5.6% and 48.7%, respectively; P = .002). Revascularization rate of abnormal MPI group was 40.0%. There were significant differences of hyperemic MBF and CFR between patients with and without referral. Hyperemic MBF was significant predictor for referral (OR 15.24, 95% CI 3.39-68.55, P < .005) and revascularization (OR 28.57, 95% CI 3.08-265.33, P < .005).
Conclusion
[¹⁵O] H₂O PET/CT MPI showed a clinical impact on decision-making regarding invasive procedure for management of CAD.



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

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[F]F PET-CT.

Borges-Rosa J, Oliveira-Santos M, Silva R, da Silva NP, ... Gonçalves L, Ferreira MJ
Background
Fluorine-18 sodium fluoride (Na[¹⁸F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[¹⁸F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients.
Methods and results
Thirty-four high CV risk individuals without previous CV events were scanned with Na[¹⁸F]F PET-CT. Cardiac Na[¹⁸F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (r_s = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (r_s = 0.61), body mass index (r_s = 0.66), abdominal perimeter (r_s = 0.74), thoracic fat volume (r_s = 0.47), and epicardial adipose tissue (r_s = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[¹⁸F]F uptake.
Conclusions
In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.



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

3D fusion between fluoroscopy angiograms and SPECT myocardial perfusion images to guide percutaneous coronary intervention.

Tang H, Bober RR, Zhao C, Zhang C, ... Xu Z, Zhou W
Background
Percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD) is commonly triggered by abnormal myocardial perfusion imaging (MPI). However, due to the possibilities of multivessel disease, serial stenoses and variability of coronary artery perfusion distribution, an opportunity exists to better align anatomic stenosis with perfusion abnormalities to improve revascularization decisions. This study aims to develop a multi-modality fusion approach to assist decision-making for PCI.
Methods and results
Coronary arteries from fluoroscopic angiography (FA) were reconstructed into 3D artery anatomy. Left ventricular (LV) epicardial surface was extracted from SPECT. The artery anatomy and epicardial surface were non-rigidly fused. The accuracy of the 3D fusion was evaluated via both computer simulation and real patient data. Simulated FA and MPI were integrated and then compared with the ground truth from a digital phantom. The distance-based mismatch errors between simulated fluoroscopy and phantom arteries were 1.86 ± 1.43 mm for left coronary arteries (LCA) and 2.21 ± 2.50 mm for right coronary arteries (RCA). FA and SPECT images in 30 patients were integrated and then compared with the ground truth from CT angiograms. The distance-based mismatch errors between the fluoroscopy and CT arteries were 3.84 ± 3.15 mm for LCA and 5.55 ± 3.64 mm for RCA. The presence of the corresponding fluoroscopy and CT arteries in the AHA-17-segment model agreed well with a Kappa value of 0.91 (CI 0.89-0.93) for LCA and a Kappa value of 0.80 (CI 0.67-0.92) for RCA.
Conclusions
Our fusion approach is technically accurate to assist PCI decision-making and is clinically feasible to be used in the catheterization laboratory. Future studies are necessary to determine if fusion improves PCI-related outcomes.



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

The effect of Vitamin-K and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial.

Bellinge JW, Francis RJ, Lee SC, Vickery A, ... Watts GF, Schultz CJ
Background
There is currently no treatment for attenuating progression of arterial calcification. ¹⁸F-sodium fluoride positron emission tomography (¹⁸F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K₁ or colchicine affected arterial calcification activity.
Methods
154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K₁ [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K₁ [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on ¹⁸F-NaF PET.
Results
149 subjects completed follow-up (vitamin-K₁: placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K₁ nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K₁.
Conclusions
In patients with type 2 diabetes, neither vitamin-K₁ nor colchicine significantly decreases coronary calcification activity, as estimated by ¹⁸F-NaF PET, over a period of 3 months.
Clinical trial registration
ACTRN12616000024448.



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

Impact of Gd-153 scanning line source attenuation correction on downstream invasive testing.

Singhvi A, Suacier S, Verma I, Felpel K, ... McMahon S, Duvall WL
Background
Attenuation correction (AC) using hardware and software solutions has been shown to increase the specificity of SPECT MPI by decreasing false positive results and improving prognostic ability. Theoretically this should reduce downstream testing and unnecessary costs. We sought to assess the consequences of the use of Gd-153 scanning line source attenuation correction during SPECT myocardial perfusion imaging (MPI) on downstream invasive testing.
Methods
All patients who underwent a clinically indicated Tc-99m stress SPECT MPI study from 2013 to 2015 at five hospitals (2 with AC and 3 without) were retrospectively reviewed. Patient demographics, results of testing, subsequent coronary angiography within 3 months, and revascularization were recorded. The results of the MPI studies, downstream angiogram utilization, and results of angiography were compared and a propensity matched subgroup analysis was performed.
Results
A total of 9968 patients underwent SPECT MPI during the study time period (6106 performed with AC and 3862 without). Out of 3928 patients included in the propensity matched cohort, there was no difference in the proportion of abnormal MPI results between the two groups (31.5% vs 30.4%, P = 0.47), however, more patients underwent coronary angiography within 90 days in the AC group (10.6% vs 8.7%, P = 0.05). There was no significant difference in the proportion of patients with angiographically significant obstructive disease (53.4% vs 56.1%, P = 0.19), however, fewer patients in the AC group with obstructive coronary disease were revascularized (36.1% vs 46.8%, P = 0.04). The findings remained consistent after sub-group analysis in patients without known coronary disease.
Conclusion
The use of scanning line source AC did not meaningfully influence the rate of abnormal MPI results or downstream invasive testing in this cohort. The clinical utility of scanning line source AC may be limited to facilitating stress-first imaging protocols.



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

Prevalence and clinical significance of incidental findings on CT attenuation correction for myocardial perfusion imaging.

Lee JC, Delaney FT
Background
The appropriate clinical approach to incidentally detected lesions (IDLs) on CT attenuation correction (CTAC) images in myocardial perfusion imaging (MPI) remains uncertain. We sought to establish their prevalence and clinical significance in a large cohort and compared to previous studies to help provide further clarity and guide future clinical practice.
Methods and results
A total of 3758 MPI studies were reviewed retrospectively. IDLs of potential clinical significance-not known before MPI - were reported in 245 (6.5%) of these cases. Following appropriate further investigation/follow-up, these were of proven clinical significance in 30 (12.2%) cases with 14 patients (5.7%) harboring previously undiagnosed or progressive malignancies. The positive predictive value (PPV) for clinically significant incidental findings on CTAC images was 17.2% and the PPV value for incidental malignant findings was 8.0%.
Conclusion
Although incidental findings on CTAC images in MPI are common and often clearly insignificant at time of MPI reporting, many are clinically significant with a relatively high positive predictive value. This is especially so for malignancies. Our findings, therefore, in combination with previous studies as described here support routine reporting and appropriate further investigation of incidental CTAC findings in MPI.



J Nucl Cardiol: 21 Mar 2021; epub ahead of print

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: 15 Mar 2021; epub ahead of print

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: 15 Mar 2021; epub ahead of print

Evaluating the use of pharmacological stress agents during single-photon emission computed tomography myocardial perfusion imaging tests after inadequate exercise stress test.

Yang H, Faust E, Gao E, Sethi S, ... Spalding JR, Xu Y
Background
Past clinical trial findings suggest that the availability of regadenoson in a nuclear imaging center may affect real-world center practices related to the transition of patients from an inadequate exercise stress test (EST) to a pharmacological stress agent (PSA).
Methods and results
This was a cross-sectional study using one-on-one telephone interviews with nuclear imaging center staff to facilitate survey development, followed by an online survey to evaluate patterns and processes around use of PSAs during single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with inadequate ESTs. Of the 50 participants, 35 (70%) used only regadenoson, 3 (6%) only adenosine, 3 (6%) regadenoson and adenosine, 7 (14%) regadenoson and dipyridamole, and 2 (4%) all 3 agents for converting patients from an inadequate EST to a PSA. Nearly all centers (94%) used protocols to guide conversions. Of 12 centers using > 1 PSA, 11 reported regadenoson to be the most preferred PSA. Total staff time required from PSA transition to post-test monitoring was shortest for regadenoson.
Conclusions
Compared to adenosine and dipyridamole, regadenoson is preferred by nuclear imaging center staff and associated with operational efficiencies after inadequate EST in real-world practice SPECT-MPI.



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

Diagnostic and prognostic value of Technetium-99m pyrophosphate uptake quantitation for transthyretin cardiac amyloidosis.

Miller RJH, Cadet S, Mah D, Pournazari P, ... Berman DS, Slomka PJ
Background
^99mTc-pyrophosphate imaging has emerged as an important non-invasive method to diagnose transthyretin cardiac amyloidosis (ATTR-CM). Quantitation of ^99mTc-pyrophosphate activity, on SPECT images, could be a marker of ATTR-CM disease burden. We assessed the diagnostic accuracy and clinical significance of ^99mTc-pyrophosphate quantitation.
Methods and results
Patients who underwent ^99mTc-pyrophosphate imaging for suspected ATTR-CM were included. Using SPECT images, radiotracer activity in the myocardium was calculated using cardiac pyrophosphate activity (CPA) and volume of involvement (VOI), with thresholds for abnormal activity derived from LVBP activity. Diagnostic accuracy was assessed using area under the receiver operating characteristic curve (AUC). In total, 124 patients were identified, mean age 73.9 ± 11.4, with ATTR-CM diagnosed in 43 (34.7%) patients. CPA had the highest diagnostic accuracy (AUC .996, 95% CI .987-1.00), and was significantly higher compared to the Perugini score (AUC .952, P = .016). In patients with ATTR-CM, CPA was associated with reduced left ventricular ejection fraction (adjusted odds ratio 1.28, P = .035) and heart failure hospitalizations (adjusted hazard ratio 1.29, P = .006).
Conclusion
Quantitative assessment of myocardial radiotracer activity with CPA or VOI have high diagnostic accuracy for ATTR-CM. Both measures are potential non-invasive markers to follow progression of disease or response to therapy.



J Nucl Cardiol: 09 Mar 2021; epub ahead of print

Global and regional cardiac dysfunction quantified by F-FDG PET scans can predict ventricular arrhythmia in patients with implantable cardioverter defibrillator.

Jing R, Sun XX, Hua W, Chen L, ... Niu HX, Zhang S
Background
A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement.
Methods
We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed.
Results
In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46).
Conclusion
Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by ¹⁸F-FDG PET may indicate a higher VA incidence after ICD placement.



J Nucl Cardiol: 08 Mar 2021; epub ahead of print

Healthcare resource utilization among patients receiving non-invasive testing for coronary artery disease in an outpatient setting: A cohort study reflecting daily practice trends.

Ananthasubramaniam K, Kitt TM, Saxena A, Feng Q, ... Spalding JR, Xu Y
Background
Accurate, early diagnosis and the initiation of appropriate treatment is central to reducing the clinical burden of coronary artery disease (CAD); however, real-world evidence characterizing healthcare resource utilization (HCRU) associated with testing for CAD is lacking.
Methods and results
Using a non-interventional, retrospective, secondary database analysis, patients aged ≥18 years who underwent outpatient non-invasive cardiac diagnostic testing were identified. The primary objective was to gain an understanding of pre- and post-assessment care pathways and the associated interventions for patients who underwent non-invasive testing for CAD in either an outpatient or emergency department setting. Overall, chest pain was the primary reason for the index visit (54.8%), followed by shortness of breath (23.7%), myocardial infarction (MI), coronary artery disease (CAD) or congestive heart failure (CHF) (3.8%), and other (46.8%); 3.0% of patients had no apparent reason for testing in the last 45 days. Single-photon emission computed tomography (SPECT) was the dominant diagnostic testing modality (40.3%). During the 90-day follow-up, 7.3% (n = 22,083) of patients were diagnosed with CAD; among these patients, 19.4% had repeat diagnostic testing, 26.0% of patients had a revascularization procedure, and 65.6% underwent cardiac catheterization. These rates varied by testing modality.
Conclusions
In this study of a large real-world data sample, variability in the use of non-invasive tests and HCRU were evident. These results may assist efforts to optimize system-wide care/diagnostic pathways and value-based treatment decisions for patients.



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

Influence of patient motion on quantitative accuracy in cardiac O-water positron emission tomography.

Nordström J, Harms HJ, Kero T, Sörensen J, Lubberink M
Background
Patient motion is a common problem during cardiac PET. The purpose of the present study was to investigate to what extent motions influence the quantitative accuracy of cardiac ¹⁵O-water PET/CT and to develop a method for automated motion detection.
Method
Frequency and magnitude of motion was assessed visually using data from 50 clinical ¹⁵O-water PET/CT scans. Simulations of 4 types of motions with amplitude of 5 to 20 mm were performed based on data from 10 scans. An automated motion detection algorithm was evaluated on clinical and simulated motion data. MBF and PTF of all simulated scans were compared to the original scan used as reference.
Results
Patient motion was detected in 68% of clinical cases by visual inspection. All observed motions were small with amplitudes less than half the LV wall thickness. A clear pattern of motion influence was seen in the simulations with a decrease of myocardial blood flow (MBF) in the region of myocardium to where the motion was directed. The perfusable tissue fraction (PTF) trended in the opposite direction. Global absolute average deviation of MBF was 3.1% ± 1.8% and 7.3% ± 6.3% for motions with maximum amplitudes of 5 and 20 mm, respectively. Automated motion detection showed a sensitivity of 90% for simulated motions ≥ 10 mm but struggled with the smaller (≤ 5 mm) simulated (sensitivity 45%) and clinical motions (accuracy 48%).
Conclusion
Patient motion can impair the quantitative accuracy of MBF. However, at typically occurring levels of patient motion, effects are similar to or only slightly larger than inter-observer variability, and downstream clinical effects are likely negligible.



J Nucl Cardiol: 01 Mar 2021; epub ahead of print

Effect of temporal sampling protocols on myocardial blood flow measurements using Rubidium-82 PET.

Koenders SS, van Dijk JD, Jager PL, Mouden M, ... Slump CH, van Dalen JA
Background
A variety of temporal sampling protocols is used worldwide to measure myocardial blood flow (MBF). Both the length and number of time frames in these protocols may alter MBF and myocardial flow reserve (MFR) measurements. We aimed to assess the effect of different clinically used temporal sampling protocols on MBF and MFR quantification in Rubidium-82 (Rb-82) PET imaging.
Methods
We retrospectively included 20 patients referred for myocardial perfusion imaging using Rb-82 PET. A literature search was performed to identify appropriate sampling protocols. PET data were reconstructed using 14 selected temporal sampling protocols with time frames of 5-10 seconds in the first-pass phase and 30-120 seconds in the tissue phase. Rest and stress MBF and MFR were calculated for all protocols and compared to the reference protocol with 26 time frames.
Results
MBF measurements differed (P ≤ 0.003) in six (43%) protocols in comparison to the reference protocol, with mean absolute relative differences up to 16% (range 5%-31%). Statistically significant differences were most frequently found for protocols with tissue phase time frames < 90 seconds. MFR did not differ (P ≥ 0.11) for any of the protocols.
Conclusions
Various temporal sampling protocols result in different MBF values using Rb-82 PET. MFR measurements were more robust to different temporal sampling protocols.



J Nucl Cardiol: 01 Mar 2021; epub ahead of print

Longitudinal analysis of atherosclerotic plaques evolution: an F-NaF PET/CT study.

Fiz F, Piccardo A, Morbelli S, Bottoni G, ... Bagnasco M, Sambuceti G
Purpose
¹⁸F-NaF-PET/CT can detect mineral metabolism within atherosclerotic plaques. To ascertain whether their ¹⁸F-NaF uptake purports progression, this index was compared with subsequent morphologic evolution.
Methods
71 patients underwent two consecutive ¹⁸F-NaF-PET/CTs (PET1/PET2). In PET1, non-calcified ¹⁸F-NaF hot spots were identified in the abdominal aorta. Their mean/max HU was compared with those of a non-calcified control region (CR) and with corresponding areas in PET2. A target-to-background ratio (TBR), mean density (HU), and calcium score (CS) were calculated on calcified atherosclerotic plaques in PET1 and compared with those in PET2. A VOI including the entire abdominal aorta was drawn; mean TBR and total CS were calculated on PET1 and compared with those PET2.
Results
Hot spots in PET1 (N = 179) had a greater HU than CR (48 ± 8 vs 37 ± 9, P < .01). Mean hot spots HU increased to 59 ± 12 in PET2 (P < .001). New calcifications appeared at the hot spots site in 73 cases (41%). Baseline atherosclerotic plaque\'s (N = 375) TBR was proportional to percent HU and CS increase (P < .01 for both). Aortic CS increased (P < .001); the whole-aorta TBR in PET1 correlated with the CS increase between the baseline and the second PET/CT (R = .63, P < .01).
Conclusions
¹⁸F-NaF-PET/CT depicts the early stages of plaques development and tracks their evolution over time.



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

Left ventricular mass on positron emission tomography: Validation against cardiovascular magnetic resonance.

Malahfji M, Ahmed AI, Han Y, Jung AK, ... Mahmarian JJ, Al-Mallah MH
Background
Left ventricular hypertrophy (LVH) is an important clinical finding that is independently associated with mortality and cardiovascular events. We aimed to assess the interstudy variability of LV mass quantitation between PET and CMR.
Methods
Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. LV mass on PET was compared against LV mass on CMR using several statistical measures of agreement.
Results
A total of 105 patients (mean age 60 ± 14 years, 67.6% male) were included. The median (interquartile range, IQR) duration between CMR and PET was 47 (11-154) days. The median (IQR) LV mass values were 168.0 g (126.0-202.0) on CMR and 174.0 g (150.0-212.0) with PET (absolute mean difference 29.42 ± 25.3). There was a good correlation (Spearman ρ = 0.81, P < 0.001; Intraclass Correlation Coefficient 0.78, 95% CI 0.70-0.85, P < 0.001) with moderate limits of agreement (95% limits of agreement - 63.78 to 83.7.) Results were consistent, albeit with moderate correlation, in subgroups of patients with LVH, in patients with myocardial infarction, in patients with LV ejection fraction < 50%, and those with limited image quality. LV mass on PET tended to be underestimated at high values compared to CMR.
Conclusion
We demonstrate good correlation and reproducibility of LV mass quantitation by PET against the reference standard of CMR across a wide range of normal and diseased hearts with a tendency of PET to underestimate mass at higher mass values.



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

Improved risk-stratification in heart failure patients with mid-range to severe abnormalities of QRS duration and systolic function using mechanical dyssynchrony assessed by myocardial perfusion-gated SPECT.

Doi T, Nakata T, Noto T, Mita T, Yuda S, Hashimoto A
Background
The use of left ventricular mechanical dyssynchrony (LVMD), which has been reported to be responsible for unfavorable outcomes, might improve conventional risk-stratification by clinical indices including QRS duration (QRSd) and systolic dysfunction in patients with heart failure (HF).
Methods and results
Following measurements of 12-lead QRSd and left ventricular ejection fraction (LVEF), three-dimensional (3-D) LVMD was evaluated as a standard deviation (phase SD) of regional mechanical systolic phase angles by gated myocardial perfusion imaging in 829 HF patients. Patients were followed up for a mean period of 37 months with a primary endpoint of lethal cardiac events (CEs). In an overall multivariate Cox proportional hazards model, phase SDs were identified as significant prognostic determinants independently. The patients were divided into 4 groups by combining with the cut-off values of LVEF (35% and 50%) and QRSd (130 ms and 150 ms). The groups with lower LVEF and prolonged QRSd more frequently had CEs than did the other groups. Patient groups with LVEF < 35% and with 35% ≦ LVEF < 50% were differentiated into low-risk and high-risk categories by using an optimal phase SD cut-off value of both QRSd thresholds.
Conclusions
3-D LVMD can risk-stratify HF patients with mid-range as well as severe abnormalities of QRSd and systolic dysfunction.



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

Incremental value of epicardial fat volume to coronary artery calcium score and traditional risk factors for predicting myocardial ischemia in patients with suspected coronary artery disease.

Yu W, Zhang F, Liu B, Wang J, ... Xu Y, Wang Y
Background
Epicardial fat volume (EFV) has been reported to be associated with coronary artery disease (CAD). CAD is the leading cause of myocardial ischemia and myocardial ischemia is closely related to major adverse cardiovascular events. We hypothesized that EFV could provide incremental value to traditional risk factors and coronary artery calcium score (CACS) in predicting myocardial ischemia in Chinese patients with suspected CAD.
Methods
We retrospectively studied 204 Chinese patients with suspected CAD who underwent single-photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) combined with computed tomography (CT). Pericardial contours were manually defined, and EFV was automatically calculated. A reversible perfusion defect with summed difference score (SDS) ≥ 2 was defined as myocardial ischemia.
Results
The myocardial ischemia group had higher EFV than normal MPI group (137.80 ± 34.95cm³ vs. 106.63 ± 29.10 cm³, P < .001). In multivariable logistic regression analysis, high EFV was significantly associated with myocardial ischemia [odds ratio (OR): 8.30, 95% CI: 3.72-18.49, P < .001]. Addition of EFV to CACS and traditional risk factors could predict myocardial ischemia more effectively, with larger AUC .82 (P < .001), positive net reclassification index .14 (P = .04) and integrated discrimination improvement .14 (P < .001). The bootstrap resampling method (times = 500) was used to internally validation and calculate the 95% confidence interval (CI) of the AUC (95% CI .75-.87). The calibration curve for the probability of myocardial ischemia demonstrated good agreement between prediction and observation.
Conclusions
In Chinese patients with suspected CAD, EFV was significantly associated with myocardial ischemia, and improved prediction of myocardial ischemia above traditional risk factors and CACS.



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

The prevalence of image degradation due to motion in rest-stress rubidium-82 imaging on a SiPM PET-CT system.

Armstrong IS, Memmott MJ, Hayden C, Arumugam P
Background
Motion of the heart is known to affect image quality in cardiac PET. The prevalence of motion blurring in routine cardiac PET is not fully appreciated due to challenges identifying subtle motion artefacts. This study utilizes a recent prototype Data-Driven Motion Correction (DDMC) algorithm to generate corrected images that are compared with non-corrected images to identify visual differences in relative rubidium-82 perfusion images due to motion.
Methods
300 stress and 300 rest static images were reconstructed with DDMC and without correction (NMC). The 600 DDMC/NMC image pairs were assigned Visual Difference Score (VDS). The number of non-diagnostic images were noted. A \"Dwell Fraction\" (DF) was derived from the data to quantify motion and predict image degradation.
Results
Motion degradation (VDS = 1 or 2) was evident in 58% of stress images and 33% of rest images. Seven NMC images were non-diagnostic-these originated from six studies giving a 2% rate of non-diagnostic studies due to motion. The DF metric was able to effectively predict image degradation. The DDMC heart identification and tracking was successful in all images.
Conclusion
Motion degradation is present in almost half of all relative perfusion images. The DDMC algorithm is a robust tool for predicting, assessing and correcting image degradation.



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

Relation between myocardial blood flow and cardiac events in diabetic patients with suspected coronary artery disease and normal myocardial perfusion imaging.

Assante R, Mainolfi CG, Zampella E, Gaudieri V, ... Cuocolo A, Acampa W
Background
We assessed the prognostic value of structural abnormalities and coronary vasodilator function in diabetic patients referred to a PET/CT for suspected coronary artery disease (CAD).
Methods
We studied 451 diabetics and 451 nondiabetics without overt CAD and normal myocardial perfusion. Myocardial blood flow (MBF) was computed from the dynamic rest and stress imaging. Myocardial flow reserve (MFR) was defined as ratio of hyperemic to baseline MBF and was considered reduced when < 2.
Results
During a mean follow-up of 44 months 33 events occurred. Annualized event rate (AER) was higher in diabetic than nondiabetic patients (1.4% vs 0.3%, P < .001). Diabetic patients with reduced MFR had higher AER compared to those with preserved MFR (3.3% vs 0.4%, P  < .001). At Cox analysis, age, BMI and reduced MFR were independent predictors of events in diabetic patients. Patients with diabetes and reduced MFR had lower event-free survival compared to nondiabetic patients and MFR < 2 (P < .001). Event-free survival was similar in patients with diabetes and normal MFR and those without diabetes and reduced MFR.
Conclusions
Diabetic patients with reduced MFR had higher AER and lower event-free survival compared to those with preserved MFR and to nondiabetic patients.



J Nucl Cardiol: 17 Feb 2021; epub ahead of print

Pattern of arterial inflammation and inflammatory markers in people living with HIV compared with uninfected people.

Taglieri N, Bonfiglioli R, Bon I, Malosso P, ... Re MC, Galié N
Study design
To compare arterial inflammation (AI) between people living with HIV (PLWH) and uninfected people as assessed by ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG)-positron emission tomography (PET).
Methods
We prospectively enrolled 20 PLWH and 20 uninfected people with no known cardiovascular disease and at least 3 traditional cardiovascular risk factors. All patients underwent ¹⁸F-FDG-PET/computed tomography (CT) of the thorax and neck. Biomarkers linked to inflammation and atherosclerosis were also determined. The primary outcome was AI in ascending aorta (AA) measured as mean maximum target-to-background ratio (TBR_max). The independent relationships between HIV status and both TBR_max and biomarkers were evaluated by multivariable linear regression adjusted for body mass index, creatinine, statin therapy, and atherosclerotic cardiovascular 10-year estimated risk (ASCVD).
Results
Unadjusted mean TBR_max in AA was slightly higher but not statistically different (P = .18) in PLWH (2.07; IQR 1.97, 2.32]) than uninfected people (2.01; IQR 1.85, 2.16]). On multivariable analysis, PLWH had an independent risk of increased mean log-TBR_max in AA (coef = 0.12; 95%CI 0.01,0.22; P = .032). HIV infection was independently associated with higher values of interleukin-10 (coef = 0.83; 95%CI 0.34, 1.32; P = .001), interferon-γ (coef. = 0.90; 95%CI 0.32, 1.47; P = .003), and vascular cell adhesion molecule-1 (VCAM-1) (coef. = 0.75; 95%CI: 0.42, 1.08, P < .001).
Conclusions
In patients with high cardiovascular risk, HIV status was an independent predictor of increased TBR_max in AA. PLWH also had an increased independent risk of IFN-γ, IL-10, and VCAM-1 levels.



J Nucl Cardiol: 09 Feb 2021; epub ahead of print

Effect of proton pump inhibitors and H2 antagonists on gastric wall uptake in myocardial perfusion scan with 99mTc-sestamibi.

Norouzi G, AsadZade A, Salimi Y, Khoshbakht S, Pirayesh E
Background
Proton pump inhibitors (PPIs) have been speculated to cause gastric wall uptake (GWU) in MPI scans. However, the uptake mechanism and prevention methods are less studied. In this prospective trial we aimed to evaluate the impact of gastroprotective medications on GWU and its solutions.
Methods
351 consecutive patients, scheduled for 2-day rest/stress 99mTc-MIBI scan, were distributed into 5 groups. 3-7 days following the baseline rest scan, the stress scan was acquired after intervention in the trial group, consisting of patients with history of PPI intake, randomly assigned to 3 subgroups: discontinuing PPIs(A), replacement with H2 blockers (B), and continuing PPIs (C). Patients receiving H2 blockers, continued it as before (D) and the remaining patients were the control group (E). GWU was graded compared to the myocardial uptake.
Results
In the rest phase, all groups had significantly higher GWU compared to the control group. In the stress phase, group A had less GWU than group B (P-value < 0.05) and both of them had significantly less GWU compared to group C (P-value < 0.001). There was no significant difference between PPI discontinuation periods of 3-5 days versus 5-7 days. There was a significant association between duration of oral PPI intake, but not IV PPIs, and GWU. GWU was significantly lower with oral compared to IV PPI administration.
Conclusion
PPIs significantly increase GWU and discontinuing them for at least 3-5 days significantly reduces GWU. H2 antagonists are a good alternative in patients who cannot tolerate dyspepsia symptoms.



J Nucl Cardiol: 31 Jan 2021; epub ahead of print

Comparison of myocardial blood flow and flow reserve with dobutamine and dipyridamole stress using rubidium-82 positron emission tomography.

Pelletier-Galarneau M, Ferro P, Patterson S, Ruddy TD, Beanlands RS, deKemp RA
Background
The objective of this study was to compare the hyperemic myocardial blood flow (MBF) and myocardial flow reserve (MFR) obtained with dobutamine to those of dipyridamole in patients referred for myocardial perfusion imaging (MPI) using ⁸²Rb positron emission tomography.
Methods
One hundred and fifty-six patients who underwent a ⁸²Rb PET MPI study with dobutamine stress were included. A matching cohort of patients who underwent a ⁸²Rb PET MPI study with dipyridamole stress was created, accounting for sex, age, history of coronary artery disease (CAD), prior revascularization, CAD risk factors, body mass index, and MPI interpretation.
Results
Global rest MBF (median [interquartile range] 0.84 [0.64-1.00] vs 0.69 [0.59-0.85]), stress MBF (2.36 [1.73-3.08] vs 1.66 [1.25-2.06]), MFR (2.75 [2.19-3.64] vs 2.29 [1.78-2.84]), and corrected MFR (2.85 [2.14-3.64] vs 2.20 [1.65-2.75]) were all significantly higher (P < 0.0001) in the dobutamine cohort compared to the dipyridamole cohort.
Conclusion
The results of this study suggest that dobutamine produces higher MBF compared to dipyridamole in a representative population referred to nuclear cardiology laboratories.



J Nucl Cardiol: 30 Jan 2021; 28:34-45

Optimal Tc activity ratio in the single-day stress-rest myocardial perfusion imaging protocol: A multi-SPECT phantom study.

Zoccarato O, Matheoud R, Lecchi M, Scabbio C, Claudio M, Brambilla M
Background
This investigation used image data generated by an anthropomorphic phantom to determine the minimal ^99mTc rest-stress activity concentration ratio (R) able to minimize the ghosting effect in the single-day stress-first myocardial perfusion imaging, using different positions of the perfusion defect (PD), scanners and reconstruction protocols.
Methods
A cardiac phantom with a simulated PD was imaged under different R using different gamma cameras and reconstruction algorithms. The residual activity from precedent stress administration was simulated by modeling effective half-times in each compartment of the phantom and assuming a delay of 3 hours between the stress and rest studies. The net contrast (NC) of the PD in the rest study was assessed for different R, PD positions and scanner/software combinations. The optimal R will be the one that minimize the NC in the rest images
Results:
The activity concentration ratio R, the position of the PD and the scanner/software combinations were all main effects with a statistically significant impact on the NC, in decreasing order of relevance. The NC diminished significantly only for R values up to 2. No further improvement was observed for NC for R values above 2 and up to 3. NC was significantly higher in anteroseptal than in posterolateral positions of the PD and higher for solid-state cameras.
Conclusions
A rest-stress activity concentration ratio R of 2 in single-day stress-first myocardial perfusion imaging is enough to achieve the maximum net contrast in the PD. This ratio should be used to optimize patient\'s radiation exposure.



J Nucl Cardiol: 30 Jan 2021; 28:338-349

Comparison of planar with tomographic pyrophosphate scintigraphy for transthyretin cardiac amyloidosis: Perils and pitfalls.

Asif T, Gomez J, Singh V, Doukky R, Nedeltcheva A, Malhotra S
Background
Tc-99m pyrophosphate (PYP) SPECT is recommended for indeterminate findings on planar imaging. We aimed to compare the findings on planar PYP scintigraphy alone to that of routinely performed PYP SPECT.
Methods
PYP scintigraphy data of 133 patients (53% men; mean age 76 years) were evaluated. SPECT was routinely performed following 1-hour planar imaging, in all cases. Semiquantitative visual score and heart-to-contralateral (H/CL) ratio were determined in all patients as recommended.
Results
PYP images from 35 patients (26%) were considered to be positive based on SPECT myocardial uptake. Among them, 20 (57%) had a H/CL ratio ≥1.5 and 34 had a visual score ≥ 2. SPECT identified myocardial uptake in one patient with a visual score < 2 and refuted the presence of myocardial uptake in two patients with a visual score ≥ 2. Visual score correlated well with SPECT (r = 0.94; P < .0001) and had an accuracy of 98% for tomographic myocardial uptake. Addition of H/CL ratio reduced the diagnostic performance of visual score.
Conclusions
Planar-derived visual score has an excellent accuracy for tomographic myocardial uptake, though it misclassifies a small proportion of patients. H/CL ratio decreases the diagnostic certainty of planar imaging. Tomographic imaging prevents misdiagnoses and should always be performed.



J Nucl Cardiol: 30 Jan 2021; 28:104-111

Prognostic value of integrative analysis of electrical and mechanical dyssynchrony in patients with acute heart failure.

Zhou Y, He Z, Liao S, Liu Y, ... Li X, Zhou W
Background
Left ventricular mechanical dyssynchrony has been shown to provide significant clinical values for chronic heart failure (HF) and cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate whether electrical dyssynchrony combined with mechanical dyssynchrony has an incremental benefit over electrical dyssynchrony or mechanical dyssynchrony alone to predict clinical events in patients with acute heart failure (AHF).
Methods
Ninety-six AHF patients who received standard 12-lead ECG, gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and echocardiography were enrolled. Thirty-two normal subjects were collected as the control group to get the normal database of mechanical dyssynchrony. The end point is the composite of all-cause death and heart transplantation. Electrical dyssynchrony was defined as QRS duration > 120 ms. Mechanical dyssynchrony was defined as > mean + 2 × SD phase standard deviation (PSD) or phase bandwidth (PBW) based on our normal database.
Results
During the follow-up of 28 ± 10 months, complete data were obtained in 92 patients. 26 (28.3%) Patients who reached the end point were classified into the event group. There were no significant differences in PSD or PBW between the event and non-event groups. However, PBW > 77.76° was independently associated with the end point in the univariate and multivariate analysis (hazard ratio 2.92, 95% confidence interval 1.00-8.47, P = .049; hazard ratio 3.89, 95% confidence interval 1.01-14.97, P = .048). The Kaplan-Meier curve with a log-rank test showed that the end point rate was significantly higher in the patients with PBW > 77.76° (log-rank P = .039). Moreover, the ROC curve analysis showed that the area under the curve (AUC) for predicting end point events by the integrative analysis of QRS > 120 ms and PBW > 77.76° was significantly improved compared to QRS duration > 120 ms (AUC: 0.75 vs 0.68, P = .001) or PBW > 77.76° (AUC: 0.75 vs 0.62, P = .049), respectively. The model of combined electrical and mechanical dyssynchrony yielded a further significantly improved risk prediction for adverse events in the global χ².
Conclusions
The combination of QRS duration > 120 ms and PBW > 77.76° was an independent predictor of all-cause death and heart transplantation in AHF patients. The integrative analysis of electrical and mechanical dyssynchrony provides incremental prognostic value for clinical use.



J Nucl Cardiol: 30 Jan 2021; 28:140-149

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 Jan 2021; epub ahead of print

Simultaneous measurements of myocardial glucose metabolism and extracellular volumes with hybrid PET/MRI using concurrent injections of Gd-DTPA and [F]FDG.

Smailovic H, Wilk B, Wisenberg G, Sykes J, ... Thiessen JD, Prato FS
Background
The aims of this study were to investigate the application of a constant infusion (CI) to mitigate the issue of constantly changing Gd-DTPA contrast levels in a bolus injection for extracellular volume (ECV) measurements by (a) comparing a CI alone to a bolus alone and a bolus followed by CI in healthy myocardium, (b) evaluating the impact of glucose suppression using heparin on ECV.
Methods
Five healthy canine subjects were imaged to compare three different protocols for injecting Gd-DTPA and FDG: bolus alone, CI alone, bolus followed by CI. Suppression of myocardial glucose uptake was induced using a continuous infusion of 20% lipid at a rate of 0.25 mL·min^-1·kg^-1 as well as 2000 units of intravenous heparin injected 20 minutes prior to FDG/Gd-DTPA injection.
Results
There was no significant effect on ECV measurement when heparin was used for glucose suppression at equilibrium irrespective of infusion protocol). Measurements of ECV in myocardium, regardless of infusion protocol showed no significant difference at all time points (P = 0.21) prior to washout.
Conclusions
The suppression of myocardial uptake of [¹⁸F]FDG with heparin did not alter the determination of myocardial ECV though a larger sample size may show differences. Further, the infusion protocol (bolus or constant infusion) had no effect on the calculated ECV.



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

Preclinical and clinical evaluation of a new method to assess cardiac insulin resistance using nuclear imaging.

Perret P, Slimani L, Barone-Rochette G, Vollaire J, ... Fagret D, Ghezzi C
Background
Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using ¹²³I-6-deoxy-6-iodo-D-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging.
Methods
The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling. Compartmental modeling was used to analyze 6DIG kinetics in basal and insulin conditions and to obtain an index of IR. As a part of a translational approach, a clinical study was then performed in 5 healthy and 6 diabetic volunteers.
Results
In rodent models, the method revealed reproducible when performed twice at 7 days apart in the same animal. Rosiglitazone, an insulin-sensitizing drug, induced a significant increase of myocardial IR index in obese Zucker rats from 0.96 ± 0.18 to 2.26 ± 0.44 (P<.05) after 7 days of an oral treatment, and 6DIG IR indexes correlated with the gold standard IR index obtained through the hyperinsulinemic-euglycemic clamp (r=.68, P<.02). In human, a factorial analysis was applied on images to obtain vascular and myocardial kinetics before compartmental modeling. 1.5-fold to 2.2-fold decreases in mean cardiac IR indexes from healthy to diabetic volunteers were observed without reaching statistical significance.
Conclusions
These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.



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

Incremental value of left ventricular shape parameters measured by gated SPECT MPI in predicting the super-response to CRT.

He Z, de Amorim Fernandes F, do Nascimento EA, Garcia EV, Mesquita CT, Zhou W
Background
The purpose of this study was to evaluate the predictive value of left ventricular (LV) shape parameters measured by gated SPECT myocardial perfusion imaging (MPI) in super-responders enrolled in the VISION-CRT trial.
Methods
One hundred and ninety-nine patients who met standard criteria for CRT from multiple centers were enrolled in this study. End-systolic eccentricity (ESE) and end-diastolic eccentricity (EDE) were measures of LV shape. Super-responders were the patients who had a relative increase in left ventricular ejection fraction (LVEF) ≥ 15%.
Results
Complete data were obtained in 165 patients, and 43.6% of them were classified as super-responders. ESE was an independent predictor of CRT super-responders in univariate (OR 12.59, 95% CI 1.56-101.35, P = .017) and multivariate analysis (OR 35.71, 95% CI 1.66-766.03, P = .006). ESE had an incremental value over significant clinical and SPECT imaging variables, including angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker, coronary artery disease, myocardial infarction, LVEF, end-diastolic volume index, and scar burden (AUC 0.82 vs. 0.80, sensitivity 0.68 vs. 0.65, specificity 0.82 vs. 0.78).
Conclusions
LV shape parameters derived from gated SPECT MPI have the promise to improve the prediction of the super-response to CRT. Moreover, ESE provides incremental value over existing clinical and nuclear imaging variables.



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

Longitudinal evaluation of diastolic dyssynchrony by SPECT gated myocardial perfusion imaging early after acute myocardial infarction and the relationship with left ventricular remodeling progression in a swine model.

Zhang F, Wang J, Shao X, Xu M, ... Li S, Wang Y
Background
Left ventricular diastolic dyssynchrony (LVDD), a dyssynchronous relaxation pattern, has been known to develop after myocardial damage. We aimed to evaluate the dynamic changes in LVDD in the early stage of acute myocardial infarction (AMI) by phase analysis of ^99mtechnetium methoxyisobutylisonitrile (^99mTc-MIBI) single-photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) and explore its relationship with the progression of left ventricular remodeling (LVR).
Methods
The left anterior descending coronary arteries of 16 Bama miniature swine were occluded with a balloon to build AMI models. Animals were imaged by SPECT GMPI before AMI and at 1 day, 1 week and 4 weeks after AMI, and quantitative analysis was performed to determine the extent of left ventricle (LV) perfusion defects, left ventricular systolic dyssynchrony (LVSD) and the LVDD parameters: phase histogram bandwidth (PBW) and phase standard deviation (PSD). Echocardiography was simultaneously applied to evaluate left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the LVDD parameters: Te-12-diff and Te-12-SD. Myocardial injury markers were measured, and 12-lead ECGs were performed. The degree of LVR progression was defined as ΔLVESV (%) = (LVESV_AMI4weeks - LVESV_AMI1day)/LVESV_AMI1day.
Results
Thirteen swine completed the study. LVDD parameters changed dynamically at different time points after AMI. LVDD occurred as early as 1 day after AMI, peaked at 1 week, and trended toward a partial recovery at 4 weeks. Phase analysis on SPECT GMPI showed a significant correlation with tissue Doppler imaging for the assessment of LVDD during the longitudinal evaluation (r = 0.569 to 0.787, both P <0.05). During the univariate and multivariate regression analyses, the LVDD parameters PBW and PSD as of 1 day after AMI were significantly associated with the progression of LVR, respectively (PBW, β = 0.004, 95% CI 0.001 to 0.007, P = 0.024; PSD, β = 0.008, 95% CI 0.000 to 0.017, P = 0.049). Adjusted smooth curve fitting and threshold effect analysis indicated PBW and PSD break-point values of 142° and 60.4°, respectively, to predict the progression of LVR after AMI.
Conclusions
Phase analysis of SPECT GMPI can accurately and reliably characterize LVDD. LVDD occurred on the first day after AMI, reached its peak at 1 week, and partially recovered at 4 weeks after AMI. LVDD as evaluated by phase analysis of SPECT GMPI early after AMI was significantly associated with the progression of LVR. The early assessment of LVDD after AMI may provide helpful information for predicting the progression of LVR in the future.



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

[C]meta-hydroxyephedrine PET evaluation in experimental pulmonary arterial hypertension: Effects of carvedilol of right ventricular sympathetic function.

Zelt JGE, Schock S, deKemp RA, Stewart DJ, ... Beanlands R, Mielniczuk LM
Background
Little is known about the sequelae of chronic sympathetic nervous system (SNS) activation in patients with pulmonary arterial hypertension (PAH) and right heart failure (RHF). We aimed to, (1) validate the use of [11C]-meta-hydroxyephedrine (HED) for assessing right ventricular (RV) SNS integrity, and (2) determine the effects of β-receptor blockade on ventricular function and myocardial SNS activity in a PAH rat model.
Methods
PAH was induced in male Sprague-Dawley rats (N = 36) using the Sugen+chronic hypoxia model. At week 5 post-injection, PAH rats were randomized to carvedilol (15 mg·kg^-1·day^-1 oral; N = 16) or vehicle (N = 16) for 4 weeks. Myocardial SNS function was assessed with HED positron emission tomography(PET).
Results
With increasing PAH disease severity, immunohistochemistry confirmed selective sympathetic denervation within the RV and sparing of parasympathetic nerves. These findings were confirmed on PET with a significant negative relationship between HED volume of distribution(DV) and right ventricular systolic pressure (RVSP) in the RV (r = -0.90, p = 0.0003). Carvedilol did not reduce hemodynamic severity compared to vehicle. RV ejection fraction (EF) was lower in both PAH groups compared to control (p < 0.05), and was not further reduced by carvedilol. Carvedilol improved SNS function in the LV with significant increases in the HED DV, and decreased tracer washout in the LV (p < 0.05) but not RV.
Conclusions
PAH disease severity correlated with a reduction in HED DV in the RV. This was associated with selective sympathetic denervation. Late carvedilol treatment did not lead to recovery of RV function. These results support the role of HED imaging in assessing SNS innervation in a failing right ventricle.



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

Visceral adipose tissue phenotype and hypoadiponectinemia are associated with aortic Fluorine-18 fluorodeoxyglucose uptake in patients with familial dyslipidemias.

Toutouzas K, Antonopoulos AS, Koutagiar I, Skoumas I, ... Anagnostopoulos CD, Tousoulis D
Background
 The role of adipose tissue (AT) in arterial inflammation in familial dyslipidaemias is poorly studied. We investigated the relationship between AT and arterial inflammation in patients with heterozygous familial hypercholesterolemia (heFH) and familial combined hyperlipidemia (FCH).
Methods and results
A total of 40 patients (20 heFH/20 FCH) and a subgroup of 20 of non-heFH/FCH patients were enrolled. Participants underwent blood sampling for serum adipokine measurements and Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT imaging. Abdominal visceral (VAT) and subcutaneous (SAT) AT volumes and AT and abdominal aorta 18F-FDG uptake were quantified. FCH patients had increased VAT (p_ANOVA = 0.004) and SAT volumes (p_ANOVA = 0.003), lower VAT metabolic activity (p_ANOVA = 0.0047), and lower adiponectin levels (p_ANOVA = 0.007) compared to heFH or the control group. Log(Serum adiponectin) levels were correlated with aortic TBR (b = - 0.118, P = 0.038). In mediation analysis, VAT volume was the major determinant of circulating adiponectin, an effect partly mediated via VAT TBR. Clustering of the population of heFH/FCH by VAT volume/TBR and serum adiponectin identified two distinct patient clusters with significant differences in aortic TBR levels (2.11 ± 0.06 vs 1.89 ± 0.05, P= 0.012).
Conclusions
VAT phenotype (increased VAT volume and/or high VAT TBR) and hypoadiponectinemia may account for the observed differences in arterial inflammation levels between heFH and FCH patients.



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

Quantifying microcalcification activity in the thoracic aorta.

Fletcher AJ, Lembo M, Kwiecinski J, Syed MBJ, ... Slomka PJ, Dweck MR
Background
Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying ¹⁸F-sodium fluoride (18F-NaF) uptake in the thoracic aorta.
Methods
Twenty patients underwent two hybrid ¹⁸F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each ¹⁸F-NaF quantification method was compared to validated cardiovascular risk scores.
Results
Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease.
Conclusions
AMA is a simple, rapid and reproducible method of quantifying global ¹⁸F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.



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

Performance of cardiac PET/CT with and without phase analysis for detection of scar in cardiac sarcoidosis: Comparison to cardiac magnetic resonance imaging.

Elwazir MY, Bird JG, AbouEzzeddine OF, Chareonthaitawee P, ... Abdellah AT, Bois JP
Background
The presence of myocardial scar in CS patients results in poor prognosis and worse outcomes. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT excels at visualizing inflammation but is suboptimal at detecting scar. We evaluated PET/CT sensitivity to detect scar and investigated the incremental diagnostic value of automated PET-derived data.
Methods
176 patients who underwent cardiac magnetic resonance (CMR) and N-13 ammonia/¹⁸F-FDG cardiac PET/CT for suspected CS within 3 months were enrolled. Scar was defined as late gadolinium enhancement (LGE) on CMR without concordant ¹⁸F-FDG uptake on ¹⁸F-FDG PET/CT. Accuracy of cardiac PET/CT at detecting scar (perfusion defect without concordant ¹⁸F-FDG uptake) was assessed before and after addition of automated PET-derived data.
Results
Sensitivity of PET/CT for scar detection was 45.3% (specificity 88.9%). Addition of PET-derived LV volumes and function in a logistic regression model improved sensitivity to 57.0% (specificity: 80.0%, AUC 0.72). Addition of phase analysis maximum segmental onset of myocardial contraction > 61 improved AUC to 0.75, correctly relabeling 16.3% of patients as scar (net reclassification index 8.2%).
Conclusion
Sensitivity of gated PET MPI alone for scar detection in CS is suboptimal. Adding PET-derived volumes/function and phase analysis data results in improved detection and characterization of scar.



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