Coronary artery calcium measurement on attenuation correction computed tomography using artificial intelligence: correlation with coronary flow capacity and prognosis.

PURPOSE: This study aimed to test whether the coronary artery calcium (CAC) burden on attenuation correction computed tomography (CTac), measured using artificial intelligence (AI-CACac), correlates with coronary flow capacity (CFC) and prognosis. MATERIALS AND METHODS: We retrospectively enrolled patients who underwent [13N]ammonia positron emission tomography (PET) between September 2021 and May 2023. CTac data were obtained from all the patients. Patients with (history of) acute coronary syndrome, previous coronary stent insertion or bypass surgery, or left ventricular ejection fraction < 40% were excluded. The total Agatston score measured using a dedicated AI-CAC quantification software on CTac was defined as AI-CACac. The correlations between AI-CACac and PET-measured myocardial blood flow (MBF) and CFC and significant ischaemia (summed difference score ≥ 7) were analysed. Their prognostic values for major cardiovascular events (MACE), including death, nonfatal myocardial infarction, hospitalisation due to angina pectoris or heart failure, and late (> 90 days) revascularisation, were also evaluated. RESULTS: In total, 289 patients were included in this study. Significant negative correlations were found between AI-CACac and stress MBF (ρ = -0.363, p < 0.001) and MFR (ρ = -0.305, p < 0.001). AI-CACac > 10 was associated with a significantly higher prevalence of impaired CFC (31% vs. 7%, p < 0.001) and significant ischaemia (20% vs. 7%), which remained significant after adjusting for other risk factors. MACE occurred in 49 (17%) patients (median follow-up, 284 days), and those who experienced MACE had significantly higher AI-CACac (median, 166 vs. 56; p = 0.039). However, multivariable analysis revealed an independent prognostic association among impaired CFC, diabetes, smoking, but not for AI-CACac. CONCLUSION: AI-measured CACac correlates well with PET-measured MBF and CFC, but its prognostic significance requires further validation.

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

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

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

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.

Comparison of diagnostic accuracy of PET-derived myocardial blood flow parameters: A meta-analysis.

BACKGROUND: Although absolute quantification of myocardial blood flow (MBF) by positron emission tomography provides additive diagnostic value to visual analysis of perfusion defect, diagnostic accuracy of different MBF parameters remain unclear. METHODS: Clinical studies regarding the diagnostic accuracy of hyperemic MBF (hMBF), myocardial flow reserve (MFR) and/or relative flow reserve (RFR) were searched and systematically reviewed. On a per-vessel basis, pooled measures of the parameters' diagnostic performances were analyzed, regarding significant coronary stenosis defined by fractional flow reserve or diameter stenosis. RESULTS: Ten studies (2,522 arteries from 1,099 patients) were finally included. Pooled sensitivity [95% confidence interval (CI)] was 0.853 (0.821-0.881) for hMBF, 0.755 (0.713-0.794) for MFR, and 0.636 (0.539-0.726) for RFR. Pooled specificity (95% CI) was 0.844 (0.827-0.860) for hMBF, 0.804 (0.784-0.824) for MFR, and 0.897 (0.860-0.926) for RFR. Pooled area under the curve ± standard error was 0.900 ± 0.020 for hMBF, 0.830 ± 0.026 for MFR, and 0.873 ± 0.048 for RFR. CONCLUSIONS: hMBF showed the best sensitivity while RFR showed the best specificity in the diagnosis of significant coronary stenosis. MFR was less sensitive than hMBF and less specific than hMBF and RFR.

Association between FDG uptake in the right ventricular myocardium and cancer therapy-induced cardiotoxicity.

BACKGROUND: The aim of this study was to investigate changes in myocardial uptake evaluated by oncologic 18F-fluorodeoxyglucose (FDG) PET/CT scans and to determine the relationship between myocardial FDG uptake and cancer therapy-induced cardiotoxicity in breast cancer patients who underwent anthracycline or trastuzumab. METHODS: We reviewed 121 consecutive patients who underwent oncologic FDG PET/CT and echocardiography at baseline and post-therapy with anthracyclines or trastuzumab for breast cancer. Grade in LV wall, uptake pattern in LV wall, and the presence of RV wall uptake were assessed by visual analysis, and the mean SUV in the LV and RV walls and the change of SUV (ΔSUV) between baseline and post-therapy PET/CT were measured by quantitative analysis. Multiple logistic regression analyses were performed to evaluate the association between PET parameters and cardiotoxicity. RESULTS: Fifteen patients (12%) showed cardiotoxicity after therapy. The cardiotoxic group tended to show more diffuse LV uptake, higher SUV, and ΔSUV of RV wall than the non-cardiotoxic group following therapy with anthracyclines or trastuzumab. Logistic regression analysis showed that the presence of RV wall uptake, SUV of RV wall (> 1.8), and ΔSUV of RV wall (> 0.4) were significantly associated with cardiotoxicity after controlling for age, radiotherapy, and treatment. CONCLUSIONS: The presence of RV wall uptake and the increase of SUV of RV wall on post-therapy PET/CT were associated with cardiotoxicity in breast cancer patients who underwent anthracycline or trastuzumab. Oncologic FDG PET/CT scans can provide information regarding cancer therapy-induced cardiotoxicity as well as tumor response.

Rationale and design of the quantification of myocardial blood flow using dynamic PET/CTA-fused imagery (DEMYSTIFY) to determine physiological significance of specific coronary lesions.

BACKGROUND: Coronary physiology assessments have been shown by multiple trials to add clinical value in detecting significant coronary artery disease and predicting cardiovascular outcomes. Fractional flow reserve (FFR) obtained during invasive coronary angiography (ICA) has become the new reference standard for hemodynamic significance detection. Absolute myocardial blood flow (MBF) quantification by means of dynamic positron emission tomography (dPET) has high diagnostic and prognostic values. FFR is an invasive measure and as such cannot be applied broadly, while MBF quantification is commonly performed on standard vascular territories intermixing normal flow from normal regions with abnormal flow from abnormal regions and consequently limiting its diagnostic power. OBJECTIVE: The aim of this study is to provide physicians with reliable software tools for the non-invasive assessment of lesion-specific physiological significance for the entire coronary tree by combining PET-derived absolute flow data and coronary computed tomography angiography (CTA)-derived anatomy and coronary centerlines. METHODS: The dynamic PET/CTA myocardial blood flow assessment with fused imagery (DEMYSTIFY) study is an observational prospective clinical study to develop algorithms and software tools to fuse coronary anatomy data obtained from CTA with dPET data to non-invasively measure absolute MBF, myocardial flow reserve, and relative flow reserve across specific coronary lesions. Patients (N = 108) will be collected from 4 institutions (Emory University Hospital, USA; Chonnam National University Hospital, South Korea; Samsung Medical Center, South Korea; Seoul National University Hospital, South Korea). These results will be compared to those obtained invasively in the catheterization laboratory and to a relatively novel non-invasive technique to estimate FFR based on CTA and computational fluid dynamics. CONCLUSIONS: Success of these developments should lead to the following benefits: (1) eliminate unnecessary invasive coronary angiography in patients with no significant lesions, (2) avoid stenting physiologically insignificant lesions, (3) guide percutaneous coronary interventions process to the location of significant lesions, (4) provide a flow-color-coded 3D roadmap of the entire coronary tree to guide bypass surgery, and (5) use less radiation and lower the cost from unnecessary procedures. TRIAL REGISTRY: The DEMYSTIFY study has been registered on ClinicalTrials.gov with registration number NCT04221594.

Vessel-specific quantification of absolute myocardial blood flow, myocardial flow reserve and relative flow reserve by means of fused dynamic 13NH3 PET and CCTA: Ranges in a low-risk population and abnormality criteria.

OBJECTIVES: The goal of the present work is to present a novel methodology for the extraction of MBF, MFR and RFR along coronary arteries by means of multimodality image fusion of dynamic PET and CCTA images. BACKGROUND: FFR is the reference standard to identify flow-limiting lesions, but its invasiveness limits broad application. New noninvasive methodologies are warranted to stratify patients and guide treatment. METHODS: A group of 16 low-risk CAD subjects who underwent both 13NH3 PET and CCTA were analyzed. Image fusion techniques were employed to align the studies and CCTA-derived anatomy used to identify coronaries trajectories. MBF was calculated by means of a 1-tissue compartmental model for the standard vascular territories and along patient-specific vessel paths from the base to the apex of the heart. RESULTS: Low-risk ranges for MBF. MFR and RFR for LAD, LCX and rPDA were computed for the entire cohort and separated by gender. Computed low-risk ranges were used to assess a prospective patient with suspected CAD. CONCLUSIONS: Our vessel-specific functional indexes and 3D displays offer promise to more closely replicate what is commonly performed during a catheterization session and have the potential of providing effective noninvasive tools for the identification of flow-limiting lesions and image-guided therapy.

Clinical values of left ventricular mechanical dyssynchrony assessment by gated myocardial perfusion SPECT in patients with acute myocardial infarction and multivessel disease.

PURPOSE: The aim of this study was to evaluate the prognostic value of additional evaluation of left ventricular mechanical dyssynchrony (LVMD) by gated myocardial perfusion single-photon emission computed tomography (GMPS) in patients with acute myocardial infarction (MI) and multivessel disease. METHODS: One hundred and nine acute MI patients with >50 % stenosis in at least one non-culprit artery who underwent GMPS within 2 weeks were enrolled. All patients underwent successful revascularization of the culprit arteries. Those with previous MI, atrial fibrillation, or frequent ventricular premature complexes, cardiac devices, significant patient motion, or procedure-related events were excluded. Phase standard deviation (PSD) and phase histogram bandwidth (PBW) were measured for assessment of LVMD. Patients were followed up for a median of 26 months after index MI, for composite major adverse cardiac events (MACE), which consisted with all-cause death, unplanned hospitalization due to heart failure and severe ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation). Independent predictors of MACE were evaluated. RESULTS: MACE occurred in 22 patients (20 %). Stress PSD (53.3 ± 17.3° vs. 35.3 ± 18.9°; p <0.001), stress PBW (147.6 ± 54.6° vs. 96.8 ± 59.2°; p = 0.001) and resting PBW (126.8 ± 37.5° vs. 96.6 ± 48.9°; p = 0.001) were significantly higher in patients with MACE compared to those without. Multivariate analysis revealed that stress PSD ≥45.5° and stress PBW ≥126.0° were predictive of MACE, as well as suboptimal non-culprit artery revascularization (SNR) and renin-angiotensin system (RAS) blockade medication. Higher stress PSD and stress PBW were associated with poorer prognosis both in patients with and without SNR, and those with RAS blockade medication, but not in those without RAS blockade medication. CONCLUSIONS: LVMD measured by GMPS showed added prognostic value in acute MI with multivessel disease. GMPS could serve as a comprehensive evaluation imaging tool in patients with acute MI and multivessel disease.

Prediction of coronary artery calcium progression by FDG uptake of large arteries in asymptomatic individuals.

PURPOSE: The purpose of this study is to evaluate whether fluorodeoxyglucose (FDG) uptake of the large arteries can predict coronary artery calcium (CAC) progression in asymptomatic individuals. METHODS: Ninety-six asymptomatic individuals who underwent FDG positron emission tomography (PET) and CAC scoring on the same day for health screening and follow-up CAC scoring ≥1 year after baseline studies (mean 4.3 years) were included. Vascular FDG uptake was measured and corrected for blood pool activity to obtain peak and average target-to-blood pool ratios (TBRpeak and TBRavg, respectively) for the carotid arteries, and ascending and abdominal aorta. CAC scores at baseline and follow-up of each individual were measured and absolute CAC change (ΔCAC), annual CAC change (ΔCAC/year), and annual CAC change rate (ΔCAC%/year) were calculated. CAC progression was defined as ΔCAC >0 for individuals with negative baseline CAC; ΔCAC/year ≥10 for those with baseline CAC of 0

Prognostic Value of Bone Scintigraphy in Cardiac Amyloidosis: A Systematic Review and Meta-analysis.

OBJECTIVES: The prognostic value of bone scintigraphy in cardiac amyloidosis (CA) remains undetermined. We conducted a systematic review and meta-analysis on the association of cardiac uptake on bone scintigraphy with mortality in known or suspected CA. PATIENTS AND METHODS: PubMed, Embase, and Cochrane library databases were searched up to November 2023 for studies that evaluated cardiac uptake on bone scintigraphy as a prognostic factor in the workup of CA. Hazards ratios (HRs) of high cardiac uptake for outcomes of all-cause or cardiac death were pooled and analyzed with stratifications according to the study populations, analytical methodologies, and radiotracers. RESULTS: Fourteen studies (3325 patients) were finally included. In studies regarding known or suspected CA, visual grades were not prognostically significant, regardless of the threshold used, with pooled HRs of 2.25 (95% confidence interval [CI], 0.93-5.48), 1.55 (95% CI, 0.89-2.68), and 1.53 (95% CI, 0.95-2.47) for visual grades ≥1, ≥2, and ≥3, respectively. By contrast, high cardiac uptake on semiquantitative measurements (heart-to-contralateral lung ratio, n = 6; heart-to-whole-body ratio, n = 1) was associated with increased mortality (pooled HR = 2.27 [95% CI, 1.87-2.76] for all semiquantitative measurements; 2.26 [1.86-2.74] for heart-to-contralateral lung ratio only). No difference in prognostic significance was found across 3 different 99mTc-radiotracers (P = 0.619). However, high cardiac uptake was not predictive of mortality in aortic stenosis-related CA (pooled HR = 1.13 [95% CI, 0.96-1.32]). CONCLUSIONS: High semiquantitative cardiac uptake on bone scintigraphy is associated with an increased risk of mortality in patients with known or suspected CA.

Prognostic value of left ventricular mechanical dyssynchrony indices derived from gated myocardial perfusion SPECT in coronary artery disease: a systematic review and meta-analysis.

PURPOSE: Left ventricular mechanical dyssynchrony (LVMD) is an important prognostic factor in coronary artery disease. A growing body of evidence indicates that LVMD parameters derived from phase analysis of gated myocardial SPECT may allow risk stratification for future cardiac events. We performed a systematic review and meta-analysis on the prognostic value of LVMD on gated SPECT in patients with coronary artery disease. METHODS: PubMed, Embase, and the Cochrane library were searched until August 25, 2022, for studies reporting the prognostic value of LVMD on gated SPECT for outcomes of all-cause death, cardiac death, or major adverse cardiovascular event (MACE) in patients with coronary artery disease. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were meta-analytically pooled using a random-effects model. RESULTS: Nine studies (26,750 patients) were included in a qualitative synthesis. Among the SPECT LVMD parameters used in various studies, high phase standard deviation, phase bandwidth, and phase entropy were widely evaluated and reported to be associated with high rates of all-cause death, cardiac death, or MACE. For five studies (23,973 patients) in the quantitative synthesis, the pooled HR of LVMD for predicting MACE was 2.81 (95% CI 2.03-3.88). Studies using combined phase parameters to define LVMD showed higher HRs than a study using phase entropy (p = 0.0180). CONCLUSION: LVMD from gated myocardial SPECT is a significant prognostic factor for coronary artery disease. Phase analysis of gated SPECT may be useful for accurate risk stratification and could be applied for clinical decision-making in such patients.

The Diagnostic Accuracy of SPECT Imaging in Patients With Suspected Pulmonary Embolism: Systematic Review and Network Meta-analysis.

BACKGROUND: This meta-analysis and systematic review assessed the diagnostic accuracy of lung SPECT compared with lung planar imaging in patients with suspected acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension. PATIENTS AND METHODS: A search of Medline, Embase, and Cochrane databases identified suitable articles published before October 2023. Meta-analyses were performed to determine the diagnostic accuracy of SPECT imaging modalities, including perfusion (Q) SPECT, ventilation (V)/Q SPECT, Q SPECT/CT, and V/Q SPECT/CT. Network meta-analyses were performed to compare the diagnostic accuracy of SPECT and planar imaging in paired-design studies. RESULTS: Twenty-four articles (total n = 6576) were included in the analysis. For suspected acute PE, the respective sensitivity and specificity of SPECT imaging modalities were as follows: Q SPECT, 0.93 (95% confidence interval [CI], 0.87-0.99; I2 = 49%) and 0.72 (95% CI, 0.54-0.95; I2 = 94%); V/Q SPECT, 0.96 (95% CI, 0.94-0.98; I2 = 51%) and 0.95 (95% CI, 0.92-0.98; I2 = 80%); Q SPECT/CT, 0.93 (95% CI, 0.87-0.98; I2 = 66%) and 0.82 (95% CI, 0.70-0.96; I2 = 87%); and V/Q SPECT/CT, 0.97 (95% CI, 0.93-1.00; I2 = 7%) and 0.98 (95% CI, 0.97-1.00; I2 = 31%). The relative sensitivity and specificity of SPECT compared with planar imaging were 1.17 (95% CI, 1.06-1.30; P < 0.001) and 1.14 (95% CI, 1.00-1.29; P = 0.05), respectively. For suspected chronic thromboembolic pulmonary hypertension, the pooled sensitivity and specificity of SPECT imaging were 0.97 (95% CI, 0.95-1.00; I2 = 0%) and 0.91 (95% CI, 0.87-0.94; I2 = 0%), respectively. CONCLUSIONS: SPECT exhibited superior diagnostic performance for PE. V/Q SPECT/CT was the most accurate modality.

68Ga-FAPI PET in Visualizing Acute Ischemic Stroke at Risk of Hemorrhagic Transformation.

ABSTRACT: Hemorrhagic transformation is a serious complication of ischemic stroke, which occurs at a rate of between 18% and 42%. 68Ga-FAPI PET can visualize acute cerebral infarction at risk of hemorrhagic transformation in the brain. We report a case of 68Ga-FAPI PET imaging in a patient with recurrent ischemic stroke. 68Ga-FAPI PET imaging revealed FAPI uptake in acute ischemic stroke with hemorrhagic transformation, but did not in some acute infarction and chronic infarction without hemorrhagic transformation. These findings suggest potential role of 68Ga-FAPI PET in the evaluation of acute ischemic stroke with the risk of hemorrhagic transformation.

Artificial intelligence-based CT-free quantitative thyroid SPECT for thyrotoxicosis: study protocol of a multicentre, prospective, non-inferiority study.

INTRODUCTION: Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves' disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT. METHODS AND ANALYSIS: The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves' disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy-SPECT/CT accuracy) for Graves' disease is greater than -0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

Discordant Uptake of Leg Thrombi Versus Pulmonary Emboli on 68 Ga-FAPI-46 PET/CT.

ABSTRACT: Fibroblast activation protein inhibitor (FAPI) PET is gaining clinical relevance for visualizing activated fibroblasts in various diseases. Here, we report discordant FAPI uptake between venous thrombi of the lower extremities and pulmonary emboli. An 86-year-old man complained of left leg swelling and acute dyspnea; he was diagnosed with deep vein thrombosis involving the left femoral vein and acute pulmonary thromboembolism. Positive FAPI uptake was observed only in the thrombi of the left femoral vein, but not in the pulmonary emboli. Such discrepancies may indicate different thrombus constituents and chronologies even in the same patient.