BACKGROUND:Noninvasive assessment of coronary artery disease (CAD) in obese patients is challenging due to suboptimal image quality. We performed a prespecified secondary analysis of obese patients from the second Phase III trial of flurpiridaz-18F positron emission tomography (PET). METHODS:In total, 604 patients with suspected CAD underwent flurpiridaz-18F PET and 99mTc-single-photon emission computerized tomography (SPECT) myocardial perfusion imaging (MPI) before invasive coronary angiography (ICA) across 48 sites. MPI images were interpreted by three blinded experts. The primary endpoint was sensitivity and specificity for diagnosing CAD (≥50% stenosis on quantitative coronary angiography), requiring the lower 95% confidence interval to exceed 60% by 2 same blinded expert core lab readers, assessed using one-sided z-test (α = 0.025). Sensitivity and specificity were compared between PET and SPECT and between obese (body mass index [BMI] ≥30 kg/m2) and nonobese patients. RESULTS:Of 578 evaluable patients, 298 (51.6%) were obese (mean age: 62.0 years, 64.4% male, mean BMI: 35.6 kg/m2) and 117 (39.3%) had CAD by ICA. In obese patients, flurpiridaz-18F PET MPI met the primary endpoint, with lower 95% confidence limits greater than 60% and one-sided P < 0.025 by the same 2 readers (Readers 1 and 2). Sensitivity across 3 readers ranged from 70.1% to 88.0% and specificity ranged from 53.6% to 74.0%. In obese patients, flurpiridaz-18F PET MPI showed significantly higher sensitivity compared to 99ᵐTc-SPECT MPI by Readers 1 and 3 (Reader 1: 72.6% vs 60.7%, P = 0.01; Reader 3: 88.0% vs 74.4%, P = 0.002), with non-inferior specificity by the same two readers (Reader 1: 68.0% vs 61.3%; Reader 3: 53.6% vs 50.8%; P < 0.01 for noninferiority, for both), noting that the primary endpoint was met by a partially overlapping reader pair (Readers 1 and 2). Diagnostic performance of flurpiridaz-18F PET was higher than SPECT across BMI categories. No statistically significant difference in diagnostic performance was observed between obese and nonobese patients (Sensitivity P = 0.26, specificity P = 0.25 and accuracy P = 1.0). CONCLUSION:Flurpiridaz-18F PET MPI demonstrates high diagnostic efficacy for detecting CAD across BMI categories in obese patients compared to ICA and 99mTc-SPECT, with no loss of diagnostic performance in obese relative to nonobese patients. CLINICAL TRIAL REGISTRATION:NCT03354273.

BACKGROUND:A recent phase 3 study of the PET perfusion tracer F-18 flurpiridaz (flurpiridaz) met the primary efficacy endpoint for the detection of CAD, demonstrating statistically higher sensitivity, non-inferior specificity compared to Tc-99m-tetrofosmin/sestamibi SPECT (Tc99m-SPECT) in the general population. This study reports a pre-specified subgroup analysis examining the diagnostic accuracy of flurpiridaz in women. METHODS:Patients with suspected CAD underwent rest-stress flurpiridaz PET and Tc99m-SPECT before invasive coronary angiography in the US, Canada, and Europe. The primary endpoint was sensitivity and specificity by 2 expert readers (majority rule between 3 blinded readers) for the diagnosis of significant CAD defined as a stenosis ≥50%. Secondary endpoints included comparison of the diagnostic performance of flurpiridaz PET and Tc99m-SPECT. RESULTS:188 women were included in the subgroup analysis. Flurpiridaz met the pre-specified primary endpoint of sensitivity [82.9% (95% CI: 71.4, 94.4), P = 0.0014] and specificity [72.8% (95%CI: 65.6, 80),P = 0.0008]. Flurpiridaz sensitivity was significantly higher than Tc99m-SPECT [82.9% vs 65.9%, difference: 17.1% (-1.5%, 35.6%), P = 0.0448] and specificity was non-inferior [72.8% vs 66%, difference:6.8% (-3.4%, 17.0%) P = 0.0004]. Diagnostic certainty was significantly higher for women undergoing flurpiridaz PET compared to Tc99m-SPECT (82.4% v 48.9%). PET perfusion image quality was better than Tc99m-SPECT for rest and pharmacological stress images (P < 0.0001). The summed difference score was significantly higher for flurpiridaz (5.3 v 3.5). Radiation exposure was significantly lower for flurpiridaz than same day rest/stress Tc99m-SPECT (6.2 v 11.2 mSv). CONCLUSIONS:This pre-specified secondary analysis of the ARORA study in women, demonstrates high diagnostic accuracy of flurpiridaz PET to detect obstructive CAD. In women, the diagnostic performance of flurpiridaz PET for detection of CAD was significantly higher than with 99mTc-SPECT.

Cardiovascular inflammation has recently emerged as a critical issue across various cardiovascular diseases. Various non-invasive imaging modalities are applied for assessing cardiovascular inflammation. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is a valuable non-invasive imaging tool for identifying active cardiovascular inflammation. It is utilized in evaluating conditions, such as cardiac sarcoidosis, endocarditis, vasculitis, and unstable atherosclerosis. Furthermore, management of cardiovascular complications after aggressive cancer therapy has increasingly been required in cancer patients. FDG PET is considered a suitable approach not only for the assessment of tumor responses to cancer therapy, but also for early and accurate detection of cardiovascular complications. This review highlights the clinical value of FDG PET under appropriate patient preparation. The future perspectives of new molecular imaging tools for assessing active cardiovascular inflammation have been described.

Cardiac amyloidosis, characterized by extracellular deposition of amyloid fibrils within the myocardium, is an increasingly recognized cause of heart failure. With the advent of disease-modifying therapies, imaging has become central to diagnosis, subtype differentiation, prognostication, and treatment monitoring. This review provides a comprehensive update on multimodality imaging in cardiac amyloidosis, emphasizing its clinical utility across the disease continuum. Echocardiography, technetium-labeled bone scintigraphy, amyloid-specific positron emission tomography, cardiac magnetic resonance, and cardiac computed tomography each contribute uniquely to detecting amyloid burden and assessing cardiac function. In addition to outlining a practical diagnostic approach, we highlight emerging imaging biomarkers for monitoring treatment response and predicting clinical outcomes. The integration of these modalities into clinical practice enhances diagnostic accuracy, enables individualized risk stratification, and supports optimized, evidence-based care for patients with cardiac amyloidosis.

Brown adipose tissue (BAT) contributes to thermoregulation and energy expenditure. Although BAT is abundant in early childhood and declines with age, its distribution across age groups remains unclear. This study examined age-related BAT distribution using fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). A total of 8695 FDG-PET/CT scans performed for clinical purposes were retrospectively reviewed. FDG accumulation with a standardized uptake value (SUV) max > 1.5 in known BAT regions was considered positive. BAT distribution patterns were classified into T-type (positive accumulation in the supraclavicular or axillary region), I-type (positive accumulation in the cervical or paravertebral region without supraclavicular or axillary involvement), lipomatous hypertrophy of the interatrial septum (LHIS)-type (positive accumulation localized only to the LHIS), and others (cases not fitting any type). BAT accumulation was observed in 78 patients (0.9

Advances in cancer treatment have improved in patient survival rate. On the other hand, management of cardiovascular complications has been increasingly required in cancer patients. Thus, cardio-oncology has attracted the attention by both oncologists and cardiologists. Cardiovascular imaging has played a key role for non-invasive assessment of cardiovascular alterations complimentary to biomarkers and clinical assessment. Suitable imaging selection and interpretation may allow early diagnosis of cardiovascular injury with potential implications for therapeutic management and improved outcomes after cancer therapy. Echocardiography has been commonly used to evaluate cardiac dysfunction in cardio-oncology area. Cardiac CT is valuable for assessing structural abnormalities of the myocardium, coronary arteries, and aorta. Molecular imaging has an important role in the assessment of the pathophysiology and future treatment strategy of cardiovascular dysfunction. Cardiac MRI is valuable for characterization of myocardial tissue. PET and SPECT molecular imaging has potential roles for quantitative assessment of cardiovascular disorders. Particularly, FDG-PET is considered as an elegant approach for simultaneous assessment of tumor response to cancer therapy and early detection of possible cardiovascular involvement as well. This review describes the promising potential of these non-invasive cardiovascular imaging modalities in cardio-oncology.

FDG PET has been widely used in oncology studies as well as for cardiovascular diseases. This technique has recently been applied to detect active cardiovascular inflammation, mainly owing to enhanced glucose utilization by the activation of granulocytes and macrophages. To identify active inflammation by FDG PET, physiological uptake in the normal myocardium should be suppressed by appropriate patient preparation. FDG PET has been used to detect active lesions and assess the response to anti-inflammatory therapy in patients with cardiac sarcoidosis. In addition, other active cardiovascular inflammations, such as endocarditis, aortitis, and unstable atherosclerosis may be identified by FDG PET. After cancer treatment, FDG PET is considered an elegant approach not only for the assessment of tumor response to cancer therapy, but also for early detection of possible cardiovascular involvement. This review summarizes the clinical values of FDG PET for the assessment of active cardiovascular inflammation under suitable patient preparation.

This study aimed to evaluate the ability of serial whole-body dynamic PET/CT to differentiate physiological from abnormal F-18-FDG uptake in the abdomen and pelvis of gynecological cancer patients. We conducted a retrospective study of 61 F-18-FDG PET/CT examinations for suspected gynecological malignancies or metastases between March 2018 and January 2020. Our protocol included four-phase dynamic whole-body scans. High-uptake foci with SUVmax > 2.5 in the abdominopelvic region caudal to the renal portal were picked up and visually evaluated as "changed" (disappeared during any phase or morphological changes in more than half of the foci) or "unchanged" in motion on the serial dynamic images. Focal F-18-FDG uptake was observed in 84 foci. Of the 58 foci determined pathologically or clinically to have pathological uptake, no change was observed on serial dynamic imaging in 54 foci (sensitivity, 93%). Of the 26 foci of physiological uptake, temporal changes in uptake were observed in 20 foci using dynamic imaging (specificity, 77%). The positive and negative predictive values were 90% and 83%, respectively, with an accuracy of 88%. Dynamic whole-body F-18-FDG PET/CT imaging allows for differentiation between pathological and physiological uptake in the abdominopelvic region of patients with gynecological cancer.

Abstract Background/Introduction Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. Purpose To further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as >50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET vs. Tc-99m SPECT in the detection of CAD in all patients and in the clinically important subgroups of women, obese [body mass index (BMI) ≥30 kg/m2], and diabetics. Also, PET and Tc-99m SPECT were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET was also evaluated. Methods 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert blinded to clinical and image data. Results 578 patients (age, 63.7±9.5 years) were evaluable. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. The secondary endpoints were also met in the overall population, in women, in obese patients, and in diabetics. Flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p<0.0001), in women (0.84 vs 0.70, p<0.01), and in obese patients (0.79 vs 0.67, p<0.001), but not in diabetics (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p<0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p<0.0001), pharmacological stress images (96% vs 78%, p<0.0001), and treadmill exercise images (97% vs 87%, p<0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT. Conclusion This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI≥30.

Serial dynamic whole-body PET imaging is valuable for assessing serial changes in tracer uptake. The purpose of this study was to evaluate the improvement of motion artifacts in patients using serial dynamic whole-body 18F-fluorodeoxyglyucose (FDG) PET/CT imaging. In 797 consecutive patients, serial 3-min dynamic whole-body FDG PET imaging was performed seven times, at 60 or 90 min after FDG administration. In cases with large body motion during imaging, we tried to improve the images by summing the images before body motion. An image quality study was performed on another 50 patients without obvious body motion using the same acquisition mode. Obvious body movement was observed in 106 of 797 cases (13.3

Nuclear cardiology has long been used to identify myocardial ischemia for appropriate treatment strategies for stable coronary artery disease (CAD). After the Ischemia Trial, it is time to reevaluate the significance of ischemia assessment. Functional imaging continues to play pivotal role in detecting microcirculatory disturbances. PET provides a clear image of blood flow distribution and is useful for the quantitative evaluation of myocardial flow reserve (MFR), which plays an important role in predicting treatment strategies and improving prognosis in CAD. Heart failure has become a major area of focus in cardiovascular medicine. Radionuclide imaging has been widely applied in this field. FDG PET is useful in identifying cardiac sarcoidosis and active inflammation. Clinical values of I-123 MIBG and BMIPP SPECT have been reported worldwide from Japan. Additionally, clinical experiences of Tc-99m pyrophosphate imaging have recently gained attention for assessing cardiac amyloidosis. Cardiac PET/CT and PET/MR imaging permit combined assessment of metabolic/functional/structural analyses of various cardiac diseases. While other non-invasive imaging modalities have rapidly been developed, the roles of radionuclide imaging remain to be valuable for early and accurate diagnosis and patient management in most cases of chronic CAD and various cardiovascular diseases.

Cancer and Cardiovascular Disease (CVD) are the most common causes of death and disability in many countries. Cancer and CVD are closely related in terms of both scientific and clinical perspectives. Oncocardiology has recently gained attention by oncologists, cardiologists, and radiologists for mutual work on pathophysiology analysis and treatment strategy [1-3]. In various clinical settings, these specialists may collaborate in the diagnosis and treatment of cancer patients with cardiovascular disease.

Positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has been commonly used in many oncological areas. High-resolution PET permits a three-dimensional analysis of FDG distributions on various lesions in vivo, which can be applied for tissue characterization, risk analysis, and treatment monitoring after chemoradiotherapy and immunotherapy. Metabolic changes can be assessed using the tumor absolute FDG uptake as standardized uptake value (SUV) and metabolic tumor volume (MTV). In addition, tumor heterogeneity assessment can potentially estimate tumor aggressiveness and resistance to chemoradiotherapy. Attempts have been made to quantify intratumoral heterogeneity using radiomics. Recent reports have indicated the clinical feasibility of a dynamic FDG PET-computed tomography (CT) in pilot cohort studies of oncological cases. Dynamic imaging permits the assessment of temporal changes in FDG uptake after administration, which is particularly useful for differentiating pathological from physiological uptakes with high diagnostic accuracy. In addition, several new parameters have been introduced for the in vivo quantitative analysis of FDG metabolic processes. Thus, a four-dimensional FDG PET-CT is available for precise tissue characterization of various lesions. This review introduces various new techniques for the quantitative analysis of FDG distribution and glucose metabolism using a four-dimensional FDG analysis with PET-CT. This elegant study reveals the important role of tissue characterization and treatment strategies in oncology.

BACKGROUND Flurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion im-aging tracer.OBJECTIVES The purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as $50% stenosis by quantitative invasive coronary angiography (ICA).METHODS In this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1-or 2-day rest-stress Tc-99m-labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data.RESULTS A total of 578 patients (age 63.7 +/- 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index $30 kg/m(2), and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flur-piridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated. CONCLUSIONS This second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273)

AbstractPurposeThis study aimed to evaluate the accuracy of deep learning (DL)‐based computed tomography (CT) ventilation imaging (CTVI).MethodsA total of 71 cases that underwent single‐photon emission CT 81mKr‐gas ventilation (SPECT V) and CT imaging were included. Sixty cases were assigned to the training and validation sets, and the remaining 11 cases were assigned to the test set. To directly transform three‐dimensional (3D) CT (free‐breathing CT) images to SPECT V images, a DL‐based model was implemented based on the U‐Net architecture. The input and output data were 3DCT‐ and SPECT V‐masked, respectively, except for whole‐lung volumes. These data were rearranged in voxel size, registered rigidly, cropped, and normalized in preprocessing. In addition to a standard estimation method (i.e., without dropout during the estimation process), a Monte Carlo dropout (MCD) method (i.e., with dropout during the estimation process) was used to calculate prediction uncertainty. To evaluate the two models’ (CTVIMCD U‐Net, CTVIU‐Net) performance, we used fivefold cross‐validation for the training and validation sets. To test the final model performances for both approaches, we applied the test set to each trained model and averaged the test prediction results from the five trained models to acquire the mean test result (bagging) for each approach. For the MCD method, the models were predicted repeatedly (sample size = 200), and the average and standard deviation (SD) maps were calculated in each voxel from the predicted results: The average maps were defined as test prediction results in each fold. As an evaluation index, the voxel‐wise Spearman rank correlation coefficient (Spearman rs) and Dice similarity coefficient (DSC) were calculated. The DSC was calculated for three functional regions (high, moderate, and low) separated by an almost equal volume. The coefficient of variation was defined as prediction uncertainty, and these average values were calculated within three functional regions. The Wilcoxon signed‐rank test was used to test for a significant difference between the two DL‐based approaches.ResultsThe average indexes with one SD (1SD) between CTVIMCD U‐Net and SPECT V were 0.76 ± 0.06, 0.69 ± 0.07, 0.51 ± 0.06, and 0.75 ± 0.04 for Spearman rs, DSChigh, DSCmoderate, and DSClow, respectively. The average indexes with 1SD between CTVIU‐Net and SPECT V were 0.72 ± 0.05, 0.66 ± 0.04, 0.48 ± 0.04, and 0.74 ± 0.06 for Spearman rs, DSChigh, DSCmoderate, and DSClow, respectively. These indexes between CTVIMCD U‐Net and CTVIU‐Net showed no significance difference (Spearman rs, p = 0.175; DSChigh, p = 0.123; DSCmoderate, p = 0.278; DSClow, p = 0.520). The average coefficient of variations with 1SD were 0.27 ± 0.00, 0.27 ± 0.01, and 0.36 ± 0.03 for the high‐, moderate‐, and low‐functional regions, respectively, and the low‐functional region showed a tendency to exhibit larger uncertainties than the others.ConclusionWe evaluated DL‐based framework for estimating lung‐functional ventilation images only from CT images. The results indicated that the DL‐based approach could potentially be used for lung‐ventilation estimation.

Objectives: We assessed the influence of annuloplasty procedures in mitral repair on left ventricular (LV) vortex flow patterns and aortic outflow patterns, and flow energy loss (EL). Methods: Twenty healthy volunteers and 14 patients who had undergone mitral valve repair were examined using 3-dimensional cine phase-contrast magnetic resonance imaging. A band group included 7 patients with semi-rigid and 2 with flexible partial bands. The ring group included 5 patients with semi-rigid complete rings. LV vortex flow patterns, aortic outflow patterns, EL, and aortic annulus changes during one cardiac cycle were evaluated. Results: Mitral repair induced different vortex flow patterns compared with that of healthy volunteers. The vortex beneath the anterior mitral leaflet with semi-rigid devices was double-stranded in early diastole, and it was single-stranded with flexible bands with a large shift toward the apex during diastole. LVEL in patients who underwent mitral repair (0.84 +/- 0.42 mW) was greater than that in healthy volunteers (0.47 +/- 0.10 mW). Complete rings disturbed aortic outflow patterns, with EL distribution changes. Smaller devices relative to patient body size disturbed LV flow patterns and caused high EL. No significant relationship was found between indexed ring orifice area and transmitral mean pressure gradient (r = -0.25, P = .414), but a negative relationship exists between indexed ring orifice area and LVEL (r = -0.84, P<.001). Conclusions: Mitral repair, especially with relatively small annuloplasty rings, induced abnormal LV flow patterns and EL elevation, which have the potential to be a novel hemodynamic evaluation method after mitral repair.

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with limited-disease small cell lung cancer (LD-SCLC). However, no solid consensus exists on their optimal target volume. The current study aimed to assess the clinical outcomes of patients with LD-SCLC who received definitive ENI or IFRT. A retrospective single-institution study of patients who received definitive radiotherapy between 2008 and 2020 was performed. All patients underwent whole-body positron emission tomography/computed tomography before three-dimensional conformal radiotherapy. Among the 37 patients analyzed, 22 and 15 received ENI and IFRT, respectively. The thoracic radiotherapy dose was mostly either 60 Gy in 30 fractions delivered in 2-Gy fractions once daily or 45 Gy in 30 fractions delivered in 1.5-Gy fractions twice daily. The median follow-up period was 21.4 months. A total of 12 patients (32%) experienced locoregional relapse: 10 within and 2 outside the irradiation fields. One patient in the IFRT group experienced isolated nodal failure. Differences in locoregional relapse-free, progression-free, and overall survival rates between ENI and IFRT were not significant. Overall, IFRT did not promote a significant increase in locoregional recurrence compared to ENI. Our findings suggested the utility of IFRT in standard clinical practice and support its use for patients with LD-SCLC.