Deep learning approach for automated segmentation of myocardium using bone scintigraphy single-photon emission computed tomography/computed tomography in patients with suspected cardiac amyloidosis.

BACKGROUND: We employed deep learning to automatically detect myocardial bone-seeking uptake as a marker of transthyretin cardiac amyloid cardiomyopathy (ATTR-CM) in patients undergoing 99mTc-pyrophosphate (PYP) or hydroxydiphosphonate (HDP) single-photon emission computed tomography (SPECT)/computed tomography (CT). METHODS: We identified a primary cohort of 77 subjects at Brigham and Women's Hospital and a validation cohort of 93 consecutive patients imaged at the University of Pennsylvania who underwent SPECT/CT with PYP and HDP, respectively, for evaluation of ATTR-CM. Global heart regions of interest (ROIs) were traced on CT axial slices from the apex of the ventricle to the carina. Myocardial images were visually scored as grade 0 (no uptake), 1 (uptakeribs). A 2D U-net architecture was used to develop whole-heart segmentations for CT scans. Uptake was determined by calculating a heart-to-blood pool (HBP) ratio between the maximal counts value of the total heart region and the maximal counts value of the most superior ROI. RESULTS: Deep learning and ground truth segmentations were comparable (p=0.63). A total of 42 (55%) patients had abnormal myocardial uptake on visual assessment. Automated quantification of the mean HBP ratio in the primary cohort was 3.1±1.4 versus 1.4±0.2 (p<0.01) for patients with positive and negative cardiac uptake, respectively. The model had 100% accuracy in the primary cohort and 98% in the validation cohort. CONCLUSION: We have developed a highly accurate diagnostic tool for automatically segmenting and identifying myocardial uptake suggestive of ATTR-CM.

PET Radiotracers in Atherosclerosis: A Review.

Traditional atherosclerosis imaging modalities are limited to late stages of disease, prior to which patients are frequently asymptomatic. Positron emission tomography (PET) imaging allows for the visualization of metabolic processes underscoring disease progression via radioactive tracer, allowing earlier-stage disease to be identified. 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) uptake largely reflects the metabolic activity of macrophages, but is unspecific and limited in its utility. By detecting areas of microcalcification, 18F-Sodium Fluoride (18F-NaF) uptake also provides insight into atherosclerosis pathogenesis. Gallium-68 DOTA-0-Tyr3-Octreotate (68Ga-DOTATATE) PET has also shown potential in identifying vulnerable atherosclerotic plaques with high somatostatin receptor expression. Finally, 11-carbon (11C)-choline and 18F-fluoromethylcholine (FMCH) tracers may identify high-risk atherosclerotic plaques by detecting increased choline metabolism. Together, these radiotracers quantify disease burden, assess treatment efficacy, and stratify risk for adverse cardiac events.

Acrophialophora: A Comprehensive Review of Clinical Guidelines and Diagnosis.

Acrophialophora is a saprotrophic genus of fungi found in both temperate and tropical regions. The genus is comprised of 16 species, with the subspecies A. fusispora and A. levis necessitating the most clinical concern. Acrophialophora is an opportunistic pathogen with a broad range of clinical manifestations; the fungus has been implicated in cases of fungal keratitis, lung infection, and brain abscess. Acrophialophora infection is particularly of concern for immunocompromised patients, who often present with a more severe disease course involving disseminated infection and may not exhibit typical symptoms. Early diagnosis and therapeutic intervention are critical to the successful clinical management of Acrophialophora infection. Guidelines for antifungal treatment have yet to be established, partially due to the lack of documented cases. Aggressive use of antifungal agents and long-term treatment is required, especially in immunocompromised patients and patients with systemic involvement, due to the potential for morbidity and mortality. In addition to outlining the rarity and epidemiology of the disease, this review provides an overview of the diagnosis and clinical management of Acrophialophora infection to facilitate an early diagnosis and appropriate interventions.

Socioeconomic Status and Burden of Atrial Fibrillation Hospitalizations Among Black US Adults: A Fifteen Year Analysis.

Socioeconomic status (SES) may help delineate inequities in atrial fibrillation (AF) among Blacks versus non-blacks. We queried the National Inpatient Sample database from January 2004 to December 2018 to determine trends in AF hospitalizations and in-hospital mortality stratified by Black race and SES. Total admissions for AF in the US has increased by 12% from 1077 to 1202 per 1 million US adults. Among patients hospitalized with AF, the proportion of Black adults is increasing. In those of low SES, both Black and non-black patients have had increases in AF hospitalizations. In those of high SES, Black patients have had a modest increase while non-black patients have had a progressive decrease in rate of hospitalizations. Overall, in-hospital mortality rates improved in Blacks and non-blacks, regardless of SES. Joint associations of SES and race can further qualify disparities in AF care.

Persistent FDG Uptake at Apical Aneurysm in a Patient With Cardiac Sarcoidosis.

We present a case of cardiac sarcoidosis with persistent, focal fluorodeoxyglucose uptake at the left ventricular apical aneurysm concerning for ongoing active inflammatory injury, prompting aggressive immunosuppressive therapy. This case highlights the importance of understanding the various clinical entities that may resemble disease activity on fluorodeoxyglucose positron emission tomography/computed tomography imaging. (Level of Difficulty: Intermediate.).

Effect of Immunosuppressive Therapy and Biopsy Status in Monitoring Therapy Response in Suspected Cardiac Sarcoidosis.

BACKGROUND: Patients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation. OBJECTIVES: This study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT. METHODS: This study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions. RESULTS: Overall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P < 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P < 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P < 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different. CONCLUSIONS: Among patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.

Assessing Coronary Artery and Aortic Calcification in Patients with Prostate Cancer Using 18F-Sodium Fluoride PET/Computed Tomography.

The aim of this study was to assess coronary artery and aortic calcification in healthy controls, angina pectoris patients, and prostate cancer patients using 18F-sodium fluoride PET/computed tomography (NaF-PET/CT). A retrospective analysis compared 33 prostate cancer patients with 33 healthy subjects and 33 patients with angina pectoris. Increased target-to-background ratio (TBR) of the coronary arteries, ascending aorta, aortic arch, and descending aorta was observed in cancer patients compared to healthy controls but not compared to angina pectoris patients. These results demonstrate the feasibility of assessing vascular microcalcification with NaF-PET/CT, with significant differences in uptake according to comorbidities.

Racial and ethnic characteristics and cancer-specific survival in Primary Malignant Cardiac Tumors.

Background: There is limited insight into the epidemiological characteristics and effect of race and ethnicity on Primary Malignant Cardiac Tumors (PMCTs). Objectives: Comparison of clinical characteristics and cancer-specific survival outcomes of major races in the United States from the Surveillance, Epidemiology and End-Result (SEER) registry. Methods: ICD-O-3 codes were used to identify PMCTs for the years 1975 to 2015. Three major races were identified-"White", "Black", and "Asian/Pacific Islander". Cancer-specific survival outcomes were compared using Kaplan-Meier analysis across and amongst races, based on tumor histology. A subgroup analysis of cancer-specific survival was performed between "Hispanics" and "non-Hispanics." Results: Seven hundred and twenty patients were identified-47% females and 79% White, mean age at diagnosis (47 ± 20 years). Black patients were significantly younger (39 ± 18 years) and presented more commonly with angiosarcomas (53%). Non-angiogenic sarcomas and lymphomas were the most common tumors in the White (38%) and Asian/Pacific Islander (34%) cohorts. For a median follow-up period of 50 (IQR3-86) months, cancer-specific survival (mean ± SD, in months) was worse in Blacks (9 ± 3) as compared to Whites (15 ± 1) and Asian/Pacific Islander (14 ± 1) (p-value; Black vs. White <0.001; Black vs. Asian/Pacific Islanders = 0.017, White vs. Asian/Pacific Islanders = 0.3). Subgroup analysis with 116 (16%) Hispanics (40% females; mean age of 40 ± 20 years) showed a longer mean cancer-specific survival of 16.9 ± 2.4 months as compared to 13.6 ± 1.1 months in non-Hispanics (p = 0.011). Conclusion: Black and non-Hispanic patients have poorer cancer-specific survival in PMCTs.

Primary Aldosteronism and Ischemic Heart Disease.

Cardiovascular disease, in particular ischemic heart disease is a major cause of morbidity and mortality worldwide. Primary aldosteronism is the leading cause of secondary hypertension, yet commonly under diagnosed, and represents a major preventable risk factor. In contrast to historical teaching, recent studies have shown that excess aldosterone production is associated with increased burden of ischemic heart disease disproportionate to the effects caused by hypertension alone. Aldosterone through its genomic and non-genomic actions exerts various detrimental cardiovascular changes contributing to this elevated risk. Recognition of primary hyperaldosteronism and understanding the distinctive pathophysiology of ischemic heart disease in primary aldosteronism is crucial to develop strategies to improve outcomes.

A nationwide cohort analysis to determine the prevalence of sinus node dysfunction and rates of pacemaker implantation in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) has been known to have various degrees of cardiac involvement. However, limited evidence exists on prevalence of heart rhythm disorders in patients with SLE who have subsequent pacemaker (PM) implantation. The purpose of this study was to examine the prevalence of sinus node dysfunction (SND) in patients with SLE. The data was retrospectively analysed from the National Inpatient Sample database for the years 2010 to 2014 using the International Classification of Disease-9 diagnosis codes for SLE and SND in patients 18 years or older. We analysed data of 158,368 patients with SLE that were admitted from 2010 to 2014. The sample of patients ranged between 18 and 101 years of age (M = 52.13 ± 17.61), were primarily female (88.2%), and were Caucasian (50.6%). The prevalence of SND was 4.3%. In patients with both SLE and SND, the prevalence of PM implantation over the five-year period of analysis was 3.6% and the majority of these patients had a dual-chamber PM (85.6%). Prevalence rates of SND in patients with SLE increased for females over this five-year period (p = 0.023). Prevalence estimates of complications associated with PM in patients with SLE and SND were venous thromboembolism (2.1%), cardiac tamponade (0.4%), sepsis and severe sepsis (0.4%), septic shock (0%), pneumothorax (0%) and PM site hematoma (1.7%). The findings of this study revealed that the prevalence of SND and the prevalence of PM in patients with both SLE and SND have remained relatively consistent over the five years that our study analysed.

Venous thromboembolism detected by FDG-PET/CT in cancer patients: a common, yet life-threatening observation.

Cancer patients are at markedly increased risk for venous thromboembolism (VTE). Early detection of VTE may decrease morbidity and mortality in this population. We conducted this study to evaluate the ability of FDG-PET/CT to detect thrombosis in cancer patients. This retrospective study included 131 cancer patients with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) referred for 2-deoxy-2-[18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). All subjects underwent PET/CT imaging 60 minutes after FDG injection. Images were visually assessed for increased FDG uptake within the venous lumen. For positive cases, clinical follow-up and Doppler ultrasonography and/or contrast-enhanced CT scans were reviewed. FDG-PET/CT revealed abnormal uptake in the venous system of 26 (19.8%) patients. Eighteen (69.2%) had a history of DVT, and 13 (50%) had a history of PE. The most common site of thrombosis was the inferior vena cava (IVC) (n=14, 53.8%), followed by lower extremities veins (n=9, 34.6%), jugular veins (n=2, 7.7%), and superior vena cava (n=1, 3.8%). The presence of thrombi was confirmed by reviewing clinical follow-up in 6 (23.1%) patients. Among this group, thrombosis was detected in lower extremity veins (n=4, 15.8%), jugular veins (n=1, 3.8%), and IVC (n=1, 3.8%). Our study demonstrates that thrombi prior to their clinical manifestation can be detected by FDG-PET/CT in cancer patients. Moving forward, physicians must carefully consider the venous system when reporting FDG-PET/CT for cancer patients.

Incremental prognostic value of visually estimated coronary artery calcium in patients undergoing positron emission tomography imaging.

OBJECTIVE: Visually estimated coronary artery calcium (VECAC) from chest CT or attenuation correction (AC)/CT obtained during positron emission tomography (PET)-myocardial perfusion imaging (MPI) is feasible. Our aim was to determine the prognostic value of VECAC beyond conventional risk factors and PET imaging parameters, including coronary flow reserve (CFR). METHODS: We analysed 608 patients without known coronary artery disease who underwent PET-MPI between 2012 and 2016 and had AC/CT and/or chest CT images. We used Cox regression to estimate the association of VECAC categories (≤10, 11-400, >400 Agatston units (AU)) with the primary outcome of all-cause death, acute coronary syndrome or stroke (mean follow-up 4.3±1.8 years). C-statistics assessed the relationship between PET parameters and VECAC with the primary outcome. RESULTS: Mean age was 58±11 years, 65% were women and 67% were black. VECAC ≤10, 11-400 and >400 AU was observed in 68%, 12% and 20% of subjects, respectively. Compared with VECAC ≤10, VECAC categories 11-400 (HR 2.25, 95% CI 1.24 to 4.08) and >400 AU (HR 3.05, 95% CI 1.87 to 4.98) were associated with the primary outcome after adjusting for traditional risk factors, MPI findings and CFR. Adding VECAC to a model that included PET-MPI, CFR and clinical risk factors improved the prognostic value for the primary outcomes (c-statistic 0.71 to 0.75 with VECAC, p=0.01). CONCLUSIONS: VECAC is a potent predictor of events beyond traditional risk factors and PET imaging markers, including CFR. These data further support the importance for routine VECAC implementation.

Emerging role of 18F-FDG PET/CT in Castleman disease: a review.

Castleman disease (CD) describes a group of rare hematologic conditions involving lymphadenopathy with characteristic histopathology and a spectrum of clinical abnormalities. CD is divided into localized or unicentric CD (UCD) and multicentric CD (MCD) by imaging. MCD is further divided based on etiological driver into human herpesvirus-8-associated MCD, POEMS-associated MCD, and idiopathic MCD. There is notable heterogeneity across MCD, but increased level of pro-inflammatory cytokines, particularly interleukin-6, is an established disease driver in a portion of patients. FDG-PET/CT can help determine UCD versus MCD, evaluate for neoplastic conditions that can mimic MCD clinico-pathologically, and monitor therapy responses. CD requires more robust characterization, earlier diagnosis, and an accurate tool for both monitoring and treatment response evaluation; FDG-PET/CT is particularly suited for this. Moving forward, future prospective studies should further characterize the use of FDG-PET/CT in CD and specifically explore the utility of global disease assessment and dual time point imaging.Trial registration ClinicalTrials.gov, NCT02817997, Registered 29 June 2016, https://clinicaltrials.gov/ct2/show/NCT02817997.

18F-FDG-PET/CT in the assessment of atherosclerosis in lung cancer.

The aim of this study was to assess the risk of atherosclerosis in patients with lung cancer compared to patients with extrapulmonary malignancies using 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). We hypothesized that patients with lung cancer would demonstrate increased FDG uptake in the thoracic aorta compared to patients with extrapulmonary cancers. Thirty-four lung cancer patients (21 male, 13 female, 64.1 ± 12.9 yo) were retrospectively compared to seventy-eight patients with extrapulmonary malignancies (46 male, 32 female, 59.6 ± 12.8 yo). Average maximum standardized uptake value (avgSUVmax) and maximum target-to-blood pool ratio (TBRmax) were measured by mapping regions of interest of the ascending aorta, aortic arch, and descending aorta. Two-tailed Student's t-test was used to assess the differences in avgSUVmax and TBRmax between the two groups and between smokers and non-smokers. Age and gender distribution between the groups were not statistically different. AvgSUVmax and TBRmax were statistically significant increase in lung cancer patients compared to extrapulmonary cancer patients in the ascending aorta, aortic arch, and descending aorta, suggesting a lung cancer-associated increased risk of atherosclerosis development. AvgSUVmax was not significantly different between smokers and non-smokers in all sections of the thoracic aorta. Moving forward, large, prospective studies that directly compare PET data between different malignancies of different stages will help determine the role of FDG-PET/CT in assessing paraneoplastic vascular disease.

An understanding of the atherosclerotic molecular calcific heterogeneity between coronary, upper limb, abdominal, and lower extremity arteries as assessed by NaF PET/CT.

We aimed to quantify the heterogeneity of atherosclerosis in upper and lower limb vessels using 18F-NaF-PET/CT and compare calcification in coronary arteries to peripheral arteries. 68 healthy controls (42±13.5 years, 35 females, 33 males) and 40 patients at-risk for cardiovascular disease (55±11.9 years, 22 females, 18 males) underwent PET/CT imaging 90 minutes after the injection of 18F-NaF (2.2 Mbq/Kg). The following arteries were examined: coronary artery (CA), ascending aorta (AS), arch of aorta (AR), descending aorta (DA), abdominal aorta (AA), common iliac artery (CIA), external iliac artery (EIA), femoral artery (FA), popliteal artery (PA). Average SUVmean (aSUVmean) was calculated for each arterial segment. A paired t-test compared the aSUVmean between CA vs. AS, AR, DA, AA, CIA, EIA, FA, and PA. CA aSUVmean in the at-risk group was higher than the healthy control group (0.74±0.04 vs. 0.67±0.04, P=0.03). Furthermore, the 18F-NaF uptake in the CA was lower than in AS, AR, DA, AA, CIA, EIA, FA, and PA in both healthy (all P≤0.0001) and at-risk (all P≤0.0001). Higher 18F-NaF uptake in non-cardiac arteries in both healthy controls and patients at-risk suggests CA calcification is a late manifestation of atherosclerosis. This differential expression of atherosclerosis is likely due to interaction of hemodynamic parameters specific to the vascular bed and systemic factors related to the development of atherosclerosis.

Prevalence and Determinants of Atrial Fibrillation-Associated In-Hospital Ischemic Stroke in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Atrial fibrillation (AF) is an established risk factor ischemic stroke (IS) and is commonly encountered in patient hospitalized with acute myocardial infarction (AMI). Uncommonly, IS can occur as a complication resulting from percutaneous coronary intervention (PCI). There is limited real world data regarding AF-associated in-hospital IS (IH-IS) in patients admitted with AMI undergoing PCI. We queried the National Inpatient Sample database from January 2010 to December 2014 to identify patients admitted with AMI who underwent PCI. In this cohort, we determined the prevalence of AF associated IH-IS and compared risk factors for IH-IS between patients with AF and without AF using multivariable logistic regression models. IH-IS was present in 0.46% (n = 5,938) of the patients with AMI undergoing PCI (n = 1,282,829). Prevalence of IH-IS in patients with AF was higher compared with patients without AF (1.05% vs 0.4%; adjusted odds ratio: 1.634, 95% confidence interval: 1.527 to 1.748, p <0.001). Regardless of AF status, prevalence and risk of IH-IS was higher in females and increased with advancing age. There was significant overlap among risk-factors associated with increased risk of IH-IS in AF and non-AF cohorts, except for obesity in AF patients (adjusted odds ratio: 1.268, 95% confidence interval: 1.023 to 1.572, p = 0.03) in contrast to renal disease, malignancy, and peripheral vascular disease in non-AF patients. In conclusion, IH-IS is a rare complication affecting patients undergoing PCI for AMI and is more likely to occur in AF patients, females, and older adults, with heterogeneity among risk factors in patients with and without AF.

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

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

A critical review of radiotracers in the positron emission tomography imaging of traumatic brain injury: FDG, tau, and amyloid imaging in mild traumatic brain injury and chronic traumatic encephalopathy.

PURPOSE: Positron emission tomography (PET) has been widely utilized in the study of traumatic brain injury (TBI) for decades. While most applications of PET have attempted to assess neuronal function after TBI, more recently, novel radiotracers have sought to image biomarkers in the context of TBI and chronic traumatic encephalopathy (CTE). METHODS: This review will begin with an overview of TBI and CTE along with the acute and chronic pathophysiological consequences of TBI. Next, glycolysis, beta-amyloid, and tau protein radiotracers will be critically assessed in light of the most recent imaging studies available. CONCLUSIONS: Based on the scientific relevance of such radiotracers to the molecular processes of TBI and CTE along with the broader evidence of radiotracer specificity and selectivity, this review will weigh the strengths and weaknesses of each radiotracer. Nonetheless, the evidence indicates that PET will continue to be a powerful modality in the diagnosis of TBI-related conditions.