QRS Fragmentation in Preserved Ejection Fraction Heart Failure: Functional Insights, Pathological Correlates, and Prognosis.

Background Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B-type natriuretic peptide/troponin levels (both P<0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all P<0.05). Patients with anterior/lateral fQRS HFpEF exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all P<0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted hazard ratio 1.90, P<0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all P<0.05) by using Cox regression models. Conclusions The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such patients with HFpEF likely benefits from targeted therapeutic interventions.

Treatment Resulting Changes in Volumes of High-18F-FDG-Uptake Adipose Tissues over Orbit and Epicardium Correlate with Treatment Response for Non-Hodgkin's Lymphoma.

BACKGROUND: A regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for non-Hodgkin's lymphoma. Brown adipose tissue possesses anti-cancer potential. This study aimed to explore practical biomarkers for non-Hodgkin's lymphoma by analyzing the metabolic activity of adipose tissue. METHODS: Twenty patients who received R-CHOP for non-Hodgkin's lymphoma were reviewed. Positron emission tomography/computed tomography (PET/CT) images, lactate dehydrogenase (LDH) levels, and body mass index (BMI) before and after treatment were collected. Regions with a high standardized uptake value (SUV) in epicardial and orbital adipose tissue were selected and analyzed by a PET/CT viewer. The initial measurements and changes in the high SUV of epicardial and orbital adipose tissues, LDH levels, and BMI of treatment responders and non-responders, and complete and partial responders, were compared. RESULTS: The volumes of high-SUV epicardial and orbital adipose tissues significantly increased in responders after R-CHOP (p = 0.03 and 0.002, respectively). There were significant differences between changes in the high-SUV volumes of epicardial and orbital adipose tissues (p = 0.03 and 0.001, respectively) and LDH levels (p = 0.03) between responders and non-responders. The changes in high-SUV epicardial adipose tissue volumes were greater among complete responders than partial responders (p = 0.04). Poorer treatment responses were observed in patients with lower high-SUV epicardial adipose tissue volumes and higher LDH levels after R-CHOP (p = 0.03 and 0.03, respectively). CONCLUSIONS: The preliminary results of greater changes in high-SUV epicardial and orbital adipose tissue volumes among responders indicate that brown adipose tissue could be considered a favorable prognostic biomarker.

Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma.

Background: De novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy. Methods: We investigated the association between 11C-acetate/18F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice. Results: Dual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with 11C-acetate uptake and negatively associated with 18F-FDG uptake. This finding represents the negative association between 11C-acetate and 18F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high 11C-acetate but low 18F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low 11C-acetate but high 18F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat. Conclusion: The proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy.

Three-dimensional semiquantitative analysis of gastric emptying SPECT.

OBJECTIVE: We used dynamic single-photon emission computed tomography (D-SPECT) to overcome the interference of the planar dynamic imaging due to the overlap of internal organs, thus more accurate physiological function can be obtained. METHODS: 3D printed gastric phantom was used to simulate gastric emptying (GE). First, the planar dynamic liquid GE procedure was used and served as the reference value; second, D-SPECT followed by repeated liquid GE procedures with three gamma cameras were used. The emptying flow rate of the gastric phantom simulated three flow rates of liquid, semisolid and solid. Third, we simulated the intestinal activity that interfered with the residual value obtained by 2D dynamic imaging, which was compared with D-SPECT. Then, we brought the 3D VOI data into the postprocessing program to obtain the residual activity curve and residual percentage. RESULTS: The residual amount obtained in the phantom at 60th minutes in the first stage is 14.57%; the residual amount of liquid emptying are Siemens: 3.33%, GE: 15.06%, PHILIPS: 1.12%; residual amount for semisolid are Siemens: 47.36%, GE: 54.25%, PHILIPS: 51.57%; residual amount for solids are Siemens: 63.98%, GE: 66.88%, PHILIPS: 63.76%. All values are within the normal range. Then, we simulated the intestinal activity that interfered with the residual value obtained by 2D dynamic imaging: 75-90 min: 10.42, 19.48, 19.51 and 11.02%; however, the residual values obtained with 3D SPECT VOI data: 75-90 min: 1.42, 1.41, 1.35 and 1.02%. These results show that the emptying data errors caused by intestinal overlap can be effectively corrected (P = 0.017). CONCLUSION: D-SPECT imaging can overcome the interference in the semiquantitative data of residual GE caused in 2D mode.

2021 Advocacy Statements for the Role of 99mTc-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin Cardiac Amyloidosis: A Report of the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China.

Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure with preserved ejection fraction. Favorable prognosis depends on early diagnosis and correct treatment strategy. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, 99mTc-labeled bone avid scintigraphy including 99mTc-pyrophosphate (PYP) scintigraphy may be of diagnostic and prognostic importance. Various international guidelines support the non-biopsy diagnosis of ATTR-CM using 99mTc-PYP scintigraphy, yet emphasize the gap in standardization of acquisition and imaging analysis protocols, as well as the appropriateness of its clinical use. Therefore, a joint expert consensus has been reached by the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China, to advocate for the application of 99mTc-PYP scintigraphy in the diagnosis of ATTR-CM. This article aims to highlight the recommendations on image acquisition, qualitative and quantitative assessments of cardiac 99mTc-PYP uptake, and diagnostic algorithms. We hope the implementation of these recommendations in Taiwan will facilitate the process and enhance the diagnostic rate of ATTR-CM.

Micro-PET imaging of [18F]fluoroacetate combined with [18F]FDG to differentiate chronic Mycobacterium tuberculosis infection from an acute bacterial infection in a mouse model: a preliminary study.

BACKGROUND: Mycobacterium tuberculosis (TB) infection is one of the deadliest infectious diseases worldwide and is responsible for 1.7 million deaths per year. The increase in multidrug-resistant TB poses formidable challenges to the global control of tuberculosis. TB infection could easily yield false-positive results in fluorine-18-fluorodeoxyglucose ([F]FDG) PET imaging for cancer detection because of its high [F]FDG uptake. We describe the combined [F]FDG PET with fluorine-18-fluoroacetate ([F]FAC), a promising analog of carbon-11-acetate, for targeting glycolysis and de novo lipogenesis, respectively, to determine the metabolic differences between chronic TB infection and acute infection. MATERIALS AND METHODS: Six-month-old BALB/c mice were inoculated with Mycobacterium bovis to induce chronic TB infection, and Escherichia coli as well as Staphylococcus aureus to induce acute infection for an in-vivo imaging study. Eighteen days after inoculation for chronic TB infection and 5 days for acute infection, both [F]FDG and [F]FAC micro-PET were performed on the infected mice. Analysis of variance and the Tukey honest ad-hoc test were carried out to determine differences among treatment with different bacterial infections. RESULTS: TB infection showed much lower [F] FAC accumulation than acute infection. However, both TB infection and acute infection exhibited high [F]FAC accumulation. CONCLUSION: The marked metabolic differences in de novo lipogenesis and glycolysis in [F]FDG and [F]FAC uptakes in micro-PET imaging, respectively, help to differentiate chronic TB infection from acute infection.

Reappraisal of the effectiveness of 99mTc-dimercaptosuccinic acid scans for selective voiding cystourethrography in children with a first febrile urinary tract infection.

Recent studies have yielded conflicting results regarding the ability of technetium-99m dimercaptosuccinic acid ((99m)Tc-DMSA) renal scans for identifying high-grade vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). This study aimed to reevaluate the effectiveness of (99m)Tc-DMSA renal scans for selective voiding cystourethrography (VCUG) in children with a first febrile UTI. The medical records of children aged ≤ 5 years who were admitted with a first febrile UTI were retrospectively reviewed. Ultrasonography (US) and DMSA renal scans were performed within 3-5 days after admission, and VCUG was performed 7-10 days after antibiotics treatment. A total of 653 children were enrolled for analysis, including 579 patients aged < 2 years (Group A) and 74 patients aged 2-5 years (Group B). In Group A, DMSA scans were abnormal for 346 patients (59.8%), and normal for 233 patients (40.2%). High-grade VUR was present in 99 of 346 patients (28.9%) with abnormal DMSA scans, but present in only 16 of 233 patients (6.9%) with normal DMSA scans (p < 0.001). Regarding the prediction of high-grade VUR, the sensitivity and negative predictive value (NPV) for the DMSA scans were 86.1% and 93.1%, respectively. In Group B, DMSA scans were abnormal for 36 patients (48.6%), and normal for 38 patients (51.4%). High-grade VUR was present in 12 of 36 patients (33.3%) with abnormal DMSA scans, whereas none of the 38 patients with normal DMSA scans had high-grade VUR (p < 0.001). The sensitivity and NPV of the DMSA scans were both 100%. Using the selective VCUG strategy, approximately 40% of Group A patients and 50% of Group B patients could be spared an unnecessary VCUG, respectively. Our study results suggest that (99m)Tc-DMSA renal scans are effective in identifying children with a first febrile UTI for selective VCUG.