[111In]In-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC Phase I clinical trial.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare malignant tumour of the parafollicular C-cells with an unpredictable clinical course and currently suboptimal diagnostic and therapeutic options, in particular in advanced disease. Overexpression of cholecystokinin-2 receptors (CCK2R) represents a promising avenue to diagnostic imaging and targeted therapy, ideally through a theranostic approach. MATERIALS AND METHODS: A translational study (GRAN-T-MTC) conducted through a Phase I multicentre clinical trial of the indium-111 labelled CP04 ([111In]In-CP04), a CCK2R-seeking ligand was initiated with the goal of developing a theranostic compound. Patients with proven advanced/metastatic MTC or short calcitonin doubling time were enrolled. A two-step concept was developed through the use of low- and high-peptide mass (10 and 50 µg, respectively) for safety assessment, with the higher peptide mass considered appropriate for therapeutic application. Gelofusine was co-infused in a randomized fashion in the second step for the evaluation of potential reduction of the absorbed dose to the kidneys. Imaging for the purpose of biodistribution, dosimetry evaluation, and diagnostic assessment were performed as well as pre-, peri-, and postprocedural clinical and biochemical assessment. RESULTS: Sixteen patients were enrolled. No serious adverse events after application of the compound at both peptide amounts were witnessed; transient tachycardia and flushing were observed in two patients. No changes in biochemistry and clinical status were observed on follow-up. Preliminary dosimetry assessment revealed the highest dose to urinary bladder, followed by the kidneys and stomach wall. The effective dose for 200 MBq of [111In]In-CP04 was estimated at 7±3 mSv and 7±1 mSv for 10 µg and 50 µg CP04, respectively. Administration of Gelofusine reduced the dose to the kidneys by 53%, resulting in the organ absorbed dose of 0.044±0.019 mSv/MBq. Projected absorbed dose to the kidneys with the use of [177Lu]Lu-CP04 was estimated at 0.9±0.4 Gy/7.4 GBq. [111In]In-CP04 scintigraphy was positive in 13 patients (detection rate of 81%) with superior diagnostic performance over conventional imaging. CONCLUSION: In the present study, [111In]In-CP04 was shown to be a safe and effective radiopharmaceutical with promising theranostic characteristics for patients with advanced MTC.

Semaglutide delays 4-hour gastric emptying in women with polycystic ovary syndrome and obesity.

AIM: To evaluate the effect of once-weekly subcutaneous semaglutide 1.0 mg on the late digestive period of gastric emptying (GE) after ingestion of a standardized solid test meal by using technetium scintigraphy, the reference method for this purpose. METHODS: We conducted a single-blind, placebo-controlled trial in 20 obese women with polycystic ovary syndrome (PCOS; mean [range] age 35 [32.3-40.8] years, body mass index 37 [30.7-39.8] kg/m2 ) randomized to subcutaneous semaglutide 1.0 mg once weekly or placebo for 12 weeks. GE was assessed after ingestion of [99mT c] colloid in a pancake labelled with radiopharmaceutical by scintigraphy using sequential static imaging and dynamic acquisition at baseline and at Week 13. Estimation of GE was obtained by repeated imaging of remaining [99mT c] activity at fixed time intervals over the course of 4 hours after ingestion. RESULTS: From baseline to the study end, semaglutide increased the estimated retention of gastric contents by 3.5% at 1 hour, 25.5% at 2 hours, 38.0% at 3 hours and 30.0% at 4 hours after ingestion of the radioactively labelled solid meal. Four hours after ingestion, semaglutide retained 37% of solid meal in the stomach compared to no gastric retention in the placebo group (P = 0.002). Time taken for half the radiolabelled meal to empty from the stomach was significantly longer in the semaglutide group than the placebo group (171 vs. 118 min; P < 0.001). CONCLUSION: Semaglutide markedly delayed 4-hour GE in women with PCOS and obesity.

Sporadic Creutzfeldt-Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network.

BACKGROUND AND PURPOSE: Although sporadic Creutzfeldt-Jakob disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, the metabolic brain network associated with sCJD was investigated and its internal network organization was explored. METHODS: We explored 2-[18 F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) brain scans of 29 sCJD patients, 56 normal controls (NCs) and 46 other dementia patients from two independent centers. sCJD-related pattern (CJDRP) was identified in a cohort of 16 pathologically proven sCJD patients and 16 age-matched NCs using scaled subprofile modeling/principal component analysis and was prospectively validated in an independent cohort of 13 sCJD patients and 20 NCs. The pattern's specificity was tested on other dementia patients and its clinical relevance by clinical correlations. The pattern's internal organization was further studied using graph theory methods. RESULTS: The CJDRP was characterized by relative hypometabolism in the bilateral caudate, thalami, middle and superior frontal gyri, parietal lobe and posterior cingulum in association with relative hypermetabolism in the hippocampi, parahippocampal gyri and cerebellum. The pattern's expression significantly discriminated sCJD from NCs and other dementia patients (p < 0.005; receiver operating characteristic analysis CJD vs. NCs area under the curve [AUC] 0.90-0.96, sCJD vs. Alzheimer's disease AUC 0.78, sCJD vs. behavioral variant of frontotemporal dementia AUC 0.84). The pattern's expression significantly correlated with cognitive, functional decline and disease duration. The metabolic connectivity analysis revealed inefficient information transfer with specific network reorganization. CONCLUSIONS: The CJDRP is a robust metabolic biomarker of sCJD. Due to its excellent clinical correlations it has the potential to monitor disease in emerging disease-modifying trials.

Brown Adipose Tissue: A New Potential Target for Glucagon-like Peptide 1 Receptor Agonists in the Treatment of Obesity.

Adipose tissue can be divided into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, according to the differences in morphology. WAT acts as a buffer for increased energy intake and decreased energy expenditure during the development of obesity, resulting in visceral and ectopic WAT accumulation. These WAT depots are strongly associated with chronic systemic inflammation, insulin resistance, and cardiometabolic risk related to obesity. They represent a primary weight loss target in anti-obesity management. Second-generation anti-obesity medications glucagon-like peptide-1 receptor agonists (GLP-1RAs) cause weight loss and improve body composition by reducing visceral and ectopic fat depots of WAT, resulting in improved cardiometabolic health. Recently, the understanding of the physiological significance of BAT beyond its primary function in generating heat through non-shivering thermogenesis has been expanded. This has raised scientific and pharmaceutical interest in the manipulation of BAT to further enhance weight reduction and body weight maintenance. This narrative review focuses on the potential impact of GLP-1 receptor agonism on BAT, particularly in human clinical studies. It provides an overview of the role of BAT in weight management and highlights the need for further research to elucidate the mechanisms by which GLP-1RAs affect energy metabolism and weight loss. Despite encouraging preclinical data, limited clinical evidence supports the notion that GLP-1RAs contribute to BAT activation.

Estimation of glomerular filtration rate based on dry lean body mass in kidney transplant recipients
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AIM: The use of glomerular filtration rate (GFR) estimating equations is not always reliable, especially in specific populations, such as patients with transplanted kidney. The purpose of this study was to improve the performance of GFR equations by taking into account dry lean body mass. MATERIALS AND METHODS: A prospective clinical study included 100 patients with kidney graft. Estimated GFR (eGFR) with Chronic Kidney Disease Epidemiology Collaboration equations with serum creatinine concentration (CKD-EPI Cr), serum cystatin C concentration (CKD-EPI CysC), or both (CKD-EPI Cr-CysC) were compared with measured GFR with 51Cr-EDTA clearance (mGFR 51Cr-EDTA). Dry lean body mass (body mass without fat mass and water) was measured with bioimpedance analysis. RESULTS: All of the eGFRs overestimated mGFR 51Cr-EDTA by a significant degree (shown as bias ± SD in mL/min/1.73m2 with 30% accuracy in parentheses): CKD-EPI Cr 15.1 ± 15.3 (50%), CKD-EPI CysC 8.0 ± 16.6 (56%), CKD-EPI Cr-CysC 10.3 ± 13.4 (55%). Dry lean body mass significantly correlated with mGFR 51Cr-EDTA (R = 0.241; p = 0.016) and all biases except the bias of CKD-EPI CysC. Considering the dry lean body mass and preexisting equations with creatinine, we developed two new equations with better performance and statistically insignificant bias: Corrected CKD-EPI Cr -1.43 ± 13.6 (67%) and Corrected CKD-EPI Cr-CysC -1.64 ± 13.4 (77%). CONCLUSION: Dry lean body mass improves the performance of GFR equations in our kidney transplant cohort.

18F-choline PET/CT for parathyroid scintigraphy: significantly lower radiation exposure of patients in comparison to conventional nuclear medicine imaging approaches.

BACKGROUND: Parathyroid subtraction scintigraphy (PSS) is the most commonly used imaging method for localisation of hyperfunctioning parathyroid glands (HPGs) in primary hyperparathyroidism (PHP), a common endocrine disorder. Hybrid (SPECT/CT) imaging with 99mTc-sestaMIBI (MIBI) at an early and delayed phase (dual-phase imaging) may be the most accurate conventional imaging approach, but includes additional radiation exposure due to added CT imaging. Recently, 18F-choline (FCH) PET/CT was introduced for HPG imaging, which can also be performed using the dual-phase approach. To date, no studies have compared organ doses and the effective dose (ED) from conventional subtraction scintigraphy, dual-phase MIBI SPECT/CT, and FCH PET/CT in the localisation of HPGs. AIM: In addition to the comparison of the diagnostic performance of FCH PET/CT and conventional scintigraphic imaging methods, the aim of the study was to measure the organ doses and the ED for conventional subtraction parathyroid imaging protocols, using dual-phase MIBI SPECT/CT as a potential conventional imaging method of choice and FCH dual-phase PET/CT as a potential future imaging method of choice for the localisation of HPGs. Materials, methods. Thirty-six patients referred for parathyroid imaging with a clinical indication of PHP underwent preoperative PSS and dual-phase SPECT/CT imaging with the addition of FCH PET/CT. The diagnostic performance of the imaging modalities was assessed by using histology results as a gold standard. Radiation exposure was calculated for the administered activities of radiopharmaceuticals using ICRP80 weighting factors and for CT exposure at hybrid imaging using dose-length products and the ImPACT CT Patient Dosimetry Calculator. RESULTS: The diagnostic performance of FCH PET/CT was significantly better than that of conventional imaging modalities (sensitivity of 97% vs 64% and 46% for MIBI SPECT/CT and PSS, respectively, with comparable specificity of over 95% for all modalities). The highest radiation exposure was caused by conventional PSS (7.4 mSv), followed by dual-phase MIBI SPECT/CT (6.8 mSv). The radiation exposure was the lowest for dual-phase FCH PET/CT imaging (2.8 mSv). The added CT imaging for both hybrid approaches did not cause significant additional radiation exposure (1.4 mSv for MIBI SPECT/CT, additional 26.4% to overall exposure; 0.8 mSv for FCH PET/CT, additional 42.4% to overall exposure). CONCLUSION: In comparison to conventional scintigraphic imaging of HPGs, emerging hybrid (SPECT/CT, PET/CT) imaging techniques combine superior diagnostic performance with lower radiation exposure to patients.

Role of dry lean body mass for estimation of glomerular filtration rate in kidney transplant recipients.

BACKGROUND: The use of equations that predict glomerular filtration rate (GFR) in patients with a kidney graft is still a matter of debate. The purpose of this study was to determine the level of accuracy of GFR equations and the relevance of dry lean body mass in the assessment of GFR. METHODS: In a prospective clinical study, 100 patients with a kidney graft were included. Estimated GFR with Modification of Diet in Renal Disease equation (MDRD), Chronic Kidney Disease Epidemiology Collaboration equation (CKD EPI) with serum creatinine concentration (CKD EPI Cr), serum cystatin C concentration (CKD EPI CysC) or both (CKD EPI Cr-CysC), and creatinine clearance calculated with Cockcroft-Gault equation (CG) was compared with GFR measured by 51Cr-EDTA clearance (mGFR 51Cr-EDTA). Dry lean body mass (body mass without fat mass and body water) was measured with bioimpedance analysis. RESULTS: All of the estimating equations overestimated mGFR 51Cr-EDTA by a significant degree (bias ± SD in mL/min/1.73m2, 30% accuracy in brackets): CG 16.8 ± 14.1 (44%), MDRD 12.5 ± 15.3 (54%), CKD EPI Cr 15.1 ± 15.3 (50%), CKD EPI CysC 8.0 ± 16.6 (56%), CKD EPI Cr-CysC 10.3 ± 13.4 (55%). Dry lean body mass significantly correlated with mGFR 51Cr-EDTA, but not with estimated GFRs. CONCLUSION: The estimating GFR equations are neither accurate nor precise in renal transplant recipients. Dry lean body mass is an important parameter that could potentially improve the GFR estimation in this population.
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Intracoronary transplantation of CD34(+) cells is associated with improved myocardial perfusion in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: We investigated the effects of intracoronary transplantation of CD34(+) cells on myocardial perfusion in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We enrolled 21 patients with DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral stem cell mobilization with granulocyte-colony stimulating factor (G-CSF). CD34(+) cells were collected by means of apheresis. Patients underwent myocardial perfusion imaging, and CD34(+) cells were injected in the coronary artery supplying viable segments with reduced myocardial perfusion and regional dysfunction. Myocardial perfusion imaging was repeated 6 months later. Clinical response to stem cell therapy was predefined as a change in LVEF >5%. The majority of patients were men (81%) with an overall mean age 53 ± 9 years, LVEF 25 ± 5%, and 6-minute walking distance 354 ± 71 m. Myocardial perfusion defects at rest were observed in 86% of patients and were more common in the left anterior descending territory (50%). At 6 months' follow-up, there was a significant improvement in rest myocardial perfusion scores (6.3 ± 5.8 vs 3.1 ± 4.3; P < .001), LVEF (25 ± 7% vs 29 ± 8%; P = .005), and 6-minute walking distance (354 ± 71 m vs 404 ± 91 m; P < .001). Responders to stem cell therapy had lower summed rest perfusion score at both baseline (3.2 ± 3.0 vs 9.1 ± 6.3; P = .015) and follow-up (1.0 ± 1.5 vs 5.0 ± 5.1; P = .028). CONCLUSIONS: CD34(+) cell transplantation may lead to improved myocardial perfusion in patients with nonischemic DCM. Patients with less severe myocardial perfusion defects at baseline may have an increased likelihood to respond to intracoronary CD34(+) cell transplantation.

Immunologic Network and Response to Intramyocardial CD34+ Stem Cell Therapy in Patients With Dilated Cardiomyopathy.

BACKGROUND: Although stem cell therapy (SCT) is emerging as a potential treatment for patients with dilated cardiomyopathy (DCM), clinical response remains variable. Our objective was to determine whether baseline differences in circulating immunologic and nonimmunologic biomarkers may help to identify patients more likely to respond to intramyocardial injection of CD34(+)-based SCT. METHODS AND RESULTS: We enrolled from January 3, 2011 to March 5, 2012 37 patients with longstanding DCM (left ventricular ejection fraction [LVEF] <40%, New York Heart Association functional class III) who underwent peripheral CD34(+) stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) and collection by means of apheresis. CD34(+) cells were labeled with (99m)Tc-hexamethylpropyleneamine oxime to allow assessment of stem cell retention at 18 hours. Response to SCT was predefined as an increase in LVEF of ≥5% at 3 months. The majority (84%) of patients were male with an overall mean LVEF of 27 ± 7% and a median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of 2,774 pg/mL. Nineteen patients (51%) were responders to SCT. There was no significant difference between responders and nonresponders regarding to age, sex, baseline LVEF, NT-proBNP levels, or 6-minute walking distance. With the use of a partial least squares (PLS) predictive model, we identified 9 baseline factors that were associated with both stem cell response and stem cell retention (mechanistic validation). Among the baseline factors positively associated with both clinical response and stem cell retention were G-CSF, SDF-1, LIF, MCP-1, and MCP-3. Among baseline factors negatively associated with both clinical response and retention were IL-12p70, FASL, ICAM-1, and GGT. A decrease in G-CSF at 3-month follow-up was also observed in responders compared with nonresponders (P = .02). CONCLUSIONS: If further validated, baseline immunologic and nonimmunologic biomarkers may help to identify patients with DCM who are more likely to respond to CD34(+)-based SCT.

Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up.

RATIONALE: CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance. OBJECTIVE: We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response. METHODS AND RESULTS: Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39). CONCLUSIONS: Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

Optimal scan time for evaluation of parathyroid adenoma with [(18)F]-fluorocholine PET/CT.

BACKGROUND: Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [(18)F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism. PATIENTS AND METHODS: 43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUVmean), retention index and lesion contrast for parathyroid and thyroid tissue were calculated. RESULTS: Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUVmean in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05). CONCLUSIONS: According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH.

Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: In an open-label blinded study, we compared intracoronary and transendocardial CD34(+) cell transplantation in patients with nonischemic dilated cardiomyopathy. METHODS AND RESULTS: Of the 40 patients with dilated cardiomyopathy, 20 were randomized to receive intracoronary injection and 20 received transendocardial CD34(+) cell delivery. In both groups, CD34(+) cells were mobilized by filgrastim, collected via apheresis, and labeled with technetium-99m radioisotope for single-photon emission computed tomographic imaging. In the intracoronary group, cells were injected intracoronarily in the artery supplying segments of greater perfusion defect on myocardial perfusion scintigraphy. In the transendocardial group, electroanatomic mapping was used to identify viable but dysfunctional myocardium, and transendocardial cell injections were performed. Nuclear single-photon emission computed tomographic imaging for quantification of myocardial retention was performed 18 hours thereafter. At baseline, groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal pro-brain natriuretic peptide levels. The number of CD34(+) cells was also comparable (105 ± 31 × 10(6) in the transendocardial group versus 103 ± 27 × 10(6) in the intracoronary group, P=0.62). At 18 hours after procedure, myocardial retention was higher in the transendocardial group (19.2 ± 4.8%) than in the intracoronary group (4.4 ± 1.2%, P<0.01). At 6 months, left ventricular ejection fraction improved more in the transendocardial group (+8.1 ± 4.3%) than in the intracoronary group (+4.2 ± 2.3%, P=0.03). The same pattern was observed for the 6-minute walk test distance (+125 ± 33 m in the transendocardial group versus +86 ± 13 m in the intracoronary group, P=0.03) and N-terminal pro-brain natriuretic peptide (-628 ± 211 versus -315 ± 133 pg/mL, P=0.04). CONCLUSIONS: In patients with dilated cardiomyopathy, transendocardial CD34(+) cell transplantation is associated with higher myocardial retention rates and greater improvement in ventricular function, N-terminal pro-brain natriuretic peptide, and exercise capacity compared with intracoronary route. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01350310.

¹8F-Fluorocholine PET/CT for localization of hyperfunctioning parathyroid tissue in primary hyperparathyroidism: a pilot study.

PURPOSE: Primary hyperparathyroidism is a common endocrine disorder which is diagnosed biochemically and for which therapy is surgical. A prerequisite for minimally invasive surgery, which minimizes morbidity and cost, is accurate localization of the involved gland(s). The aim of this study was to evaluate the usefulness of (18)F-fluorocholine PET/CT for preoperative localization of hyperfunctioning parathyroid tissue. METHODS: (18)F-Fluorocholine PET/CT and conventional parathyroid scintigraphic imaging consisting of (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI dual-phase imaging and (99m)Tc-sestaMIBI/pertechnetate subtraction imaging were performed in 24 patients. The diagnostic performance of the imaging methods was compared against histology as the gold standard and postoperative serum Ca(2+) and iPTH values. RESULTS: The sensitivity and specificity of (18)F-fluorocholine PET/CT were 92% and 100%, respectively, in contrast to 49% and 100%, 46% and 100%, and 44% and 100% for (99m)Tc-sestaMIBI SPECT/CT, (99m)Tc-sestaMIBI/pertechnetate subtraction imaging and (99m)Tc-sestaMIBI dual-phase imaging, respectively. Combined conventional scintigraphic imaging had a sensitivity and specificity of 64% and 100%, respectively. The performance of (18)F-fluorocholine PET/CT was superior particularly in patients with multiple lesions or hyperplasia. CONCLUSION: (18)F-Fluorocholine PET/CT appears to be a promising, effective imaging method for localization of hyperfunctioning parathyroid tissue.

Impact of myocardial viability assessed by myocardial perfusion imaging on ventricular tachyarrhythmias in cardiac resynchronization therapy.

BACKGROUND: The presence of myocardial fibrosis is associated with ventricular tachyarrhythmia (VT) occurrence irrespective of cardiomyopathy etiology. The aim of our study was to evaluate the impact of global and regional viability on VTs in patients undergoing cardiac resynchronization therapy (CRT). METHODS: Fifty-seven patients with advanced heart failure (age 62.3 ± 10.2; 38 men; 24 ischemic etiology) were evaluated using single-photon emission computed tomography myocardial perfusion imaging before CRT defibrillator device implantation. Global myocardial viability was determined by the number of viable segments in a 20-segment model. Regional viability was calculated as the mean tracer activity in the corresponding segments at left ventricular (LV) lead position. LV lead segments were determined at implant venography using 2 projections (left anterior oblique 30 and right anterior oblique 30) of coronary sinus tributaries. Patients were followed 30 (24-34) months for the occurrence of VTs. RESULTS: VTs were registered in 18 patients (31.6%). Patients without VTs had significantly more viable segments (17.6 ± 2.35 vs 14.2 ± 4.0; P = .002) and higher regional myocardial viability at LV lead position (66.1% ± 10.3% vs 54.8% ± 11.4% of tracer activity; P = .001) than those with VTs. In multivariate logistic regression models, the number of viable segments (OR = 0.66; 95% confidence interval (CI) 0.53-0.85; P = .001) and regional viability (OR = 0.90; 95% CI 0.85-0.97; P = .003) were the only independent predictors of VT occurrence. CONCLUSION: Global and regional myocardial viability are independently related to the occurrence of VTs in patients after CRT.

Effect of Coronary Sinus Reducer Implantation on Aerobic Exercise Capacity in Refractory Angina Patients-A CROSSROAD Study.

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina pectoris. However, there is no evidence from a randomized trial that would show an improvement in exercise capacity after this treatment. The aim of this study was to evaluate the influence of CSR treatment on maximal oxygen consumption and compare it to a sham procedure. Twenty-five patients with refractory angina pectoris (Canadian Cardiovascular Society (CCS) class II-IV) were randomized to a CSR implantation (n = 13) or a sham procedure (n = 12). At baseline and after 6 months of follow-up, the patients underwent symptom-limited cardiopulmonary exercise testing with an adjusted ramp protocol and assessment of angina pectoris using the CCS scale and Seattle angina pectoris questionnaire (SAQ). In the CSR group, maximal oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min (p = 0.03) but did not change in the sham group (p = 0.53); p for intergroup comparison was 0.03. In contrast, there was no difference in the improvement of the CCS class or SAQ domains. To conclude, in patients with refractory angina and optimized medical therapy, CSR implantation may improve oxygen consumption beyond that of optimal medical therapy.

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial.

BACKGROUND: Xerostomia is a common side effect of radiotherapy in patients with head and neck tumors that negatively affects quality of life. There is no known effective standard treatment for xerostomia. Here, we present the study protocol used to evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) derived from umbilical cord tissue. PATIENTS AND METHODS: Ten oropharyngeal cancer patients with post-radiation xerostomia and no evidence of disease recurrence 2 or more years after (chemo)irradiation (intervention group) and 10 healthy volunteers (control group) will be enrolled in this nonrandomized, open-label, phase I exploratory study. MSCs from umbilical cord tissue will be inserted under ultrasound guidance into both parotid glands and both submandibular glands of the patients. Toxicity of the procedure will be assessed according to CTCAE v5.0 criteria at days 0, 1, 5, 28, and 120. Efficacy will be assessed by measuring salivary flow and analyzing its composition, scintigraphic evaluation of MSC grafting, retention, and migration, and questionnaires measuring subjective xerostomia and quality of life. In addition, the radiological, functional, and morphological characteristics of the salivary tissue will be assessed before, at 4 weeks, and at 4 months after the procedure. In the control group subjects, only salivary flow rate and salivary composition will be determined. DISCUSSION: The use of allogeneic MSCs from umbilical cord tissue represents an innovative approach for the treatment of xerostomia after radiation. Due to the noninvasive collection procedure, flexibility of cryobanking, and biological advantages, xerostomia therapy using allogeneic MSCs from umbilical cord tissue may have an advantage over other similar therapies.

Image reconstruction using small-voxel size improves small lesion detection for positron emission tomography.

BACKGROUND: PET/CT imaging is widely used in oncology and provides both metabolic and anatomic information. Because of the relatively poor spatial resolution of PET, the detection of small lesions is limited. The low spatial resolution introduces the partial-volume effect (PVE) which negatively affects images both qualitatively and quantitatively. The aim of the study was to investigate the effect of small-voxel (2 mm in-line pixel size) vs. standard-voxel (4 mm in-line pixel size) reconstruction on lesion detection and image quality in a range of activity ratios. MATERIALS AND METHODS: The National Electrical Manufacturers Association (NEMA) body phantom and the Micro Hollow-Sphere phantom spheres were filled with a solution of [18F]fluorodeoxyglucose ([18F]FDG) in sphere-to-background ratios of 2:1, 3:1, 4:1 and 8:1. In all images reconstructed with 2 mm and 4 mm in-line pixel size the visual lesion delineation, contrast recovery coefficient (CRC) and contrast-to-noise ratio (CNR) were evaluated. RESULTS: For smaller (≤ 13 mm) phantom spheres, significantly higher CRC and CNR using small-voxel reconstructions were found, also improving visual lesion delineation. CRC did not differ significantly for larger (≥ 17 mm) spheres using 2 mm and 4 mm in-line pixel size, but CNR was significantly lower; however, lower CNR did not affect visual lesion delineation. CONCLUSIONS: Small-voxel reconstruction consistently improves precise small lesion delineation, lesion contrast and image quality.

Abnormal metabolic covariance patterns associated with multiple system atrophy and progressive supranuclear palsy.

PURPOSE: Differentiation between neurodegenerative parkinsonisms, whose early clinical presentation is similar, may be improved with metabolic brain imaging. In this study we applied a specific network analysis to 2-[18F]FDG PET brain scans to identify the characteristic metabolic patterns for multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) in a new European cohort. We also developed a new tool to recognize and estimate patients' metabolic brain heterogeneity. METHODS: 20 MSA-P patients, 20 PSP patients and 20 healthy controls (HC) underwent 2-[18F]FDG PET brain imaging. The scaled subprofile model/principal component analysis was applied to identify MSA/PSP-related patterns; MSARP and PSPRP. Additional, 56 MSA, 45 PSP, 116 PD and 61 HC subjects were analyzed for validation. We innovatively applied heat-map analysis to extract and graphically display the pattern's regional sub-scores in individual subjects. RESULTS: MSARP was characterized by hypometabolism in cerebellum and putamen, and PSPRP by hypometabolism in medial prefrontal cortices, nucleus caudatus, frontal cortices and mesencephalon. Patterns' expression discriminated between MSA/PSP patients and HCs as well as between different parkinsonian cohorts (p < 0.001). Both patterns were sensitive and specific (AUC for MSARP/PSPRP: 0.96/0.99). Heat-map analysis showed differences within MSA/PSP subjects and HCs consistent with clinical presentation. CONCLUSIONS: Replication and validation of MSARP and PSPRP confirms robustness of these metabolic biomarkers and supports its application in clinical and research practice. Heat-map analysis gives us an insight into the contribution of various pattern's regions to patterns' expression in individual subjects, which improves our insight into the heterogeneity of studied syndromes.

Detection and localization of hyperfunctioning parathyroid glands on [18F]fluorocholine PET/ CT using deep learning - model performance and comparison to human experts.

BACKGROUND: In the setting of primary hyperparathyroidism (PHPT), [18F]fluorocholine PET/CT (FCH-PET) has excellent diagnostic performance, with experienced practitioners achieving 97.7% accuracy in localising hyperfunctioning parathyroid tissue (HPTT). Due to the relative triviality of the task for human readers, we explored the performance of deep learning (DL) methods for HPTT detection and localisation on FCH-PET images in the setting of PHPT. PATIENTS AND METHODS: We used a dataset of 93 subjects with PHPT imaged using FCH-PET, of which 74 subjects had visible HPTT while 19 controls had no visible HPTT on FCH-PET. A conventional Resnet10 as well as a novel mPETResnet10 DL model were trained and tested to detect (present, not present) and localise (upper left, lower left, upper right or lower right) HPTT. Our mPETResnet10 architecture also contained a region-of-interest masking algorithm that we evaluated qualitatively in order to try to explain the model's decision process. RESULTS: The models detected the presence of HPTT with an accuracy of 83% and determined the quadrant of HPTT with an accuracy of 74%. The DL methods performed statistically worse (p < 0.001) in both tasks compared to human readers, who localise HPTT with the accuracy of 97.7%. The produced region-of-interest mask, while not showing a consistent added value in the qualitative evaluation of model's decision process, had correctly identified the foreground PET signal. CONCLUSIONS: Our experiment is the first reported use of DL analysis of FCH-PET in PHPT. We have shown that it is possible to utilize DL methods with FCH-PET to detect and localize HPTT. Given our small dataset of 93 subjects, results are nevertheless promising for further research.