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Medical Physics Nov 2019Numerous image reconstruction methodologies for positron emission tomography (PET) have been developed that incorporate magnetic resonance (MR) imaging structural... (Comparative Study)
Comparative Study
PURPOSE
Numerous image reconstruction methodologies for positron emission tomography (PET) have been developed that incorporate magnetic resonance (MR) imaging structural information, producing reconstructed images with improved suppression of noise and reduced partial volume effects. However, the influence of MR structural information also increases the possibility of suppression or bias of structures present only in the PET data (PET-unique regions). To address this, further developments for MR-informed methods have been proposed, for example, through inclusion of the current reconstructed PET image, alongside the MR image, in the iterative reconstruction process. In this present work, a number of kernel and maximum a posteriori (MAP) methodologies are compared, with the aim of identifying methods that enable a favorable trade-off between the suppression of noise and the retention of unique features present in the PET data.
METHODS
The reconstruction methods investigated were: the MR-informed conventional and spatially compact kernel methods, referred to as KEM and KEM largest value sparsification (LVS) respectively; the MR-informed Bowsher and Gaussian MR-guided MAP methods; and the PET-MR-informed hybrid kernel and anato-functional MAP methods. The trade-off between improving the reconstruction of the whole brain region and the PET-unique regions was investigated for all methods in comparison with postsmoothed maximum likelihood expectation maximization (MLEM), evaluated in terms of structural similarity index (SSIM), normalized root mean square error (NRMSE), bias, and standard deviation. Both simulated BrainWeb (10 noise realizations) and real [ F] fluorodeoxyglucose (FDG) three-dimensional datasets were used. The real [ F]FDG dataset was augmented with simulated tumors to allow comparison of the reconstruction methodologies for the case of known regions of PET-MR discrepancy and evaluated at full counts (100%) and at a reduced (10%) count level.
RESULTS
For the high-count simulated and real data studies, the anato-functional MAP method performed better than the other methods under investigation (MR-informed, PET-MR-informed and postsmoothed MLEM), in terms of achieving the best trade-off for the reconstruction of the whole brain and PET-unique regions, assessed in terms of the SSIM, NRMSE, and bias vs standard deviation. The inclusion of PET information in the anato-functional MAP method enables the reconstruction of PET-unique regions to attain similarly low levels of bias as unsmoothed MLEM, while moderately improving the whole brain image quality for low levels of regularization. However, for low count simulated datasets the anato-functional MAP method performs poorly, due to the inclusion of noisy PET information in the regularization term. For the low counts simulated dataset, KEM LVS and to a lesser extent, HKEM performed better than the other methods under investigation in terms of achieving the best trade-off for the reconstruction of the whole brain and PET-unique regions, assessed in terms of the SSIM, NRMSE, and bias vs standard deviation.
CONCLUSION
For the reconstruction of noisy data, multiple MR-informed methods produce favorable whole brain vs PET-unique region trade-off in terms of the image quality metrics of SSIM and NRMSE, comfortably outperforming the whole image denoising of postsmoothed MLEM.
Topics: Fluorodeoxyglucose F18; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Positron-Emission Tomography
PubMed: 31494961
DOI: 10.1002/mp.13812 -
Neurology Nov 2020
Topics: Fluorodeoxyglucose F18; Humans; Neurodegenerative Diseases; Semantics; Verbal Behavior
PubMed: 33004597
DOI: 10.1212/WNL.0000000000010963 -
Nihon Hoshasen Gijutsu Gakkai Zasshi 2023
Topics: Positron-Emission Tomography; Fluorodeoxyglucose F18
PubMed: 36682784
DOI: 10.6009/jjrt.2023-2144 -
Journal of Immunology (Baltimore, Md. :... Aug 2020Metabolic reprogramming plays a central role in T cell activation and differentiation, and the inhibition of key metabolic pathways in activated T cells represents a...
Metabolic reprogramming plays a central role in T cell activation and differentiation, and the inhibition of key metabolic pathways in activated T cells represents a logical approach for the development of new therapeutic agents for treating autoimmune diseases. The widely prescribed antidiabetic drug metformin and the glycolytic inhibitor 2-deoxyglucose (2-DG) have been used to study the inhibition of oxidative phosphorylation and glycolysis, respectively, in murine immune cells. Published studies have demonstrated that combination treatment with metformin and 2-DG was efficacious in dampening mouse T cell activation-induced effector processes, relative to treatments with either metformin or 2-DG alone. In this study, we report that metformin + 2-DG treatment more potently suppressed IFN-γ production and cell proliferation in activated primary human CD4 T cells than either metformin or 2-DG treatment alone. The effects of metformin + 2-DG on human T cells were accompanied by significant remodeling of activation-induced metabolic transcriptional programs, in part because of suppression of key transcriptional regulators MYC and HIF-1A. Accordingly, metformin + 2-DG treatment significantly suppressed MYC-dependent metabolic genes and processes, but this effect was found to be independent of mTORC1 signaling. These findings reveal significant insights into the effects of metabolic inhibition by metformin + 2-DG treatment on primary human T cells and provide a basis for future work aimed at developing new combination therapy regimens that target multiple pathways within the metabolic networks of activated human T cells.
Topics: Animals; CD4-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Deoxyglucose; Glycolysis; Humans; Mechanistic Target of Rapamycin Complex 1; Metabolic Networks and Pathways; Metformin; Mice; Oxidative Phosphorylation; Signal Transduction
PubMed: 32641388
DOI: 10.4049/jimmunol.2000137 -
BMJ Open Diabetes Research & Care Jun 2021Saliva collection is a non-invasive test and is convenient. 1,5-anhydroglucitol (1,5-AG) is a new indicator reflecting short-term blood glucose levels. This study aimed...
INTRODUCTION
Saliva collection is a non-invasive test and is convenient. 1,5-anhydroglucitol (1,5-AG) is a new indicator reflecting short-term blood glucose levels. This study aimed to explore the relationship between saliva 1,5-AG and insulin secretion function and insulin sensitivity.
RESEARCH DESIGN AND METHODS
Adult patients with type 2 diabetes who were hospitalized were enrolled. Based on blood glucose and C-peptide, homeostasis model assessment 2 for β cell secretion function, C-peptidogenic index (CGI), △2-hour C-peptide (2hCP)/△2-hour postprandial glucose (2hPG), ratio of 0-30 min area under the curve for C-peptide and area under the curve for glucose (AUC/AUC), and AUC/AUC were calculated to evaluate insulin secretion function, while indicators such as homeostasis model assessment 2 for insulin resistance were used to assess insulin sensitivity.
RESULTS
We included 284 subjects (178 men and 106 women) with type 2 diabetes aged 20-70 years. The saliva 1,5-AG level was 0.133 (0.089-0.204) µg/mL. Spearman's correlation analysis revealed a significantly negative correlation between saliva 1,5-AG and 0, 30, and 120 min blood glucose, glycated hemoglobin A, and glycated albumin (all p<0.05), and a significantly positive association between saliva 1,5-AG and CGI (=0.171, p=0.004) and AUC /AUC (=0.174, p=0.003). The above correlations still existed after adjusting for age, sex, body mass index, and diabetes duration. In multiple linear regression, saliva 1,5-AG was an independent factor of CGI (standardized =0.135, p=0.015) and AUC /AUC (standardized =0.110, p=0.020).
CONCLUSIONS
Saliva 1,5-AG was related to CGI and AUC/AUC in patients with type 2 diabetes.
TRIAL REGISTRATION NUMBER
ChiCTR-SOC-17011356.
Topics: Adult; China; Deoxyglucose; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Saliva
PubMed: 34167955
DOI: 10.1136/bmjdrc-2021-002199 -
Pharmacology Research & Perspectives Feb 2024Our previous work has shown a synergistic tumoricidal efficacy of combining the hexokinase (HK) inhibitor 2-deoxyglucose (2-DG) and the autophagy inhibitor chloroquine...
Our previous work has shown a synergistic tumoricidal efficacy of combining the hexokinase (HK) inhibitor 2-deoxyglucose (2-DG) and the autophagy inhibitor chloroquine (CQ) through intraperitoneal injections on HK2-addicted prostate cancers in animal models. The pharmacokinetic (PK) behaviors of these oral drugs after simultaneous oral administration have not been reported. We developed high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analytical methods for 2-DG and the clinically favored drug hydroxychloroquine (HCQ) for sera samples. Using a jugular vein-cannulated male rat model with serial blood collection before and after a single gavage dose of each drug alone or in combination, we examined their PK metrics for drug-drug interactions. The data demonstrated a rapid and complete separation of 2-DG from common monosaccharides by HPLC-MS-MS multi-reaction monitoring. Application of the HPLC-MS-MS 2-DG and HCQ methods to sera samples of nine rats showed a peak time (T ) for 2-DG of 0.5 h after 2-DG alone or with HCQ and identical post-peak half-life of approximately 1 h. With a seemingly bi-modal time course for HCQ, the T for HCQ alone (1.2 h) was faster than that for the combination (2 h; p = .017). After combination dosing, the peak concentration (C ) and area under the curve (AUC ) of 2-DG were decreased by 53.8% (p = .0004) and 53.7% (p = .0001), whereas AUC for HCQ was decreased by 30.8% (p = .0279) from the respective single dosing. Without changing the mean residence time (MRT ) of each drug, the combination affected the apparent volume of distribution (V ) and clearance (CL) of 2-DG, and CL for HCQ without affecting its V . We observed significant negative PK interactions, probably at the intestinal absorption level, between 2-DG and HCQ taken simultaneously by mouth. Future optimization efforts are warranted for their combination regimen for clinical translation.
Topics: Male; Rats; Animals; Hydroxychloroquine; Chromatography, High Pressure Liquid; Liquid Chromatography-Mass Spectrometry; Administration, Oral; Deoxyglucose
PubMed: 38294142
DOI: 10.1002/prp2.1173 -
Journal of the American Heart... May 2023Background Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in...
Background Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in the same model. We examined metabolic changes during the development of diastolic and severe systolic dysfunction in spontaneously hypertensive rats (SHR). Methods and Results We serially measured myocardial glucose uptake rates with dynamic 2-[F] fluoro-2-deoxy-d-glucose positron emission tomography in vivo in 9-, 12-, and 18-month-old SHR and Wistar Kyoto rats. Cardiac magnetic resonance imaging determined systolic function (ejection fraction) and diastolic function (isovolumetric relaxation time) and left ventricular mass in the same rats. Cardiac metabolomics was performed at 12 and 18 months in separate rats. At 12 months, SHR hearts, compared with Wistar Kyoto hearts, demonstrated increased isovolumetric relaxation time and slightly reduced ejection fraction indicating diastolic and mild systolic dysfunction, respectively, and higher (versus 9-month-old SHR decreasing) 2-[F] fluoro-2-deoxy-d-glucose uptake rates (Ki). At 18 months, only few SHR hearts maintained similar abnormalities as 12-month-old SHR, while most exhibited severe systolic dysfunction, worsening diastolic function, and markedly reduced 2-[F] fluoro-2-deoxy-d-glucose uptake rates. Left ventricular mass normalized to body weight was elevated in SHR, more pronounced with severe systolic dysfunction. Cardiac metabolite changes differed between SHR hearts at 12 and 18 months, indicating progressive defects in fatty acid, glucose, branched chain amino acid, and ketone body metabolism. Conclusions Diastolic and severe systolic dysfunction in SHR are associated with decreasing cardiac glucose uptake, and progressive abnormalities in metabolite profiles. Whether and which metabolic changes trigger progressive heart failure needs to be established.
Topics: Rats; Animals; Rats, Inbred SHR; Hypertension; Tomography, X-Ray Computed; Heart Failure; Rats, Inbred WKY; Glucose; Deoxyglucose; Blood Pressure
PubMed: 37183873
DOI: 10.1161/JAHA.122.026950 -
Nature Communications May 2024Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains...
Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8 T cells (T) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8 T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8 T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44CD62LCD8 T cells. Enhancement of CD8 T cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8 T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8 T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8 T cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials.
Topics: Glycolysis; Animals; CD8-Positive T-Lymphocytes; Humans; Cell Differentiation; Mice; Female; Breast Neoplasms; Microwaves; Immunologic Memory; Deoxyglucose; Cell Line, Tumor; Liver Neoplasms; Memory T Cells
PubMed: 38821965
DOI: 10.1038/s41467-024-49059-6 -
Journal For Immunotherapy of Cancer Nov 2022Twenty years after its initial introduction, Response Evaluation Criteria in Solid Tumors (RECIST) remains today a unique standardized tool allowing uniform objective... (Review)
Review
Twenty years after its initial introduction, Response Evaluation Criteria in Solid Tumors (RECIST) remains today a unique standardized tool allowing uniform objective evaluation of response in solid tumors in clinical trials across different treatment indications. Several attempts have been made to update or replace RECIST, but none have realized the general traction or uptake seen with RECIST. This communication provides an overview of some challenges faced by RECIST in the rapidly changing oncology landscape, including the incorporation of PET with F-fluorodeoxyglucose tracer as a tool for response assessment and the validation of criteria for use in trials involving immunotherapeutics. The latter has mainly been slow due to lack of data sharing. Work is ongoing to try to address this.We also aim to share our view as statistician representatives on the RECIST Working Group on what would be needed to validate new imaging endpoints for clinical trial use, with a specific focus on RECIST. Whether this could lead to an update of RECIST or replace RECIST altogether, depends on the changes being proposed. The ultimate goal remains to have a well defined, repeatable, confirmable and objective standard as provided by RECIST today.
Topics: Humans; Fluorodeoxyglucose F18; Neoplasms; Response Evaluation Criteria in Solid Tumors; Clinical Trials as Topic
PubMed: 36424032
DOI: 10.1136/jitc-2022-005092 -
Biomolecules Apr 2022Hydrogen sulfide (HS) and inorganic polysulfides are important signaling molecules; however, little is known about their role in adipose tissue. We examined the effect...
Hydrogen sulfide (HS) and inorganic polysulfides are important signaling molecules; however, little is known about their role in adipose tissue. We examined the effect of HS and polysulfides on insulin sensitivity of the adipose tissue in rats. Plasma glucose, insulin, non-esterified fatty acids, and glycerol were measured after administration of HS and the polysulfide donors, NaS and NaS, respectively. In addition, the effect of NaS and NaS on insulin-induced glucose uptake and inhibition of lipolysis was studied in adipose tissue explants ex vivo. NaS and NaS administered in vivo at a single dose of 100 μmol/kg had no effect on plasma glucose and insulin concentrations. In addition, NaS and NaS did not modify the effect of insulin on plasma glucose, fatty acids, and glycerol concentrations. NaS and NaShad no effect on the antilipolytic effect of insulin in adipose tissue explants ex vivo. The effect of insulin on 2-deoxyglucose uptake by adipose tissue was impaired in obese rats which was accompanied by lower insulin-induced tyrosine phosphorylation of IRS-1 and Akt. NaS, but not NaS, improved insulin signaling and increased insulin-stimulated 2-deoxyglucose uptake by adipose tissue of obese rats. The results suggest that polysulfides may normalize insulin sensitivity, at least in the adipose tissue, in obesity/metabolic syndrome.
Topics: Adipose Tissue; Animals; Blood Glucose; Deoxyglucose; Glycerol; Hydrogen Sulfide; Insulin; Insulin Resistance; Obesity; Rats; Sulfides
PubMed: 35625574
DOI: 10.3390/biom12050646