Early Post-ischemic Brain Glucose Metabolism Is Dependent on Function of TLR2: a Study Using [18F]F-FDG PET-CT in a Mouse Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Abstract Purpose The mammalian brain glucose metabolism is tightly and sensitively regulated. An ischemic brain injury caused by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) affects cerebral function and presumably also glucose metabolism. The majority of patients who survive CA suffer from cognitive deficits and physical disabilities. Toll-like receptor 2 (TLR2) plays a crucial role in inflammatory response in ischemia and reperfusion (I/R). Since deficiency of TLR2 was associated with increased survival after CA-CPR, in this study, glucose metabolism was measured using non-invasive [18F]F-FDG PET-CT imaging before and early after CA-CPR in a mouse model comparing wild-type (WT) and TLR2-deficient (TLR2−/−) mice. The investigation will evaluate whether FDG-PET could be useful as an additional methodology in assessing prognosis. Procedures Two PET-CT scans using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) tracer were carried out to measure dynamic glucose metabolism before and early after CPR. To achieve this, anesthetized and ventilated adult female WT and TLR2−/− mice were scanned in PET-CT. After recovery from the baseline scan, the same animals underwent 10-min KCL-induced CA followed by CPR. Approximately 90 min after CA, measurements of [18F]F-FDG uptake for 60 min were started. The [18F]F-FDG standardized uptake values (SUVs) were calculated using PMOD-Software on fused FDG-PET-CT images with the included 3D Mirrione-Mouse-Brain-Atlas. Results The absolute SUVmean of glucose in the whole brain of WT mice was increased about 25.6% after CA-CPR. In contrast, the absolute glucose SUV in the whole brain of TLR2−/− mice was not significantly different between baseline and measurements post CA-CPR. In comparison, baseline measurements of both mouse strains show a highly significant difference with regard to the absolute glucose SUV in the whole brain. Values of TLR2−/− mice revealed a 34.6% higher glucose uptake. Conclusions The altered mouse strains presented a different pattern in glucose uptake under normal and ischemic conditions, whereby the post-ischemic differences in glucose metabolism were associated with the function of key immune factor TLR2. There is evidence for using early FDG-PET-CT as an additional diagnostic tool after resuscitation. Further studies are needed to use PET-CT in predicting neurological outcomes.

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Early post-ischemic glucose metabolism is dependent on function of TLR2: a study using [18F]FDG PET-CT in a mouse model of cardiac arrest and cardiopulmonary resuscitation

10.21203/rs.3.rs-326507/v1 ◽

2021 ◽

Author(s):

Rika Bajorat ◽

Jens Kurth ◽

Jan Stenzel ◽

Brigitte Vollmar ◽

Bernd J. Krause ◽

...

Keyword(s):

Cardiac Arrest ◽

Glucose Metabolism ◽

Cardiopulmonary Resuscitation ◽

Mouse Model ◽

Fdg Pet ◽

Mouse Strains ◽

Whole Brain ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Abstract Purpose: An ischemic brain injury caused by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) affects cerebral function and presumably also brain glucose metabolism. The majority of patients who survive CA suffer from cognitive deficits and physical disabilities. Toll-like receptor 2 (TLR2) plays a cruical role in inflammatory response in ischemia and reperfusion (I/R). Since deficiency of TLR2 was associated with increased survival after CA-CPR, in this study glucose metabolism was measured using non-invasive [18F]FDG PET-CT imaging before and early after CA-CPR in a mouse model comparing wild type (WT) and TLR2-deficient (TLR2-/-) mice. Methods: Two PET-CT scans using [18F]FDG tracer were carried out to measure dynamic glucose metabolism before and early after CPR. To achieve this, anesthetized and ventilated adult female WT and TLR2-/- mice were scanned in PET-CT. After recovery from the baseline scan, the same animals underwent 10-minute CA followed by CPR and approximately 90 min after CA measurements of [18F]FDG uptake were started. The [18F]FDG standardized uptake values (SUVs) were calculated using PMOD-Software on fused FDG-PET-CT images with the included 3D Mirrione-Mouse-Brain-Atlas. Results: The absolute SUV of glucose in the whole brain of WT mice was increased after CA-CPR. In contrast, the absolute glucose SUV in the whole brain of TLR2-/- mice was not significantly different between basal and measurements after CA-CPR. In comparison, basal measurements of both mouse strains show a significant difference in the whole brain absolute glucose SUVs, whereby TLR2-/- mice revealed 34.6% higher values. The altered mouse strains presented a different pattern in glucose uptake under normal and ischemic conditions. Conclusion: There is evidence that the post-ischemic differences in glucose metabolism were associated with the function of TLR2 and that PET-CT imaging could be useful as an additional methodology in assessing diagnosis and prognosis during post-cardiac arrest care. Further studies are needed.

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Effects on 18F-FDG PET/CT Brain Glucose Metabolism in Rectal Cancer Patients Undergoing Neoadjuvant Chemotherapy

Clinical Nuclear Medicine ◽

10.1097/rlu.0000000000001862 ◽

2017 ◽

Vol 42 (12) ◽

pp. e484-e490 ◽

Cited By ~ 1

Author(s):

Alexei M. C. Machado ◽

Theara C. Fagundes ◽

Arnoldo Mafra ◽

Rodrigo G. Silva ◽

Ana Carolina G. Castro ◽

...

Keyword(s):

Rectal Cancer ◽

Glucose Metabolism ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Fdg Pet ◽

Brain Glucose ◽

Pet Ct ◽

18F Fdg ◽

Ct Brain ◽

Fdg Pet Ct

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Increased brain glucose metabolism in chronic severe traumatic brain injury as determined by longitudinal 18F-FDG PET/CT

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2018.08.052 ◽

2018 ◽

Vol 57 ◽

pp. 20-25 ◽

Cited By ~ 4

Author(s):

Tomohiro Yamaki ◽

Yoshio Uchino ◽

Haruko Henmi ◽

Mizuho Kamezawa ◽

Miyoko Hayakawa ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Glucose Metabolism ◽

Severe Traumatic Brain Injury ◽

Fdg Pet ◽

Brain Glucose ◽

Brain Glucose Metabolism ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

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18F-FDG PET/CT brain glucose metabolism as a marker of different types of depression comorbidity in chronic systolic heart failure patients

European Heart Journal ◽

10.1093/ehjci/ehaa946.1153 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

V Lyra ◽

J Parissis ◽

M Kallergi ◽

E Rizos ◽

G Filippatos ◽

...

Keyword(s):

Fdg Pet ◽

Nyha Class ◽

Whole Brain ◽

Brain Glucose ◽

Regional Brain ◽

Pet Ct ◽

Different Types ◽

18F Fdg ◽

Fdg Pet Ct ◽

Pet Ct Scan

Abstract Background/Introduction Depression comorbidity is an important issue in heart failure (HF) disease. Results from the recent prospective randomized trial MOOD-HF did not provide a rationale for the indiscriminate use of antidepressants in depressed HF patients. Purpose The study investigated whole-brain and regional-brain glucose metabolism in HF patients with 18F-FDG PET/CT and its association with depression comorbidity. Methods Twenty-nine hospitalized patients with symptomatic systolic HF disease (LVEF<40%), NYHA class II-IV and mean age of 55.5±12.0 years participated in the study. All patients had echocardiography, blood sampling, HF-adapted and psychometric questionnaires before discharge and a brain 18F-FDG PET/CT scan after discharge. Semi-automated PET/CT image analysis was performed on all patients and 30 matched controls. The metabolic index SUVmean was calculated for the whole-brain and three brain regions (prefrontal cortex, amygdala and hippocampus), implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing depression-related regional-brain SUVmean with the whole-brain SUVmean. Results HF patients had lower average whole-brain SUVmean (3.90±1.49 vs 5.10±1.35, p=0.001), average regional-brain SUVmean (4.57±2.31 vs 9.96±3.58, p<0.001) and average standardized SUVmean (1.28±0.60 vs 2.07±1.32, p<0.001) compared to controls. Whole-brain SUVmean had a statistically significant correlation to patient age (r=−0.39, p=0.031), NYHA class (p=0.027), LVEF in the major group of 21 NYHA III-IV patients (p=0.018), diabetes comorbidity (p=0.001), creatinine levels (r=−0.49, p=0.005) and depression (r=−0.36, p=0.049). Regional-brain SUVmean was correlated to whole-brain SUVmean (r=0.53, p=0.002) and depression (r=0.46, p=0.011). The standardized SUVmean, in particular, was found to be a robust index that could differentiate HF patients with “epiphenomenal” (>0.93) or “real” (≤0.93) depression. Conclusion HF patients with more severe disease showed whole-brain and regional-brain hypometabolism in 18F-FDG PET/CT scan, which is consistent with impaired cerebral perfusion. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between “epiphenomenal” and “real” depression. Namely, presence of whole-brain hypometabolism suggested “epiphenomenal” depression. Absence of whole-brain hypometabolism suggested “real” depression. When the pattern of whole-brain hypometabolism included significant relative, depression-related regional hypometabolism (standardized SUVmean ≤0.93), “real” depression was the most likely diagnosis. The distinction is important, as different types of comorbid depression suggest different treatment approach. Summarizing figure Funding Acknowledgement Type of funding source: None

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Abnormal Brain Glucose Metabolism in Papillary Thyroid Cancer Patients 4 Weeks After Withdrawal of Levothyroxine: A Cross-Sectional Study Using 18F-FDG PET/CT

Frontiers in Endocrinology ◽

10.3389/fendo.2021.595933 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shu-qi Wu ◽

Fang Feng ◽

Ren-jian Zou ◽

Hong-liang Fu ◽

Jia-wei Sun ◽

...

Keyword(s):

Thyroid Cancer ◽

Glucose Metabolism ◽

Mood Disorders ◽

Fdg Pet ◽

Rating Scale ◽

Depression And Anxiety ◽

Papillary Thyroid ◽

Brain Glucose ◽

Pet Ct ◽

Fdg Pet Ct

BackgroundThere is no doubt that thyroid dysfunction is associated with psychiatric disorders. A large amount of thyroid carcinoma patients displayed mood disorders after the withdrawal of levothyroxine (LT4). However, it is unclear whether the disorders are related to the transient withdrawal of LT4, and if yes, what the possible underlying mechanism is. This study aims to investigate the abnormal regional cerebral glucose metabolism (rCMRglu) in a group of papillary thyroid cancer (PTC) patients without LT4 for 4 weeks and prove the relationship between the abnormal rCMRglu with depression and anxiety.MethodsBrain 18F-FDG PET/CT data of 38 consecutive PTC patients with high/intermediate-risk from June 2016 to December 2017 have been analyzed. Of the 38 patients, 23 are in the LT4 withdrawal group (WG) and 15 in the LT4 replacement group (RG). These patients were also evaluated for depressive and anxiety symptoms within 24 h after the scans based on the Hamilton Depression Rating Scale (17 items, HRDS-17) and the Hamilton Anxiety Rating Scale (HAMA) respectively.ResultsThirty-eight patients (12 men, 26 women; age range, 25–69 years; mean age, 45.8 years) were selected in the study. Compared with the RG, patients in WG showed depression and anxiety with higher total scores of HRDS-17 and HAMA (14.7 ± 5.8 vs 3.8 ± 5.5, t = −5.74, p = 0.00; 9.3 ± 4.3 vs 2.7 ± 4.1, t = −4.74, p = 0.00, respectively). In the brain glucose metabolism analysis, the WG patients showed lower rCMRglu in Occipital_Mid_R and Postcentral_L. On the other hand, data illustrated significant rCMRglu increases in the Frontal_Sup_Orb_L. Compared with the healthy group (HG), the rCMRglu of the Postcentral_L and Precuneus_L showed hypoactivity, but the Hippocampus_R and the Temporal_Inf_L showed hyperactivity. This analysis yielded a significant correlation between abnormal rCMRglu with the free thyroxine level, the serum thyroid-stimulating hormone level, HRDS-17, and HAMA scores.ConclusionsThe findings showed that more PTC patients exhibited depression and anxiety after LT4 withdrawal for 4 weeks. More attention should be paid to these hypothyroid patients while they were in the hospital. Such a short-term LT4 withdrawal also likely induced abnormal rCMRglu. Our study attempts to explain the possible mechanism of mood disorders related to transient hypothyroidism.

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Effect of Peptide Receptor Radionuclide Therapy on Somatostatin Receptor Status and Glucose Metabolism in Neuroendocrine Tumors: Intraindividual Comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT

International Journal of Molecular Imaging ◽

10.1155/2011/524130 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 18

Author(s):

Sowon Oh ◽

Vikas Prasad ◽

Dong Soo Lee ◽

R. P. Baum

Keyword(s):

Glucose Metabolism ◽

Neuroendocrine Tumors ◽

Fdg Pet ◽

Radionuclide Therapy ◽

Somatostatin Receptor ◽

Peptide Receptor Radionuclide Therapy ◽

Receptor Expression ◽

Peptide Receptor ◽

Pet Ct ◽

Fdg Pet Ct

The heterogeneous nature of the neuroendocrine tumors (NET) makes it challenging to find one uniformly applicable management protocol which is especially true for diagnosis. The discovery of the overexpression of somatostatin receptors (SMS-R) on neuroendocrine tumor cells lead to the generalized and rapid acceptance of radiolabeled somatostatin receptor analogs for staging and restaging of NET as well as for Peptide Receptor Radionuclide Therapy (PRRNT) using Y-90 and Lu-177 DOTATATE/DOTATOC. In this present work we tried to look in to the effect of PRRNT on the glucose metabolism assessed by F-18 FDG PET/CT and SMS-R density assessed by Ga-68 DOTANOC PET/CT. We observed a complex relationship between the somatostatin receptor expression and glucose metabolism with only 56% (77/138) of the lesions showing match, while the others show mismatch between the receptor status and metabolism. The match between receptor expression and glucose metabolism increases with the grade of NET. In grade 3 NET, there is a concurrence between the changes in glucose metabolism and somatostatin receptor expression. PRRNT was found to be more effective in lesions with higher receptor expression.

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