Chronic hypoperfusion due to intracranial large artery stenosis is not associated with cerebral ß-amyloid deposition and brain atrophy.

BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION: Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral ß-amyloid deposition and neurodegeneration in humans.

CT Texture Analysis for Differentiating Bronchiolar Adenoma, Adenocarcinoma In Situ, and Minimally Invasive Adenocarcinoma of the Lung.

Purpose: This study aimed to investigate the potential of computed tomography (CT) imaging features and texture analysis to distinguish bronchiolar adenoma (BA) from adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA). Materials and Methods: Fifteen patients with BA, 38 patients with AIS, and 36 patients with MIA were included in this study. Clinical data and CT imaging features of the three lesions were evaluated. Texture features were extracted from the thin-section unenhanced CT images using Artificial Intelligence Kit software. Then, multivariate logistic regression analysis based on selected texture features was employed to distinguish BA from AIS/MIA. Receiver operating characteristics curves were performed to determine the diagnostic performance of the features. Results: By comparison with AIS/MIA, significantly different CT imaging features of BA included nodule type, tumor size, and pseudo-cavitation sign. Among them, pseudo-cavitation sign had a moderate diagnostic value for distinguishing BA and AIS/MIA (AUC: 0.741 and 0.708, respectively). Further, a total of 396 quantitative texture features were extracted. After comparation, the top six texture features showing the most significant difference between BA and AIS or MIA were chosen. The ROC results showed that these key texture features had a high diagnostic value for differentiating BA from AIS or MIA, among which the value of a comprehensive model with six selected texture features was the highest (AUC: 0.977 or 0.976, respectively) for BA and AIS or MIA. These results indicated that texture analyses can effectively improve the efficacy of thin-section unenhanced CT for discriminating BA from AIS/MIA. Conclusion: CT texture analysis can effectively improve the efficacy of thin-section unenhanced CT for discriminating BA from AIS/MIA, which has a potential clinical value and helps pathologist and clinicians to make diagnostic and therapeutic strategies.

18F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats.

A majority of blast-induced mild traumatic brain injury (mTBI) patients experience persistent neurological dysfunction with no findings on conventional structural MR imaging. It is urgent to develop advanced imaging modalities to detect and understand the pathophysiology of blast-induced mTBI. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) could detect neuronal function and activity of the injured brain, while MR spectroscopy provides complementary information and assesses metabolic irregularities following injury. This study aims to investigate the effectiveness of combining 18F-FDG PET with MR spectroscopy to evaluate acute and subacute metabolic cerebral alterations caused by blast-induced mTBI. Thirty-two adult male Sprague-Dawley rats were exposed to a single blast (mTBI group) and 32 rats were not exposed to the blast (sham group), followed by 18F-FDG PET, MRI, and histological evaluation at baseline, 1-3 h, 1 day, and 7 days post-injury in three separate cohorts. 18F-FDG uptake showed a transient increase in the amygdala and somatosensory cortex, followed by a gradual return to baseline from day 1 to 7 days post-injury and a continuous rise in the motor cortex. In contrast, decreased 18F-FDG uptake was seen in the midbrain structures (inferior and superior colliculus). Analysis of MR spectroscopy showed that inflammation marker myo-inositol (Ins), oxidative stress marker glutamine + glutamate (Glx), and hypoxia marker lactate (Lac) levels markedly elevated over time in the somatosensory cortex, while the major osmolyte taurine (Tau) level immediately increased at 1-3 h and 1 day, and then returned to sham level on 7 days post-injury, which could be due to the disruption of the blood-brain barrier. Increased 18F-FDG uptake and elevated Ins and Glx levels over time were confirmed by histology analysis which showed increased microglial activation and gliosis in the frontal cortex. These results suggest that 18F-FDG PET and MR spectroscopy can be used together to reflect more comprehensive neuropathological alterations in vivo, which could improve our understanding of the complex alterations in the brain after blast-induced mTBI.

Biological Significance of 18F-FDG PET/CT Maximum Standard Uptake Value for Predicting EGFR Mutation Status in Non-Small Cell Lung Cancer Patients.

PURPOSE: To investigate the potential of maximum standardized uptake value (SUVmax) in predicting epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) patients. METHODS: Clinical data of 311 NSCLC patients who had undergone both EGFR mutation test and 18F-FDG PET/CT scans between January 2013 and December 2017 at our hospital were retrospectively analyzed. Patients were sub-grouped by their origin of SUVmax. Univariate and multivariate analyses were performed to investigate the association between clinical factors and EGFR mutations. Receiver operating characteristic curve (ROC) analysis was performed to confirm the predictive value of clinical factors. In vitro experiments were performed to confirm the correlation between EGFR mutations and glycolysis. RESULTS: EGFR-mutant patients had higher SUVmax than the wild-type patients in both primary tumors and metastases. In the multivariate analysis, SUVmax, gender and histopathologic type were determined as independent predictors of EGFR mutation status for patients whose SUVmax were obtained from the primary tumors; while for patients whose SUVmax were obtained from the metastases, SUVmax, smoking status and histopathologic type were regarded as independent predictors. ROC analysis showed that SUVmax of the primary tumors (cut off >10.92), not of the metastases, has better predictive value than other clinical factors in predicting EGFR mutation status. The predict performance was improved after combined SUVmax with other independent predictors. In addition, our in vitro experiments demonstrated that lung cancer cells with EGFR mutations have higher aerobic glycolysis level than wild-type cells. CONCLUSION: SUVmax of the primary tumors has the potential to serve as a biomarker to predict EGFR mutation status in NSCLC patients.

White Matter Atrophy in Type 2 Diabetes Mellitus Patients With Mild Cognitive Impairment.

Type 2 diabetes mellitus (T2DM) patients are highly susceptible to developing dementia, especially for those with mild cognitive impairment (MCI), but its underlying cause is still unclear. In this study, we performed a battery of neuropsychological tests and high-resolution sagittal T1-weighted structural imaging to explore how T2DM affects white matter volume (WMV) and cognition in 30 T2DM-MCI patients, 30 T2DM with normal cognition (T2DM-NC) patients, and 30 age-, sex-, and education-matched healthy control (HC) individuals. The WMV of the whole brain was obtained with automated segmentation methods. Correlations between the WMV of each brain region and neuropsychological tests were analyzed in the T2DM patients. The T2DM-NC patients and HC individuals did not reveal any significant differences in WMV. Compared with the T2DM-NC group, the T2DM-MCI group showed statistically significant reduction in the WMV of seven brain regions, mainly located in the frontotemporal lobe and limbic system, five of which significantly correlated with Montreal Cognitive Assessment (MoCA) scores. Subsequently, we evaluated the discriminative ability of these five regions for MCI in T2DM patients. The WMV of four regions, including left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus had high diagnostic value for MCI detection in T2DM patients (AUC > 0.7). Among these four regions, left precuneus WMV presented the best diagnostic value (AUC: 0.736; sensitivity: 70.00%; specificity: 73.33%; Youden index: 0.4333), but with no significant difference relative to the minimum AUC. In conclusion, T2DM could give rise to the white matter atrophy of several brain regions. Each WMV of left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus could be an independent imaging biomarker to detect cognitive impairment at the early stage in T2DM patients and play an important role in its pathophysiological mechanism.

Brain Amyloid-ß Deposition and Blood Biomarkers in Patients with Clinically Diagnosed Alzheimer's Disease.

Brain amyloid-ß (Aß) deposition is a hallmark to define Alzheimer's disease (AD). We investigated the positive rate of brain amyloid deposition assessed with 11C-Pittsburgh compound (PiB)-PET and blood Aß levels in a cohort of probable AD patients who were diagnosed according to the 1984 NINCDS-ADRDA criteria. Eighty-four subjects with a clinical diagnosis of probable AD dementia, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) status were subjected to PiB-PET and 18F-fluorodeoxyglucose (FDG)-PET scans. Plasma biomarkers of Aß42, Aß40, and T-tau were measured using single molecule array technology. The positive rate of PiB-PET, the associations between PiB-PET status and FDG-PET, plasma biomarkers, and clinical manifestations were analyzed. PiB-PET was positive in 77.36% of probable AD patients, 31.80% of MCI patients, and 0 of NC. Plasma Aß42/Aß40 ratio was associated with PiB-PET, the ROC curve analysis revealing an AUC of 0.77 (95% CI: 0.66-0.87), with a sensitivity of 82% and specificity of 64%. Some clinical manifestations were associated with PiB-PET imaging. Our findings indicate that only three-fourths of patients diagnosed with probable AD fit the pathological criteria, suggesting that we should be cautious regarding the accuracy of AD diagnosis when no biomarker evidence is available in our clinical practice.

Validation of abnormal glucose metabolism associated with Parkinson's disease in Chinese participants based on 18F-fluorodeoxyglucose positron emission tomography imaging.

PURPOSE: We previously identified disease-related cerebral metabolic characteristics associated with Parkinson's disease (PD) in the Chinese population using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging. The present study aims to assess data reproducibility and robustness of the metabolic activity characteristics across independent cohorts. PATIENTS AND METHODS: Forty-eight patients with PD and 48 healthy controls from Chongqing district, in addition to 33 patients with PD and 33 healthy controls from Shanghai district were recruited. Each subject underwent brain 18F-FDG PET/CT imaging in a resting state. Based on the brain images, differences between the groups and PD-related cerebral metabolic activities were graphically and quantitatively evaluated. RESULTS: Both PD patient cohorts exhibited analogous cerebral patterns characterized by metabolic increase in the putamen, globus pallidus, thalamus, pons, sensorimotor cortex and cerebellum, along with metabolic decrease in parieto-occipital areas. Additionally, the metabolic pattern was highly indicative of the disease, with a significant elevation in PD patients compared with healthy controls (p<0.001) in both the derivation (Shanghai) and validation (Chongqing) cohorts. CONCLUSION: This dual-center study demonstrated the high comparability and reproducibility of PD-related cerebral metabolic activity patterns across independent Chinese cohorts and may serve as an objective diagnostic marker for the disease.

The Utility of 18F-FDG PET/CT for Monitoring Response and Predicting Prognosis after Glucocorticoids Therapy for Sarcoidosis.

Sarcoidosis has significant heterogeneity involving multiple organs; treatment of the disease is a significant therapeutic challenge due to the difficulties in accurately monitoring disease activity and estimating prognosis. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) plays an important role in assessing the metabolic activity. However, there is not enough evidence about the influence of this method in the clinical management and prognosis prediction for sarcoidosis. This study aims to investigate the clinical utility of 18F-FDG PET/CT for therapeutic evaluation and prognostic prediction in sarcoidosis. We had retrospectively enrolled 23 patients with sarcoidosis assigned to receive systemic glucocorticoids. All patients underwent baseline 18F-FDG PET/CT before initiating therapy and follow-up 18F-FDG PET/CT within 3 months after the therapy. The metabolic and clinical responses were classified. The baseline 18F-FDG PET/CT showed increased uptake in all patients. Based solely on biopsy-proven sites, the sensitivity of 18F-FDG PET/CT was 91.7%, and the sensitivity improved to 100% after excluding skin involvement. In the subsequent follow-up PET scans within 3 months after glucocorticoids therapy, the SUVmax were variously decreased except one; there are significant differences in the clinical remission rates and the relapse rates between patients with a favorable response and cases with no response on follow-up PET scan, the increasing metabolic response was associated with the increase in clinical remission rates and the reduction in recurrence rates. In conclusion, the present study shows that 18F-FDG PET/CT is an effective way to monitor the early therapeutic reaction and is helpful in predicting the long-term prognosis of sarcoidosis.

Enjoyment of Spicy Flavor Enhances Central Salty-Taste Perception and Reduces Salt Intake and Blood Pressure.

High salt intake is a major risk factor for hypertension and is associated with cardiovascular events. Most countries exhibit a traditionally high salt intake; thus, identification of an optimal strategy for salt reduction at the population level may have a major impact on public health. In this multicenter, random-order, double-blind observational and interventional study, subjects with a high spice preference had a lower salt intake and blood pressure than subjects who disliked spicy food. The enjoyment of spicy flavor enhanced salt sensitivity and reduced salt preference. Salt intake and salt preference were related to the regional metabolic activity in the insula and orbitofrontal cortex (OFC) of participants. Administration of capsaicin-the major spicy component of chili pepper-enhanced the insula and OFC metabolic activity in response to high-salt stimuli, which reversed the salt intensity-dependent differences in the metabolism of the insula and OFC. In animal study, OFC activity was closely associated with salt preference, and salty-taste information processed in the OFC was affected in the presence of capsaicin. Thus, interventions related to this region may alter the salt preference in mice through fiber fluorometry and optogenetic techniques. In conclusion, enjoyment of spicy foods may significantly reduce individual salt preference, daily salt intake, and blood pressure by modifying the neural processing of salty taste in the brain. Application of spicy flavor may be a promising behavioral intervention for reducing high salt intake and blood pressure.

Enhancement of Neural Salty Preference in Obesity.

BACKGROUND/AIMS: Obesity and high salt intake are major risk factors for hypertension and cardiometabolic diseases. Obese individuals often consume more dietary salt. We aim to examine the neurophysiologic effects underlying obesity-related high salt intake. METHODS: A multi-center, random-order, double-blind taste study, SATIETY-1, was conducted in the communities of four cities in China; and an interventional study was also performed in the local community of Chongqing, using brain positron emission tomography/computed tomography (PET/CT) scanning. RESULTS: We showed that overweight/obese individuals were prone to consume a higher daily salt intake (2.0 g/day higher compared with normal weight individuals after multivariable adjustment, 95% CI, 1.2-2.8 g/day, P < 0.001), furthermore they exhibited reduced salt sensitivity and a higher salt preference. The altered salty taste and salty preference in the overweight/obese individuals was related to increased activity in brain regions that included the orbitofrontal cortex (OFC, r = 0.44, P= 0.01), insula (r = 0.38, P= 0.03), and parahippocampus (r = 0.37, P= 0.04). CONCLUSION: Increased salt intake among overweight/obese individuals is associated with altered salt sensitivity and preference that related to the abnormal activity of gustatory cortex. This study provides insights for reducing salt intake by modifying neural processing of salty preference in obesity.

A novel use of hill function and utility of 99mTc-MIBI scintigraphy to detect earlier lower extremity microvascular perfusion in patients with type 2 diabetes.

We use the Hill function to analyze the dynamics of Tc-99m 2 methoxy-isobutyl-isonitrile (Tc-MIBI) scintigraphy data and to examine the earlier lower extremity microvascular perfusion of diabetic patients without typical clinical symptoms and with the preserved normal ankle-brachial index (ABI).Eighty-eight participants (30 healthy control, 34 diabetic patients, and 24 diabetic patients with peripheral arterial disease [PAD]) were recruited and applied Tc-MIBI scintigraphy. Fourteen diabetic patients with PAD also underwent computed tomography angiography (CTA) examination and were performed endovascular interventions.Diabetic patients with normal ABI already have significantly impaired maximum Tc-MIBI muscle perfusion counts (P < .001) and the peak times of the lower extremity muscle perfusion (P < .05). Tc-MIBI scintigraphy showed great consistent with ABI and CTA in detecting PAD. Tc-MIBI scintigraphy was also found to be effective in evaluating lower extremity circulation after endovascular interventions (P < .05).Hill function-based analysis of Tc-MIBI scintigraphy might be effective method to evaluate earlier lower extremity perfusion changes in diabetic patients.

Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity.

Brown adipose tissue (BAT) is an energy-expending organ that produces heat. Expansion or activation of BAT prevents obesity and diabetes. Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1 (UCP1) activation triggered via a ß-adrenergic pathway. Here, we report that the cold-sensing transient receptor potential melastatin 8 (TRPM8) is functionally present in mouse BAT. Challenging brown adipocytes with menthol, a TRPM8 agonist, up-regulates UCP1 expression and requires protein kinase A activation. Upon mimicking long-term cold exposure with chronic dietary menthol application, menthol significantly increased the core temperatures and locomotor activity in wild-type mice; these effects were absent in both TRPM8(-/-) and UCP1(-/-) mice. Dietary obesity and glucose abnormalities were also prevented by menthol treatment. Our results reveal a previously unrecognized role for TRPM8, suggesting that stimulation of this channel mediates BAT thermogenesis, which could constitute a promising way to treat obesity.

Application of radionuclide imaging to hepatic impact injury in rabbits.

OBJECTIVE: To investigate the role and clinical value of radionuclide imaging in hepatic impact injuries in rabbits. METHODS: Rabbits were experimentally impacted on the liver with BIM-IV bio-impact machine. Liver imaging was performed with 99mTc labeled sodium phytate. Liver blood pool imaging was performed with 99mTc-stannous pyrophosphate labeled red blood cells. The results of radionuclide imaging were compared with the anatomic results. RESULTS: There was significant difference between the images of the injured liver and the control. Radio diminution and defect were shown in the injured liver areas. Various sorts of abnormal radioactivity distribution were observed with hepatic blood pool imaging. The results of the liver imaging and liver blood pool imaging were accorded with the results of the anatomic findings. CONCLUSIONS: Radionuclide imaging may well display the changes of hepatocellular structures and functions after injury, which is valuable in locating the concrete injured position and differentiating the injured degrees of liver.

Changes of pulmonary intercellular adhesion molecule-1 and CD11b/CD18 in peripheral polymorphonuclear neutrophils and their significance at the early stage of burns.

OBJECTIVE: To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in the accumulation of polymorphonuclear neutrophils (PMN) in the lungs at the early stage of burns. METHODS: Myeloperoxidase content in lung tissues and bronchoalveolar lavage fluid (BALF) were detected. ICAM-1 and its mRNA expression in lung tissues were determined by immunohistochemical method and in situ hybridization. CD11b/CD18 expression on the peripheral PMNs was measured by flow cytometry. RESULTS: The levels of myeloperoxidase in lung tissues and BALF after burn injury were markedly higher than those of control. Expression of ICAM-1 and its mRNA in the lung tissues and CD11b/CD18 on peripheral PMNs surface was significantly increased at 2, 6, 12, 24 h after burns. CONCLUSIONS: PMNs accumulation in the lungs is related to increased ICAM-1 expression on pulmonary microvascular endothelial cells and CD11b/CD18 expression on PMN at the early stage of burn injury.