Magnetic Resonance Spectroscopy of Hypoxic-Ischemic Encephalopathy After Cardiac Arrest

Objective:To correlate brain metabolites to clinical outcome using magnetic resonance spectroscopy (MRS) in patients undergoing targeted temperature management (TTM) after cardiac arrest, and assess their relationships to MRI and EEG variables.Methods:A prospective cohort of 50 patients was studied. The primary outcome was coma recovery to follow commands. Comparison of MRS measures in the posterior cingulate gyrus, parietal white matter, basal ganglia, and brainstem were also made to 25 normative control subjects.Results:Fourteen of 50 achieved coma recovery before hospital discharge. There was a significant decrease in total N-acetyl-aspartate (NAA/Cr) and an increase in lactate (Lac/Cr) in patients who did not recover, with changes most prominent in the posterior cingulate gyrus. Patients who recovered had decrease in NAA/Cr as compared to control subjects. NAA/Cr had a strong monotonic relationship with MRI cortical apparent diffusion coefficient (ADC); lactate level exponentially increased with decreasing ADC. EEG suppression/burst suppression was universally associated with lactate elevation.Conclusions:NAA and lactate changes are associated with clinical/MRI/EEG changes consistent with hypoxic-ischemic encephalopathy (HIE) and are most prominent in the posterior cingulate gyrus. NAA/Cr decrease observed in patients with good outcomes suggests mild HIE in patients asymptomatic at hospital discharge. The appearance of cortical lactate represents a deterioration of aerobic energy metabolism and is associated with EEG background suppression, synaptic transmission failure, and severe, potentially irreversible HIE.Classification of Evidence:This study provides Class IV evidence that in patients undergoing TTM after cardiac arrest, brain MRS-determined decrease in total NAA/Cr and an increase in Lac/Cr are associated with an increased risk of not recovering.

Patterns of Distribution of 18F-THK5351 Positron Emission Tomography in Alzheimer’s Disease Continuum

Background: Alzheimer’s disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases. Objective: Using 18F-THK5351 as a tracer that binds to both tau and MAO-B, we investigated the changes in 18F-THK5351 accumulation patterns in AD continuum individuals with positive amyloid PET consisting of cognitively normal individuals (CNp), amnestic mild cognitive impairment (aMCI), and AD and cognitively normal individuals (CNn) with negative amyloid PET. Methods: We studied 69 individuals (32 CNn, 11 CNp, 9 aMCI, and 17 AD) with structural magnetic resonance imaging, 11C-Pittsburgh compound-B (PIB) and 18F-THK5351 PET, and neuropsychological assessment. 18F-THK5351 accumulation was evaluated with visual analysis, voxel-based analysis and combined region of interest (ROI)-based analysis corresponding to Braak neurofibrillary tangle stage. Results: On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351 accumulation between CNp and CNn. However, a slight increase of the bilateral posterior cingulate gyrus in aMCI and definite increase of the bilateral parietal temporal association area and posterior cingulate gyrus/precuneus in AD were detected compared with CNn. On ROI-based analyses, 18F-THK5351 accumulation correlated positively with supratentorial 11C-PIB accumulation and negatively with the hippocampal volume and neuropsychological assessment. Conclusion: The AD continuum showed an increase in 18F-THK5351 with stage progression, suggesting that 18F-THK5351 has the potential to visualize the severity of tau deposition and neurodegeneration in accordance with the AD continuum.

Relationship between Cerebrospinal Fluid Matrix Metalloproteinases Levels and Brain Amyloid Deposition in Mild Cognitive Impairment

This study aimed to explore whether cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) were associated with brain amyloid deposition, cortical glucose metabolism, and white matter lesions (WMLs) in individuals with amnestic mild cognitive impairment (MCI). A total of 33 individuals with amnestic MCI (mean age, 75.6 years) underwent 11C-Pittsburgh compound B positron emission tomography (PiB-PET), 18F-fluorodeoxyglucose positron emission tomography, magnetic resonance imaging or computed tomography, and CSF analysis. PET uptake of the frontal and temporoparietal lobes and posterior cingulate gyrus was assessed using the cerebellar cortex as the reference region. WMLs were assessed by the Fazekas scale. CSF levels of MMPs and TIMPs were measured with bead-based multiplex assays. After adjusting for covariates, multiple linear regression analysis showed that CSF levels of MMP-2 were negatively correlated with global PiB uptake (p = 0.035), especially in the parietotemporal lobe and posterior cingulate gyrus (p = 0.016 and p = 0.041, respectively). Moreover, CSF levels of MMP-7 were positively correlated with the severity of WMLs (p = 0.033). CSF levels of MMP-2 and MMP-7 are associated with brain amyloid deposition and severity of WMLs, respectively. These findings provide valuable insights into the role of MMPs in amyloid β catabolism and blood–brain barrier integration at the MCI stage.

High Glycemic Diet Is Related to Brain Amyloid Accumulation Over One Year in Preclinical Alzheimer's Disease

Objective: To test the hypothesis that high glycemic diet is related to 1-year change in brain amyloid based on our prior cross-sectional evidence that high glycemic diet is associated with brain amyloid.Methods: This longitudinal, observational study assessed the relationship between reported habitual consumption of a high glycemic diet (HGDiet) pattern and 1-year brain amyloid change measured by Florbetapir F18 PET scans in 102 cognitively normal older adults with elevated or sub-threshold amyloid status that participated in a 1-year randomized, controlled exercise trial at the University of Kansas Medical Center in Kansas City.Results: Among all participants (n = 102), higher daily intake of the HGDiet pattern (β = 0.06, p = 0.04), sugar (β = 0.07, p = 0.01), and total carbohydrate (β = 0.06, p = 0.04) were related to more precuneal amyloid accumulation. These relationships in the precuneus were accentuated in participants with elevated amyloid at enrollment (n = 70) where higher intake of the HGDiet pattern, sugar, and carbohydrate were related to more precuneal amyloid accumulation (β = 0.11, p = 0.01 for all measures). In individuals with elevated amyloid, higher intake of the HGDiet pattern was also related to more amyloid accumulation in the lateral temporal lobe (β = 0.09, p < 0.05) and posterior cingulate gyrus (β = 0.09, p < 0.05) and higher sugar and carbohydrate intake were also related to more amyloid accumulation in the posterior cingulate gyrus (β = 0.10, p < 0.05 for both measures).Conclusion: This longitudinal observational analysis suggests that a high glycemic diet relates to higher brain amyloid accumulation over 1 year in regions of the temporoparietal cortex in cognitively normal adults, particularly in those with elevated amyloid status. Further studies are required to assess whether there is causal link between a high glycemic diet and brain amyloid.Clinical Trial Registration:ClinicalTrials.gov, Identifier (NCT02000583).

Magnetic resonance spectroscopy of anoxic brain injury after cardiac arrest

Objective: We describe magnetic resonance spectroscopy (MRS) changes in comatose patients undergoing targeted temperature management (TTM) after cardiac arrest, and their relationships to relevant clinical, MRI, and EEG variables. Methods A prospective cohort of 50 patients was studied. The primary outcome was coma recovery to follow commands. Comparison of MRS measures in the posterior cingulate gyrus, parietal white matter, basal ganglia, and brainstem were also made to 25 normative control subjects. Results: Fourteen of 50 achieved coma recovery. Compared to patients who recovered, there was a significant decrease in total N-acetyl-aspartate (NAA/Cr) and glutamate; and an increase in lactate (Lac/Cr) and glutamine in patients who did not recover, with changes most prominent in the posterior cingulate gyrus. Patients who recovered had a decrease in NAA/Cr as compared to control subjects. Coma recovery was seen in patients with a moderate decrease in NAA/Cr, but the appearance of lactate resulted in a poor outcome. NAA/Cr had a linear relationship with MRI cortical apparent diffusion coefficient (ADC); lactate level exponentially increased with decreasing ADC. EEG suppression/burst suppression was universally associated with lactate elevation. Conclusions NAA and lactate changes are associated with clinical/MRI/EEG changes consistent with anoxic brain injury and are most prominent in the posterior cingulate gyrus. NAA/Cr decrease observed in patients with good outcomes suggests mild anoxic injury in patients asymptomatic at hospital discharge. The appearance of cortical lactate represents a deterioration of aerobic energy metabolism and is associated with EEG background suppression, synaptic transmission failure, and severe, potentially irreversible anoxic injury.

ANALYSIS OF RS-FMRI IMAGES CLARIFIES BRAIN ALTERATIONS IN TYPE 2 DIABETES MELLITUS PATIENTS WITH COGNITIVE IMPAIRMENT

Type 2 Diabetes Mellitus (T2DM) increases the risk of cognitive impairment (CI); however, the underlying pathophysiological mechanisms are still not well understood. We propose to clarify the altered spontaneous brain activity and functional connectivity implicated in CI of T2DM by analyzing resting state functional MRI (rs-fMRI) data. Totally 22 T2DM patients with cognitive impairment (T2DM-CI) and 31 T2DM patients with normal cognition (T2DM-NC) are included in this study. The whole brain amplitude of low frequency fluctuation (ALFF) value, regional homogeneity (ReHo) value and functional connectivity (FC) analysis using posterior cingulate cortex (PCC) as a seed region are investigated through comparison between groups of T2DM-CI and T2DM-NC. It is found that, compared with T2DM-NC, T2DM-CI demonstrates the decreased ALFF in the regions of precuneus, posterior cingulate gyrus, middle occipital gyrus and left superior/middle frontal gyrus, but the increased ALFF in the left middle frontal gyrus and left superior temporal gyrus. In T2DM-CI, ReHo decreases in bilateral posterior cingulate gyrus, right precuneus, right inferior frontal gyrus, but increases in the middle frontal gyrus and right superior occipital gyrus. Higher FC between PCC and bilateral inferior parietal lobule and right middle/inferior frontal gyrus, lower FC between PCC and bilateral precuneus and right superior frontal gyrus are observed in T2DM-CI group. Compared with T2DM-NC, patients with T2DM-CI have presented altered ALFF, ReHo and FC in and between important brain regions. The observed alterations are thought to be implicated with cognitive impairment of T2DM as the potential imaging pathophysiological basis.

Gray matter volume differences between transgender men and cisgender women: A voxel-based morphometry study

Objective: Gender dysphoria (GD) is characterized by distress due to inconsistency between gender identity and biological sex. Individuals with GD often desire to be the other gender, which is called transgender. Although altered brain volumes in transgender people, particularly transgender women, have been reported, the particular brain regions have been inconsistent among studies. This study aimed to investigate neuroanatomical differences in transgender men without physical interventions. Method: T1-weighted magnetic resonance images (MRIs) were acquired in 21 transgender men and 21 cisgender women matched for biological sex and age. Whole-brain comparisons using voxel-based morphometry (VBM) were performed to identify gray matter volume (GMV) differences between transgender men and cisgender women. Results: Transgender men showed greater GMV in the right posterior cingulate gyrus ( PFWE-corr = 3.06×10-6) and the left occipital pole ( PFWE-corr = 0.017) and lower GMV in the left middle temporal gyrus ( PFWE-corr = 0.017) than cisgender women. Even after including serum sex hormone levels as covariates, the posterior cingulate gyrus was still significant ( PFWE-corr < 0.05). In contrast, the occipital pole and the middle temporal gyrus were not significant after controlling for the sex hormone levels ( PFWE-corr > 0.05), especially affected by testosterone but not estradiol. Conclusion: These findings suggest that transgender men have altered brain structure. We suggest that larger posterior midline structures may contribute to sensitivity to self-referential processing through altered visual perception in transgender people.

Radiomics Analysis of Magnetic Resonance Imaging Facilitates the Identification of Preclinical Alzheimer’s Disease: An Exploratory Study

Diagnosing Alzheimer’s disease (AD) in the preclinical stage offers opportunities for early intervention; however, there is currently a lack of convenient biomarkers to facilitate the diagnosis. Using radiomics analysis, we aimed to determine whether the features extracted from multiparametric magnetic resonance imaging (MRI) can be used as potential biomarkers. This study was part of the Sino Longitudinal Study on Cognitive Decline project (NCT03370744), a prospective cohort study. All participants were cognitively healthy at baseline. Cohort 1 (n = 183) was divided into individuals with preclinical AD (n = 78) and controls (n = 105) using amyloid-positron emission tomography, and this cohort was used as the training dataset (80%) and validation dataset (the remaining 20%); cohort 2 (n = 51) was selected retrospectively and divided into “converters” and “nonconverters” according to individuals’ future cognitive status, and this cohort was used as a separate test dataset; cohort three included 37 converters (13 from the Alzheimer’s Disease Neuroimaging Initiative) and was used as another test set for independent longitudinal research. We extracted radiomics features from multiparametric MRI scans from each participant, using t-tests, autocorrelation tests, and three independent selection algorithms. We then established two classification models (support vector machine [SVM] and random forest [RF]) to verify the efficiency of the retained features. Five-fold cross-validation and 100 repetitions were carried out for the above process. Furthermore, the acquired stable high-frequency features were tested in cohort three by paired two-sample t-tests and survival analyses to identify whether their levels changed with cognitive decline and impact conversion time. The SVM and RF models both showed excellent classification efficiency, with an average accuracy of 89.7–95.9% and 87.1–90.8% in the validation set and 81.9–89.1% and 83.2–83.7% in the test set, respectively. Three stable high-frequency features were identified, all based on the structural MRI modality: the large zone high-gray-level emphasis feature of the right posterior cingulate gyrus, the variance feature of the left superior parietal gyrus, and the coarseness feature of the left posterior cingulate gyrus; their levels were correlated with amyloid-β deposition and predicted future cognitive decline (areas under the curve 0.649–0.761). In addition, levels of the variance feature at baseline decreased with cognitive decline and could affect the conversion time (p &lt; 0.05). In conclusion, this exploratory study shows that the radiomics features of multiparametric MRI scans could represent potential biomarkers of preclinical AD.