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.

Brain magnetic resonance imaging surface-based analysis and cortical thickness measurement in relapsing remission multiple sclerosis

Background Damage occurs in the brain tissue in MS which appears normal on standard conventional imaging (normal appearing brain tissue). This slow, evolving damage can be monitored by nonconventional advanced MR imaging techniques. New techniques for the measurement of cortical thickness have been validated against histological analysis and manual measurements. The aim of our study was to study the role of MRI surface-based analysis and cortical thickness measurement in the evaluation of patients with Relapsing Remitting Multiple Sclerosis and to detect if there is localized rather than generalized cortical atrophy in Multiple Sclerosis patients and correlating these findings with clinical data. Results 30 patients and 30 healthy control were included in this study and they were subjected to cortical thickness analysis using MRI. The patients in our study showed decreased thickness of the precentral, paracentral, postcentral, posterior cingulate cortices and mean cortical thickness in both hemispheres when compared with the normal control group. Statistical analysis was significant (P value < 0.05) for the precentral, paracentral, postcentral, posterior cingulate cortices and mean cortical thickness in both hemispheres. On the other hand, statistical analysis was not significant (P value > 0.05) for other cortices. There was a significant negative correlation between the precentral, paracentral, postcentral, posterior cingulate cortices and mean cortical thickness in both hemispheres and EDSS scores with correlation coefficients ranging from − 0.9878 to − 0.7977. Conclusions MRI and post-processing segmentation analysis for cortical thickness is non-invasive imaging techniques that can increase the level of diagnostic confidence in diagnosis of MS patients and should be included as routine modality when evaluating patients with MS.

In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naïve Young Adults with Major Depression: A [11C]PK11195 PET Study

Adiponectin is an adipokine that mediates cellular cholesterol efflux and plays important roles in neuroinflammatory processes. In this study, we undertook positron emission tomography (PET) with the translocator protein (TSPO) ligand [11C]PK11195 and measured serum adiponectin levels in groups of treatment-naïve young adult patients with major depressive disorder (MDD) and matched healthy controls. Thirty treatment-naïve MDD patients (median age: 24 years) and twenty-three healthy controls underwent [11C]PK11195 PET. We quantified TSPO availability in brain as the [11C]PK11195 binding potential (BPND) using a reference tissue model in conjunction with the supervised cluster analysis (SVCA4) algorithm. Age, sex distribution, body mass index, and serum adiponectin levels did not differ between the groups. Between-group analysis using a region-of-interest approach showed significantly higher [11C]PK11195 BPND in the left anterior and right posterior cingulate cortices in MDD patients than in controls. Serum adiponectin levels had significant negative correlations with [11C]PK11195 BPND in the bilateral hippocampus in MDD patients, but significant positive correlations in the bilateral hippocampus in the control group. Our results indicate significantly higher TSPO binding in the anterior and posterior cingulate cortices in treatment-naïve young MDD patients, suggesting microglial activation in these limbic regions, which are involved in cognitive and emotional processing. The opposite correlations between [11C]PK11195 BPND in the hippocampus with serum adiponectin levels in MDD and control groups suggest that microglial activation in the hippocampus may respond differentially to adiponectin signaling in MDD and healthy subjects, possibly with respect to microglial phenotype.

Altered functional connectivity relates to motor performance deficits in bipolar but not unipolar depression

Underpinnings of psychomotor deficits in bipolar and unipolar depression remain underexplored. Here, we hypothesize that motor performance deficits in patients may be partially explained by altered functional connectivities between hand primary motor cortex and posterior cingulate cortex with supplementary motor area. 95 participants between 18-65 years of age, including bipolar depressed, unipolar depressed, and sex-, age-, and education-matched healthy controls, participated in this observational study with two separate visits about five weeks apart, during which the patients received psychopharmacological treatment. Motor performance was measured with a finger-tapping-task and related to functional connectivity from individual seeds in hand primary motor cortex and posterior cingulate cortex as well as to the default mode and sensory motor networks from resting state functional MRI data. 79 participants (45.6% females, 21 bipolar depressed, 27 unipolar depressed and 31 healthy controls) were included in the analysis. Using a finger-tapping-task, the groups differed in motor performance (ANOVA factor group F(2,76) = 4.122; p = 0.020) and bipolar depressed but not unipolar depressed showed performance deficits compared to controls (post-hoc-test p = 0.023 and p = 0.158 respectively). Behavioral performance correlated with functional coupling of posterior cingulate cortex - supplementary motor area, but not with coupling of primary motor cortex - supplementary motor area at cluster-wise correction level p FWEc < 0.05. Correlation differences were seen in posterior cingulate cortex - supplementary motor area (healthy controls>bipolar depressed, unipolar depressed>bipolar depressed) at second visit and in primary motor cortex - supplementary motor area (bipolar depressed>unipolar depressed) at both visits at cluster-wise correction level p FWEc<0.05. Motor performance did not relate to functional coupling of sensory motor network - anterior (visit 1 p = 0.375, visit 2 p = 0.700) or - posterior (visit 1 p = 0.903, visit 2 p = 0.772) default mode network. Motor performance deficits were seen exclusively in bipolar depressed and related to reduced posterior cingulate cortex - supplementary motor area functional connectivity at rest. Our results shed new light on a possible disruption in the anticorrelation between these regions, which seems fundamental for the preservation of motor skills. Given that nuisance factors were controlled for in the study, it is unlikely that the main results are biased by lefthanders, medication load, seed volumes, or differences in movements during MRI scanning. If these findings are confirmed, new targeted non-invasive interventions, such as repetitive transcranial magnetic stimulation, may be more effective against psychomotor deficits in bipolar depression, when aimed at modulating the supplementary motor area.

Pattern of Dopamine Transporter Density, Glucose Metabolism, and Amyloid Deposition in Patients with Alpha-Synucleinopathies and Alzheimer’s Disease

Background: The group of diseases including dementia with Lewy bodies (DLB), Parkinson’s disease (PD), and Parkinson’s disease dementia (PDD) are related to synucleinopathies. In addition to Alzheimer’s disease (AD), these are common neurodegenerative diseases that share clinical features leading to difficulties in diagnosis. Hence, molecular imaging showing correlation with pathogenesis is recognized as a critical tool for improving the efficiency of differential diagnosis. Objective: To determine characteristic patterns of dopamine transporter (DAT) density using ⁹⁹ᵐTc-TRODAT-1 (TRODAT-1), glucose metabolism using ¹⁸F-fludeoxyglucose (FDG) and amyloid deposition using ¹¹C-Pittsburgh compound B (PiB) among these diseases. Materials and Methods: Twenty-five individuals participated in the present study and included four healthy controls (HC), eight DLB, two PD, six PDD, and five AD. All subjects underwent FDG and PiB positron emission tomography (PET) and TRODAT-1 single-photon emission computed tomography (SPECT), with visual and semi-quantitative analysis of imaging. Results: All subjects for synucleinopathy groups (DLB, PD, and PDD) had positive TRODAT-1 SPECT scintigraphy, while the AD and HC groups showed negative results. The positive PiB PET results were 100% in the AD, 33.33% with two of six cases in the PDD group, 37.5% with three of eight cases in the DLB group, and 0% in both the HC and PD groups. The hypometabolism patterns in PDD and AD groups were noted at parietotemporal region and parietotemporal, posterior cingulate, and precuneus regions, respectively. Meanwhile, the DLB hypometabolism pattern was found at parietotemporal, posterior cingulate, precuneus regions, and occipital lobe regions. None of the subjects in the HC or PD groups showed hypometabolism. Conclusion: Positive TRODAT-1 SPECT provided an informative pattern for differential diagnosis among alpha-synuclein-related diseases, AD, and HC. Remarkably, hypometabolism in the occipital region can be used to differentiate DLB from AD, PDD, and PD. The amyloid deposition pattern in DLB and PDD groups was not significantly different. Keywords: alpha-synucleinopathies; PET; SPECT; ⁹⁹ᵐTc-TRODAT-1; Alzheimer’s disease