Glutamate quantification by PRESS or MEGA-PRESS: Validation, repeatability, and concordance.

PURPOSE: While PRESS is often employed to measure glutamate concentrations, MEGA-PRESS enables simultaneous Glx (glutamate and glutamine) and GABA measurements. This study aimed to compare validation, repeatability, and concordance of different approaches for glutamate quantification at 3T to aid future studies in their selection of the appropriate sequence and quantification method. MATERIALS AND METHODS: Nine phantoms with different glutamate and glutamine concentrations and five healthy participants were scanned twice to assess respectively the validation and repeatability of measurements with PRESS and MEGA-PRESS. To assess concordance between the different methods, results from 95 human participants were compared. PRESS, MEGA-PRESS (i.e. difference), and the MEGA-PRESS OFF spectra were analyzed with both LCModel and Gannet. RESULTS: In vitro, excellent agreement was shown between actual and measured glutamate concentrations for all measurements (r>0.98). In vivo CVs were better for PRESS (2.9%) than MEGA-PRESS (4.9%) and MEGA-PRESS OFF (4.2%). However, the concordance between the sequences was low (PRESS and MEGA-PRESS OFF, r=0.3) to modest (MEGA-PRESS versus MEGA-PRESS OFF, r=0.8). CONCLUSION: Both PRESS and MEGA-PRESS can be employed to measure in vivo glutamate concentrations, although PRESS shows a better repeatability. Comparisons between in vivo glutamate measures of different sequences however need to be interpreted cautiously.

Simultaneous investigation of microvasculature and parenchyma in cerebral small vessel disease using intravoxel incoherent motion imaging.

INTRODUCTION: Cerebral small vessel disease (cSVD) is associated with microvascular and parenchymal alterations. Intravoxel incoherent motion (IVIM) MRI has been proposed to simultaneously measure both the microvascular perfusion and parenchymal diffusivity. This study aimed to evaluate the application of IVIM in cSVD to assess the microvasculature and parenchymal microstructure. METHODS: Seventy-three patients with cSVD (age 70 ± 11 y) and thirty-nine controls (age 69 ± 12 y) underwent IVIM imaging (3T). Group differences of the perfusion volume fraction f and the parenchymal diffusivity D were investigated using multivariable linear regression accounted for age, sex and cardiovascular factors. To examine the relation between the IVIM measures and the disease severity on structural MRI, white matter hyperintensity (WMH) load served as surrogate measure of the disease severity. RESULTS: Patients had a larger f (p < 0.024) in the normal appearing white matter (NAWM) than controls. Higher D (p < 0.031) was also observed for patients compared with controls in the NAWM and grey matter. Both f (p < 0.024) and D (p < 0.001) in the NAWM and grey matter increased with WMH load. CONCLUSIONS: The increased diffusivity reflects the predicted microstructural tissue impairment in cSVD. Unexpectedly, an increased perfusion volume fraction was observed in patients. Future studies are needed to reveal the precise nature of the increased perfusion volume fraction. IVIM imaging showed that the increases of f and D in cSVD were both related to disease severity, which suggests the potential of IVIM imaging to provide a surrogate marker for the progression of cSVD.

Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging.

Type 2 diabetes mellitus is associated with accelerated cognitive decline and various cerebral abnormalities visible on MRI. The exact pathophysiological mechanisms underlying cognitive decline in diabetes still remain to be elucidated. In addition to conventional images, MRI offers a versatile set of novel contrasts, including blood perfusion, neuronal function, white matter microstructure, and metabolic function. These more-advanced multiparametric MRI contrasts and the pertaining parameters are able to reveal abnormalities in type 2 diabetes, which may be related to cognitive decline. To further elucidate the nature of the link between diabetes, cognitive decline, and brain abnormalities, and changes over time thereof, biomarkers are needed which can be provided by advanced MRI techniques. This review summarizes to what extent MRI, especially advanced multiparametric techniques, can elucidate the underlying neuronal substrate that reflects the cognitive decline in type 2 diabetes.

Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.

Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory γ-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.

Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus.

We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.

Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study.

Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.

A control systems approach to quantify wall shear stress normalization by flow-mediated dilation in the brachial artery.

Flow-mediated dilation is aimed at normalization of local wall shear stress under varying blood flow conditions. Blood flow velocity and vessel diameter are continuous and opposing influences that modulate wall shear stress. We derived an index FMDv to quantify wall shear stress normalization performance by flow-mediated dilation in the brachial artery. In 22 fasting presumed healthy men, we first assessed intra- and inter-session reproducibilities of two indices pFMDv and mFMDv, which consider the relative peak and relative mean hyperemic change in flow velocity, respectively. Second, utilizing oral glucose loading, we evaluated the tracking performance of both FMDv indices, in comparison with existing indices [i.e., the relative peak diameter increase (%FMD), the peak to baseline diameter ratio (Dpeak/Dbase), and the relative peak diameter increase normalized to the full area under the curve of blood flow velocity with hyperemia (FMD/shearAUC) or with area integrated to peak hyperemia (FMD/shearAUC_peak)]. Inter-session and intra-session reproducibilities for pFMDv, mFMDv and %FMD were comparable (intra-class correlation coefficients within 0.521-0.677 range). Both pFMDv and mFMDv showed more clearly a reduction after glucose loading (reduction of ~45%, p≤0.001) than the other indices (% given are relative reductions): %FMD (~11%, p≥0.074); Dpeak/Dbase (~11%, p≥0.074); FMD/shearAUC_peak (~20%, p≥0.016) and FMD/shearAUC (~38%, p≤0.038). Further analysis indicated that wall shear stress normalization under normal (fasting) conditions is already far from ideal (FMDv << 1), which (therefore) does not materially change with glucose loading. Our approach might be useful in intervention studies to detect intrinsic changes in shear stress normalization performance in conduit arteries.