Many technical developments keep occurring in the field of MRI that could benefit image acquisition in the field of diagnostic neuroradiology. While there is much focus on the potential advantages of ...3T and higher field strengths, it is often unclear whether these are cosmetic only, or convey clinically relevant diagnostic value. The increased signal-to-noise at 3T is certainly beneficial in different ways particularly for the acquisition of isotropic 3D sequences like FLAIR. Single-slab 3D sequences can now be obtained with multiple contrasts in clinically attainable data acquisition times and could revolutionize MRI to evolve into a fundamentally multi-planar technique, rather similar to what has happened with the introduction of multi-detector row CT.
Anti-inflammatory glucocorticoid (GC) therapy often induces hyperglycemia due to insulin resistance and islet-cell dysfunction. Incretin-based therapies may preserve glucose tolerance and pancreatic ...islet-cell function. In this study, we hypothesized that concomitant administration of the dipeptidyl peptidase-4 inhibitor sitagliptin and prednisolone in men at high risk to develop type 2 diabetes could protect against the GC-induced diabetogenic effects.
Men with the metabolic syndrome but without diabetes received prednisolone 30 mg once daily plus sitagliptin 100 mg once daily (n=14), prednisolone (n=12) or sitagliptin alone (n=14) or placebo (n=12) for 14 days in a double-blind 2 × 2 randomized-controlled study. Glucose, insulin, C-peptide, and glucagon were measured in the fasted state and following a standardized mixed-meal test. β-cell function parameters were assessed both from a hyperglycemic-arginine clamp procedure and from the meal test. Insulin sensitivity (M-value) was measured by euglycemic clamp.
Prednisolone increased postprandial area under the curve (AUC)-glucose by 17% (P<0.001 vs placebo) and postprandial AUC-glucagon by 50% (P<0.001). Prednisolone reduced 1st and 2nd phase glucose-stimulated- and combined hyperglycemia-arginine-stimulated C-peptide secretion (all P ≤ 0.001). When sitagliptin was added, both clamp-measured β-cell function (P=NS for 1st and 2nd phase vs placebo) and postprandial hyperglucagonemia (P=NS vs placebo) remained unaffected. However, administration of sitagliptin could not prevent prednisolone-induced increment in postprandial glucose concentrations (P<0.001 vs placebo). M-value was not altered by any treatment.
Fourteen-day treatment with high-dose prednisolone impaired postprandial glucose metabolism in subjects with the metabolic syndrome. Concomitant treatment with sitagliptin improved various aspects of pancreatic islet-cell function, but did not prevent deterioration of glucose tolerance by GC treatment.
IntroductionTraumatic brain injury (TBI) in children can be associated with poor outcome in crucial functional domains, including motor, neurocognitive and behavioural functioning. However, outcome ...varies between patients and is mediated by complex interplay between demographic factors, premorbid functioning and (sub)acute clinical characteristics. At present, methods to understand let alone predict outcome on the basis of these variables are lacking, which contributes to unnecessary follow-up as well as undetected impairments in children. Therefore, this study aims to develop prognostic models for the individual outcome of children with TBI in a range of important developmental domains. In addition, the potential added value of advanced neuroimaging data and the use of machine learning algorithms in the development of prognostic models will be assessed.Methods and analysis210 children aged 4–18 years diagnosed with mild-to-severe TBI will be prospectively recruited from a research network of Dutch hospitals. They will be matched 2:1 to a control group of neurologically healthy children (n=105). Predictors in the model will include demographic, premorbid and clinical measures prospectively registered from the TBI hospital admission onwards as well as MRI metrics assessed at 1 month post-injury. Outcome measures of the prognostic models are (1) motor functioning, (2) intelligence, (3) behavioural functioning and (4) school performance, all assessed at 6 months post-injury.Ethics and disseminationEthics has been obtained from the Medical Ethical Board of the Amsterdam UMC (location AMC). Findings of our multicentre prospective study will enable clinicians to identify TBI children at risk and aim towards a personalised prognosis. Lastly, findings will be submitted for publication in open access, international and peer-reviewed journals.Trial registration numberNL71283.018.19 and NL9051.
Objectives
We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well‐powered neuroimaging findings in ...neuropsychiatric research to worldwide populations.
Methods
We report on T1‐weighted structural MRI, resting‐state functional MRI, and multi‐shell diffusion‐weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans.
Results
Human image quality measures (IQMs) and outcome measures showed smaller within‐site variation than between‐site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites.
Conclusions
Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre‐processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.
Background:
Neuroaxonal degeneration is one of the hallmarks of clinical deterioration in progressive multiple sclerosis (PMS).
Objective:
To elucidate the association between neuroaxonal ...degeneration and both local cortical and connected white matter (WM) tract pathology in PMS.
Methods:
Post-mortem in situ 3T magnetic resonance imaging (MRI) and cortical tissue blocks were collected from 16 PMS donors and 10 controls. Cortical neuroaxonal, myelin, and microglia densities were quantified histopathologically. From diffusion tensor MRI, fractional anisotropy, axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were quantified in normal-appearing white matter (NAWM) and white matter lesions (WML) of WM tracts connected to dissected cortical regions. Between-group differences and within-group associations were investigated through linear mixed models.
Results:
The PMS donors displayed significant axonal loss in both demyelinated and normal-appearing (NA) cortices (p < 0.001 and p = 0.02) compared with controls. In PMS, cortical axonal density was associated with WML MD and AD (p = 0.003; p = 0.02, respectively), and NAWM MD and AD (p = 0.04; p = 0.049, respectively). NAWM AD and WML AD explained 12.6% and 22.6%, respectively, of axonal density variance in NA cortex. Additional axonal loss in demyelinated cortex was associated with cortical demyelination severity (p = 0.002), explaining 34.4% of axonal loss variance.
Conclusion:
Reduced integrity of connected WM tracts and cortical demyelination both contribute to cortical axonal loss in PMS.
There is currently no consensus about the extent of gray matter (GM) atrophy that can be attributed to secondary changes after white matter (WM) lesions or the temporal and spatial relationships ...between the 2 phenomena. Elucidating this interplay will broaden the understanding of the combined inflammatory and neurodegenerative pathophysiology of multiple sclerosis (MS), and separating atrophic changes due to primary and secondary neurodegenerative mechanisms will then be pivotal to properly evaluate treatment effects, especially if these treatments target the different processes individually. To untangle these complex pathologic mechanisms, this systematic review provides an essential first step: an objective and comprehensive overview of the existing in vivo knowledge of the relationship between brain WM lesions and GM atrophy in patients diagnosed with MS. The overall aim was to clarify the extent to which WM lesions are associated with both global and regional GM atrophy and how this may differ in the different disease subtypes.
We searched MEDLINE (through PubMed) and Embase for reports containing direct associations between brain GM and WM lesion measures obtained by conventional MRI sequences in patients with clinically isolated syndrome and MS. No restriction was applied for publication date. The quality and risk of bias in included studies were evaluated with the Quality Assessment Tool for observational cohort and cross-sectional studies (NIH, Bethesda, MA). Qualitative and descriptive analyses were performed.
A total of 90 articles were included. WM lesion volumes were related mostly to global, cortical and deep GM volumes, and those significant associations were almost without exception negative, indicating that higher WM lesion volumes were associated with lower GM volumes or lower cortical thicknesses. The most consistent relationship between WM lesions and GM atrophy was seen in early (relapsing) disease and less so in progressive MS.
The findings suggest that GM neurodegeneration is mostly secondary to damage in the WM during early disease stages while becoming more detached and dominated by other, possibly primary neurodegenerative disease mechanisms in progressive MS.
Background:
In early multiple sclerosis (MS), thalamus atrophy and decreased integrity of the thalamocortical white matter (WM) tracts have been observed.
Objective:
To investigate the temporal ...association between thalamus volume and WM damage in the thalamocortical tract in subjects with early MS.
Methods:
At two time points, 72 subjects with early MS underwent T1, FLAIR and diffusion tensor imaging. Thalamocortical tracts were identified with probabilistic tractography using left and right thalamus as seed regions. Regression analysis was performed to identify predictors of annual percentage change in both thalamus volumes and integrity of the connected tracts.
Results:
Significant atrophy was seen in left and right thalamus (
p
< 0.001) over the follow-up period (13.7 ± 4.8 months), whereas fractional anisotropy (FA) and mean diffusivity (MD) changes of the left and right thalamus tracts were not significant, although large inter-subject variability was seen. Annual percentage change in left thalamus volume was significantly predicted by baseline FA of the left thalamus tracts
F
(1.71)
= 4.284,
p
= 0.042; while no such relation was found for the right thalamus. Annual percentage change in FA or MD of the thalamus tracts was not predicted by thalamus volume or any of the demographic parameters.
Conclusion:
Over a short follow-up time, thalamus atrophy could be predicted by decreased integrity of the thalamic tracts, but changes in the integrity of the thalamic tracts could not be predicted by thalamus volume. This is the first study showing directionality in the association between thalamus atrophy and connected WM tract damage. These results need to be verified over longer follow-up periods.
Objectives
Seven-Tesla MRI demonstrated new pathological features of multiple sclerosis (MS) using T2*-weighted sequences. However, a clinical MRI protocol at 7 T has never been investigated. We ...evaluated the clinical value of 7-T MRI by investigating the sensitivity of lesion detection compared with 3 T.
Methods
Thirty-eight MS patients and eight healthy controls underwent multi-contrast MRI using 3D T1-weighted (3D-T1w), 2D dual-echo T2-weighted (2D-T2w) and 3D fluid-attenuated inversion recovery (3D-FLAIR) at 3 and 7 T. Images were analysed for focal lesions, which were counted and categorised according to anatomical location. The study was approved by the institutional review board.
Results
Lesion-wise analysis showed increased lesion counts in cortical grey matter (GM) at 7 T of 91, 75 and 238 % for 3D-T1w, 2D-T2w and FLAIR sequences, respectively. Patient-wise analysis confirmed this for 2D-T2w and FLAIR (
P
< 0.023 and
P
< 0.001). Seven-Tesla white matter (WM) lesion detection was not increased; 3D-FLAIR even detected significantly more WM lesions at 3 T.
Conclusions
Using a clinical multi-contrast MRI protocol, increased lesion detection was observed in cortical GM but not in WM. Given the clinical relevance of GM abnormalities, this may have consequences for clinical outcome measures, prognostic classification and future diagnostic criteria incorporating GM abnormalities.
Key Points
•
Standard multi-contrast 7-T magnetic resonance imaging in multiple sclerosis is feasible.
•
Seven-Tesla MRI detects more cortical grey matter lesions than 3 T.
•
Seven-Tesla MRI fares no better than 3 T in detecting white matter lesions.
•
Grey matter abnormalities have high diagnostic and prognostic relevance in MS.
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