UltraStructural Hippocampal And White Matter Alterations In Mild Cognitive Impairment: A Diffusion Tensor Imaging Study
Fellgiebel A, Wille P, Muller MJ, Winterer G, Scheurich A, Vucurevic G, Schmidt LG, Stoeter P
Dement Geriatr Cogn Disord 2004;18(1):101-8
University of Mainz, Department of Psychiatry, Mainz, Germany
Mild Cognitive Impairment (MCI) is considered to be a transitional stage between normal aging and Dementia. In Alzheimer's Disease (AD), White Matter structural pathology is due to Wallerian Degeneration and Central Angiopathy.
However, in MCI patients, the presence and extent of White Matter alterations as a possible correlate of Impaired Memory Function and as predictor of subsequent progression to AD is not clarified yet.
Diffusion Tensor Imaging (DTI) reveals the UltraStructural integrity of Cerebral White Matter Tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI.
In our prospective study, conventional and Diffusion Tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls.
Mean Diffusivity (MD) and Fractional Anisotropy (FA) were measured in Temporal, Frontal, Parietal and Occipital White Matter regions as well as in the Corpus Callosum (Genu and Splenium) and the Hippocampus.
MCI patients showed higher MD values in the Left Centrum Semiovale (p = 0.013; Right: p = 0.026), in the Left Temporal (p = 0.006), the Right temporal (p = 0.014) and the Left Hippocampal (p = 0.002) region.
As compared to the control group, FA values of MCI patients and controls did not differ significantly in any region.
Compared to controls, AD patients had increased MD values in the Left Centrum Semiovale (p = 0.012), the Left Parietal (p = 0.001), the Right Parietal (p = 0.028), the Left Temporal (p = 0.018), the Right Temporal (p = 0.011) and the Left Hippocampal region (p = 0.002).
Decreased FA values were measured in the Left Temporal Area (p = 0.017) and in the Left Hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients.
Elevated MD values indicating Brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the Left Hippocampus.
The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%).
Therefore, the DTI technique validates the MCI concept, and Diffusion Tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.
Copyright 2004 S. Karger AG, Basel
Diffusion Tensor Imaging Of Early Relapsing/Remitting Multiple Sclerosis With Histogram Analysis Using Automated Segmentation And Brain Volume Correction
Rashid W, Hadjiprocopis A, Griffin CM, Chard DT, Davies GR, Barker GJ, Tofts PS, Thompson AJ, Miller DH
Mult Scler 2004 Feb;10(1):9-15
Institute of Neurology, University College London, MS NMR Research Unit, Department of NeuroInflammation, Queen Square, London WC1N 3BG, UK
Diffusion Tensor Magnetic Resonance Imaging (DTI) reveals measurable abnormalities in Normal-Appearing Brain Tissue (NABT) in established Multiple Sclerosis (MS). However, it is unclear how early this occurs.
Recent studies have employed Whole Brain Histogram analysis to improve sensitivity, but concern exists regarding reliability of Tissue/CerebroSpinal Fluid Segmentation and possible intersubject Brain Volume differences, which can introduce partial volume error:
To address this, 28 early Relapsing/Remitting MS subjects [median disease duration 1.6 years; median Expanded Disability Status Scale (EDSS) score 1.5].
And 20 controls were compared with Whole Brain Histogram analysis using an automated segmentation algorithm to improve reproducibility.
Brain Parenchymal Volumes (BPV) were estimated for each subject in the analysis. The mean, peak height and peak location were calculated for DTI Parameters [Fractional Anisotropy (FA), Mean Diffusivity and Volume Ratio].
An increased FA peak height in MS subject NABT was observed (P = 0.02) accounting for age, gender and BPV. Removing BPV revealed additional abnormalities in NABT.
The main conclusions are:
- A peak height is increased in NABT in early MS
- Partial volume edge effects may contribute to apparent NABT Histogram abnormalities
- Correction for Brain Volume differences should reduce potential partial volume edge effects
Altered Expression Of Ion Channel Isoforms At The Node Of Ranvier In P0-Deficient Myelin Mutants
Ulzheimer JC, Peles E, Levinson SR, Martini R
Mol Cell NeuroSci 2004 Jan;25(1):83-94
University of Wuerzburg, Department of Neurology, Section of Developmental NeuroBiology, D-97080 Wuerzburg, Germany
To elucidate the impact of Myelinating Schwann Cells on the molecular architecture of the Nodes of Ranvier, we investigated the Nodal expression of Voltage-gated Sodium Channel (VGSC) Isoforms.
And, the localization of ParaNodal and JuxtaParaNodal membrane proteins in a severely affected Schwann Cell mutant, the mouse deficient in Myelin protein zero (P0).
The abnormal Myelin formation and compaction was associated with immature Nodal cluster types of VGSC.
Most strikingly, P0-deficient Motor Nerves displayed an ectopic Nodal expression of the Na(v)1.8 isoform, where it is coexpressed with the ubiquitous Na(v)1.6 channel.
Furthermore, Caspr was distributed asymmetrically or was even absent in the mutant Nerve Fibers.
The Potassium Channel K(v)1.2 and Caspr2 were not confined to JuxtaParaNodes, but often protruding into the ParaNodes.
Thus, deficiency of P0 leads to dysregulation of Nodal VGSC isoforms and to altered localization of ParaNodal and JuxtaParaNodal components of the Nodal complex.
Diffusion Tensor Imaging As Potential Biomarker Of White Matter Injury In Diffuse Axonal Injury
Huisman TA, Schwamm LH, Schaefer PW, Koroshetz WJ, Shetty-Alva N, Ozsunar Y, Wu O, Sorensen AG
AJNR Am J NeuroRadiol 2004 Mar;25(3):370-6
Massachusetts General Hospital and Harvard Medical School, MGH-NMR Center, Division of NeuroRadiology, Boston, MA, USA
Background And Purpose
Multiple biomarkers are used to quantify the severity of Traumatic Brain Injury (TBI) and to predict outcome. Few are satisfactory.
CT and conventional MR imaging underestimate injury and correlate poorly with outcome.
New MR imaging techniques, including Diffusion Tensor Imaging (DTI), can provide information about Brain UltraStructure by quantifying Isotropic and Anisotropic Water Diffusion.
Our objective was to determine if changes in Anisotropic Diffusion in TBI correlate with acute Glasgow Coma Scale (GCS) and/or Rankin scores at discharge.
Twenty patients (15 male, five Female; mean age, 31 years) were evaluated.
Apparent Diffusion Coefficients (ADCs) and Fractional Anisotropy (FA) values were measured at multiple locations and correlated with clinical scores. Results were compared with those of 15 healthy control subjects.
ADC values were significantly reduced within the Splenium (Delta18%, P =.001). FA values were significantly reduced in the Internal Capsule (Delta14%; P < .001) and Splenium (Delta16%; P =.002).
FA values were significantly correlated with GCS (r = 0.65-0.74; P < .001) and Rankin (r = 0.68-0.71; P < .001) scores for the Internal Capsule and Splenium.
The correlation between FA and clinical markers was better than for the corresponding ADC values. No correlation was found between ADC of the Internal Capsule and GCS/Rankin scores.
DTI reveals changes in the White Matter that are correlated with both acute GCS and Rankin scores at discharge. DTI may be a valuable biomarker for the severity of tissue injury and a predictor for outcome.