Abnormalities In Normal-appearing White Matter Research Articles

Non-lesional white matter changes depicted by q-space diffusional MRI correlate with clinical disabilities in multiple sclerosis

BackgroundWe previously developed an optimized q-space diffusional MRI technique (normalized leptokurtic diffusion [NLD] map) to delineate the demyelinated lesions of multiple sclerosis (MS) patients. Herein, we evaluated the utility of NLD maps to discern the white matter abnormalities in normal-appearing white matter (NAWM) and the abnormalities' possible associations with physical and cognitive disabilities in MS. MethodsWe conducted a retrospective observational study of MS patients treated at our hospital (Jan. 2012 to Dec. 2022). Clinical and MRI data were collected; Processing Speed Test (PST) data were obtained when possible. For a quantitative analysis of the NLD maps, we calculated the NLD index as GVROI/GVREF, where GV is a mean grayscale value in the regions of interest (ROIs) and the reference area (REF; cerebrospinal fluid). ResultsOne hundred-one individuals with MS were included. The lower corpus callosum and non-lesional WM NLD index were associated with worse Expanded Disability Status Scale (EDSS) and PST scores. The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly reduced in progressive MS compared to relapsing-remitting MS. We categorized MS severity as moderate/severe (EDSS score ≥ 4 points) and mild (EDSS score < 4 points). The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly lower in the moderate/severe MS group compared to the mild MS group. ConclusionThe NLD map revealed abnormalities in the non-lesional white matter, providing valuable insights for evaluating manifestations in MS patients.

Myelin heterogeneity for assessing normal appearing white matter myelin damage in multiple sclerosis.

Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal-appearing white matter (NAWM) is likely an important contributor to MS disability. Myelin water fraction (MWF) provides quantitative measurements of myelin. Mean MWF reflects average myelin content, while MWF standard deviation (SD) describes variation in myelin within regions. The myelin heterogeneity index (MHI = SD/mean MWF) is a composite metric of myelin content and myelin variability. We investigated how mean MWF, SD, and MHI compare in differentiating MS from controls and their associations with physical and cognitive disability. Myelin water imaging data were acquired from 91 MS participants and 31 healthy controls (HC). Segmented whole-brain NAWM and corpus callosum (CC) NAWM, mean MWF, SD, and MHI were compared between groups. Associations of mean MWF, SD, and MHI with Expanded Disability Status Scale and Symbol Digit Modalities Test were assessed. NAWM and CC MHI had the highest area under the curve: .78 (95% confidence interval [CI]: .69, .86) and .84 (95% CI: .76, .91), respectively, distinguishing MS from HC. Mean MWF, SD, and MHI provide complementary information when assessing regional and global NAWM abnormalities in MS and associations with clinical outcome measures. Examining all three metrics (mean MWF, SD, and MHI) enables a more detailed interpretation of results, depending on whether regions of interest include areas that are more heterogeneous, earlier in the demyelination process, or uniformly injured.

Permanent tissue damage in multiple sclerosis lesions is associated with reduced pre-lesion myelin and axon volume fractions

Background: The use of advanced magnetic resonance imaging (MRI) techniques in MS research has led to new insights in lesion evolution and disease outcomes. It has not yet been determined if, or how, pre-lesional abnormalities in normal-appearing white matter (NAWM) relate to the long-term evolution of new lesions. Objective: To investigate the relationship between abnormalities in MRI measures of axonal and myelin volume fractions (AVF and MVF) in NAWM preceding development of black-hole (BH) and non-BH lesions in people with MS. Methods: We obtained magnetization transfer and diffusion MRI at 6-month intervals in patients with MS to estimate MVF and AVF during lesion evolution. Lesions were classified as either BH or non-BH on the final imaging visit using T1 maps. Results: Longitudinal data from 97 new T2 lesions from 9 participants were analyzed; 25 lesions in 8 participants were classified as BH 6–12 months after initial appearance. Pre-lesion MVF, AVF, and MVF/AVF were significantly lower, and T1 was significantly higher, in the lesions that later became BHs (p < 0.001) compared to those that did not. No significant pre-lesion abnormalities were found in non-BH lesions (p > 0.05). Conclusion: The present work demonstrated that pre-lesion abnormalities are associated with worse long-term lesion-level outcome.

Abnormalities in normal-appearing white matter from which multiple sclerosis lesions arise.

Normal-appearing white matter is far from normal in multiple sclerosis; little is known about the precise pathology or spatial pattern of this alteration and its relation to subsequent lesion formation. This study was undertaken to evaluate normal-appearing white matter abnormalities in brain areas where multiple sclerosis lesions subsequently form, and to investigate the spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis. Brain MRIs of pre-lesion normal-appearing white matter were analysed in participants with new T2 lesions, pooled from three clinical trials: SYNERGY (NCT01864148; n = 85 with relapsing multiple sclerosis) was the test data set; ASCEND (NCT01416181; n = 154 with secondary progressive multiple sclerosis) and ADVANCE (NCT00906399; n = 261 with relapsing-remitting multiple sclerosis) were used as validation data sets. Focal normal-appearing white matter tissue state was analysed prior to lesion formation in areas where new T2 lesions later formed (pre-lesion normal-appearing white matter) using normalized magnetization transfer ratio and T2-weighted (nT2) intensities, and compared with overall normal-appearing white matter and spatially matched contralateral normal-appearing white matter. Each outcome was analysed using linear mixed-effects models. Follow-up time (as a categorical variable), patient-level characteristics (including treatment group) and other baseline variables were treated as fixed effects. In SYNERGY, nT2 intensity was significantly higher, and normalized magnetization transfer ratio was lower in pre-lesion normal-appearing white matter versus overall and contralateral normal-appearing white matter at all time points up to 24 weeks before new T2 lesion onset. In ASCEND and ADVANCE (for which normalized magnetization transfer ratio was not available), nT2 intensity in pre-lesion normal-appearing white matter was significantly higher compared to both overall and contralateral normal-appearing white matter at all pre-lesion time points extending up to 2 years prior to lesion formation. In all trials, nT2 intensity in the contralateral normal-appearing white matter was also significantly higher at all pre-lesion time points compared to overall normal-appearing white matter. Brain atlases of normal-appearing white matter abnormalities were generated using measures of voxel-wise differences in normalized magnetization transfer ratio of normal-appearing white matter in persons with multiple sclerosis compared to scanner-matched healthy controls. We observed that overall spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis largely recapitulated the anatomical distribution of probabilities of T2 hyperintense lesions. Overall, these findings suggest that intrinsic spatial properties and/or longstanding precursory abnormalities of normal-appearing white matter tissue may contribute to the risk of autoimmune acute demyelination in multiple sclerosis.

Diffusely appearing white matter in multiple sclerosis: Insights from sodium (23Na) MRI

BackgroundIn multiple sclerosis (MS), magnetic resonance imaging (MRI) frequently shows ill-defined areas with intermediate signal intensity between the normal appearing white matter (NAWM) and focal T2-hyperintense lesions, termed “diffusely appearing white matter” (DAWM). Even though several advanced MRI techniques have shown the potential to detect and quantify subtle commonly not visible microscopic tissue changes, to date only a few advanced MRI studies investigated DAWM changes in a quantitative manner. The aim of this study was to detect and quantify tissue abnormalities in the DAWM in comparison to focal lesions and the NAWM in MS patients by sodium (23Na) MRI. Methods23Na and conventional MRI were performed in 25 MS patients with DAWM (DAWM+) and in 25 sex- and age matched MS patients without DAWM (DAWM−), as well as in ten healthy controls (HC). Mean total sodium concentrations (TSC) were quantified in the DAWM, NAWM, normal appearing grey matter (NAGM) and in focal MS lesions. ResultsIn MS DAWM+and DAWM−, TSC values were increased in the NAGM (DAWM+: 44.61 ± 4.09 mM; DAWM–: 45.37 ± 3.8 mM) and in the NAWM (DAWM+: 39.85 ± 3.89 mM; DAWM–: 39.82 ± 4.25 mM) compared to normal grey and white matter in HC (GM 40.87 ± 3.25 mM, WM 35.9 ± 1.81 mM; p < 0.05 for all comparisons). Interestingly, the DAWM showed similar sodium concentrations (39.32 ± 4.59 mM) to the NAWM (39.85 ± 3.89 mM), whereas TSC values in T1 hypointense (46.53 ± 7.87 mM) and T1 isointense (41.99 ± 6.10 mM) lesions were significantly higher than in the DAWM (p < 0.001 and 0.017 respectively). Conclusion23Na MRI is confirmed as a sensitive marker of even subtle tissue abnormalities. DAWM sodium levels are increased and comparable to the abnormalities in NAWM, suggesting pathological changes less severe than in focal lesions comparable to what is expected in the NAWM.

Investigating Microstructural Abnormalities and Neurocognition in Sub-Acute and Chronic Traumatic Brain Injury Patients with Normal-Appearing White Matter: A Preliminary Diffusion Tensor Imaging Study

For a significant percentage of subjects, with chronic traumatic brain injury (TBI), who report persisting cognitive impairment and functional loss, the diagnosis is often impeded by the fact that routine neuroimaging often does not reveal any abnormalities. In this paper, we used diffusion tensor imaging (DTI) to investigate the apparently normal white matter (as assessed by routine magnetic resonance imaging) in the brains of 19 subjects with sub-acute (9) and chronic (10) TBI. We also assessed memory, executive function, and visual-motor coordination in these subjects. Using a voxel-wise approach, we investigated if parameters of diffusion were significantly different between TBI subjects and 17 healthy controls (HC), who were demographically matched to the TBI group. We also investigated if changes in DTI parameters were associated with neuropsychological performance in either group. Our results indicate significantly increased mean and axial diffusivity (MD and AD, respectively) values in widespread brain locations in TBI subjects, while controlling for age, sex, and time since injury. HC performed significantly better than the TBI subjects on tests of memory and executive function, indicating the persisting functional loss in chronic TBI. We found no correlation between diffusion parameters and performance on test of executive function in either group. We found negative correlation between FA and composite memory scores, and positive correlation between RD and visuomotor coordination test scores, in various tracts in both groups. Our study suggests that changes in MD and AD can indicate persisting micro-structure abnormalities in normal-appearing white matter in the brains of subjects with chronic TBI. Our results also suggest that FA in major white matter tracts is correlated with memory in health and in disease, alike; larger and longitudinal studies are needed to discern potential differences in these correlations in the two groups.

The relationship between cortical lesions and periventricular NAWM abnormalities suggests a shared mechanism of injury in primary-progressive MS.

In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging.To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional rim. The supra-tentorial voxels between 2 and 6 mm of distance from the lateral ventricles were included in the periventricular NAWM mask while the voxels between 6 and 10 mm from the lateral ventricles were included in the deep NAWM mask; mean MD values were then computed separately for these two masks. Lastly, cortical lesions were assessed on phase-sensitive inversion recovery (PSIR) images and cortical thickness was quantified on volumetric T1 images.Our main result was the observation in the PPMS group of a significant correlation between periventricular NAWM MD values and cortical lesion load, with a greater cortical lesion burden being associated with more abnormal periventricular NAWM MD. Conversely, there was no correlation between cortical lesion load and deep NAWM MD values or periventricular WM lesions.Our data thus suggest that a common – and relatively selective - factor plays a role in the development of both cortical lesion and periventricular NAWM abnormalities in PPMS.

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis

ObjectiveTo assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey...

Influence of cigarette smoking on white matter in patients with clinically isolated syndrome as detected by diffusion tensor imaging.

Cigarette smoking has been associated with increased occurrence of multiple sclerosis (MS), as well as clinical disability and disease progression in MS. We aimed to assess the effects of smoking on the white matter (WM) in patients with clinically isolated syndrome (CIS) using diffusion tensor imaging. Smoker patients with CIS (n=16), smoker healthy controls (n=13), nonsmoker patients with CIS (n=17) and nonsmoker healthy controls (n=14) were included. Thirteen regions-of-interest including nonenhancing T1 hypointense lesion and perilesional WM, and 11 normal-appearing white matter (NAWM) regions were drawn on color-coded fractional anisotropy (FA) maps. Lesion load was determined in terms of number and volume of WM hyperintensities. A tendency towards greater lesion load was found in smoker patients. T1 hypointense lesions and perilesional WM had reduced FA and increased mean diffusivity to a similar degree in smoker and nonsmoker CIS patients. Compared with healthy smokers, smoker CIS patients had more extensive NAWM changes shown by increased mean diffusivity. There was no relationship between diffusion metrics and clinical disability scores, duration of the disease and degree of smoking exposure. Smoker patients showed a tendency towards having greater number of WM lesions and displayed significantly more extensive NAWM abnormalities.

Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis.

In multiple sclerosis, there is increasing evidence that demyelination, and neuronal damage occurs preferentially in cortical grey matter next to the outer surface of the brain. It has been suggested that this may be due to the effects of pathology outside the brain parenchyma, in particular meningeal inflammation or through cerebrospinal fluid mediated factors. White matter lesions are often located adjacent to the ventricles of the brain, suggesting the possibility of a similar outside-in pathogenesis, but an investigation of the relationship of periventricular normal-appearing white matter abnormalities with distance from the ventricles has not previously been undertaken. The present study investigates this relationship in vivo using quantitative magnetic resonance imaging and compares the abnormalities between secondary progressive and relapsing remitting multiple sclerosis. Forty-three patients with relapsing remitting and 28 with secondary progressive multiple sclerosis, and 38 healthy control subjects were included in this study. T1-weighted volumetric, magnetization transfer and proton density/T2-weighted scans were acquired for all subjects. From the magnetization transfer data, magnetization transfer ratio maps were prepared. White matter tissue masks were derived from SPM8 segmentations of the T1-weighted images. Normal-appearing white matter masks were generated by subtracting white matter lesions identified on the proton density/T2 scan, and a two-voxel perilesional ring, from the SPM8 derived white matter masks. White matter was divided in concentric bands, each ∼1-mm thick, radiating from the ventricles toward the cortex. The first periventricular band was excluded from analysis to mitigate partial volume effects, and normal-appearing white matter and lesion magnetization transfer ratio values were then computed for the 10 bands nearest to the ventricles. Compared with controls, magnetization transfer ratio in the normal-appearing white matter bands was significantly lower in patients with multiple sclerosis. In controls, magnetization transfer ratio was highest in the band adjacent to the ventricles and declined with increasing distance from the ventricles. In the multiple sclerosis groups, relative to controls, reductions in magnetization transfer ratio were greater in the secondary progressive multiple sclerosis compared with relapsing remitting multiple sclerosis group, and these reductions were greatest next to the ventricles and became smaller with distance from them. White matter lesion magnetization transfer ratio reductions were also more apparent adjacent to the ventricle and decreased with distance from the ventricles in both the relapsing remitting and secondary progressive multiple sclerosis groups. These findings suggest that in people with multiple sclerosis, and more so in secondary progressive than relapsing remitting multiple sclerosis, tissue structural abnormalities in normal-appearing white matter and white matter lesions are greatest near the ventricles. This would be consistent with a cerebrospinal fluid or ependymal mediated pathogenesis.

Myelin morphology and axon pathology in demyelination during experimental autoimmune encephalomyelitis.

Myelin morphology and axon pathology in demyelination during experimental autoimmune encephalomyelitis.

Magnetization transfer and adiabatic T1ρ MRI reveal abnormalities in normal-appearing white matter of subjects with multiple sclerosis

Background: Diffuse abnormalities are known to occur within the brain tissue of multiple sclerosis (MS) patients that is “normal appearing” on T1-weighted and T2-weighted magnetic resonance images. Objectives: With the goal of exploring the sensitivity of novel MRI parameters to detect such abnormalities, we implemented an inversion-prepared magnetization transfer (MT) protocol and adiabatic T1ρ and T2ρ rotating frame relaxation methods. Methods: Nine relapsing–remitting MS patients and seven healthy controls were recruited. Relaxation parameters were measured in a single slice just above the lateral ventricles and approximately parallel to the AC-PC line. Results: The MT ratio of regions encompassing the normal-appearing white matter (NAWM) was different in MS patients as compared with controls (p = 0.043); however, the T1 measured during off-resonance irradiation (T1sat) was substantially more sensitive than the MT ratio for detecting differences between groups (p = 0.0006). Adiabatic T1ρ was significantly prolonged in the NAWM of MS patents as compared to controls (by 6%, p = 0.026), while no differences were found among groups for T2ρ. No differences among groups were observed in the cortical gray matter for any relaxation parameter. Conclusions: The results suggest degenerative processes occurring in the NAWM of MS, likely not accompanied by significant abnormalities in iron content.

Advanced magnetic resonance imaging of neuromyelitis optica: a multiparametric approach

Background: Several authors have used advanced magnetic resonance imaging (MRI) techniques to investigate whether patients with neuromyelitis optica (NMO) have occult damage in normal-appearing brain tissue, similarly to multiple sclerosis (MS). To date, the literature contains no data derived from the combined use of several advanced MRI techniques in the same NMO subjects. Objective: We set out to determine whether occult damage could be detected in the normal-appearing brain tissue of a small group of patients with NMO using a multiparametric MRI approach. Methods: Eight female patients affected by NMO (age range 44–58 years) and seven sex- and age-matched healthy controls were included. The techniques used on a 1.5 T MRI imaging scanner were magnetization transfer imaging, diffusion tensor imaging, tract-based spatial statistics, spectroscopy and voxel-based morphometry in order to analyse normal-appearing white matter and normal-appearing grey matter. Results: Structural and metabolic parameters showed no abnormalities in normal-appearing white matter of patients with NMO. Conversely, tract-based spatial statistics demonstrated a selective alteration of the optic pathways and the lateral geniculate nuclei. Diffusion tensor imaging values in the normal-appearing grey matter were found to be significantly different in the patients with NMO versus the healthy controls. Moreover, voxel-based morphometry analysis demonstrated a significant density and volume reduction of the sensorimotor cortex and the visual cortex. Conclusions: Our data disclosed occult structural damage in the brain of patients with NMO, predominantly involving regions connected with motor and visual systems. This damage seems to be the direct consequence of transsynaptic degeneration triggered by lesions of the optic nerve and spine.

Diffusion tensor imaging of normal-appearing white matter in neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe attacks of optic neuritis and myelitis. Brain was classically, unlike in multiple sclerosis (MS), spared. Nevertheless recent studies showed that brain lesions can be seen with MRI. We studied the diffusion characteristics of normal-appearing white matter (NAWM) and abnormal white matter in NMO patients compared with NAWM in healthy subjects. Diffusion tensor imaging (DTI) scans of the brain and spinal cord were obtained from 25 patients with NMO and 20 age- and gender-matched healthy subjects. Region of interest (ROI) analysis of the apparent diffusivity coefficient (ADC) and fractional anisotropy (FA) was performed in brain NAWM (optic radiations, corpus callosum [CC] and anterior and posterior limbs of the internal capsule [IC]) and in spinal cord NAWM and in lesions. ADC was increased and FA decreased in NMO patients in the posterior limb of the IC in the optic radiations and in spinal cord NAWM. FA was lower in spinal cord lesions. In contrast, there was no difference between the two groups in the anterior limb of the IC nor in the CC. These results suggest that DTI abnormalities are very severe in NMO spinal cord lesions. In our study, DTI abnormalities in NAWM were restricted to optic radiations and cortico-spinal tracts, suggesting secondary Wallerian degeneration. In contrast, NAWM outside these tracts (CC and anterior IC) remained normal suggesting that, unlike what is observed in MS, there is no infra-lesional abnormality in NMO.

Multiple sclerosis normal‐appearing white matter: Pathology–imaging correlations

The study was undertaken to determine the pathologic basis of subtle abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) parameters observed in normal-appearing white matter (NAWM) in multiple sclerosis brains. Brain tissues were obtained through a rapid postmortem protocol that included in situ magnetic resonance imaging (MRI). Four types of MRI-defined regions of interest (ROIs) were analyzed: (1) regions that were abnormal on all images (T2T1MTR lesions); (2) NAWM regions with slightly abnormal MTR located close to white matter lesions (sa-WM Close); (3) NAWM regions with slightly abnormal MTR located far from lesions (sa-WM Far); and (4) NAWM regions with normal MTR (NAWM). Immunohistochemical analysis for each ROI comprised immunostaining for myelin, axonal markers, activated microglia/macrophages, astrocytes, plasma proteins, and blood vessels. Forty-eight ROIs from 4 secondary progressive MS brains were analyzed. sa-WM Close ROIs were associated with significantly more axonal swellings. There were more enlarged major histocompatibility complex II(+) microglia and macrophages detected in sa-WM Far, sa-WM Close, and T2T1MTR lesions than in NAWM. Across all ROIs, MTR and DTI measures were moderately correlated with myelin density, axonal area, and axonal counts. Excluding T2T1MTR lesions from analysis revealed that MTR and DTI measures in nonlesional white matter (WM) were correlated with activated microglia, but not with axonal or myelin integrity. The pathologic substrates for MRI abnormalities in NAWM vary based on distance from focal WM lesions. Close to WM lesions, axonal pathology and microglial activation may explain subtle MRI changes. Distant from lesions, microglial activation associated with proximity to cortical lesions might underlie MRI abnormalities.

Evaluation of Normal Appearing White Matter in Multiple Sclerosis

The aim of this study was to determine diffusion magnetic resonance imaging (MRI), magnetization transfer (MT) imaging and multivoxel MR spectroscopy findings in plaques, periplaque white matter and normal appearing white matter (NAWM) regions in multiple sclerosis (MS) and to correlate the findings with the expanded disability status scale (EDSS). A total of 30 patients with MS and 30 healthy control subjects were studied and apparent diffusion coefficient (ADC) values, MT ratio (MTR), N-acetyl-aspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) ratios were measured in plaques, periplaques and NAWM regions and compared with the control subjects. The MTR and NAA/Cr ratio were decreased more in plaques than periplaques and NAWM, in contrast ADC values and Cho/Cr ratios were highest in plaques and higher in periplaques than in NAWM. Decreased MTR and NAA/Cr in NAWM demonstrated moderate inverse correlations (r = - 0.604, p < 0.001 and r = - 0.494, p < 0.001, respectively) while Cho/Cr ratios and ADC of NAWM demonstrated weak linear correlations (r = 0.370, p = 0.004, r = 0.297, p = 0.021 respectively) with EDSS. The MS, MTR and MR spectroscopy findings were found to be useful for detecting subtle abnormalities in NAWM. Although ADC values were significantly altered in plaque and periplaque regions a significance difference was not found in NAWM.

Diffusion tensor imaging detects areas of abnormal white matter microstructure in patients with partial ornithine transcarbamylase deficiency.

OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive deficits. Nineteen adults with partial OTCD and 18 adult control subjects ages 19-59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control groups. FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with age. Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working memory.

A comparative study of MR diffusion tensor imaging histogram between clinically isolated syndrome and relapsing-remitting multiple sclerosis in normal appearing white matter and grey matter

Objective To investigate whether abnormalities can be detected in normal-appearing white matter(NAWM)and normal-appearing white matter(NAGM)in patients with clinically isolated syndrome(CIS)and comparing them to the abnormalities in relapsing-remitting multiple sclerosis(RRMS)by using diffusion tensor imaging(DTI)histogram.To detect the potential relationship between DTI indices of NAWM,NAGM and patient's clinical condition.Methods Nineteen patients with CIS,19 clinically diagnosed RRMS patients and 19 sex-and age-matched healthy volunteers were included in this study.Conventional MRI and DTI images were obtained using Siemens 1.5 T Magnetom sonata scanner.DTI histograms of NAWM and NAGM were obtained after post-processing.The mean value,peak height,peak location of the histogram were used for analysis.All data was statistically processed with SPSS for Windows.Results NAWM average MD was higher and FA was lower in RRMS[MD(0.83±0.04)×10-3mm2/s,FA 0.36±0.03]when compared to CIS[MD(0.79±0.02)×10-3mm2/s,FA 0.40±0.02]and control[MD(0.78±0.02)×10-3mm2/s,FA 0.41±0.01](P＜0.01).But no statistically significant difference was found between CIS and control.The peak height of NAWM average MD histogram was significantly lower in CIS than control(P＜0.05),while the peak location of average FA histogram shifted to the left(P＜0.01).Patients with CIS[(1.08±0.06)×10-3mm2/s]showed significantly higher NAGM average MD than control[(1.03±0.05)×10-3mm2/s](P＜0.05),but,lower than RRMS[(1.18±0.12)×10-3mm2/s](P＞0.01).There were no correlation between DTI indices and EDSS scores in patients with CIS.Moderate correlation between NAGM average MD(r=0.568,P＜0.05)and EDSS scores were found in patient with RRMS.Conclusion NAWM and NAGM abnormalities do occur in CIS which can be detected by DTI.The underlying pathological changes in NAWM and NAGM in CIS may be milder than RRMS as demonstrated by DTI histogram. Key words: Multiple sclerosis; Diffusion magnetic resonance imaging

Diffusion tensor imaging in infants with basal ganglia-thalamic lesions

We performed diffusion tensor imaging in two infants with neonatal hypoxic-ischemic encephalopathy. MRI revealed basal ganglia-thalamic lesions in both patients during the neonatal period. Patient 1 had severe neurological sequelae, whereas patient 2 achieved normal development. Conventional MRI at 12 months of age showed abnormal high-intensity areas in bilateral basal ganglia and thalami in patient 1, whereas no abnormal intensities were recognized in patient 2. Diffusion tensor tractography demonstrated poor depiction of white matter tracts above the level of centrum semiovale in patient 1. Region of interest analysis showed that fractional anisotropy of white matter of centrum semiovale and deep white matter was markedly reduced in patient 1 compared with patient 2, although apparent diffusion coefficient was not largely different between them. Our study suggested that abnormalities of diffusion property will be more widely present than those of conventional MRI. Diffusion tensor imaging will be useful to detect white matter abnormalities in normal-appearing white matter on conventional MRI.

Normal-appearing grey and white matter T1 abnormality in early relapsing–remitting multiple sclerosis: a longitudinal study

Objective To investigate the presence and evolution of T1 relaxation time abnormalities in normal-appearing white matter (NAWM) and grey matter (GM), early in the course of relapsing–remitting multiple sclerosis (MS). Methods Twenty-three patients with early relapsing–remitting MS and 14 healthy controls were imaged six monthly for up to three years. Mean follow-up was 26 months for MS patients and 24 months for controls. Dual-echo fast-spin echo and gradient-echo proton-density and T1-weighted data sets (permitting the calculation of a T1 map) were acquired in all subjects. GM and NAWM T1 histograms were produced and a hierarchical regression model was used to investigate changes in T1 over time. Results At baseline, significant patient-control differences were seen, both in NAWM (P = 0.001) and in GM (P = 0.01). At follow-up, there was no evidence for a serial change in either mean T1 or peak-location for either NAWM or GM. There was weak evidence for a decline in patient NAWM peak-height and also evidence for a decline in control GM peak-height. Conclusion There are significant and persistent abnormalities of NAWM and GM T1 in early relapsing-remitting MS. Further studies should address whether such T1 measures have a role in prognosis or therapeutic monitoring. Multiple Sclerosis 2007; 13:169–177. http://msj.sagepub.com