Reduced Mean Diffusivity Research Articles

Attention deficit/hyperactivity disorder and medication with stimulants in young children: a DTI study.

The relationship between attention deficit/hyperactivity disorder (ADHD) and white matter connectivity has not been well established yet, specially for children under 10 years of age. In addition, the effects of treatment on brain structure have not been sufficiently explored from a Diffusion Tensor Imaging (DTI) perspective. In this study, the influence of treatment with methylphenidate in the white matter of children with ADHD was investigated using two different and complementary DTI analysis methods: Tract-Based Spatial Statistics (TBSS) and a robust tractography selection method. No significant differences were found in Fractional Anisotropy (FA) between medicated, drug-naïve patients and healthy controls, but a reduced Mean Diffusivity (MD) was found in ADHD patients under treatment with respect to both healthy controls and drug-naïve ADHD patients. Also, correlations were found between MD increases and performance indicators of ADHD. These findings may help elucidate the nature of white matter alterations in ADHD, their relationship with symptoms and the effects of treatment with psychostimulants.

White matter involvement in sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P = 0.002), axial (P = 0.0003) and radial (P = 0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P < 0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P = 0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss.

Characterization of microstructural injury: a novel approach in infant abusive head trauma-initial experience.

Abusive head trauma (AHT) is the leading cause of morbidity and mortality among abused children, yet the neuroanatomical underpinnings of AHT outcome is incompletely understood. The aim of this study was to characterize white matter (WM) abnormalities in infants with AHT using diffusion tensor imaging (DTI) and determine which microstructural abnormalities are associated with poor outcome. Retrospective DTI data from 17 infants (>3 months) with a diagnosis of AHT and a comparison cohort of 34 term infants of similar post-conceptual age (PCA) were compared using a voxel-based DTI analysis of cerebral WM. AHT cases were dichotomously classified into mild/moderate versus severe outcome. Clinical variables and conventional imaging findings were also analyzed in relation to outcome. Outcomes were classified in accordance with the Pediatric Cerebral Performance Category Score (PCPCS). Reduced axial diffusivity (AD) was shown in widespread WM regions in the AHT infants compared with controls as well as in the AHT severe outcome group compared with the AHT mild/moderate outcome group. Reduced mean diffusivity (MD) was also associated with severe outcome. Radial diffusivity (RD), conventional magnetic resonance findings, brain metric measurements, and clinical/laboratory variables (with the exception of Glascow Coma Scale) did not differ among AHT outcome groups. Findings support the unique role of DTI techniques, beyond conventional imaging, in the evaluation of microstructural WM injury of AHT. Reduced AD (likely reflecting axonal damage) and MD were associated with poor clinical outcome. DTI abnormalities may uniquely reflect AHT patterns of axonal injury that are not characterized by conventional imaging, which may have both therapeutic and prognostic implications.

Application of quantitative DTI metrics in sporadic CJD

Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob–Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1) to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM) in sporadic Jakob–Creutzfeldt disease, 2) to study changes in mean diffusivity and atrophy over time and 3) to explore their relationship with clinical scales. Twenty-six sporadic Jakob–Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume), T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei), but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score) and increasing mean diffusivity.

Time-Dependent Structural Changes of the Dentatothalamic Pathway in Children Treated for Posterior Fossa Tumor

Injury to the dentatothalamic pathway that originates in the cerebellum has been suggested as a mechanism for neurologic complications in children treated for posterior fossa tumors. We hypothesized that time-dependent changes occur in the dentatothalamic pathway. Diffusion tensor evaluation was performed in 14 children (median age, 4.1 years; age range, 1-20 years) who underwent serial MR imaging at 3T as part of routine follow-up after posterior fossa tumor resection with or without adjuvant therapy. Tensor metrics were obtained in the acute (≤1 week), subacute (1 to <6 months), and chronic (≥6 months) periods after surgery. We evaluated the following dentatothalamic constituents: bilateral dentate nuclei, cerebellar white matter, and superior cerebellar peduncles. Serial dentate nuclei volumes were also obtained and compared with the patient's baseline. The most significant tensor changes to the superior cerebellar peduncles and cerebellar white matter occurred in the subacute period, regardless of the tumor pathology or therapy regimen, with signs of recovery in the chronic period. However, chronic volume loss and reduced mean diffusivity were observed in the dentate nuclei and did not reverse. This atrophy was associated with radiation therapy and symptoms of ataxia. Longitudinal diffusion MR imaging in children treated for posterior fossa tumors showed time-dependent tensor changes in components of the dentatothalamic pathway that suggest evolution of structural damage with inflammation and recovery of tissue directionality. However, the dentate nuclei did not show tensor or volumetric recovery, suggesting that the injury may be chronic.

Micro-structural assessment of short term plasticity dynamics

Diffusion MRI enables the non-invasive investigation of neuroplasticity in the human brain. A recent DTI study has shown that a short learning task of only 2h can yield changes in diffusion parameters. In the current study we aimed to discover whether a biophysical model of diffusion MRI, the CHARMED framework, which models hindered and restricted compartments within the tissue can constitute a more specific method than DTI to study structural plasticity. In addition we set to explore the time scale of the MRI learning-induced-changes. Subjects were scanned with both DTI and CHARMED before and after participating in the same car-racing task. Repetition of a shorter version of the task was done the following week. Results provide additional support to the former discovery of reduction in mean diffusivity after 2h training using DTI. In addition we show that the CHARMED framework provides a more sensitive method than DTI for discovering microstructural modification. An increase in the fraction of the restricted compartment (Fr) was found after participating in the tasks. Between tasks values of Fr returned to baseline, reflecting the dynamics of structural remodeling. By modeling different compartments in the tissue we suggest that interpretation of the biological processes that induced changes in diffusion is more straightforward, and allows improved detection of the progression of these changes.

Diffusion tensor imaging detects microstructural reorganization in the brain associated with chronic irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurring abdominal pain associated with alterations in bowel habits. We hypothesized that patients with chronic visceral pain associated with IBS may have microstructural differences in the brain compared with healthy control subjects (HCs), indicative of long-term neural reorganization of chronic pain pathways and regions associated with sensory integration. In the current study we performed population-based voxel-wise diffusion tensor imaging (DTI) comparisons and probabilistic tractography in a large sample of phenotyped patients with IBS (n=33) and in HCs (n=93). Patients had lower fractional anisotropy (FA) in thalamic regions, the basal ganglia (BG) and sensory/motor association/integration regions as well as higher FA in frontal lobe regions and the corpus callosum. In addition, patients had reduced mean diffusivity (MD) within the globus pallidus (GP) and higher MD in the thalamus, internal capsule, and coronal radiata projecting to sensory/motor regions, suggestive of differential changes in axon/dendritic density in these regions. Sex differences in FA and MD were also observed in the patients but not in HCs. Probabilistic tractography in patients confirmed a higher degree of connectivity between the thalamus and prefrontal cortex, as well as between the medial dorsal thalamic nuclei and anterior cingulate cortex, and a lower degree of connectivity between the GP and thalamus. Together, these results support the hypothesis that patients with chronically recurring visceral pain from IBS have long-term microstructural changes within the brain, particularly in regions associated with integration of sensory information and corticothalamic modulation.

Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer's disease.

Amyloid imaging studies of presymptomatic familial Alzheimer’s disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer’s disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer’s disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network.

White Matter Microstructural Integrity in Youth With Type 1 Diabetes

Decreased white and gray matter volumes have been reported in youth with type 1 diabetes mellitus (T1DM), but the effects of hyperglycemia on white matter integrity have not been quantitatively assessed during brain development. We performed diffusion tensor imaging, using two complimentary approaches—region-of-interest and voxelwise tract-based spatial statistics—to quantify white matter integrity in a large retrospective study of T1DM youth and control participants. Exposure to chronic hyperglycemia, severe hyperglycemic episodes, and severe hypoglycemia, as defined in the Diabetes Control and Complications Trial (DCCT), were estimated through medical records review, HbA1c levels, and interview of parents and youth. We found lower fractional anisotropy in the superior parietal lobule and reduced mean diffusivity in the thalamus in the T1DM group. A history of three or more severe hyperglycemic episodes was associated with reduced anisotropy and increased diffusivity in the superior parietal lobule and increased diffusivity in the hippocampus. These results add microstructural integrity of white matter to the range of structural brain alterations seen in T1DM youth and suggest vulnerability of the superior parietal lobule, hippocampus, and thalamus to glycemic extremes during brain development. Longitudinal analyses will be necessary to determine how these alterations change with age or additional glycemic exposure.

0918 Amiloride treatment ameliorates MRI surrogate markers of neurodegeneration in primary progressive multiple sclerosis

Neurodegeneration is a major substrate for permanent disability in multiple sclerosis (MS) yet current therapies target predominantly inflammatory mechanisms resulting in an unmet need for effective neuroprotective agents. Converging basic...

Quantitative diffusion tensor imaging in herpes simplex virus encephalitis

Diffusion-weighted imaging (DWI) has been employed in many brain pathologies, but with few studies only and heterogeneous results in herpes simplex virus encephalitis (HSVE). Diffusion tensor imaging (DTI) in comparison to DWI yields additional directional diffusion data, adding information and enabling a more differentiated description of brain pathologies. The authors addressed the question whether tissue changes as identified on T2-weighted magnetic resonance imaging (MRI) could be further characterized by DTI, in particular whether different forms of edema may occur in HSVE. Six patients with HSVE confirmed by positive polymerase chain reaction (PCR) from cerebrospinal fluid (CSF) samples were studied. Patients were examined with MRI including DTI in the early stage of the infection. Conventional MRI- and DTI-derived parameter maps were analyzed for signal change qualitatively and by region-of-interest (ROI) analysis of the affected brain parenchyma. All patients showed typical clinical characteristics of HSVE and lesions in the mediobasal temporal structures and insula. In two cases hemorrhagic inflammatory tissue changes were found. DTI analysis showed slightly reduced mean diffusivity (MD) and increased fractional anisotropy (FA) values in the earliest phase. Patients scanned at day 14 or later had lesions with increased MD and reduced FA in accordance with inflammatory vasogenic edema. This study confirms signal change consistent with the presence of inflammatory vasogenic edema in HSVE as the most prominent DTI finding. In the early stage slight reductions of MD may be found, which might be due to a specific mechanism of viral infection.