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Spatiotemporal maturation patterns of murine brain quantified by diffusion tensor MRI and deformation-based morphometry.

Highly heterogeneous spatiotemporal patterns of maturation of the murine brain during the first 80 postnatal days were examined by high-dimensional deformation-based morphometry applied to high-resolution diffusion tensor MRIs. The maturation profile revealed a sharp contrast between tissue anisotropy changes in the cortex and in major white-matter fibers. Radially oriented tissue anisotropy was measured during the first postnatal week in cortical regions, reflecting the underlying columnar organization of the cortex. Subsequently, tissue anisotropy reduced rapidly, potentially reflecting the growth of randomly oriented dendritic trees that reduce tissue coorientation. Distinct anisotropy patterns were also observed along layer I of the cortex and were attributed to thin fibers oriented parallel to the outer surface. Last, spatially complex patterns of maturation were measured in all major axonal pathways and in the hippocampus, caudate putamen, and cerebellum. This analysis provides a framework for quantifying normative maturation patterns against which phenotypes of mice of different genetic and environmental backgrounds can be contrasted.

Age Factors↗

Microembolic signals within 24 hours of stroke onset and diffusion-weighted MRI abnormalities.

BACKGROUND: The clinical relevance of the microembolic signals (MES) detected by transcranial Doppler sonography (TCD) in acute stroke remains unclear. In a prospective study the authors analyzed the relationship between MES and the findings on diffusion-weighted magnetic resonance imaging (DWI) in acute stroke patients. METHODS: We performed TCD for a period of 30 min to detect MES in patients within 24 h of stroke onset, and DWI was done within the initial 7 days. MES were assessed from Doppler waves obtained from the middle cerebral artery contralateral to the side of the neurological deficits. The acute ischemic lesions observed on DWI were classified by their diameter (small, medium or large) and by their site (cortical, superficial perforator territory, internal borderzone or deep perforator territory). RESULTS: We obtained Doppler waves from 39 vessels in 37 patients; 2 patients had bilateral deficits. MES were detected in 12 vessels (MES-positive group) and not detected in 27 vessels (MES-negative group). No significant differences in clinical features were observed between the 2 groups. The number of small lesions was significantly higher in the MES-positive group than in the MES-negative group (p = 0.02). The numbers of cortical and superficial perforator infarcts were significantly higher in the MES-positive group than in the MES-negative group (p = 0.002 and 0.02, respectively). CONCLUSION: In acute ischemic stroke, MES detected by TCD in the acute phase may produce small cortical and subcortical lesions found on DWI.

Acute Disease↗

Marchiafava-Bignami disease: diffusion-weighted MRI in corpus callosum and cortical lesions.

The clinical diagnosis of Marchiafava-Bignami disease (MBD) can be difficult. Acute demyelination of the corpus callosum is characteristic of the disease. The authors report the use of MR diffusion-weighted imaging (DWI) in six cases of acute MBD. They show that apparent diffusion coefficient restriction of the corpus callosum and cortical lesions were associated with a higher mortality rate and more severe cognitive sequelae.

Adult↗

Early and delayed neuroprotective effects of FK506 on experimental focal ischemia quantitatively assessed by diffusion-weighted MRI.

The immunosuppressive drug FK506 (tacrolimus) has been reported to be a powerful neuroprotective agent in the focal ischemia of animals. However, no report has been published concerning neuroprotective effect of this compound on the morphology in superacute stage. The separate analysis between early and delayed effects of FK506 on the morphology may be helpful in the study of the compound's mechanism of action which is still unknown. The goal of this study was to determine early and delayed effects of pharmacological treatment with FK506 in permanent MCA occlusion using magnetic resonance imaging (MRI). Nineteen rats were subjected to permanent MCA occlusion, and given either intravenous injection of placebo or 1 mg/kg FK506 immediately after occlusion. DWI and T(2)-weighted MRI were performed 3 and 24 h after MCA occlusion, and postmortem histological analysis was also performed. FK506 drastically reduced the ischemic damage in 3-h apparent diffusion coefficient (ADC) map. This is the first report to demonstrate the neuroprotective effects of FK506 on focal cerebral ischemia in superacute stage. In addition, postmortem ischemic damage tended to be smaller than ischemic area indicated by 3-h ADC map in the FK506 group, whereas there was an excellent equality between them in the placebo group, suggesting the possible effect of FK506 on the later ischemic period. Our findings provide direct evidence for the neuroprotective effect of FK506 on ischemic cell damage in both early stage and possibly later stage.

Animals↗

Water diffusion in the giant axon of the squid: implications for diffusion-weighted MRI of the nervous system.

To clarify the result that marked diffusional anisotropy had been found in nomyelinated nerve, and in completion of an evaluation of the role of all longitudinal axonal structures, we report NMR measurements of water diffusion in the giant axon of the squid, where diffusional anisotropy is determined by the neurofilamentary structure. The diffusion coefficients of water parallel and perpendicular to the long axis of the squid giant axon at 20 degrees C are (1.61 +/- 0.06) x 10(-5) cm2 s-1 and (1.33 +/- 0.09) x 10(-5) cm2 s-1, respectively, which yield an anisotropic diffusion ratio of 1.2 +/- 0.1. Water diffusion in the squid giant axon is therefore quite rapid and nearly isotropic, thus eliminating the possibility of a significant role for the longitudinally oriented neurofilaments in producing diffusional anisotropy within the axoplasm. In conjunction with our work on garfish nerves therefore, only membranes, either as numerous axonal membranes or as myelin (if present), remain to fulfill the role of the primary determinant of anisotropic water diffusion in nerve and in white matter.

Animals↗

Non-invasive assessment of axonal fiber connectivity in the human brain via diffusion tensor MRI.

A technique for assessing in vivo fiber connectivity in the human brain is presented. The method utilizes a novel connectivity algorithm that operates in three spatial dimensions and uses estimates of fiber tract orientation and tissue anisotropy, obtained from diffusion tensor magnetic resonance imaging, to establish the pathways of fiber tracts. Sample in vivo connectivity images from healthy human brain are presented that demonstrate connections in the white matter tracts. White matter connectivity information is potentially of interest in the study of a range of neurological, psychiatric, and developmental disorders and shows promise for following the natural history of disease.

Algorithms↗

The role of magnetization transfer and diffusion-weighted MRI in the understanding of multiple sclerosis evolution.

Conventional magnetic resonance imaging (MRI) has markedly increased our ability to detect the macroscopic abnormalities of the brain and spinal cord in patients with multiple sclerosis (MS). Magnetization transfer imaging and diffusion-weighted imaging have the potential to provide relevant and complementary information on the structural changes occurring within and outside these lesions and are contributing significantly to our understanding of the mechanisms leading to the accumulation of irreversible neurological disability in MS patients. The present review will summarize the major results achieved with the application of these two MR techniques to the assessment of the evolution of MS.

Central Nervous System↗

Diffusion tensor MRI shows abnormal brainstem crossing fibers associated with ROBO3 mutations.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is caused by mutations in the ROBO3 gene, critical for the crossing of long ascending medial lemniscal and descending corticospinal tracts in the medulla. Diffusion tensor imaging in a patient with HGGPS revealed the absence of major pontine crossing fiber tracts and no decussation of the superior cerebellar peduncles. Mutations in the ROBO3 gene lead to a widespread lack of crossing fibers throughout the brainstem.

Adult↗

High b-value q-space analyzed diffusion-weighted MRI: application to multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) which affects nearly one million people worldwide, leading to a progressive decline of motor and sensory functions, and permanent disability. High b-value diffusion-weighted MR images (b of up to 14000 s/mm(2)) were acquired from the brains of controls and MS patients. These diffusion MR images, in which signal decay is not monoexponential, were analyzed using the q-space approach that emphasizes the diffusion characteristics of the slow-diffusing component. From this analysis, displacement and probability maps were constructed. The computed q-space analyzed MR images that were compared with conventional T(1), T(2) (fluid attenuated inversion recovery (FLAIR)), and diffusion tensor imaging (DTI) images were found to be sensitive to the pathophysiological state of white matter. The indices used to construct this q-space analyzed MR maps, provided a pronounced differentiation between normal tissue and tissues classified as MS plaques by the FLAIR images. More importantly, a pronounced differentiation was also observed between tissues classified by the FLAIR MR images as normal-appearing white matter (NAWM) in the MS brains, which are known to be abnormal, and the respective control tissues. The potential diagnostic capacity of high b-value diffusion q-space analyzed MR images is discussed, and experimental data that explains the consequences of using the q-space approach once the short pulse gradient approximation is violated are presented.

Animals↗

Single-voxel MR spectroscopy and diffusion-weighted MRI in two patients with l-2-hydroxyglutaric aciduria.

l-2-Hydroxyglutaric aciduria is a rare inherited, neurometabolic disorder. The underlying metabolic defect and the pathophysiology of l-2-hydroxyglutaric aciduria have not yet been defined. We present MR spectroscopy and cranial MR imaging findings, including diffusion-weighted sequences in two male siblings (aged 10 and 12 years). MR spectroscopy revealed a multiplet at 2.10-2.50 ppm and two broad peaks at 0.9-1.6 ppm. The multiplet at 2.10-2.50 ppm might have been created by elevated glutamate and glutamine or l-2-hydroxyglutaric acid itself, which has a similar chemical structure to glutamate. Diffusion-weighted images demonstrated increased diffusion of water molecules in the white-matter lesions.

Brain↗

Serial diffusion-weighted MRI correlates with clinical course and treatment response in children with intracranial pus collections.

BACKGROUND: Accurate assessment of treatment response in children with intracranial pus collections is vital to guide appropriate therapy and reduce morbidity and mortality. OBJECTIVE: To correlate serial MR-measurable changes in diffusion-weighted imaging (DWI) with clinical response to treatment. MATERIALS AND METHODS: We retrospectively reviewed clinical notes, conventional MR sequences and DWI in eight children with intracranial pus collections. Trace DWI signal intensity and apparent diffusion coefficient (ADC) values were compared at three time points: at initial diagnosis (eight children, 13 collections), at follow-up during continued clinical infection (three children, sp collections), and at follow-up when clinical infection had resolved (seven children, 12 collections). RESULTS: At initial diagnosis all patients were septic and collections showed restricted diffusion (mean ADC 0.61+/-0.15 x 10(-3) mm(2)/s). Patients with persistent clinical sepsis at follow-up DWI had collections with persistent low ADC values (0.66+/-0.21 x 10(-3) mm(2)/s), significantly (P<0.001) below normal cortical gray matter values. Successful resolution of the infection was associated with a significant rise in ADC values (1.57+/-0.57 x 10(-3) mm(2)/s, P<0.01) compared both to patients with signs of continued sepsis and to normal gray matter values. CONCLUSION: Persistent restricted diffusion in pus collections correlates with continued sepsis. Treatment response is associated with clinical resolution of sepsis and ADC value elevation significantly above normal gray matter values.

Brain Abscess↗

Diffusion tensor MRI as a diagnostic tool of upper motor neuron involvement in amyotrophic lateral sclerosis.

BACKGROUND: Clinical identification of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS) is often difficult, particularly early in the course of the disease, or when lower motor neuron (LMN) dysfunction is prominent. Diffusion tensor MR imaging (DTI) can provide unique information on axonal organization by measuring diffusion anisotropy and the directionally independent diffusion. OBJECTIVE: The purpose of this study was to assess water diffusion changes along pyramidal tracts of the brainstem in patients with ALS and to investigate possible correlations between changes of diffusion properties and various clinical parameters. METHODS: We studied 16 patients (M:F=9:7, 50.5+/-12.4 years) with ALS as defined by clinical and electrophysiological examinations. These patients were compared with 11 healthy, age and sex-matched controls (M:F=5:6, 54.5+/-9.9 years). DTI was performed using a single shot SE-EPI with 25 noncollinear diffusion gradient directions (b=1000 s/mm(2)) and with no diffusion gradient on a 3.0-T MR system. RESULTS: By multifactorial ANOVA, the effects of group (patient versus control) and anatomical level on fractional anisotropy (FA) and mean diffusivity (MD) were significant (p<0.001 for both parameters), whereas the effect of side (left versus right) and interactions between factors (group by side and group by anatomical level) were not (p>0.05). In all subjects, FA and MD varied greatly depending on the anatomical level, and FA was highly variable even between contiguous slices in the pons and medulla, whereas relatively constant FA values were noted at the level of the midbrain. Cerebral peduncle was the only area that showed significant differences of diffusion properties between patients and controls (p<0.001 for FA, p=0.001 for MD). Correlation analysis revealed a significant inverse relationship between the FA value and the extent of UMN signs (r=-0.81, p<0.001). CONCLUSIONS: Alteration of diffusion properties in the cerebral peduncle in ALS may reflect pathological changes in structures rather than regional architectural variations of the corticospinal tracts or experimental artifacts.

Adult↗