Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-Pick Type C patient

New treatment options for Niemann-Pick Type C (NPC) have recently become available. To assess the efficiency and efficacy of these new treatment markers for disease status and progression are needed. Both the diagnosis and the monitoring of disease progression are challenging and mostly rely on clinical impression and functional testing of horizontal eye movements. Diffusion tensor imaging (DTI) provides information about the microintegrity especially of white matter. We show here in a case report how DTI and measures derived from this imaging method can serve as adjunct quantitative markers for disease management in Niemann-Pick Type C. Two approaches are taken--first, we compare the fractional anisotropy (FA) in the white matter globally between a 29-year-old NPC patient and 18 healthy age-matched controls and show the remarkable difference in FA relatively early in the course of the disease. Second, a voxelwise comparison of FA values reveals where white matter integrity is compromised locally and demonstrate an individualized analysis of FA changes before and after 1year of treatment with Miglustat. This method might be useful in future treatment trials for NPC to assess treatment effects.

Forensic application of postmortem diffusion-weighted and diffusion tensor MR imaging of the human brain in situ

DWI and DTI of the brain have proved to be useful in many neurologic disorders and in traumatic brain injury. This prospective study aimed at the evaluation of the influence of the PMI and the cause of death on the ADC and FA for the application of DWI and DTI in forensic radiology.

Diffusion tensor imaging in episodic cluster headache

Cluster headache (CH) is a rare headache disorder with severe unilateral headache bouts and autonomic symptoms. The pathophysiology of CH is not completely understood. Using a voxel-based morphometric paradigm or functional imaging, a key role of the hypothalamus and the pain matrix could be demonstrated during CH episodes. However, there are no diffusion tensor imaging (DTI) data investigating the white matter microstructure of the brain in patients with CH. Therefore, we used DTI to delineate microstructural changes in patients with CH in a headache-free state.

Optic radiation fiber tracking using anteriorly angulated diffusion tensor imaging: a tested algorithm for quick application

Fiber tracking (FT) of the optic pathways (OPs) is difficult because there is no standard for the parameters of diffusion tensor imaging (DTI), placement of seed volumes, or interpreting the results.

Spinal Cord Diffusion-Tensor Imaging and Motor-evoked Potentials in Multiple Sclerosis Patients: Microstructural and Functional Asymmetry

Purpose: To assess possible association between intrinsic structural damage and clinical disability by correlating spinal cord diffusion-tensor (DT) imaging data with electrophysiological parameters in patients with a diagnosis of multiple sclerosis (MS). Materials and Methods: This study was approved by the local ethical committee according to the declaration of Helsinki and written informed consent was obtained. DT images and T1- and T2-weighted images of the spinal cord were acquired in 28 healthy volunteers and 41 MS patients. Fractional anisotropy (FA) and apparent diffusion coefficients were evaluated in normal-appearing white matter (NAWM) at the cervical level and were correlated with motor-evoked potentials (n = 34). Asymmetry index was calculated for FA values with corresponding left and right regions of interest as percentage of the absolute difference between these values relative to the sum of the respective FA values. Statistical analysis included Spearman rank correlations, Mann-Whitney test, and reliability analysis. Results: Healthy volunteers had low asymmetry index (1.5%-2.2%). In MS patients, structural abnormalities were reflected by asymmetric decrease of FA (asymmetry index: 3.6%; P = .15). Frequently asymmetrically affected among MS patients was left and right central motor conduction time (CMCT) to abductor digiti minimi muscle (ADMM) (asymmetry index, 15%-16%) and tibialis anterior muscle (TAM) (asymmetry index, 9.5%-14.1%). Statistically significant correlations of functional (ie, electrophysiological) and structural (ie, DT imaging) asymmetries were found (P = .005 for CMCT to ADMM; P = .007 for CMCT to TAM) for the cervical lateral funiculi, which comprise the crossed pyramidal tract. Interobserver reliability for DT imaging measurements was excellent (78%-87%). Conclusion: DT imaging revealed asymmetric anatomic changes in spinal cord NAWM, which corresponded to asymmetric electrophysiological deficits for both arms and legs, and reflected a specific structure-function relationship in the human spinal cord. © RSNA, 2013.

Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

Line-scan diffusion tensor imaging of the posttraumatic brain stem: changes with neuropathologic correlation

Following trauma, imaging of brain stem lesions is often inconclusive. In a man who suffered a lethal accident, postmortem MR diffusion tensor (DT) imaging of the brain and neuropathologic examination were performed. DT imaging showed a disorganization of fibers in the brain stem that was not found in 2 controls and corresponded to changes on neuropathologic correlation. Diffusion tensor imaging provides an insight into the organization of myelinated structures of the CNS, potentially allowing diagnosis of traumatic fiber tract rupture.

Cerebral connectivity and psychotic personality traits : A diffusion tensor imaging study

This study aims to investigate the relationship between regional connectivity in the brain white matter and the presence of psychotic personality traits, in healthy subjects with psychotic traits. Thirteen healthy controls were administered the MMPI-2, to assess psychotic traits and, according to MMPI results, a dichotomization into a group of "high-psychotic" and "low-psychotic" was performed. Diffusion tensor imaging (DTI) was used as a non-invasive measure, in order to obtain information about the fractional anisotropy (FA), an intravoxel index of local connectivity and, by means of a voxelwise approach, the between-group differences of the FA values were calculated. The "high-psychotic" group showed higher FA in the left arcuate fasciculus. Subjects with low scores for psychotic traits had significantly higher FA in the corpus callosum, right arcuate fasciculus, and fronto-parietal fibers. In line with previous brain imaging studies of schizophrenia spectrum disorders, our results suggest that psychotic personality traits are related to altered connectivity and brain asymmetry.

Characterization of white matter alterations in phenylketonuria by magnetic resonance relaxometry and diffusion tensor imaging

A multimodal MR study including relaxometry, diffusion tensor imaging (DTI), and MR spectroscopy was performed on patients with classical phenylketonuria (PKU) and matched controls, to improve our understanding of white matter (WM) lesions. Relaxometry yields information on myelin loss or malformation and may substantiate results from DTI attributed to myelin changes. Relaxometry was used to determine four brain compartments in normal-appearing brain tissue (NABT) and in lesions: water in myelin bilayers (myelin water, MW), water in gray matter (GM), water in WM, and water with long relaxation times (cerebrospinal fluid [CSF]-like signals). DTI yielded apparent diffusion coefficients (ADCs) and fractional anisotropies. MW and WM content were reduced in NABT and in lesions of PKU patients, while CSF-like signals were significantly increased. ADC values were reduced in PKU lesions, but also in the corpus callosum. Diffusion anisotropy was reduced in lesions because of a stronger decrease in the longitudinal than in the transverse diffusion. WM content and CSF-like components in lesions correlated with anisotropy and ADC. ADC values in lesions and in the corpus callosum correlated negatively with blood and brain phenylalanine (Phe) concentrations. Intramyelinic edema combined with vacuolization is a likely cause of the WM alterations. Correlations between diffusivity and Phe concentrations confirm vulnerability of WM to high Phe concentrations.

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.

Volumetry and diffusion tensor imaging of hippocampal subregions in schizophrenia

Previous MRI-volumetric studies in schizophrenic psychoses have demonstrated more or less pronounced volume reductions of the hippocampus in patients. Correspondingly, neuropathological examinations on the brains of schizophrenics showed diverse structural changes of the hippocampus. Employing a high-resolution 3D-MPRAGE sequence, we found volume reductions in most hippocampal subregions of schizophrenic patients, which, however, did not reach significant levels. An analysis of co-registered diffusion tensor imaging (DTI) data revealed significant alterations of the inter-voxel coherences in single hippocampal subdivisions of these patients, supporting the assumption of characteristic microstructural tissue changes relevant for the pathogenesis of schizophrenic psychoses. Our results argue for the usage of additional MRI modalities like DTI in order to detect subtle regional alterations of hippocampal structure in schizophrenics.

Linking brain connectivity across different time scales with electroencephalogram, functional magnetic resonance imaging, and diffusion tensor imaging

Structural and functional connectivity are intrinsic properties of the human brain and represent the amount of cognitive capacities of individual subjects. These connections are modulated due to development, learning, and disease. Momentary adaptations in functional connectivity alter the structural connections, which in turn affect the functional connectivity. Thus, structural and functional connectivity interact on a broad timescale. In this study, we aimed to explore distinct measures of connectivity assessed by functional magnetic resonance imaging and diffusion tensor imaging and their association to the dominant electroencephalogram oscillatory property at rest: the individual alpha frequency (IAF). We found that in 21 healthy young subjects, small intraindividual temporal IAF fluctuations were correlated to increased blood oxygenation level-dependent signal in brain areas associated to working memory functions and to the modulation of attention. These areas colocalized with functionally connected networks supporting the respective functions. Furthermore, subjects with higher IAF show increased fractional anisotropy values in fascicles connecting the above-mentioned areas and networks. Hence, due to a multimodal approach a consistent functionally and structurally connected network related to IAF was observed.