Norbert Schuff

Background: This study reports the baseline characteristics of diffusion tensor imaging data in Parkinson's disease (PD) patients and healthy control subjects from the Parkinson's Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits.Methods: Two hundred twenty subjects (PD = 153; control = 67) from 10 imaging sites were included. All subjects had a full neurological exam, a (¹²³I)ioflupane dopamine transporter (DAT) single‐photon emission computer tomography scan, and diffusion tensor imaging. Fractional anisotropy as well as radial and axial diffusivity was computed within multiple regions across the substantia nigra.Results: A repeated‐measures analysis of variance found a marginally nonsignificant interaction between regional fractional anisotropy of the substantia nigra and disease status (P = 0.08), conflicting with an earlier study. However, a linear mixed model that included control regions in addition to the nigral regions revealed a significant interaction between regions and disease status (P = 0.002), implying a characteristic distribution of reduced fractional anisotropy across the substantia nigra in PD. Reduced fractional anisotropy in PD was also associated with diminished DAT binding ratios. Both axial and radial diffusivity were also abnormal in PD.Conclusions: Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more‐sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality. © 2015 International Parkinson and Movement Disorder Society

Background: To test the hypothesis that white matter lesions (WML) are primarily associated with regional frontal cortical volumes, and to determine the mediating effects of these regional frontal cortices on the associations of WML with depressive symptoms and cognitive dysfunction. Methods: Structural brains MRIs were performed on 161 participants: cognitively normal, cognitive impaired but not demented, and demented participants. Lobar WML volumes, regional frontal cortical volumes, depressive symptom severity, and cognitive abilities were measured. Multiple linear regression analyses were used to identify WML volume effects on frontal cortical volume. Structural equation modeling was used to determine the MRI-depression and the MRI-cognition path relationships. Results: WML predicted frontal cortical volume, particularly in medial orbirtofrontal cortex, irrespective of age, gender, education, and group status. WML directly predicted depressive score, and this relationship was not mediated by regional frontal cortices. In contrast, the association between WML and cognitive function was indirect and mediated by regional frontal cortices. Conclusions: These findings suggest that the neurobiological mechanisms underpinning depressive symptoms and cognitive dysfunction in older adults may differ.

The development of an accurate marker for Alzheimers disease (AD) at the earliest stage is an important public health goal. Modern neuroimaging techniques offer one potential approach to identify a marker for AD. This review focuses on the detection of alterations in brain perfusion as a potentially sensitive index of AD pathology using arterial spin labeling (ASL) perfusion mapping – a relatively new variant of magnetic resonance imaging (MRI). Key findings of ASL perfusion studies in AD mild cognitive impairment (MCI), a transitional stage between normal aging and AD as well as in other forms of dementia are discussed. Furthermore, the value of ASL-MRI for improved diagnosis and prediction of AD is critically reviewed.

Nonrigid registration of diffusion magnetic resonance imaging (MRI) is crucial for group analyses and building white matter and fiber tract atlases. Most current diffusion MRI registration techniques are limited to the alignment of diffusion tensor imaging (DTI) data. We propose a novel diffeomorphic registration method for high angular resolution diffusion images by mapping their orientation distribution functions (ODFs). ODFs can be reconstructed using q-ball imaging (QBI) techniques and represented by spherical harmonics (SHs) to resolve intra-voxel fiber crossings. The registration is based on optimizing a diffeomorphic demons cost function. Unlike scalar images, deforming ODF maps requires ODF reorientation to maintain its consistency with the local fiber orientations. Our method simultaneously reorients the ODFs by computing a Wigner rotation matrix at each voxel, and applies it to the SH coefficients during registration. Rotation of the coefficients avoids the estimation of principal directions, which has no analytical solution and is time consuming. The proposed method was validated on both simulated and real data sets with various metrics, which include the distance between the estimated and simulated transformation fields, the standard deviation of the general fractional anisotropy and the directional consistency of the deformed and reference images. The registration performance using SHs with different maximum orders were compared using these metrics. Results show that the diffeomorphic registration improved the affine alignment, and registration using SHs with higher order SHs further improved the registration accuracy by reducing the shape difference and improving the directional consistency of the registered and reference ODF maps.

Context Most neuroimaging studies of posttraumatic stress disorder (PTSD) have focused on potential abnormalities in the whole hippocampus, but the subfields of this structure, which have distinctive histological characteristics and specialized functions, have not been investigated. Studies of individual subfields may clarify the role of the hippocampus in PTSD. Objective To determine if PTSD is associated with structural alterations in specific subfields of the hippocampus. Design Case-control study. Participants A total of 17 male veterans with combat trauma and PTSD (mean [SD] age, 41 [12] years) and 19 age-matched male veterans without PTSD who were recruited from the outpatient mental health clinic of the San Francisco Veterans Affairs Medical Center and by advertising in the community. Interventions High-resolution magnetic resonance imaging at 4 T. Main Outcome Measure Volumes of hippocampal subfields. Results Posttraumatic stress disorder was associated with 11.4% (1.5%) (P = .02) smaller mean (SD) cornu ammonis 3 (CA3)/dentate gyrus subfield volumes, irrespective of age-related alterations, whereas other subfields were spared. Age was associated with reduced volume of the CA1 subfield (P = .03). Total hippocampal volume was also reduced in PTSD by a mean (SD) of 6.5% (0.6%) but, related to both PTSD (P = .05) and age (P = .01), was consistent with the measurements in the subfields. Conclusions The findings indicate for the first time in humans that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields, consistent with animal studies, implying that chronic stress suppresses neurogenesis and dendritic branching in these structures.

Background: Our objectives were to compare the effects of subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD) on cerebral blood flow (CBF), and then to analyze the relationship between CBF and subcortical vascular disease, measured as volume of white‐matter lesions (WMLs).Methods: Eight mildly demented patients with SIVD (mean ± SD; aged 77 ± 8 years; Mini‐Mental State Examination score 26 ± 3 years) and 14 patients with AD were compared with 18 cognitively normal elderly subjects. All subjects had CBF measured using arterial spin‐labeling magnetic resonance imaging, and brain volumes were assessed using structural magnetic resonance imaging.Results: AD and SIVD showed marked CBF reductions in the frontal (P = 0.001) and parietal (P = 0.001) cortices. In SIVD, increased subcortical WMLs were associated with reduced CBF in the frontal cortex (P = 0.04), in addition to cortical atrophy (frontal, P = 0.05; parietal, P = 0.03).Conclusions: Subcortical vascular disease is associated with reduced CBF in the cortex, irrespective of brain atrophy.