Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy.

OBJECTIVES: To date, only four small studies have investigated the effects of adjuvant chemotherapy for breast cancer on the microstructure of cerebral white matter with magnetic resonance imaging (MRI). These studies, which were conducted shortly up to 10 years post-treatment, showed that chemotherapy is associated with focal loss of microstructural white matter integrity. We investigated the long-term effect of chemotherapy on white matter microstructural integrity by comparing the brains of chemotherapy-exposed breast cancer survivors to those of a population-based sample of women without a history of cancer. EXPERIMENTAL DESIGN: Diffusion tensor imaging (DTI) MRI (1.5 T) was performed in 187 CMF (cyclophosphamide, methotrexate, and 5-flourouracil) chemotherapy-exposed breast cancer survivors, mean age 64.2 (sd = 6.5) years, who had been diagnosed with cancer on average 21.2 (sd = 4.4) years before, and 374 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were whole-brain microstructural integrity as measured by fractional anisotropy and mean/axial/radial diffusivity and focal white matter integrity, which was analyzed with tract-based spatial statistics. All analyses were adjusted for age, cardiovascular risk factors, education, and symptoms of depression. PRINCIPAL OBSERVATIONS: No significant group differences were observed in white matter integrity. However, within the breast cancer survivors, time since treatment was inversely associated with lower global and focal white matter integrity. CONCLUSIONS: This cross-sectional study suggests that among chemotherapy-exposed breast cancer survivors white matter microstructural integrity deteriorates with accumulating time since treatment. This warrants further investigation.

Multiple-echo diffusion tensor acquisition technique (MEDITATE) on a 3T clinical scanner.

This article describes the concepts and implementation of an MRI method, the multiple-echo diffusion tensor acquisition technique (MEDITATE), which is capable of acquiring apparent diffusion tensor maps in two scans on a 3T clinical scanner. In each MEDITATE scan, a set of RF pulses generates multiple echoes, the amplitudes of which are diffusion weighted in both magnitude and direction by a pattern of diffusion gradients. As a result, two scans acquired with different diffusion weighting strengths suffice for accurate estimation of diffusion tensor imaging (DTI) parameters. The MEDITATE variation presented here expands previous MEDITATE approaches to adapt to the clinical scanner platform, such as exploiting longitudinal magnetization storage to reduce T2 weighting. Fully segmented multi-shot Cartesian encoding is used for image encoding. MEDITATE was tested on isotropic (agar gel), anisotropic diffusion phantoms (asparagus) and in vivo skeletal muscle in healthy volunteers with cardiac gating. Comparisons of accuracy were performed with standard twice-refocused spin echo (TRSE) DTI in each case and good quantitative agreement was found between diffusion eigenvalues, mean diffusivity and fractional anisotropy derived from TRSE DTI and from the MEDITATE sequence. Orientation patterns were correctly reproduced in both isotropic and anisotropic phantoms, and approximately for in vivo imaging. This illustrates that the MEDITATE method of compressed diffusion encoding is feasible on the clinical scanner platform. With future development and employment of appropriate view-sharing image encoding, this technique may be used in clinical applications requiring time-sensitive acquisition of DTI parameters such as dynamical DTI in muscle.

Spatial characteristics of white matter abnormalities in schizophrenia.

There is considerable evidence implicating brain white matter (WM) abnormalities in the pathophysiology of schizophrenia; however, the spatial localization of WM abnormalities reported in the existing studies is heterogeneous. Thus, the goal of this study was to quantify the spatial characteristics of WM abnormalities in schizophrenia. One hundred and fourteen patients with schizophrenia and 138 matched controls participated in this multisite study involving the Universities of Iowa, Minnesota, and New Mexico, and the Massachusetts General Hospital. We measured fractional anisotropy (FA) in brain WM regions extracted using 3 different image-processing algorithms: regions of interest, tract-based spatial statistics, and the pothole approach. We found that FA was significantly lower in patients using each of the 3 image-processing algorithms. The region-of-interest approach showed multiple regions with lower FA in patients with schizophrenia, with overlap at all 4 sites in the corpus callosum and posterior thalamic radiation. The tract-based spatial statistic approach showed (1) global differences in 3 of the 4 cohorts and (2) lower frontal FA at the Iowa site. Finally, the pothole approach showed a significantly greater number of WM potholes in patients compared to controls at each of the 4 sites. In conclusion, the spatial characteristics of WM abnormalities in schizophrenia reflect a combination of a global low-level decrease in FA, suggesting a diffuse process, coupled with widely dispersed focal reductions in FA that vary spatially among individuals (ie, potholes).

Functional brain basis of hypnotizability.

CONTEXT: Focused hypnotic concentration is a model for brain control over sensation and behavior. Pain and anxiety can be effectively alleviated by hypnotic suggestion, which modulates activity in brain regions associated with focused attention, but the specific neural network underlying this phenomenon is not known. OBJECTIVE: To investigate the brain basis of hypnotizability. DESIGN: Cross-sectional, in vivo neuroimaging study performed from November 2005 through July 2006. SETTING: Academic medical center at Stanford University School of Medicine. PATIENTS: Twelve adults with high and 12 adults with low hypnotizability. MAIN OUTCOME MEASURES: Functional magnetic resonance imaging to measure functional connectivity networks at rest, including default-mode, salience, and executive-control networks; structural T1 magnetic resonance imaging to measure regional gray and white matter volumes; and diffusion tensor imaging to measure white matter microstructural integrity. RESULTS: High compared with low hypnotizable individuals had greater functional connectivity between the left dorsolateral prefrontal cortex, an executive-control region of the brain, and the salience network composed of the dorsal anterior cingulate cortex, anterior insula, amygdala, and ventral striatum, involved in detecting, integrating, and filtering relevant somatic, autonomic, and emotional information using independent component analysis. Seed-based analysis confirmed elevated functional coupling between the dorsal anterior cingulate cortex and the dorsolateral prefrontal cortex in high compared with low hypnotizable individuals. These functional differences were not due to any variation in brain structure in these regions, including regional gray and white matter volumes and white matter microstructure. CONCLUSIONS: Our results provide novel evidence that altered functional connectivity in the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex may underlie hypnotizability. Future studies focusing on how these functional networks change and interact during hypnosis are warranted.

Connectivity of thalamo-cortical pathway in rat brain: combined diffusion spectrum imaging and functional MRI at 11.7 T.

Fiber tracking in combination with functional MRI has recently attracted strong interest, as it may help to elucidate the structural basis for functional connectivities and may be selective in the determination of the fiber bundles responsible for a particular circuit. Diffusion spectrum imaging provides a more complex analysis of fiber circuits than the commonly used diffusion tensor imaging approach, also allowing the discrimination of crossing fibers in the brain. For the understanding of pathophysiological alterations during brain lesion and recovery, such studies need to be extended to small-animal models. In this article, we present the first study combining functional MRI with high-resolution diffusion spectrum imaging in vivo. We have chosen the well-characterized electrical forepaw stimulation paradigm in the rat to examine the thalamo-cortical pathway. Using the functionally activated areas in both thalamus and somatosensory cortex as seed and target regions for fiber tracking, we are able to characterize the fibers responsible for this stimulation pathway. Moreover, we show that the selection of the thalamic nucleus and primary somatosensory cortex on the basis of anatomical description results in a larger fiber bundle, probably encompassing connectivities between the thalamus and other areas of the somatosensory cortex, such as the hindpaw and large barrel field cortex.