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Biomedical subjects

Norbert Schuff

Publications and source records attributed to Norbert Schuff.

At least 19 recordsLinked to original sources

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease.

In Alzheimer's disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed.

Aged↗

Longitudinal stability of MRI for mapping brain change using tensor-based morphometry.

Measures of brain change can be computed from sequential MRI scans, providing valuable information on disease progression, e.g., for patient monitoring and drug trials. Tensor-based morphometry (TBM) creates maps of these brain changes, visualizing the 3D profile and rates of tissue growth or atrophy, but its sensitivity depends on the contrast and geometric stability of the images. As part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), 17 normal elderly subjects were scanned twice (at a 2-week interval) with several 3D 1.5 T MRI pulse sequences: high and low flip angle SPGR/FLASH (from which Synthetic T1 images were generated), MP-RAGE, IR-SPGR (N = 10) and MEDIC (N = 7) scans. For each subject and scan type, a 3D deformation map aligned baseline and follow-up scans, computed with a nonlinear, inverse-consistent elastic registration algorithm. Voxelwise statistics, in ICBM stereotaxic space, visualized the profile of mean absolute change and its cross-subject variance; these maps were then compared using permutation testing. Image stability depended on: (1) the pulse sequence; (2) the transmit/receive coil type (birdcage versus phased array); (3) spatial distortion corrections (using MEDIC sequence information); (4) B1-field intensity inhomogeneity correction (using N3). SPGR/FLASH images acquired using a birdcage coil had least overall deviation. N3 correction reduced coil type and pulse sequence differences and improved scan reproducibility, except for Synthetic T1 images (which were intrinsically corrected for B1-inhomogeneity). No strong evidence favored B0 correction. Although SPGR/FLASH images showed least deviation here, pulse sequence selection for the ADNI project was based on multiple additional image analyses, to be reported elsewhere.

Aged↗

A non-parametric approach for co-analysis of multi-modal brain imaging data: application to Alzheimer's disease.

We developed a new flexible approach for a co-analysis of multi-modal brain imaging data using a non-parametric framework. In this approach, results from separate analyses on different modalities are combined using a combining function and assessed with a permutation test. This approach identifies several cross-modality relationships, such as concordance and dissociation, without explicitly modeling the correlation between modalities. We applied our approach to structural and perfusion MRI data from an Alzheimer's disease (AD) study. Our approach identified areas of concordance, where both gray matter (GM) density and perfusion decreased together, and areas of dissociation, where GM density and perfusion did not decrease together. In conclusion, these results demonstrate the utility of this new non-parametric method to quantitatively assess the relationships between multiple modalities.

Aged↗

Age effects on atrophy rates of entorhinal cortex and hippocampus.

The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04+/-0.02% per year for ERC and 0.05+/-0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE epsilon4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials.

Aged↗

Summarizing complexity in high dimensions.

High-dimensional, multispectral data on complex physical systems are increasingly common. As the amount of information in data sets increases, the difficulty of effectively utilizing it also increases. For such data, summary information is required for understanding and modeling the underlying dynamics. It is here proposed to use an extension of computational mechanics [C. R. Shalizi and J. P. Crutchfield, J. Stat. Phys. 104, 817 (2001)] to arbitrary spatiotemporal and spectral dimension, for providing such summary information. An example of the use of these tools to identify state evolution in the brain, an archetypal, complex biophysical system, serves as an illustration.

Alzheimer Disease↗

Four-phase single-capillary stepwise model for kinetics in arterial spin labeling MRI.

An extended model for extracting measures of brain perfusion from pulsed arterial spin labeling (ASL) data while considering transit effects and restricted permeability of capillaries to blood water is proposed. We divided the time course of the signal difference between control and labeled images into four phases with respect to the arrival time of labeled blood water at the voxel of interest (t(A)), transit time through the arteries in the voxel (t(ex)), and duration of the bolus of labeled spins (tau). Dividing the labeled slab of blood water into many discrete segments, and adapting numerical integration methods allowed us to conveniently model restricted capillary-tissue exchange based on a modified distributed parameter model. We compared this four-phase single-capillary stepwise (FPSCS) model with models that treat water as a freely diffusible tracer, using both simulations and experimental ASL brain imaging data at 1.5T from eight healthy subjects (24-80 years old). The FPSCS model yielded less errors in the least-squares sense in fitting brain ASL data in comparison with freely diffusible tracer models of water (P = 0.055). These results imply that restricted permeability of capillaries to water should be considered when brain ASL data are analyzed.

Adult↗

Achieving sufficient spectral bandwidth for volumetric 1H echo-planar spectroscopic imaging at 4 Tesla.

Complete coverage of the in vivo proton metabolite spectrum, including downfield resonances, requires a spectral bandwidth of approximately 9 ppm. Spectral bandwidth of in vivo echo-planar spectroscopic imaging (EPSI) is primarily limited by gradient strength of the oscillating readout gradient, gradient slew rate, and limits on peripheral nerve stimulation for human subjects. Furthermore, conventional EPSI reconstruction, which utilizes even and odd readout echoes separately, makes use of only half the spectral bandwidth. In order to regain full spectral bandwidth in EPSI, it has previously been suggested to apply an interlaced Fourier transform (iFT), which uses even and odd echoes simultaneously. However, this method has not been thoroughly analyzed regarding its usefulness for in vivo 3D EPSI. In this Note, limitations of the iFT method are discussed and an alternative, cyclic spectral unwrapping, is proposed, which is based on prior knowledge of typical in vivo spectral patterns.

Adult↗

Scyllo-inositol in normal aging human brain: 1H magnetic resonance spectroscopy study at 4 Tesla.

The scyllo-inositol and myo-inositol concentrations of 24 normal human subjects were measured in vivo using 1H magnetic resonance spectroscopy at 4 T. Single-voxel short-echo (TE = 15 ms) metabolite spectra were collected from the white matter region of the corona radiata. Test-retest studies performed on 10 normal subjects demonstrated coefficient of variation for scyllo-inositol measurement of 37%, compared with 6% for N-acetyl aspartate. Comparisons between old and young subjects showed higher concentration of scyllo-inositol and myo-inositol in older subjects and a trend for a correlation between scyllo-inositol and myo-inositol levels across subjects.

Adaptation, Physiological↗

White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy.

The goal of this study was to examine the relationship between subcortical vascular disease and brain atrophy in patients with Alzheimer's disease (AD) and mixed dementia (i.e., AD and subcortical vascular disease together). MRI was performed on 77 cognitively normal (CN) subjects, 50 AD and 13 mixed dementia patients. Subcortical vascular disease was determined by white matter hyperintensities (WMH) volume and presence of subcortical lacunes. Brain atrophy was measured using total brain cortical gray matter (CGM), entorhinal cortex (ERC) and hippocampal volumes. CGM volume, but not ERC or hippocampal volume was inversely related to WMH volume in patients and controls. In contrast, no relationship was detected between CGM, ERC, or hippocampal volumes and subcortical lacunes. Furthermore, no interaction was found between WMH and diagnosis on cortical atrophy, implying that WMH affect cortical atrophy indifferently of group. These results suggest that subcortical vascular disease, manifested as WMH, may affect cortical atrophy more than ERC and hippocampal atrophy. Further, AD pathology and subcortical vascular disease may independently affect cortical atrophy.

Aged↗

Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T.

Proton magnetic resonance spectroscopy was performed at 4 T to determine effects of age, region and gender on glutamate and glutamine in the normal human brain. Furthermore, glutamate and glutamine alterations with age were tested for correlations with other cerebral metabolites. Two 8 cm3 volumes were selected in corona radiata and mesial motor cortex in normal subjects (N = 24) between 24 and 68 years old. Older subjects had lower glutamate concentration in the motor cortex compared to younger subjects (p < 0.001). In corona radiata, older subjects demonstrated a trend in higher glutamine compared to younger subjects (p = 0.05). Glutamate in the motor cortex was positively correlated with glutamine, N-acetyl aspartate and creatine. Reduced glutamate and N-acetyl aspartate in the motor cortex is consistent with neuronal loss/shrinkage with age. In conclusion, different patterns in association with normal aging in these brain regions were detected in this study.

Adult↗

Dissociations in hippocampal and frontal contributions to episodic memory performance.

The hippocampus and frontal lobes both contribute to episodic memory performance. In the present study, the authors evaluated the relative contributions of hippocampus, frontal lobes, anterior temporal cortex, and posterior cortex to memory performance in neurodegenerative patients and normal older controls. Subjects (n=42) were studied with structural MRI and a memory paradigm that measured delayed recall, semantic clustering during recall, recognition discriminability, and recognition response bias. Data were analyzed with multiple regression. Consistent with the authors' hypotheses, hippocampal volumes were the best predictor of delayed recall and recognition discriminability, whereas frontal volumes were the best predictor of semantic clustering and response bias. Smaller frontal volumes were associated with less semantic clustering during recall and a more liberal response bias. Results indicate that hippocampal and frontal contributions to episodic memory can be dissociated, with the hippocampus more important for memory accuracy, and frontal structures more important for strategic processing and decision making.

Aged↗

Sensitive and fast T1 mapping based on two inversion recovery images and a reference image.

We developed a fast method to obtain T1 relaxation maps in magnetic resonance imaging (MRI) based on two inversion recovery acquisitions and a reference acquisition, while maintaining high sensitivity by utilizing the full dynamic range of the MRI signal. Optimal inversion times for estimating T1 in the human brain were predicted using standard error propagation theory. In vivo measurements on nine healthy volunteers yielded T1 values of 1094+/-18 ms in gray matter and 746+/-40 ms in white matter, in reasonable agreement with literature values using conventional approaches. The proposed method should be useful for clinical studies because the T1 maps can be obtained within a few seconds.

Algorithms↗

Human brain: reliability and reproducibility of pulsed arterial spin-labeling perfusion MR imaging.

The Committee of Human Research of the University of California San Francisco approved this study, and all volunteers provided written informed consent. The goal of this study was to prospectively determine the global and regional reliability and reproducibility of noninvasive brain perfusion measurements obtained with different pulsed arterial spin-labeling (ASL) magnetic resonance (MR) imaging methods and to determine the extent to which within-subject variability and random noise limit reliability and reproducibility. Thirteen healthy volunteers were examined twice within 2 hours. The pulsed ASL methods compared in this study differ mainly with regard to magnetization transfer and eddy current effects. There were two main results: (a) Pulsed ASL MR imaging consistently had high measurement reliability (intraclass correlation coefficients greater than 0.75) and reproducibility (coefficients of variation less than 8.5%), and (b) random noise rather than within-subject variability limited reliability and reproducibility. It was concluded that low signal-to-noise ratios substantially limit the reliability and reproducibility of perfusion measurements.

Adult↗

Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience.

PURPOSE: To prospectively determine if pulsed arterial spin-labeling perfusion magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI), compared with perfusion in cognitively normal (CN) subjects, that is consistent with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) studies of similar populations. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty subjects with AD (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women; mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9 years) underwent arterial spin-labeling and volumetric T1-weighted structural MR imaging. Perfusion images were coregistered to structural images, corrected for partial volume effects (PVEs) with information from the structural image to determine tissue content of perfusion voxels, and normalized to a study-specific template. Analyses of perfusion differences between groups, with and without corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed fixed-effects analysis of covariance model adjusted for age. In addition, tests were performed with and without accounting for global perfusion. RESULTS: The AD group showed significant regional hypoperfusion, compared with the CN group, in the right inferior parietal cortex extending into the bilateral posterior cingulate gyri (P <.001), bilateral superior and middle frontal gyri (P <.001), and left inferior parietal lobe (P=.007). When PVEs from underlying cortical gray matter atrophy were accounted for, the AD group still showed hypoperfusion in the right inferior parietal lobe extending into the bilateral posterior cingulate gyri (P <.001) and left (P=.003) and right (P=.012) middle frontal gyri. With a more liberal voxel-level threshold of P <.01, the MCI group showed significant regional hypoperfusion relative to the CN group in the inferior right parietal lobe (P=.046), similar to the region of greatest significance in the AD group. CONCLUSION: Arterial spin-labeling MR imaging showed regional hypoperfusion with AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of similar populations; this hypoperfusion persists after accounting for underlying cortical gray matter atrophy.

Aged↗

Hippocampal volume and retention in Alzheimer's disease.

This study tested the hypothesis that the hippocampus has a relatively specific role in retaining information over delays. Thirty-seven subjects with probable Alzheimer's disease were evaluated with a verbal memory task and structural MRI. Cortical gray matter but not hippocampal volume predicted immediate free recall. In contrast, hippocampal volume was the best predictor of how well information was retained over a delay, even after controlling for levels of immediate recall. Results suggest that the role of the hippocampus is relatively specific to the consolidation of new memories.

Aged↗

Attention, learning, and memory in posttraumatic stress disorder.

This study compared attention and declarative memory in a sample of combat veterans with posttraumatic stress disorder (PTSD, n = 24) previously reported to have reduced concentrations of the hippocampal neuronal marker N-acetyl aspartate (NAA), but similar hippocampal volume compared to veteran normal comparison participants (n = 23). Healthy, well-educated males with combat-related PTSD without current depression or recent alcohol/drug abuse did not perform differently on tests of attention, learning, and memory compared to normal comparison participants. Further, hippocampal volume, NAA, or NAA/Creatine ratios did not significantly correlate with any of the cognitive measures when adjustments for multiple comparisons were made. In this study, reduced hippocampal NAA did not appear to be associated with impaired declarative memory.

Alcoholism↗

Forgetting in dementia with and without subcortical lacunes.

Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD) are common causes of dementia, often co-occur, and can present quite similarly, making differential diagnosis clinically challenging. This study tested the hypothesis that patients with SIVD retain information better than AD patients. Participants were 35 dementia patients with subcortical lacunes (SIVD group), 27 dementia patients without lacunar infarction (AD group), and 56 normal controls. Results indicated that despite comparable levels of initial acquisition, AD patients showed more rapid forgetting. Further analysis indicated that memory patterns within the SIVD group were heterogeneous, with some participants exhibiting rapid forgetting and some exhibiting good retention. SIVD participants with good retention showed a trend for greater executive impairments relative to SIVD participants with rapid forgetting and AD participants. Results suggest that rapid forgetting in SIVD may imply concomitant AD, whereas the dementia in patients with good retention may be purely vascular in origin. Three SIVD patients with rapid forgetting followed to autopsy all had AD pathology, further supporting the link between memory patterns and AD.

Aged↗