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Biomedical subjects

J H Duyn

Publications and source records attributed to J H Duyn.

At least 37 records · Page 2Linked to original sources

Age-related vasodilatory response to acetazolamide challenge in healthy adults: a dynamic contrast-enhanced MR study.

PURPOSE: We examined age-related changes in baseline regional cerebral blood volume (rCBV) and response to acetazolamide stimulation by using dynamic contrast-enhanced MR imaging. METHODS: Thirty healthy volunteers ranging widely in age (23 to 82 years) were examined before and after intravenous injection of acetazolamide with dynamic susceptibility contrast-enhanced MR imaging. rCBV values were normalized for intersubject and intrasubject comparison by estimating an arterial input function directly from the imaging data. Preacetazolamide baseline rCBV and the percentage volume change index (PVCI) of the postacetazolamide to preacetazolamide state were calculated and examined as a function of age. RESULTS: Older adults (>50 years) had lower baseline rCBV per unit tissue than did younger adults (<50 years), but higher rCBV after acetazolamide stimulation. Baseline rCBV tended to decrease with age in the medial frontal and frontoparietal gray matter regions. Response to acetazolamide stimulation, measured by PVCI, showed a significant age-related increase in gray matter, approximately 0.5% per year. CONCLUSION: rCBV can be significantly increased after acetazolamide stimulation in the healthy aged. These results support the notion that age-related decreases in rCBV measured at rest reflect reduced regional metabolic requirements rather than reduced capacity for regional substrate delivery. These data serve as a normative baseline for comparison studies of rCBV vascular reserve in aging persons with various cerebrovascular disorders.

Acetazolamide↗

Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline and during treatment with interferon beta-1b.

BACKGROUND AND PURPOSE: To determine whether occult disease fluctuates with macroscopic lesions during the natural history of multiple sclerosis (MS) and whether therapeutic interventions affect occult disease, we performed serial monthly magnetization transfer (MT) imaging in patients with relapsing-remitting MS in a crossover trial with interferon beta-lb. METHODS: Serial whole-brain magnetization transfer ratios (MTRs) in eight patients with relapsing-remitting MS and in four control subjects were plotted as normalized histograms, and MTR parameters were compared with contrast-enhancing lesions and bulk white matter lesion load. RESULTS: In patients with relapsing-remitting MS, the histographic peak of 0.25+/-0.01 and the histographic mean of 0.21+/-0.01 were statistically lower than corresponding values in control subjects, in whom the histographic peak was 0.27+/-0.01 and the histographic mean was 0.23+/-0.01. When histograms (with MTRs ranging from 0.0 to 0.5) were analyzed by quartiles (quartile 1 to quartile 4) based on histographic area, voxels with low MTRs in quartile 1 (0 to 0.12) increased during the baseline period and corresponded to bulk white matter lesion load. Interferon beta-lb reduced enhancing lesions by 91% and mean bulk white matter lesion load by 15%, but had no effect on MTR in this patient cohort. CONCLUSION: Occult disease in normal-appearing white matter of patients with relapsing-remitting MS measured by MTR parallels the waxing and waning pattern of enhancing lesions and bulk white matter lesion load during the baseline period. MTR is not altered by interferon beta-lb, which raises the possibility of ongoing disease in normal-appearing white matter (not detected by conventional MR sequences).

Adjuvants, Immunologic↗

Steady state effects in fast gradient echo magnetic resonance imaging.

Fourier methodology is applied to analyze steady state effects in fast gradient echo imaging. Simulations and MR imaging experiments on phantoms demonstrate the effectiveness of existing schemes under different experimental conditions, and modifications are introduced which result in reduced sensitivity to slow object motion as compared to conventional phase modulation schemes. In addition, phase modulation schemes are introduced which more than double temporal signal stability in human brain scans, at flip angles well above the Ernst angle and TR << T1, T2. Application of phase modulation to the measurement of higher order signals shows increased sensitivity, particularly for the highest order signals.

Blood Flow Velocity↗

Fast spiral magnetic resonance imaging with trapezoidal gradients.

A modified spiral imaging technique is presented, in which the conventional sinusoidal gradient waveforms are replaced by trapezoidal ones. In addition to allowing a reduced data acquisition time, the new waveforms circumvent specific hardware restrictions on the minimum scan repetition time.

Brain↗

Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy.

Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a "pseudodeficiency" phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder.

Acidosis, Lactic↗

Increased choline signal coinciding with malignant degeneration of cerebral gliomas: a serial proton magnetic resonance spectroscopy imaging study.

The authors tested the hypothesis that proton magnetic resonance spectroscopy (1H-MRS) imaging can be used as a supportive diagnostic tool to differentiate clinically stable brain tumors from those progressing as a result of low- to high-grade malignant transformation or posttherapeutic recurrence. Twenty-seven patients with cerebral gliomas verified on histological examination were studied repeatedly with 1H-MRS imaging over a period of 3.5 years. At the time of each 1H-MRS imaging study, clinical examination, MR imaging, positron emission tomography with 18F-fluorodeoxyglucose, and biopsy findings (when available) were used to categorize each patient as having either stable or progressive disease. Measures of the percentage changes in the choline (Cho) 1H-MRS imaging signal intensity between studies, which were obtained without knowledge of the clinical categorization, allowed the investigators to segregate the groups with a high degree of statistical significance. All progressive cases showed a Cho signal increase between studies of more than 45%, whereas all stable cases showed an elevation of less than 35%, no change, or even a decreased signal. The authors conclude that increased Cho levels coincide with malignant degeneration of cerebral gliomas and therefore may possibly be used as a supportive indicator of progression of these neoplasms.

Adult↗

Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus.

OBJECTIVE: The significance and etiology of focal brain lesions in systemic lupus erythematosus (SLE) are unknown. Our purpose was to determine whether the neurochemistry of focal lesions and normal appearing brain tissues in SLE were consistent with neuronal loss, demyelination, or ischemia. METHODS: Patients with SLE (n = 14) and controls (n = 13) were studied using magnetic resonance imaging (MRI) and spectroscopic imaging (SI) at 1.5 Tesla. RESULTS: MRI detected fixed focal brain lesions (n = 16) and SI measured brain metabolites, including N-acetylaspartate (NAA), creatine (Cre), choline (Cho), and lactate (Lac). NAA/Cre of normal appearing brain was decreased in patients with SLE compared to controls: grey matter (1.74 +/- 0.16 vs 1.92 +/- 0.18; p = 0.01), occipital white matter (1.98 +/- 0.22 vs 2.23 +/- 0.16; p = 0.004), and periventricular white matter (2.00 +/- 0.23 vs 2.33 +/- 0.23; p = 0.001). Lesions were characterized by markedly decreased NAA/Cre relative to normal appearing tissues in the same patient (1.67 +/- 0.22 vs 1.88 +/- 0.14; p = 0.0002). Elevated Cho/Cre was observed in 25% of focal lesions and 21% of normal appearing tissues. No elevation of lactate was observed in lesions or normal appearing tissues. CONCLUSION: SI detects focal and generalized brain abnormalities in SLE characterized by decreased NAA, elevated choline, and normal lactate. These findings are consistent with widespread neuronal injury and demyelination, but are not consistent with anaerobic metabolism.

Adult↗

Quantitative proton MR spectroscopic imaging of the human brain.

Multislice proton MR spectroscopic images (SI) of the brain were quantitated, using the phantom replacement technique. In 16 normal volunteers, ranging in age from 5 to 74 years, average "whole brain" concentrations of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) were found to be 2.4 +/- 0.4, 7.9 +/- 1.3, and 11.8 +/- 1.0 (mM, mean +/- SD), respectively. These values are in good general agreement with those previously determined by single-voxel localization techniques. Cortical gray matter was found to have lower Cho and NAA levels, compared to those of white matter, corpus callosum, and basal ganglia. Cho was also found to increase significantly with age in several locations. Quantitative multislice proton Si is feasible in the clinical environment, and regional and age-dependent variations occur that must be accounted for when evaluating spectra from pathological conditions.

Adolescent↗

Fast 3D functional magnetic resonance imaging at 1.5 T with spiral acquisition.

A new method to perform rapid 3D fMRI in human brain is introduced and evaluated in normal subjects, on a standard clinical scanner at 1.5 Tesla. The method combines a highly stable gradient echo technique with a spiral scan method, to detect brain activation related changes in blood oxygenation with high sensitivity. A motor activation paradigm with a duration of less than 5 min, performed on 10 subjects, consistently showed significant changes in signal intensity in the area of the motor cortex. In all subjects, these changes survived high statistical thresholds.

Brain↗

Functional magnetic resonance neuroimaging data acquisition techniques.

Functional MRI studies of human brain require rapid data acquisition techniques, to map dynamic changes with sufficient anatomical coverage. In addition, task activation studies employing functional MRI require a high scan sensitivity, in order to discriminate the small, activation-related signal changes from background noise. An overview is given of current fast scan methods, which are sensitized to detect susceptibility changes related to task-induced changes in blood oxygenation. Sources of artifacts are discussed, as well as their effect on image quality.

Artifacts↗

Functional mapping of human sensorimotor cortex with 3D BOLD fMRI correlates highly with H2(15)O PET rCBF.

Positron emission tomography (PET) functional imaging is based on changes in regional cerebral blood flow (rCBF). Functional magnetic resonance imaging (fMRI) is based on a variety of physiological parameters as well as rCBF. This study is aimed at the cross validation of three-dimensional (3D) fMRI, which is sensitive to changes in blood oxygenation, with oxygen-15-labeled water (H2(15)O) PET. Nine normal subjects repeatedly performed a simple finger opposition task during fMRI scans and during PET scans. Within-subject statistical analysis revealed significant ("activated") signal changes (p < 0.05, Bonferroni corrected for number of voxels) in contralateral primary sensorimotor cortex (PSM) in all subjects with fMRI and with PET. With both methods, 78% of all activated voxels were located in the PSM. Overlap of activated regions occurred in all subjects (mean 43%, SD 26%). The size of the activated regions in PSM with both methods was highly correlated (rho = 0.87, p < 0.01). The mean distance between centers of mass of the activated regions in the PSM for fMRI versus PET was 6.7 mm (SD 3.0 mm). Average magnitude of signal change in activated voxels in this region, expressed as z-values adapted to timeseries, zt, was similar (fMRI 5.5, PET 5.3). Results indicate that positive blood oxygen level-dependent (BOLD) signal changes obtained with 3D principles of echo shifting with a train of observations (PRESTO) fMRI are correlated with rCBF, and that sensitivity of fMRI can equal that of H2(15)O PET.

Adult↗

Whole-brain functional mapping with isotropic MR imaging.

PURPOSE: To assess the reliability and sensitivity of gradient-echo, isotropic multisection echo-planar magnetic resonance (MR) imaging for within-subject whole-brain mapping. MATERIALS AND METHODS: Eight right-handed healthy volunteers underwent gradient-echo, echo-planar MR imaging while they performed a motor task on three occasions over 2-3 months. Ninety-six whole-brain volumes were acquired in 8 minutes 48 seconds. A rigorous statistical threshold for determining activation was set at P < .05 and was Bonferroni corrected for approximately 15,000 cortical voxels. RESULTS: In all subjects, reproducible activation was demonstrated in multiple cortical areas and in the cerebellum specific to the motor system. Of the activated voxels, 75%-78% were confined to the motor areas during all sessions. No statistically significant difference was found in the proportion of activated voxels in any motor region (relative to the total number of activated voxels in the whole brain) across the three sessions. The centers of mass of the activated areas were within 2.5 resolution elements of the image across the three sessions. CONCLUSION: Isotropic multisection echo-planar MR imaging, has the potential for noninvasive, reliable within-subject mapping of whole-brain functional anatomy.

Adult↗

Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging.

OBJECTIVE: Several single-voxel proton magnetic resonance spectroscopy (1H-MRS) studies of patients with schizophrenia have found evidence of reductions of N-acetyl-aspartate (NAA) concentrations in the temporal lobes. Multislice proton magnetic resonance spectroscopy imaging (1H-MRSI) permits simultaneous acquisition and mapping of NAA, choline-containing compounds (CHO), and creatine/phosphocreatine (CRE) signal intensities from multiple whole brain slices consisting of 1.4-ml single-volume elements. We have used 1H-MRSI to assess the regional specificity of previously reported changes of metabolite signal intensities in schizophrenia. Hippocampal volume was also measured to test the relationship between 1H-MRSI findings and tissue volume in this region. METHOD: Ratios of areas under the metabolite peaks of the proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions in 10 inpatients with schizophrenia. RESULTS: Patients showed significant reductions of NAA/CRE and NAA/CHO bilaterally in the hippocampal region and in the dorsolateral prefrontal cortex. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios in the hippocampal region and its volume. CONCLUSIONS: NAA-relative signal intensity reductions in schizophrenia appear to be remarkably localized, involving primarily the hippocampal region and the dorsolateral prefrontal cortex, two regions implicated prominently in the pathophysiology of this disorder.

Adult↗

Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging.

BACKGROUND: Multislide proton magnetic resonance spectroscopic imaging (1H-MRSI) permits the simultaneous acquisition of N-acetylaspartate (NA), choline (Cho), creatine/phosphocreatine (Cre), and lactate (Lac) signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. NA is inferred to be a neuron-specific molecule, whereas Cho mainly reflects glycerophosphocholine and phosphocholine, compounds involved in phospholipid metabolism. OBJECTIVE: To assess whether 1H-MRSI could detect a regional pattern of cortical and subcortical involvement in the brain of Alzheimer's disease (AD) patients. METHODS: 1H-MRSI was performed in 15 patients with probable AD and 15 age-matched healthy controls. Regions of interest (ROIs) were selected from frontal (FC), temporal (TC), parietal (PC), occipital, and insular cortices, subcortical white matter (WM), and thalamus. RESULTS: In AD patients, we found a significant reduction of NA/Cre in the FC, TC, and PC and a significant reduction of Cho/Cre in the WM. CONCLUSIONS: This 1H-MRSI study of AD patients shows a regional pattern of neuronal damage in the associative cortices, as revealed by significant reduction of NA/Cre in the FC, TC, and PC, and regional derangement of phospholipid metabolism, as revealed by significant reduction of Cho/Cre in the WM.

Aged↗

Three-dimensional functional magnetic resonance imaging of human brain on a clinical 1.5-T scanner.

Functional magnetic resonance imaging (fMRI) is a tool for mapping brain function that utilizes neuronal activity-induced changes in blood oxygenation. An efficient three-dimensional fMRI method is presented for imaging brain activity on conventional, widely available, 1.5-T scanners, without additional hardware. This approach uses large magnetic susceptibility weighting based on the echo-shifting principle combined with multiple gradient echoes per excitation. Motor stimulation, induced by self-paced finger tapping, reliably produced significant signal increase in the hand region of the contralateral primary motor cortex in every subject tested.

Brain↗

Incorporation of lactate measurement in multi-spin-echo proton spectroscopic imaging.

An improved multi-slice, multi-spin-echo proton spectroscopic imaging method for human brain is presented. The technique allows the reconstruction of lactate images, along with choline plus creatine, N-acetylaspartate, and lipid images from one single data set processed in three separate ways. The discrimination between resonances of lipid protons and lactate methyl protons is based on homonuclear spin-spin coupling. The reliability of the separation of the lipid and lactate contribution depends on the T2 of the lipid resonances. Measurements were performed on a standard 1.5 Tesla clinical scanner on healthy volunteers and a patient with high grade CNS lymphoma, demonstrating the ability to obtain high quality metabolite maps within 11 min.

Aspartic Acid↗

Susceptibility insensitive single shot MRI combining BURST and multiple spin echoes.

A single shot MR imaging technique insensitive to magnetic susceptibility effects is introduced. The method allows multislice imaging in areas with poor magnetic field homogeneity, and can be implemented on standard clinical scanners. The design is based on the combination of a BURST excitation with multiple RF refocusing pulses. Images were obtained at 1.5 T on phantoms and human brain with a matrix size of 64 x 54 and a resolution of 4 x 4 mm in 230 ms.

Artifacts↗