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D J Dubowitz

Publications and source records attributed to D J Dubowitz.

11 recordsLinked to original sources
PubMed2001

Enhancing fMRI contrast in awake-behaving primates using intravascular magnetite dextran nanopartieles.

Functional MRI in awake-behaving primates is an emerging tool for bridging the gap between human fMRI and neurophysiology information from nonhuman primates. We report the use of magnetite dextran nanoparticles (Feridex) as a blood-pool agent to enhance fMRI contrast-to-noise (CNR) in primate FMRI. The intravascular half-life of the magnetite dextran was long compared to lanthanide chelates (T(1/2) = 198 min) with shortened T(2) relaxation observed in blood and cerebral cortex. Greater than 3-fold enhancement in the percentage MR signal change was observed using nanoparticles (13%) compared with conventional BOLD fMRI (4%). The calculated regional cerebral blood volume in macaque primary visual cortex increased 32% with photic stimulation. The increased CNR allows greater flexibility in the design of awake-behaving primate fMRI studies with the potential for improvements in resolution and significantly shortened imaging times.

Animals↗
PubMed2001

Direct comparison of visual cortex activation in human and non-human primates using functional magnetic resonance imaging.

We report a technique for functional magnetic resonance imaging (fMRI) in an awake, co-operative, rhesus macaque (Macaca mulatta) in a conventional 1.5T clinical MR scanner, thus accomplishing the first direct comparison of activation in visual cortex between humans and non-human primates with fMRI. Activation was seen in multiple areas of striate and extra-striate visual cortex and in areas for motion, object and face recognition in the monkey and in homologous visual areas in a human volunteer. This article describes T1, T2 and T2* values for macaque cortex, suitable MR imaging sequences, a training schedule, stimulus delivery apparatus and restraining hardware for monkey fMRI using a conventional 19 cm knee coil. Much of our understanding of the functional organization of the primate brain comes from physiological studies in monkeys. Direct comparison between species using fMRI such as those described here will help us to relate the wealth of existing knowledge on the functional organization of the non-human primate brain to human fMRI.

Adolescent↗
PubMed2001

Peripheral somatosensory fMRI in mouse at 11.7 T.

The feasibility of performing extremely-high resolution somatosensory fMRI in anesthetized mice using BOLD contrast at 11.7 T was investigated. A somatosensory stimulus was applied to the hindlimb of an alpha-chlorolose anesthetized mouse resulting in robust (p < 4 x 10(-3)) BOLD changes in somatosensory cortex and large veins. Percentage modulation of the MR signal in cortex exceeded 7%. Experiments that artificially modulated the inspired oxygen tension were also conducted; the results revealed large, heterogeneous, BOLD contrast changes in the mouse brain. In addition, T(1), T(2), and T(2)* values in gray matter at 11.7 T were evaluated. Discussion of the sensitivity limitations of BOLD fMRI in the tiny mouse central nervous system is presented. These methods show promise for the assessment of neurological function in mouse models of CNS injury and disease.

Animals↗
PubMed2000

High resolution magnetic resonance imaging of the brain in the dy/dy mouse with merosin-deficient congenital muscular dystrophy.

Magnetic resonance imaging (MRI) abnormalities in the cerebral white matter are a consistent feature of merosin-deficient human congenital muscular dystrophy, a disease caused by a primary defect in the expression of the laminin alpha2 chain of merosin. To investigate the relationship between imaging changes and merosin deficiency we undertook a MRI study in the dy/dy mouse, an animal model for this form of human congenital muscular dystrophy. High resolution in vivo imaging was performed on anaesthetized animals (two homozygous dy/dy mutants and two heterozygous dy/DY controls, aged 2.5 months) in a dedicated 11.7T magnetic resonance imaging scanner. T(1) and T(2) weighted images were normal in all mice and white matter changes were not seen at a stage of maturity when MRI changes are already very striking in human patients. Cerebral MRI abnormalities do not appear to be a feature of dy/dy mice, despite the virtual absence of merosin expression in the dy/dy mouse brain. Possible causes for this absence of MRI changes, and implications for the pathogenesis of the MRI changes in humans are reviewed.

Animals↗
PubMed1999

Involvement of striate and extrastriate visual cortical areas in spatial attention.

We investigated the cortical mechanisms of visual-spatial attention while subjects discriminated patterned targets within distractor arrays. Functional magnetic resonance imaging (fMRI) was used to map the boundaries of retinotopic visual areas and to localize attention-related changes in neural activity within several of those areas, including primary visual (striate) cortex. Event-related potentials (ERPs) and modeling of their neural sources, however, indicated that the initial sensory input to striate cortex at 50-55 milliseconds after the stimulus was not modulated by attention. The earliest facilitation of attended signals was observed in extrastriate visual areas, at 70-75 milliseconds. We hypothesize that the striate cortex modulation found with fMRI may represent a delayed, re-entrant feedback from higher visual areas or a sustained biasing of striate cortical neurons during attention. ERP recordings provide critical temporal information for analyzing the functional neuroanatomy of visual attention.

Adult↗
PubMed1998

Functional magnetic resonance imaging in macaque cortex.

The ability to use fMRI in a monkey model would bridge the gap between the fMRI demonstration of cerebral activation in humans and the cumulative wealth of monkey data on the functional organization of the brain from single electrode mapping, radioisotope and histology studies. We report a new technique for fMRI in an awake co-operative rhesus macaque (Macaca mulatta) in a conventional clinical 1.5T MR scanner and present the first fMRI images from a macaque. Good resolution, signal-to-noise ratio and BOLD response (2.6-4.6%) have been achieved using the manufacturer's standard volume knee coil. T1 values of macaque gray and white matter (1490 ms, 1010 ms respectively) are higher than human brain, whereas T2 values are lower (55 ms, 48 ms respectively). An MR-compatible design for restraining the monkey is also described, along with a suitable EPI sequence for BOLD images, optimized for monkey T2, with voxel sizes from 29 to 61 microl, and MPRAGE sequence for anatomical studies with 0.8 mm isotropic resolution, optimized for monkey T1.

Animals↗
PubMed1998

Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases.

OBJECTIVE: To determine cerebral energy status in patients with Huntington's disease (HD) and Parkinson's disease (PD). METHODS: The study included 15 patients with DNA-proven, symptomatic HD and five patients with medically treated, idiopathic PD, all of whom were candidates for neurotransplant treatment, as well as 20 age-related normal subjects. Quantitative noninvasive, MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia (BG), occipital gray matter, and posterior parietal white matter; in addition, quantitative phosphorus and proton-decoupled phosphorus MRS of superior biparietal white and gray matter was done. Outcome measures were quantitative metabolite ratios and millimolar concentrations of neuronal and glial markers, creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. RESULTS: In volume-corrected control BG (10.46 +/- 0.37 mM), [Cr] was 29% (p < 0.05) higher than in control gray matter (8.10 +/- 1.04 mM). In HD and PD, energy metabolism was not abnormal in the four cerebral locations measured by MRS. No increase in cerebral lactate or decrease in phosphocreatine and ATP was detected. Small, systematic abnormalities in N-acetylaspartate (NAA, decreased), Cr (decreased), choline-containing compounds (Cho, increased), and myoinositol (mI, increased) were demonstrable in all patient's individually and in summed spectra but were insufficient to make diagnosis possible in the individual patient. CONCLUSION: Previously described failure of global energy metabolism in HD was not confirmed. However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are sensitive to +/-10% alterations in key cerebral metabolites, and may be of value in noninvasive monitoring of appropriate therapies.

Adenosine Triphosphate↗
PubMed1998

MR of hypoxic encephalopathy in children after near drowning: correlation with quantitative proton MR spectroscopy and clinical outcome.

BACKGROUND AND PURPOSE: Quantitative MR spectroscopy has a proved role in the investigation of hypoxia caused by near drowning. To date, no studies have addressed the MR imaging changes that may also accompany this condition. The purpose of this study was to describe the MR imaging findings in children with hypoxic encephalopathy caused by near drowning and to compare these findings with the results of qualitative and quantitative proton MR spectroscopy and clinical outcome. METHODS: Twenty-two children (6 months to 11 years old) admitted to the pediatric intensive care unit after near drowning incidents underwent cerebral MR imaging and quantitative proton MR spectroscopy. Clinical and imaging studies were reviewed retrospectively, and subjects were grouped according to outcome: good result, persistent vegetative state, and death. Images were scored for edema, basal ganglia changes, and cortical changes, and were compared with MR spectra and outcome at days 1 to 2, 3 to 4, and 5 or more. RESULTS: Six patients had a good outcome, four remained in a persistent vegetative state, and 12 died. Generalized/occipital edema correlated with poor outcome. Indistinct lentiform nuclei margins on T1-weighted images were a frequent finding (78%). Basal ganglia T2 hyperintensity correlated with poor outcome, progressing from a patchy/peripheral distribution to diffuse high intensity. Patchy high T2 signal in the cortex or subcortical lines were specific but insensitive for poor outcome, as were brain stem infarcts. CONCLUSION: MR images in children with hypoxic encephalopathy after near drowning show a spectrum of changes. The most sensitive prognostic result may be achieved by combining MR imaging with qualitative and quantitative MR spectroscopic data.

Brain Diseases↗
PubMed1997

Problem in diagnostic imaging.

The staging of malignant disease for metastatic spread requires a sound understanding of the normal anatomy and possible anatomical variants as well as the expected pathology. This article illustrates this in the case of a young man with seminoma of the testis undergoing CT imaging to assess for para-aortic metastatic spread. A potential pitfall that may mislead the unwary is demonstrated.

Adult↗
PubMed1994

Technical note: bone SPECT of the wrist.

A technique for single photon emission computed tomography (SPECT) during bone scintigraphy of the wrist is described. The technique has been developed as a means to improve localization of abnormalities observed on 99Tcm-MDP planar bone scintigraphy. A wrist phantom and 15 wrists in 13 symptomatic patients were examined. Good spatial detail was achieved, with the pisiform readily identifiable as a separate bone in six wrists. In seven cases the tomograms permitted better localization of planar image abnormalities and in four cases additional lesions were visible which were missed on planar scintigraphy. This technique can be applied to all patients with suspected carpal injury and allows better anatomical localization and greater sensitivity than planar scintigraphy alone.

Adolescent↗