Biomedical subjects

R N Bryan

Publications and source records attributed to R N Bryan.

At least 19 recordsLinked to original sources

PubMed1996

Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.

Dopamine (DA) deficiency has been implicated in Lesch-Nyhan disease (LND), a genetic disorder that is characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury. To establish that DA deficiency is present in LND, the ligand WIN-35,428, which binds to DA transporters, was used to estimate the density of DA-containing neurons in the caudate and putamen of six patients with classic LND. Comparisons were made with 10 control subjects and 3 patients with Rett syndrome. Three methods were used to quantify the binding of the DA transporter so that its density could be estimated by a single dynamic positron emission tomography study. These approaches included the caudate- or putamen-to-cerebellum ratio of ligand at 80-90 min postinjection, kinetic analysis of the binding potential [Bmax/(Kd x Vd)] using the assumption of equal partition coefficients in the striatum and the cerebellum, and graphical analysis of the binding potential. Depending on the method of analysis, a 50-63% reduction of the binding to DA transporters in the caudate, and a 64-75% reduction in the putamen of the LND patients was observed compared to the normal control group. When LND patients were compared to Rett syndrome patients, similar reductions were found in the caudate (53-61%) and putamen (67-72%) in LND patients. Transporter binding in Rett syndrome patients was not significantly different from the normal controls. Finally, volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LND patients. To ensure that a reduction in the caudate volume would not confound the results, a rigorous partial volume correction of the caudate time activity curve was performed. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LND patients when contrasted to controls. To our knowledge, these findings provide the first in vivo documentation of a dopaminergic reduction in LND and illustrate the role of positron emission tomography imaging in investigating neurodevelopmental disorders.

Adolescent↗

PubMed1996

Relationship between T2-weighted hyperintensities (unidentified bright objects) and lower IQs in children with neurofibromatosis-1.

To address the controversy regarding the relationship between cognitive impairment (lowering of IQ) and magnetic resonance imaging (MRI) characteristics (T2-weighted hyperintensities or unidentified bright objects [UBOs]) in children with neurofibromatosis-1 (NF-1), we used a pairwise NF-1/ sibling design; we set out to predict the lowering of IQ in each child with NF-1 as a discrepancy from the IQ of an unaffected sibling (D-SIQ). Our multiple regression model included the age of the child with NF-1, familial or sporadic nature of the NF-1, number of locations in the child's brain occupied by T2-weighted hyperintensities (UBOs), and the volumetric percentage of brain tissue occupied by T2-weighted hyperintensities (UBOs). Only the number of locations occupied by UBOs accounted for IQ lowering (D-SIQ) in children with NF-1 (42% of the variance in D-SIQ). This is the first report to confirm that a continuum of lowered IQs in NF-1-affected children exists in relation to the distribution of UBOs (range 0-7), not just presence (vs. absence) of any UBOs.

Adolescent↗

PubMed1996

Proton MR spectroscopy in acute middle cerebral artery stroke.

PURPOSE: To investigate the feasibility of performing multisection proton MR spectroscopy in patients with acute stroke, and to determine whether this imaging technique can depict ischemic or infarcted brain regions. METHODS: Multisection proton MR spectroscopy, MR imaging, and MR angiography were performed within 24 hours of stroke onset (mean, 12 hours) in 12 patients who had had a stroke of the middle cerebral artery. Spectra were analyzed from brain regions containing T2 hyperintensity abnormalities on MR images, from regions immediately adjacent to these abnormalities, and from anatomically similar contralateral regions. Areas of brain containing lactate were compared with areas of T2 hyperintensities on MR images. RESULTS: One data set was discarded because of excessive artifacts from patient motion. Regions of T2 hyperintensities on MR images were found to contain elevated lactate (all 11 cases) and reduced N-acetyl-aspartate (10 of 11 cases) relative to contralateral measurements. Lactate levels in regions adjacent to T2 hyperintensities were not significantly different from those of infarcted brain. On the other hand, N-acetyl-aspartate was significantly lower in regions of infarction compared with periinfarct tissue. Areas of brain containing elevated lactate significantly exceeded those of T2 abnormality. CONCLUSIONS: Proton MR spectroscopy is feasible for imaging patients with acute stroke. In the early stages of stroke, tissue containing elevated lactate but no other spectroscopic or MR imaging abnormality can be identified. Such regions may represent an ischemic zone at risk of infarction.

Acute Disease↗

PubMed1995

Intracranial assessment of incontinentia pigmenti using magnetic resonance imaging, angiography, and spectroscopic imaging.

OBJECTIVE: To evaluate patients with incontinentia pigmenti for evidence of cerebrovascular disease using magnetic resonance imaging techniques. DESIGN: A prospective case series of seven patients (four of whom were related) with incontinentia pigmenti using magnetic resonance imaging, magnetic resonance angiography, and multislice proton (1H) magnetic resonance spectroscopic imaging. SETTING: The Johns Hopkins Medical Institutions, Baltimore, Md, a tertiary, referred care center. PATIENTS: Seven patients with a diagnosis of incontinentia pigmenti. RESULTS: Five of the seven patients had abnormal magnetic resonance imaging consistent with small-vessel occlusions. Of these five patients, four had normal magnetic resonance angiography and spectroscopic imaging, and one patient had reduced middle cerebral artery flow on magnetic resonance angiography and increased lactate level in the cerebrospinal fluid on spectroscopic imaging. The remaining two patients had normal magnetic resonance imaging and spectroscopic imaging. Of these two patients, one had normal magnetic resonance angiography and the other had a right supraclinoid internal carotid aneurysm. There was substantial concordance between clinical (ophthalmic/neurologic) and imaging abnormalities. CONCLUSIONS: The central nervous system changes in patients with incontinentia pigmenti may represent the result of small-vessel occlusive phenomena in the brain. These central nervous system findings may share a common pathophysiologic state with the vascular occlusive disease seen in the retinas of these patients. The changes in the retinal vasculature may serve as a potential marker for central nervous system disease. Physicians should be aware of the systemic and debilitating nature of incontinentia pigmenti.

Adult↗

PubMed1995

Proton magnetic resonance spectroscopy and gadolinium-DTPA perfusion imaging of asymptomatic MRI white matter lesions.

In the elderly, asymptomatic white matter hyperintensities are common on T2-weighted magnetic resonance imaging (MRI). In symptomatic patients, such MRI appearances correlate with varied postmortem findings including demyelination or stroke. What structural correlates underlie the T2 hyperintensities in patients whose lesions are asymptomatic is controversial. Therefore, in order to investigate the underlying metabolism and perfusion in white matter lesions (exhibiting T2 hyperintensity), 13 patients underwent proton magnetic resonance spectroscopy and dynamic gadolinium-DTPA perfusion-weighted MR imaging. N-acetyl aspartate (NA) levels were reduced in the lesions compared with age-matched controls (P = 0.031), implying neuronal/axonal loss. Creatine levels were also reduced (P = 0.001). Choline levels were unchanged in the lesions. Lactate was identified in the lesions of 5 of the 13 patients. Although not statistically significant, perfusion studies exhibited a trend toward lower cerebral blood volumes in patients with high grade extracranial carotid stenosis and lactate-containing lesions. These findings suggest that neuronal/axonal loss underlies the majority of T2-weighted asymptomatic lesions in the older population, and in many cases these changes may be due to chronic ischemia.

Adult↗

PubMed1995

Cerebral metabolites in patients with acute and subacute strokes: concentrations determined by quantitative proton MR spectroscopy.

OBJECTIVE: The purpose of this study was to determine the feasibility of measuring concentrations of cerebral metabolites in acute and subacute stroke patients using single-voxel localized proton MR spectroscopy and to compare these concentrations to those in contralateral brain regions and in normal healthy volunteers. SUBJECTS AND METHODS: Single-voxel proton MR spectroscopy and MR imaging were performed in 14 stroke patients, at times ranging from 2 hr to 10 days following the onset of symptoms. Signals from choline, creatine, N-acetyl-L-aspartate (NAA), and lactate were quantified in the infarcted region (n = 14) and in the hemisphere contralateral to the stroke (n = 8) and compared with data obtained from a group of 10 control subjects. RESULTS: Infarcts were characterized by significantly increased lactate (12 of 14 patients; 7.5 +/- 8.9 mumol/g wet weight, mean +/- SD) and significantly decreased NAA (12 of 14 patients; 5.5 +/- 3.2 mumol/g wet weight), compared with contralateral brain regions and control data in healthy volunteers. Significant reductions in choline, creatine, and NAA were also found in contralateral brain regions compared with the control patients. CONCLUSION: Quantitative single-voxel proton spectroscopy is feasible for use in clinical studies of acute stroke. Ratio measurements or comparison with contralateral metabolites may be misleading because all metabolites may change during infarction, and contralateral metabolite levels may also be different from normal subjects.

Acute Disease↗

PubMed1994

Neurofibromatosis type 1: the cognitive phenotype.

Visuospatial deficits have been reported in patients with neurofibromatosis type 1 (NF 1), although detailed observations regarding academic achievement are conflicting. Using neurocognitive testing and magnetic resonance imaging, we studied 12 families, each comprising one child with NF 1, an unaffected sibling of the same age range (6 to 16 years), and both biologic parents. The Full Scale IQ ranged from 70 to 130 among children with NF 1 and from 99 to 139 among unaffected siblings. A significant (p < 0.01) pairwise difference was found between each child with NF 1 and sibling on the Full Scale IQ and the Verbal IQ. On a single visuospatial test, Judgement of Line Orientation, children with NF 1 did significantly worse than siblings (p < 0.01). Children with NF 1 had significant learning disabilities in written language and reading (p < 0.05) and in neuromotor dysfunction (p < 0.005) compared with siblings. A significant correlation was found between the pairwise lowering of the Full Scale IQ and Judgment of Line Orientation scores in children with NF 1 and the number of locations in which, on magnetic resonance imaging, T2-weighted hyperintensities were seen (Full Scale IQ: p < 0.0003; Judgment of Line Orientation score: p < 0.02). We conclude that NF 1 is associated with a significantly lower Full Scale IQ, multifocal cognitive deficits (Verbal IQ, Judgment of Line Orientation score), reading disability, and neuromotor deficit. Pairwise cognitive differences correlated with the number of brain lesions on magnetic resonance imaging.

Adolescent↗

PubMed1994

Acute stroke: evaluation with serial proton MR spectroscopic imaging.

PURPOSE: To investigate the evolution of metabolic changes detectable with proton magnetic resonance (MR) spectroscopic imaging in acute stroke and to compare these findings with those of conventional MR imaging. MATERIALS AND METHODS: A patient with middle cerebral artery stroke underwent conventional proton-density (PD)- and T2-weighted MR imaging, MR angiography, and multisection proton two-dimensional MR spectroscopic imaging over a period of 3 hours to 5 months after symptom onset. RESULTS: On 3-hour MR images, no abnormal signal intensity change was detectable. Spectroscopic images obtained at 24 hours showed localized elevation of cerebral lactate levels. In most regions with high lactate levels, infarction subsequently occurred. In the chronic stage (5 months), the infarct was associated with reduced N-acetylaspartate levels, increased choline levels, and absence of lactate. CONCLUSION: Spectroscopic imaging enables mapping of ischemic and infarcted brain regions with greater sensitivity than does conventional MR imaging.

Acute Disease↗

PubMed1994

Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study.

BACKGROUND AND PURPOSE: Cerebral magnetic resonance imaging often detects abnormalities whose significance is unknown. The prevalence and correlates of findings such as ventricular enlargement, sulcal widening, and increased white matter signal intensity were examined in 303 men and women aged 65 to 95 years participating in a multicenter study of cardiovascular disease. METHODS: Cerebral magnetic resonance imaging was performed and interpreted according to a standard protocol, and findings were correlated with measures of cardiovascular disease and its risk factors. RESULTS: Measures of cerebral atrophy increased with age and were greater in men than in women (each P < .01). Ventricular enlargement and sulcal widening were associated with prior stroke, hypertension, diabetes, and white race (each P < .03). Extent of white matter hyperintensity was associated with age, prior stroke, hypertension, and use of diuretics (each P < .004). On multivariate analysis, age, male gender, white race, and prior stroke retained strong associations with increased ventricular and sulcal scores. After adjustment for age, prior stroke, and other risk factors, white matter hyperintensity was associated with atherosclerosis as measured by increased internal carotid artery thickness on ultrasound. CONCLUSIONS: Cerebral atrophy and white matter hyperintensity are common in the elderly and are associated with age, prior stroke, and known cardiovascular risk factors. Though these findings have been suggested to represent normal aging, their wide variability and associations with cardiovascular disease argue against their inevitability with advancing age and support the need to identify modifiable risk factors for these abnormalities.

Age Factors↗

PubMed1994

A method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study.

PURPOSE: To do a pilot study for the Cardiovascular Health Study (a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years of age and older designed to identify risk factors related to cerebrovascular disease, particularly stroke): (a) to determine the feasibility of adding brain MR to the full-scale study; (b) to evaluate the reliability of standardized MR image interpretation in a multicenter study; and (c) to compare the prevalence of stroke determined by MR with that by clinical history. METHODS: Protocol-defined MR studies were performed in 100 subjects with clinical histories of stroke and 203 subjects without reported histories of stroke. MR scans were independently evaluated by two trained neuroradiologists for the presence of small (< or = 3 mm) and large (> 3 mm) "infarctlike" lesions. The sizes of the cerebral sulci and lateral ventricles and the extent of white matter disease were graded on a scale of 0 to 9. RESULTS: Eighty percent of the Cardiovascular Health Study participants who were invited to undergo MR studies agreed to do so; 95% of those agreeing to the procedure successfully completed the exams. Intrareader and interreader reliability of infarctlike lesion identification was high for large lesions (kappa, 0.71 and 0.78, respectively) but not for small lesions (kappa, 0.71 and 0.32, respectively). Relaxed intrareader and interreader kappa scores for sulcal and ventricular sizes and extent of white matter disease were greater than 0.8 MR evidence of infarctlike lesions was present in 77% of the participants with histories of stroke but was also present in 23% of the participants without clinical histories of stroke. Seventy-nine percent of the infarctlike lesions were larger than 3 mm. CONCLUSIONS: This preliminary study indicates that a large, prospective, epidemiologic study of elderly subjects using MR scans of the brain for identification of cerebrovascular disease is feasible and that the interpretative results are reproducible, and suggests that MR evidence of stroke is more prevalent than reported clinical history of stroke.

Aged↗

PubMed1994

Neurofibromatosis type 1: the evolution of deep gray and white matter MR abnormalities.

PURPOSE: To investigate the evolution of deeply located high-signal-intensity abnormalities of the brain on T2-weighted MR images of patients with neurofibromatosis type 1 (NF-1). METHODS: The study consists of two patient groups: 1) retrospective evaluation of MR scans of 24 symptomatic NF-1 patients, 10 of whom were sequentially studied, and 2) prospective MR evaluations of 20 asymptomatic NF-1 subjects from 14 families; 2 of these families were sequentially studied. RESULTS: Deeply located, high-signal-intensity abnormalities on T2-weighted images were noted in 34 of 44 NF-1 subjects (77%). If NF-1 patients are grouped according to age, 28 of 30 subjects (93%) younger than 15 years had the lesions, whereas 4 of 7 subjects (57%) between 16 and 30 years, and 2 of 7 subjects (29%) older than 31 years had lesions. High-signal lesions in basal ganglia and brain stem were demonstrated in all decades with relatively high frequency. Lesions in the cerebellar white matter and dentate nuclei were mainly found in the patients younger than 10 years, and never found after the third decade. In 13 sequential studies (mean interval, 24 months), lesions appeared to increase in size in 3, remain unchanged in size in 2, and decrease in size in 7. One subject showed a mixed pattern of lesion size change. CONCLUSIONS: Deeply located high-signal-intensity lesions on T2-weighted MR images are more evident in young NF-1 patients. The underlying brain abnormality, while pathologically unproved, is probably transient.

Adolescent↗

PubMed1994

In vitro evaluation of MR hypointensity in Aspergillus colonies.

PURPOSE: To demonstrate that paramagnetic elements in fungal colonies can cause hypointensity in MR images. METHODS: Aspergillus fumigatus grown in vitro was imaged with CT and MR at the time of initial inoculation and 5 days later. CT and MR images, T2 values, scanning electron microscopy, energy-dispersive analysis, and furnace atomic absorption spectrometry were performed. RESULTS: After 5 days of growth, MR images of A fumigatus revealed curvilinear hypointensities on T2-weighted images corresponding to the fungal growth. Gradient-echo images revealed two distinct components of hypointensity with different calculated T2 values. Phase-angle-difference images revealed a phase shift characteristic of magnetic-susceptibility paramagnetic effects, which corresponded to the hypointense regions on gradient-echo images. Energy-dispersive analysis and furnace atomic absorption spectrometry confirmed the presence of paramagnetic elements. CONCLUSION: It was shown that in vitro A fumigatus concentrates metal elements contained within the nutrient broth. These focal collections of calculated T2 values are caused at least partly by magnetic susceptibility effects.

Aspergillus↗

PubMed1994

Proton MR spectroscopy in patients with seizure disorders.

PURPOSE: To evaluate the ability of proton MR spectroscopy to detect metabolic abnormalities in the seizure focus of humans with epilepsy. METHODS: Single-voxel MR spectroscopy and MR imaging was performed in a group of 13 patients with a variety of seizure disorders and in the temporal lobes of 14 healthy volunteers. Signals from choline, creatine, N-acetyl-L-aspartate, and lactate were quantitated in both the epileptogenic focus and the contralateral brain region. RESULTS: In normal temporal lobe, concentrations of choline, creatine, and N-acetyl-L-aspartate were 2.0 +/- 0.7, 7.8 +/- 1.9, and 11.0 +/- 2.1 mumol/g wet weight, respectively, with no detectable lactate. In all patients, a reduction in the N-acetyl-L-aspartate signal was observed in the electrically defined (scalp electroencephalogram) seizure focus compared with the mirror-image contralateral side. Lactate was elevated only in patients who had seizures during or immediately before the MR examination. Seven of 13 patients studied had normal MR examinations. CONCLUSIONS: Proton spectroscopy demonstrates alterations in N-acetyl-L-aspartate and lactate levels that can be used to locate the epileptogenic focus and may be a useful adjunctive diagnostic technique for the evaluation of patients with seizures who are eligible for resective surgery.

Adolescent↗

PubMed1994

Histologic abnormalities associated with gadolinium enhancement on MR in the initial hours of experimental cerebral infarction.

PURPOSE: To determine the histologic changes associated with gadopentetate dimeglumine enhancement on MR images in acute focal cerebral ischemia. METHODS: In each of two baboons, a microcatheter was used to occlude partially the middle cerebral artery and reduce cerebral blood flow for approximately 3.5 hours. The catheter was then removed allowing reperfusion for approximately 3.5 hours. In two other baboons, cerebral blood flow was completely and irreversibly interrupted by injecting liquid adhesive into the middle cerebral artery. T2-weighted and serial enhanced T1-weighted MR images were obtained. Brain specimens were studied histopathologically. RESULTS: In the animals with incomplete and reversible reduction of cerebral blood flow, postcontrast T1-weighted images obtained during the initial 3 hours of ischemia showed focal areas of hypointensity. These areas were enhanced on later images. The areas of signal abnormality were subsequently found to be necrotic and were characterized by neuronal cytolysis and vascular "plugging." In the animals with complete and irreversible interruption of cerebral blood flow, no abnormal signal intensity or enhancement was observed. Histologic abnormalities were milder in these animals. CONCLUSIONS: Contrast enhancement on MR images in the initial hours of cerebral ischemia was associated with histologic evidence of tissue necrosis but was not associated with milder ischemic changes.

Animals↗

PubMed1993

Neuroanatomy of Rett syndrome: a volumetric imaging study.

Rett syndrome is a pediatric neurological disorder of unknown etiology defined by the presence of severe neurodevelopment decline, acquired microcephaly, dementia, abnormalities of movement, autistic behavior, and seizures in young female children. In this study, the neuroanatomy of 11 females with Rett syndrome and 15 age- and gender-matched control subjects was investigated in vivo with quantitative neuroimaging techniques. Compared to control subjects, the patients with Rett syndrome were found to have significantly reduced cerebral volume; evidence of greater loss of gray matter in comparison to white matter; regional variation in cortical gray matter, with the frontal regions showing the largest decrease; and reduced volume of the caudate nucleus and midbrain, even when taking into account general reduction in the size of the brain. In addition, there was no evidence of an ongoing degenerative process in this sample of girls with Rett syndrome. The consistency of these data with results from neuropathological investigations points to the need for continued quantitative neuroimaging studies of children with this condition. In particular, research employing serial longitudinal scans of very young children manifesting early signs of the clinical syndrome holds promise for helping to elucidate the neuropathological pathways leading to the debilitating clinical manifestations of Rett syndrome.

Adolescent↗

PubMed1993

A high-field superferric NMR magnet.

Strong, extensive magnetic fringe fields are a significant problem with magnetic resonance imaging magnets. This is particularly acute with 4-T, whole-body research magnets. To date this problem has been addressed by restricting an extensive zone around the unshielded magnet or by placing external unsaturated iron shielding around the magnet. This paper describes a solution to this problem which uses superconducting coils closely integrated with fully saturated iron elements. A 4-T, 30-cm-bore prototype, based on this design principle, was built and tested. The 5 G fringe field is contained within 1 meter of the magnet bore along the z axis. Homogeneity of the raw magnetic field is 10 ppm over 30% of the magnet's diameter after passive shimming. Compared with an unshielded magnet, 20% less superconductor is required to generate the magnetic field. Images and spectra are presented to demonstrate the magnet's viability for magnetic resonance imaging and spectroscopy.

Magnetic Resonance Spectroscopy↗

PubMed1993

Receiver operating characteristic analysis of fracture and pneumonia detection: comparison of laser-digitized workstation images and conventional analog radiographs.

Forty pneumonia and 40 fracture cases were matched by patient age and gender with normal cases. Pediatric cases constituted 25% of this sample. All 160 examinations were laser-digitized at a spot size of 210 microns, a contrast resolution of 12 bits, and a spatial resolution of 2.35 line pairs per millimeter. The digitized images were transmitted 5 miles over a dedicated telephone line at a T1 rate from Francis Scott Key Hospital to Johns Hopkins Hospital (both in Baltimore, Md). At Johns Hopkins Hospital, eight radiologists interpreted the original analog radiograph and corresponding soft-copy display (1,280 x 1,024 pixels). Findings, confidence ratings, and image quality were reported for each reading. A receiver operating characteristic (ROC) analysis was conducted to compare observer performance under the analog and digital reading conditions. The overall sensitivity of the analog method was 89% versus 78% for the digital method (P < .001), while the specificity values were 96% and 92%, respectively (P > .20). ROC analysis similarly indicated a statistically significant difference in favor of analog radiographs (P = .028).

Child↗

PubMed1993

Frameless stereotaxic integration of CT imaging data: accuracy and initial applications.

To evaluate the spatial accuracy of a rapid interactive method of transferring computed tomographic (CT) information between its display on a computer screen to its source (test object, operating field), a multidimensional computer combined with a six-jointed position-sensing mechanical arm was tested with a Plexiglas model consisting of 50 rods of varied height and known location, a plastic replica of the skull, and, subsequently, three patients. The median error value between image and real location was 1-2 mm (P > .95), regardless of the registration target sites. The accuracy, however, increased with the selection of widespread registration points, and 95% of all errors were below 3.70 mm (P > .95). The results compare favorably with the four most commonly used stereotaxic framed units. A misregistration error of 0.3-2.2 mm was found during intraoperative correlation between anatomy on the CT display and actual anatomic location in the operative field.

Child↗