Biomedical subjects

T Sandor

Publications and source records attributed to T Sandor.

At least 19 recordsLinked to original sources

PubMed2000

Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease.

We used magnetic resonance imaging (MRI) measurements to determine whether persons in the prodromal phase of Alzheimer's disease (AD) could be accurately identified before they developed clinically diagnosed dementia. Normal subjects (n = 24) and those with mild memory difficulty (n = 79) received an MRI scan at baseline and were then followed annually for 3 years to determine which individuals subsequently met clinical criteria for AD. Patients with mild AD at baseline were also evaluated (n = 16). Nineteen of the 79 subjects with mild memory difficulty "converted" to a diagnosis of probable AD after 3 years of follow-up. Baseline MRI measures of the entorhinal cortex, the banks of the superior temporal sulcus, and the anterior cingulate were most useful in discriminating the status of the subjects on follow-up examination. The accuracy of discrimination was related to the clinical similarity between groups. One hundred percent (100%) of normal subjects and patients with mild AD could be discriminated from one another based on these MRI measures. When the normals were compared with the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 93%, based on the MRI measures at baseline (sensitivity = 0.95; specificity = 0.90). The discrimination of the normal subjects and the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the "questionables") was 85% and the discrimination of the questionables and converters was 75%. The apolipoprotein E genotype did not improve the accuracy of discrimination. The specific regions selected for each of these discriminations provides information concerning the hierarchical fashion in which the pathology of AD may affect the brain during its prodromal phase.

Aged↗

PubMed1999

Comments on the hypotheses underlying fracture risk assessment in osteoporosis as proposed by the World Health Organization.

It was shown in a recent multivariate analysis of lumbar vertebral (L1-L3) CT scans of 171 women without fractures and 57 fractures somewhere in their skeletons, that regional assessment of the spinal mineral distribution can result in the discrimination of the above patient groups with an accuracy of about 90%. This level of discrimination was possible even in those cases with bone densities below the fracture threshold, where the overlap of patients with and without fractures is the greatest and clinically the most significant. In this region this new analytical technique could also identify a subgroup of patients who not yet had a fracture, but for whom all three lumbar vertebrae were classified as osteoporotic. From these results it follows that the osteoporosis model proposed by the World Health Organization (WHO), which assumes that fragility depends only on a single mean value of bone mineral density (BMD) for a patient, is overly simplistic and requires upgrading to include indices representing the distribution of bone mineral.

Absorptiometry, Photon↗

PubMed1998

White matter changes with normal aging.

We evaluated brain tissue compartments in 72 healthy volunteers between the ages of 18 and 81 years with quantitative MRI. The intracranial fraction of white matter was significantly lower in the age categories above 59 years. The CSF fraction increased significantly with age, consistent with previous reports. The intracranial percentage of gray matter decreased somewhat with age, but there was no significant difference between the youngest subjects and the subjects above 59. A covariance adjustment for the volume of hyperintensities did not alter the foregoing results. The intracranial percentage of white matter volume was strongly correlated with the percentage volume of CSF. The finding of a highly significant decrease with age in white matter, in the absence of a substantial decrease in gray matter, is consistent with recent neuropathologic reports in humans and nonhuman primates.

Adolescent↗

PubMed1997

Semi-automated extraction of brain contours from MRI.

We compared brain volumes computed by trained operators using the BRAIN-MAP algorithm, which automatically extracts the contours of the brain from gradient-echo magnetic resonance images. The images of 19 subjects randomly selected from a group of normals and a group of patients with dementia were included. BRAIN-MAP found brain perimeters that were on the average ca. 3% tighter than those obtained by two experienced operators. Between-operator and within-operator reproducibility of the analyses were also estimated and found to be (-0.13 +/- 0.51)% and (-0.63 +/- 0.08)%, respectively. Replicate volume measurement by the computer alone provided a reproducibility of (0.44 +/- 0.46)%.

Adult↗

PubMed1994

Comparison of the precision of two standardized co-ordinate systems for the quantitation of brain anatomy: preliminary results.

We assessed reproducible definition of two standardized co-ordinate systems for intersubject analysis of brain images. The baselines in the two co-ordinate systems were a modification of the canthomeatal (mCM) line and the anterior-posterior commissural (AC-PC) line. Axial spin-echo MR images of four subjects at 1.5T were used. Operator error was computed from the replicate analyses of two operators. The mCM line was determined by the lens of the eye and the internal auditory canal, and the AC-PC line was determined by the intersection of AC and PC with the interhemispheric fissure. Reproducibility of the mCM markers (SD = 0.59 mm) did not differ significantly from that of the AC-PC line (SD = 0.68 mm). The measurement error of the angle of the baseline (delta alpha), however, was more than 7 times as large for the AC-PC line as for the mCM line. An additional error affecting the rostrocaudal rotation of the co-ordinate systems, attributable to the distance between the anatomic markers, was 2.1 and 3.6 degrees (3 mm and 5 mm slice thickness) for the mCM co-ordinate system and 8.2 and 11.0 degrees (3 mm and 5 mm slice thickness) for the AC-PC system. The AC-PC line based co-ordinate system is therefore, less reproducible than the mCM line based system. This could be improved if a combination of axial and sagittal images were used for the definition of the AC-PC line.

Brain↗

PubMed1993

Natural history of coronary atherosclerosis using quantitative angiography in men, and implications for clinical trials of coronary regression. The Harvard Atherosclerosis Reversibility Project Study Group.

Previous studies of the natural history of coronary disease generally relied on estimates of percent stenosis derived from visual assessment of the coronary angiogram. In a study of 26 patients, serial quantitative angiography was performed 3 years apart to determine changes in both absolute measurements of the luminal diameter and relative percent stenosis. Initially, the mean minimal diameter of 74 coronary obstructions was 1.94 +/- 0.09 mm, the mean "normal" reference diameter was 3.06 +/- 0.11 mm, and the mean percent stenosis was 37%. At follow-up, there was a mild reduction of 0.12 +/- 0.04 mm (6%) in the minimal diameter (p < 0.005), and an increase in percent stenosis to 39% (p = 0.03). The average diameter of 85 arterial segments without a focal obstruction either initially or at follow-up showed mild but significant progression (-0.11 +/- 0.04 mm; p = 0.02). Using a minimal change of 0.27 mm in arterial diameter as a categoric variable, progression occurred in 26% of 74 arterial segments, no significant change in 65%, and regression in 9%. The only significant determinant of disease progression was the initial severity of disease. Obstructed arteries with a larger initial minimal diameter and presumably milder disease progressed more rapidly than did those with a smaller diameter (r = -0.42; p = 0.0002). There was no effect of age on the rate of progression (r = 0.02; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

PubMed1993

Temporal lobe regions on magnetic resonance imaging identify patients with early Alzheimer's disease.

OBJECTIVE: The goal of the study was to examine the volume of selected brain regions in a group of mildly impaired patients with Alzheimer's disease (AD). Five regions were selected for analysis, all of which have been reported to show substantial change in the majority of patients with AD at some time in the course of disease. DESIGN: Case-control study with the experimenter "blinded." SETTING: Hospital-based magnetic resonance imaging center. PARTICIPANTS: Fifteen subjects, eight patients with the diagnosis of probable dementia of the Alzheimer type made in concordance with National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria and seven age-matched healthy control subjects. RESULTS: Three of the volumetric measures were significantly different between patients with AD and controls: the hippocampus, the temporal horn of the lateral ventricles, and the temporal lobe. Two of the measures did not significantly differentiate patients with AD and controls: the amygdala and the basal forebrain. A discriminant function analysis demonstrated that a linear combination of the volumes of the hippocampus and the temporal horn of the lateral ventricles differentiated 100% of the patients and controls from one another. CONCLUSIONS: The results suggest that the hippocampus and the temporal horn of the lateral ventricles may be useful as antemortem markers of AD in mildly impaired patients.

Aged↗

PubMed1993

Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries.

The purpose of this study was to determine the relation between vessel wall shear stress and the rate of atherosclerosis progression. Quantitative angiography was used to calculate the change in coronary arterial diameter over 3.0 years in patients enrolled in the Harvard Atherosclerosis Reversibility Project pilot study (n = 20 arterial segments). Vessel wall shear stress was calculated by means of a validated finite-difference model of the Navier-Stokes' equation that assumes a coronary flow rate of 8 ml/sec. The correlation between vessel wall shear stress and the change in arterial diameter at multiple points (mean, 70) along the length of the artery was then calculated for each of the 20 segments with a focal stenosis. In 15 of the 20 arterial segments there was a significant correlation (p < 0.05) between low shear stress and an increased rate of atherosclerosis progression. A Fisher's z transformation was then used to combine the correlation coefficients from all 20 segments. Low shear stress was significantly correlated (z = 0.37 +/- 0.00074, p < 0.0001) with an increased rate of atherosclerosis progression. This serial quantitative evaluation of human coronary arteries is consistent with previous data that have suggested that low shear stress promotes atherosclerosis progression. Variations in local vessel wall shear stress may explain the previously reported near-independent rate of atherosclerosis progression in multiple lesions within the same patient despite exposure to the same circulating lipoprotein values and systemic hemodynamics.

Computer Simulation↗

PubMed1992

Quantitative angiographic and statistical methods to assess serial changes in coronary luminal diameter and implications for atherosclerosis regression trials.

The purpose of this study was (1) to determine a threshold for categorizing individual coronary lesions as either significantly progressing or regressing, (2) to determine whether multiple lesions within individual patients progress at independent rates, and (3) to calculate sample sizes for atherosclerosis regression trials. Seventeen patients with 46 significant lesions (2.7 lesions/patient) underwent repeat coronary arteriography 3.0 years apart. With use of the standard error of the mean change in diameter from initial to repeat catheterization across 5 pairs of consecutive end-diastolic frames, individual lesions were categorized as either significantly (p less than 0.01) progressing or regressing if there was a 0.27 mm change in minimum diameter or a 7.8 percent point change in percent stenosis. The mean diameter change of a sample of lesions can also be analyzed as a continuous variable using either the lesions or the patient as the primary unit of analysis. A lesion-specific analysis can be accomplished using a multiple regression model that accounts for the intraclass correlation (rho) in the degree of change among multiple lesions within individual patients. The intraclass correlations in percent stenosis (rho = 0.01) and minimum diameter (rho = -0.24) were low, indicating that disease progression in different lesions within individual patients is nearly independent. With use of this model, 50 patients per treatment group would permit the detection of a 5.5% difference between treatment group means in the change in minimum diameter and a 2.7% percentage point (not percent) difference in the change in percent stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Comparative analysis of computed tomographic and magnetic resonance imaging scans in Alzheimer patients and controls.

Ten patients with Alzheimer's disease underwent computed tomography and magnetic resonance imaging at the same point in time. The mean Mini-Mental State examination score of the patients was 23, indicating that they were mildly impaired. Ten age-equivalent controls also obtained computed tomographic and magnetic resonance imaging scans. A semiautomated computer program analyzed nine comparable regions of interest on each set of scans. When regions of interest from both types of scans were combined in the same discriminant function analysis, the first two variables selected were from the magnetic resonance imaging data set, and they significantly differentiated 95% of the patients and controls.

Aged↗

PubMed1992

Compact and trabecular components of the spine using quantitative computed tomography.

A computer algorithm was employed to quantify separately cortical and trabecular bone mineral density (BMD) from single energy computed tomography (CT) scans of 139 vertebrae (L1-L3) of 50 normal female subjects. In addition, the trabecular-to-integral and cortical-to-integral mass ratios were determined using digital image segmentation techniques. They showed that for the central 8-mm vertebral slice, the mass of integral bone consists of about one-fifth trabecular and four-fifth cortical bone. The trabecular-to-integral volume ratios were 0.37 +/- 0.08 and 0.63 +/- 0.08, respectively. Based on cross-sectional data from this subject group, the average annual loss was -2.21 +/- 0.15 mg/cm3 or -1.84 +/- 0.12% for trabecular bone, -3.15 +/- 0.25 mg/cm3 or -1.01 +/- 0.08% for cortical bone, and -2.60 +/- 0.20 mg/cm3 or -1.09 +/- 0.09% for the integral bone. The proportions of the age-related loss of BMD from the integral bone which originated from trabecular and cortical bone were 29.5 and 70.5%, respectively.

Adult↗

PubMed1992

Characterization of cerebral infarction by multicomponent analysis of transverse magnetization decay curves.

RATIONALE AND OBJECTIVES: Individual components of the transverse magnetization decay curve (TDC) were assessed for their ability to characterize ischemia in photochemically induced cerebral infarcts. METHODS: Fifty rats were randomly divided into equal-sized experimental and control groups, which were subdivided into groups studied at five different time points, ranging from 6 hours to 22 days. All the rats received transcalvarial irradiation with 560-nm light. Five rats in each time group also received a sensitizing dye before irradiation. In these latter animals, lesions of uniform size and location developed. Lesions were compared with tissue of similar volume and location from the contralateral cortex of the experimental animals and with tissue from both hemispheres of the control animals. TDCs of all the samples were measured and fit with mono- and bi-exponential functions. RESULTS: Unlike the control tissue, infarcted tissue displayed definitive two-component TDC behavior. The time course of the bi-exponential parameters yielded information unavailable from mono-exponential analyses. CONCLUSIONS: Bi-exponential analysis of TDCs may have diagnostic use as a more sensitive indicator of cerebral infarction than mono-exponential analyses.

Animals↗

PubMed1991

Regional 1H transverse magnetization studies in perfused rabbit kidney.

A Carr-Purcell-Meiboom-Gill imaging sequence consisting of 128 echoes is used to extract transverse magnetization decay curves (TDCs) at 1.9 T from 1.7 x 1.7 x 5-mm3 voxels within the cortex, outer medulla, and inner medulla of perfused rabbit kidneys. The spatially localized TDCs within each tissue type are found to be better approximated by biexponential, as opposed to monoexponential, functions. The biexponential parameters characterizing the TDCs demonstrate an improved degree of tissue specificity over that available from monoexponential analyses. The fraction of the quickly relaxing TDC component and the relaxation rate of this component are observed to decrease from cortex to inner medulla. A two-site exchange analysis is used to convert biexponential TDC parameters into water volume fractions and exchange rates. The exchange rates between the fast and slowly relaxing pools increased from cortex to inner medulla. All exchange rates were less than 1.5 Hz, indicating a relatively slow water exchange process. The imaging methods and subsequent analyses offer the potential to generate unconventional MR images with tissue contrast dependent upon water compartmentation and exchange.

Animals↗

PubMed1991

Segmentation of brain CT images using the concept of region growing.

A method is described for extracting and isolating cerebrospinal fluid and tissue areas of brain images obtained with computed tomography. The classification of the pixels into components is based on region growing and nearest neighbor principles. To aid the performance of this method, the algorithm utilizes a priori information on the anatomic composition of the brain, and reduces the 'cupping effect' in the CT image that is attributed to beam hardening artifacts. In order to avoid subjectivity, the performance of the algorithm was tested by superimposing five computer-simulated circular lesions on different areas of the original CT scans, 8 mm thick. These images were taken at different levels in the brain, thereby accommodating different anatomy as well as the apical artifact of CT scanning. In this exploratory investigation, the false negative error of segmentation for lesions having diameter of 20 pixels was found in the order of 25% at an estimated partial volume (PV) effect of 50% that decrease further to about 5% for a PV of 80%. At that point the false positive error becomes the dominant error in the analysis.

Algorithms↗

PubMed1991

Differentiation of experimental white matter lesions using multiparametric magnetic resonance measurements.

The potential of multiparametric proton magnetic resonance (MR) measurements for characterizing white matter lesions was investigated. The authors compared acute experimental allergic encephalomyelitis (EAE), which is distinguished by inflammatory lesions, with an immunologically potentiated hyperacute form of the disease in which demyelinating lesions (DEM) also are present. Tissue samples containing cervical spinal cord and brain stem were excised and in vitro measurements of T1, T2, and two components of T2 were performed. Discriminant analysis was applied using MR parameters singly and in various combinations. When the disease was clearly manifested, discrimination between treated and normal animals was satisfactory with single parameters. The use of biexponential T2 components improved the distinction of normal from treated but asymptomatic animals, and differentiated between EAE and DEM. These results suggest that improved characterization of white matter lesions is possible with multiparametric MR in vivo, especially if sampling is performed with imaging and the T2 decay curves are obtained with a sufficient number of echoes to perform biexponential analysis.

Animals↗

PubMed1991

Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis.

The purpose of this study was to assess the effect of atherosclerosis on the regulation of limb blood flow. To examine this issue, the reactivity of resistance and conduit vessels was evaluated in 11 patients with peripheral atherosclerotic disease and six control subjects. Responsiveness of resistance vessels was measured by venous occlusion plethysmography. Responsiveness of conduit vessels was determined by quantitative angiography to measure the diameter of the superficial femoral artery. To distinguish endothelium-dependent vasodilation from that caused by direct smooth muscle relaxation, each participant received intra-arterial infusions of methacholine and nitroprusside, respectively. Flow-mediated dilation of the superficial femoral artery was determined during reactive hyperemia. Vasoconstrictor function was determined by the infusion of phenylephrine. Methacholine reduced calf vascular resistance in the control subjects but not in the patients with atherosclerosis (-64 +/- 11% versus 6 +/- 18%, p less than 0.01). Nitroprusside decreased calf vascular resistance comparably in each group (-51 +/- 5% versus -42 +/- 4%, p = NS). The vasoconstrictor effect of phenylephrine was similar in each group (105 +/- 30% versus 108 +/- 22%, p = NS). In the superficial femoral artery, the vasodilator responses to both methacholine (20 +/- 4% versus 1 +/- 4%, p less than 0.05) and nitroprusside (19 +/- 4% versus 5 +/- 4%, p less than 0.05) were blunted in the atherosclerotic patients as was the vasoconstrictive response to phenylephrine (-15 +/- 1% versus -1 +/- 5%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

PubMed1991

Glucocorticoid receptor mediated inhibition of interleukin-1 stimulated neutral metalloprotease synthesis in normal human chondrocytes.

Glucocorticoids play an important role in the therapy of arthritic diseases. We sought, firstly, to identify, characterize and localize glucocorticoid receptors (GR) in normal human chondrocytes and, secondly, to determine whether glucocorticoid suppression of human recombinant interleukin-1 beta (rhIL-1 beta)-stimulated metalloproteases (MPs) synthesis by chondrocytes requires GR occupancy. Radioligand binding studies with cultured chondrocytes revealed the presence of high affinity-low capacity [3H]dexamethasone (DEX) binding sites with the following kinetic parameters: Kd = 12.5 +/- 1.4 nmol/L, Nmax = 57,560 +/- 3,960 sites per cell. Competition studies indicated that the DEX binding site was glucocorticoid specific and the competitive hierarchy established was: DEX greater than RU-26988 greater than RU-486 greater than cortisol greater than progesterone much greater than testosterone greater than estradiol-17 beta. Immunocytochemical studies using a specific anti-human GR antiserum identified immunoreactive material primarily in the cytoplasm with cells cultured in the absence of glucocorticoids. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis-Western immunoblotting analysis of chondrocyte cytosol detected the presence of a macromolecular species comigrating with a standard protein possessing a molecular weight of 94 kilodalton. rhIL-1 beta provoked the synthesis and secretion of the MPs stromelysin and collagenase from human chondrocytes in a saturable, coordinate, and dose-dependent fashion. DEX and cortisol inhibited the cytokine-stimulated MP synthesis in similar dose-dependent fashions: DEX, IC50 for stromelysin and collagenase suppression was 1.12 X 10(-8) mol/L and 1.26 X 10(-9) mol/L, respectively and the IC50 for cortisol was 6.3 X 10(-7) mol/L and 4.9 X 10(-8) mol/L, respectively. rhIL-1 beta failed to stimulate metalloprotease synthesis and release from chondrocytes pretreated with 10 nmol/L DEX, even after 20 days of incubation. The antiglucocorticoid, RU-486 completely reversed the DEX induced suppression of MP synthesis at 10(-7) mol/L. RU-486 alone had no effect on MP synthesis. We believe there is a biochemical rationale for the therapeutic efficacy of glucocorticoid administration in the management of arthritic diseases such as osteoarthritis and rheumatoid arthritis, and cytokines such as IL-1 are likely to be involved in the increase in MP synthesis.

Adolescent↗

PubMed1991

Global and regional variations in the spinal trabecular bone: single and dual energy examinations.

Two hundred and sixty-eight vertebrae from 92 subjects (42 males and 50 females) were used to assess inter- and intravertebral variations in the mineral content of spinal trabecular bone from L1-L3. Using a computer-generated grid superimposed on the trabecular bone, the spatial distribution of the mineral content was computed for 48 subdivisions of the grid for single and dual energy computed tomographic examinations. In addition, the age dependence of the mineral content was assessed by regression analysis from each subdivision. The results demonstrated a nonhomogenous distribution of mineral density within the trabecular bone. The lateral and anterolateral subcortical regions show significantly lower mineral density than the posterolateral or anterior subcortical domains. Moreover, with increasing age, bone density was also lost in a nonuniform fashion. Finally, the analysis of regional intervertebral change for the L1-L3 vertebrae revealed a nonhomogeneous pattern of mineral distribution.

Adolescent↗