Tamas Sandor

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 Alzheimers 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. Ann Neurol 2000;47:430–439.

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.

Time course of functional and biochemical recovery of myocardium salvaged by reperfusion

To characterize the functional and biochemical recovery of myocardium salvaged by reperfusion, 19 anesthetized mongrel dogs underwent 2 hour occlusion of the proximal left anterior descending coronary artery, followed by reperfusion for up to 2 weeks. Thirteen dogs had a permanent occlusion and served as the control group. All dogs had serial two-dimensional echocardiograms and in vivo biopsies for adenosine triphosophate (ATP) and creatine phosphate after occlusion and at the time of sacrifice (6 hours, n = 15; 7 days, n = 6; or 14 days after occlusion, n = 11). The area of necrosis and area at risk of necrosis were identified in dogs sacrificed at 6 hours. After 4 hours of reperfusion, the area of necrosis determined by the triphenyltetrazolium chloride technique, expressed as a function of the area at risk by in vivo monastral blue injection, was 23.9 ± 5.8% (mean ± standard error of the mean) and largely subendocardial, compared with 89.1 ± 5.3% in dogs with permanent (6 hour) occlusion (probability [p] Thus, reperfusion after 2 hours of coronary occlusion resulted in recovery of jeopardized myocardium, in which the deterioration of function observed in nonreperfused tissue was reversed and biochemical improvement occurred over the course of 2 weeks. Computer-assisted two-dimensional echocardiography, a noninvasive but quantitative technique, appears well suited to monitor the rate of functional recovery of myocardium salvaged by reperfusion.

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)

Statistical assessment of perceptual CT scan ratings in patients with alzheimer type dementia

Three neuroradiologists perceptually evaluated CT of 24 patients with Alzheimer type dementia and 22 normal control subjects and made a dichotomous judgment for each case (i.e., normal control or Alzheimer type dementia). The mean percentage of patients correctly classified was 83.3%. The neuroradiologists also completed perceptual ratings on each scan. Thirteen regions were rated for atrophy on a scale of 0-4. Discriminant function analyses of several sets of perceptual atrophy ratings (optimized on an exploratory set and evaluated on a test set) showed that the perceptual ratings of temporal lobe regions produced an average accuracy of 88.57%. In contrast, only 74.26% of the cases were correctly classified when the discriminant functions were based on perceptual ratings of midventricular and supraventricular areas. Linear measures of atrophy correctly classified only 65.20% of the subjects. The results suggest that atrophy ratings of brain regions that show the characteristic macroscopic neuropathological changes of Alzheimer disease may be used by neuroradiologists to reach more accurate diagnostic decisions.

Compact and trabecular components of the spine using quantitative computed tomography

SummaryA 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 los of BMD from the integral bone which originated from trabecular and cortical bone were 29.5 and 70.5%, respectively.

Vasomotion of renal blood flow in essential hypertension. Oscillations in xenon transit.

To assess the frequency and magnitude of phasic renal blood flow changes in essential hypertension, we applied an analytical method based on the estimation of power spectral density to xenon transit through the kidney. Despite similar age and gender distribution of the patients and exclusion of those with accelerated hypertension, mean renal blood flow was significantly lower in 100 patients with essential hypertension (299 +/- 8 ml/100 g/min) than in the 144 normal subjects (335 +/- 6 ml/100 g/min; p less than 0.001). Normalized power, the index of oscillatory behavior, was more than twice normal in patients with essential hypertension (p less than 0.001), but there was no difference in the frequency or cycle length of the oscillation. Two maneuvers that induced renal vasoconstriction, the application of cuffs to the thighs which were then inflated to diastolic blood pressure and an emotional provocation, reduced renal blood flow much more in patients with essential hypertension (p less than 0.01) in association with a striking increase in normalized power (p less than 0.001). The oscillations, which reflected not the phasic blood pressure change but rather the phasic change in renal perfusion, provided additional evidence that renal vasoconstriction plays an active role in the pathogenesis of essential hypertension.

An interactive procedure for extracting features of the brain from magnetic resonance images: the lobes.

The human brain can be subdivided many ways depending upon the criteria used. One of the most basic approaches is to subdivide the cortical regions into functional units composed of the frontal, occipital, parietal, and temporal lobes. To date, the process of reliably extracting measurements of the human brain from MR images has been mostly dependent on subjective decisions made by operators tracing regions. We present a technique for the identification of the cortical lobes of the brain based upon an interactive extraction program. It requires an operator to identify a fixed set of neuroanatomical guides which are used along with segmentation information to map automatically in three dimensions the full extent of each lobe without further editing by the operator. The definitions of the lobes are based upon standard, fully accepted, neuroanatomical criteria which can readily be found in the stack of images obtained from each subject. We have used this technique in this report on a subset of images from both healthy control subjects and patients with clinically confirmed memory disorders in order to establish its interoperator and intraoperator reliability. Hum. Brain Mapping 5:355–363, 1997.

Two-site exchange revisited: a new method for extracting exchange parameters in biological systems.

A new analysis is presented which links real volume fractions, relaxation rates, and intracompartmental exchange rates directly with apparent volume fractions and relaxation rates obtained from biexponential fits of transverse magnetization decay curves. The analysis differs from previous methods in that measurements from two paramagnetic doping levels are used to close the two-site exchange equations. Both the new method and one previously described by Herbst and Goldstein (HG) have been applied to paramagnetically doped whole-blood data sets. Significant differences in the calculated exchange parameters are found between the two methods. A small dependence of the intracellular relaxation rate on extracellular paramagnetic agent concentration, assumed nonexistent with the HG method, is inferred from the new analysis. The analysis was also applied to published data on perfused rat hearts, and we obtained a limited assessment of two-site exchange in this system.

Quantitative computer-assisted analysis of left ventricular wall thickening and motion by 2-dimensional echocardiography in acute myocardial infarction

Quantitative regional wall motion analyses of 2-dimensional echocardiograms (2-D echo) have usually focused on large arcs (greater than 45 degrees) of the left ventricular (LV) perimeter rather than on small LV zones. Few studies have assessed changes in wall thickness. To determine normal ranges of regional LV function, the endocardial and epicardial contours of short-axis 2-D echoes obtained at the papillary muscle level of 10 normal subjects were manually traced. Then, 15 patients with acute myocardial infarction (MI) were studied, comparing their contours at admission with ranges determined from the normal subjects. In all patients with MI, 2-D echoes located abnormal wall motion involving at least the region identified as abnormal by the electrocardiogram and often extending into adjacent regions. All 9 patients with transmural MI had either decreased wall thickening or abnormal endocardial wall motion; all except 1 had focal thinning in the region of the MI. Of the 6 patients with nontransmural MI, 2 had abnormal endocardial wall motion, and all had decreased wall thickening. Evaluating regional wall motion at multiple points around the LV circumference should permit more precise delineation of LV function in health and disease than has been heretofore possible.