Faculty Bibliography

Cross-sectional cerebrospinal fluid (CSF) levels of tau and amyloid (A) beta (beta) are of diagnostic importance for Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, most longitudinal studies of tau fail to demonstrate progression. Because predominantly brain-derived proteins such as tau, have higher ventricle to lumbar ratios, we hypothesized that adjusting for the ventricular enlargement of AD would correct for the dilution of tau, and improve detection of longitudinal change. Abeta which is not exclusively brain derived, shows a ratio <1, and no benefit was expected from adjustment. In a 1 year longitudinal study of eight MCI and ten controls, we examined CSF levels of hyperphosphorylated (P) tau231, Abeta40, and Abeta42. In cross-section, MCI patients showed elevated Ptau231 and Abeta40 levels, and greater ventricular volumes. Longitudinally, only after adjusting for the ventricular volume and only for Ptau231, were increases seen in MCI. Further studies are warranted on mechanisms of tau clearance and on using imaging to interpret CSF studies

Using receiver-operating characteristic (ROC) methodology, the ability to diagnose acute appendicitis with computed tomography (CT) images displayed at varying levels of lossy compression was evaluated. Nine sequential images over the ileocecal region were obtained from 53 consecutive patients with right lower quadrant pain who were clinically suspected to have acute appendicitis. Thirty were proven surgically to have acute appendicitis, alternative diagnoses confirmed in 23. The image sets were subjected to a lossy wavelet-based compression algorithm 'Embedded Predictive Wavelet Image Coder' (EPWIC). Compression levels were: none, 8:1, 16:1, and 24:1, resulting in 4 sets of images per patient. Image sets were randomized and evaluated separately by 4 body radiologists on a 1,024 x 768-pixel SVGA color PC monitor in 512 x 512 format. The readers were aware of the clinical suspicion of appendicitis but were unaware of the positive fraction of cases. Individual and combined reader ROC and c2 analyses of sensitivity, specificity, and accuracy were determined. For all readers, sensitivity decreases at 16:1 and 24:1 levels (P <0.01, P <0.001, respectively). Accuracy decreased at 24:1 levels (P <0.01). Specificity was unaffected. By ROC analysis there was statistically significantly decreased area under the curve at 24:1 levels (P <0.02) as compared with uncompressed images. Finite levels of lossy wavelet compression may be applied to CT images without compromising diagnostic performance

In an all-male sample of schizophrenic patients stabilized by medication (n=62) and normal controls (n=27), we obtained neuropsychological test data and high-resolution whole brain magnetic resonance scans, as well as detailed psychiatric rating scales on a subset of the patients (n=47). Schizophrenic patients had significantly worse overall age-adjusted cognitive performance than normal controls (average z-score=-0.90, range=-0.60 to -1.81), which included relatively more severe deficits with different types of memory, psychomotor speed, verbal fluency and verbal abstraction. Schizophrenic patients also had significantly smaller bilateral volumes in gray but not white matter in the prefrontal region, superior temporal gyrus and whole temporal lobe, but no group differences were observed in the hippocampus and parahippocampus. Correlations between the brain regions and cognitive performance revealed different sets of significant relationships for the two groups, particularly in the prefrontal and hippocampal regions. In addition, inverse correlations were observed between certain cognitive abilities (psychomotor speed, cognitive flexibility and verbal fluency) and patients' psychiatric ratings, especially with measures of negative symptoms. The convergence of findings for schizophrenic patients regarding the prefrontal region, negative symptoms, psychomotor speed and cognitive flexibility suggests that schizophrenic negative symptoms may involve disruption of frontal-subcortical connections

We used MRI volume sampling with coregistered and atrophy corrected FDG-PET scans to test three hypotheses: 1) hippocampal formation measures are superior to temporal neocortical measures in the discrimination of normal (NL) and mild cognitive impairment (MCI); 2) neocortical measures are most useful in the separation of Alzheimer disease (AD) from NL or MCI; 3) measures of PET glucose metabolism (MRglu) have greater diagnostic sensitivity than MRI volume. Three groups of age, education, and gender matched NL, MCI, and AD subjects were studied. The results supported the hypotheses: 1) entorhinal cortex MRglu and hippocampal volume were most accurate in classifying NL and MCI; 2) both imaging modalities identified the temporal neocortex as best separating MCI and AD, whereas widespread changes accurately classified NL and AD; 3) In most between group comparisons regional MRglu measures were diagnostically superior to volume measures. These cross-sectional data show that in MCI hippocampal formation changes exist without significant neocortical changes. Neocortical changes best characterize AD. In both MCI and AD, metabolism reductions exceed volume losses

PURPOSE: To develop a low-dose magnetic resonance (MR) renographic method performed with and without an angiotensin converting enzyme (ACE) inhibitor and in conjunction with gadolinium-enhanced MR angiography in patients with suspected renovascular disease. MATERIALS AND METHODS: Thirty-two patients underwent MR renography (turbo fast low-angle shot sequence: repetition time, 5 msec; echo time, 2.3 msec; flip angle, 15 degrees; one coronal image acquired every 2 seconds for 4 minutes) following intravenous injection of 2 mL of gadopentetate dimeglumine, which was repeated following intravenous injection of an ACE inhibitor. Contrast material-enhanced MR angiography was also performed. On the basis of renographic findings, renal cortex and renal medulla enhancement curves and normalized enhancement ratios were analyzed. RESULTS: The cortex and medulla showed an early transient period of enhancement within 20 seconds (vascular phase). During 1-2 minutes, a second, gradual increase in medullary enhancement, reflecting transit of filtered contrast material, was observed that was significantly greater in patients with a serum creatinine level less than 2 mg/dL (177 micromol/L) than in those with a level of 2 mg/dL or greater (P < .01). After injection of the ACE inhibitor, patients with elevated creatinine levels showed low renal medullary enhancement regardless of the presence of renal artery stenosis (RAS). However, in patients with creatinine less than 2 mg/dL, medullary enhancement ratios after injection of the ACE inhibitor were consistently lower in patients with RAS of 50% or greater than in those without stenosis (P = .02 to .08). CONCLUSION: Low-dose MR renography can be performed in the clinical setting before and after injection of an ACE inhibitor, and its potential use for evaluating decreased renal function as a consequence of RAS is promising

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal

The relationship between the administered dose d of Gd-DTPA and the accuracy of measurements of the glomerular filtration rate G and the cardiac output O was investigated. For a wide range of values the concentration of Gd-DTPA can be uniquely derived from MR signals and precontrast longitudinal relaxation time. Fixed and random errors in these measured variables were analyzed. Depending on noise level and the level of renal function, errors in G reach a minimum for d = 1.4-2.8 mmol. Random errors in G are relatively insensitive to d as long as d > 1.5 mmol. These results establish the feasibility of dynamic MR measurements using doses of Gd-DTPA that are several times lower than current standards