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H Rusinek

Publications and source records attributed to H Rusinek.

At least 19 recordsLinked to original sources

Single breath-hold T1 measurement using low flip angle TrueFISP.

A method for estimating T1 using a single breath-hold, segmented, inversion recovery prepared, true fast imaging with steady-state precession (sIR-TrueFISP) acquisition at low flip angle (FA) was implemented in this study. T1 values measured by sIR-TrueFISP technique in a Gd-DTPA-doped water phantom and the human brain and abdomen of healthy volunteers were compared with the results of the standard IR fast spin echo (FSE) technique. A good correlation between the two methods was observed (R2=0.999 in the phantom, and R2=0.943 in the brain and abdominal tissues). The T1 values of the tissues agreed well with published results. sIR-TrueFISP enables fast measurements of T1 to be obtained within a single breath-hold with good accuracy, which is particularly important for chest and abdominal imaging.

Algorithms↗

Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment.

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.

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Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis.

BACKGROUND: To facilitate image analysis, most recent 2-[18F]fluoro-2-deoxy-d-glucose PET (FDG-PET) studies of glucose metabolism (MRglc) have used automated voxel-based analysis (VBA) procedures but paradoxically none reports hippocampus MRglc reductions in mild cognitive impairment (MCI) or Alzheimer disease (AD). Only a few studies, those using regions of interest (ROIs), report hippocampal reductions. The authors created an automated and anatomically valid mask technique to sample the hippocampus on PET (HipMask). METHODS: Hippocampal ROIs drawn on the MRI of 48 subjects (20 healthy elderly [NL], 16 MCI, and 12 AD) were used to develop the HipMask. The HipMask technique was applied in an FDG-PET study of NL (n = 11), MCI (n = 13), and AD (n = 12), and compared to both MRI-guided ROIs and VBA methods. RESULTS: HipMask and ROI hippocampal sampling produced significant and equivalent MRglc reductions for contrasts between MCI and AD relative to NL. The VBA showed typical cortical effects but failed to show hippocampal MRglc reductions in either clinical group. Hippocampal MRglc was the only discriminator of NL vs MCI (78% accuracy) and added to the cortical MRglc in classifying NL vs AD and MCI vs AD. CONCLUSIONS: The new HipMask technique provides accurate and rapid assessment of the hippocampus on PET without the use of regions of interest. Hippocampal glucose metabolism reductions are found in both mild cognitive impairment and Alzheimer disease and contribute to their diagnostic classification. These results suggest re-examination of prior voxel-based analysis 2-[18F]fluoro-2-deoxy-d-glucose PET studies that failed to report hippocampal effects.

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Atrophy rate in medial temporal lobe during progression of Alzheimer disease.

OBJECTIVE: To establish the progression of brain atrophy rates in patients with a known date of onset of Alzheimer disease (AD). METHODS: Each of 18 subjects had two high-resolution T1-weighted three-dimensional MRI examinations. The two MRIs were coregistered and the annual rate of brain tissue atrophy was derived both for the entire brain and regionally for the left and right medial temporal lobe (MTL). Time since onset (TSO) of AD, defined as the interval between the date of onset and the midpoint of MRI dates, ranged from -2.9 to 4.2 years. RESULTS: In patients with AD, TSO was a correlate of the atrophy rate for both the left MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial measurements were applied to a control group of 21 cognitively normal elderly subjects, MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. CONCLUSION: Increased annual atrophy rate in the medial temporal lobe is a potential diagnostic marker of the progression of Alzheimer disease.

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MRI and CSF studies in the early diagnosis of Alzheimer's disease.

The main goal of our studies has been to use MRI, FDG-PET, and CSF biomarkers to identify in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI), the earliest clinically detectable evidence for brain changes due to Alzheimer's disease (AD). A second goal has been to describe the cross-sectional and longitudinal interrelationships amongst anatomical, CSF and cognition measures in these patient groups. It is now well known that MRI-determined hippocampal atrophy predicts the conversion from MCI to AD. In our summarized studies, we show that the conversion of NL subjects to MCI can also be predicted by reduced entorhinal cortex (EC) glucose metabolism, and by the rate of medial temporal lobe atrophy as determined by a semi-automated regional boundary shift analysis (BSA-R). However, whilst atrophy rates are predictive under research conditions, they are not specific for AD and cannot be used as primary evidence for AD. Consequently, we will also review our effort to improve the diagnostic specificity by evaluating the use of CSF biomarkers and to evaluate their performance in combination with neuroimaging. Neuropathology studies of normal ageing and MCI identify the hippocampal formation as an early locus of neuronal damage, tau protein pathology, elevated isoprostane levels, and deposition of amyloid beta 1-42 (Abeta42). Many CSF studies of MCI and AD report elevated T-tau levels (a marker of neuronal damage) and reduced Abeta42 levels (possibly due to increased plaque sequestration). However, CSF T-tau and Abeta42 level elevations may not be specific to AD. Elevated isoprostane levels are also reported in AD and MCI but these too are not specific for AD. Importantly, it has been recently observed that CSF levels of P-tau, tau hyperphosphorylated at threonine 231 (P-tau231) are uniquely elevated in AD and elevations found in MCI are useful in predicting the conversion to AD. In our current MCI studies, we are examining the hypothesis that elevations in P-tau231 are accurate and specific indicators of AD-related changes in brain and cognition. In cross-section and longitudinally, our results show that evaluations of the P-tau231 level are highly correlated with reductions in the MRI hippocampal volume and by using CSF and MRI measures together one improves the separation of NL and MCI. The data suggests that by combining MRI and CSF measures, an early (sensitive) and more specific diagnosis of AD is at hand. Numerous studies show that neither T-tau nor P-tauX (X refers to all hyper-phosphorylation site assays) levels are sensitive to the longitudinal progression of AD. The explanation for the failure to observe longitudinal changes is not known. One possibility is that brain-derived proteins are diluted in the CSF compartment. We recently used MRI to estimate ventricular CSF volume and demonstrated that an MRI-based adjustment for CSF volume dilution enables detection of a diagnostically useful longitudinal P-tau231 elevation. Curiously, our most recent data show that the CSF isoprostane level does show significant longitudinal elevations in MCI in the absence of dilution correction. In summary, we conclude that the combined use of MRI and CSF incrementally contributes to the early diagnosis of AD and to monitor the course of AD. The interim results also suggest that a panel of CSF biomarkers can provide measures both sensitive to longitudinal change as well as measures that lend specificity to the AD diagnosis.

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Longitudinal cerebrospinal fluid tau load increases in mild cognitive impairment.

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.

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Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET).

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.

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Optimal dose of Gd-DTPA in dynamic MR studies.

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.

Cardiac Output↗

MR renography with low-dose gadopentetate dimeglumine: feasibility.

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.

Angiotensin-Converting Enzyme Inhibitors↗

Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms.

BACKGROUND: Previous research has provided evidence for brain abnormalities in schizophrenia, but their relationship to specific clinical symptoms and syndromes remains unclear. METHODS: With an all-male demographically similar sample of 53 schizophrenic patients and 29 normal control subjects, cerebral gray and white matter volumes (adjusted for intracranial volume and age were determined for regions in the prefrontal lobe and in the superficial and mesial temporal lobe using T1-weighted magnetic resonance imaging with 2.8-mm coronal slices. RESULTS: As a group, schizophrenic patients had wide-spread bilateral decrements in gray matter in the pre-frontal (7.4%) and temporal lobe regions (8.9%), but not in white matter in these regions. In the temporal lobe, gray matter reductions were found bilaterally in the superior temporal gyrus (6.0%), but not in the hippocampus and parahippocampus. While there were no overall group differences in white matter volumes, widespread decrements in prefrontal white matter in schizophrenic patients (n = 53) were related to higher levels of negative symptoms (partial r[49] = -0.42, P = .002), as measured by the Scale for the Assessment of Negative Symptoms. A post hoc analysis revealed that schizophrenic patients with high negative symptoms had generalized prefrontal white matter reductions (11.4%) that were most severe in the orbitofrontal subregion (15.1%). CONCLUSIONS: These results suggest that gray matter deficits may be a fairly common structural abnormality of schizophrenia, whereas reductions in prefrontal white matter may be associated with schizophrenic negative symptoms.

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The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease.

For 11 AD cases and four normal elderly controls, post mortem volumes of the hippocampal subdivisions were calculated by using magnetic resonance imaging and histological sections. After at least six weeks of fixation in formalin, brains were examined on a 1.5-T Philips Gyroscan imager producing T1-weighted coronal images with a 3-mm slice thickness. Brains were then processed and embedded in paraffin. Serial coronal sections, 3 mm apart and stained with Cresyl Violet, were used for the planimetry and unbiased estimation of the total numbers of neurons in the hippocampal subdivisions. For all 15 cases, magnetic resonance imaging- and histology-based measurements were performed along the whole rostrocaudal extent of the hippocampal formation and included three subvolumes: (i) the hippocampus (CA1-CA4 and the dentate gyrus); (ii) hippocampus/subiculum; and (iii) hippocampus/parahippocampal gyrus. After controlling for shrinkage, strong correlations were found between magnetic resonance imaging and histological measurements for the hippocampus (r = 0.97, P < 0.001), hippocampus/subiculum (r = 0.95, P < 0.001) and hippocampus/parahippocampal gyrus (r = 0.89, P < 0.001). We also calculated the total number of neurons in the hippocampus and hippocampus/subiculum subvolumes. Strong correlations between the magnetic resonance imaging subvolumes and neuronal counts were found for the hippocampus (r = 0.90, P < 0.001) and the hippocampus/subiculum subvolume (r = 0.84, P < 0.001). We conclude that very accurate volumetric measurements of the whole hippocampal formation can be obtained by using a magnetic resonance imaging protocol. Moreover, the strong correlations between magnetic resonance imaging-based hippocampal volumes and neuronal numbers suggest the anatomical validity of magnetic resonance imaging volume measurements.

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Fine volumetric analysis of the cerebral ventricular system in schizophrenia: further evidence for multifocal mild to moderate enlargement.

We used traditional volumetric regional analysis and a finer anterior-posterior (AP) profile volumetric analysis to examine the cerebral ventricular system in an all-male, demographically matched sample of schizophrenia patients (n = 73) and normal controls (n = 29) using 2.8-mm-thin coronal T1-weighted magnetic resonance images from a 1.5 tesla scanner. Traditional regional analysis was performed on various regions using absolute volumes after adjusting for intracranial volume (ICV) and age. The fine AP profile analysis was done by intrasubject "stacking" of contiguous coronal cross-sectional volumes (adjusted for ICV and age) across the AP plane, intersubject AP alignment of all slices relative to the mammillary bodies, and plotting of slice volumes along the AP plane with 95 percent t-test-based confidence intervals. Schizophrenia subjects had mild to moderate multifocal ventricular enlargement (overall effect size d = 0.48), which was especially prominent in the right posterior temporal horn and, more generally, in the central to posterior portions of the lateral and third ventricles. Schizophrenia subjects also had milder enlargement in the left frontal horn, but no significant differences were found in the anterior temporal horns and the right frontal horn. Post hoc analyses of demographic, clinical, and neuropsychological variables did not account for much variance in the ventriculomegaly observed in the schizophrenia group. The lack of a single locus in the observed ventricular enlargement, the nonsignificant results from schizophrenia subtypes based on regional distributions, and the strong positive correlations among the ventricular regions for the schizophrenia group suggest that the ventriculomegaly seen in this chronic population reflects a single brainwide disease process leading to a multifocal or patchy loss of integrity in brain structure.

Adult↗

Functional magnetic resonance imaging of human brain activity in a verbal fluency task.

OBJECTIVES: Functional MRI (fMRI) holds the promise of non-invasive mapping of human brain function in both health and disease. Yet its sensitivity and reliability for mapping higher cognitive function are still being determined. Using verbal fluency as a task, the objective was to ascertain the consistency of fMRI on a conventional scanner for determining the anatomic substrate of language between subjects and between sexes. Comparison was made with previous PET studies. METHODS: Using a 1.5 Tesla magnet and an echoplanar pulse sequence, whole brain fMRI was obtained from 12 normal right handed subjects (6 males and 6 females) as they performed a verbal fluency task. RESULTS: A broadly consistent pattern of response was seen across subjects. Areas showing activation changes included the left prefrontal cortex and right cerebellum, in agreement with previous PET 15O-H2O studies. In addition, significantly decreased responses were seen in the posterior cingulate and over an extensive area of mesial and dorsolateral parietal and superior temporal cortices. The male cohort showed a slight asymmetry of parietal deactivation, with more involvement on the right, whereas the female cohort showed a small region of activation in the right orbitofrontal cortex. There were individual task related regional changes in all 12 subjects with the area showing the most significant change being the left prefrontal cortex in all cases. CONCLUSIONS: Magnetic resonance scanners of conventional field strength can provide functional brain mapping data with a sensitivity at least that of PET. Activation was seen in left prefrontal and right cerebellar regions, as with PET. However, decremental responses were seen over a much larger area of the posterior cortex than had been anticipated by prior studies. The ability to see a response in each subject individually suggests that fMRI may be useful in the preinterventional mapping of pathological states, and offers a non-invasive alternative to the Wada test for assessment of hemispheric dominance. There were no gross differences in the pattern of activation between male and female subjects.

Adult↗

Pulmonary nodule detection: low-dose versus conventional CT.

PURPOSE: To quantitate the effectiveness of low-dose computed tomography (CT) in the identification of pulmonary nodules while controlling for anatomic nodule characteristics and to establish what factors lead to reduced diagnostic sensitivity at low-dose CT. MATERIALS AND METHODS: Each of six participating radiologist independently rated 200 image panels by using a four-point confidence scale. Conventional images were obtained at 200 mAs; low-dose images were obtained at 20 mAs. To fully control their characteristics, nodules were simulated with a given diameter, shape, and section thickness while preserving the resolution, noise level, and reconstruction artifacts of the original images. Panels were matched so that nodules on low-dose and conventional images had equivalent sizes, locations, and relationships to blood vessels. RESULTS: Among 864 positive panels, 259 (60%) of 432 low-dose panels and 272 (63%) of 432 conventional panels were correctly interpreted (P = .259). Lowering the x-ray dose significantly reduced the detectability of peripheral nodules (P = .019) and nodules separated from blood vessels (P = .044). Surprisingly, 3-mm nodules were detected with approximately equal sensitivity (P = .181) at conventional and low-dose CT. The specificity of low-dose images was 88% (148 of 168 panels) versus 91% (153 of 168 panels) for conventional images (P = .372). CONCLUSION: Low-dose CT is acceptable for pulmonary nodule identification, making it suitable for primary screening. These results confirm the strong effect of size, location, and angiocentricity on the sensitivity of nodule detection with conventional CT.

Computer Simulation↗

Effect of a haloperidol challenge on regional brain metabolism in neuroleptic-responsive and nonresponsive schizophrenic patients.

OBJECTIVE: The CNS metabolic response to a neuroleptic challenge in treatment-responsive and nonresponsive schizophrenic patients was measured in order to examine the relation between treatment outcome and the capacity to alter neurochemical function in response to acute receptor blockade. METHOD: Positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) were used to measure regional cerebral metabolism in seven schizophrenic patients judged to have been responsive to drug treatment previously and seven nonresponsive schizophrenic patients after a drug-free period of at least 3 weeks (baseline) and again 12 hours after administration of 5.0 mg of haloperidol. RESULTS: The haloperidol challenge caused widespread decreases in absolute metabolism in the nonresponsive patients but not the responsive patients. These group differences reflect the findings on the second (challenge) scans, since metabolic values at baseline were not statistically different in the two groups. The pattern of decreased metabolic activity in the nonresponders after the haloperidol challenge is similar to that previously observed in normal subjects. CONCLUSIONS: The metabolic response to drug challenge separates treatment responders from nonresponders and normal subjects. The results suggest that subtyping of schizophrenia (and other psychiatric disorders) can be achieved by measuring the physiologic response to a pharmacologic challenge in vivo with chemical brain-imaging techniques.

Adult↗

Structural magnetic resonance image averaging in schizophrenia.

OBJECTIVE: Intersubject averaging of structural magnetic resonance (MR) images has been infrequently used as a means to study group differences in cerebral structure throughout the brain. In the present study, the authors used linear intersubject averaging of structural MR images to evaluate the validity and utility of this technique and to extend previous research, conducted using a different approach to image averaging, in which reduction in thalamic size and abnormalities in perithalamic white matter tracts in the brains of schizophrenic patients were reported by Andreasen et al. METHOD: A 1.5-T MR scanner was used to obtain high-resolution, whole brain T1-weighted structural MR images for an age-matched sample of 25 schizophrenic patients and 25 normal control subjects. A "bounding box" procedure was used to create a single "averaged" brain for the schizophrenic group and for the control group. Differences in signal intensity between the two average brains were examined on a pixel-wise basis through use of one-tailed effect size maps. RESULTS: Effect size maps revealed widespread patchy signal intensity differences between the two groups in both cortical and periventricular areas, including major white matter tracts. The signal intensity differences were consistent with cortical thinning/sulcal widening and ventricular enlargement. No differences were found within thalamus or in immediately surrounding white matter. Effect size maps for differences (schizophrenic minus normal subjects) had only small values. CONCLUSIONS: These results are consistent with diffuse structural brain abnormalities of both gray and white matter in schizophrenic populations such as the one in this study.

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MR differential diagnosis of normal-pressure hydrocephalus and Alzheimer disease: significance of perihippocampal fissures.

PURPOSE: In the older patient with dilated ventricles, it is often difficult to differentiate normal pressure hydrocephalus (NPH) from cerebral atrophy caused by Alzheimer disease (AD). This study was undertaken to see if dilatation of the perihippocampal fissures (PHFs) could be used as a distinguishing characteristic of these two disorders. METHODS: MR images of 17 patients with AD were compared with those from an equal number of patients with NPH who improved after ventriculoperitoneal shunting. The PHFs, lateral ventricles, third ventricle, and temporal horns were graded subjectively. Objective, computer-aided volumetric measurements of the PHFs and lateral ventricles were obtained. The preshunt images of the NPH patients were evaluated. RESULTS: Significant differences between the two groups were found for the PHFs and lateral ventricles by both the subjective and objective methods, with a high degree of correlation between the two methods. CONCLUSION: The degree of dilatation of PHFs appears to be a sensitive and specific marker for differentiating AD from NPH by both subjective and objective means, with a very small overlap between the two groups. This observation may have relevance in day-to-day practice.

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Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease.

There is compelling evidence for the early involvement of the hippocampal formation in the natural history of Alzheimer's disease (AD). The evidence comes from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type histopathologic changes limited to the hippocampus have been described and may be seen in normal aging subjects. The sites of maximal neuronal loss in the hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally cognitively impaired (MCI) individuals (defined by ratings of functional capacity and psychiatric symptomatology) exhibit a neuropsychological profile that is distinct from that of the unimpaired elderly. Pathologic evidence suggests that most of these cases already have AD brain changes accentuated in the hippocampal region, and our own longitudinal studies reveal that 70% of this group develop dementia within a 4-year period. We have developed a negative-angle axial view designed to cut parallel to the anterior-posterior plane of the hippocampus. Using this modified axial plane of section in conjunction with computed tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence of hippocampal atrophy in normal aging and across severity levels of cognitively impaired elderly patients. Longitudinal study shows that hippocampal atrophy is a sensitive and specific predictor of future AD for patients with MCI. MRI volume study of AD patients, controls, and MCI patients shows specific hippocampal volume loss in MCI. We conclude that the atrophic changes associated with early AD can be visualized using qualitative techniques and are readily quantifiable with volumetry. This article is not intended to be comprehensive, but to provide an overview of some of the structural neuroimaging data from our laboratory.

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