Yawu Liu

Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke: Ischemic penumbra predicts infarct growth

BACKGROUND AND PURPOSE More effective imaging methods are needed to overcome the limitations of CT in the investigation of treatments for acute ischemic stroke. Diffusion-weighted MRI (DWI) is sensitive in detecting infarcted brain tissue, whereas perfusion-weighted MRI (PWI) can detect brain perfusion in the same imaging session. Combining these methods may help in identifying the ischemic penumbra, which is an important concept in the hemodynamics of acute stroke. The purpose of this study was to determine whether combined DWI and PWI in acute (<24 hours) ischemic stroke can predict infarct growth and final size. METHODS Forty-six patients with acute ischemic stroke underwent DWI and PWI on days 1, 2, and 8. No patient received thrombolysis. Twenty-three patients underwent single-photon emission CT in the acute phase. Lesion volumes were measured from DWI, SPECT, and maps of relative cerebral blood flow calculated from PWI. RESULTS The mean volume of infarcted tissue detected by DWI increased from 46.1 to 75.6 cm(3) between days 1 and 2 (P<0.001; n=46) and to 78.5 cm(3) after 1 week (P<0.001; n=42). The perfusion-diffusion mismatch correlated with infarct growth (r=0. 699, P<0.001). The volume of hypoperfusion on the initial PWI correlated with final infarct size (r=0.827, P<0.001). The hypoperfusion volumes detected by PWI and SPECT correlated significantly (r=0.824, P<0.001). CONCLUSIONS Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.

Diffusion tensor imaging and Tract-Based Spatial Statistics in Alzheimer's disease and mild cognitive impairment

We aimed to explore the changes in fractional anisotropy (FA) in subjects with mild cognitive impairment (MCI) and Alzheimers disease (AD) by analyzing diffusion tensor imaging (DTI) data using the Tract-Based Spatial Statistics (TBSS). DTI data were collected from 17 AD patients, 27 MCI subjects and 19 healthy controls. Voxel-based analysis with TBSS was used to compare FA among the three groups. Additionally, guided by TBSS findings, a region of interest (ROI)-based analysis along the TBSS skeleton was performed on group-level and the accuracy of the method was assessed by the back-projection of ROIs to the native space FA. Neurofiber tracts with decreased FA included: the parahippocampal white matter, cingulum, uncinate fasciculus, inferior and superior longitudinal fasciculus, corpus callosum, fornix, tracts in brain stem, and cerebellar tracts. Quantitative ROI-analysis further demonstrated the significant decrease on FA values in AD patients relative to controls whereas FA values of MCI patients were found in between the controls and AD patients. We conclude that TBSS is a promising method in examining the degeneration of neurofiber tracts in MCI and AD patients.

Multivariate analysis of MRI data for Alzheimer's disease, mild cognitive impairment and healthy controls.

We have used multivariate data analysis, more specifically orthogonal partial least squares to latent structures (OPLS) analysis, to discriminate between Alzheimers disease (AD), mild cognitive impairment (MCI) and elderly control subjects combining both regional and global magnetic resonance imaging (MRI) volumetric measures. In this study, 117 AD patients, 122 MCI patients and 112 control subjects (from the AddNeuroMed study) were included. High-resolution sagittal 3D MP-RAGE datasets were acquired from each subject. Automated regional segmentation and manual outlining of the hippocampus were performed for each image. Altogether this yielded volumes of 24 different anatomically defined structures which were used for OPLS analysis. 17 randomly selected AD patients, 12 randomly selected control subjects and the 22 MCI subjects who converted to AD at 1-year follow up were excluded from the initial OPLS analysis to provide a small external test set for model validation. Comparing AD with controls we found a sensitivity of 87% and a specificity of 90% using hippocampal measures alone. Combining both global and regional measures resulted in a sensitivity of 90% and a specificity of 94%. This increase in sensitivity and specificity resulted in an increase of the positive likelihood ratio from 9 to 15. From the external test set, the model predicted 82% of the AD patients and 83% of the control subjects correctly. Finally, 73% of the MCI subjects which converted to AD at 1 year follow-up were shown to resemble AD patients more closely than controls. This method shows potential for distinguishing between different patient groups. Combining the different MRI measures together resulted in a significantly better classification than using them separately. OPLS also shows potential for predicting conversion from MCI to AD.

Cerebral Hemodynamics in Human Acute Ischemic Stroke: A Study with Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging and SPECT

Nineteen patients with acute ischemic stroke (<24 hours) underwent diffusion-weighted and perfusion-weighted (PWI) magnetic resonance imaging at the acute stage and 1 week later. Eleven patients also underwent technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (SPECT) at the acute stage. Relative (ischemic vs. contralateral control) cerebral blood flow (relCBF), relative cerebral blood volume, and relative mean transit time were measured in the ischemic core, in the area of infarct growth, and in the eventually viable ischemic tissue on PWI maps. The relCBF was also measured from SPECT. There was a curvilinear relationship between the relCBF measured from PWI and SPECT (r = 0.854; P < 0.001). The tissue proceeding to infarction during the follow-up had significantly lower initial CBF and cerebral blood volume values on PWI maps (P < 0.001) than the eventually viable ischemic tissue had. The best value for discriminating the area of infarct growth from the eventually viable ischemic tissue was 48% for PWI relCBF and 87% for PWI relative cerebral blood volume. Combined diffusion and perfusion-weighted imaging enables one to detect hemodynamically different subregions inside the initial perfusion abnormality. Tissue survival may be different in these subregions and may be predicted.

Education increases reserve against Alzheimer’s disease—evidence from structural MRI analysis

IntroductionThe aim of this study was to determine whether years of schooling influences regional cortical thicknesses and volumes in Alzheimer’s disease (AD), mild cognitive impairment (MCI), and healthy age-matched controls.MethodsUsing an automated image analysis pipeline, 33 regional cortical thickness and 15 regional volumes measures from MRI images were determined in 121 subjects with MCI, 121 patients with AD, and 113 controls from AddNeuroMed study. Correlations with years of schooling were determined and more highly and less highly educated subjects compared, controlling for intracranial volume, age, gender, country of origin, cognitive status, and multiple testing.ResultsAfter controlling for confounding factors and multiple testing, in the control group, subjects with more education had larger regional cortical thickness in transverse temporal cortex, insula, and isthmus of cingulate cortex than subjects with less education. However, in the AD group, the subjects with more education had smaller regional cortical thickness in temporal gyrus, inferior and superior parietal gyri, and lateral occipital cortex than the subjects with less education. No significant difference was found in the MCI group.ConclusionEducation may increase regional cortical thickness in healthy controls, leading to increased brain reserve, as well as helping AD patients to cope better with the effects of brain atrophy by increasing cognitive reserve.

Evaluation of four postprocessing methods for determination of cerebral blood volume and mean transit time by dynamic susceptibility contrast imaging

Four different postprocessing methods to determine cerebral blood volume (CBV) and contrast agent mean transit time (MTT) by dynamic susceptibility contrast (DSC) MRI were compared. CBV was determined by two different methods that integrate tracer concentration–time curves numerically and by two other methods that take recirculation into account. For the two methods that use numerical integration, one method cuts the integration after the first pass while the other method integrates over the whole time series. For the two methods that account for recirculation, one method uses a gamma‐variate fit, whereas the other method utilizes tissue impulse response. All four methods determine MTT as the ratio of CBV and cerebral blood flow (CBF). In each case, CBF was obtained as the height of the impulse response obtained by deconvolving the tissue concentration–time curves with a noninvasively determined arterial input function. Monte Carlo simulations were performed to determine the reliability of the methods and the validity of the simulations was supported by observation of similar trends in 13 acute stroke patients. The method of determining CBV and subsequently MTT was found to affect the measured value especially in areas where MTT is prolonged, but had no apparent effect on the visually determined hypoperfusion volumes. Magn Reson Med 47:973–981, 2002.

The Real Estate Factor Quantifying the Impact of Infarct Location on Stroke Severity

Background and Purpose— The severity of the neurological deficit after ischemic stroke is moderately correlated with infarct volume. In the current study, we sought to quantify the impact of location on neurological deficit severity and to delineate this impact from that of volume. Methods— We developed atlases consisting of location-weighted values indicating the relative importance in terms of neurological deficit severity for every voxel of the brain. These atlases were applied to 80 first-ever ischemic stroke patients to produce estimates of clinical deficit severity. Each patient had an MRI and National Institutes of Health Stroke Scale (NIHSS) examination just before or soon after hospital discharge. The correlation between the location-based deficit predictions and measured neurological deficit (NIHSS) scores were compared with the correlation obtained using volume alone to predict the neurological deficit. Results— Volume-based estimates of neurological deficit severity were only moderately correlated with measured NIHSS scores (r=0.62). The combination of volume and location resulted in a significantly better correlation with clinical deficit severity (r=0.79, P=0.032). Conclusions— The atlas methodology is a feasible way of integrating infarct size and location to predict stroke severity. It can estimate stroke severity better than volume alone.

Analysis of regional MRI volumes and thicknesses as predictors of conversion from mild cognitive impairment to Alzheimer's disease

We determined predictors of conversion to Alzheimers disease (AD) from mild cognitive impairment (MCI) with automated magnetic resonance imaging (MRI) regional cortical volume and thickness measures. One hundred amnestic MCI subjects, 118 AD patients, and 94 age-matched healthy controls were selected from AddNeuroMed study. Twenty-four regional cortical volumes and 34 cortical thicknesses were measured with automated image processing software at baseline. Twenty-one subjects converted from MCI to AD determined with the cognitive tests at baseline and 1 year later. The hippocampus, amygdala, and caudate volumes were significantly smaller in progressive MCI subjects than in controls and stable MCI subjects. The cortical volumes achieved higher predictive accuracy than did cognitive tests or cortical thickness. Combining the volumes, thicknesses, and cognitive tests did not improve the accuracy. The volume of amygdala and caudate were independent variables in predicting conversion from MCI to AD. We conclude that regional cortical volume measures are more powerful than those common cognitive tests we used in identifying AD patients at the very earliest stage of the disease.

Effect of APOE ε4 allele on cortical thicknesses and volumes: the AddNeuroMed study.

The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimers disease (AD), but its effect on brain volumes is controversial. We explored the effect of the ε4 allele on regional cortical thickness and volume measurements using an automated pipeline in 111 subjects with mild cognitive impairment (MCI), 115 AD patients, and 107 age-matched healthy controls. The clinical data were used as covariates in the thickness and volume comparisons. The ε4 carriers had significantly smaller volume than non-carriers in caudate (p=0.028) in controls; in amygdala and caudate in the MCI group (p <or= 0.049); and in hippocampus and amygdala in the AD group (p <or= 0.001). In the female subjects, the ε4 carriers had significantly thinner cortical thickness or smaller volume than non-carriers in medial orbitofrontal gyrus and caudate in controls (p <or= 0.014); in amygdala in MCI subjects (p=0.047) and in hippocampus and amygdala in AD patients (p <or= 0.024). However, in the male subjects, there were significant differences in cortical thickness and volume between ε4 carriers and non-carriers in several structures in the MCI group, but no differences in the controls and AD patients. Compared to the non-carriers, the homozygous ε4 carriers showed significant volume loss in hippocampus, deep nuclei, and caudal anterior cingulate cortex in MCI. In the AD group, the homozygous ε4 carriers had significant volume loss in hippocampus and amygdala. We conclude that the APOE ε4 allele modulates regional cortical thickness and volume in relation to diagnostic group and gender. The ε4 allele has a dose-dependent and regionally specific effect on brain structures.

Combination analysis of neuropsychological tests and structural MRI measures in differentiating AD, MCI and control groups—The AddNeuroMed study

To study the ability of neuropsychological tests, manual MRI hippocampal volume measures, regional volume and cortical thickness measures to identify subjects with Alzheimers disease (AD), mild cognitive impairment (MCI), and healthy age-matched controls. Neuropsychological tests, manual hippocampal volume, automated regional volume and regional cortical thickness measures were performed in 120 AD patients, 120 MCI subjects, and 111 controls. The regional cortical thickness and volumes in MCI subjects were significantly decreased in limbic/paralimbic areas and temporal lobe compared to controls. Atrophy was much more extensive in the AD patients compared to MCI subjects and controls. The combination of neuropsychological tests and volumes revealed the highest accuracy (82% AD vs. MCI; 94% AD vs. control; 83% MCI vs. control). Adding regional cortical thicknesses into the discriminate analysis did not improve accuracy. We conclude that regional cortical thickness and volume measures provide a panoramic view of brain atrophy in AD and MCI subjects. A combination of neuropsychological tests and regional volumes are important when discriminating AD from healthy controls and MCI.