Increased CSF F2-isoprostane concentration in probable AD.

OBJECTIVE: To quantify F2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls. BACKGROUND: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans. Recently, we showed that F2-isoprostane concentrations are significantly elevated in CSF obtained postmortem from the lateral ventricles of patients with definite AD compared with controls. METHODS: F2-isoprostanes were quantified by gas chromatography/negative ion chemical ionization mass spectrometry. RESULTS: CSF F2-isoprostanes were increased significantly in patients with probable AD, but not in ALS patients, compared with controls. CONCLUSIONS: Increased CSF F2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD.

Effect of geometrical distortion correction in MR on image registration accuracy.

In this article we investigate the effect of geometrical distortion correction in MR images on the accuracy of the registration of X-ray CT and MR head images for both a fiducial marker (extrinsic point) method and a surface-matching technique. We use CT and T2-weighted MR image volumes acquired from seven patients who underwent craniotomies in a stereotactic neurosurgical clinical trial. Each patient had four external markers attached to transcutaneous posts screwed into the outer table of the skull. The MR images are corrected for static field inhomogeneity by using an image rectification technique and corrected for scale distortion (gradient magnitude uncertainty) by using an attached stereotactic frame as an object of known shape and size. We define target registration error (TRE) as the distance between corresponding marker positions after registration and transformation. The accuracy of the fiducial marker method is determined by using each combination of three markers to estimate the transformation and the remaining marker to calculate registration error. Surface-based registration is accomplished by fitting MR contours corresponding to the CSF-dura interface to CT contours derived from the inner surface of the skull. The mean point-based TRE using three noncollinear fiducials improved 34%-from 1.15 to 0.76 mm-after correcting for both static field inhomogeneity and scale distortion. The mean surface-based TRE improved 46%-from 2.20 to 1.19 mm. Correction of geometrical distortion in MR images can significantly improve the accuracy of point-based and surface-based registration of CT and MR head images. Distortion correction can be important in clinical situations such as stereotactic and functional neurosurgery where 1 to 2 mm accuracy is required.

Accurate localization of cortical convolutions in MR brain images.

Analysis of brain images often requires accurate localization of cortical convolutions. Although magnetic resonance (MR) brain images offer sufficient resolution for identifying convolutions in theory, the nature of tomographic imaging prevents clear definition of convolutions in individual slices. Existing methods for solving this problem rely on heuristic adaptation of brain atlases created from a small number of individuals. These methods do not usually provide high accuracy because of large biological variations among individuals. The authors propose to localize convolutions by linking realistic visualizations of the cortical surface with the original image volume. They have developed a system so that a user can quickly localize key convolutions in several visualizations of an entire brain surface. Because of the links between the visualizations and the original volume, these convolutions are simultaneously localized in the original image slices. In the process of the authors' development, they have implemented a fast and easy method for visualizing cortical surfaces in MR images, thereby making their scheme usable in practical applications.

Retrospective registration of PET and MR brain images: an algorithm and its stereotactic validation.

OBJECTIVE: We present a validation study of an algorithm for retrospective registration of PET and MR brain images. MATERIALS AND METHODS: This algorithm involves two steps. In the first step, the two volumes are reformatted by aligning their interhemispheric fissure planes (midsagittal plane). In the second step, the corresponding planes parallel to the midsagittal plane are further aligned in the reformatted volumes to produce a 3D rigid body registration of the two original volumes. It is an efficient algorithm because both steps are performed in 2D spaces, and in each step only a small number of landmarks are required. A user-friendly system has been implemented to facilitate easy and fast processing of registration and reformatting of image volumes. The accuracy of this algorithm is validated using clinical scans of neurosurgical patients with a stereotaxic frame attached to their skull. The frame-based stereotaxic system provides an effective method for transforming image coordinates from different image volumes into a common coordinate system. This common coordinate system is used for assessing the spatial correspondence of each pixel in the registered image volumes. Validation using the stereotaxic image volumes enables objective estimation of retrospective registration accuracy. RESULTS: Analysis of 11 MR/PET image pairs indicates that our registration method not only is efficient but also provides adequate accuracy for most clinical evaluation of PET studies. CONCLUSION: We have implemented and validated an efficient algorithm for retrospective registration of PET and MR brain images.

Morphometric analysis of white matter lesions in MR images: method and validation.

The analysis of MR images is evolving from qualitative to quantitative. More and more, the question asked by clinicians is how much and where, rather than a simple statement on the presence or absence of abnormalities. The authors present a study in which the results obtained with a semiautomatic, multispectral segmentation technique are quantitatively compared to manually delineated regions. The core of the semiautomatic image analysis system is a supervised artificial neural network classifier augmented with dedicated preand postprocessing algorithms, including anisotropic noise filtering and a surface-fitting method for the correction of spatial intensity variations. The study was focused on the quantitation of white matter lesions in the human brain. A total of 36 images from six brain volumes was analyzed twice by each of two operators, under supervision of a neuroradiologist. Both the intra- and interrater variability of the methods were studied in terms of the average tissue area detected per slice, the correlation coefficients between area measurements, and a measure of similarity derived from the kappa statistic. The results indicate that, compared to a manual method, the use of the semiautomatic technique not only facilitates the analysis of the images, but also has similar or lower intra- and interrater variabilities.

Automatic detection of intracranial contours in MR images.

Segmentation of the intracranial cavity in medical images is valuable in several research areas such as the quantitative analysis of normal and abnormal brain tissues, the registration of different imaging modalities (MRI, PET, CT) based on surface models of the brain, and the rendering of volume data. Because the manual delineation of the brain contour in the images can be demanding and error prone, an automatic procedure to perform this task is desirable. We have developed and tested a robust method that permits the automatic detection of the intracranial contour in transverse MR images. The method is described and its performance evaluated.

Correction of intensity variations in MR images for computer-aided tissue classification.

A number of supervised and unsupervised pattern recognition techniques have been proposed in recent years for the segmentation and the quantitative analysis of MR images. However, the efficacy of these techniques is affected by acquisition artifacts such as inter-slice, intra-slice, and inter-patient intensity variations. Here a new approach to the correction of intra-slice intensity variations is presented. Results demonstrate that the correction process enhances the performance of backpropagation neural network classifiers designed for the segmentation of the images. Two slightly different versions of the method are presented. The first version fits an intensity correction surface directly to reference points selected by the user in the images. The second version fits the surface to reference points obtained by an intermediate classification operation. Qualitative and quantitative evaluation of both methods reveals that the first one leads to a better correction of the images than the second but that it is more sensitive to operator errors.

Effects of substance abuse on ventricular and sulcal measures assessed by computerised tomography.

Computerised tomography (CT) was used to assess the possible effects of substance abuse on brain morphology. Polydrug abusers had significantly wider third ventricles than normal controls, with a positive correlation between age and ventricle:brain ratio (VBR). Assuming no effect of age, estimated quantity of substance abuse was not significantly related to ventricular and sulcal measures, except that alcohol consumption correlated positively with VBR and severity of cocaine use correlated negatively with sulcal width. When age of the subjects was partialled out, alcohol use showed a tendency for association with VBR; however, severity of cocaine use did not remain a significant predictor of cortical sulcal width. The findings suggest that chronic use of alcohol, but not necessarily of other commonly abused substances, produces brain atrophy.

Effects of fasting on ketone body concentrations in healthy men of different ages.

This work was performed to assess age effects on fasting-induced hyperketonemia and to determine if measurement of cerebral glucose utilization by positron emission tomography after 6 to 8 hr of fasting is associated with hyperketonemia that could influence cerebral glucose metabolism. Acetoacetate and 3-hydroxybutyrate were assayed in venous blood from healthy men of various ages, subjected to an 18-hr fast. At 18 hr of fasting but not at 14 hr or earlier, 3-hydroxybutyrate concentrations were correlated significantly with age; concentrations of acetoacetate and 3-hydroxybutyrate were significantly higher than at earlier times in the fast, p less than or equal to .05, with elevations of 82% and 214% over baseline, respectively. Acetoacetate and 3-hydroxybutyrate concentrations were higher on the day when cerebral glucose utilization was determined than after a comparable fast at another time. The observed level of hyperketonemia, however, would not substantially influence cerebral glucose metabolism. The findings indicate that aging is associated with increased susceptibility to fasting-induced hyperketonemia.

Neuroimaging and psychopharmacology in the diagnosis and treatment of dementia.

Contributions of noninvasive brain imaging technologies to the diagnosis of organic dementias with special reference to Alzheimer's disease are reviewed. Included among the different techniques are: a. computed tomography b. magnetic resonance imaging c. positron emission tomography. Biochemical hypotheses with possible relevance to the pathogenesis of Alzheimer's disease are presented and their therapeutic implications are discussed. Included among the different hypotheses are: a. interference with protein synthesis b. acetylcholine deficiency c. aluminum deposition. Present status of the pharmacotherapy of Alzheimer's disease is outlined.

Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography.

The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

Human brain glucose utilization and cognitive function in relation to age.

Brain oxidative metabolism was examined with positron emission tomography and [18F]2-deoxy-D-glucose in 40 healthy men aged 21 to 83 years, under conditions of reduced visual and auditory stimulation. The mean cerebral metabolic rate for glucose (CMRglc) equaled 4.6 to 4.7 mg X 100 gm-1 X min-1 and did not correlate significantly with age (p greater than 0.05). Regional cerebral metabolic rates for glucose (rCMRglc) and Q ratios (rCMRglc/CMRglc), which had lower coefficients of variation than did rCMRglc, also did not correlate with age. Hyperfrontality of cerebral metabolism was absent at all ages. Age decrements were demonstrated in the error score on the Benton Revised Visual Retention Test and in the Performance Subtest scaled score of the Wechsler Adult Intelligence Scale (WAIS) but not in the Verbal Subtest scaled score of the WAIS. The cognitive test scores did not correlate with brain metabolic rates. The results indicate that brain oxidative metabolism, when measured under resting conditions with reduced sensory input, is not reduced in relation to age in healthy men. Furthermore, no significant relations between intelligence and resting cerebral metabolism are evident.

Correlational methods for determining regional coupling of cerebral glucose metabolism: a pilot study.

The current study presents an alternate method of analyzing PET data by means of a correlational approach. Correlational or coupling patterns of regional cerebral glucose metabolism were found for normal subjects and patients with schizophrenia under electric shock stimulation. At two levels (91 mm and 78 mm) significant differences were found between the coupling patterns of normal subjects and patients with schizophrenia. For the normals, the obtained correlational maps were consistent with the sensory input. However, such patterns were not found for the patients with schizophrenia. Therefore it is suggested that the outlined analysis procedure may complement the standard approach of comparing the mean metabolic rates.

Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years.

Positron emission tomography (PET) scanning with 18F-2-deoxy-D-glucose was employed to examine hemispheric and regional rates of cerebral glucose utilization in 21 resting healthy men between the ages of 21 and 83 years. The eyes of the subjects were covered and the external auditory canals were plugged with cotton in the 45 minutes following injection of tracer. Mean hemispheric cerebral metabolic rates for glucose (CMRglc) averaged 4.3 to 4.4 mg x 100 g-1 X min-1, and mean hemispheric grey matter glucose utilization, (CMRglc)grey, averaged 5.2 to 5.3 mg x 100 g-1 X min-1. Neither parameter was correlated significantly with age, nor were their right/left ratios correlated with age (P greater than 0.05). The mean ratios, furthermore, did not differ significantly from 1. Regional cerebral metabolic rates for glucose, rCMRglc, at each of 31 identified midline and bilateral structures also were not correlated significantly with age. Mean rCMRglc ranged from 2.6 mg X 100 g-1 X min-1 at the centrum semiovale to 6.2 mg . 100 g-1 X min-1 at the precentral gyrus of the frontal lobe and precuneus of the parietal lobe. The results indicate that the cerebral metabolic rate for glucose is not correlated with age in healthy men.