Hans Olofsen

Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population

Objective: To investigate the influence of deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVWMH) on progression of cognitive decline in non-demented elderly people. Methods: All data come from the nested MRI sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We performed a 3 year follow up study on 554 subjects of the PROSPER study using both repeated magnetic resonance imaging and cognitive testing. Cognitive decline and its dependency on WMH severity was assessed using linear regression models adjusted for sex, age, education, treatment group, and test version when applicable. Results: We found that the volume of PVWMH at baseline was longitudinally associated with reduced mental processing speed (p = 0.0075). In addition, we found that the progression in PVWMH volume paralleled the decline in mental processing speed (p = 0.024). In contrast, neither presence nor progression of DWMH was associated with change in performance on any of the cognitive tests. Conclusion: PVWMH should not be considered benign but probably underlie impairment in cognitive processing speed.

Fully automatic segmentation of white matter hyperintensities in MR images of the elderly.

The role of quantitative image analysis in large clinical trials is continuously increasing. Several methods are available for performing white matter hyperintensity (WMH) volume quantification. They vary in the amount of the human interaction involved. In this paper, we describe a fully automatic segmentation that was used to quantify WMHs in a large clinical trial on elderly subjects. Our segmentation method combines information from 3 different MR images: proton density (PD), T2-weighted and fluid-attenuated inversion recovery (FLAIR) images; our method uses an established artificial intelligent technique (fuzzy inference system) and does not require extensive computations. The reproducibility of the segmentation was evaluated in 9 patients who underwent scan-rescan with repositioning; an inter-class correlation coefficient (ICC) of 0.91 was obtained. The effect of differences in image resolution was tested in 44 patients, scanned with 6- and 3-mm slice thickness FLAIR images; we obtained an ICC value of 0.99. The accuracy of the segmentation was evaluated on 100 patients for whom manual delineation of WMHs was available; the obtained ICC was 0.98 and the similarity index was 0.75. Besides the fact that the approach demonstrated very high volumetric and spatial agreement with expert delineation, the software did not require more than 2 min per patient (from loading the images to saving the results) on a Pentium-4 processor (512 MB RAM).

Shape differences of the brain ventricles in Alzheimer's disease.

The brain ventricles are surrounded by gray and white matter structures that are often affected in dementia in general and Alzheimers disease (AD) in particular. Any change of volume or shape occurring in these structures must affect the volume and shape of the ventricles. It is well known that ventricular volume is significantly higher in AD patients compared to age-matched healthy subjects. However, the large overlap between the two volume distributions makes the measurement unsuitable as a biomarker of the disease. The purpose of this work was to assess whether local shape differences of the ventricles can be detected when comparing AD patients and controls. In this work, we captured the ventricles shape and shape variations of 29 AD subjects and 25 age-matched controls, using a fully automatic shape modeling technique. By applying permutation tests on every single node of a mesh representation of the shapes, we identified local areas with significant differences. About 22% of an average surface of the ventricles presented significant difference (P < 0.05) ( approximately 14% of the left against approximately 7% of the right side). We found out that in patients with Alzheimer disease, not only the lateral horns were significantly affected, but also the areas adjacent to the anterior corpus callosum, the splenium of the corpus callosum, the amygdala, the thalamus, the tale of the caudate nuclei (especially the left one), and the head of the left caudate nucleus.

Different progression rates for deep white matter hyperintensities in elderly men and women

The authors investigated the progression of white matter hyperintensities (WMHs) in a large population of elderly men and women. After 3 years of follow-up, women had accumulated approximately twice as much deep WMH (DWMH) as men. The progression of periventricular WMH was the same for men and women. Gender differences may affect the pathogenesis of DWMH, which in turn may result in different clinical consequences in women.

Anatomic considerations of cochlear morphology and its implications for insertion trauma in cochlear implant surgery.

Hypothesis: The goal of this study is to analyze the 3-dimensional anatomy of the cochlear spiral and to investigate the consequences of its course to insertion trauma during cochlear implantation. Background: Insertion trauma in cochlear implant surgery is a feared surgical risk, potentially causing neural degeneration and altered performance of the implant. In literature, insertion trauma is reported to occur at specific locations. This has been ascribed to surgical technique and electrode design in relation to the size of the scala tympani. This study investigates whether there is an underlying anatomic substrate serving as a potential source for insertion trauma at these specific locations. Methods: The 3-dimensional path of the cochlear spiral of 8 human temporal bones was determined by segmentation, skeletonization, distance mapping, and wave propagation technique applied on microcomputer tomography images. Potential pressure points along this path were estimated with linear regression. Results: The cochlear lumen shows a noncontinuous spiraling path leading to potential pressure points during cochlear implantation at the basilar membrane in the region of 180 to 225 (12-14 mm) and 725 degrees (22-26 mm) and at the floor of the scala tympani around 0 to 90, 225 to 270, and 405 to 450 degrees. Conclusion: Our data favor the idea that the intrinsic 3-dimensional cochlear morphology contributes to the risk for insertion trauma during cochlear implantation at specific locations.

Ventricular Shape Biomarkers for Alzheimer's disease in Clinical MR images

The aim of this work was to identify ventricular shape‐based biomarkers in MR images to discriminate between patients with Alzheimers disease (AD) and healthy elderly. Clinical MR images were collected for 58 patients and 28 age‐matched healthy controls. After normalizing all the images the ventricular cerebrospinal fluid was semiautomatically extracted for each subject and an innovative technique for fully automatic shape modeling was applied to generate comparable meshes of all ventricles. The search for potential biomarkers was carried out with repeated permutation tests: results highlighted well‐defined areas of the ventricular surface being discriminating features for AD: the left inferior medial temporal horn, the right medial temporal horn (superior and inferior), and the areas close to the left anterior part of the corpus callosum and the head of the right caudate nucleus. The biomarkers were then used as features to build an intelligent machine for AD detection: a Support Vector Machine was trained on AD and healthy subjects and subsequently tested with leave‐1‐out experiments and validation tests on previously unseen cases. The results showed a sensitivity of 76% for AD, with an overall accuracy of 84%, proving that suitable biomarkers for AD can be detected in clinical MR images. Magn Reson Med 59:260–267, 2008.

MMSE scores correlate with local ventricular enlargement in the spectrum from cognitively normal to Alzheimer disease

In this work, we aimed at correlating focal atrophy in periventricular structures with cognitive function, in the spectrum from healthy subjects to severe Alzheimer disease: 28 subjects with normal cognition and 84 patients presenting various degrees of cognitive impairment were included in the study. The cognitive level of each subject was assessed with the Mini-Mental State Examination (MMSE). Atrophy in periventricular structures was inferred by modeling and analyzing local shape variations of brain ventricles: for a given subject, we distinguished between the severity of atrophy, estimated as local enlargement (in mm) of the ventricular surface relative to an average normal subject, and the extent of atrophy, defined as the percentage of the ventricular surface (global or per anatomical region) significantly different from an average control. Linear regression across subjects was performed to evaluate the correlation between atrophy and MMSE score. The severity of atrophy showed good correlation with MMSE score in the left thalamus, the left temporal horn, the left corona radiata, and the right caudate nuclei. The extent of atrophy showed no significant correlations. In conclusion, the MMSE scores correlate with localized depth of atrophy in well-defined periventricular structures.

Non-invasive tracking of avian development in vivo by MRI.

Conventional microscopic techniques, to study embryonic development, require large numbers of embryos and are invasive, making follow‐up impossible. We explored the use of in vivo MRI to study embryonic development, in general, and cardiovascular development in particular, over time. Wild‐type quail embryos (n = 11) were imaged at embryonic days 3, 5, 7, 9, and 11, covering the main time course of embryonic heart development. On each imaging day cardiac morphology was evaluated and embryonic length was measured. MRI‐embryos as well as control embryos (n = 11) were sacrificed at day 11 and scored for external malformations, while embryonic wet weight and stage were determined. In addition, venous clipped embryos (n = 4), known to develop cardiovascular malformations, were scanned at regular intervals and sacrificed at day 9 for histological analysis ex vivo. We were able to follow heart development of individual quail embryos inside their shell non‐invasively over time, with sufficient detail to study cardiac morphology in vivo. We did not find any adverse effect of the repeated MRI examinations on morphology, length, or weight. Prenatally diagnosed malformations, like ventricular septal defects and aortic arch interruptions were confirmed by histology. In conclusion, micro‐MRI can be used to evaluate in vivo early embryonic development and to diagnose cardiovascular malformations prenatally. Copyright

Magnetization transfer imaging of gray and white matter in mild cognitive impairment and Alzheimer's disease

OBJECTIVE To assess whether structural brain damage as detected by magnetization transfer imaging (MTI) in Alzheimers disease (AD) and mild cognitive impairment (MCI) is located in the gray matter (GM) and/or the white matter (WM). METHODS Fifty-five AD patients, 19 MCI patients and 43 subjects with normal cognitive function participated in this study. GM and WM segmentations were generated from dual fast spin-echo MR images. These masks were co-registrated to MT images for volumetric MTI-analysis of the GM and WM. RESULTS AD patients had a lower GM volume than controls. Both MCI and AD patients had more structural brain damage in both GM and WM than subjects with normal cognition. Cerebral lesion load in both GM and WM was associated with the degree of cognitive impairment. CONCLUSION Using MTI, structural brain changes that are related to cognitive impairment could be demonstrated in both GM and WM of patients with AD and MCI. These results suggest that cerebral changes are present in GM and WM even before patients are clinically demented.

Detection of change in CNS involvement in neuropsychiatric SLE: A magnetization transfer study

To assess whether magnetization transfer imaging (MTI) parameters change in correspondence with clinical changes in NPSLE patients.