Brain Atrophy Measures Research Articles

Cerebral Atrophy Measurement in Clinically Isolated Syndromes and Relapsing Remitting Multiple Sclerosis: A Comparison of Registration‐Based Methods

Brain atrophy is a proposed marker of disease progression in multiple sclerosis (MS). Many magnetic resonance imaging-based methods of atrophy quantification exist, but their relative sensitivity and precision is unclear. Our aim was to compare atrophy rates from the brain boundary shift integral (BBSI), structural image evaluation, using normalization of atrophy (SIENA) (both registration-based methods) and segmented brain volume difference, in patients with clinically isolated syndromes (CIS), relapsing remitting MS (RRMS), and controls. Thirty-seven CIS patients, 30 with early RRMS and 16 controls had T1-weighted volumetric imaging at baseline and 1 year. Brain atrophy rates were determined using segmented brain volume difference, BBSI, and SIENA. BBSI and SIENA were more precise than subtraction of segmented brain volumes and were more sensitive distinguishing RRMS subjects from controls. A strong correlation was observed between BBSI and SIENA. Atrophy rates were greater in CIS and RRMS subjects than controls (RRMS P < .001). With all methods, significantly greater atrophy rates were observed in CIS patients who developed clinically definite MS relative to subjects who did not. Registration-based techniques are more precise and sensitive than segmentation-based methods in measuring brain atrophy, with BBSI and SIENA providing comparable results.

Correlation between semi automated measurement of whole brain atrophy and T2W lesion load with Disability (EDSS) in multiple sclerosis

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous causing severe disability via progressive damage to white matter. Measuring brain paranchymal volume is an objective and reliable surrogate for destructive pathological process in MS. The brain parenchymal fraction (BPF) is the ratio of brain parenchymal volume to the total volume within the surface contour. MATERIALS AND METHODS In this study 20 patients (age 18-53) with definite remittingrelapsing (R-R) or slowly progressive (S-P) MS disease based on MacDonald criteria were selected. [4 slowly progressive (S-P) ,16 Remitting-relapsing (R-R) ].The neurological exam and Expanded Disability Status Score (EDSS) were enrolled by a well qualified neurologist. MR images were obtained on a 1.5 Tesla General Electric SIGNA System. T2 Fast spin echo and T1 Spin Echo sequences, covering the entire brain were gathered in the axial plane 5 mm thickness contiguously with a 256 x 256 acquisition matrix. A multi-step volume analysis was then performed using several processing tools available in semi automated software package including interactive image editing, region of interest pixel counting, registration and threshold. We measured BPF in patients with MS and 34 healthy controls. RESULTS There was strong correlation between EDSS and brain parenchymal atrophy (r=0.67 , p moderate correlation between T2w load and EDSS (r=0.34 p CONCLUSION BPF correlated negatively with expanded disability status scale (EDSS), but not with total T2 hyper intense lesion volume. We conclude that whole-brain atrophy in MS can be reliably and readily quantified by a semi automated approach References Correlation between semi automated measurement of whole brain atrophy and T2W lesion load with Disability (EDSS) in multiple sclerosis 2 of 2 Author Information Elham Rahimian, M.D. Radiologist, Tehran Medical University M. Tahsini, M.Sc. Biomedical Engineer, Sharif Technology University Roya Abolfazli, M.D. Neurologist, Tehran Medical University

Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia

Alzheimer's disease and frontotemporal dementia (FTD) can be difficult to differentiate clinically because of overlapping symptoms. Distinguishing the two dementias based on volumetric measurements of brain atrophy with MRI has been only partially successful. Whether MRI measurements of cortical thinning improve the differentiation between Alzheimer's disease and FTD is unclear. In this study, we measured cortical thickness using a set of automated tools (Freesurfer) to reconstruct the brain's cortical surface from T1-weighted structural MRI data in 22 patients with Alzheimer's disease, 19 patients with FTD and 23 cognitively normal subjects. The goals were to detect the characteristic patterns of cortical thinning in these two types of dementia, to test the relationship between cortical thickness and cognitive impairment, to determine if measurement of cortical thickness is better than that of cortical volume for differentiating between these dementias and normal ageing and improving the classification of Alzheimer's disease and FTD based on neuropsychological scores alone. Compared to cognitively normal subjects, Alzheimer's disease patients had a thinner cortex primarily in bilateral, frontal, parietal, temporal and occipital lobes (P < 0.001), while FTD patients had a thinner cortex in bilateral, frontal and temporal regions and some thinning in inferior parietal regions and the posterior cingulate (P < 0.001). Compared to FTD patients, Alzheimer's disease patients had a thinner cortex (P < 0.001) in parts of bilateral parietal and precuneus regions. Cognitive impairment was negatively correlated with cortical thickness of frontal, parietal and temporal lobes in Alzheimer's disease, while similar correlations were not significant in FTD. Measurement of cortical thickness was similar to that of cortical volume in differentiating between normal ageing, Alzheimer's disease and FTD. Furthermore, cortical thickness measurements significantly improved the classification between Alzheimer's disease and FTD based on neuropsychological scores alone, including the Mini-Mental State Examination and a modified version of the Trail-Making Test. In conclusion, the characteristic patterns of cortical thinning in Alzheimer's disease and FTD suggest that cortical thickness may be a useful surrogate marker for these types of dementia.

Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years

Reliable prognostic markers of primary progressive (PP) multiple sclerosis evolution are still needed. Diffusion tensor (DT) MRI can quantify normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis patients. We investigated whether conventional and DT-MRI-derived measures can predict the long-term clinical evolution of PP multiple sclerosis. In 54 PP multiple sclerosis patients, conventional and DT-MRI scans of the brain and T1-weighted scans of the cervical cord were acquired at baseline and after a median follow-up of 15 months. Another clinical evaluation was performed, 56 months after baseline, in 52 patients. Measures of lesion load, brain and cord atrophy were obtained. Histograms of the mean diffusivity (MD) and fractional anisotropy (FA) values from the NAWM and GM were analysed. At follow-up, 35 patients (65%) experienced a confirmed disability progression. Baseline expanded disability status scale score and average GM MD were independent predictors of subsequent clinical deterioration in a multivariable model (Nagelkerke R2: 0.44; discriminating ability: 81%). A lower level of disability and a more severe GM damage identify PP multiple sclerosis patients with an increased risk of disease progression over the subsequent 5 years. These data may be relevant to select patients for future exploratory phase II trials.

IC-P-118: Vascular risks and MRI measures of white matter hyperintensities and brain atrophy in the prediction of cognitive decline

IC-P-118: Vascular risks and MRI measures of white matter hyperintensities and brain atrophy in the prediction of cognitive decline

P2-357: Vascular risks and MRI measures of white matter hyperintensities and brain atrophy in the prediction of cognitive decline

P2-357: Vascular risks and MRI measures of white matter hyperintensities and brain atrophy in the prediction of cognitive decline

Brain atrophy after immunoablation and stem cell transplantation in multiple sclerosis

The authors measured brain atrophy in nine patients undergoing immunoablation and autologous hematopoietic stem cell transplantation for multiple sclerosis. From baseline to 1 month after treatment, atrophy was 10 times faster than before treatment. A patient with non-CNS lymphoma showed comparable acute brain atrophy after analogous therapy. These observations suggest that brain atrophy after immunoablation may not be due entirely to the resolution of edema but may be related to chemotoxicity.

Data From the VITA Study Do Not Support the Concept of Vascular Depression

Cerebrovascular lesions that are apparent in magnetic resonance scans and regioselective atrophy of the brain have been proposed as a causative or exacerbating factor in depression with late-life onset. The objective of this study was to investigate whether deep white matter or periventricular hyperintensities, small ischemic lesions, and brain atrophy contribute to late-onset depression in the nondemented elderly. Based on a group of 606 individuals of identical age (75.8 years, standard deviation: 0.45 years) residing in two districts of Vienna, the authors built a case-control cohort (ratio: 1:4) consisting of 51 individuals with late-onset major or minor depression matched with 204 subjects of identical gender and education status without depression, resulting in two groups that were homogenous with respect to age, place of residence, gender, and education. Scores for focal brain lesions, mediotemporal lobe atrophy, and ventricular enlargement as well as risk factors for vascular disease were compared with cognition and depression status. Depressed individuals had significantly lower scores than nondepressed subjects in all measures of cognitive and executive function. No significant relation was found between a diagnosis of depression and any type of discrete brain lesions, but measures of brain atrophy (Cella Media indices, mediotemporal atrophy) showed a clear statistical relation to depression. No relationship was found between depression and lipid parameters. The authors found no indication that white matter hyperintensities or minor ischemic lesions played a role in our depressed cohort, casting doubt on the vascular hypothesis of late-onset depression.

Magnetic resonance imaging measures of brain atrophy in multiple sclerosis

Magnetic resonance imaging (MRI) has been widely used to diagnose and monitor multiple sclerosis (MS). Although MRI-visible lesions are a key feature of MS, they are thought to correlate poorly with clinical progression. Neurodegeneration is increasingly being recognized as an important factor in the pathogenesis of MS, and MRI measures of brain atrophy have been suggested as surrogate markers of neuroaxonal loss and disease progression. This pathology may be more relevant to the progression of disability than focal inflammation. A number of MRI-based methods have been developed for the measurement of global and regional brain atrophy. Natural-history studies of MS and clinically isolated syndromes suggestive of MS have observed atrophy in these subjects above that seen in controls, over periods ranging from three months to years. Brain atrophy has also been incorporated as an outcome measure in therapeutic trials of disease-modifying treatments. This paper considers neuroaxonal loss and the pathological basis of brain atrophy, methods developed to quantify brain atrophy, the findings of natural-history and therapeutic studies, the relationship of brain atrophy to disability and cognition, and the future research directions and clinical applications of brain atrophy measurements.

Longitudinal MRI in progressive supranuclear palsy and multiple system atrophy: rates and regions of atrophy

The rate of brain atrophy and its relationship to clinical disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not clear. Twenty-four patients with PSP, 11 with MSA-P (Parkinsonian variant), 12 with Parkinson's disease, and 18 healthy control subjects were recruited for serial MRI scans, clinical assessments and formal neuropsychological evaluations in order to measure brain atrophy during life and its association with disease progression in PSP and MSA-P. Serial scans were registered and rates of whole brain atrophy calculated from the brain-boundary shift integral. Regional rates of atrophy were calculated in the brainstem (midbrain and pons), the cerebellum, the lateral and third ventricles as well as frontal and posterior inferior brain regions, by locally registering to a region of interest in order to derive a local boundary shift integral (BSI). 82% of recruited subjects completed serial MRI scans (17 PSP, 9 MSA-P, 9 Parkinson's disease patients and 18 healthy controls). Mean (SD) annualized rates of whole-brain atrophy were greatest in PSP: 1.2% (1.0%), three times that in controls. Mean (SD) midbrain atrophy rates in PSP, 2.2% (1.5%), were seven times greater than in healthy controls. In MSA-P, atrophy rates were greatest in the pons: 4.5% (3.2%), over 20 times that in controls and three times the rate of pontine atrophy in PSP. Atrophy rates in Parkinson's disease were not significantly different from control rates of atrophy. Variability in the atrophy rates was lower when calculated using the BSI rather than manual measurements. Worsening motor deficit was associated with midbrain atrophy in PSP, and ponto-cerebellar atrophy in MSA-P. Worsening executive dysfunction was associated with increased rates of frontal atrophy in PSP. Cerebellar atrophy rates were better discriminators of MSA-P than cross-sectional volumes. We confirm that serial MRI can be applied to measure whole brain and regional atrophy rates in PSP and MSA-P. Regional rather than whole-brain atrophy rates better discriminate PSP and MSA-P from healthy controls. Clinico-radiological associations suggest these regional atrophy rates have potential as markers of disease progression in trials of novel therapies.

Correlating brain atrophy with cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiologic findings

Results Neuropsychological impairment is a common feature of multiple sclerosis. Affected patients often have deficits in information-processing speed and memory and exhibit psychopathological states such as depression. Cognitive disorders are observed in 40 to 65% of the cases at any period of the disease. It is a major contributing factor to unemployment, accidents, impairment of daily functioning, and loss of social activity in those affected by MS. Structural brain imaging studies show a positive correlation between the extent of brain atrophy and cognitive dysfunction. However, measures of tissue atrophy including whole-brain and central atrophy are especially well correlated with and predictive of cognitive impairment. The degree and pattern of cognitive dysfunction is highly correlated with the amount and location of white-matter disease within the cerebral hemispheres. Discussion Recent studies have shown that conventional measures of brain atrophy explain more variance in neuropsychological dysfunction than do measures of lesion burden. In particular, neuropsychological outcomes correspond highly with linear measures of sub cortical atrophy such as ventricle enlargement. Continuing research focuses on the possible relationship between measures of regional brain atrophy and cognitive and emotional impairment. from International Society on Brain and Behaviour: 2nd International Congress on Brain and Behaviour Thessaloniki, Greece. 17–20 November 2005

Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: Evidence that axonal loss is a substrate of MRI-detected atrophy

Magnetic resonance imaging (MRI) measures of brain atrophy are often considered to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited. Optic neuritis is a common manifestation of MS and results in optic nerve atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of detecting axonal loss following optic neuritis. We hypothesise that if the optic nerve atrophy that develops following optic neuritis is contributed to by axonal loss, it will correlate with thinning of the RNFL. Twenty-five patients were studied at least 1 year after a single unilateral attack of optic neuritis without recurrence, with a selection bias towards incomplete recovery. They had MR quantification of optic nerve cross-sectional area and optic nerve lesion length, as well as optical coherence tomography (OCT) measurement of mean RNFL thickness and macular volume, quantitative visual testing, and visual evoked potentials (VEPs). Fifteen controls were also studied. Significant optic nerve atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls. The optic nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual acuity, visual field mean deviation, and whole field VEP amplitude but not latency. These findings suggest that axonal loss contributes to optic nerve atrophy following a single attack of optic neuritis. By inference, axonal loss due to other post-inflammatory brain lesions is likely to contribute to the global MRI measure of brain atrophy in multiple sclerosis.

Hormone replacement therapy, brain volumes and white matter in postmenopausal women aged 60–64 years

Research on the structural and functional effects of hormone replacement therapy on the brain has produced inconsistent results. This paper reports on cross-sectional associations between hormone replacement therapy use and volumes of brain structures measured using magnetic resonance imaging in 213 postmenopausal women aged 60-64 years recruited from a large population study. Of these, 64 were current hormone replacement therapy users, 69 previous users and 80 had never used hormone replacement therapy. No differences were observed between groups in total grey matter, white matter, hippocampal or amygdalar volumes, severity or volume of white matter hyperintensities, or in different measures of brain atrophy. While acknowledging the limitations of a cross-sectional study, the results argue against hormone replacement therapy being protective against brain changes associated with ageing in women in their early 60s.

Common MRI acquisition non-idealities significantly impact the output of the boundary shift integral method of measuring brain atrophy on serial MRI

Measuring rates of brain atrophy from serial magnetic resonance imaging (MRI) studies is an attractive way to assess disease progression in neurodegenerative disorders, particularly Alzheimer's disease (AD). A widely recognized approach is the boundary shift integral (BSI). The objective of this study was to evaluate how several common scan non-idealities affect the output of the BSI algorithm. We created three types of image non-idealities between the image volumes in a serial pair used to measure between-scan change: inconsistent image contrast between serial scans, head motion, and poor signal-to-noise (SNR). In theory the BSI volume difference measured between each pair of images should be zero and any deviation from zero should represent corruption of the BSI measurement by some non-ideality intentionally introduced into the second scan in the pair. Two different BSI measures were evaluated, whole brain and ventricle. As the severity of motion, noise, and non-congruent image contrast increased in the second scan, the calculated BSI values deviated progressively more from the expected value of zero. This study illustrates the magnitude of the error in measures of change in brain and ventricle volume across serial MRI scans that can result from commonly encountered deviations from ideal image quality. The magnitudes of some of the measurement errors seen in this study exceed the disease effect in AD shown in various publications, which range from 1% to 2.78% per year for whole brain atrophy and 5.4% to 13.8% per year for ventricle expansion ( Table 1). For example, measurement error may exceed 100% if image contrast properties dramatically differ between the two scans in a measurement pair. Methods to maximize consistency of image quality over time are an essential component of any quantitative serial MRI study.

Measurement of Brain and Spinal Cord Atrophy by Magnetic Resonance Imaging as a Tool to Monitor Multiple Sclerosis

Evaluation of brain and spinal cord atrophy by magnetic resonance imaging (MRI) has become an increasingly important component of understanding the multiple sclerosis (MS) disease process. These destructive aspects of the disease develop early in the disease course. A growing body of data links brain and spinal cord atrophy to clinical impairment more closely than can be linked with conventional measures of overt lesions. Thus, irreversible tissue damage may be a key factor leading to disease progression. In this review, the authors present the proposed mechanisms leading to central nervous system (CNS) atrophy. They describe the available MRI-based techniques to measure regional and global atrophy of the brain and spinal cord. They compare the rate of atrophy among MS phenotypes and summarize the emerging data linking atrophy to neurological and neuropsychological impairment. Finally, they discuss the effect of disease-modifying immunotherapies on the rate of CNS atrophy in patients with MS. Future research to clarify the etiology and pathophysiology of brain and spinal cord atrophy should provide new targets for therapeutic development.

Commentary on “Diagnosis of Alzheimer's disease: Two decades of progress.” Central role of technology in the treatment and prevention of Alzheimer's disease

Commentary on “Diagnosis of Alzheimer's disease: Two decades of progress.” Central role of technology in the treatment and prevention of Alzheimer's disease

In vivo MRI and histological evaluation of brain atrophy in APP/PS1 transgenic mice

Regional cerebral atrophy was evaluated in APP/PS1 mice harboring mutated transgenes linked to familial Alzheimer's disease, using complementary methods. In vivo high resolution MRI was selected for measurements of brain atrophy and associated cerebrospinal fluid dilation; histological analysis was performed to reveal localized atrophies and to evaluate amyloid burden. Young APP/PS1 mice examined at a pre-amyloid stage (10 weeks) showed disruption in development (reduced intracranial and brain volumes). Comparison of young and old (24 months) mice, indicated that both APP/PS1 and control brains endure growth during adulthood. Aged APP/PS1 animals showed a moderate although significant global brain atrophy and a dilation of CSF space in posterior brain regions. The locus of this atrophy was identified in the midbrain area and not, as expected, at isocortical/hippocampal levels. Atrophy was also detected in fiber tracts. The severity of brain atrophy in old APP/PS1 mice was not correlated with the extent of cerebral amyloidosis. The relevance of current transgenic mouse models for the study of brain atrophy related to Alzheimer's disease is discussed.

Morphometric Analysis of Gray Matter Volume in Demented Older Adults: Exploratory Analysis of the Cardiovascular Health Study Brain MRI Database

We tested the feasibility of a fully automated brain MRI voxel count technique – automated labeling pathway (ALP) – in a sample of 15 demented and 13 cognitively normal women (age 75–85 years) participating to the Cardiovascular Health Study (CHS). We hypothesized that ALP would replicate well-established findings of the anatomical correlates of dementia. In particular, we hypothesized that ALP volumetric measures would: (1) significantly differ between cognitively normal and demented women in those brain areas that are established markers for diagnosis of dementia (temporal and medial temporal lobes, hippocampus, amygdala and parahippocampus) but not in other brain areas (e.g., occipital lobe, visual cortex, motor cortex) and (2) correlate with visual ratings of brain disease which have been previously collected as part of the CHS. ALP required minimal operator intervention (input of brain images and verification of misalignments) and employed computer time of about 1 h per brain. ALP detected significant focal volumetric differences in the limbic system (p values between groups for hippocampus and parahippocampus: 0.002 and 0.005, respectively), temporal lobe (p < 0.0001) and caudate (p = 0.009), but not in other brain areas (e.g. occipital lobe, visual or motor cortex). Furthermore, ALP measures of medial temporal lobe atrophy strongly correlated with CHS visual ratings of ventricular enlargement (r² = 0.6, p = 0.002 for medial temporal lobe). In conclusion, ALP-detected focal brain atrophy was strongly associated with dementia. Because of its fully automated design, ALP technique is an ideal candidate to assess whether volumetric measures of specific areas can discriminate dementia better than currently available measures of global brain atrophy in large epidemiological studies.

Recent advances in the neuroimaging of multiple sclerosis

Neuroimaging studies continue to provide important insights into the central nervous system disease pathology of multiple sclerosis (MS). Although conventional magnetic resonance imaging remains the mainstay of diagnosis and laboratory assessment of therapeutic response in MS, quantitative techniques continue to extend our understanding of both macroscopic and microscopic disease processes. Over the past year, many published studies have investigated measures of brain atrophy, gray matter involvement, vascular properties, and myelin and neuronal loss and have examined their relationship to clinical disease expression, genotype, and therapy. An important trend continuing over the past year is the development of targeted agents to improve the pathologic specificity of imaging measures. Specific disease measures such as endothelial activation, microglial activation, and cell trafficking are accessible to neuroimaging and offer significant promise for improved characterization of central nervous system involvement in MS.

Interferon Beta Promotes Nerve Growth Factor Secretion Early in the Course of Multiple Sclerosis

Interferon beta therapy has been shown to reduce the rate of clinical relapse and the frequency of magnetic resonance imaging-defined T2- weighted lesions in patients with multiple sclerosis (MS). When given early, interferon beta also reduces the rate of development of brain atrophy and improves axonal integrity. Nerve growth factor (NGF) can retard the severity and course of experimental allergic encephalomyelitis. To determine whether interferon beta effects on patients with MS could be related to modulation of neurotrophin production within the central nervous system. We studied neurotrophin production by human glial and brain endothelial cells in response to coculture with MS patient-derived lymphocytes, and correlated levels of NGF secretion with clinical and magnetic resonance imaging-defined markers of disease. We demonstrate that production of NGF by human brain microvascular endothelial cells is triggered by interaction with T lymphocytes derived from MS patients. No such response was observed using human adult microglia or human fetal astrocytes. Nerve growth factor production by endothelial cells was potentiated by pretreating lymphocytes with interferon beta in vitro, and by using lymphocytes derived from MS patients treated with interferon beta in vivo. By using this assay, we show that levels of NGF induced by lymphocytes from MS patients inversely correlate with magnetic resonance imaging measures of brain atrophy and axonal injury. These findings suggest that interferon beta-mediated production of NGF at the level of the blood-brain barrier, whether acting as an immunomodulator or directly on neural cells, is another potential mechanism contributing to the magnetic resonance imaging-defined effect of interferon beta on brain atrophy when given early in the course of MS.