Boundary Shift Integral Research Articles

Brain atrophy rates in Parkinson's disease with and without dementia using serial magnetic resonance imaging

Increased rates of brain atrophy are seen in Alzheimer's disease, but whether rates are similarly increased in other dementias such as Parkinson's disease dementia (PDD) has not been well examined. We determined the rates of brain atrophy using serial magnetic resonance imaging (MRI) in PDD and compared this finding to rates seen in cognitively intact Parkinson's disease (PD) patients and age-matched control subjects. Thirty-one patients (PD = 18, PDD = 13) and 24 age-matched controls underwent serial volumetric 1.5 T MRI scans, approximately 1 year apart. Baseline and repeat scans were registered and quantification of the brain boundary shift integral was used to determine whole-brain atrophy rates. Rates of brain atrophy were significantly increased in PDD (1.12 +/- 0.98%/year) compared to PD (0.31 +/- 0.69%/year; P = 0.018) and control subjects (0.34 +/- 0.76%/year; P = 0.015). There were no differences in atrophy rates between controls and PD (P = 0.79). No correlations between increased atrophy rates and age or dementia severity (Mini-Mental State Examination score) were observed. Serial MRI may be a useful tool for monitoring disease progression in PDD and further studies should investigate its utility for early diagnosis.

Measuring atrophy in Alzheimer disease

Global brain atrophy rate calculated from serial MRI scans may be a surrogate marker of Alzheimer disease (AD) progression. Few studies have assessed atrophy in AD over short intervals. Thirty-eight patients with AD and 19 control subjects had MRI scans at baseline, 6 months, and 1 year. Ventricular change and whole-brain volume loss were calculated directly from the regions manually outlined on registered scans and using the automated (boundary shift integral [BSI]) technique. Sample sizes required to power placebo-controlled treatment trials over 6 months and 1 year were calculated using these techniques. Increased rates of ventricular expansion and whole-brain atrophy were seen in AD compared with control subjects at both 6 and 12 months using manual and automated techniques (p < 0.001). Using the BSI consistently reduced measurement variability especially for whole-brain change. In clinical trials, at 6 months, significantly fewer patients would be required using the ventricular BSI (VBSI) compared with the brain BSI (BBSI) (e.g., 165 vs 410 per arm to provide 90% power to detect a 20% reduction in rate of change). At 1 year, sample size estimates were smaller than at 6 months, and the advantage of using VBSI instead of BBSI was less marked. In short-interval studies, using the ventricular boundary shift integral instead of the brain boundary shift integral may allow for disease-modifying effects to be demonstrated using significantly smaller sample sizes. This potential benefit must be balanced against the possibility that ventricular volumes may be more likely to be affected by factors other than neurodegeneration.

Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence

Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage.

Differentiating AD from aging using semiautomated measurement of hippocampal atrophy rates

Manual segmentation of the hippocampus is the gold standard in volumetric hippocampal magnetic resonance imaging (MRI) analysis; however, this is difficult to achieve reproducibly. This study explores whether application of local registration and calculation of the hippocampal boundary shift integral (HBSI) can reduce random variation compared with manual measures. Hippocampi were outlined on the baseline and registered-repeat MRIs of 32 clinically diagnosed Alzheimer's disease (AD) patients and 47 matched controls (37–86 years) with a wide range of scanning intervals (175–1173 days). The scans were globally registered using 9 degrees of freedom and subsequently locally registered using 6 degrees of freedom and HBSI was then calculated automatically. HBSI significantly reduced the mean rate ( P < 0.01) and variation in controls ( P < 0.001) and increased group separation between AD cases and controls. When comparing HBSI atrophy rates with manually derived atrophy rates at 90% sensitivity, specificities were 98% and 81%, respectively. From logistic regression models, a 1% increase in HBSI atrophy rates was associated with an 11-fold (CI 3, 36) increase in the odds of a diagnosis of AD. For manually derived atrophy rates, the equivalent odds ratio was 3 (CI 2,4). We conclude that HBSI-derived atrophy rates reduce operator time and error, and are at least as effective as the manual equivalent as a diagnostic marker and are a potential marker of progression in longitudinal studies and trials.

Measurement of Whole‐Brain Atrophy in Multiple Sclerosis

ABSTRACTBrain atrophy reflects the net result of irreversible and destructive pathological processes in multiple sclerosis (MS). The gross morphological changes can be accurately quantified using standard magnetic resonance imaging (MRI) acquisitions and various image analysis tools. The current methods used to assess whole‐brain atrophy in patients with MS can be classified into 2 groups based on their reliance on segmentation and registration. Segmentation‐based methods employed to measure whole‐brain atrophy in MS include the brain parenchymal fraction, the index of brain atrophy, the whole‐brain ratio, the brain to intracranial capacity ratio, fuzzy connectedness/Udupa's method, 3DVIEWNIX, the Alfano method, and SIENAX. Current registration‐based methods used to measure whole‐brain atrophy in MS include the brain boundary shift integral, SIENA, statistical parametric mapping, template‐driven seg mentation, and voxel‐based morphometry. Most of the methods presented here are sensitive to subtle changes in brain structures and have been successfully applied to MS as measures of whole‐brain atrophy. Yet comparative studies of these methods are limited and are complicated by the lack of a gold standard for image acquisition, a segmentation algorithm, an image analysis method, or a reproducibility measure. Overall, the measure of whole‐brain atrophy from MRI contributes to an appreciation of the dynamics of MS pathology and its relationship to the clinical course of MS. Determination of the relative reproducibility, precision, sensitivity, and validity of these methods will promote the use of whole‐brain atrophy measures as components of comprehensive MRI‐based outcome assessment in MS clinical trials.

Measurement of whole-brain atrophy in multiple sclerosis.

Brain atrophy reflects the net result of irreversible and destructive pathological processes in multiple sclerosis (MS). The gross morphological changes can be accurately quantified using standard magnetic resonance imaging (MRI) acquisitions and various image analysis tools. The current methods used to assess whole-brain atrophy in patients with MS can be classified into 2 groups based on their reliance on segmentation and registration. Segmentation-based methods employed to measure whole-brain atrophy in MS include the brain parenchymal fraction, the index of brain atrophy, the whole-brain ratio, the brain to intracranial capacity ratio, fuzzy connectedness/Udupa's method, 3DVIEWNIX, the Alfano method, and SIENAX. Current registration-based methods used to measure whole-brain atrophy in MS include the brain boundary shift integral, SIENA, statistical parametric mapping, template-driven seg mentation, and voxel-based morphometry. Most of the methods presented here are sensitive to subtle changes in brain structures and have been successfully applied to MS as measures of whole-brain atrophy. Yet comparative studies of these methods are limited and are complicated by the lack of a gold standard for image acquisition, a segmentation algorithm, an image analysis method, or a reproducibility measure. Overall, the measure of whole-brain atrophy from MRI contributes to an appreciation of the dynamics of MS pathology and its relationship to the clinical course of MS. Determination of the relative reproducibility, precision, sensitivity, and validity of these methods will promote the use of whole-brain atrophy measures as components of comprehensive MRI-based outcome assessment in MS clinical trials.

Mannitol bolus preferentially shrinks non-infarcted brain in patients with ischemic stroke.

Changes in brain tissue volume in six patients who had acute complete middle cerebral artery (MCA) infarctions and CT evidence of midline shift were measured using the brain boundary shift integral (BBSI) on sequential T1-weighted MR images acquired before and after a 1.5-g/kg bolus infusion of mannitol. At 50 to 55 minutes after the baseline scan, total brain volume decreased by 8.1 +/- 2.8 mL (0.6%, p < 0.005). Brain in the noninfarcted hemisphere shrank more (0.8 +/- 0.4%) than in the infarcted hemisphere (0.0 +/- 0.5%, p < 0.05).

Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia.

The authors determined rates of brain atrophy, as assessed by the boundary shift integral on serial MRI, in patients with dementia with Lewy Bodies (DLB, n = 10), AD (n = 9), vascular dementia (VaD, n = 9), and age-matched controls (n = 20). Mean % +/- SD atrophy rates per year were as follows: DLB, 1.4 +/- 1.1; AD, 2.0 +/- 0.9; VaD, 1.9 +/- 1.1; and controls, 0.5 +/- 0.7. Dementia subjects had higher rates than controls (p < 0.001), but there were no significant differences between the three dementia groups. The authors found accelerating atrophy with increasing severity of cognitive impairment, further emphasizing the need for early diagnosis and intervention in dementia.

Automatic measurement of changes in brain volume on consecutive 3D MR images by segmentation propagation

This article presents a technique to automatically measure changes in the volume of a structure of interest in successive 3D magnetic resonance (MR) images and its application in the study of the brain and lateral cerebral ventricles. The only manual step is a segmentation of the structure of interest in the first image. The analysis comprises, first, precise rigid co-registration of the time series of images; second, computation of residual deformations between pairs of images; third, automatic quantification of the volume change, obtained by propagation of the segmentation of the structure of interest through the series of MR images. This approach has been applied to monitor changes in the volume of the brain and lateral cerebral ventricles in a healthy subject and a patient with primary progressive aphasia (PPA). Results are consistent with those obtained by application of the boundary shift integral (BSI) and by stereology in the same subjects.

Brain atrophy progression measured from registered serial MRI: validation and application to Alzheimer's disease.

In this paper, we validate the brain boundary shift integral (BBSI) as a measure of brain atrophy and demonstrate its application in Alzheimer's disease (AD). Nineteen normal subjects and nine patients with AD underwent serial three-dimensional MRI (6- to 30-month scan intervals). Repeat studies were registered to the baseline studies. The accuracy of the BBSI was assessed by comparison with simulated atrophy and with segmentation; it was also tested for reproducibility, linearity, and its ability to discriminate patients with AD from healthy controls. The BBSI correlated closely with simulated volumes of atrophy (r = 1.000). The mean absolute difference between repeat measures was 1.51 ml or .13% of mean brain volume. Rates of atrophy from all 18 AD scan pairs were widely separated from those of all 31 control pairs. In matched subgroups, the mean (SD) annual rate of brain atrophy in nine controls was .24% (.32%), compared with 2.78% (.92%) in nine patients with AD. We conclude that the BBSI is a linear and highly reproducible measure of atrophy with potential uses in the early diagnosis and measurement of progression in Alzheimer's disease.

The boundary shift integral: an accurate and robust measure of cerebral volume changes from registered repeat MRI

We propose the boundary shift integral (BSI) as a measure of cerebral volume changes derived from registered repeat three-dimensional (3-D) magnetic resonance (MR) [3D MR] scans. The BSI determines the total volume through which the boundaries of a given cerebral structure have moved and, hence, the volume change, directly from voxel intensities. We found brain and ventricular BSI's correlated tightly (r = 1.000 and r = 0.999) with simulated volumes of change. Applied to 21 control scan pairs and 11 scan pairs from Alzheimer's disease (AD) patients (mean interval 386 days) the BSI yielded mean brain volume loss of 1.8 cc (controls) and 34.7 cc (AD); the control group was tightly bunched (SD = 3.8 cc) and there was wide group separation, the group means differing by 8.7 control group standard deviations (SD's). A measure based on the same segmentation used by the BSI yielded similar group means, but wide spread in the control group (SD = 13.4 cc) and group overlap, the group means differing by 2.8 control group SD's. The BSI yielded mean ventricular volume losses of 0.4 cc (controls) and 10.1 cc (AD). Good linear correlation (r = 0.997) was obtained between the ventricular BSI and the difference in their segmented volumes. We conclude the BSI is an accurate and robust measure of regional and global cerebral volume changes.