Significant White Matter Hyperintensities Research Articles

Abstract TP35: A 2-Stage Recruitment Design to Reduce MRI Screening Costs for a Theoretical Clinical Trial of WMH Progression

Background: White matter hyperintensities (WMH) are associated with risk of dementia and stroke, so are an important therapeutic target for clinical trials. The cost of broad MRI screening to identify those individuals with significant WMH, however, limits the feasibility of designing clinical trials which target WMH presence and which test treatments that slow progression. Hypothesis: A low-cost retinal or clinical screening measure prior to an MRI screening stage reduces the cost of recruiting persons with significant WMH burden in a hypothetical clinical trial vs an MRI-only screening design. Method: Data were from participants in the Atherosclerosis Risk in Communities-Neurocognitive study with clinical, retinal and WMH measurements ( N = 1311) at ages 53-70 years. Significant WMH burden was defined as a Cardiovascular Health Study score >2. Three low-cost pre-screening measures were assessed: (1) retinal: a score incorporating multiple markers of abnormal retinal vasculature, (2) clinical: a score incorporating hypertension, diabetes, and age, (3) combined retinal-clinical: a score incorporating retinal and clinical factors. Given a prior published target sample for a WMH clinical trial (N= 646), we calculated a theoretical screening sample size based on the proportion of each pre-screening measure in the population multiplied by the proportion of significant WMH burden among those with a prevalent pre-screening feature. Total recruitment cost was calculated using standard retinal ($32.50) and MRI ($650) cost estimates. Results: Compared to the estimated cost of MRI-only screening (>$4.24M, requiring MRI screening 6,526 participants), pre-screening for a high clinical score reduced total cost to $2.47M, but increased the initial screening group to 52,778 participants, of whom 3,801 would be screened by MRI). A high retinal-clinical score cutoff reduced costs to $2.9M while only requiring 13,572 screened participants (of these only 3,801 would require MRI). Conclusion: A 2-stage recruitment design with a low-cost pre-screening retinal and clinical measure is a promising approach, resulting in a reduction of theoretical recruitment costs for recruiting persons with significant WMH burden compared to an MRI-only design.

Associations between adiposity and white matter hyperintensities: Cross-sectional and longitudinal analyses of 34,653 participants.

White matter hyperintensities (WMH) increase the risk of stroke and cognitive impairment. This study aims to determine the cross-sectional and longitudinal associations between adiposity and WMH. Participants were enrolled from the UK Biobank cohort. Associations of concurrent, past, and changes in overall and central adiposity with WMH were investigated by linear and nonlinear regression models. The association of longitudinal adiposity and WMH volume changes was determined by a linear mixed model. Mediation analysis investigated the potential mediating effect of blood pressure. In 34,653 participants with available adiposity measures and imaging data, the concurrent obese group had a 25.3% (β [95% CI] = 0.253 [0.222-0.284]) higher WMH volume than the ideal weight group. Increment in all adiposity measures was associated with a higher WMH volume. Among them, waist circumference demonstrated the strongest effect (β [95% CI] = 0.113 [0.101-0.125]). Past adiposity also demonstrated similar effects. Among the subset of 2664 participants with available WMH follow-up data, adiposity measures were predictive of WMH change. Regarding changes of adiposity, compared with ideal weight stable group, those who turned from ideal weight to overweight/obese had a 8.1% higher WMH volume (β [95% CI] = 0.081 [0.039-0.123]), while participants who turned from overweight/obese to ideal weight demonstrated no significant WMH volume change. Blood pressure partly meditates the associations between adiposity and WMH. Both concurrent and past adiposity were associated with a higher WMH volume. The detrimental effects of adiposity on WMH occurred throughout midlife and in the elderly and may still exist after changes in obesity status.

Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease

IntroductionThe standard of care for patients with infantile-onset Pompe disease (IOPD) is enzyme replacement therapy (ERT), which does not cross the blood brain barrier. While neuromuscular manifestations of IOPD are well-described, central nervous system (CNS) manifestations of this disorder are far less characterized. Here we describe severe CNS-related neurological manifestations including seizures and encephalopathy in six individuals with IOPD. MethodWe identified six children with IOPD who developed CNS manifestations such as seizures and/or encephalopathy. We studied their brain magnetic resonance imaging scans (MRIs) and graded the severity of white matter hyperintensities (WMHI) using the Fazekas scale scoring system as previously published. Longitudinal cognitive measures were available from 4/6 children. ResultsAll six IOPD patients (4 males/2 females) had been treated with ERT for 12–15 years. Seizures and/or encephalopathy were noted at a median age at onset of 11.9 years (range 9–15 years). All were noted to have extensive WMHI in the brain MRIs and very high Fazekas scores which preceded the onset of neurological symptoms. Longitudinal IQ scores from four of these children suggested developmental plateauing. DiscussionAmong a subset of IOPD patients on long-term ERT, CNS manifestations including hyperreflexia, encephalopathy and seizures may become prominent, and there is likely an association between these symptoms and significant WMHI on MRI. Further study is needed to identify risk factors for CNS deterioration among children with IOPD and develop interventions to prevent neurological decline.

Abstract WP12: Evolution Of Regional Flair White Matter Hyperintensities After Ischemic Stroke: A Voxel-wise Approach

Background: White matter (WM) degeneration after ischemic stroke may herald post-stroke cognitive decline. FLAIR WM hyperintensity (WMH) reflects tissue injury and accumulates around the infarct and in remote regions. But WMH volumetry is insensitive to regional progression. We compared WMH volumetry to a voxel-wise (VW) approach for detecting FLAIR WMH change longitudinally after stroke. Methods: Ischemic stroke patients enrolled in an observational cohort study underwent serial MRI acutely, at 1 month and every 3 months thereafter. Patients with 6 to 12-month follow-up were included. WMH lesion volumes were automatically segmented on serial FLAIR MRI. In the hemisphere contralateral to the infarct after 30 days, we compared longitudinal change in WMH volume to a VW regression of FLAIR signal change over time. Serial FLAIR images were nonlinearly aligned using a T1 intermediate. FLAIR intensities were normalized, corrected for local expansion/contraction, and smoothed. Within voxels identified as lesion at any timepoint, significant WMH change was determined relative to the normal appearing WM and converted to percent of total intracranial volume (TICV). Results: 22 stroke patients (mean age 73, NIHSS 4, infarct volume 10.3cc) had on average 3 follow-ups over 343 days. In the non-stroke hemisphere, volumetry revealed lesion growth in 12 participants (55%) while VW analysis revealed FLAIR signal increase in 15 (68%). For volumetry, mean lesion increase was 0.01 ± 0.20% of TICV per year while VW FLAIR intensity increased in mean 0.11 ± 0.23% of total intracranial voxels. Volumetric growth was associated with the volume of VW signal increase (Std Beta = 0.51, p = 0.02). In the stroke hemisphere, WMH expansion of peri-infarct tissue, consistent with Wallerian degeneration, was present in 10 participants (45%). WMH regression, consistent with atrophy or infarct cavitation, was present in 14 participants (64%). Stroke hemisphere WMH expansion was associated with higher NIHSS (Std B = 0.58, p = 0.009) while regression was associated with larger infarct volumes (Std B = 0.80, p < 0.001). Conclusions: In early chronic stroke, VW longitudinal WMH analysis detects progressive WM degradation with regional variation and may be more sensitive than gross volumetry.

Abstract TP18: Progressive White Matter Degeneration After Ischemic Stroke

Background: White matter degeneration after ischemic stroke may herald post-stroke cognitive decline. FLAIR white matter hyperintensity (WMH) reflects tissue injury and accumulates around the infarct and in remote regions. But WMH volumetry is insensitive to regional or short-term progression. We compared WMH volumetry to a voxel-wise approach for detecting FLAIR WMH change longitudinally after stroke. Methods: Ischemic stroke patients enrolled in an observational cohort study underwent serial MRI acutely, at 1 month and every 3 months thereafter. Patients with 6 to 12-month follow-ups were included. WMH lesion volumes were automatically segmented on serial FLAIR MRI. In the hemisphere contralateral to the infarct from 30 days onward, we compared longitudinal change in WMH volume to a voxel-wise regression of FLAIR signal change over time. We used T1 images as an intermediate to nonlinearly align serial FLAIR images to individual templates. FLAIR intensities were normalized, corrected for local expansion/contraction, and smoothed. Within voxels identified as lesion at any timepoint, significant WMH change was determined relative to the normal appearing white matter and converted to a percentage of the intracranial volume. Results: 22 ischemic stroke patients (mean age 73 ± 8 years, NIHSS 4 ± 4, infarct volume 10.3 ± 23 cc) had on average 3 follow-ups over 343 days. In the non-stroke hemisphere, volumetry revealed lesion growth in 12. Mean lesion increase was 0.01 ± 0.20% per year. In voxel-wise analysis 15 patients had increasing FLAIR signal. Intensity increased in mean 0.11 ± 0.23% of intracranial voxels. Lesion growth was associated with the volume of voxel-wise signal increase (Beta = 0.51, p = 0.018). In the stroke hemisphere, progressive WMH expansion of peri-infarct tissue, consistent with Wallerian degeneration, was present in 10 patients. WMH regression, consistent with atrophy and infarct cavitation, was present in 14. Stroke hemisphere WMH expansion was associated with initial NIHSS (B = 0.58, p = 0.0086) while regression was associated with acute infarct volume (B = 0.80, p < 0.001). Conclusions: Voxel-wise longitudinal WMH analysis detects progressive white matter degradation and regional variation continuing 30 days after stroke.

Hypertension accentuates reductions in CSF Aβ42 in elderly depressives

AbstractBackgroundHypertension (HTN) is a well‐established risk factor for Alzheimer’s disease (AD). Observations from animal and human PET studies indicate that HTN may be mechanistically linked to AD by increasing brain Aβ deposition which may represent the first pathogenetic event in the onset of AD dementia. For example, a diagnosis of HTN, has been associated with increased brain Aβ on PET imaging in humans. HTN is also common in late‐life depression (LLMD), a disorder which is also associated with increased risk for AD and altered Aβ dynamics consistent with increased brain Aβ burden including reductions in CSF Aβ42. Our group first reported a reduction in CSF Aβ42 which was unrelated to APOE status. However, the neurobiological mechanisms for the association between LLMD and altered Aβ metabolism are not fully understood and might involve co‐morbid vascular factors such as HTN. These considerations prompted us to examine the relationship between LLMD, HTN and CSF AD biomarkers in a cohort of non‐demented elderly.MethodsCSF was obtained from 47 individuals (28‐LLMD and 19 ‐controls) 60 years or older with MMSE>28 and without significant white matter hyperintensities. A general linear model was used to compare the effect of hypertension status (HTN; Hypertensive or Not Hypertensive) and diagnosis (Dx; LLMD or control) on baseline AD biomarkers (Aβ42, Aβ40).ResultsWe found that controls without HTN (mean=361 pg/ml) had sig. higher CSF Aβ42 than LLMD without HTN (mean=220 pg/ml; Tukey adj. p‐value = 0.18) and LLMD with HTN (mean=202 pg/ml; Tukey adj. p‐value = .031) given the significant interaction of HTN and Dx (p=0.05). There was also a main effect of HTN on Aβ40 (p=.025).ConclusionsThese preliminary results suggest that hypertension and LLMD are independently associated with reductions in CSF Aβ42 and that co‐morbid HTN may accentuate its reduction in LLMD. Thus, more effective treatment of depression and HTN may attenuate the increased risk for AD associated with these disorders.

Randomized Trial of Marine n-3 Polyunsaturated Fatty Acids for the Prevention of Cerebral Small Vessel Disease and Inflammation in Aging (PUFA Trial): Rationale, Design and Baseline Results.

Vascular risk factors for age-related cognitive decline are significant, and their management may ultimately prove the most successful strategy for reducing risk and sustaining cognitive health. This randomized, double-blinded, placebo-controlled trial with parallel group allocation to either marine n-3 polyunsaturated fatty acids (n-3 PUFA) or soybean oil placebo assesses the effects on the total volume of accumulation in cerebral white matter hyperintensities (WMH), a potentially modifiable neurovascular component of age-related cognitive decline. Total WMH accumulation over 3 years is the primary endpoint. The safety and efficacy of n-3 PUFA is evaluated in older adults with significant WMH and suboptimum plasma n-3 PUFA as inclusion criteria. One hundred and two non-demented older adults were enrolled with a mean age of 81.1 (±4.4) years, WMH of 19.4 (±16.1) cm3, and a plasma n-3 PUFA of 86.64 (±29.21) µg/mL. 61% were female, 28% were apolipoprotein E epsilon 4 carriers, and the mean mini-mental state exam (MMSE) was 27.9 (±1.7). This trial provides an initial evaluation of n-3 PUFA effects on WMH, a reproducible and valid risk biomarker for cognitive decline, as well as on inflammatory biomarkers thought to play a role in WMH accumulation. We present the baseline results and operational experience of enriching a study population on advanced age, blood n-3 PUFA, and magnetic resonance imaging (MRI) derived WMH with biomarker outcomes (WMH, inflammation markers) in a dementia prevention paradigm.

Risk Factors for and Clinical Relevance of Incident and Progression of Cerebral Small Vessel Disease Markers in an Asian Memory Clinic Population.

Cerebral small vessel disease (SVD) is one of the major contributors to cognitive impairment and dementia. However, data on the incidence and progression of SVD in an Asian population are lacking. The present study aims to investigate the incidence, progression, associated risk factors, and clinical relevance of SVD in a memory clinic setting. A prospective case-control study, where 346 patients underwent repeated brain MRI with a mean interval of 24.5 months, accessing white matter hyperintensities (WMH), lacunes and cerebral microbleeds (CMBs). Severity of cognitive impairment was assessed using Clinical Dementia Rating scale and change in clinical diagnosis. Data on demographics, vascular risk factors, and clinical history were collected at baseline. The prevalence of significant WMH (Fazekas ≥2) was 56.6% at baseline which progressed to 59.0% at follow-up. Overall prevalence of CMBs increased from 42.2% to 47.4% (9% new cases) and lacunes increased from 31.8% to 33.2% (2.1% new cases). Hypertension was associated with WMH progression (OR: 1.78, 95% CI: 1.01, 2.99) and increasing age was associated with incident CMBs (OR: 1.04, 95% CI: 1.01, 1.08). Moreover, the use of lipid-lowering medications decreased the incidence of lacunes (OR: 0.15, 95% CI: 0.04, 0.61). The major risk factor for incident SVD was baseline SVD lesion load. WMH progression was associated with increased severity of cognitive impairment (OR: 1.95, 95% CI: 1.16, 3.23). Vascular risk factors and baseline severity of SVD lesion load were associated with progression of SVD. Furthermore, WMH progression was linked with increased severity of cognitive impairment. Future studies should be aimed to slow cognitive deterioration by preventing SVD related brain damage by targeting vascular risk factors.

Cognitive heterogeneity among community-dwelling older adults with cerebral small vessel disease

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities. Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55 and 80 years completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant white matter hyperintensity burden (∼10 cm3). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective cognitive complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed 2 CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioral heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective cognitive complaints that may point to subtle effects of vascular pathology not evident on standardized cognitive scores.

Retinal image analytics detects white matter hyperintensities in healthy adults.

ObjectiveWe investigated whether an automatic retinal image analysis (ARIA) incorporating machine learning approach can identify asymptomatic older adults harboring high burden of white matter hyperintensities (WMH) using MRI as gold standard.MethodsIn this cross‐sectional study, we evaluated 180 community‐dwelling, stroke‐, and dementia‐free healthy subjects and performed ARIA by acquiring a nonmydriatic retinal fundus image. The primary outcome was the diagnostic performance of ARIA in detecting significant WMH on MRI brain, defined as age‐related white matter changes (ARWMC) grade ≥2. We analyzed both clinical variables and retinal characteristics using logistic regression analysis. We developed a machine learning network model with ARIA to estimate WMH and its classification.ResultsAll 180 subjects completed MRI and ARIA. The mean age was 70.3 ± 4.5 years, 70 (39%) were male. Risk factor profiles were: 106 (59%) hypertension, 31 (17%) diabetes, and 47 (26%) hyperlipidemia. Severe WMH (global ARWMC grade ≥2) was found in 56 (31%) subjects. The performance for detecting severe WMH with sensitivity (SN) 0.929 (95% CI from 0.819 to 0.977) and specificity (SP) 0.984 (95% CI from 0.937 to 0.997) was excellent. There was a good correlation between WMH volume (log‐transformed) obtained from MRI versus those estimated from retinal images using ARIA with a correlation coefficient of 0.897 (95% CI from 0.864 to 0.922).InterpretationWe developed a robust algorithm to automatically evaluate retinal fundus image that can identify subjects with high WMH burden. Further community‐based prospective studies should be performed for early screening of population at risk of cerebral small vessel disease.

The Additional Contribution of White Matter Hyperintensity Location to Post-stroke Cognitive Impairment: Insights From a Multiple-Lesion Symptom Mapping Study.

White matter hyperintensities (WMH) are common in acute ischemic stroke patients. Although WMH volume has been reported to influence post-stroke cognition, it is still not clear whether WMH location, independent of acute ischemic lesion (AIL) volume and location, contributes to cognitive impairment after stroke. Here, we proposed a multiple-lesion symptom mapping model that considers both the presence of WMH and AIL to measure the additional contribution of WMH locations to post-stroke cognitive impairment. Seventy-six first-ever stroke patients with AILs in the left hemisphere were examined by Montreal Cognitive Assessment (MoCA) at baseline and 1 year after stroke. The association between the location of AIL and WMH and global cognition was investigated by a multiple-lesion symptom mapping (MLSM) model based on support vector regression (SVR). To explore the relative merits of MLSM over the existing lesion-symptom mapping approaches with only AIL considered (mass-univariate VLSM and SVR-LSM), we measured the contribution of the significant AIL and/or WMH clusters from these models to post-stroke cognitive impairment. In addition, we compared the significant WMH locations identified by the optimal SVR-MLSM model for cognitive impairment at baseline and 1 year post stroke. The identified strategic locations of WMH significantly contributed to the prediction of MoCA at baseline (short-term) and 1 year (long-term) after stroke independent of the strategic locations of AIL. The significant clusters of WMH for short-term and long-term post-stroke cognitive impairment were mainly in the corpus callosum, corona radiata, and posterior thalamic radiation. We noted that in some regions, the AIL clusters that were significant for short-term outcome were no longer significant for long-term outcome, and interestingly more WMH clusters in these regions became significant for long-term outcome compared to short-term outcome. This indicated that there are some regions where local WMH burden has larger impact than AIL burden on the long-term post-stroke cognitive impairment. In consequence, SVR-MLSM was effective in identifying the WMH locations that have additional impact on post-stroke cognition on top of AIL locations. Such a method can also be applied to other lesion-behavior studies where multiple types of lesions may have potential contributions to a specific behavior.

The Preservation of Cognition 1 Year After Carotid Endarterectomy in Patients With Prior Cognitive Decline.

Vascular cognitive decline is critically important in the course of atherosclerosis and stroke. To explore the hypothesis that carotid endarterectomy (CEA) by removing an unstable plaque may slow the course of vascular cognitive decline in both symptomatic and asymptomatic patients. Patients with clinically significant (>60%) carotid stenosis were studied preop and 1 yr post-CEA for clinical symptoms, vascular cognitive decline, instability of carotid plaque-presence of microemboli, brain white matter changes, and medical risk factors. Forty-six percent were classically symptomatic. All patients showed vascular cognitive decline at presentation which correlated with degree of plaque instability. Significant white matter hyperintensity changes (48.7%) and cerebral emboli (25%) were also seen at baseline in both classically symptomatic and asymptomatic. One year after CEA, both groups showed no decline in cognitive function and significant improvement in 2 tests (P = .028 and P = .013). Brain white matter hyperintensities were unchanged. Microemboli were reduced but remained present (17.86%). Improvement was predicted by the presence of hypertension (P = .001), or less advanced cognitive decline preoperatively (P = .009). This study demonstrates the importance of vascular cognitive decline in atherosclerotic disease. This is a function of the degree of instability of the atherosclerotic plaque more than the presence of stroke symptoms. It further suggests that atherosclerotic vascular cognitive decline need not be inevitable, and may be modified by treating hypertension and removal of the unstable plaque. This highlights the need for continued research on the cognitive effects of cerebrovascular disease and the synergistic benefits of intensive medical and surgical therapy.

White Matter Hyperintensity Volume and Outcome of Mechanical Thrombectomy With Stentriever in Acute Ischemic Stroke.

Finding of white matter hyperintensity (WMH) has been associated with an increased risk of parenchymal hematoma and poor clinical outcomes after mechanical thrombectomy using old-generation endovascular devices. Currently, no data exist with regard to the risk of mechanical thrombectomy using stentriever devices in patients with significant WMH. We hypothesized that WMH volume will not affect the hemorrhagic and clinical outcome in patients with acute ischemic stroke undergoing thrombectomy using new-generation devices. A retrospective cohort of consecutive acute ischemic stroke patients >18-year-old receiving mechanical thrombectomy with stentriever devices at a single academic center was examined. WMH volume was assessed by a semiautomated volumetric analysis on T2 fluid attenuated inversion recovery-magnetic resonance imaging. Outcomes included the rate of any intracerebral hemorrhage, 90-day modified Rankin Score (mRS), the rate of good outcome (discharge mRS ≤2), and the rate of successful reperfusion (thrombolysis in cerebral ischemia score 2b or 3). Between June 2012 and December 2015, 56 patients with acute ischemic stroke met the study criteria. Median WMH volume was 6.76 cm3 (4.84-16.09 cm3). Increasing WMH volume did not significantly affect the odds of good outcome (odds ratio [OR], 0.811; 95% confidence interval [CI], 0.456-1.442), intracerebral hemorrhage (OR, 1.055; 95% CI, 0.595-1.871), parenchymal hematoma (OR, 0.353; 95% CI, 0.061-2.057), successful recanalization (OR, 1.295; 95% CI, 0.704-2.383), or death (OR, 1.583; 95% CI, 0.84-2.98). Mechanical thrombectomy using stentrievers seems to be safe in selected patients with acute ischemic stroke with large vessel occlusion, nonwithstanding the severity of WMH burden in this population. Larger prospective studies are warranted to validate these findings.

REVERSIBLE LEUKOENCEPHALOPATHY AS A PRESENTATION OF CEREBRAL AMYLOID ANGIOPATHY

A 73 year old man with a past medical history of hypertension, osteoathritis and asthma presented to the local district general hospital with recurrent episodes of spontaneously resolving encephalopathy.The initial...

Mobility decline in the elderly relates to lesion accrual in the splenium of the corpus callosum

In a previous cross-sectional study on baseline data, we demonstrated that the volume of brain white matter hyperintensities (WMH) in the splenium of corpus callosum (SCC) predicted the current mobility function of older persons. The primary aim of this follow-up study was to determine the relation of WMH volume change in SCC (SCC-∆WMH) with change in mobility measures. A secondary aim was to characterize the global and regional progression of WMH. Mobility function and WMH burden were evaluated at baseline and at 2 years in 77 community-dwelling individuals (baseline age, 82 ± 4). Regional WMH in SCC, as well as genu and body of corpus callosum, subregions of corona radiata, and superior longitudinal fasciculus were determined using a white matter parcellation atlas. The total WMH volume increased 3.3 ± 3.5 ml/year, mainly through enlargement. Significant WMH increases were observed in all selected regions, particularly within the corona radiata. While at baseline and follow-up we observed correlations between WMH burden and several measures of mobility, longitudinal change correlated only with change in chair rise (CR). SCC-∆WMH showed the highest correlation (r = -0.413, p = 0.0002) and was the best regional predictor of CR decline (OR = 1.5, r(2) = 0.3). The SCC-∆WMH was more than five times larger in the CR-decline group compared to the no-decline group (p = 0.0003). The SCC-∆WMH (top quartile) showed a higher sensitivity/specificity for CR decline compared to change in total WMH, 63/88% versus 52/84%, respectively. The findings suggest that accrual of WMHs in posterior areas of the brain supporting inter-hemispheric integration and processing of visual-spatial information is a mechanism contributing to age-related mobility deterioration.

A fully automated method for quantifying and localizing white matter hyperintensities on MR images

White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy-connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found ( P < 0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies (e.g. [Taylor, W.D., MacFall, J.R., Steffens, D.C., Payne, M.E., Provenzale, J.M., Krishnan, K.R., 2003. Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (3), 539–544.]), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large NeuroImage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders.

Are multiple acute small subcortical infarctions caused by embolic mechanisms?

Objective: To seek evidence of potential embolic sources or other stroke mechanisms in patients who, on chance observation, had several apparently recent small subcortical infarcts on diffusion weighted magnetic resonance...