Atrophy Measures Research Articles

An Efficient Combination among sMRI, CSF, Cognitive Score, and APOE ε4 Biomarkers for Classification of AD and MCI Using Extreme Learning Machine.

Alzheimer's disease (AD) is the most common cause of dementia and a progressive neurodegenerative condition, characterized by a decline in cognitive function. Symptoms usually appear gradually and worsen over time, becoming severe enough to interfere with individual daily tasks. Thus, the accurate diagnosis of both AD and the prodromal stage (i.e., mild cognitive impairment (MCI)) is crucial for timely treatment. As AD is inherently dynamic, the relationship between AD indicators is unclear and varies over time. To address this issue, we first aimed at investigating differences in atrophic patterns between individuals with AD and MCI and healthy controls (HCs). Then we utilized multiple biomarkers, along with filter- and wrapper-based feature selection and an extreme learning machine- (ELM-) based approach, with 10-fold cross-validation for classification. Increasing efforts are focusing on the use of multiple biomarkers, which can be useful for the diagnosis of AD and MCI. However, optimum combinations have yet to be identified and most multimodal analyses use only volumetric measures obtained from magnetic resonance imaging (MRI). Anatomical structural MRI (sMRI) measures have also so far mostly been used separately. The full possibilities of using anatomical MRI for AD detection have thus yet to be explored. In this study, three measures (cortical thickness, surface area, and gray matter volume), obtained from sMRI through preprocessing for brain atrophy measurements; cerebrospinal fluid (CSF), for quantification of specific proteins; cognitive score, as a measure of cognitive performance; and APOE ε4 allele status were utilized. Our results show that a combination of specific biomarkers performs well, with accuracies of 97.31% for classifying AD vs. HC, 91.72% for MCI vs. HC, 87.91% for MCI vs. AD, and 83.38% for MCIs vs. MCIc, respectively, when evaluated using the proposed algorithm. Meanwhile, the areas under the curve (AUC) from the receiver operating characteristic (ROC) curves combining multiple biomarkers provided better classification performance. The proposed features combination and selection algorithm effectively classified AD and MCI, and MCIs vs. MCIc, the most challenging classification task, and therefore could increase the accuracy of AD classification in clinical practice. Furthermore, we compared the performance of the proposed method with SVM classifiers, using a cross-validation method with Alzheimer's Disease Neuroimaging Initiative (ADNI) datasets.

Cultural factors related to neuropsychological performance and brain atrophy among Hispanic older adults with amnestic Mild Cognitive Impairment (aMCI): A pilot study

Objectives This study examined the association of cultural factors and literacy to neuropsychological performance and measures of regional brain atrophy among Hispanic elders diagnosed with amnestic Mild Cognitive Impairment (aMCI). Method Acculturation and literacy levels were measured among 45 subjects tested in Spanish; their primary language. Scores for measures of memory, executive functioning, and verbal fluency, as well as volumetric analysis of MRI scans of left hemisphere structures commonly affected by Alzheimer’s disease (AD) were examined. Linear regression models were employed to examine the association of acculturation and literacy to neuropsychological performance and MRI measures. Results After controlling for age, higher literacy levels were associated with better performance on phonemic verbal fluency (r = 0.300, p < .05), while higher levels of acculturation to the U.S. was associated with poorer performance on category verbal fluency (r = 0.300, p < .05). There was a significant inverse relationship after controlling for age between literacy and the left entorhinal cortex (r = –0.455, p < .05), left precuneus (r = –0.457, p < .05), and left posterior cingulate (r = –0.415, p < .05). Conclusions Results of the current pilot study indicate that high acculturation to the U.S. among aMCI immigrants from Latin-American countries may hinder performance on verbal learning measures when they are administered in one’s primary language. Moreover, in this cohort, a higher literacy level, which is indicative of greater cognitive reserve, was associated with better performance in language measures, but with greater atrophy in brain regions susceptible to neurodegenerative disease. These preliminary findings should be further examined among larger cohorts and using more diverse measures, which capture other cultural constructs.

Microglial activation and tau burden predict cognitive decline in Alzheimer's disease.

Tau pathology, neuroinflammation, and neurodegeneration are key aspects of Alzheimer's disease. Understanding whether these features predict cognitive decline, alone or in combination, is crucial to develop new prognostic measures and enhanced stratification for clinical trials. Here, we studied how baseline assessments of in vivo tau pathology (measured by 18F-AV-1451 PET), neuroinflammation (measured by 11C-PK11195 PET) and brain atrophy (derived from structural MRI) predicted longitudinal cognitive changes in patients with Alzheimer's disease pathology. Twenty-six patients (n = 12 with clinically probable Alzheimer's dementia and n = 14 with amyloid-positive mild cognitive impairment) and 29 healthy control subjects underwent baseline assessment with 18F-AV-1451 PET, 11C-PK11195 PET, and structural MRI. Cognition was examined annually over the subsequent 3 years using the revised Addenbrooke's Cognitive Examination. Regional grey matter volumes, and regional binding of 18F-AV-1451 and 11C-PK11195 were derived from 15 temporo-parietal regions characteristically affected by Alzheimer's disease pathology. A principal component analysis was used on each imaging modality separately, to identify the main spatial distributions of pathology. A latent growth curve model was applied across the whole sample on longitudinal cognitive scores to estimate the rate of annual decline in each participant. We regressed the individuals' estimated rate of cognitive decline on the neuroimaging components and examined univariable predictive models with single-modality predictors, and a multi-modality predictive model, to identify the independent and combined prognostic value of the different neuroimaging markers. Principal component analysis identified a single component for the grey matter atrophy, while two components were found for each PET ligand: one weighted to the anterior temporal lobe, and another weighted to posterior temporo-parietal regions. Across the whole-sample, the single-modality models indicated significant correlations between the rate of cognitive decline and the first component of each imaging modality. In patients, both stepwise backward elimination and Bayesian model selection revealed an optimal predictive model that included both components of 18F-AV-1451 and the first (i.e. anterior temporal) component for 11C-PK11195. However, the MRI-derived atrophy component and demographic variables were excluded from the optimal predictive model of cognitive decline. We conclude that temporo-parietal tau pathology and anterior temporal neuroinflammation predict cognitive decline in patients with symptomatic Alzheimer's disease pathology. This indicates the added value of PET biomarkers in predicting cognitive decline in Alzheimer's disease, over and above MRI measures of brain atrophy and demographic data. Our findings also support the strategy for targeting tau and neuroinflammation in disease-modifying therapy against Alzheimer's disease.

Sex-Specific Differences in Life Span Brain Volumes in Multiple Sclerosis.

Numerous sex-specific differences in multiple sclerosis (MS) susceptibility, disease manifestation, disability progression, inflammation, and neurodegeneration have been previously reported. Previous magnetic resonance imaging (MRI) studies have shown structural differences between female and male MS brain volumes. To determine sex-specific global and tissue-specific brain volume throughout the MS life span in a real-world large MRI database. A total of 2,199 MS patients (female/male ratio of 1,651/548) underwent structural MRI imaging on either a 1.5-T or 3-T scanner. Global and tissue-specific volumes of whole brain (WBV), white matter, and gray matter (GMV) were determined by utilizing Structural Image Evaluation using Normalisation of Atrophy Cross-sectional (SIENAX). Lateral ventricular volume (LVV) was determined with the Neurological Software Tool for REliable Atrophy Measurement (NeuroSTREAM). General linear models investigated sex and age interactions, and post hoc comparative sex analyses were performed. Despite being age-matched with female MS patents, a greater proportion of male MS patients were diagnosed with progressive MS and had lower normalized WBV (P<.001), GMV (P <.001), and greater LVV (P <.001). In addition to significant stand-alone main effects, an interaction between sex and age had an additional effect on the LVV (F-statistics = 4.53, P = .033) and GMV (F-statistics = 4.59, P = .032). The sex and age interaction was retained in both models of LVV (F-statistics = 3.31, P = .069) and GMV (F-statistics = 6.1, P = .003) when disease subtype and disease-modifying treatment (DMT) were also included. Although male MS patients presented with significantly greater LVV and lower GMV during the early and midlife period when compared to their female counterparts (P <.001 for LVV and P <.019 for GMV), these differences were nullified in 60+ years old patients. Similar findings were seen within a subanalysis of MS patients that were not on any DMT at the time of enrollment. There are sex-specific differences in the LVV and GMV over the MS life span.

Relationship between cortical iron and tau aggregation in Alzheimer's disease.

A growing body of evidence suggests that the dysregulation of neuronal iron may play a critical role in Alzheimer's disease. Recent MRI studies have established a relationship between iron accumulation and amyloid-β aggregation. The present study provides further insight demonstrating a relationship between iron and tau accumulation using magnetic resonance-based quantitative susceptibility mapping and tau-PET in n = 236 subjects with amyloid-β pathology (from the Swedish BioFINDER-2 study). Both voxel-wise and regional analyses showed a consistent association between differences in bulk magnetic susceptibility, which can be primarily ascribed to an increase in iron content, and tau-PET signal in regions known to be affected in Alzheimer's disease. Subsequent analyses revealed that quantitative susceptibility specifically mediates the relationship between tau-PET and cortical atrophy measures, thus suggesting a modulatory effect of iron burden on the disease process. We also found evidence suggesting the relationship between quantitative susceptibility and tau-PET is stronger in younger participants (age ≤ 65). Together, these results provide in vivo evidence of an association between iron deposition and both tau aggregation and neurodegeneration, which help advance our understanding of the role of iron dysregulation in the Alzheimer's disease aetiology.

A validation study of manual atrophy measures in patients with MultipleSclerosis.

Manual measures such as corpus callosum index, normalized corpus callosum area, and width of the third ventricle are potential biomarkers for brain atrophy. In this work, we investigate their suitability to assess the neurodegenerative component of multiple sclerosis (MS) by comparing them to volumetric measures and expanded disability status scale (EDSS). Fifty-eight patients with a clinically isolated syndrome, 48 MS patients treated with interferon β, and 26 treated with natalizumab underwent a brain MRI at baseline and after1year. Manual measures were evaluated by two observers using Jim v.6.0 at both time points. Volumetric tools (SIENA/x and Freesurfer) were used to calculate normalized brain volume, brain parenchymal fraction, annualized percentage of brain volume change, corpus callosum volume, ventricle volume, and volume of the third ventricle. Statistical analyses were performed with SPSS v.13. Usage of corpus callosum volume and third ventricle volume to validate normalized corpus callosum area and width of the third ventricle, respectively, showed very good correlations (r = 0.85, r = 0.83; p < 0.01). Width of thethird ventricle, corpus callosum index, and normalized corpus callosum area correlations were significant with EDSS in all patients and moderate to strong with normalized brain volume and brain parenchymal fraction in natalizumab-treated patients (respectively r = - 0.54, r = - 0.61; r = 0.55, r = 0.67; and r = 0.58, r = 0.67; with p < 0.05). Width of the third ventricle and normalized corpus callosum area seem the more robust manual measures regarding correlation with volumetric measures and EDSS, especially in patients with more advanced disease.

Abstract P420: Alcohol Consumption and Longitudinal Changes in Magnetic Resonance Imaging-defined Brain Abnormalities: The Cardiovascular Health Study

Introduction: Alcohol intake has been related with a complex group of associations with brain structure in cross-sectional analyses, but to our knowledge, its prospective relationship with structural brain abnormalities detected by MRI has never been reported. Hypothesis: We hypothesized that consumers of 1-&lt;7 drinks/week would have slower progression of leukoaraiosis (white matter abnormalities) but more rapid progression of brain atrophy than longer-term abstainers. Methods: As part of the Cardiovascular Health Study, 1 996 adults aged ≥65 years underwent MRI scanning in 1991-94 and again in 1997-99, having excluded 120 participants with a history of cerebrovascular disease before the initial scan. Alcohol consumption was assessed at each annual visit by self-reported intake of wine, beer and liquor. A 10-point white matter grade (WMG) and ventricular grade (VG) were assessed in a standardized and blinded manner in both scans; hippocampal and total brain volumes were also quantified on the second scan. We estimated the associations of alcohol intake in categories (as reported closest to the date of initial scan), with MRI findings at follow-up with multinomial ordered logistic regression (WMG ≤ 3 ref and ≥ 4; VG ≤ 3 ref , =4 and ≥5) using inverse probability weighting to account for attrition. Results: We observed a U-shaped association with WMG, with significantly lower risk among participants consuming 1-&lt;7 drinks/week (OR 0.38; 95% CI 0.17-0.82, table) than long-term abstainers (P quadtrend = 0.01). For VG, the association was inverse (P trend = 0.06), with significantly less progression among drinkers of 1-&lt;7 drinks/week than long-term abstainers (OR 0.62; 95% CI 0.40-0.97). We identified no significant associations of alcohol intake with quantitative mean hippocampal or total brain volumes at the second scan. Conclusions: Compared with long-term abstention, consumption of 1-&lt;7 drinks/week of alcohol was generally associated with less progression of leukoaraiosis and some measures of brain atrophy in older adults.

Study on structural atrophy changes and functional connectivity measures in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the progressive accumulation of neurofibrillary tangles associated with amyloid plaques. We used 80 resting-state functional magnetic resonance imaging and 80 images acquired using MP-RAGE (magnetization-prepared rapid acquisition gradient echo) from Alzheimer's Disease Neuroimaging Initiative data to detect atrophy changes and functional connectivity patterns of the default mode networks (DMNs). The study subjects were classified into four groups (each with ) based on their Mini-Mental State Examination (MMSE) score as follows: cognitively normal (CN), early mild cognitive impairment, late mild cognitive impairment, and AD. The resting-state functional connectivity of the DMN was examined between the groups using the CONN functional connectivity toolbox. Loss of gray matter in AD was observed. Atrophy measured by the volume of selected subcortical regions, using the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library's Integrated Registration and Segmentation Tool (FIRST), revealed significant volume loss in AD when compared to CN ( ). DMNs were selected to assess functional connectivity. The negative connectivity of DMN increased in AD group compared to controls. Graph theory parameters, such as global and local efficiency, betweenness centrality, average path length, and cluster coefficient, were computed. Relatively higher correlation between MMSE and functional metrics ( , ) was observed as compared to atrophy measures ( , ). In addition, the receiver operating characteristic analysis showed large area under the curve ( ) for functional parameters ( ), compared to morphometric changes ( ). In summary, it is observed that the functional connectivity measures may serve a better predictor in comparison to structural atrophy changes. We postulate that functional connectivity measures have the potential to evolve as a marker for the early detection of AD.

Abstract WP74: Automated Measurement of Cerebral Atrophy and Outcome in Endovascular Thrombectomy

Background and Purpose: Methods of identifying ischemic stroke patients with a greater probability of poor outcome following endovascular thrombectomy (EVT) might improve shared treatment decision-making between patients, families and physicians. Visually-graded cerebral atrophy is associated with worse functional outcome following EVT. We used an objective, automated method to measure cerebral atrophy and investigated whether this was associated with functional outcome in EVT patients. Methods: Consecutive EVT patients from a single-center registry were studied. CT brain scans were segmented with a combination of a validated U-Net and Hounsfield unit thresholding. Intracranial cerebrospinal fluid (CSF) volume was used as a marker of cerebral atrophy and calculated as a proportion of total intracranial volume. The primary outcome was functional independence, defined as a 3-month modified Rankin Scale (mRS) score of 0-2. Results: 360 EVT patients were included. Functional independence was achieved in 204 (56.7%) patients. The mean±SD CSF volume was 9.0±4.7% of total intracranial volume. Multivariable regression demonstrated that increasing CSF volume was associated with reduced functional independence (OR=0.65 per 5% increase in CSF volume; 95% CI, 0.48- 0.89; P=0.007) and higher 3-month mRS scores (common OR=1.59 per 5% increase in CSF volume; 95% CI, 1.05-2.41; P=0.03). Conclusions: Cerebral atrophy determined by automated measurement of intracranial CSF volume is associated with functional outcome in patients undergoing EVT. If validated in future studies, this simple, objective, and automated imaging marker could potentially be incorporated into decision-support tools in order to improve shared treatment decision making.

Brain MRI Predicts Worsening Multiple Sclerosis Disability over 5 Years in the SUMMIT Study.

Brain MRI-derived lesions and atrophy are related to multiple sclerosis (MS) disability. In the Serially Unified Multicenter MS Investigation (SUMMIT), from Brigham and Women's Hospital (BWH) and University of California, San Francisco (UCSF), we assessed whether MRI methodologic heterogeneity may limit the ability to pool multisite data sets to assess 5-year clinical-MRI associations. Patients with relapsing-remitting (RR) MS (n=100 from each site) underwent baseline brain MRI and baseline and 5-year clinical evaluations. Patients were matched on sex (74 women each), age, disease duration, and Expanded Disability Status Scale (EDSS) score. MRI was performed with differences between sites in both acquisition (field strength, voxel size, pulse sequences), and postprocessing pipeline to assess brain parenchymal fraction (BPF) and T2 lesion volume (T2LV). The UCSF cohort showed higher correlation than the BWH cohort between T2LV and disease duration. UCSF showed a higher inverse correlation between BPF and age than BWH. UCSF showed a higher inverse correlation than BWH between BPF and 5-year EDSS score. Both cohorts showed inverse correlations between BPF and T2LV, with no between-site difference. The pooled but not individual cohort data showed a link between a lower baseline BPF and the subsequent 5-year worsening in disability in addition to other stronger relationships in the data. MRI acquisition and processing differences may result in some degree of heterogeneity in assessing brain lesion and atrophy measures in patients with MS. Pooling of data across sites is beneficial to correct for potential biases in individual data sets.

Contribution of the Mesencephalon Indices to Differential Diagnosis of Parkinsonian Disorders.

This study aimed to assess the sensitivity and specificity of brain stem morphologic changes to differentiate the progressive supranuclear palsy (PSP) from Parkinson disease (PD) and multiple system atrophy (MSA), by single and combined magnetic resonance imaging (MRI) measurements. Peduncle angle (PA), pons area (P), mesencephalon area (M), middle cerebellar peduncles (MCPs), and superior cerebellar peduncles (SCPs) were measured in 14 PSP, 43 PD, 8 MSA patients, and 45 age-matched control participants on T1-weighted MRI. Neurologists clinically diagnosed all patients. Additionally, P/M ratio, MCPs/SCPs ratio, the previously defined Magnetic Resonance Parkinsonism Index, MRPI: (P/M) · (MCP/SCP), and also the Akdeniz Index (AKI) that we termed were calculated, AKI: (P/M) · (PA/180). Two blinded radiologists evaluated all MR images and inter-/intraobserver variations were measured. Both M and SCPs were significantly lower and P/M, MCPs/SCPs, and PA were significantly higher in PSP patients than the other groups (P < .001). This significance was related to patients with PSP and PD. But all single measurements showed some overlapping values. Therefore, previously defined MRPI was calculated and shown to distinguish patients (negative predictive values: 92%, sensitivity: 78%, specificity: 82%). In this study, interobserver correlation (0.68) was found low for MRPI. Therefore, we identified a more practical index: the Akdeniz Index, which has same diagnostic power with MRPI and higher interobserver correlation (0.91). The Akdeniz Index identified in our study is a practical index with high diagnostic power and can reinforce radiological distinguishing of PSP and PD, which are clinically difficult to distinguish.

A cross-sectional and longitudinal study on the protective effect of bilingualism against dementia using brain atrophy and cognitive measures

BackgroundEvidence from previous studies suggests that bilingualism contributes to cognitive reserve because bilinguals manifest the first symptoms of Alzheimer’s disease (AD) up to 5 years later than monolinguals. Other cross-sectional studies demonstrate that bilinguals show greater amounts of brain atrophy and hypometabolism than monolinguals, despite sharing the same diagnosis and suffering from the same symptoms. However, these studies may be biased by possible pre-existing between-group differences.MethodsIn this study, we used global parenchymal measures of atrophy and cognitive tests to investigate the protective effect of bilingualism against dementia cross-sectionally and prospectively, using a sample of bilinguals and monolinguals in the same clinical stage and matched on sociodemographic variables.ResultsOur results suggest that the two groups did not differ in their cognitive status at baseline, but bilinguals had less parenchymal volume than monolinguals, especially in areas related to brain atrophy in dementia. In addition, a longitudinal prospective analysis revealed that monolinguals lost more parenchyma and had more cognitive decline than bilinguals in a mean follow-up period of 7 months.ConclusionThese results provide the first prospective evidence that bilingualism may act as a neuroprotective factor against dementia and could be considered a factor in cognitive reserve.

Progressive multifocal leukoencephalopathy lesion and brain parenchymal segmentation from MRI using serial deep convolutional neural networks

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the JC virus and associated with substantial morbidity and mortality. Accurate MRI assessment of PML lesion burden and brain parenchymal atrophy is of decisive value in monitoring the disease course and response to therapy. However, there are currently no validated automatic methods for quantification of PML lesion burden or associated parenchymal volume loss. Furthermore, manual brain or lesion delineations can be tedious, require the use of valuable time resources by radiologists or trained experts, and are often subjective. In this work, we introduce JCnet (named after the causative viral agent), an end-to-end, fully automated method for brain parenchymal and lesion segmentation in PML using consecutive 3D patch-based convolutional neural networks. The network architecture consists of multi-view feature pyramid networks with hierarchical residual learning blocks containing embedded batch normalization and nonlinear activation functions. The feature maps across the bottom-up and top-down pathways of the feature pyramids are merged, and an output probability membership generated through convolutional pathways, thus rendering the method fully convolutional. Our results show that this approach outperforms and improves longitudinal consistency compared to conventional, state-of-the-art methods of healthy brain and multiple sclerosis lesion segmentation, utilized here as comparators given the lack of available methods validated for use in PML. The ability to produce robust and accurate automated measures of brain atrophy and lesion segmentation in PML is not only valuable clinically but holds promise toward including standardized quantitative MRI measures in clinical trials of targeted therapies. Code is available at: https://github.com/omarallouz/JCnet.

Spinal cord atrophy in a primary progressive multiple sclerosis trial: Improved sample size using GBSI

BackgroundWe aimed to evaluate the implications for clinical trial design of the generalised boundary-shift integral (GBSI) for spinal cord atrophy measurement. MethodsWe included 220 primary-progressive multiple sclerosis patients from a phase 2 clinical trial, with baseline and week-48 3DT1-weighted MRI of the brain and spinal cord (1 × 1 × 1 mm3), acquired separately. We obtained segmentation-based cross-sectional spinal cord area (CSA) at C1-2 (from both brain and spinal cord MRI) and C2-5 levels (from spinal cord MRI) using DeepSeg, and, then, we computed corresponding GBSI. ResultsDepending on the spinal cord segment, we included 67.4–98.1% patients for CSA measurements, and 66.9–84.2% for GBSI. Spinal cord atrophy measurements obtained with GBSI had lower measurement variability, than corresponding CSA. Looking at the image noise floor, the lowest median standard deviation of the MRI signal within the cerebrospinal fluid surrounding the spinal cord was found on brain MRI at the C1-2 level. Spinal cord atrophy derived from brain MRI was related to the corresponding measures from dedicated spinal cord MRI, more strongly for GBSI than CSA. Spinal cord atrophy measurements using GBSI, but not CSA, were associated with upper and lower limb motor progression. DiscussionNotwithstanding the reduced measurement variability, the clinical correlates, and the possibility of using brain acquisitions, spinal cord atrophy using GBSI should remain a secondary outcome measure in MS studies, until further advancements increase the quality of acquisition and reliability of processing.

Generalised boundary shift integral for longitudinal assessment of spinal cord atrophy

Spinal cord atrophy measurements obtained from structural magnetic resonance imaging (MRI) are associated with disability in many neurological diseases and serve as in vivo biomarkers of neurodegeneration. Longitudinal spinal cord atrophy rate is commonly determined from the numerical difference between two volumes (based on 3D surface fitting) or two cross-sectional areas (CSA, based on 2D edge detection) obtained at different time-points. Being an indirect measure, atrophy rates are susceptible to variable segmentation errors at the edge of the spinal cord. To overcome those limitations, we developed a new registration-based pipeline that measures atrophy rates directly. We based our approach on the generalised boundary shift integral (GBSI) method, which registers 2 scans and uses a probabilistic XOR mask over the edge of the spinal cord, thereby measuring atrophy more accurately than segmentation-based techniques. Using a large cohort of longitudinal spinal cord images (610 subjects with multiple sclerosis from a multi-centre trial and 52 healthy controls), we demonstrated that GBSI is a sensitive, quantitative and objective measure of longitudinal spinal cord volume change. The GBSI pipeline is repeatable, reproducible, and provides more precise measurements of longitudinal spinal cord atrophy than segmentation-based methods in longitudinal spinal cord atrophy studies.

Brain imaging measurements of fibrillar amyloid-β burden, paired helical filament tau burden, and atrophy in cognitively unimpaired persons with two, one, and no copies of the APOE ε4 allele

IntroductionWe previously characterized associations between brain imaging measurements of amyloid-β (Aβ) plaque burden and apolipoprotein E (APOE) ε4 gene dose in a small number of cognitively unimpaired late-middle-aged APOE ε4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross-sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements, classifications, and associations with age in a larger number of unimpaired HMs, HTs, and NCs over a wider age range. MethodsWe analyzed 11C Pittsburgh compound B (Aβ) positron emission tomography (PET), flortaucipir (tau) PET, and volumetric magnetic resonance imaging data from 164 study participants of age 47–86 years, including 26 APOE ε4 HMs, 48 HTs, and 90 NCs matched for age and sex. ResultsAβ PET measurements rose, plateaued at the respective ages of 68 and 76, and then declined with age in unimpaired HM and HT groups. Compared with NCs, these two groups began to have significantly higher Aβ PET measurements at ages 62 and 70, respectively, and no longer had significantly higher measurements by ages 71 and 78, respectively. They began to have significantly higher entorhinal cortex tau PET measurements at ages 66 and 70, respectively, and no longer had significantly higher measurements by ages 74 and 78, respectively. Brain atrophy measurements tended to decline slowly with age in all three genetic groups. Their elevated tau PET measurements were attributable to those with positive Aβ PET scans. 41.0%, 18.0%, and 5.0% of the 47- to 70-year-old HMs, HTs, and NCs and 25.0%, 79.0%, and 38.0% of the 71- to 86-year-old HMs, HTs, and NCs had positive Aβ PET scans, and the long-term recall memory scores are significantly higher in the older HMs than in HT and NC groups, suggesting resistance to Aβ deposition in those HMs who remained unimpaired at older ages. ConclusionsThis study provides information about Aβ plaque burden, tau tangle burden, and neurodegeneration in cognitively unimpaired persons at three levels of genetic risk for AD. Unimpaired APOE ε4 HMs can be studied before their 70s to evaluate the understanding of factors, processes, and interventions involved in the predisposition to and prevention of AD, and after their 70s, to discover factors, processes, and interventions involved in the resilience or resistance to and prevention of AD.

Bi-caudate ratio as a MRI marker of white matter atrophy in multiple sclerosis and ischemic leukocencephalopathy

BackgroundBrain atrophy measurement is now a cornerstone in basic neuro-imaging science. While assessment of white matter atrophy by visual inspection is subjective, volumetric approaches are time-consuming and not often feasible. Bi-caudate ratio represents a linear surrogate parameter of brain volume that can be derived from standard imaging sequences. This study highlights the value of the bi-caudate ratio (BCR) as a MRI marker of white matter atrophy in patients with multiple sclerosis and ischemic leukoencephalopathy and set a cut-off value to differentiate between patients with white matter atrophy and normal subjects.ResultsA total of 115 patients (54 males and 61 females) diagnosed with white matter leukoencephalopathy (MS in 51 patients and ischemic leukoencephalopathy in 64 patients) were included. Another group of 60 subjects with a normal white matter signal was recruited as a control group. BCR for the patient group ranged from 0.13 to 0.27 (mean (± SD) = 0.16 ± 0.02), while for the control group, it ranged from 0.05 mm to 0.13 (mean (± SD) = 0.09 ± 0.01). The difference between the two groups was statistically significant (P value < 0.001). A cut-off value of 0.13 was used to differentiate between the BCR in both patients and control groups with sensitivity, specificity, and accuracy of 99.2%, 100%, and 99%, respectively. The difference in BCR for patients diagnosed with MS and ischemic leukoencephalopathy was also statistically significant (P value < 0.001).ConclusionThe bi-caudate ratio represents a linear measurement of subcortical atrophy that can be useful as a surrogate marker of global supra-tentorial white matter atrophy instead of the usually performed visual and therefore subjective assessment. It is an easily obtained measure that can be performed without complex time-consuming volumetric studies. Our findings also revealed that the BCR is higher in patients with ischemic leukoencephalopathy than in patients with MS.

Automated Measurement of Cerebral Atrophy and Outcome in Endovascular Thrombectomy

Background and Purpose- Methods of identifying ischemic stroke patients with a greater probability of poor outcome following endovascular thrombectomy (EVT) might improve shared treatment decision-making between patients, families, and physicians. We used an objective, automated method to measure cerebral atrophy and investigated whether this was associated with outcome in EVT patients. Methods- Consecutive EVT patients from a single-center registry were studied. CT brain scans were segmented with a combination of a validated U-Net and Hounsfield unit thresholding. Intracranial cerebrospinal fluid (CSF) volume was used as a marker of cerebral atrophy and calculated as a proportion of total intracranial volume. The primary outcome was functional independence, defined as a 3-month modified Rankin Scale score of 0 to 2. Results- Three-hundred sixty EVT patients were included. Functional independence was achieved in 204 (56.7%) patients. The mean±SD CSF volume was 9.0±4.7% of total intracranial volume. Multivariable regression demonstrated that increasing CSF volume was associated with reduced functional independence (OR=0.65 per 5% increase in CSF volume; 95% CI, 0.48-0.89; P=0.007) and higher 3-month modified Rankin Scale scores (common OR, 1.59 per 5% increase in CSF volume; 95% CI, 1.05-2.41; P=0.03). Conclusions- Cerebral atrophy determined by automated measurement of intracranial CSF volume is associated with functional outcome in patients undergoing EVT. If validated in future studies, this simple, objective, and automated imaging marker could potentially be incorporated into decision-support tools to improve shared treatment decision-making.

Brain atrophy and patch-based grading in individuals from the CIMA-Q study: a progressive continuum from subjective cognitive decline to AD

It has been proposed that individuals developing Alzheimer’s disease (AD) first experience a phase expressing subjective complaints of cognitive decline (SCD) without objective cognitive impairment. Using magnetic resonance imaging (MRI), our objective was to verify whether SNIPE probability grading, a new MRI analysis technique, would distinguish between clinical dementia stage of AD: Cognitively healthy controls without complaint (CH), SCD, mild cognitive impairment, and AD. SNIPE score in the hippocampus and entorhinal cortex was applied to anatomical T1-weighted MRI of 143 participants from the Consortium pour l’identification précoce de la maladie Alzheimer - Québec (CIMA-Q) study and compared to standard atrophy measures (volumes and cortical thicknesses). Compared to standard atrophy measures, SNIPE score appeared more sensitive to differentiate clinical AD since differences between groups reached a higher level of significance and larger effect sizes. However, no significant difference was observed between SCD and CH groups. Combining both types of measures did not improve between-group differences. Further studies using a combination of biomarkers beyond anatomical MRI might be needed to identify individuals with SCD who are on the beginning of the clinical continuum of AD.

Optic Chiasm Morphometric Changes in Multiple Sclerosis: Feasibility of a Simplified Brain Magnetic Resonance Imaging Measure of White Matter Atrophy.

Sophisticated volume measurements of brain structures on magnetic resonance imaging (MRI) may improve specificity in determining long-term progression of multiple sclerosis (MS), but these techniques are laborious. The optic chiasm (OC) is a white matter (WM) structure clearly visible on a routine MRI and is related to the optic nerves (ONs), which are known to atrophy in MS. We hypothesized that OC morphometric measurements would show OC atrophy in MS compared to normal patients. If so, this could help establish a novel simplified brain MRI measure of WM atrophy in MS patients. We retrospectively evaluated standard brain MRIs of 97 patients with known MS and 98 normal individuals. We electronically measured eight OC morphometrics on axial T2WIs and midsagittal T1WIs: OC width and anteroposterior (AP) diameter, diameters of each ON and optic tract (OT), and angles between the ONs or OTs. Mean OC width, AP diameter, and height in MS patients were 11.83 ± 1.25 mm (95% CI 11.58-12.09), 2.99 ± 0.65 mm (95% CI 2.85-3.12), and 2.09 ± 0.37 mm (95% CI 2-2.19), respectively. In normal individuals, they were 12.1 ± 1.4 mm (95% CI 11.78-12.34), 3.43 ± 0.63 mm (95% CI 3.3-3.58), and 2.15 ± 0.37 mm (95% CI 2.07-2.23), respectively. There were statistically significant differences between MS patients and controls for AP diameter (P = 0.000), but not for width (P = 0.204) or height (P = 0.183). The ONs were significantly smaller in MS (P < 0.0017), but not the OTs. Thus, the OC is significantly atrophied in an unstratified cohort of MS patients. Future studies may establish an MRI OC morphometric index to evaluate demyelinating disease in the brain. Clin. Anat. 32:1072-1081, 2019. © 2019 Wiley Periodicals, Inc.