Emeritus Faculty - University Medical Line, Radiology - General Radiology
Current Research and Scholarly Interests
As a professor in the Medical Center Line, my primary investigative interest has been in clinical neuroradiology. This encompasses spinal cord and spine disease, degenerative and demyelinating diseases of the central nervous system, strokes and infarction, and chronic epilepsy syndromes. Facial and head and neck vascular malformations and hemangiomas have been a focus of interest for many years, with collaborative projects involving dermatology and functional restoration services.
Clinical projects utilizing magnetic resonance imaging, computed tomography, cerebral angiography and other neuroradiologic techniques are ongoing in collaboration with the vascular surgery department.
Cervical Nodal Mets in Squamous Cell Carcinoma of H&N - MRI, FDG-PET, & Histopathologic Correlation
The purpose of this study is to determine the value of novel non-invasive medical imaging methods for detecting the spread of head and neck squamous cell carcinoma to the lymph nodes in the neck by comparing their results to findings at the time of surgery.
Stanford is currently not accepting patients for this trial. For more information, please contact Quynh-Thu Le, (650) 498 - 6184.
Non-coding variability at the APOE locus contributes to the Alzheimer's risk
2019; 10: 3310
Alzheimer's disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
View details for DOI 10.1038/s41467-019-10945-z
View details for Web of Science ID 000477017000003
View details for PubMedID 31346172
View details for PubMedCentralID PMC6658518
Regional Amyloid-beta Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer's Dementia
2019; 56 (7): 4916–24
We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer's disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [18F]FDG and [18F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [18F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [18F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.
View details for DOI 10.1007/s12035-018-1405-1
View details for Web of Science ID 000483159700024
View details for PubMedID 30414086
The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
2019; 10: 1766
The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer's disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II-VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.
View details for DOI 10.1038/s41467-019-09564-5
View details for Web of Science ID 000464654700005
View details for PubMedID 30992433
View details for PubMedCentralID PMC6467911
White matter in different regions evolves differently during progression to dementia
NEUROBIOLOGY OF AGING
2019; 76: 71–79
White matter hyperintensities (WMHs) are common in individuals with mild cognitive impairment (MCI) and Alzheimer's disease. Patients with MCI with high WMH volumes are known to have an increased chance of conversion to Alzheimer's disease compared with those without WMHs. In this article, we assess the differences between patients with MCI that remain stable (N = 413) and those that progress to dementia (N = 178) in terms of WMH volume (as a surrogate of amount of tissue damage) and T1-weighted (T1w) image hypointensity (as a surrogate of severity of tissue damage) in periventricular, deep, and juxtacortical brain regions. Together, lesion volume and T1w hypointensity are used as a surrogate of vascular disease burden. Our results show a significantly greater increase of all regional WMH volumes in the MCI population that converts to dementia (p < 0.001). T1w hypointensity for the juxtacortical WMHs was significantly lower in the converter group (p < 0.0001) and was not affected by age. Conversely, T1w hypointensity in other regions showed a significant decrease with age (p < 0.0001). Within the converters, Time2Conversion was associated with both WMH volume and T1w hypointensity (p < 0.0001), and conversion to dementia was significantly associated with decreased intensity (and not volume) of periventricular and juxtacortical WMHs (p < 0.001). These changes differ according to the WM region, suggesting that different mechanisms affect the juxtacortical area in comparison to deep and periventricular regions in the process of conversion to dementia.
View details for DOI 10.1016/j.neurobiolaging.2018.12.004
View details for Web of Science ID 000459500800009
View details for PubMedID 30703628
A blood-based signature of cerebrospinal fluid A beta(1-42) status
2019; 9: 4163
It is increasingly recognized that Alzheimer's disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid β1-42 (Aβ1-42) may be an earlier indicator of Alzheimer's disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual's CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF Aβ1-42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four plasma analytes (CGA, Aβ1-42, Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF Aβ1-42 levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF Aβ1-42 levels and that the resulting model also validates reasonably across PET Aβ1-42 status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF Aβ1-42 status, the earliest risk indicator for AD, with high accuracy.
View details for DOI 10.1038/s41598-018-37149-7
View details for Web of Science ID 000460755200011
View details for PubMedID 30853713
- A review of statistical methods in imaging genetics CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE 2019; 47 (1): 108–31
A concise and persistent feature to study brain resting-state network dynamics: Findings from the Alzheimer's Disease Neuroimaging Initiative
HUMAN BRAIN MAPPING
2019; 40 (4): 1062–81
Alzheimer's disease (AD) is the most common type of dementia in the elderly with no effective treatment currently. Recent studies of noninvasive neuroimaging, resting-state functional magnetic resonance imaging (rs-fMRI) with graph theoretical analysis have shown that patients with AD and mild cognitive impairment (MCI) exhibit disrupted topological organization in large-scale brain networks. In previous work, it is a common practice to threshold such networks. However, it is not only difficult to make a principled choice of threshold values, but also worse is the discard of potential important information. To address this issue, we propose a threshold-free feature by integrating a prior persistent homology-based topological feature (the zeroth Betti number) and a newly defined connected component aggregation cost feature to model brain networks over all possible scales. We show that the induced topological feature (Integrated Persistent Feature) follows a monotonically decreasing convergence function and further propose to use its slope as a concise and persistent brain network topological measure. We apply this measure to study rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative and compare our approach with five other widely used graph measures across five parcellation schemes ranging from 90 to 1,024 region-of-interests. The experimental results demonstrate that the proposed network measure shows more statistical power and stronger robustness in group difference studies in that the absolute values of the proposed measure of AD are lower than MCI and much lower than normal controls, providing empirical evidence for decreased functional integration in AD dementia and MCI.
View details for DOI 10.1002/hbm.24383
View details for Web of Science ID 000459470400002
View details for PubMedID 30569583
- Robust Motion Regression of Resting-State Data Using a Convolutional Neural Network Model FRONTIERS IN NEUROSCIENCE 2019; 13
- The Relationship Between Hippocampal Volumes and Delayed Recall Is Modified by APOE epsilon 4 in Mild Cognitive Impairment FRONTIERS IN AGING NEUROSCIENCE 2019; 11
Evaluating trajectories of episodic memory in normal cognition and mild cognitive impairment: Results from ADNI
2019; 14 (2): e0212435
Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups.To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups.There were 219 normal subjects with mean age 75.9 (range from 59.9 to 89.6) and 52.5% male participants, and 372 MCI subjects with mean age 74.8 (range from 55.1 to 89.3) and 63.7% male participants included in the analysis. For normal subjects, six trajectories were identified. Trajectories were classified into three types, determined by the shape, each of which may comprise more than one trajectory: stable (~30% of subjects), curvilinear decline (~ 28%), and linear decline (~ 42%). Notably, none of the normal subjects assigned to the stable stratum progressed to dementia during the study period. In contrast, all trajectories identified for the MCI group tended to decline, although some participants were later re-diagnosed with normal cognition. Age, sex, and education were significantly associated with trajectory membership for both diagnostic groups, while APOE ɛ4 was only significantly associated with trajectories among MCI participants.Memory trajectory is a strong indicator of dementia risk. If likely trajectory of memory performance can be identified early, such work may allow clinicians to monitor or predict progression of individual patient cognition. This work also shows the importance of longitudinal cognitive testing and monitoring.
View details for DOI 10.1371/journal.pone.0212435
View details for Web of Science ID 000459710700013
View details for PubMedID 30802256
View details for PubMedCentralID PMC6389289
- Longitudinal Brain Atrophy Rates in Transient Ischemic Attack and Minor Ischemic Stroke Patients and Cognitive Profiles FRONTIERS IN NEUROLOGY 2019; 10
Predicting Short-term MCI-to-AD Progression Using Imaging, CSF, Genetic Factors, Cognitive Resilience, and Demographics
2019; 9: 2235
In the Alzheimer's disease (AD) continuum, the prodromal state of mild cognitive impairment (MCI) precedes AD dementia and identifying MCI individuals at risk of progression is important for clinical management. Our goal was to develop generalizable multivariate models that integrate high-dimensional data (multimodal neuroimaging and cerebrospinal fluid biomarkers, genetic factors, and measures of cognitive resilience) for identification of MCI individuals who progress to AD within 3 years. Our main findings were i) we were able to build generalizable models with clinically relevant accuracy (~93%) for identifying MCI individuals who progress to AD within 3 years; ii) markers of AD pathophysiology (amyloid, tau, neuronal injury) accounted for large shares of the variance in predicting progression; iii) our methodology allowed us to discover that expression of CR1 (complement receptor 1), an AD susceptibility gene involved in immune pathways, uniquely added independent predictive value. This work highlights the value of optimized machine learning approaches for analyzing multimodal patient information for making predictive assessments.
View details for DOI 10.1038/s41598-019-38793-3
View details for Web of Science ID 000459092800005
View details for PubMedID 30783207
View details for PubMedCentralID PMC6381141
- Diffusion MRI Indices and Their Relation to Cognitive Impairment in Brain Aging: The Updated Multi-protocol Approach in ADNI3 FRONTIERS IN NEUROINFORMATICS 2019; 13
Association of CSF CD40 levels and synaptic degeneration across the Alzheimer's disease spectrum
2019; 694: 41–45
The CD40 pathway has been implicated in microglial activation, which is considered as a key factor in the pathogenesis of Alzheimer's disease (AD). However, the association of CSF CD40 and synaptic degeneration in living human is not clear. A total of 294 subjects with different severities of cognitive impairments were included in this study: 84 participants with normal cognition, 143 patients with mild cognitive impairment (MCI) and 67 patients with mild AD. Levels of CD40 in CSF were compared among the three groups. Further, several linear regression models were conducted to explore the associations of CSF CD40 and neurogranin levels (reflecting synaptic degeneration) when controlling for age, gender, educational attainment, APOE4 genotype, clinical diagnosis, CSF Aβ42 and tau proteins. We found that CSF CD40 levels were significantly decreased in patients with mild AD compared with healthy controls and MCI patients (control vs. AD, p = 0.0026; MCI vs. AD, p = 0.0268). However, there were no significant differences in CSF CD40 levels between controls and patients with MCI (p = 0.37). In addition, CSF CD40 levels were associated with neurogranin in the pooled sample when controlling for age, gender, educational attainment, APOE4 genotype and diagnosis. In summary, our findings support the notion that the CD40 pathway may contribute to an important mechanism underlying synaptic degeneration in AD.
View details for DOI 10.1016/j.neulet.2018.11.019
View details for Web of Science ID 000459643800007
View details for PubMedID 30447377
MAPT rs242557 variant is associated with hippocampus tau uptake on F-18-AV-1451 PET in non-demented elders
2019; 11 (3): 874–84
The microtubule-associated protein tau gene (MAPT) rs242557 variant is associated with multiple tauopathies and dementia. This study investigated whether it was correlated with brain tau-PET uptake in non-demented elders. Ninety non-demented elders were identified from the Alzheimer's Disease Neuroimaging Initiative cohort. We compared standardized uptake value ratios (SUVRs) of tau-PET tracer 18F-AV-1451 between rs242557 variant carriers and non-carriers in 25 regions of interest (ROIs). The minor allele A was associated with increased hippocampus 18F-AV-1451 uptake in non-demented elders (left: β = 0.111, Bonferroni corrected p = 0.035; right: β = 0.103, Bonferroni corrected p = 0.031). Aβ-positive participants (left: β = 0.206, Bonferroni corrected p = 0.029; right: β = 0.198, Bonferroni corrected p = 0.035) and APOE ε4 non-carriers (left: β = 0.140, Bonferroni corrected p = 0.006; right: β = 0.134, Bonferroni corrected p = 0.004) exhibited approximately the same findings in hippocampus. Considering no obvious associations in other regions, we confirmed the significant correlation of MAPT rs242557 risk variant with increased hippocampus tau deposition in non-demented elders. With higher magnitude signals in the hippocampus that is more likely to be uniquely affected in AD, the tau PET ligand 18F-AV-1451 seemed to possess a specific binding property for AD-like tau pathology.
View details for DOI 10.18632/aging.101783
View details for Web of Science ID 000459482200011
View details for PubMedID 30708351
View details for PubMedCentralID PMC6382414
Random forest prediction of Alzheimer's disease using pairwise selection from time series data
2019; 14 (2): e0211558
Time-dependent data collected in studies of Alzheimer's disease usually has missing and irregularly sampled data points. For this reason time series methods which assume regular sampling cannot be applied directly to the data without a pre-processing step. In this paper we use a random forest to learn the relationship between pairs of data points at different time separations. The input vector is a summary of the time series history and it includes both demographic and non-time varying variables such as genetic data. To test the method we use data from the TADPOLE grand challenge, an initiative which aims to predict the evolution of subjects at risk of Alzheimer's disease using demographic, physical and cognitive input data. The task is to predict diagnosis, ADAS-13 score and normalised ventricles volume. While the competition proceeds, forecasting methods may be compared using a leaderboard dataset selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and with standard metrics for measuring accuracy. For diagnosis, we find an mAUC of 0.82, and a classification accuracy of 0.73 compared with a benchmark SVM predictor which gives mAUC = 0.62 and BCA = 0.52. The results show that the method is effective and comparable with other methods.
View details for DOI 10.1371/journal.pone.0211558
View details for Web of Science ID 000458763900015
View details for PubMedID 30763336
View details for PubMedCentralID PMC6375557
Predicting Alzheimer's disease progression using multi-modal deep learning approach
2019; 9: 1952
Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials.
View details for DOI 10.1038/s41598-018-37769-z
View details for Web of Science ID 000458572500013
View details for PubMedID 30760848
View details for PubMedCentralID PMC6374429
QuickNAT: A fully convolutional network for quick and accurate segmentation of neuroanatomy
2019; 186: 713–27
Whole brain segmentation from structural magnetic resonance imaging (MRI) is a prerequisite for most morphological analyses, but is computationally intense and can therefore delay the availability of image markers after scan acquisition. We introduce QuickNAT, a fully convolutional, densely connected neural network that segments a MRI brain scan in 20 s. To enable training of the complex network with millions of learnable parameters using limited annotated data, we propose to first pre-train on auxiliary labels created from existing segmentation software. Subsequently, the pre-trained model is fine-tuned on manual labels to rectify errors in auxiliary labels. With this learning strategy, we are able to use large neuroimaging repositories without manual annotations for training. In an extensive set of evaluations on eight datasets that cover a wide age range, pathology, and different scanners, we demonstrate that QuickNAT achieves superior segmentation accuracy and reliability in comparison to state-of-the-art methods, while being orders of magnitude faster. The speed up facilitates processing of large data repositories and supports translation of imaging biomarkers by making them available within seconds for fast clinical decision making.
View details for DOI 10.1016/j.neuroimage.2018.11.042
View details for Web of Science ID 000455968400064
View details for PubMedID 30502445
- Communicability disruption in Alzheimer's disease connectivity networks JOURNAL OF COMPLEX NETWORKS 2019; 7 (1): 83–100
Functional signature of conversion of patients with mild cognitive impairment
NEUROBIOLOGY OF AGING
2019; 74: 21–37
The entorhinal-hippocampal circuit is a strategic hub for cognition and the first site affected by Alzheimer's disease (AD). We investigated magnetic resonance imaging patterns of brain atrophy and functional connectivity in an Alzheimer's Disease Neuroimaging Initiative data set that included healthy controls, mild cognitive impairment (MCI), and patients with AD. Individuals with MCI were clinically evaluated 24 months after the first magnetic resonance imaging scan, and the cohort subdivided into sets of individuals who either did or did not convert to AD. The MCI group was also divided into patients who did show or not the presence of AD-related alterations in the cerebrospinal fluid. Patients with AD exhibited the collapse of the long-range hippocampal/entorhinal connectivity, pronounced cortical/subcortical atrophy, and a dramatic decline in cognitive performances. Patients with MCI who converted to AD or patients with MCI who showed the presence of AD-related alterations in the cerebrospinal fluid showed memory deficits, entorhinal/hippocampal hypoconnectivity, and concomitant atrophy of the two regions. Patients with MCI who did not convert to AD or patients with MCI who did not show the presence of AD-related alterations in the cerebrospinal fluid had no atrophy but showed hippocampal/entorhinal hyperconnectivity with selected neocortical/subcortical regions involved in memory processing and brain metastability. This hyperconnectivity may represent a compensatory strategy against the progression of cognitive impairment.
View details for DOI 10.1016/j.neurobiolaging.2018.10.004
View details for Web of Science ID 000455193900003
View details for PubMedID 30408719
Translating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs
NEUROBIOLOGY OF AGING
2019; 74: 135–46
The International Genomics of Alzheimer's Project (IGAP) is a consortium for characterizing the genetic landscape of Alzheimer's disease (AD). The identified and/or confirmed 19 single-nucleotide polymorphisms (SNPs) associated with AD are located on non-coding DNA regions, and their functional impacts on AD are as yet poorly understood. We evaluated the roles of the IGAP SNPs by integrating data from many resources, based on whether the IGAP SNP was (1) a proxy for a coding SNP or (2) associated with altered mRNA transcript levels. For (1), we confirmed that 12 AD-associated coding common SNPs and five nonsynonymous rare variants are in linkage disequilibrium with the IGAP SNPs. For (2), the IGAP SNPs in CELF1 and MS4A6A were associated with expression of their neighboring genes, MYBPC3 and MS4A6A, respectively, in blood. The IGAP SNP in DSG2 was an expression quantitative trait loci (eQTL) for DLGAP1 and NETO1 in the human frontal cortex. The IGAP SNPs in ABCA7, CD2AP, and CD33 each acted as eQTL for AD-associated genes in brain. Our approach for identifying proxies and examining eQTL highlighted potentially impactful, novel gene regulatory phenomena pertinent to the AD phenotype.
View details for DOI 10.1016/j.neurobiolaging.2018.10.017
View details for Web of Science ID 000455193900013
View details for PubMedID 30448613
View details for PubMedCentralID PMC6331247
Amyloid beta-positive subjects exhibit longitudinal network-specific reductions in spontaneous brain activity
NEUROBIOLOGY OF AGING
2019; 74: 191–201
Amyloid beta (Aβ) deposition and cognitive decline are key features of Alzheimer's disease. The relationship between Aβ status and changes in neuronal function over time, however, remains unclear. We evaluated the effect of baseline Aβ status on reference region spontaneous brain activity (SBA-rr) using resting-state functional magnetic resonance imaging and fluorodeoxyglucose positron emission tomography in patients with mild cognitive impairment. Patients (N = 62, [43 Aβ-positive]) from the Alzheimer's Disease Neuroimaging Initiative were divided into Aβ-positive and Aβ-negative groups via prespecified cerebrospinal fluid Aβ42 or 18F-florbetapir positron emission tomography standardized uptake value ratio cutoffs measured at baseline. We analyzed interaction of biomarker-confirmed Aβ status with SBA-rr change over a 2-year period using mixed-effects modeling. SBA-rr differences between Aβ-positive and Aβ-negative subjects increased significantly over time within subsystems of the default and visual networks. Changes exhibit an interaction with memory performance over time but were independent of glucose metabolism. Results reinforce the value of resting-state functional magnetic resonance imaging in evaluating Alzheimer''s disease progression and suggest spontaneous neuronal activity changes are concomitant with cognitive decline.
View details for DOI 10.1016/j.neurobiolaging.2018.10.002
View details for Web of Science ID 000455193900018
View details for PubMedID 30471630
A Novel Method to Estimate Long-Term Chronological Changes From Fragmented Observations in Disease Progression
CLINICAL PHARMACOLOGY & THERAPEUTICS
2019; 105 (2): 436–47
Clinical observations of patients with chronic diseases are often restricted in terms of duration. Therefore, obtaining a quantitative and comprehensive understanding of the chronology of chronic diseases is challenging, because of the inability to precisely estimate the patient's disease stage at the time point of observation. We developed a novel method to reconstitute long-term disease progression from temporally fragmented data by extending the nonlinear mixed-effects model to incorporate the estimation of "disease time" of each subject. Application of this method to sporadic Alzheimer's disease successfully depicted disease progression over 20 years. The covariate analysis revealed earlier onset of amyloid-β accumulation in male and female apolipoprotein E ε4 homozygotes, whereas disease progression was remarkably slower in female ε3 homozygotes compared with female ε4 carriers and males. Simulation of a clinical trial suggests patient recruitment using the information of precise disease time of each patient will decrease the sample size required for clinical trials.
View details for DOI 10.1002/cpt.1166
View details for Web of Science ID 000457465200029
View details for PubMedID 29951994
Medical Image Imputation From Image Collections
IEEE TRANSACTIONS ON MEDICAL IMAGING
2019; 38 (2): 504–14
We present an algorithm for creating high resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a generative model that captures fine-scale anatomical structure across subjects in clinical image collections and derive an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago.
View details for DOI 10.1109/TMI.2018.2866692
View details for Web of Science ID 000457604700017
View details for PubMedID 30136936
Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers
ALZHEIMERS & DEMENTIA
2019; 15 (2): 232–44
Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-β deposition.Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDG PET).Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ1-42 ("A") and three with CSF p-tau181 ("T") (corrected P < .05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy ("N"), respectively (corrected P < .05).This is the first study to show serum-based BA metabolites are associated with "A/T/N" AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.
View details for PubMedID 30337152
Accurate risk estimation of beta-amyloid positivity to identify prodromal Alzheimer's disease: Cross-validation study of practical algorithms
ALZHEIMERS & DEMENTIA
2019; 15 (2): 194–204
The aim was to create readily available algorithms that estimate the individual risk of β-amyloid (Aβ) positivity.The algorithms were tested in BioFINDER (n = 391, subjective cognitive decline or mild cognitive impairment) and validated in Alzheimer's Disease Neuroimaging Initiative (n = 661, subjective cognitive decline or mild cognitive impairment). The examined predictors of Aβ status were demographics; cognitive tests; white matter lesions; apolipoprotein E (APOE); and plasma Aβ42/Aβ40, tau, and neurofilament light.Aβ status was accurately estimated in BioFINDER using age, 10-word delayed recall or Mini-Mental State Examination, and APOE (area under the receiver operating characteristics curve = 0.81 [0.77-0.85] to 0.83 [0.79-0.87]). When validated, the models performed almost identical in Alzheimer's Disease Neuroimaging Initiative (area under the receiver operating characteristics curve = 0.80-0.82) and within different age, subjective cognitive decline, and mild cognitive impairment populations. Plasma Aβ42/Aβ40 improved the models slightly.The algorithms are implemented on http://amyloidrisk.com where the individual probability of being Aβ positive can be calculated. This is useful in the workup of prodromal Alzheimer's disease and can reduce the number needed to screen in Alzheimer's disease trials.
View details for DOI 10.1016/j.jalz.2018.08.014
View details for Web of Science ID 000457693500002
View details for PubMedID 30365928
Accuracy and generalization capability of an automatic method for the detection of typical brain hypometabolism in prodromal Alzheimer disease
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
2019; 46 (2): 334–47
The aim of this study was to verify the reliability and generalizability of an automatic tool for the detection of Alzheimer-related hypometabolic pattern based on a Support-Vector-Machine (SVM) model analyzing 18F-fluorodeoxyglucose (FDG) PET data.The SVM model processed metabolic data from anatomical volumes of interest also considering interhemispheric asymmetries. It was trained on a homogeneous dataset from a memory clinic center and tested on an independent multicentric dataset drawn from the Alzheimer's Disease Neuroimaging Initiative. Subjects were included in the study and classified based on a diagnosis confirmed after an adequate follow-up time.The accuracy of the discrimination between patients with Alzheimer Disease (AD), in either prodromal or dementia stage, and normal aging subjects was 95.8%, after cross-validation, in the training set. The accuracy of the same model in the testing set was 86.5%. The role of the two datasets was then reversed, and the accuracy was 89.8% in the multicentric training set and 88.0% in the monocentric testing set. The classification rate was also evaluated in different subgroups, including non-converter mild cognitive impairment (MCI) patients, subjects with MCI reverted to normal conditions and subjects with non-confirmed memory concern. The percent of pattern detections increased from 77% in early prodromal AD to 91% in AD dementia, while it was about 10% for healthy controls and non-AD patients.The present findings show a good level of reproducibility and generalizability of a model for detecting the hypometabolic pattern in AD and confirm the accuracy of FDG-PET in Alzheimer disease.
View details for DOI 10.1007/s00259-018-4197-7
View details for Web of Science ID 000455817600009
View details for PubMedID 30382303
Disease progression timeline estimation for Alzheimer's disease using discriminative event based modeling
2019; 186: 518–32
Alzheimer's Disease (AD) is characterized by a cascade of biomarkers becoming abnormal, the pathophysiology of which is very complex and largely unknown. Event-based modeling (EBM) is a data-driven technique to estimate the sequence in which biomarkers for a disease become abnormal based on cross-sectional data. It can help in understanding the dynamics of disease progression and facilitate early diagnosis and prognosis by staging patients. In this work we propose a novel discriminative approach to EBM, which is shown to be more accurate than existing state-of-the-art EBM methods. The method first estimates for each subject an approximate ordering of events. Subsequently, the central ordering over all subjects is estimated by fitting a generalized Mallows model to these approximate subject-specific orderings based on a novel probabilistic Kendall's Tau distance. We also introduce the concept of relative distance between events which helps in creating a disease progression timeline. Subsequently, we propose a method to stage subjects by placing them on the estimated disease progression timeline. We evaluated the proposed method on Alzheimer's Disease Neuroimaging Initiative (ADNI) data and compared the results with existing state-of-the-art EBM methods. We also performed extensive experiments on synthetic data simulating the progression of Alzheimer's disease. The event orderings obtained on ADNI data seem plausible and are in agreement with the current understanding of progression of AD. The proposed patient staging algorithm performed consistently better than that of state-of-the-art EBM methods. Event orderings obtained in simulation experiments were more accurate than those of other EBM methods and the estimated disease progression timeline was observed to correlate with the timeline of actual disease progression. The results of these experiments are encouraging and suggest that discriminative EBM is a promising approach to disease progression modeling.
View details for DOI 10.1016/j.neuroimage.2018.11.024
View details for Web of Science ID 000455968400048
View details for PubMedID 30471388
- Dual-Model Radiomic Biomarkers Predict Development of Mild Cognitive Impairment Progression to Alzheimer's Disease FRONTIERS IN NEUROSCIENCE 2019; 12
Longitudinal Functional Brain Mapping in Supernormals
2019; 29 (1): 242–52
Gene regulatory networks (GRNs) play an important role in cellular systems and are important for understanding biological processes. Many algorithms have been developed to infer the GRNs. However, most algorithms only pay attention to the gene expression data but do not consider the topology information in their inference process, while incorporating this information can partially compensate for the lack of reliable expression data. Here we develop a Bayesian group lasso with spike and slab priors to perform gene selection and estimation for nonparametric models. B-spline basis functions are used to capture the nonlinear relationships flexibly and penalties are used to avoid overfitting. Further, we incorporate the topology information into the Bayesian method as a prior. We present the application of our method on DREAM3 and DREAM4 datasets and two real biological datasets. The results show that our method performs better than existing methods and the topology information prior can improve the result.
View details for DOI 10.1093/cercor/bhx322
View details for Web of Science ID 000459518500019
View details for PubMedID 28133490
View details for PubMedCentralID PMC5241943
A delta Homolog for Dementia Case Finding with Replication in the Alzheimer's Disease Neuroimaging Initiative
JOURNAL OF ALZHEIMERS DISEASE
2019; 67 (1): 67–79
Dementia can be empirically described by the latent dementia phenotype "δ" and its various composite "homologs". We have explored δ's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To this end, we have engineered a δ homolog from observed cognitive performance measures common to both projects. Our findings were replicated in randomly selected 50% splits of TARCC data (Group 1, N = 1,747; Group 2, N = 1,755), and then independently in ADNI (N = 1,737). The new δ homolog, i.e., "dT2A" (d-TARCC to ADNI), fit the data of both studies well, and was strongly correlated with dementia severity, as rated by the Clinical Dementia Rating Scale "sum of boxes" (TARCC: r = 0.99, p < 0.001; ADNI: r = 0.96, p < 0.001). dT2A achieved an area under the receiver operating characteristic curve of 0.981 (0.976-0.985) for the discrimination of Alzheimer's disease from normal controls in TARCC, and 0.988 (0.983-0.993) in ADNI. dT2A is the 12th δ homolog published to date, and opens the door to independent replications across these and similar studies.
View details for PubMedID 30507569
Next Generation Sequencing Analysis in Early Onset Dementia Patients
JOURNAL OF ALZHEIMERS DISEASE
2019; 67 (1): 243–56
Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia.To identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing. Common-risk variants of apolipoprotein E (APOE) and prion protein (PRNP) genes were also assessed.We studied 22 EOD patients recruited in Memory Clinics, in the context of studies investigating genetic forms of dementia. Two methodological approaches were applied for the target-Next Generation Sequencing (NGS) analysis of these patients. In addition, we performed progranulin plasma dosage, C9Orf72 hexanucleotide repeat expansion analysis, and APOE genotyping.We detected three rare known pathogenic mutations in the GRN and PSEN2 genes and eleven unknown-impact mutations in the GRN, VCP, MAPT, FUS, TREM2, and NOTCH3 genes. Six patients were carriers of only common risk variants (APOE and PRNP), and one did not show any risk mutation/variant. Overall, 69% (n = 9) of our early onset Alzheimer's disease (EAOD) patients, compared with 34% (n = 13) of sporadic late onset Alzheimer's disease (LOAD) patients and 27% (n = 73) of non-affected controls (ADNI, whole genome data), were carriers of at least two rare/common risk variants in the analyzed candidate genes panel, excluding the full penetrant mutations.This study suggests that EOD patients without full penetrant mutations are characterized by higher probability to carry polygenic risk alleles that patients with LOAD forms. This finding is in line with recently reported evidence, thus suggesting that the genetic risk factors identified in LOAD might modulate the risk also in EOAD.
View details for DOI 10.3233/JAD-180482
View details for Web of Science ID 000457778000020
View details for PubMedID 30530974
Understanding disease progression and improving Alzheimer's disease clinical trials: Recent highlights from the Alzheimer's Disease Neuroimaging Initiative
ALZHEIMERS & DEMENTIA
2019; 15 (1): 106–52
The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset AD. We discuss selected topics that provide insights into AD progression and outline how this knowledge may improve clinical trials.We used standard methods to identify nearly 600 publications using ADNI data from 2016 and 2017 (listed in Supplementary Material and searchable at http://adni.loni.usc.edu/news-publications/publications/).(1) Data-driven AD progression models supported multifactorial interactions rather than a linear cascade of events. (2) β-Amyloid (Aβ) deposition occurred concurrently with functional connectivity changes within the default mode network in preclinical subjects and was followed by specific and progressive disconnection of functional and anatomical networks. (3) Changes in functional connectivity, volumetric measures, regional hypometabolism, and cognition were detectable at subthreshold levels of Aβ deposition. 4. Tau positron emission tomography imaging studies detailed a specific temporal and spatial pattern of tau pathology dependent on prior Aβ deposition, and related to subsequent cognitive decline. 5. Clustering studies using a wide range of modalities consistently identified a "typical AD" subgroup and a second subgroup characterized by executive impairment and widespread cortical atrophy in preclinical and prodromal subjects. 6. Vascular pathology burden may act through both Aβ dependent and independent mechanisms to exacerbate AD progression. 7. The APOE ε4 allele interacted with cerebrovascular disease to impede Aβ clearance mechanisms. 8. Genetic approaches identified novel genetic risk factors involving a wide range of processes, and demonstrated shared genetic risk for AD and vascular disorders, as well as the temporal and regional pathological associations of established AD risk alleles. 9. Knowledge of early pathological changes guided the development of novel prognostic biomarkers for preclinical subjects. 10. Placebo populations of randomized controlled clinical trials had highly variable trajectories of cognitive change, underscoring the importance of subject selection and monitoring. 11. Selection criteria based on Aβ positivity, hippocampal volume, baseline cognitive/functional measures, and APOE ε4 status in combination with improved cognitive outcome measures were projected to decrease clinical trial duration and cost. 12. Multiple concurrent therapies targeting vascular health and other AD pathology in addition to Aβ may be more effective than single therapies.ADNI publications from 2016 and 2017 supported the idea of AD as a multifactorial disease and provided insights into the complexities of AD disease progression. These findings guided the development of novel biomarkers and suggested that subject selection on the basis of multiple factors may lower AD clinical trial costs and duration. The use of multiple concurrent therapies in these trials may prove more effective in reversing AD disease progression.
View details for DOI 10.1016/j.jalz.2018.08.005
View details for Web of Science ID 000455493000011
View details for PubMedID 30321505
Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome
ALZHEIMERS & DEMENTIA
2019; 15 (1): 76–92
Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for confounders and multiple testing.In AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response-related genes implicated in AD showed associations with BA profiles.We report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut-liver-brain axis in the pathogenesis of AD.
View details for PubMedID 30337151
Cortical thickness atrophy in the transentorhinal cortex in mild cognitive impairment
2019; 21: 101617
This study examines the atrophy rates of subjects with mild cognitive impairment (MCI) compared to controls in four regions within the medial temporal lobe: the transentorhinal cortex (TEC), entorhinal cortex (ERC), hippocampus, and amygdala. These regions were manually segmented and then corrected for undesirable longitudinal variability via Large Deformation Diffeomorphic Metric Mapping (LDDMM) based longitudinal diffeomorphometry. Diffeomorphometry techniques were used to compare thickness measurements in the TEC with the ERC. There were more significant changes in thickness atrophy rate in the TEC than medial regions of the entorhinal cortex. Volume measures were also calculated for all four regions. Classifiers were constructed using linear discriminant analysis to demonstrate that average thickness and atrophy rate of TEC together was the most discriminating measure compared to the thickness and volume measures in the areas examined, in differentiating MCI from controls. These findings are consistent with autopsy findings demonstrating that initial neuronal changes are found in TEC before spreading more medially in the ERC and to other regions in the medial temporal lobe. These findings suggest that the TEC thickness could serve as a biomarker for Alzheimer's disease in the prodromal phase of the disease.
View details for DOI 10.1016/j.nicl.2018.101617
View details for Web of Science ID 000460337700030
View details for PubMedID 30552075
Prognosis of conversion of mild cognitive impairment to Alzheimer's dementia by voxel-wise Cox regression based on FDG PET data
2019; 21: 101637
The value of 18F-fluorodeoxyglucose (FDG) PET for the prognosis of conversion from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. In the present work, the identification of cerebral metabolic patterns with significant prognostic value for conversion of MCI patients to AD is investigated with voxel-based Cox regression, which in contrast to common categorical comparisons also utilizes time information.FDG PET data of 544 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were randomly split into two equally-sized datasets (training and test). Within a median follow-up duration of 47 months (95% CI: 46-48 months) 181 patients developed AD. In the training dataset, voxel-wise Cox regressions were used to identify regions associated with conversion of MCI to AD. These were compared to regions identified by a classical group comparison (analysis of covariance (ANCOVA) with statistical parametric mapping (SPM) 8) between converters and non-converters (both adjusted for apolipoprotein E (APOE) genotype, mini-mental state examination (MMSE) score, age, sex and education). In the test dataset, normalized FDG uptake within significant brain regions from voxel-wise Cox- and ANCOVA analyses (Cox- and ANCOVA- regions of interest (ROI), respectively) and clinical variables APOE status, MMSE score and education were tested in different Cox models (adjusted for age, sex) including: (1) only clinical variables, (2) only normalized FDG uptake in ANCOVA-ROI, (3) only normalized FDG uptake from Cox-ROI, (4) clinical variables plus FDG uptake in ANCOVA-ROI, (5) clinical variables plus FDG uptake from Cox-ROI.Conversion-related regions with relative hypometabolism comprised parts of the temporo-parietal and posterior cingulate cortex/precuneus for voxel-wise ANCOVA, plus frontal regions for voxel-wise Cox regression (both p < .01, false discovery rate (FDR) corrected). The clinical-only model (1) and the models based on normalized FDG uptake from Cox-ROI only (2) and ANCOVA-ROI only (3) all significantly predicted conversion to AD (Wald Test (WT): p < .001). The clinical model (1) was significantly improved by adding imaging information in model (4) (Akaike information criterion (AIC) relative likelihood (RL) (1) vs (4): RL < 0.018). There were no significant differences between models (2) and (3), as well as (4) and (5).Voxel-wise Cox regression identifies conversion-related patterns of cerebral glucose metabolism, but is not superior to classical group contrasts in this regard. With imaging information from both FDG PET patterns, the prediction of conversion to AD was improved.
View details for DOI 10.1016/j.nicl.2018.101637
View details for Web of Science ID 000460337700050
View details for PubMedID 30553760
Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization
2018; 18: 553–59
Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.
View details for PubMedID 29868451
INTEGRATING SEMI-SUPERVISED LABEL PROPAGATION AND RANDOM FORESTS FOR MULTI-ATLAS BASED HIPPOCAMPUS SEGMENTATION
IEEE. 2018: 154–57
A novel multi-atlas based image segmentation method is proposed by integrating a semi-supervised label propagation method and a supervised random forests method in a pattern recognition based label fusion framework. The semi-supervised label propagation method takes into consideration local and global image appearance of images to be segmented and segments the images by propagating reliable segmentation results obtained by the supervised random forests method. Particularly, the random forests method is used to train a regression model based on image patches of atlas images for each voxel of the images to be segmented. The regression model is used to obtain reliable segmentation results to guide the label propagation for the segmentation. The proposed method has been compared with state-of-the-art multi-atlas based image segmentation methods for segmenting the hippocampus in MR images. The experiment results have demonstrated that our method obtained superior segmentation performance.
View details for Web of Science ID 000455045600033
View details for PubMedID 30079126
View details for PubMedCentralID PMC6070300
PREDICTING PROGRESSIONS OF COGNITIVE OUTCOMES VIA HIGH-ORDER MULTI-MODAL MULTI-TASK FEATURE LEARNING
IEEE. 2018: 545–48
View details for Web of Science ID 000455045600124
MULTIPLE INCOMPLETE VIEWS CLUSTERING VIA NON-NEGATIVE MATRIX FACTORIZATION WITH ITS APPLICATION IN ALZHEIMER'S DISEASE ANALYSIS
IEEE. 2018: 1402–5
View details for Web of Science ID 000455045600323
Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity.
Brain imaging and behavior
Structural MRI of volunteers deemed "normal" following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as "incidental findings." Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8 % incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26 mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5 gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5 % of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as "normal variants" to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.
View details for PubMedID 27722828
Adolescent Development of Cortical and White Matter Structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking.
2016; 26 (10): 4101-4121
Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development.
View details for DOI 10.1093/cercor/bhv205
View details for PubMedID 26408800
Intravascular ultrasound as a clinical adjunct for carotid plaque characterization.
Journal of vascular surgery
2014; 59 (3): 774-780
Virtual histology intravascular ultrasound (VH IVUS) is valuable for estimating minimal lumen diameter and plaque characterization. The clinical use of IVUS in carotid intervention is not well characterized. We aim to evaluate the role of IVUS in carotid plaque characterization and determine whether it could be predictive of procedure-related microemboli.From July 2010, patients with severe carotid stenosis who underwent elective carotid stenting procedures were prospectively enrolled. IVUS evaluation was performed before stent placement. Patient demographics, comorbidities, and preoperative images were recorded. Comparison of pre- and postoperative diffusion-weighted magnetic resonance images was used to identify the number of procedure-related microemboli. IVUS-derived minimal lumen diameter and vessel wall plaque characteristics were collected. Univariate and multivariate logistic regressions were used to search for associations between IVUS-derived VH data and incidence of microemboli.A total of 38 high-risk patients receiving carotid stenting were enrolled. Among them, 25 patients had type I aortic arches and 17 of the patients were symptomatic (preoperative stroke or transient ischemic attack). VH IVUS data did not show strong associations with microemboli, however, a trend was found between the area of fibrous tissue and median or more incidence of microemboli (P = .099). IVUS-defined vessel diameter maximum was associated with median or more incidence of microemboli (P = .042). In addition, median or more incidence of microemboli showed trends with proximal common carotid artery calcification (P = .056) and with being over the age of 80 (P = .06). Contralateral carotid occlusion or high-grade stenosis was associated with postoperative contralateral microemboli (P = .036).We demonstrate that periprocedural carotid IVUS is clinically feasible. VH IVUS may be helpful in better understanding plaque morphology and determining optimal stent placement. However, its use in predicting microembolization remains limited.
View details for DOI 10.1016/j.jvs.2013.09.028
View details for PubMedID 24571941
View details for PubMedCentralID PMC3937765
Contralateral microemboli following carotid artery stenting in patients with a contralateral internal carotid artery occlusion
40th Annual Meeting of the Society-for-Clinical-Vascular-Surgery (SCVS)
MOSBY-ELSEVIER. 2013: 794–97
Subclinical microembolization identified on diffusion-weighted magnetic resonance imaging is recognized as an important outcome measure for carotid revascularization procedures. It is generally believed that arch manipulation is the primary reason for developing microemboli in the contralateral hemisphere during carotid artery stenting. However, we identified three patients who developed postprocedure microemboli of the contralateral hemisphere despite a known chronic contralateral internal carotid artery occlusion. Our cases highlight that ipsilateral microemboli may be an underappreciated but an important source of contralateral lesions through patent intracranial collateral pathways.
View details for DOI 10.1016/j.jvs.2012.11.114
View details for Web of Science ID 000323616800032
View details for PubMedID 23478504
View details for PubMedCentralID PMC3967720
Prospective neurocognitive evaluation of patients undergoing carotid interventions
40th Annual Meeting of the Society-of-Clinical-Vascular-Surgery (SCVS)
MOSBY-ELSEVIER. 2012: 1571–78
Distal cerebral embolization is a known complication of carotid interventions. We prospectively investigated whether subclinical microembolization seen on postoperative magnetic resonance imaging (MRI) leads to cognitive deficits in patients undergoing carotid revascularization procedures.Patients undergoing carotid interventions and eligible for MRI scanning were recruited. Among 247 patients who received preoperative and postoperative MRI evaluations, 51 also completed neuropsychologic testing before and at 1 month after their procedure. Cognitive evaluation included the Rey Auditory Verbal Learning Test (RAVLT) for memory evaluation and the Mini-Mental State Examination (MMSE) for general cognitive impairment screening.The 51 patients (all men), comprising 16 with carotid artery stenting (CAS) and 35 with carotid endarterectomy (CEA), were a mean age of 71 years (range, 54-89 years). Among them, 27 patients (53%) were symptomatic preoperatively, including 11 who had prior stroke and 16 who had prior preoperative transient ischemic attack symptoms. Most patients had significant medical comorbidities, including hypertension (96%), diabetes (31.3%), coronary artery disease (47%), and chronic obstructive pulmonary disease (15.7%). Two patients (4%) had prior ipsilateral CEA and eight had contralateral carotid occlusion (15.7%). Memory decline evident on RAVLT was identified in eight CAS patients and 13 CEA patients. Eleven patients had evidence of procedure-related microemboli. Although there was no significant difference in baseline cognitive function or memory change between the CEA and CAS cohorts, the CAS cohort had a significantly higher incidence of microembolic lesions. Multivariate regression analysis showed that procedure-related microembolization was associated with memory decline (P = .016) as evident by change in RAVLT. A history of neurologic symptoms was significantly associated with poor baseline cognitive function (MMSE; P = .03) and overall cognitive deterioration (change in MMSE; P = .026), as determined by Wilcoxon rank sum test and linear regression analysis, respectively.Although CEA and CAS are effective in stroke prevention, with minimal neurologic complication, neurocognitive effects remain uncertain. Procedure-associated microembolization and pre-existing neurologic symptoms are associated with poor baseline cognitive function and memory decline after the procedures. Further comprehensive cognitive evaluation to determine the benefit of carotid interventions is warranted.
View details for DOI 10.1016/j.jvs.2012.05.092
View details for Web of Science ID 000311489800014
View details for PubMedID 22889720
Safety and feasibility of a novel transcervical access neuroprotection system for carotid artery stenting in the PROOF Study
JOURNAL OF VASCULAR SURGERY
2011; 54 (5): 1317-1323
Randomized controlled trials have shown that periprocedural rates of stroke and death are higher with carotid artery stenting (CAS) than with carotid endarterectomy (CEA) in the treatment of carotid artery stenosis. Diffusion-weighted magnetic resonance imaging (DW-MRI) has shown higher rates of clinically silent new ischemic brain lesions when CAS is performed as compared with CEA. The Silk Road Medical Embolic PROtectiOn System: First-In-Man (PROOF) Study is a single-arm first-in-man study using the MICHI Neuroprotection System (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcervical access and cerebral embolic protection system. This system enables stent implantation under controlled blood flow reversal of the carotid artery, also known as Flow Altered Short Transcervical Carotid Artery Stenting (FAST-CAS).Between March 2009 and February 2010, a total of 44 subjects were enrolled into the study. The primary composite endpoint was major stroke, myocardial infarction, or death within 30 days. Forty-three patients (97.7%) completed the study through the 30-day endpoint. One patient was lost to follow-up. In a subgroup of consecutive subjects, DW-MRI examinations were performed preprocedure and within 24 to 48 hours after the stent implantation. Blinded independent neuroradiologists reviewed all DW-MRI studies and confirmed the absence or presence of new ischemic brain lesions.All enrolled patients were successfully treated, and no major adverse events were seen through the follow-up period. Thirty-one subjects had DW-MRI examinations. Of these, five patients (16%) had evidence of new ischemic brain lesions but no clinical sequelae. Transient intolerance to reverse flow was reported in 9% of cases, but in all cases, a stent was successfully placed, and the intolerance was managed by minimizing the duration of reverse flow during the procedure.In this first-in-man experience, FAST-CAS using the MICHI Neuroprotection System was shown to be a safe and feasible method for carotid revascularization. DW-MRI findings suggest controlled reverse flow provides cerebral embolic protection similar to that seen with CEA.
View details for DOI 10.1016/j.jvs.2011.04.040
View details for Web of Science ID 000296304500012
View details for PubMedID 21658889
Risk factors predictive of carotid artery stenting-associated subclinical microemboli.
The International journal of angiology : official publication of the International College of Angiology, Inc
2011; 20 (1): 25-32
Subclinical microemboli documented on diffusion-weighted magnetic resonance imaging (DWI) are common following carotid artery stenting (CAS) procedures despite absence of neurological symptoms. This study was to evaluate risk factors predictive of microemboli in patients undergoing protected CAS with a distal embolic protection device. All CAS patients who received pre- and postprocedural magnetic resonance imaging (MRI) evaluations for carotid interventions at a single academic institution from July 2004 to December 2008 were examined. Microemboli were defined by new hyperintensities on postoperative DWI with corresponding decreased diffusion. Risk factors including patient demographics, medical comorbidities, clinical symptoms, lesion morphologies, and perioperative information were examined, and logistic regression analyses were utilized to determine predictors of CAS-related microemboli. A total of 204 patients underwent carotid interventions (76 CAS and 128 carotid endarterectomies) during the study period; 167 of them, including 67 CAS patients, received both preoperative and postoperative MRIs. Among those who underwent protected CAS, the incidence of microemboli was 46.3% despite a relative low incidence of associated neurological symptoms (2.9%). Univariate and multivariate regression analyses showed that date of procedure (odds ratio [OR] 30.6 and p = 0.019) and preoperative transient ischemic attack symptoms (OR 9.24 and p = 0.009) were independent predictors of developing postoperative changes on DWI in the ipsilateral hemisphere, and age >76 years was predictive of having new lesions on DWI in the contralateral hemisphere (OR 6.11 and p = 0.026). Our study underscores that certain risk factors are significantly associated with CAS-related microemboli and that physician experience and patient selection are essential in improving outcome of CAS procedures.
View details for DOI 10.1055/s-0031-1272546
View details for PubMedID 22532767
A Prospective Evaluation of Cerebral Infarction following Transcervical Carotid Stenting with Carotid Flow Reversal
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
2010; 39 (6): 661-666
Cerebral embolisation constitutes the main source of complications during transfemoral carotid artery stenting (CAS) and is associated with a high incidence of silent brain infarction. The goal of this study is to evaluate the incidence of new ischaemic cerebral lesions following transcervical CAS with carotid flow reversal for neuroprotection.Thirty-one consecutive patients underwent transcervical CAS with carotid flow reversal. A stroke scale and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed within 24 h before and after the procedure. DW-MRI studies were compared blindly by two independent neuroradiologists. New hyper-intense DW signals were interpreted as ischaemic infarcts. The progress of all patients was followed for at least 30 days following intervention.All procedures were technically successful. Nineteen (61%) patients were symptomatic Mean carotid flow reversal time was 22 min. There were no major adverse events at 30 days. All patients remained neurologically intact without increase in the stroke scale. Thirty subjects had paired DW-MRI studies. Post-procedural DW-MRI ischaemic infarcts were found in four (12.5%) patients, all ipsilateral to the treated hemisphere and asymptomatic. During follow-up, all stents remained patent and all patients remained stroke-free.These data suggest that transcervical carotid stenting with carotid flow reversal carries a low incidence of new ischaemic infarcts, significantly lower than that reported with transfemoral CAS. The transcervical approach with carotid flow reversal may improve the safety of CAS and has the potential to produce results comparable to those of carotid endarterectomy.
View details for DOI 10.1016/j.ejvs.2010.02.006
View details for Web of Science ID 000279522700001
View details for PubMedID 20303806
Episodic encephalopathy due to an occult spinal vascular malformation complicated by superficial siderosis
CLINICAL NEUROLOGY AND NEUROSURGERY
2010; 112 (1): 82-84
Superficial siderosis (SS) of the central nervous system is a rare condition caused by chronic subarachnoid hemorrhage. Clinical manifestations typically include sensorineural hearing loss and cerebellar ataxia. Recurrent episodic encephalopathy in the setting of SS has not been reported. We describe a unique case of SS in a 67-year-old man with an 8-year history of episodic encephalopathy associated with headache and vomiting. The patient also had a history of progressive dementia, ataxia, and myelopathy. A diagnosis of superficial siderosis was made after magnetic resonance gradient-echo images showed diffuse hemosiderin staining over the cerebellum and cerebral convexities. No intracerebral source of hemorrhage was identified. The patient therefore underwent gadolinium-enhanced spinal MRI which suggested a possible vascular malformation. A therapeutic laminectomy subsequently confirmed an arteriovenous fistula which was resected. In SS, there are often long delays between symptom onset and definitive diagnosis. Early identification is facilitated by magnetic resonance imaging with gradient-echo sequences. When no source of hemorrhage is identified intracranially, then total spinal cord imaging is indicated to assess for an occult source of hemorrhage as occurred in our case.
View details for DOI 10.1016/j.clineuro.2009.09.005
View details for Web of Science ID 000273933700017
View details for PubMedID 19857921
Long-term radiographic outcomes of microemboli following carotid interventions
63rd Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS)
MOSBY-ELSEVIER. 2009: 1314–19
Subclinical microemboli on diffusion-weighted magnetic resonance imaging (DWI) have been identified immediately following carotid revascularization procedures, but the clinical significance and long-term effects are largely unknown. The purpose of this study was to evaluate long-term radiographic outcomes of these DWI lesions.Patients who underwent perioperative magnetic resonance imaging (MRI) evaluations for carotid interventions at a single institution from July 2004 to December 2008 were evaluated, particularly those who had additional follow-up MRI. DWI with apparent diffusion coefficient (ADC), fluid-attenuated inversion recovery (FLAIR), and T2-weighted MRI images were compared to determine long-term effect of microemboli.One-hundred sixty-eight consecutive patients (68 carotid artery stenting [CAS] and 100 carotid endarterectomy [CEA]) who received perioperative MRI were included. All CAS were performed with an embolic protection device. The incidence of microemboli was significantly higher in the CAS group than the CEA group (46.3% and 12%, respectively, P < .05) despite a relative low incidence of procedure-associated neurologic symptoms in both groups (2.9% vs 2%). Thirty patients (16 CAS and 14 CEA) who had follow-up MRI were further analyzed and a total of 50 postoperative DWI lesions (mean size 46.57 mm(2); range 16 to 128 mm(2)) were identified among them. During a mean MRI follow-up of 10 months (range, 2 to 23 months), residual MRI abnormalities were only identified in DWI lesions larger than 60 mm(2) on postoperative MRI and on postoperative FLAIR images (n = 5, P < .001). The CEA group had fewer but larger ipsilateral distributed emboli (total 12 lesions, mean 79 mm(2)) compared with the CAS group (total 38 lesions, mean 27.5 mm(2), P < .05).The majority of microemboli do not have long-term radiographic sequelae. Size and hyperintensity on postoperative FLAIR are predictive of residual brain structure abnormality, and further neurocognitive evaluations are warranted.
View details for DOI 10.1016/j.jvs.2009.07.105
View details for Web of Science ID 000272860900010
View details for PubMedID 19837533
Reduction of postprocedure microemboli following retrospective quality assessment and practice improvement measures for carotid angioplasty and stenting
JOURNAL OF VASCULAR SURGERY
2009; 49 (3): 607-612
We have previously demonstrated a 70% incidence of microemboli on diffusion weighted magnetic resonance imaging (DW-MRI) following carotid angioplasty and stenting (CAS). The purpose of this study is to compare the incidence of microemboli in two distinct time periods when procedural modifications were implemented into a CAS program.Following a retrospective quality review of our CAS cohort (n = 27) from November 2004 through April 2006 (period 1), we enrolled patients (n = 20) from May 2006 through February 2008 (period 2) undergoing CAS into a prospective cohort that included obtaining pre- and postprocedure DW-MRI exams. Procedural modifications during period 2 included the preferential use of closed-cell systems (60% vs 0% in period 1), early heparinization at the initiation of arterial access, and elimination of an arch angiogram. The hospital records of these 47 patients were reviewed; symptoms, comorbidities, lesion characteristics, periprocedural information, and postoperative outcomes were collected. The incidence and location of acute, postprocedural microemboli were determined using DW-MRIs.Twenty (74%) CAS patients from period 1 and seven (35%) patients from period 2 demonstrated acute microemboli on postprocedural DW-MRI (P = .02). The mean number of microemboli in period 1 was 4.1 +/- 5.3 vs 1.5 +/- 2.7 during period 2 (P = .04). Two of the 27 patients (7.4%) during period 1 experienced temporary neurologic changes that resolved within 36 hours. None of the patients during period 2 exhibited any neurologic changes. Patient demographics, comorbidities, and presenting symptoms were similar between the two groups except for smoking prevalence, female presence, and obesity (BMI > 30). Period 2 patients when compared with period 1 had more technically challenging anatomy with more calcified lesions (68% vs 27%), longer lesions (15.9 mm vs 8.2 mm), and higher incidence of ulceration (55% vs 27%) (all P < .04).Despite successful performance of 47 consecutive CAS procedures without permanent neurologic sequelae, significant reductions in periprocedural embolic events as identified via DW-MRI lesions may be achieved through implementation of quality improvement measures identified through continuous outcome analysis. The long-term neurologic benefits associated with reduced subclinical neurologic events remains to be determined.
View details for DOI 10.1016/j.jvs.2008.10.031
View details for PubMedID 19135833
Postprocedural microembolic events following carotid surgery and carotid angioplasty and stenting
21st Annual Meeting of the Western-Vascular-Society
MOSBY-ELSEVIER. 2007: 244–50
The relative safety of percutaneous carotid interventions remains controversial. Few studies have used diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate the safety of these interventions. We compared the incidence and distribution of cerebral microembolic events after carotid angioplasty and stenting (CAS) with distal protection to standard open carotid endarterectomy (CEA) using DW-MRI.From November 2004 through August 2006, 69 carotid interventions (27 CAS, and 42 CEA) were performed in 68 males at a single institution. Pre- and postprocedure DW-MRI exams were obtained on each patient undergoing CAS and the 20 most recent CEA operations. These 46 patients (47 procedures as one patient underwent bilateral CEAs in a staged fashion) constitute our study sample, and the hospital records of these patients (27 CAS and 20 CEA) were retrospectively reviewed. The incidence and location of acute, postprocedural microemboli were determined using DW-MRIs and assessed independently by two neuroradiologists without knowledge of the subjects' specific procedure.Nineteen CAS patients (70%, 95% confidence interval [CI]: 42%-81%) demonstrated evidence of postoperative, acute, cerebral microemboli by DW-MRI vs none of the CEA patients (0%, 95% CI: 0%-17%) (P < .0001). Of the 19 CAS patients with postoperative emboli, nine (47%) were ipsilateral to the index carotid lesion, three (16%) contralateral, and seven (36%) bilateral. The median number of ipsilateral microemboli identified in the CAS group was 1 (interquartile ranges [IQR]: 0-2, range 0-21). The median number of contralateral microemboli identified in the CAS group was 0 (IQR: 0-1, range 0-5). Three (11%) CAS patients experienced temporary neurologic sequelae lasting less than 36 hours. These patients suffered 12 (six ipsilateral and six contralateral), 20 (19 ipsilateral and one contralateral), and zero microemboli, respectively. By univariate analysis, performing an arch angiogram prior to CAS was associated with a higher risk of microemboli (median microemboli 5 vs none, P =.04)Although our early experience suggests that CAS may be performed safely (no permanent neurologic deficits following 27 consecutive procedures), cerebral microembolic events occurred in over two-thirds of the procedures despite the uniform use of distal protection. Open carotid surgery in this series seems to offer a lower risk of periprocedural microembolic events detected by DW-MRI.
View details for DOI 10.1016/j.j.jvs.2007.04.049
View details for PubMedID 17600657
Risk factors for developing postprocedural microemboli following carotid interventions
JOURNAL OF ENDOVASCULAR THERAPY
2007; 14 (4): 561-567
To determine risk factors predictive of microemboli found on diffusion-weighted magnetic resonance imaging (DW-MRI) following carotid angioplasty and stenting (CAS) with distal protection and carotid endarterectomy (CEA).A retrospective review was conducted of all carotid interventions at a single institution between 2004 and 2006. In that time frame, 64 carotid interventions (34 CAS, 30 CEA) were performed in 63 male patients (mean age 69.5 years, range 52 to 91) with DW-MRI scans available for review. Patient characteristics, including age, gender, smoking history, diabetes mellitus, hypertension, hyperlipidemia, obesity (body mass index >30), coronary artery disease (CAD), chronic obstructive pulmonary disease, peripheral vascular disease, and atrial fibrillation, were documented. For the CAS patients, anatomical and procedural characteristics, including fluoroscopy time, contrast volume, performance of an arch angiogram, and lesion anatomy, were recorded. Bivariate analyses were performed to determine which parameters were associated with the occurrence of acute postprocedural microemboli found on DW-MRI by 2 blinded neuroradiologists.Twenty-four (71%) of the 34 CAS patients and 1 (3%) of the 30 CEA patients demonstrated new cerebral microemboli postoperatively. In the bivariate analyses of all patient, anatomical, and procedural characteristics, only a history of CAD was associated with an increased risk of microemboli; 20 (80%) of the 25 patients who had postprocedure microemboli had CAD compared to 18 (46%) of 39 patients without microemboli (p=0.007). Twenty (53%) of the 38 (59%) patients with CAD developed microemboli compared to 5 (19%) of the 26 patients without CAD (p=0.007). All other patient, procedural, and anatomical characteristics were not found to be independent risk factors predictive of postprocedure microemboli.CAS with distal protection carries a significantly greater risk for developing new microemboli compared to CEA. Of all the risk factors analyzed, only a history of CAD emerged as an independent risk factor for the development of microemboli following carotid intervention. This finding may influence the decision to perform CAS in patients deemed high risk solely due to the presence of CAD.
View details for PubMedID 17696633
Hippocampal volume, PTSD, and alcoholism in combat veterans
AMERICAN JOURNAL OF PSYCHIATRY
2006; 163 (4): 674-681
Studies imposing rigorous control over lifetime alcohol intake have usually not found smaller hippocampal volumes in persons with posttraumatic stress disorder. Because the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. To test the hypothesis that a smaller hippocampus in PTSD is unrelated to comorbid alcoholism or to chronicity, this study estimated hippocampal volume in a relatively large group (N=99) of combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. In subjects with histories of alcoholism, unadjusted hippocampal volume was 9% smaller in persons with PTSD than in those without PTSD. In nonalcoholic subjects, the PTSD-related difference in hippocampal volume was 3%. The failure to observe a strong association between PTSD and hippocampal volume in nonalcoholic subjects was not ascribable to younger age, reduced PTSD chronicity, or lower PTSD symptom severity. The possibility that smaller hippocampal volume is limited to groups in which PTSD is compounded by comorbid alcoholism is not necessarily incompatible with results suggesting a smaller hippocampus is predispositional to PTSD. Further examination of the role of alcoholism and other comorbid conditions in studies of brain structure and function in PTSD appears warranted.
View details for Web of Science ID 000236541200020
View details for PubMedID 16585443
- reversible posterior leukoencephalopathy syndrome and bevacizumab NEJM 2006; 354 (9): 980-981
- Neurolmaging and clinical manifestations of bilateral temporal encephalopathy secondary to murine typhus infection AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION 2005; 84 (4): 310-311
Practical imaging of the spine and spinal cord.
Topics in magnetic resonance imaging
2003; 14 (6): 438-443
Magnetic resonance imaging is the imaging method of choice in most diseases of the spinal canal and cord. Many pulse sequences are available, and in this era of increased expectations and diminishing resources, a practical approach to the most efficient spine imaging is needed. Our strategy is a series of protocols tailored to the particular area of the spine and the disease process suspected.
View details for PubMedID 14872164
- Intracranial dural arteriovenous fistula causing a myelopathy SPINAL CORD 2002; 40 (9): 438-442
Imaging of cerebral and brain stem amyloidomas
AMERICAN JOURNAL OF NEURORADIOLOGY
2001; 22 (7): 1353-1356
CNS amyloidomas are rare. We describe a 51-year-old man with isolated amyloidomas in the cerebral white matter and in the pons. CT and MR imaging showed a heterogeneous, enhancing mass in the deep cerebral white matter. A second, much smaller linear serpiginous lesion was present in the pons.
View details for Web of Science ID 000170437200021
View details for PubMedID 11498426
Single- versus multi-detector row CT of the brain: Quality assessment
2001; 219 (3): 750-755
To assess the quality of brain computed tomographic (CT) studies obtained with a four-channel multi-detector row CT scanner compared with those obtained with a single-detector row CT scanner.Forty-seven patients referred for brain CT were imaged with both single- and multi-detector row scanners. Single-detector row CT images were acquired by using a 5-mm-collimated beam in the transverse mode. Multi-detector row CT images were acquired in four simultaneous 2.5-mm-thick sections, which were combined in projection space to create two contiguous 5-mm-thick sections. Two neuroradiologists blinded to the acquisition technique independently evaluated the CT image pairs, which were presented in a stacked mode on two adjacent monitors. Each study was graded by using a five-point scale for posterior fossa artifact, overall image quality, and overall preference.Multi-detector row CT studies were acquired 1.8 times faster than single-detector row CT studies (0.92 vs 0.52 section per second). Multi-detector row CT posterior fossa artifact was less than single-detector row CT posterior fossa artifact in 87 (93%) of 94 studies. Overall preference was expressed for multi-detector row CT in 84 (89%) of 94 studies. The differences in mean posterior fossa artifact scores (P <.001) and mean overall image quality scores (P =.001) were significant.Brain CT images obtained with multi-detector row CT resulted in significantly less posterior fossa artifact and were preferred to single-detector row CT images.
View details for Web of Science ID 000168864800024
View details for PubMedID 11376264
Infratentorial traumatic brain hemorrhage: May outcome be predicted by initial GCS?
49th Annual Meeting of the Congress-of-Neurosurgeons
LIPPINCOTT WILLIAMS & WILKINS. 2000: 1076–82
Overall prognosis of nonpenetrating traumatic brain hemorrhage may be predicted by neurologic function days after insult. The relationship between immediate function and outcome has not been examined for infratentorial traumatic brain hemmorhage (iTBH) identified on computed tomographic (CT) scan. Given the severity of brain stem injury, it is conceivable that immediate function may be predictive.A retrospective review of 1,500 brain injuries occurring at our institution identified 18 patients (1.2%) with iTBH on CT scan (eight brain stem, five cerebellum, five both). Demographics, supratentorial injuries, and outcome at 6 months (Glasgow Outcome Scale) were recorded.Initial Glasgow Coma Scale (GCS) in 11 patients was less than 5 (group I). Seven patients had GCS scores greater than or equal to 6 (group II). Nine patients in group I either died or were vegetative. In group II, one died; none were vegetative (p < 0.02). Regression analysis demonstrated a strong correlation between initial GCS and Glasgow Outcome Scale scores at 6 months for all patients (p < 0.001).We conclude that initial GCS score may be predictive of long-term outcome in patients with CT scan evidence of iTBH-a relationship to be explored further for prognostic information.
View details for Web of Science ID 000165909500018
View details for PubMedID 11130492
Updates and controversies in spinal imaging.
Topics in magnetic resonance imaging
2000; 11 (4): 213-217
View details for PubMedID 11133062
Sonography, CT, and MR imaging: A prospective comparison of neonates with suspected intracranial ischemia and hemorrhage
AMERICAN JOURNAL OF NEURORADIOLOGY
2000; 21 (1): 213-218
Sonography, CT, and MR imaging are commonly used to screen for neonatal intracranial ischemia and hemorrhage, yet few studies have attempted to determine which imaging technique is best suited for this purpose. The goals of this study were to compare sonography with CT and MR imaging prospectively for the detection of intracranial ischemia or hemorrhage and to determine the prognostic value(s) of neuroimaging in neonates suspected of having hypoxic-ischemic injury (HII).Forty-seven neonates underwent CT (n = 26) or MR imaging (n = 24) or both (n = 3) within the first month of life for suspected HII. Sonography was performed according to research protocol within an average of 14.4 +/- 9.6 hours of CT or MR imaging. A kappa analysis of interobserver agreement was conducted using three independent observers. Infants underwent neurodevelopmental assessment at ages 2 months (n = 47) and 2 years (n = 26).CT and MR imaging had significantly higher interobserver agreement (P < .001) for cortical HII and germinal matrix hemorrhage (GMH) (Grades I and II) compared with sonography. MR imaging and CT revealed 25 instances of HII compared with 13 identified by sonography. MR imaging and CT also revealed 10 instances of intraparenchymal hemorrhage (>1 cm, including Grade IV GMH) compared with sonography, which depicted five. The negative predictive values of neuroimaging, irrespective of technique used, were 53.3% and 58.8% at the 2-month and 2-year follow-up examinations, respectively.CT and MR imaging have significantly better interobserver agreement for cortical HII and GMH/intraventricular hemorrhage and can reveal more instances of intraparenchymal hemorrhage compared with sonography. The absence of neuroimaging findings on sonograms, CT scans, or MR images does not rule out later neurologic dysfunction.
View details for Web of Science ID 000085055900042
View details for PubMedID 10669253
In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1999; 23 (10): 1629-1636
Neuropathological studies use the presence of mammillary body (MB) pathology as a cardinal, diagnostic feature of Wernicke's encephalopathy (WE) in neuropsychiatric diseases, most notably alcoholism. Although Korsakoffs Syndrome (KS), which is marked behaviorally by dense global amnesia, is a typical sequela of WE, it remains controversial whether these two conditions necessarily co-occur and whether MB pathology is therefore a diagnostic requisite for KS.We investigated these issues by examining, in vivo, 24 nonamnesic alcoholics (ALC), 5 amnesic alcoholics (KS), and 51 normal controls with three-dimensional MRI and memory testing. MB volume was determined from successive, 1 mm thick slices.The ALC group had significantly smaller MB volumes bilaterally (mean = 54.5 +/- 22.0 mm3) than controls (mean = 66.3 +/- 17.1 mm3), and the KS group had even smaller MB volumes than the ALC group (mean = 20.7 +/- 14.8 mm3). Only 2 ALC patients met historical clinical criteria for past WE, and their MB volumes were well within range of the remaining 22 ALC patients. Although all five KS patients met historical clinical criteria for WE, three KS did not have accompanying dementia and had the same degree of MB volume loss as the ALC; the remaining two KS had accompanying dementia and MB volumes half the volume of the ALC group and of KS patients without dementia.These findings provide volumetric in vivo evidence that: (1) MB volume deficits do occur in alcoholics without amnesia, although these deficits are not present in ail such alcoholics; (2) greater MB volume deficits are present in alcoholics with clinically detectable amnesia or dementia; (3) MB shrinkage is related to severity of cognitive and memory dysfunction, which suggests a continuum of MB pathology in chronic alcoholism to KS; and (4) the presence of WE in all of the KS patients and in the two ALC patients with the greatest long-term declarative memory deficit supports the possibility of an additional and unique pathology distinguishing nonamnesic and amnesic alcoholism.
View details for Web of Science ID 000083279500011
View details for PubMedID 10549995
- Multidetector helical CT angiography: Poor cousin or contender? AMERICAN JOURNAL OF NEURORADIOLOGY 1999; 20 (5): 731-731
Neuropsychological and motor functioning after unilateral anatomically guided posterior ventral pallidotomy - Preoperative performance and three-month follow-up
NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY
1998; 11 (3): 136-145
This study presents baseline and 3-month follow-up motor and neuropsychological data for 22 patients with Parkinson's disease (PD) who underwent anatomically guided unilateral posterior ventral pallidotomy (PVP). Postsurgical improvements were seen in psychomotor speed, fine motor accuracy, and dyskinesia, whereas grip strength decreased on the side contralateral to the surgery. No change was detected in overall level of cognitive functioning, nor were changes demonstrated in memory, language, or working memory when the entire sample of patients was evaluated. When the group was divided on the basis of side of surgery, patients with left-sided pallidotomies showed a decline in verbal fluency. Patients and caregivers reported improvement in psychosocial functioning. These initial findings of improved motor performance and largely unaffected cognitive functions are consistent with results obtained with functional PVP and provide support for the use of anatomically guided posterior ventral pallidotomy in the treatment of motor symptoms of PD.
View details for Web of Science ID 000078976500004
View details for PubMedID 9742512
Familial arteriopathic leukoencephalopathy: Imaging and neuropathologic findings
AMERICAN JOURNAL OF NEURORADIOLOGY
1998; 19 (3): 469-475
We present the clinical, imaging, and neuropathologic data for a family with an autosomal dominant, nonhypertensive, progressive cerebral arteriopathy and leukoencephalopathy. Clinical presentation was characterized by progressive dementia, gait abnormalities, and, in some, Parkinson-like symptoms. MR abnormalities, consisting of white matter T2 hyperintensities and cystic-appearing T1 hypointensities, were present in seven family members. The basal ganglia also showed cystic abnormalities. Neuropathologic examination in two cases revealed numerous lacunar infarctlike lesions, extensive demyelination, and widespread hyalinization of arteriolar walls with karyolysis and granular deposits within the media. These findings appear to constitute further evidence of a genetically determined arteriopathic leukoencephalopathy.
View details for Web of Science ID 000072548100013
View details for PubMedID 9541301
Quantification of cerebellar structures with MRI
1997; 75 (3): 159-171
Methodological issues have limited neuroimaging studies of cerebellar structures. In this article we describe a method that addresses some of these limitations and phantom studies that examine the validity of the image manipulations. We compared volumes derived from 3D Spoiled Gradient Recalled Acquisition MR images sliced with respect to three different alignment methods: one based on cerebellar landmarks, another on cerebral landmarks and a third on the plane of acquisition. Examination of coefficients of variation, coefficients of error and convergent validity suggests that although regional cerebellar volumes based on cerebellar landmarks provide the best estimates of the true volumes, observed differences between volume measurements from alignments based on cerebellar or cerebral landmarks were generally not significant and were inconsequential. In this case, the measure was improved with alignment along local, relevant cerebellar landmarks. A set of phantom experiments showed that realignment, reslicing and interpolation in 3-dimensional image processing exerted, at most, trivial distortion on the estimates of actual object volumes.
View details for Web of Science ID 000071115400003
View details for PubMedID 9437773
Proton magnetic resonance spectroscopy of a gray matter heterotopia
1996; 47 (6): 1571-1574
We used proton magnetic resonance spectroscopy to examine resonances representing metabolites containing N-acetyl (NA) groups (predominantly N-acetyl aspartate), choline, and creatine within a large left-hemispheric gray matter heterotopia (GMH) in a 35-year-old man with corpus callosum agenesis. In contrast to normal brain tissue, including gray matter regions, heterotopic gray matter was characterized by relatively increased choline and creatine resonances and a normal NA signal. These data suggest increased cellular activity or persistent immature neuronal tissue in GMH relative to unaffected tissue.
View details for Web of Science ID A1996VX50700040
View details for PubMedID 8960748
Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1996; 20 (8): 1489-1495
Mammillary body and cerebellar atrophy have been described as postmorten neuropathologic markers of Korsakoff's syndrome. This study examined whether shrinkage in the mammillary bodies and cerebellum is present consistently in amnesic chronic alcoholics during life and whether the degree of abnormality in these patients differs from that in nonamnesic alcoholic and healthy controls. The severity of shrinkage in the mammillary bodies, cerebellar hemispheres, and cerebellar vermis visualizable on MRI scans was rated on a three-point scale in 33 chronic nonamnesic alcoholics, 9 amnesic alcoholics, and 20 healthy controls. Although both alcoholic groups showed significant mammillary body and cerebellar shrinkage relative to controls, the two patient groups did not differ from each other. Furthermore, four of eight amnesic patients in our sample did not demonstrate clinically significant mammillary body atrophy. These results suggest that alcoholism is associated with mammillary body and cerebellar tissue volume loss but do not provide evidence that these markers distinguish accurately between amnesic and nonamnesic patients. In addition, they suggest that visualizable mammillary body atrophy is not necessary for the development of amnesia in alcoholic patients.
View details for Web of Science ID A1996VU64400025
View details for PubMedID 8947329
Computed tomography slice-by-slice target-volume delineation for stereotactic proton irradiation of large intracranial arteriovenous malformations: An iterative approach using angiography, computed tomography, and magnetic resonance imaging
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
1996; 35 (3): 555-564
Target-volume delineation for stereotactic irradiation is problematic for large and irregularly shaped arteriovenous malformations (AVMs). The purpose of this report is to quantify modifications in the target volume that result from iterative treatment planning that incorporates multimodality imaging data.Stereotactic neuroimaging procedures were performed for 20 consecutive patients with AVM volumes > 10 cm3. Angiographically defined extrema were transformed into computed tomography (CT) space. The resulting target contours were then modified by a multidisciplinary treatment planning team after iterative review of angiographic, CT, and magnetic resonance imaging (MRI) data. Volumes of interest and dose-volume histograms for proton irradiation were calculated before and after iterative target delineation.Initial (angiographically defined) target volumes ranged from 15.3 to 96.1 cm3 (mean, 43.6 cm3). Final (iteratively defined) target volumes ranged from 10.7 to 114.0 cm3 (mean, 38.4 cm3). The volume of presumed normal tissue excluded by iterative planning ranged from 2.6 to 47.0 cm3 (mean, 15.5 cm3). Initially untargeted AVM, most commonly obscured by embolization material, was identified in all cases (range, 0.3 to 57.8 cm3; mean, 10.3 cm3). Corresponding dose-volume histograms demonstrated marked differences regarding lesion coverage and sparing of normal tissue structures.Iterative target-volume delineation resulted in significant modifications from initial, angiographically defined target volumes. Substantial amounts of apparently normal tissue were excluded from the final target, and additional abnormal vascular structures were identified for incorporation. We conclude that an iterative multimodality approach to target-volume delineation may improve the overall results for stereotactic irradiation of large and complex AVMs.
View details for Web of Science ID A1996UT72400018
View details for PubMedID 8655380
Neonatal intracranial ischemia and hemorrhage: Diagnosis with US, CT, and MR imaging
1996; 199 (1): 253-259
To assess the usefulness of ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging in the detection of intracranial hemorrhage and ischemia in newborns.Seventy-six neonates who underwent US within 72 hours of CT or MR examination were studied. Four observers rated images for the presence of germinal matrix hemorrhage (GMH), intraventricular hemorrhage (IPH), extraaxial hemorrhage, and hypoxic-ischemic encephalopathy.In 39% of neonates, CT and MR imaging provided greater confidence than US for the diagnosis or exlusion of neonatal ischemia or hemorrhage. Kappa analysis revealed significantly better interobserver agreement with CT than with US for the detection of GMH, IVH, IPH, and cortical infarction or ischemia (P <.005). Interobserver agreement was significantly better with MR imaging than with US for the detection of GMH, IVH, and cortical infarction or ischemia (P < .005).Sensitivity and interobserver agreement are better with MR imaging and CT than with US for the detection of neonatal cortical ischemia or infarction.
View details for PubMedID 8633155
Cost-effectiveness of endovascular therapy in the surgical management of cerebral arteriovenous malformations
AMERICAN JOURNAL OF NEURORADIOLOGY
1996; 17 (2): 247-254
To determine the economic effect of endovascular therapy in conjunction with surgery for cerebral arteriovenous malformations.Twenty-five patients with arteriovenous malformations treated with embolization and surgical excision or embolization alone were compared with reported results in 475 patients who underwent surgery only. Respective mean morbidity and mortality rates were calculated and a cost-effectiveness analysis was performed in terms of costs of hospitalization, professional fees, and other direct procedural and indirect costs. Quality-adjusted life-years saved were also calculated.The net effective treatment cost per cure was $71 366 (in 1992 dollars) for embolization and surgery compared with $78 506 for surgery alone. This resulted in a 9% average savings per treated patient. Cost per quality-adjusted life-year calculations resulted in a cost of $6734 for embolization and surgery and $9814 for surgical treatment alone, with savings as high as 34% when endovascular therapy was used.Endovascular therapy in conjunction with surgery resulted in significant economic benefits for treatment of cerebral arteriovenous malformations.
View details for Web of Science ID A1996TW23400015
View details for PubMedID 8938294
White matter MR hyperintensities in adult patients with congenital rubella
AMERICAN JOURNAL OF NEURORADIOLOGY
1996; 17 (1): 99-103
To observe and quantify white matter hyperintensities on MR images in adults with schizophrenialike symptoms who had had congenital rubella, in order to elucidate the neuropathologic sequelae of this perinatal viral infection and to explore the potential relationship of these lesions to schizophrenia.Eleven deaf adult patients with documented prenatal rubella virus infection and schizophrenialike symptoms were compared with 19 age-matched patients with early-onset schizophrenia who did not have congenital rubella and with 18 age-matched control subjects. All MR images (obtained at 1.5 T) were evaluated by a neuroradiologist who was blinded to diagnosis and were rated for white matter lesions on a five-point scale: 0 = no lesions; 1 = 1 lesion less than 1 mm in diameter; 2 = 1 to 4 lesions 1 mm or greater; 3 = 5 to 10 lesions; 4 = more than 10 lesions or a single lesion more than 1 cm in diameter. In addition, the white matter hyperintensities were volumed objectively with a manual threshold technique.Ratings of white matter lesions were significantly higher in the rubella patients than in the control subjects: 6 of the 11 patients had ratings greater than 1 compared with 1 of the 18 control subjects and none of the 19 schizophrenic patients. Also, MR images in five rubella patients received ratings at the highest end of the scale of abnormality (3 or 4). The white matter hyperintensities were characterized as bilateral T2 signal hyperintensities in periventricular and subcortical regions, punctate or linear in shape; they were observed predominantly in parietal lobes.This quantitative MR study of adult rubella patients disclosed abnormal white matter lesions that may correspond to neurovascular lesions known neuropathologically. They do not appear to be directly related to schizophrenialike symptoms.
View details for Web of Science ID A1996TP96800017
View details for PubMedID 8770257
- SYNCHRONOUS PRIMARY BRAIN-TUMORS ACADEMIC RADIOLOGY 1995; 2 (10): 926-929
BRAIN DYSMORPHOLOGY IN ADULTS WITH CONGENITAL-RUBELLA PLUS SCHIZOPHRENIALIKE SYMPTOMS
1995; 37 (11): 764-776
Brain morphology was quantified with magnetic resonance imaging (MRI) in adult patients with congenital rubella who also had schizophrenialike symptoms. MRIs were compared with those of adult early-onset schizophrenic patients without congenital rubella and age-matched healthy control subjects. The rubella patients had significantly smaller intracranial volumes and shorter stature than the schizophrenic patients or the controls; however, both patient groups had smaller cortical gray matter, but not white matter, volumes than the control group, even when the MRI volumes were corrected for head size and age. In addition, both patient groups showed significant enlargement of the lateral ventricles but not cortical sulci when compared with expected values of normal adults of the same age and head size. Overall, the pattern of dysmorphology was identical in the rubella and the schizophrenic groups. The observations in the rubella group are consistent with a developmental lesion that limits full brain growth, with the small intracranial volume due at least in part to a severe cortical gray matter volume deficit. Thus, the brain dysmorphology of congenital rubella may provide an instance of prenatal viral infection that models the schizophrenic pattern and provides indirect support for a developmental hypothesis of the neuropathogenesis of schizophrenia.
View details for Web of Science ID A1995RA24400002
View details for PubMedID 7647161
1995; 194 (3): 954-963
View details for Web of Science ID A1995QG91800065
COMBINED USE OF ENDOVASCULAR COILS AND SURGICAL CLIPPING FOR INTRACRANIAL ANEURYSMS
AMERICAN JOURNAL OF NEURORADIOLOGY
1995; 16 (1): 15-18
We report two cases in which combined surgical clipping and endovascular coils have been used to treat intracranial aneurysms. In one case, a 59-year-old woman with multiple episodes of subarachnoid hemorrhage had an anterior communicating artery aneurysm, which was initially treated with coils and then clipped to occlude the aneurysm securely. In the second case, a broad-based cavernous aneurysm could not be completely surgically occluded, but surgical clipping did decrease the aneurysm neck size, allowing it to be successfully treated with coils.
View details for PubMedID 7900585
STENT PLACEMENT FOR ARTERIAL AND VENOUS CEREBROVASCULAR-DISEASE - PRELIMINARY EXPERIENCE
1994; 191 (2): 441-446
To report initial clinical experience with stent placement in the cerebrovascular circulation.Four patients underwent arterial or venous stent placement. Two patients had cervical internal carotid artery dissections, with aneurysms and stenoses of the distal cervical carotid artery. Two patients had venous occlusive disease involving the major dural sinuses, with substantial pressure gradients across the stenoses.Immediately after stent placement, the true arterial lumina returned to normal diameter and both carotid aneurysms were more than 90% occluded. Follow-up angiography demonstrated continued improvement in the arterial aneurysms. Both patients with dural sinus venous occlusive disease showed substantial improvement of the sinus stenoses and substantial reversal of the pressure gradients after venous stent placement. At follow-up, these patients have done well.This preliminary experience suggests there may be a role for stents in the management of arterial and venous cerebrovascular disease, including carotid artery dissection and venous occlusive disease.
View details for PubMedID 8153318
A MECHANICALLY DETACHABLE COIL FOR THE TREATMENT OF ANEURYSMS AND OCCLUSION OF BLOOD-VESSELS
AMERICAN JOURNAL OF NEURORADIOLOGY
1994; 15 (5): 821-827
To evaluate mechanically detachable coil designs capable of controlled and instantaneous release within an aneurysm or vascular space.Three mechanically detachable coil designs, clamped ball, looped ribbon, and interlocking cylinder, were evaluated using in vitro and in vivo testing to study reliability of coil release, retractability, and coil behavior in a microcatheters. In vitro tests were performed using a glass side-wall aneurysm model and conventional microcatheters. In vivo experiments in rabbits included aneurysm models (side-wall and bifurcation) and arterial occlusions (carotid and renal).All three designs deployed coils easily and were able to retract coils after partial deployment. Motion was seen in previously released coils and in the catheter when using the clamped ball and looped ribbon designs. The interlocking cylinder design did not cause similar motion. When compared with the other two designs, the interlocking cylinder had significantly greater separation forces between coil pusher and coil while in the catheter. Frictional forces within the catheter were lower for the interlocking cylinder mechanically detachable coil design than for a commercially available conventional coil and coil pusher system. During in vivo testing, the mechanically detachable coil design operated smoothly in the catheter, providing good release and retraction in aneurysms and straight vessels.The interlocking cylinder mechanically detachable coil design is superior to the other two tested designs. The mechanically detachable coil was reliably delivered and detached in in vivo testing for the treatment of aneurysms and for the occlusion of blood vessels.
View details for PubMedID 8059648
CORRELATION OF PRESSURE MEASUREMENTS WITH ANGIOGRAPHIC CHARACTERISTICS PREDISPOSING TO HEMORRHAGE AND STEAL IN CEREBRAL ARTERIOVENOUS-MALFORMATIONS
AMERICAN JOURNAL OF NEURORADIOLOGY
1994; 15 (5): 809-813
To determine whether there is a physiologic explanation for the predisposition of patients with certain angiographic characteristics to symptoms of hemorrhage and steal.Superselective transcatheter feeding arterial pressure and mean arterial pressure measurements were obtained before embolotherapy in 32 patients with cerebral arteriovenous malformations. Pressures were correlated with previously described angioarchitectural characteristics predisposing to hemorrhage and steal. These included size of the arteriovenous malformation, feeding artery length, venous drainage pattern, and angiomatous change.The feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios were significantly decreased in patients with angiomatous change. Feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios progressively decreased as lesions went from peripheral, to mixed, to central venous drainage. A trend for lower feeding arterial pressure was also demonstrated with greater feeding pedicle length. A statistically significant correlation could not be demonstrated between feeding arterial pressure or feeding arterial pressure/mean arterial pressure ratios and size of the arteriovenous malformation, hemorrhage, or symptoms of steal.Feeding arterial pressure measurements help provide a physiologic basis for the relationship between certain angiographic characteristics and hemorrhage and steal symptoms in patients with arteriovenous malformation.
View details for Web of Science ID A1994NL03200002
View details for PubMedID 8059646
INTRAARTERIAL PAPAVERINE FOR THE TREATMENT OF VASOSPASM
AMERICAN JOURNAL OF NEURORADIOLOGY
1993; 14 (4): 822-826
The authors describe the use of intraarterial papaverine to treat vasospasm following subarachnoid hemorrhage. Two cases are reported: a 40-year-old woman with a posterior communicating artery aneurysm and a 67-year-old man with a posterior cerebral artery aneurysm. Both patients developed symptomatic, angiographically demonstrated vasospasm that responded to papaverine infusion.
View details for PubMedID 8352152
ENDOVASCULAR TREATMENT OF CEREBRAL ARTERIOVENOUS-MALFORMATIONS FOLLOWING RADIOSURGERY
AMERICAN JOURNAL OF NEURORADIOLOGY
1993; 14 (2): 297-303
Previous reports of embolization of cerebral arteriovenous malformations (AVMs) have evaluated the technique as adjunctive therapy prior to surgery or radiosurgery; our aim is to assess the role of embolization following radiosurgery.Six patients previously treated with radiosurgery and showing no response as judged by cerebral angiography were embolized 24 to 55 months (mean 34.3 months) after initial radiosurgery.In five of six, a significant volume reduction was achieved ranging from 60%-100% (mean 74%). One patient was treated with embolization alone and the AVM has remained fully thrombosed 2 years after treatment. Three patients underwent surgical resection for cure after embolization, and two patients had repeat radiosurgery to a significantly smaller AVM volume. One patient had an asymptomatic carotid dissection at embolization; however, no clinically apparent complications occurred in the treatment group.Embolization can be used after radiosurgery to assist in the management of those AVMs that have not responded to initial treatment.
View details for PubMedID 8456702
- INTERVENTIONAL NEURORADIOLOGY - A NEW APPROACH TO DIFFICULT VASCULAR-LESIONS OF THE BRAIN WESTERN JOURNAL OF MEDICINE 1993; 158 (1): 68-69
BRAIN GRAY AND WHITE MATTER VOLUME LOSS ACCELERATES WITH AGING IN CHRONIC-ALCOHOLICS - A QUANTITATIVE MRI STUDY
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1992; 16 (6): 1078-1089
Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks post-withdrawal, and 43 normal healthy controls, all right-handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using a semi-automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age-related increase in brain vulnerability to chronic alcohol abuse.
View details for Web of Science ID A1992KD40900012
View details for PubMedID 1471762
CRANIAL HYPERTROPHIC INTERSTITIAL NEUROPATHY
AMERICAN JOURNAL OF NEURORADIOLOGY
1992; 13 (6): 1552-1554
The authors describe a patient with complex cranial neuropathy caused by pathologically proved hypertrophic interstitial neuropathy. Plain and contrast-enhanced MR studies were performed prior to surgical exploration. Surgical complications caused the patient's death and a complete pathology study was done. Though nonspecific, MR proved helpful in determining the extent of disease and areas of anatomic involvement.
View details for PubMedID 1442431
INTRANIDAL ANEURYSMS IN CEREBRAL ARTERIOVENOUS-MALFORMATIONS - EVALUATION AND ENDOVASCULAR TREATMENT
1992; 183 (2): 355-360
Patients with cerebral arteriovenous malformations (AVMs) have an increased risk of hemorrhage if an intranidal aneurysm is present. Angiograms from 125 patients with cerebral AVMs were evaluated, and 15 (12%) had intranidal aneurysms. All 15 patients had a history of bleeding. Five patients underwent particulate or liquid embolization before surgical excision of or radiation therapy for the AVM. All aneurysms were thrombosed at the time of embolization. Ten patients underwent radio-surgery alone. Eight of the 10 underwent angiographic follow-up (mean, 33 months); seven patients showed complete obliteration of the AVM without residual aneurysm. Histologic evaluation showed intranidal aneurysms to be thin-walled vascular structures, and they are the likely site for AVM hemorrhage. Embolization is an effective method for achieving thrombosis of the intranidal aneurysm and may be beneficial in patients undergoing radiation therapy because of a long latency period between treatment and thrombosis of the AVM.
View details for Web of Science ID A1992HQ88400012
View details for PubMedID 1561335
CORRELATION OF XENON-ENHANCED COMPUTED-TOMOGRAPHY AND ANGIOGRAPHY IN PATIENTS WITH INTRACEREBRAL ARTERIOVENOUS-MALFORMATIONS AND CLINICAL SYMPTOMS OF STEAL
1ST INTERNATIONAL CONF ON XENON-ENHANCED / COMPUTED TOMOGRAPHY : CEREBRAL BLOOD FLOW MEASUREMENT
RAVEN PRESS. 1992: 175–182
View details for Web of Science ID A1992BU95W00032
- COIL EMBOLIZATION OF AN ACUTELY RUPTURED SACCULAR ANEURYSM AMERICAN JOURNAL OF NEURORADIOLOGY 1991; 12 (6): 1067-1069
GLIOFIBROMA - CASE-REPORT
JOURNAL OF NEUROSURGERY
1991; 75 (4): 642-646
The case history of an infant with a large gliofibroma is presented. Gliofibromas are rare mixed glialmesenchymal tumors that have been poorly characterized. The computerized tomography appearance and a detailed light and electron microscopic description are presented, along with immunoperoxidase studies of this tumor. This case is compared with gliofibromas described elsewhere in the literature.
View details for Web of Science ID A1991GG76500020
View details for PubMedID 1885984
INFLAMMATORY PSEUDOTUMOR OF THE CHOROID-PLEXUS IN SJOGRENS DISEASE
1991; 29 (2): 287-290
We report an unusual case of inflammatory pseudotumor of the choroid plexus of the right lateral ventricle, manifesting as an intraventricular mass and causing unilateral hydrocephalus in a 48-year-old man who suffered from Sjögren's disease and subacute cutaneous lupus erythematosus. The lesion obliterated the normal choroidal architecture by a mixed chronic inflammatory process that was associated with reactive connective tissue changes. Immunohistochemical studies showed no light-chain restriction in the cells, and residual islands of transthyretin-positive epithelial cells were identified, implicating the choroid plexus origin of the mass.
View details for Web of Science ID A1991FX98000023
View details for PubMedID 1886672
COMBINED (TEAM) APPROACH TO HEMANGIOMA MANAGEMENT - ARTERIOGRAPHY WITH SUPERSELECTIVE EMBOLIZATION PLUS YAG LASER SAPPHIRE-TIP RESECTION
PLASTIC AND RECONSTRUCTIVE SURGERY
1991; 88 (1): 71-82
Thirteen patients have been treated over a 2-year period utilizing a team approach between the radiology and surgical services. Initial diagnostic evaluation is directed at determining the size and anatomic extent of the hemangioma; clinical assessment of coagulation and hemodynamic status is also performed. Arteriography with superselective embolization precedes the surgical procedure, usually by 24 hours. The YAG laser with contact sapphire-tip scalpels is then utilized for resection and reconstruction of the hemangioma. Total removal of hemangioma was achieved in 9 of 13 patients, and partial or subtotal removal was achieved in the remainder. Blood loss and complications were minimal.
View details for Web of Science ID A1991FT95900013
View details for PubMedID 2052663
VASCULAR CHARACTERISTICS OF INTRACEREBRAL ARTERIOVENOUS-MALFORMATIONS IN PATIENTS WITH CLINICAL STEAL
AMERICAN JOURNAL OF NEURORADIOLOGY
1991; 12 (3): 489-496
In patients with intracerebral arteriovenous malformations (AVMs), symptoms attributed to steal can lead to progressive debilitating deficits. This study was undertaken to determine which morphologic features of the AVM could be correlated with clinical symptoms of steal. Over a 4-year period, 65 patients with intracranial AVMs were evaluated with angiography supplemented by MR (46 cases) and CT (19 cases). Eleven characteristics of AVM vascular architecture were studied; these included size, lobar location, periventricular/intraventricular location, arterial stenosis, arteriovenous fistulae, angiomatous change (the presence of dilated transcortical collateral circulation), venous drainage pattern (central, cortical, mixed), venous stenosis, venous aneurysm or ectasia, venous variation, and delayed drainage. These characteristics were correlated with a history of clinical steal, which was seen in nine (14%) of 65 patients. Three characteristics were found to correlate highly with steal: angiomatous change (p less than .0001), size (p less than .0001), and peripheral venous drainage (p = .045). The mean size of the AVM nidus was 31.3 cm3 for the entire group of patients, 105.0 cm3 for patients with steal, and 19.5 cm3 for those without steal symptoms. Angiomatous change was seen in six (9%) of 65 patients; all six of these had clinical steal. The association of clinical steal with AVM size, angiomatous change, and peripheral venous drainage may contribute to establishing a prognosis and treatment planning. When a patient's symptoms are caused by steal, treatment with subtotal excision or partial embolization may be beneficial.
View details for Web of Science ID A1991FJ90400022
View details for PubMedID 2058499
Endovascular therapy for intracranial vascular lesions.
Western journal of medicine
1990; 153 (5): 542-543
View details for PubMedID 2148042
HEMORRHAGE IN INTRACEREBRAL ARTERIOVENOUS-MALFORMATIONS - ANGIOGRAPHIC DETERMINANTS
1990; 176 (3): 807-813
The most serious and frequent complication of intracranial arteriovenous malformations (AVMs) is intracranial hemorrhage. Identification of patients at greatest risk for intracranial bleeding would be beneficial. Detailed analysis of vascular architecture was performed in 65 patients with intracranial AVMs to identify the vascular characteristics that correlated with hemorrhage. Fifteen characteristics were assessed. Hemorrhage was present in 45 patients (69%). The following characteristics correlated positively with hemorrhage (Fisher-Irwin exact test): central venous drainage (P less than .0001), periventricular or intraventricular location of the AVM (P = .0002), and intranidal aneurysm (P = .028). The following characteristics correlated negatively with hemorrhage: angiomatous change (P = .0005), peripheral venous drainage (P = .005), and mixed venous drainage (P = .021). Multivariate linear discriminant analysis demonstrated that central venous drainage, angiomatous change (negatively predictive), intranidal aneurysm, and periventricular or intraventricular location of the AVM were the most discriminating or predictive characteristics of hemorrhage. Detailed analysis of the vascular architecture of intracranial AVMs helped identify features that strongly correlate with clinical hemorrhage and have important prognostic implications for the treatment of patients with these lesions.
View details for Web of Science ID A1990DV57900040
View details for PubMedID 2389040
BENEFITS OF CONTACT AND NONCONTACT YAG LASER FOR PERIORBITAL HEMANGIOMAS
ANNALS OF PLASTIC SURGERY
1990; 24 (5): 397-408
Twenty patients with capillary/cavernous hemangiomas of the periorbital area (eyelid, eyebrow, nose extending to canthus) have been treated with a variety of techniques. Six patients were treated by yttrium-aluminum-garnet (YAG) laser photocoagulation and direct injection of steroids. Rapid shrinkage of the hemangiomas occurred in all patients, and 2 infants whose eye was totally occluded by the hemangioma had their eyes rapidly opened. YAG laser excision with or without previous photocoagulation plus injection and with arteriogram plus superselective embolization was performed in the other 14 patients. Results were satisfactory in all patients.
View details for Web of Science ID A1990DC73900002
View details for PubMedID 2350150
BENIGN VERSUS PATHOLOGICAL COMPRESSION FRACTURES OF VERTEBRAL BODIES - ASSESSMENT WITH CONVENTIONAL SPIN-ECHO, CHEMICAL-SHIFT, AND STIR MR IMAGING
1990; 174 (2): 495-502
Differentiation of benign from pathologic compression fractures of vertebral bodies was evaluated with magnetic resonance imaging in a prospective study of 53 patients. Twenty-six patients had 34 benign posttraumatic compression fractures. Twenty-seven patients had metastatic disease to the vertebral column and seven pathologic fractures. T1- and T2-weighted spin-echo (SE) sequences (1.5 T) were performed in all patients. A presaturation technique was used to obtain "fat" and "water" images to better assess the degree of normal fatty marrow replacement in fractured vertebrae. Short inversion-time inversion-recovery (STIR) images were also obtained. Discrimination between benign and pathologic compression fractures was generally possible with the SE sequences. Chronic benign fractures demonstrated isointense marrow signal intensity (SI), compared with that of normal vertebrae with all sequences. Pathologic fractures showed low SI on T1-weighted images and high SI on T2-weighted images. Fat images revealed complete replacement of normal fatty marrow, shown as absent SI in the involved vertebral body. Water and STIR images showed diffuse high SI in pathologic fractures, with STIR images having the highest contrast between abnormal and normal marrow. Acute benign compression fractures also demonstrated high SI on T2-weighted, water, and STIR images, but the SI was less pronounced and the pattern was generally more inhomogeneous than that of pathologic compressions. In general, fat images showed only partial replacement of normal fatty marrow by low SI, in contrast to the complete absence of marrow SI typical of pathologic fractures.
View details for PubMedID 2296658
COMBINATION TREATMENT FOR MASSIVE CAVERNOUS HEMANGIOMA OF THE FACE - YAG LASER PHOTOCOAGULATION PLUS DIRECT STEROID INJECTION FOLLOWED BY YAG LASER RESECTION WITH SAPPHIRE SCALPEL TIPS, AIDED BY SUPERSELECTIVE EMBOLIZATION
LASERS IN SURGERY AND MEDICINE
1990; 10 (3): 217-223
A massive cavernous hemangioma of the face in an 11 month old child has been successfully resected utilizing a combination of laser and non-laser techniques. The hemangioma was initially treated twice with YAG laser photocoagulation plus direct injection of steroids. This treatment promptly stopped the rapid growth and induced blanching as well as a 25% shrinkage with each treatment. Arteriogram with superselective embolization produced a further shrinkage of the hemangioma. Finally, the contact YAG laser with sapphire scalpel tips was utilized for complete and cosmetically satisfactory hemangioma resection. The treatment of a massive cavernous hemangioma by a combination of modalities is discussed.
View details for Web of Science ID A1990DG14700001
View details for PubMedID 2345471
DIGITAL SUBTRACTION CEREBRAL-ANGIOGRAPHY BY INTRAARTERIAL INJECTION - COMPARISON WITH CONVENTIONAL ANGIOGRAPHY
AMERICAN JOURNAL OF ROENTGENOLOGY
1983; 140 (2): 347-353
For 4 months, a prototype digital subtraction system was used to obtain images of the cerebral vasculature after intraarterial contrast injections. In 12 instances, the intraarterial injections were recorded with both a digital subtraction unit and conventional direct magnification film-screen system. The digital subtraction and conventional film subtraction images were compared and graded for quality and information content by three skilled observers. In addition, quantitative measurements of contrast-detail performance and spatial resolution were obtained on both the digital system and the screen-film imaging chain. In a clinical setting, both the digital subtraction and conventional film-screen systems provided similar quality images and angiographic information. Contrast-detail curves demonstrated that digital subtraction angiography outperformed conventional film technique for low-contrast objects. Digital subtraction angiography also reduced the time required to obtain the angiogram, markedly reduced film cost, and lowered the contrast agent burden.
View details for Web of Science ID A1983PZ93700029
View details for PubMedID 6336873
DIGITAL SUBTRACTION CEREBRAL-ANGIOGRAPHY BY INTRA-ARTERIAL INJECTION - COMPARISON WITH CONVENTIONAL ANGIOGRAPHY
AMERICAN JOURNAL OF NEURORADIOLOGY
1982; 3 (6): 593-599
View details for Web of Science ID A1982PN59000001
COMPUTERIZED CRANIAL TOMOGRAPHY IN CEREBRAL DISEASES OF WHITE MATTER
1978; 28 (6): 534-544
Computerized tomographic scans were performed on 31 patients with primary diseases of the white matter. Among 18 patients with multiple sclerosis, acute lesions were visualized in five, all with symptomatic cerebral hemisphere disease. Characteristic white matter lesions were also demonstrated in adrenoleukodystrophy, spongiform encephalopathy, progressive multifocal leukoencephalopathy, disseminated necrotizing leukoencephalopathy, and an undiagnosed leukoencephalopathy associated with malignancy. Besides identifying white matter abnormalities, the CT scan patterns were often specific enough to help distinguish among the various etiologic possibilities for the abnormalities. Useful diagnostic characteristics included the anatomic distribution of lesions, mass effect, atrophic changes, and enhancement after contrast infusion.
View details for Web of Science ID A1978FB36800002
View details for PubMedID 565883
ENLARGEMENT OF SUBARACHNOID SPACES AND LATERAL VENTRICLES IN PEDIATRIC-PATIENTS UNDERGOING CHEMOTHERAPY
JOURNAL OF PEDIATRICS
1978; 92 (4): 535-539
This retrospective study investigated the possible adverse effects of cancer therapy on the brain. Cranial computed tomographic scans of 76 patients with non-central nervous system malignancies and 25 patients with leukemia had enlarged lateral ventricles and/or cortical sulci in 19% and 40%, respectively. Leukemic patients, especially those with meningeal involvement, had the most frequent and most severe abnormalities.
View details for Web of Science ID A1978EU20100003
View details for PubMedID 305472
CT SCANNING AND DIAGNOSIS OF ADRENOLEUKODYSTROPHY
1977; 27 (9): 884-886
On computerized tomography scanning, two patients with adrenoleukodystrophy had low-density abnormalities in the parieto-occipital lobes, which enhanced anteriorly with contrast infusion. Computerized tomographic correlation with the published pathology is discussed. CT scanning may be an important diagnostic procedure in the early diagnosis of adrenoleukodystrophy.
View details for Web of Science ID A1977DU36100016
View details for PubMedID 561345
DIAGNOSIS OF PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY BY COMPUTED TOMOGRAPHY
1977; 122 (1): 137-141
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system which predominantly affects immunologically compromised hosts. The distinctive CT appearance in three documented cases includes low-density lesions of central and convolutional white matter with scalloped lateral borders. Lesions demonstrate no mass effect or contrast material enhancement. Findings are discussed with reference to other entities which may produce a similar CT appearance.
View details for Web of Science ID A1977CQ80400024
View details for PubMedID 830323
CRANIAL COMPUTED TOMOGRAPHY FINDINGS IN ANOREXIA-NERVOSA
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
1977; 1 (4): 410-414
Four patients with anorexia nervosa were studied by cranial computed tomography (CT). Three of the four demonstrated abnormal enlargement of cortical sulci and subarachnoid spaces as compared with an age-matched control group. The relationship of this finding to established neuropathological changes in anorexia nervosa is discussed.
View details for Web of Science ID A1977DY24500005
View details for PubMedID 615218
ORBITAL INVOLVEMENT BY PLASMACYTOMA - REPORT OF 2 CASES
1976; 54 (6): 755-762
Two patients with orbital involvement of plasma cell myeloma are presented. The first patient presented an isolated plasmacytoma in the orbit; the second patient had generalized plasma cell myeloma. In both cases X-rays and computed tomographic scanning gave valuable information and biopsy confirmed the diagnosis.
View details for Web of Science ID A1976CM04600008
View details for PubMedID 990023