Publications

2017
Karl-Heinz Nenning, Hesheng Liu, Satrajit S Ghosh, Mert R Sabuncu, Ernst Schwartz, and Georg Langs. 8/2017. “Diffeomorphic Functional Brain Surface Alignment: Functional Demons.” Neuroimage, 156, Pp. 456-65.Abstract
Aligning brain structures across individuals is a central prerequisite for comparative neuroimaging studies. Typically, registration approaches assume a strong association between the features used for alignment, such as macro-anatomy, and the variable observed, such as functional activation or connectivity. Here, we propose to use the structure of intrinsic resting state fMRI signal correlation patterns as a basis for alignment of the cortex in functional studies. Rather than assuming the spatial correspondence of functional structures between subjects, we have identified locations with similar connectivity profiles across subjects. We mapped functional connectivity relationships within the brain into an embedding space, and aligned the resulting maps of multiple subjects. We then performed a diffeomorphic alignment of the cortical surfaces, driven by the corresponding features in the joint embedding space. Results show that functional alignment based on resting state fMRI identifies functionally homologous regions across individuals with higher accuracy than alignment based on the spatial correspondence of anatomy. Further, functional alignment enables measurement of the strength of the anatomo-functional link across the cortex, and reveals the uneven distribution of this link. Stronger anatomo-functional dissociation was found in higher association areas compared to primary sensory- and motor areas. Functional alignment based on resting state features improves group analysis of task based functional MRI data, increasing statistical power and improving the delineation of task-specific core regions. Finally, a comparison of the anatomo-functional dissociation between cohorts is demonstrated with a group of left and right handed subjects.
Fang Ji, Ofer Pasternak, Siwei Liu, Yng Miin Loke, Boon Linn Choo, Saima Hilal, Xin Xu, Mohammad Kamran Ikram, Narayanaswamy Venketasubramanian, Christopher Li-Hsian Chen, and Juan Zhou. 8/2017. “Distinct White Matter Microstructural Abnormalities and Extracellular Water Increases Relate to Cognitive Impairment in Alzheimer's Disease with And without Cerebrovascular Disease.” Alzheimers Res Ther, 9, 1, Pp. 63.Abstract
BACKGROUND: Mixed vascular and neurodegenerative dementia, such as Alzheimer's disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown. To cover these gaps, we aimed to characterize the WM free water and tissue microstructural changes in AD and mixed dementia as well as their associations with cognition using a novel free water imaging method. METHODS: We compared WM free water and free water-corrected DTI measures as well as white matter hyperintensity (WMH) in patients with AD with and without cerebrovascular disease, patients with vascular dementia, and age-matched healthy control subjects. RESULTS: The cerebrovascular disease groups had higher free water than the non-cerebrovascular disease groups. Importantly, besides the cerebrovascular disease groups, patients with AD without cerebrovascular disease also had increased free water in normal-appearing WM compared with healthy control subjects, reflecting mild vascular damage. Such free water increases in WM or normal-appearing WM (but not WMH) contributed to dementia severity. Whole-brain voxel-wise analysis revealed a close association between widespread free water increases and poorer attention, executive functioning, visual construction, and motor performance, whereas only left hemispheric free water increases were related to language deficits. Moreover, compared with the original DTI metrics, the free water-corrected DTI metric revealed tissue damage-specific (frontal and occipital) microstructural differences between the cerebrovascular disease and non-cerebrovascular disease groups. In contrast to both lobar and subcortical/brainstem free water increases, only focal lobar microstructural damage was associated with poorer cognitive performance. CONCLUSIONS: Our findings suggest that free water analysis isolates probable mild vascular damage from WM microstructural alterations and underscore the importance of normal-appearing WM changes underlying cognitive and functional impairment in AD with and without cerebrovascular disease. Further developed, the combined free water and tissue neuroimaging assays could help in differential diagnosis, treatment planning, and disease monitoring of patients with mixed dementia.
Lipeng Ning, Kawin Setsompop, Carl-Fredrik Westin, and Yogesh Rathi. 8/2017. “New Insights about Time-varying Diffusivity and its Estimation from Diffusion MRI.” Magn Reson Med, 78, 2, Pp. 763-74.Abstract

PURPOSE: Characterizing the relation between the applied gradient sequences and the measured diffusion MRI signal is important for estimating the time-dependent diffusivity, which provides important information about the microscopic tissue structure. THEORY AND METHODS: In this article, we extend the classical theory of Stepišnik for measuring time-dependent diffusivity under the Gaussian phase approximation. In particular, we derive three novel expressions which represent the diffusion MRI signal in terms of the mean-squared displacement, the instantaneous diffusivity, and the velocity autocorrelation function. We present the explicit signal expressions for the case of single diffusion encoding and oscillating gradient spin-echo sequences. Additionally, we also propose three different models to represent time-varying diffusivity and test them using Monte-Carlo simulations and in vivo human brain data. RESULTS: The time-varying diffusivities are able to distinguish the synthetic structures in the Monte-Carlo simulations. There is also strong statistical evidence about time-varying diffusivity from the in vivo human data set. CONCLUSION: The proposed theory provides new insights into our understanding of the time-varying diffusivity using different gradient sequences. The proposed models for representing time-varying diffusivity can be utilized to study time-varying diffusivity using in vivo human brain diffusion MRI data. 

Yongxin Chen, Filemon Dela Cruz, Romeil Sandhu, Andrew L Kung, Prabhjot Mundi, Joseph O Deasy, and Allen Tannenbaum. 8/2017. “Pediatric Sarcoma Data Forms a Unique Cluster Measured via the Earth Mover's Distance.” Sci Rep, 7, 1, Pp. 7035.Abstract
In this note, we combined pediatric sarcoma data from Columbia University with adult sarcoma data collected from TCGA, in order to see if one can automatically discern a unique pediatric cluster in the combined data set. Using a novel clustering pipeline based on optimal transport theory, this turned out to be the case. The overall methodology may find uses for the classification of data from other biological networking problems.
Roxana G Burciu, Edward Ofori, Derek B Archer, Samuel S Wu, Ofer Pasternak, Nikolaus R McFarland, Michael S Okun, and David E Vaillancourt. 8/2017. “Progression Marker of Parkinson's Disease: A 4-year Multi-site Imaging Study.” Brain, 140, 8, Pp. 2183-92.Abstract
Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson's disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson's disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson's disease, which may be used in clinical trials of disease-modifying therapies.
Anna S Rydhög, Filip Szczepankiewicz, Ronnie Wirestam, André Ahlgren, Carl-Fredrik Westin, Linda Knutsson, and Ofer Pasternak. 8/2017. “Separating Blood and Water: Perfusion and Free Water Elimination from Diffusion MRI in the Human Brain.” Neuroimage, 156, Pp. 423-34.Abstract
The assessment of the free water fraction in the brain provides important information about extracellular processes such as atrophy and neuroinflammation in various clinical conditions as well as in normal development and aging. Free water estimates from diffusion MRI are assumed to account for freely diffusing water molecules in the extracellular space, but may be biased by other pools of molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM) of blood, where water molecules perfuse in the randomly oriented capillary network. The goal of this work was to separate the signal contribution of the perfusing blood from that of free-water and of other brain diffusivities. The influence of the vascular compartment on the estimation of the free water fraction and other diffusivities was investigated by simulating perfusion in diffusion MRI data. The perfusion effect in the simulations was significant, especially for the estimation of the free water fraction, and was maintained as long as low b-value data were included in the analysis. Two approaches to reduce the perfusion effect were explored in this study: (i) increasing the minimal b-value used in the fitting, and (ii) using a three-compartment model that explicitly accounts for water molecules in the capillary blood. Estimation of the model parameters while excluding low b-values reduced the perfusion effect but was highly sensitive to noise. The three-compartment model fit was more stable and additionally, provided an estimation of the volume fraction of the capillary blood compartment. The three-compartment model thus disentangles the effects of free water diffusion and perfusion, which is of major clinical importance since changes in these components in the brain may indicate different pathologies, i.e., those originating from the extracellular space, such as neuroinflammation and atrophy, and those related to the vascular space, such as vasodilation, vasoconstriction and capillary density. Diffusion MRI data acquired from a healthy volunteer, using multiple b-shells, demonstrated an expected non-zero contribution from the blood fraction, and indicated that not accounting for the perfusion effect may explain the overestimation of the free water fraction evinced in previous studies. Finally, the applicability of the method was demonstrated with a dataset acquired using a clinically feasible protocol with shorter acquisition time and fewer b-shells.
Zora Kikinis, Marc Muehlmann, Ofer Pasternak, Sharon Peled, Praveen Kulkarni, Craig Ferris, Sylvain Bouix, Yogesh Rathi, Inga K Koerte, Steve Pieper, Alexander Yarmarkovich, Caryn L Porter, Bruce S Kristal, and Martha E Shenton. 7/2017. “Diffusion Imaging of Mild Traumatic Brain Injury in the Impact Accelerated Rodent Model: A Pilot Study.” Brain Inj, 31, 10, Pp. 1376-81.Abstract
PRIMARY OBJECTIVE: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model. RESEARCH DESIGN: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls. Seven days post injury, DTI was acquired from fixed rat brains using a 7T scanner. Group comparison of Fractional Anisotropy (FA) values between traumatized and sham animals was performed using Tract-Based Spatial Statistics (TBSS), a method that we adapted for rats. MAIN OUTCOMES AND RESULTS: TBSS revealed white matter regions of the brain with increased FA values in the traumatized versus sham rats, localized mainly to the contrecoup region. Regions of increased FA included the pyramidal tract, the cerebral peduncle, the superior cerebellar peduncle and to a lesser extent the fibre tracts of the corpus callosum, the anterior commissure, the fimbria of the hippocampus, the fornix, the medial forebrain bundle and the optic chiasm. CONCLUSION: Seven days post injury, during the period of tissue reparation in the impact acceleration rat model of mTBI, microstructural changes to white matter can be detected using DTI.
Markus Nilsson, Samo Lasič, Ivana Drobnjak, Daniel Topgaard, and Carl-Fredrik Westin. 7/2017. “Resolution Limit of Cylinder Diameter Estimation by Diffusion MRI: The Impact of Gradient Waveform and Orientation Dispersion.” NMR Biomed, 30, 7.Abstract
Diffusion MRI has been proposed as a non-invasive technique for axonal diameter mapping. However, accurate estimation of small diameters requires strong gradients, which is a challenge for the transition of the technique from preclinical to clinical MRI scanners, since these have weaker gradients. In this work, we develop a framework to estimate the lower bound for accurate diameter estimation, which we refer to as the resolution limit. We analyse only the contribution from the intra-axonal space and assume that axons can be represented by impermeable cylinders. To address the growing interest in using techniques for diffusion encoding that go beyond the conventional single diffusion encoding (SDE) sequence, we present a generalised analysis capable of predicting the resolution limit regardless of the gradient waveform. Using this framework, waveforms were optimised to minimise the resolution limit. The results show that, for parallel cylinders, the SDE experiment is optimal in terms of yielding the lowest possible resolution limit. In the presence of orientation dispersion, diffusion encoding sequences with square-wave oscillating gradients were optimal. The resolution limit for standard clinical MRI scanners (maximum gradient strength 60-80 mT/m) was found to be between 4 and 8 μm, depending on the noise levels and the level of orientation dispersion. For scanners with a maximum gradient strength of 300 mT/m, the limit was reduced to between 2 and 5 μm.
M Zhang, R Liao, Adrian V Dalca, E Turk, J Luo, E Grant, and Polina Golland. 6/2017. “Frequency Diffeomorphisms for Efficient Image Registration.” Inf Process Med Imaging., 10265, Pp. 559-70.
Adrian V Dalca, K. L. Bouman, William T. Freeman, Natalia S Rost, Mert R Sabuncu, and Polina Golland. 6/2017. “Population Based Image Imputation.” Inf Process Med Imaging., 10265, 659-71.
Lena Maier-Hein, Swaroop Vedula, Stefanis Speidel, Nassir Navab, Ron Kikinis, Adrian Park, Matthias Eisenman, Hubertus Feussner, and Germain Forestier. 6/2017. “Surgical Data Science: Enabling Next-generation Surgery.” Nature Biomedical Engineering. Maier-Hein-NBE2017.pdf
Stephen SF Yip, Chintan Parmar, Daniel Blezek, Raul San Jose Estepar, Steve Pieper, John Kim, and Hugo JWL Aerts. 6/2017. “Application of the 3D Slicer Chest Imaging Platform Segmentation Algorithm for Large Lung Nodule Delineation.” PLoS One, 12, 6, Pp. e0178944.Abstract
PURPOSE: Accurate segmentation of lung nodules is crucial in the development of imaging biomarkers for predicting malignancy of the nodules. Manual segmentation is time consuming and affected by inter-observer variability. We evaluated the robustness and accuracy of a publically available semiautomatic segmentation algorithm that is implemented in the 3D Slicer Chest Imaging Platform (CIP) and compared it with the performance of manual segmentation. METHODS: CT images of 354 manually segmented nodules were downloaded from the LIDC database. Four radiologists performed the manual segmentation and assessed various nodule characteristics. The semiautomatic CIP segmentation was initialized using the centroid of the manual segmentations, thereby generating four contours for each nodule. The robustness of both segmentation methods was assessed using the region of uncertainty (δ) and Dice similarity index (DSI). The robustness of the segmentation methods was compared using the Wilcoxon-signed rank test (pWilcoxon<0.05). The Dice similarity index (DSIAgree) between the manual and CIP segmentations was computed to estimate the accuracy of the semiautomatic contours. RESULTS: The median computational time of the CIP segmentation was 10 s. The median CIP and manually segmented volumes were 477 ml and 309 ml, respectively. CIP segmentations were significantly more robust than manual segmentations (median δCIP = 14ml, median dsiCIP = 99% vs. median δmanual = 222ml, median dsimanual = 82%) with pWilcoxon~10-16. The agreement between CIP and manual segmentations had a median DSIAgree of 60%. While 13% (47/354) of the nodules did not require any manual adjustment, minor to substantial manual adjustments were needed for 87% (305/354) of the nodules. CIP segmentations were observed to perform poorly (median DSIAgree≈50%) for non-/sub-solid nodules with subtle appearances and poorly defined boundaries. CONCLUSION: Semi-automatic CIP segmentation can potentially reduce the physician workload for 13% of nodules owing to its computational efficiency and superior stability compared to manual segmentation. Although manual adjustment is needed for many cases, CIP segmentation provides a preliminary contour for physicians as a starting point.
Ariel D Stock, Sivan Gelb, Ofer Pasternak, Ayal Ben-Zvi, and Chaim Putterman. 6/2017. “The Blood Brain Barrier and Neuropsychiatric Lupus: New Perspectives in Light of Advances in Understanding the Neuroimmune Interface.” Autoimmun Rev, 16, 6, Pp. 612-9.Abstract
Experts have previously postulated a linkage between lupus associated vascular pathology and abnormal brain barriers in the immunopathogenesis of neuropsychiatric lupus. Nevertheless, there are some discrepancies between the experimental evidence, or its interpretation, and the working hypotheses prevalent in this field; specifically, that a primary contributor to neuropsychiatric disease in lupus is permeabilization of the blood brain barrier. In this commonly held view, any contribution of the other known brain barriers, including the blood-cerebrospinal fluid and meningeal barriers, is mostly excluded from the discussion. In this review we will shed light on some of the blood brain barrier hypotheses and try to trace their roots. In addition, we will suggest new research directions to allow for confirmation of alternative interpretations of the experimental evidence linking the pathology of intra-cerebral vasculature to the pathogenesis of neuropsychiatric lupus.
Christian Wachinger, Matthew Brennan, Greg C Sharp, and Polina Golland. 6/2017. “Efficient Descriptor-Based Segmentation of Parotid Glands With Nonlocal Means.” IEEE Trans Biomed Eng, 64, 7, Pp. 1492-1502.Abstract
OBJECTIVE: We introduce descriptor-based segmentation that extends existing patch-based methods by combining intensities, features, and location information. Since it is unclear which image features are best suited for patch selection, we perform a broad empirical study on a multitude of different features. METHODS: We extend nonlocal means segmentation by including image features and location information. We search larger windows with an efficient nearest neighbor search based on kd-trees. We compare a large number of image features. RESULTS: The best results were obtained for entropy image features, which have not yet been used for patch-based segmentation. We further show that searching larger image regions with an approximate nearest neighbor search and location information yields a significant improvement over the bounded nearest neighbor search traditionally employed in patch-based segmentation methods. CONCLUSION: Features and location information significantly increase the segmentation accuracy. The best features highlight boundaries in the image. SIGNIFICANCE: Our detailed analysis of several aspects of nonlocal means-based segmentation yields new insights about patch and neighborhood sizes together with the inclusion of location information. The presented approach advances the state-of-the-art in the segmentation of parotid glands for radiation therapy planning.
Miaomiao Zhang, Ruizhi Liao, Adrian V Dalca, Esra A Turk, Jie Luo, Ellen P Grant, and Polina Golland. 6/2017. “Frequency Diffeomorphisms for Efficient Image Registration.” Inf Process Med Imaging, 10265, Pp. 559-570.Abstract
This paper presents an efficient algorithm for large deformation diffeomorphic metric mapping (LDDMM) with geodesic shooting for image registration. We introduce a novel finite dimensional Fourier representation of diffeomorphic deformations based on the key fact that the high frequency components of a diffeomorphism remain stationary throughout the integration process when computing the deformation associated with smooth velocity fields. We show that manipulating high dimensional diffeomorphisms can be carried out entirely in the bandlimited space by integrating the nonstationary low frequency components of the displacement field. This insight substantially reduces the computational cost of the registration problem. Experimental results show that our method is significantly faster than the state-of-the-art diffeomorphic image registration methods while producing equally accurate alignment. We demonstrate our algorithm in two different applications of image registration: neuroimaging and in-utero imaging.
Vincent Koppelmans, Ofer Pasternak, Jacob J Bloomberg, Yiri De E Dios, Scott J Wood, Roy Riascos, Patricia A Reuter-Lorenz, Igor S Kofman, Ajitkumar P Mulavara, and Rachael D Seidler. 6/2017. “Intracranial Fluid Redistribution but No White Matter Microstructural Changes During a Spaceflight Analog.” Sci Rep, 7, 1, Pp. 3154.Abstract
The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n = 12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.
Jenna Schabdach, William M Wells, Michael Cho, and Kayhan N Batmanghelich. 6/2017. “A Likelihood-Free Approach for Characterizing Heterogeneous Diseases in Large-Scale Studies.” Inf Process Med Imaging, 10265, Pp. 170-183.Abstract
We propose a non-parametric approach for characterizing heterogeneous diseases in large-scale studies. We target diseases where multiple types of pathology present simultaneously in each subject and a more severe disease manifests as a higher level of tissue destruction. For each subject, we model theof local image descriptors as samples generated by an unknown subject-specific probability density. Instead of approximating the probability density via a parametric family, we propose to side step the parametric inference by directly estimating the divergence between subject densities. Our method maps the collection of local image descriptors to a signaturethat is used to predict a clinical measurement. We are able to interpret the prediction of the clinical variable in the population and individual levels by carefully studying the divergences. We illustrate an application this method on simulated data as well as on a large-scale lung CT study of Chronic Obstructive Pulmonary Disease (COPD). Our approach outperforms classical methods on both simulated and COPD data and demonstrates the state-of-the-art prediction on an important physiologic measure of airflow (the forced respiratory volume in one second, FEV1).
Ruizhi Liao, Lipeng Ning, Zhenrui Chen, Laura Rigolo, Shun Gong, Ofer Pasternak, Alexandra J Golby, Yogesh Rathi, and Lauren J O'Donnell. 6/2017. “Performance of Unscented Kalman Filter Tractography in Edema: Analysis of the Two-tensor Model.” Neuroimage Clin, 15, Pp. 819-31.Abstract
Diffusion MRI tractography is increasingly used in pre-operative neurosurgical planning to visualize critical fiber tracts. However, a major challenge for conventional tractography, especially in patients with brain tumors, is tracing fiber tracts that are affected by vasogenic edema, which increases water content in the tissue and lowers diffusion anisotropy. One strategy for improving fiber tracking is to use a tractography method that is more sensitive than the traditional single-tensor streamline tractography. We performed experiments to assess the performance of two-tensor unscented Kalman filter (UKF) tractography in edema. UKF tractography fits a diffusion model to the data during fiber tracking, taking advantage of prior information from the previous step along the fiber. We studied UKF performance in a synthetic diffusion MRI digital phantom with simulated edema and in retrospective data from two neurosurgical patients with edema affecting the arcuate fasciculus and corticospinal tracts. We compared the performance of several tractography methods including traditional streamline, UKF single-tensor, and UKF two-tensor. To provide practical guidance on how the UKF method could be employed, we evaluated the impact of using various seed regions both inside and outside the edematous regions, as well as the impact of parameter settings on the tractography sensitivity. We quantified the sensitivity of different methods by measuring the percentage of the patient-specific fMRI activation that was reached by the tractography. We expected that diffusion anisotropy threshold parameters, as well as the inclusion of a free water model, would significantly influence the reconstruction of edematous WM fiber tracts, because edema increases water content in the tissue and lowers anisotropy. Contrary to our initial expectations, varying the fractional anisotropy threshold and including a free water model did not affect the UKF two-tensor tractography output appreciably in these two patient datasets. The most effective parameter for increasing tracking sensitivity was the generalized anisotropy (GA) threshold, which increased the length of tracked fibers when reduced to 0.075. In addition, the most effective seeding strategy was seeding in the whole brain or in a large region outside of the edema. Overall, the main contribution of this study is to provide insight into how UKF tractography can work, using a two-tensor model, to begin to address the challenge of fiber tract reconstruction in edematous regions near brain tumors.
Adrian V Dalca, Katherine L Bouman, William T. Freeman, Natalia S Rost, Mert R Sabuncu, and Polina Golland. 6/2017. “Population Based Image Imputation.” Inf Process Med Imaging, 10265, Pp. 659-671.Abstract
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 databases of clinical images contain a wealth of information, medical acquisition constraints result in sparse scans that miss much of the anatomy. These characteristics often render computational analysis impractical as standard processing algorithms tend to fail when applied to such images. Highly specialized or application-specific algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, our goal is to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a model that captures fine-scale anatomical similarity across subjects in clinical image collections and use it to fill in the missing data in scans with large slice spacing. Our experimental results demonstrate that the proposed method outperforms current upsampling methods and promises to facilitate subsequent analysis not previously possible with scans of this quality.
Yangming Ou, Lilla Zöllei, Kallirroi Retzepi, Victor Castro, Sara V Bates, Steve Pieper, Katherine P Andriole, Shawn N Murphy, Randy L Gollub, and Patricia Ellen Grant. 6/2017. “Using Clinically Acquired MRI to Construct Age-specific Atlases: Quantifying Spatiotemporal ADC Changes from Birth to 6-year Old.” Hum Brain Mapp, 38, 6, Pp. 3052-68.Abstract
Diffusion imaging is critical for detecting acute brain injury. However, normal apparent diffusion coefficient (ADC) maps change rapidly in early childhood, making abnormality detection difficult. In this article, we explored clinical PACS and electronic healthcare records (EHR) to create age-specific ADC atlases for clinical radiology reference. Using the EHR and three rounds of multiexpert reviews, we found ADC maps from 201 children 0-6 years of age scanned between 2006 and 2013 who had brain MRIs with no reported abnormalities and normal clinical evaluations 2+ years later. These images were grouped in 10 age bins, densely sampling the first 1 year of life (5 bins, including neonates and 4 quarters) and representing the 1-6 year age range (an age bin per year). Unbiased group-wise registration was used to construct ADC atlases for 10 age bins. We used the atlases to quantify (a) cross-sectional normative ADC variations; (b) spatiotemporal heterogeneous ADC changes; and (c) spatiotemporal heterogeneous volumetric changes. The quantified age-specific whole-brain and region-wise ADC values were compared to those from age-matched individual subjects in our study and in multiple existing independent studies. The significance of this study is that we have shown that clinically acquired images can be used to construct normative age-specific atlases. These first of their kind age-specific normative ADC atlases quantitatively characterize changes of myelination-related water diffusion in the first 6 years of life. The quantified voxel-wise spatiotemporal ADC variations provide standard references to assist radiologists toward more objective interpretation of abnormalities in clinical images. Our atlases are available at https://www.nitrc.org/projects/mgh_adcatlases.

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