Publications by Year: 2019

2019
Filip Szczepankiewicz, Scott Hoge, and Carl-Fredrik Westin. 7/2019. “Linear, Planar and Spherical Tensor-valued Diffusion MRI Data by Free Waveform Encoding in Healthy Brain, Water, Oil and Liquid Crystals.” Data Brief, 25, Pp. 104208.Abstract
Recently, several biophysical models and signal representations have been proposed for microstructure imaging based on tensor-valued, or multidimensional, diffusion MRI. The acquisition of the necessary data requires non-conventional pulse sequences, and data is therefore not available to the wider diffusion MRI community. To facilitate exploration and development of analysis techniques based on tensor-valued diffusion encoding, we share a comprehensive data set acquired in a healthy human brain. The data encompasses diffusion weighted images using linear, planar and spherical diffusion tensor encoding at multiple b-values and diffusion encoding directions. We also supply data acquired in several phantoms that may support validation. The data is hosted by GitHub: https://github.com/filip-szczepankiewicz/Szczepankiewicz_DIB_2019.
Fan Zhang, Ye Wu, Isaiah Norton, Yogesh Rathi, Alexandra J Golby, and Lauren J O'Donnell. 7/2019. “Test-retest Reproducibility of White Matter Parcellation using Diffusion MRI Tractography Fiber Clustering.” Hum Brain Mapp, 40, 10, Pp. 3041-57.Abstract
There are two popular approaches for automated white matter parcellation using diffusion MRI tractography, including fiber clustering strategies that group white matter fibers according to their geometric trajectories and cortical-parcellation-based strategies that focus on the structural connectivity among different brain regions of interest. While multiple studies have assessed test-retest reproducibility of automated white matter parcellations using cortical-parcellation-based strategies, there are no existing studies of test-retest reproducibility of fiber clustering parcellation. In this work, we perform what we believe is the first study of fiber clustering white matter parcellation test-retest reproducibility. The assessment is performed on three test-retest diffusion MRI datasets including a total of 255 subjects across genders, a broad age range (5-82 years), health conditions (autism, Parkinson's disease and healthy subjects), and imaging acquisition protocols (three different sites). A comprehensive evaluation is conducted for a fiber clustering method that leverages an anatomically curated fiber clustering white matter atlas, with comparison to a popular cortical-parcellation-based method. The two methods are compared for the two main white matter parcellation applications of dividing the entire white matter into parcels (i.e., whole brain white matter parcellation) and identifying particular anatomical fiber tracts (i.e., anatomical fiber tract parcellation). Test-retest reproducibility is measured using both geometric and diffusion features, including volumetric overlap (wDice) and relative difference of fractional anisotropy. Our experimental results in general indicate that the fiber clustering method produced more reproducible white matter parcellations than the cortical-parcellation-based method.
Fabio Nery, Filip Szczepankiewicz, Leevi Kerkelä, Matt G Hall, Enrico Kaden, Isky Gordon, David L Thomas, and Chris A Clark. 6/2019. “In vivo Demonstration of Microscopic Anisotropy in the Human Kidney using Multidimensional Diffusion MRI.” Magn Reson Med.Abstract
PURPOSE: To demonstrate the feasibility of multidimensional diffusion MRI to probe and quantify microscopic fractional anisotropy (µFA) in human kidneys in vivo. METHODS: Linear tensor encoded (LTE) and spherical tensor encoded (STE) renal diffusion MRI scans were performed in 10 healthy volunteers. Respiratory triggering and image registration were used to minimize motion artefacts during the acquisition. Kidney cortex-medulla were semi-automatically segmented based on fractional anisotropy (FA) values. A model-free analysis of LTE and STE signal dependence on b-value in the renal cortex and medulla was performed. Subsequently, µFA was estimated using a single-shell approach. Finally, a comparison of conventional FA and µFA is shown. RESULTS: The hallmark effect of µFA (divergence of LTE and STE signal with increasing b-value) was observed in all subjects. A statistically significant difference between LTE and STE signal was found in the cortex and medulla, starting from b = 750 s/mm and b = 500 s/mm , respectively. This difference was maximal at the highest b-value sampled (b = 1000 s/mm ) which suggests that relatively high b-values are required for µFA mapping in the kidney compared to conventional FA. Cortical and medullary µFA were, respectively, 0.53 ± 0.09 and 0.65 ± 0.05, both respectively higher than conventional FA (0.19 ± 0.02 and 0.40 ± 0.02). CONCLUSION: The feasibility of combining LTE and STE diffusion MRI to probe and quantify µFA in human kidneys is demonstrated for the first time. By doing so, we show that novel microstructure information-not accessible by conventional diffusion encoding-can be probed by multidimensional diffusion MRI. We also identify relevant technical limitations that warrant further development of the technique for body MRI.
Christian Lepage, Marc Muehlmann, Yorghos Tripodis, Jakob Hufschmidt, Julie Stamm, Katie Green, Pawel Wrobel, Vivian Schultz, Isabelle Weir, Michael L Alosco, Christine M Baugh, Nathan G Fritts, Brett M Martin, Christine Chaisson, Michael J Coleman, Alexander P Lin, Ofer Pasternak, Nikos Makris, Robert A Stern, Martha E Shenton, and Inga K Koerte. 6/2019. “Limbic System Structure Volumes and Associated Neurocognitive Functioning in Former NFL Players.” Brain Imaging Behav, 13, 3, Pp. 725-34.Abstract
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts. CTE has been linked to disruptions in cognition, mood, and behavior. Unfortunately, the diagnosis of CTE can only be made post-mortem. Neuropathological evidence suggests limbic structures may provide an opportunity to characterize CTE in the living. Using 3 T magnetic resonance imaging, we compared select limbic brain regional volumes - the amygdala, hippocampus, and cingulate gyrus - between symptomatic former National Football League (NFL) players (n = 86) and controls (n = 22). Moreover, within the group of former NFL players, we examined the relationship between those limbic structures and neurobehavioral functioning (n = 75). The former NFL group comprised eighty-six men (mean age = 55.2 ± 8.0 years) with at least 12 years of organized football experience, at least 2 years of active participation in the NFL, and self-reported declines in cognition, mood, and behavior within the last 6 months. The control group consisted of men (mean age = 57.0 ± 6.6 years) with no history of contact-sport involvement or traumatic brain injury. All control participants provided neurobehavioral data. Compared to controls, former NFL players exhibited reduced volumes of the amygdala, hippocampus, and cingulate gyrus. Within the NFL group, reduced bilateral cingulate gyrus volume was associated with worse attention and psychomotor speed (r = 0.4 (right), r = 0.42 (left); both p < 0.001), while decreased right hippocampal volume was associated with worse visual memory (r = 0.25, p = 0.027). Reduced volumes of limbic system structures in former NFL players are associated with neurocognitive features of CTE. Volume reductions in the amygdala, hippocampus, and cingulate gyrus may be potential biomarkers of neurodegeneration in those at risk for CTE.
Björn Lampinen, Filip Szczepankiewicz, Mikael Novén, Danielle van Westen, Oskar Hansson, Elisabet Englund, Johan Mårtensson, Carl-Fredrik Westin, and Markus Nilsson. 6/2019. “Searching for the Neurite Density with Diffusion MRI: Challenges for Biophysical Modeling.” Hum Brain Mapp, 40, 8, Pp. 2529-45.Abstract
In vivo mapping of the neurite density with diffusion MRI (dMRI) is a high but challenging aim. First, it is unknown whether all neurites exhibit completely anisotropic ("stick-like") diffusion. Second, the "density" of tissue components may be confounded by non-diffusion properties such as T2 relaxation. Third, the domain of validity for the estimated parameters to serve as indices of neurite density is incompletely explored. We investigated these challenges by acquiring data with "b-tensor encoding" and multiple echo times in brain regions with low orientation coherence and in white matter lesions. Results showed that microscopic anisotropy from b-tensor data is associated with myelinated axons but not with dendrites. Furthermore, b-tensor data together with data acquired for multiple echo times showed that unbiased density estimates in white matter lesions require data-driven estimates of compartment-specific T2 values. Finally, the "stick" fractions of different biophysical models could generally not serve as neurite density indices across the healthy brain and white matter lesions, where outcomes of comparisons depended on the choice of constraints. In particular, constraining compartment-specific T2 values was ambiguous in the healthy brain and had a large impact on estimated values. In summary, estimating neurite density generally requires accounting for different diffusion and/or T2 properties between axons and dendrites. Constrained "index" parameters could be valid within limited domains that should be delineated by future studies.
Ashwati Vipin, Kwun Kei Ng, Fang Ji, Hee Youn Shim, Joseph KW Lim, Ofer Pasternak, Juan Helen Zhou, and Juan Helen Zhou. 5/2019. “Amyloid Burden Accelerates White Matter Degradation in Cognitively Normal Elderly Individuals.” Hum Brain Mapp, 40, 7, Pp. 2065-75.Abstract
Alterations in parietal and temporal white matter microstructure derived from diffusion tensor imaging occur in preclinical and clinical Alzheimer's disease. Amyloid beta (Aβ) deposition and such white matter alterations are two pathological hallmarks of Alzheimer's disease. However, the relationship between these pathologies is not yet understood, partly since conventional diffusion MRI methods cannot distinguish between cellular and extracellular processes. Thus, we studied Aβ-associated longitudinal diffusion MRI changes in Aβ-positive (N = 21) and Aβ-negative (N = 51) cognitively normal elderly obtained from the Alzheimer's Disease Neuroimaging Initiative dataset using linear mixed models. Aβ-positivity was based on Alzheimer's Disease Neuroimaging Initiative amyloid-PET recommendations using a standardized uptake value ratio cut-off of 1.11. We used free-water imaging to distinguish cellular and extracellular changes. We found that Aβ-positive subjects had increased baseline right uncinate fasciculus free-water fraction (FW), associated with worse baseline Alzheimer's disease assessment scale scores. Furthermore, Aβ-positive subjects showed faster decrease in fractional anisotropy (FW-corrected) in the right uncinate fasciculus and faster age-dependent right inferior longitudinal fasciculus FW increases over time. Right inferior longitudinal fasciculus FW increases were associated with greater memory decline. Importantly, these results remained significant after controlling for gray and white matter volume and hippocampal volume. This is the first study to illustrate the influence of Aβ burden on early longitudinal (in addition to baseline) white matter changes in cognitively normal elderly individuals at-risk of Alzheimer's disease, thus underscoring the importance of longitudinal studies in assessing microstructural alterations in individuals at risk of Alzheimer's disease prior to symptoms onset.
Alex V Nguyen, Andras Lasso, Hannah H Nam, Jennifer Faerber, Ahmed H Aly, Alison M Pouch, Adam B Scanlan, Francis X McGowan, Laura Mercer-Rosa, Meryl S Cohen, John Simpson, Gabor Fichtinger, and Matthew A Jolley. 5/2019. “Dynamic Three-Dimensional Geometry of the Tricuspid Valve Annulus in Hypoplastic Left Heart Syndrome with a Fontan Circulation.” J Am Soc Echocardiogr, 32, 5, Pp. 655-66.Abstract
BACKGROUND: Tricuspid regurgitation (TR) is a significant contributor to morbidity and mortality in patients with hypoplastic left heart syndrome. The goal of this study was to characterize the dynamic annular motion of the tricuspid valve in patients with HLHS with a Fontan circulation and assess the relation to tricuspid valve function. METHODS: Tricuspid annuli of 48 patients with HLHS with a Fontan circulation were modeled at end-diastole, mid-systole, end-systole, and mid-diastole using transthoracic three-dimensional echocardiography and custom code in 3D Slicer. The angle of the anterior papillary muscle (APM) relative to the annular plane in each systolic phase was also measured. RESULTS: Imaging was performed 5.0 years (interquartile range, 2-11 years) after Fontan operation. The tricuspid annulus varies in shape significantly throughout the cardiac cycle, changing in sphericity (P < .001) but not in annular height or bending angle. In univariate modeling, patients with significant TR had larger changes in septolateral diameter, lateral quadrant area, and posterior quadrant area (P < .05 for all) as well as lower (more laterally directed) APM angles (P < .001) than patients with mild or less TR. In multivariate modeling, a 1 mm/(body surface area) increase in the maximum change in septolateral diameter was associated with a 1.7-fold increase in having moderate or greater TR, while a 10° decrease in APM angle at mid-systole was associated with an almost 2.5-fold increase in moderate or greater TR (P ≤ .01 for all). CONCLUSIONS: The tricuspid annulus in patients with HLHS with a Fontan circulation changes in shape significantly throughout the cardiac cycle but remains relatively planar. Increased change in septolateral diameter and decreased APM angle are strongly associated with the presence of TR. These findings may inform annuloplasty methods and subvalvular interventions in these complex patients.
Filip Szczepankiewicz, Carl-Fredrik Westin, and Markus Nilsson. 5/2019. “Maxwell-compensated Design of Asymmetric Gradient Waveforms for Tensor-valued Diffusion Encoding.” Magn Reson Med.Abstract
PURPOSE: Diffusion encoding with asymmetric gradient waveforms is appealing because the asymmetry provides superior efficiency. However, concomitant gradients may cause a residual gradient moment at the end of the waveform, which can cause significant signal error and image artifacts. The purpose of this study was to develop an asymmetric waveform designs for tensor-valued diffusion encoding that is not sensitive to concomitant gradients. METHODS: The "Maxwell index" was proposed as a scalar invariant to capture the effect of concomitant gradients. Optimization of "Maxwell-compensated" waveforms was performed in which this index was constrained. Resulting waveforms were compared to waveforms from literature, in terms of the measured and predicted impact of concomitant gradients, by numerical analysis as well as experiments in a phantom and in a healthy human brain. RESULTS: Maxwell-compensated waveforms with Maxwell indices below 100 (mT/m) ms showed negligible signal bias in both numerical analysis and experiments. By contrast, several waveforms from literature showed gross signal bias under the same conditions, leading to a signal bias that was large enough to markedly affect parameter maps. Experimental results were accurately predicted by theory. CONCLUSION: Constraining the Maxwell index in the optimization of asymmetric gradient waveforms yields efficient diffusion encoding that negates the effects of concomitant fields while enabling arbitrary shapes of the b-tensor. This waveform design is especially useful in combination with strong gradients, long encoding times, thick slices, simultaneous multi-slice acquisition, and large FOVs.
Markus D Schirmer, Adrian V Dalca, Ramesh Sridharan, Anne-Katrin Giese, Kathleen L Donahue, Marco J Nardin, Steven JT Mocking, Elissa C McIntosh, Petrea Frid, Johan Wasselius, John W Cole, Lukas Holmegaard, Christina Jern, Jordi Jimenez-Conde, Robin Lemmens, Arne G Lindgren, James F Meschia, Jaume Roquer, Tatjana Rundek, Ralph L Sacco, Reinhold Schmidt, Pankaj Sharma, Agnieszka Slowik, Vincent Thijs, Daniel Woo, Achala Vagal, Huichun Xu, Steven J Kittner, Patrick F McArdle, Braxton D Mitchell, Jonathan Rosand, Bradford B Worrall, Ona Wu, Polina Golland, Natalia S Rost, and Natalia S Rost. 5/2019. “White Matter Hyperintensity Quantification in Large-scale Clinical Acute Ischemic Stroke Cohorts - The MRI-GENIE Study.” Neuroimage Clin, 23, Pp. 101884.Abstract
White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery. In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94-0.95; p < 0.01) and Pearson correlation of total brain volume (r = 0.90). Subsequently, we apply it to the large-scale clinical multi-site MRI-GENIE study (N = 2783) and identify a decrease in total brain volume of -2.4 cc/year. Additionally, we show that the resulting total brain volumes can successfully be used for quality control of image preprocessing. Finally, we obtain WMH volumes by building on an existing automatic WMH segmentation algorithm that delineates and distinguishes between different cerebrovascular pathologies. The learning method mimics expert knowledge of the spatial distribution of the WMH burden using a convolutional auto-encoder. This enables successful computation of WMH volumes of 2533 clinical AIS patients. We utilize these results to demonstrate the increase of WMH burden with age (0.950 cc/year) and show that single site estimates can be biased by the number of subjects recruited.
Lauren J O'Donnell, Alessandro Daducci, Demian Wassermann, and Christophe Lenglet. 4/2019. “Advances in Computational and Statistical Diffusion MRI.” NMR Biomed., 32, 4, Pp. e3805.Abstract
Computational methods are crucial for the analysis of diffusion magnetic resonance imaging (MRI) of the brain. Computational diffusion MRI can provide rich information at many size scales, including local microstructure measures such as diffusion anisotropies or apparent axon diameters, whole-brain connectivity information that describes the brain's wiring diagram and population-based studies in health and disease. Many of the diffusion MRI analyses performed today were not possible five, ten or twenty years ago, due to the requirements for large amounts of computer memory or processor time. In addition, mathematical frameworks had to be developed or adapted from other fields to create new ways to analyze diffusion MRI data. The purpose of this review is to highlight recent computational and statistical advances in diffusion MRI and to put these advances into context by comparison with the more traditional computational methods that are in popular clinical and scientific use. We aim to provide a high-level overview of interest to diffusion MRI researchers, with a more in-depth treatment to illustrate selected computational advances.
Fan Zhang, Lipeng Ning, Lauren J O'Donnell, and Ofer Pasternak. 4/2019. “MK-curve - Characterizing the Relation between Mean Kurtosis and Alterations in the Diffusion MRI Signal .” Neuroimage, 196, Pp. 68-80.Abstract
Diffusion kurtosis imaging (DKI) is a diffusion MRI (dMRI) technique to quantify brain microstructural properties. While DKI measures are sensitive to tissue alterations, they are also affected by signal alterations caused by imaging artifacts such as noise, motion and Gibbs ringing. Consequently, DKI often yields output parameter values (e.g. mean kurtosis; MK) that are implausible. These include implausible values that are outside of the range dictated by physics/biology, and visually apparent implausible values that form unexpected discontinuities, being too high or too low comparing with their neighborhood. These implausible values will introduce bias into any following data analyses (e.g. between-population statistical computation). Existing studies have attempted to correct implausible DKI parameter values in multiple ways; however, these approaches are not always effective. In this study, we propose a novel method for detecting and correcting voxels with implausible values to enable improved DKI parameter estimation. In particular, we focus on MK parameter estimation. We first characterize the relation between MK and alterations in the dMRI signal including diffusion weighted images (DWIs) and the baseline (b0) images. This is done by calculating MK for a range of synthetic DWI or b0 for each voxel, and generating curves (MK-curve) representing how alterations to the input dMRI signals affect the resulting output MK. We find that voxels with implausible MK values are more likely caused by artifacts in the b0 images than artifacts in DWIs with higher b-values. Accordingly, two characteristic b0 values, which define a range of synthetic b0 values that generate implausible MK values, are identified on the MK-curve. Based on this characterization, we propose an automatic approach for detection of voxels with implausible MK values by comparing a voxel's original b0 signal to the identified two characteristic b0 values, along with a correction strategy to replace the original b0 in each detected implausible voxel with a synthetic b0 value computed from the MK-curve. We evaluate the method on a DKI phantom dataset and dMRI datasets from the Human Connectome Project (HCP), and we compare the proposed correction method with other previously proposed correction methods. Results show that our proposed method is able to identify and correct most voxels with implausible DKI parameter values as well as voxels with implausible diffusion tensor parameter values.
J Nitsch, J Klein, P Dammann, K Wrede, O Gembruch, JH Moltz, H Meine, U Sure, R. Kikinis, and D Miller. 3/2019. “Automatic and Efficient MRI-US Segmentations for Improving Intraoperative Image Fusion in Image-guided Neurosurgery.” Neuroimage Clin, 22, Pp. 101766.Abstract
Knowledge of the exact tumor location and structures at risk in its vicinity are crucial for neurosurgical interventions. Neuronavigation systems support navigation within the patient's brain, based on preoperative MRI (preMRI). However, increasing tissue deformation during the course of tumor resection reduces navigation accuracy based on preMRI. Intraoperative ultrasound (iUS) is therefore used as real-time intraoperative imaging. Registration of preMRI and iUS remains a challenge due to different or varying contrasts in iUS and preMRI. Here, we present an automatic and efficient segmentation of B-mode US images to support the registration process. The falx cerebri and the tentorium cerebelli were identified as examples for central cerebral structures and their segmentations can serve as guiding frame for multi-modal image registration. Segmentations of the falx and tentorium were performed with an average Dice coefficient of 0.74 and an average Hausdorff distance of 12.2 mm. The subsequent registration incorporates these segmentations and increases accuracy, robustness and speed of the overall registration process compared to purely intensity-based registration. For validation an expert manually located corresponding landmarks. Our approach reduces the initial mean Target Registration Error from 16.9 mm to 3.8 mm using our intensity-based registration and to 2.2 mm with our combined segmentation and registration approach. The intensity-based registration reduced the maximum initial TRE from 19.4 mm to 5.6 mm, with the approach incorporating segmentations this is reduced to 3.0 mm. Mean volumetric intensity-based registration of preMRI and iUS took 40.5 s, including segmentations 12.0 s.
Kourosh Jafari-Khouzani, Kamran Paynabar, Fatemeh Hajighasemi, and Bruce Rosen. 3/2019. “Effect of Region of Interest Size on the Repeatability of Quantitative Brain Imaging Biomarkers.” IEEE Trans Biomed Eng, 66, 3, Pp. 864-872.Abstract
In the repeatability analysis, when the measurement is the mean value of a parametric map within a region of interest (ROI), the ROI size becomes important as by increasing the size, the measurement will have a smaller variance. This is important in decision-making in prospective clinical studies of brain when the ROI size is variable, e.g., in monitoring the effect of treatment on lesions by quantitative MRI, and in particular when the ROI is small, e.g., in the case of brain lesions in multiple sclerosis. Thus, methods to estimate repeatability measures for arbitrary sizes of ROI are desired. We propose a statistical model of the values of parametric map within the ROI and a method to approximate the model parameters, based on which we estimate a number of repeatability measures including repeatability coefficient, coefficient of variation, and intraclass correlation coefficient for an ROI with an arbitrary size. We also show how this gives an insight into related problems such as spatial smoothing in voxel-wise analysis. Experiments are conducted on simulated data as well as on scan-rescan brain MRI of healthy subjects. The main application of this study is the adjustment of the decision threshold based on the lesion size in treatment monitoring.
Nadya Shusharina, Barbara Fullerton, Judy A Adams, Gregory C Sharp, and Annie W Chan. 3/2019. “Impact of aeration change and beam arrangement on the robustness of proton plans.” J Appl Clin Med Phys, 20, 3, Pp. 14-21.Abstract
This study determines the impact of change in aeration in sinonasal cavities on the robustness of passive-scattering proton therapy plans in patients with sinonasal and nasopharyngeal malignancies. Fourteen patients, each with one planning CT and one CT acquired during radiotherapy were studied. Repeat and planning CTs were rigidly aligned and contours were transferred using deformable registration. The amount of air, tumor, and fluid within the cavity containing the tumor were measured on both CTs. The original plans were recalculated on the repeat CT. Dosimetric changes were measured for the targets and critical structures. Median decrease in gross tumor volume (GTV) was 19.8% and correlated with the time of rescan. The median change in air content was 7.1% and correlated with the tumor shrinkage. The median of the mean dose D change was +0.4% for GTV and +0.3% for clinical target volume. Median change in the maximum dose D of the critical structures were as follows: optic chiasm +0.66%, left optic nerve +0.12%, right optic nerve +0.38%, brainstem +0.6%. The dose to the GTV decreased by more than 5% in 1 case, and the dose to critical structure(s) increased by more than 5% in three cases. These four patients had sinonasal cancers and were treated with anterior proton fields that directly transversed through the involved sinus cavities. The change in dose in the replanning was strongly correlated with the change in aeration (P = 0.02). We found that the change in aeration in the vicinity of the target and the arrangement of proton beams affected the robustness of proton plan.
Magnus Herberthson, Cem Yolcu, Hans Knutsson, Carl-Fredrik Westin, and Evren Özarslan. 3/2019. “Orientationally-averaged Diffusion-attenuated Magnetic Resonance Signal for Locally-anisotropic Diffusion.” Sci Rep, 9, 1, Pp. 4899.Abstract
Diffusion-attenuated MR signal for heterogeneous media has been represented as a sum of signals from anisotropic Gaussian sub-domains to the extent that this approximation is permissible. Any effect of macroscopic (global or ensemble) anisotropy in the signal can be removed by averaging the signal values obtained by differently oriented experimental schemes. The resulting average signal is identical to what one would get if the micro-domains are isotropically (e.g., randomly) distributed with respect to orientation, which is the case for "powdered" specimens. We provide exact expressions for the orientationally-averaged signal obtained via general gradient waveforms when the microdomains are characterized by a general diffusion tensor possibly featuring three distinct eigenvalues. This extends earlier results which covered only axisymmetric diffusion as well as measurement tensors. Our results are expected to be useful in not only multidimensional diffusion MR but also solid-state NMR spectroscopy due to the mathematical similarities in the two fields.
Sonja Stojanovski, Daniel Felsky, Joseph D Viviano, Saba Shahab, Rutwik Bangali, Christie L Burton, Gabriel A Devenyi, Lauren J O'Donnell, Peter Szatmari, Mallar M Chakravarty, Stephanie Ameis, Russell Schachar, Aristotle N Voineskos, and Anne L Wheeler. 3/2019. “Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury.” Biol Psychiatry, 85, 5, Pp. 408-16.Abstract
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of traumatic brain injury (TBI) in youths. The objective of this study was to examine whether ADHD symptoms are differentially associated with genetic risk and brain structure in youths with and without a history of TBI. METHODS: Medical history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a community sample of youths. ADHD symptom severity was compared between those with and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the corpus callosum and corona radiata. RESULTS: Youths with TBI reported greater ADHD symptom severity compared with those without TBI. Polygenic score was positively associated with ADHD symptoms in youths without TBI but not in youths with TBI. The negative association between the caudate volume and ADHD symptoms was not moderated by a history of TBI. However, the relationship between ADHD symptoms and structure of the genu of the corpus callosum was negative in youths with TBI and positive in youths without TBI. CONCLUSIONS: The identification of distinct ADHD etiology in youths with TBI provides neurobiological insight into the clinical heterogeneity in the disorder. Results indicate that genetic predisposition to ADHD does not increase the risk for ADHD symptoms associated with TBI. ADHD symptoms associated with TBI may be a result of a mechanical insult rather than neurodevelopmental factors.
B Kocev, Horst K Hahn, L Linsend, William III M Wells, and Ron Kikinis. 3/2019. “Uncertainty-aware Asynchronous Scattered Motion Interpolation using Gaussian Process Regression.” Computerized Medical Imaging and Graphics, 72, Pp. 1-12.Abstract
We address the problem of interpolating randomly non-uniformly spatiotemporally scattered uncertain motion measurements, which arises in the context of soft tissue motion estimation. Soft tissue motion estimation is of great interest in the field of image-guided soft-tissue intervention and surgery navigation, because it enables the registration of pre-interventional/pre-operative navigation information on deformable soft-tissue organs. To formally define the measurements as spatiotemporally scattered motion signal samples, we propose a novel motion field representation. To perform the interpolation of the motion measurements in an uncertainty-aware optimal unbiased fashion, we devise a novel Gaussian process (GP) regression model with a non-constant-mean prior and an anisotropic covariance function and show through an extensive evaluation that it outperforms the state-of-the-art GP models that have been deployed previously for similar tasks. The employment of GP regression enables the quantification of uncertainty in the interpolation result, which would allow the amount of uncertainty present in the registered navigation information governing the decisions of the surgeon or intervention specialist to be conveyed.
Eve M Valera, Aihua Cao, Ofer Pasternak, Martha E Shenton, Marek Kubicki, Nikos Makris, and Noor Adra. 3/2019. “White Matter Correlates of Mild Traumatic Brain Injuries in Women Subjected to Intimate-Partner Violence: A Preliminary Study.” J Neurotrauma, 36, 5, Pp. 661-8.Abstract
A large proportion (range of 44-75%) of women who experience intimate-partner violence (IPV) have been shown to sustain repetitive mild traumatic brain injuries (mTBIs) from their abusers. Further, despite requests for research on TBI-related health outcomes, there are currently only a handful of studies addressing this issue and only one prior imaging study that has investigated the neural correlates of IPV-related TBIs. In response, we examined specific regions of white matter microstructure in 20 women with histories of IPV. Subjects were imaged on a 3-Tesla Siemens Magnetom TrioTim scanner using diffusion magnetic resonance imaging. We investigated the association between a score reflecting number and recency of IPV-related mTBIs and fractional anisotropy (FA) in the posterior and superior corona radiata as well as the posterior thalamic radiation, brain regions shown previously to be involved in mTBI. We also investigated the association between several cognitive measures, namely learning, memory, and cognitive flexibility, and FA in the white matter regions of interest. We report a negative correlation between the brain injury score and FA in regions of the posterior and superior corona radiata. We failed to find an association between our cognitive measures and FA in these regions, but the interpretation of these results remains inconclusive due to possible power issues. Overall, these data build upon the small but growing literature demonstrating potential consequences of mTBIs for women experiencing IPV, and further underscore the urgent need for larger and more comprehensive studies in this area.
Maria Angelique Di Biase, Fan Zhang, Amanda Lyall, Marek Kubicki, René CW Mandl, Iris E Sommer, and Ofer Pasternak. 2/2019. “Neuroimaging Auditory Verbal Hallucinations in Schizophrenia Patient and Healthy Populations.” Psychol Med, Pp. 1-10.Abstract
BACKGROUND: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers. METHODS: Diffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan-Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls. RESULTS: Compared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (<40 years) H-AVH and SCZ-AVH subjects displayed overlapping FA deficits across four regions (p < 0.05): the genu and splenium of the corpus callosum, as well as the anterior limbs of the internal capsule. Analyzing these regions with free-water imaging ascribed overlapping FA abnormalities to tissue-specific anisotropy changes. CONCLUSIONS: We identified white matter pathology associated with the presence of AVH, independent of diagnostic status. However, commonalities were constrained to younger and more homogenous groups, after reducing pathologic variance associated with advancing age and chronicity effects.
Matthew A Jolley, Andras Lasso, Hannah H Nam, Patrick V Dinh, Adam B Scanlan, Alex V Nguyen, Anna Ilina, Brian Morray, Andrew C Glatz, Francis X McGowan, Kevin Whitehead, Yoav Dori, Joseph H Gorman, Robert C Gorman, Gabor Fichtinger, and Matthew J Gillespie. 2/2019. “Toward Predictive Modeling of Catheter-based Pulmonary Valve Replacement into Native Right Ventricular Outflow Tracts.” Catheter Cardiovasc Interv, 93, 3, Pp. E143-E152.Abstract
BACKGROUND: Pulmonary insufficiency is a consequence of transannular patch repair in Tetralogy of Fallot (ToF) leading to late morbidity and mortality. Transcatheter native outflow tract pulmonary valve replacement has become a reality. However, predicting a secure, atraumatic implantation of a catheter-based device remains a significant challenge due to the complex and dynamic nature of the right ventricular outflow tract (RVOT). We sought to quantify the differences in compression and volume for actual implants, and those predicted by pre-implant modeling. METHODS: We used custom software to interactively place virtual transcatheter pulmonary valves (TPVs) into RVOT models created from pre-implant and post Harmony valve implant CT scans of 5 ovine surgical models of TOF to quantify and visualize device volume and compression. RESULTS: Virtual device placement visually mimicked actual device placement and allowed for quantification of device volume and radius. On average, simulated proximal and distal device volumes and compression did not vary statistically throughout the cardiac cycle (P = 0.11) but assessment was limited by small sample size. In comparison to actual implants, there was no significant pairwise difference in the proximal third of the device (P > 0.80), but the simulated distal device volume was significantly underestimated relative to actual device implant volume (P = 0.06). CONCLUSIONS: This study demonstrates that pre-implant modeling which assumes a rigid vessel wall may not accurately predict the degree of distal RVOT expansion following actual device placement. We suggest the potential for virtual modeling of TPVR to be a useful adjunct to procedural planning, but further development is needed.

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