Image Features for Brain Phenotypes Core Publications

Alireza Sedghi, Lauren J O'Donnell, Tina Kapur, Erik Learned-Miller, Parvin Mousavi, and William M Wells. 4/2021. “Image Registration: Maximum Likelihood, Minimum Entropy and Deep Learning.” Med Image Anal, 69, Pp. 101939.Abstract
In this work, we propose a theoretical framework based on maximum profile likelihood for pairwise and groupwise registration. By an asymptotic analysis, we demonstrate that maximum profile likelihood registration minimizes an upper bound on the joint entropy of the distribution that generates the joint image data. Further, we derive the congealing method for groupwise registration by optimizing the profile likelihood in closed form, and using coordinate ascent, or iterative model refinement. We also describe a method for feature based registration in the same framework and demonstrate it on groupwise tractographic registration. In the second part of the article, we propose an approach to deep metric registration that implements maximum likelihood registration using deep discriminative classifiers. We show further that this approach can be used for maximum profile likelihood registration to discharge the need for well-registered training data, using iterative model refinement. We demonstrate that the method succeeds on a challenging registration problem where the standard mutual information approach does not perform well.
Kyriakos Dalamagkas, Magdalini Tsintou, Yogesh Rathi, Lauren J O'Donnell, Ofer Pasternak, Xue Gong, Anne Zhu, Peter Savadjiev, George M Papadimitriou, Marek Kubicki, Edward H Yeterian, and Nikos Makris. 6/2020. “Individual Variations of the Human Corticospinal Tract and Its Hand-Related Motor Fibers Using Diffusion MRI Tractography.” Brain Imaging Behav, 14, 3, Pp. 696-714.Abstract
The corticospinal tract (CST) is one of the most well studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available. However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we propose a novel method, using manually drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heat maps from 37 subjects for both the aforementioned tracts, which could be utilized as a reference for future studies with clinical focus to explore neuropathology in both trauma and disease states.
Luca Canalini, Jan Klein, Dorothea Miller, and Ron Kikinis. 12/2020. “Enhanced Registration of Ultrasound Volumes by Segmentation of Resection Cavity in Neurosurgical Procedures.” Int J Comput Assist Radiol Surg, 15, 13, Pp. 1963-74.Abstract
PURPOSE: Neurosurgeons can have a better understanding of surgical procedures by comparing ultrasound images obtained at different phases of the tumor resection. However, establishing a direct mapping between subsequent acquisitions is challenging due to the anatomical changes happening during surgery. We propose here a method to improve the registration of ultrasound volumes, by excluding the resection cavity from the registration process. METHODS: The first step of our approach includes the automatic segmentation of the resection cavities in ultrasound volumes, acquired during and after resection. We used a convolution neural network inspired by the 3D U-Net. Then, subsequent ultrasound volumes are registered by excluding the contribution of resection cavity. RESULTS: Regarding the segmentation of the resection cavity, the proposed method achieved a mean DICE index of 0.84 on 27 volumes. Concerning the registration of the subsequent ultrasound acquisitions, we reduced the mTRE of the volumes acquired before and during resection from 3.49 to 1.22 mm. For the set of volumes acquired before and after removal, the mTRE improved from 3.55 to 1.21 mm. CONCLUSIONS: We proposed an innovative registration algorithm to compensate the brain shift affecting ultrasound volumes obtained at subsequent phases of neurosurgical procedures. To the best of our knowledge, our method is the first to exclude automatically segmented resection cavities in the registration of ultrasound volumes in neurosurgery.
Daniel Haehn, Loraine Franke, Fan Zhang, Suheyla Cetin-Karayumak, Steve Pieper, Lauren J O'Donnell, and Yogesh Rathi. 10/2020. “TRAKO: Efficient Transmission of Tractography Data for Visualization.” Med Image Comput Comput Assist Interv, 12267, Pp. 322-32.Abstract
Fiber tracking produces large tractography datasets that are tens of gigabytes in size consisting of millions of streamlines. Such vast amounts of data require formats that allow for efficient storage, transfer, and visualization. We present TRAKO, a new data format based on the Graphics Layer Transmission Format (glTF) that enables immediate graphical and hardware-accelerated processing. We integrate a state-of-the-art compression technique for vertices, streamlines, and attached scalar and property data. We then compare TRAKO to existing tractography storage methods and provide a detailed evaluation on eight datasets. TRAKO can achieve data reductions of over 28x without loss of statistical significance when used to replicate analysis from previously published studies.
Richard Jarrett Rushmore, Peter Wilson-Braun, George Papadimitriou, Isaac Ng, Yogesh Rathi, Fan Zhang, Lauren Jean O'Donnell, Marek Kubicki, Sylvain Bouix, Edward Yeterian, Jean-Jacques Lemaire, Evan Calabrese, Allan G Johnson, Ron Kikinis, and Nikos Makris. 9/2020. “3D Exploration of the Brainstem in 50-Micron Resolution MRI.” Front Neuroanat, 14, Pp. 40.Abstract
The brainstem, a structure of vital importance in mammals, is currently becoming a principal focus in cognitive, affective, and clinical neuroscience. Midbrain, pontine and medullary structures serve as the conduit for signals between the forebrain and spinal cord, are the epicenter of cranial nerve-circuits and systems, and subserve such integrative functions as consciousness, emotional processing, pain, and motivation. In this study, we parcellated the nuclear masses and the principal fiber pathways that were visible in a high-resolution T2-weighted MRI dataset of 50-micron isotropic voxels of a postmortem human brainstem. Based on this analysis, we generated a detailed map of the human brainstem. To assess the validity of our maps, we compared our observations with histological maps of traditional human brainstem atlases. Given the unique capability of MRI-based morphometric analysis in generating and preserving the morphology of 3D objects from individual 2D sections, we reconstructed the motor, sensory and integrative neural systems of the brainstem and rendered them in 3D representations. We anticipate the utilization of these maps by the neuroimaging community for applications in basic neuroscience as well as in neurology, psychiatry, and neurosurgery, due to their versatile computational nature in 2D and 3D representations in a publicly available capacity.
James J Levitt, Paul G Nestor, Marek Kubicki, Amanda E Lyall, Fan Zhang, Tammy Riklin-Raviv, Lauren J O Donnell, Robert W McCarley, Martha E Shenton, and Yogesh Rathi. 7/2020. “Miswiring of Frontostriatal Projections in Schizophrenia.” Schizophr Bull, 46, 4, Pp. 990-8.Abstract
We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way. We extracted diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions. We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P  = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P  = .04) with a left (P  = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P  = .045) driven by differences in left hemisphere limbic (P  = .007) and associative (P  = .01), but not sensorimotor, striatum. These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.
Fan Zhang, Suheyla Cetin Karayumak, Nico Hoffmann, Yogesh Rathi, Alexandra J Golby, and Lauren J O'Donnell. 6/2020. “Deep White Matter Analysis (DeepWMA): Fast and Consistent Tractography Segmentation.” Med Image Anal, 65, Pp. 101761.Abstract
White matter tract segmentation, i.e. identifying tractography fibers (streamline trajectories) belonging to anatomically meaningful fiber tracts, is an essential step to enable tract quantification and visualization. In this study, we present a deep learning tractography segmentation method (DeepWMA) that allows fast and consistent identification of 54 major deep white matter fiber tracts from the whole brain. We create a large-scale training tractography dataset of 1 million labeled fiber samples, and we propose a novel 2D multi-channel feature descriptor (FiberMap) that encodes spatial coordinates of points along each fiber. We learn a convolutional neural network (CNN) fiber classification model based on FiberMap and obtain a high fiber classification accuracy of 90.99% on the training tractography data with ground truth fiber labels. Then, the method is evaluated on a test dataset of 597 diffusion MRI scans from six independently acquired populations across genders, the lifespan (1 day - 82 years), and different health conditions (healthy control, neuropsychiatric disorders, and brain tumor patients). We perform comparisons with two state-of-the-art tract segmentation methods. Experimental results show that our method obtains a highly consistent tract segmentation result, where on average over 99% of the fiber tracts are successfully identified across all subjects under study, most importantly, including neonates and patients with space-occupying brain tumors. We also demonstrate good generalization of the method to tractography data from multiple different fiber tracking methods. The proposed method leverages deep learning techniques and provides a fast and efficient tool for brain white matter segmentation in large diffusion MRI tractography datasets.
Fan Zhang, Thomas Noh, Parikshit Juvekar, Sarah F Frisken, Laura Rigolo, Isaiah Norton, Tina Kapur, Sonia Pujol, William Wells, Alex Yarmarkovich, Gordon Kindlmann, Demian Wassermann, Raul San Jose Estepar, Yogesh Rathi, Ron Kikinis, Hans J Johnson, Carl-Fredrik Westin, Steve Pieper, Alexandra J Golby, and Lauren J O'Donnell. 3/2020. “SlicerDMRI: Diffusion MRI and Tractography Research Software for Brain Cancer Surgery Planning and Visualization.” JCO Clin Cancer Inform, 4, Pp. 299-309.Abstract
PURPOSE: We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health-supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors. PATIENTS AND METHODS: In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI. RESULTS: We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each. CONCLUSION: SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.
Christian Wachinger, Matthew Toews, Georg Langs, William Wells, and Polina Golland. 2/2020. “Keypoint Transfer for Fast Whole-Body Segmentation.” IEEE Trans Med Imaging, 39, 2, Pp. 273-82.Abstract
We introduce an approach for image segmentation based on sparse correspondences between keypoints in testing and training images. Keypoints represent automatically identified distinctive image locations, where each keypoint correspondence suggests a transformation between images. We use these correspondences to transfer label maps of entire organs from the training images to the test image. The keypoint transfer algorithm includes three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ segmentations. We report segmentation results for abdominal organs in whole-body CT and MRI, as well as in contrast-enhanced CT and MRI. Our method offers a speed-up of about three orders of magnitude in comparison to common multi-atlas segmentation, while achieving an accuracy that compares favorably. Moreover, keypoint transfer does not require the registration to an atlas or a training phase. Finally, the method allows for the segmentation of scans with highly variable field-of-view.
Guoqiang Xie, Fan Zhang, Laura Leung, Michael A Mooney, Lorenz Epprecht, Isaiah Norton, Yogesh Rathi, Ron Kikinis, Ossama Al-Mefty, Nikos Makris, Alexandra J Golby, and Lauren J O'Donnell. 1/2020. “Anatomical Assessment of Trigeminal Nerve Tractography Using Diffusion MRI: A Comparison of Acquisition B-Values and Single- and Multi-Fiber Tracking Strategies.” Neuroimage Clin, 25, Pp. 102160.Abstract
BACKGROUND: The trigeminal nerve (TGN) is the largest cranial nerve and can be involved in multiple inflammatory, compressive, ischemic or other pathologies. Currently, imaging-based approaches to identify the TGN mostly rely on T2-weighted magnetic resonance imaging (MRI), which provides localization of the cisternal portion of the TGN where the contrast between nerve and cerebrospinal fluid (CSF) is high enough to allow differentiation. The course of the TGN within the brainstem as well as anterior to the cisternal portion, however, is more difficult to display on traditional imaging sequences. An advanced imaging technique, diffusion MRI (dMRI), enables tracking of the trajectory of TGN fibers and has the potential to visualize anatomical regions of the TGN not seen on T2-weighted imaging. This may allow a more comprehensive assessment of the nerve in the context of pathology. To date, most work in TGN tracking has used clinical dMRI acquisitions with a b-value of 1000 s/mm and conventional diffusion tensor MRI (DTI) tractography methods. Though higher b-value acquisitions and multi-tensor tractography methods are known to be beneficial for tracking brain white matter fiber tracts, there have been no studies conducted to evaluate the performance of these advanced approaches on nerve tracking of the TGN, in particular on tracking different anatomical regions of the TGN. OBJECTIVE: We compare TGN tracking performance using dMRI data with different b-values, in combination with both single- and multi-tensor tractography methods. Our goal is to assess the advantages and limitations of these different strategies for identifying the anatomical regions of the TGN. METHODS: We proposed seven anatomical rating criteria including true and false positive structures, and we performed an expert rating study of over 1000 TGN visualizations, as follows. We tracked the TGN using high-quality dMRI data from 100 healthy adult subjects from the Human Connectome Project (HCP). TGN tracking performance was compared across dMRI acquisitions with b = 1000 s/mm, b = 2000 s/mm and b = 3000 s/mm, using single-tensor (1T) and two-tensor (2T) unscented Kalman filter (UKF) tractography. This resulted in a total of six tracking strategies. The TGN was identified using an anatomical region-of-interest (ROI) selection approach. First, in a subset of the dataset we identified ROIs that provided good TGN tracking performance across all tracking strategies. Using these ROIs, the TGN was then tracked in all subjects using the six tracking strategies. An expert rater (GX) visually assessed and scored each TGN based on seven anatomical judgment criteria. These criteria included the presence of multiple expected anatomical segments of the TGN (true positive structures), specifically branch-like structures, cisternal portion, mesencephalic trigeminal tract, and spinal cord tract of the TGN. False positive criteria included the presence of any fibers entering the temporal lobe, the inferior cerebellar peduncle, or the middle cerebellar peduncle. Expert rating scores were analyzed to compare TGN tracking performance across the six tracking strategies. Intra- and inter-rater validation was performed to assess the reliability of the expert TGN rating result. RESULTS: The TGN was selected using two anatomical ROIs (Meckel's Cave and cisternal portion of the TGN). The two-tensor tractography method had significantly better performance on identifying true positive structures, while generating more false positive streamlines in comparison to the single-tensor tractography method. TGN tracking performance was significantly different across the three b-values for almost all structures studied. Tracking performance was reported in terms of the percentage of subjects achieving each anatomical rating criterion. Tracking of the cisternal portion and branching structure of the TGN was generally successful, with the highest performance of over 98% using two-tensor tractography and b = 1000 or b = 2000. However, tracking the smaller mesencephalic and spinal cord tracts of the TGN was quite challenging (highest performance of 37.5% and 57.07%, using two-tensor tractography with b = 1000 and b = 2000, respectively). False positive connections to the temporal lobe (over 38% of subjects for all strategies) and cerebellar peduncles (100% of subjects for all strategies) were prevalent. High joint probability of agreement was obtained in the inter-rater (on average 83%) and intra-rater validation (on average 90%), showing a highly reliable expert rating result. CONCLUSIONS: Overall, the results of the study suggest that researchers and clinicians may benefit from tailoring their acquisition and tracking methodology to the specific anatomical portion of the TGN that is of the greatest interest. For example, tracking of branching structures and TGN-T2 overlap can be best achieved with a two-tensor model and an acquisition using b = 1000 or b = 2000. In general, b = 1000 and b = 2000 acquisitions provided the best-rated tracking results. Further research is needed to improve both sensitivity and specificity of the depiction of the TGN anatomy using dMRI.
Laurent Chauvin, Kuldeep Kumar, Christian Wachinger, Marc Vangel, Jacques de Guise, Christian Desrosiers, William Wells, and Matthew Toews. 1/2020. “Neuroimage Signature from Salient Keypoints is Highly Specific to Individuals and Shared by Close Relatives.” Neuroimage, 204, Pp. 116208.Abstract
Neuroimaging studies typically adopt a common feature space for all data, which may obscure aspects of neuroanatomy only observable in subsets of a population, e.g. cortical folding patterns unique to individuals or shared by close relatives. Here, we propose to model individual variability using a distinctive keypoint signature: a set of unique, localized patterns, detected automatically in each image by a generic saliency operator. The similarity of an image pair is then quantified by the proportion of keypoints they share using a novel Jaccard-like measure of set overlap. Experiments demonstrate the keypoint method to be highly efficient and accurate, using a set of 7536 T1-weighted MRIs pooled from four public neuroimaging repositories, including twins, non-twin siblings, and 3334 unique subjects. All same-subject image pairs are identified by a similarity threshold despite confounds including aging and neurodegenerative disease progression. Outliers reveal previously unknown data labeling inconsistencies, demonstrating the usefulness of the keypoint signature as a computational tool for curating large neuroimage datasets.
Jian Wang, William M Wells, Polina Golland, and Miaomiao Zhang. 12/2019. “Registration Uncertainty Quantification via Low-dimensional Characterization of Geometric Deformations.” Magn Reson Imaging, 64, Pp. 122-31.Abstract
This paper presents an efficient approach to quantifying image registration uncertainty based on a low-dimensional representation of geometric deformations. In contrast to previous methods, we develop a Bayesian diffeomorphic registration framework in a bandlimited space, rather than a high-dimensional image space. We show that a dense posterior distribution on deformation fields can be fully characterized by much fewer parameters, which dramatically reduces the computational complexity of model inferences. To further avoid heavy computation loads introduced by random sampling algorithms, we approximate a marginal posterior by using Laplace's method at the optimal solution of log-posterior distribution. Experimental results on both 2D synthetic data and real 3D brain magnetic resonance imaging (MRI) scans demonstrate that our method is significantly faster than the state-of-the-art diffeomorphic registration uncertainty quantification algorithms, while producing comparable results.
Jie Luo, Alireza Sedghi, Karteek Popuri, Dana Cobzas, Miaomiao Zhang, Frank Preiswerk, Matthew Toews, Alexandra Golby, Masashi Sugiyama, William III M Wells, and Sarah Frisken. 10/2019. “On the Applicability of Registration Uncertainty.” In MICCAI 2019, LNCS 11765: Pp. 410-9. Shenzhen, China: Springer.Abstract
Estimating the uncertainty in (probabilistic) image registration enables, e.g., surgeons to assess the operative risk based on the trustworthiness of the registered image data. If surgeons receive inaccurately calculated registration uncertainty and misplace unwarranted confidence in the alignment solutions, severe consequences may result. For probabilistic image registration (PIR), the predominant way to quantify the registration uncertainty is using summary statistics of the distribution of transformation parameters. The majority of existing research focuses on trying out different summary statistics as well as means to exploit them. Distinctively, in this paper, we study two rarely examined topics: (1) whether those summary statistics of the transformation distribution most informatively represent the registration uncertainty; (2) Does utilizing the registration uncertainty always be beneficial. We show that there are two types of uncertainties: the transformation uncertainty, Ut, and label uncertainty Ul. The conventional way of using Ut to quantify Ul is inappropriate and can be misleading. By a real data experiment, we also share a potentially critical finding that making use of the registration uncertainty may not always be an improvement.
Luo MICCAI 2019
Fan Zhang, Nico Hoffmann, Suheyla Cetin Karayumak, Yogesh Rathi, Alexandra J Golby, and Lauren J O'Donnell. 10/2019. “Deep White Matter Analysis: Fast, Consistent Tractography Segmentation Across Populations and dMRI Acquisitions.” Med Image Comput Comput Assist Interv, 11766, Pp. 599-608.Abstract
We present a deep learning tractography segmentation method that allows fast and consistent white matter fiber tract identification across healthy and disease populations and across multiple diffusion MRI (dMRI) acquisitions. We create a large-scale training tractography dataset of 1 million labeled fiber samples (54 anatomical tracts are included). To discriminate between fibers from different tracts, we propose a novel 2D multi-channel feature descriptor (FiberMap) that encodes spatial coordinates of points along each fiber. We learn a CNN tract classification model based on FiberMap and obtain a high tract classification accuracy of 90.99%. The method is evaluated on a test dataset of 374 dMRI scans from three independently acquired populations across health conditions (healthy control, neuropsychiatric disorders, and brain tumor patients). We perform comparisons with two state-of-the-art white matter tract segmentation methods. Experimental results show that our method obtains a highly consistent segmentation result, where over 99% of the fiber tracts are successfully detected across all subjects under study, most importantly, including patients with space occupying brain tumors. The proposed method leverages deep learning techniques and provides a much faster and more efficient tool for large data analysis than methods using traditional machine learning techniques.
Inês Machado, Matthew Toews, Elizabeth George, Prashin Unadkat, Walid Essayed, Jie Luo, Pedro Teodoro, Herculano Carvalho, Jorge Martins, Polina Golland, Steve Pieper, Sarah Frisken, Alexandra Golby, William Wells, and Yangming Ou. 8/2019. “Deformable MRI-Ultrasound Registration using Correlation-based Attribute Matching for Brain Shift Correction: Accuracy and Generality in Multi-site Data.” Neuroimage, 202, Pp. 116094.Abstract
Intraoperative tissue deformation, known as brain shift, decreases the benefit of using preoperative images to guide neurosurgery. Non-rigid registration of preoperative magnetic resonance (MR) to intraoperative ultrasound (US) has been proposed as a means to compensate for brain shift. We focus on the initial registration from MR to predurotomy US. We present a method that builds on previous work to address the need for accuracy and generality of MR-iUS registration algorithms in multi-site clinical data. To improve accuracy of registration, we use high-dimensional texture attributes instead of image intensities and propose to replace the standard difference-based attribute matching with correlation-based attribute matching. We also present a strategy that deals explicitly with the large field-of-view mismatch between MR and iUS images. We optimize key parameters across independent MR-iUS brain tumor datasets acquired at three different institutions, with a total of 43 tumor patients and 758 corresponding landmarks to validate the registration algorithm. Despite differences in imaging protocols, patient demographics and landmark distributions, our algorithm was able to reduce landmark errors prior to registration in three data sets (5.37 ± 4.27, 4.18 ± 1.97 and 6.18 ± 3.38 mm, respectively) to a consistently low level (2.28 ± 0.71, 2.08 ± 0.37 and 2.24 ± 0.78 mm, respectively). Our algorithm is compared to 15 other algorithms that have been previously tested on MR-iUS registration and it is competitive with the state-of-the-art on multiple datasets. We show that our algorithm has one of the lowest errors in all datasets (accuracy), and this is achieved while sticking to a fixed set of parameters for multi-site data (generality). In contrast, other algorithms/tools of similar performance need per-dataset parameter tuning (high accuracy but lower generality), and those that stick to fixed parameters have larger errors or inconsistent performance (generality but not the top accuracy). We further characterized landmark errors according to brain regions and tumor types, a topic so far missing in the literature. We found that landmark errors were higher in high-grade than low-grade glioma patients, and higher in tumor regions than in other brain regions.
Fan Zhang, Lipeng Ning, Lauren J O'Donnell, and Ofer Pasternak. 8/2019. “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.
Di Fan, Nikhil N Chaudhari, Kenneth A Rostowsky, Maria Calvillo, Sean K Lee, Nahian F Chowdhury, Fan Zhang, Lauren J O'Donnell, and Andrei Irimia. 7/2019. “Post-Traumatic Cerebral Microhemorrhages and their Effects Upon White Matter Connectivity in the Aging Human Brain.” Conf Proc IEEE Eng Med Biol Soc, 2019, Pp. 198-203.Abstract
Cerebral microbleeds (CMBs), a common manifestation of mild traumatic brain injury (mTBI), have been sporadically implicated in the neurocognitive deficits of mTBI victims but their clinical significance has not been established adequately. Here we investigate the longitudinal effects of post-mTBI CMBs upon the fractional anisotropy (FA) of white matter (WM) in 21 older mTBI patients across the first ~6 months post-injury. CMBs were segmented automatically from susceptibility-weighted imaging (SWI) by leveraging the intensity gradient properties of SWI to identify CMB-related hypointensities using gradient-based edge detection. A detailed diffusion magnetic resonance imaging (dMRI) atlas of WM was used to segment and cluster tractography streamlines whose prototypes were then identified. The correlation coefficient was calculated between (A) FA values at vertices along streamline prototypes and (B) topological (along-streamline) distances between these vertices and the nearest CMB. Across subjects, the CMB identification approach achieved a sensitivity of 97.1% ± 4.7% and a precision of 72.4% ± 11.0% across subjects. The correlation coefficient was found to be negative and, additionally, statistically significant for 12.3% ± 3.5% of WM clusters (p <; 0.05, corrected), whose FA was found to decrease, on average, by 11.8% ± 5.3% across the first 6 months post-injury. These results suggest that CMBs can be associated with deleterious effects upon peri-lesional WM and highlight the vulnerability of older mTBI patients to neurovascular injury.
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.
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.
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.