Publications by Year: 2020

2020

Zhang F, Noh T, Juvekar P, Frisken SF, Rigolo L, Norton I, Kapur T, Pujol S, Wells W, Yarmarkovich A, Kindlmann G, Wassermann D, Estepar RSJ, Rathi Y, Kikinis R, Johnson HJ, Westin CF, Pieper S, Golby AJ, Donnell LJO. SlicerDMRI: Diffusion MRI and Tractography Research Software for Brain Cancer Surgery Planning and Visualization. JCO Clin Cancer Inform. 2020;4:299–309.

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.

Zhang F, Karayumak SC, Hoffmann N, Rathi Y, Golby AJ, Donnell LJO. Deep White Matter Analysis (DeepWMA): Fast and Consistent Tractography Segmentation. Med Image Anal. 2020;65:101761.

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.

Canalini L, Klein J, Miller D, Kikinis R. Enhanced Registration of Ultrasound Volumes by Segmentation of Resection Cavity in Neurosurgical Procedures. Int J Comput Assist Radiol Surg. 2020;15(13):1963–74.

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.

Sydnor VJ, Bouix S, Pasternak O, Hartl E, Levin-Gleba L, Reid B, Tripodis Y, Guenette JP, Kaufmann D, Makris N, Fortier C, Salat DH, Rathi Y, Milberg WP, McGlinchey RE, Shenton ME, Koerte IK. Mild Traumatic Brain Injury Impacts Associations Between Limbic System Microstructure and Post-Traumatic Stress Disorder Symptomatology. Neuroimage Clin. 2020;26:102190.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a psychiatric disorder that afflicts many individuals, yet the neuropathological mechanisms that contribute to this disorder remain to be fully determined. Moreover, it is unclear how exposure to mild traumatic brain injury (mTBI), a condition that is often comorbid with PTSD, particularly among military personnel, affects the clinical and neurological presentation of PTSD. To address these issues, the present study explores relationships between PTSD symptom severity and the microstructure of limbic and paralimbic gray matter brain regions, as well as the impact of mTBI comorbidity on these relationships. METHODS: Structural and diffusion MRI data were acquired from 102 male veterans who were diagnosed with current PTSD. Diffusion data were analyzed with free-water imaging to quantify average CSF-corrected fractional anisotropy (FA) and mean diffusivity (MD) in 18 limbic and paralimbic gray matter regions. Associations between PTSD symptom severity and regional average dMRI measures were examined with repeated measures linear mixed models. Associations were studied separately in veterans with PTSD only, and in veterans with PTSD and a history of military mTBI. RESULTS: Analyses revealed that in the PTSD only cohort, more severe symptoms were associated with higher FA in the right amygdala-hippocampus complex, lower FA in the right cingulate cortex, and lower MD in the left medial orbitofrontal cortex. In the PTSD and mTBI cohort, more severe PTSD symptoms were associated with higher FA bilaterally in the amygdala-hippocampus complex, with higher FA bilaterally in the nucleus accumbens, with lower FA bilaterally in the cingulate cortex, and with higher MD in the right amygdala-hippocampus complex. CONCLUSIONS: These findings suggest that the microstructure of limbic and paralimbic brain regions may influence PTSD symptomatology. Further, given the additional associations observed between microstructure and symptom severity in veterans with head trauma, we speculate that mTBI may exacerbate the impact of brain microstructure on PTSD symptoms, especially within regions of the brain known to be vulnerable to chronic stress. A heightened sensitivity to the microstructural environment of the brain could partially explain why individuals with PTSD and mTBI comorbidity experience more severe symptoms and poorer illness prognoses than those without a history of brain injury. The relevance of these microstructural findings to the conceptualization of PTSD as being a disorder of stress-induced neuronal connectivity loss is discussed.

Rushmore RJ, Wilson-Braun P, Papadimitriou G, Ng I, Rathi Y, Zhang F, Donnell LJO, Kubicki M, Bouix S, Yeterian E, Lemaire JJ, Calabrese E, Johnson A, Kikinis R, Makris N. 3D Exploration of the Brainstem in 50-Micron Resolution MRI. Front Neuroanat. 2020;14:40.

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.

Nenning KH, Furtner J, Kiesel B, Schwartz E, Roetzer T, Fortelny N, Bock C, Grisold A, Marko M, Leutmezer F, Liu H, Golland P, Stoecklein S, Hainfellner JA, Kasprian G, Prayer D, Marosi C, Widhalm G, Woehrer A, Langs G. Distributed Changes of the Functional Connectome in Patients with Glioblastoma. Sci Rep. 2020;10(1):18312.

Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.

Zhang F, Xie G, Leung L, Mooney MA, Epprecht L, Norton I, Rathi Y, Kikinis R, Al-Mefty O, Makris N, Golby AJ, Donnell LJO. Creation of a Novel Trigeminal Tractography Atlas for Automated Trigeminal Nerve Identification. Neuroimage. 2020;220:117063.

Diffusion MRI (dMRI) tractography has been successfully used to study the trigeminal nerves (TGNs) in many clinical and research applications. Currently, identification of the TGN in tractography data requires expert nerve selection using manually drawn regions of interest (ROIs), which is prone to inter-observer variability, time-consuming and carries high clinical and labor costs. To overcome these issues, we propose to create a novel anatomically curated TGN tractography atlas that enables automated identification of the TGN from dMRI tractography. In this paper, we first illustrate the creation of a trigeminal tractography atlas. Leveraging a well-established computational pipeline and expert neuroanatomical knowledge, we generate a data-driven TGN fiber clustering atlas using tractography data from 50 subjects from the Human Connectome Project. Then, we demonstrate the application of the proposed atlas for automated TGN identification in new subjects, without relying on expert ROI placement. Quantitative and visual experiments are performed with comparison to expert TGN identification using dMRI data from two different acquisition sites. We show highly comparable results between the automatically and manually identified TGNs in terms of spatial overlap and visualization, while our proposed method has several advantages. First, our method performs automated TGN identification, and thus it provides an efficient tool to reduce expert labor costs and inter-operator bias relative to expert manual selection. Second, our method is robust to potential imaging artifacts and/or noise that can prevent successful manual ROI placement for TGN selection and hence yields a higher successful TGN identification rate.

Haehn D, Franke L, Zhang F, Cetin-Karayumak S, Pieper S, Donnell LJO, Rathi Y. TRAKO: Efficient Transmission of Tractography Data for Visualization. Med Image Comput Comput Assist Interv. 2020;12267:322–32.

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.

Wang CJ, Rost NS, Golland P. Spatial-Intensity Transform GANs for High Fidelity Medical Image-to-Image Translation. Med Image Comput Comput Assist Interv. 2020;12262:749–59.

Despite recent progress in image-to-image translation, it remains challenging to apply such techniques to clinical quality medical images. We develop a novel parameterization of conditional generative adversarial networks that achieves high image fidelity when trained to transform MRIs conditioned on a patient’s age and disease severity. The spatial-intensity transform generative adversarial network (SIT-GAN) constrains the generator to a smooth spatial transform composed with sparse intensity changes. This technique improves image quality and robustness to artifacts, and generalizes to different scanners. We demonstrate SIT-GAN on a large clinical image dataset of stroke patients, where it captures associations between ventricle expansion and aging, as well as between white matter hyperintensities and stroke severity. Additionally, SIT-GAN provides a disentangled view of the variation in shape and appearance across subjects.

Chauhan G, Liao R, Wells W, Andreas J, Wang X, Berkowitz S, Horng S, Szolovits P, Golland P. Joint Modeling of Chest Radiographs and Radiology Reports for Pulmonary Edema Assessment. Med Image Comput Comput Assist Interv. 2020;12262:529–39.

We propose and demonstrate a novel machine learning algorithm that assesses pulmonary edema severity from chest radiographs. While large publicly available datasets of chest radiographs and free-text radiology reports exist, only limited numerical edema severity labels can be extracted from radiology reports. This is a significant challenge in learning such models for image classification. To take advantage of the rich information present in the radiology reports, we develop a neural network model that is trained on both images and free-text to assess pulmonary edema severity from chest radiographs at inference time. Our experimental results suggest that the joint image-text representation learning improves the performance of pulmonary edema assessment compared to a supervised model trained on images only. We also show the use of the text for explaining the image classification by the joint model. To the best of our knowledge, our approach is the first to leverage free-text radiology reports for improving the image model performance in this application. Our code is available at: https://github.com/RayRuizhiLiao/joint_chestxray.