Publications

2020

Gao Y, Xiao X, Han B, Li G, Ning X, Wang D, Cai W, Kikinis R, Berkovsky S, Di Ieva A, Zhang L, Ji N, Liu S. Deep Learning Methodology for Differentiating Glioma Recurrence From Radiation Necrosis Using Multimodal Magnetic Resonance Imaging: Algorithm Development and Validation. JMIR Med Inform. 2020;8(11):e19805.
BACKGROUND: The radiological differential diagnosis between tumor recurrence and radiation-induced necrosis (ie, pseudoprogression) is of paramount importance in the management of glioma patients. OBJECTIVE: This research aims to develop a deep learning methodology for automated differentiation of tumor recurrence from radiation necrosis based on routine magnetic resonance imaging (MRI) scans. METHODS: In this retrospective study, 146 patients who underwent radiation therapy after glioma resection and presented with suspected recurrent lesions at the follow-up MRI examination were selected for analysis. Routine MRI scans were acquired from each patient, including T1, T2, and gadolinium-contrast-enhanced T1 sequences. Of those cases, 96 (65.8%) were confirmed as glioma recurrence on postsurgical pathological examination, while 50 (34.2%) were diagnosed as necrosis. A light-weighted deep neural network (DNN) (ie, efficient radionecrosis neural network [ERN-Net]) was proposed to learn radiological features of gliomas and necrosis from MRI scans. Sensitivity, specificity, accuracy, and area under the curve (AUC) were used to evaluate performance of the model in both image-wise and subject-wise classifications. Preoperative diagnostic performance of the model was also compared to that of the state-of-the-art DNN models and five experienced neurosurgeons. RESULTS: DNN models based on multimodal MRI outperformed single-modal models. ERN-Net achieved the highest AUC in both image-wise (0.915) and subject-wise (0.958) classification tasks. The evaluated DNN models achieved an average sensitivity of 0.947 (SD 0.033), specificity of 0.817 (SD 0.075), and accuracy of 0.903 (SD 0.026), which were significantly better than the tested neurosurgeons (P=.02 in sensitivity and P<.001 in specificity and accuracy). CONCLUSIONS: Deep learning offers a useful computational tool for the differential diagnosis between recurrent gliomas and necrosis. The proposed ERN-Net model, a simple and effective DNN model, achieved excellent performance on routine MRI scans and showed a high clinical applicability.
Hoebel K V, Patel JB, Beers AL, Chang K, Singh P, Brown JM, Pinho MC, Batchelor TT, Gerstner ER, Rosen BR, Kalpathy-Cramer J. Radiomics Repeatability Pitfalls in a Scan-Rescan MRI Study of Glioblastoma. Radiol Artif Intell. 2020;3(1):e190199.
Purpose: To determine the influence of preprocessing on the repeatability and redundancy of radiomics features extracted using a popular open-source radiomics software package in a scan-rescan glioblastoma MRI study. Materials and Methods: In this study, a secondary analysis of T2-weighted fluid-attenuated inversion recovery (FLAIR) and T1-weighted postcontrast images from 48 patients (mean age, 56 years [range, 22-77 years]) diagnosed with glioblastoma were included from two prospective studies (ClinicalTrials.gov NCT00662506 [2009-2011] and NCT00756106 [2008-2011]). All patients underwent two baseline scans 2-6 days apart using identical imaging protocols on 3-T MRI systems. No treatment occurred between scan and rescan, and tumors were essentially unchanged visually. Radiomic features were extracted by using PyRadiomics https://pyradiomics.readthedocs.io/ under varying conditions, including normalization strategies and intensity quantization. Subsequently, intraclass correlation coefficients were determined between feature values of the scan and rescan. Results: Shape features showed a higher repeatability than intensity (adjusted < .001) and texture features (adjusted < .001) for both T2-weighted FLAIR and T1-weighted postcontrast images. Normalization improved the overlap between the region of interest intensity histograms of scan and rescan (adjusted < .001 for both T2-weighted FLAIR and T1-weighted postcontrast images), except in scans where brain extraction fails. As such, normalization significantly improves the repeatability of intensity features from T2-weighted FLAIR scans (adjusted = .003 [ score normalization] and adjusted = .002 [histogram matching]). The use of a relative intensity binning strategy as opposed to default absolute intensity binning reduces correlation between gray-level co-occurrence matrix features after normalization. Conclusion: Both normalization and intensity quantization have an effect on the level of repeatability and redundancy of features, emphasizing the importance of both accurate reporting of methodology in radiomics articles and understanding the limitations of choices made in pipeline design. © RSNA, 2020See also the commentary by Tiwari and Verma in this issue.
Drakopoulos F, Tsolakis C, Angelopoulos A, Liu Y, Yao C, Kavazidi KR, Foroglou N, Fedorov A, Frisken S, Kikinis R, Golby A, Chrisochoides N. Adaptive Physics-Based Non-Rigid Registration for Immersive Image-Guided Neuronavigation Systems. Front Digit Health. 2020;2:613608.
Objective: In image-guided neurosurgery, co-registered preoperative anatomical, functional, and diffusion tensor imaging can be used to facilitate a safe resection of brain tumors in eloquent areas of the brain. However, the brain deforms during surgery, particularly in the presence of tumor resection. Non-Rigid Registration (NRR) of the preoperative image data can be used to create a registered image that captures the deformation in the intraoperative image while maintaining the quality of the preoperative image. Using clinical data, this paper reports the results of a comparison of the accuracy and performance among several non-rigid registration methods for handling brain deformation. A new adaptive method that automatically removes mesh elements in the area of the resected tumor, thereby handling deformation in the presence of resection is presented. To improve the user experience, we also present a new way of using mixed reality with ultrasound, MRI, and CT. Materials and methods: This study focuses on 30 glioma surgeries performed at two different hospitals, many of which involved the resection of significant tumor volumes. An Adaptive Physics-Based Non-Rigid Registration method (A-PBNRR) registers preoperative and intraoperative MRI for each patient. The results are compared with three other readily available registration methods: a rigid registration implemented in 3D Slicer v4.4.0; a B-Spline non-rigid registration implemented in 3D Slicer v4.4.0; and PBNRR implemented in ITKv4.7.0, upon which A-PBNRR was based. Three measures were employed to facilitate a comprehensive evaluation of the registration accuracy: (i) visual assessment, (ii) a Hausdorff Distance-based metric, and (iii) a landmark-based approach using anatomical points identified by a neurosurgeon. Results: The A-PBNRR using multi-tissue mesh adaptation improved the accuracy of deformable registration by more than five times compared to rigid and traditional physics based non-rigid registration, and four times compared to B-Spline interpolation methods which are part of ITK and 3D Slicer. Performance analysis showed that A-PBNRR could be applied, on average, in <2 min, achieving desirable speed for use in a clinical setting. Conclusions: The A-PBNRR method performed significantly better than other readily available registration methods at modeling deformation in the presence of resection. Both the registration accuracy and performance proved sufficient to be of clinical value in the operating room. A-PBNRR, coupled with the mixed reality system, presents a powerful and affordable solution compared to current neuronavigation systems.

2019

Donnell LJO, Daducci A, Wassermann D, Lenglet C. Advances in Computational and Statistical Diffusion MRI. NMR Biomed. 2019;32(4):e3805.

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.

Kocev B, Hahn HK, Linsend L, Wells WM III, Kikinis R. Uncertainty-aware Asynchronous Scattered Motion Interpolation using Gaussian Process Regression. Computerized Medical Imaging and Graphics. 2019;72:1–12.

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.

Stojanovski S, Felsky D, Viviano JD, Shahab S, Bangali R, Burton CL, Devenyi GA, Donnell LJO, Szatmari P, Chakravarty M, Ameis S, Schachar R, Voineskos AN, Wheeler AL. Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury. Biol Psychiatry. 2019;85(5):408–16.

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.

Herberthson M, Yolcu C, Knutsson H, Westin CF, Özarslan E. Orientationally-averaged Diffusion-attenuated Magnetic Resonance Signal for Locally-anisotropic Diffusion. Sci Rep. 2019;9(1):4899.

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.

Zhang F, Wu Y, Norton I, Rathi Y, Golby AJ, Donnell LJO. Test-retest Reproducibility of White Matter Parcellation using Diffusion MRI Tractography Fiber Clustering. Hum Brain Mapp. 2019;40(10):3041–57.

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.

Zhang F, Ning L, Donnell LJO, Pasternak O. MK-curve - Characterizing the Relation between Mean Kurtosis and Alterations in the Diffusion MRI Signal. Neuroimage. 2019;196:68–80.

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.