Publications by Year: 2018


Gallardo G, Wells WM III, Deriche R, Wassermann D. Groupwise Structural Parcellation of the Whole Cortex: A Logistic Random Effects Model Based Approach. Neuroimage. 2018;170:307–20.

Current theories hold that brain function is highly related to long-range physical connections through axonal bundles, namely extrinsic connectivity. However, obtaining a groupwise cortical parcellation based on extrinsic connectivity remains challenging. Current parcellation methods are computationally expensive; need tuning of several parameters or rely on ad-hoc constraints. Furthermore, none of these methods present a model for the cortical extrinsic connectivity of the cortex. To tackle these problems, we propose a parsimonious model for the extrinsic connectivity and an efficient parceling technique based on clustering of tractograms. Our technique allows the creation of single subject and groupwise parcellations of the whole cortex. The parcellations obtained with our technique are in agreement with structural and functional parcellations in the literature. In particular, the motor and sensory cortex are subdivided in agreement with the human homunculus of Penfield. We illustrate this by comparing our resulting parcels with the motor strip mapping included in the Human Connectome Project data.

Zhang F, Savadjiev P, Cai W, Song Y, Rathi Y, Tunç B, Parker D, Kapur T, Schultz RT, Makris N, Verma R, Donnell LJO. Whole Brain White Matter Connectivity Analysis using Machine Learning: An Application to Autism. Neuroimage. 2018;172:826–37.

In this paper, we propose an automated white matter connectivity analysis method for machine learning classification and characterization of white matter abnormality via identification of discriminative fiber tracts. The proposed method uses diffusion MRI tractography and a data-driven approach to find fiber clusters corresponding to subdivisions of the white matter anatomy. Features extracted from each fiber cluster describe its diffusion properties and are used for machine learning. The method is demonstrated by application to a pediatric neuroimaging dataset from 149 individuals, including 70 children with autism spectrum disorder (ASD) and 79 typically developing controls (TDC). A classification accuracy of 78.33% is achieved in this cross-validation study. We investigate the discriminative diffusion features based on a two-tensor fiber tracking model. We observe that the mean fractional anisotropy from the second tensor (associated with crossing fibers) is most affected in ASD. We also find that local along-tract (central cores and endpoint regions) differences between ASD and TDC are helpful in differentiating the two groups. These altered diffusion properties in ASD are associated with multiple robustly discriminative fiber clusters, which belong to several major white matter tracts including the corpus callosum, arcuate fasciculus, uncinate fasciculus and aslant tract; and the white matter structures related to the cerebellum, brain stem, and ventral diencephalon. These discriminative fiber clusters, a small part of the whole brain tractography, represent the white matter connections that could be most affected in ASD. Our results indicate the potential of a machine learning pipeline based on white matter fiber clustering.

Seitz J, Rathi Y, Lyall A, Pasternak O, Del Re EC, Niznikiewicz M, Nestor P, Seidman LJ, Petryshen TL, Mesholam-Gately RI, Wojcik J, McCarley RW, Shenton ME, Koerte IK, Kubicki M. Alteration of Gray Matter Microstructure in Schizophrenia. Brain Imaging Behav. 2018;12(1):54–63.

Neuroimaging studies demonstrate gray matter (GM) macrostructural abnormalities in patients with schizophrenia (SCZ). While ex-vivo and genetic studies suggest cellular pathology associated with abnormal neurodevelopmental processes in SCZ, few in-vivo measures have been proposed to target microstructural GM organization. Here, we use diffusion heterogeneity- to study GM microstructure in SCZ. Structural and diffusion magnetic resonance imaging (MRI) were acquired on a 3 Tesla scanner in 46 patients with SCZ and 37 matched healthy controls (HC). After correction for free water, diffusion heterogeneity as well as commonly used diffusion measures FA and MD and volume were calculated for the four cortical lobes on each hemisphere, and compared between groups. Patients with early course SCZ exhibited higher diffusion heterogeneity in the GM of the frontal lobes compared to controls. Diffusion heterogeneity of the frontal lobe showed excellent discrimination between patients and HC, while none of the commonly used diffusion measures such as FA or MD did. Higher diffusion heterogeneity in the frontal lobes in early SCZ may be due to abnormal brain maturation (migration, pruning) before and during adolescence and early adulthood. Further studies are needed to investigate the role of heterogeneity as potential biomarker for SCZ risk.

Nilsson M, Larsson J, Lundberg D, Szczepankiewicz F, Witzel T, Westin CF, Bryskhe K, Topgaard D. Liquid Crystal Phantom for Validation of Microscopic Diffusion Anisotropy Measurements on Clinical MRI Systems. Magn Reson Med. 2018;79(3):1817–28.

PURPOSE: To develop a phantom for validating MRI pulse sequences and data processing methods to quantify microscopic diffusion anisotropy in the human brain. METHODS: Using a liquid crystal consisting of water, detergent, and hydrocarbon, we designed a 0.5-L spherical phantom showing the theoretically highest possible degree of microscopic anisotropy. Data were acquired on the Connectome scanner using echo-planar imaging signal readout and diffusion encoding with axisymmetric b-tensors of varying magnitude, anisotropy, and orientation. The mean diffusivity, fractional anisotropy (FA), and microscopic FA (µFA) parameters were estimated. RESULTS: The phantom was observed to have values of mean diffusivity similar to brain tissue, and relaxation times compatible with echo-planar imaging echo times on the order of 100 ms. The estimated values of µFA were at the theoretical maximum of 1.0, whereas the values of FA spanned the interval from 0.0 to 0.8 as a result of varying orientational order of the anisotropic domains within each voxel. CONCLUSIONS: The proposed phantom can be manufactured by mixing three widely available chemicals in volumes comparable to a human head. The acquired data are in excellent agreement with theoretical predictions, showing that the phantom is ideal for validating methods for measuring microscopic diffusion anisotropy on clinical MRI systems. 

Stefanik L, Erdman L, Ameis SH, Foussias G, Mulsant BH, Behdinan T, Goldenberg A, Donnell LJO, Voineskos AN. Brain-Behavior Participant Similarity Networks Among Youth and Emerging Adults with Schizophrenia Spectrum, Autism Spectrum, or Bipolar Disorder and Matched Controls. Neuropsychopharmacology. 2018;43(5):1180–8.

There is considerable heterogeneity in social cognitive and neurocognitive performance among people with schizophrenia spectrum disorders (SSD), autism spectrum disorders (ASD), bipolar disorder (BD), and healthy individuals. This study used Similarity Network Fusion (SNF), a novel data-driven approach, to identify participant similarity networks based on relationships among demographic, brain imaging, and behavioral data. T1-weighted and diffusion-weighted magnetic resonance images were obtained for 174 adolescents and young adults (aged 16-35 years) with an SSD (n=51), an ASD without intellectual disability (n=38), euthymic BD (n=34), and healthy controls (n=51). A battery of social cognitive and neurocognitive tasks were administered. Data integration, cluster determination, and biological group formation were then obtained using SNF. We identified four new groups of individuals, each with distinct neural circuit-cognitive profiles. The most influential variables driving the formation of the new groups were robustly reliable across embedded resampling techniques. The data-driven groups showed considerably greater differentiation on key social and neurocognitive circuit nodes than groups generated by diagnostic analyses or dimensional social cognitive analyses. The data-driven groups were validated through functional outcome and brain network property measures not included in the SNF model. Cutting across diagnostic boundaries, our approach can effectively identify new groups of people based on a profile of neuroimaging and behavioral data. Our findings bring us closer to disease subtyping that can be leveraged toward the targeting of specific neural circuitry among participant subgroups to ameliorate social cognitive and neurocognitive deficits.

This paper presents a method for automatically calibrating and assessing the calibration quality of an externally tracked 2-D ultrasound (US) probe by scanning arbitrary, natural tissues, as opposed a specialized calibration phantom as is the typical practice. A generative topic model quantifies the posterior probability of calibration parameters conditioned on local 2-D image features arising from a generic underlying substrate. Auto-calibration is achieved by identifying the maximum a-posteriori image-to-probe transform, and calibration quality is assessed online in terms of the posterior probability of the current image-to-probe transform. Both are closely linked to the 3-D point reconstruction error (PRE) in aligning feature observations arising from the same underlying physical structure in different US images. The method is of practical importance in that it operates simply by scanning arbitrary textured echogenic structures, e.g., in-vivo tissues in the context of the US-guided procedures, without requiring specialized calibration procedures or equipment. Observed data take the form of local scale-invariant features that can be extracted and fit to the model in near real-time. Experiments demonstrate the method on a public data set of in vivo human brain scans of 14 unique subjects acquired in the context of neurosurgery. Online calibration assessment can be performed at approximately 3 Hz for the US images of pixels. Auto-calibration achieves an internal mean PRE of 1.2 mm and a discrepancy of [2 mm, 6 mm] in comparison to the calibration via a standard phantom-based method.

Zhang F, Wu W, Ning L, McAnulty G, Waber D, Gagoski B, Sarill K, Hamoda HM, Song Y, Cai W, Rathi Y, Donnell LJO. Suprathreshold Fiber Cluster Statistics: Leveraging White Matter Geometry to Enhance Tractography Statistical Analysis. Neuroimage. 2018;171:341–54.

This work presents a suprathreshold fiber cluster (STFC) method that leverages the whole brain fiber geometry to enhance statistical group difference analyses. The proposed method consists of 1) a well-established study-specific data-driven tractography parcellation to obtain white matter tract parcels and 2) a newly proposed nonparametric, permutation-test-based STFC method to identify significant differences between study populations. The basic idea of our method is that a white matter parcel’s neighborhood (nearby parcels with similar white matter anatomy) can support the parcel’s statistical significance when correcting for multiple comparisons. We propose an adaptive parcel neighborhood strategy to allow suprathreshold fiber cluster formation that is robust to anatomically varying inter-parcel distances. The method is demonstrated by application to a multi-shell diffusion MRI dataset from 59 individuals, including 30 attention deficit hyperactivity disorder patients and 29 healthy controls. Evaluations are conducted using both synthetic and in-vivo data. The results indicate that the STFC method gives greater sensitivity in finding group differences in white matter tract parcels compared to several traditional multiple comparison correction methods.

Ning L, Nilsson M, Lasič S, Westin CF, Rathi Y. Cumulant Expansions for Measuring Water Exchange using Diffusion MRI. J Chem Phys. 2018;148(7):074109.

The rate of water exchange across cell membranes is a parameter of biological interest and can be measured by diffusion magnetic resonance imaging (dMRI). In this work, we investigate a stochastic model for the diffusion-and-exchange of water molecules. This model provides a general solution for the temporal evolution of dMRI signal using any type of gradient waveform, thereby generalizing the signal expressions for the Kärger model. Moreover, we also derive a general nth order cumulant expansion of the dMRI signal accounting for water exchange, which has not been explored in earlier studies. Based on this analytical expression, we compute the cumulant expansion for dMRI signals for the special case of single diffusion encoding (SDE) and double diffusion encoding (DDE) sequences. Our results provide a theoretical guideline on optimizing experimental parameters for SDE and DDE sequences, respectively. Moreover, we show that DDE signals are more sensitive to water exchange at short-time scale but provide less attenuation at long-time scale than SDE signals. Our theoretical analysis is also validated using Monte Carlo simulations on synthetic structures.

Albi A, Meola A, Zhang F, Kahali P, Rigolo L, Tax CMW, Ciris PA, Essayed WI, Unadkat P, Norton I, Rathi Y, Olubiyi O, Golby AJ, Donnell LJO. Image Registration to Compensate for EPI Distortion in Patients with Brain Tumors: An Evaluation of Tract-Specific Effects. J Neuroimaging. 2018;28(2):173–82.

BACKGROUND AND PURPOSE: Diffusion magnetic resonance imaging (dMRI) provides preoperative maps of neurosurgical patients’ white matter tracts, but these maps suffer from echo-planar imaging (EPI) distortions caused by magnetic field inhomogeneities. In clinical neurosurgical planning, these distortions are generally not corrected and thus contribute to the uncertainty of fiber tracking. Multiple image processing pipelines have been proposed for image-registration-based EPI distortion correction in healthy subjects. In this article, we perform the first comparison of such pipelines in neurosurgical patient data. METHODS: Five pipelines were tested in a retrospective clinical dMRI dataset of 9 patients with brain tumors. Pipelines differed in the choice of fixed and moving images and the similarity metric for image registration. Distortions were measured in two important tracts for neurosurgery, the arcuate fasciculus and corticospinal tracts. RESULTS: Significant differences in distortion estimates were found across processing pipelines. The most successful pipeline used dMRI baseline and T2-weighted images as inputs for distortion correction. This pipeline gave the most consistent distortion estimates across image resolutions and brain hemispheres. CONCLUSIONS: Quantitative results of mean tract distortions on the order of 1-2 mm are in line with other recent studies, supporting the potential need for distortion correction in neurosurgical planning. Novel results include significantly higher distortion estimates in the tumor hemisphere and greater effect of image resolution choice on results in the tumor hemisphere. Overall, this study demonstrates possible pitfalls and indicates that care should be taken when implementing EPI distortion correction in clinical settings.

Machado I, Toews M, Luo J, Unadkat P, Essayed W, George E, Teodoro P, Carvalho H, Martins J, Golland P, Pieper S, Frisken S, Golby A, Wells W. Non-rigid Registration of 3D Ultrasound for Neurosurgery using Automatic Feature Detection and Matching. Int J Comput Assist Radiol Surg. 2018;13(10):1525–38.

PURPOSE: The brain undergoes significant structural change over the course of neurosurgery, including highly nonlinear deformation and resection. It can be informative to recover the spatial mapping between structures identified in preoperative surgical planning and the intraoperative state of the brain. We present a novel feature-based method for achieving robust, fully automatic deformable registration of intraoperative neurosurgical ultrasound images. METHODS: A sparse set of local image feature correspondences is first estimated between ultrasound image pairs, after which rigid, affine and thin-plate spline models are used to estimate dense mappings throughout the image. Correspondences are derived from 3D features, distinctive generic image patterns that are automatically extracted from 3D ultrasound images and characterized in terms of their geometry (i.e., location, scale, and orientation) and a descriptor of local image appearance. Feature correspondences between ultrasound images are achieved based on a nearest-neighbor descriptor matching and probabilistic voting model similar to the Hough transform. RESULTS: Experiments demonstrate our method on intraoperative ultrasound images acquired before and after opening of the dura mater, during resection and after resection in nine clinical cases. A total of 1620 automatically extracted 3D feature correspondences were manually validated by eleven experts and used to guide the registration. Then, using manually labeled corresponding landmarks in the pre- and post-resection ultrasound images, we show that our feature-based registration reduces the mean target registration error from an initial value of 3.3 to 1.5 mm. CONCLUSIONS: This result demonstrates that the 3D features promise to offer a robust and accurate solution for 3D ultrasound registration and to correct for brain shift in image-guided neurosurgery.