Bojan Kocev, Horst Karl Hahn, Lars Linsen, William M Wells, and Ron Kikinis. 2019. Uncertainty-aware asynchronous scattered motion interpolation using Gaussian process regression. Comput Med Imaging Graph, 72, Pp. 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.
Sharon Peled, Mark Vangel, Ron Kikinis, Clare M Tempany, Fiona M Fennessy, and Andrey Fedorov. 2019. Selection of Fitting Model and Arterial Input Function for Repeatability in Dynamic Contrast-Enhanced Prostate MRI. Acad Radiol, 26, 9, Pp. e241-e251.
RATIONALE AND OBJECTIVES: Analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging is notable for the variability of calculated parameters. The purpose of this study was to evaluate the level of measurement variability and error/variability due to modeling in DCE magnetic resonance imaging parameters. MATERIALS AND METHODS: Two prostate DCE scans were performed on 11 treatment-na ıve patients with suspected or confirmed prostate peripheral zone cancer within an interval of less than two weeks. Tumor-suspicious and normal-appearing regions of interest (ROI) in the prostate peripheral zone were segmented. Different Tofts-Kety based models and different arterial input functions, with and without bolus arrival time (BAT) correction, were used to extract pharmacokinetic parameters. The percent repeatability coefficient (%RC) of fitted model parameters K, v, and k was calculated. Paired t-tests comparing parameters in tumor-suspicious ROIs and in normal-appearing tissue evaluated each parameter’s sensitivity to pathology. RESULTS: Although goodness-of-fit criteria favored the four-parameter extended Tofts-Kety model with the BAT correction included, the simplest two-parameter Tofts-Kety model overall yielded the best repeatability scores. The best %RC in the tumor-suspicious ROI was 63% for k, 28% for v and 83% for K . The best p values for discrimination between tissues were p <10 for k and K, and p = 0.11 for v. Addition of the BAT correction to the models did not improve repeatability. CONCLUSION: The parameter k, using an arterial input functions directly measured from blood signals, was more repeatable than K. Both K and k values were highly discriminatory between healthy and diseased tissues in all cases. The parameter v had high repeatability but could not distinguish the two tissue types.
Teresa Nordin, Peter Zsigmond, Sonia Pujol, Carl-Fredrik Westin, and Karin Wårdell. 2019. White Matter Tracing Combined with Electric Field Simulation - A Patient-specific Approach for Deep Brain Stimulation. Neuroimage Clin, 24, Pp. 102026.
OBJECTIVE: Deep brain stimulation (DBS) in zona incerta (Zi) is used for symptom alleviation in essential tremor (ET). Zi is positioned along the dentato-rubro-thalamic tract (DRT). Electric field simulations with the finite element method (FEM) can be used for estimation of a volume where the stimulation affects the tissue by applying a fixed isolevel (V). This work aims to develop a workflow for combined patient-specific electric field simulation and white matter tracing of the DRT, and to investigate the influence on the V from different brain tissue models, lead design and stimulation modes. The novelty of this work lies in the combination of all these components. METHOD: Patients with ET were implanted in Zi (lead 3389, n = 3, voltage mode; directional lead 6172, n = 1, current mode). Probabilistic reconstruction from diffusion MRI (dMRI) of the DRT (n = 8) was computed with FSL Toolbox. Brain tissue models were created for each patient (two homogenous, one heterogenous isotropic, one heterogenous anisotropic) and the respective V (n = 48) calculated from the Comsol Multiphysics FEM simulations. The DRT and V were visualized with 3DSlicer and superimposed on the preoperative T2 MRI, and the common volumes calculated. Dice Coefficient (DC) and level of anisotropy were used to evaluate and compare the brain models. RESULT: Combined patient-specific tractography and electric field simulation was designed and evaluated, and all patients showed benefit from DBS. All V overlapped the reconstructed DRT. Current stimulation showed prominent difference between the tissue models, where the homogenous grey matter deviated most (67 < DC < 69). Result from heterogenous isotropic and anisotropic models were similar (DC > 0.95), however the anisotropic model consistently generated larger volumes related to a greater extension of the electric field along the DBS lead. Independent of tissue model, the steering effect of the directional lead was evident and consistent. CONCLUSION: A workflow for patient-specific electric field simulations in combination with reconstruction of DRT was successfully implemented. Accurate tissue classification is essential for electric field simulations, especially when using the current control stimulation. With an accurate targeting and tractography reconstruction, directional leads have the potential to tailor the electric field into the desired region.
Nadine Spahr, Smita Thoduka, Nasreddin Abolmaali, Ron Kikinis, and Andrea Schenk. 2019. Multimodal image registration for liver radioembolization planning and patient assessment. Int J Comput Assist Radiol Surg, 14, 2, Pp. 215-25.
PURPOSE: Multimodal imaging plays a key role in patient assessment and treatment planning in liver radioembolization. It will reach its full potential for convenient use in combination with deformable image registration methods. A registration framework is proposed for multimodal liver image registration of multi-phase CT, contrast-enhanced late-phase T1, T2, and DWI MRI sequences. METHODS: A chain of four pair-wise image registrations based on a variational registration framework using normalized gradient fields as distance measure and curvature regularization is introduced. A total of 103 cases of 35 patients was evaluated based on anatomical landmarks and deformation characteristics. RESULTS: Good anatomical correspondence and physical plausibility of the deformation fields were attained. The global mean landmark errors vary from 3.20 to 5.36 mm, strongly influenced by low resolved images in z-direction. Moderate volume changes are indicated by mean minimum and maximum Jacobian determinants of 0.44 up to 1.88. No deformation foldings were detected. The mean average divergence of the deformation fields range from 0.08 to 0.16 and the mean harmonic energies vary from 0.08 to 0.58. CONCLUSION: The proposed registration solutions enable the combined use of information from multimodal imaging and provide an excellent basis for patient assessment and primary planning for liver radioembolization.


Guillermo Gallardo, William M Wells, Rachid Deriche, and Demian Wassermann. 2018. Groupwise Structural Parcellation of the Whole Cortex: A Logistic Random Effects Model Based Approach. Neuroimage, 170, Pp. 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.

Johanna Seitz, Yogesh Rathi, Amanda Lyall, Ofer Pasternak, Elisabetta C Del Re, Margaret Niznikiewicz, Paul Nestor, Larry J Seidman, Tracey L Petryshen, Raquelle I Mesholam-Gately, Joanne Wojcik, Robert W McCarley, Martha E Shenton, Inga K Koerte, and Marek Kubicki. 2018. Alteration of Gray Matter Microstructure in Schizophrenia. Brain Imaging Behav, 12, 1, Pp. 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.

Markus Nilsson, Johan Larsson, Dan Lundberg, Filip Szczepankiewicz, Thomas Witzel, Carl-Fredrik Westin, Karin Bryskhe, and Daniel Topgaard. 2018. Liquid Crystal Phantom for Validation of Microscopic Diffusion Anisotropy Measurements on Clinical MRI Systems. Magn Reson Med, 79, 3, Pp. 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. 

Fan Zhang, Peter Savadjiev, Weidong Cai, Yang Song, Yogesh Rathi, Birkan Tunç, Drew Parker, Tina Kapur, Robert T Schultz, Nikos Makris, Ragini Verma, and Lauren J O Donnell. 2018. Whole Brain White Matter Connectivity Analysis using Machine Learning: An Application to Autism. Neuroimage, 172, Pp. 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.

Matthew Toews and William M Wells. 2018. Phantomless Auto-Calibration and Online Calibration Assessment for a Tracked Freehand 2-D Ultrasound Probe. IEEE Trans Med Imaging, 37, 1, Pp. 262-72.

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.

Laura Stefanik, Lauren Erdman, Stephanie H Ameis, George Foussias, Benoit H Mulsant, Tina Behdinan, Anna Goldenberg, Lauren J O Donnell, and Aristotle N Voineskos. 2018. Brain-Behavior Participant Similarity Networks Among Youth and Emerging Adults with Schizophrenia Spectrum, Autism Spectrum, or Bipolar Disorder and Matched Controls. Neuropsychopharmacology, 43, 5, Pp. 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.