Publications

2018
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. 5/2018. “Whole Brain White Matter Connectivity Analysis using Machine Learning: An Application to Autism.” Neuroimage, 172, Pp. 826-37.Abstract
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.
Laura Stefanik, Lauren Erdman, Stephanie H Ameis, George Foussias, Benoit H Mulsant, Tina Behdinan, Anna Goldenberg, Lauren J O'Donnell, and Aristotle N Voineskos. 4/2018. “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.Abstract
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.
Simon McCarthy-Jones, Lena KL Oestreich, Amanda E Lyall, Zora Kikinis, Dominick T Newell, Peter Savadjiev, Martha E Shenton, Marek Kubicki, Ofer Pasternak, Thomas J Whitford, and Thomas J Whitford. 4/2018. “Childhood Adversity Associated with White Matter Alteration in the Corpus Callosum, Corona Radiata, and Uncinate Fasciculus of Psychiatrically Healthy Adults.” Brain Imaging Behav, 12, 2, Pp. 449-58.Abstract
Diffusion tensor imaging studies report childhood adversity (CA) is associated with reduced fractional anisotropy (FA) in multiple white matter tracts in adults. Reduced FA may result from changes in tissue, suggesting myelin/axonal damage, and/or from increased levels of extracellular free-water, suggesting atrophy or neuroinflammation. Free-water imaging can separately identify FA in tissue (FA) and the fractional volume of free-water (FW). We tested whether CA was associated with altered FA, FA, and FW in seven white matter regions of interest (ROI), in which FA changes had been previously linked to CA (corona radiata, corpus callosum, fornix, cingulum bundle: hippocampal projection, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus). Tract-based spatial statistics were performed in 147 psychiatrically healthy adults who had completed a self-report questionnaire on CA primarily stemming from parental maltreatment. ROI were extracted according to the protocol provided by the ENIGMA-DTI working group. Analyses were performed both treating CA as a continuous and a categorical variable. CA was associated with reduced FA in all ROI (although categorical analyses failed to find an association in the fornix). In contrast, CA was only associated with reduced FAin the corona radiata, corpus callosum, and uncinate fasciculus (with the continuous measure of CA finding evidence of a negative relation between CA and FAin the fornix). There was no association between CA on FW in any ROI. These results provide preliminary evidence that childhood adversity is associated with changes to the microstructure of white matter itself in adulthood. However, these results should be treated with caution until they can be replicated by future studies which address the limitations of the present study.
Guillermo Gallardo, William M Wells III, Rachid Deriche, and Demian Wassermann. 4/2018. “Groupwise Structural Parcellation of the Whole Cortex: A Logistic Random Effects Model Based Approach.” Neuroimage, 170, Pp. 307-20.Abstract

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.

Walid I Essayed, Prashin Unadkat, Ahmed Hosny, Sarah Frisken, Marcio S Rassi, Srinivasan Mukundan, James C Weaver, Ossama Al-Mefty, Alexandra J Golby, and Ian F Dunn. 3/2018. “3D Printing and Intraoperative Neuronavigation Tailoring for Skull Base Reconstruction after Extended Endoscopic Endonasal Surgery: Proof of Concept .” J Neurosurg, Pp. 1-8.Abstract
OBJECTIVE Endoscopic endonasal approaches are increasingly performed for the surgical treatment of multiple skull base pathologies. Preventing postoperative CSF leaks remains a major challenge, particularly in extended approaches. In this study, the authors assessed the potential use of modern multimaterial 3D printing and neuronavigation to help model these extended defects and develop specifically tailored prostheses for reconstructive purposes. METHODS Extended endoscopic endonasal skull base approaches were performed on 3 human cadaveric heads. Preprocedure and intraprocedure CT scans were completed and were used to segment and design extended and tailored skull base models. Multimaterial models with different core/edge interfaces were 3D printed for implantation trials. A novel application of the intraoperative landmark acquisition method was used to transfer the navigation, helping to tailor the extended models. RESULTS Prostheses were created based on preoperative and intraoperative CT scans. The navigation transfer offered sufficiently accurate data to tailor the preprinted extended skull base defect prostheses. Successful implantation of the skull base prostheses was achieved in all specimens. The progressive flexibility gradient of the models' edges offered the best compromise for easy intranasal maneuverability, anchoring, and structural stability. Prostheses printed based on intraprocedure CT scans were accurate in shape but slightly undersized. CONCLUSIONS Preoperative 3D printing of patient-specific skull base models is achievable for extended endoscopic endonasal surgery. The careful spatial modeling and the use of a flexibility gradient in the design helped achieve the most stable reconstruction. Neuronavigation can help tailor preprinted prostheses.
Jeffrey P Guenette, Robert A Stern, Yorghos Tripodis, Alicia S Chua, Vivian Schultz, Valerie J Sydnor, Nathaniel Somes, Sarina Karmacharya, Christian Lepage, Pawel Wrobel, Michael L Alosco, Brett M Martin, Christine E Chaisson, Michael J Coleman, Alexander P Lin, Ofer Pasternak, Nikos Makris, Martha E Shenton, and Inga K Koerte. 3/2018. “Automated versus Manual Segmentation of Brain Region Volumes in Former Football Players.” Neuroimage Clin, 18, Pp. 888-96.Abstract
Objectives: To determine whether or not automated FreeSurfer segmentation of brain regions considered important in repetitive head trauma can be analyzed accurately without manual correction. Materials and methods: 3 T MR neuroimaging was performed with automated FreeSurfer segmentation and manual correction of 11 brain regions in former National Football League (NFL) players with neurobehavioral symptoms and in control subjects. Automated segmentation and manually-corrected volumes were compared using an intraclass correlation coefficient (ICC). Linear mixed effects regression models were also used to estimate between-group mean volume comparisons and to correlate former NFL player brain volumes with neurobehavioral factors. Results: Eighty-six former NFL players (55.2 ± 8.0 years) and 22 control subjects (57.0 ± 6.6 years) were evaluated. ICC was highly correlated between automated and manually-corrected corpus callosum volumes (0.911), lateral ventricular volumes (right 0.980, left 0.967), and amygdala-hippocampal complex volumes (right 0.713, left 0.731), but less correlated when amygdalae (right -0.170, left -0.090) and hippocampi (right 0.539, left 0.637) volumes were separately delineated and also less correlated for cingulate gyri volumes (right 0.639, left 0.351). Statistically significant differences between former NFL player and controls were identified in 8 of 11 regions with manual correction but in only 4 of 11 regions without such correction. Within NFL players, manually corrected brain volumes were significantly associated with 3 neurobehavioral factors, but a different set of 3 brain regions and neurobehavioral factor correlations was observed for brain region volumes segmented without manual correction. Conclusions: Automated FreeSurfer segmentation of the corpus callosum, lateral ventricles, and amygdala-hippocampus complex may be appropriate for analysis without manual correction. However, FreeSurfer segmentation of the amygdala, hippocampus, and cingulate gyrus need further manual correction prior to performing group comparisons and correlations with neurobehavioral measures.
Adam B Scanlan, Alex V Nguyen, Anna Ilina, Andras Lasso, Linnea Cripe, Anusha Jegatheeswaran, Elizabeth Silvestro, Francis X McGowan, Christopher E Mascio, Stephanie Fuller, Thomas L Spray, Meryl S Cohen, Gabor Fichtinger, and Matthew A Jolley. 3/2018. “Comparison of 3D Echocardiogram-Derived 3D Printed Valve Models to Molded Models for Simulated Repair of Pediatric Atrioventricular Valves.” Pediatr Cardiol, 39, 3, Pp. 538-47.Abstract
Mastering the technical skills required to perform pediatric cardiac valve surgery is challenging in part due to limited opportunity for practice. Transformation of 3D echocardiographic (echo) images of congenitally abnormal heart valves to realistic physical models could allow patient-specific simulation of surgical valve repair. We compared materials, processes, and costs for 3D printing and molding of patient-specific models for visualization and surgical simulation of congenitally abnormal heart valves. Pediatric atrioventricular valves (mitral, tricuspid, and common atrioventricular valve) were modeled from transthoracic 3D echo images using semi-automated methods implemented as custom modules in 3D Slicer. Valve models were then both 3D printed in soft materials and molded in silicone using 3D printed "negative" molds. Using pre-defined assessment criteria, valve models were evaluated by congenital cardiac surgeons to determine suitability for simulation. Surgeon assessment indicated that the molded valves had superior material properties for the purposes of simulation compared to directly printed valves (p < 0.01). Patient-specific, 3D echo-derived molded valves are a step toward realistic simulation of complex valve repairs but require more time and labor to create than directly printed models. Patient-specific simulation of valve repair in children using such models may be useful for surgical training and simulation of complex congenital cases.
Amanda E Lyall, Ofer Pasternak, DG Robinson, D Newell, JW Trampush, JA Gallego, M Fava, AK Malhotra, KH Karlsgodt, Marek Kubicki, and PR Szeszko. 3/2018. “Greater Extracellular Free-Water in First-Episode Psychosis Predicts Better Neurocognitive Functioning.” Mol Psychiatry, 23, 3, Pp. 701-7.Abstract

Free Water Imaging is a novel diffusion magnetic resonance (MR) imaging method that is able to separate changes affecting the extracellular space from those that reflect changes in neuronal cells and processes. A previous Free Water Imaging study in schizophrenia identified significantly greater extracellular water volume in the early stages of the disorder; however, its clinical and functional sequelae have not yet been investigated. Here, we applied Free Water Imaging to a larger cohort of 63 first-episode patients with psychosis and 70 healthy matched controls to better understand the functional significance of greater extracellular water. We used diffusion MR imaging data and the Tract-Based Spatial Statistics analytic pipeline to first analyze fractional anisotropy (FA), the most commonly employed metric for assessing white matter. This comparison was then followed by Free Water Imaging analysis, where two parameters, the fractional volume of extracellular free-water (FW) and cellular tissue FA (FA-t), were estimated and compared across the entire white matter skeleton between groups, and correlated with cognitive measures at baseline and following 12 weeks of antipsychotic treatment. Our results indicated lower FA across the whole brain in patients compared with healthy controls that overlap with significant increases in FW, with only limited decreases in FA-t. In addition, higher FW correlated with better neurocognitive functioning following 12 weeks of antipsychotic treatment. We believe this is the first study to suggest that an extracellular water increase during the first-episode of psychosis, which may be indicative of an acute neuroinflammatory process, and/or cerebral edema may predict better functional outcome.

Angela Albi, Antonio Meola, Fan Zhang, Pegah Kahali, Laura Rigolo, Chantal MW Tax, Pelin Aksit Ciris, Walid I Essayed, Prashin Unadkat, Isaiah Norton, Yogesh Rathi, Olutayo Olubiyi, Alexandra J Golby, and Lauren J O'Donnell. 3/2018. “Image Registration to Compensate for EPI Distortion in Patients with Brain Tumors: An Evaluation of Tract-Specific Effects.” J Neuroimaging, 28, 2, Pp. 173-82.Abstract
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.
Markus Nilsson, Johan Larsson, Dan Lundberg, Filip Szczepankiewicz, Thomas Witzel, Carl-Fredrik Westin, Karin Bryskhe, and Daniel Topgaard. 3/2018. “Liquid Crystal Phantom for Validation of Microscopic Diffusion Anisotropy Measurements on Clinical MRI Systems.” Magn Reson Med, 79, 3, Pp. 1817-28.Abstract
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. 
T Guttuso, Niels Bergsland, J Hagemeier, DG Lichter, Ofer Pasternak, and R Zivadinov. 3/2018. “Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease.” AJNR Am J Neuroradiol, 39, 3, Pp. 479-84.Abstract
BACKGROUND AND PURPOSE: Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. MATERIALS AND METHODS: Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. RESULTS: Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline (< .001 and= .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases (= .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. CONCLUSIONS: Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known posterior-to-anterior substantia nigra degeneration that occurs over time in idiopathic Parkinson disease.
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. 2/2018. “Alteration of Gray Matter Microstructure in Schizophrenia.” Brain Imaging Behav, 12, 1, Pp. 54-63.Abstract
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.
Lipeng Ning, Markus Nilsson, Samo Lasič, Carl-Fredrik Westin, and Yogesh Rathi. 2/2018. “Cumulant Expansions for Measuring Water Exchange using Diffusion MRI.” J Chem Phys, 148, 7, Pp. 074109.Abstract
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.
Yukiko Saito, Marek Kubicki, Inga Koerte, Tatsui Otsuka, Yogesh Rathi, Ofer Pasternak, Sylvain Bouix, Ryan Eckbo, Zora Kikinis, Christian Clemm von Hohenberg, Tomohide Roppongi, Elisabetta Del Re, Takeshi Asami, Sang-Hyuk Lee, Sarina Karmacharya, Raquelle I Mesholam-Gately, Larry J Seidman, James Levitt, Robert W McCarley, Martha E Shenton, and Margaret A Niznikiewicz. 2/2018. “Impaired White Matter Connectivity between Regions Containing Mirror Neurons, and Relationship to Negative Symptoms and Social Cognition, in Patients with First-Episode Schizophrenia.” Brain Imaging Behav, 12, 1, Pp. 229-37.Abstract
In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.
David Black, Michael Unger, Nele Fischer, Ron Kikinis, Horst Hahn, Thomas Neumuth, and Bernhard Glaser. 1/2018. “Auditory Display as Feedback for a Novel Eye-tracking System for Sterile Operating Room Interaction.” Int J Comput Assist Radiol Surg, 13, 1, Pp. 37-45.Abstract
PURPOSE: The growing number of technical systems in the operating room has increased attention on developing touchless interaction methods for sterile conditions. However, touchless interaction paradigms lack the tactile feedback found in common input devices such as mice and keyboards. We propose a novel touchless eye-tracking interaction system with auditory display as a feedback method for completing typical operating room tasks. Auditory display provides feedback concerning the selected input into the eye-tracking system as well as a confirmation of the system response. METHODS: An eye-tracking system with a novel auditory display using both earcons and parameter-mapping sonification was developed to allow touchless interaction for six typical scrub nurse tasks. An evaluation with novice participants compared auditory display with visual display with respect to reaction time and a series of subjective measures. RESULTS: When using auditory display to substitute for the lost tactile feedback during eye-tracking interaction, participants exhibit reduced reaction time compared to using visual-only display. In addition, the auditory feedback led to lower subjective workload and higher usefulness and system acceptance ratings. CONCLUSION: Due to the absence of tactile feedback for eye-tracking and other touchless interaction methods, auditory display is shown to be a useful and necessary addition to new interaction concepts for the sterile operating room, reducing reaction times while improving subjective measures, including usefulness, user satisfaction, and cognitive workload.
David Black, Horst K Hahn, Ron Kikinis, Karin Wårdell, and Neda Haj-Hosseini. 1/2018. “Auditory Display for Fluorescence-guided Open Brain Tumor Surgery.” Int J Comput Assist Radiol Surg, 13, 1, Pp. 25-35.Abstract
PURPOSE: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon. METHODS: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training. RESULTS: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate. CONCLUSION: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.
Evren Özarslan, Cem Yolcu, Magnus Herberthson, Hans Knutsson, and Carl-Fredrik Westin. 1/2018. “Influence of the Size and Curvedness of Neural Projections on the Orientationally Averaged Diffusion MR Signal .” Front Phys, 6.Abstract
Neuronal and glial projections can be envisioned to be tubes of infinitesimal diameter as far as diffusion magnetic resonance (MR) measurements via clinical scanners are concerned. Recent experimental studies indicate that the decay of the orientationally-averaged signal in white-matter may be characterized by the power-law, () ∝ , where is the wavenumber determined by the parameters of the pulsed field gradient measurements. One particular study by McKinnon . [1] reports a distinctively faster decay in gray-matter. Here, we assess the role of the size and curvature of the neurites and glial arborizations in these experimental findings. To this end, we studied the signal decay for diffusion along general curves at all three temporal regimes of the traditional pulsed field gradient measurements. We show that for curvy projections, employment of longer pulse durations leads to a disappearance of the decay, while such decay is robust when narrow gradient pulses are used. Thus, in clinical acquisitions, the lack of such a decay for a fibrous specimen can be seen as indicative of fibers that are curved. We note that the above discussion is valid for an intermediate range of -values as the true asymptotic behavior of the signal decay is () ∝ for narrow pulses (through Debye-Porod law) or steeper for longer pulses. This study is expected to provide insights for interpreting the diffusion-weighted images of the central nervous system and aid in the design of acquisition strategies.
Matthew Toews and William M Wells. 1/2018. “Phantomless Auto-Calibration and Online Calibration Assessment for a Tracked Freehand 2-D Ultrasound Probe.” IEEE Trans Med Imaging, 37, 1, Pp. 262-72.Abstract
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.
Adrian V Dalca, Katherine L Bouman, William T Freeman, Natalia S Rost, Mert R Sabuncu, and Polina Golland. 2018. “Medical Image Imputation from Image Collections.” IEEE Trans Med Imaging.Abstract
We present an algorithm for creating high resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a generative model that captures fine-scale anatomical structure across subjects in clinical image collections and derive an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago.
Vivian Schultz, Robert A Stern, Yorghos Tripodis, Julie Stamm, Pawel Wrobel, Christian Lepage, Isabelle Weir, Jeffrey P Guenette, Alicia Chua, Michael L Alosco, Christine M Baugh, Nathan G Fritts, Brett M Martin, Christine E Chaisson, Michael J Coleman, Alexander P Lin, Ofer Pasternak, Martha E Shenton, and Inga K Koerte. 2018. “Age at First Exposure to Repetitive Head Impacts Is Associated with Smaller Thalamic Volumes in Former Professional American Football Players.” J Neurotrauma, 35, 2, Pp. 278-85.Abstract
Thalamic atrophy has been associated with exposure to repetitive head impacts (RHI) in professional fighters. The aim of this study is to investigate whether or not age at first exposure (AFE) to RHI is associated with thalamic volume in symptomatic former National Football League (NFL) players at risk for chronic traumatic encephalopathy (CTE). Eighty-six symptomatic former NFL players (mean age = 54.9 ± 7.9 years) were included. T1-weighted data were acquired on a 3T magnetic resonance imager, and thalamic volumes were derived using FreeSurfer. Mood and behavior, psychomotor speed, and visual and verbal memory were assessed. The association between thalamic volume and AFE to playing football and to number of years playing was calculated. Decreased thalamic volume was associated with more years of play (left: p = 0.03; right: p = 0.03). Younger AFE was associated with decreased right thalamic volume (p = 0.014). This association remained significant after adjusting for total years of play. Decreased left thalamic volume was associated with worse visual memory (p = 0.014), whereas increased right thalamic volume was associated with fewer mood and behavior symptoms (p = 0.003). In our sample of symptomatic former NFL players at risk for CTE, total years of play and AFE were associated with decreased thalamic volume. The effect of AFE on right thalamic volume was almost twice as strong as the effect of total years of play. Our findings confirm previous reports of an association between thalamic volume and exposure to RHI. They suggest further that younger AFE may result in smaller thalamic volume later in life.

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