Publications by Year: 2018


Danielle F Pace, Adrian Dalca, Tom Brosch, Tal Geva, Andrew J Powell, Jürgen Weese, Mehdi H Moghari, and Polina Golland. 2018. Iterative Segmentation from Limited Training Data: Applications to Congenital Heart Disease. Deep Learn Med Image Anal Multimodal Learn Clin Decis Support (2018), 11045, Pp. 334-42.

We propose a new iterative segmentation model which can be accurately learned from a small dataset. A common approach is to train a model to directly segment an image, requiring a large collection of manually annotated images to capture the anatomical variability in a cohort. In contrast, we develop a segmentation model that recursively evolves a segmentation in several steps, and implement it as a recurrent neural network. We learn model parameters by optimizing the intermediate steps of the evolution in addition to the final segmentation. To this end, we train our segmentation propagation model by presenting incomplete and/or inaccurate input segmentations paired with a recommended next step. Our work aims to alleviate challenges in segmenting heart structures from cardiac MRI for patients with congenital heart disease (CHD), which encompasses a range of morphological deformations and topological changes. We demonstrate the advantages of this approach on a dataset of 20 images from CHD patients, learning a model that accurately segments individual heart chambers and great vessels. Compared to direct segmentation, the iterative method yields more accurate segmentation for patients with the most severe CHD malformations.

Jian Wang, William M Wells, Polina Golland, and Miaomiao Zhang. 2018. Efficient Laplace Approximation for Bayesian Registration Uncertainty Quantification. Med Image Comput Comput Assist Interv, 11070, Pp. 880-8.

This paper presents a novel approach to modeling the pos terior distribution in image registration that is computationally efficient for large deformation diffeomorphic metric mapping (LDDMM). We develop a Laplace approximation of Bayesian registration models entirely in a bandlimited space that fully describes the properties of diffeomorphic transformations. In contrast to current methods, we compute the inverse Hessian at the mode of the posterior distribution of diffeomorphisms directly in the low dimensional frequency domain. This dramatically reduces the computational complexity of approximating posterior marginals in the high dimensional imaging space. Experimental results show that our method is significantly faster than the state-of-the-art diffeomorphic image registration uncertainty quantification algorithms, while producing comparable results. The efficiency of our method strengthens the feasibility in prospective clinical applications, e.g., real- time image-guided navigation for brain surgery.

Amanda E Lyall, Ofer Pasternak, D G Robinson, D Newell, J W Trampush, J A Gallego, M Fava, A K Malhotra, K H Karlsgodt, Marek Kubicki, and P R Szeszko. 2018. Greater Extracellular Free-Water in First-Episode Psychosis Predicts Better Neurocognitive Functioning. Mol Psychiatry, 23, 3, Pp. 701-7.
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.
Christian Lepage, Amicie de Pierrefeu, Inga K Koerte, Michael J Coleman, Ofer Pasternak, Gerald Grant, Christine E Marx, Rajendra A Morey, Laura A Flashman, Mark S George, Thomas W McAllister, Norberto Andaluz, Lori Shutter, Raul Coimbra, Ross D Zafonte, Murray B Stein, Martha E Shenton, and Sylvain Bouix. 2018. White Matter Abnormalities in Mild Traumatic Brain Injury with and without Post-Traumatic Stress Disorder: A Subject-Specific Diffusion Tensor Imaging Study. Brain Imaging Behav, 12, 3, Pp. 870-81.
Mild traumatic brain injuries (mTBIs) are often associated with posttraumatic stress disorder (PTSD). In cases of chronic mTBI, accurate diagnosis can be challenging due to the overlapping symptoms this condition shares with PTSD. Furthermore, mTBIs are heterogeneous and not easily observed using conventional neuroimaging tools, despite the fact that diffuse axonal injuries are the most common injury. Diffusion tensor imaging (DTI) is sensitive to diffuse axonal injuries and is thus more likely to detect mTBIs, especially when analyses account for the inter-individual variability of these injuries. Using a subject-specific approach, we compared fractional anisotropy (FA) abnormalities between groups with a history of mTBI (n = 35), comorbid mTBI and PTSD (mTBI + PTSD; n = 22), and healthy controls (n = 37). We compared all three groups on the number of abnormal FA clusters derived from subject-specific injury profiles (i.e., individual z-score maps) along a common white matter skeleton. The mTBI + PTSD group evinced a greater number of abnormally low FA clusters relative to both the healthy controls and the mTBI group without PTSD (p < .05). Across the groups with a history of mTBI, increased numbers of abnormally low FA clusters were significantly associated with PTSD symptom severity, depression, post-concussion symptoms, and reduced information processing speed (p < .05). These findings highlight the utility of subject-specific microstructural analyses when searching for mTBI-related brain abnormalities, particularly in patients with PTSD. This study also suggests that patients with a history of mTBI and comorbid PTSD, relative to those without PTSD, are at increased risk of FA abnormalities.
Adam B Scanlan, Alex 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. 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.
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.
David Black, Michael Unger, Nele Fischer, Ron Kikinis, Horst Hahn, Thomas Neumuth, and Bernhard Glaser. 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.
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. 2018. Auditory Display for Fluorescence-guided Open Brain Tumor Surgery. Int J Comput Assist Radiol Surg, 13, 1, Pp. 25-35.
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.
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. 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.
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.
T Guttuso, Niels Bergsland, J Hagemeier, D G Lichter, Ofer Pasternak, and R Zivadinov. 2018. Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease. AJNR Am J Neuroradiol, 39, 3, Pp. 479-84.
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.
Marco Duering, Sofia Finsterwalder, Ebru Baykara, Anil Man Tuladhar, Benno Gesierich, Marek J Konieczny, Rainer Malik, Nicolai Franzmeier, Michael Ewers, Eric Jouvent, Geert Jan Biessels, Reinhold Schmidt, Frank-Erik de Leeuw, Ofer Pasternak, and Martin Dichgans. 2018. Free Water Determines Diffusion Alterations and Clinical Status in Cerebral Small Vessel Disease. Alzheimers Dement, 14, Pp. 764-74.
INTRODUCTION: Diffusion tensor imaging detects early tissue alterations in Alzheimer’s disease and cerebral small vessel disease (SVD). However, the origin of diffusion alterations in SVD is largely unknown. METHODS: To gain further insight, we applied free water (FW) imaging to patients with genetically defined SVD (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL], n = 57), sporadic SVD (n = 444), and healthy controls (n = 28). We modeled freely diffusing water in the extracellular space (FW) and measures reflecting fiber structure (tissue compartment). We tested associations between these measures and clinical status (processing speed and disability). RESULTS: Diffusion alterations in SVD were mostly driven by increased FW and less by tissue compartment alterations. Among imaging markers, FW showed the strongest association with clinical status (Rup to 34%, P < .0001). Findings were consistent across patients with CADASIL and sporadic SVD. DISCUSSION: Diffusion alterations and clinical status in SVD are largely determined by extracellular fluid increase rather than alterations of white matter fiber organization.