Designed especially for neurobiologists, FluoRender is an interactive tool for multi-channel fluorescence microscopy data visualization and analysis.
Deep brain stimulation
BrainStimulator is a set of networks that are used in SCIRun to perform simulations of brain stimulation such as transcranial direct current stimulation (tDCS) and magnetic transcranial stimulation (TMS).
Developing software tools for science has always been a central vision of the SCI Institute.

Image Analysis

SCI's imaging work addresses fundamental questions in 2D and 3D image processing, including filtering, segmentation, surface reconstruction, and shape analysis. In low-level image processing, this effort has produce new nonparametric methods for modeling image statistics, which have resulted in better algorithms for denoising and reconstruction. Work with particle systems has led to new methods for visualizing and analyzing 3D surfaces. Our work in image processing also includes applications of advanced computing to 3D images, which has resulted in new parallel algorithms and real-time implementations on graphics processing units (GPUs). Application areas include medical image analysis, biological image processing, defense, environmental monitoring, and oil and gas.


ross

Ross Whitaker

Segmentation
sarang

Sarang Joshi

Shape Statistics
Segmentation
Brain Atlasing
tolga

Tolga Tasdizen

Image Processing
Machine Learning
chris

Chris Johnson

Diffusion Tensor Analysis

shireen

Shireen Elhabian

Image Analysis
Computer Vision


Image Analysis Project Sites:


Publications in Image Analysis:


Determining uranium ore concentrates and their calcination products via image classification of multiple magnifications,
C. Ly, C. Vachet, I. Schwerdt, E. Abbott, A. Brenkmann, L.W. McDonald, T. Tasdizen. In Journal of Nuclear Materials, 2020.

Many tools, such as mass spectrometry, X-ray diffraction, X-ray fluorescence, ion chromatography, etc., are currently available to scientists investigating interdicted nuclear material. These tools provide an analysis of physical, chemical, or isotopic characteristics of the seized material to identify its origin. In this study, a novel technique that characterizes physical attributes is proposed to provide insight into the processing route of unknown uranium ore concentrates (UOCs) and their calcination products. In particular, this study focuses on the characteristics of the surface structure captured in scanning electron microscopy (SEM) images at different magnification levels. Twelve common commercial processing routes of UOCs and their calcination products are investigated. Multiple-input single-output (MISO) convolution neural networks (CNNs) are implemented to differentiate the processing routes. The proposed technique can determine the processing route of a given sample in under a second running on a graphics processing unit (GPU) with an accuracy of more than 95%. The accuracy and speed of this proposed technique enable nuclear scientists to provide the preliminary identification results of interdicted material in a short time period. Furthermore, this proposed technique uses a predetermined set of magnifications, which in turn eliminates the human bias in selecting the magnification during the image acquisition process.



Adversarial regression training for visualizing the progression of chronic obstructive pulmonary disease with chest x-rays,
R.B. Lanfredi, J.D. Schroeder, C. Vachet, T. Tasdizen. In Arxiv, In International Conference on Medical Image Computing and Computer-Assisted Intervention, 2019.

Knowledge of what spatial elements of medical images deep learning methods use as evidence is important for model interpretability, trustiness, and validation. There is a lack of such techniques for models in regression tasks. We propose a method, called visualization for regression with a generative adversarial network (VR-GAN), for formulating adversarial training specifically for datasets containing regression target values characterizing disease severity. We use a conditional generative adversarial network where the generator attempts to learn to shift the output of a regressor through creating disease effect maps that are added to the original images. Meanwhile, the regressor is trained to predict the original regression value for the modified images. A model trained with this technique learns to provide visualization for how the image would appear at different stages of the disease. We analyze our method in a dataset of chest x-rays associated with pulmonary function tests, used for diagnosing chronic obstructive pulmonary disease (COPD). For validation, we compute the difference of two registered x-rays of the same patient at different time points and correlate it to the generated disease effect map. The proposed method outperforms a technique based on classification and provides realistic-looking images, making modifications to images following what radiologists usually observe for this disease. Implementation code is available athttps://github.com/ricbl/vrgan.



A Cooperative Autoencoder for Population-Based Regularization of CNN Image Registration
R. Bhalodia, S. Y. Elhabian, L. Kavan, R. T. Whitaker. In Medical Image Computing and Computer Assisted Intervention – MICCAI 2019, In Medical Image Computing and Computer Assisted Intervention -- MICCAI 2019, Springer International Publishing, pp. 391--400. 2019.

Spatial transformations are enablers in a variety of medical image analysis applications that entail aligning images to a common coordinate systems. Population analysis of such transformations is expected to capture the underlying image and shape variations, and hence these transformations are required to produce anatomically feasible correspondences. This is usually enforced through some smoothness-based generic metric or regularization of the deformation field. Alternatively, population-based regularization has been shown to produce anatomically accurate correspondences in cases where anatomically unaware (i.e., data independent) regularization fail. Recently, deep networks have been used to generate spatial transformations in an unsupervised manner, and, once trained, these networks are computationally faster and as accurate as conventional, optimization-based registration methods. However, the deformation fields produced by these networks require smoothness penalties, just as the conventional registration methods, and ignores population-level statistics of the transformations. Here, we propose a novel neural network architecture that simultaneously learns and uses the population-level statistics of the spatial transformations to regularize the neural networks for unsupervised image registration. This regularization is in the form of a bottleneck autoencoder, which learns and adapts to the population of transformations required to align input images by encoding the transformations to a low dimensional manifold. The proposed architecture produces deformation fields that describe the population-level features and associated correspondences in an anatomically relevant manner and are statistically compact relative to the state-of-the-art approaches while maintaining computational efficiency. We demonstrate the efficacy of the proposed architecture on synthetic data sets, as well as 2D and 3D medical data.



Which Two-dimensional Radiographic Measurements of Cam Femoroacetabular Impingement Best Describe the Three-dimensional Shape of the Proximal Femur?
P. R. Atkins, Y. Shin, P. Agrawal, S. Y. Elhabian, R. T. Whitaker, J. A. Weiss, S. K. Aoki, C. L. Peters, A. E. Anderson. In Clinical Orthopaedics and Related Research, Vol. 477, No. 1, 2019.

BACKGROUND:

Many two-dimensional (2-D) radiographic views are used to help diagnose cam femoroacetabular impingement (FAI), but there is little consensus as to which view or combination of views is most effective at visualizing the magnitude and extent of the cam lesion (ie, severity). Previous studies have used a single image from a sequence of CT or MR images to serve as a reference standard with which to evaluate the ability of 2-D radiographic views and associated measurements to describe the severity of the cam lesion. However, single images from CT or MRI data may fail to capture the apex of the cam lesion. Thus, it may be more appropriate to use measurements of three-dimensional (3-D) surface reconstructions from CT or MRI data to serve as an anatomic reference standard when evaluating radiographic views and associated measurements used in the diagnosis of cam FAI.

QUESTIONS/PURPOSES:

The purpose of this study was to use digitally reconstructed radiographs and 3-D statistical shape modeling to (1) determine the correlation between 2-D radiographic measurements of cam FAI and 3-D metrics of proximal femoral shape; and 2) identify the combination of radiographic measurements from plain film projections that were most effective at predicting the 3-D shape of the proximal femur.

METHODS:

This study leveraged previously acquired CT images of the femur from a convenience sample of 37 patients (34 males; mean age, 27 years, range, 16-47 years; mean body mass index [BMI], 24.6 kg/m, range, 19.0-30.2 kg/m) diagnosed with cam FAI imaged between February 2005 and January 2016. Patients were diagnosed with cam FAI based on a culmination of clinical examinations, history of hip pain, and imaging findings. The control group consisted of 59 morphologically normal control participants (36 males; mean age, 29 years, range, 15-55 years; mean BMI, 24.4 kg/m, range, 16.3-38.6 kg/m) imaged between April 2008 and September 2014. Of these controls, 30 were cadaveric femurs and 29 were living participants. All controls were screened for evidence of femoral deformities using radiographs. In addition, living control participants had no history of hip pain or previous surgery to the hip or lower limbs. CT images were acquired for each participant and the surface of the proximal femur was segmented and reconstructed. Surfaces were input to our statistical shape modeling pipeline, which objectively calculated 3-D shape scores that described the overall shape of the entire proximal femur and of the region of the femur where the cam lesion is typically located. Digital reconstructions for eight plain film views (AP, Meyer lateral, 45° Dunn, modified 45° Dunn, frog-leg lateral, Espié frog-leg, 90° Dunn, and cross-table lateral) were generated from CT data. For each view, measurements of the α angle and head-neck offset were obtained by two researchers (intraobserver correlation coefficients of 0.80-0.94 for the α angle and 0.42-0.80 for the head-neck offset measurements). The relationships between radiographic measurements from each view and the 3-D shape scores (for the entire proximal femur and for the region specific to the cam lesion) were assessed with linear correlation. Additionally, partial least squares regression was used to determine which combination of views and measurements was the most effective at predicting 3-D shape scores.

RESULTS:

Three-dimensional shape scores were most strongly correlated with α angle on the cross-table view when considering the entire proximal femur (r = -0.568; p < 0.001) and on the Meyer lateral view when considering the region of the cam lesion (r = -0.669; p < 0.001). Partial least squares regression demonstrated that measurements from the Meyer lateral and 90° Dunn radiographs produced the optimized regression model for predicting shape scores for the proximal femur (R = 0.405, root mean squared error of prediction [RMSEP] = 1.549) and the region of the cam lesion (R = 0.525, RMSEP = 1.150). Interestingly, views with larger differences in the α angle and head-neck offset between control and cam FAI groups did not have the strongest correlations with 3-D shape.

CONCLUSIONS:

Considered together, radiographic measurements from the Meyer lateral and 90° Dunn views provided the most effective predictions of 3-D shape of the proximal femur and the region of the cam lesion as determined using shape modeling metrics.

CLINICAL RELEVANCE:

Our results suggest that clinicians should consider using the Meyer lateral and 90° Dunn views to evaluate patients in whom cam FAI is suspected. However, the α angle and head-neck offset measurements from these and other plain film views could describe no more than half of the overall variation in the shape of the proximal femur and cam lesion. Thus, caution should be exercised when evaluating femoral head anatomy using the α angle and head-neck offset measurements from plain film radiographs. Given these findings, we believe there is merit in pursuing research that aims to develop the framework necessary to integrate statistical shape modeling into clinical evaluation, because this could aid in the diagnosis of cam FAI.



Identifying surface morphological characteristics to differentiate between mixtures of U3O8 synthesized from ammonium diuranate and uranyl peroxide,
S. T. Heffernan, N. Ly, B. J. Mower, C. Vachet, I. J. Schwerdt, T. Tasdizen, L. W. McDonald IV. In Radiochimica Acta, 2019.

In the present study, surface morphological differences of mixtures of triuranium octoxide (U3O8), synthesized from uranyl peroxide (UO4) and ammonium diuranate (ADU), were investigated. The purity of each sample was verified using powder X-ray diffractometry (p-XRD), and scanning electron microscopy (SEM) images were collected to identify unique morphological features. The U3O8 from ADU and UO4 was found to be unique. Qualitatively, both particles have similar features being primarily circular in shape. Using the morphological analysis of materials (MAMA) software, particle shape and size were quantified. UO4 was found to produce U3O8 particles three times the area of those produced from ADU. With the starting morphologies quantified, U3O8 samples from ADU and UO4 were physically mixed in known quantities. SEM images were collected of the mixed samples, and the MAMA software was used to quantify particle attributes. As U3O8 particles from ADU were unique from UO4, the composition of the mixtures could be quantified using SEM imaging coupled with particle analysis. This provides a novel means of quantifying processing histories of mixtures of uranium oxides. Machine learning was also used to help further quantify characteristics in the image database through direct classification and particle segmentation using deep learning techniques based on Convolutional Neural Networks (CNN). It demonstrates that these techniques can distinguish the mixtures with high accuracy as well as showing significant differences in morphology between the mixtures. Results from this study demonstrate the power of quantitative morphological analysis for determining the processing history of nuclear materials.



Quantifying Impurity Effects on the Surface Morphology of α-U3O8,
A. B. Hanson, R. N. Lee, C. Vachet, I. J. Schwerdt, T. Tasdizen, L. W. McDonald IV. In Analytical Chemistry, 2019.
DOI: doi:10.1021/acs.analchem.9b02013

The morphological effect of impurities on α-U3O8 has been investigated. This study provides the first evidence that the presence of impurities can alter nuclear material morphology, and these changes can be quantified to aid in revealing processing history. Four elements: Ca, Mg, V, and Zr were implemented in the uranyl peroxide synthesis route and studied individually within the α-U3O8. Six total replicates were synthesized, and replicates 1–3 were filtered and washed with Millipore water (18.2 MΩ) to remove any residual nitrates. Replicates 4–6 were filtered but not washed to determine the amount of impurities removed during washing. Inductively coupled plasma mass spectrometry (ICP-MS) was employed at key points during the synthesis to quantify incorporation of the impurity. Each sample was characterized using powder X-ray diffraction (p-XRD), high-resolution scanning electron microscopy (HRSEM), and SEM with energy dispersive X-ray spectroscopy (SEM-EDS). p-XRD was utilized to evaluate any crystallographic changes due to the impurities; HRSEM imagery was analyzed with Morphological Analysis for MAterials (MAMA) software and machine learning classification for quantification of the morphology; and SEM-EDS was utilized to locate the impurity within the α-U3O8. All samples were found to be quantifiably distinguishable, further demonstrating the utility of quantitative morphology as a signature for the processing history of nuclear material.



Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study
K. A. Johnson, P. T. Fletcher, D. Servello, A. Bona, M. Porta, J. L. Ostrem, E. Bardinet, M. Welter, A. M. Lozano, J. C. Baldermann, J. Kuhn, D. Huys, T. Foltynie, M. Hariz, E. M. Joyce, L. Zrinzo, Z. Kefalopoulou, J. Zhang, F. Meng, C. Zhang, Z. Ling, X. Xu, X. Yu, A. YJM Smeets, L. Ackermans, V. Visser-Vandewalle, A. Y. Mogilner, M. H. Pourfar, L. Almeida, A. Gunduz, W. Hu, K. D. Foote, M. S. Okun, C. R. Butson. In Journal of Neurology, Neurosurgery & Psychiatry, BMJ Publishing Group, 2019.
DOI: 10.1136/jnnp-2019-320379

BACKGROUND:
Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.

METHODS:
We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases.
RESULTS:
Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi.
CONCLUSION:
The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.



A High-Resolution Head and Brain Computer Model for Forward and Inverse EEG Simulation
A. Warner, J. Tate, B. Burton,, C.R. Johnson. In bioRxiv, Cold Spring Harbor Laboratory, Feb, 2019.
DOI: 10.1101/552190

To conduct computational forward and inverse EEG studies of brain electrical activity, researchers must construct realistic head and brain computer models, which is both challenging and time consuming. The availability of realistic head models and corresponding imaging data is limited in terms of imaging modalities and patient diversity. In this paper, we describe a detailed head modeling pipeline and provide a high-resolution, multimodal, open-source, female head and brain model. The modeling pipeline specifically outlines image acquisition, preprocessing, registration, and segmentation; three-dimensional tetrahedral mesh generation; finite element EEG simulations; and visualization of the model and simulation results. The dataset includes both functional and structural images and EEG recordings from two high-resolution electrode configurations. The intermediate results and software components are also included in the dataset to facilitate modifications to the pipeline. This project will contribute to neuroscience research by providing a high-quality dataset that can be used for a variety of applications and a computational pipeline that may help researchers construct new head models more efficiently.



Clustering With Pairwise Relationships: A Generative Approach
Y.Y. Yu, S.Y. Elhabian, R.T. Whitaker. In CoRR, 2018.

Semi-supervised learning (SSL) has become important in current data analysis applications, where the amount of unlabeled data is growing exponentially and user input remains limited by logistics and expense. Constrained clustering, as a subclass of SSL, makes use of user input in the form of relationships between data points (e.g., pairs of data points belonging to the same class or different classes) and can remarkably improve the performance of unsupervised clustering in order to reflect user-defined knowledge of the relationships between particular data points. Existing algorithms incorporate such user input, heuristically, as either hard constraints or soft penalties, which are separate from any generative or statistical aspect of the clustering model; this results in formulations that are suboptimal and not sufficiently general. In this paper, we propose a principled, generative approach to probabilistically model, without ad hoc penalties, the joint distribution given by user-defined pairwise relations. The proposed model accounts for general underlying distributions without assuming a specific form and relies on expectation-maximization for model fitting. For distributions in a standard form, the proposed approach results in a closed-form solution for updated parameters.



Latent Space Non-Linear Statistics
L. Kuhnel, T. Fletcher, S. Joshi, S. Sommer. In CoRR, 2018.

Given data, deep generative models, such as variational autoencoders (VAE) and generative adversarial networks (GAN), train a lower dimensional latent representation of the data space. The linear Euclidean geometry of data space pulls back to a nonlinear Riemannian geometry on the latent space. The latent space thus provides a low-dimensional nonlinear representation of data and classical linear statistical techniques are no longer applicable. In this paper we show how statistics of data in their latent space representation can be performed using techniques from the field of nonlinear manifold statistics. Nonlinear manifold statistics provide generalizations of Euclidean statistical notions including means, principal component analysis, and maximum likelihood fits of parametric probability distributions. We develop new techniques for maximum likelihood inference in latent space, and adress the computational complexity of using geometric algorithms with high-dimensional data by training a separate neural network to approximate the Riemannian metric and cometric tensor capturing the shape of the learned data manifold.



Skeletal Shape Correspondence through Entropy
L. Tu, M. Styner, J. Vicory, S. Elhabian, R. Wang, J. Hong, B. Paniagua, J.C. Prieto, D. Yang, R. Whitaker, M. Pizer. In IEEE Transactions on Medical Imaging, Vol. 37, No. 1, IEEE, pp. 1--11. Jan, 2018.
DOI: 10.1109/tmi.2017.2755550

We present a novel approach for improving the shape statistics of medical image objects by generating correspondence of skeletal points. Each object's interior is modeled by an s-rep, i.e., by a sampled, folded, two-sided skeletal sheet with spoke vectors proceeding from the skeletal sheet to the boundary. The skeleton is divided into three parts: the up side, the down side, and the fold curve. The spokes on each part are treated separately and, using spoke interpolation, are shifted along that skeleton in each training sample so as to tighten the probability distribution on those spokes' geometric properties while sampling the object interior regularly. As with the surface/boundary-based correspondence method of Cates et al., entropy is used to measure both the probability distribution tightness and the sampling regularity, here of the spokes' geometric properties. Evaluation on synthetic and real world lateral ventricle and hippocampus data sets demonstrate improvement in the performance of statistics using the resulting probability distributions. This improvement is greater than that achieved by an entropy-based correspondence method on the boundary points.



F. Mesadi, E. Erdil, M. Cetin, T. Tasdizen
Image segmentation using disjunctive normal Bayesian shape, appearance models. In IEEE Transactions on Medical Imaging, Vol. 37, No. 1, IEEE, pp. 293--305. Jan, 2018.
DOI: 10.1109/tmi.2017.2756929

The use of appearance and shape priors in image segmentation is known to improve accuracy; however, existing techniques have several drawbacks. For instance, most active shape and appearance models require landmark points and assume unimodal shape and appearance distributions, and the level set representation does not support construction of local priors. In this paper, we present novel appearance and shape models for image segmentation based on a differentiable implicit parametric shape representation called a disjunctive normal shape model (DNSM). The DNSM is formed by the disjunction of polytopes, which themselves are formed by the conjunctions of half-spaces. The DNSM's parametric nature allows the use of powerful local prior statistics, and its implicit nature removes the need to use landmarks and easily handles topological changes. In a Bayesian inference framework, we model arbitrary shape and appearance distributions using nonparametric density estimations, at any local scale. The proposed local shape prior results in accurate segmentation even when very few training shapes are available, because the method generates a rich set of shape variations by locally combining training samples. We demonstrate the performance of the framework by applying it to both 2-D and 3-D data sets with emphasis on biomedical image segmentation applications.



A virtual reality visualization tool for neuron tracing
W Usher, P Klacansky, F Federer, PT Bremer, A Knoll, J. Yarch, A. Angelucci, V. Pascucci . In IEEE Transactions on Visualization and Computer Graphics, Vol. 24, No. 1, IEEE, pp. 994--1003. Jan, 2018.
DOI: 10.1109/tvcg.2017.2744079

racing neurons in large-scale microscopy data is crucial to establishing a wiring diagram of the brain, which is needed to understand how neural circuits in the brain process information and generate behavior. Automatic techniques often fail for large and complex datasets, and connectomics researchers may spend weeks or months manually tracing neurons using 2D image stacks. We present a design study of a new virtual reality (VR) system, developed in collaboration with trained neuroanatomists, to trace neurons in microscope scans of the visual cortex of primates. We hypothesize that using consumer-grade VR technology to interact with neurons directly in 3D will help neuroscientists better resolve complex cases and enable them to trace neurons faster and with less physical and mental strain. We discuss both the design process and technical challenges in developing an interactive system to navigate and manipulate terabyte-sized image volumes in VR. Using a number of different datasets, we demonstrate that, compared to widely used commercial software, consumer-grade VR presents a promising alternative for scientists.



Neighbourhood looking glass: 360º automated characterisation of the built environment for neighbourhood effects research
Q.C. Nguyen, M. Sajjadi, M. McCullough, M. Pham, T.T. Nguyen, W. Yu, H. Meng, M. Wen, F. Li, K.R. Smith, K. Brunisholz, T, Tasdizen. In Journal of Epidemiology and Community Health, BMJ, Jan, 2018.
DOI: 10.1136/jech-2017-209456

Background
Neighbourhood quality has been connected with an array of health issues, but neighbourhood research has been limited by the lack of methods to characterise large geographical areas. This study uses innovative computer vision methods and a new big data source of street view images to automatically characterise neighbourhood built environments.

Methods
A total of 430 000 images were obtained using Google's Street View Image API for Salt Lake City, Chicago and Charleston. Convolutional neural networks were used to create indicators of street greenness, crosswalks and building type. We implemented log Poisson regression models to estimate associations between built environment features and individual prevalence of obesity and diabetes in Salt Lake City, controlling for individual-level and zip code-level predisposing characteristics.

Results
Computer vision models had an accuracy of 86%–93% compared with manual annotations. Charleston had the highest percentage of green streets (79%), while Chicago had the highest percentage of crosswalks (23%) and commercial buildings/apartments (59%). Built environment characteristics were categorised into tertiles, with the highest tertile serving as the referent group. Individuals living in zip codes with the most green streets, crosswalks and commercial buildings/apartments had relative obesity prevalences that were 25%–28% lower and relative diabetes prevalences that were 12%–18% lower than individuals living in zip codes with the least abundance of these neighbourhood features.

Conclusion
Neighbourhood conditions may influence chronic disease outcomes. Google Street View images represent an underused data resource for the construction of built environment features.



Image reconstruction using priors from deep learning
D. Ayyagari, N. Ramesh, D. Yatsenko, T. Tasdizen, C. Atria. In Medical Imaging 2018: Image Processing, SPIE, March, 2018.

Tomosynthesis, i.e. reconstruction of 3D volumes using projections from a limited perspective is a classical inverse, ill-posed or under constrained problem. Data insufficiency leads to reconstruction artifacts that vary in severity depending on the particular problem, the reconstruction method and also on the object being imaged. Machine learning has been used successfully in tomographic problems where data is insufficient, but the challenge with machine learning is that it introduces bias from the learning dataset. A novel framework to improve the quality of the tomosynthesis reconstruction that limits the learning dataset bias by maintaining consistency with the observed data is proposed. Convolutional Neural Networks (CNN) are embedded as regularizers in the reconstruction process to introduce the expected features and characterstics of the likely imaged object. The minimization of the objective function keeps the solution consistent with the observations and limits the bias introduced by the machine learning regularizers, improving the quality of the reconstruction. The proposed method has been developed and studied in the specific problem of Cone Beam Tomosynthesis Flouroscopy (CBT-fluoroscopy)1 but it is a general framework that can be applied to any image reconstruction problem that is limited by data insufficiency.



Domain adaptation for biomedical image segmentation using adversarial training
M. Javanmardi, T. Tasdizen. In 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018), IEEE, pp. 554-558. April, 2018.
DOI: 10.1109/isbi.2018.8363637

Many biomedical image analysis applications require segmentation. Convolutional neural networks (CNN) have become a promising approach to segment biomedical images; however, the accuracy of these methods is highly dependent on the training data. We focus on biomedical image segmentation in the context where there is variation between source and target datasets and ground truth for the target dataset is very limited or non-existent. We use an adversarial based training approach to train CNNs to achieve good accuracy on the target domain. We use the DRIVE and STARE eye vasculture segmentation datasets and show that our approach can significantly improve results where we only use labels of one domain in training and test on the other domain. We also show improvements on membrane detection between MIC-CAI 2016 CREMI challenge and ISBI2013 EM segmentation challenge datasets.



Semi-supervised learning for cell tracking in microscopy images
N. Ramesh, T. Tasdizen. In 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018), IEEE, April, 2018.

This paper discusses an algorithm for semi-supervised learning to predict cell division and motion in microscopy images. The cells for tracking are detected using extremal region selection and are depicted using a graphical representation. The supervised loss minimizes the error in predictions for the division and move classifiers. The unsupervised loss constrains the incoming links for every detection such that only one of the links is active. Similarly for the outgoing links, we enforce at-most two links to be active. The supervised and un-supervised losses are embedded in a Bayesian framework for probabilistic learning. The classifier predictions are used to model flow variables for every edge in the graph. The cell lineages are solved by formulating it as an energy minimization problem with constraints using integer linear programming. The unsupervised loss adds a significant improvement in the prediction of the division classifier.



Improving the robustness of convolutional networks to appearance variability in biomedical images
T. Tasdizen, M. Sajjadi, M. Javanmardi, N. Ramesh. In 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018), IEEE, April, 2018.
DOI: 10.1109/isbi.2018.8363636

While convolutional neural networks (CNN) produce state-of-the-art results in many applications including biomedical image analysis, they are not robust to variability in the data that is not well represented by the training set. An important source of variability in biomedical images is the appearance of objects such as contrast and texture due to different imaging settings. We introduce the neighborhood similarity layer (NSL) which can be used in a CNN to improve robustness to changes in the appearance of objects that are not well represented by the training data. The proposed NSL transforms its input feature map at a given pixel by computing its similarity to the surrounding neighborhood. This transformation is spatially varying, hence not a convolution. It is differentiable; therefore, networks including the proposed layer can be trained in an end-to-end manner. We demonstrate the advantages of the NSL for the vasculature segmentation and cell detection problems.



High resolution and high field diffusion MRI in the visual system of primates (P3.086)
O. Abdullah, L. Dai, J. Tippetts, B. Zimmerman, A. Van Hoek, S. Joshi, E. Hsu. In Neurology, Vol. 90, No. 15 Supplement, Wolters Kluwer Health, Inc, 2018.
ISSN: 0028-3878

Objective: Establishing a primate multiscale genetic brain network linking key microstructural brain components to social behavior remains an elusive goal.

Background: Diffusion MRI, which quantifies the magnitude and anisotropy of water diffusion in brain tissues, offers unparalleled opportunity to link the macroconnectome (resolution of ~0.5mm) to histological-based microconnectome at synaptic resolution.

Design/Methods: We tested the hypothesis that the simplest (and most clinically-used) reconstruction technique (known as diffusion tensor imaging, DTI) will yield similar brain connectivity patterns in the visual system (from optic chiasm to visual cortex) compared to more sophisticated and accurate reconstruction methods including diffusion spectrum imaging (DSI), q-ball imaging (QBI), and generalized q-sampling imaging. We obtained high resolution diffusion MRI data on ex vivo brain from Macaca fascicularis: MRI 7T, resolution 0.5 mm isotropic, 515 diffusion volumes up to b-value (aka diffusion sensitivity) of 40,000 s/mm2 with scan time ~100 hrs.

Results: Tractography results show that despite the limited ability of DTI to resolve crossing fibers at the optic chiasm, DTI-based tracts mapped to the known projections of layers in lateral geniculate nucleus and to the primary visual cortex. The other reconstructions were superior in localized regions for resolving crossing regions.

Conclusions: In conclusion, despite its simplifying assumptions, DTI-based fiber tractography can be used to generate accurate brain connectivity maps that conform to established neuroanatomical features in the visual system.



Real-Time Patient-Specific Lung Radiotherapy Targeting using Deep Learning
M.D. Foote, B. Zimmerman, A. Sawant, S. Joshi. In 1st Conference on Medical Imaging with Deep Learning (MIDL 2018), Amsterdam, The Netherlands, 2018.

Radiation therapy has presented a need for dynamic tracking of a target tumor volume. Fiducial markers such as implanted gold seeds have been used to gate radiation delivery but the markers are invasive and gating significantly increases treatment time. Pretreatment acquisition of a 4DCT allows for the development of accurate motion estimation for treatment planning. A deep convolutional neural network and subspace motion tracking is used to recover anatomical positions from a single radiograph projection in real-time. We approximate the nonlinear inverse of a diffeomorphic transformation composed with radiographic projection as a deep network that produces subspace coordinates to define the patient-specific deformation of the lungs from a baseline anatomic position. The geometric accuracy of the subspace projections on real patient data is similar to accuracy attained by original image registration between individual respiratory-phase image volumes.