Imaging Informatics and the Human Brain Project: the Role of Structure, Review

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Image registration and visualization of in situ gene expression images.

In the age of high-throughput molecular biology techniques, scientists have incorporated the methodology of in-situ hybridization to map spatial patterns of gene expression. In order to compare expression patterns within a common tissue structure, these images need to be registered or organized into a common coordinate system for alignment to a reference or atlas images. We use three different image registration methodologies (manual; correlation based; mutual information based) to determine the common coordinate system for the reference and in-situ hybridization images. All three methodologies are incorporated into a Matlab tool to visualize the results in a user friendly way and save them for future work. Our results suggest that the user-defined landmark method is best when considering images from different modalities; automated landmark detection is best when the images are expected to have a high degree of consistency; and the mutual information methodology is useful when the images are from the same modality

The ACROBAT 2022 Challenge: Automatic Registration Of Breast Cancer Tissue

The alignment of tissue between histopathological whole-slide-images (WSI) is crucial for research and clinical applications. Advances in computing, deep learning, and availability of large WSI datasets have revolutionised WSI analysis. Therefore, the current state-of-the-art in WSI registration is unclear. To address this, we conducted the ACROBAT challenge, based on the largest WSI registration dataset to date, including 4,212 WSIs from 1,152 breast cancer patients. The challenge objective was to align WSIs of tissue that was stained with routine diagnostic immunohistochemistry to its H&E-stained counterpart. We compare the performance of eight WSI registration algorithms, including an investigation of the impact of different WSI properties and clinical covariates. We find that conceptually distinct WSI registration methods can lead to highly accurate registration performances and identify covariates that impact performances across methods. These results establish the current state-of-the-art in WSI registration and guide researchers in selecting and developing methods

Discrete Visual Perception

International audienceComputational vision and biomedical image have made tremendous progress of the past decade. This is mostly due the development of efficient learning and inference algorithms which allow better, faster and richer modeling of visual perception tasks. Graph-based representations are among the most prominent tools to address such perception through the casting of perception as a graph optimization problem. In this paper, we briefly introduce the interest of such representations, discuss their strength and limitations and present their application to address a variety of problems in computer vision and biomedical image analysis

Registration and Analysis of Developmental Image Sequences

Mapping images into the same anatomical coordinate system via image registration is a fundamental step when studying physiological processes, such as brain development. Standard registration methods are applicable when biological structures are mapped to the same anatomy and their appearance remains constant across the images or changes spatially uniformly. However, image sequences of animal or human development often do not follow these assumptions, and thus standard registration methods are unsuited for their analysis. In response, this dissertation tackles the problems of i) registering developmental image sequences with spatially non-uniform appearance change and ii) reconstructing a coherent 3D volume from serially sectioned images with non-matching anatomies between the sections. There are three major contributions presented in this dissertation. First, I develop a similarity metric that incorporates a time-dependent appearance model into the registration framework. The proposed metric allows for longitudinal image registration in the presence of spatially non-uniform appearance change over time—a common medical imaging problem for longitudinal magnetic resonance images of the neonatal brain. Next, a method is introduced for registering longitudinal developmental datasets with missing time points using an appearance atlas built from a population. The proposed method is applied to a longitudinal study of young macaque monkeys with incomplete image sequences. The final contribution is a template-free registration method to reconstruct images of serially sectioned biological samples into a coherent 3D volume. The method is applied to confocal fluorescence microscopy images of serially sectioned embryonic mouse brains.Doctor of Philosoph

Landmark-Matching Transformation with Large Deformation Via n-dimensional Quasi-conformal Maps

We propose a new method to obtain landmark-matching transformations between n-dimensional Euclidean spaces with large deformations. Given a set of feature correspondences, our algorithm searches for an optimal folding-free mapping that satisfies the prescribed landmark constraints. The standard conformality distortion defined for mappings between 2-dimensional spaces is first generalized to the n-dimensional conformality distortion K(f) for a mapping f between n-dimensional Euclidean spaces (n ≥ 3). We then propose a variational model involving K(f) to tackle the landmark-matching problem in higher dimensional spaces. The generalized conformality term K(f) enforces the bijectivity of the optimized mapping and minimizes its local geometric distortions even with large deformations. Another challenge is the high computational cost of the proposed model. To tackle this, we have also proposed a numerical method to solve the optimization problem more efficiently. Alternating direction method with multiplier is applied to split the optimization problem into two subproblems. Preconditioned conjugate gradient method with multi-grid preconditioner is applied to solve one of the sub-problems, while a fixed-point iteration is proposed to solve another subproblem. Experiments have been carried out on both synthetic examples and lung CT images to compute the diffeomorphic landmark-matching transformation with different landmark constraints. Results show the efficacy of our proposed model to obtain a folding-free landmark-matching transformation between n-dimensional spaces with large deformations

Model-Based Identification of Anatomical Boundary Conditions in Living Tissues

International audienceIn this paper, we present a novel method dealing with the identification of boundary conditions of a deformable organ, a particularly important step for the creation of patient-specific biomechani-cal models of the anatomy. As an input, the method requires a set of scans acquired in different body positions. Using constraint-based finite element simulation, the method registers the two data sets by solving an optimization problem minimizing the energy of the deformable body while satisfying the constraints located on the surface of the registered organ. Once the equilibrium of the simulation is attained (i.e. the organ registration is computed), the surface forces needed to satisfy the constraints provide a reliable estimation of location, direction and magnitude of boundary conditions applied to the object in the deformed position. The method is evaluated on two abdominal CT scans of a pig acquired in flank and supine positions. We demonstrate that while computing a physically admissible registration of the liver, the resulting constraint forces applied to the surface of the liver strongly correlate with the location of the anatomical boundary conditions (such as contacts with bones and other organs) that are visually identified in the CT images

INTEGRATION OF BIOMEDICAL IMAGING AND TRANSLATIONAL APPROACHES FOR MANAGEMENT OF HEAD AND NECK CANCER

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We used anatomical MRIs for the RT dose adaptation purpose. Our findings showed that after proper standardization of the immobilization and image acquisition techniques, we can achieve high geometric accuracy. These images can then be used to monitor the shrinkage of tumors during RT and optimize the clinical target volumes accordingly. Our results also showed that this MR-guided dose adaptation technique has a dosimetric advantage over the standard of care and was associated with a reduction in normal tissue doses that translated into a reduction of the odds of long-term RT-induced toxicity. In the second aim, we used quantitative MRIs to determine its benefit for prediction of oncologic outcomes and characterization of RT-induced normal tissue toxicity. Our findings showed that delta changes of apparent diffusion coefficient parameters derived from diffusion-weighted images at mid-RT can be used to predict local recurrence and recurrence free-survival. We also showed that Ktrans and Ve vascular parameters derived from dynamic contrast-enhanced MRIs can characterize the mandibular areas of osteoradionecrosis. In the final clinical aim, we used CT images of recurrence and baseline CT planning images to develop a methodology and workflow that involves the application of deformable image registration software as a tool to standardize image co-registration in addition to granular combined geometric- and dosimetric-based failure characterization to correctly attribute sites and causes of locoregional failure. We then successfully applied this methodology to identify the patterns of failure following postoperative and definitive IMRT in HNC patients. Using this methodology, we showed that most recurrences occurred in the central high dose regions for patients treated with definitive IMRT compared with mainly non-central high dose recurrences after postoperative IMRT. We also correlated recurrences with pretreatment FDG-PET and identified that most of the central high dose recurrences originated in an area that would be covered by a 10-mm margin on the volume of 50% of the maximum FDG uptake. In the translational component of this work, we integrated radiomic features derived from pre-RT CT images with whole-genome measurements using TCGA and TCIA data. Our results demonstrated a statistically significant associations between radiomic features characterizing different tumor phenotypes and different genomic features. These findings represent a promising potential towards non-invasively tract genomic changes in the tumor during treatment and use this information to adapt treatment accordingly. In the final project of this dissertation, we developed a high-throughput approach to identify effective systemic agents against aggressive head and neck tumors with poor prognosis like anaplastic thyroid cancer. We successfully identified three candidate drugs and performed extensive in vitro and in vivo validation using orthotopic and PDX models. Among these drugs, HDAC inhibitor and LBH-589 showed the most effective tumor growth inhibition that can be used in future clinical trials