Comparison of physics-based deformable registration methods for image-guided neurosurgery.

This paper compares three finite element-based methods used in a physics-based non-rigid registration approach and reports on the progress made over the last 15 years. Large brain shifts caused by brain tumor removal affect registration accuracy by creating point and element outliers. A combination of approximation- and geometry-based point and element outlier rejection improves the rigid registration error by 2.5 mm and meets the real-time constraints (4 min). In addition, the paper raises several questions and presents two open problems for the robust estimation and improvement of registration error in the presence of outliers due to sparse, noisy, and incomplete data. It concludes with preliminary results on leveraging Quantum Computing, a promising new technology for computationally intensive problems like Feature Detection and Block Matching in addition to finite element solver; all three account for 75% of computing time in deformable registration.

Real-Time Dynamic Data Driven Deformable Registration for Image-Guided Neurosurgery: Computational Aspects.

Current neurosurgical procedures utilize medical images of various modalities to enable the precise location of tumors and critical brain structures to plan accurate brain tumor resection. The difficulty of using preoperative images during the surgery is caused by the intra-operative deformation of the brain tissue (brain shift), which introduces discrepancies concerning the preoperative configuration. Intra-operative imaging allows tracking such deformations but cannot fully substitute for the quality of the pre-operative data. Dynamic Data Driven Deformable Non-Rigid Registration (D4NRR) is a complex and time-consuming image processing operation that allows the dynamic adjustment of the pre-operative image data to account for intra-operative brain shift during the surgery. This paper summarizes the computational aspects of a specific adaptive numerical approximation method and its variations for registering brain MRIs. It outlines its evolution over the last 15 years and identifies new directions for the computational aspects of the technique.

Adaptive Physics-Based Non-Rigid Registration for Immersive Image-Guided Neuronavigation Systems.

Objective: In image-guided neurosurgery, co-registered preoperative anatomical, functional, and diffusion tensor imaging can be used to facilitate a safe resection of brain tumors in eloquent areas of the brain. However, the brain deforms during surgery, particularly in the presence of tumor resection. Non-Rigid Registration (NRR) of the preoperative image data can be used to create a registered image that captures the deformation in the intraoperative image while maintaining the quality of the preoperative image. Using clinical data, this paper reports the results of a comparison of the accuracy and performance among several non-rigid registration methods for handling brain deformation. A new adaptive method that automatically removes mesh elements in the area of the resected tumor, thereby handling deformation in the presence of resection is presented. To improve the user experience, we also present a new way of using mixed reality with ultrasound, MRI, and CT. Materials and methods: This study focuses on 30 glioma surgeries performed at two different hospitals, many of which involved the resection of significant tumor volumes. An Adaptive Physics-Based Non-Rigid Registration method (A-PBNRR) registers preoperative and intraoperative MRI for each patient. The results are compared with three other readily available registration methods: a rigid registration implemented in 3D Slicer v4.4.0; a B-Spline non-rigid registration implemented in 3D Slicer v4.4.0; and PBNRR implemented in ITKv4.7.0, upon which A-PBNRR was based. Three measures were employed to facilitate a comprehensive evaluation of the registration accuracy: (i) visual assessment, (ii) a Hausdorff Distance-based metric, and (iii) a landmark-based approach using anatomical points identified by a neurosurgeon. Results: The A-PBNRR using multi-tissue mesh adaptation improved the accuracy of deformable registration by more than five times compared to rigid and traditional physics based non-rigid registration, and four times compared to B-Spline interpolation methods which are part of ITK and 3D Slicer. Performance analysis showed that A-PBNRR could be applied, on average, in <2 min, achieving desirable speed for use in a clinical setting. Conclusions: The A-PBNRR method performed significantly better than other readily available registration methods at modeling deformation in the presence of resection. Both the registration accuracy and performance proved sufficient to be of clinical value in the operating room. A-PBNRR, coupled with the mixed reality system, presents a powerful and affordable solution compared to current neuronavigation systems.

The clinical utility of multimodal MR image-guided needle biopsy in cerebral gliomas.

PURPOSE: Our aim was to evaluate the diagnostic value of multimodal Magnetic Resonance (MR) Image in the stereotactic biopsy of cerebral gliomas, and investigate its implications. MATERIALS AND METHODS: Twenty-four patients with cerebral gliomas underwent (1)H Magnetic Resonance Spectroscopy ((1)H-MRS)- and intraoperative Magnetic Resonance Imaging (iMRI)-supported stereotactic biopsy, and 23 patients underwent only the preoperative MRI-guided biopsy. The diagnostic yield, morbidity and mortality rates were analyzed. In addition, 20 patients underwent subsequent tumor resection, thus the diagnostic accuracy of the biopsy was further evaluated. RESULTS: The diagnostic accuracies of biopsies evaluated by tumor resection in the trial groups were better than control groups (92.3% and 42.9%, respectively, p = 0.031). The diagnostic yield in the trial groups was better than the control groups, but the difference was not statistically significant (100% and 82.6%, respectively, p = 0.05). The morbidity and mortality rates were similar in both groups. CONCLUSIONS: Multimodal MR image-guided glioma biopsy is practical and valuable. This technique can increase the diagnostic accuracy in the stereotactic biopsy of cerebral gliomas. Besides, it is likely to increase the diagnostic yield but requires further validation.

A nonrigid registration method for correcting brain deformation induced by tumor resection.

PURPOSE: This paper presents a nonrigid registration method to align preoperative MRI with intraoperative MRI to compensate for brain deformation during tumor resection. This method extends traditional point-based nonrigid registration in two aspects: (1) allow the input data to be incomplete and (2) simulate the underlying deformation with a heterogeneous biomechanical model. METHODS: The method formulates the registration as a three-variable (point correspondence, deformation field, and resection region) functional minimization problem, in which point correspondence is represented by a fuzzy assign matrix; Deformation field is represented by a piecewise linear function regularized by the strain energy of a heterogeneous biomechanical model; and resection region is represented by a maximal simply connected tetrahedral mesh. A nested expectation and maximization framework is developed to simultaneously resolve these three variables. RESULTS: To evaluate this method, the authors conducted experiments on both synthetic data and clinical MRI data. The synthetic experiment confirmed their hypothesis that the removal of additional elements from the biomechanical model can improve the accuracy of the registration. The clinical MRI experiments on 25 patients showed that the proposed method outperforms the ITK implementation of a physics-based nonrigid registration method. The proposed method improves the accuracy by 2.88 mm on average when the error is measured by a robust Hausdorff distance metric on Canny edge points, and improves the accuracy by 1.56 mm on average when the error is measured by six anatomical points. CONCLUSIONS: The proposed method can effectively correct brain deformation induced by tumor resection.

An ITK implementation of a physics-based non-rigid registration method for brain deformation in image-guided neurosurgery.

As part of the ITK v4 project efforts, we have developed ITK filters for physics-based non-rigid registration (PBNRR), which satisfies the following requirements: account for tissue properties in the registration, improve accuracy compared to rigid registration, and reduce execution time using GPU and multi-core accelerators. The implementation has three main components: (1) Feature Point Selection, (2) Block Matching (mapped to both multi-core and GPU processors), and (3) a Robust Finite Element Solver. The use of multi-core and GPU accelerators in ITK v4 provides substantial performance improvements. For example, for the non-rigid registration of brain MRIs, the performance of the block matching filter on average is about 10 times faster when 12 hyperthreaded multi-cores are used and about 83 times faster when the NVIDIA Tesla GPU is used in Dell Workstation.

Toward a real time multi-tissue Adaptive Physics-Based Non-Rigid Registration framework for brain tumor resection.

This paper presents an adaptive non-rigid registration method for aligning pre-operative MRI with intra-operative MRI (iMRI) to compensate for brain deformation during brain tumor resection. This method extends a successful existing Physics-Based Non-Rigid Registration (PBNRR) technique implemented in ITKv4.5. The new method relies on a parallel adaptive heterogeneous biomechanical Finite Element (FE) model for tissue/tumor removal depicted in the iMRI. In contrast the existing PBNRR in ITK relies on homogeneous static FE model designed for brain shift only (i.e., it is not designed to handle brain tumor resection). As a result, the new method (1) accurately captures the intra-operative deformations associated with the tissue removal due to tumor resection and (2) reduces the end-to-end execution time to within the time constraints imposed by the neurosurgical procedure. The evaluation of the new method is based on 14 clinical cases with: (i) brain shift only (seven cases), (ii) partial tumor resection (two cases), and (iii) complete tumor resection (five cases). The new adaptive method can reduce the alignment error up to seven and five times compared to a rigid and ITK's PBNRR registration methods, respectively. On average, the alignment error of the new method is reduced by 9.23 and 5.63 mm compared to the alignment error from the rigid and PBNRR method implemented in ITK. Moreover, the total execution time for all the case studies is about 1 min or less in a Linux Dell workstation with 12 Intel Xeon 3.47 GHz CPU cores and 96 GB of RAM.

A mesh generation and machine learning framework for Drosophila gene expression pattern image analysis.

BACKGROUND: Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions. RESULTS: We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/. CONCLUSIONS: Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.

Estimating loop length from CryoEM images at medium resolutions.

BACKGROUND: De novo protein modeling approaches utilize 3-dimensional (3D) images derived from electron cryomicroscopy (CryoEM) experiments. The skeleton connecting two secondary structures such as α-helices represent the loop in the 3D image. The accuracy of the skeleton and of the detected secondary structures are critical in De novo modeling. It is important to measure the length along the skeleton accurately since the length can be used as a constraint in modeling the protein. RESULTS: We have developed a novel computational geometric approach to derive a simplified curve in order to estimate the loop length along the skeleton. The method was tested using fifty simulated density images of helix-loop-helix segments of atomic structures and eighteen experimentally derived density data from Electron Microscopy Data Bank (EMDB). The test using simulated density maps shows that it is possible to estimate within 0.5 Å of the expected length for 48 of the 50 cases. The experiments, involving eighteen experimentally derived CryoEM images, show that twelve cases have error within 2 Å. CONCLUSIONS: The tests using both simulated and experimentally derived images show that it is possible for our proposed method to estimate the loop length along the skeleton if the secondary structure elements, such as α-helices, can be detected accurately, and there is a continuous skeleton linking the α-helices.

Non-rigid alignment of pre-operative MRI, fMRI, and DT-MRI with intra-operative MRI for enhanced visualization and navigation in image-guided neurosurgery.

OBJECTIVE: The usefulness of neurosurgical navigation with current visualizations is seriously compromised by brain shift, which inevitably occurs during the course of the operation, significantly degrading the precise alignment between the pre-operative MR data and the intra-operative shape of the brain. Our objectives were (i) to evaluate the feasibility of non-rigid registration that compensates for the brain deformations within the time constraints imposed by neurosurgery, and (ii) to create augmented reality visualizations of critical structural and functional brain regions during neurosurgery using pre-operatively acquired fMRI and DT-MRI. MATERIALS AND METHODS: Eleven consecutive patients with supratentorial gliomas were included in our study. All underwent surgery at our intra-operative MR imaging-guided therapy facility and have tumors in eloquent brain areas (e.g. precentral gyrus and cortico-spinal tract). Functional MRI and DT-MRI, together with MPRAGE and T2w structural MRI were acquired at 3 T prior to surgery. SPGR and T2w images were acquired with a 0.5 T magnet during each procedure. Quantitative assessment of the alignment accuracy was carried out and compared with current state-of-the-art systems based only on rigid registration. RESULTS: Alignment between pre-operative and intra-operative datasets was successfully carried out during surgery for all patients. Overall, the mean residual displacement remaining after non-rigid registration was 1.82 mm. There is a statistically significant improvement in alignment accuracy utilizing our non-rigid registration in comparison to the currently used technology (p<0.001). CONCLUSIONS: We were able to achieve intra-operative rigid and non-rigid registration of (1) pre-operative structural MRI with intra-operative T1w MRI; (2) pre-operative fMRI with intra-operative T1w MRI, and (3) pre-operative DT-MRI with intra-operative T1w MRI. The registration algorithms as implemented were sufficiently robust and rapid to meet the hard real-time constraints of intra-operative surgical decision making. The validation experiments demonstrate that we can accurately compensate for the deformation of the brain and thus can construct an augmented reality visualization to aid the surgeon.