More than half of all cancer patients receive radiotherapy in their treatment process. However, our understanding of abnormal transcriptional responses to radiation remains poor. In this study, we employ an extended definition of Ollivier-Ricci curvature based on LI-Wasserstein distance to investigate genes and biological processes associated with ionizing radiation (IR) and ultraviolet radiation (UV) exposure using a microarray dataset. Gene expression levels were modeled on a gene interaction topology downloaded from the Human Protein Reference Database (HPRD). This was performed for IR, UV, and mock datasets, separately. The difference curvature value between IR and mock graphs (also between UV and mock) for each gene was used as a metric to estimate the extent to which the gene responds to radiation. We found that in comparison of the top 200 genes identified from IR and UV graphs, about 20~30% genes were overlapping. Through gene ontology enrichment analysis, we found that the metabolic-related biological process was highly associated with both IR and UV radiation exposure.
We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist's expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia.
We propose a method for the automated identification of key white matter fiber tracts for neurosurgical planning, and we apply the method in a retrospective study of 18 consecutive neurosurgical patients with brain tumors. Our method is designed to be relatively robust to challenges in neurosurgical tractography, which include peritumoral edema, displacement, and mass effect caused by mass lesions. The proposed method has two parts. First, we learn a data-driven white matter parcellation or fiber cluster atlas using groupwise registration and spectral clustering of multi-fiber tractography from healthy controls. Key fiber tract clusters are identified in the atlas. Next, patient-specific fiber tracts are automatically identified using tractography-based registration to the atlas and spectral embedding of patient tractography. Results indicate good generalization of the data-driven atlas to patients: 80% of the 800 fiber clusters were identified in all 18 patients, and 94% of the 800 fiber clusters were found in 16 or more of the 18 patients. Automated subject-specific tract identification was evaluated by quantitative comparison to subject-specific motor and language functional MRI, focusing on the arcuate fasciculus (language) and corticospinal tracts (motor), which were identified in all patients. Results indicate good colocalization: 89 of 95, or 94%, of patient-specific language and motor activations were intersected by the corresponding identified tract. All patient-specific activations were within 3mm of the corresponding language or motor tract. Overall, our results indicate the potential of an automated method for identifying fiber tracts of interest for neurosurgical planning, even in patients with mass lesions.
The structural heterogeneity of tumor tissue can be probed by diffusion MRI (dMRI) in terms of the variance of apparent diffusivities within a voxel. However, the link between the diffusional variance and the tissue heterogeneity is not well-established. To investigate this link we test the hypothesis that diffusional variance, caused by microscopic anisotropy and isotropic heterogeneity, is associated with variable cell eccentricity and cell density in brain tumors. We performed dMRI using a novel encoding scheme for diffusional variance decomposition (DIVIDE) in 7 meningiomas and 8 gliomas prior to surgery. The diffusional variance was quantified from dMRI in terms of the total mean kurtosis (MKT), and DIVIDE was used to decompose MKT into components caused by microscopic anisotropy (MKA) and isotropic heterogeneity (MKI). Diffusion anisotropy was evaluated in terms of the fractional anisotropy (FA) and microscopic fractional anisotropy (μFA). Quantitative microscopy was performed on the excised tumor tissue, where structural anisotropy and cell density were quantified by structure tensor analysis and cell nuclei segmentation, respectively. In order to validate the DIVIDE parameters they were correlated to the corresponding parameters derived from microscopy. We found an excellent agreement between the DIVIDE parameters and corresponding microscopy parameters; MKA correlated with cell eccentricity (r=0.95, p<10(-7)) and MKI with the cell density variance (r=0.83, p<10(-3)). The diffusion anisotropy correlated with structure tensor anisotropy on the voxel-scale (FA, r=0.80, p<10(-3)) and microscopic scale (μFA, r=0.93, p<10(-6)). A multiple regression analysis showed that the conventional MKT parameter reflects both variable cell eccentricity and cell density, and therefore lacks specificity in terms of microstructure characteristics. However, specificity was obtained by decomposing the two contributions; MKA was associated only to cell eccentricity, and MKI only to cell density variance. The variance in meningiomas was caused primarily by microscopic anisotropy (mean±s.d.) MKA=1.11±0.33 vs MKI=0.44±0.20 (p<10(-3)), whereas in the gliomas, it was mostly caused by isotropic heterogeneity MKI=0.57±0.30 vs MKA=0.26±0.11 (p<0.05). In conclusion, DIVIDE allows non-invasive mapping of parameters that reflect variable cell eccentricity and density. These results constitute convincing evidence that a link exists between specific aspects of tissue heterogeneity and parameters from dMRI. Decomposing effects of microscopic anisotropy and isotropic heterogeneity facilitates an improved interpretation of tumor heterogeneity as well as diffusion anisotropy on both the microscopic and macroscopic scale.
The question whether our brain pathways adhere to a geometric grid structure has been a popular topic of debate in the diffusion imaging and neuroscience societies. Wedeen et al. (2012a, b) proposed that the brain's white matter is organized like parallel sheets of interwoven pathways. Catani et al. (2012) concluded that this grid pattern is most likely an artifact, resulting from methodological biases that cause the tractography pathways to cross in orthogonal angles. To date, ambiguities in the mathematical conditions for a sheet structure to exist (e.g. its relation to orthogonal angles) combined with the lack of extensive quantitative evidence have prevented wide acceptance of the hypothesis. In this work, we formalize the relevant terminology and recapitulate the condition for a sheet structure to exist. Note that this condition is not related to the presence or absence of orthogonal crossing fibers, and that sheet structure is defined formally as a surface formed by two sets of interwoven pathways intersecting at arbitrary angles within the surface. To quantify the existence of sheet structure, we present a novel framework to compute the sheet probability index (SPI), which reflects the presence of sheet structure in discrete orientation data (e.g. fiber peaks derived from diffusion MRI). With simulation experiments we investigate the effect of spatial resolution, curvature of the fiber pathways, and measurement noise on the ability to detect sheet structure. In real diffusion MRI data experiments we can identify various regions where the data supports sheet structure (high SPI values), but also areas where the data does not support sheet structure (low SPI values) or where no reliable conclusion can be drawn. Several areas with high SPI values were found to be consistent across subjects, across multiple data sets obtained with different scanners, resolutions, and degrees of diffusion weighting, and across various modeling techniques. Under the strong assumption that the diffusion MRI peaks reflect true axons, our results would therefore indicate that pathways do not form sheet structures at every crossing fiber region but instead at well-defined locations in the brain. With this framework, sheet structure location, extent, and orientation could potentially serve as new structural features of brain tissue. The proposed method can be extended to quantify sheet structure in directional data obtained with techniques other than diffusion MRI, which is essential for further validation.
Significant efforts have been dedicated to minimizing invasiveness associated with surgical interventions, most of which have been possible thanks to the developments in medical imaging, surgical navigation, visualization and display technologies. Image-guided interventions have promised to dramatically change the way therapies are delivered to many organs. However, in spite of the development of many sophisticated technologies over the past two decades, other than some isolated examples of successful implementations, minimally invasive therapy is far from enjoying the wide acceptance once envisioned. This paper provides a large-scale overview of the state-of-the-art developments, identifies several barriers thought to have hampered the wider adoption of image-guided navigation, and suggests areas of research that may potentially advance the field.
The National Alliance for Medical Image Computing (NA-MIC) was launched in 2004 with the goal of investigating and developing an open source software infrastructure for the extraction of information and knowledge from medical images using computational methods. Several leading research and engineering groups participated in this effort that was funded by the US National Institutes of Health through a variety of infrastructure grants. This effort transformed 3D Slicer from an internal, Boston-based, academic research software application into a professionally maintained, robust, open source platform with an international leadership and developer and user communities. Critical improvements to the widely used underlying open source libraries and tools-VTK, ITK, CMake, CDash, DCMTK-were an additional consequence of this effort. This project has contributed to close to a thousand peer-reviewed publications and a growing portfolio of US and international funded efforts expanding the use of these tools in new medical computing applications every year. In this editorial, we discuss what we believe are gaps in the way medical image computing is pursued today; how a well-executed research platform can enable discovery, innovation and reproducible science ("Open Science"); and how our quest to build such a software platform has evolved into a productive and rewarding social engineering exercise in building an open-access community with a shared vision.
Using image-based descriptors to investigate clinical hypotheses and therapeutic implications is challenging due to the notorious "curse of dimensionality" coupled with a small sample size. In this paper, we present a low-dimensional analysis of anatomical shape variability in the space of diffeomorphisms and demonstrate its benefits for clinical studies. To combat the high dimensionality of the deformation descriptors, we develop a probabilistic model of principal geodesic analysis in a bandlimited low-dimensional space that still captures the underlying variability of image data. We demonstrate the performance of our model on a set of 3D brain MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our model yields a more compact representation of group variation at substantially lower computational cost than models based on the high-dimensional state-of-the-art approaches such as tangent space PCA (TPCA) and probabilistic principal geodesic analysis (PPGA).
We introduce a method for registration of brain images acquired in clinical settings. The algorithm relies on three-dimensional patches in a discrete registration framework to estimate correspondences. Clinical images present significant challenges for computational analysis. Fast acquisition often results in images with sparse slices, severe artifacts, and variable fields of view. Yet, large clinical datasets hold a wealth of clinically relevant information. Despite significant progress in image registration, most algorithms make strong assumptions about the continuity of image data, failing when presented with clinical images that violate these assumptions. In this paper, we demonstrate a non-rigid registration method for aligning such images. The method explicitly models the sparsely available image information to achieve robust registration. We demonstrate the algorithm on clinical images of stroke patients. The proposed method outperforms state of the art registration algorithms and avoids catastrophic failures often caused by these images. We provide a freely available open source implementation of the algorithm.
We offer a blazingly brief review of evolution of shape analysis methods in medical imaging. As the representations and the statistical models grew more sophisticated, the problem of shape analysis has been gradually redefined to accept images rather than binary segmentations as a starting point. This transformation enabled shape analysis to take its rightful place in the arsenal of tools for extracting and understanding patterns in large clinical image sets. We speculate on the future developments in shape analysis and potential applications that would bring this mathematically rich area to bear on clinical practice.
We present a robust method to correct for motion and deformations in in-utero volumetric MRI time series. Spatio-temporal analysis of dynamic MRI requires robust alignment across time in the presence of substantial and unpredictable motion. We make a Markov assumption on the nature of deformations to take advantage of the temporal structure in the image data. Forward message passing in the corresponding hidden Markov model (HMM) yields an estimation algorithm that only has to account for relatively small motion between consecutive frames. We demonstrate the utility of the temporal model by showing that its use improves the accuracy of the segmentation propagation through temporal registration. Our results suggest that the proposed model captures accurately the temporal dynamics of deformations in in-utero MRI time series.
Emphysema is one of the hallmarks of Chronic Obstructive Pulmonary Disorder (COPD), a devastating lung disease often caused by smoking. Emphysema appears on Computed Tomography (CT) scans as a variety of textures that correlate with disease subtypes. It has been shown that the disease subtypes and textures are linked to physiological indicators and prognosis, although neither is well characterized clinically. Most previous computational approaches to modeling emphysema imaging data have focused on supervised classification of lung textures in patches of CT scans. In this work, we describe a generative model that jointly captures heterogeneity of disease subtypes and of the patient population. We also describe a corresponding inference algorithm that simultaneously discovers disease subtypes and population structure in an unsupervised manner. This approach enables us to create image-based descriptors of emphysema beyond those that can be identified through manual labeling of currently defined phenotypes. By applying the resulting algorithm to a large data set, we identify groups of patients and disease subtypes that correlate with distinct physiological indicators.
PURPOSE: The aim of this study was to present a tractography algorithm using a two-tensor unscented Kalman filter (UKF) to improve the modeling of the corticospinal tract (CST) by tracking through regions of peritumoral edema and crossing fibers. METHODS: Ten patients with brain tumors in the vicinity of motor cortex and evidence of significant peritumoral edema were retrospectively selected for the study. All patients underwent 3-T magnetic resonance imaging (MRI) including functional MRI (fMRI) and a diffusion-weighted data set with 31 directions. Fiber tracking was performed using both single-tensor streamline and two-tensor UKF tractography methods. A two-region-of-interest approach was used to delineate the CST. Results from the two tractography methods were compared visually and quantitatively. fMRI was applied to identify the functional fiber tracts. RESULTS: Single-tensor streamline tractography underestimated the extent of tracts running through the edematous areas and could only track the medial projections of the CST. In contrast, two-tensor UKF tractography tracked fanning projections of the CST despite peritumoral edema and crossing fibers. Based on visual inspection, the two-tensor UKF tractography delineated tracts that were closer to motor fMRI activations, and it was apparently more sensitive than single-tensor streamline tractography to define the tracts directed to the motor sites. The volume of the CST was significantly larger on two-tensor UKF than on single-tensor streamline tractography ([Formula: see text]). CONCLUSION: Two-tensor UKF tractography tracks a larger volume CST than single-tensor streamline tractography in the setting of peritumoral edema and crossing fibers in brain tumor patients.
Hengameh Mirzaalian, Lipeng Ning, Peter Savadjiev, Ofer Pasternak, Sylvain Bouix, Oleg Michailovich, G Grant, CE Marx, RA Morey, LA Flashman, MS George, TW McAllister, N Andaluz, L Shutter, R Coimbra, Ross Zafonte, Michael J Coleman, Marek Kubicki, Carl-Fredrik Westin, M.B. Stein, Martha E Shenton, and Yogesh Rathi. 7/2016. “Inter-site and Inter-scanner Diffusion MRI Data Harmonization.” Neuroimage, 135, Pp. 311-23.Abstract
We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.
We propose a unified Bayesian framework for detecting genetic variants associated with disease by exploiting image-based features as an intermediate phenotype. The use of imaging data for examining genetic associations promises new directions of analysis, but currently the most widely used methods make sub-optimal use of the richness that these data types can offer. Currently, image features are most commonly selected based on their relevance to the disease phenotype. Then, in a separate step, a set of genetic variants is identified to explain the selected features. In contrast, our method performs these tasks simultaneously in order to jointly exploit information in both data types. The analysis yields probabilistic measures of clinical relevance for both imaging and genetic markers. We derive an efficient approximate inference algorithm that handles the high dimensionality of image and genetic data. We evaluate the algorithm on synthetic data and demonstrate that it outperforms traditional models. We also illustrate our method on Alzheimer's Disease Neuroimaging Initiative data.
This work describes a new diffusion MR framework for imaging and modeling of microstructure that we call q-space trajectory imaging (QTI). The QTI framework consists of two parts: encoding and modeling. First we propose q-space trajectory encoding, which uses time-varying gradients to probe a trajectory in q-space, in contrast to traditional pulsed field gradient sequences that attempt to probe a point in q-space. Then we propose a microstructure model, the diffusion tensor distribution (DTD) model, which takes advantage of additional information provided by QTI to estimate a distributional model over diffusion tensors. We show that the QTI framework enables microstructure modeling that is not possible with the traditional pulsed gradient encoding as introduced by Stejskal and Tanner. In our analysis of QTI, we find that the well-known scalar b-value naturally extends to a tensor-valued entity, i.e., a diffusion measurement tensor, which we call the b-tensor. We show that b-tensors of rank 2 or 3 enable estimation of the mean and covariance of the DTD model in terms of a second order tensor (the diffusion tensor) and a fourth order tensor. The QTI framework has been designed to improve discrimination of the sizes, shapes, and orientations of diffusion microenvironments within tissue. We derive rotationally invariant scalar quantities describing intuitive microstructural features including size, shape, and orientation coherence measures. To demonstrate the feasibility of QTI on a clinical scanner, we performed a small pilot study comparing a group of five healthy controls with five patients with schizophrenia. The parameter maps derived from QTI were compared between the groups, and 9 out of the 14 parameters investigated showed differences between groups. The ability to measure and model the distribution of diffusion tensors, rather than a quantity that has already been averaged within a voxel, has the potential to provide a powerful paradigm for the study of complex tissue architecture.
The Surgical Planning Laboratory at Brigham and Women's Hospital, Harvard Medical School, developed the SPL Ear Atlas. The atlas was derived from a high-resolution flat-panel computed tomography (CT) scan (aprox 140 µm high contrast resultion), using semi-automated image segmentation and three-dimensional reconstruction techniques [Gupta, Bartling, et al. AJNR Am J Neuroradiol. 2004.]. The current version consists of: 1. the original CT scan; 2. a set of detailed label maps; 3. a set of three-dimensional models of the labeled anatomical structures; 4. mrb (Medical Reality Bundle) file archive that contains the mrml scene file and all data for loading into Slicer 4 for displaying the volumes in 3D Slicer version 4.0 or greater; 5. several pre-defined 3D-views (“anatomy teaching files”). The SPL Ear Atlas provides important reference information for surgical planning, anatomy teaching, and template driven segmentation. Visualization of the data requires 3D Slicer. This software package can be downloaded from here. We are pleased to make this atlas available to our colleagues for free download. Please note that the data is being distributed under the Slicer license. By downloading these data, you agree to acknowledge our contribution in any of your publications that result form the use of this atlas. This work is funded as part of the Neuroimaging Analysis Center, grant number P41 RR013218, by the NIH's National Center for Research Resources (NCRR) and grant number P41 EB015902, by the NIH's National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Google Faculty Research Award.
Background. Imaging biomarkers hold tremendous promise for precision medicine clinical applications. Development of such biomarkers relies heavily on image post-processing tools for automated image quantitation. Their deployment in the context of clinical research necessitates interoperability with the clinical systems. Comparison with the established outcomes and evaluation tasks motivate integration of the clinical and imaging data, and the use of standardized approaches to support annotation and sharing of the analysis results and semantics. We developed the methodology and tools to support these tasks in Positron Emission Tomography and Computed Tomography (PET/CT) quantitative imaging (QI) biomarker development applied to head and neck cancer (HNC) treatment response assessment, using the Digital Imaging and Communications in Medicine (DICOM(®)) international standard and free open-source software. Methods. Quantitative analysis of PET/CT imaging data collected on patients undergoing treatment for HNC was conducted. Processing steps included Standardized Uptake Value (SUV) normalization of the images, segmentation of the tumor using manual and semi-automatic approaches, automatic segmentation of the reference regions, and extraction of the volumetric segmentation-based measurements. Suitable components of the DICOM standard were identified to model the various types of data produced by the analysis. A developer toolkit of conversion routines and an Application Programming Interface (API) were contributed and applied to create a standards-based representation of the data. Results. DICOM Real World Value Mapping, Segmentation and Structured Reporting objects were utilized for standards-compliant representation of the PET/CT QI analysis results and relevant clinical data. A number of correction proposals to the standard were developed. The open-source DICOM toolkit (DCMTK) was improved to simplify the task of DICOM encoding by introducing new API abstractions. Conversion and visualization tools utilizing this toolkit were developed. The encoded objects were validated for consistency and interoperability. The resulting dataset was deposited in the QIN-HEADNECK collection of The Cancer Imaging Archive (TCIA). Supporting tools for data analysis and DICOM conversion were made available as free open-source software. Discussion. We presented a detailed investigation of the development and application of the DICOM model, as well as the supporting open-source tools and toolkits, to accommodate representation of the research data in QI biomarker development. We demonstrated that the DICOM standard can be used to represent the types of data relevant in HNC QI biomarker development, and encode their complex relationships. The resulting annotated objects are amenable to data mining applications, and are interoperable with a variety of systems that support the DICOM standard.
The ability to detect neuronal currents with high spatiotemporal resolution using magnetic resonance imaging (MRI) is important for studying human brain function in both health and disease. While significant progress has been made, we still lack evidence showing that it is possible to measure an MR signal time-locked to neuronal currents with a temporal waveform matching concurrently recorded local field potentials (LFPs). Also lacking is evidence that such MR data can be used to image current distribution in active tissue. Since these two results are lacking even in vitro, we obtained these data in an intact isolated whole cerebellum of turtle during slow neuronal activity mediated by metabotropic glutamate receptors using a gradient-echo EPI sequence (TR=100ms) at 4.7T. Our results show that it is possible (1) to reliably detect an MR phase shift time course matching that of the concurrently measured LFP evoked by stimulation of a cerebellar peduncle, (2) to detect the signal in single voxels of 0.1mm3, (3) to determine the spatial phase map matching the magnetic field distribution predicted by the LFP map, (4) to estimate the distribution of neuronal current in the active tissue from a group-average phase map, and (5) to provide a quantitatively accurate theoretical account of the measured phase shifts. The peak values of the detected MR phase shifts were 0.27-0.37°, corresponding to local magnetic field changes of 0.67-0.93nT (for TE=26ms). Our work provides an empirical basis for future extensions to in vivo imaging of neuronal currents.
PURPOSE: Diffusion encoding with asymmetric gradient waveforms is appealing because the asymmetry provides superior efficiency. However, concomitant gradients may cause a residual gradient moment at the end of the waveform, which can cause significant signal error and image artifacts. The purpose of this study was to develop an asymmetric waveform designs for tensor-valued diffusion encoding that is not sensitive to concomitant gradients. METHODS: The "Maxwell index" was proposed as a scalar invariant to capture the effect of concomitant gradients. Optimization of "Maxwell-compensated" waveforms was performed in which this index was constrained. Resulting waveforms were compared to waveforms from literature, in terms of the measured and predicted impact of concomitant gradients, by numerical analysis as well as experiments in a phantom and in a healthy human brain. RESULTS: Maxwell-compensated waveforms with Maxwell indices below 100 (mT/m) ms showed negligible signal bias in both numerical analysis and experiments. By contrast, several waveforms from literature showed gross signal bias under the same conditions, leading to a signal bias that was large enough to markedly affect parameter maps. Experimental results were accurately predicted by theory. CONCLUSION: Constraining the Maxwell index in the optimization of asymmetric gradient waveforms yields efficient diffusion encoding that negates the effects of concomitant fields while enabling arbitrary shapes of the b-tensor. This waveform design is especially useful in combination with strong gradients, long encoding times, thick slices, simultaneous multi-slice acquisition, and large FOVs.
Computational biomechanics of the brain for neurosurgery is an emerging area of research recently gaining in importance and practical applications. This review paper presents the contributions of the Intelligent Systems for Medicine Laboratory and its collaborators to this field, discussing the modeling approaches adopted and the methods developed for obtaining the numerical solutions. We adopt a physics-based modeling approach and describe the brain deformation in mechanical terms (such as displacements, strains, and stresses), which can be computed using a biomechanical model, by solving a continuum mechanics problem. We present our modeling approaches related to geometry creation, boundary conditions, loading, and material properties. From the point of view of solution methods, we advocate the use of fully nonlinear modeling approaches, capable of capturing very large deformations and nonlinear material behavior. We discuss finite element and meshless domain discretization, the use of the total Lagrangian formulation of continuum mechanics, and explicit time integration for solving both time-accurate and steady-state problems. We present the methods developed for handling contacts and for warping 3D medical images using the results of our simulations. We present two examples to showcase these methods: brain shift estimation for image registration and brain deformation computation for neuronavigation in epilepsy treatment.
Jean-Jacques Lemaire, Antonio De Salles, Guillaume Coll, Youssef El Ouadih, Rémi Chaix, Jérôme Coste, Franck Durif, Nikos Makris, and Ron Kikinis. 8/2019. “MRI Atlas of the Human Deep Brain.” Front Neurol, 10, Pp. 851.Abstract
Mastering detailed anatomy of the human deep brain in clinical neurosciences is challenging. Although numerous pioneering works have gathered a large dataset of structural and topographic information, it is still difficult to transfer this knowledge into practice, even with advanced magnetic resonance imaging techniques. Thus, classical histological atlases continue to be used to identify structures for stereotactic targeting in functional neurosurgery. Physicians mainly use these atlases as a template co-registered with the patient's brain. However, it is possible to directly identify stereotactic targets on MRI scans, enabling personalized targeting. In order to help clinicians directly identify deep brain structures relevant to present and future medical applications, we built a volumetric MRI atlas of the deep brain (MDBA) on a large scale (infra millimetric). Twelve hypothalamic, 39 subthalamic, 36 telencephalic, and 32 thalamic structures were identified, contoured, and labeled. Nineteen coronal, 18 axial, and 15 sagittal MRI plates were created. Although primarily designed for direct labeling, the anatomic space was also subdivided in twelfths of AC-PC distance, leading to proportional scaling in the coronal, axial, and sagittal planes. This extensive work is now available to clinicians and neuroscientists, offering another representation of the human deep brain ([https://hal.archives-ouvertes.fr/] [hal-02116633]). The atlas may also be used by computer scientists who are interested in deciphering the topography of this complex region.
Intraoperative tissue deformation, known as brain shift, decreases the benefit of using preoperative images to guide neurosurgery. Non-rigid registration of preoperative magnetic resonance (MR) to intraoperative ultrasound (US) has been proposed as a means to compensate for brain shift. We focus on the initial registration from MR to predurotomy US. We present a method that builds on previous work to address the need for accuracy and generality of MR-iUS registration algorithms in multi-site clinical data. To improve accuracy of registration, we use high-dimensional texture attributes instead of image intensities and propose to replace the standard difference-based attribute matching with correlation-based attribute matching. We also present a strategy that deals explicitly with the large field-of-view mismatch between MR and iUS images. We optimize key parameters across independent MR-iUS brain tumor datasets acquired at three different institutions, with a total of 43 tumor patients and 758 corresponding landmarks to validate the registration algorithm. Despite differences in imaging protocols, patient demographics and landmark distributions, our algorithm was able to reduce landmark errors prior to registration in three data sets (5.37 ± 4.27, 4.18 ± 1.97 and 6.18 ± 3.38 mm, respectively) to a consistently low level (2.28 ± 0.71, 2.08 ± 0.37 and 2.24 ± 0.78 mm, respectively). Our algorithm is compared to 15 other algorithms that have been previously tested on MR-iUS registration and it is competitive with the state-of-the-art on multiple datasets. We show that our algorithm has one of the lowest errors in all datasets (accuracy), and this is achieved while sticking to a fixed set of parameters for multi-site data (generality). In contrast, other algorithms/tools of similar performance need per-dataset parameter tuning (high accuracy but lower generality), and those that stick to fixed parameters have larger errors or inconsistent performance (generality but not the top accuracy). We further characterized landmark errors according to brain regions and tumor types, a topic so far missing in the literature. We found that landmark errors were higher in high-grade than low-grade glioma patients, and higher in tumor regions than in other brain regions.
PURPOSE: In image-guided surgery for glioma removal, neurosurgeons usually plan the resection on images acquired before surgery and use them for guidance during the subsequent intervention. However, after the surgical procedure has begun, the preplanning images become unreliable due to the brain shift phenomenon, caused by modifications of anatomical structures and imprecisions in the neuronavigation system. To obtain an updated view of the resection cavity, a solution is to collect intraoperative data, which can be additionally acquired at different stages of the procedure in order to provide a better understanding of the resection. A spatial mapping between structures identified in subsequent acquisitions would be beneficial. We propose here a fully automated segmentation-based registration method to register ultrasound (US) volumes acquired at multiple stages of neurosurgery. METHODS: We chose to segment sulci and falx cerebri in US volumes, which remain visible during resection. To automatically segment these elements, first we trained a convolutional neural network on manually annotated structures in volumes acquired before the opening of the dura mater and then we applied it to segment corresponding structures in different surgical phases. Finally, the obtained masks are used to register US volumes acquired at multiple resection stages. RESULTS: Our method reduces the mean target registration error (mTRE) between volumes acquired before the opening of the dura mater and during resection from 3.49 mm (± 1.55 mm) to 1.36 mm (± 0.61 mm). Moreover, the mTRE between volumes acquired before opening the dura mater and at the end of the resection is reduced from 3.54 mm (± 1.75 mm) to 2.05 mm (± 1.12 mm). CONCLUSION: The segmented structures demonstrated to be good candidates to register US volumes acquired at different neurosurgical phases. Therefore, our solution can compensate brain shift in neurosurgical procedures involving intraoperative US data.