Sonia Pujol

3D Slicer as an image computing platform for the Quantitative Imaging Network

Quantitative analysis has tremendous but mostly unrealized potential in healthcare to support objective and accurate interpretation of the clinical imaging. In 2008, the National Cancer Institute began building the Quantitative Imaging Network (QIN) initiative with the goal of advancing quantitative imaging in the context of personalized therapy and evaluation of treatment response. Computerized analysis is an important component contributing to reproducibility and efficiency of the quantitative imaging techniques. The success of quantitative imaging is contingent on robust analysis methods and software tools to bring these methods from bench to bedside. 3D Slicer is a free open-source software application for medical image computing. As a clinical research tool, 3D Slicer is similar to a radiology workstation that supports versatile visualizations but also provides advanced functionality such as automated segmentation and registration for a variety of application domains. Unlike a typical radiology workstation, 3D Slicer is free and is not tied to specific hardware. As a programming platform, 3D Slicer facilitates translation and evaluation of the new quantitative methods by allowing the biomedical researcher to focus on the implementation of the algorithm and providing abstractions for the common tasks of data communication, visualization and user interface development. Compared to other tools that provide aspects of this functionality, 3D Slicer is fully open source and can be readily extended and redistributed. In addition, 3D Slicer is designed to facilitate the development of new functionality in the form of 3D Slicer extensions. In this paper, we present an overview of 3D Slicer as a platform for prototyping, development and evaluation of image analysis tools for clinical research applications. To illustrate the utility of the platform in the scope of QIN, we discuss several use cases of 3D Slicer by the existing QIN teams, and we elaborate on the future directions that can further facilitate development and validation of imaging biomarkers using 3D Slicer.

Multimodal Neuroimaging Feature Learning for Multiclass Diagnosis of Alzheimer's Disease

The accurate diagnosis of Alzheimers disease (AD) is essential for patient care and will be increasingly important as disease modifying agents become available, early in the course of the disease. Although studies have applied machine learning methods for the computer-aided diagnosis of AD, a bottleneck in the diagnostic performance was shown in previous methods, due to the lacking of efficient strategies for representing neuroimaging biomarkers. In this study, we designed a novel diagnostic framework with deep learning architecture to aid the diagnosis of AD. This framework uses a zero-masking strategy for data fusion to extract complementary information from multiple data modalities. Compared to the previous state-of-the-art workflows, our method is capable of fusing multimodal neuroimaging features in one setting and has the potential to require less labeled data. A performance gain was achieved in both binary classification and multiclass classification of AD. The advantages and limitations of the proposed framework are discussed.

The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery

Diffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography‐derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop.

Early diagnosis of Alzheimer's disease with deep learning

The accurate diagnosis of Alzheimers disease (AD) plays a significant role in patient care, especially at the early stage, because the consciousness of the severity and the progression risks allows the patients to take prevention measures before irreversible brain damages are shaped. Although many studies have applied machine learning methods for computer-aided-diagnosis (CAD) of AD recently, a bottleneck of the diagnosis performance was shown in most of the existing researches, mainly due to the congenital limitations of the chosen learning models. In this study, we design a deep learning architecture, which contains stacked auto-encoders and a softmax output layer, to overcome the bottleneck and aid the diagnosis of AD and its prodromal stage, Mild Cognitive Impairment (MCI). Compared to the previous workflows, our method is capable of analyzing multiple classes in one setting, and requires less labeled training samples and minimal domain prior knowledge. A significant performance gain on classification of all diagnosis groups was achieved in our experiments.

Extended Broca's area in the functional connectome of language in adults: combined cortical and subcortical single-subject analysis using fMRI and DTI tractography.

Traditional models of the human language circuitry encompass three cortical areas, Broca’s, Geschwind’s and Wernicke’s, and their connectivity through white matter fascicles. The neural connectivity deep to these cortical areas remains poorly understood, as does the macroscopic functional organization of the cortico-subcortical language circuitry. In an effort to expand current knowledge, we combined functional MRI (fMRI) and diffusion tensor imaging to explore subject-specific structural and functional macroscopic connectivity, focusing on Broca’s area. Fascicles were studied using diffusion tensor imaging fiber tracking seeded from volumes placed manually within the white matter. White matter fascicles and fMRI-derived clusters (antonym-generation task) of positive and negative blood-oxygen-level-dependent (BOLD) signal were co-registered with 3-D renderings of the brain in 12 healthy subjects. Fascicles connecting BOLD-derived clusters were analyzed within specific cortical areas: Broca’s, with the pars triangularis, the pars opercularis, and the pars orbitaris; Geschwind’s and Wernicke’s; the premotor cortex, the dorsal supplementary motor area, the middle temporal gyrus, the dorsal prefrontal cortex and the frontopolar region. We found a functional connectome divisible into three systems—anterior, superior and inferior—around the insula, more complex than previously thought, particularly with respect to a new extended Broca’s area. The extended Broca’s area involves two new fascicles: the operculo-premotor fascicle comprised of well-organized U-shaped fibers that connect the pars opercularis with the premotor region; and (2) the triangulo-orbitaris system comprised of intermingled U-shaped fibers that connect the pars triangularis with the pars orbitaris. The findings enhance our understanding of language function.

Multimodal neuroimaging computing: a review of the applications in neuropsychiatric disorders

Multimodal neuroimaging is increasingly used in neuroscience research, as it overcomes the limitations of individual modalities. One of the most important applications of multimodal neuroimaging is the provision of vital diagnostic data for neuropsychiatric disorders. Multimodal neuroimaging computing enables the visualization and quantitative analysis of the alterations in brain structure and function, and has reshaped how neuroscience research is carried out. Research in this area is growing exponentially, and so it is an appropriate time to review the current and future development of this emerging area. Hence, in this paper, we review the recent advances in multimodal neuroimaging (MRI, PET) and electrophysiological (EEG, MEG) technologies, and their applications to the neuropsychiatric disorders. We also outline some future directions for multimodal neuroimaging where researchers will design more advanced methods and models for neuropsychiatric research.

Multi-Channel neurodegenerative pattern analysis and its application in Alzheimer's disease characterization.

Neuroimaging has played an important role in non-invasive diagnosis and differentiation of neurodegenerative disorders, such as Alzheimers disease and Mild Cognitive Impairment. Various features have been extracted from the neuroimaging data to characterize the disorders, and these features can be roughly divided into global and local features. Recent studies show a tendency of using local features in disease characterization, since they are capable of identifying the subtle disease-specific patterns associated with the effects of the disease on human brain. However, problems arise if the neuroimaging database involved multiple disorders or progressive disorders, as disorders of different types or at different progressive stages might exhibit different degenerative patterns. It is difficult for the researchers to reach consensus on what brain regions could effectively distinguish multiple disorders or multiple progression stages. In this study we proposed a Multi-Channel pattern analysis approach to identify the most discriminative local brain metabolism features for neurodegenerative disorder characterization. We compared our method to global methods and other pattern analysis methods based on clinical expertise or statistics tests. The preliminary results suggested that the proposed Multi-Channel pattern analysis method outperformed other approaches in Alzheimers disease characterization, and meanwhile provided important insights into the underlying pathology of Alzheimers disease and Mild Cognitive Impairment.

Multifold Bayesian Kernelization in Alzheimer’s Diagnosis

The accurate diagnosis of Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI) is important in early dementia detection and treatment planning. Most of current studies formulate the AD diagnosis scenario as a classification problem and solve it using various machine learners trained with multi-modal biomarkers. However, the diagnosis accuracy is usually constrained by the performance of the machine learners as well as the methods of integrating the multi-modal data. In this study, we propose a novel diagnosis algorithm, the Multifold Bayesian Kernelization (MBK), which models the diagnosis process as a synthesis analysis of multi-modal biomarkers. MBK constructs a kernel for each biomarker that maximizes the local neighborhood affinity, and further evaluates the contribution of each biomarker based on a Bayesian framework. MBK adopts a novel diagnosis scheme that could infer the subjects diagnosis by synthesizing the output diagnosis probabilities of individual biomarkers. The proposed algorithm, validated using multimodal neuroimaging data from the ADNI baseline cohort with 85 AD, 169 MCI and 77 cognitive normal subjects, achieves significant improvements on all diagnosis groups compared to the state-of-the-art methods.

Using 3D Modeling Techniques to Enhance Teaching of Difficult Anatomical Concepts

RATIONALE AND OBJECTIVES Anatomy is an essential component of medical education as it is critical for the accurate diagnosis in organs and human systems. The mental representation of the shape and organization of different anatomical structures is a crucial step in the learning process. The purpose of this pilot study is to demonstrate the feasibility and benefits of developing innovative teaching modules for anatomy education of first-year medical students based on three-dimensional (3D) reconstructions from actual patient data. MATERIALS AND METHODS A total of 196 models of anatomical structures from 16 anonymized computed tomography datasets were generated using the 3D Slicer open-source software platform. The models focused on three anatomical areas: the mediastinum, the upper abdomen, and the pelvis. Online optional quizzes were offered to first-year medical students to assess their comprehension in the areas of interest. Specific tasks were designed for students to complete using the 3D models. RESULTS Scores of the quizzes confirmed a lack of understanding of 3D spatial relationships of anatomical structures despite standard instruction including dissection. Written task material and qualitative review by students suggested that interaction with 3D models led to a better understanding of the shape and spatial relationships among structures, and helped illustrate anatomical variations from one body to another. CONCLUSIONS The study demonstrates the feasibility of one possible approach to the generation of 3D models of the anatomy from actual patient data. The educational materials developed have the potential to supplement the teaching of complex anatomical regions and help demonstrate the anatomical variation among patients.

A 3D difference-of-Gaussian-based lesion detector for brain PET

Positron emission tomography (PET) plays an important role in neurodegenerative disorder diagnosis and neurooncology applications, especially detecting the early metabolism anomalies in human brains. Current lesion detection algorithms can be roughly classified into voxel-based, region of interest (ROI)-based, and global algorithms. These methods may capture the scale and/or location of the lesions in brain, but other important properties, such as lesion metabolism rate and contrast to non-lesion parts are often ignored. To capture these important features, we propose a novel lesion detector with three lesion-centric feature descriptors for brain PET. We analyze the lesion patterns of 331 PET datasets from the ADNI baseline cohort and further perform t-test between different disorder groups to validate the new lesion-centric features. The preliminary results show that the proposed lesion detector is robust in capturing the brain lesions and has a great potential to be a predictive biomarker for neurological disorders.