Exploring the potential of representation and transfer learning for anatomical neuroimaging: Application to psychiatry.

The perspective of personalized medicine for brain disorders requires efficient learning models for anatomical neuroimaging-based prediction of clinical conditions. There is now a consensus on the benefit of deep learning (DL) in addressing many medical imaging tasks, such as image segmentation. However, for single-subject prediction problems, recent studies yielded contradictory results when comparing DL with Standard Machine Learning (SML) on top of classical feature extraction. Most existing comparative studies were limited in predicting phenotypes of little clinical interest, such as sex and age, and using a single dataset. Moreover, they conducted a limited analysis of the employed image pre-processing and feature selection strategies. This paper extensively compares DL and SML prediction capacity on five multi-site problems, including three increasingly complex clinical applications in psychiatry namely schizophrenia, bipolar disorder, and Autism Spectrum Disorder (ASD) diagnosis. To compensate for the relative scarcity of neuroimaging data on these clinical datasets, we also evaluate three pre-training strategies for transfer learning from brain imaging of the general healthy population: self-supervised learning, generative modeling and supervised learning with age. Overall, we find similar performance between randomly initialized DL and SML for the three clinical tasks and a similar scaling trend for sex prediction. This was replicated on an external dataset. We also show highly correlated discriminative brain regions between DL and linear ML models in all problems. Nonetheless, we demonstrate that self-supervised pre-training on large-scale healthy population imaging datasets (N≈10k), along with Deep Ensemble, allows DL to learn robust and transferable representations to smaller-scale clinical datasets (N≤1k). It largely outperforms SML on 2 out of 3 clinical tasks both in internal and external test sets. These findings suggest that the improvement of DL over SML in anatomical neuroimaging mainly comes from its capacity to learn meaningful and useful abstract representations of the brain anatomy, and it sheds light on the potential of transfer learning for personalized medicine in psychiatry.

Automated neurosurgical stereotactic planning for intraoperative use: a comprehensive review of the literature and perspectives.

The creation of intracranial stereotactic trajectories, from entry point to target point, is still mostly done manually by the neurosurgeon. The development of automated stereotactic planning tools has been described in the literature. This systematic review aims to assess the effectiveness of stereotactic planning procedure automation and develop tools for patients undergoing neurosurgical stereotactic procedures. PubMed/MEDLINE, EMBASE, Google Scholar, CINAHL, PsycINFO, and Cochrane Register of Controlled Trials databases were searched from inception to September 1, 2019, at the exception of Google Scholar (from 1 January 2010 to September 1, 2019) in French and English. Eligible studies included all studies proposing automated stereotactic planning. A total of 1543 studies were screened. Forty-two studies were included in the systematic review, including 18 (42.9%) conference papers. The surgical procedures planned automatically were mainly deep brain stimulation (n = 14, 33.3%), stereoelectroencephalography (n = 12, 28.6%), and not specified (n = 10, 23.8%). The most frequently used surgical constraints to plan the trajectory were blood vessels (n = 32, 76.2%), cerebral sulci (n = 27, 64.3%), and cerebral ventricles (n = 23, 54.8%). The distance from blood vessels ranged from 1.96 to 4.78 mm for manual trajectories and from 2.47 to 7.0 mm for automated trajectories. At least one neurosurgeon was involved in 36 studies (85.7%). The automated stereotactic trajectory was preferred in 75.4% of the studied cases (range 30-92.9). Only 3 (7.1%) studies were multicentric. No study reported prospective use of the planning software. Stereotactic planning automation is a promising tool to provide valuable stereotactic trajectories for clinical applications.

Comprehensive Review of 3D Segmentation Software Tools for MRI Usable for Pelvic Surgery Planning.

Patient-specific 3D modeling is the first step towards image-guided surgery, the actual revolution in surgical care. Pediatric and adolescent patients with rare tumors and malformations should highly benefit from these latest technological innovations, allowing personalized tailored surgery. This study focused on the pelvic region, located at the crossroads of the urinary, digestive, and genital channels with important vascular and nervous structures. The aim of this study was to evaluate the performances of different software tools to obtain patient-specific 3D models, through segmentation of magnetic resonance images (MRI), the reference for pediatric pelvis examination. Twelve software tools freely available on the Internet and two commercial software tools were evaluated using T2-w MRI and diffusion-weighted MRI images. The software tools were rated according to eight criteria, evaluated by three different users: automatization degree, segmentation time, usability, 3D visualization, presence of image registration tools, tractography tools, supported OS, and potential extension (i.e., plugins). A ranking of software tools for 3D modeling of MRI medical images, according to the set of predefined criteria, was given. This ranking allowed us to elaborate guidelines for the choice of software tools for pelvic surgical planning in pediatric patients. The best-ranked software tools were Myrian Studio, ITK-SNAP, and 3D Slicer, the latter being especially appropriate if nerve fibers should be included in the 3D patient model. To conclude, this study proposed a comprehensive review of software tools for 3D modeling of the pelvis according to a set of eight criteria and delivered specific conclusions for pediatric and adolescent patients that can be directly applied to clinical practice.

MRI Atlas of IDH Wild-Type Supratentorial Glioblastoma: Probabilistic Maps of Phenotype, Management, and Outcomes.

Background Tumor location is a main prognostic parameter in patients with glioblastoma. Probabilistic MRI-based brain atlases specifying the probability of tumor location associated with important demographic, clinical, histomolecular, and management data are lacking for isocitrate dehydrogenase (IDH) wild-type glioblastomas. Purpose To correlate glioblastoma location with clinical phenotype, surgical management, and outcomes by using a probabilistic analysis in a three-dimensional (3D) MRI-based atlas. Materials and Methods This retrospective study included all adults surgically treated for newly diagnosed IDH wild-type supratentorial glioblastoma in a tertiary adult surgical neuro-oncology center (2006-2016). Semiautomated tumor segmentation and spatial normalization procedures to build a 3D MRI-based atlas were validated. The authors performed probabilistic analyses by using voxel-based lesion symptom mapping technology. The Liebermeister test was used for binary data, and the generalized linear model was used for continuous data. Results A total of 392 patients (mean age, 61 years ± 13; 233 men) were evaluated. The authors identified the preferential location of glioblastomas according to subventricular zone, age, sex, clinical presentation, revised Radiation Therapy Oncology Group-Recursive Partitioning Analysis class, Karnofsky performance status, O6-methylguanine DNA methyltransferase promoter methylation status, surgical management, and survival. The superficial location distant from the eloquent area was more likely associated with a preserved functional status at diagnosis (348 of 392 patients [89%], P < .05), a large surgical resection (173 of 392 patients [44%], P < .05), and prolonged overall survival (163 of 334 patients [49%], P < .05). In contrast, deep location and location within eloquent brain areas were more likely associated with an impaired functional status at diagnosis (44 of 392 patients [11%], P < .05), a neurologic deficit (282 of 392 patients [72%], P < .05), treatment with biopsy only (183 of 392 patients [47%], P < .05), and shortened overall survival (171 of 334 patients [51%], P < .05). Conclusion The authors identified the preferential location of isocitrate dehydrogenase wild-type glioblastomas according to parameters of interest and provided an image-based integration of multimodal information impacting survival results. This suggests the role of glioblastoma location as a surrogate and multimodal parameter integrating several known prognostic factors. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Huang in this issue.

Tubular structures segmentation of pediatric abdominal-visceral ceCT images with renal tumors: Assessment, comparison and improvement.

Renal tubular structures, such as ureters, arteries and veins, are very important for building a complete digital 3D anatomical model of a patient. However, they can be challenging to segment from ceCT images due to their elongated shape, diameter variation and intra- and inter-patient contrast heterogeneity. This task is even more difficult in pediatric and pathological subjects, due to high inter-subject anatomical variations, potential presence of tumors, small volume of these structures compared to the surrounding, and small available labeled datasets. Given the limited literature on methods dedicated to children, and in order to find inspirational approaches, a complete assessment of state-of-the-art methods for the segmentation of renal tubular structures on ceCT images on adults is presented. Then, these methods are tested and compared on a private pediatric and pathological dataset of 79 abdominal-visceral ceCT images with arteriovenous phase acquisitions. To the best of our knowledge, both assessment and comparison in this specific case are novel. Eventually, we also propose a new loss function which leverages for the first time the use of vesselness functions on the predicted segmentation. We show that the combination of this loss function with state-of-the-art methods improves the topological coherence of the segmented tubular structures.2.

A Multicenter Network Analysis Examining the Psychological Effects of the COVID-19 Pandemic on Patients with Eating Disorders versus Their Healthy Siblings.

(1) Background: The impact of the COVID-19 pandemic on individuals with eating disorders (EDs) has been recorded all over the world; the traumatic effects of COVID-19 have exacerbated specific and general psychopathologies in those with EDs. Comparing patients' and their healthy siblings' responses might help one evaluate whether there are significant differences between healthy individuals and those struggling with EDs in regard to posttraumatic psychological symptoms. (2) Methods: A sample of 141 ED patients and 99 healthy siblings were enrolled in this study in two different centers specializing in ED treatment. All participants completed the posttraumatic stress disorder (PTSD) checklist and an eating and general psychopathological self-report questionnaire. Network analysis was then applied to evaluate the differences between the populations. (3) Results: No significant differences emerged between the network structures despite the significant differences between patients and their healthy siblings in regard to posttraumatic symptoms, eating, and general psychopathology. (4) Conclusion: The complex nature of the interaction between environmental and personal factors should be evaluated further in individuals with EDs due to how they respond to traumatic events, which exacerbate patients' psychopathology.

Clinica: An Open-Source Software Platform for Reproducible Clinical Neuroscience Studies.

We present Clinica (www.clinica.run), an open-source software platform designed to make clinical neuroscience studies easier and more reproducible. Clinica aims for researchers to (i) spend less time on data management and processing, (ii) perform reproducible evaluations of their methods, and (iii) easily share data and results within their institution and with external collaborators. The core of Clinica is a set of automatic pipelines for processing and analysis of multimodal neuroimaging data (currently, T1-weighted MRI, diffusion MRI, and PET data), as well as tools for statistics, machine learning, and deep learning. It relies on the brain imaging data structure (BIDS) for the organization of raw neuroimaging datasets and on established tools written by the community to build its pipelines. It also provides converters of public neuroimaging datasets to BIDS (currently ADNI, AIBL, OASIS, and NIFD). Processed data include image-valued scalar fields (e.g., tissue probability maps), meshes, surface-based scalar fields (e.g., cortical thickness maps), or scalar outputs (e.g., regional averages). These data follow the ClinicA Processed Structure (CAPS) format which shares the same philosophy as BIDS. Consistent organization of raw and processed neuroimaging files facilitates the execution of single pipelines and of sequences of pipelines, as well as the integration of processed data into statistics or machine learning frameworks. The target audience of Clinica is neuroscientists or clinicians conducting clinical neuroscience studies involving multimodal imaging, and researchers developing advanced machine learning algorithms applied to neuroimaging data.

Double Diffeomorphism: Combining Morphometry and Structural Connectivity Analysis.

The brain is composed of several neural circuits which may be seen as anatomical complexes composed of grey matter structures interconnected by white matter tracts. Grey and white matter components may be modeled as 3-D surfaces and curves, respectively. Neurodevelopmental disorders involve morphological and organizational alterations which cannot be jointly captured by usual shape analysis techniques based on single diffeomorphisms. We propose a new deformation scheme, called double diffeomorphism, which is a combination of two diffeomorphisms. The first one captures changes in structural connectivity, whereas the second one recovers the global morphological variations of both grey and white matter structures. This deformation model is integrated into a Bayesian framework for atlas construction. We evaluate it on a data-set of 3-D structures representing the neural circuits of patients with Gilles de la Tourette syndrome (GTS). We show that this approach makes it possible to localise, quantify, and easily visualise the pathological anomalies altering the morphology and organization of the neural circuits. Furthermore, results also indicate that the proposed deformation model better discriminates between controls and GTS patients than a single diffeomorphism.

A Bayesian framework for joint morphometry of surface and curve meshes in multi-object complexes.

We present a Bayesian framework for atlas construction of multi-object shape complexes comprised of both surface and curve meshes. It is general and can be applied to any parametric deformation framework and to all shape models with which it is possible to define probability density functions (PDF). Here, both curve and surface meshes are modelled as Gaussian random varifolds, using a finite-dimensional approximation space on which PDFs can be defined. Using this framework, we can automatically estimate the parameters balancing data-terms and deformation regularity, which previously required user tuning. Moreover, it is also possible to estimate a well-conditioned covariance matrix of the deformation parameters. We also extend the proposed framework to data-sets with multiple group labels. Groups share the same template and their deformation parameters are modelled with different distributions. We can statistically compare the groups'distributions since they are defined on the same space. We test our algorithm on 20 Gilles de la Tourette patients and 20 control subjects, using three sub-cortical regions and their incident white matter fiber bundles. We compare their morphological characteristics and variations using a single diffeomorphism in the ambient space. The proposed method will be integrated with the Deformetrica software package, publicly available at www.deformetrica.org.

Parsimonious Approximation of Streamline Trajectories in White Matter Fiber Bundles.

Fiber bundles stemming from tractography algorithms contain many streamlines. They require therefore a great amount of computer memory and computational resources to be stored, visualised and processed. We propose an approximation scheme for fiber bundles which results in a parsimonious representation of weighted prototypes. Prototypes are chosen among the streamlines and they represent groups of similar streamlines. Their weight is related to the number of approximated streamlines. Both streamlines and prototypes are modelled as weighted currents. This computational model does not need point-to-point correspondences and two streamlines are considered similar if their endpoints are close to each other and if their pathways follow similar trajectories. Moreover, the space of weighted currents is a vector space with a closed-form metric. This permits easy computation of the approximation error and the selection of the prototypes is based on the minimisation of this error. We propose an iterative algorithm which approximates independently and simultaneously all the fascicles of the bundle in a fast and accurate way. We show that the resulting representation preserves the shape of the bundle and it can be used to accurately reconstruct the original structural connectivity. We evaluate our algorithm on bundles obtained from both deterministic and probabilistic tractography algorithms. The resulting approximations use on average only 2% of the original streamlines as prototypes. This drastically reduces the computational burden of the processes where the geometry of the streamlines is considered. We demonstrate its effectiveness using as example the registration between two fiber bundles.

Joint Morphometry of Fiber Tracts and Gray Matter Structures Using Double Diffeomorphisms.

This work proposes an atlas construction method to jointly analyse the relative position and shape of fiber tracts and gray matter structures. It is based on a double diffeomorphism which is a composition of two diffeomorphisms. The first diffeomorphism acts only on the white matter keeping fixed the gray matter of the atlas. The resulting white matter, together with the gray matter, are then deformed by the second diffeomorphism. The two diffeomorphisms are related and jointly optimised. In this way, the, first diffeomorphisms explain the variability in structural connectivity within the population, namely both changes in the connected areas of the gray matter and in the geometry of the pathway of the tracts. The second diffeomorphisms put into correspondence the homologous anatomical structures across subjects. Fiber bundles are approximated with weighted prototypes using the metric of weighted currents. The atlas, the covariance matrix of deformation parameters and the noise variance of each structure are automatically estimated using a Bayesian approach. This method is applied to patients with Tourette syndrome and controls showing a variability in the structural connectivity of the left cortico-putamen circuit.

A prototype representation to approximate white matter bundles with weighted currents.

Quantitative and qualitative analysis of white matter fibers resulting from tractography algorithms is made difficult by their huge number. To this end, we propose an approximation scheme which gives as result a more concise but at the same time exhaustive representation of a fiber bundle. It is based on a novel computational model for fibers, called weighted currents, characterised by a metric that considers both the pathway and the anatomical locations of the endpoints of the fibers. Similarity has therefore a twofold connotation: geometrical and related to the connectivity. The core idea is to use this metric for approximating a fiber bundle with a set of weighted prototypes, chosen among the fibers, which represent ensembles of similar fibers. The weights are related to the fibers represented b y t he prototypes. The algorithm is divided into two steps. First, the main modes of the fiber bundle are detected using a modularity based clustering algorithm. Second, a prototype fiber selection process is carried on in each cluster separately. This permits to explain the main patterns of the fiber bundle in a fast and accurate way.

Bayesian atlas estimation for the variability analysis of shape complexes.

In this paper we propose a Bayesian framework for multiobject atlas estimation based on the metric of currents which permits to deal with both curves and surfaces without relying on point correspondence. This approach aims to study brain morphometry as a whole and not as a set of different components, focusing mainly on the shape and relative position of different anatomical structures which is fundamental in neuro-anatomical studies. We propose a generic algorithm to estimate templates of sets of curves (fiber bundles) and closed surfaces (sub-cortical structures) which have the same "form" (topology) of the shapes present in the population. This atlas construction method is based on a Bayesian framework which brings to two main improvements with respect to previous shape based methods. First, it allows to estimate from the data set a parameter specific to each object which was previously fixed by the user: the trade-off between data-term and regularity of deformations. In a multi-object analysis these parameters balance the contributions of the different objects and the need for an automatic estimation is even more crucial. Second, the covariance matrix of the deformation parameters is estimated during the atlas construction in a way which is less sensitive to the outliers of the population.