Restauration d'images en IRM anatomique pour l'étude préclinique des marqueurs du vieillissement cérébral

Les maladies neurovasculaires et neurodégénératives liées à l'âge sont en forte augmentation. Alors que ces changements pathologiques montrent des effets sur le cerveau avant l'apparition de symptômes cliniques, une meilleure compréhension du processus de vieillissement normal du cerveau aidera à distinguer l'impact des pathologies connues sur la structure régionale du cerveau. En outre, la connaissance des schémas de rétrécissement du cerveau dans le vieillissement normal pourrait conduire à une meilleure compréhension de ses causes et peut-être à des interventions réduisant la perte de fonctions cérébrales associée à l'atrophie cérébrale. Par conséquent, ce projet de thèse vise à détecter les biomarqueurs du vieillissement normal et pathologique du cerveau dans un modèle de primate non humain, le singe marmouset (Callithrix Jacchus), qui possède des caractéristiques anatomiques plus proches de celles des humains que de celles des rongeurs. Cependant, les changements structurels (par exemple, de volumes, d'épaisseur corticale) qui peuvent se produire au cours de leur vie adulte peuvent être minimes à l'échelle de l'observation. Dans ce contexte, il est essentiel de disposer de techniques d'observation offrant un contraste et une résolution spatiale suffisamment élevés et permettant des évaluations détaillées des changements morphométriques du cerveau associé au vieillissement. Cependant, l'imagerie de petits cerveaux dans une plateforme IRM 3T dédiée à l'homme est une tâche difficile car la résolution spatiale et le contraste obtenus sont insuffisants par rapport à la taille des structures anatomiques observées et à l'échelle des modifications attendues. Cette thèse vise à développer des méthodes de restauration d'image pour les images IRM précliniques qui amélioreront la robustesse des algorithmes de segmentation. L'amélioration de la résolution spatiale des images à un rapport signal/bruit constant limitera les effets de volume partiel dans les voxels situés à la frontière entre deux structures et permettra une meilleure segmentation tout en augmentant la reproductibilité des résultats. Cette étape d'imagerie computationnelle est cruciale pour une analyse morphométrique longitudinale fiable basée sur les voxels et l'identification de marqueurs anatomiques du vieillissement cérébral en suivant les changements de volume dans la matière grise, la matière blanche et le liquide cérébral.Age-related neurovascular and neurodegenerative diseases are increasing significantly. While such pathological changes show effects on the brain before clinical symptoms appear, a better understanding of the normal aging brain process will help distinguish known pathologies' impact on regional brain structure. Furthermore, knowledge of the patterns of brain shrinkage in normal aging could lead to a better understanding of its causes and perhaps to interventions reducing the loss of brain functions. Therefore, this thesis project aims to detect normal and pathological brain aging biomarkers in a non-human primate model, the marmoset monkey (Callithrix Jacchus) which possesses anatomical characteristics more similar to humans than rodents. However, structural changes (e.g., volumes, cortical thickness) that may occur during their adult life may be minimal with respect to the scale of observation. In this context, it is essential to have observation techniques that offer sufficiently high contrast and spatial resolution and allow detailed assessments of the morphometric brain changes associated with aging. However, imaging small brains in a 3T MRI platform dedicated to humans is a challenging task because the spatial resolution and the contrast obtained are insufficient compared to the size of the anatomical structures observed and the scale of the xpected changes with age. This thesis aims to develop image restoration methods for preclinical MR images that will improve the robustness of the segmentation algorithms. Improving the resolution of the images at a constant signal-to-noise ratio will limit the effects of partial volume in voxels located at the border between two structures and allow a better segmentation while increasing the results' reproducibility. This computational imaging step is crucial for a reliable longitudinal voxel-based morphometric analysis and for the identification of anatomical markers of brain aging by following the volume changes in gray matter, white matter and cerebrospinal fluid

Unveiling the future of breast cancer assessment: a critical review on generative adversarial networks in elastography ultrasound

Elastography Ultrasound provides elasticity information of the tissues, which is crucial for understanding the density and texture, allowing for the diagnosis of different medical conditions such as fibrosis and cancer. In the current medical imaging scenario, elastograms for B-mode Ultrasound are restricted to well-equipped hospitals, making the modality unavailable for pocket ultrasound. To highlight the recent progress in elastogram synthesis, this article performs a critical review of generative adversarial network (GAN) methodology for elastogram generation from B-mode Ultrasound images. Along with a brief overview of cutting-edge medical image synthesis, the article highlights the contribution of the GAN framework in light of its impact and thoroughly analyzes the results to validate whether the existing challenges have been effectively addressed. Specifically, This article highlights that GANs can successfully generate accurate elastograms for deep-seated breast tumors (without having artifacts) and improve diagnostic effectiveness for pocket US. Furthermore, the results of the GAN framework are thoroughly analyzed by considering the quantitative metrics, visual evaluations, and cancer diagnostic accuracy. Finally, essential unaddressed challenges that lie at the intersection of elastography and GANs are presented, and a few future directions are shared for the elastogram synthesis research

Multi-scale Transformer Network with Edge-aware Pre-training for Cross-Modality MR Image Synthesis

Cross-modality magnetic resonance (MR) image synthesis can be used to generate missing modalities from given ones. Existing (supervised learning) methods often require a large number of paired multi-modal data to train an effective synthesis model. However, it is often challenging to obtain sufficient paired data for supervised training. In reality, we often have a small number of paired data while a large number of unpaired data. To take advantage of both paired and unpaired data, in this paper, we propose a Multi-scale Transformer Network (MT-Net) with edge-aware pre-training for cross-modality MR image synthesis. Specifically, an Edge-preserving Masked AutoEncoder (Edge-MAE) is first pre-trained in a self-supervised manner to simultaneously perform 1) image imputation for randomly masked patches in each image and 2) whole edge map estimation, which effectively learns both contextual and structural information. Besides, a novel patch-wise loss is proposed to enhance the performance of Edge-MAE by treating different masked patches differently according to the difficulties of their respective imputations. Based on this proposed pre-training, in the subsequent fine-tuning stage, a Dual-scale Selective Fusion (DSF) module is designed (in our MT-Net) to synthesize missing-modality images by integrating multi-scale features extracted from the encoder of the pre-trained Edge-MAE. Further, this pre-trained encoder is also employed to extract high-level features from the synthesized image and corresponding ground-truth image, which are required to be similar (consistent) in the training. Experimental results show that our MT-Net achieves comparable performance to the competing methods even using $70\%$ of all available paired data. Our code will be publicly available at https://github.com/lyhkevin/MT-Net.Comment: 13 pages, 15 figure

SynthSR: A public AI tool to turn heterogeneous clinical brain scans into high-resolution T1-weighted images for 3D morphometry

Every year, millions of brain magnetic resonance imaging (MRI) scans are acquired in hospitals across the world. These have the potential to revolutionize our understanding of many neurological diseases, but their morphometric analysis has not yet been possible due to their anisotropic resolution. We present an artificial intelligence technique, "SynthSR," that takes clinical brain MRI scans with any MR contrast (T1, T2, etc.), orientation (axial/coronal/sagittal), and resolution and turns them into high-resolution T1 scans that are usable by virtually all existing human neuroimaging tools. We present results on segmentation, registration, and atlasing of >10,000 scans of controls and patients with brain tumors, strokes, and Alzheimer's disease. SynthSR yields morphometric results that are very highly correlated with what one would have obtained with high-resolution T1 scans. SynthSR allows sample sizes that have the potential to overcome the power limitations of prospective research studies and shed new light on the healthy and diseased human brain

Compressed Sensing Accelerated Magnetic Resonance Spectroscopic Imaging

abstract: Magnetic resonance spectroscopic imaging (MRSI) is a valuable technique for assessing the in vivo spatial profiles of metabolites like N-acetylaspartate (NAA), creatine, choline, and lactate. Changes in metabolite concentrations can help identify tissue heterogeneity, providing prognostic and diagnostic information to the clinician. The increased uptake of glucose by solid tumors as compared to normal tissues and its conversion to lactate can be exploited for tumor diagnostics, anti-cancer therapy, and in the detection of metastasis. Lactate levels in cancer cells are suggestive of altered metabolism, tumor recurrence, and poor outcome. A dedicated technique like MRSI could contribute to an improved assessment of metabolic abnormalities in the clinical setting, and introduce the possibility of employing non-invasive lactate imaging as a powerful prognostic marker. However, the long acquisition time in MRSI is a deterrent to its inclusion in clinical protocols due to associated costs, patient discomfort (especially in pediatric patients under anesthesia), and higher susceptibility to motion artifacts. Acceleration strategies like compressed sensing (CS) permit faithful reconstructions even when the k-space is undersampled well below the Nyquist limit. CS is apt for MRSI as spectroscopic data are inherently sparse in multiple dimensions of space and frequency in an appropriate transform domain, for e.g. the wavelet domain. The objective of this research was three-fold: firstly on the preclinical front, to prospectively speed-up spectrally-edited MRSI using CS for rapid mapping of lactate and capture associated changes in response to therapy. Secondly, to retrospectively evaluate CS-MRSI in pediatric patients scanned for various brain-related concerns. Thirdly, to implement prospective CS-MRSI acquisitions on a clinical magnetic resonance imaging (MRI) scanner for fast spectroscopic imaging studies. Both phantom and in vivo results demonstrated a reduction in the scan time by up to 80%, with the accelerated CS-MRSI reconstructions maintaining high spectral fidelity and statistically insignificant errors as compared to the fully sampled reference dataset. Optimization of CS parameters involved identifying an optimal sampling mask for CS-MRSI at each acceleration factor. It is envisioned that time-efficient MRSI realized with optimized CS acceleration would facilitate the clinical acceptance of routine MRSI exams for a quantitative mapping of important biomarkers.Dissertation/ThesisDoctoral Dissertation Bioengineering 201

Deep Learning Methods for Classification of Gliomas and Their Molecular Subtypes, From Central Learning to Federated Learning

The most common type of brain cancer in adults are gliomas. Under the updated 2016 World Health Organization (WHO) tumor classification in central nervous system (CNS), identification of molecular subtypes of gliomas is important. For low grade gliomas (LGGs), prediction of molecular subtypes by observing magnetic resonance imaging (MRI) scans might be difficult without taking biopsy. With the development of machine learning (ML) methods such as deep learning (DL), molecular based classification methods have shown promising results from MRI scans that may assist clinicians for prognosis and deciding on a treatment strategy. However, DL requires large amount of training datasets with tumor class labels and tumor boundary annotations. Manual annotation of tumor boundary is a time consuming and expensive process.The thesis is based on the work developed in five papers on gliomas and their molecular subtypes. We propose novel methods that provide improved performance. \ua0The proposed methods consist of a multi-stream convolutional autoencoder (CAE)-based classifier, a deep convolutional generative adversarial network (DCGAN) to enlarge the training dataset, a CycleGAN to handle domain shift, a novel federated learning (FL) scheme to allow local client-based training with dataset protection, and employing bounding boxes to MRIs when tumor boundary annotations are not available.Experimental results showed that DCGAN generated MRIs have enlarged the original training dataset size and have improved the classification performance on test sets. CycleGAN showed good domain adaptation on multiple source datasets and improved the classification performance. The proposed FL scheme showed a slightly degraded performance as compare to that of central learning (CL) approach while protecting dataset privacy. Using tumor bounding boxes showed to be an alternative approach to tumor boundary annotation for tumor classification and segmentation, with a trade-off between a slight decrease in performance and saving time in manual marking by clinicians. The proposed methods may benefit the future research in bringing DL tools into clinical practice for assisting tumor diagnosis and help the decision making process