José V. Manjón

Sergio Morell-Ortega, Ángela González-Cebrián, Boris Mansencal et al.

Large-scale automated morphometric analysis of brain MRI is limited by the thick-slice, anisotropic acquisitions prevalent in routine clinical practice. Existing generative super-resolution (SR) methods produce visually compelling isotropic volumes but often introduce anatomical hallucinations, systematic volumetric overestimation, and structural distortions that compromise downstream quantitative analysis and diagnostic safety. To address this, we propose CAHAL (Clinically Applicable resolution enHAncement for Low-resolution MRI scans), a hallucination-robust, physics-informed resolution enhancement framework that operates directly in the patient's native acquisition space. CAHAL employs a deterministic bivariate Mixture of Experts (MoE) architecture routing each input through specialised residual 3D U-Net experts conditioned on both volumetric resolution and acquisition anisotropy, two independent descriptors of clinical MRI acquisition. Experts are optimised with a composite loss combining edge-penalised spatial reconstruction, Fourier-domain spectral coherence matching, and a segmentation-guided semantic consistency constraint. Training pairs are generated on-the-fly via physics-based degradation sampled from a large-scale real-world database, ensuring robust generalisation. Validated on T1-weighted and FLAIR sequences against generative baselines, CAHAL achieves state-of-the-art results, improving the best related methods in terms of accuracy and efficiency.

Sergio Morell-Ortega, Marina Ruiz-Perez, Marien Gadea et al.

This paper introduces a novel multimodal and high-resolution human brain cerebellum lobule segmentation method. Unlike current tools that operate at standard resolution ($1 \text{ mm}^{3}$) or using mono-modal data, the proposed method improves cerebellum lobule segmentation through the use of a multimodal and ultra-high resolution ($0.125 \text{ mm}^{3}$) training dataset. To develop the method, first, a database of semi-automatically labelled cerebellum lobules was created to train the proposed method with ultra-high resolution T1 and T2 MR images. Then, an ensemble of deep networks has been designed and developed, allowing the proposed method to excel in the complex cerebellum lobule segmentation task, improving precision while being memory efficient. Notably, our approach deviates from the traditional U-Net model by exploring alternative architectures. We have also integrated deep learning with classical machine learning methods incorporating a priori knowledge from multi-atlas segmentation, which improved precision and robustness. Finally, a new online pipeline, named DeepCERES, has been developed to make available the proposed method to the scientific community requiring as input only a single T1 MR image at standard resolution.

José V. Manjón, Sergio Morell-Ortega, Marina Ruiz-Perez et al.

In this paper, we introduce a novel structural holistic Atlas (holiAtlas) of the human brain anatomy based on multimodal and high-resolution MRI that covers several anatomical levels from the organ to the substructure level, using a new densely labelled protocol generated from the fusion of multiple local protocols at different scales. This atlas was constructed by averaging images and segmentations of 75 healthy subjects from the Human Connectome Project database. Specifically, MR images of T1, T2 and WMn (White Matter nulled) contrasts at 0.125 $mm^{3}$ resolution were selected for this project. The images of these 75 subjects were nonlinearly registered and averaged using symmetric group-wise normalisation to construct the atlas. At the finest level, the proposed atlas has 350 different labels derived from 7 distinct delineation protocols. These labels were grouped at multiple scales, offering a coherent and consistent holistic representation of the brain across different levels of detail. This multiscale and multimodal atlas can be used to develop new ultra-high-resolution segmentation methods, potentially improving the early detection of neurological disorders. We make it publicly available to the scientific community.

Marina Ruiz-Perez, Sergio Morell-Ortega, Marien Gadea et al.

The implication of the thalamus in multiple neurological pathologies makes it a structure of interest for volumetric analysis. In the present work, we have designed and implemented a multimodal volumetric deep neural network for the segmentation of thalamic nuclei at ultra-high resolution (0.125 mm3). Current tools either operate at standard resolution (1 mm3) or use monomodal data. To achieve the proposed objective, first, a database of semiautomatically segmented thalamic nuclei was created using ultra-high resolution T1, T2 and White Matter nulled (WMn) images. Then, a novel Deep learning based strategy was designed to obtain the automatic segmentations and trained to improve its robustness and accuaracy using a semisupervised approach. The proposed method was compared with a related state-of-the-art method showing competitive results both in terms of segmentation quality and efficiency. To make the proposed method fully available to the scientific community, a full pipeline able to work with monomodal standard resolution T1 images is also proposed.

Pierrick Coupé, Boris Mansencal, José V. Manjón et al.

The differential diagnosis of neurodegenerative diseases, characterized by overlapping symptoms, may be challenging. Brain imaging coupled with artificial intelligence has been previously proposed for diagnostic support, but most of these methods have been trained to discriminate only isolated diseases from controls. Here, we develop a novel machine learning framework, named lifespan tree of brain anatomy, dedicated to the differential diagnosis between multiple diseases simultaneously. It integrates the modeling of volume changes for 124 brain structures during the lifespan with non-linear dimensionality reduction and synthetic sampling techniques to create easily interpretable representations of brain anatomy over the course of disease progression. As clinically relevant proof-of-concept applications, we constructed a cognitive lifespan tree of brain anatomy for the differential diagnosis of six causes of neurodegenerative dementia and a motor lifespan tree of brain anatomy for the differential diagnosis of four causes of parkinsonism using 37594 MRI as a training dataset. This original approach enhanced significantly the efficiency of differential diagnosis in the external validation cohort of 1754 cases, outperforming existing state-of-the art machine learning techniques. Lifespan tree holds promise as a valuable tool for differential diagnostic in relevant clinical conditions, especially for diseases still lacking effective biological markers.

Kilian Hett, Vinh-Thong Ta, José V. Manjón et al.

The prediction of subjects with mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD) is clinically relevant, and may above all have a significant impact on accelerate the development of new treatments. In this paper, we present a new MRI-based biomarker that enables us to predict conversion of MCI subjects to AD accurately. In order to better capture the AD signature, we introduce two main contributions. First, we present a new graph-based grading framework to combine inter-subject similarity features and intra-subject variability features. This framework involves patch-based grading of anatomical structures and graph-based modeling of structure alteration relationships. Second, we propose an innovative multiscale brain analysis to capture alterations caused by AD at different anatomical levels. Based on a cascade of classifiers, this multiscale approach enables the analysis of alterations of whole brain structures and hippocampus subfields at the same time. During our experiments using the ADNI-1 dataset, the proposed multiscale graph-based grading method obtained an area under the curve (AUC) of 81% to predict conversion of MCI subjects to AD within three years. Moreover, when combined with cognitive scores, the proposed method obtained 85% of AUC. These results are competitive in comparison to state-of-the-art methods evaluated on the same dataset.

Rémi Giraud, Vinh-Thong Ta, Nicolas Papadakis et al.

Automatic segmentation methods are important tools for quantitative analysis of Magnetic Resonance Images (MRI). Recently, patch-based label fusion approaches have demonstrated state-of-the-art segmentation accuracy. In this paper, we introduce a new patch-based label fusion framework to perform segmentation of anatomical structures. The proposed approach uses an Optimized PAtchMatch Label fusion (OPAL) strategy that drastically reduces the computation time required for the search of similar patches. The reduced computation time of OPAL opens the way for new strategies and facilitates processing on large databases. In this paper, we investigate new perspectives offered by OPAL, by introducing a new multi-scale and multi-feature framework. During our validation on hippocampus segmentation we use two datasets: young adults in the ICBM cohort and elderly adults in the EADC-ADNI dataset. For both, OPAL is compared to state-of-the-art methods. Results show that OPAL obtained the highest median Dice coefficient (89.9% for ICBM and 90.1% for EADC-ADNI). Moreover, in both cases, OPAL produced a segmentation accuracy similar to inter-expert variability. On the EADC-ADNI dataset, we compare the hippocampal volumes obtained by manual and automatic segmentation. The volumes appear to be highly correlated that enables to perform more accurate separation of pathological populations.