SynthSeg: Domain Randomisation for Segmentation of Brain MRI Scans of any Contrast and Resolution

Despite advances in data augmentation and transfer learning, convolutional neural networks (CNNs) have difficulties generalising to unseen target domains. When applied to segmentation of brain MRI scans, CNNs are highly sensitive to changes in resolution and contrast: even within the same MR modality, decreases in performance can be observed across datasets. We introduce SynthSeg, the first segmentation CNN agnostic to brain MRI scans of any contrast and resolution. SynthSeg is trained with synthetic data sampled from a generative model inspired by Bayesian segmentation. Crucially, we adopt a \textit{domain randomisation} strategy where we fully randomise the generation parameters to maximise the variability of the training data. Consequently, SynthSeg can segment preprocessed and unpreprocessed real scans of any target domain, without retraining or fine-tuning. Because SynthSeg only requires segmentations to be trained (no images), it can learn from label maps obtained automatically from existing datasets of different populations (e.g., with atrophy and lesions), thus achieving robustness to a wide range of morphological variability. We demonstrate SynthSeg on 5,500 scans of 6 modalities and 10 resolutions, where it exhibits unparalleled generalisation compared to supervised CNNs, test time adaptation, and Bayesian segmentation. The code and trained model are available at https://github.com/BBillot/SynthSeg.

Unsupervised learning of MRI tissue properties using MRI physics models

In neuroimaging, MRI tissue properties characterize underlying neurobiology, provide quantitative biomarkers for neurological disease detection and analysis, and can be used to synthesize arbitrary MRI contrasts. Estimating tissue properties from a single scan session using a protocol available on all clinical scanners promises to reduce scan time and cost, enable quantitative analysis in routine clinical scans and provide scan-independent biomarkers of disease. However, existing tissue properties estimation methods - most often $\mathbf{T_1}$ relaxation, $\mathbf{T_2^*}$ relaxation, and proton density ($\mathbf{PD}$) - require data from multiple scan sessions and cannot estimate all properties from a single clinically available MRI protocol such as the multiecho MRI scan. In addition, the widespread use of non-standard acquisition parameters across clinical imaging sites require estimation methods that can generalize across varying scanner parameters. However, existing learning methods are acquisition protocol specific and cannot estimate from heterogenous clinical data from different imaging sites. In this work we propose an unsupervised deep-learning strategy that employs MRI physics to estimate all three tissue properties from a single multiecho MRI scan session, and generalizes across varying acquisition parameters. The proposed strategy optimizes accurate synthesis of new MRI contrasts from estimated latent tissue properties, enabling unsupervised training, we also employ random acquisition parameters during training to achieve acquisition generalization. We provide the first demonstration of estimating all tissue properties from a single multiecho scan session. We demonstrate improved accuracy and generalizability for tissue property estimation and MRI synthesis.

Robust joint registration of multiple stains and MRI for multimodal 3D histology reconstruction: Application to the Allen human brain atlas

Joint registration of a stack of 2D histological sections to recover 3D structure (3D histology reconstruction) finds application in areas such as atlas building and validation of in vivo imaging. Straighforward pairwise registration of neighbouring sections yields smooth reconstructions but has well-known problems such as banana effect (straightening of curved structures) and z-shift (drift). While these problems can be alleviated with an external, linearly aligned reference (e.g., Magnetic Resonance images), registration is often inaccurate due to contrast differences and the strong nonlinear distortion of the tissue, including artefacts such as folds and tears. In this paper, we present a probabilistic model of spatial deformation that yields reconstructions for multiple histological stains that that are jointly smooth, robust to outliers, and follow the reference shape. The model relies on a spanning tree of latent transforms connecting all the sections and slices, and assumes that the registration between any pair of images can be see as a noisy version of the composition of (possibly inverted) latent transforms connecting the two images. Bayesian inference is used to compute the most likely latent transforms given a set of pairwise registrations between image pairs within and across modalities. Results on synthetic deformations on multiple MR modalities, show that our method can accurately and robustly register multiple contrasts even in the presence of outliers. The 3D histology reconstruction of two stains (Nissl and parvalbumin) from the Allen human brain atlas, show its benefits on real data with severe distortions. We also provide the correspondence to MNI space, bridging the gap between two of the most used atlases in histology and MRI. Data is available at https://openneuro.org/datasets/ds003590 and code at https://github.com/acasamitjana/3dhirest.

HyperMorph: Amortized Hyperparameter Learning for Image Registration

We present HyperMorph, a learning-based strategy for deformable image registration that removes the need to tune important registration hyperparameters during training. Classical registration methods solve an optimization problem to find a set of spatial correspondences between two images, while learning-based methods leverage a training dataset to learn a function that generates these correspondences. The quality of the results for both types of techniques depends greatly on the choice of hyperparameters. Unfortunately, hyperparameter tuning is time-consuming and typically involves training many separate models with various hyperparameter values, potentially leading to suboptimal results. To address this inefficiency, we introduce amortized hyperparameter learning for image registration, a novel strategy to learn the effects of hyperparameters on deformation fields. The proposed framework learns a hypernetwork that takes in an input hyperparameter and modulates a registration network to produce the optimal deformation field for that hyperparameter value. In effect, this strategy trains a single, rich model that enables rapid, fine-grained discovery of hyperparameter values from a continuous interval at test-time. We demonstrate that this approach can be used to optimize multiple hyperparameters considerably faster than existing search strategies, leading to a reduced computational and human burden and increased flexibility. We also show that this has several important benefits, including increased robustness to initialization and the ability to rapidly identify optimal hyperparameter values specific to a registration task, dataset, or even a single anatomical region - all without retraining the HyperMorph model. Our code is publicly available at http://voxelmorph.mit.edu.

Joint super-resolution and synthesis of 1 mm isotropic MP-RAGE volumes from clinical MRI exams with scans of different orientation, resolution and contrast

Most existing algorithms for automatic 3D morphometry of human brain MRI scans are designed for data with near-isotropic voxels at approximately 1 mm resolution, and frequently have contrast constraints as well - typically requiring T1 scans (e.g., MP-RAGE). This limitation prevents the analysis of millions of MRI scans acquired with large inter-slice spacing ("thick slice") in clinical settings every year. The inability to quantitatively analyze these scans hinders the adoption of quantitative neuroimaging in healthcare, and precludes research studies that could attain huge sample sizes and hence greatly improve our understanding of the human brain. Recent advances in CNNs are producing outstanding results in super-resolution and contrast synthesis of MRI. However, these approaches are very sensitive to the contrast, resolution and orientation of the input images, and thus do not generalize to diverse clinical acquisition protocols - even within sites. Here we present SynthSR, a method to train a CNN that receives one or more thick-slice scans with different contrast, resolution and orientation, and produces an isotropic scan of canonical contrast (typically a 1 mm MP-RAGE). The presented method does not require any preprocessing, e.g., skull stripping or bias field correction. Crucially, SynthSR trains on synthetic input images generated from 3D segmentations, and can thus be used to train CNNs for any combination of contrasts, resolutions and orientations without high-resolution training data. We test the images generated with SynthSR in an array of common downstream analyses, and show that they can be reliably used for subcortical segmentation and volumetry, image registration (e.g., for tensor-based morphometry), and, if some image quality requirements are met, even cortical thickness morphometry. The source code is publicly available at github.com/BBillot/SynthSR.

3D Reconstruction and Segmentation of Dissection Photographs for MRI-free Neuropathology

Neuroimaging to neuropathology correlation (NTNC) promises to enable the transfer of microscopic signatures of pathology to in vivo imaging with MRI, ultimately enhancing clinical care. NTNC traditionally requires a volumetric MRI scan, acquired either ex vivo or a short time prior to death. Unfortunately, ex vivo MRI is difficult and costly, and recent premortem scans of sufficient quality are seldom available. To bridge this gap, we present methodology to 3D reconstruct and segment full brain image volumes from brain dissection photographs, which are routinely acquired at many brain banks and neuropathology departments. The 3D reconstruction is achieved via a joint registration framework, which uses a reference volume other than MRI. This volume may represent either the sample at hand (e.g., a surface 3D scan) or the general population (a probabilistic atlas). In addition, we present a Bayesian method to segment the 3D reconstructed photographic volumes into 36 neuroanatomical structures, which is robust to nonuniform brightness within and across photographs. We evaluate our methods on a dataset with 24 brains, using Dice scores and volume correlations. The results show that dissection photography is a valid replacement for ex vivo MRI in many volumetric analyses, opening an avenue for MRI-free NTNC, including retrospective data. The code is available at https://github.com/htregidgo/DissectionPhotoVolumes.

Learning Multi-Modal Image Registration without Real Data

We introduce a learning-based strategy for multi-modal registration of images acquired with any modality, without requiring real data during training. While classical registration methods can accurately align multi-modal image pairs, they solve a costly optimization problem for every new pair of images. Learning-based techniques are fast at test time, but can only register images of the specific anatomy and modalities they were trained on. In contrast, our approach leverages a generative model to synthesize label maps and gray-scale images that expose a network to a wide range of anatomy and contrast during training. We demonstrate that this strategy enables robust registration of arbitrary modalities, without the need to retrain for a new modality. Critically, we show that input labels need not be of actual anatomy: training on randomly synthesized shapes, or supervoxels, results in competitive registration performance and makes the network agnostic to anatomy and contrast, all while eradicating the need for real data. We present extensive experiments demonstrating that this strategy enables registration of modalities not seen during training and surpasses the state of art in cross-contrast registration. Our code is integrated with the VoxelMorph library at: http://voxelmorph.csail.mit.edu

Cortical surface registration using unsupervised learning

Non-rigid cortical registration is an important and challenging task due to the geometric complexity of the human cortex and the high degree of inter-subject variability. A conventional solution is to use a spherical representation of surface properties and perform registration by aligning cortical folding patterns in that space. This strategy produces accurate spatial alignment but often requires a high computational cost. Recently, convolutional neural networks (CNNs) have demonstrated the potential to dramatically speed up volumetric registration. However, due to distortions introduced by projecting a sphere to a 2D plane, a direct application of recent learning-based methods to surfaces yields poor results. In this study, we present SphereMorph, a diffeomorphic registration framework for cortical surfaces using deep networks that addresses these issues. SphereMorph uses a UNet-style network associated with a spherical kernel to learn the displacement field and warps the sphere using a modified spatial transformer layer. We propose a resampling weight in computing the data fitting loss to account for distortions introduced by polar projection, and demonstrate the performance of our proposed method on two tasks, including cortical parcellation and group-wise functional area alignment. The experiments show that the proposed SphereMorph is capable of modeling the geometric registration problem in a CNN framework and demonstrate superior registration accuracy and computational efficiency.

A Learning Strategy for Contrast-agnostic MRI Segmentation

We present a deep learning strategy that enables, for the first time, contrast-agnostic semantic segmentation of completely unpreprocessed brain MRI scans, without requiring additional training or fine-tuning for new modalities. Classical Bayesian methods address this segmentation problem with unsupervised intensity models, but require significant computational resources. In contrast, learning-based methods can be fast at test time, but are sensitive to the data available at training. Our proposed learning method, SynthSeg, leverages a set of training segmentations (no intensity images required) to generate synthetic sample images of widely varying contrasts on the fly during training. These samples are produced using the generative model of the classical Bayesian segmentation framework, with randomly sampled parameters for appearance, deformation, noise, and bias field. Because each mini-batch has a different synthetic contrast, the final network is not biased towards any MRI contrast. We comprehensively evaluate our approach on four datasets comprising over 1,000 subjects and four types of MR contrast. The results show that our approach successfully segments every contrast in the data, performing slightly better than classical Bayesian segmentation, and three orders of magnitude faster. Moreover, even within the same type of MRI contrast, our strategy generalizes significantly better across datasets, compared to training using real images. Finally, we find that synthesizing a broad range of contrasts, even if unrealistic, increases the generalization of the neural network. Our code and model are open source at https://github.com/BBillot/SynthSeg.

FastSurfer -- A fast and accurate deep learning based neuroimaging pipeline

Traditional neuroimage analysis pipelines involve computationally intensive, time-consuming optimization steps, and thus, do not scale well to large cohort studies with thousands or tens of thousands of individuals. In this work we propose a fast and accurate deep learning based neuroimaging pipeline for the automated processing of structural human brain MRI scans, including surface reconstruction and cortical parcellation. To this end, we introduce an advanced deep learning architecture capable of whole brain segmentation into 95 classes in under 1 minute, mimicking FreeSurfer's anatomical segmentation and cortical parcellation. The network architecture incorporates local and global competition via competitive dense blocks and competitive skip pathways, as well as multi-slice information aggregation that specifically tailor network performance towards accurate segmentation of both cortical and sub-cortical structures. Further, we perform fast cortical surface reconstruction and thickness analysis by introducing a spectral spherical embedding and by directly mapping the cortical labels from the image to the surface. This approach provides a full FreeSurfer alternative for volumetric analysis (within 1 minute) and surface-based thickness analysis (within only around 1h run time). For sustainability of this approach we perform extensive validation: we assert high segmentation accuracy on several unseen datasets, measure generalizability and demonstrate increased test-retest reliability, and increased sensitivity to disease effects relative to traditional FreeSurfer.