Learning General-Purpose Biomedical Volume Representations using Randomized Synthesis

Current volumetric biomedical foundation models struggle to generalize as public 3D datasets are small and do not cover the broad diversity of medical procedures, conditions, anatomical regions, and imaging protocols. We address this by creating a representation learning method that instead anticipates strong domain shifts at training time itself. We first propose a data engine that synthesizes highly variable training samples that enable generalization to new biomedical contexts. To then train a single 3D network for any voxel-level task, we develop a contrastive learning method that pretrains the network to be stable against nuisance imaging variation simulated by the data engine, a key inductive bias for generalization. This network's features can be used as robust representations of input images for downstream tasks and its weights provide a strong, dataset-agnostic initialization for finetuning on new datasets. As a result, we set new standards across both multimodality registration and few-shot segmentation, a first for any 3D biomedical vision model, all without (pre-)training on any existing dataset of real images.

Towards Automatic Abdominal MRI Organ Segmentation: Leveraging Synthesized Data Generated From CT Labels

Deep learning has shown great promise in the ability to automatically annotate organs in magnetic resonance imaging (MRI) scans, for example, of the brain. However, despite advancements in the field, the ability to accurately segment abdominal organs remains difficult across MR. In part, this may be explained by the much greater variability in image appearance and severely limited availability of training labels. The inherent nature of computed tomography (CT) scans makes it easier to annotate, resulting in a larger availability of expert annotations for the latter. We leverage a modality-agnostic domain randomization approach, utilizing CT label maps to generate synthetic images on-the-fly during training, further used to train a U-Net segmentation network for abdominal organs segmentation. Our approach shows comparable results compared to fully-supervised segmentation methods trained on MR data. Our method results in Dice scores of 0.90 (0.08) and 0.91 (0.08) for the right and left kidney respectively, compared to a pretrained nnU-Net model yielding 0.87 (0.20) and 0.91 (0.03). We will make our code publicly available.

SE-Equivariant and Noise-Invariant 3D Motion Tracking in Medical Images

Rigid motion tracking is paramount in many medical imaging applications where movements need to be detected, corrected, or accounted for. Modern strategies rely on convolutional neural networks (CNN) and pose this problem as rigid registration. Yet, CNNs do not exploit natural symmetries in this task, as they are equivariant to translations (their outputs shift with their inputs) but not to rotations. Here we propose EquiTrack, the first method that uses recent steerable SE(3)-equivariant CNNs (E-CNN) for motion tracking. While steerable E-CNNs can extract corresponding features across different poses, testing them on noisy medical images reveals that they do not have enough learning capacity to learn noise invariance. Thus, we introduce a hybrid architecture that pairs a denoiser with an E-CNN to decouple the processing of anatomically irrelevant intensity features from the extraction of equivariant spatial features. Rigid transforms are then estimated in closed-form. EquiTrack outperforms state-of-the-art learning and optimisation methods for motion tracking in adult brain MRI and fetal MRI time series. Our code is available at github.com/BBillot/equitrack.

Quantifying white matter hyperintensity and brain volumes in heterogeneous clinical and low-field portable MRI

Brain atrophy and white matter hyperintensity (WMH) are critical neuroimaging features for ascertaining brain injury in cerebrovascular disease and multiple sclerosis. Automated segmentation and quantification is desirable but existing methods require high-resolution MRI with good signal-to-noise ratio (SNR). This precludes application to clinical and low-field portable MRI (pMRI) scans, thus hampering large-scale tracking of atrophy and WMH progression, especially in underserved areas where pMRI has huge potential. Here we present a method that segments white matter hyperintensity and 36 brain regions from scans of any resolution and contrast (including pMRI) without retraining. We show results on six public datasets and on a private dataset with paired high- and low-field scans (3T and 64mT), where we attain strong correlation between the WMH ($\rho$=.85) and hippocampal volumes (r=.89) estimated at both fields. Our method is publicly available as part of FreeSurfer, at: http://surfer.nmr.mgh.harvard.edu/fswiki/WMH-SynthSeg.

AnyStar: Domain randomized universal star-convex 3D instance segmentation

Star-convex shapes arise across bio-microscopy and radiology in the form of nuclei, nodules, metastases, and other units. Existing instance segmentation networks for such structures train on densely labeled instances for each dataset, which requires substantial and often impractical manual annotation effort. Further, significant reengineering or finetuning is needed when presented with new datasets and imaging modalities due to changes in contrast, shape, orientation, resolution, and density. We present AnyStar, a domain-randomized generative model that simulates synthetic training data of blob-like objects with randomized appearance, environments, and imaging physics to train general-purpose star-convex instance segmentation networks. As a result, networks trained using our generative model do not require annotated images from unseen datasets. A single network trained on our synthesized data accurately 3D segments C. elegans and P. dumerilii nuclei in fluorescence microscopy, mouse cortical nuclei in micro-CT, zebrafish brain nuclei in EM, and placental cotyledons in human fetal MRI, all without any retraining, finetuning, transfer learning, or domain adaptation. Code is available at https://github.com/neel-dey/AnyStar.

Domain-agnostic segmentation of thalamic nuclei from joint structural and diffusion MRI

The human thalamus is a highly connected subcortical grey-matter structure within the brain. It comprises dozens of nuclei with different function and connectivity, which are affected differently by disease. For this reason, there is growing interest in studying the thalamic nuclei in vivo with MRI. Tools are available to segment the thalamus from 1 mm T1 scans, but the contrast of the lateral and internal boundaries is too faint to produce reliable segmentations. Some tools have attempted to incorporate information from diffusion MRI in the segmentation to refine these boundaries, but do not generalise well across diffusion MRI acquisitions. Here we present the first CNN that can segment thalamic nuclei from T1 and diffusion data of any resolution without retraining or fine tuning. Our method builds on a public histological atlas of the thalamic nuclei and silver standard segmentations on high-quality diffusion data obtained with a recent Bayesian adaptive segmentation tool. We combine these with an approximate degradation model for fast domain randomisation during training. Our CNN produces a segmentation at 0.7 mm isotropic resolution, irrespective of the resolution of the input. Moreover, it uses a parsimonious model of the diffusion signal at each voxel (fractional anisotropy and principal eigenvector) that is compatible with virtually any set of directions and b-values, including huge amounts of legacy data. We show results of our proposed method on three heterogeneous datasets acquired on dozens of different scanners. An implementation of the method is publicly available at https://freesurfer.net/fswiki/ThalamicNucleiDTI.

Robust machine learning segmentation for large-scale analysis of heterogeneous clinical brain MRI datasets

Every year, millions of brain MRI scans are acquired in hospitals, which is a figure considerably larger than the size of any research dataset. Therefore, the ability to analyse such scans could transform neuroimaging research. Yet, their potential remains untapped, since no automated algorithm can cope with the high variability in clinical acquisitions (MR contrast, resolution, orientation, etc.). Here we present SynthSeg+, an AI segmentation suite that enables, for the first time, robust analysis of heterogeneous clinical datasets. Specifically, in addition to whole-brain segmentation, SynthSeg+ also performs cortical parcellation, intracranial volume estimation, and automated detection of faulty segmentations (mainly caused by scans of very low quality). We demonstrate SynthSeg+ in seven experiments, including an ageing study on 14,000 scans, where it accurately replicates atrophy patterns observed on data of much higher quality. SynthSeg+ is publicly released as a ready-to-use tool to unlock the potential of quantitative morphometry in wide-ranging settings.

Robust Segmentation of Brain MRI in the Wild with Hierarchical CNNs and no Retraining

Retrospective analysis of brain MRI scans acquired in the clinic has the potential to enable neuroimaging studies with sample sizes much larger than those found in research datasets. However, analysing such clinical images "in the wild" is challenging, since subjects are scanned with highly variable protocols (MR contrast, resolution, orientation, etc.). Nevertheless, recent advances in convolutional neural networks (CNNs) and domain randomisation for image segmentation, best represented by the publicly available method SynthSeg, may enable morphometry of clinical MRI at scale. In this work, we first evaluate SynthSeg on an uncurated, heterogeneous dataset of more than 10,000 scans acquired at Massachusetts General Hospital. We show that SynthSeg is generally robust, but frequently falters on scans with low signal-to-noise ratio or poor tissue contrast. Next, we propose SynthSeg+, a novel method that greatly mitigates these problems using a hierarchy of conditional segmentation and denoising CNNs. We show that this method is considerably more robust than SynthSeg, while also outperforming cascaded networks and state-of-the-art segmentation denoising methods. Finally, we apply our approach to a proof-of-concept volumetric study of ageing, where it closely replicates atrophy patterns observed in research studies conducted on high-quality, 1mm, T1-weighted scans. The code and trained model are publicly available at https://github.com/BBillot/SynthSeg.

Accurate super-resolution low-field brain MRI

The recent introduction of portable, low-field MRI (LF-MRI) into the clinical setting has the potential to transform neuroimaging. However, LF-MRI is limited by lower resolution and signal-to-noise ratio, leading to incomplete characterization of brain regions. To address this challenge, recent advances in machine learning facilitate the synthesis of higher resolution images derived from one or multiple lower resolution scans. Here, we report the extension of a machine learning super-resolution (SR) algorithm to synthesize 1 mm isotropic MPRAGE-like scans from LF-MRI T1-weighted and T2-weighted sequences. Our initial results on a paired dataset of LF and high-field (HF, 1.5T-3T) clinical scans show that: (i) application of available automated segmentation tools directly to LF-MRI images falters; but (ii) segmentation tools succeed when applied to SR images with high correlation to gold standard measurements from HF-MRI (e.g., r = 0.85 for hippocampal volume, r = 0.84 for the thalamus, r = 0.92 for the whole cerebrum). This work demonstrates proof-of-principle post-processing image enhancement from lower resolution LF-MRI sequences. These results lay the foundation for future work to enhance the detection of normal and abnormal image findings at LF and ultimately improve the diagnostic performance of LF-MRI. Our tools are publicly available on FreeSurfer (surfer.nmr.mgh.harvard.edu/).

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.