How to build the best medical image segmentation algorithm using foundation models: a comprehensive empirical study with Segment Anything Model

Automated segmentation is a fundamental medical image analysis task, which enjoys significant advances due to the advent of deep learning. While foundation models have been useful in natural language processing and some vision tasks for some time, the foundation model developed with image segmentation in mind - Segment Anything Model (SAM) - has been developed only recently and has shown similar promise. However, there are still no systematic analyses or ``best-practice'' guidelines for optimal fine-tuning of SAM for medical image segmentation. This work summarizes existing fine-tuning strategies with various backbone architectures, model components, and fine-tuning algorithms across 18 combinations, and evaluates them on 17 datasets covering all common radiology modalities. Our study reveals that (1) fine-tuning SAM leads to slightly better performance than previous segmentation methods, (2) fine-tuning strategies that use parameter-efficient learning in both the encoder and decoder are superior to other strategies, (3) network architecture has a small impact on final performance, (4) further training SAM with self-supervised learning can improve final model performance. We also demonstrate the ineffectiveness of some methods popular in the literature and further expand our experiments into few-shot and prompt-based settings. Lastly, we released our code and MRI-specific fine-tuned weights, which consistently obtained superior performance over the original SAM, at https://github.com/mazurowski-lab/finetune-SAM.

Rethinking Perceptual Metrics for Medical Image Translation

Modern medical image translation methods use generative models for tasks such as the conversion of CT images to MRI. Evaluating these methods typically relies on some chosen downstream task in the target domain, such as segmentation. On the other hand, task-agnostic metrics are attractive, such as the network feature-based perceptual metrics (e.g., FID) that are common to image translation in general computer vision. In this paper, we investigate evaluation metrics for medical image translation on two medical image translation tasks (GE breast MRI to Siemens breast MRI and lumbar spine MRI to CT), tested on various state-of-the-art translation methods. We show that perceptual metrics do not generally correlate with segmentation metrics due to them extending poorly to the anatomical constraints of this sub-field, with FID being especially inconsistent. However, we find that the lesser-used pixel-level SWD metric may be useful for subtle intra-modality translation. Our results demonstrate the need for further research into helpful metrics for medical image translation.

Deep learning automates Cobb angle measurement compared with multi-expert observers

Scoliosis, a prevalent condition characterized by abnormal spinal curvature leading to deformity, requires precise assessment methods for effective diagnosis and management. The Cobb angle is a widely used scoliosis quantification method that measures the degree of curvature between the tilted vertebrae. Yet, manual measuring of Cobb angles is time-consuming and labor-intensive, fraught with significant interobserver and intraobserver variability. To address these challenges and the lack of interpretability found in certain existing automated methods, we have created fully automated software that not only precisely measures the Cobb angle but also provides clear visualizations of these measurements. This software integrates deep neural network-based spine region detection and segmentation, spine centerline identification, pinpointing the most significantly tilted vertebrae, and direct visualization of Cobb angles on the original images. Upon comparison with the assessments of 7 expert readers, our algorithm exhibited a mean deviation in Cobb angle measurements of 4.17 degrees, notably surpassing the manual approach's average intra-reader discrepancy of 5.16 degrees. The algorithm also achieved intra-class correlation coefficients (ICC) exceeding 0.96 and Pearson correlation coefficients above 0.944, reflecting robust agreement with expert assessments and superior measurement reliability. Through the comprehensive reader study and statistical analysis, we believe this algorithm not only ensures a higher consensus with expert readers but also enhances interpretability and reproducibility during assessments. It holds significant promise for clinical application, potentially aiding physicians in more accurate scoliosis assessment and diagnosis, thereby improving patient care.

ContourDiff: Unpaired Image Translation with Contour-Guided Diffusion Models

Accurately translating medical images across different modalities (e.g., CT to MRI) has numerous downstream clinical and machine learning applications. While several methods have been proposed to achieve this, they often prioritize perceptual quality with respect to output domain features over preserving anatomical fidelity. However, maintaining anatomy during translation is essential for many tasks, e.g., when leveraging masks from the input domain to develop a segmentation model with images translated to the output domain. To address these challenges, we propose ContourDiff, a novel framework that leverages domain-invariant anatomical contour representations of images. These representations are simple to extract from images, yet form precise spatial constraints on their anatomical content. We introduce a diffusion model that converts contour representations of images from arbitrary input domains into images in the output domain of interest. By applying the contour as a constraint at every diffusion sampling step, we ensure the preservation of anatomical content. We evaluate our method by training a segmentation model on images translated from CT to MRI with their original CT masks and testing its performance on real MRIs. Our method outperforms other unpaired image translation methods by a significant margin, furthermore without the need to access any input domain information during training.

Medical Image Segmentation with InTEnt: Integrated Entropy Weighting for Single Image Test-Time Adaptation

Test-time adaptation (TTA) refers to adapting a trained model to a new domain during testing. Existing TTA techniques rely on having multiple test images from the same domain, yet this may be impractical in real-world applications such as medical imaging, where data acquisition is expensive and imaging conditions vary frequently. Here, we approach such a task, of adapting a medical image segmentation model with only a single unlabeled test image. Most TTA approaches, which directly minimize the entropy of predictions, fail to improve performance significantly in this setting, in which we also observe the choice of batch normalization (BN) layer statistics to be a highly important yet unstable factor due to only having a single test domain example. To overcome this, we propose to instead integrate over predictions made with various estimates of target domain statistics between the training and test statistics, weighted based on their entropy statistics. Our method, validated on 24 source/target domain splits across 3 medical image datasets surpasses the leading method by 2.9% Dice coefficient on average.

Anatomically-Controllable Medical Image Generation with Segmentation-Guided Diffusion Models

Diffusion models have enabled remarkably high-quality medical image generation, which can help mitigate the expenses of acquiring and annotating new images by supplementing small or imbalanced datasets, along with other applications. However, these are hampered by the challenge of enforcing global anatomical realism in generated images. To this end, we propose a diffusion model for anatomically-controlled medical image generation. Our model follows a multi-class anatomical segmentation mask at each sampling step and incorporates a \textit{random mask ablation} training algorithm, to enable conditioning on a selected combination of anatomical constraints while allowing flexibility in other anatomical areas. This also improves the network's learning of anatomical realism for the completely unconditional (unconstrained generation) case. Comparative evaluation on breast MRI and abdominal/neck-to-pelvis CT datasets demonstrates superior anatomical realism and input mask faithfulness over state-of-the-art models. We also offer an accessible codebase and release a dataset of generated paired breast MRIs. Our approach facilitates diverse applications, including pre-registered image generation, counterfactual scenarios, and others.

SegmentAnyBone: A Universal Model that Segments Any Bone at Any Location on MRI

Magnetic Resonance Imaging (MRI) is pivotal in radiology, offering non-invasive and high-quality insights into the human body. Precise segmentation of MRIs into different organs and tissues would be highly beneficial since it would allow for a higher level of understanding of the image content and enable important measurements, which are essential for accurate diagnosis and effective treatment planning. Specifically, segmenting bones in MRI would allow for more quantitative assessments of musculoskeletal conditions, while such assessments are largely absent in current radiological practice. The difficulty of bone MRI segmentation is illustrated by the fact that limited algorithms are publicly available for use, and those contained in the literature typically address a specific anatomic area. In our study, we propose a versatile, publicly available deep-learning model for bone segmentation in MRI across multiple standard MRI locations. The proposed model can operate in two modes: fully automated segmentation and prompt-based segmentation. Our contributions include (1) collecting and annotating a new MRI dataset across various MRI protocols, encompassing over 300 annotated volumes and 8485 annotated slices across diverse anatomic regions; (2) investigating several standard network architectures and strategies for automated segmentation; (3) introducing SegmentAnyBone, an innovative foundational model-based approach that extends Segment Anything Model (SAM); (4) comparative analysis of our algorithm and previous approaches; and (5) generalization analysis of our algorithm across different anatomical locations and MRI sequences, as well as an external dataset. We publicly release our model at https://github.com/mazurowski-lab/SegmentAnyBone.

The Effect of Intrinsic Dataset Properties on Generalization: Unraveling Learning Differences Between Natural and Medical Images

This paper investigates discrepancies in how neural networks learn from different imaging domains, which are commonly overlooked when adopting computer vision techniques from the domain of natural images to other specialized domains such as medical images. Recent works have found that the generalization error of a trained network typically increases with the intrinsic dimension ($d_{data}$) of its training set. Yet, the steepness of this relationship varies significantly between medical (radiological) and natural imaging domains, with no existing theoretical explanation. We address this gap in knowledge by establishing and empirically validating a generalization scaling law with respect to $d_{data}$, and propose that the substantial scaling discrepancy between the two considered domains may be at least partially attributed to the higher intrinsic "label sharpness" ($K_F$) of medical imaging datasets, a metric which we propose. Next, we demonstrate an additional benefit of measuring the label sharpness of a training set: it is negatively correlated with the trained model's adversarial robustness, which notably leads to models for medical images having a substantially higher vulnerability to adversarial attack. Finally, we extend our $d_{data}$ formalism to the related metric of learned representation intrinsic dimension ($d_{repr}$), derive a generalization scaling law with respect to $d_{repr}$, and show that $d_{data}$ serves as an upper bound for $d_{repr}$. Our theoretical results are supported by thorough experiments with six models and eleven natural and medical imaging datasets over a range of training set sizes. Our findings offer insights into the influence of intrinsic dataset properties on generalization, representation learning, and robustness in deep neural networks.

How to Efficiently Annotate Images for Best-Performing Deep Learning Based Segmentation Models: An Empirical Study with Weak and Noisy Annotations and Segment Anything Model

Deep neural networks (DNNs) have been deployed for many image segmentation tasks and achieved outstanding performance. However, preparing a dataset for training segmentation DNNs is laborious and costly since typically pixel-level annotations are provided for each object of interest. To alleviate this issue, one can provide only weak labels such as bounding boxes or scribbles, or less accurate (noisy) annotations of the objects. These are significantly faster to generate and thus result in more annotated images given the same time budget. However, the reduction in quality might negatively affect the segmentation performance of the resulting model. In this study, we perform a thorough cost-effectiveness evaluation of several weak and noisy labels. We considered 11 variants of annotation strategies and 4 datasets. We conclude that the common practice of accurately outlining the objects of interest is virtually never the optimal approach when the annotation time is limited, even if notable annotation time is available (10s of hours). Annotation approaches that stood out in such scenarios were (1) contour-based annotation with rough continuous traces, (2) polygon-based annotation with few vertices, and (3) box annotations combined with the Segment Anything Model (SAM). In situations where unlimited annotation time was available, precise annotations still lead to the highest segmentation model performance.

Domain Generalization for Medical Image Analysis: A Survey

Medical Image Analysis (MedIA) has become an essential tool in medicine and healthcare, aiding in disease diagnosis, prognosis, and treatment planning, and recent successes in deep learning (DL) have made significant contributions to its advances. However, DL models for MedIA remain challenging to deploy in real-world situations, failing for generalization under the distributional gap between training and testing samples, known as a distribution shift problem. Researchers have dedicated their efforts to developing various DL methods to adapt and perform robustly on unknown and out-of-distribution data distributions. This paper comprehensively reviews domain generalization studies specifically tailored for MedIA. We provide a holistic view of how domain generalization techniques interact within the broader MedIA system, going beyond methodologies to consider the operational implications on the entire MedIA workflow. Specifically, we categorize domain generalization methods into data-level, feature-level, model-level, and analysis-level methods. We show how those methods can be used in various stages of the MedIA workflow with DL equipped from data acquisition to model prediction and analysis. Furthermore, we include benchmark datasets and applications used to evaluate these approaches and analyze the strengths and weaknesses of various methods, unveiling future research opportunities.