Deformable MRI Sequence Registration for AI-based Prostate Cancer Diagnosis

The PI-CAI (Prostate Imaging: Cancer AI) challenge led to expert-level diagnostic algorithms for clinically significant prostate cancer detection. The algorithms receive biparametric MRI scans as input, which consist of T2-weighted and diffusion-weighted scans. These scans can be misaligned due to multiple factors in the scanning process. Image registration can alleviate this issue by predicting the deformation between the sequences. We investigate the effect of image registration on the diagnostic performance of AI-based prostate cancer diagnosis. First, the image registration algorithm, developed in MeVisLab, is analyzed using a dataset with paired lesion annotations. Second, the effect on diagnosis is evaluated by comparing case-level cancer diagnosis performance between using the original dataset, rigidly aligned diffusion-weighted scans, or deformably aligned diffusion-weighted scans. Rigid registration showed no improvement. Deformable registration demonstrated a substantial improvement in lesion overlap (+10% median Dice score) and a positive yet non-significant improvement in diagnostic performance (+0.3% AUROC, p=0.18). Our investigation shows that a substantial improvement in lesion alignment does not directly lead to a significant improvement in diagnostic performance. Qualitative analysis indicated that jointly developing image registration methods and diagnostic AI algorithms could enhance diagnostic accuracy and patient outcomes.

Uncertainty-Aware Semi-Supervised Learning for Prostate MRI Zonal Segmentation

Quality of deep convolutional neural network predictions strongly depends on the size of the training dataset and the quality of the annotations. Creating annotations, especially for 3D medical image segmentation, is time-consuming and requires expert knowledge. We propose a novel semi-supervised learning (SSL) approach that requires only a relatively small number of annotations while being able to use the remaining unlabeled data to improve model performance. Our method uses a pseudo-labeling technique that employs recent deep learning uncertainty estimation models. By using the estimated uncertainty, we were able to rank pseudo-labels and automatically select the best pseudo-annotations generated by the supervised model. We applied this to prostate zonal segmentation in T2-weighted MRI scans. Our proposed model outperformed the semi-supervised model in experiments with the ProstateX dataset and an external test set, by leveraging only a subset of unlabeled data rather than the full collection of 4953 cases, our proposed model demonstrated improved performance. The segmentation dice similarity coefficient in the transition zone and peripheral zone increased from 0.835 and 0.727 to 0.852 and 0.751, respectively, for fully supervised model and the uncertainty-aware semi-supervised learning model (USSL). Our USSL model demonstrates the potential to allow deep learning models to be trained on large datasets without requiring full annotation. Our code is available at https://github.com/DIAGNijmegen/prostateMR-USSL.

Medical diffusion on a budget: textual inversion for medical image generation

Diffusion-based models for text-to-image generation have gained immense popularity due to recent advancements in efficiency, accessibility, and quality. Although it is becoming increasingly feasible to perform inference with these systems using consumer-grade GPUs, training them from scratch still requires access to large datasets and significant computational resources. In the case of medical image generation, the availability of large, publicly accessible datasets that include text reports is limited due to legal and ethical concerns. While training a diffusion model on a private dataset may address this issue, it is not always feasible for institutions lacking the necessary computational resources. This work demonstrates that pre-trained Stable Diffusion models, originally trained on natural images, can be adapted to various medical imaging modalities by training text embeddings with textual inversion. In this study, we conducted experiments using medical datasets comprising only 100 samples from three medical modalities. Embeddings were trained in a matter of hours, while still retaining diagnostic relevance in image generation. Experiments were designed to achieve several objectives. Firstly, we fine-tuned the training and inference processes of textual inversion, revealing that larger embeddings and more examples are required. Secondly, we validated our approach by demonstrating a 2\% increase in the diagnostic accuracy (AUC) for detecting prostate cancer on MRI, which is a challenging multi-modal imaging modality, from 0.78 to 0.80. Thirdly, we performed simulations by interpolating between healthy and diseased states, combining multiple pathologies, and inpainting to show embedding flexibility and control of disease appearance. Finally, the embeddings trained in this study are small (less than 1 MB), which facilitates easy sharing of medical data with reduced privacy concerns.

Prototypical few-shot segmentation for cross-institution male pelvic structures with spatial registration

The prowess that makes few-shot learning desirable in medical image analysis is the efficient use of the support image data, which are labelled to classify or segment new classes, a task that otherwise requires substantially more training images and expert annotations. This work describes a fully 3D prototypical few-shot segmentation algorithm, such that the trained networks can be effectively adapted to clinically interesting structures that are absent in training, using only a few labelled images from a different institute. First, to compensate for the widely recognised spatial variability between institutions in episodic adaptation of novel classes, a novel spatial registration mechanism is integrated into prototypical learning, consisting of a segmentation head and an spatial alignment module. Second, to assist the training with observed imperfect alignment, support mask conditioning module is proposed to further utilise the annotation available from the support images. Extensive experiments are presented in an application of segmenting eight anatomical structures important for interventional planning, using a data set of 589 pelvic T2-weighted MR images, acquired at seven institutes. The results demonstrate the efficacy in each of the 3D formulation, the spatial registration, and the support mask conditioning, all of which made positive contributions independently or collectively. Compared with the previously proposed 2D alternatives, the few-shot segmentation performance was improved with statistical significance, regardless whether the support data come from the same or different institutes.

Few-shot image segmentation for cross-institution male pelvic organs using registration-assisted prototypical learning

The ability to adapt medical image segmentation networks for a novel class such as an unseen anatomical or pathological structure, when only a few labelled examples of this class are available from local healthcare providers, is sought-after. This potentially addresses two widely recognised limitations in deploying modern deep learning models to clinical practice, expertise-and-labour-intensive labelling and cross-institution generalisation. This work presents the first 3D few-shot interclass segmentation network for medical images, using a labelled multi-institution dataset from prostate cancer patients with eight regions of interest. We propose an image alignment module registering the predicted segmentation of both query and support data, in a standard prototypical learning algorithm, to a reference atlas space. The built-in registration mechanism can effectively utilise the prior knowledge of consistent anatomy between subjects, regardless whether they are from the same institution or not. Experimental results demonstrated that the proposed registration-assisted prototypical learning significantly improved segmentation accuracy (p-values<0.01) on query data from a holdout institution, with varying availability of support data from multiple institutions. We also report the additional benefits of the proposed 3D networks with 75% fewer parameters and an arguably simpler implementation, compared with existing 2D few-shot approaches that segment 2D slices of volumetric medical images.

Report-Guided Automatic Lesion Annotation for Deep Learning-Based Prostate Cancer Detection in bpMRI

Deep learning-based diagnostic performance increases with more annotated data, but manual annotation is a bottleneck in most fields. Experts evaluate diagnostic images during clinical routine, and write their findings in reports. Automatic annotation based on clinical reports could overcome the manual labelling bottleneck. We hypothesise that dense annotations for detection tasks can be generated using model predictions, guided by sparse information from these reports. To demonstrate efficacy, we generated clinically significant prostate cancer (csPCa) annotations, guided by the number of clinically significant findings in the radiology reports. We included 7,756 prostate MRI examinations, of which 3,050 were manually annotated and 4,706 were automatically annotated. We evaluated the automatic annotation quality on the manually annotated subset: our score extraction correctly identified the number of csPCa lesions for $99.3\%$ of the reports and our csPCa segmentation model correctly localised $83.8 \pm 1.1\%$ of the lesions. We evaluated prostate cancer detection performance on 300 exams from an external centre with histopathology-confirmed ground truth. Augmenting the training set with automatically labelled exams improved patient-based diagnostic area under the receiver operating characteristic curve from $88.1\pm 1.1\%$ to $89.8\pm 1.0\%$ ($P = 1.2 \cdot 10^{-4}$) and improved lesion-based sensitivity at one false positive per case from $79.2 \pm 2.8\%$ to $85.4 \pm 1.9\%$ ($P<10^{-4}$), with $mean \pm std.$ over 15 independent runs. This improved performance demonstrates the feasibility of our report-guided automatic annotations. Source code is made publicly available at https://github.com/DIAGNijmegen/Report-Guided-Annotation. Best csPCa detection algorithm is made available at https://grand-challenge.org/algorithms/bpmri-cspca-detection-report-guided-annotations/.

Fully Automatic Deep Learning Framework for Pancreatic Ductal Adenocarcinoma Detection on Computed Tomography

Early detection improves prognosis in pancreatic ductal adenocarcinoma (PDAC) but is challenging as lesions are often small and poorly defined on contrast-enhanced computed tomography scans (CE-CT). Deep learning can facilitate PDAC diagnosis, however current models still fail to identify small (<2cm) lesions. In this study, state-of-the-art deep learning models were used to develop an automatic framework for PDAC detection, focusing on small lesions. Additionally, the impact of integrating surrounding anatomy was investigated. CE-CT scans from a cohort of 119 pathology-proven PDAC patients and a cohort of 123 patients without PDAC were used to train a nnUnet for automatic lesion detection and segmentation (nnUnet_T). Two additional nnUnets were trained to investigate the impact of anatomy integration: (1) segmenting the pancreas and tumor (nnUnet_TP), (2) segmenting the pancreas, tumor, and multiple surrounding anatomical structures (nnUnet_MS). An external, publicly available test set was used to compare the performance of the three networks. The nnUnet_MS achieved the best performance, with an area under the receiver operating characteristic curve of 0.91 for the whole test set and 0.88 for tumors <2cm, showing that state-of-the-art deep learning can detect small PDAC and benefits from anatomy information.

Anatomical and Diagnostic Bayesian Segmentation in Prostate MRI $-$Should Different Clinical Objectives Mandate Different Loss Functions?

We hypothesize that probabilistic voxel-level classification of anatomy and malignancy in prostate MRI, although typically posed as near-identical segmentation tasks via U-Nets, require different loss functions for optimal performance due to inherent differences in their clinical objectives. We investigate distribution, region and boundary-based loss functions for both tasks across 200 patient exams from the publicly-available ProstateX dataset. For evaluation, we conduct a thorough comparative analysis of model predictions and calibration, measured with respect to multi-class volume segmentation of the prostate anatomy (whole-gland, transitional zone, peripheral zone), as well as, patient-level diagnosis and lesion-level detection of clinically significant prostate cancer. Notably, we find that distribution-based loss functions (in particular, focal loss) are well-suited for diagnostic or panoptic segmentation tasks such as lesion detection, primarily due to their implicit property of inducing better calibration. Meanwhile, (with the exception of focal loss) both distribution and region/boundary-based loss functions perform equally well for anatomical or semantic segmentation tasks, such as quantification of organ shape, size and boundaries.

Cine-MRI detection of abdominal adhesions with spatio-temporal deep learning

Adhesions are an important cause of chronic pain following abdominal surgery. Recent developments in abdominal cine-MRI have enabled the non-invasive diagnosis of adhesions. Adhesions are identified on cine-MRI by the absence of sliding motion during movement. Diagnosis and mapping of adhesions improves the management of patients with pain. Detection of abdominal adhesions on cine-MRI is challenging from both a radiological and deep learning perspective. We focus on classifying presence or absence of adhesions in sagittal abdominal cine-MRI series. We experimented with spatio-temporal deep learning architectures centered around a ConvGRU architecture. A hybrid architecture comprising a ResNet followed by a ConvGRU model allows to classify a whole time-series. Compared to a stand-alone ResNet with a two time-point (inspiration/expiration) input, we show an increase in classification performance (AUROC) from 0.74 to 0.83 ($p<0.05$). Our full temporal classification approach adds only a small amount (5%) of parameters to the entire architecture, which may be useful for other medical imaging problems with a temporal dimension.

The Medical Segmentation Decathlon

International challenges have become the de facto standard for comparative assessment of image analysis algorithms given a specific task. Segmentation is so far the most widely investigated medical image processing task, but the various segmentation challenges have typically been organized in isolation, such that algorithm development was driven by the need to tackle a single specific clinical problem. We hypothesized that a method capable of performing well on multiple tasks will generalize well to a previously unseen task and potentially outperform a custom-designed solution. To investigate the hypothesis, we organized the Medical Segmentation Decathlon (MSD) - a biomedical image analysis challenge, in which algorithms compete in a multitude of both tasks and modalities. The underlying data set was designed to explore the axis of difficulties typically encountered when dealing with medical images, such as small data sets, unbalanced labels, multi-site data and small objects. The MSD challenge confirmed that algorithms with a consistent good performance on a set of tasks preserved their good average performance on a different set of previously unseen tasks. Moreover, by monitoring the MSD winner for two years, we found that this algorithm continued generalizing well to a wide range of other clinical problems, further confirming our hypothesis. Three main conclusions can be drawn from this study: (1) state-of-the-art image segmentation algorithms are mature, accurate, and generalize well when retrained on unseen tasks; (2) consistent algorithmic performance across multiple tasks is a strong surrogate of algorithmic generalizability; (3) the training of accurate AI segmentation models is now commoditized to non AI experts.