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One area of medical imaging that has recently experienced innovative deep learning advances is diffusion MRI (dMRI) streamline tractography with recurrent neural networks (RNNs). Unlike traditional imaging studies which utilize voxel-based learning, these studies model dMRI features at points in continuous space off the voxel grid in order to propagate streamlines, or virtual estimates of axons. However, implementing such models is nontrivial, and an open-source implementation is not yet widely available. Here, we describe a series of considerations for implementing tractography with RNNs and demonstrate they allow one to approximate a deterministic streamline propagator with comparable performance to existing algorithms. We release this trained model and the associated implementations leveraging popular deep learning libraries. We hope the availability of these resources will lower the barrier of entry into this field, spurring further innovation. 

The Segment Anything Model (SAM) is a recently proposed prompt-based segmentation model in a generic zero-shot segmentation approach. With the zero-shot segmentation capacity, SAM achieved impressive flexibility and precision on various segmentation tasks. However, the current pipeline requires manual prompts during the inference stage, which is still resource intensive for biomedical image segmentation. In this paper, instead of using prompts during the inference stage, we introduce a pipeline that utilizes the SAM, called all-in-SAM, through the entire AI development workflow (from annotation generation to model finetuning) without requiring manual prompts during the inference stage. Specifically, SAM is first employed to generate pixel-level annotations from weak prompts (e.g., points, bounding box). Then, the pixel-level annotations are used to finetune the SAM segmentation model rather than training from scratch. Our experimental results reveal two key findings: 1) the proposed pipeline surpasses the state-of-the-art (SOTA) methods in a nuclei segmentation task on the public Monuseg dataset, and 2) the utilization of weak and few annotations for SAM finetuning achieves competitive performance compared to using strong pixel-wise annotated data. 

The segment anything model (SAM) was released as a foundation model for image segmentation. The promptable segmentation model was trained by over 1 billion masks on 11M licensed and privacy-respecting images. The model supports zero-shot image segmentation with various seg- mentation prompts (e.g., points, boxes, masks). It makes the SAM attractive for medical image analysis, especially for digital pathology where the training data are rare. In this study, we eval- uate the zero-shot segmentation performance of SAM model on representative segmentation tasks on whole slide imaging (WSI), including (1) tumor segmentation, (2) non-tumor tissue segmen- tation, (3) cell nuclei segmentation. Core Results: The results suggest that the zero-shot SAM model achieves remarkable segmentation performance for large connected objects. However, it does not consistently achieve satisfying performance for dense instance object segmentation, even with 20 prompts (clicks/boxes) on each image. We also summarized the identified limitations for digital pathology: (1) image resolution, (2) multiple scales, (3) prompt selection, and (4) model fine-tuning. In the future, the few-shot fine-tuning with images from downstream pathological seg- mentation tasks might help the model to achieve better performance in dense object segmentation. 

Multiplex immunofluorescence (MxIF) is an advanced molecular imaging technique that can simultaneously provide biologists with multiple (i.e., more than 20) molecular markers on a single histological tissue section. Unfortunately, due to imaging restrictions, the more routinely used hematoxylin and eosin (H&E) stain is typically unavailable with MxIF on the same tissue section. As biological H&E staining is not feasible, previous efforts have been made to obtain H&E whole slide image (WSI) from MxIF via deep learning empowered virtual staining. However, the tiling effect is a long-lasting problem in high-resolution WSI-wise synthesis. The MxIF to H&E synthesis is no exception. Limited by computational resources, the cross-stain image synthesis is typically performed at the patch-level. Thus, discontinuous intensities might be visually identified along with the patch boundaries assembling all individual patches back to a WSI. In this work, we propose a deep learning based unpaired high-resolution image synthesis method to obtain virtual H&E WSIs from MxIF WSIs (each with 27 markers/stains) with reduced tiling effects. Briefly, we first extend the CycleGAN framework by adding simultaneous nuclei and mucin segmentation supervision as spatial constraints. Then, we introduce a random sliding window shifting strategy during the optimized inference stage to alleviate the tiling effects. The validation results show that our spatially constrained synthesis method achieves a 56% performance gain for the downstream cell segmentation task. The proposed inference method reduces the tiling effects by using 50% fewer computation resources without compromising performance. The proposed random sliding window inference method is a plug-and-play module, which can be generalized and used for other high-resolution WSI image synthesis applications. The source code with our proposed model are available at https://github.com/MASILab/RandomWalkSlidingWindow.git 

Deep learning has made great strides in medical imaging, enabled by hardware advances in GPUs. One major constraint for the development of new models has been the saturation of GPU memory resources during training. This is especially true in computational pathology, where images regularly contain more than 1 billion pixels. These pathological images are traditionally divided into small patches to enable deep learning due to hardware limitations. In this work, we explore whether the shared GPU/CPU memory architecture on the M1 Ultra systems-on-a-chip (SoCs) recently released by Apple, Inc. may provide a solution. These affordable systems (less than $5000) provide access to 128 GB of unified memory (Mac Studio with M1 Ultra SoC). As a proof of concept for gigapixel deep learning, we identified tissue from background on gigapixel areas from whole slide images (WSIs). The model was a modified U-Net (4492 parameters) leveraging large kernels and high stride. The M1 Ultra SoC was able to train the model directly on gigapixel images (16000×64000 pixels, 1.024 billion pixels) with a batch size of 1 using over 100 GB of unified memory for the process at an average speed of 1 minute and 21 seconds per batch with Tensorflow 2/Keras. As expected, the model converged with a high Dice score of 0.989 ± 0.005. Training up until this point took 111 hours and 24 minutes over 4940 steps. Other high RAM GPUs like the NVIDIA A100 (largest commercially accessible at 80 GB, ∼$15000) are not yet widely available (in preview for select regions on Amazon Web Services at $40.96/hour as a group of 8). This study is a promising step towards WSI-wise end-to-end deep learning with prevalent network architectures.