This study explores the efficacy of diffusion probabilistic models for generating synthetic histopathological images, specifically canine Perivascular Wall Tumours (cPWT), to supplement limited datasets for deep learning applications in digital pathology. This research evaluates an open-source medical domain-focused diffusion model called Medfusion, where the model was trained on a small (1,000 patches) and a large dataset (17,000 patches) of cPWT images to compare performance on the different sized datasets. A Receiver Operating Characteristic (ROC) study was implemented to investigate the ability of six veterinary medical professionals and pathologists to discern between generated and real cPWT patch images. The participants engaged in two separate rounds, where each round corresponded to models that had been trained on the two different sized datasets. The ROC study revealed mean average Area Under the Curve (AUC) values close to 0.5 for both rounds. The results from this study suggests that diffusion models can create histopathological patch images that are convincingly realistic where our participants often struggled to reliably differentiate between generated and real images. This underscores the potential of these models as a valuable tool for augmenting digital pathology datasets.
The effectiveness of untrained convolutional layers for feature extraction in a computational pathology task using real-world data from a necrosis detection dataset is investigated. The study aims to determine whether ImageNet pretrained layers from deep CNNs combined with frozen untrained weights are sufficient for effective necrosis detection in canine Perivascular Wall Tumour (cPWT) whole slide images. Additionally, the authors investigate the impact of pruning CNNs, and whether it can be effective for necrosis detection as this technique can contribute towards reducing memory requirements and improve inference speed in diagnostic settings. The study found that fine-tuning the last (deepest) layers of a pretrained ImageNet model for necrosis detection in cPWT produces the highest test F1-score (0.715) when compared to alternative set ups. This score is further improved to 0.754 when the results are optimised using an optimal threshold predetermined on maximising the validation set F1-score. Resetting weights (untrained) and freezing the last few convolutional layers in the last dense block also demonstrated some capability in necrosis detection with an optimised F1-score of 0.747, still outperforming models trained from scratch as well as an ImageNet pretrained feature extraction model. Pruning the fine-tuned model using lower thresholds also showed the potential to improve performance, however thresholds higher than 0.40 negatively impacted performance.
The scarcity of large histopathological datasets can be problematic for Deep Learning in medical imaging and digital pathology. However, transfer Learning has been shown to be promising for the effective training of classifiers on smaller datasets. ImageNet is a popular dataset that is commonly used for transfer learning in various domains. The features extracted from the ImageNet dataset are generalizable and can be applied to alternative tasks and datasets. Deep Learning typically requires a vast amount of data for training, however, in our study we interrogated two datasets with patches extracted from only 30 whole slide images (WSIs) and 60 WSIs respectively. As a consequence, we decided to extract features and feed them into separate classifier models such as a fully connected softmax layer, Support Vector Machines (SVM) and Logistic Regression. This study demonstrated that for the small dataset, the best pretrained feature extractor was DenseNet201, whereas the best model for training was a fully connected softmax layer with a reported accuracy of 88.20% and an average f1-score of 0.881. For the larger dataset size, the best feature extractor was InceptionResNetV2 where the highest accuracy and f1-score of 90.60% and 0.908 was produced when classified using a fully connected softmax layer. All models, apart from ResNet50 demonstrated an improvement in performance when pretraining using ImageNet for bottleneck feature extraction.
Complex ‘Big Data’ questions that involve machine learning require large datasets for training. This is particularly problematic for Deep Learning methods in the biomedical imaging domain and specifically Digital Pathology. Transfer Learning has been shown to be a promising method for training classifiers on smaller sized datasets. In this work we investigate the effectiveness of aggregated Transfer Learning using VGG19 trained on ImageNet and then fine-tuning parameters with tissue histopathological patches from breast cancer metastatic tissue patches to classify soft tissue sarcoma patches. We compare results with and without transfer learning, and fine tuning applied to different layers. From the results, it is apparent that fine-tuning earlier VGG19 convolutional blocks with breast cancer patches and applying bottleneck feature extraction to soft tissue sarcoma can have an adverse effect on accuracy and other performance measures. Nevertheless, the aggregated approach is a promising method for digital pathology and requires much more investigation.
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