Robert B. West

Okyaz Eminaga, Mahmoud Abbas, Christian Kunder et al.

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2,603 histology images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor-grade disagreement between vPatho and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. Concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessels, and lymph cell infiltrations. However, concordance in tumor grading showed a decline when applied to prostatectomy specimens (kappa = 0.44) compared to biopsy cores (kappa = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5% to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (kappa from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with discordance. Notably, grade discordance with vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin of a pathologist. This approach can help uncover limitations in AI adoption and the current grading system for prostate cancer pathology.

Saibo Geng, Sankalp Gambhir, Chris Wendler et al.

Tokenization is an important preprocessing step in the training and inference of large language models (LLMs). While there has been extensive research on the expressive power of the neural achitectures used in LLMs, the impact of tokenization has not been well understood. In this work, we demonstrate that tokenization, irrespective of the algorithm used, acts as an inverse homomorphism between strings and tokens. This suggests that the character space of the source language and the token space of the tokenized language are homomorphic, preserving the structural properties of the source language. Additionally, we explore the concept of proper tokenization, which refers to an unambiguous tokenization returned from the tokenizer. Our analysis reveals that the expressiveness of neural architectures in recognizing context-free languages is not affected by tokenization.

Okyaz Eminaga, Yuri Tolkach, Christian Kunder et al.

The current study detects different morphologies related to prostate pathology using deep learning models; these models were evaluated on 2,121 hematoxylin and eosin (H&E) stain histology images captured using bright field microscopy, which spanned a variety of image qualities, origins (whole slide, tissue micro array, whole mount, Internet), scanning machines, timestamps, H&E staining protocols, and institutions. For case usage, these models were applied for the annotation tasks in clinician-oriented pathology reports for prostatectomy specimens. The true positive rate (TPR) for slides with prostate cancer was 99.7% by a false positive rate of 0.785%. The F1-scores of Gleason patterns reported in pathology reports ranged from 0.795 to 1.0 at the case level. TPR was 93.6% for the cribriform morphology and 72.6% for the ductal morphology. The correlation between the ground truth and the prediction for the relative tumor volume was 0.987 n. Our models cover the major components of prostate pathology and successfully accomplish the annotation tasks.