Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.07.11.603091

Closing the gap in the clinical adoption of computational pathology: a standardized, open-source framework to integrate deep-learning algorithms into the laboratory information system

Abstract

Digital pathology (DP) has revolutionized cancer diagnostics, allowing the development of deep-learning (DL) models supporting pathologists in their daily work and contributing to the improvement of patient care. However, the clinical adoption of such models remains challenging. Here we describe a proof-of-concept framework that, leveraging open-source DP software and Health Level 7 (HL7) standards, allows the integration of DL models in the clinical workflow. Development and testing of the workflow were carried out in a fully digitized Italian pathology department. A Python-based server-client architecture was implemented to interconnect the anatomic pathology laboratory information system (AP-LIS) with an external artificial intelligence decision support system (AI-DSS) containing 16 pre-trained DL models through HL7 messaging. Open-source toolboxes for DL model deployment, including WSInfer and WSInfer-MIL, were used to run DL model inference. Visualization of model predictions as colored heatmaps was performed in QuPath. As soon as a new slide is scanned, DL model inference is automatically run on the basis of the slides tissue type and staining. In addition, pathologists can initiate the analysis on-demand by selecting a specific DL model from the virtual slides tray. In both cases the AP-LIS transmits an HL7 message to the AI-DSS, which processes the message, runs DL model inference, and creates the appropriate type of colored heatmap on the basis of the employed classification model. The AI-DSS transmits model inference results to the AP-LIS, where pathologists can visualize the output in QuPath and/or directly from the virtual slides tray. The developed framework supports multiple DL toolboxes and it is thus suitable for a broad range of applications. In addition, this integration workflow is a key step to enable the future widespread adoption of DL models in pathology diagnostics.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Angeloni, M., Rizzi, D., Schoen, S., Caputo, A., Merolla, F., Hartmann, A., Ferrazzi, F., Fraggetta, F.. 2024-07-16. Closing the gap in the clinical adoption of computational pathology: a standardized, open-source framework to integrate deep-learning algorithms into the laboratory information system. https://doi.org/10.1101/2024.07.11.603091

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Negative association between nodular stromal fibrosis and large lipid droplets in human choroid plexus epithelial cells

Fibrosis is an age-related change within the human choroid plexus that is likely to affect its function negatively. We systematically analyzed nodular stromal fibrosis present in postmortem tissue from a large repository encompassing the human lifespan. Following manual annotation of sampled images from 81 specimens of choroid plexus from the atrium of the lateral ventricle, a deep learning model was trained to assess stages of fibrosis (dense, hyalinized, and mineralized) occurring in papillae across whole slide images of hematoxylin and eosin-stained sections from 204 cases. The percentage of affected papillae and the relative area of fibrosis at all three stages of severity increased with age. Affected papillae were significantly clustered across the choroid plexus, with areas of high and low fibrotic density. Choroid plexus epithelial cells (CPECs) associated with fibrotic papillae were less likely to contain large lipid droplets than were non-fibrotic papillae, as assessed by another deep learning model. Across papillae within a case, the area of each stage of fibrosis was negatively correlated with the prevalence of CPECs containing large lipid droplets. Finally, individuals displaying more nodular fibrosis had significantly fewer CPECs containing large lipid droplets. Thus, age-related nodular stromal fibrosis may negatively impact lipid storage and homeostasis for the choroid plexus and brain.

pathology↗

SilencioM: silencing connected interfering oligonucleotides against MAPT as a potential disease modifying therapeutic for tauopathies

Tauopathies are a diverse group of neurodegenerative diseases whose pathogenesis involves brain accumulation of misfolded, pathological tau (Microtubule Associated Protein Tau, MAPT). More than twenty tauopathies have been identified thus far that collectively impact millions of people worldwide, of which the most common is Alzheimer's disease (AD). Despite substantial efforts to develop drugs for tauopathies, no effective treatments currently exist, highlighting the urgent need for therapeutics to combat these prevalent and ruinous neurodegenerative diseases. Strategies that target tau are likely to have the greatest impact since tau is the proximal cause of their pathogenesis. Small interfering RNAs (siRNAs) have emerged as a powerful class of precision therapeutics that silence disease-causing genes through RNA interference with favorable safety profiles. Delivery challenges are rapidly being addressed, and siRNA-based approaches are poised to transform the therapeutic landscape of neurological diseases. In this study, we describe SilencioM (Silencing connected interfering oligonucleotides against MAPT) and show its efficacy in markedly reducing tau pathology after a single intracerebroventricular injection in PS19 mice, a mouse model of severe tauopathy. SilencioM targets human, primate, rat and mouse ortholog genes; thus, the same compound can proceed from efficacy studies to Investigational New Drug Application (IND)-enabling studies. SilencioM is simple to manufacture and is administered without encapsulation in lipid nanoparticles and without requirements for lipophilic conjugation, making it a promising candidate for further development as a novel therapeutic for tauopathies, including AD.

pathology↗

SilencioMA: A single compound that targets both MAPT and APP as a potential disease modifying therapeutic for Alzheimer's Disease

Alzheimer's Disease (AD) is the most common age-related neurodegenerative disease and the leading cause of dementia worldwide. AD pathogenesis involves aggregation of amyloid-beta (A{beta}), produced from amyloidogenic proteolytic processing of Amyloid Precursor Protein (APP), and accumulation of misfolded, pathological tau (Microtubule Associated Protein Tau, MAPT). Current efforts focus on developing disease modifying therapeutics (DMTs) against single targets: A{beta} or tau. However, DMTs that concurrently target both tau and A{beta} are likely to have the greatest impact since they target both culprits of AD pathogenesis. Here we describe the development of SilencioMA, a single compound that targets both MAPT and APP messenger RNAs (mRNAs) based on silencing connected interfering oligonucleotides against MAPT and APP. Cerebrospinal fluid (CSF) administration of SilencioMA reduces A{beta} and tau and pathology after a single intracerebroventricular injection in 5XFAD/PS19 mice, an animal model of severe amyloidosis and tauopathy. SilencioMA does not rely on lipid nanoparticles or lipophilic conjugates for CSF administration. At the same time its modular design permits conjugation of ligands that facilitate transcytosis through the blood brain barrier, allowing systemic administration. Our findings provide proof-of-concept for a strategy that targets the dual A{beta} and tau pathologies of AD, and establishes a compelling foundation for further development of SilencioMA as a next-generation DMT for AD.

pathology↗