Bridging the Gap Between (AI-) Services and Their Application in Research and Clinical Settings Through Interoperability: the OMI-Protocol

Artificial Intelligence (AI) in research and clinical contexts is transforming the areas of medical and life sciences permanently. Aspects like findability, accessibility, interoperability, and reusability are often neglected for AI-based inference services. The Open Medical Inference (OMI) protocol aims to support remote inference by addressing the aforementioned aspects. Key component of the proposed protocol is an interoperable registry for remote inference services, which addresses the issue of findability for algorithms. It is complemented by information on how to invoke services remotely. Together, these components lay the basis for the implementation of distributed inference services beyond organizational borders. The OMI protocol considers prior work for aspects like data representation and transmission standards wherever possible. Based on Business Process Modeling of prototypical use cases for the service registry and common inference processes, a generic information model for remote services was inferred. Based on this model, FHIR resources were identified to represent AI-based services. The OMI protocol is first introduced using AI-services in radiology but is designed to be generalizable to other application domains as well. It provides an accessible, open specification as blueprint for the introduction and implementation of remote inference services.Anwendungen der Künstliche Intelligenz (KI) im Forschungs- und klinischen Bereich werden die Medizin- und Biowissenschaften nachhaltig verändern. Aspekte wie Auffindbarkeit, Zugänglichkeit, Interoperabilität und Wiederverwendbarkeit werden bei KI-basierten Inferenzdiensten derzeit jedoch oft vernachlässigt. Das Open Medical Inference (OMI) Protokoll zielt darauf ab KI-Algorithmen als Service über institutionelle Grenzen hinweg verfügbar zu machen, indem es die o.g. Aspekte adressiert. Schlüsselkomponente des Protokolls ist ein interoperables Register für Inferenzdienste, welches die Auffindbarkeit von Algorithmen erleichtert. Enthalten sind Informationen, wie Dienste aus der Ferne aufgerufen werden können. Zusammen bilden diese Komponenten die Grundlage für den Aufbau und die Umsetzung von verteilten Inferenzdiensten. Das OMI-Protokoll berücksichtigt aktive Initiativen und Standards für Aspekte wie Datentransport und Datendarstellung. Basierend auf Geschäftsprozessmodellen für Anwendungsfälle innerhalb der Service Registry und Inferenzprozessen wurde ein generisches Informationsmodell abgeleitet. Auf der Grundlage des Informationsmodells wurden FHIR-Ressourcen identifiziert, um KI-Dienste zu repräsentieren. Diese Ressourcen werden profiliert, um erwartete Ein- und Ausgabedatentypen und -formate zu definieren. Das OMI-Protokoll wird zunächst anhand von Anwendungsfällen in der Radiologie beispielhaft abgebildet, ist aber generisch ausgelegt, sodass auch andere Anwendungsdomänen unterstützt werden. Es bietet eine zugängliche, offene Spezifikation als Grundgerüst für die Einführung und Umsetzung von Fern-Inferenz

Fully automated preoperative liver volumetry incorporating the anatomical location of the central hepatic vein

The precise preoperative calculation of functional liver volumes is essential prior major liver resections, as well as for the evaluation of a suitable donor for living donor liver transplantation. The aim of this study was to develop a fully automated, reproducible, and quantitative 3D volumetry of the liver from standard CT examinations of the abdomen as part of routine clinical imaging. Therefore, an in-house dataset of 100 venous phase CT examinations for training and 30 venous phase ex-house CT examinations with a slice thickness of 5 mm for testing and validating were fully annotated with right and left liver lobe. Multi-Resolution U-Net 3D neural networks were employed for segmenting these liver regions. The Sorensen-Dice coefficient was greater than 0.9726 +/- 0.0058, 0.9639 +/- 0.0088, and 0.9223 +/- 0.0187 and a mean volume difference of 32.12 +/- 19.40 ml, 22.68 +/- 21.67 ml, and 9.44 +/- 27.08 ml compared to the standard of reference (SoR) liver, right lobe, and left lobe annotation was achieved. Our results show that fully automated 3D volumetry of the liver on routine CT imaging can provide reproducible, quantitative, fast and accurate results without needing any examiner in the preoperative work-up for hepatobiliary surgery and especially for living donor liver transplantation.Projekt DEA

Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions.

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Contrast agent dose reduction in computed tomography with deep learning using a conditional generative adversarial network

Objectives!#!To reduce the dose of intravenous iodine-based contrast media (ICM) in CT through virtual contrast-enhanced images using generative adversarial networks.!##!Methods!#!Dual-energy CTs in the arterial phase of 85 patients were randomly split into an 80/20 train/test collective. Four different generative adversarial networks (GANs) based on image pairs, which comprised one image with virtually reduced ICM and the original full ICM CT slice, were trained, testing two input formats (2D and 2.5D) and two reduced ICM dose levels (-50% and -80%). The amount of intravenous ICM was reduced by creating virtual non-contrast series using dual-energy and adding the corresponding percentage of the iodine map. The evaluation was based on different scores (L1 loss, SSIM, PSNR, FID), which evaluate the image quality and similarity. Additionally, a visual Turing test (VTT) with three radiologists was used to assess the similarity and pathological consistency.!##!Results!#!The -80% models reach an SSIM of > 98%, PSNR of > 48, L1 of between 7.5 and 8, and an FID of between 1.6 and 1.7. In comparison, the -50% models reach a SSIM of > 99%, PSNR of > 51, L1 of between 6.0 and 6.1, and an FID between 0.8 and 0.95. For the crucial question of pathological consistency, only the 50% ICM reduction networks achieved 100% consistency, which is required for clinical use.!##!Conclusions!#!The required amount of ICM for CT can be reduced by 50% while maintaining image quality and diagnostic accuracy using GANs. Further phantom studies and animal experiments are required to confirm these initial results.!##!Key points!#!• The amount of contrast media required for CT can be reduced by 50% using generative adversarial networks. • Not only the image quality but especially the pathological consistency must be evaluated to assess safety. • A too pronounced contrast media reduction could influence the pathological consistency in our collective at 80%

Individualized scan protocols for CT angiography: an animal study for contrast media or radiation dose optimization

Abstract Background We investigated about optimization of contrast media (CM) dose or radiation dose in thoracoabdominal computed tomography angiography (CTA) by automated tube voltage selection (ATVS) system configuration and CM protocol adaption. Methods In six minipigs, CTA-optimized protocols were evaluated regarding objective (contrast-to-noise ratio, CNR) and subjective (6 criteria assessed by Likert scale) image quality. Scan parameters were automatically adapted by the ATVS system operating at 90-kV semi-mode and configured for standard, CM saving, or radiation dose saving (image task, quality settings). Injection protocols (dose, flow rate) were adapted manually. This approach was tested for normal and simulated obese conditions. Results Radiation exposure (volume-weighted CT dose index) for normal (obese) conditions was 2.4 ± 0.7 (5.0 ± 0.7) mGy (standard), 4.3 ± 1.1 (9.0 ± 1.3) mGy (CM reduced), and 1.7 ± 0.5 (3.5 ± 0.5) mGy (radiation reduced). The respective CM doses for normal (obese) settings were 210 (240) mgI/kg, 155 (177) mgI/kg, and 252 (288) mgI/kg. No significant differences in CNR (normal; obese) were observed between standard (17.8 ± 3.0; 19.2 ± 4.0), CM-reduced (18.2 ± 3.3; 20.5 ± 4.9), and radiation-saving CTAs (16.0 ± 3.4; 18.4 ± 4.1). Subjective analysis showed similar values for optimized and standard CTAs. Only the parameter diagnostic acceptability was significantly lower for radiation-saving CTA compared to the standard CTA. Conclusions The CM dose (-26%) or radiation dose (-30%) for thoracoabdominal CTA can be reduced while maintaining objective and subjective image quality, demonstrating the feasibility of the personalization of CTA scan protocols. Key points • Computed tomography angiography protocols could be adapted to individual patient requirements using an automated tube voltage selection system combined with adjusted contrast media injection. • Using an adapted automated tube voltage selection system, a contrast media dose reduction (-26%) or radiation dose reduction (-30%) could be possibl

AI-based digital histopathology for perihilar cholangiocarcinoma: A step, not a jump

Introduction: Perihilar cholangiocarcinoma (PHCC) is a rare malignancy with limited survival prediction accuracy. Artificial intelligence (AI) and digital pathology advancements have shown promise in predicting outcomes in cancer. We aimed to improve prognosis prediction for PHCC by combining AI-based histopathological slide analysis with clinical factors. Methods: We retrospectively analyzed 317 surgically treated PHCC patients (January 2009–December 2018) at the University Hospital of Essen. Clinical data, surgical details, pathology, and outcomes were collected. Convolutional neural networks (CNN) analyzed whole-slide images. Survival models incorporated clinical and histological features. Results: Among 142 eligible patients, independent survival predictors were tumor grade (G), tumor size (T), and intraoperative transfusion requirement. The CNN-based model combining clinical and histopathological features demonstrates proof of concept in prognosis prediction, limited by histopathological complexity and feature extraction challenges. However, the CNN-based model generated heatmaps assisting pathologists in identifying areas of interest. Conclusion: AI-based digital pathology showed potential in PHCC prognosis prediction, though refinement is necessary for clinical relevance. Future research should focus on enhancing AI models and exploring novel approaches to improve PHCC patient prognosis prediction

Fully Automated MR Based Virtual Biopsy of Cerebral Gliomas

Objective: The aim of this study was to investigate the diagnostic accuracy of a radiomics analysis based on a fully automated segmentation and a simplified and robust MR imaging protocol to provide a comprehensive analysis of the genetic profile and grading of cerebral gliomas for everyday clinical use. Methods: MRI examinations of 217 therapy-naïve patients with cerebral gliomas, each comprising a non-contrast T1-weighted, FLAIR and contrast-enhanced T1-weighted sequence, were included in the study. In addition, clinical and laboratory parameters were incorporated into the analysis. The BraTS 2019 pretrained DeepMedic network was used for automated segmentation. The segmentations generated by DeepMedic were evaluated with 200 manual segmentations with a DICE score of 0.8082 ± 0.1321. Subsequently, the radiomics signatures were utilized to predict the genetic profile of ATRX, IDH1/2, MGMT and 1p19q co-deletion, as well as differentiating low-grade glioma from high-grade glioma. Results: The network provided an AUC (validation/test) for the differentiation between low-grade gliomas vs. high-grade gliomas of 0.981 ± 0.015/0.885 ± 0.02. The best results were achieved for the prediction of the ATRX expression loss with AUCs of 0.979 ± 0.028/0.923 ± 0.045, followed by 0.929 ± 0.042/0.861 ± 0.023 for the prediction of IDH1/2. The prediction of 1p19q and MGMT achieved moderate results, with AUCs of 0.999 ± 0.005/0.711 ± 0.128 for 1p19q and 0.854 ± 0.046/0.742 ± 0.050 for MGMT. Conclusion: This fully automated approach utilizing simplified MR protocols to predict the genetic profile and grading of cerebral gliomas provides an easy and efficient method for non-invasive tumor decoding

Deep learning‐based assessment of body composition and liver tumour burden for survival modelling in advanced colorectal cancer

Abstract Background Personalized therapy planning remains a significant challenge in advanced colorectal cancer care, despite extensive research on prognostic and predictive markers. A strong correlation of sarcopenia or overall body composition and survival has been described. Here, we explore whether automated assessment of body composition and liver metastases from standard of care CT images can add to clinical parameters in personalized survival risk prognostication. Methods We retrospectively analysed clinical imaging data from 85 patients (50.6% female, mean age 58.9 SD 12.2 years) with colorectal cancer and synchronous liver metastases. Pretrained deep learning models were used to assess body composition and liver metastasis geometry from abdominal CT images before the initiation of systemic treatment. Abdominal muscle‐to‐bone ratio (MBR) was calculated by dividing abdominal muscle volume by abdominal bone volume. MBR was compared with body mass index (BMI), abdominal muscle volume, and abdominal muscle volume divided by height squared. Differences in overall survival based on body composition and liver metastasis parameters were compared using Kaplan–Meier survival curves. Results were correlated with clinical and biomarker data to develop a machine learning model for survival risk prognostication. Results The MBR, unlike abdominal muscle volume or BMI, was significantly associated with overall survival (HR 0.39, 95% CI: 0.19–0.80, P = 0.009). The MBR (P = 0.022), liver metastasis surface area (P = 0.01) and primary tumour sidedness (P = 0.007) were independently associated with overall survival in multivariate analysis. Body composition parameters did not correlate with KRAS mutational status or primary tumour sidedness. A prediction model based on MBR, liver metastasis surface area and primary tumour sidedness achieved a concordance index of 0.69. Conclusions Automated segmentation enables to extract prognostic parameters from routine imaging data for personalized survival modelling in advanced colorectal cancer patients