Jan-Philipp Redlich

Jan-Philipp Redlich, Friedrich Feuerhake, Stefan Nikolin et al.

Glioblastoma, IDH-wildtype (GBM-IDHwt) is the most common malignant brain tumor. Histomorphology is a crucial component of the integrated diagnosis of GBM-IDHwt. Artificial intelligence (AI) methods have shown promise to extract additional prognostic information from histological whole-slide images (WSI) of hematoxylin and eosin-stained glioblastoma tissue. Here, we present an explainable AI-based method to support systematic interpretation of histomorphological features associated with survival. It combines an explainable multiple instance learning (MIL) architecture with a sparse autoencoder (SAE) to relate human-interpretable visual patterns of tissue to survival. The MIL architecture directly identifies prognosis-relevant image tiles and the SAE maps these tiles post-hoc to visual patterns. The MIL method was trained and evaluated using a new real-world dataset that comprised 720 GBM-IDHwt cases from three hospitals and four cancer registries in Germany. The SAE was trained using 1878 WSIs of glioblastoma from five independent public data collections. Despite the many factors influencing survival time, our method showed some ability to discriminate between patients living less than 180 days or more than 360 days solely based on histomorphology (AUC: 0.67; 95% CI: 0.63-0.72). Cox proportional hazards regression confirmed a significant difference in survival time between the predicted groups after adjustment for established prognostic factors (hazard ratio: 1.47; 95% CI: 1.26-1.72). Our method identified multiple interpretable visual patterns associated with survival. Three neuropathologists separately found that 21 of the 24 most strongly associated patterns could be clearly attributed to seven histomorphological categories. Necrosis and hemorrhage appeared to be associated with shorter survival while highly cellular tumor areas were associated with longer survival.

André Homeyer, Júlia Blanka Sziládi, Jan-Philipp Redlich et al.

Breath acetone represents a promising non-invasive biomarker for monitoring fat oxidation during exercise. However, its utility is limited by confounding factors, as well as by the fact that significant changes in concentration occur only hours post-exercise, which makes real-time assessment difficult. We performed an untargeted screening for volatile organic compounds (VOCs) that could serve as markers of fat oxidation beyond acetone, and investigated whether breath measurements taken during exercise could predict post-exercise changes in fat oxidation. Nineteen participants completed two 25-min cycling sessions separated by a brief 5-min rest period. VOC emissions were analysed using proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) during exercise and after a 90-min recovery period. Blood $β$-hydroxybutyrate (BOHB) concentrations served as the reference marker for fat oxidation. Among 773 relevant analytical features detected in the PTR-TOF-MS measurements, only four signals exhibited strong correlations with BOHB ($ρ$ $\geq$ 0.82, p = 0.0002)-all attributable to acetone or its isotopologues or fragments. End-of-exercise measurements of these signals enabled accurate prediction of participants with substantial post-exercise BOHB changes (F1 score $\geq$ 0.83, accuracy = 0.89). Our study did not reveal any novel breath-based biomarkers of fat oxidation, but it confirmed acetone as the key marker. Moreover, our findings suggest that breath acetone measurements during exercise may already enable basic predictions of post-exercise fat oxidation.

Jan-Philipp Redlich, Friedrich Feuerhake, Joachim Weis et al.

In recent years, the diagnosis of gliomas has become increasingly complex. Analysis of glioma histopathology images using artificial intelligence (AI) offers new opportunities to support diagnosis and outcome prediction. To give an overview of the current state of research, this review examines 83 publicly available research studies that have proposed AI-based methods for whole-slide histopathology images of human gliomas, covering the diagnostic tasks of subtyping (23/83), grading (27/83), molecular marker prediction (20/83), and survival prediction (29/83). All studies were reviewed with regard to methodological aspects as well as clinical applicability. It was found that the focus of current research is the assessment of hematoxylin and eosin-stained tissue sections of adult-type diffuse gliomas. The majority of studies (52/83) are based on the publicly available glioblastoma and low-grade glioma datasets from The Cancer Genome Atlas (TCGA) and only a few studies employed other datasets in isolation (16/83) or in addition to the TCGA datasets (15/83). Current approaches mostly rely on convolutional neural networks (63/83) for analyzing tissue at 20x magnification (35/83). A new field of research is the integration of clinical data, omics data, or magnetic resonance imaging (29/83). So far, AI-based methods have achieved promising results, but are not yet used in real clinical settings. Future work should focus on the independent validation of methods on larger, multi-site datasets with high-quality and up-to-date clinical and molecular pathology annotations to demonstrate routine applicability.