Mapping tumor heterogeneity and hypoxia within a living intact organism is essential for understanding the processes involved in cancer progression and assessing long-term responses to therapies. Efficient investigations into tumor hypoxia mechanisms have been hindered by the lack of intravital imaging tools capable of multiparametric probing of entire solid tumors with high spatial and temporal resolution. Here, we exploit volumetric multispectral optoacoustic tomography (vMSOT) for accurate, label-free delineation of tumor heterogeneity and dynamic oxygenation behavior. Mice bearing orthotopic MDA-MB-231 breast cancer xenografts were imaged noninvasively during rest and oxygen stress challenge, attaining time-lapse three-dimensional oxygenation maps across entire tumors with 100 mm spatial resolution. Volumetric quantification of the hypoxic fraction rendered values of 3.9% to 21.2%, whereas the oxygen saturation (sO 2) rate declined at 1.7% to 2.3% per mm in all tumors when approaching their core. Three distinct functional areas (the rim, hypoxic, and normoxic cores) were clearly discernible based on spatial sO 2 profiles and responses to oxygen challenge. Notably, although sO 2 readings were responsive to the challenge, deoxyhemoglobin (HbR) trends exhibited little to no variations in all mice. Dynamic analysis further revealed the presence of cyclic hypoxia patterns with a 21% average discrepancy between cyclic fractions assessed via sO 2 (42.2% AE 17.3%) and HbR fluctuations (63% AE 14.1%) within the hypoxic core. These findings corroborate the strong potential of vMSOT for advancing preclinical imaging of cancer and informing clinical decisions on therapeutic interventions. Significance: vMSOT provides quantitative measures of volumetric hypoxic fraction and cyclic hypoxia in a label-free and noninvasive manner, providing new readouts to aid tumor staging and treatment decision making.

Machine Learning (ML) has become an essential asset for the life sciences and medicine. We selected 300 articles describing ML applications from 17 journals sampling 26 different fields between 2011 and 2018. Independent evaluation by two readers highlighted three results.First, only half of the articles shared software, 64% shared data, and 81% applied any kind of evaluation. Although these aspects are crucial to ensure validity and reliability of ML applications, they were met more by publications in lower-ranked journals. Second, the authors' scientific background highly influenced how technical aspects were addressed: reproducibility and computational evaluation methods were more prominent with computational co-authors; experimental proofs more with experimentalists. Third, 73% of the ML applications resulted from interdisciplinary collaborations comprising authors from at least two of the three disciplines: computational sciences, experimental biology, medicine._deleted_ The data suggested collaborations between computational and experimental scientists to generate more computationally sound and impactful work integrating knowledge.Furthermore, such collaborations provide opportunities to both sides: computational scientists are given access to novel and challenging real-world biological data increasing the scientific impact of their research, and experimentalists benefit from more in-depth computational analyses improving the technical correctness of work.

Tracking of biodynamics across entire living organisms is essential for understanding complex biology and disease progression. The presently available small‐animal functional and molecular imaging modalities remain constrained by factors including long image acquisition times, low spatial resolution, limited penetration or poor contrast. Here flash scanning volumetric optoacoustic tomography (fSVOT), a new approach for high‐speed imaging of fast kinetics and biodistribution of optical contrast agents in whole mice that simultaneously provides reference images of vascular and organ anatomy with unrivaled fidelity and contrast, is presented. The imaging protocol employs continuous overfly scanning of a spherical matrix array transducer, accomplishing a 200 µm resolution 3D scan of the whole mouse body within 45 s without relying on signal averaging. This corresponds to an imaging speed gain of more than an order of magnitude compared with existing state‐of‐the‐art implementations of comparable resolution performance. Volumetric tracking and quantification of gold nanoagent and near infrared (NIR)‐II dye kinetics and their differential uptake in various organs are demonstrated. fSVOT thus offers unprecedented capabilities for multiscale imaging of pharmacokinetics and biodistribution with high contrast, resolution, and speed.