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 μm spatial resolution. Volumetric quantification of the hypoxic fraction rendered values of 3.9% to 21.2%, whereas the oxygen saturation (sO2) 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 sO2 profiles and responses to oxygen challenge. Notably, although sO2 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 sO2 (42.2% ± 17.3%) and HbR fluctuations (63% ± 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.

Respiratory motion in living organisms is known to result in image blurring and loss of resolution, chiefly due to the lengthy acquisition times of the corresponding image acquisition methods. Optoacoustic tomography can effectively eliminate in vivo motion artifacts due to its inherent capacity for collecting image data from the entire imaged region following a single nanoseconds-duration laser pulse. However, multi-frame image analysis is often essential in applications relying on spectroscopic data acquisition or for scanning-based systems. Thereby, efficient methods to correct for image distortions due to motion are imperative. Herein, we demonstrate that efficient motion rejection in optoacoustic tomography can readily be accomplished by frame clustering during image acquisition, thus averting excessive data acquisition and post-processing. The algorithm’s efficiency for two- and three-dimensional imaging was validated with experimental whole-body mouse data acquired by spiral volumetric optoacoustic tomography (SVOT) and full-ring cross-sectional imaging scanners.

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.

Goal. The purpose of this computer modeling study is to validate the feasibility of a home monitoring system for wrist bone mineral density (BMD) measurement which is based on the parametric electrical impedance tomography (pEIT) method. Methods. A solution to the forward problem of the developing potential around the wrist due to current injection was developed using a Matlab numerical simulation of an adult computer human phantom. The backward problem is solved by building a lookup table of different bone densities which represent different disease stages. Results. The real part of the complex potential exhibits an average change of 30.7%–12% (between the most sensitive and the least sensitive electrodes) per BMD decrease of 23%. A 2 times higher sensitivity to a deterioration of the cortical bone than of the trabecular bone alone was found. A signal to noise ratio (SNR) level above 30 dB is required for a maximal performance of the system. The robustness to a deposition of the electrodes array in different directions is limited. Conclusion. It was found that the cortical BMD changes govern the model. The required SNR level is within the specs of similar systems. In a real device, the issue of sensors repositioning should be addressed. The proposed pEIT system makes self-monitoring of wrist BMD possible. It brings an added-value by enabling the monitoring of BMD between treatments and between traditional DEXA screenings.