The characteristics of tumour development and metastasis relate not only to genomic heterogeneity but also to spatial heterogeneity, associated with variations in the intratumoural arrangement of cell populations, vascular morphology and oxygen and nutrient supply. While optical (photonic) microscopy is commonly employed to visualize the tumour microenvironment, it assesses only a few hundred cubic microns of tissue. Therefore, it is not suitable for investigating biological processes at the level of the entire tumour, which can be at least four orders of magnitude larger. In this study, we aimed to extend optical visualization and resolve spatial heterogeneity throughout the entire tumour volume. We developed an optoacoustic (photoacoustic) mesoscope adapted to solid tumour imaging and, in a pilot study, offer the first insights into cancer optical contrast heterogeneity in vivo at an unprecedented resolution of <50 μm throughout the entire tumour mass. Using spectral methods, we resolve unknown patterns of oxygenation, vasculature and perfusion in three types of breast cancer and showcase different levels of structural and functional organization. To our knowledge, these results are the most detailed insights of optical signatures reported throughout entire tumours in vivo, and they position optoacoustic mesoscopy as a unique investigational tool linking microscopic and macroscopic observations.
Miniaturized optical detectors of ultrasound represent a promising alternative to piezoelectric technology and may enable new minimally invasive clinical applications, particularly in the field of optoacoustic imaging. However, the use of such detectors has so far been limited to controlled lab environments, and has not been demonstrated in the presence of mechanical disturbances, common in clinical imaging scenarios. Additionally, detection sensitivity has been inherently limited by laser noise, which hindered the use of sensing elements such as optical fibers, which exhibit a weak response to ultrasound. In this work, coherence‐restored pulse interferometry (CRPI) is introduced – a new paradigm for interferometric sensing in which shot‐noise limited sensitivity may be achieved alongside robust operation. CRPI is implemented with a fiber‐based resonator, demonstrating over an order of magnitude higher sensitivity than that of conventional 15 MHz intravascular ultrasound probes. The performance of the optical detector is showcased in a miniaturized all‐optical optoacoustic imaging catheter.
Broadband optoacoustic waves generated by biological tissues excited with nanosecond laser pulses carry information corresponding to a wide range of geometrical scales. Typically, the frequency content present in the signals generated during optoacoustic imaging is much larger compared to the frequency band captured by common ultrasonic detectors, the latter typically acting as bandpass filters. To image optical absorption within structures ranging from entire organs to microvasculature in three dimensions, we implemented optoacoustic tomography with two ultrasound linear arrays featuring a center frequency of 6 and 24 MHz, respectively. In the present work, we show that complementary information on anatomical features could be retrieved and provide a better understanding on the localization of structures in the general anatomy by analyzing multi-bandwidth datasets acquired on a freshly excised kidney.
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