Optoacoustic Imaging Detects Hormone-Related Physiological Changes of Breast Parenchyma.

PURPOSE: Optoacoustic imaging with ultrasound (OPUS) can assess in-vivo perfusion/oxygenation through surrogate measures of oxy, deoxy and total hemoglobin content in tissues. The primary aim of our study was to evaluate the ability of OPUS to detect physiological changes in the breast during the menstrual cycle and to determine qualitative/quantitative metrics of normal parenchymal tissue in pre-/post-menopausal women. The secondary aim was to assess the technique's repeatability. MATERIALS AND METHODS: We performed a prospective ethically approved study in volunteers using OPUS (700, 800 and 850 nm wavelengths) in the proliferative/follicular and secretory phase of the menstrual cycle. Regions of interest (ROIs) were drawn on the most superficial region of fibroglandular tissue and same-day intra-observer repeatability was assessed. We used t-tests to interrogate differences in the OPUS measurements due to hormonal changes and interclass correlation coefficients/Bland-Altman plots to evaluate the repeatability of mean ROI signal intensities. RESULTS: 22 pre-menopausal and 8 post-menopausal volunteers were recruited. 21 participants underwent repeatability examinations. OPUS intensity values were significantly higher (p < 0.0001) at all excitation wavelengths in the secretory compared to the proliferative/follicular phase. Post-menopausal volunteers showed similar optoacoustic values to the proliferative/follicular phase of pre-menopausal volunteers. The repeatability of the technique was comparable to other handheld ultrasound modalities. CONCLUSION: OPUS detects changes in perfusion/vascularity related to the menstrual cycle and menopausal status of breast parenchyma.

Oxygen Enhanced Optoacoustic Tomography (OE-OT) Reveals Vascular Dynamics in Murine Models of Prostate Cancer.

Poor oxygenation of solid tumours has been linked with resistance to chemo- and radio-therapy and poor patient outcomes, hence non-invasive imaging of oxygen supply and demand in tumours could improve disease staging and therapeutic monitoring. Optoacoustic tomography (OT) is an emerging clinical imaging modality that provides static images of endogenous haemoglobin concentration and oxygenation. Here, we demonstrate oxygen enhanced (OE)-OT, exploiting an oxygen gas challenge to visualise the spatiotemporal heterogeneity of tumour vascular function. We show that tracking oxygenation dynamics using OE-OT reveals significant differences between two prostate cancer models in nude mice with markedly different vascular function (PC3 & LNCaP), which appear identical in static OT. LNCaP tumours showed a spatially heterogeneous response within and between tumours, with a substantial but slow response to the gas challenge, aligned with ex vivo analysis, which revealed a generally perfused and viable tumour with marked areas of haemorrhage. PC3 tumours had a lower fraction of responding pixels compared to LNCaP with a high disparity between rim and core response. While the PC3 core showed little or no dynamic response, the rim showed a rapid change, consistent with our ex vivo findings of hypoxic and necrotic core tissue surrounded by a rim of mature and perfused vasculature. OE-OT metrics are shown to be highly repeatable and correlate directly on a per-tumour basis to tumour vessel function assessed ex vivo. OE-OT provides a non-invasive approach to reveal the complex dynamics of tumour vessel perfusion, permeability and vasoactivity in real time. Our findings indicate that OE-OT holds potential for application in prostate cancer patients, to improve delineation of aggressive and indolent disease as well as in patient stratification for chemo- and radio-therapy.