The Potential of Photoacoustic Imaging in Radiation Oncology

Abstract

Radiotherapy is recognized globally as a mainstay of treatment in most solid tumors and is essential in both curative and palliative settings. Ionizing radiation is frequently combined with surgery, either preoperatively or postoperatively, and with systemic chemotherapy. Recent advances in imaging have enabled precise targeting of solid lesions yet substantial intratumoral heterogeneity means that treatment planning and monitoring remains a clinical challenge as therapy response can take weeks to manifest on conventional imaging and early indications of progression can be misleading. Photoacoustic imaging (PAI) is an emerging modality for molecular imaging of cancer, enabling non-invasive assessment of endogenous tissue chromophores with optical contrast at unprecedented spatio-temporal resolution. Preclinical studies in mouse models have shown that PAI could be used to assess response to radiotherapy and chemoradiotherapy based on changes in the tumor vascular architecture and blood oxygen saturation, which are closely linked to tumor hypoxia. Given the strong relationship between hypoxia and radio-resistance, PAI assessment of the tumor microenvironment has the potential to be applied longitudinally during radiotherapy to detect resistance at much earlier time-points than currently achieved by size measurements and tailor treatments based on tumor oxygen availability and vascular heterogeneity. Here, we review the current state-of-the-art in PAI in the context of radiotherapy research. Based on these studies, we identify promising applications of PAI in radiation oncology and discuss the future potential and outstanding challenges in the development of translational PAI biomarkers of early response to radiotherapy.

Keywords: image guidance; photoacoustic (optoacoustic) imaging; quantitative imaging biomarker; radiation oncology; radiotherapy; translational research.

Figure 1

Macroscopic and mesoscopic photoacoustic imaging can monitor treatment-induced vascular changes and disease stage. (A) Multispectral optoacoustic tomography (MSOT)-derived quantitative blood oxygen saturation map (sO₂) overlaid on co-registered ultrasound axial slice of a head & neck patient-derived xenograft tumor before and after a single dose of 15 Gy (top panel), and before and after combined 7.5 Gy of radiotherapy and administration of chemotherapeutic cetuximab. Increased sO₂ 24h after treatment was associated with decreased tumor volume two weeks later. (B) Hemodynamic stimulation challenge of salivary glands before and after a single dose of 15 Gy with decreased change in sO₂ response post-radiotherapy suggesting radiation-induced damage. (C) Clinical XZ maximal intensity projection of mesoscopic PAI of graded atopic dermatitis in human skin. Vascular and structural scoring could accurately grade dermatitis and such score could potentially be translated for grading radiation-induced toxicity in RT. Panels (A, B) adapted from Rich et al. (60), and panel (C) adapted from Yew et al. (61). EP, Epidermis; DR, Dermis; LF, low frequency; HF, high frequency; RT, radiotherapy; %sO₂, percent blood oxygen saturation; CRT, chemoradiotherapy.

Figure 2

The potential role of photoacoustic imaging in the clinical radiotherapy framework. (A) Portable bedside PAI can be employed in-room before and/or after RT fractions due to its accessibility, portability and fast acquisitions. (B) PAI could map vascular features of tumors across scales, including blood oxygen saturation. (C) Dual ultrasound and PAI systems provide combined anatomical and molecular imaging features. (D) PAI could be introduced in the clinical RT framework pre-treatment, for diagnostics and pre-operative patient stratification, or for predictive imaging in parallel with CT simulation for radiation dose modulation. During radiotherapy, PAI could be used for monitoring response in the treatment room. After radiotherapy, PAI could further monitor tumor response based on blood oxygen saturation evaluations, which have been associated with local tumor control. PAI could also provide information for response assessment and insights into radiation-induced toxicity at early timepoints. Panel (C) provided in kind by Dr. Oshaani Abeyakoon. Created with BioRender.