In a study published in Nature Biomedical Engineering, raster-scanning optoacoustic mesoscopy (RSOM) provided an unprecedented means of studying tumor vasculature during therapy. Commercialized by the Munich-based company iThera Medical, this technology enabled non-invasive investigation of in vivo tumor response in high resolution.

In the ongoing search for new and better means of combating cancer, localized treatments offer attractive opportunities to slow tumor growth or even eradicate existing masses without harming normal tissue. Tumors hijack the body’s normal blood supply, thereby siphoning the oxygen and nutrients required to sustain their growth. By specifically targeting this pathway, it is possible to cut off blood flow to the diseased tissue and effectively starve the tumor. A key approach in this strategy involves anti-vascular therapies – particularly vascular-targeted photodynamic therapy (VTP). In VTP, a light-sensitive agent is injected and activated with low-power laser light within the tumor region, triggering localized destruction of blood vessels that feed the tumor and ultimately leading to tumor death.

However, a complete understanding of the underlying mechanism of VTP treatment requires sensitive imaging modalities. Current standard imaging techniques like MRI, CT or ultrasound are limited by their insufficient spatial resolution, while high-resolution approaches require tissue specimens and are not suitable for in vivo measurements. In this study, researchers at the Memorial Sloan Kettering Cancer Center, Weizmann Institute of Science, Technical University Munich and Helmholtz Center Munich used RSOM to noninvasively acquire high-resolution images of the entire tumor microvasculature and surrounding vascular network solely via the intrinsic optical properties of hemoglobin.

“With this study, we revealed several processes behind this therapy which until now were unidentified”, says lead author Dr. Katja Haedicke. “RSOM offers a great platform to study many different tumor therapies and discover new mechanisms of action in detail.”

As demonstrated by Haedicke et al., RSOM provides an exceptionally detailed look into the tortuous network of blood vessels encasing implanted tumors in mice. Following VTP, RSOM revealed exactly how tumor vasculature responds to treatment. With the ability to distinguish between oxygenated and deoxygenated hemoglobin, RSOM captured time-resolved oxygenation changes that elucidate specific mechanisms behind VTP. Furthermore, RSOM can discriminate between responsive and non-responsive tumors earlier than other imaging modalities – potentially leading to improved treatment parameters as well as earlier treatment outcome predictions.

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