The need to deliver the intended, optimal radiation dose to a tumor while sparing the healthy tissue surrounding the cancer is critical to cancer treatments using radiation therapy. Now, with a real-time, 3D imaging system developed at the University of Michigan (UM), doctors and other medical professionals may be able to direct radiation with more precision, limiting the exposure of adjacent tissue. The UM researchers developed a volumetric, ionizing radiation acoustic imaging (iRAI) system that maps the radiation dose and monitors the radiation’s interactions with tissues within the body as therapy is being administered. The technique provides medical professionals with adaptive feedback in real time to help guide radiation treatments. According to the researchers, the iRAI system offers a first-of-its-kind view of the interaction between radiation treatment and the targeted area. “Once you start delivering radiation, the body is pretty much a black box,” professor Xueding Wang said. “We don’t know exactly where the x-rays are hitting inside the body, and we don’t know how much radiation we’re delivering to the target. And each body is different, so making predictions for both aspects is tricky.” According to Wang, the imaging mechanism holds volumetric capabilities, or the ability to capture a 3D volume of activity from 2D imagery, because the dose distribution in the body during radiation therapy is 3D. As a result, Wang said, 3D volumetric imaging of the dose is necessary to assess actual dose distribution. The iRAI system images dose accumulation using acoustic waves that originate from the absorption of pulsed ionizing radiation beams in the soft tissue. When the radiation is absorbed by the body, it is turned into thermal energy. The heat from the radiation causes the tissue to expand rapidly, and the expansion creates a sound wave. The acoustic wave is weak and usually undetectable by typical ultrasound technology. To ensure the success of the method and its implementation, Wang said, the researchers could turn to experiences with another, similar technique: photoacoustic imaging. “Since both photoacoustic imaging (PAI) and iRAI are based on the thermo-acoustic effect, the two are common in many ways,” Wang told Photonics Media via email. The two approaches can be described by the same wave equation, and they can be generated via the same computed tomography method, Wang said. The experimental setup for UM’s iRAI system (metal box on left) using a lard 'phantom' (cylinder at center) that approximates the human body. The ability to track radiation treatment in real time could lead to safer, more effective cancer therapy. Courtesy of UM Optical Imaging Laboratory. To enable the iRAI system to detect the wave created by an x-ray, the researchers designed an array of ultrasonic transducers, which is positioned on the patient’s side. The 2D matrix array has a central frequency and bandwidth to match the spectrum of the acoustic wave induced by a 4-µs radiation pulse. This approach, together with the specially designed transducer elements, enhances the sensitivity of the iRAI system, giving it the ability to detect the weak, radiation-induced acoustic signal. To further improve the detection sensitivity of the iRAI system, the researchers integrated a custom-designed, low-noise, multichannel preamplifier board with the matrix array, to achieve signal amplification before the signals are acquired by an ultrasound system. After the signal is amplified, it is transferred into an ultrasound device for image reconstruction. With the images in hand, an oncology clinic can alter the level or trajectory of radiation during therapy to ensure safer and more effective treatments. To promote the clinical translation of the iRAI system, the researchers built a clinical-grade system and demonstrated its ability to image temporal dose accumulation in 3D. First, the team demonstrated the iRAI system in a tissue-mimicking phantom. Next, the researchers verified semiquantitative iRAI relative dose measurements in an in vivo rabbit model. Finally, the iRAI system was used to demonstrate real-time visualization of the 3D radiation dose delivered to a patient with liver metastases. The experimental work showed the potential of the iRAI system to monitor and quantify the 3D radiation dose deposition during treatment. The system could improve radiotherapy treatment efficacy by facilitating real-time adaptive treatment. “In the future, we could use the imaging information to compensate for uncertainties that arise from positioning, organ motion, and anatomical variation during radiation therapy,” researcher Wei Zhang said. “That would allow us to deliver the dose to the cancer tumor with pinpoint accuracy.” The technology can be easily added to current radiation therapy equipment without drastically changing the processes that clinicians are used to, the researchers said. “In future applications, this technology can be used to personalize and adapt each radiation treatment to assure normal tissues are kept to a safe dose and that the tumor receives the dose intended,” professor Kyle Cuneo said. “This technology would be especially beneficial in situations where the target is adjacent to radiation-sensitive organs such as the small bowel or stomach.” Further, according to Wang, additional knowledge that researchers have obtained from the use of PAI can be adapted to iRAI. “The main challenge for iRAI when compared to PAI is its even weaker signal amplitude,” Wang said. “The signal level of iRAI during the regular x-ray radiation therapy is orders of magnitude lower than photoacoustic signal.” UM has applied for patent protection and is seeking partners to help bring the technology to market. The research was published in Nature Biotechnology (www.doi.org/10.1038/s41587-022-01593-8).