Radiation therapy (RT) has been shown to improve the outcomes of patients with cancer and provide palliation of related symptoms. Successful RT is contingent on delivering intended sufficient radiation dose to tumor while sparing surrounding normal tissues. Achieving such a desired therapeutic ratio, that is, maximizing tumor control while minimizing toxicity, requires that the planned radiation dose is delivered accurately. To improve the efficacy of RT, advanced image-guided delivery technologies have been proposed and developed over the past decades. Technologies such as intensity modulated RT and volumetric modulated arc RT can offset some of the limitations associated with three-dimensional (3D) conformal RT; however, targeting of moving lesions remains challenging. Several studies have highlighted discrepancies between planned and delivered RT and their impact on tumor control. These differences are exacerbated by setup errors, organ motion, as well as anatomical deformations, which may markedly alter the intended doses delivered to the target or adjacent normal tissues over the course of treatment. Therefore, there is a long-standing clinical need for more effective imaging technologies capable of volumetric, real-time, in vivo dose delivery monitoring during RT for feedback guidance.
Ionizing radiation acoustic imaging (iRAI) is a noninvasive imaging technology that reconstructs the radiation dose using acoustic waves stemming from the absorption of pulsed ionizing radiation beams in soft tissue. iRAI has the potential to map the dose deposition and monitor the dose accumulation at in-depth anatomical structures in real time during RT. In contrast to other dose mapping methods, iRAI is directly proportional to the radiation dose absorbed by the targeted tissue. With pre-calibration of the Grüneisen parameter, medium density, pulse time profile and sensor sensitivity, the linear relationship between the absorbed dose and deposited dose could enable iRAI to both localize and quantify the absolute dose deposition during RT.
Our group was among the pioneers to demonstrate the feasibility of iRAI, as a novel imaging modality, for mapping the radiation dose during RT. Our team was the first to achieve real-time iRAI-ultrasound dual-modality imaging in an animal model in vivo, preparing the technology for clinical applications (Figure 1). Also for the first time, our team validated that iRAI has the unique capability to map and quantify dose in soft tissues treated by FLASH mode RT with single-pulse precision, which was featured by Physics World (Figure 2). Most recently, our team, for the first time, developed a prototype 3D volumetric iRAI system to achieve mapping of radiation dose delivery with a clinical treatment plan in human patients, which was published in a recent issue of Nature Biotechnology and featured by numerous news media (Figure 3 and 4). All these studies demonstrate that iRAI offers a unique tool to the radiation oncology clinic for quantifying the accuracy of dose deposition during RT, and holds a great potential to improve the treatment accuracy and enable online adaptive RT.
Figure 1. IRAI and US real-time dual-modality imaging of an in vivo rabbit liver, demonstrating the capability for tracking tissue movement with respect to the X-ray beam. (a) The setup for validating the capability of the system in real-time tracking the movement of the target tissue with respect to the position of the X-ray beam illuminating on a live rabbit. (b) The iRAI and US combined images at different time points (1, 11, 21, 31, and 41 seconds) during the real-time imaging over a period of 50 seconds. In each combined image, the xRAI image in pseudocolor presenting the location of the X-ray dose deposition (marked by the yellow dashed box) is superimposed on the US image in grayscale showing the tissue structure.
Figure 2. Comparison of ionizing radiation acoustic imaging (IRAI) dose measurement and film measurement. (a) The iRAI dose measurement compared with film measurement along with different source-axis distance; (b) The linearity of iRAI dosimetric measurement.
Figure 3. iRAI system schematic and the experimental setup. (a) 3D schematic of the iRAI system for mapping the dose deposition in a patient during RT delivery. (b) CAD view of a 2D matrix array with an integrated preamplifier board. The xyz coordinate system for the 3D iRAI imaging space is marked. (c) The experimental setup for the phantom studies. (d) The side view of the rabbit experiment setup in a clinical environment. (e) Details regarding the transducer position and coupling of the rabbit experiment.
Figure 4. In vivo iRAI imaging versus the treatment plan on a patient. (a) A photograph of the iRAI imaging on a patient taken during RT. (b) The dose distribution of only the two static sagittal beams of the treatment plan with a liver mask fused onto the CT scan anatomy structure. Scale bar, 5 cm. (c) The iRAI measurement of dose with a liver mask fused onto the CT anatomy structure with the same position as b. The yellow dashed box indicates the field of view of the 2D matrix array. (d) Dose distribution (>50%) of the treatment plan with a liver mask fused on the CT anatomy structure. (e) The 50 and 90% isodose lines in the iRAI measurement and the treatment plan. Scale bar, 2 cm. The red line in b–d indicates the boundary of the liver.