The goal of this application is to develop a dosimeter that is capable to directly measure linear energy transfer (LET) to allow physicians, medical physicists, and radiobiologists to study biological effects of different types of ionizing radiatio used in external beam cancer therapy. In addition to the traditionally used photon beams generated from radioactive sources (Gamma Knife) or using Megavolt Electron LINACS, the last decades have seen dramatic advances in the development of heavy charged particle beams for cancer therapy. The use of hadrons (protons or heavy ions) in radiation cancer therapy offers several advantages over traditional X-ray, gamma, or electron beams. Heavy charged particles exhibit a unique depth dose profile with low dose at the entrance to the patient and a distinct dose peak at the end of range (Bragg peak) with minimum dose delivered beyond the Bragg peak. This allows hadrons to deliver a high physical dose (i.e. energy deposited per unit mass) to deep-seated tumors or tumors near critical structures with better sparing of normal and critical structures than can be achieved using megavoltage photon and electron beams. These physical advantages alone make hadron therapy very attractive for modern cancer radiation therapy, but additional research has shown that heavy ions are more effective in cell killing because they create denser ionization events along the particle track, which causes more irreparable damage to the DNA. This is described by the quantity of Relative Biological Effectiveness (RBE). The RBE of a test beam is defined as the ratio of the physical dose required using photons to the physical dose needed using the beam modality under study (i.e. Heavy charged particles) to produce the same biological effect, for example 10% cell survival: RBE=D x-ray/D particle 10% survival. This enhanced biological effectiveness was the main driver of the development of carbon ion therapy centers in Europe and Japan and more recently is responsible for the increased interest in the United States in upgrading from the widespread use of proton beam therapy to heavy ion therapy. Additionally, it has been widely recognized that even proton beams do not have a constant biological effectiveness along the beam path and the enhanced biological effectiveness near the end of range can no longer be ignored in cases of tumors close to critical structures. The physics quantity that can characterize such biological damage is the LET, the mean locally imparted energy to the medium by a particle. Even though LET has been shown to be a good surrogate for radiobiological effect and beam quality, incorporating it in clinical use is still extremely challenging. This is mainly due to the lack of an instrument for experimental verification of LET (and thereby RBE) distributions. Within the scope of this exploratory application we propose to develop a dosimeter enabling for the first time direct real-time measurements of LET delivered by the treatment beams to the target region with millimeter resolution and clinically relevant precision. This will be achieved by forming a ratio of dose measurements obtained with a liquid-filled ion chamber (LIC) co-located with an air-filled ion chamber (IC). This ratio of LIC/IC can then be calibrated against a calculated LET of a realistic treatment beam injected into a water phantom to generate a map of LET vs. LIC/IC for later applications in clinical settings. In addition, the proposed device will be small enough (about 5mm in both diameter and length) so that it can be implanted inside the tumor of a patient using endoscopic methods to monitor LET/RBE distributions of the applied radiation fields. The application is designed to overcome an important biomedical engineering challenge with major impact to health science and radiobiology. The proposed device is based on a novel scheme using coupled ionization chambers filled with different media with a common cathode, whose ratio of response can directly be translated into a LET value, following initial calibration using beams of known RBE. After experimentally commissioning of the system using various x-ray sources and heavy ion beams we will have provided the very first user friendly direct LET measuring dosimeter. With the rapid rise of interest in hadron therapy the proposed work will have an immediate impact on cancer research benefiting patients by significantly improving our understanding of the biological effect of hadron beams, and thus providing much better radiotherapy treatment plans by fully exploiting the advantages of hadron therapy and enabling more advanced treatment techniques proposed by the community such as LET painting irradiation, which may lead to cures for currently untreatable cases. Instrumentation that can provide physical and radiobiological parameters of various types of radiation is paramount to the understanding of their biological effects. The proposed research will also benefit the biological research communities in general studies of cell response to ionizing radiation, genetic modifications due to environmental exposure, and radiation safety aspects at the work place and during space travel.
Cancer is a leading cause of death. Radiation therapy is one of our most effective tools for combating cancers. Successful radiation treatment to cancer hinges on the ability to accurately calculate physical and biological dose distributions inside th patient due to ionizing irradiations, which allows us to estimate the amount of tumor cells killed and the damage to the healthy tissues and structures. While physical dose can be calculated and measured accurately, biological dose is not. This application aims to develop a device that for the first time allows physicians, medical physicists, and radiobiologists to directly measure LET, a well-accepted surrogate of biological dose and radiation beam quality. This capability will have an immediate impact on cancer research and treatments, benefiting patients by significantly improving our understanding of the biological effect of ionizing radiation, and thus providing much better radiotherapy treatment plans. The research is directed at solving a challenging public health related problem.
