A novel range telescope concept for proton CT

Proton beam therapy can potentially offer improved treatment for cancers of the head and neck and in paediatric patients. There has been asharp uptake of proton beam therapy in recent years as improved delivery techniques and patient benefits are observed. However, treatments are currently planned using conventional x-ray CT images due to the absence of devices able to perform high quality proton computed tomography(pCT) under realistic clinical conditions. A new plastic-scintillator-based range telescope concept, named ASTRA, is proposed here to measure the proton’s energy loss in a pCT system. Simulations conducted using GEANT4 yield an expected energy resolution of 0.7%. If calorimetric information is used the energy resolution could be further improved to about 0.5%. In addition, the ability of ASTRA to track multiple protons simultaneously is presented. Due to its fast components, ASTRA is expected to reach unprecedented data collection rates, similar to 10^8 protons/s.The performance of ASTRA has also been tested by simulating the imaging of phantoms. The results show excellent image contrast and relative stopping power reconstruction.

Investigation of the confinement of high energy non-neutral proton beam in a bent magnetic mirror

By using the Particle-In-Cell(PIC) simulation method, we study how the proton beam is confined in a bent magnetic mirror. It is found that the loss rate of the charged particles in a bent mirror is less than that in the axi-symmetric mirror. For a special bent mirror with the deflection angle of the coils $\alpha=45^{\circ}$, it is found that the loss rate reaches maximum value at certain ion number density where the ion electrostatic oscillation frequency is equal to the ion cyclotron frequency. In addition, the loss rate is irrelevant to the direction of the proton beam. Our results may be helpful to devise a mirror. In order to obtain the least loss rate, we may choose a appropriate deflection angle, and have to avoid a certain ion number density at which the ion electrostatic oscillation frequency is equal to the ion cyclotron frequency.

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results

Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

ATM and RAD51 Repair Pathways in Human Lymphocytes Irradiated with 70 MeV Therapeutic Proton Beam

The repair of radiation-induced DNA damage is a key factor differentiating patients in terms of the therapeutic efficacy and toxicity to surrounding normal tissue. Proton energy substantially determines the types of cancers that can be treated. The present work investigated the DNA double-strand break repair systems, represented by phosphorylated ATM and Rad51. The status of proton therapy energy used to treat major types of cancer is summarized. Here, human lymphocytes from eight healthy donors (male and female) were irradiated with a spread-out Bragg peak using a therapeutic 70 MeV proton beam or with reference X rays. For both types of radiation, the kinetics of pATM and Rad51 repair protein activation (0–24 h) were estimated as determinants of homologous and non-homologous double-strand break repair. Additionally, γ-H2AX was used as the gold standard marker of double-strand breaks. Our results showed that at 30 min postirradiation there was significantly greater accumulation of γ-H2AX (0.6-fold), pATM (2.0-fold), and Rad51 (0.6-fold) in the proton-irradiated cells compared with the X-ray-treated cells. At 24 h post irradiation, for both types of radiation and all investigated proteins, the foci number was still significantly higher when compared with control. Furthermore, the mean value of pATM and Rad51 repair effectiveness was higher in cells exposed to protons than in cells exposed to X rays; however, the difference was significant only for pATM. The largest inter-individual differences in the repair capabilities were noted for Rad51. The association between the frequency of repair protein foci and the frequency of lymphocyte viability at 1 h post irradiation showed a positive correlation for protons but a negative correlation for X rays. These findings indicate that the accumulation of radiation-induced repair protein foci after proton versus X-ray irradiation differs between patients, consequently affecting the cellular responses to particle therapy and conventional radiation therapy.

Longitudinal Changes in Brain Diffusion MRI Indices during and after Proton Beam Therapy in a Child with Pilocytic Astrocytoma: A Case Report

Proton beam therapy (PBT) is an effective pediatric brain tumor treatment. However, the resulting microstructural changes within and around irradiated tumors are unknown. We retrospectively applied diffusion tensor imaging (DTI) and free-water imaging (FWI) on diffusion-weighted magnetic resonance imaging (dMRI) data to monitor microstructural changes during the PBT and after 8 months in a pilocytic astrocytoma (PA) and normal-appearing white matter (NAWM). We evaluated the conventional MRI- and dMRI-derived indices from six MRI sessions (t0–t5) in a Caucasian child with a hypothalamic PA: at baseline (t0), during the PBT (t1–t4) and after 8 months (t5). The tumor voxels were classified as “solid” or “fluid” based on the FWI. While the tumor volume remained stable during the PBT, the dMRI analyses identified two different response patterns: (i) an increase in fluid content and diffusivity with anisotropy reductions in the solid voxels at t1, followed by (ii) smaller variations in fluid content but higher anisotropy in the solid voxels at t2–t4. At follow-up (t5), the tumor volume, fluid content, and diffusivity in the solid voxels increased. The NAWM showed dose-dependent microstructural changes. The use of the dMRI and FWI showed complex dynamic microstructural changes in the irradiated mass during the PBT and at follow-up, opening new avenues in our understanding of radiation-induced pathophysiologic mechanisms in tumors and the surrounding tissues.