240 I. J. Radiation Oncology 0 Biology 0 Physics Volume 36, Number 1, Supplement, 1996

163 EVALUATION OF A CLINICAL MEGAVOLTAGE Ih’lAGER BASED ON ACTIVE MATRIX, FLAT-PANEL TECHNOLOGY

Lany E. Antonuk, Youcef El-Mohri, Weidong Huang, Kyung-Wook Jee, Howard Sandier, Victor E. Scarpine, Jeffrey H. Siewerdsen, John Yorkston

Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI 48109

Purpose: The quantitative performance evaluation of an active matrix, flat-panel imager for megavoltage imaging is reported. The imager was developed as a clinical prototype to investigate the use of this technology for radiotherapy. A variety of imager properties including the signal-to- noise performance have been investigated in the context of the application. The results of an observer-dependent study of the contrast-detail sensitivity of the imager under a variety of conditions are presented and the results are compared to those obtained with a standard radiotherapy film cassette Clinical images acquired &der a variety of conditions (energy, dose, patient site) are presented and discussed.

Materials & Methods: The clinical prototype imager is based upon a recently developed 26x26 cm2 flat-panel array with a 512x512 pixel format and a 508 pm pixel-to-pixel pitch. This array incorporates a variety of significant improvements compared to an earlier -23x25 cm2 array with a 512x560 pixel format and a 450 pm pitch which was incorporated in an engineering prototype imager. These improvements include a larger optical till factor (-82% compared to -63%), a lower number of pixel and line defects, and a new passivation layer which has considerably reduced the pixel dark current and eliminated dark current drift. The clinical imager also incorporates a recently completed external electronic acquisition system. This system was custom-built to allow investigations into how the properties of the array (e.g. large signal capacity, low noise, excellent optical transfer efficiency, and high readout rate) could be exploited to obtain maximum clinical benefit. Given the optically sensitive nature of the arrays, the signal and noise properties were examined both with radiotherapy sources and with a controlled light source (an LED). An observer-dependent study of the contrast-detail sensitivity of the imager was performed with an aluminum phantom in which holes of various diameters and depths were drilled.

Results: The signal-to-noise analysis of the imager performance, based on a cascaded systems approach, suggests that the high optical transfer efficiency of the system allows input quantum limited imaging over a wide range of operational conditions. While the performance of the array and the acquisition system have undergone substantial improvements, further significant optimization of these components and the x-ray converter appears feasible and remains to be explored. As a direct result of the reduction in pixel dark current and elimination of dark current drift, it was possible to extend the use of this technology to radiographic imaging (i.e. the production of an image following a brief irradiation) for the first time. Consequently, high quality contrast-detail phantom and patient radiographic images at low doses were readily acquired with the system. At 6 MV and I MU, thresholds of -0.3% contrast at 11 mm diameter and I .9% contrast at 1.6 mm diameter are indicated. Interestingly, the contrast-detail thresholds at 15 MV are only slightly worse. In all cases, the corresponding results for film, even after digitization, are poorer. Finally, even at irradiations as low as 1 MU, the patient images at 6 and 15 MV show substantial amounts of detail and contrast and are of comparable quality. Furthermore, the array images appear to be superior in quality to film images taken under comparable conditions.

Conclusions: The high image quality demonstrated by the clinical prototype imager, even at low doses and high energy, supports the conclusion that flat-panel imaging technology has evolved to the point where it offers a significant, powerful, new tool for localization and verification in radiotherapy. Further investigations including performance optimization of all system components, examination of dual-energy and tomographic imaging techniques utilizing such imagers in the treatment room, as well as quantification of the clinical utility and benefits offered by this technology in the context of the radiotherapy application are planned.

This work was supported in part by NIH grant no. ROI CA51397.

164

The Wild Type ~53 Gone Radiosensitizes Malignant Cells and Tumors

David Galhudo M.D. and William McBride Ph.D.

Department of Radiation Oncology, University of California, Los Angeles.

Purpo&Objective: To investigate the use of the wild-type ~53 gene as a radiosensitizez of human malignant cells and tumors.

hlatuials and Methods: An ovarian carcinoma cell line (SKOV) lacking the p53 gene was transfected in vitro with El deleted adenovirus containing the wild type ~53 gene (Ad/pS3). SKOV cells expressing the p53 protein were tested for intrinsic radiosensitivity with clonogenic survival assays. SKOV tumors grotig in the flanks of SCID mice were injected with 1X10(9) PF’U of Ad/p53 or Ad/luciferase. Injected tumors were either irradiated to 24 Gy in 4 Gy fractions or not irradiated. Tumor diameters were then monitored.

Results: Cells expressing the ~53 gene product were more sensitive to radiation than control cells expressing the luciferase gene in in vitro clonogenic survival assays. SKOV tumors injected with the Ad/p53 virus expressed the ~53 protein as demonstrated through immunohistochemical analysis.. Tumors injected with Ad/p53 grew more slowly than tumors injected with Ad/h&erase or saline. After irradiation with 24Gy. tumors injected with Ad/p53 were controlled while those injected with Ad/h&erase were not.

Concl~ions: Our results formally demonstrate that transfer of the wild-type ~53 gene can increase the intrinsic radiation sensitivity of a malignant cell line lacking the ~53 gene. We also demonstrate that intra-tumoral injection of an adenovial vector containing the wild type ~53 gene increases the radiation responsiveness of established tumors, consistent with the radiosensitizing activity of the wild type ~53 gene demonstrated in vitro. These studies support clinical trials using ~53 gene transfer to potentiaJly improve the efficacy of radiation therapy in human malignancies.