Paul M. Medin

Use of the BrainLAB ExacTrac X-Ray 6D System in Image-Guided Radiotherapy

The ExacTrac X-Ray 6D image-guided radiotherapy (IGRT) system will be described and its performance evaluated. The system is mainly an integration of 2 subsystems: (1) an infrared (IR)-based optical positioning system (ExacTrac) and (2) a radiographic kV x-ray imaging system (X-Ray 6D). The infrared system consists of 2 IR cameras, which are used to monitor reflective body markers placed on the patients skin to assist in patient initial setup, and an IR reflective reference star, which is attached to the treatment couch and can assist in couch movement with spatial resolution to better than 0.3 mm. The radiographic kV devices consist of 2 oblique x-ray imagers to obtain high-quality radiographs for patient position verification and adjustment. The position verification is made by fusing the radiographs with the simulation CT images using either 3 degree-of-freedom (3D) or 6 degree-of-freedom (6D) fusion algorithms. The position adjustment is performed using the infrared system according to the verification results. The reliability of the fusion algorithm will be described based on phantom and patient studies. The results indicated that the 6D fusion method is better compared to the 3D method if there are rotational deviations between the simulation and setup positions. Recently, the system has been augmented with the capabilities for image-guided positioning of targets in motion due to respiration and for gated treatment of those targets. The infrared markers provide a respiratory signal for tracking and gating of the treatment beam, with the x-ray system providing periodic confirmation of patient position relative to the gating window throughout the duration of the gated delivery.

A Method for Evaluating Quality Assurance Needs in Radiation Therapy

The increasing complexity of modern radiation therapy planning and delivery techniques challenges traditional prescriptive quality control and quality assurance programs that ensure safety and reliability of treatment planning and delivery systems under all clinical scenarios. Until now quality management (QM) guidelines published by concerned organizations (e.g., American Association of Physicists in Medicine [AAPM], European Society for Therapeutic Radiology and Oncology [ESTRO], International Atomic Energy Agency [IAEA]) have focused on monitoring functional performance of radiotherapy equipment by measurable parameters, with tolerances set at strict but achievable values. In the modern environment, however, the number and sophistication of possible tests and measurements have increased dramatically. There is a need to prioritize QM activities in a way that will strike a balance between being reasonably achievable and optimally beneficial to patients. A systematic understanding of possible errors over the course of a radiation therapy treatment and the potential clinical impact of each is needed to direct limited resources in such a way to produce maximal benefit to the quality of patient care. Task Group 100 of the AAPM has taken a broad view of these issues and is developing a framework for designing QM activities, and hence allocating resources, based on estimates of clinical outcome, risk assessment, and failure modes. The report will provide guidelines on risk assessment approaches with emphasis on failure mode and effect analysis (FMEA) and an achievable QM program based on risk analysis. Examples of FMEA to intensity-modulated radiation therapy and high-dose-rate brachytherapy are presented. Recommendations on how to apply this new approach to individual clinics and further research and development will also be discussed.

INVESTIGATIONS OF A MINIMALLY INVASIVE METHOD FOR TREATMENT OF SPINAL MALIGNANCIES WITH LINAC STEREOTACTIC RADIATION THERAPY: ACCURACY AND ANIMAL STUDIES

PURPOSE A new method for stereotactic irradiation of spinal malignancies is presented, with evaluations of the theoretic and practical limitations of localization accuracy and the implementation of the method in swine. MATERIALS AND METHODS In a percutaneous procedure, a minimum of three small (1.7-mm-diameter) titanium markers are permanently affixed to a vertebra. Markers are localized on biplanar radiographs while isocenter positions are determined on CT. An external fiducial frame defines a three-dimensional coordinate system through the patient. Radiographs coupled with a rigid body rotation algorithm account for daily differences in patient position. Phantom studies were used to verify theoretic uncertainty calculations from a simulation program. A swine model was used to evaluate the difficulty and duration of the implant technique, the suitability of the vertebral process as an implant site, vertebral motion due to normal respiration, and the ability to target one vertebra with markers in an adjacent vertebra. RESULTS Theoretic accuracy studies confirmed that localization accuracy is a function of marker separation. Phantom studies involving 296 measurements showed that individual implants could be localized within +/-0.25 mm. The largest targeting error observed in 3,600 measurements of 100 implant configurations was 1.17 mm. The implant procedure took 5-10 minutes per site. No significant migration of implants was observed up to 35 days postimplantation, and respiratory motion had no detectable influence on vertebral position. Adjacent vertebrae may be useful for targeting one another with a small sacrifice in localization accuracy. CONCLUSIONS The use of implanted markers for localization of spinal malignancies has potential for applications in stereotactic radiotherapy. Phantom measurements suggest that localization accuracy similar to intracranial stereotactic radiotherapy techniques is achievable. Swine studies suggest that the implant technique is expedient and feasible for tumor targeting purposes.

Infrared patient positioning for stereotactic radiosurgery of extracranial tumors

We report on a novel, non-invasive patient positioning system for radiosurgery of extracranial tumors. The system consisted of infrared cameras and reflective markers attached to the skin. Because localization accuracy is critical in radiosurgery, we performed a theoretical analysis of the accuracy of the system. A computer simulation program modeled errors in marker position, and was used to predict errors in targeting and study methods for minimizing errors. The use of redundant markers improved the overall accuracy of targeting. Experimental data was collected using a rigid torso phantom and correlated with theoretical results. The accuracy of the infrared system was compared with existing systems.

Reduction of Hippocampal-Kindled Seizure Activity in Rats by Stereotactic Radiosurgery ☆

Radiosurgery may provide an alternative therapy for intractable epilepsy by eliminating or modifying abnormally active pacemaker neurons in epileptic foci. In the present study, the effect of radiosurgery on rat hippocampal kindling was examined. Rats received daily hippocampal stimulus trains until they were fully kindled. They then underwent radiosurgery of the kindled focus, receiving a single-dose of 0-, 10-, or 40-Gy. The 40-Gy group demonstrated an acute decrease in seizure threshold (3-5 days). Three months after radiosurgery, the threshold for seizures increased and the duration of afterdischarges decreased in the 40-Gy radiosurgery group compared to controls. The changes to both seizure threshold and afterdischarge duration were not significant in the 10-Gy group. These data suggest that radiosurgery is an effective means of reducing the epileptogenic activity of seizure foci.

Spinal Cord Tolerance to Single-Fraction Partial-Volume Irradiation: A Swine Model

PURPOSE To determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine. METHODS AND MATERIALS A 5-cm-long cervical segment was irradiated in 38-47-week-old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. The radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. The dose was prescribed to the 90% isodose line. A total of 26 pigs were stratified into eight dose groups of 12-47 Gy. The mean maximum spinal cord dose was 16.9 ± 0.1, 18.9 ± 0.1, 21.0 ± 0.1, 23.0 ± 0.2, and 25.3 ± 0.3 Gy in the 16-, 18-, 20-, 22-, and 24-Gy dose groups, respectively. The mean percentage of spinal cord volumes receiving ≥ 10 Gy for the same groups were 43% ± 3%, 48% ± 4%, 51% ± 2%, 57% ± 2%, and 59% ± 4%. The study endpoint was motor neurologic deficit determined by a change in gait during a 1-year follow-up period. RESULTS A steep dose-response curve was observed with a median effective dose for the maximum dose point of 20.0 Gy (95% confidence interval, 18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histologic change. All the minipigs with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of the gray matter. The histologic findings were unremarkable in the minipigs with normal neurologic status. CONCLUSIONS Our results have indicated that for a dose distribution with a steep lateral gradient, the pigs had a lower median effective dose for paralysis than has been observed in rats and more closely resembles that for rats, mice, and guinea pigs receiving uniform spinal cord irradiation.

An arteriovenous malformation model for stereotactic radiosurgery research

OBJECTIVE To introduce the utilization of a swine arteriovenous malformation (AVM) model for stereotactic radiosurgery research and to describe the morphological changes in the vessels after radiation. METHODS The model was created in six animals by creation of a right-sided carotid-jugular fistula. Pre- and postsurgical hemodynamic evaluation was performed. The left rete was radiated in four animals; two animals were not radiated. All animals were sacrificed 4 months after surgery, and the bilateral retia were obtained at autopsy. RESULTS There were no procedure-related complications. A pressure gradient of 20 mmHg across the nidus was obtained after surgery. The peak velocity in the arterial feeder increased from 18.5 to 83 cm/s. Microscopic examination of the control animals showed intimal hyperplasia and disrupted internal elastic lamina, similar to human AVMs. The radiated retia showed more prominent intimal hyperplasia. This was confirmed by histometric studies showing greater luminal occlusion in radiated specimens. Adventitial fibrosis was prominent in the radiated retia and was absent in the control animals. Immunohistochemical studies showed proliferating smooth muscle cells in the intima. The adventitial fibrosis consisted of smooth muscle cells surrounded by collagen Type IV extracellular matrix. CONCLUSION The nidus component and high-flow vasculopathy make this an attractive model for stereotactic radiosurgery research. Histology of the radiated models is similar to those described in radiated human AVMs. Further studies of the model are warranted to gain a better understanding of the cellular and molecular events in AVM vessels after stereotactic radiosurgery.

Spinal cord tolerance to reirradiation with single-fraction radiosurgery: a swine model.

PURPOSE This study was performed to determine swine spinal cord tolerance to single-fraction, partial-volume irradiation 1 year after receiving uniform irradiation to 30 Gy in 10 fractions. METHODS AND MATERIALS A 10-cm length of spinal cord (C3-T1) was uniformly irradiated to 30 Gy in 10 consecutive fractions and reirradiated 1 year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter, which was positioned laterally to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9 ± 0.1 Gy (n = 2), 17.1 ± 0.3 Gy (n = 3), 19.0 ± 0.1 Gy (n = 5), 21.2 ± 0.1 Gy (n = 5), 23.4 ± 0.2 Gy (n = 5), and 25.4 ± 0.4 Gy (n = 3). The mean percentage of spinal cord volumes receiving ≥10 Gy for the same groups were 34% ± 1%, 40% ± 1%, 46% ± 3%, 52% ± 1%, 56 ± 3%, and 57% ± 1%. The study endpoint was motor neurologic deficit as determined by a change in gait during a 1- year follow-up period. RESULTS A steep dose-response curve was observed with a 50% incidence of paralysis (ED(50)) for the maximum point dose of 19.7 Gy (95% confidence interval, 17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status, while all animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of gray matter. Histologic comparison with a companion study of de novo irradiated animals revealed that retreatment responders had more extensive tissue damage, including infarction of gray matter, only at prescription doses >20 Gy. CONCLUSION Pigs receiving spinal radiosurgery 1 year after receiving 30 Gy in 10 fractions were not at significantly higher risk of developing motor deficits than pigs that received radiosurgery alone.

Targeting accuracy of an image guided gating system for stereotactic body radiotherapy

Recently, a commercial system capable of x-ray image guided patient positioning and respiratory gated delivery has become available. Here we describe the operational principles of this system and investigate its geometric targeting accuracy under controlled conditions. The system tracks breathing via infrared (IR) detection of reflective markers located on the patients abdomen. Localization kilovoltage (kV) x-rays are triggered from within the gated delivery window portion of the breathing trace and after positioning, the tumour will cross the linac isocentre during gated delivery. We tested geometric accuracy of this system by localizing and delivering gated fields to a moving phantom. Effects of phantom speed, gating window location, timing errors and phantom rotations on positioning and gating accuracy were investigated. The system delivered gated fields to both a moving and static phantom with equal accuracy. The position of the gating window affects accuracy only to the extent that an asymmetric breathing motion could affect dose distribution within its boundaries. Positioning errors were found to be less then 0.5 +/- 0.2 mm for phantom rotations up to 5 degrees. We found and corrected a synchronization error caused by a faulty x-ray duration setting and detected a 60 +/- 20 ms time delay in our linear accelerator.

A review of radiation dosimetry applications using the MCNP Monte Carlo code

The Monte Carlo code MCNP (Monte Carlo N-Particle) has a significant history dating to the early years of the Manhattan Project. More recently, MCNP has been used successfully to solve many problems in the field of medical physics. In radiotherapy applications MCNP has been used successfully to calculate the bremsstrahlung spectra from medical linear accelerators, for modeling the dose distributions around high dose rate brachytherapy sources, and for evaluating the dosimetric properties of new radioactive sources used in intravascular irradiation for prevention of restenosis following angioplasty. MCNP has also been used for radioimmunotherapy and boron neutron capture therapy applications. It has been used to predict fast neutron activation of shielding and biological materials. One area that holds tremendous clinical promise is that of radiotherapy treatment planning. In diagnostic applications, MCNP has been used to model X-ray computed tomography and positron emission tomography scanners, to compute the dose delivered from CT procedures, and to determine detector characteristics of nuclear medicine devices. MCNP has been used to determine particle fluxes around radiotherapy treatment devices and to perform shielding calculations in radiotherapy treatment rooms. This manuscript is intended to provide to the reader a comprehensive summary of medical physics applications of the MCNP code.