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Objective: The objective of this study was to develop a murine system for the delivery of laser interstitial thermotherapy (LITT) with probe-based thermometry as a model for human glioblastoma treatment to investigate thermal diffusion in heterogeneous brain tissue., Methods: First, the tissue heating properties were characterized using a diode-pumped solid-state near-infrared laser in a homogeneous tissue model. The laser was adapted for use with a repurposed stereotactic surgery frame utilizing a micro laser probe and Hamilton syringe. The authors designed and manufactured a stereotactic frame attachment to work as a temperature probe stabilizer. Application of this novel design was used as a precise method for real-time thermometry at known distances from the thermal ablative center mass during murine LITT studies., Results: Temperature measurements were achieved during LITT that verified the direct thermometry capability of the system without the need for MR-based thermal monitoring. Application of multiple stereotactic design iterations led to an accurately reproducible surgical laser ablation procedure. Histological staining confirmed precise thermal ablation and controllable lesion size based on time and temperature control. Treatment of a syngeneic intracranial glioma model highly resistant to conventional therapy resulted in a modest survival benefit., Conclusions: The authors have successfully developed a murine model system of LITT with direct in situ thermometry for investigation into the effects of thermal ablation and combinatorial treatments in murine brain tumor models.

Objective: The safety of single-treatment stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) with radiographic evidence of brainstem compression but without motor deficit is controversial. Data on linear accelerator (linac)-based SRS in this setting are scarce. We address this with an outcomes report from an unselected series of patients with VS with radiographic brainstem compression treated with linac SRS., Methods: We included 139 patients with unilateral VS (any size) with radiographic brainstem compression (all without serious brainstem neurological deficits). The SRS prescription dose was 12.5 Gy (single fraction) using 6MV linac-produced photon beams, delivered with a multiple arc technique. Inclusion criteria required at least 1 year of radiographic follow-up with magnetic resonance imaging. The primary endpoint was freedom from serious brainstem toxicity (≥grade 3 Common Terminology Criteria for Adverse Events v5); the secondary was freedom from enlargement (tumor progression or any requiring intervention). We assessed serious cranial nerve complications, excluding hearing loss, defined as Common Terminology Criteria for Adverse Events v5 grade 3 toxicity., Results: Median magnetic resonance imaging follow-up time was 5 years, and median tumor size was 2.5 cm in greatest axial dimension and 5 ml in volume. The median brainstem D0.03 ml=12.6 Gy and median brainstem V10 Gy=0.4 ml. At 5 years, the actuarial freedom from serious brainstem toxicity was 100%, and freedom from tumor enlargement (requiring surgery and/or due to progression) was 90%. Severe facial nerve damage in patients without tumor enlargement was 0.9%., Conclusion: Linac-based SRS, as delivered in our series for VS with radiographic brainstem compression, is safe and effective., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Among the diverse areas of 3D printing, high-quality silicone printing is one of the least available and most restrictive. However, silicone-based components are integral to numerous advanced technologies and everyday consumer products. We developed a silicone 3D printing technique that produces precise, accurate, strong, and functional structures made from several commercially available silicone formulations. To achieve this level of performance, we developed a support material made from a silicone oil emulsion. This material exhibits negligible interfacial tension against silicone-based inks, eliminating the disruptive forces that often drive printed silicone features to deform and break apart. The versatility of this approach enables the use of established silicone formulations in fabricating complex structures and features as small as 8 micrometers in diameter.

Background: Data are scarce on the efficacy of a second radiosurgery (SRS) treatment of vestibular schwannoma that has progressed following initial treatment with SRS. We sought to report the outcome of our repeat SRS series with long-term imaging follow-up., Materials and Methods: We retrospectively analyzed 6 patients who met the following criteria: Repeat SRS at our institution between 1995 and 2018; solitary unilateral tumor; no evidence of neurofibromatosis; and magnetic resonance (MR) planning for both SRS treatments. All treatments were delivered with a linear accelerator-based system using head frame immobilization. The prescribed dose to the periphery of the tumor was 12.5 Gy in all initial and repeat SRS treatments, except for one repeat treatment to 10 Gy., Results: Follow-up with MR scan following the second SRS treatment was a median 8.4 years. The tumor control rate (lack of progression) following the second SRS treatment was 83% (5/6). Actuarial 10-year outcomes following repeat SRS were: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention before initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade ≥ 3 toxicity from repeat SRS was a case of infraorbital nerve deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit., Conclusion: There was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (© 2022 Greater Poland Cancer Centre.)

Though potentially beneficial, proton beam stereotactic radiosurgery has not been adopted widely secondary to the technical challenge of safely delivering multiple focused beams of proton radiation. In this study, we describe the design and characterization of a proton beam stereotactic radiosurgery system that can be adopted by existing passive scattering systems. This system utilizes a helmet-like device in which patient-specific brass apertures required for final beam collimation are positioned on a scaffold that is separate from the treatment gantry. The proton snout is then fitted with a generic aperture to focus the primary proton beam onto the patient specific apertures that are in the helmet-like device. The patient-specific apertures can all be placed at the start of the treatment, thus treatment with multiple beams can be accomplished without the delay of switching the apertures. In this report we describe a prototype design of this collimation system and dosimetric testing to verify efficacy. Subsequently, we describe a custom 3D printing of a prototype device and report on overall localization accuracy using Winston-Lutz tests. Our results show that it is possible to develop an add-on device for proton beam radiosurgery that is safe and efficient and capable of wide adoption on existing proton delivery systems., (© 2021 IOP Publishing Ltd.)

Purpose: The purpose of this study was to evaluate the performance of three common deformable image registration (DIR) packages across algorithms and institutions., Methods and Materials: The Deformable Image Registration Evaluation Project (DIREP) provides ten virtual phantoms derived from computed tomography (CT) datasets of head-and-neck cancer patients over a single treatment course. Using the DIREP phantoms, DIR results from 35 institutions were submitted using either Velocity, MIM, or Eclipse. Submitted deformation vector fields (DVFs) were compared to ground-truth DVFs to calculate target registration error (TRE) for six regions of interest (ROIs). Statistical analysis was performed to determine the variability between each DIR software package and the variability of users within each algorithm., Results: Overall mean TRE was 2.04 ± 0.35 mm for Velocity, 1.10 ± 0.29 mm for MIM, and 2.35 ± 0.15 mm for Eclipse. The MIM mean TRE was significantly different than both Velocity and Eclipse for all ROIs. Velocity and Eclipse mean TREs were not significantly different except for when evaluating the registration of the cord or mandible. Significant differences between institutions were found for the MIM and Velocity platforms. However, these differences could be explained by variations in Velocity DIR parameters and MIM software versions., Conclusions: Average TRE was shown to be <3 mm for all three software platforms. However, maximum errors could be larger than 2 cm indicating that care should be exercised when using DIR. While MIM performed statistically better than the other packages, all evaluated algorithms had an average TRE better than the largest voxel dimension. For the phantoms studied here, significant differences between algorithm users were minimal suggesting that the algorithm used may have more impact on DIR accuracy than the particular registration technique employed. A significant difference in TRE was discovered between MIM versions showing that DIR QA should be performed after software upgrades as recommended by TG-132., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

For many patients, stereotactic radiosurgery (SRS) offers a minimally invasive, curative option when surgical techniques are not possible. To date, the literature supporting the efficacy and safety of SRS treatment techniques uses photon beams. However, with the number of proton therapy facilities exponentially growing and the favorable physical properties of proton beam radiation therapy, there is an opportunity to develop proton therapy techniques for SRS. The goal of this paper is to determine the ability of clinical proton treatment planning systems to model small field dosimetry accurately and to compare various planning metrics used to evaluate photon SRS to determine the optimum beam configurations and settings for proton SRS (PSRS) treatment plans. Once established, these plan settings were used to perform a planning comparison on a variety of different SRS cases and compare SRS metrics between the PSRS plans and HyperArc™ (VMAT) SRS plans., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Chimeric antigen receptor (CAR) T-cell therapy targeting solid tumors has stagnated as a result of tumor heterogeneity, immunosuppressive microenvironments, and inadequate intratumoral T cell trafficking and persistence. Early (≤3 days) intratumoral presentation of CAR T cells post-treatment is a superior predictor of survival than peripheral persistence. Therefore, we have co-opted IL-8 release from tumors to enhance intratumoral T-cell trafficking through a CAR design for maximal antitumor activity in solid tumors. Here, we demonstrate that IL-8 receptor, CXCR1 or CXCR2, modified CARs markedly enhance migration and persistence of T cells in the tumor, which induce complete tumor regression and long-lasting immunologic memory in pre-clinical models of aggressive tumors such as glioblastoma, ovarian and pancreatic cancer.

Objective: The purpose of this study was to develop a road map for rapid construction of anthropomorphic phantoms from computational human phantoms for use in diagnostic imaging dosimetry studies. These phantoms are ideal for performing pregnant-patient dosimetry because the phantoms imitate the size and attenuation properties of an average-sized pregnant woman for multiple gestational periods., Materials and Methods: The method was derived from methods and materials previously described but adapted for 3D printing technology. A 3D printer was used to transform computational models into a physical duplicate with small losses in spatial accuracy and to generate tissue-equivalent materials characterized for diagnostic energy x-rays. A series of pregnant abdomens were selected as prototypes because of their large size and complex modeling. The process involved the following steps: segmentation of anatomy used for modeling; transformation of the computational model into a printing file format; preparation, characterization, and introduction of phantom materials; and model removal and phantom assembly., Results: The density of the homogenized soft tissue-equivalent substitute was optimized by combining 9.0% by weight of urethane filler powder and 91.0% urethane polymer, which resulted in a mean density of 1.041 g/cm 3 measured over 20 samples. Density varied among all of the samples by 0.0026 g/cm 3 . The total variation in density was 0.00261 g/cm 3 . The half-value layer of the bone material was measured to be 1.7 mm of bone material at 120 kVp and when simulated by use of the density of the bone tissue-equivalent substitute (1.60 g/cm 3 ) was determined to be 1.61 mm of bone tissue. For dosimetry purposes the phantom provided excellent results for evaluating a site's protocol based on scan range., Conclusion: The 3D printing technology is applicable to the fabrication of phantoms used for performing dosimetry. The tissue-equivalent materials used to substitute for the soft tissue were developed to be highly adaptable for optimization based on the dosimetry application. Use of this method resulted in more automated phantom construction with decreased construction time and increased out-of-slice spatial resolution of the phantoms.

Objectives: To determine the long-term outcome after stereotactic radiosurgery (SRS) for temporal bone paragangliomas., Materials and Methods: We retrospectively reviewed the medical records of 11 patients with temporal bone paragangliomas (10 patients with a glomus jugulare tumor and 1 patient with a glomus tympanicum tumor) treated between January 1997 and July 2012 at the University of Florida with SRS to a median dose of 15 Gy in 1 fraction. Ten previously unirradiated patients received SRS as did 1 patient who received prior fractionated radiotherapy (FRT) and then received salvage SRS for a local recurrence. The major outcome endpoint was local control, meaning no further growth or shrinkage on follow-up computed tomography or magnetic resonance imaging scans., Results: The median follow-up time was 5.3 years. Two patients developed a local recurrence after SRS, including the patient who received salvage SRS after prior FRT. The overall local control rates at 5 and 10 years were both 81%. The cause-specific survival rates at 5 and 10 years were both 88%. The distant metastasis-free survival rates at 5 and 10 years were both 100%. The overall survival rates at 5 and 10 years were both 78%. There were no severe complications., Conclusions: SRS for benign head and neck paragangliomas is a safe and efficacious treatment associated with minimal morbidity. SRS is suitable for patients with skull base tumors <3 cm when FRT is logistically unsuitable. Surgery is reserved for patients in good health whose risk of associated morbidity is low. Observation is a reasonable option for asymptomatic patients with a limited life expectancy.

Objective: The objective of this pilot study was to describe the application and first preliminary data of a novel MRI and CT compatible patient-specific facemask for stereotactic brain biopsy of intracranial lesions in dogs., Methods: Five client-owned dogs presenting for neurological deficits consistent with forebrain disease were included in the study. All dogs had MRI findings consistent with an intracranial lesion. Using images obtained from either MRI or CT, a virtual three-dimensional model of each dog's face was generated. The contact surface of each dog's face was selected for facemask design and a target point for biopsy was chosen using specialised software and toolkits. A patient-specific facemask with an attached biopsy port with premeasured and preselected trajectory was then fabricated by a 3D printer. The facemasks were sterilised and used intraoperatively to obtain biopsy samples. Biopsy samples were submitted for both cytological and histopathological evaluation., Results: The diagnostic yield based on specific histological diagnosis was 80%. The one case in which a histological diagnosis could not be confirmed had a cytological interpretation consistent with meningioma. No major complications were observed during or immediately after brain biopsy and all dogs were discharged from the hospital within 72 hours postprocedure., Clinical Significance: In conclusion, patient-specific facemasks appear to be a safe and effective method of brain biopsy in dogs, with minimal complications observed., (© 2017 British Small Animal Veterinary Association.)

Spinal instrumentation often involves placing implants without direct visualization of their trajectory or proximity to adjacent neurovascular structures. Two-dimensional fluoroscopy is commonly used to navigate implant placement, but with the advent of computed tomography, followed by the invention of a mobile scanner with an open gantry, three-dimensional (3D) navigation is now widely used. This article critically appraises the available literature to assess the influence of 3D navigation on radiation exposure, accuracy of instrumentation, operative time, and patient outcomes. Also explored is the latest technological advance in 3D neuronavigation: the manufacturing of, via 3D printers, patient-specific templates that direct implant placement., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Deep brain stimulation (DBS) is an effective treatment for multiple movement disorders and shows substantial promise for the treatment of some neuropsychiatric and other disorders of brain neurocircuitry. Optimal neuroanatomical lead position is a critical determinant of clinical outcomes in DBS surgery. Lead migration, defined as an unintended post-operative displacement of the DBS lead, has been previously reported. Despite several reports, however, there have been no systematic investigations of this issue. This study aimed to: 1) quantify the incidence of lead migration in a large series of DBS patients, 2) identify potential risk factors contributing to DBS lead migration, and 3) investigate the practical importance of this complication by correlating its occurrence with clinical outcomes., Methods: A database of all DBS procedures performed at UF was queried for patients who had undergone multiple post-operative DBS lead localization imaging studies separated by at least two months. Bilateral DBS implantation has commonly been performed as a staged procedure at UF, with an interval of six or more months between sides. To localize the position of each DBS lead, a head CT is acquired ~4 weeks after lead implantation and fused to the pre-operative targeting MRI. The fused targeting images (MR + stereotactic CT) acquired in preparation for the delayed second side lead implantation provide an opportunity to repeat the localization of the first implanted lead. This paradigm offers an ideal patient population for the study of delayed DBS lead migration because it provides a large cohort of patients with localization of the same implanted DBS lead at two time points. The position of the tip of each implanted DBS lead was measured on both the initial post-operative lead localization CT and the delayed CT. Lead tip displacement, intracranial lead length, and ventricular indices were collected and analyzed. Clinical outcomes were characterized with validated rating scales for all cases, and a comparison was made between outcomes of cases with lead migration versus those where migration of the lead did not occur., Results: Data from 138 leads in 132 patients with initial and delayed lead localization CT scans were analyzed. The mean distance between initial and delayed DBS lead tip position was 2.2 mm and the mean change in intracranial lead length was 0.45 mm. Significant delayed migration (>3 mm) was observed in 17 leads in 16 patients (12.3% of leads, 12.1% of patients). Factors associated with lead migration were: technical error, repetitive dystonic head movement, and twiddler's syndrome. Outcomes were worse in dystonia patients with lead migration (p = 0.035). In the PD group, worse clinical outcomes trended in cases with lead migration., Conclusions: Over 10% of DBS leads in this large single center cohort were displaced by greater than 3 mm on delayed measurement, adversely affecting outcomes. Multiple risk factors emerged, including technical error during implantation of the DBS pulse generator and failure of lead fixation at the burr hole site. We hypothesize that a change in surgical technique and a more effective lead fixation device might mitigate this problem.

Benchmarking is a process in which standardized tests are used to assess system performance. The data produced in the process are important for comparative purposes, particularly when considering the implementation and quality assurance of DIR algorithms. In this work, five commercial DIR algorithms (MIM, Velocity, RayStation, Pinnacle, and Eclipse) were benchmarked using a set of 10 virtual phantoms. The phantoms were previously developed based on CT data collected from real head and neck patients. Each phantom includes a start of treatment CT dataset, an end of treatment CT dataset, and the ground-truth deformation vector field (DVF) which links them together. These virtual phantoms were imported into the commercial systems and registered through a deformable process. The resulting DVFs were compared to the ground-truth DVF to determine the target registration error (TRE) at every voxel within the image set. Real treatment plans were also recalculated on each end of treatment CT dataset and the dose transferred according to both the ground-truth and test DVFs. Dosimetric changes were assessed, and TRE was correlated with changes in the DVH of individual structures. In the first part of the study, results show mean TRE on the order of 0.5 mm to 3 mm for all phan-toms and ROIs. In certain instances, however, misregistrations were encountered which produced mean and max errors up to 6.8 mm and 22 mm, respectively. In the second part of the study, dosimetric error was found to be strongly correlated with TRE in the brainstem, but weakly correlated with TRE in the spinal cord. Several interesting cases were assessed which highlight the interplay between the direction and magnitude of TRE and the dose distribution, including the slope of dosimetric gradients and the distance to critical structures. This information can be used to help clinicians better implement and test their algorithms, and also understand the strengths and weaknesses of a dose adaptive approach.

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well-defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause-specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy., (© 2013 John Wiley & Sons Ltd.)

Hematopoietic stem cell (HSC)-derived cells are involved in wound healing responses throughout the body. Unfortunately for mammals, wound repair typically results in scarring and nonfunctional reparation. Among vertebrates, none display such an extensive ability for adult regeneration as urodele amphibians, including 1 of the more popular models: the axolotl. However, a lack of knowledge of axolotl hematopoiesis hinders the use of this animal for the study of hematopoietic cells in scar-free wound healing and tissue regeneration. We used white and cytomegalovirus:green fluorescent protein(+) transgenic white axolotl strains to map sites of hematopoiesis and develop hematopoietic cell transplant methodology. We also established a fluorescence-activated cell sorter enrichment technique for major blood lineages and colony-forming unit assays for hematopoietic progenitors. The liver and spleen are both active sites of hematopoiesis in adult axolotls and contain transplantable HSCs capable of long-term multilineage blood reconstitution. As in zebrafish, use of the white axolotl mutant allows direct visualization of homing, engraftment, and hematopoiesis in real time. Donor-derived hematopoiesis occurred for >2 years in recipients generating stable hematopoietic chimeras. Organ segregation, made possible by embryonic microsurgeries wherein halves of 2 differently colored embryos were joined, indicate that the spleen is the definitive site of adult hematopoiesis., (© 2014 by The American Society of Hematology.)

Background: Despite the conformity of stereotactic radiosurgery (SRS) treatment, there are concerns about the risk of malignancy., Objective: We compared the number of cancer cases observed after treatment in a group of SRS patients to the number of cancer cases that would be expected in an age- and gender-matched group., Methods: We collected data from the University of Florida SRS database for patients treated for meningiomas, intracranial schwannomas, arteriovenous malformations (AVMs), trigeminal neuralgia, pituitary adenomas, cavernous angiomas, and metastases. We used the Florida Cancer Data System (FCDS) to determine the actual cancer rates for SRS-treated patients, and we compared these to the cancer rates in similar groups of non-SRS-treated patients based on rates available from the SEER (surveillance epidemiology and end results) database., Results: A total of 2,369 patients were analyzed. Of these, 862 were patients with metastases who were analyzed only to ensure the sensitivity of using the FCDS to determine malignancy rates. The results for patients with more than 5 years of follow-up are reported. Without the metastases patients, a total of 627 patients had more than 5 years of follow-up data. Follow-up in patient-years was 1,711 for the meningioma patients, 1,851 for the schwannoma patients, 1,407 for the AVM patients and 338 for patients with a diagnosis of 'other'. The observed cancer rate in the meningioma patients was 3.96% compared to the expected rate of 10% (binomial 95% confidence interval, CI = 1.85-7.94). The observed cancer rate in the schwannoma patients was 4.93% compared to the expected rate of 12.5% (95% CI = 2.61-8.89). The observed cancer rate in the AVM patients was 3.64% compared to the expected rate of 4.43% (95% CI = 1.49-8.10). The observed cancer rate in patients treated for other diagnoses (e.g. pituitary adenoma or trigeminal neuralgia) was 0% compared to the expected rate of 6.36% (95% CI = 0-11.7)., Conclusions: In a large population of SRS-treated patients, there was no increased risk of malignancy compared to the general population., (© 2014 S. Karger AG, Basel.)

Purpose: Deformable image registration (DIR) is being used increasingly in various clinical applications. However, the underlying uncertainties of DIR are not well-understood and a comprehensive methodology has not been developed for assessing a range of interfraction anatomic changes during head and neck cancer radiotherapy. This study describes the development of a library of clinically relevant virtual phantoms for the purpose of aiding clinicians in the QA of DIR software. These phantoms will also be available to the community for the independent study and comparison of other DIR algorithms and processes., Methods: Each phantom was derived from a pair of kVCT volumetric image sets. The first images were acquired of head and neck cancer patients prior to the start-of-treatment and the second were acquired near the end-of-treatment. A research algorithm was used to autosegment and deform the start-of-treatment (SOT) images according to a biomechanical model. This algorithm allowed the user to adjust the head position, mandible position, and weight loss in the neck region of the SOT images to resemble the end-of-treatment (EOT) images. A human-guided thin-plate splines algorithm was then used to iteratively apply further deformations to the images with the objective of matching the EOT anatomy as closely as possible. The deformations from each algorithm were combined into a single deformation vector field (DVF) and a simulated end-of-treatment (SEOT) image dataset was generated from that DVF. Artificial noise was added to the SEOT images and these images, along with the original SOT images, created a virtual phantom where the underlying "ground-truth" DVF is known. Images from ten patients were deformed in this fashion to create ten clinically relevant virtual phantoms. The virtual phantoms were evaluated to identify unrealistic DVFs using the normalized cross correlation (NCC) and the determinant of the Jacobian matrix. A commercial deformation algorithm was applied to the virtual phantoms to show how they may be used to generate estimates of DIR uncertainty., Results: The NCC showed that the simulated phantom images had greater similarity to the actual EOT images than the images from which they were derived, supporting the clinical relevance of the synthetic deformation maps. Calculation of the Jacobian of the "ground-truth" DVFs resulted in only positive values. As an example, mean error statistics are presented for all phantoms for the brainstem, cord, mandible, left parotid, and right parotid., Conclusions: It is essential that DIR algorithms be evaluated using a range of possible clinical scenarios for each treatment site. This work introduces a library of virtual phantoms intended to resemble real cases for interfraction head and neck DIR that may be used to estimate and compare the uncertainty of any DIR algorithm.

Background: Surgical education is moving rapidly to the use of simulation for technical training of residents and maintenance or upgrading of surgical skills in clinical practice. To optimize the learning exercise, it is essential that both visual and haptic cues are presented to best present a real-world experience. Many systems attempt to achieve this goal through a total virtual interface., Objective: To demonstrate that the most critical aspect in optimizing a simulation experience is to provide the visual and haptic cues, allowing the training to fully mimic the real-world environment., Methods: Our approach has been to create a mixed-reality system consisting of a physical and a virtual component. A physical model of the head or spine is created with a 3-dimensional printer using deidentified patient data. The model is linked to a virtual radiographic system or an image guidance platform. A variety of surgical challenges can be presented in which the trainee must use the same anatomic and radiographic references required during actual surgical procedures., Results: Using the aforementioned techniques, we have created simulators for ventriculostomy, percutaneous stereotactic lesion procedure for trigeminal neuralgia, and spinal instrumentation. The design and implementation of these platforms are presented., Conclusion: The system has provided the residents an opportunity to understand and appreciate the complex 3-dimensional anatomy of the 3 neurosurgical procedures simulated. The systems have also provided an opportunity to break procedures down into critical segments, allowing the user to concentrate on specific areas of deficiency.

Purpose: To employ and compare probabilistic diffusion tractography (PDT) for the explicit localization of connections from the thalamus to somatosensory cortex (S1) and primary motor cortex (M1) / supplementary motor area (SMA) with microelectrode electrophysiology in patients undergoing deep brain stimulation (DBS) surgery., Materials and Methods: These tractography-derived connections were used to categorize voxels in the thalamus as corresponding to sensory or motor physiology. A novel model (referred to in this work as the "mixture" model) to delineate PDT-based thalamic functional subregions by thresholding fiber intensities, ie, connectivity-defined regions (CDR), was devised. Regions created using this classification method were compared with the most commonly used model (referred to in this work as the "separation" or "winner takes all" model) for defining CDRs., Results: Electrophysiology data corresponded better for S1 CDRs created using the mixture model for both sensory and motor cells. Separation model CDRs showed poor correspondence against electrophysiology, with few sensory cells corresponding to the S1 separation model CDR., Conclusion: Mixture model-based CDRs may offer a significant improvement in delineation of functional subregions of subcortical structures., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Targeting in deep brain stimulation (DBS) relies heavily on the ability to accurately localize particular anatomic brain structures. Direct targeting of subcortical structures has been limited by the ability to visualize relevant DBS targets., Methods and Results: In this work, we describe the development and implementation, of a methodology utilized to create a three dimensional deformable atlas for DBS surgery. This atlas was designed to correspond to the print version of the Schaltenbrand-Bailey atlas structural contours. We employed a smoothing technique to reduce artifacts inherent in the print version., Conclusions: We present the methodology used to create a three dimensional patient specific DBS atlas which may in the future be tested for clinical utility.

Over the course of radiation therapy, a patient's anatomy may change substantially. The relatively recent addition of frequent in-room imaging to assist with patient localization has provided a database of images that may be used to recalculate dose distributions for adaptive radiotherapy purposes. The TomoTherapy Hi-Art II unit (Accuray Inc., Sunnyvale, CA, USA) uses a helical scanning geometry and a megavoltage (MV) beam to acquire volumetric patient images. This study evaluated the uncertainty of dose calculations performed on megavoltage CT (MVCT) images as a function of temporal Hounsfield Unit (HU) variations observed in the imaging system over three years on two machines. A baseline error between dose calculations performed on kVCT and MVCT images was established using a series of phantoms. This baseline error ranged from -1.4% to 0.6%. Materials of differing densities were imaged and MVCT numbers were measured periodically. The MVCT number of solid water varied from 5 to 103 HU and consistently increased prior to target replacement. Finally, the dosimetric uncertainty of the temporal HU variation was assessed using MVCT images of typical head and neck, lung and prostate cancer patients. Worst-case MVCT recalculation errors could approach 5%, 7% and 10% for the head and neck, lung and prostate images, respectively. However, if a tolerance of ±30 HU were maintained for the MVCT number of solid water, dosimetric errors were limited to ±2.5%, ±3% and ±4%, respectively.

Stereotactic radiosurgery is the term coined by Lars Leksell to describe the application of a single, high dose of radiation to a stereotactically defined target volume. In the 1970s, reports began to appear documenting the successful obliteration of arteriovenous malformations (AVMs) with radiosurgery. When an AVM is treated with radiosurgery, a pathologic process appears to be induced that is similar to the response-to-injury model of atherosclerosis. Radiation injury to the vascular endothelium is believed to induce the proliferation of smooth-muscle cells and the elaboration of extracellular collagen, which leads to progressive stenosis and obliteration of the AVM nidus thereby eliminating the risk of hemorrhage. The advantages of radiosurgery - compared to microsurgical and endovascular treatments - are that it is noninvasive, has minimal risk of acute complications, and is performed as an outpatient procedure requiring no recovery time for the patient. The primary disadvantage of radiosurgery is that cure is not immediate. While thrombosis of the lesion is achieved in the majority of cases, it commonly does not occur until two or three years after treatment. During the interval between radiosurgical treatment and AVM thrombosis, the risk of hemorrhage remains. Another potential disadvantage of radiosurgery is possible long term adverse effects of radiation. Finally, radiosurgery has been shown to be less effective for lesions over 10 cc in volume. For these reasons, selection of the optimal treatment for an AVM is a complex decision requiring the input of experts in endovascular, open surgical, and radiosurgical treatment. In the pages below, we will review the world's literature on radiosurgery for AVMs. Topics reviewed will include the following: radiosurgical technique, radiosurgery results (gamma knife radiosurgery, particle beam radiosurgery, linear accelerator radiosurgery), hemorrhage after radiosurgery, radiation induced complications, repeat radiosurgery, and radiosurgery for other types of vascular malformation.

Understanding the inherent radiosensitivity and repair capacity of canine transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to treat this disease. The objective of this study was to evaluate the parameters surviving fraction at 2 Gy (SF(2) ), α/β ratio and capacity for sublethal damage repair (SLDR) in response to radiation. Dose-response and split-dose studies were performed using the clonogenic assay. The mean SF(2) for three established TCC cell lines was high at 0.61. All the three cell lines exhibited a low to moderate α/β ratio, with the mean being 3.27. Two cell lines exhibited statistically increased survival at 4 and 24 h in the dose-response assay. Overall, our results indicate that the cell lines are moderately radioresistant, have a high repair capacity and behave similarly to a late-responding normal tissue. These findings indicate that the radiation protocols utilizing higher doses with less fractionation may be more effective for treating TCC., (© 2011 Blackwell Publishing Ltd.)

Background: Nonvestibular schwannomas are uncommon tumors of the brain often treated by surgical resection. Surgery may be associated with high morbidity., Objective: We present a series of nonvestibular schwannomas treated with linear accelerator radiosurgery during a 19-year period., Methods: This is a retrospective analysis of patients who underwent treatment of nonvestibular schwannomas at the University of Florida with linear accelerator radiosurgery between August 1989 and February 2008. Forty-nine patients underwent treatment during the study period, and 6 were lost to follow up. The mean age was 51 years (range, 17-82 years), 39% had previous surgical resection, and 67% presented with preradiosurgery cranial nerve deficits. There were 25 trigeminal, 18 jugular foramen, 2 facial, 2 oculomotor, 1 hypoglossal, and 1 high cervical schwannomas. The median tumor volume was 5.3 mL (range, 0.3-24.5 mL), treated with a median dose of 1250 cGy (range, 1000-1500 cGy). Study endpoints were actuarial local tumor control and neurological outcome., Results: Forty-three patients were available for a median follow-up of 37 months (range, 6-210 months). Actuarial local tumor control was 97% at 1 year, 91% at 4.5 years, and 83% at 5 years. There were 4 new cranial nerve deficits (9%) including facial numbness (2 patients), anesthesia dolorosa (1 patient), and facial weakness (1 patient). Thirty-nine percent had documented clinical and/or symptomatic improvement. There were no other morbidity and no mortality with treatment., Conclusion: Radiosurgery for nonvestibular schwannomas offers good actuarial local tumor control and has superior morbidity compared with surgical resection. This is the largest linear accelerator radiosurgical series, and the second largest radiosurgical series reported to date.

Radiosurgery first became a clinical option in the 1960's because of the Gamma Knife, and the technology proliferated in the 1980's due to the availability of linear accelerator radiosurgery. The technology has continued to develop with both Gamma Knife and linac radiosurgery due primarily to advances in computer technology and robotic automation. Many of these advances include planning systems that enhance the conformity of the dose distribution, and delivery systems that can more safely and efficiently delivery these more complex treatment plans. This manuscript details the evolution of technologies in stereotactic localization and delivery for intracranial radiosurgery.

Object: The radiosurgery-based arteriovenous malformation (AVM) score (RBAS) is a grading system designed to predict patient outcomes after Gamma Knife surgery for AVMs. This study seeks to validate independently the predictive nature of the RBAS, not only after single treatment but for retreatment, and to assess the overall outcome regardless of number of radiosurgeries., Methods: The authors analyzed 403 patients treated with linear accelerator (LINAC) radiosurgery for AVMs between May 1988 and June 2008. The AVM scores were determined by the following equation: AVM score = (0.1 x volume in cm(3)) + (0.02 x age in years) + (0.3 x location). The location values are as follows: frontal/temporal = 0, parietal/occipital/corpus callosum/cerebellar = 1, and basal ganglia/thalamus/brainstem = 2., Results: Testing demonstrated that the RBAS correlated with excellent outcomes after single or repeat radiosurgery (p < 0.001 for both variables). One hundred sixty-two (49%) of 330 patients had excellent outcomes (obliteration without deficit) after a single treatment. Excellent outcomes were achieved in 74, 64, 50, and 11% of patients with AVM scores of < 1.0 (Group 1), between 1.0 and < 1.8 (Group 2), between 1.8 and < 2.5 (Group 3), and >or= 2.5 (Group 4), respectively. Fifty-one patients (70%) obtained radiosurgical cure and 46 (63%) achieved excellent outcomes after repeat radiosurgery. Of these, 100% achieved excellent outcomes in Group 1, 70% did so in Group 2, 47% in Group 3, and 14% in Group 4. The RBAS correlated with excellent outcomes after overall treatment (p < 0.001). Two hundred seventy-seven patients (69%) obtained AVM obliteration, and 62% achieved excellent outcomes. In Group 1, 87% achieved excellent outcomes, 75% did so in Group 2, 61% in Group 3, and 24% in Group 4., Conclusions: The RBAS is a good predictor of patient outcomes after LINAC radiosurgery.

Image guided surgery is currently performed using frame-based as well as frameless approaches. In order to reduce the invasive nature of stereotactic guidance as well as to reduce the cost in both equipment and time required within the operating room we investigated the use of rapid prototyping (RP) technology. In our approach we fabricated custom patient specific face-masks and guides that can be applied to the patient during surgery. These guides provide a stereotactic reference for the accurate placement of surgical tools to a pre-planned target along a pre-planned trajectory. While the use of RP machines has previously been shown to be satisfactory for the accuracy standpoint, one of our design criteria, completing the entire built and introduction into the sterile field in less than 120 minutes, was unobtainable. Our primary problems were the fabrication time and the non-resistance of the built material to high-temperature sterilization. In the current study, we have investigated the use of subtractive rapid prototyping (SRP) machines to perform the same quality of surgical guidance while improving the fabrication time and allowing for choosing materials suitable for sterilization. Because SRP technology does not offer the same flexibility as RP in term of prototype shape and complexity, our software program was adapted to provide new guide designs suitable for SRP fabrication. The biopsy guide was subdivided for a more efficient built with the parts being uniquely assembled to form the final guide. The accuracy of the assembly was then assessed using a modified Brown-Roberts-Wells phantom base that allows measuring the position of a biopsy needle introduced into the guide and comparing it with the actual planned target. These tests showed that 1) SRP machines provide an average accuracy of 0.77 mm with a standard deviation of 0.05 mm (plus or minus one image pixel) and 2) SRP allows for fabrication and sterilization within three and a half hours after diagnostic image acquisition and we are confident that that further improvements can reduce this time to less than two hours. Further tests will determine the accuracy of the positioning of the face mask on the patient's head under an IRB-approved trial judged against actual frame-based and frameless systems.

DBS depends on precise placement of the stimulating electrode into an appropriate target region. Image-based (direct) targeting has been limited by the ability of current technology to visualize DBS targets. We have recently developed and employed a Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) 3T MRI sequence to more reliably visualize these structures. The FGATIR provides significantly better high resolution thin (1 mm) slice visualization of DBS targets than does either standard 3T T1 or T2-weighted imaging. The T1 subcortical image revealed relatively poor contrast among the targets for DBS, though the sequence did allow localization of striatum and thalamus. T2 FLAIR scans demonstrated better contrast between the STN, SNr, red nucleus (RN), and pallidum (GPe/GPi). The FGATIR scans allowed for localization of the thalamus, striatum, GPe/GPi, RN, and SNr and displayed sharper delineation of these structures. The FGATIR also revealed features not visible on other scan types: the internal lamina of the GPi, fiber bundles from the internal capsule piercing the striatum, and the boundaries of the STN. We hope that use of the FGATIR to aid initial targeting will translate in future studies to faster and more accurate procedures with consequent improvements in clinical outcomes.

Objective: In this paper, the authors review the results of a single-center experience using linear accelerator (LINAC) radiosurgery for the treatment of cavernous sinus meningiomas., Methods: This is a retrospective analysis with a median follow-up of 50 months. All patients were treated on an outpatient basis. Fifty-five patients were treated and 6 patients were lost to follow-up. Changes in preradiosurgery cranial nerve deficits and symptoms as well as actuarial local tumor control were evaluated., Results: The actuarial local tumor control was 100% at 5 years and 98% at 10 years. One patient had enlargement of tumor. Sixty-five percent had improvement in preradiosurgery cranial nerve deficits, 31% were unchanged and 1 patient (3.5%) was worse. Only 1 patient developed a new neurologic deficit., Conclusions: This is the largest LINAC radiosurgery experience for cavernous sinus meningiomas reported to date. Radiosurgery appears to offer greatly superior tumor control and much lower morbidity than surgical resection of cavernous sinus meningiomas., ((c) 2009 S. Karger AG, Basel.)

Objective: To develop an IM xenograft model of canine osteosarcoma in mice for the purpose of evaluating effects of radiation therapy on tumors., Animals: 27 athymic nude mice., Procedures: Mice were randomly assigned to 1 of 3 groups of 9 mice each: no treatment (control group), radiation at 10 Gy, or radiation at 15 Gy. Each mouse received 5 x 10(5) highly metastasizing parent osteosarcoma cells injected into the left gastrocnemius muscle. Maximum tumor diameter was determined with a metric circles template to generate a tumor growth curve. Conscious mice were restrained in customized plastic jigs allowing local tumor irradiation. The behavior and development of the tumor xenograft were assessed via evaluations of the interval required for tumor-bearing limbs to reach diameters of 8 and 13 mm, extent of tumor vasculature, histomorphology of tumors, degree of tumor necrosis, and existence of pulmonary metastasis and clinical disease in affected mice., Results: Tumor-bearing limbs grew to a diameter of 8 mm (0.2-g tumor mass) in a mean +/- SEM interval of 7.0 +/- 0.2 days in all mice. Interval to grow from 8 to 13 mm was significantly prolonged for both radiation therapy groups, compared with that of the control group. Histologic evaluation revealed the induced tumors were highly vascular and had characteristics consistent with those of osteosarcoma. Pulmonary metastasis was not detected, and there was no significant difference in percentage of tumor necrosis between groups., Conclusions and Clinical Relevance: A reliable, repeatable, and easily produced IM xenograft model was developed for in vivo assessment of canine osteosarcoma.

This article is a tribute to the pioneering medical physicists over the last 50 years who have participated in the research, development, and commercialization of stereotactic radiosurgery (SRS) and stereotactic radiotherapy utilizing a wide range of technology. The authors have described the evolution of SRS through the eyes of physicists from its beginnings with the Gamma Knife in 1951 to proton and charged particle therapy; modification of commercial linacs to accommodate high precision SRS setups; the multitude of accessories that have enabled fine tuning patients for relocalization, immobilization, and repositioning with submillimeter accuracy; and finally the emerging technology of SBRT. A major theme of the article is the expanding role of the medical physicist from that of advisor to the neurosurgeon to the current role as a primary driver of new technology that has already led to an adaptation of cranial SRS to other sites in the body, including, spine, liver, and lung. SRS continues to be at the forefront of the impetus to provide technological precision for radiation therapy and has demonstrated a host of downstream benefits in improving delivery strategies for conventional therapy as well. While this is not intended to be a comprehensive history, and the authors could not delineate every contribution by all of those working in the pursuit of SRS development, including physicians, engineers, radiobiologists, and the rest of the therapy and dosimetry staff in this important and dynamic radiation therapy modality, it is clear that physicists have had a substantial role in the development of SRS and theyincreasingly play a leading role in furthering SRS technology.

Objective: To characterize the radiosensitivity and capacity for sublethal damage repair (SLDR) of radiation-induced injury in 4 canine osteosarcoma cell lines., Sample Population: 4 canine osteosarcoma cell lines (HMPOS, POS, COS 31, and D17)., Procedures: A clonogenic colony-forming assay was used to evaluate the cell lines' intrinsic radiosensitivities and SLDR capacities. Dose-response curves for the cell lines were generated by fitting the surviving fractions after radiation doses of 0 (control cells), 1, 2, 3, 6, and 9 Gy to a linear quadratic model. To evaluate SLDR, cell lines were exposed to 2 doses of 3 Gy (split-dose experiments) at an interval of 0 (single 6-Gy dose), 2, 4, 6, or 24 hours, after which the surviving fractions were assessed., Results: Mean surviving fraction did not differ significantly among the 4 cell lines at the radiation doses tested. Mean surviving fraction at 2 Gy was high (0.62), and the alpha/beta ratios (predictor of tissue sensitivity to radiation therapy) for the cell lines were low (mean ratio, 3.47). The split-dose experiments revealed a 2.8- to 3.9-fold increase in cell survival when the radiation doses were applied at an interval of 24 hours, compared with cell survival after radiation doses were applied consecutively (0-hour interval)., Conclusions and Clinical Relevance: Results indicated that these canine osteosarcoma cell lines are fairly radioresistant; alpha/beta ratios were similar to those of nonneoplastic, late-responding tissues. Future clinical investigations should involve increasing the fraction size in a manner that maximizes tumor killing without adverse effects on the nonneoplastic surrounding tissues.

Purpose: Nonspecific stimulation of cells of the immune system may be useful in generating an anti-tumor response for a variety of cancers and may work synergistically with currently available cytotoxic therapies. In this study we examined the response of syngeneic rat gliomas to treatment with several nonspecific stimulators of dendritic cells and macrophages alone or in combination with radiation therapy., Experimental Design: RG-2 gliomas were implanted subcutaneously and treated with intratumoral (IT) injections of the toll-like receptor (TLR) ligands lipopolysaccharide (LPS) and zymosan A (ZymA) and the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). Combination treatment with IT LPS and single-fraction external beam radiotherapy (EBRT) was also evaluated., Results: Treatment with IT LPS and ZymA delayed tumor growth compared to saline controls. Multiple doses of both substances were superior to single doses, and led to complete tumor regression in 71% (LPS) and 50% (ZymA) of animals. GM-CSF showed no anti-tumor effects in this study. Combinations of IT LPS and EBRT appeared to have a synergistic effect in delaying tumor growth. Rechallenge studies and IT LPS treatment of RG-2 tumors in nude rats suggested the importance of T cells in this treatment paradigm., Conclusions: Direct IT treatment with the TLR ligands LPS and ZymA are effective in generating an anti-tumor response. These treatments may synergize with cytotoxic therapies such as EBRT, and appear to require T cells for a successful outcome.

Object: The goal in this study was to review the effects of treatment plan quality on outcomes after radiosurgery for vestibular schwannoma (VS)., Methods: Between July 1988 and August 2005, 390 patients were treated. The results of this experience have been published recently. In this study the authors looked at dosimetry variables: conformity of treatment plan and steepness of dose gradient, in the same group of patients. Over the duration of this study, dosimetry evolved from a single isocenter with marginal conformity to multiple isocenters with high conformity. Multivariate statistics were used to determine the effects of these variables on tumor control and on two types of complication, facial weakness and facial numbness., Results: The 5-year actuarial tumor control was 91%. Dosimetry had no effect on tumor control. Eighteen patients (4.6%) reported new-onset facial weakness and 14 (3.6%) reported new-onset facial numbness. Since 1994, when peripheral treatment doses were lowered to 1250 cGy, only three (1%) of 298 patients have experienced facial weakness and two (0.7%) of 298 have experienced facial numbness. Statistical analysis confirms, as in the prior study, that treatment volume and treatment dose are significant predictors of both facial weakness and facial numbness. In this model, prior tumor growth was also significant. Dosimetry, however, is definitely not a significant predictor of either complication., Conclusions: Treatment dose appears to be much more important than treatment plan quality in the prevention of facial numbness or weakness after radiosurgery for VS.

The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.

The last decade has seen the introduction of advanced technologies that have enabled much more precise application of therapeutic radiation. These relatively new technologies include multileaf collimators, 3-dimensional conformal radiotherapy planning, and intensity modulated radiotherapy in radiotherapy. Therapeutic dose distributions have become more conformal to volumes of disease, sometimes utilizing sharp dose gradients to deliver high doses to target volumes while sparing nearby radiosensitive structures. Thus, accurate patient positioning has become even more important, so that the treatment delivered to the patient matches the virtual treatment plan in the computer treatment planning system. Optical and image-guided radiation therapy systems offer the potential to improve the precision of patient treatment by providing a more robust fiducial system than is typically used in conventional radiotherapy. The ability to accurately position internal targets relative to the linac isocenter and to provide real-time patient tracking theoretically enables significant reductions in the amount of normal tissue irradiated. This report reviews the concepts, technology, and clinical applications of optical tracking systems currently in use for stereotactic radiation therapy. Applications of radiotherapy optical tracking technology to respiratory gating and the monitoring of implanted fiducial markers are also discussed.

Image-guided surgery can be broken down into two broad categories: frame-based guidance and frameless guidance. In order to reduce both the invasive nature of stereotactic guidance and the cost in equipment and time, we have developed a new guidance technique based on rapid prototyping (RP) technology. This new system first builds a computer model of the patient anatomy and then fabricates a physical reference frame that provides a precise and unique fit to the patient anatomy. This frame incorporates a means of guiding the surgeon along a preplanned surgical trajectory. This process involves (1) obtaining a high-resolution CT or MR scan, (2) building a computer model of the region of interest, (3) developing a surgical plan and physical guide, (4) designing a frame with a unique fit to the patient's anatomy with a physical linkage to the surgical guide, and (5) fabricating the frame using an RP unit. Software was developed to support these processes. To test the accuracy of this process, we first scanned and reproduced a plastic phantom fabricated to validate the system's ability to build an accurate virtual model. A target on the phantom was then identified, a surgical approach planned, a surgical guide designed, and the accuracy and precision of guiding a probe to that target were determined. Steps 1 through 5 were also evaluated using a head phantom. The results show that the RP technology can replicate an object from CT scans with submillimeter resolution. The fabricated reference frames, when positioned on the surface of the phantom and used to guide a surgical probe, can position the probe tip with an accuracy of 1.7 mm at the probe tip. These results demonstrate that the RP technology can be used for the fabrication of customized positioning frames for use in image-guided surgery.

Object: Radiosurgery has become a popular treatment for small vestibular schwannomas (VSs). The aim of this study was to review an extensive, single-institution experience with linear accelerator (LINAC) radiosurgery for VSs., Methods: Between July 1988 and August 2005, 390 patients with VSs were treated with LINAC-based radiosurgery at the authors' institution. Patient and treatment variables were prospectively maintained in a computer database. Outcomes were tracked through periodic clinical examinations and annual scanning studies. Multivariate and actuarial statistics were used to analyze rates of local tumor control and complications, including facial and trigeminal neuropathies, after treatment. One- and 2-year actuarial control rates were both 98%, and the 5-year actuarial control rate was 90%. Only four patients (1%) required surgery for tumor growth. Seventeen patients (4.4%) reported facial weakness and 14 patients (3.6%) reported facial numbness after radiosurgery. The risk of these complications rose with increasing tumor volume or increasing radiosurgical dose to the tumor periphery. Since 1994, when doses were deliberately lowered to 1250 cGy, only two patients (0.7%) have experienced facial weakness and two (0.7%) have experienced facial numbness., Conclusions: Radiosurgery provides a safe and effective therapeutic alternative to surgery for small VSs.

Object: Frameless neuronavigation has been established as a useful adjunct to intracranial surgery; however, the procedure is limited in young children by the need for rigid skull fixation with pins. Pin fixation is difficult and hazardous for patients younger than 2 years of age. Minor risks have been associated with pin fixation in older patients also, including scalp laceration, skull fracture, and epidural hematoma., Methods: The authors adapted a pinless head fixation system, consisting of a beanbag device, for use with frameless neuronavigation. This system was used to perform intracranial neurosurgical procedures in nine patients., Conclusions: This pinless, frameless method provides a new option for children who are unable to sustain rigid head fixation. It is also an alternative to rigid pin fixation for patients of any age.

Objective: To review a single-institution's 12-year experience of treating malignant gliomas with linear accelerator-based radiosurgery., Methods: One hundred patients were treated for malignant gliomas at the University of Florida between May 1, 1989, and June 12, 2002. Patient variables were entered into a radiosurgery database in a prospective manner. The endpoint of the study was length of survival from the time of diagnosis. The minimum length of follow-up was 18 months or until death. In an attempt to control for selection bias, we used the Radiation Oncology Therapy Group's (RTOG) recursive partitioning categories to compare survival in our group of radiosurgically boosted patients with the RTOG historical database., Results: Recursive partitioning analysis classification was significantly associated with survival. Compared with historical controls, this cohort of patients demonstrated a decreased survival for recursive partitioning analysis Class I and II patients, similar survival for Class III and IV patients, and increased median survival for Class V patients. Other variables demonstrating a statistically significant impact on survival were eloquent location and recurrent disease., Conclusion: The results of this study and those of RTOG 93-05 suggest that the reported benefit of upfront radiosurgical boost for malignant gliomas is the result of selection bias. The possibility remains that radiosurgical boost is of benefit in recurrent tumors, especially those in RTOG Class V.

Object: In this paper the authors review the results of a single-center experience in the use of linear accelerator (LINAC) surgery for radiosurgical treatment of meningiomas., Methods: A retrospective analysis of all patients treated with LINAC surgery for meningiomas between May 1989 and December 2001 was performed. All patients participated in follow-up review for a minimum of 2 years, and no patients were excluded. Two hundred ten patients were treated during the study interval. The actuarial local control rate for benign tumors was 100% at both 1 and 2 years, and 96% at 5 years. The actuarial local control rate for atypical tumors was 100% at 1 year, 92% at 2 years, and 77% at 5 years; and that for malignant tumors was 100% at both 1 and 2 years, and only 19% at 5 years. Of the 210 patients 13 (6.2%) experienced temporary radiation-induced complications, and only five (2.3%) experienced permanent complications. In all patients with a permanent complication the histological characteristics of the meningioma were malignant., Conclusions: Linear accelerator surgery produced high local control rates and very low rates of permanent morbidity in patients harboring benign meningiomas.

Conventional methods of inverse planning for intensity-modulated radiotherapy (IMRT) and intensity-modulated radiosurgery (IMRS) are generally based upon optimizing a set of beam fluence profiles according to a set of dose-volume constraints specified by a human planner. This optimization is generally carried out through an iterative approach that relies upon the optimization of a score, driving the plan's ability to satisfy the user-provided constraints. Following optimization of the fluence distribution, the non-trivial problem of converting the fluence distribution into a set of deliverable, intensity-modulated beams must be solved. A novel approach to solving this IMRS total inverse problem is presented in this paper. The proposed method uses a class solution that provides an optimized dose gradient and a method of designing a conformal plan based on an existing geometrically based optimization algorithm. After developing an optimal fluence distribution, the process then arranges the fluence into a set of simple and efficient MLC beam delivery sequences. The algorithm presented here offers several potential advantages for the application of intensity modulation to radiosurgery treatment planning. The geometrically based optimization process' simplicity requires far less human user input and decision making in the specification of dose and dose-volume constraints than do conventional inverse planning algorithms. This simplicity allows the optimization process to be completed much faster than conventional inverse-planning algorithms, literally seconds compared with at least several minutes. Likewise, the fluence conversion step is a simplified process (compared to conventional IMRT planning), which takes advantage of some simplifications uniquely appropriate to the problem at hand (IMRS). The converted, deliverable IMRS beams allow superior conformity and dose gradient relative to conventional IMRS planning or 3DCRT radiosurgery planning. Another benefit is that the number of beam intensity levels is greatly reduced, from hundreds to as few as a half-dozen intensity levels. Finally, since the treatment plan optimization process is based upon proven principles applicable to optimizing radiosurgery (rather than the general problem of optimizing fractionated radiotherapy plans), the plans generated and deliverable with this method of IMRS are potentially superior to those produced by conventional inverse-planning methods of IMRT/IMRS.

Intracranial stereotactic positioning systems (ISPSs) are used to position patients prior to precise radiation treatment of localized lesions of the brain. Often, the lesion is located in close proximity to critical anatomic features whose functions should be maintained. Many types of ISPSs have been described in the literature and are commercially available. These are briefly reviewed. ISPS systems provide two critical functions. The first is to establish a coordinate system upon which a guided therapy can be applied. The second is to provide a method to reapply the coordinate system to the patient such that the coordinates assigned to the patient's anatomy are identical from application to application. Without limiting this study to any particular approach to ISPSs, this report introduces nomenclature and suggests performance tests to quantify both the stability of the ISPS to map diagnostic data to a coordinate system, as well as the ISPS's ability to be realigned to the patient's anatomy. For users who desire to develop a new ISPS system, it may be necessary for the clinical team to establish the accuracy and precision of each of these functions. For commercially available systems that have demonstrated an acceptable level of accuracy and precision, the clinical team may need to demonstrate local ability to apply the system in a manner consistent with that employed during the published testing. The level of accuracy and precision required of an individual ISPS system is dependent upon the clinical protocol (e.g., fractionation, margin, pathology, etc.). Each clinical team should provide routine quality assurance procedures that are sufficient to support the assumptions of accuracy and precision used during the planning process. The testing of ISPS systems can be grouped into two broad categories, type testing, which occurs prior to general commercialization, and site testing, performed when a commercial system is installed at a clinic. Guidelines to help select the appropriate tests as well as recommendations to help establish the required frequency of testing are provided. Because of the broad scope of different systems, it is important that both the manufacturer and user rigorously critique the system and set QA tests appropriate to the particular device and its possible weaknesses. Major recommendations of the Task Group include: introduction of a new nomenclature for reporting repositioning accuracy; comprehensive analysis of patient characteristics that might adversely affect positioning accuracy; performance of testing immediately before each treatment to establish that there are no gross positioning errors; a general request to the Medical Physics community for improved QA tools; implementation of weekly portal imaging (perhaps cone beam CT in the future) as a method of tracking fractionated patients (as per TG 40); and periodic routine reviews of positioning accuracy., (© 2005 American Association of Physicists in Medicine.)

Optical tracking determines an object's position by measuring light either emitted or reflected from the object. The hallmark of optical tracking systems is their high spatial resolution and measurement in real time; such systems can resolve the position of a point source within a fraction of a millimeter and report at a rate of 10 Hz or faster. Several systems have been developed for radiation therapy, all of which track infrared markers attached to the patient's external surface. The positions of the optical markers relative to the target volume, together with the desired marker positions relative to treatment isocenter, are determined during computed tomography simulation. In the treatment room, the real marker positions are measured relative to isocenter; rigid-body mathematics then determine marker displacements from their desired positions and hence target displacement from isocenter. Real-time feedback allows one to correct the patient's position. The first systems were used for intracranial stereotaxis radiotherapy; rigid arrays of optical markers were attached to the patient via a biteplate linkage. Subsequent systems for extracranial radiotherapy tracked external markers to determine patient position and/or gate the radiation beam based on patient motion. Lastly, optical tracking has been integrated with ultrasound or stereoscopic x-ray imaging to determine the position of internal anatomy targets relative to isocenter.

Stereotactic radiosurgery (SRS) involves precise delivery of a single large dose of radiation to a designated tumor target. This report describes use of SRS in combination with a frameless stereotactic localization system to treat 11 dogs with appendicular osteosarcomas. Five dogs were treated with SRS alone; 6 were treated with a combination of SRS and chemotherapy. Overall median survival time was 363 days (range, 145 to 763 days), with 6 dogs still alive 90, 142, 234, 367, 633, and 763 days after SRS. Limb function was good or excellent in all 6 dogs that were still alive. Results in these dogs suggest that SRS may be a viable option for dogs with appendicular osteosarcoma, with the potential to provide long-term local tumor control and improvement in limb function, especially when combined with chemotherapy. Because of the destructive nature of osteosarcoma and limitations of SRS, dogs with tumors that are small and have caused minimal bone destruction would likely be the best candidates for this procedure.

Objective: To review a 12-year experience treating metastatic brain disease with linear accelerator-based stereotactic radiosurgery (SRS)., Methods: We performed a retrospective analysis of all patients treated between 1989 and 2001 with linear accelerator radiosurgery for brain metastases. Patients were followed up both clinically and with imaging studies to document local control, regional control, and survival. Demographic data, dosing parameters, number of lesions, histology, history of whole-brain radiation therapy, and other factors were obtained prospectively. Cox proportional-hazards regression with multivariate and univariate analysis was performed with Stata 8.0 software., Results: A total of 383 patients received SRS for brain metastases during the study interval. Median survival was 9 months. Patients with tumor-type melanoma or multiple metastatic lesions had decreased survival. Actuarial 1-year local control was 75%. Differences in regional control rates were not statistically significant between patients treated with SRS and whole-brain radiation therapy versus SRS alone., Conclusion: Radiosurgery is an effective and safe method for treating selected patients with brain metastases.

Object: The authors sought to determine which morphological features of arteriovenous malformations (AVMs) are statistically predictive of preradiosurgical hemorrhage, postradiosurgical hemorrhage, and neuroimaging-defined failure of radiosurgical treatment. In addition, correlation between computerized tomography (CT) scanning and angiography for the identification of AVM structures was investigated., Methods: Archived CT dosimetry and available angiographic and clinical data for 268 patients in whom AVMs were treated with linear accelerator radiosurgery were retrospectively reviewed. Many of the morphological features of AVMs, including location, volume, compact or diffuse nidus, neovascularity, ease of nidus identification, number of feeding arteries, location (deep or superficial) of feeding arteries, number of draining veins, deep or superficial venous drainage, venous stenoses, venous ectasias, and the presence of intranidal aneurysms, were analyzed. In addition, a number of patient and treatment factors, including patient age, presenting symptoms, radiation dose, repeated treatment, and radiological outcome, were subjected to multivariate analyses. Two hundred twenty-seven patients were treated with radiosurgery for the first time and 41 patients underwent repeated radiosurgery. Eighty-one patients presented with a history of AVM hemorrhage and 91 patients had AVMs in a periventricular location. Twenty-six patients (10%) experienced a hemorrhage following radiosurgery. Of the 268 patients, 81 (30%) experienced angiographically defined cures, and 37 (14%) experienced MR imaging-defined cures. Eighty-six patients (32%) experienced neuroimaging-defined treatment failure, and 64 underwent insufficiently long follow up. A larger AVM volume (odds ratio [OR] 0.349; p = 0.004) was associated with a decreased rate of pretreatment hemorrhage, whereas periventricular location (OR 6.358; p = 0.000) was associated with an increased rate of pretreatment hemorrhage. None of the analyzed factors was predictive of hemorrhage following radiosurgery. A higher radiosurgical dose was strongly correlated with neuroimaging-defined success (OR 3.743; p = 0.006), whereas a diffuse nidus structure (OR 0.246; p = 0.008) and associated neovascularity (OR 0.428; p = 0.048) were each associated with a lower neuroimaging-defined cure rate. A strong correlation between CT scanning and angiography was noted for both nidus structure (p = 0.000; Fisher exact test) and neovascularity (p = 0.002; Fisher exact test)., Conclusions: Patients presenting with AVMs that are small or periventricular were at higher risk for experiencing hemorrhage. A higher radiosurgical dose correlated strongly with neuroimaging-defined success. Patients in whom the AVM had a diffuse structure or associated neovascularity were at higher risk for neuroimaging-defined failure of radiosurgery. A strong correlation between CT scanning and angiography in the assessment of AVM structure was demonstrated.

Objective: To describe the exposure obtained through six approaches to the perimesencephalic cisterns with an emphasis on exposure of the posterior cerebral artery and its branches., Methods: Dissections in 12 hemispheres exposed the crural, ambient, and quadrigeminal cisterns and related segments of the posterior cerebral artery. A Stealth Image Guidance workstation (Medtronic Surgical Navigation Technologies, Louisville, CO) was used to compare the approaches., Results: The transsylvian approach exposed the interpeduncular and crural cisterns. The subtemporal approach exposed the interpeduncular and crural cisterns as well as the lower half of the ambient cistern. Temporal lobe retraction and the position of the vein of Labbé limited exposure of the quadrigeminal cistern. Occipital transtentorial and infratentorial supracerebellar approaches exposed the quadrigeminal and lower two-thirds of the ambient cistern. Transchoroidal approaches exposed the posterior third of the crural cistern, the upper two-thirds of the ambient cistern, and the proximal quadrigeminal cistern. Transchoroidal approaches exposed the posterior portion of the P2 segment (P2p) in 9 of 10 hemispheres and were the only approaches that exposed the lateral posterior choroidal arteries and the plexal segment of the anterior choroidal artery. Occipital transtentorial and infratentorial supracerebellar approaches provided access to the P3 segment in all cases and exposed the P2p segment in 4 of 10 hemispheres. The subtemporal approach provided access to the cisternal and crural segments of the anterior choroidal and medial posterior choroidal arteries and exposed the P2p segment in 3 of 10 hemispheres., Conclusion: Surgical approaches to lesions of the perimesencephalic cisterns must be tailored to the site of the pathological findings. The most challenging area to expose is the upper half of the ambient cistern, particularly the P2p segment of the posterior cerebral artery.