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Purpose: We studied the sensitivity of a novel transmission fiber scintillator array designed and built for in line treatment verification. The purpose of this project is to assess the capability of the fiber detector array technology to detecttreatment errors in real time without false positives to enhance patient safety.Methods: We developed a linear scintillator array detector using radiation hard scintillating fibers and high speed parallel signal conditioning and data acquisition to monitor external beam treatment fluence in real time. The detector captures and resolves the time and amplitude of each linac pulse at each MLC segment. The detector has 60 fibers aligned to each MLC leaf and two output channels per fiber. The data is captured by a high speed parallel digitizer to determine the IMRT beam output delivered to a patient in real time. We evaluated the detector peak pulse linearity according to dose rate, MLC positioning, and beam energy. We analyzed the detector sensitivity, signal to noise ratio, and pulse distribution statistics to determine beam output and fluence in real time. Results: We analyzed the response of the detector to 6 MV and 10 MV photon beams. The statistical analysis of the detectedlinac pulses indicates that a minimum of 20 pulses are required to evaluate MLC positioning and fluence with 3 mm and 3% resolution, respectively. During testing, no false positives were detected. Linearity with respect to output rate, MLC or jaw opening, and fluence is within 2%. Conclusions: Measured sensitivity and signal to noise ratio of a real time linear fiber array detector show that delivered beam fluence can be monitored every 55 msec, with no observed false positives during treatment to provide in vivo real time patient safety and beam monitoring.

Purpose: Cone beam CT(CBCT) is a well established technique to localize patients using bone and soft tissueanatomy. Current protocols are limited to one weekly CBCT due to the considerable imaging dose delivered to the patient. The purpose of this project is to develop and validate a low dose CBCT algorithm to reduce dose and imaging time of current 3D imaging localization procedures using a novel iterative tomosynthesis algorithm to allow daily CBCT for patient positioning and target localization. Methods: The algorithm is based on the combination of a tomosynthesis filtered back propagation (TFBP) acquisition geometry algorithm and a maximum likelihood expectation maximization (MLEM) iterative reconstruction. Circular or arc acquisition trajectory, projection number, and angular projection position are optimized according to the anatomical treatment site and region of interest. The TFBP method provides the first 3D image estimate, and the MLEM improves its quality. In this study, we focused on head and neck treatment localization imaging.Results: We studied the performance of our tomosynthesis algorithm imaging resolution on an anthropomorphic head and neck phantom to determine image quality as a function of dose reduction techniques. Reconstructedanatomy shows that a 1/8 dose reduction provides similar image quality and resolution as current CBCT protocols. Seven iterations show an optimal compromise between image quality and reconstruction time. Tomosynthesisimages provide digitally reconstructedradiographs with similar resolution and contrast as full CBCT. We verified that the iterative process eliminates phantom images originated by the acquired sparse angular data projections. Conclusions: We developed and validated an iterative algorithm for low dose cone beam CT based on circular or arc tomosynthesis geometries and iterative reconstruction techniques. The algorithm combines the strengths of both techniques to provide a novel low dose method to image patient anatomy for patient positioning and target localization.

Iterative reconstruction (IR) reduces noise, thereby allowing dose reduction in computed tomography (CT) while maintaining comparable image quality to filtered back-projection (FBP). This study sought to characterize image quality metrics, delineation, dosimetric assessment, and other aspects necessary to integrate IR into treatment planning.CT images (Brilliance Big Bore v3.6, Philips Healthcare) were acquired of several phantoms using 120 kVp and 25-800 mAs. IR was applied at levels corresponding to noise reduction of 0.89-0.55 with respect to FBP. Noise power spectrum (NPS) analysis was used to characterize noise magnitude and texture. CT to electron density (CT-ED) curves were generated over all IR levels. Uniformity as well as spatial and low contrast resolution were quantified using a CATPHAN phantom. Task specific modulation transfer functions (MTF task) were developed to characterize spatial frequency across objects of varied contrast. A prospective dose reduction study was conducted for 14 patients undergoing interfraction CT scans for high-dose rate brachytherapy. Three physicians performed image quality assessment using a six-point grading scale between the normal-dose FBP (reference), low-dose FBP, and low-dose IR scans for the following metrics: image noise, detectability of the vaginal cuff/bladder interface, spatial resolution, texture, segmentation confidence, and overall image quality. Contouring differences between FBP and IR were quantified for the bladder and rectum via overlap indices (OI) and Dice similarity coefficients (DSC). Line profile and region of interest analyses quantified noise and boundary changes. For two subjects, the impact of IR on external beam dose calculation was assessed via gamma analysis and changes in digitally reconstructed radiographs (DRRs) were quantified.NPS showed large reduction in noise magnitude (50%), and a slight spatial frequency shift (∼ 0.1 mm(-1)) with application of IR at L6. No appreciable changes were observed for CT-ED curves between FBP and IR levels [maximum difference ∼ 13 HU for bone (∼ 1% difference)]. For uniformity, differences were ∼ 1 HU between FBP and IR. Spatial resolution was well conserved; the largest MTFtask decrease between FBP and IR levels was 0.08 A.U. No notable changes in low-contrast detectability were observed and CNR increased substantially with IR. For the patient study, qualitative image grading showed low-dose IR was equivalent to or slightly worse than normal dose FBP, and is superior to low-dose FBP (p0.001 for noise), although these did not translate to differences in CT number, contouring ability, or dose calculation. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using the most aggressive IR level [-1.2 ± 4.9 HU (range: -17.6-12.5 HU)]. No clinically significant contour differences were found between IR and FBP, with OIs and DSCs ranging from 0.85 to 0.95. Negligible changes in dose calculation were observed. DRRs preserved anatomical detail with2% difference in intensity from FBP combined with aggressive IRL6.These results support integrating IR into treatment planning. While slight degradation in edges and shift in texture were observed in phantom, patient results show qualitative image grading, contouring ability, and dosimetric parameters were not adversely affected.

Purpose: Small animal irradiation can provide preclinical insights necessary for clinical advancement. In order to provide clinically relevant data, these small animal irradiations must be designed such that the treatment methods and results are comparable to clinical protocols, regardless of variations in treatment size and modality. Methods: Small animal treatments for four treatment sites (brain, liver, lung and spine) were investigated, accounting for change in treatment energy and target size. Up to five orthovoltage (300kVp) beams were used in the preclinical treatments, using circular, square, and conformal tungsten apertures, based on the treatment site. Treatments were delivered using the image guided micro irradiator (microIGRT). The plans were delivered to a mouse sized phantom and dose measurements in axial and coronal planes were performed using radiochromic film. The results of the clinical and preclinical protocols were characterized in terms of conformality number, CTV coverage, dose nonuniformity ratio, and organ at risk sparing. Results: Preclinical small animal treatment conformality was within 1–16% of clinical results for all treatment sites. The volume of the CTV receiving 100% of the prescription dose was typically within 10% of clinical values. The dose non-uniformity was consistently higher for preclinical treatments compared to clinical treatments, indicating hot spots in the target. The ratios of the mean dose in the target to the mean dose in an organ at risk were comparable if not better for preclinical versus clinical treatments. Finally, QUANTEC dose constraints were applied and the recommended morbidity limits were satisfied in each small animal treatment site. Conclusion: We have shown that for four treatment sites, preclinical 3D conformal small animal treatments can be clinically comparable if clinical protocols are followed. Using clinical protocols as the standard, preclinical irradiation methods can be altered and iteratively improved to achieve a clinically relevant irradiation model.

Purpose: An in vivo transmission scintillation fiber detector was developed to monitor patient treatment in real time for the enhancement of patient safety and treatment accuracy. The detector system is capable of monitoring each pulse from a medical LINAC during treatment to determine the dose delivered as treatment progresses. Methods: The detector system consists of 60 parallel scintillating fibers coupled to fast data processing optoelectronics that can monitor the beam fluence in real time. Each 2.5mm2 square fiber is aligned with an MLC leaf pair and is long enough to capture a 40cm field. The fibers are embedded within a water equivalent polymer substrate that is secured in the LINAC accessory tray. The fibers are coupled to high speed photosensors and front end amplifiers that filter noise and pass each pulse to a high speed analog-to-digital converter. The system components are capable of detecting pulse repetition times shorter than what is delivered by a medical LINAC to ensure true real time data acquisition. Results: The system was able to capture and record the signal from each linac pulse and display the information in real time with no pulse pile up. It was found that the fiber array attenuates 2.65% of the beam which can easily be compensated for in treatment planning. The fibers responded linearly with dose, are independent of clinical beam energies, and are independent of dose rate. Calibration of the system was performed as a function of beam energy, beam size, dose rate, and monitor units to optimize beam fluence error detection. Conclusion: The detector system presented provides true real time in vivo beam monitoring to enhance patient safety and treatment delivery accuracy. Furthermore, the detector can be used for current patient specific QA.

Purpose: The purpose of this study was to compare the techniques and protocols used in clinical radiation therapy and recently developed preclinical image guided micro irradiation to establish a link between small animal conformal irradiation and clinical treatment protocols. This work will establish protocols that, according to treatment site, will facilitate the translation of conclusions from radiobiological experiments to clinical applications, fostering the advancement of radiotherapy.Methods: Data was gathered using our small animal image guided micro irradiation device, the microIGRT, as an example of preclinical techniques which mimic equivalent clinical treatment protocols. The microIGRT utilizes fractionated treatments, multibeam irradiations, modulated beams, image guided treatment verification, and doses to emulate clinical protocols. Consequently, it is well suited to establish parametric comparisons between clinical and preclinical techniques. In this study, we concentrated on two treatment sites, brain and lung, to define treatment conformality index, homogeneity, penumbra, PDD, and fractionated doses to establish a link to guide radiobiological experiments using clinical protocols as a gold standard. Results: Three and five beam irradiations were delivered to a small animal body and head phantom with radiochromic film to simulate lung and braintreatment. A three beam irradiation to the lung yielded a 625 um penumbra. Compare this value with a human treatment penumbra of 1 cm, and penumbra scales as the ratio between body sizes. The homogeneity of our system is similar to the 10% typically used in clinical treatment planning.Conclusions: By comparing preclinical and clinical treatment metrics, the extent of translation can be determined and improved, leading to better understanding of preclinical results and improved correlation with clinical procedures. This will lead to more clinically based preclinical experiments and improve translation efficiency between the two testing environments, thus providing new clinical treatment strategies and improved human cancer treatment.

Purpose: Implementation of a small animal phase contrastcomputed tomographyscanner to obtain high resolution small animal anatomical images at dose levels that are acceptable for radiobiological preclinical experiments. Methods: The scanner is constructed using a micro focus x‐ray source, a rotating small animal bed, and high resolution amorphous silicondetector. The x‐ray source is a 50 W, 80kVp micro focus x‐ray source with a 10×10 um2 focal spot. The animal bed consists of a rotating base supporting a small animal holder and non‐rebreathing isoflurane anesthesia delivery system. The final component is a flat panel detector with 2048×1024 pixels with a pixel size of 48 um. The detector is mounted on two linear stages orthogonally positioned allowing for fine adjustment of detector positioning and to scan the detector on the image plane to acquire projection images with a matrix area of 2048×2048 pixels by adjoining complementary portions of a projection. The animal holder is located at 25 cm and the detector is at 70 cm from the micro focus source for a system with a magnification of 2.8. Results: MicroPCCT reconstructed tomographic data with a resolution of 50 μm is achievable using 512 projections. The images show the characteristic features of phase contrastimages such as an increase in the contrast at bone/tissue and tissue interfaces when compared with standard microCT images. The images are reconstructed using an adaptation of the Feldkamp's cone beam CT algorithm to enhance the boundaries definition of the phase contrast tomographic images. Conclusions: We evaluated the performance of a microPCCT system by imaging murine models for radiobiological experiments. The system demonstrates the feasibility of acquiring phase contrastimages with bench top equipment and a maximum achievable resolution of 50 μm.

Purpose: We have built a high resolution real time scintillating fiber detector prototype to determine in real time the accuracy of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) treatments when only a fraction of the planned dose was delivered. The motivation of this work is to enhance dose delivery accuracy and to achieve error free radiosurgery. Methods: A high density array of scintillating fibers and a high speed photo detectors array were integrated to implement a high resolution real time dosimeter that can sample with high resolution pulsed SRS and SBRT beams cross sections. The high efficiency of the developed system allows to read each linac pulse in real time and to compute the accumulated dose and dose errors when only a fraction of the beam was delivered. The fibers are highly packed in a substrate that is directly coupled to two 128 pixel arrays with a pitch matching the fiber spacing to achieve accurate spatial localization. The small cross section of the fiber array allows stacking multiple fiber arrays to measure independent angular profiles that are digitally processed in parallel for real time dosimetry. Results: We implemented a high density array detector prototype with a pitch of 0.5more » mm, readout speed of 1.2 msec, and a response time of 0.5 usec. The fast reading speed has the capability to determining the dose in flattening free filter beams. The detector can be installed in transmission mode at the output port of a micro-MLC. Treatment deviations smaller than 3% are detected when less than 1/100 of the planned dose was delivered. Conclusions: We built a prototype of a high resolution fiber scintillator array detector for SRS and SBRT in vivo dosimetry. Results show that the developed detector has the potential to assure error free SRS and SBRT treatments.« less

Purpose: Radiation oncology patients receiving stereotactic body radiation therapy (SBRT) are treated with high dose and high dose rate treatment procedures in which delivered dose should be recorded, and verified for quality assurance and patient safety. We implemented a high resolution scintillating fiber detector array to perform high resolution dosimetry of SBRT fields. Materials: Scintillating fibers have a water equivalent attenuation coefficient, excellent reproducibility, stability and a linear response versus dose, do not require any polarizing voltage, and are water impermeable. We constructed a high resolution dosimeter based on an array of sub‐millimeter organic fiber sensors mounted on a supporting frame that provides support, alignment, and buildup material. The fiber detector interface consists of a high density linear array of high speed linear photodetectors. The analog output is transmitted to a high throughput parallel data acquisition system integrated with a dedicated computer for signal processing, analysis, and recording. The detector was specially designed to perform high resolution dosimetric verification of small SBRT fields delivered with conventional dose rates (600 MU/min) to high dose rate flattening filter free beams (up to 2400 MU/min). Results: We determined fiber sensor sensitivity and linearity response with respect to beam intensity field size and dose. Detector spatial resolution is 0.5 mm and linearity response with respect to beam intensity and field size was within 2% for photon beams from 6MV to 18 MV and electron beams from 6 MeV to 20 MeV. Spatial beam profiles were compared with film dosimetry showing excellent agreement within 3% in the penumbra region. Conclusions: The development of this technology addresses the need for high resolution dosimeters for SBRT. The developed detector provides accurate dose, beam localization, and beam profile verification and will be a valuable tool for quality assurance of SBRT treatments.

Purpose: The purpose of this study was to accurately commission and characterize our small animalimage guided micro irradiator, the microIGRT, for preclinical translational radiobiological research. The microIGRT has a dual gantry architecture with a microCT subsystem gantry for low dose high resolution anatomical imaging and treatment planning, and a second coaxial microRT subsystem gantry for conformal image guided orthovoltage irradiation. Methods: The microCT image resolution, contrast, and dose were evaluated with specialized phantoms and animal models. The micro RT subsystem percent depth dose, beam profile, multibeam irradiation precision and conformality, animal repositioning accuracy, mechanical resolution, and dosimetric accuracy were measured using specialized phantoms equipped with radiochromic film. For each measurement, results were compared with standards adapted from external beam Linac and patient quality assurance protocols scaled to animal dimensions and orthovoltage energies. Results: The microCT dose is 4.15 cGy/scan for 100 um imaging resolution, up to 33.2 cGy/scan for 800 um imaging resolution. The percent depth dose for a 300 kVp beam with 3.8 mm of Cu HVL is 2.7 cGy/mm with a buildup of 2.8 mm. A 1 cm2 standard square field has a 265 um penumbra, 7% homogeneity, and 9% symmetry. Anatomical positioning is within 500 um for fractionated treatments and multibeam isocentric irradiation central axis uncertainty is within a 150 um radius for three, four, and five coplanar beam treatments. Conclusions: We characterized the small animal microIGRT developed by our group to provide complete parameterization of the instrument's imaging and treatment capabilities. Anatomical imaging, irradiation distributions, and beam dosimetry indicate that our system satisfies requirements established by scaling clinical imaging and radiotherapy protocols to animal models to perform clinically relevant translational radiobiological experiments.

Purpose: To develop a tomosynthesis cone beam reconstruction algorithm for LINAC cone beam CT with the goal to achieve a dose reduction better than 1/5 in current cone beam imaging protocols for patient positioning and portal beam verification while maintaining the required image quality for patient positioning and beam delivery verification. Methods: Tomosynthesis is the process of reconstructing tomographic images with fewer acquired projection images and additional synthetically generated projections to preserve image resolution and contrast. We developed a tomosynthesis cone beam reconstruction algorithm based on combining Feldkamp' s cone beam reconstruction algorithm and an iterative maximum likelihood reconstruction algorithm. The Feldkamp method is used to reconstruct the first estimate of the tomographic data and the iterative maximum likelihood algorithm improves the resolution, contrast and considerably eliminates ghost images from the first estimate. Results: The algorithm tests show image reconstruction with the adequate image quality, contrast and resolution for patient positioning and beam delivery verification with a 1/8 dose delivered reduction using current cone beam imaging set‐up protocols. Imaging time is reduced with the same proportion allowing higher patient throughput. The algorithm has been tested using patient data for head and neck and brain treatment sites. On both treatment sites, portal beam and patient localization can be effectively performed within 3 mm accuracy using digitally reconstructed radiographs generated from the tomosynthesisreconstructed patient anatomical image. The reconstruction is executed on a desktop computer with 2GHz CPU and 4 Gb RAM in less than 5 minutes. Conclusions: We developed a tomosynthesis algorithm capable of reconstructingimages with adequate resolution to perform beam delivery verification and patient positioning. This dose reduction will allow the daily use of cone beam CT in patients that require daily set‐up verification which currently is impractical because of dose and time constraints.

Purpose: To study the feasibility of implementing a low cost, high speed in vivo real time dosimeter based on scintillating fiber arrays to verify intensity modulated radiation therapy(IMRT) to enhance treatmentsafety and delivered dose verification. Methods: Detector construction is performed by mounting linear scintillating fiber sensors in a water equivalent plastic support to form a homogenous water equivalent array. The fibers are aligned to match each MLC leaf pair and the detector is placed in the accessory tray of a clinical LINAC for beam output determination. Each fiber is coupled to a high speed photodetector and front end amplifier to process the detector output which is digitized and analyzed using in house developed software to compute the beam fluence, dose rate, and MLC opening. Results: The detector response correlates linearly with the LINAC beam intensity and MLC positions. The sensor and front end amplifier has a time response of 0.2 usec, thus every 2 usec LINAC pulse is recorded to determine the beam fluence with a precision better than 1%. The array offers a minimum beam attenuation of 2.4%, allowing the use of this technology as an in vivo transmission detector. We determined that the detector is capable of measuring the MLC opening with a precision of 2 mm per leaf. Conclusions: We have proven the feasibility of constructing a scintillating fiber sensor array for in vivo real time dosimetry to enhance patient safety during IMRTtreatment and measure actual dose delivered to the patient. The technical highlight of this detector is based on the high speed of the linear sensors and front end amplifier which allows real time verification of the IMRT fluence output, dose rate, and leaf opening with a minimum of perturbation or absorption of the delivered beam.

Purpose: Implementation of a conformal small animal image guided microirradiation therapy instrument (microIGRT) consisting of a cone beam microCT subsystem for submillimeter low dose structural imagingimage guided radiotherapy and orthovoltage conformal microirradiation with high dose rate and high throughput. Method and Materials: The microCT subsystem is based on an 80kVp micro‐focus x‐ray source with 75×75 μm2 focal spot and a flat panel amorphous silicondetector with 1024×1024 pixels. The irradiator consists of a high power commercially available 320 kVp orthovoltage source with a 0.4×0.4 mm2 focal spot that can be operated at a nominal power of 800W. The beam characteristics are controlled with two variable jaws used to pre‐collimate the radiation beam along each orthogonal direction. An aperture exchange mechanism is used to conform the beam cross section by using computer generated apertures. The microCT radiationdose the orthovoltage source spectral output and dose rate are under evaluation using a mouse digital phantom and a pencil beam algorithm. Results:CTimaging with micrometric resolution is achievable using 128 projections and a maximum radiationdose of 2cGy. Automatic animal positioning and handling is performed within sub‐millimeter precision. The treatment beam can be aimed at different latitude and longitude angles and translated with 500 μm steps. The source was tested to deliver a radiationdose rate of 20 Gy/min when is filtered to a half‐value layer of 4.6 mm Cu. Conclusion: We present our progress and initial tests of a highly conformal image guided small animal microirradiator.