H Sakhalkar

A comprehensive evaluation of the PRESAGE/optical-CT 3D dosimetry system

This work presents extensive investigations to evaluate the robustness (intradosimeter consistency and temporal stability of response), reproducibility, precision, and accuracy of a relatively new 3D dosimetry system comprising a leuco-dye doped plastic 3D dosimeter (PRESAGE) and a commercial optical-CT scanner (OCTOPUS 5x scanner from MGS Research, Inc). Four identical PRESAGE 3D dosimeters were created such that they were compatible with the Radiologic Physics Center (RPC) head-and-neck (H&N) IMRT credentialing phantom. Each dosimeter was irradiated with a rotationally symmetric arrangement of nine identical small fields (1 x 3 cm2) impinging on the flat circular face of the dosimeter. A repetitious sequence of three dose levels (4, 2.88, and 1.28 Gy) was delivered. The rotationally symmetric treatment resulted in a dose distribution with high spatial variation in axial planes but only gradual variation with depth along the long axis of the dosimeter. The significance of this treatment was that it facilitated accurate film dosimetry in the axial plane, for independent verification. Also, it enabled rigorous evaluation of robustness, reproducibility and accuracy of response, at the three dose levels. The OCTOPUS 5x commercial scanner was used for dose readout from the dosimeters at daily time intervals. The use of improved optics and acquisition technique yielded substantially improved noise characteristics (reduced to approximately 2%) than has been achieved previously. Intradosimeter uniformity of radiochromic response was evaluated by calculating a 3D gamma comparison between each dosimeter and axially rotated copies of the same dosimeter. This convenient technique exploits the rotational symmetry of the distribution. All points in the gamma comparison passed a 2% difference, 1 mm distance-to-agreement criteria indicating excellent intradosimeter uniformity even at low dose levels. Postirradiation, the dosimeters were all found to exhibit a slight increase in opaqueness with time. However, the relative dose distribution was found to be extremely stable up to 90 h postirradiation indicating excellent temporal stability. Excellent interdosimeter reproducibility was also observed between the four dosimeters. Gamma comparison maps between each dosimeter and the average distribution of all four dosimeters showed full agreement at the 2% difference, 2 mm distance-to-agreement level. Dose readout from the 3D dosimetry system was found to agree better with independent film measurement than with treatment planning system calculations in penumbral regions and was generally accurate to within 2% dose difference and 2 mm distance-to-agreement. In conclusion, these studies demonstrate excellent precision, accuracy, robustness, and reproducibility of the PRESAGE/optical-CT system for relative 3D dosimetry and support its potential integration with the RPC H&N credentialing phantom for IMRT verification.

Three-dimensional imaging of whole rodent organs using optical computed and emission tomography

We explore the potential of optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) in a new area-whole organ imaging. The techniques are implemented on an in-house prototype benchtop system with improved image quality and the capacity to image larger samples (up to 3 cm) than previous systems based on stereo microscopes. Imaging performance tests confirm high geometrical accuracy, accurate relative measurement of linear attenuation coefficients, and the ability to image features at the 50-microm level. Optical labeling of organ microvasculature was achieved using two stains deposited via natural in vivo circulatory processes: a passive absorbing ink-based stain and an active fluorescin FITC-lectin conjugate. The lectin protein binds to the endothelial lining, and FITC fluorescense enables optical-ECT imaging. Three-dimensional (3-D) optical-CT images have been acquired of a normal rat heart and left lung and a mouse right lung showing exquisite detail of the functional vasculature and relative perfusion distribution. Coregistered optical-ECT images were also acquired of the mouse lung and kidney. Histological sections confirmed effective labeling of microvasculature throughout the organs. The advantages of optical-CT and optical-ECT include the potential for a unique combination of high resolution and high contrast and compatibility with a wide variety of optical probes, including gene expression labeling fluorescent reporter proteins.

Three-dimensional imaging of xenograft tumors using optical computed and emission tomography

The physical basis and preliminary applications of optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) are introduced, as new techniques with potential to provide unique 3D information on a variety of aspects of tumor structure and function. A particular focus here is imaging tumor micro-vasculature, and the spatial distribution of viable tumor cells, although the techniques have the potential for much wider application. The principle attractiveness of optical-CT and optical-ECT are that high resolution (<20 microm) and high contrast co-registered 3D images of structure and function can be acquired for relatively large intact samples. The unique combination of high contrast and resolution offers advantages over micro-CT and micro-MRI, and the lack of requirement for sectioning offers advantages over confocal microscopy, conventional microscopy, and histological sectioning techniques. Optical-CT/ECT are implemented using in-house custom apparatus and a commercial dissecting microscope capable of both transmission and fluorescence imaging. Basic studies to characterize imaging performance are presented. Negligible geometrical distortion and accurate reconstruction of relative attenuation coefficients was observed. Optical-CT and optical-ECT are investigated here by application to high resolution imaging of HCT116 xenograft tumors, about 1 cc in dimension, which were transfected with constitutive red fluorescent protein (RFP). Tumor microvasculature was stained in vivo by tail vein injection of either passive absorbing dyes or active fluorescent markers (FITC conjugated lectin). Prior to imaging, the tumors were removed (ex vivo) and optically cleared in a key process to make the samples amenable to light transmission. The cleared tumors were imaged in three modes (i) optical-CT to image the 3D distribution of microvasculature as indicated by absorbing dye, (ii) optical-ECT using the FITC excitation and emission filter set, to determine microvasculature as indicated by lectin-endothelial binding, and (iii) optical-ECT using the DSRed2 filter set to determine the 3D distribution of viable tumor as indicated by RFP emission. A clear correlation was observed between the independent vasculature imaging modes (i) and (ii) and postimaging histological sections, providing substantial validation of the optical-CT and optical-ECT techniques. Strong correlation was also observed between the RFP imaging of mode iii, and modes i and ii, supporting the intuitive conclusion that well-perfused regions contain significant viable tumor. In summary, optical-CT and optical-ECT, when combined with new optical clearing techniques, represent powerful new imaging modalities with potential for providing unique information on the structure and function of tumors.

An investigation into the robustness of Optical-CT dosimetry of a radiochromic dosimeter compatible with the RPC Head-and-Neck Phantom

The potential of the PRESAGE™/Optical-CT system as a comprehensive 3D dosimetry tool has been demonstrated. The current study focused on detailed characterization of robustness (intra-dosimeter uniformity and temporal stability) and reproducibility (inter-dosimeter reproducibility) of PRESAGE™ inserts compatible with the RPC H&N phantom. In addition, the accuracy and precision of PRESAGE dose measurement was also evaluated. Four identical PRESAGE™ dosimeters (10cm diameter and 7cm height cylinders) were irradiated with the same rotationally symmetric treatment plan using a Varian accelerator. The treatment plan was designed to rigorously evaluate robustness and reproducibility for multiple dose levels and in 3D. All dosimeters were scanned by optical-CT at daily intervals to study temporal stability. Dose comparisons were made between PRESAGE, ECLIPSE, and independent measurement with EBT film at a select depth. The use of improved optics and acquisition technique yielded substantially higher quality 3D dosimetry data from PRESAGE than has been achieved previously (noise reduced to ~1%, accuracy to within 3%). Data analysis showed excellent intra-dosimeter uniformity, temporal stability and inter-dosimeter reproducibility of relative radiochromic response. In general, the PRESAGE™ dose-distribution was found to agree better with EBT (~99% pass rate) than with ECLIPSE calculations (~92% pass rate) especially in penumbral regions for a 3% dose-difference and 3 mm distance-to-agreement evaluation criteria. The results demonstrate excellent robustness and reproducibility of the PRESAGE™ for relative 3D-dosimetry and represent a significant step towards incorporation in the RadOnc-clinic (e.g. integration with RPC phantom).

Investigating the Feasibility of 3D Dosimetry in the RPC IMRT H&N Phantom.

An urgent requirement for 3D dosimetry has been recognized because of high failure rate (~25%) in RPC credentialing, which relies on point and 2D dose measurements. Comprehensive 3D dosimetry is likely to resolve more errors and improve IMRT quality assurance. This work presents an investigation of the feasibility of PRESAGE/optical-CT 3D dosimetry in the Radiologic Physics Center (RPC) IMRT H&N phantom. The RPC H&N phantom (with standard and PRESAGE dosimetry inserts alternately) was irradiated with the same IMRT plan. The TLD and EBT film measurement data from standard insert irradiation was provided by RPC. The 3D dose measurement data from PRESAGE insert irradiation was readout using the OCTOPUS™ 5X optical-CT scanner at Duke. TLD, EBT and PRESAGE dose measurements were inter-compared with Eclipse calculations to evaluate consistency of planning and delivery. Results showed that the TLD point dose measurements agreed with Eclipse calculations to within 5% dose-difference. Relative dose comparison between Eclipse dose, EBT dose and PRESAGE dose was conducted using profiles and gamma comparisons (4% dose-difference and 4 mm distance-to-agreement). Profiles showed good agreement between measurement and calculation except along steep dose gradient regions where Eclipse modelling might be inaccurate. Gamma comparisons showed that the measurement and calculation showed good agreement (>96%) if edge artefacts in measurements are ignored. In conclusion, the PRESAGE/optical-CT dosimetry system was found to be feasible as an independent dosimetry tool in the RPC IMRT H&N phantom.

Towards four dimensional (4D) dosimetry for radiation-therapy

The development of accurate and convenient dosimetry tools with the capacity to comprehensively verify advanced four-dimensional treatments is an important and urgent goal for radiation therapy physicists. At present, implementation into the clinic is being severely hampered and delayed by the difficulty in adequately verifying these techniques using traditional dosimetry methods. The work presented here represents an important step towards providing a solution.

A dual-purpose CCD based micro-optical-CT scanning system.

The concept of three dimensional (3D) dosimetry by optical-computed-tomography (optical-CT) of radiation induced optical contrast was first introduced in 1996 (Gore J C, Ranade M, Maryanski M J and Schulz R J 1996 Phys. Med. Biol. 41 2695-2704 and Maryanski M J, Zastavker Y Z and Gore J C 1996 Phys. Med. Biol. 41 2705-2717) and developed later by other groups. These works describe a first generation optical-CT system based on measurement of the transmission of single scanning laser beam that scanned the dosimeter in a rastering manner. Second generation systems can be categorized as macroscopic scanners developed for 3D dosimetry, and microscopic scanners developed for embryo imaging. Here we introduce a new system that bridges this divide. It is designed to be a dual purpose, micro-optical-CT system, with capability to perform both 3D micro-dosimetry on dosimeters up to 5 cm diameter, and to image structure and function of optically cleared tissue samples in transmission mode (optical-CT) and emission mode (optical-ECT).

TU‐E‐304A‐06: A 3D Solution for Advanced Photon Arc Therapy Quality Assurance

Purpose: Recently, radiation treatment technology has out‐paced the advances in QA technology, and a critical gap has been created within the arc motion delivery systems such as Rapid Arc®, High Art®, and VMAT®. Gantry position, speed and MU rate create extra degrees of complexity unaccounted for by several traditional 2D QA verifications due to directional dependence and/or inadequate spatial resolution. We present the 1st 3D dosimetry verification of a Rapid Arc treatment and general dosimetry technique based on a radio‐chromic plastic (PRESAGE™)/optical‐CT (OCTOPUS™) combination suitable for todays complex treatment technology. Method and Materials: A radio‐chromic plastic cylinder 17cm diameter × 11cm height was used to verify a simplistic Rapid Arc 6MV prostate plan. The radiation induced OD change (proportional to dosedelivered) was acquired by an optical‐CT scanner with a voxel size of 1×1×2.5mm3. The measured distribution was then compared with the corresponding dose distribution calculated by the treatment planning system (Eclipse® AAA, voxel size 2.5×2.5×2.5mm3). Comparisons between the two dose distributions were made using dose profiles and stacked 2D gamma maps (with criteria 3% dose difference and 3mm distance to agreement) for a quasi 3D gamma volume. Results: The 3D dose distribution measured profiles in the dosimeter showed agreement amongst the calculated treatment plan down to lower dose regions (down to ∼35%). Gamma map comparisons show the dosimeter measurements generally agree with the calculated treatment plan with a few low dose bath problem areas superior and inferior. More traditional QA techniques showed the same discrepancy areas of the plan. This aided in the verification of the system commissioning process. Conclusion: Radio‐chromic plastic/optical‐CT dosimetry techniques are capable of providing 3D, high spatial resolution verification for patient QA with advanced treatment techniques or commissioning, and the potential for its use at other treatment sites where the fluence is more complex.

SU‐FF‐I‐153: First Experience of High Resolution 3D Optical‐CT Scanning of An Anthropomorphic, Leuco‐Dye Doped, Radiochromic Plastic Dosimeter

Purpose: To investigate feasibility of high‐resolution three dimensional (3D) optical‐CT scanning of an anthropomorphic leuco‐dye doped radiochromic plastic dosimeter. Method and Materials: An anthropomorphic head phantom made out of PRESAGE™ (a leuco‐dye‐doped radiochromic plastic) was from Heuris Pharma. Co‐planar alignment marks (visible on x‐ray CT and optical‐CT) were placed on the surface. These were used to setup the phantom for x‐ray CT and treatment and for registration of measured dose from optical‐CT with the eclipse treatment planning system calculations. A RapidArc™ treatment for braintumor was delivered and radiochromic response was scanned using optical‐CT. Optical‐CT (pre‐irradiation and post‐irradiation) was with a commercial laser beamscanner called OCTOPUS‐5X™ (MGS Research Inc). The following imaging parameters were used: Image matrix of 418×418, pixel size of 0.5 mm, 1200 projections at 0.3 degree angular increments and inter‐slice spacing of 2.5 mm. The relationship between post‐irradiation radiochromic response and dose was established by irradiation of 1 cm path‐length cuvettes to a known dose and measuring the corresponding optical density change. Results: Pre‐irradiation and post‐irradiation optical‐CT scans of the head‐phantom were promising with artefacts generally confined to the edge because of refractive index mismatch between scanning fluid and phantom material. Even with a refractive index mismatch, challenging surfaces like the nose and ears were reconstructed with clarity. A profile through the center of the reconstructed central slice was flat suggesting uniform optical density. Further improvements to optical‐CT images are possible by satisfying the Nyquist sampling‐sufficiency criteria and with precise refractive index matching. Cuvette irradiations confirmed that the relationship between delivered dose and radiochromic response was linear with a slope of 0.0144 OD change per Gray. Conclusion: Results suggest that anthropomorphic dosimetry phantoms could be used for patient specific 3D quality‐assurance in the near future, which represents a major advance in the field of 3D dosimetry.

SU‐FF‐T‐314: Patient‐Specific Quality Assurance Techniques for RapidArc Radiotherapy

Purpose: To develop a patient‐specific quality assurance protocol for RapidArc™ radiotherapy.Method and Materials: Following the commissioning of RapidArc™ treatment delivery, we tested several methods of patient‐specific quality assurance (QA). Ion chamber and film measurements were used as the “gold standard”. One ion chamber measurement was taken in a region of low‐dose gradient. Four film measurements were taken in three planes: axial, sagittal, coronal, and a coronal180° (testing setup uncertainty). Measurements were also taken using the Matrixx® device (IBA Dosimetry, Bartlett, TN) in two orientations, sagittal and coronal. The Matrixx® consists of a 24×24cm2 grid of ion chambers, providing a 2D absolute dose comparison. All plans were designed and calculated using Eclipse (Varian Medical Systems, Palo Alto, CA). Eleven patient plans were evaluated, consisting of 4 brain, 1 head&neck boost, and 6 prostate radiotherapy treatments. Results:Ion chamber measurements were typically ∼2% greater than those predicted by Eclipse. Using a gamma index with 3%, 3mm, 5% threshold criteria, 88% of films had gamma pass rates of >90%. Three of 7 axial films failed, but passed with thresholds of 30–40%. Similarly, Matrixx® measurements had gamma pass rates of >90% for 100% of measurements. The average reading of 4 Matrixx ion chambers was significantly correlated with the single ion chamber results (Pearson correlation coefficient = 0.839, p = 0.002), and the 2D Matrixx results agreed well with film measurements (gamma pass rate >90% for 10 of 11 comparisons). Conclusion: These QA measurements produced good agreement between planned and measured doses. Through utilizing ion chamber and film measurements, we have gained confidence in the Matrixx® for RapidArc QA. The chosen passing criteria were +/−3% for ion chamber readings, and gamma passing rates of >90% for film and Matrixx® with 3%, 3mm, and 5% threshold.