Eric Elder

A quality assurance program for the on-board imager ®

To develop a quality assurance (QA) program for the On-Board Imager (OBI) system and to summarize the results of these QA tests over extended periods from multiple institutions. Both the radiographic and cone-beam computed tomography (CBCT) mode of operation have been evaluated. The QA programs from four institutions have been combined to generate a series of tests for evaluating the performance of the On-Board Imager. The combined QA program consists of three parts: (1) safety and functionality, (2) geometry, and (3) image quality. Safety and functionality tests evaluate the functionality of safety features and the clinical operation of the entire system during the tube warm-up. Geometry QA verifies the geometric accuracy and stability of the OBI/CBCT hardware/software. Image quality QA monitors spatial resolution and contrast sensitivity of the radiographic images. Image quality QA for CBCT includes tests for Hounsfield Unit (HU) linearity, HU uniformity, spatial linearity, and scan slice geometry, in addition. All safety and functionality tests passed on a daily basis. The average accuracy of the OBI isocenter was better than 1.5mm with a range of variation of less than 1mm over 8 months. The average accuracy of arm positions in the mechanical geometry QA was better than 1mm, with a range of variation of less than 1mm over 8 months. Measurements of other geometry QA tests showed stable results within tolerance throughout the test periods. Radiographic contrast sensitivity ranged between 2.2% and 3.2% and spatial resolution ranged between 1.25 and 1.6lp∕mm. Over four months the CBCT images showed stable spatial linearity, scan slice geometry, contrast resolution (1%; <7mm disk) and spatial resolution (>6lp∕cm). The HU linearity was within ±40HU for all measurements. By combining test methods from multiple institutions, we have developed a comprehensive, yet practical, set of QA tests for the OBI system. Use of the tests over extended periods show that the OBI system has reliable mechanical accuracy and stable image quality. Nevertheless, the tests have been useful in detecting performance deficits in the OBI system that needed recalibration. It is important that all tests are performed on a regular basis.

Patient‐specific quality assurance method for VMAT treatment delivery

Volumetric modulated arc therapy (VMAT) is a system for intensity-modulated radiotherapy treatment delivery that achieves high dose conformality by optimizing the dose rate, gantry speed, and the leaf positions of the dynamic multileaf collimator (DMLC). The aim of this work is to present a practical approach for patient-specific volumetric reconstruction of the dose delivered of a VMAT treatment using the DMLC and treatment controller log (Dynalog) files. The accuracy of VMAT delivery was analyzed for five prostate patients. For each patient, a clinical treatment was delivered and values recorded in the log files for the gantry angle, dose rate, and leaf positions were converted to a new DICOM-compliant plan using a custom-developed software system. The plan was imported in a treatment planning system and the dose distribution was recreated on the original CT by simply recomputing the dose. Using the standard evaluation tools, it is straightforward to assess if reconstructed dose meets clinical endpoints, as well as to compare side-by-side reconstructed and original plans. The study showed that log files can be directly used for dose reconstruction without resorting to phantom measurements or setups. In all cases, analysis of the leaf positions showed a maximum error of -0.26 mm (mean of 0.15 mm). Gantry angle deviation was less than 1degree and the total MU was within 0.5 from the planned value. Differences between the reconstructed and the intended dose matrices were less than 1.46% for all cases. Measurements using the MATRIXX system in a phantom were used to validate the dosimetric accuracy of the proposed method, with an agreement of at least 96% in all pixels as measured using the gamma index. The methodology provides a volumetric evaluation of the dose reconstructed by VMAT plans which is easily achieved by automated analysis of Dynalog files without additional measurements or phantom setups. This process provides a valuable platform for adaptive therapy in the future.

GVHD after haploidentical transplantation: a novel, MHC-defined rhesus macaque model identifies CD28− CD8+ T cells as a reservoir of breakthrough T-cell proliferation during costimulation blockade and sirolimus-based immunosuppression

We have developed a major histocompatibility complex-defined primate model of graft-versus-host disease (GVHD) and have determined the effect that CD28/CD40-directed costimulation blockade and sirolimus have on this disease. Severe GVHD developed after haploidentical transplantation without prophylaxis, characterized by rapid clinical decline and widespread T-cell infiltration and organ damage. Mechanistic analysis showed activation and possible counter-regulation, with rapid T-cell expansion and accumulation of CD8(+) and CD4(+) granzyme B(+) effector cells and FoxP3(pos)/CD27(high)/CD25(pos)/CD127(low) CD4(+) T cells. CD8(+) cells down-regulated CD127 and BCl-2 and up-regulated Ki-67, consistent with a highly activated, proliferative profile. A cytokine storm also occurred, with GVHD-specific secretion of interleukin-1 receptor antagonist (IL-1Ra), IL-18, and CCL4. Costimulation Blockade and Sirolimus (CoBS) resulted in striking protection against GVHD. At the 30-day primary endpoint, CoBS-treated recipients showed 100% survival compared with no survival in untreated recipients. CoBS treatment resulted in survival, increasing from 11.6 to 62 days (P < .01) with blunting of T-cell expansion and activation. Some CoBS-treated animals did eventually develop GVHD, with both clinical and histopathologic evidence of smoldering disease. The reservoir of CoBS-resistant breakthrough immune activation included secretion of interferon-γ, IL-2, monocyte chemotactic protein-1, and IL-12/IL-23 and proliferation of cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-resistant CD28(-) CD8(+) T cells, suggesting adjuvant treatments targeting this subpopulation will be needed for full disease control.

Dosimetric performance of the new high‐definition multileaf collimator for intracranial stereotactic radiosurgery

The objective was to evaluate the performance of a high‐definition multileaf collimator (MLC) of 2.5 mm leaf width (MLC2.5) and compare to standard 5 mm leaf width MLC (MLC5) for the treatment of intracranial lesions using dynamic conformal arcs (DCA) technique with a dedicated radiosurgery linear accelerator. Simulated cases of spherical targets were created to study solely the effect of target volume size on the performance of the two MLC systems independent of target shape complexity. In addition, 43 patients previously treated for intracranial lesions in our institution were retrospectively planned using DCA technique with MLC2.5 and MLC5 systems. The gross tumor volume ranged from 0.07 to 40.57 cm3 with an average volume of 5.9 cm3. All treatment parameters were kept the same for both MLC‐based plans. The plan evaluation was performed using figures of merits (FOM) for a rapid and objective assessment on the quality of the two treatment plans for MLC2.5 and MLC5. The prescription isodose surface was selected as the greatest isodose surface covering ≥95% of the target volume and delivering 95% of the prescription dose to 99% of target volume. A Conformity Index (CI) and conformity distance index (CDI) were used to quantifying the dose conformity to a target volume. To assess normal tissue sparing, a normal tissue difference (NTD) was defined as the difference between the volume of normal tissue receiving a certain dose utilizing MLC5 and the volume receiving the same dose using MLC2.5. The CI and normal tissue sparing for the simulated spherical targets were better with the MLC2.5 as compared to MLC5. For the clinical patients, the CI and CDI results indicated that the MLC2.5 provides better treatment conformity than MLC5 even at large target volumes. The CIs range was 1.15 to 2.44 with a median of 1.59 for MLC2.5 compared to 1.60–2.85 with a median of 1.71 for MLC5. Improved normal tissue sparing was also observed for MLC2.5 over MLC5, with the NTD always positive, indicating improvement, and ranging from 0.1 to 8.3 for normal tissue receiving 50% (NTV50), 70% (NTV70) and 90% (NTV90) of the prescription dose. The MLC2.5 has a dosimetric advantage over the MLC5 in Linac‐based radiosurgery using DCA method for intracranial lesions, both in treatment conformity and normal tissue sparing when target shape complexity increases. PACS number: 87.56J‐, 87.56 jk

Six degrees of freedom CBCT‐based positioning for intracranial targets treated with frameless stereotactic radiosurgery

Frameless radiosurgery is an attractive alternative to the framed procedure if it can be performed with comparable precision in a reasonable time frame. Here, we present a positioning approach for frameless radiosurgery based on in‐room volumetric imaging coupled with an advanced six‐degrees‐of‐freedom (6 DOF) image registration technique which avoids use of a bite block. Patient motion is restricted with a custom thermoplastic mask. Accurate positioning is achieved by registering a cone‐beam CT to the planning CT scan and applying all translational and rotational shifts using a custom couch mount. System accuracy was initially verified on an anthropomorphic phantom. Isocenters of delineated targets in the phantom were computed and aligned by our system with an average accuracy of 0.2 mm, 0.3 mm, and 0.4 mm in the lateral, vertical, and longitudinal directions, respectively. The accuracy in the rotational directions was 0.1°, 0.2°, and 0.1° in the pitch, roll, and yaw, respectively. An additional test was performed using the phantom in which known shifts were introduced. Misalignments up to 10 mm and 3° in all directions/rotations were introduced in our phantom and recovered to an ideal alignment within 0.2 mm, 0.3 mm, and 0.4 mm in the lateral, vertical, and longitudinal directions, respectively, and within 0.3° in any rotational axis. These values are less than couch motion precision. Our first 28 patients with 38 targets treated over 63 fractions are analyzed in the patient positioning phase of the study. Mean error in the shifts predicted by the system were less than 0.5 mm in any translational direction and less than 0.3° in any rotation, as assessed by a confirmation CBCT scan. We conclude that accurate and efficient frameless radiosurgery positioning is achievable without the need for a bite block by using our 6 DOF registration method. This system is inexpensive compared to a couch‐based 6 DOF system, improves patient comfort compared to systems that utilize a bite block, and is ideal for the treatment of pediatric patients with or without general anesthesia, as well as of patients with dental issues. From this study, it is clear that only adjusting for 4 DOF may, in some cases, lead to significant compromise in PTV coverage. Since performing the additional match with 6 DOF in our registration system only adds a relatively short amount of time to the overall process, we advocate making the precise match in all cases. PACS number: 87.55.tm; 87.55.Qr; 87.57.nj

Performance evaluation of an automated image registration algorithm using an integrated kilovoltage imaging and guidance system.

Image‐guided radiation therapy delivery may be used to assess the position of the tumor and anatomical structures within the body as opposed to relying on external marks. The purpose of this manuscript is to evaluate the performance of the image registration software for automatically detecting and repositioning a 3D offset of a phantom using a kilovoltage onboard imaging system. Verification tests were performed on both a geometric rigid phantom and an anthropomorphic head phantom containing a humanoid skeleton to assess the precision and accuracy of the automated positioning system. From the translation only studies, the average deviation between the detected and known offset was less than 0.75 mm for each of the three principal directions, and the shifts did not show any directional sensitivity. The results are given as the measurement with standard deviation in parentheses. The combined translations and rotations had the greatest average deviation in the lateral, longitudinal, and vertical directions. For all dimensions, the magnitude of the deviation does not appear to be correlated with the magnitude of the actual translation introduced. The On‐Board Imager™ (OBI) system has been successfully integrated into a feasible online radiotherapy treatment guidance procedure. Evaluation of each patients resulting automatch should be performed by therapists before each treatment session for adequate clinical oversight. PACS numbers: 87.53.‐j, 87.53.Xd, 87.57.Gg

EARLY CLINICAL EXPERIENCE WITH KILOVOLTAGE IMAGE-GUIDED RADIATION THERAPY FOR INTERFRACTION MOTION MANAGEMENT

Interest in image-guided radiation therapy (IGRT) reflects the desire to minimize interfraction positioning variability. Using a kilovoltage (kV) imaging unit mounted to a traditional LINAC allows daily matching of kV images to planning digitally reconstructed radiographs (DRRs). We quantify and evaluate the significance of calculated deviation from the intended isocenter. Since September 2004, 117 patients with various malignancies were treated using the On-Board Imaging (OBI) system, with 2088 treatment sessions. Patients were positioned by the treating therapist; orthogonal images were then obtained with the OBI unit. Couch shifts were made, aligning bony anatomy to the initial simulation image. Routine port films were performed weekly (after that days OBI session). Ninety percent of all lateral, longitudinal, and vertical shifts were less than 0.8 cm, 0.6 cm, and 0.7 cm, respectively. The median vector shift for each anatomic site was: 0.42 cm for head and neck, 0.40 cm for CNS, 0.59 cm for GU/prostate, and 0.73 cm for breast; shift magnitude did not change with successive OBI sessions. The use of OBI effectively corrects setup variability. These shifts are typically small and random. The use of OBI likely can replace weekly port films for isocenter verification; however, OBI does not provide field shape verification.

CD8-predominant T-cell CNS infiltration accompanies GVHD in primates and is improved with immunoprophylaxis.

To the editor: A recently published article in Blood showed that, in mice, the central nervous system (CNS) is a target of graft-versus-host-disease (GVHD).[1][1] However, diagnosing CNS GVHD in the clinic is challenging,[2][2][⇓][3]-[4][4] and until now, evidence in a large-animal model has been

Automated Quality Assurance for Image-Guided Radiation Therapy

The use of image‐guided patient positioning requires fast and reliable Quality Assurance (QA) methods to ensure the megavoltage (MV) treatment beam coincides with the integrated kilovoltage (kV) or volumetric cone‐beam CT (CBCT) imaging and guidance systems. Current QA protocol is based on visually observing deviations of certain features in acquired kV in‐room treatment images such as markers, distances, or HU values from phantom specifications. This is a time‐consuming and subjective task because these features are identified by human operators. The method implemented in this study automated an IGRT QA protocol by using specific image processing algorithms that rigorously detected phantom features and performed all measurements involved in a classical QA protocol. The algorithm was tested on four different IGRT QA phantoms. Image analysis algorithms were able to detect QA features with the same accuracy as the manual approach but significantly faster. All described tests were performed in a single procedure, with acquisition of the images taking approximately 5 minutes, and the automated software analysis taking less than 1 minute. The study showed that the automated image analysis based procedure may be used as a daily QA procedure because it is completely automated and uses a single phantom setup. PACS numbers: 87.56.Fc

Transitioning glass-ceramic scintillators for diagnostic x-ray imaging from the laboratory to commercial scale

This study sought to mitigate risk in transitioning newly developed glass-ceramic scintillator technology from a laboratory concept to commercial product by identifying the most significant hurdles to increased scale. These included selection of cost effective raw material sources, investigation of process parameters with the most significant impact on performance, and synthesis steps that could see the greatest benefit from participation of an industry partner that specializes in glass or optical component manufacturing. Efforts focused on enhancing the performance of glass-ceramic nanocomposite scintillators developed specifically for medical imaging via composition and process modifications that ensured efficient capture of incident X-ray energy and emission of scintillation light. The use of cost effective raw materials and existing manufacturing methods demonstrated proof-of-concept for economical viable alternatives to existing benchmark materials, as well as possible disruptive applications afforded by novel geometries and comparatively lower cost per volume. The authors now seek the expertise of industry to effectively navigate the transition from laboratory demonstrations to pilot scale production and testing to evince the industry of the viability and usefulness of composite-based scintillators.