Commissioning, clinical implementation, and initial experience with a new brain tumor treatment package on a low-field MR-linac.

To evaluate the image quality, dosimetric properties, setup reproducibility, and planar cine motion detection of a high-resolution brain coil and integrated stereotactic brain immobilization system that constitute a new brain treatment package (BTP) on a low-field magnetic resonance imaging (MRI) linear accelerator (MR-linac). Image quality of the high-resolution brain coil was evaluated with the 17 cm diameter spherical phantom and the American College of Radiology (ACR) Large MRI Phantom. Patient imaging studies approved by the institutional review board (IRB) assisted in selecting image acquisition parameters. Radiographic and dosimetric evaluation of the high-resolution brain coil and the associated immobilization devices was performed using dose calculations and ion chamber measurements. End-to-end testing was performed simulating a cranial lesion in a phantom. Inter-fraction setup variability and motion detection tests were evaluated on four healthy volunteers. Inter-fraction variability was assessed based on three repeat setups for each volunteer. Motion detection was evaluated using three-plane (axial, coronal, and sagittal) MR-cine imaging sessions, where volunteers were asked to perform a set of specific motions. The images were post-processed and evaluated using an in-house program. Contrast resolution of the high-resolution brain coil is superior to the head/neck and torso coils. The BTP receiver coils have an average HU value of 525 HU. The most significant radiation attenuation (3.14%) of the BTP, occurs through the lateral portion of the overlay board where the high-precision lateral-profile mask clips attach to the overlay. The greatest inter-fraction setup variability occurred in the pitch (average 1.08 degree) and translationally in the superior/inferior direction (average 4.88 mm). Three plane cine imaging with the BTP was able to detect large and small motions. Small voluntary motions, sub-millimeter in magnitude (maximum 0.9 mm), from motion of external limbs were detected. Imaging tests, inter-fraction setup variability, attenuation, and end-to-end measurements were quantified and performed for the BTP. Results demonstrate better contrast resolution and low contrast detectability that allows for better visualization of soft tissue anatomical changes relative to head/neck and torso coil systems.

Impact of MRI resolution for Linac-based stereotactic radiosurgery.

Objective: Magnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS. Materials/Methods: Four T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness (SE5mm, SE3mm) and two gradient echo 3D acquisitions (TFE, BRAVO). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm3, respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53-25.0 cm3) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and the ratio between reconstructed and true volume (Ratiovol ). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index ( C I p a d d i c k t r u e ), calculated with true target volume, was correlated with quality of observer volume. Results: All measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO. The improvement in DSC, HD and MDA was statistically significant (p<0.01). Dosimetrically, C I p a d d i c k t r u e   strongly correlated with DSC of the planning observer volume (Pearson's r=0.94, p<0.00001). Conclusions: Significant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided.

Dosimetric Evaluation of Fractionated Stereotactic Radiation Therapy for Skull Base Meningiomas Using HyperArc and Multicriteria Optimization.

PURPOSE: Treatment planning of skull based meningiomas can be difficult due to the irregular shaped target volumes and proximity to critical optic structures. This study evaluated the use of HyperArc (HA) radiosurgery optimization and delivery in conjunction with multicriteria optimization (MCO) to create conformal and efficient treatment plans for conventionally fractionated radiation therapy to difficult base-of-skull (BOS) lesions. METHODS AND MATERIALS: Twelve patients with BOS meningioma were retrospectively planned with HA-specific optimization algorithm, stereotactic normal tissue objective (SRS-NTO), and conventional automatic normal tissue objective to evaluate normal brain sparing (mean dose and V20 Gy). MCO was used on both SRS-NTO and automatic normal tissue objective plans to further decrease organ-at-risk doses and target dose maximum to within clinically acceptable constraints. Delivery efficiency was evaluated based on planned monitor units. RESULTS: The SRS-NTO in HA can be used to improve the mid- and low-dose spread to normal brain tissue in the irradiation of BOS meningiomas. Improvement in normal brain sparing can be seen in larger, more irregular shaped lesions and less so in smaller spherical targets. MCO can be used in conjunction with the SRS-NTO to reduce target dose maximum and dose to organ at risk without sacrificing the gain in normal brain sparing. CONCLUSIONS: HA can be beneficial both in treatment planning by using the SRS-NTO and in delivery efficiency through the decrease in monitor units and automated delivery.

Targeting accuracy at couch kick for a frameless image guided radiosurgery system.

PURPOSE/OBJECTIVES: Targeting accuracy at all possible couch angles needs to be carefully evaluated prior to initiating a frameless image-guided stereotactic radiosurgery program on a Linac for treating functional disorders such as trigeminal neuralgia. In this study, we report positioning accuracy with stereoscopic x-ray imaging over the complete range of couch rotation using anthropomorphic head phantoms. MATERIALS/METHODS: An anthropomorphic head phantom with three 5 mm tungsten BBs as hidden targets was CT simulated. A group of 7 arcs was planned with couch angles from 0 to 90° in 15° increments. A pair of stereoscopic x-ray images that auto-matches to planning CT according to bony anatomy was utilized to position each BB to machine isocenter at all planned couch angles. Targeting accuracy was measured by stereoscopic x-ray imaging of the BB itself, which provides the distance from the centroid of BB to the x-ray imaging isocenter. For each BB, the hidden target test was repeated 5 times at couch 0° and 3 times at other couch angles, resulting in a total of 69 measurements, each with random initial setup deviation. Following the same workflow, a second anthropomorphic head phantom with two 5 mm BBs was utilized to evaluate localization accuracy at couch angles of 0 through 270° in 15° increments, resulting in another 18 measurements. RESULTS: Residual setup deviation following image guidance in the first head phantom was 0.6±0.1, 0.4±0.1, and 0.4±0.1 mm, respectively, at the three BBs, and 0.5±0.1 mm overall (N=69). Comparable results of 0.4±0.1 mm (N=18) were achieved with the second head phantom. Combining results from both phantoms, the targeting accuracy was 0.5±0.1 mm (range 0.2-0.8 mm). No apparent correlation was observed between targeting accuracy and couch rotation. CONCLUSIONS: Accurate positioning within 1 mm can be achieved with stereoscopic x-ray imaging at any couch angle. Frameless image-guided stereotactic radiosurgery could achieve targeting accuracy similar to that of frame-based systems for high dose treatment of trigeminal neuralgia.

The safety of magnetic resonance imaging-guided laser interstitial thermal therapy for cerebral radiation necrosis.

Cerebral radiation necrosis (CRN) is a known complication of radiation therapy. Treatment options are limited and include steroids, bevacizumab, and surgery. This study seeks to determine the safety of laser interstitial thermal therapy (LITT) for CRN and identify the pattern of post-ablation volume change over time. Patients undergoing LITT for tumor treatment at Henry Ford Hospital between November 2013 and January 2016 with biopsy-confirmed CRN were prospectively collected and retrospectively reviewed with attention to ablation volume, survival, demographic data, steroid dose, and complications. Imaging occurred at set intervals beginning pre-ablation. Ten patients with 11 ablations were evaluated. Four patients had a primary diagnosis of high-grade glioma, while six had metastatic lesions. An average of 86% of CRN volume was ablated. Ablation volume increased to 430% of initial CRN volume at 1-2 weeks before decreasing to 69% after 6 months. No patient had a decline in baseline neurological examination while in the hospital. Four patients developed delayed neurological deficits likely due to post-operative edema, of which three improved back to baseline. The 6-month survival was 77.8% and the 1-year survival was 64.8% based on Kaplan-Meier curve estimates. In this study, LITT was a relatively safe treatment for CRN, providing both a diagnostic and therapeutic solution for refractory patients. Significant increase in ablation volume was noted at 1-2 months, gradually decreasing in size to less than the original volume by 6 months. Further studies are needed to better define the role of LITT in the treatment of CRN.

American Association of Physicists in Medicine Task Group 263: Standardizing Nomenclatures in Radiation Oncology.

A substantial barrier to the single- and multi-institutional aggregation of data to supporting clinical trials, practice quality improvement efforts, and development of big data analytics resource systems is the lack of standardized nomenclatures for expressing dosimetric data. To address this issue, the American Association of Physicists in Medicine (AAPM) Task Group 263 was charged with providing nomenclature guidelines and values in radiation oncology for use in clinical trials, data-pooling initiatives, population-based studies, and routine clinical care by standardizing: (1) structure names across image processing and treatment planning system platforms; (2) nomenclature for dosimetric data (eg, dose-volume histogram [DVH]-based metrics); (3) templates for clinical trial groups and users of an initial subset of software platforms to facilitate adoption of the standards; (4) formalism for nomenclature schema, which can accommodate the addition of other structures defined in the future. A multisociety, multidisciplinary, multinational group of 57 members representing stake holders ranging from large academic centers to community clinics and vendors was assembled, including physicists, physicians, dosimetrists, and vendors. The stakeholder groups represented in the membership included the AAPM, American Society for Radiation Oncology (ASTRO), NRG Oncology, European Society for Radiation Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), Children's Oncology Group (COG), Integrating Healthcare Enterprise in Radiation Oncology (IHE-RO), and Digital Imaging and Communications in Medicine working group (DICOM WG); A nomenclature system for target and organ at risk volumes and DVH nomenclature was developed and piloted to demonstrate viability across a range of clinics and within the framework of clinical trials. The final report was approved by AAPM in October 2017. The approval process included review by 8 AAPM committees, with additional review by ASTRO, European Society for Radiation Oncology (ESTRO), and American Association of Medical Dosimetrists (AAMD). This Executive Summary of the report highlights the key recommendations for clinical practice, research, and trials.

Evaluation of adaptive treatment planning for patients with non-small cell lung cancer.

The purpose of this study was to develop metrics to evaluate uncertainties in deformable dose accumulation for patients with non-small cell lung cancer (NSCLC). Initial treatment plans (primary) and cone-beam CT (CBCT) images were retrospectively processed for seven NSCLC patients, who showed significant tumor regression during the course of treatment. Each plan was developed with IMRT for 2 Gy × 33 fractions. A B-spline-based DIR algorithm was used to register weekly CBCT images to a reference image acquired at fraction 21 and the resultant displacement vector fields (DVFs) were then modified using a finite element method (FEM). The doses were calculated on each of these CBCT images and mapped to the reference image using a tri-linear dose interpolation method, based on the B-spline and FEM-generated DVFs. Contours propagated from the planning image were adjusted to the residual tumor and OARs on the reference image to develop a secondary plan. For iso-prescription adaptive plans (relative to initial plans), mean lung dose (MLD) was reduced, on average from 17.3 Gy (initial plan) to 15.2, 14.5 and 14.8 Gy for the plans adapted using the rigid, B-Spline and FEM-based registrations. Similarly, for iso-toxic adaptive plans (considering MLD relative to initial plans) using the rigid, B-Spline and FEM-based registrations, the average doses were 69.9 ± 6.8, 65.7 ± 5.1 and 67.2 ± 5.6 Gy in the initial volume (PTV1), and 81.5 ± 25.8, 77.7 ± 21.6, and 78.9 ± 22.5 Gy in the residual volume (PTV21), respectively. Tumor volume reduction was correlated with dose escalation (for isotoxic plans, correlation coefficient = 0.92), and with MLD reduction (for iso-fractional plans, correlation coefficient = 0.85). For the case of the iso-toxic dose escalation, plans adapted with the B-Spline and FEM DVFs differed from the primary plan adapted with rigid registration by 2.8 ± 1.0 Gy and 1.8 ± 0.9 Gy in PTV1, and the mean difference between doses accumulated using the B-spline and FEM DVF's was 1.1 ± 0.6 Gy. As a dose mapping-induced energy change, energy defect in the tumor volume was 20.8 ± 13.4% and 4.5 ± 2.4% for the B-spline and FEM-based dose accumulations, respectively. The energy defect of the B-Spline-based dose accumulation is significant in the tumor volume and highly correlated to the difference between the B-Spline and FEM-accumulated doses with their correlation coefficient equal to 0.79. Adaptive planning helps escalate target dose and spare normal tissue for patients with NSCLC, but deformable dose accumulation may have a significant loss of energy in regressed tumor volumes when using image intensity-based DIR algorithms. The metric of energy defect is a useful tool for evaluation of adaptive planning accuracy for lung cancer patients.

Characterization and evaluation of 2.5 MV electronic portal imaging for accurate localization of intra- and extracranial stereotactic radiosurgery.

2.5 MV electronic portal imaging, available on Varian TrueBeam machines, was characterized using various phantoms in this study. Its low-contrast detectability, spatial resolution, and contrast-to-noise ratio (CNR) were compared with those of conventional 6 MV and kV planar imaging. Scatter effect in large patient body was simulated by adding solid water slabs along the beam path. The 2.5 MV imaging mode was also evaluated using clinically acquired images from 24 patients for the sites of brain, head and neck, lung, and abdomen. With respect to 6 MV, the 2.5 MV achieved higher contrast and preserved sharpness on bony structures with only half of the imaging dose. The quality of 2.5 MV imaging was comparable to that of kV imaging when the lateral separation of patient was greater than 38 cm, while the kV image quality degraded rapidly as patient separation increased. Based on the results of patient images, 2.5 MV imaging was better for cranial and extracranial SRS than the 6 MV imaging.

Use of jaw tracking in intensity modulated and volumetric modulated arc radiation therapy for spine stereotactic radiosurgery.

PURPOSE: This study was conducted to evaluate the advantages of jaw tracking for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) in spine radiosurgery. METHODS AND MATERIALS: VMAT and IMRT plans were retrospectively generated for 10 RTOG 0631 spine radiosurgery protocol patients. A total of 8 plans for each patient were created for a Varian TrueBeam equipped with a Millennium 120 multileaf collimator. Plans were created to compare IMRT and VMAT plans with and without jaw tracking, as well as with different flattening-filter-free energies: 6 MV unflattened (6U) and 10 MV unflattened (10U). The plans were prescribed to the 90% isodose line to either 16 or 18 Gy in 1 fraction. Planning target volume coverage, conformity index, dose to the spinal cord, and distance to falloff from the 90% to 50% isodose line were evaluated. Ion chamber and film measurements were performed to verify calculated dose distributions. RESULTS: Jaw tracking decreased spinal cord dose for both IMRT and VMAT plans, but a larger decrease was seen with the IMRT plans (P = .004 vs P = .04). The average D(10%) for the spinal cord (dose that covered 10% of the spinal cord) was least for the 6U IMRT plan with jaw tracking and was greatest for the 10U IMRT plan without jaw tracking. Measurements showed greater than 98.5% agreement for planar dose gamma analysis and less than 2.5% for point dose analysis. CONCLUSIONS: The addition of jaw tracking to IMRT and VMAT can decrease spinal cord dose without a change in calculation accuracy. A lower dose to the spinal cord was achieved with 6U than with 10U, although in some cases, 10U may be justified.

Characteristics of X-ray attenuation in electrospun bismuth oxide/polylactic acid nanofibre mats.

The characteristics of the X-ray attenuation in electrospun nano(n)- and micro(m)-Bi2O3/polylactic acid (PLA) nanofibre mats with different Bi2O3 loadings were compared as a function of energy using mammography (i.e. tube voltages of 22-49 kV) and X-ray absorption spectroscopy (XAS) (7-20 keV). Results indicate that X-ray attenuation by electrospun n-Bi2O3/PLA nanofibre mats is distinctly higher than that of m-Bi2O3/PLA nanofibre mats at all energies investigated. In addition, with increasing filler loading (n-Bi2O3 or m-Bi2O3), the porosity of the nanofibre mats decreased, thus increasing the X-ray attenuation, except for the sample containing 38 wt% Bi2O3 (the highest loading in the present study). The latter showed higher porosity, with some beads formed, thus resulting in a sudden decrease in the X-ray attenuation.

Suitability of radiochromic films for dosimetry of very-low energy X-rays.

This study examined the response characteristics of three commercially available radiochromic films when exposed to low energy (50 kVp) X-rays. The aim was to evaluate the films for potential use in 2D dosimetry for a low-kV intraoperative radiotherapy (IORT) device known as the 'Intrabeam'. Dose-response relationships were obtained for Gafchromic EBT, XR-RV2, and XR-QA film in water at several distances from the Intrabeam device. It was found that the dose rates from the source were excessive for use of the XR-QA film, and that all three film types showed significant energy dependence within the limits of measurement uncertainty. Basic modeling of primary X-ray spectra indicated large changes in the lower energy components with distance from the source, and it is hypothesized that the changes in film response are a result of changes in film energy response. This is in contrast to previous studies indicating less or negligible energy response. All films showed non-linearity in response over the ranges examined. These results imply significant limitations for the use of these films for low-kV dosimetry.

Charge redistribution in oxidized and semiquinone E. coli DNA photolyase upon photoexcitation: stark spectroscopy reveals a rationale for the position of Trp382.

The electronic structure of the two lowest excited electronic states of FAD and FADH(*) in folate-depleted E. coli DNA photolyase (PL(OX) and PL(SQ), respectively) was measured using absorption Stark spectroscopy. The experimental analysis was supported by TDDFT calculations of both the charge redistribution and the difference dipole moments for the transitions of both oxidation states using lumiflavin as a model. The difference dipole moments and polarizabilities for PL(OX) are similar to those obtained in our previous work for flavins in simple solvents and in an FMN-containing flavoprotein. No such comparison can be made for PL(SQ), as we believe this to be the first experimental report of the direction and magnitude of excited-state charge redistribution in any flavosemiquinone. The picture that emerges from these studies is discussed in the context of electron transfer in photolyase, particularly for the semiquinone photoreduction process, which involves nearby tryptophan residues as electron donors. The direction of charge displacement derived from an analysis of the Stark spectra rationalizes the positioning of the critical Trp382 residue relative to the flavin for efficient vectorial electron transfer leading to photoreduction. The ramifications of vectorial charge redistribution are discussed in the context of the wider class of flavoprotein blue light photoreceptors.