Dosimetric comparison of glioblastoma radiotherapy treatment plans on a low-field MRI-guided linear accelerator compared to conventional C-arm linear accelerator.

INTRODUCTION: Magnetic resonance imaging (MRI)-guided radiation therapy has proven to provide many benefits such as real-time tracking, dose escalation, and the ability to perform online adaptive therapy. The objective of this study is to compare curative treatment plans for glioblastoma tumors on a low-field MR-guided linac vs a C-arm linac and evaluate if they are comparable in terms of coverage, organ at risk sparing, delivery time, and deliverability. METHODS: This is a retrospective study that consisted of 15 previously treated patients who received radiation therapy for glioblastoma on a C-arm linac. The CT simulation data used for the original clinical plans was imported into the MR-linac treatment planning system (TPS) and utilized for MR-linac plan generation. The plans were evaluated utilizing the dose volumetric histogram (DVH) and isodose lines, then compared in terms of plan quality consisting of PTV coverage, dose distributions, and OAR constraints. Statistical analysis was performed to compare differences between the two planning techniques. QA was performed on a subset of the plans to verify deliverability. RESULTS: Plans generated on the MR-linac were more heterogenous compared to C-arm linac plans. A statistically significant difference was found in the homogeneity index (HI) and the PTV V105% volume (cc) values. The volume of the normal brain receiving 30 Gy also showed a statistically significant (p = 0.0479) difference, where on average an additional 41.5 cc's of the normal brain tissue received 30 Gy in the MR-linac plans. The maximum dose to the normal brain structure also increased in the MR-linac plans on average by 2.6 Gy (p = 0.0002). Similarly, the average maximum dose to the scalp 4 mm structure was 6.5 Gy higher in the MR-linac plans compared to C-arm linac plans (p = 0.0103). The total MU's were higher in the MR-linac plans compared to the C-arm linac plans (p = 0.0015). CONCLUSIONS: Both MR-linac and C-arm linac plans met constraints for PTV coverage and OAR sparing, were deliverable, and resulted to be clinically acceptable. However, our study showed that MR-linac plans were not as conformal or as homogenous as C-arm linac plans utilizing noncoplanar beams.

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.

Mito-nuclear discordance within Anthozoa, with notes on unique properties of their mitochondrial genomes.

Whole mitochondrial genomes are often used in phylogenetic reconstruction. However, discordant patterns in species relationships between mitochondrial and nuclear phylogenies are commonly observed. Within Anthozoa (Phylum Cnidaria), mitochondrial (mt)-nuclear discordance has not yet been examined using a large and comparable dataset. Here, we used data obtained from target-capture enrichment sequencing to assemble and annotate mt genomes and reconstruct phylogenies for comparisons to phylogenies inferred from hundreds of nuclear loci obtained from the same samples. The datasets comprised 108 hexacorals and 94 octocorals representing all orders and > 50% of extant families. Results indicated rampant discordance between datasets at every taxonomic level. This discordance is not attributable to substitution saturation, but rather likely caused by introgressive hybridization and unique properties of mt genomes, including slow rates of evolution driven by strong purifying selection and substitution rate variation. Strong purifying selection across the mt genomes caution their use in analyses that rely on assumptions of neutrality. Furthermore, unique properties of the mt genomes were noted, including genome rearrangements and the presence of nad5 introns. Specifically, we note the presence of the homing endonuclease in ceriantharians. This large dataset of mitochondrial genomes further demonstrates the utility of off-target reads generated from target-capture data for mt genome assembly and adds to the growing knowledge of anthozoan evolution.

Pneumocystis jirovecii Infections Among COVID-19 Patients: A Case Series and Literature Review.

Background: Pneumocystis jirovecii pneumonia (PCP) is a serious, emerging complication of coronavirus disease 2019 (COVID-19). Methods: We performed a systematic review of published cases. We describe 6 new cases of PCP/COVID-19 coinfection. Among our cases (n = 6) and those in the literature (n = 69) with available data, the median age (interquartile range [IQR]) was 59 (44-77) years (n = 38), 72% (47/65) were male, and the mortality rate was 30.9% (21/68). Results: Long-term corticosteroid use was noted in 45.1% (23/51), advanced HIV infection (defined as a CD4 count <200 cells/µL) in 17.6% (9/51), and antineoplastic chemotherapy in 13.7% (7/51), consistent with known PCP risk factors. Notably, 56.7% (38/47) had verifiable risk factors for PCP (high-dose corticosteroids, immunosuppressive therapy, and HIV infection) before COVID-19 infection. A median absolute lymphocyte count (IQR) of 0.61 (0.28-0.92) ×103 cells/mm3 (n = 23) and CD4 count (IQR) of 66 (33-291.5) cells/mm3 (n = 20) were also discovered among the study population. Conclusions: These findings suggest a need for greater attention to PCP risk factors among COVID-19 patients and consideration of PCP prophylaxis in these high-risk populations.

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.

Postoperative Respiratory Failure After Elective Abdominal Surgery: A Case-Control Study.

INTRODUCTION: Postoperative respiratory failure (PRF) contributes significantly to morbidity and mortality. We sought to identify patient characteristics and perioperative risk factors associated with PRF in patients undergoing elective abdominal surgery to improve patient outcomes. METHODS: We retrospectively reviewed patients undergoing elective abdominal surgery from 2011 to 2016 at our institution. An experimental group consisting of adult patients with the Patient Safety Indicator 11 diagnosis of PRF was compared with a time-matched control group. RESULTS: Each group consisted of 233 patients. Comorbidities associated with PRF included ascites, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus type II, hypertension, and hypoalbuminemia (P < 0.05). American Society of Anesthesiologists score IV (20.2% versus 3.95%; P < 0.001), operative time (4.13 versus 2.55 h; P < 0.001), laparotomy with open operation (77.7% versus 45.5%; P < 0.001), and net intraoperative fluid balance (3635 versus 2410 mL; P < 0.001) were higher in patients with PRF. On multivariate analysis, age, American Society of Anesthesiologists score, chronic obstructive pulmonary disease, diabetes mellitus type II, laparotomy, and net intraoperative fluid balance maintained significance (P < 0.05). CONCLUSIONS: We identified contributing pre- and intra-operative risk factors for PRF undergoing elective abdominal surgery. These findings may help identify those at increased risk for respiratory failure and mitigate complications.

How does CBCT reconstruction algorithm impact on deformably mapped targets and accumulated dose distributions?

PURPOSE: We performed quantitative analysis of differences in deformable image registration (DIR) and deformable dose accumulation (DDA) computed on CBCT datasets reconstructed using the standard (Feldkamp-Davis-Kress: FDK_CBCT) and a novel iterative (iterative_CBCT) CBCT reconstruction algorithms. METHODS: Both FDK_CBCT and iterative_CBCT images were reconstructed for 323 fractions of treatment for 10 prostate cancer patients. Planning CT images were deformably registered to each CBCT image data set. After daily dose distributions were computed, they were mapped to planning CT to obtain deformed doses. Dosimetric and image registration results based CBCT images reconstructed by two algorithms were compared at three levels: (A) voxel doses over entire dose calculation volume, (B) clinical constraint results on targets and sensitive structures, and (C) contours propagated to CBCT images using DIR results based on three algorithms (SmartAdapt, Velocity, and Elastix) were compared with manually delineated contours as ground truth. RESULTS: (A) Average daily dose differences and average normalized DDA differences between FDK_CBCT and iterative_CBCT were ≤1 cGy. Maximum daily point dose differences increased from 0.22 ± 0.06 Gy (before the deformable dose mapping operation) to 1.33 ± 0.38 Gy after the deformable dose mapping. Maximum differences of normalized DDA per fraction were up to 0.80 Gy (0.42 ± 0.19 Gy). (B) Differences in target minimum doses were up to 8.31 Gy (-0.62 ± 4.60 Gy) and differences in critical structure doses were 0.70 ± 1.49 Gy. (C) For mapped prostate contours based on iterative_CBCT (relative to standard FDK_CBCT), dice similarity coefficient increased by 0.10 ± 0.09 (p < 0.0001), mass center distances decreased by 2.5 ± 3.0 mm (p < 0.00005), and Hausdorff distances decreased by 3.3 ± 4.4 mm (p < 0.00015). CONCLUSIONS: The new iterative CBCT reconstruction algorithm leads to different mapped volumes of interest, deformed and cumulative doses than results based on conventional FDK_CBCT.

Chamber-enriched gene expression profiles in failing human hearts with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) constitutes 50% of HF hospitalizations and is characterized by high rates of mortality. To explore the underlying mechanisms of HFrEF etiology and progression, we studied the molecular and cellular differences in four chambers of non-failing (NF, n = 10) and HFrEF (n = 12) human hearts. We identified 333 genes enriched within NF heart subregions and often associated with cardiovascular disease GWAS variants. Expression analysis of HFrEF tissues revealed extensive disease-associated transcriptional and signaling alterations in left atrium (LA) and left ventricle (LV). Common left heart HFrEF pathologies included mitochondrial dysfunction, cardiac hypertrophy and fibrosis. Oxidative stress and cardiac necrosis pathways were prominent within LV, whereas TGF-beta signaling was evident within LA. Cell type composition was estimated by deconvolution and revealed that HFrEF samples had smaller percentage of cardiomyocytes within the left heart, higher representation of fibroblasts within LA and perivascular cells within the left heart relative to NF samples. We identified essential modules associated with HFrEF pathology and linked transcriptome discoveries with human genetics findings. This study contributes to a growing body of knowledge describing chamber-specific transcriptomics and revealed genes and pathways that are associated with heart failure pathophysiology, which may aid in therapeutic target discovery.

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.

A Comparison of Clinical Reasoning Among Rehabilitation Students During Experiential Learning.

Fieldwork and clinical experiences are an academic requirement that occupational and physical therapy students are required to complete to obtain their professional degree. There is limited knowledge on the quantitative change in clinical reasoning among rehabilitation students participating in 3:1 collaborative or 1:1 traditional learning model during a terminal fieldwork or clinical experience. The purpose of the study was to compare change in clinical reasoning scores of rehabilitation science students who participated in a collaborative vs traditional learning model during a terminal fieldwork or clinical experience. A total of 102 cumulative clinical reasoning scores were obtained from rehabilitation students who completed the Health Science Reasoning Test (HSRT) pre and post-completion of a terminal fieldwork or clinical experience at a large health care institution. A mixed-model ANOVA was done to determine the change in clinical reasoning scores among students who participated in a collaborative versus traditional learning model. Paired t-tests were completed to further analyze and interpret the discipline by model interaction. A statistically significant difference was found in discipline x time interaction. For individual disciplines, occupational therapy students had a significant change in clinical reasoning scores post-completion of a terminal fieldwork experience; however, physical therapy students did not have a significant change in clinical reasoning.

Technical Note: Comparison of the internal target volume (ITV) contours and dose calculations on 4DCT, average CBCT, and 4DCBCT imaging for lung stereotactic body radiation therapy (SBRT).

PURPOSE: To investigate the differences between internal target volumes (ITVs) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT) and determine the dose delivered on 4D planning technique. METHODS: For nine patients, 4DCBCTs were acquired before each fraction to assess tumor motion. An ITV was contoured on each phase of the 4DCBCT and a union of the 10 ITVs was used to create a composite ITV. Another ITV was drawn on the average 3DCBCT (avgCBCT) to compare with current clinical practice. The Dice coefficient, Hausdorff distance, and center of mass (COM) were averaged over four fractions to compare the ITVs contoured on the 4DCT, avgCBCT, and 4DCBCT for each patient. Planning was done on the average CT, and using the online registration, plans were calculated on each phase of the 4DCBCT and on the avgCBCT. Plan dose calculations were tested by measuring ion chamber dose in the CIRS lung phantom. RESULTS: The Dice coefficients were similar for all three comparisons: avgCBCT-to-4DCBCT (0.7 ± 0.1), 4DCT-to-avgCBCT (0.7 ± 0.1), and 4DCT-to-4DCBCT (0.7 ± 0.1); while the mean COM differences were also comparable (2.6 ± 2.2mm, 2.3 ± 1.4mm, and 3.1 ± 1.1mm, respectively). The Hausdorff distances for the comparisons with 4DCBCT (8.2 ± 2.9mm and 8.1 ± 3.2mm) were larger than the comparison without (6.5 ± 2.5mm). The differences in ITV D95% between the treatment plan and avgCBCT calculations were 4.3 ± 3.0% and -0.5 ± 4.6%, between treatment plan and 4DCBCT plans, respectively, while the ITV V100% coverages were 99.0 ± 1.9% and 93.1 ± 8.0% for avgCBCT and 4DCBCT, respectively. CONCLUSION: There is great potential for 4DCBCT to evaluate the extent of tumor motion before treatment, but image quality challenges the clinician to consistently delineate lung target volumes.

Modeling AeroForm tissue expander for postmastectomy radiation therapy.

The AeroForm chest wall tissue expander (TE) is a silicon shell containing a metallic CO2 reservoir, placed surgically after mastectomy. The patient uses a remote control to release compressed CO2 from the reservoir to inflate the expander. AeroForm poses challenges in a radiation therapy setting: The high density of the metallic reservoir causes imaging artifacts on the planning CT, which encumber structure definition and cause misrepresentation of density information, in turn affecting dose calculation. Additionally, convolution-based dose calculation algorithms may not be well-suited to calculate dose in and around high-density materials. In this study, a model of the AeroForm TE was created in Eclipse treatment planning system (TPS). The TPS model was validated by comparing measured to calculated transmission through the AeroForm. Transmission was measured with various geometries using radiochromic film. Dose was calculated with both Varian's Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB) algorithms. AAA and AXB were compared using dose profile and gamma analyses. While both algorithms modeled direct transmission well, AXB better modeled lateral scatter from the AeroForm TE. Clinical significance was evaluated using clinical data from four patients with AeroForm TEs. The AeroForm TPS model was applied, and RT plans were optimized using AAA, then re-calculated with AXB. Structures of clinical significance were defined and dose volume histogram analysis was performed. Compared to AXB, AAA overestimates dose in the AeroForm device. Changes in clinically significant regions were patient- and plan-specific. This study proposes a clinical procedure for modeling the AeroForm in a commercial TPS, and discusses the limitations of dose calculation in and around the device. An understanding of dose calculation accuracy in the vicinity of the AeroForm is critical for assessing individual plan quality, appropriateness of different planning techniques and dose calculation algorithms, and even the decision to use the AeroForm in a postmastectomy radiation therapy setting.

Evaluation and Clinical Application of a Commercially Available Iterative Reconstruction Algorithm for CBCT-Based IGRT.

PURPOSE: We have quantitatively evaluated the image quality of a new commercially available iterative cone-beam computed tomography reconstruction algorithm over standard cone-beam computed tomography image reconstruction results. METHODS: This iterative cone-beam computed tomography reconstruction pipeline uses a finite element solver (AcurosCTS)-based scatter correction and a statistical (iterative) reconstruction in addition to a standard kernel-based correction followed by filtered back-projection-based Feldkamp-Davis-Kress cone-beam computed tomography reconstruction. Standard full-fan half-rotation Head, half-fan full-rotation Head, and standard Pelvis cone-beam computed tomography protocols have been investigated to scan a quality assurance phantom via the following image quality metrics: uniformity, HU constancy, spatial resolution, low contrast detection, noise level, and contrast-to-noise ratio. An anthropomorphic head phantom was scanned for verification of noise reduction. Clinical patient image data sets for 5 head/neck patients and 5 prostate patients were qualitatively evaluated. RESULTS: Quality assurance phantom study results showed that relative to filtered back-projection-based cone-beam computed tomography, noise was reduced from 28.8 ± 0.3 HU to a range between 18.3 ± 0.2 and 5.9 ± 0.2 HU for Full-Fan Head scans, from 14.4 ± 0.2 HU to a range between 12.8 ± 0.3 and 5.2 ± 0.3 HU for Half-Fan Head scans, and from 6.2 ± 0.1 HU to a range between 3.8 ± 0.1 and 2.0 ± 0.2 HU for Pelvis scans, with the iterative cone-beam computed tomography algorithm. Spatial resolution was marginally improved while results for uniformity and HU constancy were similar. For the head phantom study, noise was reduced from 43.6 HU to a range between 24.8 and 13.0 HU for a Full-Fan Head and from 35.1 HU to a range between 22.9 and 14.0 HU for a Half-Fan Head scan. The patient data study showed that artifacts due to photon starvation and streak artifacts were all reduced, and image noise in specified target regions were reduced to 62% ± 15% for 10 patients. CONCLUSION: Noise and contrast-to-noise ratio image quality characteristics were significantly improved using the iterative cone-beam computed tomography reconstruction algorithm relative to the filtered back-projection-based cone-beam computed tomography method. These improvements will enhance the accuracy of cone-beam computed tomography-based image-guided applications.

Multi-institutional evaluation of end-to-end protocol for IMRT/VMAT treatment chains utilizing conventional linacs.

We conducted a multi-institutional assessment of a recently developed end-to-end monthly quality assurance (QA) protocol for external beam radiation therapy treatment chains. This protocol validates the entire treatment chain against a baseline to detect the presence of complex errors not easily found in standard component-based QA methods. Participating physicists from 3 institutions ran the end-to-end protocol on treatment chains that include Imaging and Radiation Oncology Core (IROC)-credentialed linacs. Results were analyzed in the form of American Association of Physicists in Medicine (AAPM) Task Group (TG)-119 so that they may be referenced by future test participants. Optically stimulated luminescent dosimeter (OSLD), EBT3 radiochromic film, and A1SL ion chamber readings were accumulated across 10 test runs. Confidence limits were calculated to determine where 95% of measurements should fall. From calculated confidence limits, 95% of measurements should be within 5% error for OSLDs, 4% error for ionization chambers, and 4% error for (96% relative gamma pass rate) radiochromic film at 3% agreement/3 mm distance to agreement. Data were separated by institution, model of linac, and treatment protocol (intensity-modulated radiation therapy [IMRT] vs volumetric modulated arc therapy [VMAT]). A total of 97% of OSLDs, 98% of ion chambers, and 93% of films were within the confidence limits; measurements were found outside these limits by a maximum of 4%, < 1%, and < 1%, respectively. Data were consistent despite institutional differences in OSLD reading equipment and radiochromic film calibration techniques. Results from this test may be used by clinics for data comparison. Areas of improvement were identified in the end-to-end protocol that can be implemented in an updated version. The consistency of our data demonstrates the reproducibility and ease-of-use of such tests and suggests a potential role for their use in broad end-to-end QA initiatives.

On the improvement of CBCT image quality for soft tissue-based SRS localization.

PURPOSE: We explore the optimal cone-beam CT (CBCT) acquisition parameters to improve CBCT image quality to enhance intracranial stereotactic radiosurgery (SRS) localization and also assess the imaging dose levels associated with each imaging protocol. METHODS: Twenty-six CBCT acquisition protocols were generated on an Edge® linear accelerator (Varian Medical Systems, Palo Alto, CA) with different x-ray tube current and potential settings, gantry rotation trajectories, and gantry rotation speeds. To assess image quality, images of the Catphan 504 phantom were analyzed to evaluate the following image quality metrics: uniformity, HU constancy, spatial resolution, low contrast detection, noise level, and contrast-to-noise ratio (CNR). To evaluate the imaging dose for each protocol, the cone-beam dose index (CBDI) was measured. To validate the phantom results, further analysis was performed with an anthropomorphic head phantom as well as image data acquired for a clinical SRS patient. RESULTS: The Catphan data indicates that adjusting acquisition parameters had direct effects on the image noise level, low contrast detection, and CNR, but had minimal effects on uniformity, HU constancy, and spatial resolution. The noise level was reduced from 34.5 ± 0.3 to 18.5 ± 0.2 HU with a four-fold reduction in gantry speed, and to 18.7 ± 0.2 HU with a four-fold increase in tube current. Overall, the noise level was found to be proportional to inverse square root of imaging dose, and imaging dose was proportional to the product of total tube current-time product and the cube of the x-ray potential. Analysis of the anthropomorphic head phantom data and clinical SRS imaging data also indicates that noise is reduced with imaging dose increase. CONCLUSIONS: Our results indicate that optimization of the imaging protocol, and thereby an increase in the imaging dose, is warranted for improved soft-tissue visualization for intracranial SRS.

Evaluation and verification of the QFix EncompassTM couch insert for intracranial stereotactic radiosurgery.

The QFix EncompassTM stereotactic radiosurgery (SRS) immobilization system consists of a thermoplastic mask that attaches to the couch insert to immobilize patients treated with intracranial SRS. This study evaluates the dosimetric impact and verifies a vendor provided treatment planning system (TPS) model in the Eclipse TPS. A thermoplastic mask was constructed for a Lucy 3D phantom, and was scanned with and without the EncompassTM system. Attenuation measurements were performed in the Lucy phantom with and without the insert using a pinpoint ion chamber for energies of 6xFFF, 10xFFF and 6X, with three field sizes (2 × 2, 4 × 4, and 6 × 6 cm2 ). The measurements were compared to two sets of calculations. The first set utilized the vendor provided Encompass TPS model (EncompassTPS ), which consists of two structures: the Encompass and Encompass base structure. Three HU values for the Encompass (200, 300, 400) and Encompass Base (-600, -500, -400) structures were evaluated. The second set of calculations consists of the Encompass insert included in the external body contour (EncompassEXT ) for dose calculation. The average measured percent attenuation in the posterior region of the insert ranged from 3.4%-3.8% for the 6xFFF beam, 2.9%-3.4% for the 10xFFF, and 3.3%-3.6% for the 6X beam. The maximum attenuation occurred at the region where the mask attaches to the insert, where attenuation up to 17% was measured for a 6xFFF beam. The difference between measured and calculated attenuation with either the EncompassEXT or EncompassTPS approach was within 0.5%. HU values in the EncompassTPS model that provided the best agreement with measurement was 400 for the Encompass structure and -400 for the Encompass base structure. Significant attenuation was observed at the area where the mask attaches to the insert. Larger differences can be observed when using few static beams compared to rotational treatment techniques.

A prediction model of radiation-induced necrosis for intracranial radiosurgery based on target volume.

PURPOSE: This study aims to extend the observation that the 12 Gy-radiosurgical-volume (V12Gy) correlates with the incidence of radiation necrosis in patients with intracranial tumors treated with radiosurgery by using target volume to predict V12Gy. V12Gy based on the target volume was used to predict the radiation necrosis probability (P) directly. Also investigated was the reduction in radiation necrosis rates (ΔP) as a result of optimizing the prescription isodose lines for linac-based SRS. METHODS: Twenty concentric spherical targets and 22 patients with brain tumors were retrospectively studied. For each case, a standard clinical plan and an optimized plan with prescription isodose lines based on gradient index were created. V12Gy were extracted from both plans to analyze the correlation between V12Gy and target volume. The necrosis probability P as a function of V12Gy was evaluated. To account for variation in prescription, the relation between V12Gy and prescription was also investigated. RESULTS: A prediction model for radiation-induced necrosis was presented based on the retrospective study. The model directly relates the typical prescribed dose and the target volume to the radionecrosis probability; V12Gy increased linearly with the target volume (R2  > 0.99). The linear correlation was then integrated into a logistic model to predict P directly from the target volume. The change in V12Gy as a function of prescription was modeled using a single parameter, s (=-1.15). Relatively large ΔP was observed for target volumes between 7 and 28 cm3 with the maximum reduction (8-9%) occurring at approximately 18 cm3 . CONCLUSIONS: Based on the model results, optimizing the prescription isodose line for target volumes between 7 and 28 cm3 results in a significant reduction in necrosis probability. V12Gy based on the target volume could provide clinicians a predictor of radiation necrosis at the contouring stage thus facilitating treatment decisions.

Investigating the dosimetric effects of grid size on dose calculation accuracy using volumetric modulated arc therapy in spine stereotactic radiosurgery.

PURPOSE: Sharp dose gradients between the target and the spinal cord are critical to achieve dose constraints in spine stereotactic radiosurgery (SRS), however the accuracy of the doses to the spinal cord at these high dose gradients is sensitive to the how the dose is sampled across the structure using a discretized isotropic calculation grid. In this study, the effect of the grid size (GS) on the dosimetric accuracy of volumetric modulated arc therapy (VMAT) spine SRS plans was investigated. METHODS: The Eclipse v11.0 Anisotropic Analytical Algorithm (AAA) algorithm was used for dose calculation. Plan qualities of fifty treatment plans were evaluated with a GS of 2.5 (AAA's default value), 1.5 and 1mm. All plans were prescribed to the 90% isodose line in 1 fraction. Parameters used for plan comparison included the distance-to-fall-off (DTF) between the 90% and 50% isodose levels in the axial plane, planning tumor volume (PTV) coverage to 99%, 95%, 5% and 0.03cc, dose to 10% (Cord_D10%) and 0.03cc (Cord_D0.03cc) of the spinal cord sub volume. The dosimetric accuracy was evaluated based on film dosimetry percent gamma pass rate, line profile through the cord. Calculation times between different grid sizes as well as DVH algorithm differences between two treatment planning systems (Eclipse vs Velocity) were compared. Paired t-test was used to investigate the statistical significance. RESULTS: The DTF decreased for all plans with 1mm compared to 1.5mm and 2.5mm GS (2.52±0.54mm, 2.83±0.58mm, 3.30±0.64, p<0.001). Relative to the 1mm GS, Cord_D0.03cc and Cord_D10% increased by 6.24% and 7.81% with the 1.5mm GS, and 9.80% and 13% with the 2.5mm GS. Film analysis demonstrated higher gamma pass rates for 1.5mm GS compared to 1 and 2.5mm GS (95.9%±5.4%, 94.3%±6.0%, 93.6%±5.4%, p<0.001), however 1mm GS showed better agreement in the high dose gradient near the cord. Calculation times for 1mm GS plans increased for 1.5 and 2.5mm GS (61% and 84%, p<0.001). The average difference between the two treatment planning systems was approximately 0-1.2%. A maximum difference of 5.9% occurred for Cord_D0.03cc for the 1mm GS. CONCLUSION: Plans calculated with a 1mm grid size resulted in the most accurate representation of the dose delivered to the cord, however resulted in less uniform dose distributions in the high dose region of the PTV. The use of a 1.5mm grid size may balance accurate cord dose and PTV coverage, while also being more practical with respect to computation time.

Development and evaluation of a clinical model for lung cancer patients using stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning.

The purpose of this study was to describe the development of a clinical model for lung cancer patients treated with stereotactic body radiotherapy (SBRT) within a knowledge-based algorithm for treatment planning, and to evaluate the model performance and applicability to different planning techniques, tumor locations, and beam arrangements. 105 SBRT plans for lung cancer patients previously treated at our institution were included in the development of the knowledge-based model (KBM). The KBM was trained with a combination of IMRT, VMAT, and 3D CRT techniques. Model performance was validated with 25 cases, for both IMRT and VMAT. The full KBM encompassed lesions located centrally vs. peripherally (43:62), upper vs. lower (62:43), and anterior vs. posterior (60:45). Four separate sub-KBMs were created based on tumor location. Results were compared with the full KBM to evaluate its robustness. Beam templates were used in conjunction with the optimizer to evaluate the model's ability to handle suboptimal beam placements. Dose differences to organs-at-risk (OAR) were evaluated between the plans gener-ated by each KBM. Knowledge-based plans (KBPs) were comparable to clinical plans with respect to target conformity and OAR doses. The KBPs resulted in a lower maximum spinal cord dose by 1.0 ± 1.6 Gy compared to clinical plans, p = 0.007. Sub-KBMs split according to tumor location did not produce significantly better DVH estimates compared to the full KBM. For central lesions, compared to the full KBM, the peripheral sub-KBM resulted in lower dose to 0.035 cc and 5 cc of the esophagus, both by 0.4Gy ± 0.8Gy, p = 0.025. For all lesions, compared to the full KBM, the posterior sub-KBM resulted in higher dose to 0.035 cc, 0.35 cc, and 1.2 cc of the spinal cord by 0.2 ± 0.4Gy, p = 0.01. Plans using template beam arrangements met target and OAR criteria, with an increase noted in maximum heart dose (1.2 ± 2.2Gy, p = 0.01) and GI (0.2 ± 0.4, p = 0.01) for the nine-field plans relative to KBPs planned with custom beam angles. A knowledge-based model for lung SBRT consisting of multiple treatment modalities and lesion loca-tions produced comparable plan quality to clinical plans. With proper training and validation, a robust KBM can be created that encompasses both IMRT and VMAT techniques, as well as different lesion locations.