Verification of surface-guided radiation therapy (SGRT) alignment for proton breast and chest wall patients by comparison to CT-on-rails and kV-2D alignment.

BACKGROUND: Surface-guided radiation therapy (SGRT) systems have been widely installed and utilized on linear accelerators. However, the use of SGRT with proton therapy is still a newly developing field, and published reports are currently very limited. PURPOSE: To assess the clinical application and alignment agreement of SGRT with CT-on-rails (CTOR) and kV-2D image-guided radiation therapy (IGRT) for breast treatment using proton therapy. METHODS: Four patients receiving breast or chest wall treatment with proton therapy were the subjects of this study. Patient #1's IGRT modalities were a combination of kV-2D and CTOR. CTOR was the only imaging modality for patients #2 and #3, and kV-2D was the only imaging modality for patient #4. The patients' respiratory motions were assessed using a 2-min surface position recorded by the SGRT system during treatment. SGRT offsets reported after IGRT shifts were recorded for each fraction of treatment. The agreement between SGRT and either kV-2D or CTOR was evaluated. RESULTS: The respiratory motion amplitude was <4 mm in translation and <2.0° in rotation for all patients. The mean and maximum amplitude of SGRT offsets after application of IGRT shifts were ≤(2.6 mm, 1.6° ) and (6.8 mm, 4.5° ) relative to kV-2D-based IGRT; ≤(3.0 mm, 2.6° ) and (5.0 mm, 4.7° ) relative to CTOR-based IGRT without breast tissue inflammation. For patient #3, breast inflammation was observed for the last three fractions of treatment, and the maximum SGRT offsets post CTOR shifts were up to (14.0 mm, 5.2° ). CONCLUSIONS: Due to the overall agreement between SGRT and IGRT within reasonable tolerance, SGRT has the potential to serve as a valuable auxiliary IGRT tool for proton breast treatment and may improve the efficiency of proton breast treatment.

Initial clinical evaluation of a novel combined biometric, radio-frequency identification, and surface imaging system.

PURPOSE: To evaluate and characterize the overall clinical functionality and workflow of the newly released Varian Identify system (version 2.3). METHODS: Three technologies included in the Varian Identify system were evaluated: patient biometric authentication, treatment accessory device identification, and surface-guided radiation therapy (SGRT) function. Biometric authentication employs a palm vein reader. Treatment accessory device verification utilizes two technologies: device presence via Radio Frequency Identification (RFID) and position via optical markers. Surface-guidance was evaluated on both patient orthopedic setup at loading position and surface matching and tracking at treatment isocenter. A phantom evaluation of the consistency and accuracy for Identify SGRT function was performed, including a system consistency test, a translational shift and rotational accuracy test, a pitch and roll accuracy test, a continuous recording test, and an SGRT vs Cone-Beam CT (CBCT) agreement test. RESULTS: 201 patient authentications were verified successfully with palm reader. All patient treatment devices were successfully verified for their presences and positions (indexable devices). The patient real-time orthopedic pose was successfully adjusted to match the reference surface captured at simulation. SGRT-reported shift consistency against couch readout was within (0.1 mm, 0.030). The shift accuracy was within (0.3 mm, 0.10). In continuous recording mode, the maximum variation was 0.2 ± 0.12 mm, 0.030 ± 0.020. The difference between Identify SGRT offset and CBCT was within (1 mm, 10). CONCLUSIONS: This clinical evaluation confirms that Identify accurately functions for patient palm identification and patient treatment device presence and position verification. Overall SGRT consistency and accuracy was within (1 mm, 10), within the 2 mm criteria of AAPM TG302.

Technical note: Clinical evaluation of a newly released surface-guided radiation therapy system on DIBH for left breast radiation therapy.

BACKGROUND: It has been shown that a significant reduction of mean heart dose and left anterior descending artery (LAD) dose can be achieved through the use of DIBH for left breast radiation therapy. Surface-guided DIBH has been widely adopted during the last decade, and there are mainly three commercially available SGRT systems. The reports of the performance of a newly released SGRT system for DIBH application are currently very limited. PURPOSE: To evaluate the clinical performance of a newly released SGRT system on DIBH for left breast radiation therapy. METHODS: Twenty-five left breast cancer patients treated with DIBH utilizing Varian's Identify system were included (total 493-fraction treatments). Four aspects of the clinical performance were evaluated: Identify offsets of free breathing post patient setup from tattoos, Identify offsets during DIBH, Identify agreement with radiographic ports during DIBH, and DIBH reference surface re-capture post patient shifts. The systematic and random errors of free breathing Identify offsets post patient setup were calculated for each patient, as well as for offsets during DIBH. Radiographic ports were taken when the patient's DIBH position was within the clinical tolerance of (± 0.3 cm, ± 30 ), and these were then compared with treatment field DRRs. If the ports showed that the patient alignment did not agree with the DRRs within 3 mm, a patient shift was performed. A new reference surface was captured and verification ports were taken. RESULTS: The all-patient average systematic and random errors of Identify offsets for free breathing were within (0.4 cm, 1.50 ) post tattoo setup. The maximum per-patient systematic and random errors were (1.1 cm, 6.20 ) and (0.9 cm, 20 ), and the maximum amplitude of Identify offsets were (2.59 cm, 90 ). All 493-fraction DIBH treatments were delivered and successfully guided by the Identify SGRT system. The systematic and random errors of Identify offsets for DIBH were within (0.2 cm, 2.30 ). Seven patients needed re-captured surface references due to surface variation or position shifts based on the ports. All patient DIBH verification ports guided by Identify were approved by attending physicians. CONCLUSION: This evaluation showed that the Identify system performed effectively for surface-guided patient setup and surface-guided DIBH imaging and treatment delivery. The feature of color-coded real-time patient surface matching feedback facilitated the evaluation of the patient alignment accuracy and the adjustment of the patient position to match the reference.

Adipose Tissue Distribution and Body Mass Index (BMI) Correlation With Daily Image-Guided Radiotherapy (IGRT) Shifts of Abdominal Radiation Therapy Patients.

Purpose There are several studies suggesting a correlation between image-guided radiotherapy (IGRT) setup errors and body mass index (BMI). However, abdominal fat content has visceral and subcutaneous components, which may affect setup errors differently. This study aims to analyze a potential workflow for characterizing adipose content and distribution in the region of the target that would allow a quickly calculated metric of abdominal fat content to stratify these patients. Methods IGRT shift data was retrospectively tabulated from daily fan-beam CT-on-rails pre-treatment alignment for 50 abdominal radiation therapy (RT) patients, and systematic and random errors in the daily setup were characterized by tabulating average and standard deviations of shift data for each patient and looking at differences for different distributions of adipose content. Visceral and subcutaneous fat content were defined by visceral fat area (VFA) and subcutaneous fat area (SFA) using a region-growing algorithm to contour adipose tissue on CT simulation scans. All contours were created for a single slice at the treatment isocenter, on which the VFA and SFA were calculated. A log-rank test was used to test trends in shifts over quartiles of adiposity. Results VFA ranged from 1.9-342.8c m2, and SFA from 11.8-756.0 cm2. The standard definition (SD) of random error (σ) in the lateral axis for Q1 vs. Q4 VFA was 0.10cm vs. 0.29cm, 0.12cm vs. 0.28cm for SFA, and 0.12cm vs. 0.31cm for BMI. The percentage of longitudinal shifts greater than 10mm for Q1 vs. Q4 VFA was 0% vs. 9%, 2% vs. 19% for SFA, and 0% vs. 20% for BMI. Statistically significant trends in shifts vs. the BMI quartile were seen for both pitch and the longitudinal direction, as well as for pitch corrections vs. the VFA quartile. Conclusion Within this dataset, abdominal cancer patients showed statistically significant trends in shift probability vs. BMI and VFA. Also, patients in the upper quartiles of all adiposity metrics showed an increased SD of σ in the lateral direction and increased shifts over 10 mm in the longitudinal direction. However, despite these relationships, neither VFA nor SFA offered discernible advantages in their relationship to shift uncertainty relative to BMI.

Measurements of fetal dose with Mevion S250i proton therapy system with HYPERSCAN.

PURPOSE: To characterize potential dose to the fetus for all modes of delivery (dynamic adaptive aperture, static adaptive aperture, and no adaptive aperture) for the Mevion S250i Proton Therapy System with HYPERSCAN and compare the findings with those of other available proton systems. MATERIALS AND METHODS: Fetal dose measurements were performed for all three modes of dose delivery on the Mevion S250i Proton therapy system with HYPERSCAN (static aperture, dynamic aperture and uncollimated). Standard treatment plans were created in RayStation for a left-sided brain lesion treated with a vertex field, a left lateral field, and a posterior field. Measurements were performed using WENDI and the RANDO with the detector placed at representative locations to mimic the growth and movement of the fetus at different gestational stages. RESULTS: The fetal dose measurements varied with fetus position and the largest measured dose was 64.7 µSv per 2 Gy (RBE) fraction using the dynamic aperture. The smallest estimated fetal dose was 45.0 µSv per 2 Gy (RBE) at the base of the RANDO abdomen (47 cm from isocenter to the outer width of WENDI and 58.5 cm from the center of the WENDI detector) for the static aperture delivery. The vertex fields at all depths had larger contributions to the total dose than the other two and the dynamic aperture plans resulted in the highest dose measured for all depths. CONCLUSION: The reported doses are lower than reported doses using a double-scattering system. This work suggests that avoiding vertex fields and using the static aperture will help minimize dose to the fetus.

Surface-Guided Patient Setup Versus Traditional Tattoo Markers for Radiation Therapy: Is Tattoo-Less Setup Feasible for Thorax, Abdomen and Pelvis Treatment?

PURPOSE: In this study, patient setup accuracy was compared between surface guidance and tattoo markers for radiation therapy treatment sites of the thorax, abdomen and pelvis. METHODS AND MATERIALS: A total of 608 setups performed on 59 patients using both surface-guided and tattoo-based patient setups were analyzed. During treatment setup, patients were aligned to room lasers using their tattoos, and then the six-degree-of-freedom (6DOF) surface-guided offsets were calculated and recorded using AlignRT system. While the patient remained in the same post-tattoo setup position, target localization imaging (radiographic or ultrasound) was performed and these image-guided shifts were recorded. Finally, surface-guided vs tattoo-based offsets were compared to the final treatment position (based on radiographic or ultrasound imaging) to evaluate the accuracy of the two setup methods. RESULTS: The overall average offsets of tattoo-based and surface-guidance-based patient setups were comparable within 3.2 mm in three principal directions, with offsets from tattoo-based setups being slightly less. The maximum offset for tattoo setups was 2.2 cm vs. 4.3 cm for surface-guidance setups. Larger offsets (ranging from 2.0 to 4.3 cm) were observed for surface-guided setups in 14/608 setups (2.3%). For these same cases, the maximum observed tattoo-based offset was 0.7 cm. Of the cases with larger surface-guided offsets, 13/14 were for abdominal/pelvic treatment sites. Additionally, larger rotations (>3°) were recorded in 18.6% of surface-guided setups. The majority of these larger rotations were observed for abdominal and pelvic sites (~84%). CONCLUSIONS: The small average differences observed between tattoo-based and surface-guidance-based patient setups confirm the general equivalence of the two potential methods, and the feasibility of tattoo-less patient setup. However, a significant number of larger surface-guided offsets (translational and rotational) were observed, especially in the abdominal and pelvic regions. These cases should be anticipated and contingency setup methods planned for.

Technical note: Evaluation of a silicone-based custom bolus for radiation therapy of a superficial pelvic tumor.

PURPOSE: Use of standard-of-care radiation therapy boluses may result in air-gaps between the target surface and bolus, as they may not adequately conform to each patient's unique topography. Such air-gaps can be particularly problematic in cases of superficial pelvic tumor radiation, as the density variation may result in the radiation delivered to the target site being inconsistent with the prescribed dose. To increase bolus fit and thereby dose predictability and homogeneity, we designed and produced a custom silicone bolus for evaluation against the clinical standard. METHODS: A custom bolus was created for the pelvic regions of both an anthropomorphic phantom and a pelvic patient with squamous cell carcinoma of the penile shaft. Molds were designed using computed tomography (CT) scans, then 3D-printed and cast with silicone rubber to yield the boluses. Air-gap measurements were performed on custom and standard-of-care Superflab gel sheet boluses by analyzing total volume between the bolus and target surface, as measured from CT scans. Therapeutic doses of radiation were delivered to both boluses. Radiation dose was measured and compared to the expected dose using nine optically stimulated luminescent dosimeters (OSLDs) placed on the phantom. RESULTS: Mean air-gap volume between the bolus and phantom was decreased from 314 ± 141 cm3 with the standard bolus to 4.56 ± 1.59 cm3 using the custom device. In the case of the on-treatment patient, air-gap volume was reduced from 169 cm3 with the standard bolus to 46.1 cm3 with the custom. Dosimetry testing revealed that the mean absolute difference between expected and received doses was 5.69%±4.56% (15.1% maximum) for the standard bolus and 1.91%±1.31% (3.51% maximum) for the custom device. Areas of greater dose difference corresponded to areas of larger air-gap. CONCLUSIONS: The custom bolus reduced air-gap and increased predictability of radiation dose delivered compared to the standard bolus. The custom bolus could increase the certainty of prescribed dose-delivery of radiation therapy for superficial tumors.

Characterizing a deformable registration algorithm for surface-guided breast radiotherapy.

PURPOSE: Surface-guided radiation therapy (SGRT) is a nonionizing imaging approach for patient setup guidance, intra-fraction monitoring, and automated breath-hold gating of radiation treatments. SGRT employs the premise that the external patient surface correlates to the internal anatomy, to infer the treatment isocenter position at time of treatment delivery. Deformations and posture variations are known to impact the correlation between external and internal anatomy. However, the degree, magnitude, and algorithm dependence of this impact are not intuitive and currently no methods exist to assess this relationship. The primary aim of this work was to develop a framework to investigate and understand how a commercial optical surface imaging system (C-RAD, Uppsala, Sweden), which uses a nonrigid registration algorithm, handles rotations and surface deformations. METHODS: A workflow consisting of a female torso phantom and software-introduced transformations to the corresponding digital reference surface was developed. To benchmark and validate the approach, known rigid translations and rotations were first applied. Relevant breast radiotherapy deformations related to breast size, hunching/arching back, distended/deflated abdomen, and an irregular surface to mimic a cover sheet over the lower part of the torso were investigated. The difference between rigid and deformed surfaces was evaluated as a function of isocenter location. RESULTS: For all introduced rigid body transformations, C-RAD computed isocenter shifts were determined within 1 mm and 1˚. Additional translational shifts to correct for rotations as a function of isocenter location were determined with the same accuracy. For yaw setup errors, the difference in shift corrections between a plan with an isocenter placed in the center of the breast (BrstIso) and one located 12 cm superiorly (SCFIso) was 2.3 mm/1˚ in lateral direction. Pitch setup errors resulted in a difference of 2.1 mm/1˚ in vertical direction. For some of the deformation scenarios, much larger differences up to 16 mm and 7˚ in the calculated shifts between BrstIso and SCFIso were observed that could lead to large unintended gaps or overlap between adjacent matched fields if uncorrected. CONCLUSIONS: The methodology developed lends itself well for quality assurance (QA) of SGRT systems. The deformable C-RAD algorithm determined accurate shifts for rigid transformations, and this was independent of isocenter location. For surface deformations, the position of the isocenter had considerable impact on the registration result. It is recommended to avoid off-axis isocenters during treatment planning to optimally utilize the capabilities of the deformable image registration algorithm, especially when multiple isocenters are used with fields that share a field edge.

Functional Liver Imaging and Dosimetry to Predict Hepatotoxicity Risk in Cirrhotic Patients With Primary Liver Cancer.

PURPOSE: Mitigating radiation-induced liver disease (RILD) is an ongoing need in patients with hepatocellular carcinoma. We hypothesize that [99mTc]-sulfur colloid (SC) single photon emission computed tomography (SPECT)/computed tomography (CT) scans can provide global functional liver metrics and functional liver dosimetric parameters that are predictive of hepatotoxicity risk in patients with primary liver cancer with cirrhosis. MATERIALS AND METHODS: We retrospectively reviewed 47 patients (n = 26 proton, n = 21 stereotactic body radiation therapy) with Child-Pugh (CP)-A (62%) or CP-B (38%) cirrhosis who underwent SC SPECT/CT scans for radiation therapy planning. SC SPECT scans were mined for image intensity threshold-based functional liver volumes (FLV), mean liver-spleen uptake ratio (L/Smean), and total liver function (TLF = FLV*L/Smean). Radiation therapy doses were voxel-wise converted to the biologically equivalent dose (EQD2a/b=3) and relative biological effectiveness (GyRBE). Normal liver (liver minus gross tumor volume [GTV]) and FLV mean doses, absolute and relative dose-volumes (VGy[cc], VGy[%]), and relative dose-function histogram quantiles in 10 GyEQD2 increments were calculated. Logistic regression was performed for correlation to CP score increase of 2 or higher (CP+2). Cox regression was performed for correlation to RILD-specific survival (RILD-SS) and overall survival. RESULTS: The strongest predictors of RILD-SS were FLV V20 and liver-GTV F20. FLV mean dose, but not CT-derived anatomic mean dose, was predictive of RILD-SS. TLF and L/Smean were the only parameters that were associated with CP+2 after adjusting for baseline CP score. Optimal cutoffs to mitigate risk RILD-SS were identified: FLV mean dose <23 GyEQD2, liver-GTV V20 <36%, FLV V20 <36%, liver-GTV F20 <36%, FLV <32% (350 cc), L/Smean >0.75, TLF >0.60, tumor volume <40 cm3, and CP score A5-6 versus B7-C10. A narrower therapeutic window was observed in CP-B/C patients. The discriminatory power for RILD-SS within CP-B/C classes was improved with the addition of a functional dosimetric constraint, resulting in low- and high-risk subgroups (P = 3 × 10-6). CONCLUSIONS: Functional liver metrics and dosimetric parameters derived from pretreatment SC SPECT/CT scans were complementary predictors of hepatotoxicity and may provide useful clinical decision support in the management of cirrhotic patients with primary liver cancer.

Regional Radiation Dose-Response Modeling of Functional Liver in Hepatocellular Carcinoma Patients With Longitudinal Sulfur Colloid SPECT/CT: A Proof of Concept.

PURPOSE: Hepatotoxicity risk in patients with hepatocellular carcinoma (HCC) is modulated by radiation dose delivered to normal liver tissue, but reported dose-response data are limited. Our prior work established baseline [99mTc]sulfur colloid (SC) single-photon emission computed tomography (SPECT)/computed tomography (CT) liver function imaging biomarkers that predict clinical outcomes. We conducted a proof-of-concept investigation with longitudinal SC SPECT/CT to characterize patient-specific radiation dose-response relationships as surrogates for liver radiosensitivity. METHODS AND MATERIALS: SC SPECT/CT images of 15 patients with HCC with variable Child-Pugh (CP) status (8 CP-A, 7 CP-B/C) were acquired in treatment position before and 1 month (nominal) after stereotactic body radiation therapy (n = 6) or proton therapy (n = 9). Localized rigid registrations between pre/posttreatment CT to planning CT scans were performed, and transformations were applied to pre/posttreatment SC SPECT images. Radiation therapy doses were converted to EQD2 and Gy RBE (relative biological effectiveness) and binned in 5 GyEQD2 increments within tumor-subtracted livers. Mean dose and percent change (%ΔSC) between pre- and posttreatment SPECT uptake, normalized to regions receiving <5 GyEQD2, were calculated in each binned dose region. Dose-response data were parameterized by sigmoid functions (double exponential) consisting of maximum reduction (%ΔSCmax), dose midpoint (Dmid), and dose-response slope (αmid) parameters. RESULTS: Individual patient sigmoid dose-response curves had high goodness-of-fit (median R2 = 0.96, range 0.76-0.99). Large interpatient variability was observed, with median (range) in %ΔSCmax of 44% (20%-75%), Dmid of 13 Gy (4-27 GyEQD2), and αmid of 0.11 GyEQD2-1 (0.04-0.29 GyEQD2-1), respectively. Eight of 15 patients had %ΔSCmax of 20% to 45%, whereas 7 of 15 had %ΔSCmax of 60% to 75%, with subgroups made up of variable baseline liver function status and radiation treatment modality. Fatal hepatotoxicity occurred in patients (2 of 15) with low total liver funcation (<0.12) and low Dmid (<7 GyEQD2). CONCLUSIONS: Longitudinal SC SPECT/CT imaging revealed patient-specific variations in dose-response and may identify patients with poor baseline liver function and increased sensitivity to radiation therapy. Validation of this regional liver dose-response modeling concept as a surrogate for patient-specific radiosensitivity has potential to guide HCC therapy regimen selection and planning constraints.

Using synthetic CT for partial brain radiation therapy: Impact on image guidance.

PURPOSE: Recent advancements in synthetic computed tomography (synCT) from magnetic resonance (MR) imaging data have made MRI-only treatment planning feasible in the brain, although synCT performance for image guided radiation therapy (IGRT) is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT. METHODS AND MATERIALS: Ten brain cancer patients (12 lesions, 7 postsurgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and fluid attenuation inversion recovery datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index, Dice similarity coefficient, and Jaccard index. Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2-dimensional (2D)-2D rigid registrations using normalized mutual information. Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3-dimensional vector difference. A total of 1490 rigid registrations were assessed. RESULTS: DRR agreements in anteroposterior and lateral views for overlap index, Dice similarity coefficient, and Jaccard index were >0.95. Normalized mutual information results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (P < .05). The population average absolute shifts were 0.77 ± 0.58 and 0.76 ± 0.59 mm for CT and synCT, respectively, for all axes/quadrants. Three-dimensional vectors were <2 mm in 77.7 ± 10.8% and 76.5 ± 7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in postsurgical cases (vector displacements >2 mm in affected quadrants). CONCLUSIONS: DRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in postsurgical settings.

Optimization of a novel large field of view distortion phantom for MR-only treatment planning.

PURPOSE: MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution. METHOD AND MATERIALS: To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously published 1.0 T results, and integrated into the 3D Slicer application platform. RESULTS: All foam samples provided sufficient MR image contrast with paintball landmarks. Urethane foam (compressive strength ∼1000 psi, density ~20 lb/ft3 ) was selected for its accurate machinability and weight characteristics. For smaller bores, a phantom version with the following parameters was used: 15 foam plates, 55 × 55 × 37.5 cm3 (L×W×H), 5,082 landmarks, and weight ~30 kg. To accommodate > 70 cm wide bores, an extended build used 20 plates spanning 55 × 55 × 50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization software was implemented as an external module into 3D Slicer's plugin framework and results agreed with the literature. CONCLUSION: The design and implementation of a modular, extendable distortion phantom was optimized for several bore configurations. The phantom and analysis software will be available for multi-institutional collaborations and cross-validation trials to support MR-only planning.

Impact of incorporating visual biofeedback in 4D MRI.

Precise radiation therapy (RT) for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast in 4D CT. 4D MRI offers improved con-trast although long scan times and irregular breathing patterns can be limiting. To address this, visual biofeedback (VBF) was introduced into 4D MRI. Ten volunteers were consented to an IRB-approved protocol. Prospective respiratory-triggered, T2-weighted, coronal 4D MRIs were acquired on an open 1.0T MR-SIM. VBF was integrated using an MR-compatible interactive breath-hold control system. Subjects visually monitored their breathing patterns to stay within predetermined tolerances. 4D MRIs were acquired with and without VBF for 2- and 8-phase acquisitions. Normalized respiratory waveforms were evaluated for scan time, duty cycle (programmed/acquisition time), breathing period, and breathing regularity (end-inhale coefficient of variation, EI-COV). Three reviewers performed image quality assessment to compare artifacts with and without VBF. Respiration-induced liver motion was calculated via centroid difference analysis of end-exhale (EE) and EI liver contours. Incorporating VBF reduced 2-phase acquisition time (4.7 ± 1.0 and 5.4 ± 1.5 min with and without VBF, respectively) while reducing EI-COV by 43.8% ± 16.6%. For 8-phase acquisitions, VBF reduced acquisition time by 1.9 ± 1.6 min and EI-COVs by 38.8% ± 25.7% despite breathing rate remaining similar (11.1 ± 3.8 breaths/min with vs. 10.5 ± 2.9 without). Using VBF yielded higher duty cycles than unguided free breathing (34.4% ± 5.8% vs. 28.1% ± 6.6%, respectively). Image grading showed that out of 40 paired evaluations, 20 cases had equivalent and 17 had improved image quality scores with VBF, particularly for mid-exhale and EI. Increased liver excursion was observed with VBF, where superior-inferior, anterior-posterior, and left-right EE-EI displacements were 14.1± 5.8, 4.9 ± 2.1, and 1.5 ± 1.0 mm, respectively, with VBF compared to 11.9 ± 4.5, 3.7 ± 2.1, and 1.2 ± 1.4 mm without. Incorporating VBF into 4D MRI substantially reduced acquisition time, breathing irregularity, and image artifacts. However, differences in excursion were observed, thus implementation will be required throughout the RT workflow.

Image Guided Radiation Therapy Using Synthetic Computed Tomography Images in Brain Cancer.

PURPOSE: The development of synthetic computed tomography (CT) (synCT) derived from magnetic resonance (MR) images supports MR-only treatment planning. We evaluated the accuracy of synCT and synCT-generated digitally reconstructed radiographs (DRRs) relative to CT and determined their performance for image guided radiation therapy (IGRT). METHODS AND MATERIALS: Magnetic resonance simulation (MR-SIM) and CT simulation (CT-SIM) images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images (n=37) were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism. RESULTS: Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4 ± 0.5 mm (range, -0.6 to 1.6 mm), 0.0 ± 0.5 mm (range, -0.9 to 1.2 mm), and 0.1 ± 0.3 mm (range, -0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6 ± 0.4 mm (range, -0.2 to 1.6 mm), 0.2 ± 0.4 mm (range, -0.3 to 1.2 mm), and 0.2 ± 0.3 mm (range, -0.2 to 1.2 mm) for the S-I, L-R, and A-P axes, respectively. The CT-SIM and synCT derived margins were <0.3 mm different. CONCLUSION: DRRs generated by synCT were in close agreement with CT-SIM. Planar and volumetric image registrations to synCT-derived targets were comparable with CT for phantom and patients. This validation is the next step toward MR-only planning for the brain.

Technical Note: Characterization and correction of gradient nonlinearity induced distortion on a 1.0 T open bore MR-SIM.

PURPOSE: Distortions in magnetic resonance imaging (MRI) compromise spatial fidelity, potentially impacting delineation and dose calculation. We characterized 2D and 3D large field of view (FOV), sequence-independent distortion at various positions in a 1.0 T high-field open MR simulator (MR-SIM) to implement correction maps for MRI treatment planning. METHODS: A 36 × 43 × 2 cm(3) phantom with 255 known landmarks (∼1 mm(3)) was scanned using 1.0 T high-field open MR-SIM at isocenter in the transverse, sagittal, and coronal axes, and a 465 × 350 × 168 mm(3) 3D phantom was scanned by stepping in the superior-inferior direction in three overlapping positions to achieve a total 465 × 350 × 400 mm(3) sampled FOV yielding >13 800 landmarks (3D Gradient-Echo, TE/TR/α = 5.54 ms/30 ms/28°, voxel size = 1 × 1 × 2 mm(3)). A binary template (reference) was generated from a phantom schematic. An automated program converted MR images to binary via masking, thresholding, and testing for connectivity to identify landmarks. Distortion maps were generated by centroid mapping. Images were corrected via warping with inverse distortion maps, and temporal stability was assessed. RESULTS: Over the sampled FOV, non-negligible residual gradient distortions existed as close as 9.5 cm from isocenter, with a maximum distortion of 7.4 mm as close as 23 cm from isocenter. Over six months, average gradient distortions were -0.07 ± 1.10 mm and 0.10 ± 1.10 mm in the x and y directions for the transverse plane, 0.03 ± 0.64 and -0.09 ± 0.70 mm in the sagittal plane, and 0.4 ± 1.16 and 0.04 ± 0.40 mm in the coronal plane. After implementing 3D correction maps, distortions were reduced to <1 pixel width (1 mm) for all voxels up to 25 cm from magnet isocenter. CONCLUSIONS: Inherent distortion due to gradient nonlinearity was found to be non-negligible even with vendor corrections applied, and further corrections are required to obtain 1 mm accuracy for large FOVs. Statistical analysis of temporal stability shows that sequence independent distortion maps are consistent within six months of characterization.

Intrafraction variability and deformation quantification in the breast.

PURPOSE: To evaluate intrafraction variability and deformation of the lumpectomy cavity (LC), breast, and nearby organs. METHODS AND MATERIALS: Sixteen left-sided postlumpectomy and 1 bilateral breast cancer cases underwent free-breathing CT (FBCT) and 10-phase 4-dimensional CT (4DCT). Deformable image registration was used for deformation analysis and contour propagation of breast, heart, lungs, and LC between end-exhale and end-inhale 4DCT phases. Respiration-induced motion was calculated via centroid analysis. Two planning target volumes (PTVs) were compared: PTV(FBCT) from the FBCT volume with an isotropic 10 mm expansion (5 mm excursion and 5 mm setup error) and PTV(4DCT) generated from the union of 4DCT contours with isotropic 5 mm margin for setup error. Volume and geometry were evaluated via percent difference and bounding box analysis, respectively. Deformation correlations between breast/cavity, breast/lung, and breast/heart were evaluated. Associations were tested between cavity deformation and proximity to chest wall and breast surface. RESULTS: Population-based 3-dimensional vector excursions were 2.5 ± 1.0 mm (range, 0.8-3.8 mm) for the cavity and 2.0 ± 0.8 mm (range, 0.7-3.0 mm) for the ipsilateral breast. Cavity excursion was predominantly in the anterior and superior directions (1.0 ± 0.8 mm and -1.8 ± 1.2 mm, respectively). Similarly, for all cases, LCs and ipsilateral breasts yielded median deformation values in the superior direction. For 14 of 17 patients, the LCs and breast interquartile ranges tended toward the anterior direction. The PTV(FBCT) was 51.5% ± 10.8% larger (P<.01) than PTV(4DCT). Bounding box analysis revealed that PTV(FBCT) was 9.8 ± 1.2 (lateral), 9.0 ± 2.2 (anterior-posterior), and 3.9 ± 1.8 (superior-inferior) mm larger than PTV(4DCT). Significant associations between breast and cavity deformation were found for 6 of 9 axes. No dependency was found between cavity deformation and proximity to chest wall or breast surface. CONCLUSIONS: Lumpectomy cavity and breast deformation and motion demonstrated large variability. A PTV(4DCT) approach showed value in patient-specific margins, particularly if robust interfraction setup analysis can be performed.

Characterization of a commercial hybrid iterative and model-based reconstruction algorithm in radiation oncology.

PURPOSE: Iterative reconstruction (IR) reduces noise, thereby allowing dose reduction in computed tomography (CT) while maintaining comparable image quality to filtered back-projection (FBP). This study sought to characterize image quality metrics, delineation, dosimetric assessment, and other aspects necessary to integrate IR into treatment planning. METHODS: CT images (Brilliance Big Bore v3.6, Philips Healthcare) were acquired of several phantoms using 120 kVp and 25-800 mAs. IR was applied at levels corresponding to noise reduction of 0.89-0.55 with respect to FBP. Noise power spectrum (NPS) analysis was used to characterize noise magnitude and texture. CT to electron density (CT-ED) curves were generated over all IR levels. Uniformity as well as spatial and low contrast resolution were quantified using a CATPHAN phantom. Task specific modulation transfer functions (MTF task) were developed to characterize spatial frequency across objects of varied contrast. A prospective dose reduction study was conducted for 14 patients undergoing interfraction CT scans for high-dose rate brachytherapy. Three physicians performed image quality assessment using a six-point grading scale between the normal-dose FBP (reference), low-dose FBP, and low-dose IR scans for the following metrics: image noise, detectability of the vaginal cuff/bladder interface, spatial resolution, texture, segmentation confidence, and overall image quality. Contouring differences between FBP and IR were quantified for the bladder and rectum via overlap indices (OI) and Dice similarity coefficients (DSC). Line profile and region of interest analyses quantified noise and boundary changes. For two subjects, the impact of IR on external beam dose calculation was assessed via gamma analysis and changes in digitally reconstructed radiographs (DRRs) were quantified. RESULTS: NPS showed large reduction in noise magnitude (50%), and a slight spatial frequency shift (∼ 0.1 mm(-1)) with application of IR at L6. No appreciable changes were observed for CT-ED curves between FBP and IR levels [maximum difference ∼ 13 HU for bone (∼ 1% difference)]. For uniformity, differences were ∼ 1 HU between FBP and IR. Spatial resolution was well conserved; the largest MTFtask decrease between FBP and IR levels was 0.08 A.U. No notable changes in low-contrast detectability were observed and CNR increased substantially with IR. For the patient study, qualitative image grading showed low-dose IR was equivalent to or slightly worse than normal dose FBP, and is superior to low-dose FBP (p < 0.001 for noise), although these did not translate to differences in CT number, contouring ability, or dose calculation. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using the most aggressive IR level [-1.2 ± 4.9 HU (range: -17.6-12.5 HU)]. No clinically significant contour differences were found between IR and FBP, with OIs and DSCs ranging from 0.85 to 0.95. Negligible changes in dose calculation were observed. DRRs preserved anatomical detail with <2% difference in intensity from FBP combined with aggressive IRL6. CONCLUSIONS: These results support integrating IR into treatment planning. While slight degradation in edges and shift in texture were observed in phantom, patient results show qualitative image grading, contouring ability, and dosimetric parameters were not adversely affected.