Purpose

To characterize potential advantages of online-adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (SBRT) to treat oligometastatic disease of the non-liver abdomen and central thorax.

Methods and Materials

Ten patients treated with RT for unresectable primary or oligometastatic disease of the non-liver abdomen (n=5) or central thorax (n=5) underwent imaging throughout treatment on a clinical MR image guided RT system. The SBRT plans were created on the basis of tumor/organ at risk (OAR) anatomy at initial computed tomography simulation (PI), and simulated adaptive plans were created on the basis of observed MR image set tumor/OAR “anatomy of the day” (PA). Each PA was planned under workflow constraints to simulate online-adaptive RT. Prescribed dose was 50 Gy/5 fractions, with goal coverage of 95% planning target volume (PTV) by 95% of the prescription, subject to hard OAR constraints. The PI was applied to each MR dataset and compared with PA to evaluate changes in dose delivered to tumor/OARs, with dose escalation when possible.

Results

Hard OAR constraints were met for all PIs based on anatomy from initial computed tomography simulation, and all PAs based on anatomy from each daily MR image set. Application of the PI to anatomy of the day caused OAR constraint violation in 19 of 30 cases. Adaptive planning increased PTV coverage in 21 of 30 cases, including 14 cases in which hard OAR constraints were violated by the nonadaptive plan. For 9 PA cases, decreased PTV coverage was required to meet hard OAR constraints that would have been violated in a nonadaptive setting.

Conclusions

Online-adaptive MRI-guided SBRT may allow PTV dose escalation and/or simultaneous OAR sparing compared with nonadaptive SBRT. A prospective clinical trial is underway at our institution to evaluate clinical outcomes of this technique.

Abstract

When discussing local treatment modalities, physicians often quip that there can be no blind surgeons, suggesting that an inherent advantage to surgery is the ability to precisely visualize the target. Advances in radiation therapy (RT) technology over the years have significantly improved the radiation oncologists’ abilities to precisely sculpt high-dose radiation to a variety of targets, simultaneously improving local control and toxicity profiles. However, even the most sophisticated methods of CT-based image-guided radiotherapy (IGRT) are hampered by limitations that can compromise target localization and motion management. Additionally, real- time adaptive radiotherapy (ART) programs, wherein radiation plans can be molded to fit the often malleable anatomy of tumors and organs-at-risk, have not yet been developed. For these reasons, MRI-guided RT is considered the next frontier of radiation oncology. However, the development of integrated MRI/RT-delivery platforms is complicated by several technical challenges that have precluded development of MRI-guided linear accelerators. By virtue of employing a low-field (0.35 T) MRI and three 60Co sources, a newly available tri-60Co teletherapy system (MRIdian SystemTM, ViewRayTM, Cleveland, OH, USA) has tackled these technical concerns and has thus become the first MRI-guided RT platform with FDA approval for medical use. In this Review, we describe the abilities of this device to accomplish the goals of MRI-guided RT—improved target localization, sophisticated motion management, and on-line ART—by exploring published feasibility, proof-of-principle, and proof-of-practice studies.

Purpose

For the first time, MRI-guided radiation therapy systems can acquire cine images to dynamically monitor in-treatment internal organ motion. However, the complex head and neck (H&N) structures and low-contrast/resolution of on-board cine MRI images make automatic motion tracking a very challenging task. In this study, the authors proposed an integrated model-driven method to automatically track the in-treatment motion of the H&N upper airway, a complex and highly deformable region wherein internal motion often occurs in an either voluntary or involuntary manner, from cine MRI images for the analysis of H&N motion patterns.

Methods

Considering the complex H&N structures and ensuring automatic and robust upper airway motion tracking, the authors firstly built a set of linked statistical shapes (including face, face-jaw, and face-jaw-palate) using principal component analysis from clinically approved contours delineated on a set of training data. The linked statistical shapes integrate explicit landmarks and implicit shape representation. Then, a hierarchical model-fitting algorithm was developed to align the linked shapes on the first image frame of a to-be-tracked cine sequence and to localize the upper airway region. Finally, a multifeature level set contour propagation scheme was performed to identify the upper airway shape change, frame-by-frame, on the entire image sequence. The multifeature fitting energy, including the information of intensity variations, edge saliency, curve geometry, and temporal shape continuity, was minimized to capture the details of moving airway boundaries. Sagittal cine MR image sequences acquired from three H&N cancer patients were utilized to demonstrate the performance of the proposed motion tracking method.

Results

The tracking accuracy was validated by comparing the results to the average of two manual delineations in 50 randomly selected cine image frames from each patient. The resulting average dice similarity coefficient (93.28%  ±  1.46%) and margin error (0.49  ±  0.12 mm) showed good agreement between the automatic and manual results. The comparison with three other deformable model-based segmentation methods illustrated the superior shape tracking performance of the proposed method. Large interpatient variations of swallowing frequency, swallowing duration, and upper airway cross-sectional area were observed from the testing cine image sequences.

Conclusions

The proposed motion tracking method can provide accurate upper airway motion tracking results, and enable automatic and quantitative identification and analysis of in-treatment H&N upper airway motion. By integrating explicit and implicit linked-shape representations within a hierarchical model-fitting process, the proposed tracking method can process complex H&N structures and low-contrast/resolution cine MRI images. Future research will focus on the improvement of method reliability, patient motion pattern analysis for providing more information on patient-specific prediction of structure displacements, and motion effects on dosimetry for better H&N motion management in radiation therapy.

Abstract

A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image-guided radiation therapy (MR-IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient’s total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam-on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected dose rate. To predict the remain­ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of the proposed prediction algorithm is sufficient to support patient treatment appointment scheduling. This developed software tool is currently applied in use on a daily basis in our clinic, and could also be used as an important indicator for treatment plan complexity.

Purpose

To first demonstrate the viability of applying an image processing technique for tracking regions on low-contrast cine-MR images acquired during image-guided radiation therapy, and then outline a scheme that uses tracking data for optimizing gating results in a patient-specific manner.

Methods

A first-generation MR-IGRT system—treating patients since January 2014—integrates a 0.35 T MR scanner into an annular gantry consisting of three independent Co-60 sources. Obtaining adequate frame rates for capturing relevant patient motion across large fields-of-view currently requires coarse in-plane spatial resolution. This study initially (1) investigate the feasibility of rapidly tracking dense pixel correspondences across single, sagittal plane images (with both moderate signal-to-noise and spatial resolution) using a matching objective for highly descriptive vectors called scale-invariant feature transform (SIFT) descriptors associated to all pixels that describe intensity gradients in local regions around each pixel. To more accurately track features, (2) harmonic analysis was then applied to all pixel trajectories within a region-of-interest across a short training period. In particular, the procedure adjusts the motion of outlying trajectories whose relative spectral power within a frequency bandwidth consistent with respiration (or another form of periodic motion) does not exceed a threshold value that is manually specified following the training period. To evaluate the tracking reliability after applying this correction, conventional metrics—including Dice similarity coefficients (DSCs), mean tracking errors (MTEs), and Hausdorff distances (HD)—were used to compare target segmentations obtained via tracking to manually delineated segmentations. Upon confirming the viability of this descriptor-based procedure for reliably tracking features, the study (3) outlines a scheme for optimizing gating parameters—including relative target position and a tolerable margin about this position—derived from a probability density function that is constructed using tracking results obtained just prior to treatment.

Results

The feasibility of applying the matching objective for SIFT descriptors toward pixel-by-pixel tracking on cine-MR acquisitions was first retrospectively demonstrated for 19 treatments (spanning various sites). Both with and without motion correction based on harmonic analysis, sub-pixel MTEs were obtained. A mean DSC value spanning all patients of 0.916±0.001 was obtained without motion correction, with DSC values exceeding 0.85 for all patients considered. While most patients show accurate tracking without motion correction, harmonic analysis does yield substantial gain in accuracy (defined using HDs) for three particularly challenging subjects. An application of tracking toward a gating optimization procedure was then demonstrated that should allow a physician to balance beam-on time and tissue sparing in a patient-specific manner by tuning several intuitive parameters.

Conclusions

Tracking results show high fidelity in assessing intrafractional motion observed on cine-MR acquisitions. Incorporating harmonic analysis during a training period improves the robustness of the tracking for challenging targets. The concomitant gating optimization procedure should allow for physicians to quantitatively assess gating effectiveness quickly just prior to treatment in a patient-specific manner.

Abstract

We evaluated the feasibility of planning stereotactic body radiotherapy (SBRT) for large central early- stage non-small cell lung cancer with a tri-cobalt-60 (tri-60Co) system equipped with real-time magnetic resonance imaging (MRI) guidance, as compared to linear accelerator (LINAC)–based SBRT. In all, 20 patients with large central early-stage non-small cell lung cancer who were treated between 2010 and 2015 with LINAC-based SBRT were replanned using a tri-60Co system for a prescription dose of 50 Gy in 4 fractions. Doses to organs at risk were evaluated based on established MD Anderson constraints for central lung SBRT. R100 values were calculated as the total tissue volume receiving 100% of the dose (V100) divided by the planning target volume and compared to assess dose conformity. Dosimetric comparisons between LINAC-based and tri-60Co SBRT plans were performed using Student's t-test and Wilcoxon Ranks test. Blinded reviews by radiation oncologists were performed to assess the suitability of both plans for clinical delivery. The mean planning target volume was 48.3 cc (range: 12.1 to 139.4 cc). Of the tri-60Co SBRT plans, a mean 97.4% of dosimetric parameters per patient met MD Anderson dose constraints, whereas a mean 98.8% of dosimetric parameters per patient were met with LINAC-based SBRT planning (p = 0.056). R100 values were similar between both plans (1.20 vs 1.21, p = 0.79). Upon blinded review by 4 radiation oncologists, an average of 90% of the tri-60Co SBRT plans were considered acceptable for clinical delivery compared with 100% of the corresponding LINAC-based SBRT plans (p = 0.17). SBRT planning using the tri-60Co system with built-in MRI is feasible and achieves clinically acceptable plans for most central lung patients, with similar target dose conformity and organ at risk dosimetry. The added benefit of real-time MRI-guided therapy may further optimize tumor targeting while improving normal tissue sparing, which warrants further investigation in a prospective feasibility clinical trial.

Purpose

Magnetic resonance imaging (MRI)-guided Co-60 provides daily and intrafractional MRI soft tissue imaging for improved target and critical organ tracking. To increase delivery efficiency, the system uses three Co-60 sources at 120° apart, allowing up to 600 cGy combined dose rate at isocenter. Despite the potential tripling in output, creating a delivery plan that uses all three sources is considerably unintuitive. Here, the authors computerize the triplet orientation optimization using column generation, an approach that was demonstrated effective in integrated beam orientation and fluence optimization for noncoplanar therapies. To achieve a better plan quality without increasing the treatment time, the authors then solve a fluence map optimization (FMO) problem while regularizing the fluence maps to reduce the number of deliverable MLC segments.

Methods

Three patients—one prostate, one lung, and one head and neck boost plan (H&NBoost)—were evaluated in this study. For each patient, the beamlet doses were calculated using Monte Carlo, under a 0.35 T magnetic field, for 180 equally spaced coplanar beams grouped into 60 triplets. The beamlet size is 1.05 × 0.5 cm determined by the MLC leaf thickness and step size. The triplets were selected using the column generation algorithm. The FMO problem was formulated using an L2-norm dose fidelity term and an L1-norm anisotropic total variation regularization term, which allows controlling the number of MLC segments, and hence the treatment time, with minimal degradation to the dose. The authors’ Fluence Regularization and Optimized Selection of Triplets (FROST) plans were compared against the clinical treatment plans (CLNs) produced by an experienced dosimetrist. PTV homogeneity, max dose, mean dose, D95, D98, and D99 were evaluated. OAR max and mean doses, as well as R50, defined as the ratio of the 50% isodose volume over the planning target volume were investigated.

Results

The mean PTV D95, D98, and D99 differ by +0.04%, +0.07%, and +0.25% of the prescription dose between planning methods. The mean PTV homogeneity was virtually same with values at 0.8788 (FROST) and 0.8812 (CLN). R50 decreased by 0.67 comparing FROST to CLN. On average, FROST reduced Dmax and Dmean of OARs by 7.30% and 6.08% of the prescription dose, respectively. The manual CLN planning processes required numerous trial and error runs. The FROST plans on the other hand required minimal human intervention.

Conclusions

Efficient delivery of MRI-guided Co-60 therapy needs the output of multiple sources yet suffers from unintuitive and laborious manual beam selection processes. Computerized triplet orientation optimization improves both planning efficiency and plan dosimetry. The novel fluence map regularization provides additional controls over the number of MLC segments and treatment time.

Abstract

The aim of this study is to investigate the delivery accuracy of intensity-modulated radiation therapy (IMRT) plans in the two-headed mode of the ViewRay™ system in comparison with that of the normal operation treatment plan of the machine. For this study, a total of eight IMRT plans and corresponding verification plans were generated (four head and neck, two liver, and two prostate IMRT plans). The delivered dose distributions were measured using ArcCHECK™ with the insertion of an ionization chamber. We measured the delivered dose distributions in three-headed mode (normal operation of the machine), two-headed mode with head 1 disabled, two-headed mode with head 2 disabled, and two-headed mode with head 3 disabled. Therefore, a total of four measurements were performed for each IMRT plan. The global gamma passing rates (3%/3 mm) in three-headed mode, head 1 disabled, head 2 disabled, and head 3 disabled were 99.9±0.1%, 99.8±0.3%, 99.6±0.7%, and 99.7±0.4%, respectively. The difference in the gamma passing rates of the three- and two-headed modes was insignificant. With 2%/2 mm, the rates were 96.6±3.6%, 97.2±3.5%, 95.7±6.2%, and 95.5±4.3%, respectively. Between three-headed mode and head 3 disabled, a statistically significant difference was observed with a p-value of 0.02; however, the difference was minimal (1.1%). The chamber readings showed differences of approximately 1% between three- and two-headed modes, which were minimal. Therefore, the treatment plan delivery in the two-headed mode of the ViewRay™ system seems accurate and robust.

Objective

Prior studies have relied on CT to assess alterations in anatomy among patients undergoing radiation for head and neck cancer. We sought to determine the feasibility of using MRI-based image-guided radiotherapy to quantify these changes and to ascertain their potential dosimetric implications.

Methods

6 patients with head and neck cancer were treated with intensity-modulated radiotherapy (IMRT) on a novel tri-60Co teletherapy system equipped with a 0.35-T MRI (VR, ViewRay Incorporated, Oakwood Village, OH) to 66–70 Gy in 33 fractions (fx). Pre-treatment MRIs on Fx 1, 5, 10, 15, 20, 25, 30 and 33 were imported into a contouring interface, where the primary gross tumour volume (GTV) and parotid glands were delineated. The centre of mass (COM) shifts for these structures were assessed relative to Day 1. Dosimetric data were co-registered with the MRIs, and doses to the GTV and parotid glands were assessed.

Results

Primary GTVs decreased significantly over the course of IMRT (median % volume loss, 38.7%; range, 29.5–72.0%; p < 0.05) at a median rate of 1.2%/fx (range, 0.92–2.2%/fx). Both the ipsilateral and contralateral parotid glands experienced significant volume loss (p < 0.05, for all) and shifted medially during IMRT. Weight loss correlated significantly with parotid gland volume loss and medial COM shift (p < 0.05).

Conclusion

Integrated on-board MRI can be used to accurately contour and analyze primary GTVs and parotid glands over the course of IMRT. COM shifts and significant volume reductions were observed, confirming the results of prior CT-based exercises.

Purpose

Magnetokinetic changes may affect crystal orientation and polymerization within the active layer of radiochromic film (RCF). This effect is investigated in a magnetic resonance image-guided radiotherapy unit within the context of film dosimetry.

Methods

Gafchromic EBT2 RCF was irradiated in a 30 × 30 × 30 cm3 solid water phantom using a Co-60 MRI guided radiotherapy system (B = 0.35 T) under normal operating conditions, and under the exact conditions and setup without a magnetic field. Fifteen 20.3 × 25.4 cm2 EBT2 film sheets were placed at three different depths (d = 0.5, 5, and 10 cm) using five different treatment plans. The plans were computed using the MRIdian (ViewRay, Inc.) treatment planning system to deliver doses between 0 and 17.6 Gy. Films were analyzed before and after irradiation to obtain the net optical density (netOD) for each color channel separately. Scanning electron microscope (SEM) images were obtained to compare the active layer of selected samples.

Results

The results indicated that the red channel netOD decreased between 0.013 and 0.123 (average of 0.060 ± 0.033) for doses above 2.8 Gy, with a linear increase in this effect for higher doses. Green channel netOD showed similar results with a decrease between 0.012 and 0.105 (average of 0.041 ± 0.027) for doses above 3.5 Gy. The blue channel showed the weakest effect with a netOD decrease between 0.013 and 0.029 (average of 0.020 ± 0.006) for doses above 8.0 Gy. SEM images show changes in crystal orientation within active layer in RCF exposed in a magnetic field.

Conclusions

The presence of a magnetic field affects crystal orientation and polymerization during irradiation, where netOD decreased by an average of 8.7%, 8.0%, and 4.3% in the red, green, and blue channels, respectively. The under response was dependent on dose and differed by up to 15% at 17.6 Gy.