Yingli Yang

4π Non-Coplanar Liver SBRT: A Novel Delivery Technique

PURPOSE To improve the quality of liver stereotactic body radiation therapy (SBRT) treatments, a novel 4π framework was developed with accompanying algorithms to optimize non-coplanar beam orientations and fluences. The dose optimization is performed on a patient-specific deliverable beam geometry solution space, parameterized with patient and linear accelerator gantry orientations. METHODS AND MATERIALS Beams causing collision between the gantry and the couch or patient were eliminated by simulating all beam orientations using a precise computer assisted design model of the linear accelerator and a human subject. Integrated beam orientation and fluence map optimizations were performed on remaining beams using a greedy column generation method. Testing of the new method was performed on 10 liver SBRT cases previously treated with 50 to 60 Gy in 5 fractions using volumetric modulated arc therapy (VMAT). For each patient, both 14 and 22 non-coplanar fields were selected and optimized to meet the objective of ≥95% of the planning target volume (PTV) covered by 100% of the prescription dose. Doses to organs at risk, normal liver volumes receiving <15 Gy, integral dose, and 50% dose spillage volumes were compared against the delivered clinical VMAT plans. RESULTS Compared with the VMAT plans, the 4π plans yielded reduced 50% dose spillage volume and integral dose by 22% (range 10%-40%) and 19% (range 13%-26%), respectively. The mean normal liver volume receiving <15 Gy was increased by 51 cc (range 21-107 cc) with a 31% reduction of the mean normal liver dose. Mean doses to the left kidney and right kidney and maximum doses to the stomach and spinal cord were on average reduced by 70%, 51%, 67%, and 64% (P≤.05). CONCLUSIONS This novel 4π non-coplanar radiation delivery technique significantly improved dose gradient, reduced high dose spillage, and improved organ at risk sparing compared with state of the art VMAT plans.

4π noncoplanar stereotactic body radiation therapy for centrally located or larger lung tumors.

PURPOSE To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4π planning system. METHODS AND MATERIALS This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4π plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4π without violating dose limits set by the clinical plans. The deliverability of 4π plans was preliminarily tested. RESULTS Using 4π plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P≤.001), respectively, and R50 was reduced by more than 50%. Lung V20, V10, and V5 were reduced by 64%, 53%, and 32% (P≤.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4π plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. CONCLUSIONS We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4π plans yielded significantly and consistently improved tumor coverage and critical organ sparing. Given the known challenges in central structure dose constraints in stereotactic body radiation therapy to the lung, 4π planning may increase efficacy and reduce toxicity.

Feasibility of prostate robotic radiation therapy on conventional C-arm linacs

PURPOSE Significant dosimetric improvement for radiation therapy using optimized noncoplanar fields has been previously demonstrated. The purpose here is to study the feasibility of optimized robotic noncoplanar radiation therapy, termed 4π therapy, for prostate cancer treatments on a conventional C-arm linac. METHODS AND MATERIALS Twelve low-risk prostate cancer patients previously treated by 2-arc volumetric modulated arc therapy (VMAT) were selected. Forty gray in 5 fractions were prescribed to cover 95% of the prostate planning target volume (PTV). To replan by 4π therapy, a column generation method was used to optimize beam orientations and fluence. A total of 30 beams were selected for each patient. RESULTS Both planning methods provided adequate PTV coverage. Compared against VMAT plans, the 4π plan reduced the rectum V50%, V80%, V90%, D1cc, and the penile bulb maximum doses by 50%, 28%, 19% 11%, and 9% (P < .005), respectively, and the mean body dose was reduced from 2.07 Gy to 1.75 Gy (P = .0001). The bladder dose was only slightly reduced. CONCLUSIONS By optimizing beam angles and fluences in the noncoplanar solution space, superior prostate treatment plan quality was achieved compared against state of the art VMAT plans. The dosimetric potential for 4π therapy is established on an existing C-arm linac platform.

Longitudinal diffusion MRI for treatment response assessment: Preliminary experience using an MRI-guided tri-cobalt 60 radiotherapy system

PURPOSE To demonstrate the preliminary feasibility of a longitudinal diffusion magnetic resonance imaging (MRI) strategy for assessing patient response to radiotherapy at 0.35 T using an MRI-guided radiotherapy system (ViewRay). METHODS Six patients (three head and neck cancer, three sarcoma) who underwent fractionated radiotherapy were enrolled in this study. A 2D multislice spin echo single-shot echo planar imaging diffusion pulse sequence was implemented on the ViewRay system and tested in phantom studies. The same pulse sequence was used to acquire longitudinal diffusion data (every 2-5 fractions) on the six patients throughout the entire course of radiotherapy. The reproducibility of the apparent diffusion coefficient (ADC) measurements was assessed using reference regions and the temporal variations of the tumor ADC values were evaluated. RESULTS In diffusion phantom studies, the ADC values measured on the ViewRay system matched well with reference ADC values with <5% error for a range of ground truth diffusion coefficients of 0.4-1.1 × 10(-3) mm(2)/s. The remote reference regions (i.e., brainstem in head and neck patients) had consistent ADC values throughout the therapy for all three head and neck patients, indicating acceptable reproducibility of the diffusion imaging sequence. The tumor ADC values changed throughout therapy, with the change differing between patients, ranging from a 40% drop in ADC within the first week of therapy to gradually increasing throughout therapy. For larger tumors, intratumoral heterogeneity was observed. For one sarcoma patient, postradiotherapy biopsy showed less than 10% necrosis score, which correlated with the observed 40% decrease in ADC from the fifth fraction to the eighth treatment fraction. CONCLUSIONS This pilot study demonstrated that longitudinal diffusion MRI is feasible using the 0.35 T ViewRay MRI. Larger patient cohort studies are warranted to correlate the longitudinal diffusion measurements to patient outcomes. Such an approach may enable response-guided adaptive radiotherapy.

Accuracy of UTE-MRI-based patient setup for brain cancer radiation therapy.

PURPOSE Radiation therapy simulations solely based on MRI have advantages compared to CT-based approaches. One feature readily available from computed tomography (CT) that would need to be reproduced with MR is the ability to compute digitally reconstructed radiographs (DRRs) for comparison against on-board radiographs commonly used for patient positioning. In this study, the authors generate MR-based bone images using a single ultrashort echo time (UTE) pulse sequence and quantify their 3D and 2D image registration accuracy to CT and radiographic images for treatments in the cranium. METHODS Seven brain cancer patients were scanned at 1.5 T using a radial UTE sequence. The sequence acquired two images at two different echo times. The two images were processed using an in-house software to generate the UTE bone images. The resultant bone images were rigidly registered to simulation CT data and the registration error was determined using manually annotated landmarks as references. DRRs were created based on UTE-MRI and registered to simulated on-board images (OBIs) and actual clinical 2D oblique images from ExacTrac™. RESULTS UTE-MRI resulted in well visualized cranial, facial, and vertebral bones that quantitatively matched the bones in the CT images with geometric measurement errors of less than 1 mm. The registration error between DRRs generated from 3D UTE-MRI and the simulated 2D OBIs or the clinical oblique x-ray images was also less than 1 mm for all patients. CONCLUSIONS UTE-MRI-based DRRs appear to be promising for daily patient setup of brain cancer radiotherapy with kV on-board imaging.

Respiratory motion resolved, self-gated 4D-MRI using Rotating Cartesian K-space (ROCK).

Purpose To propose and validate a respiratory motion resolved, self‐gated (SG) 4D‐MRI technique to assess patient‐specific breathing motion of abdominal organs for radiation treatment planning. Methods The proposed 4D‐MRI technique was based on the balanced steady‐state free‐precession (bSSFP) technique and 3D k‐space encoding. A novel rotating cartesian k‐space (ROCK) reordering method was designed which incorporates repeatedly sampled k‐space centerline as the SG motion surrogate and allows for retrospective k‐space data binning into different respiratory positions based on the amplitude of the surrogate. The multiple respiratory‐resolved 3D k‐space data were subsequently reconstructed using a joint parallel imaging and compressed sensing method with spatial and temporal regularization. The proposed 4D‐MRI technique was validated using a custom‐made dynamic motion phantom and was tested in six healthy volunteers, in whom quantitative diaphragm and kidney motion measurements based on 4D‐MRI images were compared with those based on 2D‐CINE images. Results The 5‐minute 4D‐MRI scan offers high‐quality volumetric images in 1.2 × 1.2 × 1.6 mm3 and eight respiratory positions, with good soft‐tissue contrast. In phantom experiments with triangular motion waveform, the motion amplitude measurements based on 4D‐MRI were 11.89% smaller than the ground truth, whereas a −12.5% difference was expected due to data binning effects. In healthy volunteers, the difference between the measurements based on 4D‐MRI and the ones based on 2D‐CINE were 6.2 ± 4.5% for the diaphragm, 8.2 ± 4.9% and 8.9 ± 5.1% for the right and left kidney. Conclusion The proposed 4D‐MRI technique could provide high‐resolution, high‐quality, respiratory motion‐resolved 4D images with good soft‐tissue contrast and are free of the “stitching” artifacts usually seen on 4D‐CT and 4D‐MRI based on resorting 2D‐CINE. It could be used to visualize and quantify abdominal organ motion for MRI‐based radiation treatment planning.

Feasibility evaluation of diffusion-weighted imaging using an integrated MRI-radiotherapy system for response assessment to neoadjuvant therapy in rectal cancer

OBJECTIVE To evaluate the feasibility of on-board diffusion-weighted imaging (DWI) with an integrated low-field MRI radiotherapy system to assess responses to neoadjuvant chemoradiation (NAC) in rectal cancer. METHODS A spin echo-based planar imaging diffusion sequence on a 0.35-T MRI radiotherapy system was acquired over the course of NAC. The apparent diffusion coefficients (ADCs) from the tumour regions of interest (ROIs) were calculated. A functional diffusion map (fDM) was created showing a pixelwise ADC analysis of the ROI over the course of treatment. Surgical pathology was correlated with ADC data. RESULTS Consecutive patients treated on a 0.35-T MRI radiotherapy system were evaluated. Patient A had the worst pathological response to NAC with a tumour regression score of 1 and was the only patient with a negative slope in the change of ADC values over the entire course of NAC, and during both the first and second half of NAC. The fDM from the first half of NAC for Patient A showed discrete dark areas in the tumour ROI, reflecting subregions with decreasing ADC values during NAC. Patient C had the most favourable pathological response to NAC with a Grade 3 response and was the only patient who had an increase in the slope in the change of ADC values from the first to the second half of NAC. CONCLUSION DWI using a low-field MRI radiotherapy system for evaluating the responses to NAC is feasible. Advances in knowledge: ADC values obtained using a 0.35-T MRI radiotherapy system over the course of NAC for rectal cancer correlate with pathological responses.

Characterization of spatial distortion in a 0.35 T MRI-guided radiotherapy system

Spatial distortion results in image deformation that can degrade accurate targeting and dose calculations in MRI-guided adaptive radiotherapy. The authors present a comprehensive assessment of a 0.35 T MRI-guided radiotherapy systems spatial distortion using two commercially-available phantoms with regularly spaced markers. Images of the spatial integrity phantoms were acquired using five clinical protocols on the MRI-guided radiotherapy machine with the radiotherapy gantry positioned at various angles. Software was developed to identify and localize all phantom markers using a template matching approach. Rotational and translational corrections were implemented to account for imperfect phantom alignment. Measurements were made to assess uncertainties arising from susceptibility artifacts, image noise, and phantom construction accuracy. For a clinical 3D imaging protocol with a 1.5 mm reconstructed slice thickness, 100% of spheres within a 50 mm radius of isocenter had a 3D deviation of 1 mm or less. Of the spheres within 100 mm of isocenter, 99.9% had a 3D deviation less than 1 mm. 94.8% and 100% of the spheres within 175 mm were found to be within 1 mm and 2 mm of the expected positions in 3D respectively. Maximum 3D distortions within 50 mm, 100 mm and 175 mm of isocenter were 0.76 mm, 1.15 mm and 1.88 mm respectively. Distortions present in images acquired using the real-time imaging sequence were less than 1 mm for 98.1% and 95.0% of the cylinders within 50 mm and 100 mm of isocenter. The corresponding maximum distortion in these regions was 1.10 mm and 1.67 mm. These results may be used to inform appropriate planning target volume (PTV) margins for 0.35 T MRI-guided radiotherapy. Observed levels of spatial distortion should be explicitly considered when using PTV margins of 3 mm or less or in the case of targets displaced from isocenter by more than 50 mm.

Online Adaptive Radiation Therapy: Implementation of a New Process of Care

Onboard magnetic resonance imaging (MRI) guided radiotherapy is now clinically available in nine centers in the world. This technology has facilitated the clinical implementation of online adaptive radiotherapy (OART), or the ability to alter the daily treatment plan based on tumor and anatomical changes in real-time while the patient is on the treatment table. However, due to the time sensitive nature of OART, implementation in a large and busy clinic has many potential obstacles as well as patient-related safety considerations. In this work, we have described the implementation of this new process of care in the Department of Radiation Oncology at the University of California, Los Angeles (UCLA). We describe the rationale, the initial challenges such as treatment time considerations, technical issues during the process of re-contouring, re-optimization, quality assurance, as well as our current solutions to overcome these challenges. In addition, we describe the implementation of a coverage system with a physician of the day as well as online planners (physicists or dosimetrists) to oversee each OART treatment with patient-specific ‘hand-off’ directives from the patient’s treating physician. The purpose of this effort is to streamline the process without compromising treatment quality and patient safety. As more MRI-guided radiotherapy programs come online, we hope that our experience can facilitate successful adoption of OART in a way that maximally benefits the patient.

Distortion-free diffusion MRI using an MRI-guided Tri-Cobalt 60 radiotherapy system: Sequence verification and preliminary clinical experience

Purpose: Monitoring tumor response during the course of treatment and adaptively modifying treatment plan based on tumor biological feedback may represent a new paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing and predicting tumor response to radiotherapy. However, the conventional diffusion‐weighted single‐shot echo‐planar‐imaging (DW‐ssEPI) technique suffers from limited resolution, severe distortion, and possibly inaccurate ADC at low field strength. The purpose of this work was to develop a reliable, accurate and distortion‐free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0.35 T MRI‐guided radiotherapy system. Methods: A diffusion‐prepared turbo spin echo readout (DP‐TSE) sequence was developed and compared with the conventional diffusion‐weighted single‐shot echo‐planar‐imaging sequence on a 0.35 T MRI‐guided radiotherapy system (ViewRay). A spatial integrity phantom was used to quantitate and compare the geometric accuracy of the two diffusion sequences for three orthogonal orientations. The apparent diffusion coefficient (ADC) accuracy was evaluated on a diffusion phantom under both 0 °C and room temperature to cover a diffusivity range between 0.40 × 10−3 and 2.10 × 10−3 mm2/s. Ten room temperature measurements repeated on five different days were conducted to assess the ADC reproducibility of DP‐TSE. Two glioblastoma (GBM) and six sarcoma patients were included to examine the in vivo feasibility. The target registration error (TRE) was calculated to quantitate the geometric accuracy where structural CT or MR images were co‐registered to the diffusion images as references. ADC maps from DP‐TSE and DW‐ssEPI were calculated and compared. A tube phantom was placed next to patients not treated on ViewRay, and ADCs of this reference tube were also compared. Results: The proposed DP‐TSE passed the spatial integrity test (< 1 mm within 100 mm radius and < 2 mm within 175 mm radius) under the three orthogonal orientations. The detected errors were 0.474 ± 0.355 mm, 0.475 ± 0.287 mm, and 0.546 ± 0.336 mm in the axial, coronal, and sagittal plane. DW‐ssEPI, however, failed the tests due to severe distortion and low signal intensity. Noise correction must be performed for the DW‐ssEPI to avoid ADC quantitation errors, whereas it is optional for DP‐TSE. At 0 °C, the two sequences provided accurate quantitation with < 3% variation with the reference. In the room temperature study, discrepancies between ADCs from DP‐TSE and the reference were within 4%, but could be as high as 8% for DW‐ssEPI after the noise correction. Excellent ADC reproducibility with a coefficient of variation < 5% was observed among the 10 measurements of DP‐TSE, indicating desirable robustness for ADC‐based tumor response assessment. In vivo TRE in DP‐TSE was less than 1.6 mm overall, whereas it could be greater than 12 mm in DW‐ssEPI. For GBM patients, the CSF and brain tissue ADCs from DP‐TSE were within the ranges found in literature. ADC differences between the two techniques were within 8% among the six sarcoma patients. For the reference tube that had a relatively low diffusivity, the two diffusion sequences provided matched measurements. Conclusion: A diffusion technique with excellent geometric fidelity, accurate, and reproducible ADC measurement was demonstrated for longitudinal tumor response assessment using a low‐field MRI‐guided radiotherapy system.