Accurate, repeatable, and geometrically precise diffusion-weighted imaging on a 0.35 T magnetic resonance imaging-guided linear accelerator.

Background and purpose: Diffusion weighted imaging (DWI) allows for the interrogation of tissue cellularity, which is a surrogate for cellular proliferation. Previous attempts to incorporate DWI into the workflow of a 0.35 T MR-linac (MRL) have lacked quantitative accuracy. In this study, accuracy, repeatability, and geometric precision of apparent diffusion coefficient (ADC) maps produced using an echo planar imaging (EPI)-based DWI protocol on the MRL system is illustrated, and in vivo potential for longitudinal patient imaging is demonstrated. Materials and methods: Accuracy and repeatability were assessed by measuring ADC values in a diffusion phantom at three timepoints and comparing to reference ADC values. System-dependent geometric distortion was quantified by measuring the distance between 93 pairs of phantom features on ADC maps acquired on a 0.35 T MRL and a 3.0 T diagnostic scanner and comparing to spatially precise CT images. Additionally, for five sarcoma patients receiving radiotherapy on the MRL, same-day in vivo ADC maps were acquired on both systems, one of which at multiple timepoints. Results: Phantom ADC quantification was accurate on the 0.35 T MRL with significant discrepancies only seen at high ADC. Average geometric distortions were 0.35 (±0.02) mm and 0.85 (±0.02) mm in the central slice and 0.66 (±0.04) mm and 2.14 (±0.07) mm at 5.4 cm off-center for the MRL and diagnostic system, respectively. In the sarcoma patients, a mean pretreatment ADC of 910x10-6 (±100x10-6) mm2/s was measured on the MRL. Conclusions: The acquisition of accurate, repeatable, and geometrically precise ADC maps is possible at 0.35 T with an EPI approach.

Treatment of Central Nervous System Tumors on Combination MR-Linear Accelerators: Review of Current Practice and Future Directions.

Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face.

Magnetic Resonance-Guided Stereotactic Body Radiation Therapy/Hypofractionated Radiation therapy for Metastatic and Primary Central and Ultracentral Lung Lesions.

Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions. Methods: Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation. Central lesions were defined as per the Radiation Therapy Oncology Group and UC as per the HILUS study definitions: (1) group A or tumors less than 1 cm from the trachea and/or mainstem bronchi; or (2) group B or tumors less than 1 cm from the lobar bronchi. The Kaplan-Meier estimate and log-rank test were used to estimate survival. Associations between toxicities and other patient factors were tested using the Mann-Whitney U test and Fisher's exact test. Results: A total of 47 patients were included with a median follow-up of 22.9 months (95% confidence interval: 16.4-29.4). Most (53%) had metastatic disease. All patients had central lesions and 55.3% (n = 26) had UC group A. The median distance from the proximal bronchial tree was 6.0 mm (range: 0.0-19.0 mm). The median biologically equivalent dose (α/ß = 10) was 105 Gy (range: 75-151.2). The most common radiation schedule was 60 Gy in eight fractions (40.4%). Most (55%) had previous systemic therapy, 32% had immunotherapy and 23.4% had previous thoracic radiation therapy. There were 16 patients who underwent daily adaptation. The 1-year overall survival was 82% (median = not reached), local control 87% (median = not reached), and progression-free survival 54% (median = 15.1 mo, 95% confidence interval: 5.1-25.1). Acute toxicity included grade 1 (26%) and grade 2 (21%) with only two patients experiencing grade 3 (4.3%) in the long term. No grade 4 or 5 toxicities were seen. Conclusions: Previous studies noted high rates of toxicity after SBRT to central and UC lung lesions, with reports of grade 5 toxicities. In our cohort, the use of MRgSBRT/MRgHRT with high biologically effective doses was well tolerated, with two grade 3 toxicities and no grade 4/5.

Methodology for computed tomography characterization of commercially available 3D printing materials for use in radiology/radiation oncology.

3D printing in medical physics provides opportunities for creating patient-specific treatment devices and in-house fabrication of imaging/dosimetry phantoms. This study characterizes several commercial fused deposition 3D printing materials with some containing nonstandard compositions. It is important to explore their similarities to human tissues and other materials encountered in patients. Uniform cylinders with infill from 50 to 100% at six evenly distributed intervals were printed using 13 different filaments. A novel approach rotating infill angle 10o between each layer avoids unwanted patterns. Five materials contained high-Z/metallic components. A clinical CT scanner with a range of tube potentials (70, 80, 100, 120, 140 kVp) was used. Density and average Hounsfield unit (HU) were measured. A commercial GAMMEX phantom mimicking various human tissues provides a comparison. Utility of the lookup tables produced is demonstrated. A methodology for calibrating print materials/parameters for a desired HU is presented. Density and HU were determined for all materials as a function of tube voltage (kVp) and infill percentage. The range of HU (-732.0-10047.4 HU) and physical densities (0.36-3.52 g/cm3 ) encompassed most tissues/materials encountered in radiology/radiotherapy applications with many overlapping those of human tissues. Printing filaments doped with high-Z materials demonstrated increased attenuation due to the photoelectric effect with decreased kVp, as found in certain endogenous materials (e.g., bone). HU was faithfully reproduced (within one standard deviation) in a 3D-printed mimic of a commercial anthropomorphic phantom section. Characterization of commercially available 3D print materials facilitates custom object fabrication for use in radiology and radiation oncology, including human tissue and common exogenous implant mimics. This allows for cost reduction and increased flexibility to fabricate novel phantoms or patient-specific devices imaging and dosimetry purposes. A formalism for calibrating to specific CT scanner, printer, and filament type/batch is presented. Utility is demonstrated by printing a commercial anthropomorphic phantom copy.

Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions.

Stereotactic body radiotherapy (SBRT) is an effective radiation therapy technique that has allowed for shorter treatment courses, as compared to conventionally dosed radiation therapy. As its name implies, SBRT relies on daily image guidance to ensure that each fraction targets a tumor, instead of healthy tissue. Magnetic resonance imaging (MRI) offers improved soft-tissue visualization, allowing for better tumor and normal tissue delineation. MR-guided RT (MRgRT) has traditionally been defined by the use of offline MRI to aid in defining the RT volumes during the initial planning stages in order to ensure accurate tumor targeting while sparing critical normal tissues. However, the ViewRay MRIdian and Elekta Unity have improved upon and revolutionized the MRgRT by creating a combined MRI and linear accelerator (MRL), allowing MRgRT to incorporate online MRI in RT. MRL-based MR-guided SBRT (MRgSBRT) represents a novel solution to deliver higher doses to larger volumes of gross disease, regardless of the proximity of at-risk organs due to the (1) superior soft-tissue visualization for patient positioning, (2) real-time continuous intrafraction assessment of internal structures, and (3) daily online adaptive replanning. Stereotactic MR-guided adaptive radiation therapy (SMART) has enabled the safe delivery of ablative doses to tumors adjacent to radiosensitive tissues throughout the body. Although it is still a relatively new RT technique, SMART has demonstrated significant opportunities to improve disease control and reduce toxicity. In this review, we included the current clinical applications and the active prospective trials related to SMART. We highlighted the most impactful clinical studies at various tumor sites. In addition, we explored how MRL-based multiparametric MRI could potentially synergize with SMART to significantly change the current treatment paradigm and to improve personalized cancer care.

Triggered kV Imaging During Spine SBRT for Intrafraction Motion Management.

Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.

Optical emission-based phantom to verify coincidence of radiotherapy and imaging isocenters on an MR-linac.

PURPOSE: Demonstrate a novel phantom design using a remote camera imaging method capable of concurrently measuring the position of the x-ray isocenter and the magnetic resonance imaging (MRI) isocenter on an MR-linac. METHODS: A conical frustum with distinct geometric features was machined out of plastic. The phantom was submerged in a small water tank, and aligned using room lasers on a MRIdian MR-linac (ViewRay Inc., Cleveland, OH). The phantom physical isocenter was visualized in the MR images and related to the DICOM coordinate isocenter. To view the x-ray isocenter, an intensified CMOS camera system (DoseOptics LLC., Hanover, NH) was placed at the foot of the treatment couch, and centered such that the optical axis of the camera was coincident with the central axis of the treatment bore. Two or four 8.3mm x 24.1cm beams irradiated the phantom from cardinal directions, producing an optical ring on the conical surface of the phantom. The diameter of the ring, measured at the peak intensity, was compared to the known diameter at the position of irradiation to determine the Z-direction offset of the beam. A star-shot method was employed on the front face of the frustum to determine X-Y alignment of the MV beam. Known shifts were applied to the phantom to establish the sensitivity of the method. RESULTS: Couch translations, demonstrative of possible isocenter misalignments, on the order of 1mm were detectable for both the radiotherapy and MRI isocenters. Data acquired on the MR-linac demonstrated an average error of 0.28mm(N=10, R2 =0.997, σ=0.37mm) in established Z displacement, and 0.10mm(N=5, σ=0.34mm) in XY directions of the radiotherapy isocenter. CONCLUSIONS: The phantom was capable of measuring both the MRI and radiotherapy treatment isocenters. This method has the potential to be of use in MR-linac commissioning, and could be streamlined to be valuable in daily constancy checks of isocenter coincidence.

Visual Isocenter Position Enhanced Review (VIPER): a Cherenkov imaging-based solution for MR-linac daily QA.

PURPOSE: This study demonstrates a robust Cherenkov imaging-based solution to MR-Linac daily QA, including mechanical-imaging-radiation isocenter coincidence verification. METHODS: A fully enclosed acrylic cylindrical phantom was designed to be mountable to the existing jig, indexable to the treatment couch. An ABS plastic conical structure was fixed inside the phantom, held in place with 3D-printed spacers, and filled with water allowing for high edge contrast on MR imaging scans. Both a star shot plan and a four-angle sheet beam plan were delivered to the phantom; the former allowed for radiation isocenter localization in the x-z plane (A/P and L/R directions) relative to physical landmarks on the phantom, and the latter allowed for the longitudinal position of the sheet beam to be encoded as a ring of Cherenkov radiation emitted from the phantom, allowing for isocenter localization on the y-axis (S/I directions). A custom software application was developed to perform near-real-time analysis of the data by any clinical user. RESULTS: Calibration procedures show that linearity between longitudinal position and optical ring diameter is high (R2  > 0.99), and that RMSE is low (0.184 mm). The star shot analysis showed a minimum circle radius of 0.34 mm. The final isocenter coincidence measurements in the lateral, longitudinal, and vertical directions were -0.61 mm, 0.55 mm, and -0.14 mm, respectively, and the total 3D distance coincidence was 0.83 mm, with each of these being below 2 mm tolerance. CONCLUSION: This novel system provided an efficient, MR safe, all-in-one method for acquisition and near-real-time analysis of isocenter coincidence data. This represents a direct measurement of the 3D isocentricity. The combination of this phantom and the custom analysis application makes this solution readily clinically deployable after the longitudinal analysis of performance consistency.

Error detection and classification in patient-specific IMRT QA with dual neural networks.

PURPOSE: Despite being the standard metric in patient-specific quality assurance (QA) for intensity-modulated radiotherapy (IMRT), gamma analysis has two shortcomings: (a) it lacks sensitivity to small but clinically relevant errors (b) it does not provide efficient means to classify the error sources. The purpose of this work is to propose a dual neural network method to achieve simultaneous error detection and classification in patient-specific IMRT QA. METHODS: For a pair of dose distributions, we extracted the dose difference histogram (DDH) for the low dose gradient region and two signed distance-to-agreement (sDTA) maps (one in x direction and one in y direction) for the high dose gradient region. An artificial neural network (ANN) and a convolutional neural network (CNN) were designed to analyze the DDH and the two sDTA maps, respectively. The ANN was trained to detect and classify six classes of dosimetric errors: incorrect multileaf collimator (MLC) transmission (±1%) and four types of monitor unit (MU) scaling errors (±1% and ±2%). The CNN was trained to detect and classify seven classes of spatial errors: incorrect effective source size, 1 mm MLC leaf bank overtravel or undertravel, 2 mm single MLC leaf overtravel or undertravel, and device misalignment errors (1 mm in x- or y direction). An in-house planar dose calculation software was used to simulate measurements with errors and noise introduced. Both networks were trained and validated with 13 IMRT plans (totaling 88 fields). A fivefold cross-validation technique was used to evaluate their accuracy. RESULTS: Distinct features were found in the DDH and the sDTA maps. The ANN perfectly identified all four types of MU scaling errors and the specific accuracies for the classes of no error, MLC transmission increase, MLC transmission decrease were 98.9%, 96.6%, and 94.3%, respectively. For the CNN, the largest confusion occurred between the 1-mm-MLC bank overtravel class and the 1-mm-device alignment error in x-direction class, which brought the specific accuracies down to 90.9% and 92.0%, respectively. The specific accuracy for the 2-mm-single MLC leaf undertravel class was 93.2% as it misclassified 5.7% of the class as being error free (false negative). Otherwise, the specific accuracy was above 95%. The overall accuracies across the fivefold were 98.3 ± 0.7% and 95.6% ± 1.5% for the ANN and the CNN, respectively. CONCLUSIONS: Both the DDH and the sDTA maps are suitable features for error classification in IMRT QA. The proposed dual neural network method achieved simultaneous error detection and classification with excellent accuracy. It could be used in complement with the gamma analysis to potentially shift the IMRT QA paradigm from passive pass/fail analysis to active error detection and root cause identification.

Optical imaging method to quantify spatial dose variation due to the electron return effect in an MR-linac.

PURPOSE: Treatment planning systems (TPSs) for MR-linacs must employ Monte Carlo-based simulations of dose deposition to model the effects of the primary magnetic field on dose. However, the accuracy of these simulations, especially for areas of tissue-air interfaces where the electron return effect (ERE) is expected, is difficult to validate due to physical constraints and magnetic field compatibility of available detectors. This study employs a novel dosimetric method based on remotely captured, real-time optical Cherenkov and scintillation imaging to visualize and quantify the ERE. METHODS: An intensified CMOS camera was used to image two phantoms with designed ERE cavities. Phantom A was a 40 cm × 10 cm × 10 cm clear acrylic block drilled with five holes of increasing diameters (0.5, 1, 2, 3, 4 cm). Phantom B was a clear acrylic block (25 cm × 20 cm × 5 cm) with three cavities of increasing diameter (3, 2, 1 cm) split into two halves in the transverse plane to accommodate radiochromic film. Both phantoms were imaged while being irradiated by 6 MV flattening filter free (FFF) beams within a MRIdian Viewray (Viewray, Cleveland, OH) MR-linac (0.34 T primary field). Phantom A was imaged while being irradiated by 6 MV FFF beams on a conventional linac (TrueBeam, Varian Medical Systems, San Jose, CA) to serve as a control. Images were post processed in Matlab (Mathworks Inc., Natick, MA) and compared to TPS dose volumes. RESULTS: Control imaging of Phantom A without the presence of a magnetic field supports the validity of the optical image data to a depth of 6 cm. In the presence of the magnetic field, the optical data shows deviations from the commissioned TPS dose in both intensity and localization. The largest air cavity examined (3 cm) indicated the largest dose differences, which were above 20% at some locations. Experiments with Phantom B illustrated similar agreement between optical and film dosimetry comparisons with TPS data in areas not affected by ERE. CONCLUSION: There are some appreciable differences in dose intensity and spatial dose distribution observed between the novel experimental data set and the dose models produced by the current clinically implemented MR-IGRT TPS.

Cherenkov-excited luminescence scanned imaging using scanned beam differencing and iterative deconvolution in dynamic plan radiation delivery in a human breast phantom geometry.

PURPOSE: The purpose of this study was to demonstrate high resolution optical luminescence sensing, referred to as Cherenkov excited luminescence scanning imaging (CELSI), could be achieved during a standard dynamic treatment plan for a whole breast radiotherapy geometry. METHODS: The treatment plan beams induce Cherenkov light within tissue, and this excitation projects through the beam trajectory across the medium, inducing luminescence where there can be molecular reporter. Broad beams generally produce higher signal but low spatial resolution, yet for dynamic plans the scanning of the multileaf collimator allows for a beam-narrowing strategy by recursively temporal differencing each of the Cherenkov images and associated luminescence images. Then reconstruction from each of these size-reduced beamlets defined by the differenced Cherenkov images provides a well-conditioned matrix inversion, where the spatial frequencies are limited by the higher signal-to-noise ratio beamlets. A built-in stepwise convergence relies on stepwise beam size reduction, which is associated with a widening of the bandwidth of Cherenkov spatial frequency and resultant increase in spatial resolution. For the phantom experiments, europium nanoparticles were used as luminescent probes and embedded at depths ranging from 3 to 8 mm. An intensity modulated radiotherapy (IMRT) plan was used to test this. RESULTS: The Cherenkov images spatially guided where the luminescence was measured from, providing high lateral resolution, and iterative reconstruction convergence showed that optimization of the initial and stopping beamlet widths could be achieved with 15 and 4.5 mm, respectively, using a luminescence imaging frame rate of 5/s. With the IMRT breast plan, the original lateral resolution was improved 2X, that is, 0.08-0.24 mm for target depths of 3-8 mm. In comparison, a dynamic wedge (DW) plan showed an inferior image fidelity, with relative contrast recovery decreasing from 0.86 to 0.79. The methodology was applied to a three-dimensional dataset to reconstruct Cherenkov excited luminescence intensity distributions showing volumetric recovery of a 0.5 mm diameter object composed of 0.5 µM luminescent microbeads. CONCLUSIONS: High resolution CELSI was achieved with a clinical breast external beam radiotherapy (EBRT) plan. It is anticipated that this method can allow visualization and localization for luminescence/fluorescence tagged vasculature, lymph nodes, or superficial tagged regions with most dynamic treatment plans.

Rapid Multisite Remote Surface Dosimetry for Total Skin Electron Therapy: Scintillator Target Imaging.

PURPOSE: The goal of this work is to produce a surface-dosimetry method capable of accurately and remotely measuring skin dose for patients undergoing total skin electron therapy (TSET) without the need for postexposure dosimeter processing. A rapid and wireless surface-dosimetry system was developed to improve clinical workflow. Scintillator-surface dosimetry was conducted on patients undergoing TSET by imaging scintillator targets with an intensified camera during TSET delivery. METHODS AND MATERIALS: Disc-shaped scintillator targets were attached to the skin surface of patients undergoing TSET and imaged with an intensified, time-gated, and linear accelerator-synchronized camera. Optically stimulated luminescence dosimeters (OSLDs) were placed directly adjacent to scintillators at several dosimetry sites to serve as an absolute dose reference. Real-time image-processing methods were used to produce background-subtracted intensity maps of Cherenkov and scintillation emission. Rapid conversion of scintillator-light output to dose was achieved by using a custom fitting algorithm and calibration factor. Surface doses measured by scintillators were compared with those from OSLDs. RESULTS: Absolute surface-dose measurements for 99 dosimetry sites were evaluated. According to paired OSLD estimates, scintillator dosimeters were able to report dose with <3% difference in 88 of 99 observed dosimetry sites and <5% difference in 98 of 99 observed dosimetry sites. Fitting a linear regression to dose data reported by scintillator versus OSLD, per dosimetry site, yielded an R2 = 0.94. CONCLUSIONS: Scintillators were able to report dose within <3% accuracy of OSLDs. Imaging of calibrated scintillator targets via an intensified, linear accelerator-synchronized camera provides rapid absolute surface-dosimetry measurements for patients treated with TSET. This technique has the potential to reduce the amount of time and effort necessary to conduct full-body dosimetry and can be adopted for use in any surface-dosimetry setting where the region of interest is observable throughout treatment.

Improving treatment geometries in total skin electron therapy: Experimental investigation of linac angles and floor scatter dose contributions using Cherenkov imaging.

PURPOSE: The purpose of this study was to identify the optimal treatment geometry for total skin electron therapy (TSET) using a new optimization metric from Cherenkov image analysis, and to investigate the sensitivity of the Cherenkov imaging method to floor scatter effects in this unique treatment setup. METHODS: Cherenkov imaging using an intensified charge coupled device (ICCD) was employed to measure the relative surface dose distribution as a 2D image in the total skin electron treatment plane. A 1.2 m × 2.2 m × 1 cm white polyethylene sheet was placed vertically at a source to surface distance (SSD) of 300 cm, and irradiated with 6 MeV high dose rate TSET beams. The linear accelerator coordinate system used stipulates 0° is the bottom of the gantry arc, and progresses counterclockwise so that gantry angle 270° produces a horizontal beam orthogonal to the treatment plane. First, all unique pairs of treatment beams were analyzed to determine the performance of the currently recommended symmetric treatment angles (±20° from the horizontal), compared to treatment geometries unconstrained to upholding gantry angle symmetry. This was performed on two medical linear accelerators (linacs). Second, the extent of the floor scatter contributions to measured surface dose at the extended SSD required for TSET were imaged using three gantry angles of incidence: 270° (horizontal), 253° (-17°), and 240° (-30°). Images of the surface dose profile at each angle were compared to the standard concrete floor when steel plates, polyvinyl chloride (PVC), and solid water were placed on the ground at the base of the treatment plane. Postprocessing of these images allowed for comparison of floor material-based scatter profiles with previously published simulation results. RESULTS: Analysis of the symmetric treatment geometry (270 ± 20°) and the identified optimal treatment geometry (270 + 23° and 270 - 17°) showed a 16% increase in the 90% isodose area for the latter field pair on the first linac. The optimal asymmetric pair for the second linac (270 + 25° and 270 - 17°) provided a 52% increase in the 90% isodose area when compared to the symmetric geometry. Difference images between Cherenkov images captured with test materials (steel, PVC, and solid water) and the control (concrete floor) demonstrated relative changes in the two-dimensional (2D) dose profile over a 1 × 1.9 m region of interest (ROI) that were consistent with published simulation data. Qualitative observation of the residual images demonstrates localized increases and decreases with respect to the change in floor material and gantry angle. The most significant changes occurred when the beam was most directly impinging the floor (gantry angle 240°, horizontal -30°), where the PVC floor material decreased scatter dose by 1-3% in 7.2% of the total ROI area, and the steel plate increased scatter dose by 1-3% in 7.0% of the total ROI area. CONCLUSIONS: An updated Cherenkov imaging method identified asymmetric, machine-dependent TSET field angle pairs that provided much larger 90% isodose areas than the commonly adopted symmetric geometry suggested by Task Group 30 Report 23. A novel demonstration of scatter dose Cherenkov imaging in the TSET field was established.

Remote Cherenkov imaging-based quality assurance of a magnetic resonance image-guided radiotherapy system.

PURPOSE: Tools to perform regular quality assurance of magnetic resonance image-guided radiotherapy (MRIgRT) systems should ideally be independent of interference from the magnetic fields. Remotely acquired optical Cherenkov imaging-based dosimetry measurements in water were investigated for this purpose, comparing measures of dose accuracy, temporal dynamics, and overall integrated IMRT delivery. METHODS: A 40 × 30.5 × 37.5 cm3 water tank doped with 1 g/L of quinine sulfate was imaged using an intensified charge-coupled device (ICCD) to capture the Cherenkov emission while being irradiated by a commercial MRIgRT system (ViewRay™). The ICCD was placed down-bore at the end of the couch, 4 m from treatment isocenter and behind the 5-Gauss line of the 0.35-T MRI. After establishing optimal camera acquisition settings, square beams of increasing size (4.2 × 4.2 cm2 , 10.5 × 10.5 cm2 , and 14.7 × 14.7 cm2 ) were imaged at 0.93 frames per second, from an individual cobalt-60 treatment head, to develop projection measures related to percent depth dose (PDD) curves and cross beam profiles (CPB). These Cherenkov-derived measurements were compared to ionization chamber (IC) and radiographic film dosimetry data, as well as simulation data from the treatment planning system (TPS). An intensity-modulated radiotherapy (IMRT) commissioning plan from AAPM TG-119 (C4:C-Shape) was also imaged at 2.1 frames per second, and the single linear sum image from 509 s of plan delivery was compared to the dose volume prediction generated by the TPS using gamma index analysis. RESULTS: Analysis of standardized test target images (1024 × 1024 pixels) yielded a pixel resolution of 0.37 mm/pixel. The beam width measured from the Cherenkov image-generated projection CBPs was within 1 mm accuracy when compared to film measurements for all beams. The 502 point measurements (i.e., pixels) of the Cherenkov image-based projection percent depth dose curves (pPDDs) were compared to pPDDs simulated by the treatment planning system (TPS), with an overall average error of 0.60%, 0.56%, and 0.65% for the 4.2, 10.5, and 14.7 cm square beams, respectively. The relationships between pPDDs and central axis PDDs derived from the TPS were used to apply a weighting factor to the Cherenkov pPDD, so that the Cherenkov data could be directly compared to IC PDDs (average error of -0.07%, 0.10%, and -0.01% for the same sized beams, respectively). Finally, the composite image of the TG-119 C4 treatment plan achieved a 95.1% passing rate using 4%/4 mm gamma index agreement criteria between Cherenkov intensity and TPS dose volume data. CONCLUSIONS: This is the first examination of Cherenkov-generated pPDDs and pCBPs in an MR-IGRT system. Cherenkov imaging measurements were fast to acquire, and minimal error was observed overall. Cherenkov imaging also provided novel real-time data for IMRT QA. The strengths of this imaging are the rapid data capture ability providing real-time, high spatial resolution data, combined with the remote, noncontact nature of imaging. The biggest limitation of this method is the two-dimensional (2D) projection-based imaging of three-dimensional (3D) dose distributions through the transparent water tank.

Time-gated scintillator imaging for real-time optical surface dosimetry in total skin electron therapy.

The purpose of this study was to measure surface dose by remote time-gated imaging of plastic scintillators. A novel technique for time-gated, intensified camera imaging of scintillator emission was demonstrated, and key parameters influencing the signal were analyzed, including distance, angle and thickness. A set of scintillator samples was calibrated by using thermo-luminescence detector response as reference. Examples of use in total skin electron therapy are described. The data showed excellent room light rejection (signal-to-noise ratio of scintillation SNR ≈ 470), ideal scintillation dose response linearity, and 2% dose rate error. Individual sample scintillation response varied by 7% due to sample preparation. Inverse square distance dependence correction and lens throughput error (8% per meter) correction were needed. At scintillator-to-source angle and observation angle <50°, the radiant energy fluence error was smaller than 1%. The achieved standard error of the scintillator cumulative dose measurement compared to the TLD dose was 5%. The results from this proof-of-concept study documented the first use of small scintillator targets for remote surface dosimetry in ambient room lighting. The measured dose accuracy renders our method to be comparable to thermo-luminescent detector dosimetry, with the ultimate realization of accuracy likely to be better than shown here. Once optimized, this approach to remote dosimetry may substantially reduce the time and effort required for surface dosimetry.

Algorithm development for intrafraction radiotherapy beam edge verification from Cherenkov imaging.

Imaging of Cherenkov light emission from patient tissue during fractionated radiotherapy has been shown to be a possible way to visualize beam delivery in real time. If this tool is advanced as a delivery verification methodology, then a sequence of image processing steps must be established to maximize accurate recovery of beam edges. This was analyzed and developed here, focusing on the noise characteristics and representative images from both phantoms and patients undergoing whole breast radiotherapy. The processing included temporally integrating video data into a single, composite summary image at each control point. Each image stack was also median filtered for denoising and ultimately thresholded into a binary image, and morphologic small hole removal was used. These processed images were used for day-to-day comparison computation, and either the Dice coefficient or the mean distance to conformity values can be used to analyze them. Systematic position shifts of the phantom up to 5 mm approached the observed variation values of the patient data. This processing algorithm can be used to analyze the variations seen in patients being treated concurrently with daily Cherenkov imaging to quantify the day-to-day disparities in delivery as a quality audit system for position/beam verification.

Online Combination of EPID & Cherenkov Imaging for 3-D Dosimetry in a Liquid Phantom.

Online acquisition of Cherenkov and portal imaging data was combined with a reconstruction scheme called EC3-D, providing a full 3-D dosimetry of megavoltage X-ray beams in a water tank. The methodology was demonstrated and quantified in a single static beam. Furthermore, the dynamics and visualization of the 3-D dose reconstruction were demonstrated with a volumetric modulated arc therapy plan for TG-119 C-Shape geometry. The developed algorithm combines depth dose information, provided by Cherenkov images, with the lateral dose distribution, provided by the electronic portal imaging device. The strength of our approach lies in the acquisition of both imaging data streams with sub-millimeter theoretical resolution at 5-Hz frame-rate, which can be concurrently processed by the fast Fourier transform-based analysis, thus providing means for an efficient real-time 3-D dosimetry.

Beam and tissue factors affecting Cherenkov image intensity for quantitative entrance and exit dosimetry on human tissue.

This study's goal was to determine how Cherenkov radiation emission observed in radiotherapy is affected by predictable factors expected in patient imaging. Factors such as tissue optical properties, radiation beam properties, thickness of tissues, entrance/exit geometry, curved surface effects, curvature and imaging angles were investigated through Monte Carlo simulations. The largest physical cause of variation of the correlation ratio between of Cherenkov emission and dose was the entrance/exit geometry (˜50%). The largest human tissue effect was from different optical properties (˜45%). Beyond these, clinical beam energy varies the correlation ratio significantly (˜20% for X-ray beams), followed by curved surfaces (˜15% for X-ray beams and ˜8% for electron beams), and finally, the effect of field size (˜5% for X-ray beams). Other investigated factors which caused variations less than 5% were tissue thicknesses and source to surface distance. The effect of non-Lambertian emission was negligible for imaging angles smaller than 60 degrees. The spectrum of Cherenkov emission tends to blue-shift along the curved surface. A simple normalization approach based on the reflectance image was experimentally validated by imaging a range of tissue phantoms, as a first order correction for different tissue optical properties.

Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy.

PURPOSE: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). METHODS: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. RESULTS: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R(2) = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R(2) = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. CONCLUSIONS: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments.

Cherenkov radiation fluence estimates in tissue for molecular imaging and therapy applications.

Cherenkov radiation has recently emerged as an interesting phenomenon for a number of applications in the biomedical sciences. Its unique properties, including broadband emission spectrum, spectral weight in the ultraviolet and blue wavebands, and local generation of light within a given tissue, have made it an attractive new source of light within tissue for molecular imaging and phototherapy applications. While several studies have investigated the total Cherenkov light yield from radionuclides in units of [photons/decay], further consideration of the light propagation in tissue is necessary to fully consider the utility of this signal in vivo. Therefore, to help further guide the development of this novel field, quantitative estimates of the light fluence rate of Cherenkov radiation from both radionuclides and radiotherapy beams in a biological tissue are presented for the first time. Using Monte Carlo simulations, these values were found to be on the order of 0.01-1 nW cm(-2) per MBq g(-1) for radionuclides, and 1-100 µW cm(-2) per Gy s(-1) for external radiotherapy beams, dependent on the given waveband, optical properties, and radiation source. For phototherapy applications, the total light fluence was found to be on the order of nJ cm(-2) for radionuclides, and mJ cm(-2) for radiotherapy beams. The results indicate that diagnostic potential is reasonable for Cherenkov excitation of molecular probes, but phototherapy may remain elusive at such exceedingly low fluence values. The results of this study are publicly available for distribution online at www.dartmouth.edu/optmed/.