Voxel-wise dose rate calculation in clinical pencil beam scanning proton therapy.

OBJECTIVE: Clinical outcomes after proton therapy have shown some variability that is not fully understood. Different approaches have been suggested to explain the biological outcome, but none has yet provided a comprehensive and satisfactory rationale for observed toxicities. The relatively recent transition from passive scattering (PS) to pencil beam scanning (PBS) treatments has significantly increased the voxel-wise dose rate in proton therapy. In addition, the dose rate distribution is no longer uniform along the cross section of the target but rather highly heterogeneous, following the spot placement. We suggest investigating dose rate as potential contributor to a more complex proton RBE model. Approach. Due to the time structure of the PBS beam delivery the instantaneous dose rate is highly variable voxel by voxel. Several possible parameters to represent voxel-wise dose rate for a given clinical PBS treatment plan are detailed. These quantities were implemented in the scripting environment of our treatment planning system, and computations experimentally verified. Sample applications to treated patient plans are shown. Main Results. Computed dose rates we experimentally confirmed. Dose rate maps vary depending on which method is used to represent them. Mainly, the underlying time and dose intervals chosen determine the topography of the resultant distributions. The maximum dose rates experienced by any target voxel in a given PBS treatment plan in our system range from ~100 to ~450 Gy(RBE)/min, a factor of 10 - 100 increase compared to PS. These dose rate distributions are very heterogeneous, with distinct hot spots. Significance. Voxel-wise dose rates for current clinical PBS treatment plans vary greatly from clinically established practice with PS. The exploration of different dose rate measures to evaluate potential correlations with observed clinical outcomes is suggested, potentially adding a missing component in the understanding of proton RBE.

Remote dose imaging from Cherenkov light using spatially resolved CT calibration in breast radiotherapy.

PURPOSE: Imaging Cherenkov light during radiotherapy allows the visualization and recording of frame-by-frame relative maps of the dose being delivered to the tissue at each control point used throughout treatment, providing one of the most complete real-time means of treatment quality assurance. In non-turbid media, the intensity of Cherenkov light is linear with surface dose deposited, however the emission from patient tissue is well-known to be reduced by absorbing tissue components such as hemoglobin, fat, water, and melanin, and diffused by the scattering components of tissue. Earlier studies have shown that bulk correction could be achieved by using the patient planning computed tomography (CT) scan for attenuation correction. METHODS: In this study, CT maps were used for correction of spatial variations in emissivity. Testing was completed on Cherenkov images from radiotherapy treatments of post-lumpectomy breast cancer patients (n = 13), combined with spatial renderings of the patient radiodensity (CT number) from their planning CT scan. RESULTS: The correction technique was shown to provide a pixel-by-pixel correction that suppressed many of the inter- and intra-patient differences in the Cherenkov light emitted per unit dose. This correction was established from a calibration curve that correlated Cherenkov light intensity to surface-rendered CT number ( R 6 MV 2 = 0.70 $R_{6{\rm{MV}}}^2 = 0.70$ and R 10 MV 2 = 0.72 $R_{10{\rm{MV}}}^2 = 0.72$ ). The corrected Cherenkov intensity per unit dose standard error was reduced by nearly half (from ∼30% to ∼17%). CONCLUSIONS: This approach provides evidence that the planning CT scan can mitigate some of the tissue-specific attenuation in Cherenkov images, allowing them to be translated into near surface dose images.

Optimization of in vivo Cherenkov imaging dosimetry via spectral choices for ambient background lights and filtering.

SIGNIFICANCE: The Cherenkov emission spectrum overlaps with that of ambient room light sources. Choice of room lighting devices dramatically affects the efficient detection of Cherenkov emission during patient treatment. AIM: To determine optimal room light sources allowing Cherenkov emission imaging in normally lit radiotherapy treatment delivery rooms. APPROACH: A variety of commercial light sources and long-pass (LP) filters were surveyed for spectral band separation from the red to near-infrared Cherenkov light emitted by tissue. Their effects on signal-to-noise ratio (SNR), Cherenkov to background signal ratio, and image artifacts were quantified by imaging irradiated tissue equivalent phantoms with an intensified time-gated CMOS camera. RESULTS: Because Cherenkov emission from tissue lies largely in the near-infrared spectrum, a controlled choice of ambient light that avoids this spectral band is ideal, along with a camera that is maximally sensitive to it. An RGB LED light source produced the best SNR out of all sources that mimic room light temperature. A 675-nm LP filter on the camera input further reduced ambient light detected (optical density > 3), achieving maximal SNR for Cherenkov emission near 40. Reduction of the room light signal reduced artifacts from specular reflection on the tissue surface and also minimized spurious Cherenkov signals from non-tissue features such as bolus. CONCLUSIONS: LP filtering during image acquisition for near-infrared light in tandem with narrow band LED illuminated rooms improves image quality, trading off the loss of red wavelengths for better removal of room light in the image. This spectral filtering is also critically important to remove specular reflection in the images and allow for imaging of Cherenkov emission through clear bolus. Beyond time-gated external beam therapy systems, the spectral separation methods can be utilized for background removal for continuous treatment delivery methods including proton pencil beam scanning systems and brachytherapy.

Estimation of diffuse Cherenkov optical emission from external beam radiation build-up in tissue.

SIGNIFICANCE: Optical imaging of Cherenkov emission during radiation therapy could be used to verify dose delivery in real-time if a more comprehensive quantitative understanding of the factors affecting emission intensity could be developed. AIM: This study aims to explore the change in diffuse Cherenkov emission intensity with x-ray beam energy from irradiated tissue, both theoretically and experimentally. APPROACH: Derivation of the emitted Cherenkov signal was achieved using diffusion theory, and experimental studies with 6 to 18 MV energy x-rays were performed in tissue phantoms to confirm the model predictions as related to the radiation build-up factor with depth into tissue. RESULTS: Irradiation at lower x-ray energies results in a greater surface dose and higher build-up slope, which results in a ∼46 % greater diffusely emitted Cherenkov signal per unit dose at 6 MV relative to 18 MV x-rays. However, this phenomenon competes with a decrease in signal from less Cherenkov photons being generated at lower energies, a ∼44 % reduction at 6 versus 18 MV. The result is an emitted Cherenkov signal that is nearly constant with beam energy. CONCLUSIONS: This study explains why the observed Cherenkov emission from tissue is not a strong function of beam energy, despite the known strong correlation between Cherenkov intensity and particle energy in the absence of build-up and scattering effects.

Verification of field match lines in whole breast radiation therapy using Cherenkov imaging.

PURPOSE: In mono-isocentric radiation therapy treatment plans designed to treat the whole breast and supraclavicular lymph nodes, the fields meet at isocenter, forming the match line. Insufficient coverage at the match line can lead to recurrence, and overlap over weeks of treatment can lead to increased risk of healthy tissue toxicity. Cherenkov imaging was used to assess the accuracy of delivery at the match line and identify potential incidents during patient treatments. METHODS AND MATERIALS: A controlled calibration was constructed from the deconvolved Cherenkov images from the delivery of a modified patient treatment plan to an anthropomorphic phantom with introduced separation and overlap. The trend from this calibration was then used to evaluate the field match line for accuracy and inter-fraction consistency for two patients. RESULTS: The intersection point between matching field profiles was directly correlated to the distance (gap/overlap) between the fields (anthropomorphic phantom R2 = 0.994 "breath hold" and R2 = 0.990 "free breathing"). The profile intersection points from two patients' imaging sessions yielded an average of +1.40 mm offset (overlap) and -1.32 mm offset (gap), thereby introducing roughly a 25.0% over-dose and a -23.6% under-dose (R2 = 0.994). CONCLUSIONS: This study shows that field match regions can be detected and quantified by taking deconvolved Cherenkov images and using their product image to create steep intensity gradients, causing match lines to stand out. These regions can then be quantitatively translated into a dose consequence. This approach offers a high sensitivity detection method which can quantify match line variability and errors in vivo.

Initial Clinical Experience of Cherenkov Imaging in External Beam Radiation Therapy Identifies Opportunities to Improve Treatment Delivery.

PURPOSE: The value of Cherenkov imaging as an on-patient, real-time, treatment delivery verification system was examined in a 64-patient cohort during routine radiation treatments in a single-center study. METHODS AND MATERIALS: Cherenkov cameras were mounted in treatment rooms and used to image patients during their standard radiation therapy regimen for various sites, predominantly for whole breast and total skin electron therapy. For most patients, multiple fractions were imaged, with some involving bolus or scintillators on the skin. Measures of repeatability were calculated with a mean distance to conformity (MDC) for breast irradiation images. RESULTS: In breast treatments, Cherenkov images identified fractions when treatment delivery resulted in dose on the contralateral breast, the arm, or the chin and found nonideal bolus positioning. In sarcoma treatments, safe positioning of the contralateral leg was monitored. For all 199 imaged breast treatment fields, the interfraction MDC was within 7 mm compared with the first day of treatment (with only 7.5% of treatments exceeding 3 mm), and all but 1 fell within 7 mm relative to the treatment plan. The value of imaging dose through clear bolus or quantifying surface dose with scintillator dots was examined. Cherenkov imaging also was able to assess field match lines in cerebral-spinal and breast irradiation with nodes. Treatment imaging of other anatomic sites confirmed the value of surface dose imaging more broadly. CONCLUSIONS: Daily radiation therapy can be imaged routinely via Cherenkov emissions. Both the real-time images and the posttreatment, cumulative images provide surrogate maps of surface dose delivery that can be used for incident discovery and/or continuous improvement in many delivery techniques. In this initial 64-patient cohort, we discovered 6 minor incidents using Cherenkov imaging; these otherwise would have gone undetected. In addition, imaging provides automated, quantitative metrics useful for determining the quality of radiation therapy delivery.

Correcting Cherenkov light attenuation in tissue using spatial frequency domain imaging for quantitative surface dosimetry during whole breast radiation therapy.

Imaging Cherenkov emission during radiotherapy permits real-time visualization of external beam delivery on superficial tissue. This signal is linear with absorbed dose in homogeneous media, indicating potential for quantitative dosimetry. In humans, the inherent heterogeneity of tissue optical properties (primarily from blood and skin pigment) distorts the linearity between detected Cherenkov signal and absorbed dose. We examine the potential to correct for superficial vasculature using spatial frequency domain imaging (SFDI) to map tissue optical properties for large fields of view. In phantoms, applying intensity corrections to simulate blood vessels improves Cherenkov image (CI) negative contrast by 24% for a vessel 1.9-mm-in diameter. In human trials, SFDI and CI are acquired for women undergoing whole breast radiotherapy. Applied corrections reduce heterogeneity due to vasculature within the sampling limits of the SFDI from a 22% difference as compared to the treatment plan, down to 6% in one region and from 14% down to 4% in another region. The optimal use for this combined imaging system approach is to correct for small heterogeneities such as superficial blood vessels or for interpatient variations in blood/melanin content such that the corrected CI more closely represents the surface dose delivered.