Technical Note: A novel dosimeter improves total skin electron therapy surface dosimetry workflow.

PURPOSE: The novel scintillator-based system described in this study is capable of accurately and remotely measuring surface dose during Total Skin Electron Therapy (TSET); this dosimeter does not require post-exposure processing or annealing and has been shown to be re-usable, resistant to radiation damage, have minimal impact on surface dose, and reduce chances of operator error compared to existing technologies e.g. optically stimulated luminescence detector (OSLD). The purpose of this study was to quantitatively analyze the workflow required to measure surface dose using this new scintillator dosimeter and compare it to that of standard OSLDs. METHODS: Disc-shaped scintillators were attached to a flat-faced phantom and a patient undergoing TSET. Light emission from these plastic discs was captured using a time-gated, intensified, camera during irradiation and converted to dose using an external calibration factor. Time required to complete each step (daily QA, dosimeter preparation, attachment, removal, registration, and readout) of the scintillator and OSLD surface dosimetry workflows was tracked. RESULTS: In phantoms, scintillators and OSLDs surface doses agreed within 3% for all data points. During patient imaging it was found that surface dose measured by OSLD and scintillator agreed within 5% and 3% for 35/35 and 32/35 dosimetry sites, respectively. The end-to-end time required to measure surface dose during phantom experiments for a single dosimeter was 78 and 202 sec for scintillator and OSL dosimeters, respectively. During patient treatment, surface dose was assessed at 7 different body locations by scintillator and OSL dosimeters in 386 and 754 sec, respectively. CONCLUSION: Scintillators have been shown to report dose nearly twice as fast as OSLDs with substantially less manual work and reduced chances of human error. Scintillator dose measurements are automatically saved to an electronic patient file and images contain a permanent record of the dose delivered during treatment.

Mesoscopic characterization of prostate cancer using Raman spectroscopy: potential for diagnostics and therapeutics.

OBJECTIVE: To test if Raman spectroscopy (RS) is an appropriate tool for the diagnosis and possibly grading of prostate cancer (PCa). PATIENTS AND METHODS: Between 20 and 50 Raman spectra were acquired from 32 fresh and non-processed post-prostatectomy specimens using a macroscopic handheld RS probe. Each measured area was characterized and categorized according to histopathological criteria: tissue type (extraprostatic or prostatic); tissue malignancy (benign or malignant); cancer grade (Grade Groups [GGs] 1-5); and tissue glandular level. The data were analysed using machine-learning classification with neural network. RESULTS: The RS technique was able to distinguish prostate from extraprostatic tissue with a sensitivity of 82% and a specificity of 83% and benign from malignant tissue with a sensitivity of 87% and a specificity of 86%. In an exploratory fashion, RS differentiated benign from GG1 in 726/801 spectra (91%; sensitivity 80%, specificity 91%), from GG2 in 588/805 spectra (73%; sensitivity 76%, specificity 73%), from GG3 in 670/797 spectra (84%; sensitivity 86%, specificity 84%), from GG4 in 711/802 spectra (88%; sensitivity 77%, specificity 89%) and from GG5 in 729/818 spectra (89%; sensitivity 90%, specificity 89%). CONCLUSION: Current diagnostic approaches of PCa using needle biopsies have suboptimal cancer detection rates and a significant risk of infection. Standard non-targeted random sampling results in false-negative biopsies in 15-30% of patients, which affects clinical management. RS, a non-destructive tissue interrogation technique providing vibrational molecular information, resolved the highly complex architecture of the prostate and detect cancer with high accuracy using a fibre optic probe to interrogate radical prostatectomy (RP) specimens from 32 patients (947 spectra). This proof-of-principle paves the way for the development of in vivo tumour targeting spectroscopy tools for informed biopsy collection to address the clinical need for accurate PCa diagnosis and possibly to improve surgical resection during RP as a complement to histopathological analysis.

Raman spectroscopy in microsurgery: impact of operating microscope illumination sources on data quality and tissue classification.

Ambient light artifacts can confound Raman spectroscopy measurements performed in a clinical setting such as during open surgery. However, requiring light sources to be turned off during intraoperative spectral acquisition can be impractical because it can slow down the procedure by requiring surgeons to acquire data under light conditions different from the routine clinical practice. Here a filter system is introduced allowing in vivo Raman spectroscopy measurements to be performed with the light source of a neurosurgical microscope turned on, without interfering with the standard procedure. Ex vivo and in vivo results on calf and human brain, respectively, show that when the new filter system is used there is no significant difference between Raman spectra acquired under pitch dark conditions or with the microscope light source turned on. This is important for the clinical translation of Raman spectroscopy because of the resulting decrease in total imaging time for each measurement and because the surgeon can now acquire spectroscopic data with no disruption of the surgical workflow.

Sub-diffuse interstitial optical tomography to improve the safety of brain needle biopsies: a proof-of-concept study.

The extraction of tissue samples during brain needle biopsy can cause life-threatening hemorrhage because of significant blood vessel injury during the procedure. Vessel rupture can have significant consequences for patient health, ranging from transient neurological deficits to death. Here, we present a sub-diffuse optical tomography technique that can be integrated into neurosurgical workflow to detect the presence of blood vessels. A proof-of-concept study performed on a realistic brain tissue phantom is presented and demonstrates that interstitial optical tomography (iOT) can detect several 1 mm diameter high-contrast absorbing objects located <2 mm from the needle.

Characterization of Cherenkov imaging parameters and positional constraints on an O-ring linear accelerator.

Objective. With the introduction of Cherenkov imaging technology on the Halcyon O-ring linear accelerator platform, we seek to demonstrate the imaging feasibility and optimize camera placement.Approach. Imaging parameters were probed by acquiring triggering data Cherenkov image frames for simplistic beams on the Halcyon and comparing the analyzed metrics with those from the TrueBeam platform. Camera position was analyzed by performing 3D rendering of patient treatment plans for various sites and iterating over camera positions to assess treatment area visibility.Main results. Commercial Cherenkov imaging systems are compatible with the pulse timing of the Halcyon, and this platform design favorably impacts signal to noise in Cherenkov image frames. Additionally, ideal camera placement is treatment site dependent and is always within a biconical zone of visibility centered on the isocenter. Visibility data is provided for four treatment sites, with suggestions for camera placement based on room dimensions. Median visibility values were highest for right breast plans, with values of 80.33% and 68.49% for the front and rear views respectively. Head and neck plans presented with the lowest values at 26.44% and 38.18% respectively.Significance. This work presents the first formal camera positional analysis for Cherenkov imaging on any platform and serves as a template for performing similar work for other irradiation platforms. Additionally, this study confirms the Cherenkov imaging parameters do not need to be changed for optimal imaging on the Halcyon. Lastly, the presented methodology provides a framework which could be further expanded to other optical imaging systems which rely on line of sight visibility to the patient.

One Year of Clinic-Wide Cherenkov Imaging for Discovery of Quality Improvement Opportunities in Radiation Therapy.

PURPOSE: Cherenkov imaging is clinically available as a radiation therapy treatment verification tool. The aim of this work was to discover the benefits of always-on Cherenkov imaging as a novel incident detection and quality improvement system through review of all imaging at our center. METHODS AND MATERIALS: Multicamera Cherenkov imaging systems were permanently installed in 3 treatment bunkers, imaging continuously over a year. Images were acquired as part of normal treatment procedures and reviewed for potential treatment delivery anomalies. RESULTS: In total, 622 unique patients were evaluated for this study. We identified 9 patients with treatment anomalies occurring over their course of treatment, which were only detected with Cherenkov imaging. Categorizing each event indicated issues arising in simulation, planning, pretreatment review, and treatment delivery, and none of the incidents were detected before this review by conventional measures. The incidents identified in this study included dose to unintended areas in planning, dose to unintended areas due to positioning at treatment, and nonideal bolus placement during setup. CONCLUSIONS: Cherenkov imaging was shown to provide a unique method of detecting radiation therapy incidents that would have otherwise gone undetected. Although none of the events detected in this study reached the threshold of reporting, they identified opportunities for practice improvement and demonstrated added value of Cherenkov imaging in quality assurance programs.

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.

Computational dose visualization & comparison in total skin electron treatment suggests superior coverage by the rotational versus the Stanford technique.

INTRODUCTION/BACKGROUND: The goal of Total Skin Electron Therapy (TSET) is to achieve a uniform surface dose, although assessment of this is never really done and typically limited points are sampled. A computational treatment simulation approach was developed to estimate dose distributions over the body surface, to compare uniformity of (i) the 6 pose Stanford technique and (ii) the rotational technique. METHODS: The relative angular dose distributions from electron beam irradiation was calculated by Monte Carlo simulation for cylinders with a range of diameters, approximating body part curvatures. These were used to project dose onto a 3D body model of the TSET patient's skin surfaces. Computer animation methods were used to accumulate the dose values, for display and analysis of the homogeneity of coverage. RESULTS: The rotational technique provided more uniform coverage than the Stanford technique. Anomalies of under dose were observed in lateral abdominal regions, above the shoulders and in the perineum. The Stanford technique had larger areas of low dose laterally. In the rotational technique, 90% of the patient's skin was within ±10% of the prescribed dose, while this percentage decreased to 60% or 85% for the Stanford technique, varying with patient body mass. Interestingly, the highest discrepancy was most apparent in high body mass patients, which can be attributed to the loss of tangent dose at low angles of curvature. DISCUSSION/CONCLUSION: This simulation and visualization approach is a practical means to analyze TSET dose, requiring only optical surface body topography scans. Under- and over-exposed body regions can be found, and irradiation could be customized to each patient. Dose Area Histogram (DAH) distribution analysis showed the rotational technique to have better uniformity, with most areas within 10% of the umbilicus value. Future use of this approach to analyze dose coverage is possible as a routine planning tool.

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.

Computer animation body surface analysis of total skin electron radiation therapy dose homogeneity via Cherenkov imaging.

Purpose: Quality assurance (QA) of dose homogeneity in total skin electron therapy (TSET) is challenging since each patient is positioned in six standing poses with two beam angles. Our study tested the feasibility of a unique approach for TSET QA through computational display of the cumulative dose, constructed and synthesized by computer animation methods. Approach: Dose distributions from Cherenkov emission images were projected onto a scanned 3D body model. Topographically mapped surfaces of the patient were recorded in each of six different delivery positions, while a Cherenkov camera acquired images. Computer animation methods allowed a fitted 3D human body model of the patient to be created with deformation of the limbs and torso to each position. A two-dimensional skin map was extracted from the 3D model of the full surface of the patient. This allowed the dose mapping to be additively accumulated independent of body position, with the total dose summed in a 2D map and reinterpreted on the 3D body display. Results: For the body model, the mean Hausdorff error distance was below 2 cm, setting the spatial accuracy limit. The dose distribution over the patient's 3D model generally matched the Cherenkov/dose images. The dose distribution mapping was estimated to be near 1.5 cm accuracy based upon a phantom study. The body model must most closely match at the edges of the mesh to ensure that high dose gradients are not projected onto the wrong location. Otherwise 2 to 3 cm level errors in positioning in the mesh do not appear to cause larger than 5% dose errors. The cumulative dose images showed regions of overlap laterally and regions of low intensity in the posterior arms. Conclusions: The proposed modeling and animation can be used to visualize and analyze the accumulated dose in TSET via display of the summed dose/Cherenkov images on a single body surface.

Experimentally Observed Cherenkov Light Generation in the Eye During Radiation Therapy.

PURPOSE: Patients have reported sensations of seeing light flashes during radiation therapy, even with their eyes closed. These observations have been attributed to either direct excitation of retinal pigments or generation of Cherenkov light inside the eye. Both in vivo human and ex vivo animal eye imaging was used to confirm light intensity and spectra to determine its origin and overall observability. METHODS AND MATERIALS: A time-gated and intensified camera was used to capture light exiting the eye of a patient undergoing stereotactic radiosurgery in real time, thereby verifying the detectability of light through the pupil. These data were compared with follow-up mechanistic imaging of ex vivo animal eyes with thin radiation beams to evaluate emission spectra and signal intensity variation with anatomic depth. Angular dependency of light emission from the eye was also measured. RESULTS: Patient imaging showed that light generation in the eye during radiation therapy can be captured with a signal-to-noise ratio of 68. Irradiation of ex vivo eye samples confirmed that the spectrum matched that of Cherenkov emission and that signal intensity was largely homogeneous throughout the entire eye, from the cornea to the retina, with a slight maximum near 10 mm depth. Observation of the signal external to the eye was possible through the pupil from 0° to 90°, with a detected emission near 2500 photons per millisecond (during peak emission of the ON cycle of the pulsed delivery), which is over 2 orders of magnitude higher than the visible detection threshold. CONCLUSIONS: By quantifying the spectra and magnitude of the signal, we now have direct experimental observations that Cherenkov light is generated in the eye during radiation therapy and can contribute to perceived light flashes. Furthermore, this technique can be used to further study and measure phosphenes in the radiation therapy clinic.

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.

Technical Note: Quality assurance and relative dosimetry testing of a 60 Co total body irradiator using optical imaging.

PURPOSE: The aim of this study was to create an optical imaging-based system for quality assurance (QA) testing of a dedicated Co-60 total body irradiation (TBI) machine. Our goal is to streamline the QA process by minimizing the amount time necessary for tests such as verification of dose rate and field homogeneity. METHODS: Plastic scintillating rods were placed directly on the patient treatment couch of a dedicated TBI 60 Co irradiator. A tripod-mounted intensified camera was placed directly adjacent to the couch. Images were acquired over a 30-s period once the cobalt source was fully exposed. Real-time image filtering was used; cumulative images were flatfield corrected as well as background and darkfield subtracted. Scintillators were used to measure light-radiation field correspondence, dose rate, field homogeneity, and symmetry. Dose rate effects were measured by modifying the height of the treatment couch and scintillator response was compared to ionization chamber (IC) measurements. Optically stimulated luminesce detector (OSLD) used as reference dosimeters during field symmetry and homogeneity testing. RESULTS: The scintillator-based system accurately reported changes in dose rate. When comparing normalized output values for IC vs scintillators over a range of source-to-surface distances, a linear relationship (R2  = 0.99) was observed. Normalized scintillator signal matched OSLD measurements with <1.5% difference during field homogeneity and symmetry testing. Beam symmetry across both axes of the field was within 2%. The light field was found to correspond to 90 ± 3% of the isodose maximum along the longitudinal and latitudinal axis, respectively. Scintillator imaging output results using a single image stack requiring no postexposure processing (needed for OSLD) or repeat manual measurements (needed for IC). CONCLUSION: Imaging of scintillation light emission from plastic rods is a viable and efficient method for carrying out TBI 60 Co irradiator QA. We have shown that this technique can accurately measure field homogeneity, symmetry, light-radiation field correspondence, and dose rate effects.

Structured light imaging for breast-conserving surgery, part II: texture analysis and classification.

Subdiffuse spatial frequency domain imaging (sd-SFDI) data of 42 freshly excised, bread-loafed tumor resections from breast-conserving surgery (BCS) were evaluated using texture analysis and a machine learning framework for tissue classification. Resections contained 56 regions of interest (RoIs) determined by expert histopathological analysis. RoIs were coregistered with sd-SFDI data and sampled into ∼4 × 4 mm2 subimage samples of confirmed and homogeneous histological categories. Sd-SFDI reflectance textures were analyzed using gray-level co-occurrence matrix pixel statistics, image primitives, and power spectral density curve parameters. Texture metrics exhibited statistical significance (p-value < 0.05) between three benign and three malignant tissue subtypes. Pairs of benign and malignant subtypes underwent texture-based, binary classification with correlation-based feature selection. Classification performance was evaluated using fivefold cross-validation and feature grid searching. Classification using subdiffuse, monochromatic reflectance (illumination spatial frequency of fx = 1.37 mm − 1, optical wavelength of λ = 490 nm) achieved accuracies ranging from 0.55 (95% CI: 0.41 to 0.69) to 0.95 (95% CI: 0.90 to 1.00) depending on the benign­malignant diagnosis pair. Texture analysis of sd-SFDI data maintains the spatial context within images, is free of light transport model assumptions, and may provide an alternative, computationally efficient approach for wide field-of-view (cm2) BCS tumor margin assessment relative to pixel-based optical scatter or color properties alone.

Improvements to an optical scintillator imaging-based tissue dosimetry system.

Previous work has shown that capturing optical emission from plastic discs attached directly to the skin can be a viable means to accurately measure surface dose during total skin electron therapy. This method can provide accurate dosimetric information rapidly and remotely without the need for postprocessing. The objective of this study was to: (1) improve the robustness and usability of the scintillators and (2) enhance sensitivity of the optical imaging system to improve scintillator emission detection as related to tissue surface dose. Baseline measurements of scintillator optical output were obtained by attaching the plastic discs to a flat tissue phantom and simultaneously irradiating and imaging them. Impact on underlying surface dose was evaluated by placing the discs on-top of the active element of an ionization chamber. A protective coating and adhesive backing were added to allow easier logistical use, and they were also subjected to disinfection procedures, while verifying that these changes did not affect the linearity of response with dose. The camera was modified such that the peak of detector quantum efficiency better overlapped with the emission spectra of the scintillating discs. Patient imaging was carried out and surface dose measurements were captured by the updated camera and compared to those produced by optically stimulated luminescence detectors (OSLD). The updated camera was able to measure surface dose with < 3 % difference compared to OSLD­Cherenkov emission from the patient was suppressed and scintillation detection was enhanced by 25 × and 7 × , respectively. Improved scintillators increase underlying surface dose on average by 5.2 ± 0.1 % and light output decreased by 2.6 ± 0.3 % . Disinfection had < 0.02 % change on scintillator light output. The enhanced sensitivity of the imaging system to scintillator optical emission spectrum can now enable a reduction in physical dimensions of the dosimeters without loss in ability to detect light output.

Cherenkov imaging for linac beam shape analysis as a remote electronic quality assessment verification tool.

PURPOSE: A remote imaging system tracking Cherenkov emission was analyzed to verify that the linear accelerator (linac) beam shape could be quantitatively measured at the irradiation surface for Quality Audit (QA). METHODS: The Cherenkov camera recorded 2D dose images delivered on a solid acrylonitrile butadiene styrene (ABS) plastic phantom surface for a range of square beam sizes, and 6 MV photons. Imaging was done at source to surface distance (SSD) of 100 cm and compared to GaF film images and linac light fields of the same beam sizes, ranging over 5 × 5 cm2 up to 20 × 20 cm2 . Line profiles of each field were compared in both X and Y jaw directions. Each measurement was repeated on two different Clinac2100 machines. An interreader comparison of the beam width interpretation was completed using procedures commonly employed for beam to light field coincidence verification. Cherenkov measurements are also done for beams of complex treatment plan and isocenter QA. RESULTS: The Cherenkov image widths matched with the measured GaF images and light field images, with accuracy in the range of ±1 mm standard deviation. The differences between the measurements were minor and within tolerance of geometrical requirement of standard linac QA procedures conducted by human setup verification, which had a similar error range. The measurement made by the remote imaging system allowed for beam shape extraction of radiation fields at the SSD location of the beam. CONCLUSIONS: The proposed Cherenkov image acquisition system provides a valid way to remotely confirm radiation field sizes and provides similar information to that obtained from the linac light field or GaF film estimates of the beam size. The major benefit of this approach is that with a fixed installation of the camera, testing could be done completely under software control with automated image analysis, potentially simplifying conventional QA procedures with appropriate calibration of boundary definitions, and the natural extension to capturing dynamic treatment beamlets at SSD could have future value, such as verification of beam plans with complex beam shapes, like IMRT or "star-shot" QA for the isocenter.

Challenges and opportunities in clinical translation of biomedical optical spectroscopy and imaging.

Medical devices face many hurdles before they enter routine clinical practice to address unmet clinical needs. This is also the case for biomedical optical spectroscopy and imaging systems that are used here to illustrate the opportunities and challenges involved. Following initial concept, stages in clinical translation include instrument development, preclinical testing, clinical prototyping, clinical trials, prototype-to-product conversion, regulatory approval, commercialization, and finally clinical adoption and dissemination, all in the face of potentially competing technologies. Optical technologies face additional challenges from their being extremely diverse, often targeting entirely different diseases and having orders-of-magnitude differences in resolution and tissue penetration. However, these technologies can potentially address a wide variety of unmet clinical needs since they provide rich intrinsic biochemical and structural information, have high sensitivity and specificity for disease detection and localization, and are practical, safe (minimally invasive, nonionizing), and relatively affordable.

Combining high wavenumber and fingerprint Raman spectroscopy for the detection of prostate cancer during radical prostatectomy.

For prostate cancer (PCa) patients, radical prostatectomy (complete removal of the prostate) is the only curative surgical option. To date, there is no clinical technique allowing for real-time assessment of surgical margins to minimize the extent of residual cancer. Here, we present a tissue interrogation technique using a dual excitation wavelength Raman spectroscopy system capable of sequentially acquiring fingerprint (FP) and high wavenumber (HWN) Raman spectra. Results demonstrate the ability of the system to detect PCa in post-prostatectomy specimens. In total, 477 Raman spectra were collected from 18 human prostate slices. Each area measured with Raman spectroscopy was characterized as either normal or cancer based on histopathological analyses, and each spectrum was classified based on supervised learning using support vector machines (SVMs). Based on receiver operating characteristic (ROC) analysis, FP (area under the curve [AUC] = 0.89) had slightly superior cancer detection capabilities compared with HWN (AUC = 0.86). Optimal performance resulted from combining the spectral information from FP and HWN (AUC = 0.91), suggesting that the use of these two spectral regions may provide complementary molecular information for PCa detection. The use of leave-one-(spectrum)-out (LOO) or leave-one-patient-out (LOPO) cross-validation produced similar classification results when combining FP with HWN. Our findings suggest that the application of machine learning using multiple data points from the same patient does not result in biases necessarily impacting the reliability of the classification models.

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.