A simulation study on the radiation-induced immune response of tumors after single fraction high-dose irradiation.

PURPOSE: We investigated radiation-induced antitumor immunity and its suppression by hypoxia-inducible factor (HIF-1α) for radiosurgery (SRS) using an improved cellular automata (CA) model. METHOD: A two-dimensional Cellular Automata (CA) model was employed to simulate the impact of radiation on cancer cell death and subsequent immune responses. Cancer cells died from direct cell death from radiation and indirect cell death due to radiation-induced vascular damage. The model also incorporated radiation-induced immunity and immuno-suppression. It was incorporated into the model assuming that the death of cancer cells generates effector cells, forming complexes with cancer cells, and high radiation doses lead to vascular damage, inducing tumor hypoxia and increasing HIF-1α expression. The model was validated and subjected to sensitivity analysis by evaluating tumor volume changes post-irradiation and exploring the effects and sensitivity of radiation-induced immune responses. RESULTS: The ratios of the tumor volume at 360 days post-irradiation and the SRS day (rTV) decreased with a higher PME, a higher Pcomp, and a lower ThHIF. The rTVs were 4.6 and 2.0 for PME = 0.1 and 0.9, 12.0 and 2.2 for Pcomp = 0.1 and 0.9, and 1.5 and 15.3 for ThHIF = 0.1 and 10.0, respectively. CONCLUSIONS: By modeling the activation and deactivation of the effectors, the improved CA model showed that the radiation-induced immunogenic cell death in the tumor caused a decrease in the post-irradiation volume by a factor of four for the therapeutic doses relative to non-immune reaction cases. Furthermore, the suppressive effects of HIF-1α induced by hypoxia decreased radiation-induced immune effects by more than 50.

Comparison of Gamma Knife (GK) and Linear Accelerator (LINAC) radiosurgery of brain metastasis resection cavity: a systematic review and proportional meta-analysis.

PURPOSE: Stereotactic radiosurgery (SRS) to the resection cavity is essential in the treatment of brain metastasis (BM) amenable to surgical resection. The two most common platforms for SRS delivery include Gamma Knife (GK) and LINAC. Here we collated the available peer-reviewed literature and performed a meta-analysis on clinical outcomes after GK or LINAC resection cavity SRS. METHODS: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include all studies evaluating each post-operative SRS modality. Local control, overall survival, radiation necrosis, and leptomeningeal disease were evaluated from the available data. A proportional meta-analysis was performed via R using the metafor package to pool the outcomes of studies and a moderator effect to assess the significance between groups. RESULTS: We identified 21 GK studies (n = 2009) and 28 LINAC studies (n = 2219). The radiosurgery doses employed were comparable between GK and LINAC studies. The pooled estimate of 1-year local control, 1-year overall survival, and risk of leptomeningeal disease were statistically comparable between GK and LINAC (81.7 v 85.8%; 61.4 v 62.7%; 10.6 v 12.5%, respectively). However, the risk of radiation necrosis (RN) was higher for LINAC resection cavity SRS (5.4% vs. 10%, p = 0.036). The volume of the resection cavity was a significant modifying factor for RN in both modalities (p = 0.007) with a 0.5% and 0.7% increase in RN risk with every 1 cm3 increase in tumor volume for GK and LINAC, respectively. CONCLUSIONS: Our meta-analysis suggests that GK and LINAC SRS of resection cavity achieve comparable 1-year local control and survival. However, resection cavity treated with GK SRS was associated with lowered RN risk relative to those treated with LINAC SRS.

Bactericidal Ability of Well-Controlled Cationic Polymer Brush Surfaces and the Interaction Analysis by Quartz Crystal Microbalance with Dissipation.

In this study, cationic poly(2-(methacryloyloxy)ethyl) trimethylammonium chloride) (PMTAC) brush surfaces were prepared by surface-initiated atom transfer radical polymerization (SI-ATRP), and their properties were systematically investigated to discuss the factors affecting their bactericidal properties and interactions with proteins. Model equations for the analysis of electrophoretic behaviors were considered for accurate parameter estimation to indicate the charge density at the interface. The zeta potential dependency of the PMTAC brushes was successfully analyzed using Smolchowski's equation and the Gouy-Chapman model, which describes the diffusive electric double layer. The analysis of the quartz crystal microbalance with dissipation (QCM-D) indicated that the electrostatic interaction promoted protein adsorption, with a large quantity of a negatively charged protein, bovine serum albumin (BSA), being adsorbed. The bactericidal efficiency of the high-graft-density polymer brush (0.45 chains nm-2) was higher than that of the low-graft-density polymer brush (0.06 chains nm-2). To investigate the mechanism of this phenomenon, we applied the dissipation change (ΔD) of QCM-D analysis. The BSA was likewise adsorbed when the brush structure was changed; however, the negative ΔD indicated that the BSA-adsorbed, high-graft-density PMTAC brush became a rigid state. In the bacteria culture media, the behaviors were the same as BSA adsorption, and the high-graft-density polymer brush was also estimated to be more rigid than the low-graft-density polymer brush. Moreover, for S. aureus adhesion after incubating in TSB, a small slope of ΔD/ΔF plots considered initial adsorption of bacteria on the high-graft-density polymer brush strongly interacted compared to that of the low-graft-density polymer brush. The scattered value of the slope of ΔD/ΔF on the high-graft-density polymer brush was considered to be due to the dead bacteria between the bacteria and the polymer brush interface. These investigations for a well-defined cationic polymer brush will contribute to the design of antibacterial surfaces.

Use of a Commercial 7-T MRI Scanner for Clinical Brain Imaging: Indications, Protocols, Challenges, and Solutions-A Single-Center Experience.

The first commercially available 7-T MRI scanner (Magnetom Terra) was approved by the FDA in 2017 for clinical imaging of the brain and knee. After initial protocol development and sequence optimization efforts in volunteers, the 7-T system, in combination with an FDA-approved 1-channel transmit/32-channel receive array head coil, can now be routinely used for clinical brain MRI examinations. The ultrahigh field strength of 7-T MRI has the advantages of improved spatial resolution, increased SNR, and increased CNR but also introduces an array of new technical challenges. The purpose of this article is to describe an institutional experience with the use of the commercially available 7-T MRI scanner for routine clinical brain imaging. Specific clinical indications for which 7-T MRI may be useful for brain imaging include brain tumor evaluation with possible perfusion imaging and/or spectroscopy, radiotherapy planning; evaluation of multiple sclerosis and other demyelinating diseases, evaluation of Parkinson disease and guidance of deep brain stimulator placement, high-detail intracranial MRA and vessel wall imaging, evaluation of pituitary pathology, and evaluation of epilepsy. Detailed protocols, including sequence parameters, for these various indications are presented, and implementation challenges (including artifacts, safety, and side effects) and potential solutions are explored.

ACR-ABS-ASTRO Practice Parameter for the Performance of Low-Dose-Rate Brachytherapy.

AIM/OBJECTIVES/BACKGROUND: The American College of Radiology (ACR), the American Brachytherapy Society (ABS), and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for the performance of low-dose-rate (LDR) brachytherapy. LDR brachytherapy is the application of radioactive sources in or on tumors in a clinical setting with therapeutic intent. The advantages of LDR brachytherapy include improving therapeutic ratios with lower doses to nontarget organs-at-risk and higher doses to a specific target. METHODS: This practice parameter was developed according to the process described under the heading. The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO. RESULTS: This practice parameter was developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of LDR brachytherapy including personnel qualifications, quality assurance standards, indications, and suggested documentation. This includes a contemporary literature search. CONCLUSIONS: This practice parameter is a tool to guide the use of LDR brachytherapy and does not assess relative clinical indication for LDR brachytherapy when compared with other forms of brachytherapy or external beam therapy, but to focus on the best practices required to deliver LDR brachytherapy safely and effectively, when clinically indicated. Comparative costs of versus other modalities therapy may also need to be considered.

A practical strategy for incorporating the convolution algorithm in Leksell GammaPlan for routine treatment planning†.

Purpose: This study aims to establish criteria for convolution dose calculations and an efficient procedure to include the heterogeneity effects in GammaKnife radiosurgery (GKRS) treatment plans. Methods and materials: We analyzed 114 GKRS cases of various disease types, tumor locations, sizes, the number of fractions, and prescription doses. There was a total of 205 tumors. CT scans were performed in addition to routine MRI scans for all treatments. All treatment plans were created using the TMR10 algorithm (TMR10). We repeated the dose calculations for this study with the convolution algorithm (Conv). We calculated the ratios between Conv and TMR10 of the treatment volume (TxtVol), the volume covered by half of the prescription dose (TxtVol2), the minimum, maximum, and mean doses in the tumor (minDose, maxDose, and meanDose), and the volume of tumor covered by the prescription isodose (covVol). We then categorized those quantities for locations of tumors represented by the shortest distance of the skull surface from the tumor center (distC) and the tumor edge (distE). [Table: see text]. Results: All six ratios increased with increasing distC and distE. For example, the median minDose ratio increased from 0.885 to 0.933 as distE increased. There was a statistically significant difference in the minDose ratio between tumors of distE < 2 cm and distE ≥ 2 cm. On the other hand, the median maxDose ratio was about 0.933 [0.928-0.939], being almost independent of distE. This suggested a 6.1% overestimation of the delivered dose with TMR10. Conclusion: The heterogeneity effects must be considered for the volume dose calculations by applying the convolution algorithm when the distance of the skull surface from the closest point of the tumor is less than 2 cm to achieve less than 3% accuracy.

Improved cellular automata model shows that indirect apoptotic cell death due to vascular damage enhances the local control of tumors by single fraction high-dose irradiation.

We investigated the effects of indirect apoptotic cell death due to vascular damage on tumor response to a single large dose with an improved two-dimensional cellular automata model. The tumor growth was simulated by considering the oxygen and nutrients supplied to the tumor through the blood vessels. The cell damage processes were modeled by taking account of the direct cell death and the indirect death due to the radiation-induced vascular damages. The radiation increased the permeation of oxygen and nutrients through the blood vessel or caused the breakdown of the vasculature. The amount of oxygen in cancer cells affected the response of cancer cells to radiation and the tumor growth rate after irradiation. The lack of oxygen led to the apoptotic death of cancer cells. We calculated the tumor control probability (TCP) at different radiation doses, the probability of apoptotic death, the threshold of the oxygen level for indirect apoptotic death, the average oxygen level in cancer cells and the vessel survival probability after radiation damage. Due to the vessel damage, indirect cell death led to a 4% increase in TCP for the dose ranging from 15 Gy to 20 Gy. TCP increased with increasing the probability of apoptotic death and the threshold of the oxygen level for indirect apoptotic death due to increased apoptotic death. The variation of TCP as a function of the average oxygen level exhibited the minimum at the average oxygen level of 2.7%. The apoptosis increased as the average oxygen level decreased, leading to an increasing TCP. On the other hand, the direct radiation damage increased, and the apoptosis decreased for higher average oxygen level, resulting in a higher TCP. We showed by modeling the radiation damage of blood vessels in a 2D CA simulation that the indirect apoptotic death of cancer cells, caused by the reduction of the oxygen level due to vascular damage after high dose irradiation, increased TCP.

Utilization of CBCT to improve the delivery accuracy of Gamma Knife radiosurgery with G-frame.

PURPOSE: To quantify the G-frame based stereotactic coordinate definition accuracy of Leksell coordinate G-frame-based Gamma Knife radiosurgery (GKRS) by the on-board cone-beam CT (CBCT) and establish remedial action rules to minimize the delivery errors. METHODS: We analyzed the data of 108 patients (a total of 201 tumors) treated by GKRS with G-frame for head fixation. After co-registering the CBCT images and plan reference images, the Leksell GammaPlan (LGP) treatment planning system provided the amount of geometric translation and rotation required to minimize the position difference between the plan and treatment. The software also calculated maximum displacement, which characterizes the position shift more clearly. We studied how much these predicted dosimetric quantities changed if the treatment was delivered without correcting the patient's position. RESULTS: The maximum displacement of the patient position obtained from the co-registration of CBCT and plan reference images was 0.81 ± 0.38 mm (0.24-2.03 mm). The target coverage decreased by 3.3 ± 7.0% on average (-48.5% to +35.7%). The decrease of the target coverage, however, became smaller as the target volume increased. In particular, if the volume was greater than 2 cm3 , the %change in target coverage was always less than -5%. CONCLUSIONS: The position differences reported by the registration module of LGP were within the accuracy limit of image registration for most clinical cases, but the errors could be larger in some cases. Therefore, we propose the following decision process. We do not advise position adjustment for G-frame based GKRS if the maximum displacement is less than 1 mm. When this limit is exceeded, however, another criterion should be applied to the decision making by considering the tumor size (or the treatment volume) together with the acceptable change of the tumor coverage.

A radiomics-based model for predicting local control of resected brain metastases receiving adjuvant SRS.

PURPOSE: Adjuvant radiosurgery to the cavities of surgically resected brain metastases provides excellent local tumor control while reducing the risk of deleterious cognitive decline associated with whole brain radiotherapy. A subset of these patients, however, will develop disease recurrence following radiosurgery. In this study, we sought to assess the predictive capability of radiomic-based models, as compared with standard clinical features, in predicting local tumor control. METHODS: We performed a retrospective chart review of patients treated with adjuvant radiosurgery for resected brain metastases at the "Institution" from 2009 to 2019. Shape, intensity and texture based radiomics features of the cavities were extracted from the pre-radiosurgery treatment planning MRI scans and trained using a gradient boosting technique with K-fold cross validation. RESULTS: In total, 71 cavities from 67 treated patients were included for analysis. The 6 and 12 month local control estimates were 86% and 76%, respectively. The 6 and 12 month overall survival was 78% and 55%, respectively. Thirty-six patients developed intracranial failures outside of the surgical cavity. The predictive model for local control trained on imaging features from the whole cavity achieved an area-under-the-curve (AUC) of 0.73 on the validation set versus an AUC of 0.40 for the clinical features. CONCLUSIONS: Here we report a single institutional experience using radiomic-based predictive modeling of local tumor control following adjuvant Gamma Knife radiosurgery for resected brain metastases. We found the radiomics features to provide more robust predictive models of local control rates versus clinical features alone. Such techniques could potentially prove useful in the clinical setting and warrant further investigation.

Evaluation of two calibration methods for MRI-based polymer gel dosimetry.

Polymer gel dosimetry (PGD) can provide three-dimensional (3D) dose data for evaluation of the dose calculation algorithms used by treatment planning systems (TPS). Although the PGD technique, particularly with MRI, is now ready for clinical applications, an accurate calibration method is vital for treatment validation in 3D. This study evaluated the single-phantom electron beam (SPE) method that used the depth-dose data of a 9 MeV electron beam. This technique was compared with the multi-vial x-ray (MVX) method that used nine small vials irradiated with various doses. We tested two regression equations, i.e., third-order polynomial and tangent functions, and two dose-normalization methods, i.e., one-point and two-point methods. These methods were evaluated using a dose distribution generated by a 3 cm × 3 cm open arc beam. We used MAGAT polymer gel manufactured in-house. We found that the SPE method required a smaller dose scaling for the dose comparison. The tangent function showed better data fitting than the polynomial function with smaller uncertainty of the estimated coefficients. We did not observe a distinct advantage of the SPE method over the MVX method for the 3D dose comparison with the test case. From this study, we infer that the SPE method with the tangent function as the regression equation and one-point dose normalization is a good calibration option for the MRI-based polymer gel dosimetry.

A Case of Percutaneous Thrombectomy for Internal Carotid Artery Occlusion due to In-Stent Thrombosis Following Stent-Assisted Intra-Aneurysmal Embolization.

Objective: In-stent thrombosis (IST) is a known complication after stent-assisted coil (SAC) embolization. We report a case of mechanical thrombectomy using a stent retriever (SR) for IST and share our experience with this treatment to prevent a poor outcome in future cases. Case Presentation: The patient was a 62-year-old man. SAC embolization for an unruptured left internal carotid artery (ICA) aneurysm was performed. Three weeks after discharge, right hemiparesis and aphasia developed. Magnetic resonance imaging (MRI) demonstrated cerebral infarction in the left middle cerebral artery (MCA) territory and the left ICA was occluded. His relatives told us that the patient discontinued taking antiplatelet drugs. IST was diagnosed and emergency thrombectomy was performed. First, we tried to introduce an aspiration catheter or balloon catheter into the occluded lesion, but they were unable to be sufficiently inserted to the distal site. Therefore, we used a SR even though it carried a risk of friction on the deployed stent. The occluded artery was finally recanalized using the SR, but the stent became shortened. For the treatment strategy, sufficient medication (antithrombogenic agents and edaravone) should be administered first, followed by mechanical treatment. In mechanical treatment, thrombus fragmentation with a guidewire or balloon and aspiration should be attempted first. New aspiration catheters to carry the devices to the far distal site easily are now available. Conclusion: SRs cannot be utilized for thrombectomy with a stent. In emergency situations, careful consideration during troubleshooting rather than using a SR is needed.

Accreditation Program for Excellence (APEx): A Catalyst for Quality Improvement.

PURPOSE: In 2014 the American Society for Radiation Oncology's Accreditation Program for Excellence (APEx) was created in response to the Target Safely campaign. APEx is a powerful tool to measure and drive quality improvement in radiation oncology practices. METHODS AND MATERIALS: A task group from the American Society for Radiation Oncology's Practice Accreditation Committee was formed to provide an overview of the APEx accreditation program including analysis from specific program data. RESULTS: Through initiatives encouraged by the APEx program, participants are able to evaluate teamwork and effectiveness, implement documented procedures aimed at improving quality and safety, and establish quality management at the practice. The program's Self-Assessment measures performance with program requirements and indicates where compliance lacks standardization. Methods to address these deficiencies form part of on-going quality improvement. These quality outcomes promote the delivery of safe, high-quality care. CONCLUSION: The accreditation process through APEx is a commitment to an ongoing safety culture. Any worthwhile accreditation program should provide a meaningful assessment of practice operations, supply the tools to identify deficiencies and provide the opportunity to showcase growth and development. A commitment to completing APEx is a commitment to excellence for patients and all those who care for them.

Evaluating the biologically effective dose (BED) concept using a dynamic tumor simulation model.

PURPOSE: To evaluate three different formulae for calculating the biologically effective dose (BED) by use of a multipopulation reaction-diffusion simulation to determine whether these formulae produce equivalent effects for different treatment regimes. METHODS: The standard BED formula, BEDs , was updated to account both for spacial nonuniformity in dose and for cellular regrowth between fractions, by creating two new formulae: BEDϕ and BEDϕT . These BED formulae were used to calculate dose per fraction values for two, three, and five fraction treatments and to compare the tumor volumes of those treatments to those of a single fraction. A spherical tumor model based on the reaction-diffusion equation was used to calculate the final volume of each tumor 185 days after the delivery of the first fraction. The percent difference in volume between single-fraction and multiple-fraction treatments was used as a measure to test the accuracy of each BED formula. RESULTS: Percent differences in volume between single- and multiple-fraction treatment regimes varied up to approximately 18.5% if the dose per fraction was calculated using BEDs but the delivered dose was nonuniform. Proper application of spacial nonuniformity in dose and tumor regrowth correction factors modified the dose per fraction values by no more than 5%, but resulted in the improvement of simulated tumor volumes down to around 2% or lower difference in volume. CONCLUSIONS: Treatment regimes with the same BED value should have the same effect. However, small changes in the dose per fraction delivered in multiple-fraction treatments can have a large effect on the tumor volume of a treatment when the dose is delivered nonuniformly or when tumor regrowth between fractions is ignored. Inclusion of these correction factors is important for the underlying assumption that treatments with equal BED will have equal effects on the clinically observed tumor volume.

Optimization of irradiation interval for fractionated stereotactic radiosurgery by a cellular automata model with reoxygenation effects.

The current study aims to determine the optimal irradiation interval of fractionated stereotactic radiosurgery (SRS) by using an improved cellular automata (CA) model. The tumor growth process was simulated by considering the amount of oxygen and the density of blood vessels, which supplied oxygen and nutrient required for cell growth. Cancer cells died by the mitotic death process due to radiation, which was quantified by the LQ-model, or the apoptosis due to the lack of nutrients. The radiation caused increased permeation of plasma protein through the blood vessel or the breakdown of the vasculature. Consequently, these changes lead to a change in radiation sensitivity of cancer cells and tumor growth rate after irradiation. The optimal model parameters were determined with experimental data of the rat tumor volume. The tumor control probability (TCP) was defined as the ratio of the number of histories in which all cancer cells died after the irradiation to the total number of the histories per simulation. The optimal irradiation interval was defined as the irradiation interval that TCP was the maximum. For one fractionation treatment, the ratio of hypoxic cells to the total number of cancer cells kept decreasing until day 16th after irradiation; whereas the number of surviving cancer cells begun increasing immediately after irradiation. This intricate relationship between the hypoxia (or reoxygenation) and the number of cancer cells lead to an optimal irradiation interval for the second irradiation. The optimal irradiation interval for two-fraction SRS was six days. The optimum intervals for the first-second irradiations and the second-third irradiations were five and two days, respectively, for three fraction SRS. For 4 and 5-fraction treatments, the optimum first-interval was five days, which was similar to three fraction treatment. The remaining intervals should be one day. We showed that the improved CA model could be used to optimize the irradiation interval by explicitly including the reoxygenation after irradiation in the model.

Predicting the Local Response of Metastatic Brain Tumor to Gamma Knife Radiosurgery by Radiomics With a Machine Learning Method.

PURPOSE: The current study proposed a model to predict the response of brain metastases (BMs) treated by Gamma knife radiosurgery (GKRS) using a machine learning (ML) method with radiomics features. The model can be used as a decision tool by clinicians for the most desirable treatment outcome. METHODS AND MATERIAL: Using MR image data taken by a FLASH (3D fast, low-angle shot) scanning protocol with gadolinium (Gd) contrast-enhanced T1-weighting, the local response (LR) of 157 metastatic brain tumors was categorized into two groups (Group I: responder and Group II: non-responder). We performed a radiomics analysis of those tumors, resulting in more than 700 features. To build a machine learning model, first, we used the least absolute shrinkage and selection operator (LASSO) regression to reduce the number of radiomics features to the minimum number of features useful for the prediction. Then, a prediction model was constructed by using a neural network (NN) classifier with 10 hidden layers and rectified linear unit activation. The training model was evaluated with five-fold cross-validation. For the final evaluation, the NN model was applied to a set of data not used for model creation. The accuracy and sensitivity and the area under the receiver operating characteristic curve (AUC) of the prediction model of LR were analyzed. The performance of the ML model was compared with a visual evaluation method, for which the LR of tumors was predicted by examining the image enhancement pattern of the tumor on MR images. RESULTS: By the LASSO analysis of the training data, we found seven radiomics features useful for the classification. The accuracy and sensitivity of the visual evaluation method were 44 and 54%. On the other hand, the accuracy and sensitivity of the proposed NN model were 78 and 87%, and the AUC was 0.87. CONCLUSIONS: The proposed NN model using the radiomics features can help physicians to gain a more realistic expectation of the treatment outcome than the traditional method.

[Corticospinal Tract Mapping by Calculating the Ratio of Subcortical to Cortical Stimulation Intensity:A Technical Note].

OBJECTIVE: Motor evoked potentials(MEPs)have been developed and utilized as safe surgical procedures. A correlation between the threshold intensity of direct stimulation MEPs and the distance of the corticospinal tract(CST)has been already established. However, MEPs are affected by anesthesia and patient-related conditions. Here, we describe a unique technique to avoid these effects. METHOD: When tumors developed in proximity to the CST, the transcortical MEP monitoring was done by placing grid electrodes on the primary motor cortex continuously while direct subcortical MEP mapping was conducted with a monopolar probe. The ratios of the subcortical to the transcortical stimulation intensity were calculated. The point at which the ratios reached 50% was defined as the surgical excision limit. DISCUSSION: MEPs are affected by anesthesia, paralysis, body temperature, and other factors. By measuring the ratio of the cortical stimulation intensity instead of the absolute value of the white matter stimulation intensity, various affecting factors can be avoided, and more accurate monitoring can become possible. CONCLUSION: By calculating the ratio of subcortical to cortical stimulation intensity, the corticospinal tract mapping is less likely to be influenced by the stimulation condition or facility setup, and this warrants further investigation.

Space-variant deconvolution of Cerenkov light images acquired from a curved surface.

PURPOSE: Cerenkov photons are generated by high-energy radiation used in external beam radiation therapy (EBRT). This study expands upon the Cerenkov light dosimetry formula previously developed to relate an image of Cerenkov photons to the primary beam fluence. Extension of this formulation allows for deconvolution to be performed on images acquired from curved geometries. METHODS: The integral equation, which represented the formation of Cerenkov photon image from an incident high-energy photon beam, was expanded to allow for space-variance of the convolution kernel called as the Cerenkov scatter function (CSF). The GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations) Monte Carlo (MC) particle simulation software was used to obtain the CSF for different incident beam angles. The image of a curved surface was first projected to a flat plane by using a perspective correction method. Then, the planar image was partitioned into small segments (or blocks), where a CSF corresponding to a specific beam incident angle was applied for deconvolution. The block size and the margin around the block were optimized by studying the effects of those parameters on the deconvolution accuracy for a test image. We evaluated three deconvolution techniques: Richardson-Lucy, Blind, and Total Variation minimization (TV/L2) algorithms, to select the most accurate method for the current applications. RESULTS: Analysis of deconvolution algorithms showed that the TV/L2 method provided the most accurate solution to the deconvolution problem for Cerenkov imaging. Optimization of space-variant deconvolution parameters showed that including a margin that is at least 42.9% of the image width provided the most accurate product image. There was no optimal size for the deconvolution area and should be chosen based on the presence of unique CSF kernels within an image. Space-variant deconvolution improved measured field size in Cerenkov photon images by 7.37%, as compared with 1.74% by space-invariant deconvolution. Space-variant deconvolution improved measured penumbra by 99.3%, as compared with 76.7% by space-invariant deconvolution. Space-variant deconvolution introduced artifacts in flat regions of the beam. Artifacts were avoided through selective space-variant deconvolution in only the penumbra region. CONCLUSIONS: Primary photon fluence distributions of a curved surface can be obtained by using space-variant deconvolution methods in Cerenkov light dosimetry. The TV/L2 algorithm is the best method for deconvolution of Cerenkov photon images from an open-field beam derived from either a flat or curved surface. The partition size chosen for space-variant deconvolution should be at least six times the full width at half maximum (FWHM) of the corresponding scatter kernel used in deconvolution. Space-variant deconvolution is necessary if the incident beam angle difference is larger than 6 ∘ between regions of an image.

Intraoperative Fluorescence Cerebral Angiography by Laser Surgical Microscopy: Comparison With Xenon Microscopy and Simultaneous Observation of Cerebral Blood Flow and Surrounding Structures.

BACKGROUND: Laser surgical microscopes should enable uniform illumination of the operative field, and require less luminous energy compared with existing xenon surgical microscopes. OBJECTIVE: To examine the utility of laser illumination in fluorescence cerebral angiography. METHODS: Fluorescein sodium (fluorescein) was used as a fluorescent dye. We first compared the clarity of cerebral blood flow images collected by fluorescence angiography between the laser illumination and xenon illumination methods. We then assessed use of the laser illuminator for simultaneous observation of blood flow and surrounding structures during fluorescence angiography. Furthermore, the study was designed to evaluate usefulness of the thus determined excitation light in clinical cases. RESULTS: Fluorescence angiography using blue light laser for excitation provided higher clarity and contrast blood flow images compared with using blue light generated from a xenon lamp. Further, illumination with excitation light consisting of a combination of 3 types of laser (higher level of blue light, no green light, and lower level of red light) enabled both blood flow and surrounding structures to be observed through the microscope directly by the surgeon. CONCLUSION: Laser-illuminated fluorescence angiography provides high clarity and contrast images of cerebral blood flow. Further, a laser providing strong blue light and weak red light for excitation light enables simultaneous visual observation of fluorescent blood flow and surrounding structures by the surgeon using a surgical microscope. Overall, these data suggest that laser surgical microscopes are useful for both ordinary operative manipulations and fluorescence angiography.

Characterization of the Cerenkov scatter function: a convolution kernel for Cerenkov light dosimetry.

Cerenkov light is created in clinical applications involving high-energy radiation such as in radiation therapy. There is considerable interest in using Cerenkov light as a means to perform in vivo dosimetry during radiation therapy; however, a better understanding of the light-to-dose relationship is needed. One such method to solve this relationship is that of a deconvolution formulation, which relies on the Cerenkov scatter function (CSF). The CSF describes the creation of Cerenkov photons by a pencil beam of high-energy radiation, and the subsequent scattering that occurs before emission from the irradiated medium surface. This study investigated the dependence of the CSF on common radiation beam parameters (beam energy and incident angle) and the type of irradiated medium. An analytical equation with fitting coefficients of the CSF was obtained for common beam energies in a stratified skin model and optical phantom. Perturbation analysis was performed to investigate the dependence of the deconvolved Cerenkov images on the full-width at half-maximum and amplitude of the CSF. The irradiated material and beam angle had a large impact on the deconvolution process, whereas the beam energy had little effect.

A mathematical deconvolution formulation for superficial dose distribution measurement by Cerenkov light dosimetry.

PURPOSE: Cerenkov photons are created by high-energy radiation beams used for radiation therapy. In this study, we developed a Cerenkov light dosimetry technique to obtain a two-dimensional dose distribution in a superficial region of medium from the images of Cerenkov photons by using a deconvolution method. METHODS: An integral equation was derived to represent the Cerenkov photon image acquired by a camera for a given incident high-energy photon beam by using convolution kernels. Subsequently, an equation relating the planar dose at a depth to a Cerenkov photon image using the well-known relationship between the incident beam fluence and the dose distribution in a medium was obtained. The final equation contained a convolution kernel called the Cerenkov dose scatter function (CDSF). The CDSF function was obtained by deconvolving the Cerenkov scatter function (CSF) with the dose scatter function (DSF). The GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations) Monte Carlo particle simulation software was used to obtain the CSF and DSF. The dose distribution was calculated from the Cerenkov photon intensity data using an iterative deconvolution method with the CDSF. The theoretical formulation was experimentally evaluated by using an optical phantom irradiated by high-energy photon beams. RESULTS: The intensity of the deconvolved Cerenkov photon image showed linear dependence on the dose rate and the photon beam energy. The relative intensity showed a field size dependence similar to the beam output factor. Deconvolved Cerenkov images showed improvement in dose profiles compared with the raw image data. In particular, the deconvolution significantly improved the agreement in the high dose gradient region, such as in the penumbra. Deconvolution with a single iteration was found to provide the most accurate solution of the dose. Two-dimensional dose distributions of the deconvolved Cerenkov images agreed well with the reference distributions for both square fields and a multileaf collimator (MLC) defined, irregularly shaped field. CONCLUSIONS: The proposed technique improved the accuracy of the Cerenkov photon dosimetry in the penumbra region. The results of this study showed initial validation of the deconvolution method for beam profile measurements in a homogeneous media. The new formulation accounted for the physical processes of Cerenkov photon transport in the medium more accurately than previously published methods.