Initial evaluation of intrafraction motion using frameless CyberKnife VSI system

Aim

To analyze intrafraction movement in patients undergoing frameless robotic radiosurgery and evaluate the influence of image acquisition frequency on global accuracy.

Background

Stereotactic radiosurgery requires high spatial accuracy in dose delivery. In conventional radiosurgery, a rigid frame is used to guarantee a correct target alignment and no subsequent movement. Frameless radiosurgery with thermoplastic mask for immobilization cannot completely eliminate intrafraction patient movement. In such cases, it is necessary to evaluate its influence on global treatment accuracy.

Materials and methods

We analyzed the intrafraction motion of the first 15 patients undergoing intracranial radiosurgery (39 fractions) with the CyberKnife VSI system at our institution. Patient position was measured at a 15–90-s interval and was used to estimate intrafraction patient movement.

Results

With our acquisition image protocol and immobilization device, the 99% displacement error was lower than 0.85 mm. The systematic movement components were lower than 0.05 mm and the random component was lower than 0.3 mm in the 3 translational axes. Clear linear time dependence was found in the random component.

Conclusions

Selection of the X-ray image acquisition time is necessary to meet the accuracy required for radiosurgery procedures with the CyberKnife VSI system. We verified that our image acquisition protocol met the 1-mm criterion.     

Dosimetric and localization accuracy of Elekta high definition dynamic radiosurgery

Background and PurposeWith the increasingly prominent role of stereotactic radiosurgery in radiation therapy, there is a clinical need for robust, efficient, and accurate solutions for targeting multiple sites with one patient setup. The end-to-end accuracy of high definition dynamic radiosurgery with Elekta treatment planning and delivery systems was investigated in this study.Materials and MethodsA patient-derived CT scan was used to create a radiosurgery plan to seven targets in the brain. Monaco was used for treatment planning using 5 VMAT non-coplanar arcs. Prior to delivery, 3D-printed phantoms from RTsafe were ordered including a gel phantom for 3D dosimetry, phantom with 2D film insert, and an ion chamber phantom for point dose measurement. Delivery was performed using the Elekta VersaHD, XVI cone-beam CT, and HexaPOD six degree of freedom tabletop.ResultsAbsolute dose accuracy was verified within 2%. 3D global gamma analysis in the film measurement revealed 3%/2 mm passing rates >95%. Gel dosimetry 3D global gamma analysis (3%/2 mm) were above 90% for all targets with the exception of one. Results were indicative of typical end-to-end accuracies (<1 mm spatial uncertainty, 2% dose accuracy) within 4 cm of isocenter. Beyond 4 cm, 2 mm accuracy was found.ConclusionsHigh definition dynamic radiosurgery expands clinically acceptable stereotactic accuracy to a sphere around isocenter allowing for radiosurgery of several targets with one setup with a high degree of dosimetric precision. Gel dosimetry proved to be an essential tool for the validation of the 3D dose distributions in this technique.     

Contact microscopy with synchrotron radiation

Soft X-ray contact microscopy with synchrotron radiation offers the biologist, and especially the microscopist, a way to morphologically study specimens that could not be imaged by conventional TEM, STEM, or SEM methods (i.e., hydrated samples, samples easily damaged by an electron beam, electron-dense samples, thick specimens, unstained, low-contrast specimens) at spatial resolutions approaching those of the TEM, with the additional possibility to obtain compositional (elemental) information about the sample as well. Although flash X-ray sources offer faster exposure times, synchrotron radiation provides a highly collimated, intense radiation that can be tuned to select specific discrete ranges of X-ray wavelengths or specific individual wavelengths that optimize imaging or microanalysis of a specific sample. This paper presents an overview of the applications of X-ray contact microscopy to biological research and some current research results using monochromatic synchrotron radiation to image biological samples.     

Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT)

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25–75 micron-wide microplanar beams separated by wider (100–400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified.SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.     

Stereotactic Radiosurgery for Gynecologic Cancer

Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, intricate treatment planning, on-board imaging, and reduced number of ablative radiation doses to cancer targets usually refractory to chemotherapy and conventional radiation. Steep SBRT radiation dose drop-off permits narrow ''pencil beam'' treatment fields to be used for ablative radiation treatment condensed into 1 to 3 treatments.Treating physicians must appreciate that SBRT comes at a bigger danger of normal tissue injury and chance of geographic tumor miss. Both must be tackled by immobilization of cancer targets and by high-precision treatment delivery. Cancer target immobilization has been achieved through use of indexed customized Styrofoam casts, evacuated bean bags, or body-fix molds with patient-independent abdominal compression.^1-3 Intrafraction motion of cancer targets due to breathing now can be reduced by patient-responsive breath hold techniques,⁴ patient mouthpiece active breathing coordination,⁵ respiration-correlated computed tomography,⁶ or image-guided tracking of fiducials implanted within and around a moving tumor.^7-9 The Cyberknife system (Accuray [Sunnyvale, CA]) utilizes a radiation linear accelerator mounted on a industrial robotic arm that accurately follows patient respiratory motion by a camera-tracked set of light-emitting diodes (LED) impregnated on a vest fitted to a patient.¹⁰ Substantial reductions in radiation therapy margins can be achieved by motion tracking, ultimately rendering a smaller planning target volumes that are irradiated with submillimeter accuracy.^11-13Cancer targets treated by SBRT are irradiated by converging, tightly collimated beams. Resultant radiation dose to cancer target volume histograms have a more pronounced radiation "shoulder" indicating high percentage target coverage and a small high-dose radiation "tail." Thus, increased target conformality comes at the expense of decreased dose uniformity in the SBRT cancer target. This may have implications for both subsequent tumor control in the SBRT target and normal tissue tolerance of organs at-risk. Due to the sharp dose falloff in SBRT, the possibility of occult disease escaping ablative radiation dose occurs when cancer targets are not fully recognized and inadequate SBRT dose margins are applied. Clinical target volume (CTV) expansion by 0.5 cm, resulting in a larger planning target volume (PTV), is associated with increased target control without undue normal tissue injury.^7,8 Further reduction in the probability of geographic miss may be achieved by incorporation of 2-[¹⁸F]fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography (PET).⁸ Use of ¹⁸F-FDG PET/CT in SBRT treatment planning is only the beginning of attempts to discover new imaging target molecular signatures for gynecologic cancers.     

High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the surprising tolerance of normal tissues to very high radiation doses (hundreds of Gy). Based on this well described normal tissue sparing effect of microplanar beams, we developed a new irradiation geometry which allows the delivery of a high uniform dose deposition at a given brain target whereas surrounding normal tissues are irradiated by well tolerated parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced arrays of 10 microplanar beams (52 µm wide, spaced 200 µm on-center, 50 to 350 keV in energy range), targeted from 4 different ports, with a peak entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of 7 mm³ in the caudate nucleus. Magnetic resonance imaging follow-up of rats showed a highly localized increase in blood vessel permeability, starting 1 week after irradiation. Contrast agent diffusion was confined to the target volume and was still observed 1 month after irradiation, along with histopathological changes, including damaged blood vessels. No changes in vessel permeability were detected in the normal brain tissue surrounding the target. The interlacing radiation-induced reduction of spontaneous seizures of epileptic rats illustrated the potential pre-clinical applications of this new irradiation geometry. Finally, Monte Carlo simulations performed on a human-sized head phantom suggested that synchrotron photons can be used for human radiosurgical applications. Our data show that interlaced microbeam irradiation allows a high homogeneous dose deposition in a brain target and leads to a confined tissue necrosis while sparing surrounding tissues. The use of synchrotron-generated X-rays enables delivery of high doses for destruction of small focal regions in human brains, with sharper dose fall-offs than those described in any other conventional radiation therapy.     

A Translatable Predictor of Human Radiation Exposure

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.     

Physical and biological organ dosimetry analysis for international space station astronauts

In this study, we analyzed the biological and physical organ dose equivalents for International Space Station (ISS) astronauts. Individual physical dosimetry is difficult in space due to the complexity of the space radiation environment, which consists of protons, heavy ions and secondary neutrons, and the modification of these radiation types in tissue as well as limitations in dosimeter devices that can be worn for several months in outer space. Astronauts returning from missions to the ISS undergo biodosimetry assessment of chromosomal damage in lymphocyte cells using the multicolor fluorescence in situ hybridization (FISH) technique. Individual-based pre-flight dose responses for lymphocyte exposure in vitro to gamma rays were compared to those exposed to space radiation in vivo to determine an equivalent biological dose. We compared the ISS biodosimetry results, NASA's space radiation transport models of organ dose equivalents, and results from ISS and space shuttle phantom torso experiments. Physical and biological doses for 19 ISS astronauts yielded average effective doses and individual or population-based biological doses for the approximately 6-month missions of 72 mSv and 85 or 81 mGy-Eq, respectively. Analyses showed that 80% or more of organ dose equivalents on the ISS are from galactic cosmic rays and only a small contribution is from trapped protons and that GCR doses were decreased by the high level of solar activity in recent years. Comparisons of models to data showed that space radiation effective doses can be predicted to within about a +/-10% accuracy by space radiation transport models. Finally, effective dose estimates for all previous NASA missions are summarized.     

Olminska and colleagues’ study, “Conversion of the helical tomotherapy plans to the step-and-shoot IMRT plans for patients with hip prosthesis during radiotherapy for prostate cancer” was interesting to read

Olmińska and colleagues’ study, Olmińska et al. (2016) was interesting to read [1]. While prasining the authors for their great work, I want to emphasize e few points.In the recent years, with the development of new device technology, Intensity Modulated Radiotherapy (IMRT) and complex treatment modalities such as stereotactic radiosurgery and helical tomotherapy were started to be implemented. Thus, due to increased local control of tumor growth and reduction of dose received by surrounding critical organs, serious complications were avoided. In this new treatment modality, while calculating appropriate dose, all the parameters such as patient anatomy and characteristics of radiation should be taken into account. Besides, during conformal radiotherapy, if hip prosthesis is located around or in the clinical target volume (CTV), type, thickness and density of biomaterial should be considered to avoid dose differences.     

Dosimetric and bremsstrahlung performance of a single convergent beam for teletherapy device

The present work investigates preliminary feasibility and characteristics of a new type of radiation therapy modality based on a single convergent beam of photons. The proposal consists of the design of a device capable of generating convergent X-ray beams useful for radiotherapy. The main goal is to achieve high concentrated dose delivery. The first step is an analytical approach in order to characterize the dosimetric performance of the hypothetical convergent photon beam. Then, the validated FLUKA Monte Carlo main code is used to perform complete radiation transport to account also for scattering effects. The proposed method for producing convergent X-rays is mainly based on the bremsstrahlung effect. Hence the operating principle of the proposed device is described in terms of bremsstrahlung production. The work is mainly devoted characterizing the effect on the bremsstrahlung yield due to accessories present in the device, like anode material and geometry, filtration and collimation systems among others.The results obtained for in-depth dose distributions, by means of analytical and stochastic approaches, confirm the presence of a high dose concentration around the irradiated target, as expected. Moreover, it is shown how this spot of high dose concentration depends upon the relevant physical properties of the produced convergent photon beam.In summary, the proposed design for producing single convergent X-rays attained satisfactory performance for achieving high dose concentration around small targets depending on beam spot size that may be used for some applications in radiotherapy, like radiosurgery.     

Comparative clinical dosimetry with X-knife and gamma knife

X-knife and gamma knife techniques are well-established for cranial stereotactic radiosurgery (SRS). Due to differences in their radiation delivery methods, some of the dosimetric parameters of these two techniques differ which may have clinical significance. There are many dosimetric studies comparing linear accelerator based techniques such as X-knife with gamma knife but generally from different institutions. We carried out a retrospective comparative study of the dosimetric parameters of the SRS treatments performed at our centre with X-knife (circular cones) and gamma knife. Our results indicate that the dose conformity and dose fall-off in the vicinity of the target volumes were better for patients treated with gamma knife as compared to X-knife. However, the dose fall-off pattern shows a reversal at a larger distance from the target. It was better for the X-knife as compared to gamma knife in the low dose region.     

Monte Carlo modeling of converging small-field contrast-enhanced radiotherapy of prostate

Radiation therapy using a kilovoltage X-ray source to irradiate a target previously loaded with a radiological contrast agent, contrast-enhanced radiotherapy (CERT), has been shown both theoretically and in a preliminary experimental study to represent a potential alternative to high-energy treatments. It has also been shown, however, to produce an integral dose that can be up to twice that resulting from a conventional megavoltage treatment. In this work, using a realistic patient model and Monte Carlo simulation, a CERT prostate treatment plan is designed that makes use of a plurality of small circular beams aimed at the target in such a way as to minimize the radiological trajectory to the target volume. Gold nanoparticles are assumed to be the contrast agent. Two cases are examined, one with a concentration level in the target of 10 mg-Au per gram of tissue and the second with a concentration of 3 mg-Au per gram of tissue in the target. A background concentration of 1 mg of contrast agent per gram of tissue was assumed everywhere else in both cases. The Cimmino feasibility algorithm was then used to find each beam weight in order to obtain the prescribed target dose, set at 72 Gy to 100% of the tumor volume. It is shown that the approach using the small circular fields, a radiosurgery treatment, produces treatment plans with excellent absorbed dose distributions while at the same time it reduces by up to 60% the non-tumor integral dose imparted to the irradiated subject. A brief discussion on the technology necessary to clinically implement this treatment modality is also presented.     

“Edge-on” MOSkin detector for stereotactic beam measurement and verification

Dosimetry in small radiation field is challenging and complicated because of dose volume averaging and beam perturbations in a detector. We evaluated the suitability of the “Edge-on” MOSkin (MOSFET) detector in small radiation field measurement. We also tested the feasibility for dosimetric verification in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). “Edge-on” MOSkin detector was calibrated and the reproducibility and linearity were determined. Lateral dose profiles and output factors were measured using the “Edge-on” MOSkin detector, ionization chamber, SRS diode and EBT2 film. Dosimetric verification was carried out on two SRS and five SRT plans. In dose profile measurements, the “Edge-on” MOSkin measurements concurred with EBT2 film measurements. It showed full width at half maximum of the dose profile with average difference of 0.11 mm and penumbral width with difference of ±0.2 mm for all SRS cones as compared to EBT2 film measurement. For output factor measurements, a 1.1% difference was observed between the “Edge-on” MOSkin detector and EBT2 film for 4 mm SRS cone. The “Edge-on” MOSkin detector provided reproducible measurements for dose verification in real-time. The measured doses concurred with the calculated dose for SRS (within 1%) and SRT (within 3%). A set of output correction factors for the “Edge-on” MOSkin detector for small radiation fields were derived from EBT2 film measurement and presented. This study showed that the “Edge-on” MOSkin detector is a suitable tool for dose verification in small radiation field.     

A true 'advanced imaging assisted' skull-mounted stereotactic system

A stereotactic system has been designed based upon a series of interlocking discs secured to the skull with self-tapping screws. Unlike previous skull-mounted systems, this system is a true, advanced imaging based stereotactic device with the capabilities and accuracy of more traditional, frame based devices. It has been used in a range of applications, from simple biopsies to interstitial radiation implant procedures. Well tolerated by the patient, it allows reaccess to the intracranial target without rescanning. It is convenient for the physician to utilize, both mechanically and timewise, is adaptable to MRI, DSA, and conventional X-ray techniques without modification, and is affordable.     

A model-based approach of scatter dose contributions and efficiency of apron shielding for radiation protection in CT

Given the contribution of scattered radiations to patient dose in CT, apron shielding is often used for radiation protection. In this study the efficiency of apron was assessed with a model-based approach of the contributions of the four scatter sources in CT, i.e. external scattered radiations from the tube and table, internal scatter from the patient and backscatter from the shielding. For this purpose, CTDI phantoms filled with thermoluminescent dosimeters were scanned without apron, and then with an apron at 0, 2.5 and 5 cm from the primary field. Scatter from the tube was measured separately in air. The scatter contributions were separated and mathematically modelled. The protective efficiency of the apron was low, only 1.5% in scatter dose reduction on average. The apron at 0 cm from the beam lowered the dose by 7.5% at the phantom bottom but increased the dose by 2% at the top (backscatter) and did not affect the centre. When the apron was placed at 2.5 or 5 cm, the results were intermediate to the one obtained with the shielding at 0 cm and without shielding. The apron effectiveness is finally limited to the small fraction of external scattered radiation.     

Interaction between radiation-induced adaptive response and bystander mutagenesis in mammalian cells

Two conflicting phenomena, the bystander effect and the adaptive response, are important in determining biological responses at low doses of radiation and have the potential to have an impact on the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we reported previously that nonirradiated cells acquired mutagenesis through direct contact with cells whose nuclei had previously been traversed with either a single or 20 alpha particles each. Here we show that pretreatment of cells with a low dose of X rays 4 h before alpha-particle irradiation significantly decreased this bystander mutagenic response. Furthermore, bystander cells showed an increase in sensitivity after a subsequent challenging dose of X rays. Results from the present study address some of the pressing issues regarding both the actual target size and the radiation dose response and can improve on our current understanding of radiation risk assessment.     

A novel fast kilovoltage switching dual-energy CT with deep learning: Accuracy of CT number on virtual monochromatic imaging and iodine quantification

PurposeA novel fast kilovoltage switching dual-energy CT with deep learning [Deep learning based-spectral CT (DL-Spectral CT)], which generates a complete sinogram for each kilovolt using deep learning views that complement the measured views at each energy, was commercialized in 2020. The purpose of this study was to evaluate the accuracy of CT numbers in virtual monochromatic images (VMIs) and iodine quantifications at various radiation doses using DL-Spectral CT.Materials and methodsTwo multi-energy phantoms (large and small) using several rods representing different materials (iodine, calcium, blood, and adipose) were scanned by DL-Spectral CT at varying radiation doses. Images were reconstructed using three reconstruction parameters (body, lung, bone). The absolute percentage errors (APEs) for CT numbers on VMIs at 50, 70, and 100 keV and iodine quantification were compared among different radiation dose protocols.ResultsThe APEs of the CT numbers on VMIs were <15% in both the large and small phantoms, except at the minimum dose in the large phantom. There were no significant differences among radiation dose protocols in computed tomography dose index volumes of 12.3 mGy or larger. The accuracy of iodine quantification provided by the body parameter was significantly better than those obtained with the lung and bone parameters. Increasing the radiation dose did not always improve the accuracy of iodine quantification, regardless of the reconstruction parameter and phantom size.ConclusionThe accuracy of iodine quantification and CT numbers on VMIs in DL-Spectral CT was not affected by the radiation dose, except for an extremely low radiation dose for body size.     

Development of head docking device for linac-based radiosurgery with a Neptun 10 PC linac

Stereotactic radiosurgery is a method for focused irradiation of intracranial lesions. Linac-based radiosurgery is currently performed by two techniques: couch mounted and pedestal mounted. In the first technique a device is required to affix the patient's head to the couch and neoreover to translate it accurately. Structure of such a device constructed by the authors plus acceptance test performed for evaluation is described in the article.A head docking device has been designed and constructed according to geometry of linac's couch and also desired functions. The device is cornpletely made from aluminum and consists of four major components: attachment bar, lower structure with four moveing accuracy mechanical stability and isocentric accuracy were assessed in the frame of acceptance test.Translating accuracy, mechanical stability and isocentric accuracy were found to be respectively: 1 mm, 1.64 mm and 3.2 mm with accuracy of 95%.According to AAPM report no. 54, a head docking device should translate head with an accuracy of 1 mm; this recommendation has been met. Moreover, we have demonstrated that the isocentric accuracy and mechanical stability of the device are sufficient that the device on confidently be used in stereotactic treatment.     

Comparison of (125)I stereotactic brachytherapy and LINAC radiosurgery modalities based on physical dose distribution and radiobiological efficacy

The goal of this study was to make a comparison between stereotactic brachytherapy implants and linear accelerator-based radiosurgery of brain tumors with respect to physical dose distributions and radiobiological efficacy. Twenty-four treatment plans made for irradiation of brain tumors with low-dose-rate (125)I brachytherapy and multiple-arc LINAC-based radiosurgery were analyzed. Using the dose-volume histograms and the linear-quadratic model, the brachytherapy doses were compared to the brachytherapy-equivalent LINAC radiosurgery doses with respect to the predicted late effects of radiation on normal brain tissue. To characterize the conformity and homogeneity of dose distributions, the conformal index, external volume index, and relative homogeneity index were calculated for each dose plan and the mean values were compared. The average tumor volume was 5.6 cm(3) (range: 0.1-19.3 cm(3)). At low doses, the calculated radiobiological late effect on normal tissue was equivalent for external-beam and brachytherapy dose delivery. For brachytherapy at doses greater than 30 Gy, the calculated equivalent dose to normal tissues was less than for external-beam radiosurgery. However, the dose-calculated homogeneity was better for the LINAC radiosurgery, with a mean relative homogeneity index of 0.62 compared to the calculated value of 0.19 for the brachytherapy (P=0.0002). These results are only predictions based on calculations concerning normal tissue tolerance. More data and research are needed to understand the clinical relevance of these findings.