Microbeam Radiation Research Articles

"Towards melanoma in situ vaccination with multiple ultra-narrow X-ray beams".

Despite the recent progress, current treatment modalities are not able to eradicate cancer. We show that Microbeam Radiotherapy (MRT), an innovative type of Spatially Fractionated Radiotherapy, can control murine melanoma by activating the host's own immune system. The beneficial effects are very pronounced in comparison to uniform radiotherapy, traditionally employed in the clinic. Our results displayed that MRT increased antigen presentation, activating Cytotoxic T Lymphocytes (CTLs) which are essential to MRT's treatment efficacy in melanoma. Depletion of CTLs abrogated treatment response. Multiplex nucleic acid hybridization technology revealed key features of lymphocyte populations such as proliferation, differentiation, and ligand-receptor interactions. In addition, CTLs were shown to be essential for locoregional metastatic control and systemic abscopal effects confirmed by activation of antigen presenting cells and CTL trafficking in the tumour-draining lymph nodes. MRT induces a robust antitumour immune response, matching the characteristics of in situ vaccination, that could be exploited to treat a variety of treatment-resistant malignancies.

Tumor growth and vascular redistribution contributes to the dosimetric preferential effect of microbeam radiotherapy: a Monte Carlo study

The radiobiological mechanisms behind the favorable response of tissues to microbeam radiation therapy (MRT) are not fully described yet. Among other factors, the differential action to tumor and normal tissue vasculature is considered to contribute to MRT efficacy. This computational study evaluates the relevance of tumor growth stage and associated vascular redistribution to this effect. A multiscale approach was employed with two simulation softwares: TOPAS and CompuCell3D. Segmentation images of the angioarchitecture of a non-bearing tumor mouse brain were used. The tumor vasculature at different tumor growth stages was obtained by simulating the tumor proliferation and spatial vascular redistribution. The radiation-induced damage to vascular cells and consequent change in oxygen perfusion were simulated for normal and tumor tissues. The multiscale model showed that oxygen perfusion to tissues and vessels decreased as a function of the tumor proliferation stage, and with the decrease in uniformity of the vasculature spatial distribution in the tumor tissue. This led to an increase in the fraction of hypoxic (up to 60%) and necrotic (10%) tumor cells at advanced tumor stages, whereas normal tissues remained normoxic. These results showed that tumor stage and spatial vascular distribution contribute to the preferential effect of MRT in tumors.

Study of a gel dosimeter based on Ag nanoparticles for applications in radiation therapy with synchrotron X-rays at ultrahigh dose rate compared to 60Co γ-rays

A silver nitrate (AgNO3) gel was developed and evaluated as a dosimeter for synchrotron X-ray-based studies in microbeam radiation therapy (MRT) and FLASH radiation therapy. The gel was irradiated at the European Synchrotron Radiation Facility (ID17 Biomedical beamline) with a continuous X-ray spectrum in the 50-600 keV range and a dose rate of 11.6kGy/s. The spectrophotometric response after irradiation at this beamline was compared with the response at a conventional 60Co γ-ray source providing a dose rate of 0.27 Gy/s. Ag+ ions in the gel dosimeter undergo reduction to Ago nanoparticles, as detected at 450 nm, which is a surface plasmon resonance band. The intensity of this band increased linearly with increasing absorbed dose up to 100 Gy, and improved with the addition of glycerol. The gel dosimeter exhibited the lowest detectable dose (LDD) of 75.9% lower and a dose deposition of 76% higher for ID17 beamline irradiation than for 60Co irradiation. The theoretical relative response HQ,Qo for the gel irradiated at the synchrotron was 1.70, which is in close agreement with the experimental relative response FQ,Qo = 1.76. These results confirm the dose enhancement in the gel irradiated with orthovoltage X-rays. The good properties of the silver nitrate gel, together with its increased sensitivity to orthovoltage X-ray irradiation and modest overall uncertainty of 5.8% (2σ), confirm that the gel is a valid dosimeter for measurements at ultrahigh dose rates for synchrotron radiotherapy. The dosimeter is also a promising candidate for dose enhancement factor measurements in nanoparticle-based radiotherapy techniques.

The impact of synchrotron microbeam radiation therapy combined with broad beam in a pre-clinical breast cancer model

The impact of synchrotron microbeam radiation therapy combined with broad beam in a pre-clinical breast cancer model

Advances in Targeted Microbeam Irradiation Methods for Live Caenorhabditis elegans

Advances in Targeted Microbeam Irradiation Methods for Live Caenorhabditis elegans

On the significance of the different geometrical and dosimetric parameters in microbeam and minibeam radiation therapy a retrospective evaluation.

Spatially Fractionated Radiation Therapy (SFRT) is an unconventional therapeutic approach with the potential to disrupt the classical paradigms of conventional radiation therapy. The high spatial dose modulation in SFRT is believed to activate distinct radiobiological mechanisms which lead to remarkable increases in normal tissue tolerance. To make optimal use of SFRT and its benefits, a deeper understanding of the biological response and its relationship with the complex dosimetric and geometric components of SFRT is essential. A retrospective evaluation of preclinical studies was conducted to gain insight into the dosimetric and geometric parameters that are most correlated with normal tissue response. Current literature evaluates the response of tissue to MBRT and MRT according to various end points, e.g. the level of desquamation, degree of necrosis, or the amount of malcalcification. A set of metrics was developed to allow a quantitative comparison of these results. The strongest correlations were observed with the doses in both the peaks and valleys as well as the ratio of the area covered by the peak over the total area. This emphasises the geometry of the beam. MBRT challenged previous uniform dose-distribution paradigms by highlighting the critical role of Peak Dose alongside Valley Dose in tissue sparing whereas MRT underscores the significant influence of geometric beam parameters on tissue preservation. The data exhibits variability in the results obtained using different animal models and endpoints and additional research is warranted to explore the trends observed in this study under controlled conditions.

A clustering tool for generating biological geometries for computational modeling in radiobiology.

To develop a computational tool that converts biological images into geometries compatible with computational software dedicated to the Monte Carlo simulation of radiation transport (TOPAS), and subsequent biological tissue responses (CompuCell3D). The depiction of individual biological entities from segmentation images is essential in computational radiobiological modeling for two reasons: image pixels or voxels representing a biological structure, like a cell, should behave as a single entity when simulating biological processes, and the action of radiation in tissues is described by the association of biological endpoints to physical quantities, as radiation dose, scored the entire group of voxels assembling a cell.
Approach: The tool is capable of cropping and resizing the images and performing clustering of image voxels to create independent entities (clusters) by assigning a unique identifier to these voxels conforming to the same cluster. The clustering algorithm is based on the adjacency of voxels with image values above an intensity threshold to others already assigned to a cluster. The performance of the tool to generate geometries that reproduced original images was evaluated by the Dice Similarity Coefficient (DSC), and by the number of individual entities in both geometries. A set of tests consisting of segmentation images of cultured neuroblastoma cells, two cell nucleus populations, and the vasculature of a mouse brain were used.
Main results: The DSC was 1.0 in all images, indicating that original and generated geometries were identical, and the number of individual entities in both geometries agreed, proving the ability of the tool to cluster voxels effectively following user-defined specifications. The potential of this tool in computational radiobiological modeling, was shown by evaluating the spatial distribution of DNA Double-Strand-Breaks after microbeam irradiation in a segmentation image of a cell culture.
Significance: This tool enables the use of realistic biological geometries in computational radiobiological studies.

138: Effects of minibeam and microbeam radiation therapy on tumor growth delay in human tumor xenografts

138: Effects of minibeam and microbeam radiation therapy on tumor growth delay in human tumor xenografts

1691: Clinical transfer of synchrotron microbeam radiation therapy: Canine brain tumor phase I study

1691: Clinical transfer of synchrotron microbeam radiation therapy: Canine brain tumor phase I study

3077: Microbeam Radiation controls in vivo tumors more effectively than conventional radiation treatment

3077: Microbeam Radiation controls in vivo tumors more effectively than conventional radiation treatment

Review on high spatial resolution dosimetry with pixelated semiconductor detectors for radiation therapy

Current and emerging radiation therapy treatment techniques are characterized by complex and spatially non-uniform dose distributions with steep dose gradients delivered through high-precision dose placement with small radiation fields. Such approaches necessitate advanced verification tools. For accurate dose profile representation in stereotactic radiation therapy using megavoltage X-rays, the Nyquist theorem places the minimum sampling step as 2.5 mm that determines the required spatial resolution of the detectors for dose verification. For techniques such as micro- and mini-beam radiotherapy, micron-scale sampling is required, and sub-millimeter for particle therapy. Silicon semiconductor detectors provide the possibility of producing small sensitive volumes (including in arrays) without compromising mechanical robustness or sensitivity, therefore allowing for high spatial resolution dosimetry. They exhibit many properties of an ideal detector, while the properties of silicon detectors known to negatively influence response can be compensated for and minimized. As such, this work reviews the current status of semiconductor radiation detectors providing dose sampling by diodes with submillimeter sensitive volumes and a pitch of 2.5 mm or smaller for relative dosimetry in X-ray and electron external beam radiation therapy, brachytherapy, microbeam radiation therapy, proton, and heavy ion therapy. The following types of devices are discussed in this work, including commercial systems and those under development: one-dimensional and two-dimensional pixelated arrays (monolithic and single diode based).

Neuro-Oncologic Veterinary Trial for the Clinical Transfer of Microbeam Radiation Therapy: Acute to Subacute Radiotolerance after Brain Tumor Irradiation in Pet Dogs.

Synchrotron Microbeam Radiation Therapy (MRT) has repeatedly proven its superiority compared with conventional radiotherapy for glioma control in preclinical research. The clinical transfer phase of MRT has recently gained momentum; seven dogs with suspected glioma were treated under clinical conditions to determine the feasibility and safety of MRT. We administered a single fraction of 3D-conformal, image-guided MRT. Ultra-high-dose rate synchrotron X-ray microbeams (50 µm-wide, 400 µm-spaced) were delivered through five conformal irradiation ports. The PTV received ~25 Gy peak dose (within microbeams) per port, corresponding to a minimal cumulated valley dose (diffusing between microbeams) of 2.8 Gy. The dogs underwent clinical and MRI follow-up, and owner evaluations. One dog was lost to follow-up. Clinical exams of the remaining six dogs during the first 3 months did not indicate radiotoxicity induced by MRT. Quality of life improved from 7.3/10 [±0.7] to 8.9/10 [±0.3]. Tumor-induced seizure activity decreased significantly. A significant tumor volume reduction of 69% [±6%] was reached 3 months after MRT. Our study is the first neuro-oncologic veterinary trial of 3D-conformal Synchrotron MRT and reveals that MRT does not induce acute to subacute radiotoxicity in normal brain tissues. MRT improves quality of life and leads to remarkable tumor volume reduction despite low valley dose delivery. This trial is an essential step towards the forthcoming clinical application of MRT against deep-seated human brain tumors.

Dosimetry of microbeam radiotherapy by flexible hydrogenated amorphous silicon detectors

Objective. Detectors that can provide accurate dosimetry for microbeam radiation therapy (MRT) must possess intrinsic radiation hardness, a high dynamic range, and a micron-scale spatial resolution. In this work we characterize hydrogenated amorphous silicon detectors for MRT dosimetry, presenting a novel combination of flexible, ultra-thin and radiation-hard features. Approach. Two detectors are explored: an n-type/intrinsic/p-type planar diode (NIP) and an NIP with an additional charge selective layer (NIP + CSC). Results. The sensitivity of the NIP + CSC detector was greater than the NIP detector for all measurement conditions. At 1 V and 0 kGy under the 3T Cu–Cu synchrotron broadbeam, the NIP + CSC detector sensitivity of (7.76 ± 0.01) pC cGy−1 outperformed the NIP detector sensitivity of (3.55 ± 0.23) pC cGy−1 by 219%. The energy dependence of both detectors matches closely to the attenuation coefficient ratio of silicon against water. Radiation damage measurements of both detectors out to 40 kGy revealed a higher radiation tolerance in the NIP detector compared to the NIP + CSC (17.2% and 33.5% degradations, respectively). Percentage depth dose profiles matched the PTW microDiamond detector’s performance to within ±6% for all beam filtrations except in 3T Al–Al due to energy dependence. The 3T Cu–Cu microbeam field profile was reconstructed and returned microbeam width and peak-to-peak values of (51 ± 1) μm and (405 ± 5) μm, respectively. The peak-to-valley dose ratio was measured as a function of depth and agrees within error to the values obtained with the PTW microDiamond. X-ray beam induced charge mapping of the detector revealed minimal dose perturbations from extra-cameral materials. Significance. The detectors are comparable to commercially available dosimeters for quality assurance in MRT. With added benefits of being micron-sized and possessing a flexible water-equivalent substrate, these detectors are attractive candidates for quality assurance, in-vivo dosimetry and in-line beam monitoring for MRT and FLASH therapy.

Hard X-ray imaging and tomography at the Biomedical Imaging and Therapy beamlines of Canadian Light Source.

The Biomedical Imaging and Therapy facility of the Canadian Light Source comprises two beamlines, which together cover a wide X-ray energy range from 13 keV up to 140 keV. The beamlines were designed with a focus on synchrotron applications in preclinical imaging and veterinary science as well as microbeam radiation therapy. While these remain a major part of the activities of both beamlines, a number of recent upgrades have enhanced the versatility and performance of the beamlines, particularly for high-resolution microtomography experiments. As a result, the user community has been quickly expanding to include researchers in advanced materials, batteries, fuel cells, agriculture, and environmental studies. This article summarizes the beam properties, describes the endstations together with the detector pool, and presents several application cases of the various X-ray imaging techniques available to users.

What's Changed in 75 Years of RadRes? - An Australian Perspective on Selected Topics.

Several scientific themes are reviewed in the context of the 75-year period relevant to this special platinum issue of Radiation Research. Two criteria have been considered in selecting the scientific themes. One is the exposure of the associated research activity in the annual meetings of the Radiation Research Society (RRS) and in the publications of the Society's Journal, thus reflecting the interest of members of RRS. The second criteria is a focus on contributions from Australian members of RRS. The first theme is the contribution of radiobiology to radiation oncology, featuring two prominent Australian radiation oncologists, the late Rod Withers and his younger colleague, Lester Peters. Two other themes are also linked to radiation oncology; preclinical research aimed at developing experimental radiotherapy modalities, namely microbeam radiotherapy (MRT) and Auger endoradiotherapy. The latter has a long history, in contrast to MRT, especially in Australia, given that the associated medical beamline at the Australian Synchrotron in Melbourne only opened in 2011. Another theme is DNA repair, which has a trajectory parallel to the 75-year period of interest, given the birth of molecular biology in the 1950s. The low-dose radiobiology theme has a similar timeline, predominantly prompted by the nuclear era, which is also connected to the radioprotector theme, although radioprotectors also have a long-established potential utility in cancer radiotherapy. Finally, two themes are associated with biodosimetry. One is the micronucleus assay, highlighting the pioneering contribution from Michael Fenech in Adelaide, South Australia, and the other is the γ-H2AX assay and its widespread clinical applications.

Single-Event Effect Responses of CMOS Integrated Planar Multiturn Inductors in LC-Tank Oscillators Under Heavy-Ion Microbeam Irradiation

Single-Event Effect Responses of CMOS Integrated Planar Multiturn Inductors in <i>LC</i>-Tank Oscillators Under Heavy-Ion Microbeam Irradiation

Cerenkov free micro-dosimetry in small-field radiation therapy technique

Objective. Optical fiber-based scintillating dosimetry is a recent promising technique owing to the miniature size dosimeter and quality measurement in modern radiation therapy treatment. Despite several advantages, the major issue of using scintillating dosimeters is the Cerenkov effect and predominantly requires extra measurement corrections. Therefore, this work highlighted a novel micro-dosimetry technique to ensure Cerenkov-free measurement in radiation therapy treatment protocol by investigating several dosimetric characteristics. Approach. A micro-dosimetry technique was proposed with the performance evaluation of a novel infrared inorganic scintillator detector (IR-ISD). The detector essentially consists of a micro-scintillating head based on IR-emitting micro-clusters with a sensitive volume of 1.5 × 10−6 mm3. The proposed system was evaluated under the 6 MV LINAC beam used in patient treatment. Overall measurements were performed using IBATM water tank phantoms by following TRS-398 protocol for radiotherapy. Cerenkov measurements were performed for different small fields from 0.5 × 0.5 cm2 to 10 × 10 cm2 under LINAC. In addition, several dosimetric parameters such as percentage depth dose (PDD), high lateral resolution beam profiling, dose linearity, dose rate linearity, repeatability, reproducibility, and field output factor were investigated to realize the performance of the novel detector. Main results. This study highlighted a complete removal of the Cerenkov effect using a point-like miniature detector, especially for small field radiation therapy treatment. Measurements demonstrated that IR-ISD has acceptable behavior with dose rate variability (maximum standard deviation ∼0.18%) for the dose rate of 20–1000 cGy s−1. An entire linear response (R 2 = 1) was obtained for the dose delivered within the range of 4–1000 cGy, using a selected field size of 1 × 1 cm2. Perfect repeatability (max 0.06% variation from average) with day-to-day reproducibility (0.10% average variation) was observed. PDD profiles obtained in the water tank present almost identical behavior to the reference dosimeter with a build-up maximum depth dose at 1.5 cm. The small field of 0.5 × 0.5 cm2 profiles have been characterized with a high lateral resolution of 100 µm. Significance. Unlike recent plastic scintillation detector systems, the proposed micro-dosimetry system in this study requires no Cerenkov corrections and showed efficient performance for several dosimetric parameters. Therefore, it is expected that considering the detector correction factors, the IR-ISD system can be a suitable dose measurement tool, such as in small-field dose measurements, high and low gradient dose verification, and, by extension, in microbeam radiation and FLASH radiation therapy.

136: First evaluation of temporal and spatial fractionation in Microbeam Radiation Therapy (MRT)

136: First evaluation of temporal and spatial fractionation in Microbeam Radiation Therapy (MRT)

2471: Microbeam radiation therapy for lung cancer treatment: a systematic review of the literature

2471: Microbeam radiation therapy for lung cancer treatment: a systematic review of the literature

Radioluminescence-based fibre-optic dosimeters in radiotherapy: a review

Since their conception in the early 1990s, radioluminescence-based fibre-optic dosimeters (FODs) have attracted great interest for dosimetric applications in radiotherapy (RT). Over the years, many scintillating materials, both organic and inorganic, have been developed and tested by multiple research groups around the world. In parallel, reliable techniques for removing or subtracting the stem effect, one of the main drawbacks of FODs, have been proposed in the literature. To date, several prototype systems are widespread, some of which prove to be viable commercial solutions. This review aims to trace the efforts over the years that have enabled FODs to become reliable tools for dosimetry in the current RT procedures and promising options for future scenarios. After a first section devoted to a thorough discussion of the stem effect issue, the use of FODs in various applications of interest to RT, primarily small-field dosimetry and in vivo dosimetry, are addressed. Their use both in external beam RT, including hadrontherapy, and in brachytherapy are considered. A special focus is given to the peculiarities of MRI LINAC dosimetry and the contributions of FODs in this context. Finally, the state of the art concerning the development and characterization of FODs for monitoring ultra-high dose rate radiation beams, typical of FLASH therapy and microbeam RT are presented, highlighting the challenges still open.