Array Of Microbeams Research Articles

Differential capacitive mass sensing based on mode localization in coupled microbeam arrays

In this paper, we developed a multi-physics model of an electrostatic MEMS resonator made of an array of mechanically-coupled beams and investigate its potential use for mass detection applications. Experiments were conducted on two- and three-coupled beams under electrostatic actuation to verify the capability of the model to predict the mechanical response of coupled beam arrays. The fabricated device, comprising polysilicon-coupled microbeams, is produced using the Multi-User MEMS Processes, followed by an experimental investigation. Numerical results were found in good agreement with their experimental counterparts. The developed model was used to demonstrate the possible adjustment of the electrostatic actuation to enhance the sensitivity of the dynamic response of the coupled MEMS resonator to mass perturbations. By leveraging the mode localization phenomenon and incorporating a novel differential capacitance sensing mechanism, a notable 84% improvement in sensitivity when switching from two-beam to three-beam system while operating near the second mode in the linear regime. Actuating the MEMS device at higher voltages enabled to achieve higher sensitivity thanks to the activation of nonlinear effects such as bifurcation and softening. We observed the transition from nonlinear to nearly-linear dynamic response of the coupled beams upon the addition of mass and demonstrated how bifurcations that cause a sudden shift to a high-amplitude motion can be utilized in differential capacitance-based mass sensing. Additionally, the suggested detection mechanism allows for overcoming the inherent parasitic capacitance, thereby mitigating low signal-to-noise ratios.

The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model.

Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy. No acute or subacute adverse effects were observed within the first week after irradiation up to MRT peak doses of 400 Gy. No significant differences were seen between irradiated animals and non-irradiated controls in motor function and sensitivity, open field test and somatosensory evoked potentials (SSEP). After irradiation with MRT peak doses of 450-800 Gy, dose-dependent neurologic signs occurred. Provided that long-term studies do not reveal significant morbidity due to late toxicity, an MRT dose of 400 Gy can be considered safe for the spinal cord in the tested beam geometry and field size.

MRT-boost as the last fraction may be the most efficient irradiation schedule for increased survival times in a rat glioma model.

Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident synchrotron beam into arrays of parallel microbeams, typically a few tens of micrometres wide and depositing several hundred Gray. This high dose, high dose rate, spatially fractionated radiotherapy has a high therapeutic impact on tumors, especially in intracranial locations. MRT leads to better control of incurable high-grade glioma than from homogeneous radiotherapy. The schedule of MRT within a conventional irradiation protocol (three fractions of 11 Gy) of brain tumors was evaluated on the 9L glioma model in rats. MRT delivered as a first fraction increased the median survival time of the animals by four days compared with conventional radiotherapy, while the last MRT fraction improved the lifespan by 148% (+15.5 days compared with conventional radiotherapy, p < 0.0001). The most efficient radiation regimen was obtained when the MRT-boost was applied as the last fraction, following two conventional clinical exposures.

Diffraction of a Laguerre-Gaussian beam in Raman interaction with a spatially periodic pump field

We studied Fresnel diffraction of a Laguerre-Gaussian beam ${\text{LG}}_{p,l}$ with arbitrary azimuthal $l$ and radial $p$ indices on a grating induced during its Raman interaction with a spatially periodic pump field in an atomic medium. The diffraction pattern turned out to be more complex than the classical Talbot effect observed when a plane wave illuminates a two-dimensional grating. The simulation results show that, under certain conditions, at distances corresponding to the classical Talbot planes (integer and fractional), periodic amplitude-phase distributions appear. The diffraction patterns are not a probe-field image in the induced grating plane, but a regular array of vortex annular-shaped microbeams with an inhomogeneous intensity distribution depending on the $l$ and $p$ indices and with a topological charge equal to that of the initial probe beam. The intensity and spatial distribution of diffraction patterns can be controlled by Raman amplification in the induced grating by varying the pump-field intensity or the Raman detuning.

Proof of concept of an air-coupled electrostatic ultrasonic transducer based on lateral motion

An alternative implementation of an electrostatic MUT (Micromachined Ultrasonic Transducer), relying on multiple beams that displace along the chip’s surface instead of a single membrane displacing perpendicular to it, is presented in this work. With this approach, a design requiring a low bias voltage (24 V) and occupying a small area (3.3 ×3.3 mm², 2 D / λ ≈ 0.77 ) was shown to generate a sound pressure level of 82 dB (re. 20 µPa-rms) at 40 kHz and a distance of 8.9 cm. The high level of damping allows this transducer to operate in a wide frequency range (35–63 kHz). The operation of this device as an ultrasonic receiver was also proven. An implementation of this transducer as a rangefinder requires a strong reduction in the noise level, particularly coming from radio-frequency interference, in order to increase its detection range. • A transducer concept based on lateral motion (instead of vertical) is used for transmitting and receiving airborne ultrasound. • A high fluidic damping was observed, enabling a transmission bandwidth of nearly an octave (35–65 kHz). • This electrostatic device is based on an array of microbeams and has a sidelength smaller than half a wavelength.

Toward Neuro-Oncologic Clinical Trials of High-Dose-Rate Synchrotron Microbeam Radiation Therapy: First Treatment of a Spontaneous Canine Brain Tumor

The high potential of microbeam radiation therapy (MRT) in improving tumor control while reducing side effects has been shown by numerous preclinical studies. MRT offers a widened therapeutic window by using the periodical spatial fractionation of synchrotron generated x-rays into an array of intense parallel microbeams. MRT now enters a clinical transfer phase. As proof of principle and cornerstone for the safe clinical transfer of MRT, we conducted a "first in dog" trial under clinical conditions. In this report, we evaluated whether a 3-dimensional conformal MRT can be safely delivered as exclusive radiosurgical treatment in animal patients METHODS AND MATERIALS: We irradiated a 17.5-kg French bulldog for a spontaneous brain tumor (glioma suspected on magnetic resonance imaging) with conformal high-dose-rate microbeam arrays (50-µm-wide microbeams, replicated with a pitch of 400 μm) of synchrotron-generated x-rays. The dose prescription adjusted a minimal cumulated valley dose of 2.8 Gy to the plnning target volume (PTV) (cinical target volume (CTV)+1 mm). Thus, each beam delivered 20 to 25 Gy to the target as peak doses, and ∼1 Gy as valley doses RESULTS: The treatment was successfully delivered. Clinical follow-up over 3 months showed a significant improvement of the dog's quality of life: the symptoms disappeared. Magnetic resonance imaging, performed 3 months after irradiation, revealed reduction in tumor size (-87.4%) and mass effect with normalization of the left lateral ventricle. To our knowledge, this neuro-oncologic veterinary trial is the first 3-dimensional conformal synchrotron x-ray MRT treatment of a spontaneous intracranial tumor in a large animal. It is an essential last step toward the clinical transfer of MRT in the near future to demonstrate the feasibility and safety of treating deep-seated tumors using synchrotron-generated microbeams.

A high-resolution dose calculation engine for X-ray microbeams radiation therapy.

BackgroundMicrobeam radiation therapy (MRT) is a treatment modality based on spatial fractionation of synchrotron generated X‐rays into parallel, high dose, microbeams of a few microns width. MRT is still an underdevelopment radiosurgery technique for which, promising preclinical results on brain tumors and epilepsy encourages its clinical transfer.PurposeA safe clinical transfer of MRT needs a specific treatment planning system (TPS) that provides accurate dose calculations in human patients, taking into account the MRT beam's properties (high‐dose gradients, spatial fractionation, polarization effects). So far, the most advanced MRT TPS, based on a hybrid dose calculation algorithm, is limited to a macroscopic rendering of the dose and does not account for the complex dose distribution inherent to MRT if delivered as conformal irradiations with multiple incidences. For overcoming these limitations, a multi‐scale full Monte‐Carlo calculation engine called penMRT has been developed and benchmarked against two general‐purpose Monte Carlo (MC) codes: penmain based on PENELOPE and Gate based on Geant4.MethodsPenMRT, is based on the PENELOPE (2018) MC code, modified to take into account the voxelized geometry of the patients (computed tomography [CT]‐scans) and is offering an adaptive micrometric dose calculation grid independent of the CT size, location, and orientation. The implementation of the dynamic memory allocation in penMRT, makes the simulations feasible within a huge number of dose scoring bins. The possibility of using a source replication approach to simulate arrays of microbeams, and the parallelization using OpenMPI have been added to penMRT in order to increase the calculation speed for clinical usages. This engine can be implemented in a TPS as a dose calculation core.ResultsThe performance tests highlight the reliability of penMRT to be used for complex irradiation conditions in MRT. The benchmarking against a standard PENELOPE code did not show any significant difference for calculations in centimetric beams, for a single microbeam and for a microbeam array. The comparisons between penMRT and Gate as an independent MC code did not show any difference in the beam paths, whereas, in valley regions, relative differences between the two codes rank from 1% to 7.5% which are probably due to the differences in physics lists that are used in these two codes. The reliability of the source replication approach has also been tested and validated with an underestimation of no more than 0.6% in low‐dose areas.ConclusionsGood agreements (a relative difference between 0% and 8%) were found when comparing calculated peak to valley dose ratio values using penMRT, for irradiations with a full microbeam array, with calculated values in the literature. The high‐resolution calculated dose maps obtained with penMRT are used to extract differential and cumulative dose–volume histograms (DVHs) and analyze treatment plans with much finer metrics regarding the irradiation complexity. To our knowledge, these are the first high‐resolution dose maps and associated DVHs ever obtained for cross‐fired microbeams irradiation, which is bringing a significant added value to the field of treatment planning in spatially fractionated radiation therapy.

Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner.

Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. We conducted a morphological analysis of MRT-irradiated normal liver, lung and skin tissues as well as lung and melanoma tumours. MRT induced distinct patterns of DNA damage, reflecting the geometry of the microbeam array. Macrophages infiltrated these regions of peak dose deposition at variable timepoints post-irradiation depending on the tissue type. In normal liver and lung tissue, macrophages clearly demarcated the beam path by 48 h and 7 days post-irradiation, respectively. This was not reflected, however, in normal skin tissue, despite clear DNA damage marking the beam path. Persistent DNA damage was observed in MRT-irradiated lung carcinoma, with an accompanying geometry-specific influx of mixed M1/M2-like macrophage populations. These data indicate the unique potential of MRT as a tool to induce a remarkable accumulation of macrophages in an organ/tissue-specific manner. Further characterization of these macrophage populations is warranted to identify their organ-specific roles in normal tissue sparing and anti-tumour responses.

Imaging of transient phenomena with low coherence lasers comprising arrays of independent microbeams: A laser version of Harold Edgerton’s stroboscope

A longstanding barrier to laser imaging with high spatial and temporal resolution is speckle, the granular interference pattern arising from the coherent interaction of laser radiation with the topography of an illuminated surface. Over the past five decades, scores of mechanical and optical approaches to mitigating or eliminating the impact of speckle have been proposed, including dynamic diffusers, degenerate optical cavities, and random lasers. We describe a laser resonator architecture that allows the spatial coherence and the associated speckle contrast ratio (C) of the laser output to be varied continuously while providing the power necessary for optical imaging of dynamic objects and phenomena with sub-10 ns resolution. Stabilization of a Fabry–Pérot optical cavity with an internal array of microlenses generates thousands of mutually incoherent, parallel microlaser beams, which merge in the far field to form a single beam having a near-Gaussian transverse intensity distribution. For this laser illuminator, C scales as 1/N, where N is the number of microlasers in the array. When Ti:Al2O3 serves as the gain medium, composite beams comprising N &amp;gt; 1000 microbeams are generated with a divergence angle of ∼5 mrad and C &amp;lt; 0.03 for single pulse energies of 8 mJ (∼1 MW peak power). To illustrate the capability of this tunable spatial-coherence laser, images of Drosophila melanogaster in flight and turbomolecular pump vanes rotating at 56 000 rpm are presented. Owing to the brightness and pulse energies available with this laser, imaging a target at a distance of 5 m through dense fog with ∼250 μm resolution has been demonstrated.

Tolerance of Normal Rabbit Facial Bones and Teeth to Synchrotron X-Ray Microbeam Irradiation.

Microbeam radiation therapy, an alternative radiosurgical treatment under preclinical investigation, aims to safely treat muzzle tumors in pet animals. This will require data on the largely unknown radiation toxicity of microbeam arrays for bones and teeth. To this end, the muzzle of six young adult New Zealand rabbits was irradiated by a lateral array of microplanar beamlets with peak entrance doses of 200, 330 or 500 Gy. The muzzles were examined 431 days postirradiation by computed microtomographic imaging (micro-CT) ex vivo, and extensive histopathology. The boundaries of the radiation field were identified histologically by microbeam tracks in cartilage and other tissues. There was no radionecrosis of facial bones in any rabbit. Conversely, normal incisor teeth exposed to peak entrance doses of 330 Gy or 500 Gy developed marked caries-like damage, whereas the incisors of the two rabbits exposed to 200 Gy remained unscathed. A single, unidirectional array of microbeams with a peak entrance dose ≤200 Gy (valley dose14 Gy) did not damage normal bone, teeth and soft tissues of the muzzle of normal rabbits longer than one year after irradiation. Because of that, Microbeam radiation therapy of muzzle tumors in pet animals is unlikely to cause sizeable damage to normal teeth, bone and soft tissues, if a single array as used here delivers a limited entrance dose of 200 Gy and a valley dose of ≤14 Gy.

Unexpected Benefits of Multiport Synchrotron Microbeam Radiation Therapy for Brain Tumors

Simple SummaryWe unveiled the potential of an innovative irradiation technique that ablates brain cancer while sparing normal tissues. Spatially fractionating the incident beam into arrays of micrometer-wide beamlets of X-rays (MRT for Microbeam Radiation Therapy) has led to significantly increased survival and tumor control in preclinical studies. Multiport MRT versus conventional irradiations, for the same background continuous dose, resulted in unexpectedly high equivalent biological effects in rats that have not been achieved with any other radiotherapeutic method. These hallmarks of multiport MRT, i.e., minimal impact on normal tissues and exceptional tumor control, may promote this method towards clinical applications, possibly increasing survival and improving long-term outcomes in neuro-oncology patients.Delivery of high-radiation doses to brain tumors via multiple arrays of synchrotron X-ray microbeams permits huge therapeutic advantages. Brain tumor (9LGS)-bearing and normal rats were irradiated using a conventional, homogeneous Broad Beam (BB), or Microbeam Radiation Therapy (MRT), then studied by behavioral tests, MRI, and histopathology. A valley dose of 10 Gy deposited between microbeams, delivered by a single port, improved tumor control and median survival time of tumor-bearing rats better than a BB isodose. An increased number of ports and an accumulated valley dose maintained at 10 Gy delayed tumor growth and improved survival. Histopathologically, cell death, vascular damage, and inflammatory response increased in tumors. At identical valley isodose, each additional MRT port extended survival, resulting in an exponential correlation between port numbers and animal lifespan (r2 = 0.9928). A 10 Gy valley dose, in MRT mode, delivered through 5 ports, achieved the same survival as a 25 Gy BB irradiation because of tumor dose hot spots created by intersecting microbeams. Conversely, normal tissue damage remained minimal in all the single converging extratumoral arrays. Multiport MRT reached exceptional ~2.5-fold biological equivalent tumor doses. The unique normal tissue sparing and therapeutic index are eminent prerequisites for clinical translation.

Perspectives for microbeam irradiation at the SYRMEP beamline.

It has been shown previously both in vitro and in vivo that microbeam irradiation (MBI) can control malignant tumour cells more effectively than the clinically established concepts of broad beam irradiation. With the aim to extend the international capacity for microbeam research, the first MBI experiment atthe biomedical beamline SYRMEP of the Italian synchrotron facility ELETTRA has been conducted. Using a multislit collimator produced by the company TECOMET, arrays of quasi-parallel microbeams were successfully generated with a beam width of 50 µm and a centre-to-centre distance of 400 µm. Murine melanoma cell cultures were irradiated with a target dose of approximately 65 Gy at a mean photon energy of ∼30 keV with a dose rate of70 Gy s-1 and a peak-to-valley dose of ∼123. This work demonstrated a melanoma cell reduction of approximately 80% after MBI. It is suggested that, while a high energy is essential to achieve high dose rates in order to deposit high treatment doses in a short time in a deep-seated target, for in vitro studies and for the treatment of superficial tumours a spectrum in the lower energy range might be equally suitable or even advantageous.

Study of the X-ray radiation interaction with a multislit collimator for the creation of microbeams in radiation therapy.

Microbeam radiation therapy (MRT) is a developing radiotherapy, based on the use of beams only a few tens of micrometres wide, generated by synchrotron X-ray sources. The spatial fractionation of the homogeneous beam into an array of microbeams is possible using a multislit collimator (MSC), i.e. a machined metal block with regular apertures. Dosimetry in MRT is challenging and previous works still show differences between calculated and experimental dose profiles of 10-30%, which are not acceptable for a clinical implementation of treatment. The interaction of the X-rays with the MSC may contribute to the observed discrepancies; the present study therefore investigates the dose contribution due to radiation interaction with the MSC inner walls and radiation leakage of the MSC. Dose distributions inside a water-equivalent phantom were evaluated for different field sizes and three typical spectra used for MRT studies at the European Synchrotron Biomedical beamline ID17. Film dosimetry was utilized to determine the contribution of radiation interaction with the MSC inner walls; Monte Carlo simulations were implemented to calculate the radiation leakage contribution. Both factors turned out to be relevant for the dose deposition, especially for small fields. Photons interacting with the MSC walls may bring up to 16% more dose in the valley regions, between the microbeams. Depending on the chosen spectrum, the radiation leakage close to the phantom surface can contribute up to 50% of the valley dose for a 5 mm × 5 mm field. The current study underlines that a detailed characterization of the MSC must be performed systematically and accurate MRT dosimetry protocols must include the contribution of radiation leakage and radiation interaction with the MSC in order to avoid significant errors in the dose evaluation at the micrometric scale.

Design of capacitive acoustic sensors using highly compliant microbeam arrays

We have previously shown that the viscous forces acting on a periodic array of infinitesimally thin micro-beams due to air-borne sound are frequency-independent and directional [Mahdi Farahikia and Ronald Miles, “Viscous flow sensing using micro-beam arrays,” J. Acoust. Soc. Am. 146(4), 2837–2837 (2019)]. Utilizing this phenomenon in the design of acoustic sensors requires a means of converting their structural motion into electronic signals. Capacitive sensing, as a method for this purpose, requires the combination of both fixed and moving electrodes while eliminating the instability associated with high bias voltages [Ronald N. Miles, “A compliant capacitive sensor for acoustics: Avoiding electrostatic forces at high bias voltages,” IEEE Sens. J. 18(14), 5691–5698 (2018)]. In this study, the motion of moving micro-beams adjacent to fixed micro-breams in periodic arrays due to air-borne sound is examined through the finite element method. It is concluded that thinner, narrower micro-beams lead to a desired flat frequency response. The optimum gap between the micro-beams is found to be between 0.5 and 1 times the micro-beam width. The results from this study are fundamental in implementing a capacitive sensing mechanism to fabricate miniature acoustic sensors using micro-beam arrays.

Synchrotron X-Ray Boost Delivered by Microbeam Radiation Therapy After Conventional X-Ray Therapy Fractionated in Time Improves F98 Glioma Control

Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly collimated synchrotron beam into arrays of parallel microbeams depositing several hundred grays. It appears relevant to combine MRT with a conventional treatment course, preparing a treatment scheme for future patients in clinical trials. The efficiency of MRT delivered after several broad-beam (BB) fractions to palliate F98 brain tumors in rats in comparison with BB fractions alone was evaluated in this study. Rats bearing 106 F98 cells implanted in the caudate nucleus were irradiated by 5 fractions in BB mode (3 × 6 Gy + 2 × 8 Gy BB) or by 2 boost fractions in MRT mode to a total of 5 fractions (3 × 6 Gy BB + MRT 2 × 8 Gy valley dose; peak dose 181 Gy [50/200 μm]). Tumor growth was evaluated invivo by magnetic resonance imaging follow-up at T-1, T7, T12, T15, T20, and T25 days after radiation therapy and by histology and flow cytometry. MRT-boosted tumors displayed lower cell density and cell proliferation compared with BB-irradiated tumors. The MRT boost completely stopped tumor growth during ∼4 weeks and led to a significant increase in median survival time, whereas tumors treated with BB alone recurred within a few days after the last radiation fraction. The first evidence is presented that MRT, delivered as a boost of conventionally fractionated irradiation by orthovoltage broad x-ray beams, is feasible and more efficient than conventional radiation therapy alone.

On thickness-shear vibration and frequency shift of a quartz crystal resonator carrying an array of micro-beams adhered with tip nano-particles

We established the coupled dynamic model of a quartz crystal resonator carrying an array of micro-beams with tip nano-particles to study the frequency shift of QCR-beams sensors induced by nano-particles with different size and mass density. The appearance of nano-particles increases the inertia of the micro-beams and lower the system frequency unless the resonance occurs and the frequency will jump. The frequency response of QCR-microbeams sensors to nano-particles is nonlinear and much more sensitive and complicate than conventional bare QCR. By choosing appropriate micro-beams length allows the QCR-beams to approach the resonance state, the frequency shift and mass sensitivity of the composite sensor can be significantly improved, but they also change with the size and mass density of the nano-particles. The outcomes are helpful in the particle detection and characterizing using the QCR-microbeams sensor.

A proof of principle experiment for microbeam radiation therapy at the Munich compact light source.

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3Gy or 5Gy and tumor growth delay was measured. Microbeams had a width of 50µm and a center-to-center distance of 350µm with peak doses of either 21Gy or 35Gy. A dose rate of up to 5Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

Film dosimetry studies for patient specific quality assurance in microbeam radiation therapy

Microbeam radiation therapy (MRT) uses synchrotron arrays of X-ray microbeams to take advantage of the spatial fractionation effect for normal tissue sparing. In this study, radiochromic film dosimetry was performed for a treatment where MRT is introduced as a dose boost in a hypofractionated stereotactic radiotherapy (SRT) scheme. The isocenter dose was measured using an ionization chamber and two dimensional dose distributions were determined using radiochromic films. To compare the measured dose distribution to the MRT treatment plan, peak and valley were displayed in separate dosemaps. The measured and computed isocenter doses were compared and a two-dimensional 2%/2 mm normalized γ-index analysis with a 90% passing rate criterion was computed. For SRT, a difference of 2.6% was observed in the dose at the isocenter from the treatment plan and film measurement, with a passing rate of 96% for the γ-index analysis. For MRT, peak and valley doses differences of 25.6% and 8.2% were observed, respectively but passing rates of 96% and 90% respectively were obtained from the normalized γ-index maps. The differences in isocenter doses measured in MRT should be further investigated. We present the methodology of patient specific quality assurance (QA) for studying MRT dose distributions and discuss ideas to improve absolute dosimetry. This patient specific QA will be used for large animal trials quality assurance where MRT will be administered as a dose boost in conventional SRT. The observed remaining discrepancies should be studied against approximations in the TPS phantom materials, beams characteristics or film read-out procedures.

A rebirth of radiation therapy with kV X-rays?

Novel clinical approaches using kV X-ray beams are currently under study, such as selective dose enhancement in malignant tissues due to the enhanced presence of atoms with high atomic number, Z, in tumors relative to normal tissues or the use of heavily spatially fractionated kV X-ray irradiation.Local dose enhancement by high Z atoms: A substantial dose gradient between normal and malignant tissues can be achieved by biologic targeting the cells to be “destroyed” with high Z atoms and its irradiation with photons in the energy region of tens of keV, such as synchrotron produced X-rays of energy above the K-edge. The selective accumulation of high Z atoms can be achieved by various techniques, such as by intravenous administration of a) contrast enhancement agents, b) some chemotherapeutic drugs c) nanoparticles and d) DNA precursors loaded with Z-atoms. Taking into account the limited availability and the high cost of GeV synchrotrons, brachytherapy sources could be used.Microbeam radiation therapy: Studies carried out in experimental models using spatially micro- fractionated beams have shown drastically elevated tissue radiation tolerance, with higher tissue sparing in healthy tissues than in malignant ones. This phenomenon is attributed by some investigators to the proliferation and migration of cells from the “low” dosed regions (~10 Gy) to the adjacent “heavily” dosed regions (many hundreds of grays). Multi-slit collimators allow for the production of X-ray microbeam arrays at 3rd generation synchrotron units. Monte Carlo simulations were tested versus direct dose measurements. Promising preclinical studies carried out so far, trigger studies on the development of alternative less expensive technologies.

Synchrotron-generated microbeams induce hippocampal transections in rats

Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated γ-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis.