Simple high-resolution 3D microscopy by a dielectric microsphere: a proof of concept.

We present a simple high-resolution approach for 3D and quantitative phase imaging (QPI). Our method makes the most of a glass microsphere (MS) for microscopy and a glass plate for lateral shearing self-referencing interferometry. The single MS serves all the functions of a microscope objective (MO) in digital holographic microscopy (DHM) while offering the advantages of compactness, lightness, and affordability. A proof-of-concept experiment is performed on a standard diffraction grating, and various effective parameters on the imaging performance are investigated. The results are validated by atomic force microscopy and Mirau-DHM, and 3D morphometric information of the sample under inspection is obtained. The technique is then applied for 3D quantitative measurement and visualization of a human red blood cell, proving the principle of our easy-to-implement and vibration-immune arrangement for high-contrast label-free QPI of biological samples, and its utility in cell morphology, identification, and classification.

Mitigating disruptions, and scalability of radiation oncology physics work during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has led to disorder in work and livelihood of a majority of the modern world. In this work, we review its major impacts on procedures and workflow of clinical physics tasks, and suggest alternate pathways to avoid major disruption or discontinuity of physics tasks in the context of small, medium, and large radiation oncology clinics. We also evaluate scalability of medical physics under the stress of "social distancing". METHODS: Three models of facilities characterized by the number of clinical physicists, daily patient throughput, and equipment were identified for this purpose. For identical objectives of continuity of clinical operations, with constraints such as social distancing and unavailability of staff due to system strain, however with the possibility of remote operations, the performance of these models was investigated. General clinical tasks requiring on-site personnel presence or otherwise were evaluated to determine the scalability of the three models at this point in the course of disease spread within their surroundings. RESULTS: The clinical physics tasks within three models could be divided into two categories. The former, which requires individual presence, include safety-sensitive radiation delivery, high dose per fraction treatments, brachytherapy procedures, fulfilling state and nuclear regulatory commission's requirements, etc. The latter, which can be handled through remote means, include dose planning, physics plan review and supervision of quality assurance, general troubleshooting, etc. CONCLUSION: At the current level of disease in the United States, all three models have sustained major system stress in continuing reduced operation. However, the small clinic model may not perform if either the current level of infections is maintained for long or staff becomes unavailable due to health issues. With abundance, and diversity of innovative resources, medium and large clinic models can sustain further for physics-related radiotherapy services.

A Monte Carlo based analytic model of the in-room neutron ambient dose equivalent for a Mevion gantry-mounted passively scattered proton system.

The goal of this study was to develop a Monte Carlo (MC)-based analytical model that can predict the in-room ambient dose equivalent from a Mevion gantry-mounted passively scattered proton system. The Mevion S250 and treatment vault were simulated using the MCNPX MC code. The results of the in-room neutron dose measurements, using an FHT 762 WENDI-II detector, were employed to benchmark the MC-derived values. After tuning the MCNPX MC code, for the same beam delivery parameters, the code was used to calculate the neutron spectra and ambient dose equivalent in the vault and at varying angles from the isocenter. Then, based on the calculations, an analytical model was reconstructed and data were fitted to derive the model parameters at 95% confidence intervals (CI). The MCNPX codes were tuned to within about 19% of the measured values for most of the measurements in the vault. For the maze, up to 0.08 mSv Gy-1 discrepancies were found between the experimental measurements and MCNPX calculated results. The analytical model showed up to 18% discrepancy for distances between 100 and 600 cm from the isocenter compared to the MC calculations. The model may underestimate the neutron ambient dose equivalent up to 21% for distances less than 100 cm from the isocenter. The proposed analytical model can be used to estimate the contribution of the secondary neutron dose from the Mevion S250 for the design of local shielding inside the proton therapy treatment vault.

Influence of the background medium on imaging performance of microsphere-assisted super-resolution microscopy.

We demonstrated the importance of the refractive index of the background medium containing the microsphere in microsphere-assisted super-resolution microscopy. We performed numerical simulation and showed that the photonic nanojet properties of a microlens can be optimized by adjusting the index of the background medium surrounding it. Our simulation results, in qualitative agreement with experimental observations, demonstrated that for the same refractive index contrast between the microsphere and its surrounding medium, a high-index microsphere embedded in a medium provides sharper focusing and better imaging quality compared with its low-index counterpart working in air. Our results are of interest for various applications that require optimization of nanojet properties of microspheres, and will inform on the design of novel microparticle-embedded devices for high-resolution imaging.

Proton therapy dosimetry using the scintillation of the silica fibers.

We investigate the feasibility of proton therapy dose measurement by using scintillation of a bare silica glass fiber. The emission spectra of the optical fiber at various depths in tissue-mimicking phantoms, irradiated with proton beams of energies 100-225 MeV show two distinct peaks at 460 and 650 nm whose nature is connected with the silica point defects. Our experimental results and Monte Carlo simulation showed that the Cerenkov radiation cannot be responsible for such a phenomenon. We showed that the intensity of the peak at 650 nm correlates with the proton dose with a minimal effect of ionization quenching, while the intensity peak at 460 nm under-reports the radiation dose.

Optical super-resolution imaging by high-index microspheres embedded in elastomers.

We demonstrated feasibility of super-resolution imaging through high-index microspheres embedded in transparent elastomers. We performed imaging, with resolution improvement by a factor of two, by using implanted barium titanate glass microspheres (diameters ∼30-150 µm and refractive index ∼1.9-2.1) in a thin film of polydimethylsiloxane elastomer placed over the specimen. Microsphere-assisted imaging technique is a promising candidate for applications in cancer research. As a proof-of-principle, we used microsphere-assisted imaging technique for the observation of radiation-induced γ-H2AX foci formation in U87 human glioblastoma cells irradiated by clinical proton beams.

A dataset of digital holograms of normal and thalassemic cells.

Digital holographic microscopy (DHM) is an intriguing medical diagnostic tool due to its label-free and quantitative nature, providing high-contrast images of phase samples. By capturing both intensity and phase information, DHM enables the numerical reconstruction of quantitative phase images. However, the lateral resolution is limited by the diffraction limit, which prompted the recent suggestion of microsphere-assisted DHM to enhance the DHM resolution straightforwardly. The use of such a technique as a medical diagnostic tool requires testing and validation of the proposed assays to prove their feasibility and viability. This paper publishes 760 and 609 microsphere-assisted DHM images of normal and thalassemic red blood cells obtained from a normal and thalassemic male individual, respectively.

High spatiotemporal resolution scintillation imaging of pulsed pencil beam scanning proton beams produced by a gantry-mounted synchrocyclotron.

BACKGROUND: A dosimeter with high spatial and temporal resolution would be of significant interest for pencil beam scanning (PBS) proton beams' characterization, especially when facing small fields and beams with high temporal dynamics. Optical imaging of scintillators has potential in providing sub-millimeter spatial resolution with pulse-by-pulse basis temporal resolution when the imaging system is capable of operating in synchrony with the beam-producing accelerator. PURPOSE: We demonstrate the feasibility of imaging PBS proton beams as they pass through a plastic scintillator detector to simultaneously obtain multiple beam parameters, including proton range, pencil beam's widths at different depths, spot's size, and spot's position on a pulse-by-pulse basis with sub-millimeter resolution. MATERIALS AND METHODS: A PBS synchrocyclotron was used for proton irradiation. A BC-408 plastic scintillator block with 30 × 30 × 5 cm3 size, and another block with 30 × 30 × 0.5 cm3 size, positioned in an optically sealed housing, were used sequentially to measure the proton range, and spot size/location, respectively. A high-speed complementary metal-oxide-semiconductor (CMOS) camera system synchronized with the accelerator's pulses through a gating module was used for imaging. Scintillation images, captured with the camera directly facing the 5-cm-thick scintillator, were corrected for background (BG), and ionization quenching of the scintillator to obtain the proton range. Spots' position and size were obtained from scintillation images of the 0.5-cm-thick scintillator when a 45° mirror was used to reflect the scintillation light toward the camera. RESULTS: Scintillation images with 0.16 mm/pixel resolution corresponding to all proton pulses were captured. Pulse-by-pulse analysis showed that variations of the range, spots' position, and size were within ± 0.2% standard deviation of their average values. The absolute ranges were within ± 1 mm of their expected values. The average spot-positions were mostly within ± 0.8 mm and spots' sigma agreed within 0.2 mm of the expected values. CONCLUSION: Scintillation-imaging PBS beams with high-spatiotemporal resolution is feasible and may help in efficient and cost-effective acceptance testing and commissioning of existing and even emerging technologies such as FLASH, grid, mini-beams, and so forth.

Proton 3D dose measurement with a multi-layer strip ionization chamber (MLSIC) device.

Objective. In current clinical practice for quality assurance (QA), intensity modulated proton therapy (IMPT) fields are verified by measuring planar dose distributions at one or a few selected depths in a phantom. A QA device that measures full 3D dose distributions at high spatiotemporal resolution would be highly beneficial for existing as well as emerging proton therapy techniques such as FLASH radiotherapy. Our objective is to demonstrate feasibility of 3D dose measurement for IMPT fields using a dedicated multi-layer strip ionization chamber (MLSIC) device.Approach.Our developed MLSIC comprises a total of 66 layers of strip ion chamber (IC) plates arranged, alternatively, in thexandydirection. The first two layers each has 128 channels in 2 mm spacing, and the following 64 layers each has 32/33 IC strips in 8 mm spacing which are interconnected every eight channels. A total of 768-channel IC signals are integrated and sampled at a speed of 6 kfps. The MLSIC has a total of 19.2 cm water equivalent thickness and is capable of measurement over a 25 × 25 cm2field size. A reconstruction algorithm is developed to reconstruct 3D dose distribution for each spot at all depths by considering a double-Gaussian-Cauchy-Lorentz model. The 3D dose distribution of each beam is obtained by summing all spots. The performance of our MLSIC is evaluated for a clinical pencil beam scanning (PBS) plan.Main results.The dose distributions for each proton spot can be successfully reconstructed from the ionization current measurement of the strip ICs at different depths, which can be further summed up to a 3D dose distribution for the beam. 3D Gamma Index analysis indicates acceptable agreement between the measured and expected dose distributions from simulation, Zebra and MatriXX.Significance.The dedicated MLSIC is the first pseudo-3D QA device that can measure 3D dose distribution in PBS proton fields spot-by-spot.

Formation of polarized beams in chains of dielectric spheres and cylinders.

Using numerical modeling, it is shown that chains of dielectric spheres and cylinders act as polarizers. The mechanism is based on gradual filtering of periodically focused modes with a certain polarization propagating with minimal losses due to Brewster angles conditions, whereas orthogonally polarized modes are strongly attenuated. It is shown that chains of cylinders filter linearly polarized beams, whereas chains of spheres filter radially polarized beams. In the geometrical optics limit, we show that in a range of sphere refractive indices 1.68-1.80 a degree of radial polarization in excess of 0.9 can be obtained in 10-sphere-long chains.

Dielectric microspheres enhance microscopy resolution mainly due to increasing the effective numerical aperture.

Microsphere-assisted microscopy utilizing a microsphere in immediate proximity of the specimen boosts the imaging resolution mainly as a result of an increase in the effective numerical aperture of the system.

Simulation study of a novel small animal FLASH irradiator (SAFI) with integrated inverse-geometry CT based on circularly distributed kV X-ray sources.

Ultra-high dose rate (UHDR) radiotherapy (RT) or FLASH-RT can potentially reduce normal tissue toxicity. A small animal irradiator that can deliver FLASH-RT treatments similar to clinical RT treatments is needed for pre-clinical studies of FLASH-RT. We designed and simulated a novel small animal FLASH irradiator (SAFI) based on distributed x-ray source technology. The SAFI system comprises a distributed x-ray source with 51 focal spots equally distributed on a 20 cm diameter ring, which are used for both FLASH-RT and onboard micro-CT imaging. Monte Carlo simulation was performed to estimate the dosimetric characteristics of the SAFI treatment beams. The maximum dose rate, which is limited by the power density of the tungsten target, was estimated based on finite-element analysis (FEA). The maximum DC electron beam current density is 2.6 mA/mm2, limited by the tungsten target's linear focal spot power density. At 160 kVp, 51 focal spots, each with a dimension of [Formula: see text] mm2 and 10° anode angle, can produce up to 120 Gy/s maximum DC irradiation at the center of a cylindrical water phantom. We further demonstrate forward and inverse FLASH-RT planning, as well as inverse-geometry micro-CT with circular source array imaging via numerical simulations.

Evaluation of pitting corrosion by dynamic speckle pattern analysis.

There is an increasing interest in non-destructive and real-time high-resolution approaches for corrosion studies in metals. In this paper, we propose the dynamic speckle pattern method as a low-cost, easy-to-implement, and quasi in-situ optical technique for the quantitative evaluation of pitting corrosion. This type of corrosion occurs in a specific area of a metallic structure and causes holes formation leading to structural failure. A Custom 450 stainless steel sample, placed in 3.5 wt% NaCl solution and applied to a [Formula: see text] potential to initiate the corrosion, is used as the sample. The speckle patterns formed by the scattering of a He-Ne laser light is changed over time due to any corrosion in the sample. The analysis of the time-integrate speckle pattern suggests that the growth rate of pitting decreases with time.

Ultra-high dose rate dosimetry: Challenges and opportunities for FLASH radiation therapy.

The clinical translation of FLASH radiotherapy (RT) requires challenges related to dosimetry and beam monitoring of ultra-high dose rate (UHDR) beams to be addressed. Detectors currently in use suffer from saturation effects under UHDR regimes, requiring the introduction of correction factors. There is significant interest from the scientific community to identify the most reliable solutions and suitable experimental approaches for UHDR dosimetry. This interest is manifested through the increasing number of national and international projects recently proposed concerning UHDR dosimetry. Attaining the desired solutions and approaches requires further optimization of already established technologies as well as the investigation of novel radiation detection and dosimetry methods. New knowledge will also emerge to fill the gap in terms of validated protocols, assessing new dosimetric procedures and standardized methods. In this paper, we discuss the main challenges coming from the peculiar beam parameters characterizing UHDR beams for FLASH RT. These challenges vary considerably depending on the accelerator type and technique used to produce the relevant UHDR radiation environment. We also introduce some general considerations on how the different time structure in the production of the radiation beams, as well as the dose and dose-rate per pulse, can affect the detector response. Finally, we discuss the requirements that must characterize any proposed dosimeters for use in UDHR radiation environments. A detailed status of the current technology is provided, with the aim of discussing the detector features and their performance characteristics and/or limitations in UHDR regimes. We report on further developments for established detectors and novel approaches currently under investigation with a view to predict future directions in terms of dosimetry approaches, practical procedures, and protocols. Due to several on-going detector and dosimetry developments associated with UHDR radiation environment for FLASH RT it is not possible to provide a simple list of recommendations for the most suitable detectors for FLASH RT dosimetry. However, this article does provide the reader with a detailed description of the most up-to-date dosimetric approaches, and describes the behavior of the detectors operated under UHDR irradiation conditions and offers expert discussion on the current challenges which we believe are important and still need to be addressed in the clinical translation of FLASH RT.

Synchronized high-speed scintillation imaging of proton beams, generated by a gantry-mounted synchrocyclotron, on a pulse-by-pulse basis.

BACKGROUND: With the emergence of more complex and novel proton delivery techniques, there is a need for quality assurance tools with high spatiotemporal resolution to conveniently measure the spatial and temporal properties of the beam. In this context, scintillation-based dosimeters, if synchronized with the radiation beam and corrected for ionization quenching, are appealing. PURPOSE: To develop a synchronized high-speed scintillation imaging system for characterization and verification of the proton therapy beams on a pulse-by-pulse basis. MATERIALS AND METHODS: A 30 cm × 30 cm × 5 cm block of BC-408 plastic scintillator placed in a light-tight housing was irradiated by proton beams generated by a Mevion S250 proton therapy synchrocyclotron. A high-speed camera system, placed perpendicular to the beam direction and facing the scintillator, was synchronized to the accelerator's pulses to capture images. Opening and closing of the camera's shutter was controlled by setting a proper time delay and exposure time, respectively. The scintillation signal was recorded as a set of two-dimensional (2D) images. Empirical correction factors were applied to the images to correct for the nonuniformity of the pixel sensitivity and quenching of the scintillator. Proton range and modulation were obtained from the corrected images. RESULTS: The camera system was able to capture all data on a pulse-by-pulse basis at a rate of ∼504 frames per second. The applied empirical correction method for ionization quenching was effective and the corrected composite image provided a 2D map of dose distribution. The measured range (depth of distal 90%) through scintillation imaging agreed within 1.2 mm with that obtained from ionization chamber measurement. CONCLUSION: A high-speed camera system capable of capturing scintillation signals from individual proton pulses was developed. The scintillation imaging system is promising for rapid proton beam characterization and verification.

A reconstruction approach for proton computed tomography by modeling the integral depth dose of the scanning proton pencil beam.

PURPOSE: To present a proton computed tomography (pCT) reconstruction approach that models the integral depth dose (IDD) of the clinical scanning proton beam into beamlets. Using a multilayer ionization chamber (MLIC) as the imager, the proposed pCT system and the reconstruction approach can minimize extra ambient neutron dose and simplify the beamline design by eliminating an additional collimator to confine the proton beam. METHODS: Monte Carlo simulation was applied to digitally simulate the IDDs of the exiting proton beams detected by the MLIC. A forward model was developed to model each IDD into a weighted sum of percentage depth doses of the constituent beamlets separated laterally by 1 mm. The water equivalent path lengths (WEPLs) of the beamlets were determined by iteratively minimizing the squared L2-norm between the forward projected and simulated IDDs. The final WEPL values were reconstructed to pCT images, that is, proton stopping power ratio (SPR) maps, through simultaneous algebraic reconstruction technique with total variation regularization. The reconstruction process was tested with a digital cylindrical water-based phantom and an ICRP adult reference computational phantom. The mean of SPR within regions of interest (ROIs) and the WEPL along a 4 mm-wide beam ( WEP L 4 mm ${\rm{WEP}}{{\rm{L}}_{4{\rm{mm}}}}$ ) were compared with the reference values. The spatial resolution was analyzed at the edge of a cortical insert of the cylindrical phantom. RESULTS: The percentage deviations from reference SPR were within ±1% in all selected ROIs. The mean absolute error of the reconstructed SPR was 0.33%, 0.19%, and 0.27% for the cylindrical phantom, the adult phantom at the head and lung region, respectively. The corresponding percentage deviations from reference WEP L 4 mm ${\rm{WEP}}{{\rm{L}}_{4{\rm{mm}}}}$ were 0.48 ± 0.64%, 0.28 ± 0.48%, and 0.22 ± 0.49%. The full width at half maximum of the line spread function (LSF) derived from the radial edge spread function (ESF) of a cortical insert was 0.13 cm. The frequency at 10% of the modulation transfer function (MTF) was 6.38 cm-1 . The mean signal-to-noise ratio (SNR) of all the inserts was 2.45. The mean imaging dose was 0.29 and 0.25 cGy at the head and lung region of the adult phantom, respectively. CONCLUSION: A new pCT reconstruction approach was developed by modeling the IDDs of the uncollimated scanning proton beams in the pencil beam geometry. SPR accuracy within ±1%, spatial resolution of better than 2 mm at 10% MTF, and imaging dose at the magnitude of mGy were achieved. Potential side effects caused by neutron dose were eliminated by removing the extra beam collimator.

Development of Ultra-High Dose-Rate (FLASH) Particle Therapy.

Research efforts in FLASH radiotherapy have increased at an accelerated pace recently. FLASH radiotherapy involves ultra-high dose rates and has shown to reduce toxicity to normal tissue while maintaining tumor response in pre-clinical studies when compared to conventional dose rate radiotherapy. The goal of this review is to summarize the studies performed to-date with proton, electron, and heavy ion FLASH radiotherapy, with particular emphasis on the physical aspects of each study and the advantages and disadvantages of each modality. Beam delivery parameters, experimental set-up, and the dosimetry tools used are described for each FLASH modality. In addition, modeling efforts and treatment planning for FLASH radiotherapy is discussed along with potential drawbacks when translated into the clinical setting. The final section concludes with further questions that have yet to be answered before safe clinical implementation of FLASH radiotherapy.

A multi-layer strip ionization chamber (MLSIC) device for proton pencil beam scan quality assurance.

Objective. Proton pencil beam scanning (PBS) treatment fields needs to be verified before treatment deliveries to ensure patient safety. In current practice, treatment beam quality assurance (QA) is measured at a few selected depths using film or a 2D detector array, which is insensitive and time-consuming. A QA device that can measure all key dosimetric characteristics of treatment beams spot-by-spot within a single beam delivery is highly desired.Approach. We developed a multi-layer strip ionization chamber (MLSIC) prototype device that comprises of two layers of strip ionization chambers (IC) plates for spot position measurement and 64 layers of plate IC for beam energy measurement. The 768-channel strip ion chamber signals are integrated and sampled at a speed of 3.125 kHz. It has a 25.6 cm × 25.6 cm maximum measurement field size and 2 mm spatial resolution for spot position measurement. The depth resolution and maximum depth were 2.91 mm and 18.6 cm for 1.6 mm thick IC plate, respectively. The relative weight of each spot was determined from total charge by all IC detector channels.Main results. The MLSIC is able to measure ionization currents spot-by-spot. The depth dose measurement has a good agreement with the ground truth measured using a water tank and commercial one-dimensional (1D) multi-layer plate chamber. It can verify the spot position, energy, and relative weight of clinical PBS beams and compared with the treatment plans.Significance. The MLSIC is a highly efficient QA device that can measure the key dosimetric characteristics of proton treatment beams spot-by-spot with a single beam delivery. It may improve the quality and efficiency of clinical proton treatments.

Contact focusing multimodal microprobes for ultraprecise laser tissue surgery.

Focusing of multimodal beams by chains of dielectric microspheres assembled directly inside the cores of hollow waveguides is studied by using numerical ray tracing. The device designs are optimized for laser surgery in contact mode with strongly absorbing tissue. By analyzing a broad range of parameters it is demonstrated that chains formed by three or five spheres with a refractive index of 1.65-1.75 provide a two-fold improvement in spatial resolution over single spheres at the cost of 0.2-0.4 attenuation in peak intensity of the central focused beam. Potential applications include ultra precise laser ablation or coagulation in the eye and brain, cellular surgery, and the coupling of light into photonic nanostructures.

Fiber coupling to BaTiO3 glass microspheres in an aqueous environment.

Compact microspheres with high-quality (Q) whispering gallery modes are required for many applications involving liquid immersion, such as sensing nanoparticles and studying resonant radiative pressure effects. We show that high-index (1.9 and 2.1) barium titanate glass (BTG) microspheres are perfect candidates for these applications due to their high-Q (∼10(4) in the 1100-1600 nm range) resonances evanescently excited in spheres with diameters of 4-15 µm. By reattaching the spheres at different positions along a tapered optical fiber, we show that the coupling constant exponentially increases with thinner fiber diameters. We demonstrate the close to critical coupling regime with intrinsic Q=3×10(4) for water immersed 14 µm BTG spheres.