Focused Proton Beam Research Articles

Laser-plasma accelerated proton beam transport system using high-field pulsed solenoid magnet

An energetic proton beam with a high divergence cone angle of ∼10°, generated by the interaction of a 25 fs, 800 nm Ti: Sapphire laser pulse with a thin metal foil target, was transported and focused at a specified distance from the source. A pulsed high-voltage solenoid, which generates a magnetic field of 5.7 T at a current of 8 kA, was developed in-house for this purpose. The profile of the proton beam was monitored online at various positions using a combination of a fast thin plastic scintillator and a CCD camera. The effect of solenoid misalignment on the focused proton beam was also investigated experimentally. In addition, the proton beam was transported out of the vacuum chamber into the ambient air for radiography application. A proton flux of ∼2 × 108 protons (energy >4 MeV) was transported and focused at a distance of 1.27 m from the target with a transmission efficiency of 30 % in a single shot. Detailed simulations incorporating particle tracing and transfer matrix method were performed to highlight the role of beam chromaticity and the impact of spherical harmonics on the focusing characteristics of the solenoid. The simulation results qualitatively reproduce the experimental observations. The solenoid provides energy-selective proton focusing for a broad energy proton beam. The proton beam was used for the radiography of reference meshes and has the potential to be used for radiobiological irradiation studies.

Efficient Optical Waveguiding Enabled by Focused Proton Beam Writing in Nd:YCOB Crystal

We report on microfabrication and optical characterization of buried channel waveguides defined in Nd:YCOB crystal by focused proton beam writing (PBW). In the fabrication process, the focused proton beam irradiation creates a local material modification region with geometrically symmetric positive index changes at the end of the proton trajectory, where efficient optical waveguiding can be locally supported within a fiber-like channel structure. The impact of the proton fluence (with different values ranging from 1015 to 1016 cm−2) on the optical waveguiding performance is well studied. The experimental results of the optical waveguide properties are in fairly good agreement with the simulation results.

Sharp dose profiles for high precision proton therapy using strongly focused proton beams

The main objective of radiotherapy is to exploit the curative potential of ionizing radiation while inflicting minimal radiation-induced damage to healthy tissue and sensitive organs. Proton beam therapy has been developed to irradiate the tumor with higher precision and dose conformity compared to conventional X-ray irradiation. The dose conformity of this treatment modality may be further improved if narrower proton beams are used. Still, this is limited by multiple Coulomb scattering of protons through tissue. The primary aim of this work was to develop techniques to produce narrow proton beams and investigate the resulting dose profiles. We introduced and assessed three different proton beam shaping techniques: (1) metal collimators (100/150 MeV), (2) focusing of conventional- (100/150 MeV), and (3) focusing of high-energy (350 MeV, shoot-through) proton beams. Focusing was governed by the initial value of the Twiss parameter alpha (alpha _0), and can be implemented with magnetic particle accelerator optics. The dose distributions in water were calculated by Monte Carlo simulations using Geant4, and evaluated by target to surface dose ratio (TSDR) in addition to the transverse beam size (sigma _T) at the target. The target was defined as the location of the Bragg peak or the focal point. The different techniques showed greatly differing dose profiles, where focusing gave pronouncedly higher relative target dose and efficient use of primary protons. Metal collimators with radii <,2~mathrm{mm} gave low TSDRs (<~0.7) and large sigma _T(>~3.6~hbox {mm}). In contrast, a focused beam of conventional (150~hbox {MeV}) energy produced a very high TSDR (>~80) with similar sigma _T as a collimated beam. High-energy focused beams were able to produce TSDRs >~100 and sigma _T around 1.5 mm. From this study, it appears very attractive to implement magnetically focused proton beams in radiotherapy of small lesions or tumors in close vicinity to healthy organs at risk. This can also lead to a paradigm change in spatially fractionated radiotherapy. Magnetic focusing would facilitate FLASH irradiation due to low losses of primary protons.

Total Knee Replacement with an Uncemented Porous Tantalum Tibia Component: A Failure Analysis.

Porous tantalum has been extensively used in orthopaedic surgery, including uncemented total knee arthroplasty (TKA). Favourable results were reported with earlier monobloc tibial components and the design evolved to modular implants. We aimed to analyse possible causes for extensive medial tibia bone loss, resulting in modular porous tantalum tibia baseplate fracture after primary TKA. Retrieved tissue samples were scanned with 3 MeV focused proton beam for Proton-Induced X-ray Emission (micro-PIXE) elemental analysis. Fractographic and microstructural analysis were performed by stereomicroscopy. A full 3D finite-element model was made for numerical analysis of stress–strain conditions of the tibial baseplate. Histological examination of tissue underneath the broken part of the tibial baseplate revealed dark-stained metal debris, which was confirmed by micro-PIXE to consist of tantalum and titanium. Fractographic analysis and tensile testing showed that the failure of the tibial baseplate fulfilled the criteria of a typical fatigue fracture. Microstructural analysis of the contact surface revealed signs of bone ingrowth in 22.5% of the surface only and was even less pronounced in the medial half of the tibial baseplate. Further studies are needed to confirm the responsibility of metal debris for an increased bone absorption leading to catastrophic tibial tray failure.

The potentialities of ultrasound as an alternative to chemical etching for proton beam writing micropatterning

AbstractIn this paper, we explore the potentialities of using ultrasound waves as a post‐irradiation treatment after proton beam writing (PBW) patterning of PTFE. To that end, 2‐mm‐thick foils of PTFE were irradiated with 2.2 MeV protons with an average current of 50 pA. Straight line structures were patterned on the polymer with a 3.5 × 3.5 μm2 focused proton beam. Post‐irradiation polymers were placed in a heat bath at 60 °C and immersed either in distilled water or in a 6 M solution of NaOH under the action of 40 kHz ultrasound waves for developing the patterned structures. The results indicate that distilled water submitted to ultrasound waves is very efficient for removing rough structures created by the proton irradiation and thus providing a good aspect ratio to the PBW microstructures. On the other hand, the use of 6 M NaOH instead of water did not improve the quality of the structures patterned with the proton beam. The results are discussed in terms of the parameters that characterize the interaction of ultrasound waves with the liquid media and the polymer.

Focused proton beam generating pseudo Bragg peak for FLASH therapy

FLASH effect refers to ultra-high dose rates and ultra-fast irradiation that could reduce normal tissue damage while maintaining tumor control. An isochronous proton cyclotron can generate high-intensity continuous beams, making it ideal for potential FLASH proton therapy. However, generating the dose Bragg peak requires an energy degrader, leading to a drastic decrease in dose rate that is inadequate for FLASH therapy. This paper proposes a shoot-through beam modality by abandoning the energy degrader to increase beam intensity significantly. However, this results in the overall path dose being too high to be accepted. We investigate using focused proton beams to concentrate the dose into a small target volume to form a pseudo-Bragg-peak dose distribution. Simulations show that it can significantly reduce the integrated entrance and exit dose compared to the original parallel beam when delivering the same dose to the target volume, sparing the surrounding healthy tissue.

Beamline design with weak-focusing magnetic field for applications of laser-driven proton beams

&lt;sec&gt;With the development of high-power laser technology, laser plasma acceleration has developed rapidly due to its excellent acceleration structure. Nearly one-hundred-MeV proton beams and several GeV electron outputs are obtained. The laser-driven proton beams have excellent quality of μm-scale sizes and ps-scale pulse lengths. Owing to the existence of the accelerating laser field, direct application is difficult, so the proton beams need to be transmitted to the application terminal through the beamline. However, the wide energy spectrum and large divergence angle bring difficulties in transmitting the beam. The weak focusing in the constant gradient magnetic field is neglected in the transmission of laser-driven particle beams because of the relatively weak focusing force. But weak focusing has special advantages: simultaneous focusing in the horizontal direction and the vertical direction, energy analysis in the horizontal direction, focusing force in the horizontal and vertical direction distributed by the field index &lt;i&gt;n&lt;/i&gt;, and smaller influence of chromatic aberration effect.&lt;/sec&gt;&lt;sec&gt;In this paper, we propose the beam transmission with weak-focusing magnet. The requirements for the focusing of proton beams with the same energy and different divergence angles in the &lt;i&gt;X&lt;/i&gt; direction and &lt;i&gt;Y&lt;/i&gt; direction in the weak-focusing magnetic field are explored by studying the linear beam dynamics of the beams. Then the conditions of precise energy analysis for particle beams with large divergence angle can be determined. For beams with 2% energy spread, the lengths of the drift space before and after the weak-focusing magnet and deflection radius are scanned to find out the minimum beam size and the shortest pulse length after transmission. It is found that a certain combination of drift space and deflection radius can minimize the beam size or the pulse length. Focusing and energy selection can be achieved while compressing the pulse length and effectively reducing the size of the beamline, which has significant advantages. When the deflection radius is 0.65 m, the proton beam with 20 MeV energy, 2% energy spread, and an initial divergence angle of ±50 mrad has the root-mean-square size of 108 μm in both the &lt;i&gt;X&lt;/i&gt; direction and the &lt;i&gt;Y&lt;/i&gt; direction, and a pulse length of 154 ps at the application terminal.&lt;/sec&gt;&lt;sec&gt;Comparing with common beam transmission elements such as quadrupole lenses and deflection magnets, the laser-accelerated ion beam benefits from the integration of focusing and energy analysis of weak-focusing magnetic fields (focusing and energy analysis exist at the same time and continuously change with deflection angle), as well as the horizontal and vertical focusing forces can be distributed by the magnetic field index &lt;i&gt;n&lt;/i&gt; (the larger the &lt;i&gt;n&lt;/i&gt;, the stronger the focusing force in the vertical direction is and the weaker the focusing force in the horizontal direction). When the proton beam is transmitted in a weak-focusing magnetic field, the advantages of the focusing element and the energy selection element are combined, so the influence of the chromatic aberration effect can be reduced, the pulse length can be compressed, and the beamline size can be effectively reduced.&lt;/sec&gt;

FLASH proton irradiation setup with a modulator wheel for a single mouse eye.

Recent studies indicate that FLASH irradiation, which involves ultra-high dose rates in a short time window (usually >40Gy/s in <500ms), might be equally efficient against tumors but less harmful to healthy tissues, compared to conventional irradiation with the same total dose. Aiming to verify the latter claim for ocular proton radiotherapy, in vivo experiments with mice are being carried out by Charité - Universitätsmedizin Berlin. This work presents the implemented setup for delivering FLASH proton radiation to a single eye of mice at the Helmholtz-Zentrum Berlin für Materialien und Energie (HZB). The HZB cyclotron is tuned to provide a high-intensity 68MeV focused proton beam. Outside the vacuum beamline, the protons hit a single scatterer, which also serves as range shifter, and a rotating modulator wheel, which produces a flat depth-dose distribution. Two transmission ionization chambers in between, read out by fast electronics, are used as dose monitors for triggering an in-vacuum beam shutter, which blocks the beam once the desired dose has been delivered. A collimating aperture shapes the radiation field at the isocenter, which is measured by a radioluminescent screen and a CCD camera. At the same position, a parallel-plate ionization chamber of type Advanced Markus® is used for absolute dosimetry and characterization of the spread-out Bragg peak inside a water phantom. A thin-foil mirror of adjustable tilt in the beam path assists the correct alignment of the target through side illumination. Radiochromic films of type EBT3 are used to supplement the dosimetry and assist the alignment. A dose rate of 75Gy/s has been measured, delivering within 200ms 15Gy (RBE) with a reproducibility better than ±1%. A depth-dose curve with a range of 5.2mm in water, 0.9mm distal fall-off (90%-10%), and ±2.5% ripple has been demonstrated, with a PTV of 6.3mm diameter, 1.7mm lateral penumbra (90%-10%), 8% uniformity, and 3% symmetry. The implemented setup is able to accommodate ocular irradiation of narcotized mice with protons, targeting selectively the left or the right eye, under conventional and FLASH conditions. Switching between these two modes can be done within half an hour, including the calibration of the dose monitors and the verification of the dose delivery. Further upgrades are planned after the completion of the on-going experiment.

Nitrogen-Vacancy Color Centers Created by Proton Implantation in a Diamond.

We present an experimental study of the longitudinal and transverse relaxation of ensembles of negatively charged nitrogen-vacancy (NV) centers in a diamond monocrystal prepared by 1.8 MeV proton implantation. The focused proton beam was used to introduce vacancies at a 20 m depth layer. Applied doses were in the range of to ions/cm. The samples were subsequently annealed in vacuum which resulted in a migration of vacancies and their association with the nitrogen present in the diamond matrix. The proton implantation technique proved versatile to control production of nitrogen-vacancy color centers in thin films.

Physical and dosimetric characteristics of radiophotoluminescent glass from two-photon excitation microscopy

We investigate the physical and dosimetric characteristics of Ag-activated phosphate glass exposed to proton beams with various energies. We present time-resolved blue and orange radiophotoluminescent (RPL) spectra and examine the dependence of the peak wavelengths and RPL area intensities on gate time. Moreover, we consider various micro-scale 3D patterns written on Ag-activated glass by a focused proton beam and evaluate their orange and blue RPL axial-profiles using two-photon excitation microscopy. Finally, we discuss the remarkable broadening of the Bragg curve observed in Ag-activated glass and argue that it should be attributed to the saturation effect and/or non-linearity effect from the viewpoint of the relation between the dose delivered and the signal.

Investigation of the second harmonic influence on focusing of moderate energy protons in travelling wave accelerating structure

For proton acceleration in the traveling wave mode with backward n=-1 spatial harmonic the faster main harmonic n=0, having a larger amplitude, influences on proton beam focusing. In the report an additional focusing by the faster main harmonic n=0 is estimated in acceleration of proton beam with energy above 15 MeV assuming the traveling wave accelerating structure in the S band frequency range.

A Case of Metastatic Small Cell Neuroendocrine Carcinoma Presenting as Intractable Back Pain

A 59 year old male with a past medical history of cholecystectomy and essential hypertension, presented to the emergency department with severe back pain, abdominal discomfort, poor appetite, generalized fatigue and progressive weight loss of 10 kgs over a three-month period. He has never been a smoker and drinks alcohol occasionally. He has no known allergies and no familial history of cancer. His current home medication includes beta blocker; angiotensin receptor blocker and low dose acetylsalicylic acid. His back pain started two months prior to presentation; it is not well localized to specific vertebra, not irradiating to lower limbs and sometimes related to weight lifting and cough. It is rarely exacerbated at night. His orthopedic surgeon attributed it to osteoarthritis since the patient used to practice hard manual work and weights lifting at his shop. He has been treated since that time with NSAIDs, muscle relaxant and opioids without complete analgesic response. At presentation, he had no fever, chills or night sweats. He had no urinary or sexual complaints that would suggest prostatic disease and was otherwise asymptomatic. The physical examination showed diffuse pain on lumbar vertebral percussion and abdominal tenderness in the right upper quadrant. He has no skin lesions and no palpable peripheral lymph nodes. His neurologic examination was also normal. On admission, significant laboratory findings showed hemoglobin 11.8 g/dl, platelets of 97,000 k/ul, white blood count 4,400 k/ul, ESR=40, creatinine 0.4 mg/dl,CRP 7.5 mg/L, lactate dehydrogenase 2256 U/L, alanine aminotransferase (ALAT) 70 U/L, gamma-glutamyl transferase (GGT) 1500 U/L, total bilirubin 2.32 mg/dl, and a creatine kinase (CK) 167 U/L. Prostatic specific antigen (PSA) was normal and equal to 1.17 ng/ml. Peripheral smear displayed normal pattern and thyroid tests were all within normal ranges. He was negative for salmonellosis, brucellosis and HIV. Tuberculin PPD test was negative as well. His chest X-ray was normal and abdominopelvic ultrasound showed only multiple liver nodules and mild prostate hypertrophy without ascites or significant abdominal lymph nodes. Lumbar MRI done one week before his admission revealed multiple vertebral lytic lesions without spinal cord compression. PET/CT done on the third day at hospital revealed a significant uptake of radiotracer by multiple small nodules in the right lung, in the liver and by multiple lymph nodes within the abdominal cavity. Moreover there were many lytic lesions in the dorsal and lumbar vertebrae. Surprisingly, the scan also showed focal, intense uptake of the prostate with a SUVmax of 8, 28 with evidence of seminal vesicles invasion. Both gastroscopy and colonoscopy was normal as well as his brain MRI. Ultrasound-guided liver nodules biopsies performed on the fifth day after stopping the acetylsalicylic acid revealed neuroendocrine small cell carcinoma as it showed immunohistochemical (IHC) positivity for synaptophysin and CD56. IHC was negative for TTF1 and PSA. Ultrasound-guided biopsy of the prostate was not performed for medical reasons as on his hospital day 7, the patient started feeling numbness and muscle weakness in his lower limbs more severe on the left side associated with urinary incontinence and revealing a spinal cord compression by secondary bone lesions. Regarding this rapidly progressive disease, high dose dexamethasone subcutaneous therapy and ten sessions of focused proton beam radiotherapy has been conducted on daily basis to release the spinal cord compression without significant improvement. Meanwhile, and based on liver biopsy findings, treatment by octreotide 100mg S/C twice daily was started, followed by chemotherapy with Carboplatin, Etoposide, and Atezolizumab (TECENTRIQ) 1200mg. Few days after, the patient developed severe prolonged pancytopenia requiring blood and platelets transfusions and treatment with double dose of granulocyte stimulating growth factor. His prolonged neutropenia was complicated by CMV colitis with unretractable diarrhea, bilateral pneumonia and pseudomonas aeroginosa septicemia. After one month of large spectrum antibiotics, antiviral and antifungal treatment, and while he was still neutropenic, bone marrow biopsy revealed severe infiltration by neuroendocrine small cell carcinoma. The patient was still deteriorating clinically and showing further weight and appetite loss, total muscle weakness and asthenia. At this point, he was no longer a candidate for chemotherapy but only symptomatic treatment was maintained. He died 45 days after his admission.

Development of Advanced Biodevices Using Quantum Beam Microfabrication Technology

Biodevices with engineered micro- and nanostructures are strongly needed for advancements in medical technology such as regenerative medicine, drug discovery, diagnostic reagents, and drug delivery to secure high quality of life. The authors produced functional biocompatible plastics and hydrogels with physical and chemical properties and surface microscopic shapes that can be freely controlled in three dimensions during the production process using the superior properties of quantum beams. Nanostructures on a biocompatible poly(L-lactic acid) surface were fabricated using a focused ion beam. Soft hydrogels based on polysaccharides were micro-fabricated using a focused proton beam. Gelatin hydrogels were fabricated using γ-rays and electron beam, and their microstructures and stiffnesses were controlled for biological applications. HeLa cells proliferated three-dimensionally on the radiation-crosslinked gelatin hydrogels and, furthermore, their shapes can be controlled by the micro-fabricated surface of the hydrogel. Long-lasting hydrophilic concave structures were fabricated on the surface of silicone by radiation-induced crosslinking and oxidation. The demonstrated advanced biodevices have potential applications in three-dimensional cell culture, gene expression control, stem cell differentiation induction/suppression, cell aggregation into arbitrary shapes, tissue culture, and individual diagnosis in the medical field.

Design and fabrication of three-dimensional single-mode waveguide arrays in bulk diamond through direct focused proton beam implantation

We demonstrate the feasibility of creating three-dimensional photonic devices through the realization of multi-level waveguides inside diamond by a series of systematic combined simulations grounded on Monte-Carlo statistics and Maxwell solver algorithms. Further, we have fabricated the counterparts of the multi-level waveguides buried in single crystalline diamond using a process based on several proton beam irradiation steps with different energies and fluences. On top of that, we draw a thorough comparison between the simulation results and the experimental observations, and find that they are in a good agreement with each other. Moreover, the simulation results also provide additional information such as the working fluence range of single-mode light (1550 nm) wave-guiding, the effective refractive index, and the polarization direction. The proof-of-concept of producing three-dimensional optical and photonic structures by direct focused proton beam implantation would open up a variety of new opportunities in designing and fabricating optical modulators, photonic components and quantum-computing related functional devices in bulk diamond, thus further promoting the development of three-dimensional diamond photonics.

The radiobiology beam line facility at the Centre for Ion Beam Applications, National University of Singapore

A new beam line facility dedicated to investigations into the radiobiology of biological single cells has been constructed at the Centre for Ion Beam Applications, National University of Singapore. This facility, which has a horizontal layout, has some novel features including post lens magnetic ion deflection and scanning and provision for a diamond exit window and confocal fluorescence microscope for high performance online investigations.The radiobiology facility uses a system of Oxford Microbeam compact magnetic quadrupole lenses enabling high demagnifications (up to 123 × 51) at the cell plane, and a relatively short lens to cell distances (22.5 cm). Beam optics and SRIM calculations have indicated a theoretical design performance of up to 450 nm for the proton spot size at the cell surface.To measure the spatial resolution of the proton beam at the cell position, we positioned a gold calibration grid inside the external cell chamber at a position normally occupied by cells. Preliminary results were obtained by scanning a 2 MeV focused beam over a grid and using a surface barrier detector to construct a STIM image of the grid we have measured an in-air spot size of sub-500 nm at the cell position.In this paper, the design of the new radiobiology beam line, preliminary results of resolution tests, as well as presenting first investigations into the damage caused by focused proton beam irradiation of human liver cancer cells by detecting DNA damage markers gamma-H2AX and 53BP1.

Experimental validation of magnetically focused proton beams for radiosurgery

We performed experiments using a triplet of quadrupole permanent magnets to focus protons and compared their dose distributions with unfocused collimated beams using energies and field sizes typically employed in proton radiosurgery. Experiments were performed in a clinical treatment room wherein small-diameter proton beams were focused by a magnet triplet placed immediately upstream of a water tank. The magnets consisted of segments of Sm2Co17 rare-earth permanent magnetic material adhered into Halbach cylinders with nominal field gradients of 100, 150, 200, and 250 T m−1. Unmodulated beams with initial diameters of 3 mm–20 mm were delivered using a single scattering system with nominal energies of 127 and 157 MeV (respective ranges of ~10 cm and 15 cm in water), commonly used for proton radiosurgery at our institution. For comparison, small-diameter unfocused collimated beams were similarly delivered. Transverse and depth dose distributions were measured using radiochromic film and a diode detector, respectively, and compared between the focused and unfocused beams (UNF). The focused beams produced low-eccentricity beam spots (defined by the 80% dose contour) at Bragg depth, with full width at 80% maximum dose values ranging from 3.8 to 7.6 mm. When initial focused beam diameters were larger than matching unfocused diameters (19 of 29 cases), the focused beams peak-to-entrance dose ratios were 13% to 73% larger than UNF. In addition, in 17 of these cases the efficiency of dose delivery to the target was 1.3× to 3.3× larger. Both peak-to-entrance dose ratios and efficiency tended to increase with initial beam diameter, while efficiency also tended to increase with magnet gradient. These experimental results are consistent with our previous Monte Carlo (MC) studies and suggest that a triplet of quadrupole Halbach cylinders could be clinically useful for irradiating small-field radiosurgical targets with fewer beams, lower entrance dose, and shorter treatment times.

Micro-PIXE studies on prehistoric chert tools: elemental mapping to determine Palaeolithic lithic procurement

This paper contributes to an understanding of the distances and choices involved in raw material procurement strategies by Upper Palaeolithic communities through a Pyrenean geo-archaeological case study. Methodologically, it involved using Particle Induced X-ray Emission (PIXE) with a focused proton beam to determine the concentration and distribution of elements in geological samples from three natural primary outcrops belonging to two geological formations outcropping in the French side of the Pyrenees. While it was not possible to distinguish the formation through reference to major and minor elements, some variations were revealed at the trace elemental level. With the aim to determine if these elements were associated with the Si matrix or to a specific inclusion, elemental maps were acquired, and the elemental composition of the identified inclusions were also determined. These chemical signatures were then compared to those generated from archaeological artefacts from sites in northern Spain as a means of reconstructing the catchment areas used by prehistoric groups for their chert procurement. The results indicate the existence of trans-Pyrenean long distance procurement strategies during the Magdalenian (13,700 to the 18,800 cal BP).

Single-mode light guiding in diamond waveguides directly written by a focused proton beam.

Ion-implanted waveguides were directly written in bulk single-crystal diamond by scanning a focused 2MeV proton beam. By controlling the fluence and the lateral size of the proton beam, a bright and near-circular single-mode profile was observed. Propagation loss and effective refractive index of the guided mode were measured by the Fabry-Pérot technique, confirming single-mode guiding. Micro-Raman maps of the waveguides were used to visualize damage profiles and defect distributions induced by the proton beam. The demonstration of single-mode light guiding in our waveguides shows that direct proton beam writing is a promising tool in the rapid manufacture of integrated optical circuits in bulk diamond.

Monte Carlo evaluation of magnetically focused proton beams for radiosurgery

The purpose of this project is to investigate the advantages in dose distribution and delivery of proton beams focused by a triplet of quadrupole magnets in the context of potential radiosurgery treatments. Monte Carlo simulations were performed using various configurations of three quadrupole magnets located immediately upstream of a water phantom. Magnet parameters were selected to match what can be commercially manufactured as assemblies of rare-earth permanent magnetic materials. Focused unmodulated proton beams with a range of ~10 cm in water were target matched with passive collimated beams (the current beam delivery method for proton radiosurgery) and properties of transverse dose, depth dose and volumetric dose distributions were compared. Magnetically focused beams delivered beam spots of low eccentricity to Bragg peak depth with full widths at the 90% reference dose contour from ~2.5 to 5 mm. When focused initial beam diameters were larger than matching unfocused beams (10 of 11 cases) the focused beams showed 16%–83% larger peak-to-entrance dose ratios and 1.3 to 3.4-fold increases in dose delivery efficiency. Peak-to-entrance and efficiency benefits tended to increase with larger magnet gradients and larger initial diameter focused beams. Finally, it was observed that focusing tended to shift dose in the water phantom volume from the 80%–20% dose range to below 20% of reference dose, compared to unfocused beams. We conclude that focusing proton beams immediately upstream from tissue entry using permanent magnet assemblies can produce beams with larger peak-to-entrance dose ratios and increased dose delivery efficiencies. Such beams could potentially be used in the clinic to irradiate small-field radiosurgical targets with fewer beams, lower entrance dose and shorter treatment times.

Hydrogel Nanosensors for Colorimetric Detection and Dosimetry in Proton Beam Radiotherapy.

Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation. A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristic of protons, which results in superior healthy tissue sparing. This results in fewer unwanted side effects and improved outcomes for patients. Currently available dosimeters are intrinsic, complex, and expensive and are not routinely used to determine the dose delivered to the tumor. Here, we report a hydrogel-based plasmonic nanosensor for detecting clinical doses used in conventional and hyperfractionated proton beam radiotherapy. In this nanosensor, gold ions, encapsulated in a hydrogel, are reduced to gold nanoparticles following irradiation with proton beams. Formation of gold nanoparticles renders a color change to the originally colorless hydrogel. The intensity of the color can be used to calibrate the hydrogel nanosensor in order to quantify different radiation doses employed during proton treatment. The potential of this nanosensor for clinical translation was demonstrated using an anthropomorphic phantom mimicking a clinical radiotherapy session. The simplicity of fabrication, detection range in the fractionated radiotherapy regime, and ease of detection with translational potential makes this a first-in-kind plasmonic colorimetric nanosensor for applications in clinical proton beam therapy.