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.

Proton Stimulation Targeting Plaque Magnetite Reduces Amyloid-β Plaque and Iron Redox Toxicity and Improves Memory in an Alzheimer’s Disease Mouse Model

Background: The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer’s disease (AD), and the formation of amyloid-β (Aβ) plaques induces critical impairment of cognitive function. Objective: This study aimed to investigate the therapeutic effect of proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. Methods: A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aβ plaques by electron emission from magnetite. The reduction in Aβ plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aβ-magnetite and Aβ fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. Results: Single PS induced a 48–87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aβ plaque burden (68–82%) and (94–97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p < 0.001). Analysis of amyloid fibrils after exposure to a single 2 or 4 Gy proton transmission beam demonstrated that the protein matrix was broken down only in magnetite-associated Aβ fibrils. Conclusion: Single PS targeting plaque magnetite effectively decreases the amyloid plaque burden and the ferrous-containing magnetite level, and this effect is useful for memory recovery.

Dosimetric Comparison of Passive Scattering and Active Scanning Proton Therapy Techniques Using GATE Simulation

Background: In this study, two proton beam delivery designs, i.e. passive scattering proton therapy (PSPT) and pencil beam scanning (PBS), were quantitatively compared in terms of dosimetric indices. The GATE Monte Carlo (MC) particle transport code was used to simulate the proton beam system; and the developed simulation engines were benchmarked with respect to the experimental measurements.Method: A water phantom was used to simulate system energy parameters using a set of depth-dose data in the energy range of 120-235 MeV. To compare the performance of PSPT against PBS, multiple dosimetric parameters including Bragg peak width (BPW50), peak position, range, peak-to-entrance dose ratio, and dose volume histogram have been analyzed under the same conditions. Furthermore, the clinical test cases introduced by AAPM TG-119 were simulated in both beam delivery modes to compare the relevant clinical values obtained from Dose Volume Histogram (DVH) analysis. Results: The parametric comparison in the water phantom between the two techniques revealed that the value of peak-to-entrance dose ratio in PSPT is considerably higher than that from PBS by a factor of 8%. In addition, the BPW50 in PSPT was increased by a factor of 7% compared to the corresponding value obtained from PBS model. TG-119 phantom simulations showed that the difference of PTV mean dose between PBS and PSPT techniques are up to 1.8 % while the difference of max dose to organ at risks (OARs) exceeds 50%. Conclusion: The results demonstrated that the active scanning proton therapy systems was superior in adapting to the target volume, better dose painting, and lower out-of-field dose compared to passive scattering design.

Focused VHEE (very high energy electron) beams and dose delivery for radiotherapy applications

This paper presents the first demonstration of deeply penetrating dose delivery using focused very high energy electron (VHEE) beams using quadrupole magnets in Monte Carlo simulations. We show that the focal point is readily modified by linearly changing the quadrupole magnet strength only. We also present a weighted sum of focused electron beams to form a spread-out electron peak (SOEP) over a target region. This has a significantly reduced entrance dose compared to a proton-based spread-out Bragg peak (SOBP). Very high energy electron (VHEE) beams are an exciting prospect in external beam radiotherapy. VHEEs are less sensitive to inhomogeneities than proton and photon beams, have a deep dose reach and could potentially be used to deliver FLASH radiotherapy. The dose distributions of unfocused VHEE produce high entrance and exit doses compared to other radiotherapy modalities unless focusing is employed, and in this case the entrance dose is considerably improved over existing radiations. We have investigated both symmetric and asymmetric focusing as well as focusing with a range of beam energies.

Evaluation of Given Dose Accuracy in Radiation Therapy of Patient with Breast Cancer Using Diode In-vivo Dosimetry

Background: The main goal of radiation therapy is to deliver the highest dose to the tumor and at the same time the lowest dose to the surrounding normal tissue. In vivo dosimetry is a quality control procedure that, instead of controlling the components separately, directly examines the dose reached to the tumor area. Objectives: In this study, the entrance, exit, and middle dose of the breast and supraclavicular area of patients with breast cancer under radiation therapy were measured and compared with calculations. Methods: In this experimental study, the entrance and exit doses of 33 patients with breast tumors treated with 6 MV and 18MV photons were measured simultaneously. The measurement was done, using p-type diodes after calibration and, then, the midpoint dose was calculated, using the transfer method and arithmetic mean method. Also, the entrance dose, exit dose, and midline dose measured with dosimeter were compared with the calculated values in the treatment planning system. Results: There was no significant difference between calculated and measured doses in the entrance, exit, and midline point in breast regions (P > 0.05), but in the supraclavicular region, a challenge was observed. The difference in entrance and midline point between calculation and measurement is not significant based on the transfer method, but there is a significant error based on the arithmetic mean method (P < 0.05). Conclusions: In vivo dosimetry by measured real given dose to the patient can perform a basic role in the quality control of the radiotherapy department. It seems in the entrance dose, the relative error is smaller but due to the smaller value of exit dose, the relative error in small values is more apparent.

Biological and Mechanical Synergies to Deal With Proton Therapy Pitfalls: Minibeams, FLASH, Arcs, and Gantryless Rooms

Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate “FLASH” irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.

Evaluation of VMAT Planning Strategies for Prostate Patients with Bilateral Hip Prosthesis

Purpose: In this study, we investigate linac volumetric-modulated arc therapy (VMAT) planning strategies for bilateral hip prostheses prostate patients with respect to plan quality and deliverability, while limiting entrance dose to the prostheses. Methods: Three VMAT plans were retrospectively created for 20 patients: (1) partial arcs (PA), (2) 2 full arcs optimized with 500 cGy max prostheses dose (MD), and (3) 2 full arcs optimized with max dose-volume histogram (DVH) constraint of 500 cGy to 10% prostheses volume (MDVH). PA techniques contained 6 PA with beam angles that avoid entering each prosthesis. For each patient, other than prostheses constraints, the same Pinnacle VMAT optimization objectives were used. Plans were normalized with PTV D95% = 79.2 Gy prescription dose. Organ-at-risk DVH metrics, monitor units (MUs), conformality, gradient, and homogeneity indices were evaluated for each plan. Mean entrance prosthesis dose was determined in Pinnacle by converting each arc into static beams and utilizing only control points traversing each prosthesis. Plan deliverability was evaluated with SunNuclear ArcCheck measurements (gamma criteria 3%/2 mm) on an Elekta machine. Results: MD and MDVH had similar dosimetric quality, both improved DVH metrics for rectum and bladder compared to PA. Plan complexities among all plans were similar (average MUs: 441-518). Conformality, homogeneity, and gradient indices were significantly improved in MD and MDVH versus PA ( P < .001). Gamma pass rates for MD (99.0 ± 1.2%) and MDVH (99.2 ± 0.99%) were comparable. A significant difference over PA was observed (96.8 ± 1.6%, P < .001). Field-by-field analysis demonstrated 12/20 PA plans resulted in fields with pass rates <95% versus 1/20 plans for MD and none for MDVH. Cumulative mean entrance doses to each prosthesis were 62.9 ± 17.7 cGy for MD plans and 83.4 ± 27.5 cGy for MDVH plans. Conclusion: MD and MDVH plans had improved dosimetric quality and deliverability over PA plans with minimal entrance doses (∼1% of prescription) to each prosthesis and are an improved alternative for bilateral prostheses prostate patients.

Point-of-Care Tomosynthesis Imaging of the Wrist

ABSTRACT Introduction Musculoskeletal injury to extremities is a common issue for both stateside and deployed military personnel, as well as the general public. Superposition of anatomy can make diagnosis difficult using standard clinical techniques. There is a need for increased diagnostic accuracy at the point-of-care for military personnel in both training and operational environments, as well as assessment during follow-up treatment to optimize care and expedite return to service. Orthopedic tomosynthesis is rapidly emerging as an alternative to digital radiography (DR), exhibiting an increase in sensitivity for some clinical tasks, including diagnosis and follow-up of fracture and arthritis. Commercially available digital tomosynthesis systems are large complex devices. A compact device for extremity tomosynthesis (TomoE) was previously demonstrated using carbon nanotube X-ray source array technology. The purpose of this study was to prepare and evaluate the prototype device for an Institutional Review Board-approved patient wrist imaging study and provide initial patient imaging results. Materials and Methods A benchtop device was constructed using a carbon nanotube X-ray source array and a flat panel digital detector. Twenty-one X-ray projection images of cadaveric specimens and human subjects were acquired at incident angles from −20 to +20 degrees in various clinical orientations, with entrance dose calibrated to commercial digital tomosynthesis wrist scans. The projection images were processed with an iterative reconstruction algorithm in 1 mm slices. Reconstruction slice images were evaluated by a radiologist for feature conspicuity and diagnostic accuracy. Results The TomoE image quality was found to provide more diagnostic information than DR, with reconstruction slices exhibiting delineation of joint space, visual conspicuity of trabecular bone, bone erosions, fractures, and clear depiction of normal anatomical features. The scan time was 15 seconds and the skin entrance dose was verified to be 0.2 mGy. Conclusions The TomoE device image quality has been evaluated using cadaveric specimens. Dose was calibrated for a patient imaging study. Initial patient images depict a high level of anatomical detail and an increase in diagnostic value compared to DR.