Purpose: Small animal irradiation is crucial to the investigation of radiobiological mechanisms. The paradigm of clinical radiation therapy is trending toward high- precision, stereotactic treatment. However, translating this scheme to small animal irradiation is challenging owing to the lack of high-quality image guidance. To overcome this obstacle, we developed a multimodality image guided precision radiation platform. Methods and Materials: The platform consists of 4 modules: x-ray computed tomography (CT), bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and radiation therapy. CT provides animal anatomy and material density for radiation dose calculation, as well as body contour for BLT and FMT reconstruction. BLT and FMT provide tumor localization to guide radiation beams and molecular activity to evaluate treatment outcome. Furthermore, we developed a Monte Carlo-based treatment planning system (TPS) for 3-dimensional dose calculation, calibrated it using radiochromic films sandwiched in a water-equivalent phantom, and validated it using in vivo dosimeters surgically implanted into euthanized mice (n = 4). Finally, we performed image guided irradiation on mice bearing orthotopic breast and prostate tumors and confirmed radiation delivery using gamma H2AX histology. Results: The Monte Carlo-based TPS was successfully calibrated by benchmarking simulation dose against film measurement. For in vivo dosimetry measured in the euthanized mice, the average difference between the TPS calculated dose and measured dose was 3.86% +/- 1.12%. Following the TPS-generated treatment plan, we successfully delivered 20 Gy dose to an animal bearing an orthotopic prostate tumor using 4 BLT-guided radiation beams and 5 Gy dose to an animal bearing an orthotopic breast tumor using a single FMT-guided radiation beam. gamma H2AX histology presented significantly more DNA damage in irradiated tumors and thus validated the dose delivery accuracy. Conclusions: Combined with Monte Carlo TPS, this multimodality CT/BLT/FMT image guided small animal radiation platform can specifically localize tumors, accurately calculate dose distribution, precisely guide radiation delivery, and molecularly evaluate treatment response. It provides an advanced toolset for radiobiology and translational cancer research. (C) 2020 Elsevier Inc. All rights reserved.

PURPOSE:The response of well-type ionization chambers used, for example, in brachytherapy and nuclear medicine, depends on the location of the source. In cases where the source length is variable (typically in nuclear medicine), it is also dependent on length of the source. Here, the combined effect on chamber sensitivity of both source position and length is investigated in detail. This analysis is important if nominal values for source location and length are prescribed as (arbitrary but fixed) values in order to precisely define a chamber's sensitivity. During measurement, the actual values for source location and length can deviate from the nominal ones, altering sensitivity and thus giving rise to measurement uncertainties which, in turn, directly affect the doses administered to patients. Our aim is to investigate these uncertainties and minimize them with an optimized ion chamber design.METHODS:An analytical model for the chamber response is used to describe the variation of chamber sensitivity with respect to the two parameters, source position and length. The influence of the relative magnitude of uncertainty in both parameters is also accounted for. The effect of their combined variation on chamber sensitivity is required to be minimal and, employing differential geometry tools, a relationship is derived between them and the optimal height of the ionization chamber's sensitive volume.RESULTS:This relationship provides the chamber height h which minimizes its response variation for given nominal value of source location (quantified as insertion depth d) and prescribed source length l: h=2d-ρ(ρ)l, where ρ = δd/δl is defined as the quotient of uncertainty in insertion depth, δd, and uncertainty in source length, δl, and ρρ=4/9+ρ21+4ρ2, so that the optimal ionization chamber length varies between h=2d-12l and h=2d-23l. Alternatively, if h is given, suitable combinations of d and l can be deduced.CONCLUSIONS:The analysis presented here provides a tool for reducing the uncertainty budget of any cylindrically designed ionization chambers utilized for measuring extended on-axis sources. In particular, these results can be applied to a calibration-type ionization chamber design recently proposed for the cross-calibration of unsealed radionuclides.

OBJECTIVE: Shot-within-shot (SWS) optimization is a new planning technique that relies on various combinations of shot weighting and prescription isodose line (IDL) to reduce beam-on time. The method differs from other planning techniques that incorporate mixed collimation, multiple stereotactic coordinates, and traditionally low prescription IDLs (<60%). In this work, we evaluate the percentage of brain metastasis for which the method can be applied, the magnitude of the resultant time savings, and the possible tradeoffs in plan quality. METHODS: A retrospective analysis was performed on 75 patients treated for 241 metastatic lesions in the brain. For each lesion, the original planning metrics related to target coverage, conformity, gradient, and beam-on time were recorded. A subset of lesions were selected for replanning using the SWS technique based on size, shape, and proximity to critical structures. Two replans were done, a reference plan was prescribed at the 50% IDL, and an optimized plan was prescribed at an IDL typically >50%. Planning metrics were then compared among the original plan and the 2 replans. RESULTS: More than a third (39%) of the brain metastases were eligible for the SWS technique. For these lesions, the differences between the original plan and reference SWS plan were as follows: Delta V-12Gy < 0.5 cc in 93% of cases, Delta V-12Gy < 0.5 cc in 100% of cases, Delta selectivity < 0.1 in 79% of cases. Negligible differences were seen between the 2 replans in terms of Delta selectivity and Delta V-12Gy; Delta GI < 5% in 99% of cases. After optimization, beam-on time was reduced by 25% -30% in approximately 40% -50% of eligible lesions when compared with the reference SWS plan (Delta T-max = 42%). In comparison with the original plan, beam-on time was reduced even further, Delta T > 50% in 20% of cases (Delta T-max = 70%). CONCLUSIONS: This work demonstrates clinically that optimization using the shot-within-shot technique can reduce beam-on time without degrading treatment plan quality.