Computer animation body surface analysis of total skin electron radiation therapy dose homogeneity via Cherenkov imaging.

Purpose: Quality assurance (QA) of dose homogeneity in total skin electron therapy (TSET) is challenging since each patient is positioned in six standing poses with two beam angles. Our study tested the feasibility of a unique approach for TSET QA through computational display of the cumulative dose, constructed and synthesized by computer animation methods. Approach: Dose distributions from Cherenkov emission images were projected onto a scanned 3D body model. Topographically mapped surfaces of the patient were recorded in each of six different delivery positions, while a Cherenkov camera acquired images. Computer animation methods allowed a fitted 3D human body model of the patient to be created with deformation of the limbs and torso to each position. A two-dimensional skin map was extracted from the 3D model of the full surface of the patient. This allowed the dose mapping to be additively accumulated independent of body position, with the total dose summed in a 2D map and reinterpreted on the 3D body display. Results: For the body model, the mean Hausdorff error distance was below 2 cm, setting the spatial accuracy limit. The dose distribution over the patient's 3D model generally matched the Cherenkov/dose images. The dose distribution mapping was estimated to be near 1.5 cm accuracy based upon a phantom study. The body model must most closely match at the edges of the mesh to ensure that high dose gradients are not projected onto the wrong location. Otherwise 2 to 3 cm level errors in positioning in the mesh do not appear to cause larger than 5% dose errors. The cumulative dose images showed regions of overlap laterally and regions of low intensity in the posterior arms. Conclusions: The proposed modeling and animation can be used to visualize and analyze the accumulated dose in TSET via display of the summed dose/Cherenkov images on a single body surface.

Cherenkov imaging for total skin electron therapy (TSET).

BACKGROUND: Total skin electron therapy (TSET) utilizes high-energy electrons to treat malignancies on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interactions between the high-energy electron beam and tissue. METHODS AND MATERIALS: With a time-gated intensified camera system, the Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real time. Fifteen patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. Each patient was monitored during TSET via in vivo detectors (IVD) in nine locations. For accurate Cherenkov imaging, a comparison between IVD and Cherenkov profiles was conducted using a polyvinyl chloride board to establish the perspective corrections. RESULTS AND DISCUSSION: With proper corrections developed in this study including the perspective and inverse square corrections, the Cherenkov imaging provided two-dimensional maps proportional to dose and projected on patient skin. The results of ratio between chest and umbilicus points were in good agreement with in vivo point dose measurements, with a standard deviation of 2.4% compared to OSLD measurements. CONCLUSIONS: Cherenkov imaging is a viable tool for validating patient-specific dose distributions during TSET.

Characterization of the Megavoltage Cone-Beam Computed Tomography (MV-CBCT) System on HalcyonTM for IGRT: Image Quality Benchmark, Clinical Performance, and Organ Doses.

Purpose: The Varian Halcyon includes an ultrafast 6 MV flattening filter free (FFF) cone-beam computed tomography (MV-CBCT). Although a kV-CBCT add-on is available, in the basic configuration MV is used for image guided radiotherapy (IGRT). We characterized the MV-CBCT imager in terms of reproducibility, linearity, field of view (FOV) dependence, detectability of soft-tissue, and the effect of metal implants. The performance of the MV-CBCT in the clinic, including resulting dose to organs, is also discussed herein. Methods: A Gammex phantom was scanned using a Halcyon MV-CBCT and a 120 kVp Siemens Definition Edge CT. Mean and standard deviation of Hounsfield Units (HUs) for different electron density relative to water ( ρ e W ) inserts were extracted. Doses to clinical patients due to MV-CBCT are calculated within Eclipse during treatment planning. Results: A stable and near-linear HU-to- ρ e W curve was obtained using the MV-CBCT. As the scan length increased from 10 to 28cm, the linearity of curve improved while the mean HUs decreased by 30%. All soft tissue inserts in the Gammex phantom were distinguishable. A crescent artifact affected HU measurements by up to 40 HUs. Soft-tissue contrast was sufficient for clinical online image-guidance in the low dose (5 MU) mode. Mean doses per fraction to organs-at-risk (OARs) were as high as 6 cGy for head and neck, 5 cGy for breast, and 4 cGy for pelvis patients. Metal rods did not affect HU values or introduce noticeable artifacts. Conclusions: Halcyon's MV-CBCT has sufficient soft tissue contrast for IGRT and lacks metal-induced artifacts. Even though the absolute HU values vary with phantom size and scanning length, the HU-to- ρ e W conversions are linear and stable day-to-day. In clinical cases, highest tissue doses from MV-CBCT ranged from 2-7cGy per fraction for various treatment sites, which could be significant for some organs at risk. Dose to out-of-treatment-field organs can be limited by reducing the scan length definition during planning and using the low dose mode. The high quality imaging mode did not provide material advantages over the low dose mode. Adequate IGRT was successfully delivered to multiple tumor sites using MV-CBCT.

Spine SBRT With Halcyon™: Plan Quality, Modulation Complexity, Delivery Accuracy, and Speed.

Purpose: Spine SBRT requires treatment plans with steep dose gradients and tight limits to the cord maximal dose. A new dual-layer staggered 1-cm MLC in Halcyon™ treatment platform has improved leakage, speed, and DLG compared to 120-Millennium (0.5-cm) and High-Definition (0.25-cm) MLCs in the TrueBeam platform. Halcyon™ 2.0 with SX2 MLC modulates fluence with the upper and lower MLCs, while in Halcyon™ 1.0 with SX1 only the lower MLC modulates the fluence and the upper MLC functions as a back-up jaw. We investigated the effects of four MLC designs on plan quality for spine SBRT treatments. Methods: 15 patients previously treated at our institution were re-planned according to the NRG-BR-002 guidelines with a prescription of 3,000 cGy in 3 fractions, 6xFFF, 800 MU/min, and 3-arc VMAT technique. Planning objectives were adjusted manually by an experienced planner to generate optimal plans and kept the same for different MLCs within the same platform. Results: All treatment plans were able to achieve adequate target coverage while meeting NRG-BR002 dosimetric constraints. Planning parameters were evaluated including: conformity index, homogeneity index, gradient measure, and global point dose maximum. Delivery accuracy, modulation complexity, and delivery time were also analyzed for all MLCs. Conclusion: The Halcyon™ dual-layer MLC can generate comparable and clinically equivalent spine SBRT plans to TrueBeam plans with less rapid dose fall-off and lower conformity. MLC width leaf can impact maximum dose to organs at risk and plan quality, but does not cause limitations in achieving acceptable plans for spine SBRT treatments.

A hybrid phantom Monte Carlo-based method for historical reconstruction of organ doses in patients treated with cobalt-60 for Hodgkin's lymphoma.

Historical radiotherapy treatment plans lack 3D images sets required for estimating mean organ doses to patients. Alternatively, Monte Carlo-based models of radiotherapy devices coupled with whole-body computational phantoms can permit estimates of historical in-field and out-of-field organ doses as needed for studies associating radiation exposure and late tissue toxicities. In recreating historical patient treatments with 60Co based systems, the major components to be modeled include the source capsule, surrounding shielding layers, collimators (both fixed and adjustable), and trimmers as needed to vary field size. In this study, a computational model and experimental validation of the Theratron T-1000 are presented. Model validation is based upon in-field commissioning data collected at the University of Florida, published out-of-field data from the British Journal of Radiology (BJR) Supplement 25, and out-of-field measurements performed at the University of Wisconsin's Accredited Dosimetry Calibration Laboratory (UWADCL). The computational model of the Theratron T-1000 agrees with central axis percentage depth dose data to within 2% for 6 × 6 to 30 × 30 cm2 fields. Out-of-field doses were found to vary between 0.6% to 2.4% of central axis dose at 10 cm from field edge and 0.42% to 0.97% of central axis dose at 20 cm from the field edge, all at 5 cm depth. Absolute and relative differences between computed and measured out-of-field doses varied between ±2.5% and ±100%, respectively, at distances up to 60 cm from the central axis. The source-term model was subsequently combined with patient-morphometry matched computational hybrid phantoms as a method for estimating in-field and out-of-field organ doses for patients treated for Hodgkin's Lymphoma. By changing field size and position, and adding patient-specific field shaping blocks, more complex historical treatment set-ups can be to recreated, particularly those for which 2D or 3D image sets are unavailable.

Combined Mössbauer Spectral and Density Functional Study of an Eight-Coordinate Iron(II) Complex.

The iron-57 Mössbauer spectra of the eight-coordinate complex, [Fe(L(N4))2](BF4)2, where L(N4) is the tetradentate N(1)(E),N(2)(E)-bis[(1-methyl-1H-imidazol-2-yl)methylene]-1,2-benzenediimine ligand, have been measured between 4.2 and 295 K and fit with a quadrupole doublet. The fit at 4.2 K yields an isomer shift, δ(Fe), of 1.260(1) mm/s and a quadrupole splitting, ΔE(Q), of 3.854(2) mm/s, values that are typical of a high-spin iron(II) complex. The temperature dependence of the isomer shift yields a Mössbauer temperature, Θ(M), of 319(27) K and the temperature dependence of the logarithm of the Mössbauer spectral absorption area yields a Debye temperature, Θ(D), of 131(6) K, values that are indicative of high-spin iron(II). Nonrelativistic single point density functional calculations with the B3LYP functional, the full 6-311++G(d,p) basis set, and the known X-ray structures for [Mn(L(N4))2](2+), [Mn(L(N4))2](ClO4)2, 1, [Fe(L(N4))2](2+), and [Fe(L(N4))2](BF4)2, 2, yield small electric field gradients for the manganese(II) complexes and electric field gradients and s-electron densities at the iron-57 nuclide that are in good to excellent agreement with the Mössbauer spectral parameters. The structure of 2 with a distorted square-antiprism C1 iron(II) coordination symmetry exhibits four different Fe-N(imid) bonds to the imidazole nitrogens with an average bond distance of 2.253(2) Å and four different Fe-N(imine) bonds to the benzenediimine nitrogens, with an average bond distance of 2.432(2) Å; this large difference yields the large observed ΔE(Q). An optimization of the [Fe(L(N4))2](2+) structure leads to a highly symmetric eight-coordination environment with S4 symmetry and four equivalent Fe-N(imid) bond distances of 2.301(2) Å and four equivalent Fe-N(imine) bond distances of 2.487(2) Å. In contrast, an optimization of the [Mn(LN4)2](2+) structure leads to an eight-coordination manganese(II) environment with D(2d) symmetry and four equivalent Mn-N(imid) bond distances of 2.350(3) Å and four equivalent Mn-N(imine) bond distances of 2.565(3) Å.

Excitable actin dynamics in lamellipodial protrusion and retraction.

Many animal cells initiate crawling by protruding lamellipodia, consisting of a dense network of actin filaments, at their leading edge. We imaged XTC cells that exhibit flat lamellipodia on poly-L-lysine-coated coverslips. Using active contours, we tracked the leading edge and measured the total amount of F-actin by summing the pixel intensities within a 5-µm band. We observed protrusion and retraction with period 130-200 s and local wavelike features. Positive (negative) velocities correlated with minimum (maximum) integrated actin concentration. Approximately constant retrograde flow indicated that protrusions and retractions were driven by fluctuations of the actin polymerization rate. We present a model of these actin dynamics as an excitable system in which a diffusive, autocatalytic activator causes actin polymerization; F-actin accumulation in turn inhibits further activator accumulation. Simulations of the model reproduced the pattern of actin polymerization seen in experiments. To explore the model's assumption of an autocatalytic activation mechanism, we imaged cells expressing markers for both F-actin and the p21 subunit of the Arp2/3 complex. We found that integrated Arp2/3-complex concentrations spike several seconds before spikes of F-actin concentration. This suggests that the Arp2/3 complex participates in an activation mechanism that includes additional diffuse components. Response of cells to stimulation by fetal calf serum could be reproduced by the model, further supporting the proposed dynamical picture.