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Supplementary Data from Orthovoltage X-Rays Exhibit Increased Efficacy Compared with γ-Rays in Preclinical Irradiation

Radionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. Amidst concerns of radiological terrorism, there are institutional initiatives to replace radionuclide sources with lower energy X-ray sources. As researchers transition, questions remain regarding whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays because different energies may induce divergent biological effects. We therefore sought to compare the effects of orthovoltage X-rays with 1-mm Cu or Thoraeus filtration and 137Cs γ-rays using mouse models of acute radiation syndrome. Following whole-body irradiation, 30-day overall survival was assessed, and the lethal dose to provoke 50% mortality within 30-days (LD50) was calculated by logistic regression. LD50 doses were 6.7 Gy, 7.4 Gy, and 8.1 Gy with 1-mm Cu-filtered X-rays, Thoraeus-filtered X-rays, and 137Cs γ-rays, respectively. Comparison of bone marrow, spleen, and intestinal tissue from mice irradiated with equivalent doses indicated that injury was most severe with 1-mm Cu-filtered X-rays, which resulted in the greatest reduction in bone marrow cellularity, hematopoietic stem and progenitor populations, intestinal crypts, and OLFM4+ intestinal stem cells. Thoraeus-filtered X-rays provoked an intermediate phenotype, with 137Cs showing the least damage. This study reveals a dichotomy between physical dose and biological effect as researchers transition to orthovoltage X-rays. With decreasing energy, there is increasing hematopoietic and intestinal injury, necessitating dose reduction to achieve comparable biological effects.Significance:Understanding the significance of physical dose delivered using energetically different methods of radiation treatment will aid the transition from radionuclide γ-irradiators to orthovoltage X-irradiators.

Radionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. Amidst concerns of radiological terrorism, there are institutional initiatives to replace radionuclide sources with lower energy X-ray sources. As researchers transition, questions remain regarding whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays because different energies may induce divergent biological effects. We therefore sought to compare the effects of orthovoltage X-rays with 1-mm Cu or Thoraeus filtration and 137Cs γ-rays using mouse models of acute radiation syndrome. Following whole-body irradiation, 30-day overall survival was assessed, and the lethal dose to provoke 50% mortality within 30-days (LD50) was calculated by logistic regression. LD50 doses were 6.7 Gy, 7.4 Gy, and 8.1 Gy with 1-mm Cu-filtered X-rays, Thoraeus-filtered X-rays, and 137Cs γ-rays, respectively. Comparison of bone marrow, spleen, and intestinal tissue from mice irradiated with equivalent doses indicated that injury was most severe with 1-mm Cu-filtered X-rays, which resulted in the greatest reduction in bone marrow cellularity, hematopoietic stem and progenitor populations, intestinal crypts, and OLFM4+ intestinal stem cells. Thoraeus-filtered X-rays provoked an intermediate phenotype, with 137Cs showing the least damage. This study reveals a dichotomy between physical dose and biological effect as researchers transition to orthovoltage X-rays. With decreasing energy, there is increasing hematopoietic and intestinal injury, necessitating dose reduction to achieve comparable biological effects. Significance: Understanding the significance of physical dose delivered using energetically different methods of radiation treatment will aid the transition from radionuclide γ-irradiators to orthovoltage X-irradiators.

PURPOSE Liver-directed therapy after transarterial chemoembolization (TACE) can lead to improvement in survival for selected patients with unresectable hepatocellular carcinoma (HCC). However, there is uncertainty in the appropriate application and modality of therapy in current clinical practice guidelines. The aim of this study was to develop a proof-of-concept, machine learning (ML) model for treatment recommendation in patients previously treated with TACE and select patients who might benefit from additional treatment with combination stereotactic body radiotherapy (SBRT) or radiofrequency ablation (RFA). METHODS This retrospective observational study was based on data from an urban, academic hospital system selecting for patients diagnosed with stage I-III HCC from January 1, 2008, to December 31, 2018, treated with TACE, followed by adjuvant RFA, SBRT, or no additional liver-directed modality. A feedforward, ML ensemble model provided a treatment recommendation on the basis of pairwise assessments evaluating each potential treatment option and estimated benefit in survival. RESULTS Two hundred thirty-seven patients met inclusion criteria, of whom 54 (23%) and 49 (21%) received combination of TACE and SBRT or TACE and RFA, respectively. The ML model suggested a different consolidative modality in 32.7% of cases among patients who had previously received combination treatment. Patients treated in concordance with model recommendations had significant improvement in progression-free survival (hazard ratio 0.5; P = .007). The most important features for model prediction were cause of cirrhosis, stage of disease, and albumin-bilirubin grade (a measure of liver function). CONCLUSION In this proof-of-concept study, an ensemble ML model was able to provide treatment recommendations for HCC who had undergone prior TACE. Additional treatment in line with model recommendations was associated with significant improvement in progression-free survival, suggesting a potential benefit for ML-guided medical decision making.

Highlights • DCA in most cases is superior to VMAT for multi metastases single isocenter SRS. • Normal brain V12Gy was significantly reduced with DCA, predicting for lower S-NEC. • Maximum doses to critical organs-at-risk were significantly lower with DCA. • Conformity was comparable between VMAT and DCA., Background and purpose Whole brain radiation therapy use has decreased in favor of stereotactic radiosurgery (SRS) for the treatment of multiple brain metastases due to reduced neurotoxicity. Here we compare two single isocenter radiosurgery planning techniques, volumetric modulated arc therapy (VMAT) and dynamic conformal arcs (DCA) in terms of their dosimetric and delivery performance. Materials and methods Sixteen patients with 2– 18 brain metastases (total 103; median 4) previously treated with single fraction SRS were replanned for multiple lesion single isocenter treatments using VMAT and DCA using different treatment planning systems for each and three different plan geometries for DCA. Plans were evaluated using the Paddick conformity index, normal tissue V12Gy, the probability for symptomatic brain necrosis (S-NEC), maximum organ-at-risk (OAR) point doses, and total number of monitor units (MU). Results Conformity was not significantly different between VMAT and DCA plans. VMAT plans showed a trend towards higher MU with a median difference between 18% and 24% (p ≤ 0.09). Median V12Gy differences were 7.0 cm3–8.6 cm3 favoring DCA plans (p

Megavoltage computed tomography (MVCT) image quality metrics were evaluated on an Accuray Radixact unit to recommend scan settings for the implementation of a consistent adaptive radiotherapy program. Megavoltage computed tomography image quality was evaluated and compared to a kilovoltage CT (kVCT) simulator using a commercial cone beam computed tomography image quality phantom. Megavoltage computed tomographies were acquired on the Accuray Radixact using fine, normal, and coarse pitches, with all available reconstruction slice thicknesses, each of which were reconstructed using standard and iterative reconstruction (IR). Image quality metrics (IQM) were evaluated using DoseLab: automatically and manually calculated spatial resolution, subject contrast, and contrast‐to‐noise ratio (CNR). Scanning time was 15.6 s/cm for fine, 8.1 s/cm for normal, and 5.6 s/cm for coarse pitch. Automatically evaluated spatial resolutions ranged from 0.39, 0.41, to 0.42 lp/mm for standard reconstruction and from 0.24, 0.21, to 0.18 lp/mm for soft‐tissue IR, respectively, with general IR yielding values in between these. Spatial resolution for kVCT was measured to be at least 0.42 lp/mm. Contrast was consistent across MVCT settings with 8.1 ± 0.2%, while kVCT contrast was 10.27 ± 0.05%. CNR was calculated to be 3.3 ± 0.4 for standard reconstruction, 7.4 ± 0.4 for general IR, and 12.0 ± 1.9 for soft‐tissue IR. It was found that increasing reconstruction slice thickness for a given pitch does not improve IQMs. Based on the consistency of contrast metrics across pitch values and the only slightly reduced spatial resolution using normal compared to fine pitch, we recommend the use of normal pitch with 2 mm slice thickness to maximize image quality for ART while limiting scanning time. Only for sites for which improved CNR is required and reduced spatial resolution is acceptable, soft‐tissue IR is recommended.

To quantify the clinical performance of a machine learning (ML) algorithm for organ-at-risk (OAR) dose prediction for lung stereotactic body radiation therapy (SBRT) and estimate the treatment planning benefit from having upfront access to these dose predictions.ML models were trained using multi-center data consisting of 209 patients previously treated with lung SBRT. Two prescription levels were investigated, 50 Gy in five fractions and 54 Gy in three fractions. Models were generated using a gradient-boosted regression tree algorithm using grid searching with fivefold cross-validation. Twenty patients not included in the training set were used to test OAR dose prediction performance, ten for each prescription. We also performed blinded re-planning based on OAR dose predictions but without access to clinically delivered plans. Differences between predicted and delivered doses were assessed by root-mean square deviation (RMSD), and statistical differences between predicted, delivered, and re-planned doses were evaluated with one-way analysis of variance (ANOVA) tests.ANOVA tests showed no significant differences between predicted, delivered, and replanned OAR doses (all p ≥ 0.36). The RMSD was 2.9, 3.9, 4.3, and 1.7Gy for max dose to the spinal cord, great vessels, heart, and trachea, respectively, for 50 Gy in five fractions. Average improvements of 1.0, 1.4, and 2.0 Gy were seen for spinal cord, esophagus, and trachea max doses in blinded replans compared to clinically delivered plans with 54 Gy in three fractions, and 1.8, 0.7, and 1.5 Gy, respectively, for the esophagus, heart and bronchus max doses with 50 Gy in five fractions. Target coverage was similar with an average PTV V100% of 94.7% for delivered plans compared to 97.3% for blinded re-plans for 50 Gy in five fractions, and respectively 98.4% versus 99.2% for 54 Gy in three fractions.This study validated ML-based OAR dose prediction for lung SBRT, showing potential for improved OAR dose sparing and more consistent plan quality using dose predictions for patient-specific planning guidance.

Nanoparticle-derived radiosensitization has been investigated by several groups using Monte Carlo simulations and biological modeling. In this work we replicated the physical simulation and biological modeling of previously published research for 50 nm gold nanoparticles irradiated with monoenergetic photons, various 250 kVp photon spectra, and spread-out Bragg peak (SOBP) protons. Monte Carlo simulations were performed using TOPAS and used condensed history Penelope low energy physics models for macroscopic dose deposition and interaction with the nanoparticle; simulation of the microscopic dose deposition from nanoparticle secondaries was performed using Geant4-DNA track structure physics. Biological modeling of survival fractions was performed using a local effect model-type approach for MDA-MB-231 breast cancer cells. Physical simulation results agreed extraordinarily well at all distances (1 nm to 10 μm from nanoparticle) for monoenergetic photons and SOBP protons in terms of dose per interaction, dose kernel ratio (often labeled dose enhancement factor), and secondary electron spectra. For 250 kVp photons the influence of the gold K-edge was investigated and found to appreciably affect the results. Calculated survival fractions similarly agreed well within one order of magnitude at macroscopic doses (i.e. without nanoparticle contribution) from 1 Gy to 10 Gy. Several 250 kVp spectra were tested to find one yielding closest agreement with previous results. This highlights the importance of a detailed description of the low energy (< 150 keV) component of photon spectra used for in-silico, as well as in-vitro, and in-vivo studies to ensure reproducibility of the experiments by the scientific community. Both, Monte Carlo simulations of physical interactions of the nanoparticle with photons and protons, as well as the biological modelling of cell survival curves agreed extraordinarily well with previously published data. Further investigation of the stochastic nature of nanoparticle radiosenstiziation is ongoing.

PurposeRadionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. There are institutional initiatives to replace radionuclide sources with lower-energy X-ray sources amidst concerns of radiological terrorism. As researchers transition, there are questions whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays, since different energy may cause different biological effects. We, therefore, sought to compare the effects of orthovoltage X-rays and 137Cs γ-rays using mouse models of acute radiation syndrome.Experimental Design137Cs γ-rays were compared with Orthovoltage X-rays, generated at 300 kVp, 10 mA with 1 mm Cu or Thoraeus filtration. We assessed 30-day overall survival following whole-body irradiation and calculated LD50 by logistic regression. Comparing equivalent doses delivered with different average energies (Ē), we assessed bone marrow, spleen, and intestinal histology and flow cytometry.ResultsThe LD50 doses are 6.7 Gy, 7.4 Gy and 8.1 Gy with 1 mm Cu filtered (Ē=120 keV), and Thoraeus filtered X-rays (Ē=160 keV), and 137Cs (E=662 keV), respectively. At constant dose, hematopoietic injury was most severe with 1 mm Cu filtered X-rays with the greatest reduction in bone marrow cellularity, stem and progenitor populations, and intestinal crypts and OLFM4+ intestinal stem cells. Thoraeus filtered X-rays provoked an intermediate phenotype, with 137Cs showing the least damage.ConclusionsOur study reveals a dichotomy between physical dose and biological effect relevant as researchers transition to orthovoltage X-rays. With decreasing energy, there is increasing hematopoietic and intestinal injury, necessitating dose-reduction to achieve comparable biological effects.Statement of Translational RelevanceRadiation is used in translational studies in fields ranging from hematopoiesis and stem cell biology to cancer radiotherapy, with 137Cs and 60Co radionuclide sources serving as the most common irradiators. Due to the threat of radiological terrorism using stolen radionuclides, there are institutional initiatives to replace these sources with orthovoltage X-ray irradiators. Yet, as shown in this study, the biological effects of radiation are highly dependent on radiation energy. Lower energy orthovoltage X-rays are absorbed differently than higher energy radionuclide γ-rays, provoking more severe hematopoietic, immunologic, and gastrointestinal radiation injury. Thus, an identical physical dose delivered with beams of differing energy does not produce the same biologic effect. As researchers transition between these sources, it is critical that we appreciate that radiation doses are not interchangeable between them. Understanding the significance of physical dose delivered using different methods will allow us to contextualize past results with future studies.

Disease recurrence and distant metastases (DM) are major concerns for oropharyngeal cancer (OPC) patients receiving definitive chemo-radiotherapy. Here, we investigated whether pre-treatment primary tumor positron emission tomography (PET) features could predict progression-free survival (PFS) or DM.Primary tumors were delineated on pre-treatment PET scans for patients treated between 2005 and 2018 using gradient-based segmentation. Radiomic image features were extracted, along with SUV metrics. Features with zero variance and strong correlation to tumor volume, stage, p16 status, age or smoking were excluded. A random forest model was used to identify features associated with PFS. Kaplan-Meier methods, Cox regression and logistic regression with receiver operating characteristics (ROC) and 5-fold cross-validated areas-under-the-curve (CV-AUCs) were used.A total of 114 patients were included. With median follow-up 40 months (range: 3-138 months), 14 patients had local recurrence, 21 had DM and 38 died. Two-year actuarial local control, distant control, PFS and overall survival was 89%, 84%, 70% and 84%, respectively. The wavelet_LHL_GLDZM_LILDE feature slightly improved PFS prediction compared to clinical features alone (CV-AUC 0.73 vs. 0.71). Age 65 years (HR = 2.64 (95%CI: 1.36-5.2), p = 0.004) and p16-negative disease (HR = 3.38 (95%CI: 1.72-6.66), p 0.001) were associated with poor PFS. A binary radiomic classifier strongly predicted DM with multivariable HR = 3.27 (95%CI: 1.15-9.31), p = 0.027, specifically for patients with p16-negative disease with 2-year DM-free survival 83% for low-risk vs. 38% for high-risk patients (p = 0.004).A radiomics signature strongly associated with DM risk could provide a tool for improved risk stratification, potentially adding adjuvant immunotherapy for high-risk patients.

Purpose To perform a three-dimensional (3D) concurrent isocentricity measurement of a clinical linear accelerator's (linac) using a single 3D dosimeter, PRESAGE. Methods A 3D dosimeter, PRESAGE, set up on the treatment couch of a Varian TrueBeam LINAC using the setup lasers, was irradiated under gantry angles of 0 ∘ , 50 ∘ , 160 ∘ , and 270 ∘ with the couch fixed at 0 ∘ and subsequently, under couch angles of 10 ∘ , 330 ∘ , 300 ∘ , and 265 ∘ with the gantry fixed at 270 ∘ . The 1 cm 2 (at 100 cm SAD) square fields were delivered at 6 MV with 800 MU/field. After irradiation, the dosimeter was scanned using a single-beam optical scanner and images were reconstructed with submillimeter resolution using filtered back-projection. Postprocessing was used to extract views parallel to the star-shot planes from which beam trajectories and the smallest circles enclosing these were drawn and extracted. These circles and information from the view orthogonal to both star-shots were used to represent the rotational centers as spheroids. The linac isocenter was defined by the distribution of midpoints between any, randomly selected, points lying inside the center spheroids defined by the table and gantry rotations; isocenter location and size were defined by the average midpoint and the distribution's semi-axes. Collimator rotations were not included in this study. Results Relative to the setup center defined by lasers, the table and gantry rotation center coordinates (lat., long., vert.) were measured in units of millimeters, to be (-0.24, 0.18, -0.52) and (0.10, 0.53, -0.52), respectively. Displacements from the setup center were 0.60 and 0.75 mm for the table and gantry centers, while the distance between them measured 0.49 mm. The linac's radiation isocenter was calculated to be at (-0.07, -0.17, 0.51) relative to the setup lasers and its size was found to be most easily described by a spheroid prolate in vertical direction with semi-axis lengths of 0.13 and 0.23 mm for the lateral-longitudinal and vertical directions, respectively. Conclusions This study demonstrates how to measure the location and sizes of rotational centers in 3D with one setup. The proposed method provides a more comprehensive view on the isocentricity of LINAC than the conventional two-dimensional film measurements. Additionally, a new definition of isocenter and its size was proposed.

Purpose/objective(s) To assess outcomes after definitive chemo-irradiation in HIV patients with anal cancer, and evaluate hemato-immunologic (HI) toxicity by dynamics of CD4+ cell counts and lymphocytes and their association with the dose received by active bone marrow (ABM). Materials/methods Patients treated for anal cancer with HIV infection at a single institution between 2007-2020 were identified. Characteristics were tabulated along with CD4+ cell counts and lymphocytes ranging from before treatment to length of follow-up. Dose to ABM was derived by overlaying the bone contours and 3D dose matrix on a pre-treatment PET/CT scan using deformable registration. Parts of the bone with greater than the mean PET standardized uptake value (SUV) in the bone were designated as ABM. Differences in HI parameters over time points were compared using Wilcoxon rank sum tests; risk of recurrence, overall survival (OS) and progression-free survival (PFS) were modeled using Kaplan-Meier methods. Results A total of 44 patients with anal cancer and HIV were identified, of which 7 had detectable HIV viral load pre-treatment. Radiation was most commonly 50.4-54 Gy via IMRT; 3 patients underwent RT alone. Chemotherapy was 5-fluorouracil+mitomycin (n = 27), Capecitabine+mitomycin (n = 11), or other (n = 3). With median follow-up 59 months (range: 5-164) there were 7 loco-regional recurrences, 2 distant metastases and 9 deaths. The 2- and 5-year OS for patients with stage I/II disease was 100% and 93.3% vs. 88.1% and 66.6% for stage III, the 2- and 5-year PFS were both 93.8% for stage I/II disease vs. 76.5% and 56.7% for stage III. Outcomes with 5FU vs. capecitabine were comparable with 2-year OS of 92.3% and 90.9% (P = 0.89) and PFS of 77.4% and 90.9% (P = 0.26). CD4 counts dropped from a pre-treatment median of 320 cells/ul to 101 at nadir (after ∼3 months), to 163 at 1 year and 214 at 2 years post IMRT. Lymphocyte counts changed from 1,600 per ul to 400 at nadir, to 1,200 and 1,400 at 1 and 2 years. Patients with distant or locoregional recurrence showed trends (P Conclusion Outcomes after definitive chemo-IMRT were promising with excellent OS and PFS in this vulnerable patient group, with no difference when substituting 5-fluorouracil for capecitabine. There was some acute HI toxicity with worse recovery in patients who experienced disease recurrence and strategies to better spare ABM including dose de-escalation are ongoing.

The simulation of proton Spread-Out Bragg Peaks (SOBPs) was implemented using the Geant4-based TOPAS Monte Carlo software. Dynamic proton energy switching was implemented using TOPAS time features, while beam weights were calculated using an empirical power law formalism with Bragg peaks spaced by 0.5 mm. To find power parameters yielding flat SOBPs we sampled power parameters for maximum kinetic energies of 50 MeV to 250 MeV and SOBP widths of 15% to 40% of the depth of the distal SOBP end. Simulations were run in a 50 cm cubic water phantom using a uniform squared proton beam. Depth dose was scored along the central axis in a binned cylinder with 1 cm diameter in 2.5 mm increments. Power parameters yielding a flat SOBPs were found to vary with, both energy and SOBP width and differed significantly from previously reported values based on simulations with MCNPX.

Purpose Cherenkov light emission has been shown to correlate with ionizing radiation dose delivery in solid tissue. An important clinical application of Cherenkov light is the real-time verification of radiation treatment delivery in vivo. To test the feasibility of treatment field verification, Cherenkov light images were acquired concurrent with radiation beam delivery to standard and anthropomorphic phantoms. Specifically, we tested two clinical treatment scenarios: (a) Observation of field overlaps or gaps in matched 3D fields and (b) Patient positioning shifts during intensity modulated radiation therapy (IMRT) field delivery. Further development of this technique would allow real-time detection of treatment delivery errors on the order of millimeters so that patient safety and treatment quality can be improved. Methods Cherenkov light emission was captured using a PI-MAX4 intensified charge coupled device (ICCD) system (Princeton Instruments). All radiation delivery was performed using a Varian Trilogy linear accelerator (linac) operated at 6 MV or 18 MV for photon and 6 MeV or 16 MeV for electron studies. Field matching studies were conducted with photon and electron beams at gantry angles of 0°, 15°, and 45°. For each modality and gantry angle, a total of three data sets were acquired. Overlap and gap distances of 0, 2, 5, and 10 mm were tested and delivered to solid phantom material of 30 × 30 × 5 cm3 . Phantom materials used were white plastic water and brown solid water. Tests were additionally performed on an anthropomorphic phantom with an irregular surface. Positioning shift studies were performed using IMRT fields delivered to a thoracic anthropomorphic phantom. For thoracic phantom measurements, the camera was placed laterally to observe the entire right side of the phantom. Fields were delivered with known translational patient positioning shifts in four directions. Changes in the Cherenkov fluence were evaluated through the generation of difference maps from unshifted Cherenkov images. All images were evaluated using ImageJ, Python, and MATLAB software packages. Results For matched fields, Cherenkov images were able to quantitate matched field separations with discrepancies between 2 and 4 mm, depending on gantry angle and beam energy or modality. For all photon and electron beams delivered at a gantry angle of 0°, image analysis indicated average discrepancies of less than 2 mm for all field gaps and overlaps, with 83% of matched fields exhibiting discrepancies less than 1 mm. Beams delivered obliquely to the phantom surface exhibited average discrepancies as high as 4 mm for electron beams delivered at large oblique angles. Finally, for IMRT field delivery, vertical and lateral patient positioning shifts of 2 mm were detected in some cases, indicating the potential detectability threshold of using this technique alone. Conclusions Our study indicates that Cherenkov imaging can be used to support and bolster current treatment delivery verification techniques, improving our ability to recognize and rectify millimeter-scale delivery and positioning errors.

Purpose The precise dosimetric and geometric characteristics of small animal irradiators are essential to achieving reproducible dose delivery, especially in cases where image-guidance is utilized. Currently, radiochromic film is the established measurement tool used to evaluate beam characteristics for these systems. However, only 2D information can be acquired with film. This study characterized both the dosimetric and geometric properties of the small animal research radiation platform (SARRP, Xstrahl) for commissioning purposes using a 3D radiochromic dosimetry system with a submillimeter resolution optical computed tomography (OCT) scanner. Methods Like a modern clinical linear accelerator, the SARRP features both a beam delivery system and a cone beam computed tomography (CBCT) imaging system. Dosimetric and geometric characteristics of the SARRP were studied using EBT3 radiochromic film and 3D PRESAGE dosimeters. Dosimetric measurements included percent depth dose (PDD) curves and beam profiles. For geometric evaluation, the isocenter sizes of the treatment stage and gantry rotations as well as their coincidence were measured using star shot patterns. A commercial Epson Expression 11000XL flatbed scanner was used for readout of irradiated EBT3 films at 300 dpi resolution. Each irradiated PRESAGE dosimeter was scanned using a submillimeter resolution single laser beam OCT scanner. Acquired data were reconstructed with a resolution of 0.3 mm/pixel. Results PDD data measured from films and 3D dosimeters agree to within ±3% for depths up to 5 cm, for both 3 × 3 and 10 × 10 mm2 fixed collimation. Profiles were analyzed at 10, 20, and 30 mm depth for 3 × 3 mm2 and 10 × 10 mm2 fields. The FWHM measurements for both dosimeters agreed to within 0.01 mm, and the penumbras agreed to within 0.1 mm for 3 × 3 mm2 and 0.5 mm for 10 × 10 mm2 . Gantry and treatment stage isocenter sizes were determined to be 0.21 and 0.43 mm using EBT3 film, and 1.72 and 0.75 mm using PRESAGE dosimeters. Absolute isocenter shifts, evaluated with 3D phantoms, were 0.80 mm for the gantry rotation isocenter (treatment isocenter) with respect to the laser-defined setup isocenter, and 0.71 mm for the gantry rotation isocenter relative to treatment stage rotation isocenter (CBCT isocenter). The difference between CBCT isocenter and laser-defined setup isocenter was 0.68 mm. Conclusions This study demonstrated that 3D PRESAGE dosimeters can be used for verification of precise targeting for the SARRP. This 3D dosimetry system can be utilized to obtain information on both geometric and dosimetric properties, as well as acquire beam data parameters for the purpose of commissioning image-guided small animal irradiator systems.

Objectives: We conducted the first systematic literature review and analysis of psychiatric manifestations in Niemann-Pick disease type C (NPC) to describe: (1) time of occurrence of psychiatric ma...

We assessed the dosimetric safety of a potential diapeutic Gadolinium-based contrast agent for diagnostic MR imaging and MR-guided radiotherapy by calculating depth-dependent reactions rates in a spread-out Bragg peak (SOBP) in water. Energy-dependent cross-sections for inelastic proton reactions on Gadolinium were folded with proton energy spectra at depth. Particle transport, dose, and phase space scoring was performed using Geant4-based TOPAS Monte Carlo software. The isotopic Terbium yield at depth was calculated to be between 103 to 105 atoms/mmolnatGd per Gray SOBP dose in a 2.4 cm3 volume. At currently achievable Gadolinium concentrations of 0.2 μmol/cm3 this yields approximately 26 atoms/(cm3 GySOBP), corresponding to less than 1 Bq activity. Additional dose from evaporation neutrons and subsequent capture gammas is on the order of 1 μSv/GySOBP. Thus, use of this long-lived contrast agent is dosimetrically safe at current concentrations and induced radioactivity is negligible.

Background Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. Methods This retrospective, observational chart review included patients with NP-C from five expert NP-C centers. Patient disability scores were recorded using three published NP-C disability scales, and a unified disability scale was developed to allow comparison of data from each scale. Disease progression was represented by scores on the unified NP-C disability scale. Patients were stratified as infantile (

Klassiker kann man nicht besser machen, behaupten viele. Die Entwickler der Literaturverwaltungssoftware Endnote beweisen das Gegenteil. Durch Implementierung von Onlinefunktionen ist Endnote zu einem Allroundtalent fur Literatursuche und Literaturverwaltung geworden.

Objective There is a need for fast, minimally invasive sutureless replacement of mitral valves. Methods Unchanged FDA-approved biological valve prostheses were sutured to Nitinol attachment rings (Endosmart, Stutensee, Germany) that were covered with textile (devices). The lower flange of the device was stretched in ice water and maintained in a stretched position with stretching sutures. In 9 acute pig experiments through a limited left thoracotomy, a single suture was placed around the mitral annulus, the device was positioned, the annular suture tied, the stretching sutures retracted, and the device activated by warm saline. Position of the device, heart and valve function, coronary arteries, left ventricular outflow tract, and surrounding structures were observed with transoesophageal echocardiography, left ventricular and coronary angiograms, and pathologic examination at autopsy. Results The devices could be easily navigated to the mitral valve annulus and actuated within seconds. Three devices were placed with warm blood in the operative field and were tilted or dislocated at autopsy. In the other 6 devices, transesophageal echocardiography and left ventricular and coronary angiography demonstrated normal prosthetic valve and heart function, without valvular or para-device leakage, and with normal aortic valve and coronary arteries. At autopsy in these 6 cases, the devices were strongly fixed at the anatomic mitral valve annulus, without abnormalities of the device, heart valve prosthesis, left ventricular outflow tract, or aortic valve ostium. Conclusions Nitinol attachments rings combined with unchanged biological valve prostheses can make fast and strong sutureless replacement of the mitral valve feasible in acute pig experiments. Applicators that constrain and release the device mechanically need to be developed.