A Systematic Analysis of Errors in Target Localization and Treatment Delivery for Stereotactic Radiosurgery Using 2D/3D Image Registration

PURPOSE: To determine the localization uncertainties associated with 2-dimensional/3-dimensional image registration in comparison to 3-dimensional/3-dimensional image registration in 6 dimensions on a Varian Edge Linac under various imaging conditions. METHODS: The systematic errors in 6 dimensions were assessed by comparing automatic 2-dimensional/3-dimensional (kV/MV vs computed tomography) with 3-dimensional/3-dimensional (cone beam computed tomography vs computed tomography) image registrations under various conditions encountered in clinical applications. The 2-dimensional/3-dimensional image registration uncertainties for 88 patients with different treatment sites including intracranial and extracranial were evaluated by statistically analyzing 2-dimensional/3-dimensional pretreatment verification shifts of 192 fractions in stereotactic radiosurgery and stereotactic body radiotherapy. RESULTS: The systematic errors of 2-dimensional/3-dimensional image registration using kV-kV, MV-kV, and MV-MV image pairs were within 0.3 mm and 0.3° for the translational and rotational directions within a 95% confidence interval. No significant difference ( P \u3e .05) in target localization was observed with various computed tomography slice thicknesses (0.8, 1, 2, and 3 mm). Two-dimensional/3-dimensional registration had the best accuracy when pattern intensity and content filter were used. For intracranial sites, means ± standard deviations of translational errors were -0.20 ± 0.70 mm, 0.04 ± 0.50 mm, and 0.10 ± 0.40 mm for the longitudinal, lateral, and vertical directions, respectively. For extracranial sites, means ± standard deviations of translational errors were -0.04 ± 1.00 mm, 0.2 ± 1.0 mm, and 0.1 ± 1.0 mm for the longitudinal, lateral, and vertical directions, respectively. Two-dimensional/3-dimensional image registration for intracranial and extracranial sites had comparable systematic errors that were approximately 0.2 mm in the translational direction and 0.08° in the rotational direction. CONCLUSION: The standard 2-dimensional/3-dimensional image registration tool available on the Varian Edge radiosurgery device, a state-of-the-art system, is helpful for robust and accurate target positioning for image-guided stereotactic radiosurgery

Targeting Accuracy of Image-Guided Radiosurgery for Intracranial Lesions: A Comparison Across Multiple Linear Accelerator Platforms

PURPOSE: To evaluate the overall positioning accuracy of image-guided intracranial radiosurgery across multiple linear accelerator platforms. METHODS: A computed tomography scan with a slice thickness of 1.0 mm was acquired of an anthropomorphic head phantom in a BrainLAB U-frame mask. The phantom was embedded with three 5-mm diameter tungsten ball bearings, simulating a central, a left, and an anterior cranial lesion. The ball bearings were positioned to radiation isocenter under ExacTrac X-ray or cone-beam computed tomography image guidance on 3 Linacs: (1) ExacTrac X-ray localization on a Novalis Tx; (2) cone-beam computed tomography localization on the Novalis Tx; (3) cone-beam computed tomography localization on a TrueBeam; and (4) cone-beam computed tomography localization on an Edge. Each ball bearing was positioned 5 times to the radiation isocenter with different initial setup error following the 4 image guidance procedures on the 3 Linacs, and the mean (µ) and one standard deviation (σ) of the residual error were compared. RESULTS: Averaged overall 3 ball bearing locations, the vector length of the residual setup error in mm (µ ± σ) was 0.6 ± 0.2, 1.0 ± 0.5, 0.2 ± 0.1, and 0.3 ± 0.1 on ExacTrac X-ray localization on a Novalis Tx, cone-beam computed tomography localization on the Novalis Tx, cone-beam computed tomography localization on a TrueBeam, and cone-beam computed tomography localization on an Edge, with their range in mm being 0.4 to 1.1, 0.4 to 1.9, 0.1 to 0.5, and 0.2 to 0.6, respectively. The congruence between imaging and radiation isocenters in mm was 0.6 ± 0.1, 0.7 ± 0.1, 0.3 ± 0.1, and 0.2 ± 0.1, for the 4 systems, respectively. CONCLUSIONS: Targeting accuracy comparable to frame-based stereotactic radiosurgery can be achieved with image-guided intracranial stereotactic radiosurgery treatment

Highly pressurized partially miscible liquid-liquid flow in a micro-T-junction. I. Experimental observations

© 2017 American Physical Society, https://doi.org/10.1103/PhysRevE.95.043110This is the first part of a two-part study on a partially miscible liquid-liquid flow (liquid carbon dioxide and deionized water) which is highly pressurized and confined in a microfluidic T-junction. Our main focuses are to understand the flow regimes as a result of varying flow conditions and investigate the characteristics of drop flow distinct from coflow, with a capillary number, Ca-c, that is calculated based on the continuous liquid, ranging from 10(-3) to 10(-2) (10(-4) for coflow). Here in part I, we present our experimental observation of drop formation cycle by tracking drop length, spacing, frequency, and after-generation speed using high-speed video and image analysis. The drop flow is chronologically composed of a stagnating and filling stage, an elongating and squeezing stage, and a truncating stage. The common "necking" time during the elongating and squeezing stage (with Ca-c similar to 10(-3)) for the truncation of the dispersed liquid stream is extended, and the truncation point is subsequently shifted downstream from the T-junction corner. This temporal postponement effect modifies the scaling function reported in the literature for droplet formation with two immiscible fluids. Our experimental measurements also demonstrate the drop speed immediately following their generations can be approximated by the mean velocity from averaging the total flow rate over the channel cross section. Further justifications of the quantitative analysis by considering the mass transfer at the interface of the two partially miscible fluids are provided in part II.University of TorontoUniversity of Waterlo

Highly pressurized partially miscible liquid-liquid flow in a micro-T-junction. II. Theoretical justifications and modeling

© 2017 American Physical Society, https://doi.org/10.1103/PhysRevE.95.043111This is the second part of a two-part study on a partially miscible liquid-liquid flow ( carbon dioxide and deionized water) that is highly pressurized and confined in a microfluidic T-junction. In the first part of this study, we reported experimental observations of the development of flow regimes under various flow conditions and the quantitative characteristics of the drop flow including the drop length, after-generation drop speed, and periodic spacing development between an emerging drop and the newly produced one. Here in part II we provide theoretical justifications to our quantitative studies on the drop flow by considering ( 1) CO2 hydration at the interface with water, ( 2) the diffusion-controlled dissolution of CO2 molecules in water, and ( 3) the diffusion distance of the dissolved CO2 molecules. Our analyses show that ( 1) the CO2 hydration at the interface is overall negligible, ( 2) a saturation scenario of the dissolved CO2 molecules in the vicinity of the interface will not be reached within the contact time between the two fluids, and ( 3) molecular diffusion does play a role in transferring the dissolved molecules, but the diffusion distance is very limited compared with the channel geometry. In addition, mathematical models for the drop length and the drop spacing are developed based on the observations in part I, and their predictions are compared to our experimental results.China Scholarship Council: 20120491016

Hydrodynamic shrinkage of liquid CO2 Taylor drops in a straight microchannel

This is an author-created, un-copyedited version of an article accepted for publication in Journal of Physics: Condensed Matter. The publisher is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.1088/1361-648X/aaa81cHydrodynamic shrinkage of liquid CO2 drops in water under a Taylor flow regime is studied using a straight microchannel (length/width similar to 100). A general form of a mathematical model of the solvent-side mass transfer coefficient (k(s)) is developed first. Based on formulations of the surface area (A) and the volume (V) of a general Taylor drop in a rectangular microchannel, a specific form of k(s) is derived. Drop length and speed are experimentally measured at three specified positions of the straight channel, namely, immediately after drop generation (position 1), the midpoint of the channel (position 2) and the end of the channel (position 3). The reductions of drop length (L-x, x = 1, 2, 3) from position 1 to 2 and down to 3 are used to quantify the drop shrinkage. Using the specific model, k(s) is calculated mainly based on Lx and drop flowing time (t). Results show that smaller CO2 drops produced by lower flow rate ratios (Q(LCO2)/Q(H2O)) are generally characterized by higher (nearly three times) ks and Sherwood numbers than those produced by higher Q(LCO2)/Q(H2O), which is essentially attributed to the larger effective portion of the smaller drop contributing in the mass transfer under same levels of the flowing time and the surface-to-volume ratio (similar to 10(4) m(-1)) of all drops. Based on calculated pressure drops of the segmented flow in microchannel, the Peng-Robinson equation of state and initial pressures of drops at the T-junction in experiments, overall pressure drop (Delta P-t) in the straight channel as well as the resulted drop volume change are quantified. Delta P-t from position 1-3 is by average 3.175 kPa with a similar to 1.6% standard error, which only leads to relative drop volume changes of 0.3 parts per thousand to 0.52 parts per thousand

Gold Nanoparticle (AuNP) as a Therapeutic Enhancer for Radio – And Immunotherapy Therapy Combination in Triple Negative Breast Cancer

Purpose/Objective(s): Triple negative breast cancer (TNBC) is the most aggressive breast cancer (BC) form, with a high metastases rate and a very low survival. The aggressiveness of TNBC coupled with a significant toxicity and suboptimal chemotherapy outcomes underscores the urgency for new TNBC treatments. In recent years, immunotherapy has emerged as a promising option. In particular, immune checkpoint blockers (ICB) targeting PD-L1/PD1 inhibitory T cell check point pathway showed clinical responses and have been explored for TNBC. Unfortunately, the response rates to standalone ICB therapy are low (15-20%), indicating the presence of inhibitory immune mechanisms. Radiation therapy (RT) has been widely used in BC therapies. In addition to antitumor (antiproliferative) effects, RT has been evidenced to stimulate immune tumor rejection through immunomodulation of the tumor microenvironment (TME) that has been shown to enhance the response to immunotherapy in mouse BC models. Antitumor RT effects, including TME immunomodulation, can be improved by using radiosensitizers, such as gold nanoparticles (AuNPs). We hypothesize that AuNP potentiates RT-induced immunomodulatory effects, leading to a more efficient response to ICB in TNBC. To test this hypothesis, we used AuNP as an enhancer of RT-induced immunological TME changes, to improve ICB therapy response in murine orthotopic syngeneic 4T1Luc TNBC model. Materials/Methods: Female Balb/c mice bearing 4T1Luc tumors received intratumoral injections of 14 nm AuNPs. After 24h mice were irradiated with fractionated regimen of 3 × 6 Gy dose using 225 kV photons. After the 3rd RT dose, mice received 3 doses of anti-PD-L1 antibody that were 4 days apart. Therapeutic efficiency was determined by assessing the tumor growth and animal survival. Tumor tissue immunohistochemistry determined the expression of TME immunological markers and immune cell tumor infiltration. Results: AuNPs improved response to anti PD-L1 treatment in mice receiving RT, shown by significant delay in tumor growth and increase in survival compared to the animals receiving RT+ AuNP (p\u3c0.01) and to the animals receiving RT+ anti PD-L1 or RT alone (p\u3c0.05). These results were accompanied with changes in the expression of TME immunological markers and T cell and macrophage infiltration. Conclusion: In TNBC patients, induction of antitumor immune response may play a critical role in improving clinical outcomes. Here we show that AuNP enhanced the effect of a fractionated RT regimen that has significantly improved the response to anti PD-L1 treatment in 4T1Luc TNBC mouse model. This effect was measured by a delay in tumor growth and an increase in animal survival. These findings support the role of immunological mechanisms in TNBC and provide a platform for designing multimodal TNBC RT formulations with novel radiosensitizers or immunotherapy

Cluster analysis for symptomatic management of Neisseria gonorrhoea and Chlamydia trachomatis in sexually transmitted infections related clinics in China

Objective: This study aimed to perform a cluster analysis of symptoms linked with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) and to identify which cluster of symptoms was associated with a higher risk of NG and CT. Study design: From 15 April to 16 May 2018, a cross-sectional study was conducted, and patients attending sexually transmitted infections (STI) related clinics were recruited from 22 medical institutions in six districts of Shenzhen city. Methods: A structured questionnaire was used to collect social-demographic information as well as STI symptoms, and urine samples were collected for nucleic acid detection. Cluster analysis and logistic regression were applied. Results: Among 8,207 participants, the prevalence of CT and NG infection was 9.04% (742/8,207) and 2.36% (194/8,207), respectively. Among male outpatients, four clusters with distinct symptomatic patterns were identified. Unmarried, having casual sexual partners in the past 6 months, cluster 2 (OR = 6.70, 95% CI = 3.36–13.35) and cluster 4 (OR = 24.53, 95% CI = 12.96–46.44) were risk factors associated with NG infection. Unmarried, cluster 2 (OR = 2.54, 95% CI = 1.83–3.53) and cluster 4 (OR = 3.31, 95% CI = 2.37–4.61) were risk factors associated with CT infection. Among female outpatients, five clusters with distinct symptomatic patterns were identified. Aged 24 years or below and cluster 3 (OR = 3.68, 95% CI = 1.61–8.39) were risk factors associated with NG infection. Aged 24 years or below, unmarried, having a high school/secondary technical school education, and having junior high school or below education were risk factors associated with CT infection. Conclusion: The cluster of symptoms integrated into risk assessment for CT and NG infections suggests a new strategy of symptomatic management. Healthcare providers in STI clinics and resource-limited places may use this strategy to identify more potential patients and deliver adequate, acceptable, and equitable STI care for outpatients with a high risk of STI

On nonequilibrium shrinkage of supercritical CO2 droplets in a water-carrier microflow

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. The following article appeared in Applied Physics Letters, 113(3), 033703 and may be found at https://doi.org/10.1063/1.5039507.We report an experimental study on the hydrodynamic shrinkage of supercritical carbon dioxide (scCO(2)) microdroplets during a nonequilibrium process. After scCO(2 )microdroplets are generated by water shearing upon a scCO(2) flow in a micro T-junction, they are further visualized and characterized at the midpoint and the ending point of a straight rectangular microchannel (width x depth x length: 150 mu m x 100 mu m x 1.5 mm). The measured decreases in droplet size by 8%-36% indicate and simply quantify the droplet shrinkage which results from the interphase mass transfer between the droplet and the neighboring water. Using a mathematical model, the shrinkage of scCO(2) droplets is characterized by solvent-side mass transfer coefficients (k(s): 1.5 x 10(-4)-7.5 x 10(-4) m/s) and the Sherwood number (Sh: 7-37). In general, k(s) here is two orders of magnitude larger than that of hydrostatic liquid CO2 droplets in water. The magnitude of Sh numbers highlights the stronger effect of local convections than that of diffusion in the interphase mass transfer. Our results, as reported here, have essential implications for scCO(2)-based chemical extractions and carbon storage in deep geoformations. Published by AIP Publishing.Carbon Management Canada: C39