Investigation on the proton range uncertainty with spectral CT-based virtual monoenergetic images.

OBJECTIVE: The stopping power ratio (SPR) prediction error will contribute to the range uncertainty of proton therapy. Spectral CT is promising in reducing the uncertainty in SPR estimation. The purpose of this research is to determine the optimal energy pairs of SPR prediction for each tissue and to evaluate the dose distribution and range difference between the spectral CT with the optimal energy pairs method and the single energy CT (SECT) method. METHODS: A new method was proposed based on image segmentation to calculate the proton dose with spectral CT images for the head and body phantom. CT number of each organ region were converted to SPR with the optimal energy pairs of each organ. The CT images were segmented into different organ parts with thresholding method. Virtual monoenergetic (VM) images from 70 keV to 140 keV were investigated to determine the optimal energy pairs for each organ based on Gammex 1467 phantom. The beam data of Shanghai Advanced Proton Therapy facility (SAPT) was employed in matRad (an open-source software for radiation treatment planning) for the dose calculation. RESULTS: The optimal energy pairs were obtained for each tissue. The dose distribution of two tumor sites (brain and lung) were calculated with the aforementioned optimal energy pairs. The maximum dose deviation between spectral CT and SECT at the target region was 2.57% and 0.84% for the lung tumor and brain tumor respectively. The range difference between spectral and SECT was significant with 1.8411 mm for the lung tumor. γ passing rate was 85.95% and 95.49% for the lung tumor and brain tumor with the criterion 2%/2 mm. CONCLUSIONS: This work presents a way to determine the optimal energy pairs for each organ and to calculate the dose distribution based on the more accurate SPR prediction.

GPU accelerated voxel-driven forward projection for iterative reconstruction of cone-beam CT.

BACKGROUND: For cone-beam computed tomography (CBCT), which has been playing an important role in clinical applications, iterative reconstruction algorithms are able to provide advantageous image qualities over the classical FDK. However, the computational speed of iterative reconstruction is a notable issue for CBCT, of which the forward projection calculation is one of the most time-consuming components. METHOD AND RESULTS: In this study, the cone-beam forward projection problem using the voxel-driven model is analysed, and a GPU-based acceleration method for CBCT forward projection is proposed with the method rationale and implementation workflow detailed as well. For method validation and evaluation, computational simulations are performed, and the calculation times of different methods are collected. Compared with the benchmark CPU processing time, the proposed method performs effectively in handling the inter-thread interference problem, and an acceleration ratio as high as more than 100 is achieved compared to a single-threaded CPU implementation. CONCLUSION: The voxel-driven forward projection calculation for CBCT is highly paralleled by the proposed method, and we believe it will serve as a critical module to develop iterative reconstruction and correction methods for CBCT imaging.

[Association of CYP3A5 and MDR1 genetic polymorphisms with the blood concentration of tacrolimus in Chinese liver and renal transplant recipients].

OBJECTIVE: To investigate the association of CYP3A5 and MDR1 genetic polymorphisms with the concentration/ dose (C/D) ratio of tacrolimus for the feasibility of individualized medication. METHODS: The concentration of tacrolimus was detected by enzyme-multiplied immunoassay technique, and was adjusted by weight and dosage to C/D ratios. The single nucleotide polymorphisms of CYP3A5 A6986G and MDR1 C3435T, G2677T/ A, T1236C were determined by TaqMan RT-PCR. The differences of C/D ratio were compared among all of the genotype groups. RESULTS: There were 5 cases with CYP3A5 *1/*1, 22 cases with CYP3A5 *1/*3, and 33 cases with CYP3A5 *3/*3. The C/D ratios of the patients with at least one CYP3A5 *1 allele (130.40 +/- 53.94) was significantly lower than those with CYP3A5 *3/*3 (198.12 +/- 90.80) (P < 0.01). For MDR1, there were 22, 23 and 15 recipients carried C/C, C/T and T/T respectively in C3435T, and 8, 32 and 20 recipients carried T/T, T/ C and C/C respectively in T1236C. The carriers with G/G, G/T, G/A, T/A, T/T were 9, 24, 5, 8 and 14 respectively in G2677T/A. No significant difference was found in the C/D ratios of tacrolimus among different MDR1 genotypes. CONCLUSIONS: Determination of CYP3A5 genotype could help individualize tacrolimus dose regimen prospectively. The patients with CYP3A5 *3 *3 require less dose of tacrolimus to reach the same concentrations comparing with the patients with at least one CYP3A5 * 1 allele.

A Circular Total Focusing Method With Eccentricity Correction and Intensity Compensation for Endoscopic Ultrasound Imaging of Dual-Layered Media.

Present endoscopic ultrasound (EUS) imaging methods for circular array (CA) suffer from the nonuniform spatial resolution in the imaging of a dual-layered media, such as the tubes' immersion EUS inspection. The problem is mainly attributed to the restricted focus and beam de-focusing at the interface. In this article, a circular total focusing method (CTFM) is proposed, which leverages the concept of the conventional total focusing method (TFM) and makes three vital improvements to overcome the challenges. First, to obtain the accurate time-of-flight (TOF) in the dual-layered media, a fourth-order equation of Snell's law is built and solved in polar coordinate system. Second, a fast geometric approximation method is derived to correct the TOF distortion caused by the transducer's eccentricity. Third, the intensity compensation is applied to flatten the imaging intensity at different positions by considering the directivity of element, transmission at interface, and divergence in media. The CTFM is validated on a tube's immersion EUS using a 10 MHz CA with 128 elements. Experimental results demonstrate that the proposed CTFM outperforms existing imaging methods. The lateral and axial resolutions are 0.71 and 0.30 mm, which are 27.5% and 33.3% higher than those of the classic delay-and-sum (DAS) method. The CTFM image shows high and uniform signal-to-noise ratio (SNR) which is 33.6% higher than that of DAS images. The CTFM provides a novel EUS imaging modality which can be applied in both medical and nondestructive testing domains.

End-to-End QA with Polymer Gel Dosimeter for Photon Beam Radiation Therapy.

With the complexity and high demands on quality assurance (QA) of photon beam radiation therapy, end-to-end (E2E) QA is necessary to validate the entire treatment workflow from pre-treatment imaging to beam delivery. A polymer gel dosimeter is a promising tool for three-dimensional (3D) dose distribution measurement. The purpose of this study is to design a fast "one delivery" polymethyl methacrylate (PMMA) phantom with a polymer gel dosimeter for the E2E QA test of the photon beam. The one delivery phantom is composed of ten calibration cuvettes for the calibration curve measurement, two 10 cm gel dosimeter inserts for the dose distribution measurement, and three 5.5 cm gel dosimeters for the square field measurement. The one delivery phantom holder is comparable in size and shape to that of a human thorax and abdomen. In addition, an anthropomorphic head phantom was employed to measure the patient-specific dose distribution of a VMAT plan. The E2E dosimetry was verified by undertaking the whole RT procedure (immobilization, CT simulation, treatment planning, phantom set-up, imaged-guided registration, and beam delivery). The calibration curve, field size, and patient-specific dose were measured with a polymer gel dosimeter. The positioning error can be mitigated with the one-delivery PMMA phantom holder. The delivered dose measured with a polymer gel dosimeter was compared with the planned dose. The gamma passing rate is 86.64% with the MAGAT-f gel dosimeter. The results ascertain the feasibility of the one delivery phantom with a polymer gel dosimeter for a photon beam in E2E QA. The QA time can be reduced with the designed one delivery phantom.

A General Approach for Optimization of Ultrasonic Array Parameter and Setup Using Principal Component Regression.

When an optimization approach is taken for ultrasonic array design, the relationship between imaging performance and acoustic beam characteristics (ABCs) needs to be considered. A general optimization approach for ultrasonic array design is proposed based on principal component regression (PCR), which is used to establish the relationship between imaging performance indicators (IPIs) and ABC. A linear and a circular ultrasonic array design scenarios are simulated to demonstrate the effectiveness of the proposed approach. A set of beam and reflector response simulations are implemented to collect beam characteristics and IPIs, an explicit mapping function between which is built by PCR. Then, the mapping function is applied as an objective function to form an optimization model. The global optimization algorithm is used to locate the optimal solution of array parameters and setup. Simulation results demonstrate that the acoustic beam and imaging performance are associated quantitatively by PCR mapping, making the relationship explicitly interpretable, that the beam and imaging can be optimized simultaneously, and that acoustic response modeling may be skipped during iterative optimization, speeding up the approach.

Engineering Multifunctional Hydrogel-Integrated 3D Printed Bioactive Prosthetic Interfaces for Osteoporotic Osseointegration.

3D printed porous titanium alloy implants is an advanced orthopedic material for joint replacement. However, the high risk of aseptic loosening and periprosthetic infection is difficult to avoid, and the declined autophagy of osteoporosis-derived bone marrow mesenchymal stem cells (OP-BMSCs) further severely impairs the osseointegration under the osteoporotic circumstance. It is thus becoming urgently significant to develop orthopedic materials with autophagy regulation and antibacterial bioactivity. In this regard, a novel class of multifunctional hydrogel-integrated 3D printed bioactive prosthetic interfaces is engineered for in situ osseointegration in osteoporosis. The hydrogel is fabricated from the dynamic crosslinking of synthetic polymers, natural polymers, and silver nanowires to deliver autophagy-regulated rapamycin. Therefore, the resultant soft material exhibits antibacterial ability, biocompatibility, degradability, conductive, self-healing, and stimuli-responsive abilities. In vitro experiments demonstrate that the hydrogel-integrated 3D printed bioactive prosthetic interfaces can restore the declined cellular activities of OP-BMSCs by upregulating the autophagy level and show excellent antibacterial activity against S. aureus and MRSA. More remarkably, the multifunctional 3D printed bioactive prosthetic interfaces significantly improve osseointegration and inhibit infection in osteoporotic environment in vivo. This study provides an efficient strategy to develop novel prosthetic interfaces to reduce complications after arthroplasty for patients with osteoporosis.

Development and Validation of Independent Dual-Focusing Transducer for Internal Inspection of Tubes.

Controllable and focused ultrasonic beams in 3-D cylindrical space are essential when inspecting tubes or tubular objects. In this article, we develop an independent dual-focusing (IDF) array ultrasonic transducer composed of 64 prefocused elements and validate the feasibility of this design. Using k-Wave toolbox based on the k-space pseudospectral method, we simulate the acoustic pressure fields in the time domain and analyze beam profiles in circumferential-radial plane, axial-radial plane and 3-D space. The simulation results prove that the structure of IDF array transducer with the designed delay laws is capable of forming focused beam. A four-element aperture with 15 mm element radius shows narrow beams on both the circumferential and axial directions. On the basis of the simulation results, we fabricate a prototype transducer, test its electrical and acoustical performance, and implement internal inspection of a tube with an inner diameter of 13 mm. The echoes of four-element aperture show a higher amplitude than others, and this is consistent with the simulation. The eight longitudinal grooves and eight ring grooves of no more than 0.5 mm width are applied in inspection experiments, and the results demonstrate that the detection sensitivity of the IDF transducer can reach 0.2 mm in both the circumferential and axial directions. The results demonstrate that forming regulable and focused beam in 3-D cylindrical space is feasible using the IDF array which can be applied when inspecting tubes.

Simulation and performance study of circular ultrasonic array for tubes' internal inspection.

A circular array (CA) transducer is developed and validated to implement internal inspection of the small diameter tubes, one of whose potential application targets is the heat exchanger tubes in Modular High Temperature Gas-cooled Reactor. A geometric model of the transducer and the delay law are proposed according to the inspection setup. Using k-Wave, an open source acoustic simulation toolbox, the beam profiles of various aperture sizes are analyzed to select a suitable aperture. The beams with different focal depths are compared to verify the delay law and to choose a preferable focus. Reflector responses are simulated to predict the transducer's detection sensitivity. To validate the simulation results, a prototype transducer composed of 64 elements is fabricated. Its electrical and acoustical performances are acquired with a pulser-receiver. A 4-element aperture with the focal depth of 1.0 mm is selected to perform internal inspection experiment according to the simulation results. The eight longitudinal grooves with widths of 0.2, 0.3, 0.4, and 0.5 mm on inner and outer tube walls are applied as typical reflectors to test circumferential detection sensitivity. The other five grooves with depths from 0.1 mm to 0.5 mm are chosen to verify radial detection sensitivity. The experiment results demonstrate the detection sensitivity of the CA transducer reaches at least 0.2 mm in circumferential direction and 0.1 mm in radial direction. The CA is proven capable of inspecting small diameter tubes.

[Clinical pharmacokinetics/pharmacodynamics study on pazufloxacin methanesulphonate injection].

OBJECTIVE: To identify rational dosage regimen for pazufloxacin methanesulphonate injection through a pharmacokinetics/pharmacodynamics (PK/PD) study. METHODS: Pazufloxacin methanesulphonate at the doses of 300 mg and 500 mg were injected to 24 healthy volunteers. The plasma concentrations of pazufloxacin were measured by RPHPLC-UV. The MICs of pazufloxacin against 130 strains of 7 species of bacterias, as well as the MPCs of pazufloxacin against 5 species of bacterias were measured by double broth dilution method. RESULTS: The AUC0-24/MIC50 of pazufloxacin methanesulphonate at a stabilized concentration state against methicillin-sensitive Staphylococcus aureus (MSSA) and S. pneumoniae were 215.36 and 107.68 at the dose of 300 mg, and 309.60 and 154.80 at the dose of 500 mg, respectively. The Cmax/MIC50 were 57.52 and 28.76 at the dose of 300 mg, and 81.28 and 40.64 at the dose of 500 mg, respectively. However, the AUC0-24/MIC of pazufloxacin methanesulphonate against methicillin-resistant staphylococcus aureus (MRSA) were far less than 40. Both the AUC0-24/MIC50 and the Cmax/MIC50 of pazufloxacin against P. aeruginosa at the doses of 300 mg and 500 mg exceeded the defined criteria 100 and 10. Whereas the AUC0-24/MIC and Cmax/MIC of pazufloxacin against E. coli, K. pneumoniae and A. baumanii were much less than 100 and 10. The capability of pazufloxacin methanesulphonate to prevent mutations of MSSA was strong at the dose of 500 mg, but not for other pathogenic bacteria either at 300 mg or 500 mg. CONCLUSION: Pazufloxacin methanesulphonate at the dose of 300 mg and 500 mg have similar efficacy in treating acute bacterial infections. The dosage regimen of 300 mg Q12h intravenous infusion is recommended.

Spatial Uniformity Assessment of Particles Distributed in a Spherical Fuel Element Using a Non-Destructive Approach.

In many manufacturing procedures, a large number of identical particles need to be disseminated uniformly into a given space. The uniformity of the spatial distribution of the particles can be critical to the properties of the final products. We proposed an image processing-based non-destructive technique to evaluate the particles' spatial uniformity in a spherical space imaged with computed tomography. Both graphic (qualitative) and numerical (quantitative) methods were developed to demonstrate the (non-) uniformity of the particles. Simulation results indicated that the technique helped detecting the non-uniformity in the particles' spatial distribution accurately. We conclude that the proposed technique can be used to test whether a number of particles in a sphere are uniformly distributed statistically and graphically.

Evaluation of hybrid SART + OS + TV iterative reconstruction algorithm for optical-CT gel dosimeter imaging.

Optical computed tomography (optical-CT) is a high-resolution, fast, and easily accessible readout modality for gel dosimeters. This paper evaluates a hybrid iterative image reconstruction algorithm for optical-CT gel dosimeter imaging, namely, the simultaneous algebraic reconstruction technique (SART) integrated with ordered subsets (OS) iteration and total variation (TV) minimization regularization. The mathematical theory and implementation workflow of the algorithm are detailed. Experiments on two different optical-CT scanners were performed for cross-platform validation. For algorithm evaluation, the iterative convergence is first shown, and peak-to-noise-ratio (PNR) and contrast-to-noise ratio (CNR) results are given with the cone-beam filtered backprojection (FDK) algorithm and the FDK results followed by median filtering (mFDK) as reference. The effect on spatial gradients and reconstruction artefacts is also investigated. The PNR curve illustrates that the results of SART + OS + TV finally converges to that of FDK but with less noise, which implies that the dose-OD calibration method for FDK is also applicable to the proposed algorithm. The CNR in selected regions-of-interest (ROIs) of SART + OS + TV results is almost double that of FDK and 50% higher than that of mFDK. The artefacts in SART + OS + TV results are still visible, but have been much suppressed with little spatial gradient loss. Based on the assessment, we can conclude that this hybrid SART + OS + TV algorithm outperforms both FDK and mFDK in denoising, preserving spatial dose gradients and reducing artefacts, and its effectiveness and efficiency are platform independent.