Metabolomics-derived biomarkers for biosafety assessment of Gd-based nanoparticle magnetic resonance imaging contrast agents.

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography-electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF4 and PEG-NaGdF4 nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF4 group than those in the PEG-NaGdF4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF4 nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine.

Characterization of a novel VenusX orthogonal dual-layer multileaf collimator.

PURPOSE: To investigate and characterize the performance of a novel orthogonal dual-layer alpha multileaf collimator (αMLC) mounted on the LinaTech VenusX linac. METHODS: We evaluated leaf positioning accuracy and reproducibility using an electronic portal imaging device through the picket fence test. The average, interleaf, intraleaf, and leaf tip transmissions of the single and dual layers were measured using an ionization chamber. Square and rhombus fields were used to evaluate the leaf penumbra of αMLC. To investigate the advantages of the orthogonal dual-layer multileaf collimator (MLC) in field shaping, right triangular and circular pattern fields were formed using both the dual layers and single layers of the αMLC. RESULTS: The average maximum positioning deviations of the upper and lower αMLC over 1 year were 0.76 ± 0.09 mm and 0.62 ± 0.07 mm, respectively. The average transmissions were 1.87%, 1.83%, and 0.03% for the upper-, lower- and dual-layer αMLC, respectively. The maximum interleaf transmissions of the lower- and dual-layer were 2.43% and 0.17%, respectively. The leaf tip transmissions were 9.34% and 0.25%, respectively. The penumbra of the square field was 6.2 mm in the X direction and 8.0 mm in the Y direction. The average penumbras of the rhombus fields with side lengths of 5 and 10 cm were 3.6 and 4.9 mm, respectively. For the right triangular and circular fields, the fields shaped by the dual-layer leaves were much closer to the set field than those shaped by single-layer leaves. The dose undulation amplitude of the 50% isodose lines and leaf stepping angle change of the dual-layer leaves were smaller than those of the single-layer leaves. CONCLUSIONS: The αMLC benefits from its orthogonal dual-layer design. Leaf transmission, dose undulations at the field edge, and MLC field dependence of the leaf stepping angle of the dual-layer αMLC were remarkably reduced.

The lateral center-edge angle as radiographic selection criteria for periacetabular osteotomy for developmental dysplasia of the hip in patients aged above 13 years.

BACKGROUND: This retrospective study sought to delineate the radiographic characteristics of DDH patients over 13 years of age and investigate whether the lateral center-edge angle (LCEA) could serve as radiographic selection criteria for periacetabular osteotomy. METHODS: We enrolled patients with Hartofilakidis type I DDH without dislocation who underwent periacetabular osteotomy between August 2009 and August 2012. LCEA, anterior central edge angle (ACEA), femoral neck-shaft angle (FNSA), Shenton line and Tönnis acetabular index (AI) were evaluated by anteroposterior and 65° false⁃profile pelvic X-ray radiographs in the standing position. Femoral neck anteversion angle (FNA), labral lesion, labral inversion and cartilage lesion were evaluated by direct magnetic resonance arthrography. DDH was categorized by LCEA into four grades (grade I: 10° ≤ LCEA< 20°, grade II: 0° ≤ LCEA< 10°, grade III: -10° ≤ LCEA< 0°, grade IV: LCEA<-10) and osteoarthritis (OA) severity was assessed using Tönnis OA classification. Pearson correlation analysis was done between LCEA and other variables. RESULTS: Totally patients (274 hips) with a mean age of 27.3 years (range 13-47 years) were included. The mean LCEA was 3.5° (range: - 30° to 20°). Based on LCEA grades, grade I DDH was present in 104 hips, grade II in 40 hips, grade III in 76 hips, and grade IV in 54 hips. Based on Tönnis OA classification, 54.5% hips (150/274) were grade 0, 33.1% hips (91/274) grade 1, 8.4% hips (23/274) grade 2 and 4% hips (11/274) grade 3. Pearson correlation analysis showed a negative correlation between LCEA grade and Tönnis OA grades (r = 0.3987; P < 0.001). Cochran-Armitage trend test further showed a positive correlation between LCEA grades and labral lesion (P < 0.001) and interrupted Shenton line (P < 0.001). CONCLUSION: The LCEA classification scheme offers a simple and practical approach to categorize the level of acetabulum coverage on the femoral head, hip deformity and characteristics of DDH. Our findings could provide clinically useful guidance for orthopedic surgeons in preparation for periacetabular osteotomy in DDH patients aged above 13 years.

Automatic segmentation and applicator reconstruction for CT-based brachytherapy of cervical cancer using 3D convolutional neural networks.

In this study, we present deep learning-based approaches to automatic segmentation and applicator reconstruction with high accuracy and efficiency in the planning computed tomography (CT) for cervical cancer brachytherapy (BT). A novel three-dimensional (3D) convolutional neural network (CNN) architecture was proposed and referred to as DSD-UNET. The dataset of 91 patients received CT-based BT of cervical cancer was used to train and test DSD-UNET model for auto-segmentation of high-risk clinical target volume (HR-CTV) and organs at risk (OARs). Automatic applicator reconstruction was achieved with DSD-UNET-based segmentation of applicator components followed by 3D skeletonization and polynomial curve fitting. Digitization of the channel paths for tandem and ovoid applicator in the planning CT was evaluated utilizing the data from 32 patients. Dice similarity coefficient (DSC), Jaccard Index (JI), and Hausdorff distance (HD) were used to quantitatively evaluate the accuracy. The segmentation performance of DSD-UNET was compared with that of 3D U-Net. Results showed that DSD-UNET method outperformed 3D U-Net on segmentations of all the structures. The mean DSC values of DSD-UNET method were 86.9%, 82.9%, and 82.1% for bladder, HR-CTV, and rectum, respectively. For the performance of automatic applicator reconstruction, outstanding segmentation accuracy was first achieved for the intrauterine and ovoid tubes (average DSC value of 92.1%, average HD value of 2.3 mm). Finally, HDs between the channel paths determined automatically and manually were 0.88 ± 0.12 mm, 0.95 ± 0.16 mm, and 0.96 ± 0.15 mm for the intrauterine, left ovoid, and right ovoid tubes, respectively. The proposed DSD-UNET method outperformed the 3D U-Net and could segment HR-CTV, bladder, and rectum with relatively good accuracy. Accurate digitization of the channel paths could be achieved with the DSD-UNET-based method. The proposed approaches could be useful to improve the efficiency and consistency of treatment planning for cervical cancer BT.

Comparison of hyperdry amniotic membrane transplantation and conjunctival autografting for primary pterygium.

BACKGROUND: The purpose of this study was to evaluate the safety and effectiveness of the hyperdry amniotic membrane transplantation compared with conjunctival autografting for the treatment of primary pterygium. METHODS: One hundred and forty-one eyes from 130 patients with primary pterygium were treated with excision followed by hyperdry amniotic membrane or conjunctival autografting after random selection. Seventy-nine eyes from 71 patients received hyperdry amniotic membrane transplantation (HD-AM group), and 62 eyes from 59 patients received conjunctival autografting (CG group). Patients were followed up at one week and one, three, six, and 12 months post-surgery. Recurrence rate, postoperative complications, and final follow-up patient visits were prospectively evaluated. RESULTS: The mean follow-up duration was 12.56 ± 4.35 months in the HD-AM group and 12.85 ± 3.90 months in the CG group. Recurrences were detected in four eyes (5.06%) in the HD-AM group and 13 eyes (20.97%) in the CG group. A statistically significant difference in frequency of recurrence between the two groups (P = 0.003) was observed. The cumulative non-recurrence rates at six and 12 months in all patients stratified by age and sex were not significantly different (P = 0.642 and P = 0.451, respectively, by log-rank test). Graft retraction and necrosis were not detected in the two groups during the follow-up period. CONCLUSION: Hyperdry amniotic membrane transplantation was effective in preventing pterygium recurrence when compared with conjunctival autografting and can be considered a preferable and safe grafting procedure for primary pterygium. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900270 , Retrospectively registered (Date of registration: 3 May 2018).

Toll-like Receptor Agonist CBLB502 Protects Against Cisplatin-induced Liver and Kidney Damage in Mice.

BACKGROUND/AIM: CBLB502, a Toll-like receptor-5 agonist derived from Salmonella flagellin, exerts protective roles against irradiation and chemical drugs in mammalian tissues and stimulates tissue regeneration. This study aimed to investigate whether CBLB502 can protect against liver and kidney damage induced by the chemotherapeutic drug cisplatin (CDDP) and the underlying mechanism of the protective effect. MATERIALS AND METHODS: Mice were pretreated with CBLB502 [0.2 mg/kg, intraperitoneal (i.p.) injection] 0.5 h prior to administration of CDDP (20 mg/kg, i.p. injection), and analyses of the liver and kidney indices, blood biochemistry, and histopathology were performed. RESULTS: Pretreatment with CBLB502 alleviated CDDP-induced liver and kidney damage. RNA sequencing and bioinformatic analysis indicated that CDDP induced a similar damage-promoting gene regulation pattern in the liver and kidney. CBLB502 protected against liver and kidney damage only after CDDP treatment primarily via different pathways. However, some CBLB502-regulated genes were common between the liver and kidney, including those involved in blood coagulation, fibrinolysis, hemostasis, apoptotic regulation, NF-kappaB signaling, and response to lipopolysaccharide, suggesting a general protective effect by CBLB502. CONCLUSION: Our data provide insights into the protective mechanism of CBLB502 against CDDP-induced tissue damage in the liver and kidney and might provide a basis for future studies on functional genes and regulatory mechanisms that mediate protection against chemoradiotherapy-induced damage.

Liposclerosing myxofibrous tumor of the distal femur: A case report.

Introduction: Liposclerosing myxofibrous tumor (LSMFT) is a rare benign fibro-osseous tumor that most frequently occurs in the proximal femur. The reported literature shows that the proximal femur, ilium, tibia, humerus, rib, and skull have occurred, but so far, the female distal femur has not been characterized in detail. This, we think, is the first single comprehensive case report of the female distal femur. To prevent misdiagnosis and overtreatment of this illness, it is critical for us to continue strengthening our knowledge of it and to add it to the differential diagnosis of the space-occupying lesion of the female distal femur. Case summary: Two months ago, a 55-year-old female patient was found to have a space-occupying lesion of the left distal femur and the pain symptom was aggravated. She underwent thorough curettage and bone grafting without additional treatment to relieve the current symptoms and determine the nature of the lesion in our hospital. The intraoperative specimens were submitted to the pathology laboratory for analysis, and the result was reported as LSMFT. And six months after the operation, the patient returned to our hospital for another x-ray examination and we found that she had recovered well without any signs of recurrence. The patient self-reported that she had now resumed her daily life without any uncomfortable symptoms. Conclusion: The incidence of LSMFT itself is relatively low, and the occurrence of the distal femur is even rarer. However, it is recommended to add LSMFT into the differential diagnosis of the occupying lesions of the distal femur. Once the diagnosis is made, thorough curettage and bone grafting without additional special treatment can achieve better postoperative outcomes. The patient gave her agreement after learning that information about the case will be submitted for publication.

An integrated navigation system based on a dedicated breast support device for MRI-guided breast biopsy.

PURPOSE: Breast cancer is currently the cancer type with the highest incidence in the world, and it is extremely harmful to women's health. MRI-guided breast biopsy is a common method in clinical examination of breast cancer. However, traditional breast biopsy is less accurate and takes a long time. In this study, an integrated navigation system (INS) based on a dedicated breast support device (DBSD) was proposed to assist doctors in biopsy. METHODS: The grid-shaped DBSD can reduce the displacement and deformation of the breast during the biopsy operation and is convenient for puncture. The robot system based on the DBSD is designed to assist doctors in performing puncture action. The software system has functions such as registration, path planning, and real-time tracking of biopsy needles based on the DBSD, which can assist doctors in completing the entire biopsy procedure. A series of experiments are designed to verify the feasibility and accuracy of the system. RESULTS: Experiments prove that the robot system has reasonable structure and meets the requirements of MR compatibility. The latency of the INS during intraoperative navigation is 0.30 ± 0.03 s. In the phantom puncture experiment, the puncture error under the navigation of the INS is 1.04 ± 0.15 mm. CONCLUSION: The INS proposed in this paper can be applied to assist doctors in breast biopsy in MR environment, improve the accuracy of biopsy and shorten the time of biopsy. The experimental results show that the system is feasible and accurate.

THE INFLUENCE OF LOW-DOSE OCCUPATIONAL RADIATION EXPOSURE ON PERIPHERAL BLOOD CELLS IN A COHORT OF CHINESE MEDICAL RADIATION WORKERS.

OBJECTIVES: The study aims to assess the change of peripheral blood cell numbers following protracted low-dose radiation exposure among medical radiation workers. METHODS: A cohort of 375 Chinese medical workers were followed for 5 years (2015-19) and recorded the changes in blood cells and cumulative doses. T-test, least significant difference-T test, variance analysis and correlation analysis were utilized in this study. RESULTS: Compared with the control group, the white blood cells, hemoglobin counts and the ratio of eosinophils in the study group showed a downward trend. The differences in blood cells between groups were mainly found in the number of red blood cells. In a short cumulative time, such as 1 or 3 years, a correlation between the cumulative dose and the quantity of blood cells was detected, but not at 5 years. CONCLUSIONS: There is no significant difference in the blood cell counts between different types of work, and the long-term cumulative dose has not been statistically correlated with the number of blood cells. So that the number of peripheral blood cells can no longer be used as a good indicator of radiation damage.

Artificial Intelligence-Based Automated Treatment Planning of Postmastectomy Volumetric Modulated Arc Radiotherapy.

As a useful tool, artificial intelligence has surpassed human beings in many fields. Artificial intelligence-based automated radiotherapy planning strategies have been proposed in lots of cancer sites and are the future of treatment planning. Postmastectomy radiotherapy (PMRT) decreases local recurrence probability and improves overall survival, and volumetric modulated arc therapy (VMAT) has gradually become the mainstream technique of radiotherapy. However, there are few customized effective automated treatment planning schemes for postmastectomy VMAT so far. This study investigated an artificial intelligence based automated planning using the MD Anderson Cancer Center AutoPlan (MDAP) system and Pinnacle treatment planning system (TPS), to effectively generate high-quality postmastectomy VMAT plans. In this study, 20 patients treated with PMRT were retrospectively investigated, including 10 left- and 10 right-sided postmastectomy patients. Chest wall and the supraclavicular, subclavicular, and internal mammary regions were delineated as target volume by radiation oncologists, and 50 Gy in 25 fractions was prescribed. Organs at risk including heart, spinal cord, left lung, right lung, and lungs were also contoured. All patients were planned with VMAT using 2 arcs. An optimization objective template was summarized based on the dose of clinical plans and requirements from oncologists. Several treatment planning parameters were investigated using an artificial intelligence algorithm, including collimation angle, jaw collimator mode, gantry spacing resolution (GSR), and number of start optimization times. The treatment planning parameters with the best performance or that were most preferred were applied to the automated treatment planning method. Dosimetric indexes of automated treatment plans (autoplans) and manual clinical plans were compared by the paired t-test. The jaw tracking mode, 2-degree GSR, and 3 rounds of optimization were selected in all the PMRT autoplans. Additionally, the 350- and 10-degree collimation angles were selected in the left- and right-sided PMRT autoplans, respectively. The uniformity index and conformity index of the planning target volume, mean heart dose, spinal cord D0.03cc, mean lung dose, and V5Gy and V20Gy of the lung of autoplans were significantly better compared with the manual clinical plans. An artificial intelligence-based automated treatment planning method for postmastectomy VMAT has been developed to ensure plan quality and improve clinical efficiency.

No effects of pulsed electromagnetic fields on expression of cell adhesion molecules (integrin, CD44) and matrix metalloproteinase-2/9 in osteosarcoma cell lines.

Pulsed electromagnetic fields (PEMF) could enhance the cytocidal effects of chemotherapeutic drugs on malignant tumor cell lines, but metastasis effects of PEMF on tumor cells have not been investigated. We investigated the effects of PEMF exposure on the expression levels of some metastasis-related molecules, including integrin α subunits (α1, α2, α3, α4, α5, α6, αv), integrin ß subunits (ß1, ß2, ß3, ß4), CD44, and matrix metalloproteinase-2/9 (MMP-2/9) in four human osteosarcoma cell lines (HOS, MG-63, SAOS-2, NY) and two mouse osteosarcoma cell lines (DOS, LM8) by using FACScan analysis, gelatin zymography, and Western blot analysis. Our results indicate that PEMF exposure has no effect on the expression of some molecules that are associated with tumor cell invasion and metastasis, and therefore suggest that PEMF exposure may be safely applied to chemotherapy for osteosarcoma.

Design and implementation of a new cable-driven robot for MRI-guided breast biopsy.

BACKGROUND: Breast cancer is one of the most common cancer diagnosed among US women. Early and accurate diagnosis using breast biopsy techniques is essential in detecting cancer. METHODS: In this paper, we present a new cable-driven robot for MRI-guided breast biopsy. A compact three degree-of-freedom (DOF) semi-automated robot driven by ultrasonic motors is designed with non-magnetic materials. Next, a novel insertion trajectory planning algorithm based on the breast holder that we created is proposed and designed, which can help radiologists locate the lesion and calculate the insertion trajectory. To improve the accuracy of insertion, kinematic analysis and accuracy compensation methods are introduced. RESULTS: An experimental study based on image recognition and positioning is performed to validate the performance of the new robot. The results show that the mean position accuracy is 0.7 ± 0.04 mm. CONCLUSIONS: Application of the new robot can improve breast biopsy accuracy and reduce surgery time.

TightRope vs Clavicular Hook Plate for Rockwood III-V Acromioclavicular Dislocations: A Meta-Analysis.

OBJECTIVE: To assess and compare the clinical outcomes and complications of TightRope® fixation vs hook plate fixation for the treatment of Rockwood III-VI Acromioclavicular joint (ACJ) dislocations. METHODS: Relevant studies were identified by searching PubMed, Embase, and Web of Science databases, from their inception to 12 April, 2019. The main outcomes of interest included Constant Score, University of California Los Angeles (UCLA) Shoulder Score, Visual Analogue Scale (VAS), coracoclavicular distance (CCD), and complications. Weight mean difference (WMD) with 95% confidence intervals (95% CIs) or risk ratio (RR) with 95% CIs was used to calculate the data. RESULTS: Four studies with a total of 179 patients were included in this study. Compared with hook plate, TightRope® fixation was associated with a significantly less VAS score for pain (WMD = -0.69, 95% CI: -1.10, -0.27; P = 0.001). However, there were no significant differences between the two surgical techniques in terms of Constant Score (WMD = 6.12, 95% CI: -3.84, 16.08; P = 0.229), UCLA (WMD = 7.96, 95% CI: -5.76, 21.68; P = 0.256), CCD (WMD = 0.24, 95% CI: -0.67, 1.15; P = 0.602), and complication rate. CONCLUSION: Both TightRope® and hook plate techniques offered effective outcomes in relieving the pain of dislocation and improving function of ACJ. However, TightRope® fixation showed an advantage over hook plate in terms of postoperative pain. Further larger-scale RCTs are needed to verify our findings.

Assessing cumulative dose distributions in combined external beam radiotherapy and intracavitary brachytherapy for cervical cancer by treatment planning based on deformable image registration.

BACKGROUND: This study aimed to validate the feasibility of deformable image registration (DIR) in assessing the cumulative dose distributions in combined external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) for cervical cancer. METHODS: This retrospective study included 23 patients with stage IIB disease treated with combined EBRT to the whole pelvis (50.4 Gy in 28 fractions) using an intensity-modulated radiotherapy technique with 6-MV X-ray, followed by three-dimensional (3D) ICBT (28 Gy in 4 fractions). Tumor gross target volume at diagnosis (GTV-Tinit), tumor gross target volume before brachytherapy, high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), and parametrium and organs at risk were recontoured on computed tomography images of EBRT and ICBT, respectively. The dose-volume parameters were also determined. The DIR results were reviewed using MIM Maestro (Reg Review) and modified by function (Reg Refine). To evaluate the accuracy of DIR, DIR-based cumulative dose-volume histogram (DVH) parameters and simple DVH parameter addition were compared using Wilcoxon rank-sum tests. RESULTS: The cumulative dose distributions of EBRT and four ICBT sessions were successfully illustrated using DIR. The mean tumor diameters were 68.35 cm3 at diagnosis and 29.63 cm3 at ICBT initiation. The mean tumor regression was 56.6%. The median minimum dose covering 90% (D90) of HR-CTV, GTV-Tinit, IR-CTV, and parametrium were 69.58±4.94, 68.81±7.98, 59.28±3.78, and 60.97±1.1 Gyα/ß=10, respectively, for DIR and 69.11±5.68, 68.49±8.62, 58.89±3.59, and 61±1.49 Gyα/ß=10, respectively, with conventional simple DVH parameter addition.No statistically significant differences in dosimetric parameters were observed between the two methods. CONCLUSIONS: Although there were limitations in the DIR accuracy, DIR-based dose accumulation was significantly beneficial in visually showing the cumulative dose distribution in the target area to clinicians in combined radiotherapy for cervical cancer in routine clinical practice.

Role of clip markers placed by endoscopic ultrasonography in contouring gross tumor volume for thoracic esophageal squamous cell carcinoma: one prospective study.

BACKGROUND: We aimed to analyze the value of metal clip markers guided and placed by endoscopic ultrasonography (EUS) in the delineation of gross tumor volume (GTV) for thoracic esophageal squamous cell carcinoma. METHODS: From September 2016 to September 2018, patients with thoracic esophageal squamous cell carcinoma in Tianjin Medical University Cancer Institute and Hospital were recruited in the prospective trial, NCT02959385. They underwent titanium clips placement on tumor superior and inferior boundaries under EUS by a single expert endosonographer before radiotherapy computed tomography (CT) simulation. According to the clip markers, the reference GTVs were contoured by one experienced radiation oncologist. With the help of the Eclipse treatment planning system, clip markers on CT were concealed. Afterward, two other radiation oncologists with expertise in esophageal cancer delineated GTVs, defined as conventional GTVs, based on endoscopy and barium radiography findings. The two GTVs were compared and analyzed. Subgroup analysis was conducted in different T stage [early (T1 + T2) vs. advanced (T3 + T4)], focus location (upper vs. middle vs. lower segment), and tumor length (<5 vs. >5 cm) groups. RESULTS: The trial recruited 55 patients with 60 thoracic esophageal cancer foci. A total of 111 titanium clips were guided and implanted by EUS. Before CT simulation, two titanium clips at two foci fell off. After the procedure, no case of intolerable esophageal pain, hemorrhage, or perforation occurred. Compared to reference GTVs', discrepancies of conventional GTVs' superior borders were 0.91±0.82 cm (P<0.001), while differences of inferior borders were 0.74±0.63 cm (P<0.001). On the contrary, conventional GTVs' lengths were not significantly different from reference GTVs' with discrepancies 0.08±1.30 cm (P=0.64). Regardless of T stage, tumor location, and tumor length, conventional GTVs' superior and inferior borders were significantly different from reference GTVs', while GTVs' lengths differed insignificantly. CONCLUSIONS: This study confirmed that EUS-placed titanium clips could correct contouring of GTVs in thoracic esophageal cancer in different T stages, tumor locations, and lengths.

Individualized and inverse optimized needle configuration for combined intracavitary-interstitial brachytherapy in locally advanced cervical cancer.

OBJECTIVES: The aim of this study is to address the limitation of combined intracavitary-interstitial (IC/IS) brachytherapy (BT) in locally advanced cervical cancer using standardized applicators and to determine the optimal dose distribution in patients with challenging tumors, innovative methods of customizing and optimizing the IS needle configuration for combined IC/IS BT are proposed and investigated. MATERIALS AND METHODS: A software module that could customize the IS needle configuration and subsequently generate the digital model of guiding template for three-dimensional printing was developed and integrated into our in-house treatment planning system for BT. The inverse optimization method based on the technique of mixed-integer linear programming was introduced to determine the needle tracks out of a candidate pool and dwell times at corresponding locations to best meet dose objectives. A treatment planning study was conducted to evaluate the feasibility and performance of the proposed methods. RESULTS: The workflow for combined IC/IS BT with customized and inverse optimized IS needle configuration was presented. Dosimetric results of the treatment planning study showed that sufficient target coverage could be obtained with the customized IS needle configuration for challenging cases. The proposed dose-based optimization method for IS needle configuration was feasible and effective. Improved target coverage and organ-at-risk sparing were achieved using the inverse planning method. CONCLUSIONS: Using the proposed methods of customizing and optimizing the IS needle configuration, the limitation in the standardized design of combined IC/IS applicators can be addressed, and sufficient target coverage is obtained in cervical cancer patients with unfavorable tumor topography and/or extra lateral expansion.

Design and analysis of a tendon-based computed tomography-compatible robot with remote center of motion for lung biopsy.

Nowadays, biopsy is a decisive method of lung cancer diagnosis, whereas lung biopsy is time-consuming, complex and inaccurate. So a computed tomography-compatible robot for rapid and precise lung biopsy is developed in this article. According to the actual operation process, the robot is divided into two modules: 4-degree-of-freedom position module for location of puncture point is appropriate for patient's almost all positions and 3-degree-of-freedom tendon-based orientation module with remote center of motion is compact and computed tomography-compatible to orientate and insert needle automatically inside computed tomography bore. The workspace of the robot surrounds patient's thorax, and the needle tip forms a cone under patient's skin. A new error model of the robot based on screw theory is proposed in view of structure error and actuation error, which are regarded as screw motions. Simulation is carried out to verify the precision of the error model contrasted with compensation via inverse kinematics. The results of insertion experiment on specific phantom prove the feasibility of the robot with mean error of 1.373 mm in laboratory environment, which is accurate enough to replace manual operation.