Superficial vessel-based near infrared-assisted patient position recognition and real-time monitoring system (VIPS) for radiotherapy: A proof-of-concept study.

BACKGROUND: The accuracy and precision of patient position in radiotherapy process have dramatic impacts on the tumor local control and therapy-related side effects, and there exist demands to explore effective positioning solutions, particularly in the era with great progress in imaging recognition and matching. PURPOSE: Superficial vessel-based near infrared-assisted patient position recognition and real-time monitoring system (VIPS) was proposed to develop an automated, operator-independent and skin marker-free imaging system to improve patient setup and intrafractional motion monitoring. METHODS: VIPS includes two components, the imaging module and the image alignment software. Using a simulated blood vessel model, multiple NIR sources with various wavelength and bolus (pseudo-skin) were evaluated in terms of imaging quality to determine the optimal light source and the upper limit of superficial fatty tissue thickness. Then the performance of VIPS with reference to either CBCT or laser setup system was conducted using 3D phantom and clinical cases enrolled into the registered clinical trial. The position displacement from VIPS and laser system was compared, as well as the systematic and random errors of VIPS setup procedure. RESULTS: The NIR light source with the combined wavelengths of 760 nm + 940 nm (S760+940 nm ) provided the best performance among multiple tested light sources. The bolus (superficial fatty layer) thickness over 5 mm could dramatically compromise the NIR detection of vessels beneath. In the phantom study, the translational positional displacements according to VIPS guidance were within the submillimeter level with reference to CBCT, indicative of high setup accuracy. The clinical trial showed the prototype VIPS could effectively detect and control position displacement of patients in translational and rotational directions within an acceptable range, which was non-inferior to conventional laser/skin marker system. CONCLUSION: This proof-of-concept study validated the feasibility and reliability of VIPS in guiding radiotherapy setup. However, limitations and technical challenges should be resolved prior to further clinical evaluation, including isocenter alignment, potential NIR image distortion and the impact of the superficial tissues on the recognition of vessels.

Dosimetric Study of Deep Learning-Guided ITV Prediction in Cone-beam CT for Lung Stereotactic Body Radiotherapy.

Purpose: The purpose of this study was to evaluate the accuracy of a lung stereotactic body radiotherapy (SBRT) treatment plan with the target of a newly predicted internal target volume (ITVpredict) and the feasibility of its clinical application. ITVpredict was automatically generated by our in-house deep learning model according to the cone-beam CT (CBCT) image database. Method: A retrospective study of 45 patients who underwent SBRT was involved, and Mask R-CNN based algorithm model helped to predict the internal target volume (ITV) using the CBCT image database. The geometric accuracy of ITVpredict was verified by the Dice Similarity Coefficient (DSC), 3D Motion Range (R3D), Relative Volume Index (RVI), and Hausdorff Distance (HD). The PTVpredict was generated by ITVpredict, which was registered and then projected on free-breath CT (FBCT) images. The PTVFBCT was margined from the GTV on FBCT images gross tumor volume on free-breath CT (GTVFBCT). Treatment plans with the target of Predict planning target volume on CBCT images (PTVpredict) and planning target volume on free-breath CT (PTVFBCT) were respectively re-established, and the dosimetric parameters included the ratio of the volume of patients receiving at least the prescribed dose to the volume of PTV (R100%), the ratio of the volume of patients receiving at least 50% of the prescribed dose to the volume of PTV in the Radiation Therapy Oncology Group (RTOG) 0813 Trial (R50%), Gradient Index (GI), and the maximum dose 2 cm from the PTV (D2cm), which were evaluated via Plan4DCT, plan which based on PTVpredict (Planpredict), and plan which based on PTVFBCT (PlanFBCT). Result: The geometric results showed that there existed a good correlation between ITVpredict and ITV on the 4-dimensional CT [ITV4DCT; DSC= 0.83 ±0.18]. However, the average volume of ITVpredict was 10% less than that of ITV4DCT (p = 0.333). No significant difference in dose coverage was found in V100% for the ITV with 99.98 ± 0.04% in the ITV4DCT vs. 97.56 ± 4.71% in the ITVpredict (p = 0.162). Dosimetry parameters of PTV, including R100%, R50%, GI and D2cm showed no statistically significant difference between each plan (p > 0.05). Conclusion: Dosimetric parameters of Planpredict are clinically comparable to those of the original Plan4DCT. This study confirmed that the treatment plan based on ITVpredict produced by our model could automatically meet clinical requirements. Thus, for patients undergoing lung SBRT, the model has great potential for using CBCT images for ITV contouring which can be used in treatment planning.

Unravelling the molecular mechanisms of abscisic acid-mediated drought-stress alleviation in pomegranate (Punica granatum L.).

Pomegranate (Punica granatum L.), a fruit tree of great economic and nutritional importance, is sensitive to drought stress, which largely affects its transplantation survival rate, fruit yield and quality. Abscisic acid (ABA) treatment can reduce the drought-induced adverse impacts on plants. However, our knowledge on the molecular mechanisms behind ABA-mediated drought tolerance in pomegranates is still limited. In this study, we treated the pomegranates under drought stress with exogenous ABA of different concentrations (30, 60 and 90 µM) and found that, compared to those without treatment, ABA can improve pomegranate's growth condition and related physiological responding processes. We also performed comparative transcriptome analysis between the ABA-treated and untreated pomegranates to reveal the ABA-induced mechanisms in response to drought-stress. Our results showed that exogenous ABA application substantially enhanced pomegranate drought resistance by strengthening some metabolic pathways, such as brassinosteroid synthesis, peroxisome biogenesis, photosynthesis and hemicelluloses synthesis. Furthermore, the over-dose treatment of exogenous ABA was found to trigger ABA degradation process and a feedback loop in pomegranate to balances the ABA accumulation that exceeds the optimal ABA requirement, at the cost of suppressed growth process and stress resistance. Our findings provide new insights into the molecular regulation mechanisms underlying the ABA-mediated drought-stress resistance in pomegranates.

Adoption of Biologically Effective Dose of the Non-Target Lung Volume to Predict Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy With Variable Fractionations for Lung Cancer.

Background: This study aims to establish lung biologically effective dose (BED)-based uniform dosimetric constraints for minimizing the risk of symptomatic radiation pneumonitis (SRP) from stereotactic body radiation therapy (SBRT) using variable fractionations in patients with lung tumors. Materials and Methods: A total of 102 patients with primary or oligometastatic lung tumors treated with SBRT in our institution were enrolled into this study. The associations between the clinical and dosimetric parameters and the incidences of SRP were analyzed using univariate and multivariate Cox regression hazard models. The receiver operating characteristic (ROC) curve was generated to evaluate the predictive performance of lung BED on the SRP risk compared with the physical dose. Results: SRP occurred in 11 patients (10.8%). In univariate analysis, the mean lung dose (p = 0.002), V5 (p = 0.005), V20 (p < 0.001), and the percentage of non-target normal lung volume receiving more than a BED of 5-170 Gy (VBED5-170, p < 0.05) were associated with SRP. Multivariate logistic regression analysis showed that there existed a significant statistical correlation between SRP and VBED70 (p < 0.001), which performed better than V5 or V20 on the ROC curves, resulting in an optimal cut-off value of lung VBED70 of 2.22%. Conclusions: This retrospective study indicated that non-target lung BED may better predict SRP from patients with SBRT-treated lung cancer. Limiting the lung VBED70 below 2.22% may be favorable to reduce the incidence of SRP, which warranted further prospective validation.

Scintillator-Based Nanohybrids with Sacrificial Electron Prodrug for Enhanced X-ray-Induced Photodynamic Therapy.

X-ray-induced photodynamic therapy (X-PDT) has high depth of penetration and has considerable potential for applications in cancer therapy. Scintillators and heavy metals have been adopted to absorb X-rays and transmit the energy to photosensitizers. However, the low efficiency of converting X-rays to reactive oxygen species (ROS) presents a challenge for the use of X-PDT to cure cancer. In this study, a new method based on LiLuF4:Ce@SiO2@Ag3PO4@Pt(IV) nanoparticles (LAPNP) is presented that could be used to enhance the curative effects of X-PDT. To make full use of the fluorescence produced by nanoscintillators (LiLuF4:Ce), a cisplatin prodrug Pt(IV) was utilized as a sacrificial electron acceptor to increase the yield of hydroxyl radicals (·OH) by increasing the separation of electrons and holes in photosensitizers (Ag3PO4). Additionally, cisplatin is produced upon the acceptance of electrons by Pt(IV) and further enhances the damage caused by ·OH. Via two-step amplification, the potential of LAPNP to enhance the effects of X-PDT has been demonstrated.

Dual-Energy Computed Tomography-Based Iodine Quantitation for Response Evaluation of Lung Cancers to Chemoradiotherapy/Radiotherapy: A Comparison With Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography-Based Positron Emission Tomography/Computed Tomography Response Evaluation Criterion in Solid Tumors.

OBJECTIVE: The objective of this study was to investigate the correlation between dual-energy computed tomography (DECT)-based iodine quantitation and fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for response evaluation of lung cancers to treatment. METHODS: In this prospective study, a total of 32 pairs of DECT and F-FDG PET/CT imaging acquired consecutively from 13 patients with primary or metastatic lung cancers receiving either radiotherapy alone or chemoradiotherapy were analyzed. Imaging examinations were performed before, immediately, and no later than 6 months after treatment for response evaluation. Iodine-related parameters including the total iodine uptake (TIU) and vital volume (VIV) from DECT and metabolic metrics such as the standardized uptake value normalized to lean body mass (SULpeak), metabolic tumor volume (MTV), and the total lesion glycolysis (TLG) from F-FDG-PET/CT were generated and measured by semiautomatic approaches. Dual-energy CT and PET/CT metrics were calculated and followed up with comparison with response evaluation criteria in solid tumors (RECIST). RESULTS: Analysis of pretreatment imaging data revealed a strong correlation between DECT metrics (RECIST, TIU, and VIV) and F-FDG PET/CT metrics (MTV, TLG) with coefficients of R ranging from 0.86 to 0.90 (P < 0.01). With the delivery of treatment, all measured DECT and PET/CT metrics significantly decreased whereas the descending amplitude in RECIST was significantly smaller than that of the remaining parameters (P < 0.05). During follow-up examinations, both metrics followed a similar changing pattern. Overall, strong consistency was found between RECIST, TIU, VIV and SULpeak, MTV, TLG (R covers 0.78-0.96, P < 0.05). CONCLUSIONS: Semiautomatic iodine-related quantitation in DECT correlated well with metabolism-based measurements in F-FDG PET/CT, suggesting that DECT-based iodine quantitation might be a feasible substitute for assessment of lung cancer response to chemoradiotherapy/radiotherapy with comparison with F-FDG PET/CT.

The Feasibility and Efficiency of Volumetric Modulated Arc Therapy-Based Breath Control Stereotactic Body Radiotherapy for Liver Tumors.

There are strong evidences showing the promising oncologic results of stereotactic body radiotherapy for liver tumors. This study aims to investigate the feasibility, plan quality, and delivery efficiency of image-guided volumetric modulated arc therapy-based voluntary deep exhale breath-holding technique in the stereotactic body radiotherapy for liver tumors. Treatment was planned using volumetric modulated arc therapy with 2 modified partial arc and replanned using intensity modulated radiation therapy technique for comparison. Dosimetric parameters were calculated for plan quality assessment. Quality assurance studies included both point and multiple planar dose verifications. Daily cone beam computed tomography imaging was used to measure and correct positional errors for target volumes and critical structures immediately prior to and during treatment delivery. Total monitor units and delivery times were also evaluated. No significant dosimetric difference was found between volumetric-modulated arc therapy and conventional intensity modulated radiation therapy plans. Both techniques were able to minimize doses to organs at risk including normal liver, kidneys, spinal cord, and stomach. However, the average monitor units with volumetric-modulated arc therapy were significantly lower (29.2%) than those with intensity modulated radiation therapy (P = .012). The average beam-on time in volumetric-modulated arc therapy plans was 22.2% shorter than that in intensity modulated radiation therapy plans. In conclusion, it is feasible to utilize volumetric modulated arc therapy in the treatment planning of stereotactic body radiotherapy for liver tumors under breath control mode. In comparison to conventional intensity modulated radiation therapy plans, volumetric modulated arc therapy plans are of high efficiency with less monitor units, shorter beam-on time, tolerable intrafractional errors as well as better dosimetrics, meriting further investigations, and clinical evaluations.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements.

The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er(3+) nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues.