Yuenan Wang

Increasing pulmonary nodule presentations in lung adenocarcinoma patients reveal diagnostic limitations of CT-based invasiveness assessment. The critical unmet need lies in developing non-invasive biomarkers differentiating invasive adenocarcinoma from premalignant lesions and benign nodules, while characterizing metabolic trajectory from health to metastatic disease. Untargeted metabolomics analyzed plasma samples from 102 subjects stratified into four cohorts: confirmed adenocarcinoma (n = 35), benign nodules (n = 22), precursor lesions (n = 24), and healthy controls (n = 21). Multivariate analysis identified discriminative metabolites for constructing an infiltration prediction model. Three diagnostic groups exhibited distinct metabolic profiles. Hexaethylene glycol, tetraethylene glycol, and Met-Thr showed stage-dependent concentration gradients. Progressive malignancy correlated with elevated levels of 41 metabolites. An eight-metabolite panel achieved AUC 0.933 (0.873–0.994) in distinguishing precursors from early malignancies, sustained through internal validation (AUC 0.934, 0.905–0.966). Met-Thr depletion inversely correlates with malignancy progression, while eight-metabolite signatures demonstrate diagnostic potential for preoperative infiltration assessment in nodular adenocarcinoma.

Background: We hypothesize generative adversarial networks (GAN) combined with self‐attention (SA) and aggregated residual transformations (ResNeXt) perform better than conventional deep learning models in differentiating hepatocellular carcinoma (HCC). Attention modules facilitate concentrating on salient features and suppressing redundancies, while residual transformations can reuse relevant features. Therefore, we aim to propose a GAN+SA+ResNeXt deep learning model to improve HCC prediction accuracy.Methods: 228 multiphase CTs from 57 patients were retrospectively analyzed with local IRB's approval, where 30 patients were pathologically confirmed with HCC and the rest 27 were non‐HCC. Pre‐processing of automatic liver segmentation and Hounsfield unit (HU) normalization was performed, followed by deep learning training with five‐fold cross validation in a conventional 3D GAN, a 3D GAN+A, and a 3D GAN+A+ ResNeXt, respectively (training: testing ∼ 4:1). Area under receiver operating characteristics curves (AUROC), accuracy, sensitivity and specificity of HCC prediction were evaluated.Results: Results showed the proposed method had larger AUROC (95%), better accuracy (91%) and sensitivity (93%) with acceptable specificity (88%) and prediction time (0.04s). Deep GAN with attentions and residual transformations for HCC diagnosis using multiphase CT is feasible and favorable with improved accuracy and efficiency, which harbors clinical potentials in differentiating HCC from other benign or malignant liver lesions.

Purpose: Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. Dihydroartemisinin (DHA) is an anti‐malaria agent and recent evidence indicates a broad anti‐cancer activity. Radiotherapy (RT) is the cornerstone of cancer treatment and often has synergistic effects when combined with chemotherapy or targeted therapy. We aim to investigate whether synergistic effect exists for RT combined with DHA in a preliminary animal study of CRC treatment.Methods: Twenty‐four BALB/c nude mice were subcutaneously injected with 5.0 × 10⁶ cells of the murine CRC cell line CT26. When tumor xenografts were formed (∼ 100 mm³), mice were randomly allocated into four groups (n = 6 per group) and the tumor‐bearing mice were intra‐abdominally injected at Day 7, 9, 11 with PBS (control), 6Gy irradiation (RT), DHA (50mg/Kg), and DHA with irradiation (DHA+RT). All RT was performed on a medical linear accelerator using collimated anterior posterior 6MV photon beam conformal to tumor xenografts. The tumor volume was measured using an electronic caliper and was calculated based on the length (L) and the width of the tumor using the formula V = (L x W²)/2. Tumor weight was also measured after mice sacrificed. Histological assay was conducted, including using gammaH2AX for DNA double strand breaks (DSB) analysis.Results: The tumor weight was 2.4±0.8g, 2.5±0.6g, 0.4±0.2g, and 0.4±0.1g for the control, DHA, RT, and DHA+RT groups, respectively. Significant difference was observed between the control and RT groups, and between the control and DHA+RT groups (p<0.05). However, there was almost no difference between the RT alone and DHA+RT groups. The longitudinal change in tumor volume showed tumor progression inhibition in the RT and DHA+RT groups, but not so obvious in the DHA group, which was consistent with histological assay.Conclusion: Similar treatment efficacy is observed in the RT alone and concurrent DHA+RT group. No significant difference in tumor volume or weight or tumor progression inhibition is observed between the RT alone and concurrent DHA+RT groups, demonstrating that DHA might not provide synergistic effect with RT for the proposed hypofractionated radiation dose regimen.

Beam‐matched linear accelerators (linacs) enable flexible patient scheduling and efficient treatment delivery in the event of unexpected machine downtime. The purpose of this study was to test the feasibility of 3D gamma index as an additional metric beyond standard measurement‐based comparisons for more efficient evaluation of treatment plans between linacs with nominally matched beam models to ensure safe patient transfer. Seventeen 3D conformal radiotherapy (3DCRT) plans and thirty‐six volumetric‐modulated radiation therapy (VMAT) plans for different disease sites were selected from the original linac. An in‐house script was used to automatically create new plans for the target linac and calculate dose using parameters of the original plans. 3D gamma analysis was performed to compare plan dose distributions between the target and original linacs using PyMedPhys. The 2%/2 mm gamma pass (γ≤1) rate was >99.99% for all 3DCRT plans. The median 1%/1 mm pass rate was 99.86% but two cases failed (< 90%). For VMAT plans, the median and minimum 2%/2 mm gamma pass rates were 99.43% and 93.81%. For 1%/1 mm, the median pass rate was 92.02% but ten cases failed. The results indicated using 3D gamma index can enhance the confidence and add an extra layer for safe patient transfer.

Radiation‐induced heart disease (RIHD) is a serious complication but difficult to assess in patients undergoing thoracic radiotherapy (RT). We aim to analyze RIHD using heart ultrasound and elastic modulus, exploring relationships between functional, anatomical or biomechanical changes of the heart and radiation dose.Twenty BALB/c mice were divided into four groups (control, 10 Gy, 20 Gy and 25 Gy) with a single fraction of image‐guided volumetric modulated arc radiotherapy (VMAT) to murine heart on a linear accelerator. Transthoracic echocardiography (TTE) was performed on a small‐animal ultrasound imaging system with a handheld microscan transducer. E‐wave/A‐wave ratio (E/A) and myocardial performance index (MPI) for diastolic performance were noninvasively evaluated weekly, as well as ejection fraction (EF%), fractional shortening (FS%), left ventricle (LV) mass and heart wall thickening for systolic performance. At the end of the fifth week, all mice were sacrificed for elastic modulus measurement on a dynamic mechanical analyzer (DMA) and for histopathological staining. All experiments were conducted in accordance with the local institution's animal research committee guideline.Significant difference was observed in E/A ratio between the control and 25 Gy irradiated groups (1.8±0.5 and 0.7±0.9, respectively; p<0.05), indicating reduced diastolic performance and increased stiffness in left ventricle after high‐dose heart radiation. Diastolic dysfunction in irradiated groups was also observed with significantly increased MPI. In contrast, posterior wall thickness, aortic peak velocity, heart rate, EF and FS were not significantly different after RT. Heart elasticity was reduced substantially with the increased radiation dose. HE and Masson Trichrome staining confirmed more fibrosis deposition in irradiated hearts.RIHD evaluation with ultrasound imaging noninvasively and biomechanical modulus measurement invasively in the image guided, precision dose‐escalated murine heart irradiation is feasible. Increased myocardial stiffness, abnormal diastolic relaxation, more collagen deposition, and reduced tissue elasticity are observed in irradiated heart tissue. This study may facilitate our understanding of RIHD and facilitate improving patients’ quality of life in the future.

Purpose: We aim to perform image‐guided, dose‐escalated, well‐controlled liver‐irradiated animal studies and subsequently evaluate radiation induced liver injury (RILI) using longitudinal CT.Methods: Eighteen 6–8 weeks mice were divided into three groups: control, 15Gy and 30Gy irradiated groups. The animal protocol was approved by the animal care ethics committee of our institution. Precision radiotherapy started with CT simulation, followed by treatment planning using volumetric modulated arc therapy (VMAT), image guidance with cone beam CT (CBCT) and radiation delivery on a medical linear accelerator. Weekly CT was conducted on the same CT simulator using same scanning parameters. At the end of fifth week, all mice were sacrificed, and histological staining was performed. Body weight, liver volume, HU values and histogram distributions were analyzed.Results: Body weight of irradiation groups was significantly reduced compared to that of the control group (pp _{control vs. 15Gy} < 0.05, p control vs. 30Gy < 0.05). A linear relationship between liver HU and radiation dose was found. Furthermore, HU histogram changes with time and dose showed not only density but also structure might be affected by radiation. HE and Masson Trichrome staining confirmed histological change and increased collagen deposition in irradiated liver.Conclusion: Longitudinal unenhanced CT is a useful imaging tool to evaluate the severity and progression of radiation induced liver injury.

Background and purpose: This study aims to explore the advantages and robustness of the partial arc combined with prone position planning technique for radiotherapy in rectal cancer patients. Adaptive radiotherapy is recalculated and accumulated on the synthesis CT (sCT) obtained by deformable image registration between planning CT and cone beam CT (CBCT). Full and partial volume modulation arc therapy (VMAT) with the prone position on gastrointestinal and urogenital toxicity, based on the probability of normal tissue complications (NTCP) model in rectal cancer patients were evaluated. Materials and methods: Thirty-one patients were studied retrospectively. The contours of different structures were outlined in 155 CBCT images. First, full VMAT (F-VMAT) and partial VMAT (P-VMAT) planning techniques were designed and calculated using the same optimization constraints for each individual patient. The Acuros XB (AXB) algorithm was used in order to generate more realistic dose distributions and DVH, considering the air cavities. Second, the Velocity 4.0 software was used to fuse the planning CT and CBCT to obtain the sCT. Then, the AXB algorithm was used in the Eclipse 15.6 software to conduct re-calculation based on the sCT to obtain the corresponding dose. Furthermore, the NTCP model was used to analyze its radiobiological side effects on the bladder and the bowel bag. Results: With a CTV coverage of 98%, when compared with F-VMAT, P-VMAT with the prone position technique can effectively reduce the mean dose of the bladder and the bowel bag. The NTCP model showed that the P-VMAT combined with the prone planning technique resulted in a significantly lower complication probability of the bladder (1.88 ± 2.08 vs 1.62 ± 1.41, P = 0.041) and the bowel bag (1.28 ± 1.70 vs 0.95 ± 1.52, P < 0.001) than the F-VMAT. In terms of robustness, P-VMAT was more robust than F-VMAT, considering that less dose and NTCP variation was observed in the CTV, bladder and bowel bag. Conclusion: This study analyzed the advantages and robustness of the P-VMAT in the prone position from three aspects, based on the sCT fused by CBCT. Whether it is in regards to dosimetry, radiobiological effects or robustness, P-VMAT in the prone position has shown comparative advantages.

The COVID-19 pandemic imposes a severe challenge to the health care providers and patients in dental clinics as the dental procedures produce abundant airborne materials. Although dental practices use a multi-layered protective procedure to reduce the potential danger from dental aerosols, it is still beneficial to suppress the aerosol generation from the origin as much as possible. Reducing the aerosol generation (especially the droplets of smaller diameters) from the very beginning will ease the burden on all subsequent layers of protection. In this work, we first provide a relatively complete picture of the structure of the spray produced by the air turbine handpiece. We found that the spray consists of two domains: one is the canopy shaped centrifugal zone and the other is a dense ballistic spray core. The droplets from the centrifugal zone are much smaller than those of the spray core and, hence, are more prone to stay in the air. The location of the centrifugal zone also makes it more challenging to be contained by the mouth or rubber dam. To suppress the atomization of the centrifugal zone, we used the food-additive carboxymethylcellulose sodium (CMC-Na) water solutions of different concentrations. The data show that the viscoelastic property of the 0.5 wt. % CMC-Na water solution can effectively suppress the aerosol generation of the centrifugal zone.

Objectives: Setup error is a key factor affecting postmastectomy radiotherapy (PMRT) and irradiation of the internal mammary lymph nodes is the most investigated aspect for PMRT patients. In this study, we evaluated the robustness, radiobiological, and dosimetric benefits of the hybrid volumetric modulated arc therapy (H-VMAT) planning technique based on the setup error in dose accumulation using a surface-guided system for radiation therapy.Methods: We retrospectively selected 32 patients treated by a radiation oncologist and evaluated the clinical target volume (CTV), including internal lymph node irradiation (IMNIs), and considered the planning target volume (PTV) margin to be 5 mm. Three different planning techniques were evaluated: tangential-VMAT (T-VMAT), intensity-modulated radiation therapy (IMRT), and H-VMAT. The interfraction and intrafraction setup errors were analyzed in each field and the accumulated dose was evaluated as the patients underwent daily surface-guided monitoring. These parameters were included while evaluating CTV coverage, the dose required for the left anterior descending artery (LAD) and the left ventricle (LV), the normal tissue complication probability (NTCP) for the heart and lungs, and the second cancer complication probability (SCCP) for contralateral breast (CB).Results: When the setup error was accounted for dose accumulation, T-VMAT (95.51%) and H-VMAT (95.48%) had a higher CTV coverage than IMRT (91.25%). In the NTCP for the heart, H-VMAT (0.04%) was higher than T-VMAT (0.01%) and lower than IMRT (0.2%). However, the SCCP (1.05%) of CB using H-VMAT was lower than that using T-VMAT (2%) as well as delivery efficiency. And T-VMAT (3.72) and IMRT (10.5).had higher plan complexity than H-VMAT (3.71).Conclusions: In this study, based on the dose accumulation of setup error for patients with left-sided PMRT with IMNI, we found that the H-VMAT technique was superior for achieving an optimum balance between target coverage, OAR dose, complication probability, plan robustness, and complexity.