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Full-Text Articles in Physics

Evaluation Of An End-To-End Radiotherapy Treatment Planning Pipeline For Prostate Cancer, Mohammad Daniel El Basha, Court Laurence, Carlos Eduardo Cardenas, Julianne Pollard-Larkin, Steven Frank, David T. Fuentes, Falk Poenisch, Zhiqian H. Yu May 2024

Evaluation Of An End-To-End Radiotherapy Treatment Planning Pipeline For Prostate Cancer, Mohammad Daniel El Basha, Court Laurence, Carlos Eduardo Cardenas, Julianne Pollard-Larkin, Steven Frank, David T. Fuentes, Falk Poenisch, Zhiqian H. Yu

Dissertations & Theses (Open Access)

Radiation treatment planning is a crucial and time-intensive process in radiation therapy. This planning involves carefully designing a treatment regimen tailored to a patient’s specific condition, including the type, location, and size of the tumor with reference to surrounding healthy tissues. For prostate cancer, this tumor may be either local, locally advanced with extracapsular involvement, or extend into the pelvic lymph node chain. Automating essential parts of this process would allow for the rapid development of effective treatment plans and better plan optimization to enhance tumor control for better outcomes.

The first objective of this work, to automate the treatment …


Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley May 2024

Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley

Dissertations & Theses (Open Access)

The Monte Carlo particle simulator TOPAS, the multiphysics solver COMSOL., and

several analytical radiation transport methods were employed to perform an in-depth proof-ofconcept

for a high dose rate, high precision converging beam small animal irradiation platform.

In the first aim of this work, a novel carbon nanotube-based compact X-ray tube optimized for

high output and high directionality was designed and characterized. In the second aim, an

optimization algorithm was developed to customize a collimator geometry for this unique Xray

source to simultaneously maximize the irradiator’s intensity and precision. Then, a full

converging beam irradiator apparatus was fit with a multitude …


Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia Dec 2023

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …


An Ngqd Based Diagnostic Tool For Pancreatic Cancer, Ryan Ketan Ajgaonkar, Bong Lee, Alina Valimukhametova, Anton Naumov, Giridhar Akkaraju Sep 2023

An Ngqd Based Diagnostic Tool For Pancreatic Cancer, Ryan Ketan Ajgaonkar, Bong Lee, Alina Valimukhametova, Anton Naumov, Giridhar Akkaraju

Research Symposium

Background: Pancreatic cancer remains difficult to detect at early stages which contributes to a poor five-yearsurvival rate. Therefore, early detection approaches based on novel technologies should be explored to address this critical health issue. Nanomaterials have recently emerged as frontrunners for diagnostic applications due to their small size in the 1-100 nm range, which facilitates one-on-one interactions with a variety of biomolecules like oligonucleotides and makes them suitable for a plethora of detection and delivery applications. In this work, the presence of specific pancreatic cancer miRNA (pre-miR-132) is detected utilizing the fluorescence properties of highly biocompatible nitrogen-doped graphene quantum dots …


Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker May 2023

Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker

Undergraduate Honors Theses

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (RCAP) and length (LCAP) would be greater in male rats.

Male (n=4) and female (n=4) with intact …


The Safe And Effective Clinical Deployment Of Artificial Intelligence Tools, Kelly Nealon May 2023

The Safe And Effective Clinical Deployment Of Artificial Intelligence Tools, Kelly Nealon

Dissertations & Theses (Open Access)

18 million new cancer cases are diagnosed each year. Roughly half of these patients will be treated with radiation therapy, a complex technique that requires an interdisciplinary team of clinical staff and expensive equipment to be delivered safely. Cancer centers in Low- and Middle-Income Countries (LMIC) have an especially difficult time meeting the demands of radiation therapy as the complexity of treatment techniques increase, with only 37% of patients in these regions having access to the care they need. Artificial Intelligence (AI) based tools are being developed to simplify the treatment planning and quality assurance processes to increase the number …


Alignment And Range Verification In Proton Therapy Using Proton Radiography And Proton Ct, Joseph Piet Jan 2023

Alignment And Range Verification In Proton Therapy Using Proton Radiography And Proton Ct, Joseph Piet

Graduate Research Theses & Dissertations

Protons are used in radiation therapy to lower doses to healthy tissues by utilizing their Bragg peak. Protons can be used both in imaging and treatment. One of the uses of protons in imaging we tested is its use to align patients using a single beam's eye proton radiograph (pRad). By using a beam's eye pRad, and comparing the water equivalent thickness (WET) to proton digitally reconstructed radiographs (pDRRs), we show that we can measure the best alignment on six axes, three translational and three rotational. This is done by defining a cost function, chi squared, which quantifies the misalignment …


Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey Jan 2023

Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey

CMC Senior Theses

Trans-arterial radioembolization (TARE) is a protracted modality of radiation therapy where radionuclides labeled with Yttrium-90 (90Y) are inserted inside a patient's hepatic artery to treat hepatocellular carcinoma (HCC). While TARE has been shown to be a clinically effective and safe treatment, there is little understanding of the radiobiological relationship between absorbed dose and tissue response, and thus there is no dosimetric standard for treatment planning. The Biologically Effective Dose (BED) formalism, derived from the Linear-Quadratic model of radiobiology, is used to weigh the absorbed dose by the time pattern of delivery. BED is a virtual dose that can …


Quantifying The Magnitude Of Total Dose Deviation Caused By Various Sources Of Error Among Iroc Phantom Irradiation Results, Sharbacha S. Edward Dec 2022

Quantifying The Magnitude Of Total Dose Deviation Caused By Various Sources Of Error Among Iroc Phantom Irradiation Results, Sharbacha S. Edward

Dissertations & Theses (Open Access)

The Imaging and Radiation Oncology Core (IROC) phantoms are used as an end-to-end test of an institution’s radiotherapy processes, and for clinical trial credentialing. Phantoms are treated like patients, and evaluation of the doses received by the thermoluminescent dosimeters (TLDs) inside the phantom, reflects the accuracy with which an institution can image, plan and irradiate a phantom or patient. Recent phantom results show that among the hundreds of various IROC phantoms irradiated annually, 8-17% of institutions fail this test. The purpose of this work was to investigate the various types of errors that may occur during the treatment process and …


Sars-Cov-2 Spike Conformation Determines Plasma Neutralizing Activity Elicited By A Wide Panel Of Human Vaccines, John E. Bowen, Young-Jun Park, Cameron Stewart, Jack T. Brown, William K. Sharkey, Alexandra C. Walls, Anshu Joshi, Kumail Ahmed, Asefa Shariq, Najeeha Talat Iqbal Nov 2022

Sars-Cov-2 Spike Conformation Determines Plasma Neutralizing Activity Elicited By A Wide Panel Of Human Vaccines, John E. Bowen, Young-Jun Park, Cameron Stewart, Jack T. Brown, William K. Sharkey, Alexandra C. Walls, Anshu Joshi, Kumail Ahmed, Asefa Shariq, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated …


Evaluation And Clinical Implementation Of A Dual-Energy Ct Stopping-Power Ratio Mapping Technique For Proton-Therapy Treatment Planning, Maria Jose Medrano Matamoros Aug 2022

Evaluation And Clinical Implementation Of A Dual-Energy Ct Stopping-Power Ratio Mapping Technique For Proton-Therapy Treatment Planning, Maria Jose Medrano Matamoros

McKelvey School of Engineering Theses & Dissertations

Proton radiotherapy has the potential to treat tumors with better conformal dose distribution than competing modalities when the rapid dose falloff at the end of the proton-beam range is correctly aligned to the edge of the clinical target volume (CTV). However, its clinical potential is dependent on the accurate localization of the Bragg-peak position from predicted stopping-power ratio maps. The method that is most commonly used in today’s clinical practice for predicting stopping-power ratio (SPR) consists of a stoichiometric calibrationtechnique based on single-energy CT (SECT) for direct estimation of patient-specific SPR distribution from vendor-reconstructed Hounsfield Unit (HU) images. Unfortunately, this …


Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez Aug 2022

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations & Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …


In-Phantom Film Measurements Of Two Treatment Planning Systems For Single-Fraction Spine Sbrt, Michael J. Taylor May 2022

In-Phantom Film Measurements Of Two Treatment Planning Systems For Single-Fraction Spine Sbrt, Michael J. Taylor

LSU Master's Theses

Purpose: Treatment planning accuracy for spine stereotactic body radiation therapy (SBRT) varies depending on the dose calculation algorithm utilized in the treatment planning system (TPS). This project compared the end-to-end accuracy between spine SBRT plans calculated in a convolution-superposition based TPS (TPSCS) and Monte Carlo based TPS (TPSMC) with radiochromic film measurements. The hypothesis was that TPSMC would calculate the dose gradient in the critical region between the vertebral body and the spinal cord more accurately than TPSCS.

Methods: Single-fraction spine SBRT treatments following RTOG 0631 and local institutional guidelines were planned in …


Hepatocellular Carcinoma Image-Guided Intervention: Quantitative Characterization Of Reagents For Thermochemical Ablation, Emily A. Thompson May 2022

Hepatocellular Carcinoma Image-Guided Intervention: Quantitative Characterization Of Reagents For Thermochemical Ablation, Emily A. Thompson

Dissertations & Theses (Open Access)

Thermochemical ablation (TCA) is a minimally invasive therapy under development for hepatocellular carcinoma, a leading cause of cancer death worldwide. TCA utilizes acid-base chemistry delivered simultaneously to induce local ablation when administered. When delivered via a mixing catheter placed directly into the tumor, acid (e.g., AcOH) and base (e.g., NaOH) react to completion at the catheter tip, producing the acetate salt, water, and releasing heat (Δ>50°C) in sufficient quantities to induce lethal osmotic and thermal stress in tumor cells. However, these two reagents are not distinguishable from tissues with noninvasive imaging modalities, which makes monitoring the delivery of TCA …


Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi May 2022

Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi

Electrical & Computer Engineering Faculty Publications

Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids …


Seizure Prediction In Epilepsy Patients, Gary Dean Cravens Feb 2022

Seizure Prediction In Epilepsy Patients, Gary Dean Cravens

NSU REACH and IPE Day

Purpose/Objective: Characterize rigorously the preictal period in epilepsy patients to improve the development of seizure prediction techniques. Background/Rationale: 30% of epilepsy patients are not well-controlled on medications and would benefit immensely from reliable seizure prediction. Methods/Methodology: Computational model consisting of in-silico Hodgkin-Huxley neurons arranged in a small-world topology using the Watts-Strogatz algorithm is used to generate synthetic electrocorticographic (ECoG) signals. ECoG data from 18 epilepsy patients is used to validate the model. Unsupervised machine learning is used with both patient and synthetic data to identify potential electrophysiologic biomarkers of the preictal period. Results/Findings: The model has shown states corresponding to …


Investigating The Uncertainties In Ct Non-Small Cell Lung Cancer Radiomics, Gary Ge Jan 2022

Investigating The Uncertainties In Ct Non-Small Cell Lung Cancer Radiomics, Gary Ge

Theses and Dissertations--Radiation Medicine

Radiomics is a technique that extracts quantitative features, termed radiomic features, from medical images using data-characterization algorithms. These radiomic features can be used to identify tissue characteristics and radiologic phenotyping that are not observable by clinicians in a non-invasive, low-cost manner, potentially generating image biomarkers for clinical decision. To date, there are still many uncertainties involved in radiomics which limit its clinical implementation. Herein, we propose to explore the impact of each component in the radiomics pipeline on predicting clinical outcomes. In Chapter II, we conduct a thorough review of CT lung cancer radiomics studies to examine the typical feature …


System Measurements For X-Ray Phase And Diffraction Imaging, Erik Wolfgang Tripi Jan 2022

System Measurements For X-Ray Phase And Diffraction Imaging, Erik Wolfgang Tripi

Legacy Theses & Dissertations (2009 - 2024)

In medical imaging, X rays are used to look inside the body to find fractures in bones, abnormal masses, cavities in teeth, and so on. What makes X rays so good at looking at these types of structures is the X ray’s penetration power. When imaging soft tissue to search for tumors, X-ray images tend to have difficulty performing well. The reason for this is that the background structures, such as fat or fibro glandular tissue have similar absorption coefficients as the tumor. Mammography tends to have a high false positive rate and can miss tumors entirely as well. There …


Multi-Modality Automatic Lung Tumor Segmentation Method Using Deep Learning And Radiomics, Siqiu Wang Jan 2022

Multi-Modality Automatic Lung Tumor Segmentation Method Using Deep Learning And Radiomics, Siqiu Wang

Theses and Dissertations

Delineation of the tumor volume is the initial and fundamental step in the radiotherapy planning process. The current clinical practice of manual delineation is time-consuming and suffers from observer variability. This work seeks to develop an effective automatic framework to produce clinically usable lung tumor segmentations. First, to facilitate the development and validation of our methodology, an expansive database of planning CTs, diagnostic PETs, and manual tumor segmentations was curated, and an image registration and preprocessing pipeline was established. Then a deep learning neural network was constructed and optimized to utilize dual-modality PET and CT images for lung tumor segmentation. …


Comparing Semi-Automated Segmentation Of Traditional-Resolution And High-Resolution Hyperpolarized 129xe Mri On Covid-19 Survivors, Tingting Wu Aug 2021

Comparing Semi-Automated Segmentation Of Traditional-Resolution And High-Resolution Hyperpolarized 129xe Mri On Covid-19 Survivors, Tingting Wu

Undergraduate Student Research Internships Conference

Hyperpolarized gas MRI using inert gases like Xe is a valuable tool in visualizing lung ventilation in patients, and can be used as a longitudinal monitoring tool for patients with lung diseases. However, use of this method requires segmentation and quantification of parameters such as ventilation defect percentage (VDP), which is often very subjective depending on the observer. This study aimed to determine the accuracy and consistency of VDP calculation using the same MRI scans from COVID-19 patients, but with high resolution and low (traditional) resolution versions. Using a MATLAB script developed previously, it was found that in general, using …


Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta Aug 2021

Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta

Dissertations & Theses (Open Access)

We have used a 3D age-scalable computational phantom for over two decades for retrospective dose reconstruction studies of childhood cancer survivors (CCS) treated with 2D historic radiotherapy (RT). However, our phantom and its age scaling functions (ASF) must be updated so that it can be used in studies that include survivors treated with contemporary RT. We aimed to implement our phantom and its age scaling functions in DICOM format and determine the feasibility of applying our ASFs to accurately scale the whole-body CT-based anatomies.

In the implementation study, we developed Python scripts that model the phantom and ASFs in a …


Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton Aug 2021

Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton

MSU Graduate Theses

Diethylene glycol monoethyl ether (DEGEE) is a promising solvent component in topical cream formulations due to its superior solubilizing abilities with certain active pharmaceutical ingredients. One of the goals of this study is to characterize the effects of pH on the physical and chemical stabilities of topical cream formulations containing particularly high concentrations of DEGEE by characterizing a full topical pH profile of 3.5 – 9.0. The second goal is to evaluate the presence, amount, and characteristics of lyotropic liquid crystals (LLCs), molecularly structured in a lamellar phase, in a model cream emulsion utilizing polarized light microscopy (PLM). The presence …


Quantitative Magnetic Resonance Imaging For The Early Prediction Of Treatment Response In Triple Negative Breast Cancer, Benjamin C. Musall Aug 2021

Quantitative Magnetic Resonance Imaging For The Early Prediction Of Treatment Response In Triple Negative Breast Cancer, Benjamin C. Musall

Dissertations & Theses (Open Access)

Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer which lacks upregulated hormone receptors. Because of this, it is not vulnerable to clinically available targeted therapies. When treated with standard of care neoadjuvant systemic therapy (NAST), TNBC only shows approximately a 40% rate of pathologic complete response (pCR). A biomarker which could predict TNBC response to NAST early during treatment would be useful, as it would allow for non-responders to be triaged to alternative therapies and potentially allow for the treatment of responders to be de-escalated.

Quantitative Magnetic Resonance Imaging (MRI) may be used to probe and …


Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar Jul 2021

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.


Structural Shielding Considerations For Vmat, Ana Lucia Dieguez Jul 2021

Structural Shielding Considerations For Vmat, Ana Lucia Dieguez

LSU Master's Theses

Introduction: As noted in National Council on Radiation Protection and Measurements (NCRP) Report 151, the medical physicist or other qualified expert has the responsibility to keep abreast of any new technology or treatment method that could potentially impact structural shielding design. Volumetric arc therapy (VMAT) became prevalent after the publication of Report 151 and thus was not explicitly addressed in Report 151. If the shielding-related characteristics of VMAT differ enough from the expectations of Report 151, especially in the circumstance of a vault utilized exclusively for VMAT, a shielding design based on Report 151 could potentially be inadequate. The …


A Direct Machine-Specific Parameters Incorporated Spot-Scanning Proton Arc (Sparc) Algorithm, Gang Liu, Lewei Zhao, Di Yan, Xiaoqiang Li, Xuanfeng Ding Jun 2021

A Direct Machine-Specific Parameters Incorporated Spot-Scanning Proton Arc (Sparc) Algorithm, Gang Liu, Lewei Zhao, Di Yan, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.


Investigate The Delivery Efficiency And Accuracy Of Spot-Scanning Proton Arc (Sparc) In Comparison With Conventional Impt, Automatic Step-And-Shoot Multifield Impt, Lewei Zhao, Gang Liu, Di Yan, Xiaoqiang Li, Xuanfeng Ding Jun 2021

Investigate The Delivery Efficiency And Accuracy Of Spot-Scanning Proton Arc (Sparc) In Comparison With Conventional Impt, Automatic Step-And-Shoot Multifield Impt, Lewei Zhao, Gang Liu, Di Yan, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.


Develop A Rotational Robust Optimized Spot-Scanning Proton Arc (Sparc) Algorithm, Shupeng Chang, Gang Liu, Lewei Zhao, Weili Zheng, An Qin, Di Yan, Xiaoqiang Li, Xuanfeng Ding Jun 2021

Develop A Rotational Robust Optimized Spot-Scanning Proton Arc (Sparc) Algorithm, Shupeng Chang, Gang Liu, Lewei Zhao, Weili Zheng, An Qin, Di Yan, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.


The First Modeling Of The Spot-Scanning Proton Arc (Sparc) Delivery Sequence And Investigating Its Efficiency Improvement In The Clinical Proton Treatment Workflow, Gang Liu, Lewei Zhao, Di Yan, Rohan Deraniyagala, Craig Stevens, Xiaoqiang Li, Xuanfeng Ding Jun 2021

The First Modeling Of The Spot-Scanning Proton Arc (Sparc) Delivery Sequence And Investigating Its Efficiency Improvement In The Clinical Proton Treatment Workflow, Gang Liu, Lewei Zhao, Di Yan, Rohan Deraniyagala, Craig Stevens, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

No abstract provided.


Impact Of Flattening Filter-Free Field On Online Adaptive Radiotherapy Using Virtual Couch Shift (Vcs) Technique, Q Liu, J Liang, D Yan Jun 2021

Impact Of Flattening Filter-Free Field On Online Adaptive Radiotherapy Using Virtual Couch Shift (Vcs) Technique, Q Liu, J Liang, D Yan

Conference Presentation Abstracts

No abstract provided.