550 research outputs found

    The study of renal function and toxicity using zebrafish (Danio rerio) larvae as a vertebrate model

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    Zebrafish (Danio rerio) is a powerful model in biomedical and pharmaceutical sciences. The zebrafish model was introduced to toxicological sciences in 1960, followed by its use in biomedical sciences to investigate vertebrate gene functions. As a consequence of many research projects in this field, the study of human genetic diseases became instantly feasible. Consequently, zebrafish have been intensively used in developmental biology and associated disciplines. Due to the simple administration of medicines and the high number of offspring, zebrafish larvae became widely more popular in pharmacological studies in the following years. In the past decade, zebrafish larvae were further established as a vertebrate model in the field of pharmacokinetics and nanomedicines. In this PhD thesis, zebrafish larvae were investigated as an earlystage in vivo vertebrate model to study renal function, toxicity, and were applied in drug-targeting projects using nanomedicines. The first part focused on the characterization of the renal function of three-to four-dayold zebrafish larvae. Non-renal elimination processes were additionally described. Moreover, injection techniques, imaging parameters, and post-image processing scripts were established to serve as a toolbox for follow-up projects. The second part analyzed the impact of gentamicin (a nephrotoxin) on the morphology of the pronephros of zebrafish larvae. Imaging methodologies such as fluorescent-based laser scanning microscopy and X-ray-based microtomography were applied. A profound comparison study of specimens acquired with different laboratory X-ray-based microtomography devices and a radiation facility was done to promote the use of X-ray-based microtomography for broader biomedical applications. In the third part, the toxicity of nephrotoxins on mitochondria in renal epithelial cells of proximal tubules was assessed using the zebrafish larva model. Findings were compared with other teleost models such as isolated renal tubules of killifish (Fundulus heteroclitus). In view of the usefulness and high predictability of the zebrafish model, it was applied to study the pharmacokinetics of novel nanoparticles in the fourth part. Various in vivo pharmacokinetic parameters such as drug release, transfection of mRNA/pDNA plasmids, macrophage clearance, and the characterization of novel drug carriers that were manipulated with ultrasound were assessed in multiple collaborative projects. Altogether, the presented zebrafish model showed to be a reliable in vivo vertebrate model to assess renal function, toxicity, and pharmacokinetics of nanoparticles. The application of the presented model will hopefully encourage others to reduce animal experiments in preliminary studies by fostering the use of zebrafish larvae

    Deep learning for accelerated magnetic resonance imaging

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    Medical imaging has aided the biggest advance in the medical domain in the last century. Whilst X-ray, CT, PET and ultrasound are a form of imaging that can be useful in particular scenarios, they each have disadvantages in cost, image quality, ease-of-use and ionising radiation. MRI is a slow imaging protocol which contributes to its high cost to run. However, MRI is a very versatile imaging protocol allowing images of varying contrast to be easily generated whilst not requiring the use of ionising radiation. If MRI can be made to be more efficient and smart, the effective cost of running MRI may be more affordable and accessible. The focus of this thesis is decreasing the acquisition time involved in MRI whilst maintaining the quality of the generated images and thus diagnosis. In particular, we focus on data-driven deep learning approaches that aid in the image reconstruction process and streamline the diagnostic process. We focus on three particular aspects of MR acquisition. Firstly, we investigate the use of motion estimation in the cine reconstruction process. Motion allows us to combine an abundance of imaging data in a learnt reconstruction model allowing acquisitions to be sped up by up to 50 times in extreme scenarios. Secondly, we investigate the possibility of using under-acquired MR data to generate smart diagnoses in the form of automated text reports. In particular, we investigate the possibility of skipping the imaging reconstruction phase altogether at inference time and instead, directly seek to generate radiological text reports for diffusion-weighted brain images in an effort to streamline the diagnostic process. Finally, we investigate the use of probabilistic modelling for MRI reconstruction without the use of fully-acquired data. In particular, we note that acquiring fully-acquired reference images in MRI can be difficult and nonetheless may still contain undesired artefacts that lead to degradation of the dataset and thus the training process. In this chapter, we investigate the possibility of performing reconstruction without fully-acquired references and furthermore discuss the possibility of generating higher quality outputs than that of the fully-acquired references.Open Acces

    Application of Advanced MRI to Fetal Medicine and Surgery

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    Robust imaging is essential for comprehensive preoperative evaluation, prognostication, and surgical planning in the field of fetal medicine and surgery. This is a challenging task given the small fetal size and increased fetal and maternal motion which affect MRI spatial resolution. This thesis explores the clinical applicability of post-acquisition processing using MRI advances such as super-resolution reconstruction (SRR) to generate optimal 3D isotropic volumes of anatomical structures by mitigating unpredictable fetal and maternal motion artefact. It paves the way for automated robust and accurate rapid segmentation of the fetal brain. This enables a hierarchical analysis of volume, followed by a local surface-based shape analysis (joint spectral matching) using mathematical markers (curvedness, shape index) that infer gyrification. This allows for more precise, quantitative measurements, and calculation of longitudinal correspondences of cortical brain development. I explore the potential of these MRI advances in three clinical settings: fetal brain development in the context of fetal surgery for spina bifida, airway assessment in fetal tracheolaryngeal obstruction, and the placental-myometrial-bladder interface in placenta accreta spectrum (PAS). For the fetal brain, MRI advances demonstrated an understanding of the impact of intervention on cortical development which may improve fetal candidate selection, neurocognitive prognostication, and parental counselling. This is of critical importance given that spina bifida fetal surgery is now a clinical reality and is routinely being performed globally. For the fetal trachea, SRR can provide improved anatomical information to better select those pregnancies where an EXIT procedure is required to enable the fetal airway to be secured in a timely manner. This would improve maternal and fetal morbidity outcomes associated with haemorrhage and hypoxic brain injury. Similarly, in PAS, SRR may assist surgical planning by providing enhanced anatomical assessment and prediction for adverse peri-operative maternal outcome such as bladder injury, catastrophic obstetric haemorrhage and maternal death

    Undergraduate and Graduate Course Descriptions, 2023 Spring

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    Wright State University undergraduate and graduate course descriptions from Spring 2023

    Evaluation of automated organ segmentation for total-body PET-CT

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    The ability to diagnose rapidly and accurately and treat patients is substantially facilitated by medical images. Radiologists' visual assessment of medical images is crucial to their study. Segmenting images for diagnostic purposes is a crucial step in the medical imaging process. The purpose of medical image segmentation is to locate and isolate ‘Regions of Interest’ (ROI) within a medical image. Several medical uses rely on this procedure, including diagnosis, patient management, and medical study. Medical image segmentation has applications beyond just diagnosis and treatment planning. Quantitative information from medical images can be extracted by image segmentation and employed in the research of new diagnostic and treatment procedures. In addition, image segmentation is a critical procedure in several programs for image processing, including image fusion and registration. In order to construct a single, high-resolution, high-contrast image of an item or organ from several images, a process called "image registration" is used. A more complete picture of the patient's anatomy can be obtained through image fusion, which entails integrating numerous images from different modalities such as computed tomography (CT) and Magnetic resonance imaging (MRI). Once images are obtained using imaging technologies, they go through post-processing procedures before being analyzed. One of the primary and essential steps in post-processing is image segmentation, which involves dividing the images into parts and utilizing only the relevant sections for analysis. This project explores various imaging technologies and tools that can be utilized for image segmentation. Many open-source imaging tools are available for segmenting medical images across various applications. The objective of this study is to use the Jaccard index to evaluate the degree of similarity between the segmentations produced by various medical image visualization and analysis programs

    Generative Adversarial Network (GAN) for Medical Image Synthesis and Augmentation

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    Medical image processing aided by artificial intelligence (AI) and machine learning (ML) significantly improves medical diagnosis and decision making. However, the difficulty to access well-annotated medical images becomes one of the main constraints on further improving this technology. Generative adversarial network (GAN) is a DNN framework for data synthetization, which provides a practical solution for medical image augmentation and translation. In this study, we first perform a quantitative survey on the published studies on GAN for medical image processing since 2017. Then a novel adaptive cycle-consistent adversarial network (Ad CycleGAN) is proposed. We respectively use a malaria blood cell dataset (19,578 images) and a COVID-19 chest X-ray dataset (2,347 images) to test the new Ad CycleGAN. The quantitative metrics include mean squared error (MSE), root mean squared error (RMSE), peak signal-to-noise ratio (PSNR), universal image quality index (UIQI), spatial correlation coefficient (SCC), spectral angle mapper (SAM), visual information fidelity (VIF), Frechet inception distance (FID), and the classification accuracy of the synthetic images. The CycleGAN and variant autoencoder (VAE) are also implemented and evaluated as comparison. The experiment results on malaria blood cell images indicate that the Ad CycleGAN generates more valid images compared to CycleGAN or VAE. The synthetic images by Ad CycleGAN or CycleGAN have better quality than those by VAE. The synthetic images by Ad CycleGAN have the highest accuracy of 99.61%. In the experiment on COVID-19 chest X-ray, the synthetic images by Ad CycleGAN or CycleGAN have higher quality than those generated by variant autoencoder (VAE). However, the synthetic images generated through the homogenous image augmentation process have better quality than those synthesized through the image translation process. The synthetic images by Ad CycleGAN have higher accuracy of 95.31% compared to the accuracy of the images by CycleGAN of 93.75%. In conclusion, the proposed Ad CycleGAN provides a new path to synthesize medical images with desired diagnostic or pathological patterns. It is considered a new approach of conditional GAN with effective control power upon the synthetic image domain. The findings offer a new path to improve the deep neural network performance in medical image processing

    Zein-based smart coatings for drug-eluting stents: investigations via static and microfluidic approaches

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    Coronary heart disease is currently responsible for a significant percentage of global mortality in developed and developing nations alike. This occurrence takes place despite the advancement in medical technology and improved treatment options, such as stenting procedures. Due to complications with restenosis and stent thrombosis that are associated with current commercial stents, there has been a growing interest in stent research and development in order to eradicate the causes of such clinical events. The selection of an antioxidant, non-thrombogenic coating has been a major obstacle to the development of drug-eluting stents (DES), and, to date, a truly biocompatible stent platform remains elusive. Moreover, there is a need to assess stent coatings within an in vitro platform prior to in vivo and clinical studies in order to minimize adverse effects. Even if considerable progress has been made over the last two decades in the development of flow chambers to monitor and study thrombus formation outside of the circulation, blood-material interactions are still little investigated under static and dynamic modes. In order to avoid some of the drawbacks of synthetic polymers, such as their undesirable degradation products, long-lasting presence, or potential biocompatibility issues, the aim of this PhD thesis was to investigate zein as a green and abundant plant-derived protein as a coating material for DES applications. This study aimed to understand the potential uses of zein as a controlled release matrix for drug delivery systems, in addition to developing a microfluidic platform to assess the behavior and hemocompatibility of the proposed plant-based stent coatings under flow conditions
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