Bioimaging and Biomedical Optics Commons^™

Single Fluorogens And Orientation-Localization Microscopy For Quantifying Chemical And Biomolecular Dynamics At The Nanoscale, Yiyang Chen, Yuanxin Qiu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Many chemical systems look uniform only because ensemble measurements average over their most interesting molecules. Electron-transfer rates vary across electrode surfaces; lipid membranes contain nanodomains with distinct packing and fluidity; peptide aggregates exhibit local polymorphism; and biomolecular condensates contain transient networks of interactions that are blurred in ensemble images. A central challenge in chemical imaging is not simply to see smaller structures, but to measure chemical variables such as polarity, redox potential, and molecular confinement at the single-molecule level. In this Account, we describe how fluorogens, molecules whose brightness, blinking, spectral shifts, orientation, rotational mobility, and motion are directly shaped …

Sensing Negative-Cone Rotational Diffusion Of Dipole-Like Emitters, Yuanxin Qiu, Kaizhi A. Nie, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Fluorescence anisotropy and single-molecule orientation-localization microscopy (SMOLM) are powerful techniques that quantify the rotational diffusion of dipole-like emitters, which is important for sensing molecular interactions and chemical environments at the nanoscale. Numerous theoretical and experimental studies have thoroughly characterized single-molecule rotations even when those rotations are much faster than the detector integration time. Here, we extend the theory of measuring rotational diffusion to situations where a single dipole rotates uniformly everywhere outside of an isotropic cone of a certain size, termed a negative cone. This scenario corresponds to negative fluorescence anisotropy 𝑟 and has been observed in emitters exhibiting strong …

Single-Molecule Orientation And Localization Microscopy, Sophie Brasselet, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Single-molecule localization microscopy (SMLM) offers enhanced spatial resolution in optical microscopy, providing detailed insights into the spatial organization of proteins in cells at the nanoscale. Over the past decade, SMLM has progressively incorporated the capability to retrieve the orientations of single molecules using their polarized dipolar emission pattern. Here we explore recent advancements in single-molecule orientation and localization microscopy (SMOLM), which yields super-resolved images of molecular three-dimensional (3D) orientations, wobble and 3D positions. This advancement opens possibilities to explore the nanoscale organization and conformation of biological molecules as well as to monitor and design local 3D optical fields in nanophotonics. …

Ac Electric Fields Manipulate And Concentrate Dna Molecules On Electrodes, Akila Wijesinghe, Dharmakeerthi Nawarathna

Graduate Student Government Association Research Conference

Point-of-care (POC) electric field-based biosensors have emerged as a promising tool to detect early cancer biomarkers such as circulating tumor DNA (ctDNA), microRNA (miRNA), and proteins. To be effective in screening in clinical settings, these biosensors must be simple and easy to use. In this study, we have studied the manipulation of short DNA molecules suspended in a sessile drop to achieve this goal. Alternative current (AC) electric fields were used to polarize DNA molecules and produce dielectrophoretic (DEP) force on DNA molecules. DEP force is used to manipulate polarized DNA molecules towards the higher electric field gradients (toward the …

Deep Learning In Lung Cancer Pre- And Post-Radiation Therapy: Diagnosis Of Malignancy And Radiation-Induced Lung Injury From 3d X-Ray Ct., Benjamin Peter Veasey

Electronic Theses and Dissertations

Lung cancer remains the leading cause of cancer-related mortality worldwide, with early detection and accurate diagnosis being critical for improving patient outcomes. Additionally, the progression of Radiation-Induced Lung Injury (RILI) following Stereotactic Body Radiation Therapy (SBRT) for lung cancer presents a significant diagnostic challenge. This dissertation addresses these challenges by developing deep learning-based diagnostic tools for both pre-treatment lung nodule malignancy classification and post-treatment RILI identification using 3D X-ray CT imaging. The research is divided into two primary objectives. First, for lung nodule malignancy classification, we developed a biopsy-confirmed dataset, called NLSTx, to train and evaluate deep learning models while …

Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

No abstract provided.

Advancing Electrical Stimulation: Full-Head Mri Segmentation For Abnormal Brain Anatomy With Tdcs, Andrew Birnbaum

Dissertations and Theses

Evaluating the effectiveness of transcranial direct current stimulation (tDCS) is essential for guiding its integration into therapeutic and performance-enhancement applications. In our laboratory, we investigate the efficacy of tDCS across multiple experimental models, including both animal and human studies. I have contributed significantly to the execution and analysis of these experiments, which include studies in rats and healthy human participants aimed at evaluating whether electrical stimulation of the motor cortex can enhance motor learning. These studies assess improvements in fine motor performance resulting from tDCS. In stroke patients, I contribute to our investigation of tDCS as a rehabilitative intervention, particularly …

A Method For Ultrasound Servo Tracking For Puncture Needle, Shitong Ye, Bo Yang, Hao Quan, Shan Liu, Minyu Tang, Jiawei Tian

Electrical & Computer Engineering Faculty Publications

Computer-aided surgical navigation technology helps and guides doctors to complete the operation smoothly, which simulates the whole surgical environment with computer technology, and then visualizes the whole operation link in three dimensions. At present, common image-guided surgical techniques such as computed tomography (CT) and X-ray imaging (X-ray) will cause radiation damage to the human body during the imaging process. To address this, we propose a novel Extended Kalman filter-based model that tracks the puncture needle-point using an ultrasound probe. To address the limitations of Kalman filtering methods based on position and velocity, our method of Kalman filtering uses the position …

Cochlear Electrode Insertion Training Model, Sarah Powell, Kaelyn E. Kraley, Nathan J. Smith

Williams Honors College, Honors Research Projects

Cochlear implant surgery is a delicate procedure performed by Otolaryngologists (ENTs) to implant an electronic device into the inner ear to provide a sense of sound for people who are profoundly deaf or hard of hearing. The current practices of training involve cadavers and 3D-printed models. Cadavers are commonly used but are expensive, single-use, and do not provide visual and haptic feedback, which are essential for medical students. 3D printed models are less commonly used and are hard to fabricate and not as realistic. If medical students are not properly trained for this delicate procedure, then risks are significantly increased …

Hypoxic Incubator: Improving Robustness/Reliability And Demonstrating Physiological Efficacy, Damon Dennis Tan

Master's Theses

The Microphysiological Systems Laboratory aims to develop colorectal cancer tumor models under a hypoxic environment to assess model response to pharmaceutical compounds in vitro. To perform relevant studies, researchers have attempted to use different hypoxic inducing strategies such as a nitrogen pod and hypoxic incubator to recreate in vivo physiological responses to hypoxia. However, studies would be interrupted due to incubator functionality failure. To ensure successful and physiologically relevant studies, I improved and verified the robustness and reliability of a hypoxic incubator previously designed and manufactured in the lab. Through the testing and iterating design processes, I engineered and implemented …

Denoising And Super-Resolution Of In-Vitro 4e Flow Mri In A Stenotic Phantom Model Using Physics-Informed Neural Networks., Shrouk M. Wally

Electronic Theses and Dissertations

In recent years, the use of 4D flow MRI has revolutionized cardiovascular imag- ing by providing comprehensive data on blood flow dynamics over time. However, the limited spatial and temporal resolution of this imaging modality can hinder the accurate assessment of complex hemodynamic phenomena. This thesis explores the application of Physics-Informed Neural Networks (PINNs) to enhance the resolution of 4D flow MRI data, thereby improving its clinical utility. PINNs are a class of neural networks that integrate physical laws into their training process. By embedding these physics equations, PINNs can discover the underlying physics of fluid dynamics to produce more …

Segmentation And Classification Of Left Ventricular Abnormalities In Cardiac Mri Using Initial Point Prediction Based Deformable Model, Md. Asadur Rahman, Md. Al Noman, A. B. M. Aowlad Hossain

Future Computing and Informatics Journal

The shape of the left ventricle (LV) of a cardiac magnetic resonance image (CMRI) helps physicians to diagnose different cardiac abnormalities. The similarity of pixel intensity and shape of LV with neighbor tissues, the imprecision of boundaries, and the presence of noise are the challenges to accurate segmentation of LV. This paper contributes to the successful implementation of an automatic edge contouring method to segment LV area from CMRI and detect whether the ventricle belongs to abnormalities. This method proposes the regression-based artificial neural network to predict the possible initial position of the deformable edge-based active contour model for precise …

Single-Molecule Orientation Imaging Reveals The Nano-Architecture Of Amyloid Fibrils Undergoing Growth And Decay, Brian Sun, Tianben Ding, Weiyan Zhou, Tara S. Porter, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Amyloid-beta (Aβ42) aggregates are characteristic Alzheimer’s disease signatures, but probing how their nanoscale architectures influence their growth and decay remains challenging using current technologies. Here, we apply time-lapse single-molecule orientation-localization microscopy (SMOLM) to measure the orientations and rotational “wobble” of Nile blue (NB) molecules transiently binding to Aβ42 fibrils. We correlate fibril architectures measured by SMOLM with their growth and decay over the course of 5 to 20 min visualized by single-molecule localization microscopy (SMLM). We discover that stable Aβ42 fibrils tend to be well-ordered and signified by well-aligned NB orientations and small wobble. SMOLM also shows that increasing order …

Resolving The Nanoscale Structure Of Β-Sheet Peptide Self-Assemblies Using Single-Molecule Orientation–Localization Microscopy, Weiyan Zhou, Conor L. O'Neill, Tianben Ding, Oumeng Zhang, Jai S. Rudra, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Synthetic peptides that self-assemble into cross-β fibrils are versatile building blocks for engineered biomaterials due to their modularity and biocompatibility, but their structural and morphological similarities to amyloid species have been a long-standing concern for their translation. Further, their polymorphs are difficult to characterize using spectroscopic and imaging techniques that rely on ensemble averaging to achieve high resolution. Here, we utilize Nile red (NR), an amyloidophilic fluorogenic probe, and single-molecule orientation-localization microscopy (SMOLM) to characterize fibrils formed by the designed amphipathic enantiomers KFE8^L and KFE8^D and the pathological amyloid-beta peptide Aβ42. Importantly, NR SMOLM reveals the helical (bilayer) …

6d Single-Fluorogen Orientation-Localization Microscopy For Elucidating The Architecture Of Beta-Sheet Assemblies And Biomolecular Condensates, Tingting Wu, Weiyan Zhou, Jai S. Rudra, Rohit V. Pappu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

We develop six-dimensional single-molecule orientation-localization microscopy (SMOLM) to measure the 3D positions and 3D orientations simultaneously of single fluorophores. We show how careful optimization of phase and polarization modulation components can encode phase, polarization, and angular spectrum information from each fluorescence photon into a microscope’s dipole-spread function. We used the transient binding and blinking of Nile red (NR) to characterize the helical structure of fibrils formed by designed amphipathic peptides, KFE8^L and KFE8^D, and the pathological amyloid-beta peptide Aβ42. We also deployed merocyanine 540 to uncover the interfacial architectures of biomolecular condensates.

Multi-Magnetic Material Transcranial Magnetic Stimulation Coils Development And Electric Field Measurement & Modeling Using Machine Learning, Mohannad Tashli

Theses and Dissertations

Transcranial Magnetic Stimulation (TMS) is a safe, effective, and non-invasive therapy for treating several psychiatric and neurological disorders. TMS is Food and Drug Administration (FDA) approved treatment and is commonly applied to patients who do not respond to medications for the treatment of clinical depression, smoking cessation, obsessive-compulsive disorder and migraine. Recently, there has been an increase in the development of electromagnetic neuromodulation techniques targeted at enhancing the effectiveness of TMS devices for the treatment of mental diseases. In TMS stimulation, focality is an important factor which determines the specificity of the pulses induced in different brain tissues. The electromagnetic …

Domain Adaptive Federated Learning For Multi-Institution Molecular Mutation Prediction And Bias Identification, W. Farzana, M. A. Witherow, I. Longoria, M. S. Sadique, A. Temtam, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Deep learning models have shown potential in medical image analysis tasks. However, training a generalized deep learning model requires huge amounts of patient data that is usually gathered from multiple institutions which may raise privacy concerns. Federated learning (FL) provides an alternative to sharing data across institutions. Nonetheless, FL is susceptible to a few challenges including inversion attacks on model weights, heterogenous data distributions, and bias. This study addresses heterogeneity and bias issues for multi-institution patient data by proposing domain adaptive FL modeling using several radiomics (volume, fractal, texture) features for O6-methylguanine-DNA methyltransferase (MGMT) classification across multiple institutions. The proposed …

Design Of Asic Based Electrical Impedance Tomography Microendoscopic System For Prostate Cancer Surgical Marginal Assessment, Mohsen Shahghasemi

Dartmouth College Ph.D Dissertations

Prostate cancer is the second most common cancer in the United States. It is typically treated by surgically excising the cancerous section of the prostate. Because there is not always a visible distinction between the healthy and cancerous sections, surgery often leaves some cancerous tissue behind. This is referred to as a positive surgical margin and it requires adjuvant treatment with adverse side effects. Electrical impedance tomography (EIT) is a low-cost low-form-factor method that can be used to assess surgical marginal intraoperatively to ensure that no cancerous tissue is left behind. EIT-based surgical margin assessment works on the principle that …

List Of 121 Papers Citing One Or More Skin Lesion Image Datasets, Neda Alipour

Other resources

No abstract provided.

Portable Diffuse Reflectance Spectroscopy For Non-Invasive And Quantitative Assessment Of The Parathyroid Glands Viability During Surgery, Mark Romine, Linh Luong, Alex Moazzen, Katie Cho, Paul Lee

Symposium of Student Scholars

Portable Diffuse Reflectance Spectroscopy for Non-invasive and Quantitative Assessment of the Parathyroid Glands Viability During Surgery

Mark Romine, Linh Luong, Alex Moazzen, Katie Cho and Paul Lee

The parathyroid glands (PTGs) are responsible for the regulation of calcium levels in the blood by secreting a parathyroid hormone. This parathyroid hormone then regulates the body’s absorption, storage, and secretion of calcium, which can directly affect the way muscles and nerves operate. PTGs are often at risk of damage, or accidental removal during thyroid surgeries, because it is challenging to identify PTGs and to determine their viability. Current methods of visual inspections …

Wireless, Handheld Diffuse Reflectance Spectroscopy To Quantify Tissue Microvascular Hemodynamics, Linh Luong, Alex Moazzen, Mark Romine, Katie Cho, Paul Lee

Symposium of Student Scholars

Diffuse Reflectance Spectroscopy (DRS) is a non-invasive optical method to characterize tissue optical properties for disease diagnosis and health monitoring. Two optical fibers are often used in a DRS system: one to deliver light to the tissue and the other to gather diffuse reflectance spectra, which provide quantitative details about the structure and composition of the tissue. The conventional DRS system, however, is expensive, bulky, and composed of fragile optical fibers and multiple electrical connections. Here we propose to build a wireless, handheld, and fiber-less diffuse optical spectroscopy system. Unfortunately, the diffusion approximation utilized for data analysis of the conventional …

Computational Design Of Fiber-Optic Probes For Biosensing, Suwarna Karna

Electrical Engineering Theses

This thesis presents a study on the optical characteristics of hollow-core photonic crystal fibers (HC-PCFs) with a band gap cladding structure and their applications in optical fiber sensing. This 800B HC-PCF exhibited excellent optical properties and has a flexible structure, which makes them suitable for a wide range of industrial applications. Finite element simulations and structural optimization designs were conducted using the surface plasmon resonance (SPR) technique to determine the optimal performance parameters of the 800B HC-PCF. The fiber was further modified using the SPR technique to improve its practical detection capabilities. The performance of the modified fiber was observed …

Efficient Scopeformer: Towards Scalable And Rich Feature Extraction For Intracranial Hemorrhage Detection Using Hybrid Convolution And Vision Transformer Networks, Yassine Barhoumi

Theses and Dissertations

The field of medical imaging has seen significant advancements through the use of artificial intelligence (AI) techniques. The success of deep learning models in this area has led to the need for further research. This study aims to explore the use of various deep learning algorithms and emerging modeling techniques to improve training paradigms in medical imaging. Convolutional neural networks (CNNs) are the go-to architecture for computer vision problems, but they have limitations in mapping long-term dependencies within images. To address these limitations, the study explores the use of techniques such as global average pooling and self-attention mechanisms. Additionally, the …

Ultrasensitive Tapered Optical Fiber Refractive Index, Erem Ujah, Meimei Lai, Gymama Slaughter

Electrical & Computer Engineering Faculty Publications

Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate highly sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5-45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due …

Small-Separation Speckle Contrast Optical Spectroscopy For Intraoperative Assessment Of Parathyroid Glands Viability During Thyroid Surgery, Connor Berger

Symposium of Student Scholars

The parathyroid glands (PTGs) are often damaged during thyroid surgeries due to a lack of methods identifying PTGs and assessing their viability. Damage to PTGs can cause hypocalcemia, a deficiency of calcium in the body. This complication can lead to detrimental consequences with economic burden. The surgeon’s current method of viability assessment is qualitative and subjective. Our technical solution is to employ an optical technique called speckle contrast optical spectroscopy (SCOS) that noninvasively quantifies the blood flow index (Db) of biological tissues at deep tissue levels (>1cm). The goal of this project is to verify SCOS at small source-detector-separation …

Six-Dimensional Single-Molecule Imaging With Isotropic Resolution Using A Multi-View Reflector Microscope, Oumeng Zhang, Zijian Guo, Yuanyuan He, Tingting Wu, Michael D. Vahey, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Imaging of both the positions and orientations of single fluorophores, termed single-molecule orientation-localization microscopy, is a powerful tool for the study of biochemical processes. However, the limited photon budget associated with single-molecule fluorescence makes high-dimensional imaging with isotropic, nanoscale spatial resolution a formidable challenge. Here we realize a radially and azimuthally polarized multi-view reflector (raMVR) microscope for the imaging of the three-dimensional (3D) positions and 3D orientations of single molecules, with precisions of 10.9 nm and 2.0° over a 1.5-μm depth range. The raMVR microscope achieves 6D super-resolution imaging of Nile red molecules transiently bound to lipid-coated spheres, accurately resolving …

Improving The Performance And Evaluation Of Computer-Assisted Semen Analysis, Ji-Won Choi

Dissertations

Semen analysis is performed routinely in fertility clinics to analyze the quality of semen and sperm cells of male patients. The analysis is typically performed by trained technicians or by Computer-Assisted Semen Analysis (CASA) systems. Manual semen analysis performed by technicians is subjective, time-consuming, and laborious, and yet most fertility clinics perform semen analysis in this manner. CASA systems, which are designed to perform the same tasks automatically, have a considerable market share, yet many studies still express concerns about their accuracy and consistency. In this dissertation, the focus is on detection, tracking, and classification of sperm cells in semen …

Assessing Structural And Functional Brain Alterations And Work-Related Fatigue In Non-Hyposmic And Hyposmic Covid-19 Survivors, Rakibul Hafiz

Dissertations

In the year 2019, life began to change at the advent of a global pandemic caused by the novel coronavirus. Mask mandates and mass vaccinations have mitigated the effects significantly, yet cases keep rising with new variants, especially, in densely populated countries, like India. Recent neuroimaging evidence shows the virus can attack the central nervous system (CNS). However, exactly which brain regions undergo structural and functional changes remain largely unknown. Many patients experience 'loss of/reduced sense of smell' (i.e., hyposmic) and an alarming number of survivors develop persistent symptoms ('long-COVID') for several months after initial infection. Fatigue is the most …

Resolving The Three-Dimensional Rotational And Translational Dynamics Of Single Molecules Using Radially And Azimuthally Polarized Fluorescence, Oumeng Zhang, Weiyan Zhou, Jin Lu, Tingting Wu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

We report a radially and azimuthally polarized (raPol) microscope for high detection and estimation performance in single-molecule orientation-localization microscopy (SMOLM). With 5000 photons detected from Nile red (NR) transiently bound within supported lipid bilayers (SLBs), raPol SMOLM achieves 2.9 nm localization precision, 1.5° orientation precision, and 0.17 sr precision in estimating rotational wobble. Within DPPC SLBs, SMOLM imaging reveals the existence of randomly oriented binding pockets that prevent NR from freely exploring all orientations. Treating the SLBs with cholesterol-loaded methyl-β-cyclodextrin (MβCD-chol) causes NR’s orientational diffusion to be dramatically reduced, but curiously NR’s median lateral displacements drastically increase from 20.8 to …

Design Of Miniaturized Antipodal Vivaldi Antennas And A Microwave Head Imaging System For The Detection Of Blood Clots In The Brain, Farhana Parveen

Electronic Theses and Dissertations, 2020-2023

Traditional brain imaging modalities, for example, MRI, CT scan, X-ray, etc. can provide precise and high-resolution images of the brain for diagnosing lesions, tumors or clots inside the brain. However, these modalities require bulky and expensive test setups accessible only at specialized diagnostic centers, and hence may not be suitable or affordable to many patients. Furthermore, the inherent health risks limit the usability of these modalities for frequent monitoring. Microwave imaging is deemed a promising alternative due to its being cost-effective, portable, non-ionizing, non-intrusive. Therefore, this work aims to design an effective microwave head imaging system for the detection of …