Timothy Muldoon

Timothy Muldoon
University of Arkansas | U of A · Department of Biomedical Engineering

M.D., Ph.D.

About

77
Publications
7,033
Reads
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971
Citations
Citations since 2016
47 Research Items
627 Citations
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
Additional affiliations
August 2012 - present
University of Arkansas
Position
  • Professor (Assistant)
August 2012 - present
University of Arkansas
Position
  • Professor (Assistant)
August 2012 - present
University of Arkansas
Position
  • Professor (Assistant)

Publications

Publications (77)
Article
Full-text available
Metronomic chemotherapy (MET) has been developed to address the shortcomings of maximum-tolerated chemotherapy (MTD) in regard to toxicity and development of resistance mechanisms in the tumor. In colorectal cancer (CRC), MET is a promising novel strategy to treat locally advanced malignancies when used as neoadjuvant chemotherapy (NAC). However, s...
Article
In biomedical research, the outcome of longitudinal studies has been traditionally analyzed using the repeated measures analysis of variance (rm‐ANOVA) or more recently, linear mixed models (LMEMs). Although LMEMs are less restrictive than rm‐ANOVA as they can work with unbalanced data and non‐constant correlation between observations, both methodo...
Article
Full-text available
Ulcerative colitis (UC) is a gastrointestinal, autoimmune disease that causes ulceration and inflammation of the colon with an incidence 10 out of every 100,000 people in North America and Western Europe. Though the specific cause is unknown, several studies have demonstrated that inflammatory cells as well as environmental variables, genetics, and...
Article
Full-text available
Background Immunotherapy in colorectal cancer (CRC) regulates specific immune checkpoints and, when used in combination with chemotherapy, can improve patient prognosis. One specific immune checkpoint is the recruitment of circulating monocytes that differentiate into tumor-associated macrophages (TAMs) and promote tumor angiogenesis. Changes in va...
Preprint
Full-text available
Metronomic chemotherapy (MET) has been developed to address the shortcomings of maximum-tolerated chemotherapy (MTD) in regard to toxicity and development of resistance mechanisms in the tumor. In colorectal cancer (CRC), MET is a promising novel strategy to treat locally advanced malignancies when used as neoadjuvant chemotherapy (NAC). However, s...
Conference Paper
Purpose: Colorectal cancer is the fourth most common cancer in the United States, accounting for more than 50,000 deaths annually1. The standard treatment is 5-fluorouracil (5-FU)-based chemotherapy, but emerging methods of immunotherapy have gained the attention of investigators and clinicians. A specific cytokine-based strategy for immunotherapy...
Preprint
Ulcerative colitis (UC) is a gastrointestinal, autoimmune disease that causes ulceration and inflammation of the colon with an incidence 10 out of every 100,000 people in North America and Western Europe. Though the exact etiology is uncertain, a number of studies have shown that inflammatory cells along with environmental factors, genetics, and li...
Preprint
Full-text available
In biomedical research, the outcome of longitudinal studies has been traditionally analyzed using the repeated measures analysis of variance (rm-ANOVA) or more recently, linear mixed models (LMEMs). Although LMEMs are less restrictive than rm-ANOVA in terms of correlation and missing observations, both methodologies share an assumption of linearity...
Article
Magnetohydrodynamics (MHD) is a unique approach for pumping fluids on a microscale and is highly suitable for enabling multiple functions for chemical analysis on a chip. An ionic current, j , is established in the fluid between selectively-activated electrodes in the presence of a magnetic field, B , that is perpendicular to the current, to genera...
Article
Full-text available
Low-cost imaging systems that utilize exogenous fluorescent dyes, such as acridine orange (AO), have recently been developed for use as point-of-care (POC) blood analyzers. AO-based fluorescence imaging exploits variations in emission wavelength within different cell types to enumerate and classify leukocyte subpopulations from whole blood specimen...
Article
Full-text available
Background Calcific aortic valve disease (CAVD) pathophysiology is a complex, multistage process, usually diagnosed at advanced stages after significant anatomical and hemodynamic changes in the valve. Early detection of disease progression is thus pivotal in the development of prevention and mitigation strategies. In this study, we developed a die...
Article
Full-text available
Significance: Many studies in colorectal cancer (CRC) use murine ectopic tumor models to determine response to treatment. However, these models do not replicate the tumor microenvironment of CRC. Physiological information of treatment response derived via diffuse reflectance spectroscopy (DRS) from murine primary CRC tumors provide a better unders...
Conference Paper
A densely-packed, custom multi-pixel photodetector probe permits spatially resolved diffuse reflectance (SRDR) measurements of phantoms of varying thicknesses, showing high signal contrast between thin phantoms and high depth sensitivity.
Article
Full-text available
Colorectal cancer (CRC) is the fourth most common cancer type and is the second leading cause of cancer deaths annually in the United States. Conventional treatment options include postoperative (adjuvant) and preoperative (neoadjuvant) chemotherapy and radiotherapy. Although these treatment modalities have shown to decrease tumor burden, a major l...
Article
Full-text available
A urinary tract infection (UTI) can be diagnosed via urinalysis, consisting of a dipstick test and manual microscopic examination. Point-of-care (POC) image-based systems have been designed to automate the microscopic examination for low-volume laboratories or low-resource clinics. In this pilot study, acridine orange (AO) was evaluated as a fluore...
Article
Full-text available
Background Colorectal cancer remains the second leading cause of cancer death in the United States, and increased risk in patients with ulcerative colitis (a subset of inflammatory bowel disease) has motivated studies into early markers of dysplasia. The development of clinically translatable multiphoton imaging systems has allowed for the potentia...
Article
Diffuse reflectance spectroscopy (DRS) is a probe-based spectral biopsy technique used in cancer studies to quantify tissue reduced scattering (μs') and absorption (μa) coefficients and vary in source-detector separation (SDS) to fine-tune sampling depth. In subcutaneous murine tumor allografts or xenografts, a key design requirement is ensuring th...
Article
Spatial frequency domain imaging (SFDI) is a widefield, noncontact, and label-free imaging modality that is currently being explored as a new tool for longitudinal tracking of cancer therapies in the preclinical setting. We describe a two-layer look-up-table (LUT) inversion algorithm for SFDI that better accounts for the skin (top layer) and tumor...
Article
We present the merging of two technologies to perform continuous high-resolution fluorescence imaging of cellular suspensions in a deep microfluidics chamber with no moving parts. An epitaxial light sheet confocal microscope (e-LSCM) was used to image suspensions enabled by fluid transport via redox-magnetohydrodynamics (R-MHD). The e-LSCM features...
Article
Diffuse reflectance spectroscopy (DRS) has been used in murine studies to quantify tumor perfusion and therapeutic response. These studies frequently use inhaled isoflurane anesthesia, which depresses the respiration rate and results in the desaturation of arterial oxygen saturation, potentially affecting tissue physiological parameters. However, t...
Article
Full-text available
Fiber bundle microendoscopic imaging of colorectal tissue has shown promising results, for both qualitative and quantitative analysis. A quantitative image quality control and image feature extraction algorithm was previously designed for quantitative image feature analysis of proflavine-stained ex vivo colorectal tissue. We investigated fluorescei...
Article
There exists a broad range of techniques that can be used to classify and count white blood cells in a point-of-care (POC) three-part leukocyte differential test. Improvements in lenses, light sources, and cameras for image-based POC systems have renewed interest in acridine orange (AO) as a contrast agent, whereby subpopulations of leukocytes can...
Conference Paper
We present a light sheet confocal microscope (LSCM) capable of high-resolution imaging of cell suspensions in a microfluidic environment. In lieu of conventional pressure-driven flow or mechanical translation of the samples, we have employed a novel method of fluid transport, redox-magnetohydrodynamics (redox-MHD). This method achieves fluid motion...
Conference Paper
Point-of-care approaches for 3-part leukocyte differentials (granulocyte, monocyte, and lymphocyte), traditionally performed using a hematology analyzer within a panel of tests called a complete blood count (CBC), are essential not only to reduce cost but to provide faster results in low resource areas. Recent developments in lab-on-a-chip devices...
Article
The development of prognostic indicators of breast cancer metastatic risk could reduce the number of patients receiving chemotherapy for tumors with low metastatic potential. Recent evidence points to a critical role for cell metabolism in driving breast cancer metastasis. Endogenous fluorescence intensity of nicotinamide adenine dinucleotide (NADH...
Article
Recent fiber-bundle microendoscopy techniques enable non-invasive analysis of in vivo tissue using either imaging techniques or a combination of spectroscopy techniques. Combining imaging and spectroscopy techniques into a single optical probe may provide a more complete analysis of tissue health. In this article, two dissimilar modalities are comb...
Article
Full-text available
The role of valvular interstitial cell (VIC) architecture in regulating cardiac valve function and pathology is not well understood. VICs are known to be more elongated in a hypertensive environment compared to those in a normotensive environment. We have previously reported that valve tissues cultured under hypertensive conditions are prone to acu...
Article
Qualitative screening for colorectal polyps via fiber bundle microendoscopy imaging has shown promising results, with studies reporting high rates of sensitivity and specificity, as well as low interobserver variability with trained clinicians. A quantitative image quality control and image feature extraction algorithm (QFEA) was designed to lessen...
Article
Full-text available
Intraepithelial dysplasia of the oral mucosa typically originates in the proliferative cell layer at the basement membrane and extends to the upper epithelial layers as the disease progresses. Detection of malignancies typically occurs upon visual inspection by non-specialists at a late-stage. In this manuscript, we validate a quantitative hybrid i...
Conference Paper
Spatially–resolved diffuse reflectance (SRDR) measurements provide photon path information, and enable layered tissue analysis. This paper presents experimental SRDR measurements on two-layer PDMS skin tissue-mimicking phantoms of varying top layer thicknesses, and bulk phantoms of varying optical properties using concentric multi-pixel photodiode...
Conference Paper
Two-photon excitation of label-free tissue is of increasing interest, as advances have been made in endoscopic clinical application of multiphoton microscopy, such as second harmonic generation (SHG) scanning endoscopy used to monitor cervical collagen in mice¹. We used C57BL mice as a model to investigate the progression of gastrointestinal struct...
Conference Paper
In the non-keratinized epithelia, dysplasia typically arises near the basement membrane and proliferates into the upper epithelial layers over time. We present a non-invasive, multimodal technique combining high-resolution fluorescence imaging and broadband sub-diffuse reflectance spectroscopy (sDRS) to monitor health at various tissue layers. This...
Article
Full-text available
Resistance to conventional antibiotics is a growing public health concern that is quickly out-pacing the development of new antibiotics. This has led the Infectious Diseases Society of America (IDSA) to designate Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spe...
Article
Early detection of structural or functional changes in dysplastic epithelia may be crucial for improving long-term patient care. Recent work has explored myriad non-invasive or minimally invasive "optical biopsy" techniques for diagnosing early dysplasia, such as high-resolution microendoscopy, a method to resolve sub-cellular features of apical ep...
Chapter
Noble metal nanostructures are appealing for therapeutic, diagnostics, and sensing applications because of their unique optical properties and biocompatibility. The collective oscillation of electrons in a metal nanostructure resonates with particular wavelengths of light, generating the localized surface plasmon resonance (LSPR). The LSPR results...
Conference Paper
Full-text available
Imaging cells in a microfluidic chamber with an area scan camera is difficult due to motion blur and data loss during frame readout causing discontinuity of data acquisition as cells move at relatively high speeds through the chamber. We have developed a method to continuously acquire high-resolution images of cells in motion through a microfluidic...
Article
Full-text available
Linear image sensors have been widely used in numerous research and industry applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was characterized for a custom microfluidic chamb...
Article
Full-text available
Proflavine hemisulfate, an acridine-derived fluorescent dye, can be used as a rapid stain for cytologic examination of biological specimens. Proflavine fluorescently stains cell nuclei and cytoplasmic structures, owing to its small amphipathic structure and ability to intercalate DNA. In this manuscript, we demonstrated the use of proflavine as a r...
Article
A decrease in white blood cell count below the normal range is known as leucopenia. Neutropenia is an absolute neutrophil count of less than 1500 cells per microliter of blood. This is the most common and clinically significant form of leucopenia. In cases where patients have a count of less than 500 cells per microliter of blood, the body’s normal...
Article
An important need in miniaturizing technology for applications in point-of-care medicine and environmental monitoring is the ability to manipulate small volumes of fluids to perform sample preparation and multiple steps for chemical analysis in an automated fashion. We are pioneering the use of magnetohydrodynamics (MHD) for this purpose, which off...
Article
Full-text available
Colorectal cancer is the second leading cause of cancer deaths in the United States, affecting more than 130,000 Americans every year(1). Determining tumor margins prior to surgical resection is essential to providing optimal treatment and reducing recurrence rates. Colorectal cancer recurrence can occur in up to 20% of cases, commonly within three...
Article
Due to their robust optical properties, biological inertness, and readily adjustable surface chemistry, gold nanostructures have been demonstrated as contrast agents in a variety of biomedical imaging applications. One application is dynamic imaging of live cells using bioconjugated gold nanoparticles to monitor molecule trafficking mechanisms with...
Conference Paper
Many cases of epithelial cancer originate in basal layers of tissue and are initially undetected by conventional microendoscopy techniques. We present a bench-top, fiber-bundle microendoscope capable of providing high resolution images of surface cell morphology. Additionally, the microendoscope has the capability to interrogate deeper into materia...
Article
Optical phantoms are used in the development of various imaging systems. For certain applications, the development of thin phantoms that simulate the physical size and optical properties of tissue is important. Here, we demonstrate a method for producing thin phantom layers with tunable optical properties using poly(dimethylsiloxane) (PDMS) as a su...
Conference Paper
Fiber bundle microendoscopy has shown promise as a point-of-care imaging system for epithelial dysplasia visualization. Here we present the use of this technology as a means to characterize lesions in colorectal cancer.
Conference Paper
An optofluidics screening system as a point-of-care tool for early disease detection in low-resource settings. The current prototype uses a high-speed fluorescence microscope and microfluidics to image fluorescently stained oral cells in suspension.
Conference Paper
A method for producing thin film PDMS optical phantoms using a spin coater can be used to simulate epithelial tissues. These PDMS phantoms may be used to evaluate the performance and depth sensitivity of optical imaging systems.
Conference Paper
Techniques for capturing functional information from the living brain including high-speed multispectral optical intrinsic signal imaging (MS-OISI) and dual-beam in-vivo two-photon microscopy, and their applications to understanding brain blood flow control will be described.
Article
Full-text available
Evaluation of suspicious skin lesions by dermatologists is usually accomplished using white light examination and direct punch or surgical biopsy. However, these techniques can be imprecise for estimating a lesion's margin or level of dermal invasion when planning surgical resection. Laminar optical tomography (LOT) is an imaging technique capable...
Article
Full-text available
The purpose of this study was to evaluate the ability of high-resolution microendoscopy to image and quantify changes in cellular and architectural features seen in early oral neoplasia in vivo. A high-resolution microendoscope (HRME) was used to image intact, resected oral squamous carcinoma specimens. HRME images were reviewed and classified as n...
Article
Confocal endomicroscopy has revolutionized endoscopy by offering subcellular images of the GI epithelium; however, the field of view is limited. Multiscale endoscopy platforms that use widefield imaging are needed to better direct the placement of high-resolution probes. Feasibility study. This study evaluated the feasibility of a single agent, pro...
Article
Full-text available
This prospective pilot study evaluates the potential of high-resolution fiber optic microscopy (HRFM) to identify lymph node metastases in breast cancer patients. 43 lymph nodes were collected from 14 consenting breast cancer patients. Proflavine dye was topically applied to lymph nodes ex vivo to allow visualization of nuclei. 242 images were coll...
Article
Full-text available
Early detection of neoplasia in patients with Barrett's esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barrett's esophagus. Nine patients with pathologically confirmed Barr...
Conference Paper
This ex vivo study evaluates widefield and high-resolution fluorescence imaging with vital-dye enhancement to improve endoscopic evaluation of metaplasia, dysplasia, and cancer in the gastrointestinal tract. Differences in epithelial features were observed.
Article
Background: Early detection of dysplasia and cancer in the oral cavity dramatically improves patient survival, however, early stage disease can be difficult to identify with a conventional oral examination. Non-invasive, molecular-specific optical imaging has the potential to rapidly and simultaneously assess expression of multiple biomarkers that...
Article
This report describes the clinical evaluation of a novel, low-cost, high-resolution endoscopic microscope for obtaining fluorescent images of the cellular morphology of the epithelium of regions of the esophagus with Barrett's metaplasia. This noninvasive point imaging system offers a method for obtaining real-time histologic information during end...
Conference Paper
A simple and robust fiber bundle microendoscope can be used for high-resolution contact imaging within living tissue. Combining this technique with molecular imaging strategies enables monitoring of biological systems over time at the subcellular level.
Article
Full-text available
Conventional histopathology involves sampling, sectioning and staining of tissue specimens prior to microscopic evaluation, and provides diagnostic information at a single location and point in time. In vivo microscopy and molecular-targeted optical labeling are two rapidly developing fields, which together have the potential to provide anatomical...

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