Arthur F. Gmitro

Bio: Arthur F. Gmitro is an academic researcher from University of Arizona. The author has contributed to research in topics: Confocal & Confocal microscopy. The author has an hindex of 34, co-authored 169 publications receiving 4402 citations. Previous affiliations of Arthur F. Gmitro include Yale University.

Acid-Mediated Tumor Invasion: a Multidisciplinary Study

Abstract: The acid-mediated tumor invasion hypothesis proposes altered glucose metabolism and increased glucose uptake, observed in the vast majority of clinical cancers by fluorodeoxyglucose-positron emission tomography, are critical for development of the invasive phenotype. In this model, increased acid production due to altered glucose metabolism serves as a key intermediate by producing H(+) flow along concentration gradients into adjacent normal tissue. This chronic exposure of peritumoral normal tissue to an acidic microenvironment produces toxicity by: (a) normal cell death caused by the collapse of the transmembrane H(+) gradient inducing necrosis or apoptosis and (b) extracellular matrix degradation through the release of cathepsin B and other proteolytic enzymes. Tumor cells evolve resistance to acid-induced toxicity during carcinogenesis, allowing them to survive and proliferate in low pH microenvironments. This permits them to invade the damaged adjacent normal tissue despite the acid gradients. Here, we describe theoretical and empirical evidence for acid-mediated invasion. In silico simulations using mathematical models provide testable predictions concerning the morphology and cellular and extracellular dynamics at the tumor-host interface. In vivo experiments confirm the presence of peritumoral acid gradients as well as cellular toxicity and extracellular matrix degradation in the normal tissue exposed to the acidic microenvironment. The acid-mediated tumor invasion model provides a simple mechanism linking altered glucose metabolism with the ability of tumor cells to form invasive cancers.

Confocal microscopy through a fiber-optic imaging bundle

Abstract: The concept for a new type of confocal microscope with a fiber-optic imaging bundle is presented, and experimental results are shown to demonstrate the principle. The primary advantage of the system is the flexbility of imaging samples that would otherwise be inaccessible to confocal microscopy.

Errors in the measurements of T2 using multiple-echo MRI techniques. I. Effects of radiofrequency pulse imperfections.

Abstract: In principle, multiple-echo magnetic resonance imaging (MRI) can be used to estimate the spin-spin relaxation time, T2, which can then be used for quantitative tissue characterization. Although multiple echoes can be used to enhance the signal-to-noise ratio in an image, by echo addition, rf pulse imperfections modify the echo amplitudes resulting in significant errors in the estimate of T2. Imperfect 180 degree pulses do not completely invert the transverse magnetization so that the magnitude of the transverse component is reduced and a longitudinal component is generated. Successive application of such imperfect pulses generates many components that interact in a complex manner. The amplitudes of successive echoes are affected whenever the transverse components refocus, whereas the longitudinal components may be rotated into the transverse plane by subsequent pulses and may often add to the image signal or give rise to an image artifact. These effects have been analyzed theoretically and have been demonstrated for a wide range of rf pulse imperfections using both simple and composite pulses, through computer simulations based on the numerical solution of the Bloch equations. The theoretical and simulation results have been substantiated through experiments performed on a mineral oil phantom using a resistive prototype MR scanner operating at 6.35 MHz. In this paper we report the effects of improper pulse amplitude or duration for nonselective rf pulses on resonance. We separately describe the other types of imperfections caused by off-resonance effects and the use of selective pulses.

Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology

Abstract: To correlate the amount of bone marrow edema (BME) calculated by magnetic resonance imaging(MRI) with clinical findings, histopathology, and radiographic findings, in patients with advanced hip osteoarthritis(OA). The study was approved by The Institutional Human Subject Protection Committee. Coronal MRI of hips was acquired in 19 patients who underwent hip replacement. A spin echo (SE) sequence with four echoes and separate fast spin echo (FSE) proton density (PD)-weighted SE sequences of fat (F) and water (W) were acquired with water and fat suppression, respectively. T2 and water:fat ratio calculations were made for the outlined regions of interest. The calculated MRI values were correlated with the clinical, radiographic, and histopathologic findings. Analyses of variance were done on the MRI data for W/(W + F) and for T2 values (total and focal values) for the symptomatic and contralateral hips. The values were significantly higher in the study group. Statistically significant correlations were found between pain and total W/(W + F), pain and focal T2 values, and the number of microfractures and calculated BME for the focal W/(W + F) in the proximal femora. Statistically significant correlations were found between the radiographic findings and MRI values for total W/(W + F), focal W/(W + F) and focal T2 and among the radiographic findings, pain, and hip movement. On histopathology, only a small amount of BME was seen in eight proximal femora. The amount of BME in the OA hip, as measured by MRI, correlates with the severity of pain, radiographic findings, and number of microfractures.

Slit-scanning confocal microendoscope for high-resolution in vivo imaging

Abstract: We discuss the design and construction of a novel imaging system in which a fiber-optic imaging bundle and miniature optical and mechanical components are used to allow confocal fluorescence microscopy in remote locations. The instrumentation has been developed specifically for cellular examination of tissue for optical biopsy. Miniaturization of various components makes the device usable in a clinical setting. The numerical aperture of the beam in the tissue is 0.5, and the field of view is 430 µm. The measured lateral resolution of the system is 3.0 µm. The axial point and the axial planar response functions of the confocal system were measured with a FWHM of 10 and 25 µm, respectively. In vitro and in vivo images obtained with cell cultures, human tissue specimens, and animal models indicate that the performance of the device is adequate for microscopic evaluation of cells.

Multi-Ethnic Study of Atherosclerosis: Objectives and Design

Abstract: The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.

Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis

Abstract: Fatty acid synthase (FASN) catalyses the synthesis of fatty acids, and this synthetic pathway is upregulated in many tumours. How might FASN and increased lipogenesis be involved in cancer, and is FASN a valid therapeutic target? There is a renewed interest in the ultimate role of fatty acid synthase (FASN) — a key lipogenic enzyme catalysing the terminal steps in the de novo biogenesis of fatty acids — in cancer pathogenesis. Tumour-associated FASN, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, appears to necessarily accompany the natural history of most human cancers. A recent identification of cross-talk between FASN and well-established cancer-controlling networks begins to delineate the oncogenic nature of FASN-driven lipogenesis. FASN, a nearly-universal druggable target in many human carcinomas and their precursor lesions, offers new therapeutic opportunities for metabolically treating and preventing cancer.

A survey of the Hough transform

Abstract: We present a comprehensive review of the Hough transform, HT, in image processing and computer vision. It has long been recognized as a technique of almost unique promise for shape and motion analysis in images containing noisy, missing, and extraneous data but its adoption has been slow due to its computational and storage complexity and the lack of a detailed understanding of its properties. However, in recent years much progress has been made in these areas. In this review we discuss ideas for the efficient implementation of the HT and present results on the analytic and empirical performance of various methods. We also report the relationship of Hough methods and other transforms and consider applications in which the HT has been used. It seems likely that the HT will be an increasingly used technique and we hope that this survey will provide a useful guide to quickly acquaint researchers with the main literature in this research area.

Osteoarthritis: A Disease of the Joint as an Organ

Abstract: Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1) Often OA is referred to as degenerative joint disease “(DJD)” This is a misnomer because OA is not simply a process of wear and tear but rather abnormal remodeling of joint tissues driven by a host of inflammatory mediators within the affected joint The most common risk factors for OA include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors, including malalignment and abnormal joint shape (2, 3) Despite the multifactorial nature of OA, the pathological changes seen in osteoarthritic joints have common features that affect the entire joint structure resulting in pain, deformity and loss of function The pathologic changes seen in OA joints (Figures 1 and ​and2)2) include degradation of the articular cartilage, thickening of the subchondral bone, osteophyte formation, variable degrees of synovial inflammation, degeneration of ligaments and, in the knee, the menisci, and hypertrophy of the joint capsule There can also be changes in periarticular muscles, nerves, bursa, and local fat pads that may contribute to OA or the symptoms of OA The findings of pathological changes in all of the joint tissues are the impetus for considering OA as a disease of the joint as an organ resulting in “joint failure” In this review, we will summarize the key features of OA in the various joint tissues affected and provide an overview of the basic mechanisms currently thought to contribute to the pathological changes seen in these tissues Open in a separate window Figure 1 Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow) Image courtesy of Drs Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY