Two-Photon Autofluorescence Imaging of Fixed Tissues: Feasibility and Potential Values for Biomedical Applications.

The value of optical redox imaging (ORI) of cells/tissues based on the intrinsic fluorescences of NADH (nicotinamide adenine dinucleotide) and oxidized flavoproteins (containing flavin adenine dinucleotide, i.e., FAD) has been demonstrated for potential biomedical applications including diagnosis, prognosis, and determining treatment response.

Optical Redox Imaging of Fixed Unstained Muscle Slides Reveals Useful Biological Information.

Purpose: Optical redox imaging (ORI) technique images cellular autofluorescence of nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp containing FAD, i.e., flavin adenine dinucleotide).

Two-channel autofluorescence analysis for oral cancer.

We created a two-channel autofluorescence test to detect oral cancer. The wavelengths 375 and 460 nm, with filters of 479 and 525 nm, were designed to excite and detect reduced-form nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) autofluorescence. Patients with oral cancer or with precancerous lesions, and a control group with healthy oral mucosae, were enrolled.

Novel quantitative analysis of autofluorescence images for oral cancer screening.

Objectives: VELscope® was developed to inspect oral mucosa autofluorescence. However, its accuracy is heavily dependent on the examining physician's experience. This study was aimed toward the development of a novel quantitative analysis of autofluorescence images for oral cancer screening.

Continuous Wave Spectroscopy with Diffusion Theory for Quantification of Optical Properties: Comparison Between Multi-distance and Multi-wavelength Data Fitting Methods.

Typically, continuous wave spectroscopy (CWS) can be used to accurately quantify biological tissue optical properties (μ a and μ s ') by employing the diffuse reflectance information acquired at multiple source-detector separations (multi-distance). On the other hand, sample optical properties can also be obtained by fitting multi-wavelength light reflectance acquired at a single source detector separation to the diffusion theory equation. To date, multi-wavelength and multi-distance methods have not yet been rigorously compared for their accuracy in quantification of the sample optical properties.

Imaging heterogeneity in the mitochondrial redox state of premalignant pancreas in the pancreas-specific PTEN-null transgenic mouse model.

Background: Metabolic alteration is one of the hallmarks of carcinogenesis. We aimed to identify certain metabolic biomarkers for the early detection of pancreatic cancer (PC) using the transgenic PTEN-null mouse model. Pancreas-specific deletion of PTEN in mouse caused progressive premalignant lesions such as highly proliferative ductal metaplasia.

Breast cancer detection of large size to DCIS by hypoxia and angiogenesis using NIRS.

This investigation aimed to test all tumor-bearing patients who undergo biopsy to see if angiogenesis and hypoxia can detect cancer. We used continuous-wave near-infrared spectroscopy (NIRS) to measure blood hemoglobin concentration to obtain blood volume or total hemoglobin [Hbtot] and oxygen saturation for the angiogenesis and hypoxic biomarkers. The contralateral breast was used as a reference to derive the difference from breast tumor as a difference in total hemoglobin Δ[HBtot] and a difference in deoxygenation Δ([Hb]-[HbO2]).

Characterizing the metabolic heterogeneity in human breast cancer xenografts by 3D high resolution fluorescence imaging.

We previously reported that tumor mitochondrial redox state and its heterogeneity distinguished between the aggressive and the indolent breast cancer xenografts, suggesting novel metabolic indices as biomarkers for predicting tumor metastatic potential. Additionally, we reported that the identified redox biomarkers successfully differentiated between the normal breast tissue and the cancerous breast tissue from breast cancer patients. The aim of the present study was to further characterize intratumor heterogeneity by its distribution of mitochondrial redox state and glucose uptake pattern in tumor xenografts and to further investigate the metabolic heterogeneity of the clinical biopsy samples.

Optical tecnology developments in biomedicine: history, current and future.

Biomedical optics is a rapidly emerging field for medical imaging and diagnostics. This paper reviews several biomedical optical technologies that have been developed and translated for either clinical or pre-clinical applications. Specifically, we focus on the following technologies: 1) near-infrared spectroscopy and tomography, 2) optical coherence tomography, 3) fluorescence spectroscopy and imaging, and 4) optical molecular imaging.

IMAGING REDOX STATE HETEROGENEITY WITHIN INDIVIDUAL EMBRYONIC STEM CELL COLONIES.

Redox state mediates embryonic stem cell (ESC) differentiation and thus offers an important complementary approach to understanding the pluripotency of stem cells. NADH redox ratio (NADH/(Fp + NADH)), where NADH is the reduced form of nicotinamide adenine dinucleotide and Fp is the oxidized flavoproteins, has been established as a sensitive indicator of mitochondrial redox state. In this paper, we report our redox imaging data on the mitochondrial redox state of mouse ESC (mESC) colonies and the implications thereof.

Heterogeneity of mitochondrial redox state in premalignant pancreas in a PTEN null transgenic mouse model.

Pancreas-specific deletion of PTEN in mice revealed progressive premalignant lesions such as ductal metaplasia with infrequent malignant transformation. In this study, we aimed at evaluating the mitochondrial redox state of the metaplastic pancreas in a pancreas-specific PTEN null transgenic mouse model. The two intrinsic fluorophores, reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) such as flavin adenine dinucleotide (FAD), in the respiratory chain in mitochondria are sensitive indicators of mitochondrial redox states and have been applied to the studies of mitochondrial function with energy-linked processes.

Quantitative mitochondrial redox imaging of breast cancer metastatic potential.

Predicting tumor metastatic potential remains a challenge in cancer research and clinical practice. Our goal was to identify novel biomarkers for differentiating human breast tumors with different metastatic potentials by imaging the in vivo mitochondrial redox states of tumor tissues. The more metastatic (aggressive) MDA-MB-231 and less metastatic (indolent) MCF-7 human breast cancer mouse xenografts were imaged with the low-temperature redox scanner to obtain multi-slice fluorescence images of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp).

Comparisons of muscle oxygenation changes between arm and leg muscles during incremental rowing exercise with near-infrared spectroscopy.

Our purpose is to compare the changes in muscle oxygenation in the vastus lateralis (VL) and biceps brachii (BB) muscles simultaneously using near-infrared spectroscopy (NIRS) during incremental rowing exercise in eight rowers. Based on the BB and VL muscle oxygenation patterns, two points are used to characterize the muscle oxygenation kinetics in both the arm and the leg muscles. The first point is the breaking point (Bp), which refers to an accelerated fall in muscle oxygenation that correlates with the gas exchange threshold (GET).

QUANTITATIVE REDOX SCANNING OF TISSUE SAMPLES USING A CALIBRATION PROCEDURE.

The fluorescence properties of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) including flavin adenine dinucleotide (FAD) in the respiratory chain are sensitive indicators of intracellular metabolic states and have been applied to the studies of mitochondrial function with energy-linked processes. The redox scanner, a three-dimensional (3D) low temperature imager previously developed by Chance , measures the metabolic properties of tissue samples by acquiring fluorescence images of NADH and Fp. The redox ratios, i.

MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES.

Mitochondrial redox states provide important information about energy-linked biological processes and signaling events in tissues for various disease phenotypes including cancer. The redox scanning method developed at the Chance laboratory about 30 years ago has allowed 3D high-resolution (~ 50 × 50 × 10 m) imaging of mitochondrial redox state in tissue on the basis of the fluorescence of NADH (reduced nicotinamide adenine dinucleotide) and Fp (oxidized flavoproteins including flavin adenine dinucleotide, i.e.

Noninvasive determination of exercise-induced vasodilation during bicycle exercise using near infrared spectroscopy.

Background: The purpose of this study was to examine the changes in total hemoglobin (Delta[tHb]) response during bicycle exercise at various constant workloads using near infrared continuous wave spectroscopy (NIRcws) in humans. We hypothesized that the Delta[tHb] during exercise may progressively increase as a result of a dilation of the vascular bed and/or capillary recruitment at lower constant work rates.

Material/methods: Seven healthy subjects performed bicycle exercise at 20, 40, 60, 80, and 100% of maximal work rates (Wmax) for 5 min.

Histological basis of MR/optical imaging of human melanoma mouse xenografts spanning a range of metastatic potentials.

Predicting tumor aggressiveness will greatly facilitate cancer treatment. We have previously reported investigations utilizing various MR/optical imaging methods to differentiate human melanoma mouse xenografts spanning a range of metastatic potentials. The purpose of this study was to explore the histological basis of the previously reported imaging findings.

Pharmacokinetic-rate images of indocyanine green for breast tumors using near-infrared optical methods.

In this paper, we develop a method of forming pharmacokinetic-rate images of indocyanine green (ICG) and apply our method to in vivo data obtained from three patients with breast tumors. To form pharmacokinetic-rate images, we first obtain a sequence of ICG concentration images using the differential diffuse optical tomography technique. We next employ a two-compartment model composed of plasma, and extracellular-extravascular space (EES), and estimate the pharmacokinetic rates and concentrations in each compartment using the extended Kalman filtering framework.

Characterization of breast tumors with NIR methods using optical indices.

This work describes the characterization efficiency of optical properties of breast tumors based on the features obtained using in vivo near-infrared (NIR) spectroscopy measurements. Three features, relative blood concentration, oxygen saturation and the size of the tumor, are used to diagnose benign and malignant tumors. The performance of the proposed set of features are evaluated by various classifiers using data acquired from 44 patients with malignant tumors, and 72 patients with benign tumors.

Reconstruction of spatially resolved pharmacokinetic rate images of fluorescence agents in FDOT.

In this work, we propose a method to reconstruct spatially resolved pharmacokinetic rate images of fluorescence agents directly from the boundary photon flux measurements. We use a compartmental modeling scheme to model the pharmacokinetics of fluorescence agents. We coupled this model with the fluorescence diffuse optical tomography (FDOT) forward model to form a state space model which is then iteratively solved by extended Kalman filtering (EKF) algorithm.

Comparison of low- and high-intensity resistance exercise on lipid peroxidation: role of muscle oxygenation.

The purpose of this study was to examine the effect of low- vs. high-intensity resistance exercise on lipid peroxidation. In addition, the role of muscle oxygenation on plasma malondialdehyde (MDA) concentrations was explored.

Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study.

This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO(2)), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO(2), and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO(2), and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks.

Skeletal muscle energetics with PNMR: personal views and historic perspectives.

This article reviews historical and current NMR approaches to describing in vivo bioenergetics of skeletal muscles in normal and diseased populations. It draws upon the first author's more than 70 years of personal experience in enzyme kinetics and the last author's physiological approaches. The development of in vivo PNMR jointly with researchers around the world is described.