Using FDA-approved drugs as off-label fluorescent dyes for optical biopsies: from in silico design toproof-of-concept.

Optical biopsies bring the microscope to the patient rather than the tissue to the microscope, and may complement or replace the tissue-harvesting component of the traditional biopsy process with its associated risks. In general, optical biopsies are limited by the lack of endogenous tissue contrast and the small number of clinically approveddyes. This study tests multiple FDA-approved drugs that have structural similarity to research dyes as off-labelfluorescent alternatives to standardhematoxylin & eosin tissue stain.

Investigation of confocal microscopy for differentiation of renal cell carcinoma versus benign tissue. Can an optical biopsy be performed?

Objective: Novel optical imaging modalities are under development with the goal of obtaining an "optical biopsy" to efficiently provide pathologic details. One such modality is confocal microscopy which allows visualization of cells within a layer of tissue and imaging of cellular-level structures. The goal of this study is to validate the ability of confocal microscopy to quickly and accurately differentiate between normal renal tissue and cancer.

Improvement in optical fiber bundle-based imaging using synchronized fiber motion.

Image quality in fiber bundle-based imaging systems is inherently limited by the size and spacing of the individual fiber cores. The fiber bundle limits the achievable spatial resolution and superimposes a fixed pattern of signal variability across the image. To overcome these limitations, piezoelectric tubes were used to synchronously dither the fiber bundle on both ends.

Characterization of TCP-1 probes for molecular imaging of colon cancer.

Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m ((99m)Tc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). (99m)Tc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling.

Pilot Clinical Evaluation of a Confocal Microlaparoscope for Ovarian Cancer Detection.

Objective: The aim of this study is to evaluate the performance of a confocal fluorescence microlaparoscope for in vivo detection of ovarian cancer.

Methods/materials: Seventy-one patients scheduled for open or laparoscopic oophorectomy were consented for the imaging study. High-resolution confocal microlaparoscopic images of the epithelial surface of the ovary were acquired in vivo or ex vivo after tissue staining using acridine orange.

Fluorescence and reflectance spectral imaging system for a murine mammary window chamber model.

A spectral imaging system was developed to study the development of breast cancer xenografts in a murine mammary window chamber model. The instrument is configured to work with either a laser to excite fluorescence or a broadband light source for diffuse reflectance imaging. Two applications were demonstrated.

Analysis of multimode fiber bundles for endoscopic spectral-domain optical coherence tomography.

A theoretical analysis of the use of a fiber bundle in spectral-domain optical coherence tomography (OCT) systems is presented. The fiber bundle enables a flexible endoscopic design and provides fast, parallelized acquisition of the OCT data. However, the multimode characteristic of the fibers in the fiber bundle affects the depth sensitivity of the imaging system.

Dynamic oxygenation measurements using a phosphorescent coating within a mammary window chamber mouse model.

Phosphorescent lifetime imaging was employed to measure the spatial and temporal distribution of oxygen partial pressure in tissue under the coverslip of a mammary window chamber breast cancer mouse model. A thin platinum-porphyrin coating, whose phosphorescent lifetime varies monotonically with oxygen partial pressure, was applied to the coverslip surface. Dynamic temporal responses to induced modulations in oxygenation levels were measured using this approach.

Design and Performance of a Multi-Point Scan Confocal Microendoscope.

Confocal fluorescence microendoscopy provides high-resolution cellular-level imaging via a minimally invasive procedure, but requires fast scanning to achieve real-time imaging . Ideal confocal imaging performance is obtained with a point scanning system, but the scan rates required for biomedical imaging can be difficult to achieve. By scanning a line of illumination in one direction in conjunction with a stationary confocal slit aperture, very high image acquisition speeds can be achieved, but at the cost of a reduction in image quality.

Confocal microlaparoscope for imaging the fallopian tube.

Recent evidence suggests that ovarian cancer can originate in the fallopian tube. Unlike many other cancers, poor access to the ovary and fallopian tubes has limited the ability to study the progression of this deadly disease and to diagnosis it during the early stage when it is most amenable to therapy. A rigid confocal microlaparoscope system designed to image the epithelial surface of the ovary in vivo was previously reported.

Multi-modality imaging of a murine mammary window chamber for breast cancer research.

Window chamber models have been developed and utilized as a means to study the complex microenvironment in which cancers develop, proliferate, and metastasize in small animals. Here we utilize rapid prototyping printer technology to construct a new plastic orthotopic mammary window chamber that is compatible with magnetic resonance imaging, nuclear imaging, and optical imaging. Optical imaging allows for high-resolution cellular and molecular level analysis of tissues; magnetic resonance imaging provides quantitative measures of tumor size, perfusion, diffusion, fat/water content relaxation parameters; and a nuclear imaging technique, called the Beta Imager, supports functional and metabolic imaging.

Multimodality pH imaging in a mouse dorsal skin fold window chamber model.

Upregulate levels of expression and activity of membrane H ion pumps in cancer cells drives the extracellular pH (pH,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pH could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pH in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described.

Ultrathin single-channel fiberscopes for biomedical imaging.

Ultrathin flexible fiberscopes typically have separate illumination and imaging channels and are available in diameters ranging from 0.5 to 2.5 mm.

Error analysis of ratiometric imaging of extracellular pH in a window chamber model.

Ratiometric fluorescence-imaging technique is commonly used to measure extracellular pH in tumors and surrounding tissue within a dorsal skin-fold window chamber. Using a pH-sensitive fluorophore such as carboxy SNARF-1 one can measure pH distributions with high precision. However, it is often observed that the measured pH is lower than expected, with a bias that varies from one image to another.

Dual modality fluorescence confocal and spectral-domain optical coherence tomography microendoscope.

Optical biopsy facilitates in vivo disease diagnoses by providing a real-time in situ view of tissue in a clinical setting. Fluorescence confocal microendoscopy and optical coherence tomography (OCT) are two methods that have demonstrated significant potential in this context. These techniques provide complementary viewpoints.

Errors in confocal fluorescence ratiometric imaging microscopy due to chromatic aberration.

Confocal fluorescence ratiometric imaging is an optical technique used to measure a variety of important biological parameters. A small amount of chromatic aberration in the microscope system can introduce a variation in the signal ratio dependent on the fluorophore concentration gradient along the optical axis and lead to bias in the measurement. We present a theoretical model of this effect.

Statistical analysis and optimization of frequency-domain fluorescence lifetime imaging microscopy using homodyne lock-in detection.

Fluorescence lifetime imaging microscopy is used widely in biological research, but the accuracy and precision of lifetime measurements are limited. Photon noise is an inherent error source that cannot be eliminated. In this paper, we present a general approach to compute the probability density of the estimated lifetime for frequency-domain fluorescence lifetime imaging microscopy using homodyne lock-in detection.

In vivo imaging of ovarian tissue using a novel confocal microlaparoscope.

Objective: The objective of the study was to develop a clinical confocal microlaparoscope for imaging ovary epithelium in vivo with the long-term objective of diagnosing cancer in vivo.

Study Design: A confocal microlaparoscope was developed and used to image the ovaries of 21 patients in vivo using fluorescein sodium and acridine orange as the fluorescent contrast agents.

Results: The device was tested in vivo and demonstrated to be safe and function as designed.

Clinical confocal microlaparoscope for real-time in vivo optical biopsies.

Successful treatment of cancer is highly dependent on the stage at which it is diagnosed. Early diagnosis, when the disease is still localized at its origin, results in very high cure rates-even for cancers that typically have poor prognosis. Biopsies are often used for diagnosis of disease.

Monte Carlo characterization of parallelized fluorescence confocal systems imaging in turbid media.

We characterize and compare the axial and lateral performance of fluorescence confocal systems imaging in turbid media. The aperture configurations studied are a single pinhole, a slit, a Nipkow disk, and a linear array of pinholes. Systems with parallelized apertures are used clinically because they enable high-speed and real-time imaging.

Rapid water and lipid imaging with T2 mapping using a radial IDEAL-GRASE technique.

Three-point Dixon methods have been investigated as a means to generate water and fat images without the effects of field inhomogeneities. Recently, an iterative algorithm (IDEAL, iterative decomposition of water and fat with echo asymmetry and least squares estimation) was combined with a gradient and spin-echo acquisition strategy (IDEAL-GRASE) to provide a time-efficient method for lipid-water imaging with correction for the effects of field inhomogeneities. The method presented in this work combines IDEAL-GRASE with radial data acquisition.

Multispectral confocal microendoscope for in vivo and in situ imaging.

We describe the design and operation of a multispectral confocal microendoscope. This fiber-based fluorescence imaging system consists of a slit-scan confocal microscope coupled to an imaging catheter that is designed to be minimally invasive and allow for cellular level imaging in vivo. The system can operate in two imaging modes.

Spectral background and transmission characteristics of fiber optic imaging bundles.

The emission and transmission properties of three commercially produced coherent fiber optic imaging bundles were evaluated. Full fluorescence excitation versus emission data were collected from 250 to 650 nm excitation for high-resolution Sumitomo, Fujikura, and Schott fiber bundles. The results generated show regions of autofluorescence and inelastic Raman scattering in the imaging bundles that represent a wavelength-dependent background signal when these fibers are used for imaging applications.

Direct imaging of radionuclide-produced electrons and positrons with an ultrathin phosphor.

Unlabelled: Current electron detectors are either unable to image in vivo or lack sufficient spatial resolution because of electron scattering in thick detector materials. This study was aimed at developing a sensitive high-resolution system capable of detecting electron-emitting isotopes in vivo.

Methods: The system uses a lens-coupled charge-coupled-device camera to capture the scintillation light excited by an electron-emitting object near an ultrathin phosphor.

Computer-aided identification of ovarian cancer in confocal microendoscope images.

The confocal microendoscope is an instrument for imaging the surface of the human ovary. Images taken with this instrument from normal and diseased tissue show significant differences in cellular distribution. A real-time computer-aided system to facilitate the identification of ovarian cancer is introduced.