Imaging in optic nerve coloboma.
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BACKGROUND: Optical coherence tomography (OCT) is a new method of catheter based micron scale imaging. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than sound waves. OBJECTIVE: To demonstrate the ability of OCT to perform high resolution imaging of arterial tissue in vivo. METHODS: OCT imaging of the abdominal aorta of New Zealand white rabbits was performed using a 2.9 F OCT imaging catheter. Using an ultrashort pulse laser as a light source for imaging, an axial resolution of 10 micrometer was achieved. RESULTS: Imaging was performed at 4 frames/second and data were saved in either super VHS or digital format. Saline injections were required during imaging because of the signal attenuation caused by blood. Microstructure was sharply defined within the arterial wall and correlated with histology. Some motion artefacts were noted at 4 frames/second. CONCLUSIONS: In vivo imaging of the rabbit aorta was demonstrated at a source resolution of 10 micrometer, but required the displacement of blood with saline. The high resolution of OCT allows imaging to be performed near the resolution of histopathology, offering the potential to have an impact both on the identification of high risk plaques and the guidance of interventional procedures.
Area V4 occupies a central position among the areas of the primate cerebral cortex involved with object recognition and analysis. Consistent with this role, neurons in V4 are selective for many visual attributes including color, orientation, and binocular disparity. However, it is uncertain whether cells within V4 are organized with respect to these properties. In this study we used in vivo optical imaging and electrophysiology in macaque visual cortex to show that cells that share certain physiological properties are indeed grouped together in V4. Our results revealed regions containing cells with common orientation selectivity. These regions were similar in size to those seen in V2 and much larger than those seen in V1 and were confirmed by appropriately targeted single-unit recording. Surprisingly, orientation organization visible through imaging was limited to the portion of V4 representing the central visual fields. Optical imaging also revealed a functional organization related to stimulus size. Size-sensitive regions (S regions) contained cells that were strongly suppressed by large stimuli. In contrast to V2, S regions in V4 contain orientation domains. These results suggest that V4 contains modular assemblies of cells related to particular aspects of form analysis. Such organization may contribute to the construction of object-based representations.
Endoscopic imaging systems that perform as the "eye" of the operator during endoscopic surgical procedures have developed rapidly due to various technological developments. In addition, since the most recent turn of the century robotic surgery has increased its scope through the utilization of systems such as Intuitive Surgical's da Vinci System. To optimize the imaging required for precise robotic surgery, a unique endoscope has been developed, consisting of both a two dimensional (2D) image optical system for wider observation of the entire surgical field, and a three dimensional (3D) image optical system for observation of the more precise details at the operative site. Additionally, a "near infrared radiation" endoscopic system is under development to detect the sentinel lymph node more readily. Such progress in the area of endoscopic imaging is expected to enhance the surgical procedure from both the patient's and the surgeon's point of view.
BACKGROUND: A duplex optical image is created when the ablation zone formed by excimer photorefractive keratectomy is smaller than the entrance pupil. Visual performance and secondary effects are analyzed using a theoretical model of the optical image. METHODS: A point-spread function having a centered in-focus component surrounded by an annular out-of-focus component is calculated from pupil size, ablation size, refractive error, and photoreceptor directional sensitivity. The line-spread, edge-spread, and optical transfer functions are derived. RESULTS: In the line- and edge-spread functions, secondary maxima and curvilinear ramps are most evident with low refractive errors. The half-height widths of the point- and line-spread functions change little. The optical transfer function is reduced in proportion to the distribution of light between the image components. CONCLUSIONS: Stable point and line half-height widths explain why Snellen visual acuity is insensitive to annular blur. Contrast sensitivity correlates with symptoms of haze and fog. Halos and ghost images are associated with secondary optical maxima and curvilinear ramps. Neither visual acuity nor contrast sensitivity can predict halos or ghost images. Halos and ghost images will be most prevalent in low illumination and for low refractive corrections. High refractive errors will produce fewer visual side effects than low refractive errors.
Site-specific delivery of drugs and contrast agents to tumors protects normal tissues from the cytotoxic effects of drugs and enhances the contrast between normal and pathologic tissues. One approach to achieve selectivity is to target overexpressed receptors on the membranes of tumor cells and to visualize the tumors by a noninvasive optical imaging method. Accordingly, we conjugated fluorescein and carbocyanine dyes to somatostatin and bombesin receptor-avid peptides and examined their receptor binding affinities. We also prepared potential dual imaging probes consisting of a bioactive peptide for tumor targeting, a biocompatible dye for optical imaging, and a radioactive or paramagnetic metal chelator for scintigraphic or magnetic resonance imaging of tumors. Using these approaches, the resulting carbocyanine derivatives of somatostatin and bombesin analogues retained high binding for their respective receptors. Further evaluation of representative molecules in rats bearing somatostatin- and bombesin-positive tumors showed selective uptake of the agents by the tumor cells. Unlike carbocyanine derivatives, the receptor binding of fluorescein-somatostatin peptide conjugates was highly sensitive to the type of linker and the site of fluorescein attachment on the nonreceptor binding region of the peptide. In general, the presence of flexible linkers disrupted binding affinity, possibly due to the interaction of the linker's thiourea group with the peptide's cyclic disulfide bond. While the receptor binding affinity of the dual probes was not dependent on the type of chelating group examined, it was affected by the relative positions of fluorescein and chelator on the lysine linker. For somatostatin compounds, best results were obtained when the chelator was on the alpha-amino lysine linker and fluorescein was on the epsilon-amino group. In contrast, conjugation of the chelator to epsilon- and fluorescein to the alpha-amino lysine linker of bombesin peptides resulted in high receptor binding. These findings indicate that despite their small size, conjugation of dyes to truncated somatostatin and bombesin peptide analogues results in promising diagnostic agents that retain high receptor binding activity in vitro. The results further show that these contrast agents can selectively and specifically localize in receptor-positive tumors in rat models.
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In serial studies of multiple sclerosis lesions, reductions in magnetization transfer ratio (MTR) are thought to be due to demyelination and axonal loss, with later rises due to remyelination. This study followed serial changes in MTR in acute optic neuritis in combination with clinical and electrophysiological measurements to determine if the MTR changes over time mirror the picture in multiple sclerosis lesions, further validating MTR as a marker of tissue integrity. Twenty-nine patients were recruited who had acute optic neuritis for a median of 13 days (range 7-24 days) since the onset of visual symptoms. A clinical examination and measurement of visual evoked potentials (VEP) was performed on each patient. Their optic nerves were imaged with a fat-saturated fast spin echo (FSE) sequence and a magnetization transfer sequence. Twenty-one had multiple subsequent examinations over the course of 1 year. In addition, 27 control subjects had their optic nerves imaged up to three times over 1 year. A blinded observer segmented the optic nerves from the MTR maps. Lesions were defined on the acute FSE images and, from the coordinates, the ratio of mean lesion MTR : healthy nerve MTR (lesion ratio) was calculated for each dataset. The time-averaged mean MTR in control optic nerves was 47.7 per cent units (pu). In diseased optic nerves, baseline mean MTR was 47.3 pu, with a mean lesion ratio of 0.98. The diseased optic nerve MTR and lesion ratio declined over time with a nadir at about 240 days at a mean MTR value of 44.2 pu and mean lesion ratio of 0.91. Subsequently, diseased optic nerve MTR appeared to rise; after 1 year the diseased optic nerve mean MTR was 45.1 pu (mean lesion ratio 0.93), although the difference was not significant compared with the nadir value. For each 0.01 increase in time-averaged lesion ratio logMAR visual acuity recovery improved by 0.03 (95% CI, 0.002, 0.08, P = 0.02). Time-averaged VEP central field latency was shorter by 6.1 ms (95% CI 1.5, 10.7, P = 0.012) per 1 pu rise in time-averaged diseased optic nerve MTR. The early fall in diseased optic nerve MTR is consistent with demyelination and Wallerian degeneration of transected axons. The late nadir compared with studies of multiple sclerosis lesions may have been due to slow clearance of myelin debris. Remyelination may have influenced subsequent MTR changes. The observations support using MTR to monitor symptomatic demyelinating lesions.
One of the primary applications of diffuse optical imaging is to localize and quantify the changes in the cerebral oxygenation during functional brain activation. Up to now, data from an optical imager are simply presented as a two-dimensional (2D) topographic map using the modified Beer-Lambert law that assumes homogeneous optical properties beneath each optode. Due to the highly heterogeneous nature of the optical properties in the brain, the assumption is evidently invalid, leading to both low spatial resolution and inaccurate quantification in the assessment of haemodynamic changes. To cope with these difficulties, we propose a nonlinear tomographic image reconstruction algorithm for a two-layered slab geometry that uses time-resolved reflected light. The algorithm is based on the previously developed generalized pulse spectrum technique, and implemented within a semi-three-dimensional (3D) framework to conform to the topographic visualization and to reduce computational load. We demonstrate the advantages of the algorithm in quantifying simulated changes in haemoglobin concentrations and investigate its robustness to the uncertainties in the cortical structure and optical properties, as well as the effects of random noises on image quality. The methodology is also validated by experiments using a solid layered phantom.
We present an overview of recent progress in "plasmonics". We focus our study on the observation and excitation of surface plasmon polaritons (SPPs) with optical near-field microscopy. We discuss in particular recent applications of photon scanning tunnelling microscope (PSTM) for imaging of SPP propagating in metal and dielectric wave guides. We show how near-field scanning optical microscopy (NSOM) can be used to optically and actively address remote nano objects such as quantum dots. Additionally we compare results obtained with near-field microcopy to those obtained with other optical far-field methods of analysis such as leakage radiation microscopy (LRM).
Hitachi medical corporation developed and produced a new modality called Optical Topography System "ETG-100". This system uses near infrared light as in spectroscopy. ETG-100 measures the oxy hemoglobin, deoxy hemoglobin and total hemoglobin volume changes in cerebral cortex. This optical topography system has various features, i.e., displaying the hemoglobin volume change in 2 dimensional images, non-invasiveness, compactness, low cost and less patient restraint. This system is now being used for the research of higher-order brain functions, for example language function, language recognition. Research of brain function disease of new born babies, cerebral blood flow infarction detection are expected.
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PURPOSE: To report and validate an optical imaging system that provides measurements of higher order ocular aberrations and light scatter in human eyes. METHODS: An optical imaging system has been established that provides for combined measurements of ocular aberrations and light scatter. A laser beam was expanded and focused to a point on the retina by the optics of the eye. Wavefront sensing was performed with a Shack-Hartmann aberrometer to determine the wavefront aberration function and calculate the point spread function, giving information on ocular aberrations. A cylindrical lens was placed in the path of the incident laser beam path, and the line spread function was derived from the laser slit, giving information on combined ocular aberrations and light scatter. A relative index for ocular light scatter was determined by subtracting the area under the two line spread functions. Measurements were performed in one eye of 20 normal healthy subjects. The subjects' ages ranged between 21 and 78 years, and the average for all the eyes was 43 +/- 17 years (mean +/- SD). RESULTS: Higher order ocular aberrations were correlated with subjects' ages (r = 0.6; p = 0.01; N = 20). Combined higher order ocular aberrations and light scatter were correlated with age (r = 0.7; p = 0.0002; N = 20). Light scatter was correlated with age (r = 0.6; p = 0.002; N = 20). CONCLUSIONS: A method was established to measure age-related changes in ocular higher order aberrations and light scatter. Differentiating the contribution of ocular aberrations and light scatter to the retinal image quality has potential value for anticipating the outcome of procedures that attempt to compensate for ocular aberrations and for providing information on factors that degrade the optical performance of the eye in health and disease.
An experimental system that combines optical imaging of voltage-sensitive dyes with an in vitro isolated cerebellum preparation is described. The optical imaging system is based on a photodiode array and two rather simple amplification stages. The isolated cerebellum preparation preserves the integrity of the neuronal circuitry, thus allowing the exploration of the path of information flow. In this study, we characterize the nature and sources of the optical signal evoked in the cerebellar cortex by surface stimulation. We show that this signal reflects inhibitory and excitatory synaptic potentials generated by cell bodies and dendrites of cortical neurons, whereas action potentials of the parallel fibers are not detected by the system. The spatial distribution of the optical signals agrees with the classical view of cerebellar activity following surface stimulation. Hence, this experimental system provides a powerful means to explore the functional organization, in time and space, of the cerebellar cortex.
Optical imaging methods make monitoring of the membrane potential feasible. With this technique, one can observe different optical signals depending on optical properties, in response to membrane potential, using voltage-sensitive dyes. We used the multiple-site optical imaging system to investigate membrane potentials of the isolated, cultured spiral ganglion cells (SCGs) from newborn mice. We used a voltage-sensitive absorption dye. With high potassium (150 mM K+) exposure, the absorbency of SGCs stained with voltage-sensitive dye increased temporarily under a 700-nm interference filter at approximately 0.3%. This detection of the depolarization of SGCs using an optical recording technique with a voltage-sensitive dye is important because it shows that the simultaneous measurement of activity in a variety of regions is possible, as is the exploring of the intercellular signalling pathway.
Advances in computer technology continue to bring new innovations to departments of anatomic pathology. This article briefly reviews the present status of digital optical imaging, and explores the directions that this technology may lead over the next several years. Technical requirements for digital microscopic and gross imaging, and the available options for image archival and retrieval are summarized. The advantages of digital images over conventional photography in the conference room, and the usefulness of digital imaging in the frozen section suite and gross room, as an adjunct to surgical signout and as a resource for training and education, are discussed. An approach to the future construction of digital histologic sections and the computer as microscope is described. The digital technologic applications that are now available as components of the surgical pathologist's workstation are enumerated. These include laboratory information systems, computerized voice recognition, and on-line or CD-based literature searching, texts and atlases and, in some departments, on-line image databases. The authors suggest that, in addition to these resources that are already available, tomorrow's surgical pathology workstation will include network-linked digital histologic databases, on-line software for image analysis and 3-D image enhancement, expert systems, and ultimately, advanced pattern recognition capabilities. In conclusion, the authors submit that digital optical imaging is likely to have a significant and positive impact on the future development of anatomic pathology.
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RATIONALE AND OBJECTIVES: To evaluate the efficacy of a novel tumor receptor-specific small-peptide-near-infrared dye conjugate for tumor detection by optical imaging. METHODS: A novel, near-infrared dye-peptide conjugate was synthesized and evaluated for tumor-targeting efficacy in a well-characterized rat tumor model (CA20948) known to express receptors for the chosen peptide. A simple continuous-wave optical imaging system, consisting of a near-infrared laser diode, a cooled CCD camera, and an interference filter, was used in this study. RESULTS: Tumor retention of two non-tumor-specific dyes, indocyanine green and its derivatized analogue, bis-propanoic acid cyanine dye (cypate), was negligible. In contrast, the receptor-specific peptide-cypate conjugate (cytate) was retained in the CA20948 tumor, with an excellent tumor-tonormal-tissue ratio in the six rats examined. CONCLUSIONS: Optical detection of tumors with a receptor-targeted fluorescent contrast agent has been demonstrated. This result represents a new direction in cancer diagnosis and patient management.