Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1998-05-15
2001-08-14
Lateef, Marvin M. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S310000, C356S432000
Reexamination Certificate
active
06275726
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the fields of biomedical engineering, medicine and imaging. More particularly, it concerns a new process to increase light transmission in biological media by using either index matching agents to reduce the amount of random reflection and refraction in tissue which, in turn, reduces light scattering or agents that reduce absorption and allow improved tissue imaging and delivery of light into tissues for diagnoses and treatment.
2. Description of Related Art
Many biological media or tissues, such as human skin, are optically turbid and highly light scattering because of the refractive index (n) variations among water and various inter/intra cellular components. The refractive index of water is 1.33 while many cellular components have higher refractive indices. For instance, melanin has a refractive index of 1.7 (Vitkin et al., 1994), nucleus has a refractive index of 1.36 Hiramoto, 1979) and dehydrated collagen has a refactive index of 1.53 (Wang et al., 1996). Reflection and refraction occur when light travels from a medium with one refractive index to another medium having a different index. Greater index mis-match generally increases the amount of light reflection and refraction As a result, light scatters randomly inside tissues mainly due to the index mis-match between cellular/subcellular water and the spatial distribution of various cellular components.
Imaging through tissue is always degraded by the strong optical scattering in biological tissue and any imaging technique must either discriminate in favor of the unscattered “ballistic” light signal (which is usually extremely weak) or must take account of the multiple scattering in some image reconstruction algorithm based on inverse scattering. Both approaches limit the visualization of the underlying tissue and in many cases turbid tissues cannot be sufficiently distinguished from each other. Thus many optical diagnostic and therapeutic techniques have limited capabilities.
Many current medical monitoring techniques require puncturing the skin to draw blood. For example, diabetics must measure the glucose concentration in blood samples which is extremely inconvenient and invasive, especially when one has to perform this task up to twenty times per day. A non-invasive blood glucose monitoring method is a goal of intensive research worldwide. One method uses the blood spectral absorbance to quantitatively determine glucose level, but the small glucose optical signature relative to noise and filtering associated with scattered light remains a serious constraint which has prevented the widespread adoption of this method for monitoring. Non-invasive devices are being developed to perform this absorbance measurement, but the signal to noise limitation must be reduced in order for these devices to be successful.
Development of noninvasive techniques appear to be further advanced for the visualization of the eye sclera, especially for the detection of cancers and cataracts. But these techniques have not been successfully applied to other tissues.
There are techniques which temporarily alter tissue optical properties such as stretching, coagulation and dehydration which cause the packing of cellular components to reduce reflection/refraction due to the cellular-water interface. Color dyes have been used to enhance local light absorption (DeCoste et al., 1992). Each of these techniques has limited applicability to living animals.
Radiation dispersing agents, irradiation and fluorescence have been used in combination to visualize and photosensitive tumor cells (U.S. Pat. No. 4,612,938). But this technique is designed to enhance visualization of tumor cells on the interior surface of hollow organ cavities instead of improving visualization of subsurface, non-oncogenic turbid tissues. Moderate mechanical compression has been used to increase local cellular concentration to enhance light absorption and reduce light scattering in order to improve the contrast between bone/teeth structure and skin (U.S. Pat. No. 5,429,120); however, this technique has very limited ability to improve the visualization of soft or turbid tissues and their structure.
None of these techniques provide the desired visualization of tissues which are normally turbid for diagnosis and treatment. Alternative techniques are needed to improve visualization for the diagnosis and monitoring of a variety of injuries and diseases and to enhance certain laser treatments and therapies. In addition, imaging modalities, such as optical coherence tomography (OCT) and confocal imaging, that are used for the diagnosis of pathological sites would benefit from an increased imaging distance.
SUMMARY OF THE INVENTION
The present invention provides new and effective methods of reducing light attenuation in biological media or tissue that include index matching the cellular components of the biological media such that the amount of light reflection and refraction by the tissue is reduced or the use of agents that reduce absorption of light. Thus light penetration of the biological media is enhanced and visualization of underlying tissues is improved.
As used in this specification and the appended claims and in accordance with long-standing patent law practice, the singular forms “a” “an” and “the” generally mean “at least one”, “one or more”, and other plural references unless the context clearly dictates otherwise. Thus, for example, references to “a tissue”, “a medium” and “a method” include mixtures of tissues, one or more media and a plurality of methods of the type described; and reference to “a tissue” includes different species of such tissue, for example, muscle, neural and connective tissues, and so forth.
Biological media or tissue is normally turbid, that is, the random reflection and refraction of light by tissue reduces the penetration of the light into the tissue and reduces the visualization of tissues beneath the exterior surface. Light penetration is further decreased by absorption in the tissue. Herein, “biological media or tissue” is defined as including tissue from a plant, animal or person as well as tissue phantoms and other artificial tissues, such as artificial skin, created by the hand of man.
In one aspect the invention comprises a method of index matching the biological media by replacing inter and/or intrastitial (extracellular) fluid with another (replacement) fluid that has a refractive index more similar to that of the inter/intra cellular components of the biological media than water or the tissue fluid.
Herein, “light attenuation” is defined as reducing light scattering and/or light absorption. “Index matching” is defined as altering the ratio of the inter- and intracellular refractive indices of one or more tissue constituents to light such that the ratio more closely approximates one (1) than the native state. “Light” is defined as electromagnetic radiation which comprises wavelengths from about 4000 angstroms (extreme violet) to about 7700 angstroms (extreme red). Such electromagnetic radiation may also be referred to as light radiation or visible radiation and comprise any wavelength within this range. Thus in certain cases, electromagnetic radiation also refers to infrared (IR) and ultraviolet (UV) radiation. “Absorption” is defined as the energy of light radiation that is transferred to a medium through which the light radiation is passing.
In one embodiment of the invention the replacement fluid has a lower absorption coefficient than water.
In another embodiment the replacement fluid comprises glycerol, a dextrose solution or a perfluorocarbon.
In one aspect of the invention the density of the biological tissue is increased.
In another aspect of the invention the water content of the tissue is decreased.
In yet another aspect of the invention the average index of refraction of the tissue is increased.
In yet a further embodiment the reduction in light reflection and refraction is reversible.
The invention further provides a method of enhancin
Barton Jennifer K.
Chan Eric K.
Welch Ashley J.
Board of Regents , The University of Texas System
Fulbright & Jaworski LLP
Lateef Marvin M.
Shaw Shawna J.
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