Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
2002-12-09
2004-05-18
Hindenburg, Max F. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S473000, C600S556000
Reexamination Certificate
active
06738652
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to characterization of tissue. More particularly the invention relates to methods of classifying a live subject according to optical thickness of skin, utilizing noninvasive NIR spectroscopy techniques.
BACKGROUND OF THE INVENTION
Introduction
For many years near infrared (NIR) spectroscopy has been used in the food and agriculture industries to analyze ground wheat and other turbid samples. See P. Williams, K. H. Norris, eds.,
Near Infrared Technology in the Agricultural and Food Industries
, American Association of Food Chemists, St. Paul Minn. (1987). Recently, NIR has found increasing use in biomedical applications, including the nondestructive monitoring of pharmaceuticals and the transcutaneous measurement of analytes in biological tissue. See C. M. Horland, B. Davies,
Proc. SPIE
1320, 46 (1990). Also see M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, P. L. Robinson,
Clin. Chem.,
38:1618-1622 (1992); or J. J. Burmeister, M. A. Arnold, G. W. Small,
Diabetes Technology and Therapeutics,
1:5-16 (2000); or S. F. Malin, T. L. Ruchti, T. B. Blank, S. N. Thennadil, S. L. Monfre,
Clin. Chem.,
45:1651-1658 (1999) 1999; or O. S. Khalil,
Clin. Chem.,
45:165-177 (1999). All such applications are possible due to the ability of NIR spectroscopy to extract chemical information from complex, highly scattering materials.
Structure of Human Skin
The structure and pigmentation of human skin vary widely among individuals, as well as between different sites on the same individual. Skin consists of a stratified, cellular epidermis, and an underlying dermis of connective tissue. Below the dermis is the subcutaneous fatty layer or adipose tissue. The epidermis is the thin outer layer that provides a barrier to infection and moisture loss, while the dermis is the thick inner layer that provides mechanical strength and elasticity. The epidermis layer is 10-150 &mgr;m thick and can be divided into three layers, the basal, middle and superficial layers. The basal layer borders the dermis and contains pigment-forming melanocyte cells, keratinocyte cells, Langherhan cells and Merkel cells. See Ebling, F. J.
The Normal Skin
. In
Textbook of Dermatology,
2
nd
ed.; Rook, A.; Wilkinson, D. S.; Ebling, F. J. G., Eds.; Blackwell Scientific: Oxford, 1972; pp 4-24. The superficial layer is also known as the stratum corneum.
The stratum corneum, the outermost layer of the mammalian epidermis, is formed and continuously replenished by the slow upward migration of aqueous keratinocyte cells from the germinative basal layer of the epidermis. It is replenished about every two weeks in mature adults. See W. Montagna,
The Structure and Function of Skin,
2
nd
ed., p 454, Academic, New York (1961). This complex process, involving intracellular dehydration and synthesis of an insoluble protein, keratin, results in keratin-filled, biologically inactive, shrunken cells. These flat, dehydrated, hexagonal cells are tightly bound to their neighbors and each is approximately 30 &mgr;m wide and 0.8 &mgr;m deep. See Baker, H.
The Skin as a Barrier
. In
Textbook of Dermatology,
2
nd
ed.; Rook, A.; Wilkinson, D. S.; Ebling, F. J. G., Eds.; Blackwell Scientific: Oxford, 1972; pp 249-255. There are about 12 to 20 cell layers over most of the body surface. The stratum corneum is typically 10-20 &mgr;m thick, except on the palms and soles, where it is considerably thicker. See A. M. Kligman,
The biology of the stratum corneum
, in:
The Epidermis
, W. Montagna, W. C. Lobitz, eds., 387-433 Academic Press, New York (1964).
The major constituent of the dermis, apart from water, is a fibrous protein, collagen, which is embedded in a ground substance composed mainly of protein and glycosaminoglycans. The glycosaminoglycans play a key role in regulating the assembly of collagen fibrils and tissue permeability to water and other molecules. See K. Trier, S. B. Olsen, T. Ammitzboll,
Acta. Ophthalmol.,
69:304-306 (1999). Collagen is the most abundant protein in the human body. Elastin fibers are also plentiful though they constitute only a small proportion of the bulk. The dermis also contains other cellular constituents, and has a very rich blood supply, though no vessels pass the dermo-epidermal junction. See Ebling, F. J.
The Normal Skin
. In
Textbook of Dermatology,
2
nd
ed.; Rook, A.; Wilkinson, D. S.; Ebling, F. J. G., Eds.; Blackwell Scientific: Oxford, 1972; pp 4-24. The blood vessels nourish the skin and control body temperature. In humans, the thickness of the dermis ranges from 0.5 mm over the eyelid to 4 mm on the back and averages approximately 1.2 mm over most of the body. See S. B. Wilson, V. A. Spence,
Phys. Med. Biol.,
33:894-897 (1988).
Optical Properties of Human Skin
When a beam of light beam impinges on the skin, a part of it is reflected, while the remaining part penetrates the skin. The proportion of reflected light energy is strongly dependent on the angle of incidence. At nearly perpendicular incidence, about four percent of the incident beam is reflected due to the change in refractive index between air (&eegr;
D
=1.0) and dry stratum corneum (&eegr;
D
=1.55). For normally incident radiation, this specular reflectance component may be as high as seven percent, because the very rigid and irregular surface of the stratum corneum produces off-normal angles of incidence. Regardless of skin color, specular reflectance of a nearly perpendicular beam from normal skin is always between four and seven percent over the entire spectrum from 250-3000 nm. See J. A. Parrish, R. R. Anderson, F. Urbach, D. Pitts,
UV
-
A: Biologic Effects of Ultraviolet Radiation with Emphasis on Human Responses to Longwave Ultraviolet
, Plenum Press, New York (1978). Only the air-stratum corneum border gives rise to a regular reflection. Results from a previous study indicate that the indices of refraction of most soft tissue (skin, liver, heart, etc) lie within the 1.38-1.41 range with the exception of adipose tissue, which has a refractive index of approximately 1.46. See F. P Bolin, L. E. Preuss, R. C. Taylor, R. J. Ference,
Appl. Opt.,
28:2297-2303 (1989). Therefore, these differences in refractive indices between the different layers of the skin are too small to produce a noticeable reflection. The differences are expected to be even more insignificant when the stratum corneum is hydrated, because of refractive index matching.
The ninety-three to ninety-six percent of the incident beam that enters the skin is attenuated due to absorption or scattering within any of the layers of the skin. These two processes taken together essentially determine the penetration of light into skin, as well as remittance of scattered light from the skin. Diffuse reflectance or remittance is defined as that fraction of incident optical radiation that is returned from a turbid sample. Absorption by the various skin constituents mentioned above accounts for the spectral extinction of the beam within each layer. Scattering is the only process by which the beam may be returned to contribute to the diffuse reflectance of the skin. Scattering results from differences in a medium's refractive index, corresponding to differences in the physical characteristics of the particles that make up the medium. The spatial distribution and intensity of scattered light depends upon the size and shape of the particles relative to the wavelength, and upon the difference in refractive index between the medium and the constituent particles.
The reduced scattering coefficient of biological tissue depends on many uncontrollable factors, including: concentration of interstitial water, density of structural fibers, and the shapes and sizes of cellular structures. Scattering b y collagen fibers is of major importance in determining the penetration of optical radiation within the dermis. See R. R. Anderson, J. A. Parrish,
J. Invest. Dermatol.,
77:13-19 (1981). The greater the diffusing power of a medium is, the greater the absorption due to multi
Blank Thomas B.
Makarewicz Marcy R.
Mattu Mutua
Rosenhan Branden
Glenn Michael A.
Glenn Patent Group
Hindenburg Max F.
Kremer Matthew
Sensys Medical Inc.
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