Chemical apparatus and process disinfecting – deodorizing – preser – Analyzer – structured indicator – or manipulative laboratory... – Means for analyzing liquid or solid sample
Reexamination Certificate
1998-10-30
2001-08-14
Snay, Jeffrey (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Analyzer, structured indicator, or manipulative laboratory...
Means for analyzing liquid or solid sample
C436S068000
Reexamination Certificate
active
06274086
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to imaging of body portions of humans and animals via phosphorimetry, and more particularly, to optical methods for imaging oxygen pressure in human and animal tissue using oxygen-dependent quenching of phosphorescence to generate two- and three-dimensional images of oxygen partial pressure.
BACKGROUND OF THE INVENTION
As known oxygen has a quenching effect on the molecular luminescence of various chemical compounds. This effect has been exploited for imaging oxygen concentrations (partial pressure) in various body portions of humans and animals. Information about the distribution and concentration of various oxygen partial pressure in various body locales is useful as an indication of tissue health, structure, defects, abnormalities and diseases. For example, in traumatic injury, the primary threat to life is often the loss of blood and resulting hemorrhagic shock. The latter results in hypotension, under perfusion of tissue and the blood flow which does occur is abnormally distributed among and within the tissues. As a result, regions in the tissue become hypoxic or relatively devoid of oxygen, the fasculature becomes leaky, and tissue function is compromised. If the damage is sufficiently severe and/or involves essential organs, surgical repair of the traumatic injury and reinfusion of blood may not be sufficient to sustain life. Treatment of trauma victims during transit to the site where surgical repair will occur is designed to alleviate the loss of blood volume, usually by plasma expanders, in an effort to maintain blood pressure. This is believed to improve oxygen delivery to the tissue and therefor stabilize its condition until surgery can be performed. A reliable method for measuring the oxygen pressure in tissue would be an invaluable asset in the critical period between the occurrence of trauma and completion of surgery. The extent of compromise of oxygen delivery to tissue can be accurately followed, helping in such decisions as to whether intervention is necessary, the choice of treatment modality and evaluation of treatment efficacy.
For examples of oxygen mapping devices, see U.S. Pat. No. 5,593,899, which discloses methods and apparatus for imaging internal body structures of animals. The apparatus and methods disclosed in this application are directed to measuring tissue oxygenation through the skin using oxygen dependent quenching of phosphorescence. In addition, there have been additional patents directed to this technology.
U.K. patent application No. GB 2,132,348A, published Jul. 4, 1984, discloses the use of fluorescent materials to measure levels of oxygen in blood both in vitro and in vivo using a fiber optic probe or catheter.
The prior art has disclosed indwelling devices for use during measurement of various blood parameters. For example, U.S. Pat. No. 3,787,119 discloses a catheter having a microlamp and a photosensitive element and other elements including a cup-like element for use in receiving blood and providing electrical output signals by means of wires extending through the catheter.
U.S. Pat. No. 3,814,081 discloses an optical measuring oxygen saturation in blood, as well as blood pressure.
U.S. Pat. No. 4,200,110 discloses a fiber optic pH probe which includes an ion permeable membrane which encloses a guide containing solid material comprised of a hydrophilic copolymer having a pH sensitive dye attached thereto. The probe functions by optically detecting a change in color of the pH sensitive dye when excited by light. A phenol red dye is employed so that it absorbs light at a particular wavelength, with the amount of light being absorbed varying in dependence upon the pH level.
U.S. Pat. No. 4,476,870 discloses a fiberoptic oxygen partial pressure probe. This probe includes a hydrophobic gas permeable envelope which contains an adsorptive support which contains a fluorescent dye. Use of the probe for measuring partial pressure of gaseous oxygen in the bloodstream is based on the principle of dye fluorescent oxygen quenching. With the probe in place with a bloodstream, fluorescent dye is excited by light having a blue wavelength, thus causing the dye to fluoresce at a green wavelength with the intensity of emitted light decreasing (quenching) with increasing levels of the partial pressure of gaseous oxygen in the bloodstream.
U.S. Pat. No. 5,127,405 discloses a fiber optic probe incorporating a luminescent composition which is used to monitor conditions of a subject. A response light from the fiber optic probe is detected and a frequency domain presentation of the response light is derived. Characteristics of the frequency domain representation are used to derive values for luminescent lifetimes or similar decay parameters and these values in turn are translated into the values of the conditions to be sensed.
Finally, U.S. Pat. No. 4,898,175 discloses an apparatus in which an illuminating light is fed by a device emitted from the tip part of an insertable endoscope. The endoscope is inserted into a body cavity and is radiated onto a part of the body to be observed. This illuminating light, having passed through a living body tissue, is imaged by an imaging device provided outside the body. The imaging device delivers a picture image signal to a signal processing device. The signal processing device processes the signal and outputs a video signal to a display device. This device displays the image observed within the living body. See also U.S. Pat. No. 4,974,850.
In addition to the above technologies, oxygen electrodes have also been designed for transcutaneous oxygen measurements. Oxygen electrodes, in contrast to systems which are based on the oxygen dependent quenching of phosphorescence, utilize substantial amounts of oxygen. The oxygen permeability of the skin is low and oxygen consumption by the electrodes can seriously deplete the oxygen pressure at the surface of the skin, resulting in measured oxygen values which are artificially low and which are strongly dependent upon blood flow in the immediate vicinity of the electrodes. In general an oxygen electrode system must compensate by heating the skin to well above normal values in order to maximally dilate the vessels. In the phosphorescence method, the negligible oxygen consumption by the measuring system will permit the use of only one modest heating, primarily to overcome possible vasoconstriction due to depressed body temperature to assure uniform conditions among subjects. Oxygen electrodes further require calibration before each use. The calibration cannot alter with the time of measurement.
See also for example, U.S. Pat. No. 4,474,850, in which there is described a method and associated apparatus for imaging an oxygen-containing internal body portion of a host animal comprising, inter alia, adding to a body fluid of the host animal a phosphorescent composition (e.g., zinc verdin or a metal porphyrin compound) compatible with the body fluid, and in which the phosphorescence of the composition is quenchable with oxygen in the body portion, irradiating the body portion with a pulse of light at a wavelength and for a time sufficient to effect phosphorescence of the composition to be emitted as light from the body portion, scanning across the body portion to measure the decay of the emitted phosphorescence across the body portion, relating any variations in the decay measured across the body portion to variations in structure of the body portion based on oxygen contained by the body portion, and displaying an image of said body portion.
Further, in U.S. Pat. No. 5,501,225, there is described yet another method and apparatus for imaging internal body structure of humans and animals. By this method and apparatus, light focused through an epifluorescence attachment excites a phosphorescent material within a body portion or tissue, with the light emanating from the phosphorescent material being collected from outside of the tissue. However, this method and apparatus suffers from the drawback of not being convenient for isolating and measu
Vinogradov Sergei A.
Wilson David F.
Dilworth Paxson LLP
McConathy Evelyn H.
Snay Jeffrey
The Trustees of the University of Pennsylvania
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