Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2002-10-11
2004-07-20
Mercader, Eleni Mantis (Department: 3736)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S475000, C600S326000, C600S364000
Reexamination Certificate
active
06766188
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to medical devices for use in assessing reduced oxygen delivery to regional tissue beds. Specifically, the invention relates to devices and methods for measuring tissue oxygenation either alone or in combination with other parameters such as pH, by using optical reflectance spectrum of the tissue.
BACKGROUND
Tissue levels of oxygen are an important indicator of the metabolic status of cells. If tissue oxygen falls below cellular demands, then cells perish. Organs, particularly those with high metabolic rates, are especially susceptible to incurring irreversible damage when oxygen is inadequate. It has previously been shown that tissue pH is a useful indicator of anaerobic metabolism, and as such can indicate cells at risk. However, tissue oxygen levels change prior to a drop in pH, so that detection of a low oxygen level could provide an earlier indication of a potential problem. Measurement of tissue oxygenation could also provide a useful early measure to assess the degree of success in restoring oxygen to oxygen-deficient tissue.
Cellular processes are complex, and beyond the question of whether oxygen is transported to the cells in sufficient quantity, one may ask whether the cells are able to use the available oxygen. The combination of a tissue pH measurement and a tissue oxygen measurement would be useful in determining whether a given tissue bed can actually utilize oxygen which is delivered. In a recent paper, applicant has shown that the simultaneous measurement of tissue pH and oxygenation can be used to indicate the onset of dysoxia (defined as the mismatch between oxygen demand and supply). Soller et al., “Application of fiberoptic sensors for the study of hepatic dysoxia in swine hemorrhagic shock,” Crit. Care Med, 29:1438-1444 (2001). The detection of the onset of dysoxia in this manner may therefore permit earlier or more effective preventive interventions in humans. However, the technology for measuring these parameters is at present limited.
Solving this need would be a major contribution to clinical practice. Clinically, oxygen levels can change as a result of many causes: bleeding, trauma, poor cardiac performance, low blood pressure and impaired circulation, among others. Diabetic patients often have compromised tissue perfusion, particularly in their legs and feet. This may result in ulcers and ultimately require amputation. For management of such a chronic condition, it would be especially desirable to possess a technique or sensor for dependably monitoring tissue oxygenation.
Tissue oxygenation is traditionally determined through the measurement of the partial pressure of oxygen (PO
2
) present in the cells or the interstitial fluid. Typically, tissue PO
2
is measured by inserting an invasive PO
2
sensor (such as an electrode-based sensor or a dye-coated fiber optic sensor) into the tissue that is to be monitored.
Ideally, it would be advantageous if this measurement could be made spectroscopically, such that the measurement process is non-invasive and does not physically penetrate or stress the tissue. A number of researchers have investigated spectroscopic methods to determine tissue oxygenation. In doing so, they have typically relied upon quantifying some related parameter. For example, some researchers have considered the spectroscopic measurement of arterial or venous blood oxygen to constitute a suitable measure of tissue oxygenation. Arterial blood levels do not, however, respond rapidly to regional changes in reduced oxygen, so this indicator may fail to reflect prevailing tissue oxygenation at a site of interest. Local or regional measurement of venous oxygen saturation, on the other hand, is a satisfactory measure of tissue oxygenation, since local venous blood is collected blood returning from the local tissue. Hutchinson Technology of Hutchinson, Minn. has an existing product which measures venous hemoglobin oxygen saturation in tissue, such as muscle tissues, at depths up to several inches using near infrared (NIR) light. The technology is described, for example, in U.S. Pat. No. 5,879,294 and possibly other patents, and also in promotional material or research publications of that group. Another company, Somonetics, sells a NIR device which measures a combination of venous and arterial oxygen saturation in the brain. A large number of issued patents are also directed to various optical methods of measuring blood and tissue levels of oxygenated hemoglobin or oxygen saturation. These include, for example, U.S. Pat. Nos. 5,515,864, 5,593,899, 5,931,799, 6,015,969, 6,123,597, and 6,216,021. Dr. Britton Chance at the University of Pennsylvania has also patented a number of inventions in this area.
In general, known devices and methods for evaluating the level of oxygen have tended to rely on secondary or related measurements, or upon relatively invasive sensors or slower assays.
It would therefore be desirable to have a system that determines tissue PO
2
directly and non-invasively in a local tissue region.
SUMMARY OF THE INVENTION
A device in accordance with one aspect of the invention determines the oxygen partial pressure (PO
2
) of a tissue, which may, for example, be disposed underneath a covering tissue, such as skin, of a patient, or which may be directly contacted or imaged by the device. The device includes a light source for irradiating the tissue with optical radiation such that the light is reflected from the tissue, and also includes a probe for collecting the reflected light to form a reflection spectrum. The device further includes a spectral processor that determines the PO
2
level in tissue by processing this spectrum and a mathematical model relating optical properties to PO
2
of the tissue.
A method of the invention includes the step of first illuminating the tissue with optical radiation to irradiate the underlying tissue, and collecting a reflection spectrum from the illuminated tissue. The method also includes the step of determining tissue PO
2
by processing the collected spectrum with a mathematical model relating optical properties to PO
2
of the tissue.
The invention also includes a spectral calibration model for tissue PO
2
. The model is constructed from a previously compiled calibration data set comprised of direct PO
2
measurements and a set of spectral samples collected in coordination with the measurements.
By “tissue”, as used herein, is meant any tissue or organ present, e.g., in a patient. This definition encompasses any collection of cells, e.g., epithelial cells, muscle cells, skin cells, or any specific organ, e.g., the heart, kidney, or liver, in the patient. The optical radiation preferably is visible and near infrared radiation or includes a substantial range of near infrared radiation. The radiation may be between about 400 and about 2500 nm, and preferably, the radiation is between 450 and 1100 nm.
The mathematical model of the invention is constructed prior to processing a collected spectrum by first compiling a calibration data set. The calibration data set is formed by collecting multiple optical spectra from a representative tissue sample of a subject, and also measuring the tissue PO
2
value simultaneously (e.g., by conventional means). Preferably such data sets are collected from multiple subjects and over a wide range of PO
2
values. The optical spectra and known PO
2
values are then processed with a mathematical multivariate calibration algorithm, such as a partial least-squares (PLS) fitting algorithm described below, to determine a model, e.g. a formula or calibration equation, relating PO
2
to the spectral values collected from the sample. In constructing the model, other parameters, such as pH, temperature and the like may also be measured and fitted to the model, and these subject pH, temperature or other parameters may also be measured at run time for enhanced accuracy. In another embodiment, one or more parameters such as pH, temperature or the like may be varied during acquisition of the calibration data set, s
Fish & Richardson P.C.
Mantis Mercader Eleni
University of Massachusetts
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