Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
2001-12-26
2004-07-13
Jastrzab, Jeffrey R. (Department: 3762)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S549000
Reexamination Certificate
active
06763261
ABSTRACT:
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to methods of identifying in a living vessel an atherosclerotic plaque at risk of rupture or thrombosis. More particularly, the invention relates to such methods that include detecting sites of inflammation in a vessel wall exhibiting about 0.2°-5° C. temperature elevation above adjacent or ambient vessel wall temperature. The invention also relates to intravascular and non-invasive devices for measuring vessel wall temperatures and detecting about 0.2-5° C. temperature differences between regions of living vessel wall.
2. Description of the Related Art
Despite the declining age-specific mortality of coronary atherosclerosis, many people who feel well and have no known cardiovascular disease continue to die suddenly of a first myocardial infarction or cardiac arrest. An estimated 35% of these patients had neither symptoms nor a diagnosis of coronary artery disease (Casscells et al.
Lancet
347:1147-1149 (1996); Falk et al.
Circulation
92:657-671 (1995); Davies et al.
Lancet
347:1422-1423 (1996); Falk et al.
Am J Cardiol
63:114E-120E (1989)). Rupture and/or thrombosis of an atherosclerotic plaque is the immediate cause of most myocardial infarctions and strokes. Myocardial infarction is not predictable by presently available clinical means, which greatly hampers prognosis and treatment of patients suffering from cardiovascular disease (Fuster et al.
Circulation
82:1147-1159 (1990); Davies et al.
Brit Heart J
53:363-373 (1985); Libby, P.
Circulation
91:2844-2850 (1995); Liuzzao et al.
N Engl J Med
331:417-424 (1994); Itoh et al.
Coronary Artery Disease
6:645-650 (1995); and Ridker et al.
N Engl J Med
336:973-979 (1997)).
In most instances of myocardial infarction, cardiac arrest, or stroke, it is found that only one of the potential obstructions, or plaques, has in fact, ruptured, fissured, or ulcerated. The rupture, fissure, or ulcer causes a large thrombus or blood clot to form on the inside of the artery, which may completely occlude the flow of blood through the artery, thereby injuring the heart or brain. It is known that approximately one-half of the unstable coronary atherosclerotic plaques are in arteries with 50% or less luminal diameter narrowing. See, for example, Fuster, V., et al.,
N Engl J Med
326:242-250 and 310-318 (1992). These are lesions that are usually considered insignificant anatomically. Thus, it would be highly desirable if methods and devices were available to detect the unstable atherosclerotic plaque, independent of the degree of luminal diameter narrowing, and treat it before unstable angina and/or acute myocardial infarction and their consequences occur.
These culprit lesions, referred to as “vulnerable,” “dangerous,” “unstable” or “at-risk” plaques, have some unique histopathologic features. These features include: a lipid core containing a substantial amount of free and esterified cholesterol, and other necrotic debris; infiltrated macrophages (and less frequently lymphocytes, monocytes and mast cells); less abundant smooth muscle cells; and, consequentially, low content of collagen and other matrix proteins.
The lipid core characterizing most ruptured plaque is mainly a large pool of cholesterol resulting from insudation and from the release of the contents of foam cells following degradation of the cell wall. The low content of collagen and matrix proteins associated with at-risk plaque contributes to an important feature of the unstable plaque—the thin plaque cap. The release of matrix-digesting enzymes by the inflammatory cells is thought to contribute to plaque rupture. Small blood clots, particularly microthrombi, are also frequently found on non-ruptured but inflamed ulcerated plaque surfaces.
The rupture process is not completely understood, but it is known that the plaques most likely to rupture are those that have both a thin collagen cap (fibrous scar) and a point of physical weakness in the underlying plaque. Such points are thought to be located (as determined by modeling studies and pathologic analysis) at junctures where pools of cholesterol meet a more cellular and fibrous part of the plaque. It has been observed that plaques with inflamed surfaces or a high density of activated-macrophages and a thin overlying cap are at risk of thrombosis. Van der Wal, et al.,
Circulation
89:36-44 (1994); Shah, et al.,
Circulation
244 (1995); Davies, et al.,
Br Heart J
53:363-373 (1985); Farb, et al.,
Circulation
92:1701-1709 (1995); Van Damme, et al.,
Cardiovasc Pathol
3:9-17 (1994).
Identifying Vulnerable Plaque
The development of medically feasible techniques to identify those plaques that are most likely to rupture, thrombose or rapidly progress in severity of vascular stenosis is an area of intense investigative activity. Most of the techniques undergoing study at the present time focus on the histological features of dangerous plaque. Modalities such as intravascular ultrasound, which might identify plaque vulnerability on the basis of cap thinness has been proven to be incapable of identifying which plaques are at risk of rupturing (de Feytia et al.
Circulation
92:1408-13 (1995). Perhaps this is because the average cap thickness at the time of rupture is estimated to be 50 &mgr;m (Burke et al.
N Engl J Med
336:1276-82 (1997); Mann et al.
Circulation
; 94:928-31 (1996); and Falk et al.
id
. (1995)).
Moreno et al. (
Circulation
Suppl 17:1-1016 (1998) employ NIR spectroscopy to correlate the NIR spectra of plaque with the histological features of thin fibrous cap, lipid pool, macrophages and calcium content in an atherosclerotic rabbit model.
In U.S. Pat. No. 5,935,075 (issued to Casscells, et al.) (U.S. patent application Ser. No. 08/717,449) some of the present inventors demonstrated for the first time that there is thermal heterogeneity in human atherosclerotic arteries and that inflamed plaques give off more heat than non-inflamed plaques. These inflamed regions, sometimes called “hot” plaques, are regions of atherosclerotic plaque that exhibit temperatures that are elevated about 0.4-4.0° C. above non-inflamed adjacent vessel wall temperature. Previously, local heat had not been identified in atherosclerosis and exploited for diagnosing vulnerable plaque based on the association of inflammation and macrophages with plaque rupture.
Recently, Stefanadis et al. (
Circulation
99:1965-1971 (1999)) has reported a confirmatory study in patients suffering acute myocardial infarction showing substantial thermal heterogeneity (1.7° C.) at points along their coronary arteries, as measured by a catheter-mounted thermistor in contact with the vessel wall.
U.S. Pat. No. 5,935,075 (Ser. No. 08/717,449) (Casscells et al.) also discloses a method of detecting heat-producing inflammatory cells at sites along a vessel wall using an infrared-sensing catheter, or other invasive or non-invasive temperature measuring devices. One exemplary catheter includes an infrared-transparent balloon enclosing a group of optical fibers.
U.S. Pat. No. 5,871,449 (issued to Brown) describes another infrared fiber optic catheter intended for measuring vessel wall temperature to reveal inflamed plaques. One problem with currently-available infrared optical fibers is that they are not made of biocompatible material, and are therefore unsuitable for directly contacting tissues and fluids inside a human blood vessel. Also, the somewhat brittle nature of conventional infrared optical fibers makes them incapable of bending sufficiently to be aimed directly into a plaque (i.e., perpendicular to the linear axis of the vessel). Infrared fiber optic catheter designs must also take into account the interference by blood, saline or other vessel fluids with the infrared signal.
Catheter-Based Temperature Sensing Devices
A number of devices and procedures have been employed to diagnose, treat or inhibit vascular obstructions, and in some of these devices a temperature sensing elem
Casscells, III S. Ward
Guo Bujin
Naghavi Morteza
Willerson James T.
Board of Regents , The University of Texas System
Canter Bruce M.
Jastrzab Jeffrey R.
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