Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1999-06-24
2001-03-27
Jeffery, John A. (Department: 3742)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S478000, C600S342000, C606S015000, C356S301000
Reexamination Certificate
active
06208887
ABSTRACT:
BACKGROUND OF THE INVENTION
The technical field of this invention is low resolution Raman spectroscopy for invivo analysis of a sample, for example, analysis of blood vessels for atherosclerotic plaques using low resolution Raman spectroscopy.
It is well known that deposits of plaque on cardiovascular tissues, such as on the interior walls of arteries, can severely restrict or completely block the flow of blood. Plaques typically exists in two forms, namely, as calcified plaques or as fibrous plaques. Calcified plaques are more rigid and more difficult to remove than fibrous plaques. Previous studies suggest that plaque composition rather than the actual size or volume of the plaque determine acceleration of clinical symptoms (Loree et al. (1994)
Artheroscler. Thromb.
14, 230-234). Thus, methods for detecting deposits of calcified plaque or fibrous plaque on blood vessels, and determining their composition, have substantial utility in the diagnosis and treatment of atherosclerosis and related cardiovascular ailments.
A variety of spectroscopic methods have been used to characterize arterial disease in situ (See e.g., Clarke et al. (1988)
Lasers Surg. Med.
8: 45-59; Deckelbaum et al. (1995)
Lasers Surg. Med.
16: 226-234; Yan et al. (1995)
Lasers Surg. Med
16: 164-178; Manoharan et al. (1993)
Artheroschlerosis
103: 181-193 and Baraga et al. (1992)
Proc. Natl. Acad. Sci.
89: 3473-3477). By delivering excitation light and collecting emitted light through flexible optical fibers, fluorescence spectra from a coronary artery can be collected and used to differentiate normal tissue from abnormal tissue (Bartorelli et al. (1991)
J. Am. Coll. Cardiol.
17:160B-168B and Richards-Kortrum et al. (1989)
Am. Heart J.
118: 381-391). However, due to the limited difference in fluorescence spectra of chemical compounds, these spectra typically provide insufficient chemical composition information.
In contrast, Raman spectroscopic methods provide more detailed spectra capable of providing greater compositional information and an ability to differentiate normal from abnormal tissue. For example, Clarke et al. discuss using visible Raman spectroscopy to analyze the surface of diseased and healthy tissue sites on post-mortem specimens of calcified aortic valves and coronary artery segments (see Clarke et al. (1988)
Lasers in Surgery and Medicine,
8, 45-49).
In Raman Spectroscopy of Atherosclerotic Plaque: Implications for Laser Angioplasty,” Radiology, 177, 262 (1990), Redd et al. also disclose using visible Raman spectroscopy to analyze human cadaveric aorta, percutaneous peripheral atherectomy, and surgical endarterectomy samples and conclude that Raman spectroscopy allows fatty plaque to be distinguished from a normal artery.
Recently, Brennen et al. described using IR Raman spectroscopy to analyze the chemical composition of human coronary artery from homogenized coronary artery samples (Brennen et al. (1997)
Applied Spec.
52; 201-20).
However, prior approaches to the use of Raman spectroscopy have been largely, if not entirely, limited to the characterization ex-vivo of specimens removed from the subject by excision or extraction. The limitation of Raman spectroscopy to post-surgical (or post-mortem) analysis was due to the large optical systems needed to obtain a high resolution spectrum.
Another drawback to IR Raman spectroscopy has been its expense of operation. A significant component of that expense is the laser system required to produce quality, high-resolution spectra. Even using a laser diode as the scattering source, the laser remains one of the major expenses in developing cost-effective Raman systems.
Thus, there exists a need for a low cost, simple Raman spectroscopic system for in-vivo analysis of a sample. Moreover, there exists a specific need for systems for analyzing the chemical components of atherosclerotic plaques in-vivo.
SUMMARY OF THE INVENTION
The present invention is directed to low resolution Raman spectroscopic systems for in-vivo detection and analysis of a lesion in a lumen of a subject, for example, analysis of blood vessels for atherosclerotic plaques. In one aspect of the invention, a multi-mode laser is employed in making in-vivo Raman spectroscopic measurements of the lumen. The system can also include a light collector and/or a light dispersion element as well as a detector to measure spectral patterns that indicate the presence of the lesion. Based on the spectral response of a target (e.g. a lumen), the presence (or absence) of a lesion can be determined. Furthermore, the components of the lesion can also be identified based on the unique Raman spectrum associated with each component.
Accordingly, in one aspect, the present invention provides a system for detecting the presence of a lesion in the lumen of a subject using low resolution Raman spectroscopy. The system can include a catheter comprising an excitation fiber through which multi-mode radiation can propagate to irradiate a target region of a lumen,
a multi-mode laser for irradiating the target region to produce a Raman spectrum consisting of scattered electromagnetic radiation,
a low resolution dispersion element positioned to receive and separate the scattered radiation into different wavelength components,
a detection array, optically aligned with the dispersion element for detecting at least some of the wavelength components of the scattered light, and
a processor for processing data from the detector array.
In use, the multi-mode laser irradiates the target to produce a Raman spectrum. The Raman spectrum is composed of scattered electromagnetic radiation characterized by a particular distribution of wavelengths. The Raman spectrum is a result of the scattering of the laser radiation as it interacts with the target.
The collector element collects the radiation scattered from the target. The collection element can be an optical fiber. The collection fiber can have a first end positioned for collecting scattered radiation, and a second end positioned in selected proximity to the dispersion element. One or more filters can also be employed in the systems of the present invention to reduce or attenuate optical “noise”. For example, a notch filter can be coupled to the first end of the collection fiber for filtering the excitation source background.
The dispersion element distributes the scattered radiation into different wavelength components. The detection array detects the scattered radiation in different wavelength ranges, and a processor processes the detected array data to detect the presence and/or the components of the lesion.
The system further includes a catheter comprising a light directing element, where the excitation fiber has a first end coupled to the multi-mode laser, and a second end coupled to the light directing element to direct the laser radiation to the lesion. The excitation fiber transmits the laser radiation from the multi-mode laser to the light directing element which directs the laser radiation to the lesion in the lumen.
In some features of the present invention, the resolution of the apparatus is determined in part by the full-width at half-maximum (FWHM) of the spectral distribution of the multi-mode laser, and, in part, by the dispersion element. In one embodiment, the apparatus preferably has a resolution of between 10 cm and 100 cm
−1
and most preferably between 30 cm and 50 cm.
According to some features of the present invention, the multi-mode laser element produces laser radiation having a wavelength between about 700 nanometers (nm) and about 2.4 micrometers (&mgr;M), more preferably between 700 nm and about 1.1 &mgr;M. Preferably, the multi-mode laser produces radiation having a line width of at least 2 nm. The multi-mode laser preferably has a power between about 50 milliwatts (mW) and about 1000 mW, and more preferably, greater than about 150 mW in some applications. One example of a multi-mode laser element for use with the present invention is a 785 nm GaAs laser diode. This GaAs multi-mode laser has a spectral distribution FWHM o
Engellenner Thomas J.
Jeffery John A.
Nutter & McClennen & Fish LLP
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