Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
2001-02-22
2003-02-25
Winakur, Eric F. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S322000, C600S476000
Reexamination Certificate
active
06526299
ABSTRACT:
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority under 35 U.S.C. §119 (b) to British Patent Application No. 0103030.3 filed Feb. 7, 2001, the disclosure of which is incorporated herein by reference in its entitety.
FIELD OF THE INVENTION
The invention relates to a method of processing a spectrum, in particular an elastic scattering spectrum taken from tissue and to apparatus including a spectrum processor for carrying out the method.
BACKGROUND ART
Elastic scattering spectroscopy is a known technique for investigating tissue. In essence, light is shone into human tissue, generally living human tissue, and a photoreceptor measures the light transmitted to the photoreceptor through scattering in the tissue. The spectrum of light passing through the tissue is then recorded, and used to assist in diagnosis of any of a number of medical conditions that the patient may have. Thus, the technique may be described as optical biopsy.
Prior art apparatus for carrying out optical biopsy is presented in WO98/27865 to David Benaron, and in U.S. Pat. No. 5,303,026 to Stroble et al. The latter patent describes a system having a light source feeding into a reference optical fiber and a probe optical fiber. The probe optical fiber being brought to a probe tip. The probe tip has another optical fiber arranged adjacently of it, which collects light and brings it to a detection system which compares its intensity to the intensity of light on the reference optical fiber. When the probe tip is brought against human tissue the detection system can record the difference as a between the reference signal strength and that of the light scattered by the human tissue as a function of wavelength to obtain an optical biopsy spectrum.
The use of an elastic scattering spectrum to diagnose a number of medical conditions is described in a number of papers. Zhengfang GE et al describe in the paper “Identification of Colonic Dysplasia and Neoplasia by Diffuse Reflectance Spectroscopy and Pattern Recognition techniques”, Applied Spectroscopy Volume 52 number 6 (1998) p 833, a method of identifying colonic dysplasia and neoplasia. The paper describes a number of different pattern recognition techniques used to evaluate the samples.
One of these is multiple linear regression analysis, which is used to fit to reflectance intensities measured at 26 different wavelengths every 16 nm in the range 350 nm to 750 nm. An output score is obtained from the formula:
score
=
k
+
∑
j
=
1
26
a
j
D
i
(
λ
j
)
The coefficients a
j
are fitted coefficients arranged such that the score is +1 for adenomatous polyps and −1 for hyperplastic polyps. D
i
&lgr;
i
is the reflectance value for the ith tissue sample at the jth wavelength.
Another approach described in the paper by Zhengfang et al is linear discriminant analysis. This is a method of classifying a test into one of k groups using a classification score that can be computed from a formula. The test is classified into the group which gives the lowest classification score.
The classification of a test object X
i
=(x
1
,x
2
, . . . x
d
) containing d independent integers is assigned to one of k gropus using the classification score defined as
D
k
2
=(
X
i
−&mgr;
k
)
T
M
−1
(
X
i
−&mgr;
k
)
where M
−1
is the inverse of the pooled covariance matrix over all classes
M
=
1
n
∑
k
∑
i
=
1
n
k
(
X
i
-
μ
k
)
(
X
i
-
μ
k
)
T
.
A third approach is backpropagating neural network analysis using a multilayer neural network with n input nodes, a hidden layer and an output layer. Neural network techniques have been widely reported and will not be discussed further here.
Other papers describe the use of elastic scattering spectroscopy in the diagnosis of a number of conditions. Backman et al describe the detection of precancerous epithelial cells in “Detection of Preinvasive Cancer Cells”, Nature, vol 406 p35 (2000). Perelman et al, in “Observation of Periodic Fine Structure in Reflectance from Biological Tissue: A New Technique for Measuring Nuclear Size Distribution”, Phys. Rev. Lett. vol 80 p627 (1998) describe periodic fine structure in mucosal membranes. The diagnosis of bladder cancer is described in “Spectroscopic Diagnosis of Bladder Cancer with Elastic Light Scattering” Mourant et al, Lasers in Surgery and Medicine, Volume 17 page 350 (1995). The use of elastic scattering to diagnose pathologies in the gastrointestinal tract is described in “Elastic Scattering Spectroscopy as a diagnostic tool for differentiating pathologies in the Gastrointestinal tract: preliminary testing”, Mourant et al, Journal of Biomedical optics, Vol 1 p192, and in “Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic scattering spectroscopy”, Bigio and Mourant Phys. Med. Biol. Volume 42 p803 (1997).
It is thus clear that the use of elastic scattering spectroscopy is attracting interest as a diagnostic tool. In spite of this research interest the most reliable approach presently used for detection of cancer in tissue and other conditions is histology. However, this is time consuming and laborious and in many situations, especially for diagnosing cancer, multiple biopsies may be needed.
There is thus a need to develop optical techniques further. One application is to guide conventional biopsies, avoiding false negatives and reducing the number taken while increasing yield. The long-term goal is to develop the techniques to a point where they can be used rapidly, efficiently and reliably to diagnose conditions without the need for histology.
SUMMARY OF THE INVENTION
According to the invention there is provided a method of processing a broadband elastic scattering spectrum obtained from tissue comprising the steps of: obtaining, in a plurality of fitting ranges of wavelength, fitting parameters giving the best fit to the spectrum in the respective fitting ranges; and recording the fitting parameters as a parameter data set representing the spectrum; wherein in at least one fitting range the fit is to the absorption of at least one predetermined component, and in the remainder of the fitting ranges the fit is to a smooth function.
By fitting in a number of different fitting regions to known absorption spectra and to a smooth function a measured spectrum including a large number of data points can be reduced to the very much smaller number of data points, i.e. the fitting parameters. Subsequent data processing using the fitting parameters instead of the whole spectrum (as used in the prior art discussed above) may allow simpler, more reliable and more rapid assessment of the patient's condition.
The method can be thought of as using model dependent fitting, i.e. of analysing the spectrum using a model of the absorption with certain absorbing components absorbing at certain frequencies before carrying out any diagnosis or discrimination.
The fit to the absorption of at least one predetermined component may be to the absorption line shape of the at least one predetermined absorbing component. In particular, the fit may use a parabolic approximation to the peak of absorption of that absorbing component.
The fit to the absorption of at least one predetermined component may be a fit to an absorption spectrum previously measured using an optical biopsy probe on a sample of the predetermined absorbing component in a tissue-like matrix. This absorption spectrum, in general, differs from the simple absorption spectrum due to scattering obtained from a conventional optical transmission cell and available in most textbooks. The use of a spectrum measured using an optical biopsy probe on a sample in a tissue-like substrate has not previously been suggested, as far as the inventor is aware.
Alternatively, especially for single component systems, the fit may be nothing more than determining the excess of absorption in the spectrum at a predetermined frequency over the background spectral lineshape due to scattering calculated by extrapolating a st
Darby & Darby
Kremer Matthew
University College London
Winakur Eric F.
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