Abstract

We are investigating spectroscopic devices designed to make in vivo cervical tissue measurements to detect pre-cancerous and cancerous lesions. All devices have the same design and ideally should record identical measurements. However, we observed consistent differences among them. An experiment was designed to study the sources of variation in the measurements recorded. Here we present a log additive statistical model that incorporates the sources of variability we identified. Based on this model, we estimated correction factors from the experimental data needed to eliminate the inter-device variability and other sources of variation. These correction factors are intended to improve the accuracy and repeatability of such devices when making future measurements on patient tissue.

© 2014 Optical Society of America

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References

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  1. J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
    [CrossRef] [PubMed]
  2. J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
    [CrossRef] [PubMed]
  3. B. Yu, H. L. Fu, N. Ramanujam, “Instrument independent diffuse reflectance spectroscopy,” J. Biomed. Opt. 16(1), 011010 (2011).
    [CrossRef] [PubMed]
  4. B. Yu, H. Fu, T. Bydlon, J. E. Bender, N. Ramanujam, “Diffuse reflectance spectroscopy with a self-calibrating fiber optic probe,” Opt. Lett. 33(16), 1783–1785 (2008).
    [CrossRef] [PubMed]
  5. J. L. Devore, Probability and Statistics for Engineering and the Sciences (Cengage Learning, 2011, 8th ed.), Chap.11.
  6. B. G. Lipták, Instrument Engineers' Handbook, Volume Two: Process Control and Optimization. (CRC Press, 2010.)

2012 (1)

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

2011 (1)

B. Yu, H. L. Fu, N. Ramanujam, “Instrument independent diffuse reflectance spectroscopy,” J. Biomed. Opt. 16(1), 011010 (2011).
[CrossRef] [PubMed]

2008 (1)

2007 (1)

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Adewole, I.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

Atkinson, E. N.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Bender, J. E.

Buys, T. P.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

Bydlon, T.

Cantor, S. B.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

Cox, D. D.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Davies, K.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

Follen, M.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Freeberg, J. A.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Fu, H.

Fu, H. L.

B. Yu, H. L. Fu, N. Ramanujam, “Instrument independent diffuse reflectance spectroscopy,” J. Biomed. Opt. 16(1), 011010 (2011).
[CrossRef] [PubMed]

MacAulay, C.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

McKinnon, N.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Pikkula, B.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Price, R.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Ramanujam, N.

Richards-Kortum, R.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Serachitopol, D. M.

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

Yamal, J. M.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

Yu, B.

Zewdie, G. A.

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

J. A. Freeberg, D. M. Serachitopol, N. McKinnon, R. Price, E. N. Atkinson, D. D. Cox, C. MacAulay, R. Richards-Kortum, M. Follen, B. Pikkula, “Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe,” J. Biomed. Opt. 12(3), 034015 (2007).
[CrossRef] [PubMed]

J. M. Yamal, G. A. Zewdie, D. D. Cox, E. N. Atkinson, S. B. Cantor, C. MacAulay, K. Davies, I. Adewole, T. P. Buys, M. Follen, “Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings,” J. Biomed. Opt. 17(4), 047002 (2012).
[CrossRef] [PubMed]

B. Yu, H. L. Fu, N. Ramanujam, “Instrument independent diffuse reflectance spectroscopy,” J. Biomed. Opt. 16(1), 011010 (2011).
[CrossRef] [PubMed]

Opt. Lett. (1)

Other (2)

J. L. Devore, Probability and Statistics for Engineering and the Sciences (Cengage Learning, 2011, 8th ed.), Chap.11.

B. G. Lipták, Instrument Engineers' Handbook, Volume Two: Process Control and Optimization. (CRC Press, 2010.)

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Figures (5)

Fig. 1
Fig. 1

(a) MDC3 device. (b) The spectroscopic probe inserted into the standard receptacle.

Fig. 2
Fig. 2

Plots of the measured spectra color-coded by device.

Fig. 3
Fig. 3

(a) (b) - light intensities after applying the correction factors (Log10 plot with original y-axis scale); (c) (d) - residuals plotted by devices in same scale.

Fig. 4
Fig. 4

Correction factors by device (exp(lCFDi(λ)) and standard (exp(lCFSj(λ)), with 95% confidence intervals.

Fig. 5
Fig. 5

Amplitude correction factors (ACijk = exp(lAC ijk)) estimates for filter set 1. The red lines separate the sessions. The color codes indicate sets of 5 measurements. Missing values are left blank.

Tables (2)

Tables Icon

Table 1 Wavelength ranges for the excitation and detection light.

Tables Icon

Table 2 Percentage of variance explained by each factor (averaged across wavelength)

Equations (6)

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y i j k ( λ ) = log Y i j k ( λ ) = μ ( λ ) + l C F D i ( λ ) + l C F S j ( λ ) + l A C i j k + ε i j k ( λ )
l C F ^ D i ( λ ) = ( j = 1 4 k = 1 N i j y i j k ( λ ) j = 1 4 N i j μ ^ ( λ ) ) , l C F ^ S j ( λ ) = ( i = 1 4 k = 1 N i j y i j k ( λ ) i = 1 4 N i j μ ^ ( λ ) )
ε ^ i j k ( 1 ) ( λ ) = y i j k ( λ ) μ ^ ( λ ) l C F ^ D i ( λ ) l C F ^ S j ( λ )
log Y i j k C F ( λ ) = log Y i j k ( λ ) l C F ^ D i ( λ ) l C F ^ S j ( λ ) l A C ^ i j k
l C F ^ D i ( λ ) ± 1.96 ( 1 w i ) 2 var ( y ¯ i ) + j i w j 2 var ( y ¯ j )
y ¯ i ( λ ) = j = 1 4 k = 1 N i j y i j k ( λ ) j = 1 4 N i j , w i = j = 1 4 N i j i = 1 4 j = 1 4 N i j , var ( y ¯ i ) = j = 1 4 k = 1 N i j ε ^ i j k 2 ( λ ) j = 1 4 N i j 1 .

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