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1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenko a , Dmitry N. Artemyev a , Oleg O. Myakinin a , Julia A. Kristophorova a , Alexander A. Moryatov b , Sergey V. Kozlov b and Valery P. Zakharov a a - Samara National Research University b - Samara State Medical University 2.6.2017 Oulu

Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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Page 1: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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Towards virtual biopsy. Multimodal spectroscopy for

cancer detection

Ivan A. Bratchenkoa, Dmitry N. Artemyeva, Oleg O. Myakinina, Julia A. Kristophorovaa, Alexander A. Moryatovb,

Sergey V. Kozlovb and Valery P. Zakharova

a - Samara National Research University b - Samara State Medical University

2.6.2017 Oulu

Page 2: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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MOTIVATIONS

SETUP

AF STIMULATED BY 785 NM LASER

AF STIMULATED BY 457 NM LASER

RAMAN SPECTROSCOPY

DA AND PCA ANALYSIS

IN VIVO STUDIES

CONCLUSIONS

Page 3: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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MOTIVATIONS

Fig. 3 – Cancer mortality-to-incidence ratio (Lancet Oncol.)

UK

USA

RUS

Fig. 2 – Causes of death (BMJ) Fig. 1 – Skin cancer mortality

melanoma

other

76%

heart disease

cancer

medical error

other

36% 34%

15%15%

Page 4: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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MOTIVATIONS

Fig. 4 – Skin structure

Page 5: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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MOTIVATIONS

Raman spectroscopy (RS) measures weak inelastic scattering of light on tissue components; diagnostic accuracy near 90% and 85% in internal organs and skin pathologies studies.

Autofluorescence (AF) is light emission from tissue components after the light absorption; diagnostic accuracy near 70 – 90%.

• RS: Amide bands, collagens, proteins, etc.

• AF VIS: flavins, porphyrins, lipids

• AF NIR: melanin

Page 6: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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SETUP

Fig. 5 – Experimental setup. L: lenses, M: Mirrors, BPF: band-pass filters, LPF: long-pass filters

Page 7: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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AF STIMULATED BY 457 NM LASER

Fluorophore Excitation, nm Emission, nm

Lipo-pigments

Protoporphyrin

Protoporphyrin

Flavins 450 535

Fig. – AF spectra of skin tissues

Page 8: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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AF STIMULATED BY 457 NM LASER

Fig. 7 – Skin tissues classification

Fλ457 =|λnorm-λtumor| FI457 = I610/I570

Page 9: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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AF STIMULATED BY 785 NM LASER

Fig. 8 – AF spectra of skin tissues Fig. – Approximation of melanoma spectrum

𝐼𝑎𝑝 λ = 𝐹𝐼785 ∗ 𝑒𝑥𝑝𝐹λ785

λ

λ𝑚𝑎𝑥 + 𝑐

FI785 is the convex or concave of the approximating curve

Fλ785 characterizes the AF spectra curvature degree

𝜆𝑚𝑎𝑥 = 870 is the right boundary of the approximation interval

Page 10: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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AF STIMULATED BY 785 NM LASER

Fig. – Skin tissues classification with AF NIR criteria

Page 11: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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RAMAN SPECTROSCOPY

Fig. 11 – Raman spectra of skin tissues

Raman scatterer Raman band, cm-1

stretching mode C = N

twisting, wagging of bending mode CH2

CH2 deformations of proteins and lipids

1440 - 1460

stretching mode C = O in amide I

1640 - 1680

Page 12: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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PHASE PLANE AND PCA ANALYSIS

Fig. 13 – MM vs BCC by PCA

Fig. 12 – MM vs BCC by phase plane line discriminant analysis(AF vis and AF NIR criteria)

Page 13: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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IN VIVO STUDIES

Fig. 13 – In vivo studies design

Page 14: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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IN VIVO STUDIES. PLS ANALYSIS

Fig. 14 – Normalized AF + Raman spectra and VIP scores

Page 15: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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SKIN TISSUES CLASSIFICATION

Method Sensitivity Specificity Accuracy

Raman 97.4% 62.2% 80.3%

NIR AF 92.3% 37.5% 64.6%

VIS AF 80% 77.8% 78.4%

VIS AF + NIR AF 70% 92.6% 86.5%

Raman + NIR AF 94.9% 92.5% 93.7%

Raman + AF 100% 96.3% 97.3%

PLS in vivo 89.5% 78.4% 82.1%

Benign vs Malignant 100% 100% 100%

Page 16: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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CONCLUSIONS

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•Multiparametric method demonstrates high-precision in MM and BCCseparation (>95% accuracy), thus it may be used for mass screeningapplications.

•Proposed method of spectral coefficients DA can be implemented as PLSanalysis; PLS-DA provides high accuracy for skin tumors classification evenwith low-cost equipment.

•Further enhancement of diagnostics effectiveness may be achieved byincluding of imaging modalities i.e. OCT and hyperspectral imaging.

Page 17: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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BioPhotonics Lab Team

Page 18: Towards virtual biopsy. Multimodal spectroscopy for cancer detection spectroscopy.pdf · 1 Towards virtual biopsy. Multimodal spectroscopy for cancer detection Ivan A. Bratchenkoa,

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Bratchenko, Ivan A.Associate Prof. of Laser and Biotechnical Systems

Dept., Leading researcher of “Photonics” Laboratory of

Samara National Research University

443086 Russia, Samara, Lukacheva str., 39b, office 314

Email: [email protected]: + 7 (846) 267-45-50