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1
Multimode imaging applied toward diagnosis of skin
cancer (SkinSpect)
Fartash Vasefi a, Nicholas MacKinnon a, and Daniel L. Farkas a, b
a Spectral Molecular Imaging Inc., 250 N. Robertson Blvd, Beverly Hills
b Biomedical Engineering, University of Southern California, Los Angeles
Spectral Molecular Imaging Inc.
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Safe Harbor
“Safe Harbor” Statement under the Private Securities Litigation Reform Act of 1995. A number
of the matters and subject areas discussed in this presentation that are not historical or
current facts deal with potential future circumstances and developments. The discussion of
such matters and subject areas is qualified by the inherent risks and uncertainties
surrounding future expectations generally and also may materially differ from Spectral
Molecular Imaging’s (SMI’s) future experience involving any of or more of such matters and
subject areas. Such risks and uncertainties include: the early stage of products in
development, the uncertainty of market acceptance of products, the uncertainty of
development or effectiveness of distribution channels, the intense competition in the medical
device industry, the uncertainty of capital to develop products, the uncertainty of regulatory
approval of products, dependence on licensed intellectual property, as well as those that are
more fully described from time to time under the heading “Risk Factors” in SMI’s filed with
the SEC, including SMI’s Report on Form 10-K for the fiscal year ended December 31, 2010
and subsequent quarterly reports.
2
"Financial support from NIH and the USDHHS Qualifying Therapeutic Discovery Program is gratefully
acknowledged".
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Outline
• Motivation
• Dermoscopes using Biological Models Vs. Statistical classifiers
• To address misestimations in current melanin and hemoglobin quantifications in
pigmented skin lesions
• Objective
• To evaluate the performance of a quantitative imaging approach that combines two
depth-sensitive imaging techniques, polarization and hyperspectral imaging, to produce
a new multimode dermoscopy method that accurately maps melanin and hemoglobin
oxygenation distribution in human skin.
• Methods
• Multimode imaging dermoscope and tissue measurements
• Rapid quantification model for preliminary data validation
• Results
• Measurements of human in vivo skin with melanocytic nevus and venous occlusion
3
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Recent News
Nature: Scientific Reports - May 12, 2014
4
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
• Spectral Molecular Imaging (SMI), Inc., a subsidiary of Cascade Technologies
Corp., is developing high-resolution, hyperspectral imaging for early and
accurate diagnosis of cancer and other major diseases
• SkinSpectTM
is a hyperspectral imaging system designed to meet the need for
accurate diagnosisof skin cancer.
Spectral Molecular Imaging - SkinSpectTM
5
Melanoma Incidence
Melanoma Mortality
W.H.O. - 2004
USA/Canada
94,000/yr
13,000/yr
Europe
65,000/yr
28,000/yr
Melanoma Prevalence and Mortality
(per 100,000)
0
5
10
15
20
25
30
1975 1980 1985 1990 1995 2000 2005 2010
Year
Melanoma Prevalence
Modeled Rate
Melanoma Mortality
Modeled Rate
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Biological Models vs. Statistical Classifiers (Black Boxes)
Black Box
• Need big trials to have sufficient data for BlackBox algorithm
validation
• Exceptional data qualification/validation through standards and well
developed data quality algorithms
Biological Model (Method we have adopted)
• Directly linked to tissue properties with well developed scientific
basis
• Biological plausibility that is easily understood by clinicians (and
makes sense to regulatory authorities)
•6
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Melanin vs. hemoglobin misestimations
7
Hb estimation Mel estimation
• Instances of results that are contrary to
physiological expectations:
– Local variation in oxygen saturation under
perfectly normal pigmented nevi1
– Data showing that people of different races have
different regional oxygen saturation2,3
– Collagen fluorescence is different under
pigmented and non-pigmented regions4
– A poor correlation between the SIAscans and
histopathological findings in pigmented skin
lesions5
1. Kapsokalyvas, D., et al. Spectral morphological analysis of skin lesions with a polarization
multispectral dermoscope. , Opt Express, 21, 4826-4840 (2013)
2. Vyas, S., Banerjee, A., & Burlina, P. Estimating physiological skin parameters from hyperspectral
signatures. , J Biomed Opt, 18, 057008 (2013)
3. Yudovsky, D. & Pilon, L. Retrieving skin properties from in vivo spectral reflectance
measurements. ,J Biophotonics, 4, 305–314 (2011)
4. Na, R., Stender, I. M., Henriksen, M., & Wulf, H. C. Autofluorescence of human skin is age-
related after correction for skin pigmentation and redness. , J. Invest Derm, 116, 536-540 (2001)
5. Terstappen, K., Suurküla, M., Hallberg, H., Ericson M. B., & Wennberg, A. M., Poor correlation between
spectrophotometric intracutaneous analysis and histopathology in melanoma and nonmelanoma lesions.
, J Biomed Opt, 18, 061223 (2013)
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Hemoglobin misestimation using ratiometric analysis
8
Diebele, I., A. Bekina, A. Derjabo, J. Kapostinsh, I. Kuzmina, and J. Spigulis. "Analysis of skin basalioma and melanoma by multispectral imaging." In Proc.
SPIE, vol. 8427, p. 842732. 2012.
M = 100 (OD650 – OD700), E = 100 (OD560 – OD650),
Melanin masking Hb estimation
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Spectral
Molecular
Imaging
Hemoglobin misestimation using ratiometric analysis (cont.)
9
Kapsokalyvas, D., et al. Spectral morphological analysis of skin lesions with a polarization multispectral dermoscope. , Opt Express, 21, 4826-4840 (2013)
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
SkinSpect – clinical vs research prototype
10
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Spectral
Molecular
Imaging
SkinSpect™ overview
11
RGB: P-polarized
RGB: X-polarized
Fluorescence:
P and X-polarized
Reflectance datacube : P-polarized
Reflectance datacube : X-polarized
Wavebands ( ~ 33)
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
SkinSpect Data output (Overview)
•
12
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Visible Light Hand Imaging Characteristics
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Spectral
Molecular
Imaging
SkinSpect Key Specifications
Spatial
• Total FOV Dia ~ 11 mm
• Each pixel in the FOV = 27 µm
• Each pixel in the camera: 6.45 µm
• Detection lens system:
×0.5 Magnification
• The minimum spatially resolvable line-
width detected by the P and X cameras
was approximately 110 µm, measured
by imaging a USAF 1951 resolution
test target.
Spectral
• RGB: 50nm FWHM
– OneLight®
• Spectral scanning
– 468nm – 857nm (33 wavelengths)
– FWHM: 22 nm
– Average Wavelength interval: 12.2 nm
14
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
SkinSpect Data analysis
15
• Calibrating datacubes:
• Apol spectral function:
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
SkinSpect Data analysis (Cont.)
16
• Estimation of relative deep melanin concentration map:
• Estimation of relative oxy- and deoxy-hemoglobin concentration maps using melanin
corrected Apol (500 nm -600 nm):
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Apol spectra in highly pigmented skin
17
RGB ┴
OD ┴
Apol
Deep melanin estimation using Apol
Melanin estimation using OD ┴
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Hemoglobin concentration misestimation
18
oHb
tHb
tHb
OSP
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Melanin corrected Hemoglobin relative concentration
maps
19
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Melanin corrected Hemoglobin relative concentration
maps
20
Mel
A A’
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
SkinSpect functional mapping- proof of concept
21
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Summary
Melanoma detection: “Blackbox” versus “biological model”
– Lack of specificity
– We want to address it by multimode imaging concept
SkinSpect Research prototype system and measurements
– Spatial and spectral specification
Two-layer skin optical model proposed for preliminary data
validation
– Effect of crosstalk between melanin and deoxy-hemoglobin
– Our approach: Two-step least square solver in different wavelength range
This dermoscope and its quantitative skin analysis algorithm allows
us to characterize highly pigmented lesions more accurately, and is
to improve detection of potentially cancerous lesions.
22
Spectral
Molecular
Imaging
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
2014 CMBEC37 Conference
Vancouver, BC
May 21 – 23, 2014
Nature: Scientific Reports - May 12, 2014
Questions?
23

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Cmbec37 skin spect may 2014

  • 1. 1 Multimode imaging applied toward diagnosis of skin cancer (SkinSpect) Fartash Vasefi a, Nicholas MacKinnon a, and Daniel L. Farkas a, b a Spectral Molecular Imaging Inc., 250 N. Robertson Blvd, Beverly Hills b Biomedical Engineering, University of Southern California, Los Angeles Spectral Molecular Imaging Inc. 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014
  • 2. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Safe Harbor “Safe Harbor” Statement under the Private Securities Litigation Reform Act of 1995. A number of the matters and subject areas discussed in this presentation that are not historical or current facts deal with potential future circumstances and developments. The discussion of such matters and subject areas is qualified by the inherent risks and uncertainties surrounding future expectations generally and also may materially differ from Spectral Molecular Imaging’s (SMI’s) future experience involving any of or more of such matters and subject areas. Such risks and uncertainties include: the early stage of products in development, the uncertainty of market acceptance of products, the uncertainty of development or effectiveness of distribution channels, the intense competition in the medical device industry, the uncertainty of capital to develop products, the uncertainty of regulatory approval of products, dependence on licensed intellectual property, as well as those that are more fully described from time to time under the heading “Risk Factors” in SMI’s filed with the SEC, including SMI’s Report on Form 10-K for the fiscal year ended December 31, 2010 and subsequent quarterly reports. 2 "Financial support from NIH and the USDHHS Qualifying Therapeutic Discovery Program is gratefully acknowledged".
  • 3. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Outline • Motivation • Dermoscopes using Biological Models Vs. Statistical classifiers • To address misestimations in current melanin and hemoglobin quantifications in pigmented skin lesions • Objective • To evaluate the performance of a quantitative imaging approach that combines two depth-sensitive imaging techniques, polarization and hyperspectral imaging, to produce a new multimode dermoscopy method that accurately maps melanin and hemoglobin oxygenation distribution in human skin. • Methods • Multimode imaging dermoscope and tissue measurements • Rapid quantification model for preliminary data validation • Results • Measurements of human in vivo skin with melanocytic nevus and venous occlusion 3
  • 4. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Recent News Nature: Scientific Reports - May 12, 2014 4
  • 5. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 • Spectral Molecular Imaging (SMI), Inc., a subsidiary of Cascade Technologies Corp., is developing high-resolution, hyperspectral imaging for early and accurate diagnosis of cancer and other major diseases • SkinSpectTM is a hyperspectral imaging system designed to meet the need for accurate diagnosisof skin cancer. Spectral Molecular Imaging - SkinSpectTM 5 Melanoma Incidence Melanoma Mortality W.H.O. - 2004 USA/Canada 94,000/yr 13,000/yr Europe 65,000/yr 28,000/yr Melanoma Prevalence and Mortality (per 100,000) 0 5 10 15 20 25 30 1975 1980 1985 1990 1995 2000 2005 2010 Year Melanoma Prevalence Modeled Rate Melanoma Mortality Modeled Rate
  • 6. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Biological Models vs. Statistical Classifiers (Black Boxes) Black Box • Need big trials to have sufficient data for BlackBox algorithm validation • Exceptional data qualification/validation through standards and well developed data quality algorithms Biological Model (Method we have adopted) • Directly linked to tissue properties with well developed scientific basis • Biological plausibility that is easily understood by clinicians (and makes sense to regulatory authorities) •6
  • 7. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Melanin vs. hemoglobin misestimations 7 Hb estimation Mel estimation • Instances of results that are contrary to physiological expectations: – Local variation in oxygen saturation under perfectly normal pigmented nevi1 – Data showing that people of different races have different regional oxygen saturation2,3 – Collagen fluorescence is different under pigmented and non-pigmented regions4 – A poor correlation between the SIAscans and histopathological findings in pigmented skin lesions5 1. Kapsokalyvas, D., et al. Spectral morphological analysis of skin lesions with a polarization multispectral dermoscope. , Opt Express, 21, 4826-4840 (2013) 2. Vyas, S., Banerjee, A., & Burlina, P. Estimating physiological skin parameters from hyperspectral signatures. , J Biomed Opt, 18, 057008 (2013) 3. Yudovsky, D. & Pilon, L. Retrieving skin properties from in vivo spectral reflectance measurements. ,J Biophotonics, 4, 305–314 (2011) 4. Na, R., Stender, I. M., Henriksen, M., & Wulf, H. C. Autofluorescence of human skin is age- related after correction for skin pigmentation and redness. , J. Invest Derm, 116, 536-540 (2001) 5. Terstappen, K., Suurküla, M., Hallberg, H., Ericson M. B., & Wennberg, A. M., Poor correlation between spectrophotometric intracutaneous analysis and histopathology in melanoma and nonmelanoma lesions. , J Biomed Opt, 18, 061223 (2013)
  • 8. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Hemoglobin misestimation using ratiometric analysis 8 Diebele, I., A. Bekina, A. Derjabo, J. Kapostinsh, I. Kuzmina, and J. Spigulis. "Analysis of skin basalioma and melanoma by multispectral imaging." In Proc. SPIE, vol. 8427, p. 842732. 2012. M = 100 (OD650 – OD700), E = 100 (OD560 – OD650), Melanin masking Hb estimation
  • 9. 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Spectral Molecular Imaging Hemoglobin misestimation using ratiometric analysis (cont.) 9 Kapsokalyvas, D., et al. Spectral morphological analysis of skin lesions with a polarization multispectral dermoscope. , Opt Express, 21, 4826-4840 (2013)
  • 10. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 SkinSpect – clinical vs research prototype 10
  • 11. 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Spectral Molecular Imaging SkinSpect™ overview 11 RGB: P-polarized RGB: X-polarized Fluorescence: P and X-polarized Reflectance datacube : P-polarized Reflectance datacube : X-polarized Wavebands ( ~ 33)
  • 12. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 SkinSpect Data output (Overview) • 12
  • 13. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Visible Light Hand Imaging Characteristics
  • 14. 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Spectral Molecular Imaging SkinSpect Key Specifications Spatial • Total FOV Dia ~ 11 mm • Each pixel in the FOV = 27 µm • Each pixel in the camera: 6.45 µm • Detection lens system: ×0.5 Magnification • The minimum spatially resolvable line- width detected by the P and X cameras was approximately 110 µm, measured by imaging a USAF 1951 resolution test target. Spectral • RGB: 50nm FWHM – OneLight® • Spectral scanning – 468nm – 857nm (33 wavelengths) – FWHM: 22 nm – Average Wavelength interval: 12.2 nm 14
  • 15. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 SkinSpect Data analysis 15 • Calibrating datacubes: • Apol spectral function:
  • 16. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 SkinSpect Data analysis (Cont.) 16 • Estimation of relative deep melanin concentration map: • Estimation of relative oxy- and deoxy-hemoglobin concentration maps using melanin corrected Apol (500 nm -600 nm):
  • 17. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Apol spectra in highly pigmented skin 17 RGB ┴ OD ┴ Apol Deep melanin estimation using Apol Melanin estimation using OD ┴
  • 18. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Hemoglobin concentration misestimation 18 oHb tHb tHb OSP
  • 19. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Melanin corrected Hemoglobin relative concentration maps 19
  • 20. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Melanin corrected Hemoglobin relative concentration maps 20 Mel A A’
  • 21. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 SkinSpect functional mapping- proof of concept 21
  • 22. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Summary Melanoma detection: “Blackbox” versus “biological model” – Lack of specificity – We want to address it by multimode imaging concept SkinSpect Research prototype system and measurements – Spatial and spectral specification Two-layer skin optical model proposed for preliminary data validation – Effect of crosstalk between melanin and deoxy-hemoglobin – Our approach: Two-step least square solver in different wavelength range This dermoscope and its quantitative skin analysis algorithm allows us to characterize highly pigmented lesions more accurately, and is to improve detection of potentially cancerous lesions. 22
  • 23. Spectral Molecular Imaging 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 2014 CMBEC37 Conference Vancouver, BC May 21 – 23, 2014 Nature: Scientific Reports - May 12, 2014 Questions? 23

Editor's Notes

  1. We first start to describe the motivation behind SkinSpect system for melanoma detection application, We also represent recent literatures regarding the misestimating in current melanin and hemoglobin quantifications Our Objective is to show our evaluation of combining polarization and hyperspectral imaging as a new multimode dermoscope that intend to accurately maps melanin and hemoglobin distribution in human skin We will talk about the multimode imaging system characteristics and our proposed quantification model for preliminary data validation, I will cover our in vivo skin analysis with melanocytic nevus as an example of high melanin skin as well as venous occlusion as an example of hemoglobin increase in skin.
  2. erythema index values correlate almost linearly with the amount of Hb in the superficial plexus. Takiwaki, Hirotsugu. "Measurement of skin color: practical application and theoretical considerations." Journal of Medical Investigation 44 (1998): 121-126.