Continuous-wave Circular Polarization Terahertz Imaging of Nonmelanoma

Skin Cancers By Jillian Martin

Introduction •  Reflective continuous-wave (CW) terahertz (THz) imaging system utilizing linear

polarization (LP) detection –  Delineate tumor margins for nonmelanoma skin cancers1

–  Determine reflectivity differences between normal and cancerous colon2

•  Aim: Investigate circular polarization (CP) sensitive detection

–  Demonstrated at optical wavelengths3

–  Potential to demonstrate increased contrast

–  Results may shed light on mechanism behind contrast

[1] Joseph et al. J. Biophotonics 2014, 7.5, 295-303. [2] Doradla et al. J. Biomed. Opt. 18, 090504 (2013). [3] Morgan & Stockford Opt. Lett. 2003, 28.2, 114-116.

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Motivation •  Each year, approximately 3.5 million cases of nonmelanoma skin cancer

(NMSC) are diagnosed in the U.S.4

–  Common forms include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)

•  Annual cost of NMSC treatment in the U.S. is $4.8 billion5

•  Mohs Micrographic Surgery (MMS)6

–  Highest treatment success rate –  Remove tumor gradually: excise one slice at a time and process for frozen hematoxylin and

eosin (H&E) histopathology –  Surgeon maps tumor margins, removing cancer and conserving healthy tissue –  Disadvantages: time- and cost-inefficient, and labor intensive6

[4] American Cancer Society, “Cancer Facts & Figures 2015.” [5] Guy et al. Am. J. Prev. Med 2015, 48.2, 183-187. [6] National Cancer Institute, Sun Protection. “Cancer Trends Progress Report – 2009/2010 Update.”

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An intraoperative imaging modality capable of delineating tumor margins in vivo has the potential to improve NMSC treatment.

Diagram of the electromagnetic spectrum.

•  Non-ionizing

•  High sensitivity to water content

•  Better inherent resolution compared to microwaves

•  Contains characteristic resonant frequencies of biological molecules7

[7] B.M. Fischer et. al. Phys. Med. Biol. 47(2002) 3807-3814

Background The THz Spectral Regime

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Background

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Incident Co-polarized reflection Cross-polarized reflection

Z-cut quartz slide Tissue specimen

Saline-soaked gauze

Aluminum backing

Linearly Polarized THz Radiation Interaction

•  Interfaces generate Fresnel reflections •  LP radiation reflected from interfaces maintains initial polarization, whereas CP

radiation experiences a reverse in helicity •  LP cross-polarized and CP co-polarized reflected signals are predominantly from

within the tissue volume

Incident Cross-polarized reflection Co-polarized reflection

Z-cut quartz slide Tissue specimen

Saline-soaked gauze

Aluminum backing

Circularly Polarized THz Radiation Interaction Linearly Polarized (LP) Radiation Interaction Circularly Polarized (CP) Radiation Interaction

Materials & Methods

CW THz Source: CO2 Optically-Pumped FIR Gas Laser •  Frequency: 584 GHz

•  Wavelength: 513 µm •  Output power: 10.2 mW

•  Polarization: Linearly Polarized THz Detector: •  Liquid Helium Cooled Silicon

Bolometer

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Materials & Methods

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CP Illumination & Detection LP Illumination & Detection

•  Wire grid polarizer (WGP) selects polarization detected at B

−  Transmission axis vertical for co-polarized (Co LP) measurement

−  Transmission axis horizontal for cross-polarized (Cross LP) measurement

•  Crystalline quartz quarter-wave plate (QWP) generates CP radiation

•  Wire grid polarizer (WGP) selects polarization

−  Transmission axis horizontal, incident beam angle at 45°

−  Reflects cross-polarized (Cross CP) signal to Detector A

−  Transmits co-polarized (Co CP) signal to Detector B

Materials & Methods

•  Fresh excess skin samples were obtained within 2 hours of MMS at Massachusetts General Hospital (MGH) using appropriate IRB approved protocols

•  Samples were transferred to UML within 45 minutes, where samples were thawed and mounted

•  A custom designed sample holder was used to sandwich skin tissue between a 1mm-thick, z-cut quartz slide and saline-soaked gauze

•  Tissue samples were imaged within 6 hours of mounting

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Sample Handling & Preparation

THz Radiation

Side-view of custom designed sample holder.

Materials & Methods Image Calibration & Post-Processing

•  Co-polarized and cross-polarized images were obtained using both linearly- and circularly-polarized imaging modalities

•  Images were calibrated by measuring the return signal from a flat, front surface mirror

•  Images were post-processed using a bilinear interpolation, followed by a Gaussian low pass filter at one standard deviation

•  Final processed THz images were displayed in logarithmic space, with off-sample areas removed

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Materials & Methods Histology & Image Correlation

•  Histological Processing: –  Skin tissue samples were frozen and cut using en-face sectioning technique8,9

–  Frozen en-face tissue sections, 5µm thick, were placed on glass slides and stained with hematoxylin and eosin (H&E)

•  Image Correlation: –  H&E slides were compared to THz reflectance images obtained

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[8] Gross et al., Mohs surgery: fundamentals and techniques. (Mosby, 1999). [9] Mohs, F. E., “Chemosurgery: a microscopically controlled method of cancer excision,” Archives of Surgery, 42, 279 (1941).

Results

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(a) Photograph of skin specimen with z-cut quartz cover slide and saline-soaked gauze backing. (b) H&E stained histology with dotted outline demarcating tumor region.

**THz reflectance images corresponding to (c) cross-polarized and (d) co-polarized detection arms for LP illumination and to (e) co-polarized and (f) cross-polarized detection arms for CP illumination.

[10] Martin et al., J. Biomed. Opt. 21(7), 070502 (Jul 14, 2016)

Results

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•  Tumor in histology correlates with low reflectivity in cross-polarized LP and co-polarized CP images

•  Signal levels in cross-polarized LP image were higher than those in co-polarized CP image

−  Initial Hypothesis: CP detection will separate specular reflections more effectively than LP detection, leading to higher signal levels in co-polarized CP image

Discussion

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Contrast observed in “non-Fresnel” detection channels :

•  Possible Explanation:

−  Normal skin scatters THz radiation more due to higher variation in refractive index caused by the presence of structures

Signal level differences between “non-Fresnel” detection channels: •  Possible Explanation: CP radiation achieved greater penetration depth, and

thus experienced greater attenuation than LP radiation

−  Difference in penetration depth has been examined at optical wavelengths3, but has yet to be investigated at THz frequencies

[10] Martin et al., J. Biomed. Opt. 21(7), 070502 (Jul 14, 2016)

Conclusions

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•  A reflective, continuous-wave terahertz imaging system capable of illuminating fresh ex vivo tissue specimens with linearly-polarized (LP) and circularly-polarized (CP) radiation was constructed

•  A fresh human skin specimen containing basal cell carcinoma was imaged with both LP and CP illumination modalities

−  Non-Fresnel LP and CP terahertz images correlated

−  Non-Fresnel images correlated better to histology than images containing Fresnel reflections

Acknowledgements

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Biomedical Terahertz Technology Center Director: Dr. Robert Giles Program Manager: Dr. Cecil Joseph Undergraduates: WaiYuen Tang, Will Chambers

Advanced Biophotonics Laboratory Director: Dr. Anna Yaroslavsky Undergraduate: Nathan Perry

Department of Dermatology (MGH & HMS) Dr. Victor Neel Julie O’Neill

Submillimeter Wave Technology Laboratory Laser Systems Manager: Dr. Thomas Goyette THz Laser Technician: Lawrence Horgan