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
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