COLLAGEN ULTRASTRUCTURE CHANGES IN LENTIGINOUS MELANOMA CHARACTERIZED BY SECOND-HARMONIC GENERATION MICROSCOPY

Martynas Riauka1, Viktoras Mazeika1, Mykolas Maciulis1, Edvardas Zurauskas2, Lukas Kontenis1, 3, Virginijus Barzda1, 4

1 Laser Research Centre, Faculty of Physics, Vilnius University, Sauletekis Avenue 3, LT-10222, Vilnius, Lithuania

2 Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, M.K. Ciurlionio St 21/27, LT-03101, Vilnius, Lithuania

3 Light Conversion, Keramiku st 2B, LT-10234, Vilnius, Lithuania

4 Department of Physics, Department of Chemical and Physical Sciences, University of Toronto, 3359 Mississauga Rd North, Mississauga, L5L 1C6, Canada

[email protected]

Development and spread of cancer are known to cause changes in the structure of extracellular matrix (ECM). A substantial portion of ECM is comprised of collagen, which is a noncentrosymmetric structure. Due to this, it is known to produce second-harmonic generation (SHG) signals. Furthermore, the SHG signals, produced in collagen, are strongly dependent on the angle between the collagen fibers and the incoming light polarization, hence the structural changes of collagen can be studied using polarimetric second-harmonic generation microscopy [1].

A reduced polarimetric SHG microscopy techniques, namely linear polarization-in, polarization-out (PIPO) microscopy, is applied for skin tissue imaging. In PIPO case, for each orientation of linearly polarized incoming laser radiation a set of linearly polarized states of outgoing second harmonic signal is measured [2].

In this work, PIPO technique was applied to obtain the intensity, achiral susceptibility ratio $R$ and collagen fiber orientation angle distributions in pT1b stage lentiginous melanoma histological sections. The parameter distributions were extracted by performing a pixel by pixel fitting procedure of the intensity variations in the image using the SHG intensity equation for the PIPO case [2]. The same sample contained normal (intersection between healthy epidermis and dermis) and cancerous tissue (intersection between tumor tissue and dermis), therefore these parameters were used to investigate the structural differences between the two cases.

PIPO data analysis revealed the differences in collagen fiber orientations as well as increase in $R$ ratio and decrease in SHG intensity in cancerous tissues, which suggests a modified collagen structure. Therefore, the differences in the polarimetric parameters of collagen can be applied for melanoma research and diagnostics.

Figure 1
Fig. 1. Nonlinear microscopy of melanoma in H&E histopathology samples. H&E stained cancerous (a) and normal (d) tissues with corresponding SHG intensity and R ratio distribution maps in cancerous (b, c) and normal (e, f) tissues.

Acknowledgments: The work was supported by grant No. 1.2.2.-LMT-K-718-02-0016.


[1] Masood Samim, Serguei Krouglov, and Virginijus Barzda, "Double Stokes Mueller polarimetry of second-harmonic generation in ordered molecular structures," J. Opt. Soc. Am. B 32, 451-461 (2015).

[2] A. Golaraei, Polarimetric second-harmonic generation microscopy for histopathology. PhD thesis, University of Toronto, 2018.