Lithuanian Journal of Physics article / Lietuvos fizikos žurnalo straipsnis

OPTICAL SPECTROSCOPIC METHODS FOR DIAGNOSTICS OF INTERVERTEBRAL DISC DEGENERATION
Juozas Vidmantis Vaitkus^a, Darius Varanius^a,b, Ignas Čiplys^a,b, Vilmantas Gėgžna^a,b, Gunaras Terbetas^d, Jurgita Ušinskienė^c, and Aurelija Vaitkuvienė^a
^aInstitute of Photonics and Nanotechnology, Vilnius University, Saulėtekio 3, 10257 Vilnius, Lithuania
^bInstitute of Biosciences, Life Sciences Centre, Vilnius University, Saulėtekio 7, 10257 Vilnius, Lithuania
^cNational Cancer Institute, Vilnius University, Santariškių 1, 08660 Vilnius, Lithuania
^dFaculty of Medicine, Vilnius University, M. K. Čiurlionio 21, 03101 Vilnius, Lithuania
E-mail: juozas.vaitkus@ff.vu.lt
Received 15 September 2017; revised 10 May 2018; accepted 21 June 2018

The level of degeneration (LOD) in the human intervertebral disc (IVD) could determine the choice of patient treatment strategy, thus there is a need for methods applicable at a point of care that enable quick medical decisions. In this paper, infrared light absorption, FT-Raman scattering and fluorescence spectroscopy were used to analyse the same specimens from different groups of IVD samples.
Samples from the lumbar part of spine of 37 patients (mean age 48.2 years old) were included in the study. The gender distribution was 27 women and 10 men. The distribution by LOD in the Pfirrmann scale was as follows: grade 3 (40.5%), grade 4 (48.6%) and grade 5 (10.8%) were evaluated in our samples. Spectroscopic signals were measured and analysed. Features such as medical condition (LOD), patient’s age and gender were taken into account. All three methods of spectroscopy revealed age-dependent spectroscopic features related to LOD. For the first time a promissing possibility was found to recognize the LOD by fluorescence spectra in human IVD material taking gender and age into account. The findings create a background for the design of equipment and the design of experiment of more advanced clinical trials. FT-IR absorption and FT-Raman scattering spectra demonstrated the age dependences of a few components. The Raman peak at 2707 cm^–1 seems promising for recognition of lumbar IVD LOD, but a higher number of specimens is necessary.

Keywords: optical biopsy, tissue fluorescence, Raman spectroscopy, FT-IR absorption, biomedical diagnostics
PACS: 87.64.km, 87.64.kp, 87.64.kv

OPTINĖS SPEKTROSKOPIJOS METODAI STUBURO TARPSLANKSTELINIO DISKO DEGENERACIJOS DIAGNOSTIKAI
Juozas Vidmantis Vaitkus^a, Darius Varanius^a,b, Ignas Čiplys^a,b, Vilmantas Gėgžna^a,b, Gunaras Terbetas^d, Jurgita Ušinskienė^c, Aurelija Vaitkuvienė^a

^aVilniaus universiteto Fotonikos ir nanotechnologijų institutas, Vilnius, Lietuva
^bVilniaus universiteto Gyvybės mokslų centro Biomokslų institutas, Vilnius, Lietuva
^cNacionalinis vėžio institutas, Vilnius,Lietuva
^dVilniaus universiteto Medicinos fakultetas, Vilnius, Lietuva

Stuburo tarpslankstelinio disko degeneracijos laipsnis gali turėti įtakos parenkant gydymo strategiją, todėl ieškomi metodai, leisiantys tai atlikti chirurgo darbo vietoje. Šiame darbe atlikta infraraudonosios šviesos sugerties, Ramano sklaidos ir fluorescencijos spektrų analizė, atliekant skirtingų spektrinių požymių grupių mėginių palyginimą statistiniais metodais. Tyrime dalyvavo 37 pacientai (27 moterys ir 10 vyrų; vidutinis tiriamųjų amžius 48,2 metai). Mėginiai buvo paimti iš juosmeninės stuburo srities. Nustatyta 3-as (40,5 %), 4-tas (48,6 %) ir 5-tas (10,8 %) degeneracijos lygmuo pagal Pfirrmanno degeneracijos vertinimo metodiką. Visais trimis tyrimo metodais atrasti požymiai priklauso nuo pacientų amžiaus, lyties ir disko degeneracijos laipsnio.
Nustatyta, kad duomenų sklaida skirtinguose mėginiuose juos tiriant infraraudonosios šviesos sugerties ir Ramano sklaidos metodais yra per didelė. Gauti rezultatai nėra pakankamai patikimi, kad siūlomą metodą galėtume rekomenduoti ar taikyti nustatant tarpslankstelinio disko degeneraciją. Su tarpslankstelinio disko degeneracija galimai susijusį Ramano sklaidos spektrų komponentą, išskirtą ties 2707 cm^–1, tikslinga tirti pasitelkiant didesnį kiekį mėginių. Fluoroforų, esančių audiniuose, fluorescencijos spektrai persikloja, tačiau atrastos spektro sritys, kuriose rasti požymiai pakankamai patikimai leidžia įvertinti disko degeneracijos laipsnį ir aptikti su tuo susijusius tarpslankstelinio disko biocheminius pokyčius. Šios išvados galėtų lemti pažangesnių eksperimentinių klinikinių tyrimų projektus ateityje. Optinė diagnostika teikia galimybę atskirti senėjimo ir degeneracijos procesus abiems lytims.

References / Nuorodos

[1] J.P.G. Urban and S. Roberts, Degeneration of the intervertebral disc, Arthritis Res. Ther. 5(3), 120–130 (2003),
https://doi.org/10.1186/ar629
[2] T. Tan, S.L. Borkowski, S. Sangiorgio, P. Campbell, and E. Ebramzadeh, Imaging criteria for the quantification of disc degeneration: A systematic review, J. Bone Joint Surg. 3(2), 1–10 (2015),
https://doi.org/10.2106/JBJS.RVW.N.00056
[3] L.M. Benneker, P.F. Heini, S.E. Anderson, M. Alini, and K. Ito, Correlation of radiographic and MRI parameters to morphological and biochemical assessment of intervertebral disc degeneration, Eur. Spine J. 14(1), 27–35 (2005),
https://doi.org/10.1007/s00586-004-0759-4
[4] C. Pfirrmann, A. Metzdorf, M. Zanetti, J. Hodler, and N. Boos, Magnetic resonance classification of lumbar intervertebral disc degeneration, Spine 26(17), 1873–1878 (2001),
https://doi.org/10.2147/JPR.S122380
[5] G. Livshits, M. Popham, I. Malkin, P.N. Sambrook, A.J. MacGregor, T. Spector, and F.M.K. Williams, Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study, Ann. Rheum. Dis. 70(10), 1740–1745 (2011),
https://doi.org/10.1136/ard.2010.137836
[6] K. Luoma, H. Riihimaki, R. Luukkonen, R. Raininko, E. Viikari-Juntura, and A. Lamminen, Low back pain in relation to lumbar disc degeneration, Spine 25(23), 487–492 (2000),
https://doi.org/10.1097/00007632-200002150-00016
[7] M. Hancock, C. Maher, P. Macaskill, J. Latimer, W. Kos, and J. Pik, MRI findings are more common in selected patients with acute low back pain than controls? Eur. Spine J. 21(2), 240–246 (2012),
https://doi.org/10.1007/s00586-011-1955-7
[8] M.A. van den Bosch, W. Hollingworth, A.L. Kinmonth, and A.K. Dixon, Evidence against the use of lumbar spine radiography for low back pain, Clin. Radiol. 59(1), 69–76 (2004),
https://doi.org/10.1016/j.crad.2003.08.012
[9] B. Schenk, P.A. Brouwer, W.C. Peul, and M.A. van Buchem, Percutaneous laser disk decompression: a review of the literature, AJNR Am. J. Neuroradiol. 27(1), 232–235 (2006),
http://www.ajnr.org/content/27/1/232
[10] R. Alfano and Y. Pu, Optical biopsy for cancer detection, in: Lasers for Medical Applications, ed. H. Jelinkova (Woodhead Publishing Limited, 2013) pp. 325–367,
https://doi.org/10.1533/9780857097545.3.325
[11] C. af Klinteberg, J. Wang-Nordman, C. Lindquist, K. Svanberg, and A. Vaitkuviene, Laser induced fluorescence studies of premalignant and benign lesions in the female genital tract, Proc. SPIE 3197, 34–40 (1997),
https://doi.org/10.1117/12.297947
[12] M.J. DeWeert, J. Oyama, E. McLaughlin, E. Jacobson, J. Hakansson, G.S. Bignami, U.P. Gustafsson, P. Troy, V. Poskiene, K. Kriukelyte, et al., Analysis of spatial variability in hyperspectral imagery of the uterine cervix in vivo, Proc. SPIE 4959, 67–76 (2003),
https://doi.org/10.1117/12.479495
[13] T. Hoell, G. Huschak, A. Beier, G. Hüttmann, Y. Minkus, H.J. Holzhausen, and H.J. Meisel, Auto fluorescence of intervertebral disc tissue: A new diagnostic tool, Eur. Spine J., 15(Supplement 3), 345–353 (2006),
https://doi.org/10.1007/s00586-006-0157-1
[14] D. Varanius, G. Terbetas, J.V. Vaitkus, and A. Vaitkuviene, Spinal hernia tissue autofluorescence spectrum, Lasers Med. Sci. 28(2), 423–430 (2013),
https://doi.org/10.1007/s10103-012-1077-4
[15] B. Gefvert, Raman Spectroscopy: Spectroscopy system outperforms MRI for invasive cancer detection, BioOptics World 10(9) (2017),
https://www.bioopticsworld.com/articles/print/volume-10/issue-9/raman-spectroscopy-spectroscopy-system-outperforms-mri-for-invasive-cancer-detection.html
[16] R Core Team, R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria, 2016),
https://www.R-project.org/
[17] D. Hopkins, Chemometrics in action. Shoot-out 2002: transfer of calibration for content of active in a pharmaceutical tablet, NIR News 14(5), 10–13 (2003),
https://doi.org/10.1255/nirn.735
[18] T. Fawcett, An introduction to ROC analysis, Pattern Recognit. Lett. 27(8), 859–928 (2006),
https://doi.org/10.1016/j.patrec.2005.10.010
[19] K.H. Brodersen, C.S. Ong, K.E. Stephan, and J.M. Buhmann, The balanced accuracy and its posterior distribution, in: Proceedings of the 20th International Conference on Pattern Recognition (ICPR) (IEEE, Istanbul, 2010),
https://doi.org/10.1109/ICPR.2010.764
[20] S.-Y. Lin, M.-J. Li, and W.-T. Cheng, FT-IR and Raman vibrational microspectroscopies used for spectral biodiagnosis of human tissues, Spectroscopy 21(1), 1–30,
https://doi.org/10.1155/2007/278765
[21] D. Naumann, Infrared spectroscopy in microbiology, in: Encyclopedia of Analytical Chemistry, ed. R. A. Meyers (John Wiley & Sons Ltd, Chichester, 2000) pp. 102–131,
https://doi.org/10.1002/9780470027318.a0117.pub2
[22] A. Adams, Intervertebral disc tissues, in: Mechanical Properties of Aging Soft Tissues, eds. B. Derby and R. Akhtar (Springer International Publishing, 2015) pp. 7–35,
https://doi.org/10.1007/978-3-319-03970-1_2
[23] Z. Movasaghi, S. Rehman, and I. Rehman, Raman spectroscopy of biological tissues, Appl. Spectrosc. Rev. 42(5), 493–541 (2007),
https://doi.org/10.1080/05704920701551530
[24] M.N. Slipchenko, T.T. Le, H. Chen, and J.- X. Cheng, High-speed vibrational imaging and spectral analysis of lipid bodies by compound Raman microscopy, J. Phys. Chem. B 113(21), 7681–7686 (2009),
https://doi.org/10.1021/jp902231y
[25] K. Czamara, K. Majzner, M.Z. Pacia, K. Kochan, A. Kaczor, and M. Baranska, Raman spectroscopy of lipids: A review, J. Raman Spectrosc. 46(1), 4–20 (2015),
https://doi.org/10.1002/jrs.4607
[26] J. De Gelder, K. De Gussem, P. Vandenabeele, and L. Moens, Reference database of Raman spectra of biological molecules, J. Raman Spectrosc. 38(9), 1133–1147 (2007),
https://doi.org/10.1002/jrs.1734
[27] C. Krafft, L. Neudert, T. Simat, and R. Salzer, Near infrared Raman spectra of human brain lipids, Spectrochim. Acta A Mol. Biomol. Spectrosc. 61(7), 1529–1535 (2005),
https://doi.org/10.1016/j.saa.2004.11.017
[28] D.S.J. Choy, Percutaneous laser disc decompression: history and scientific rationale, Tech. Reg. Anesth. Pain Manag. 9(1), 50–55 (2005),
https://doi.org/10.1053/j.trap.2005.01.005
[29] V.E. Arpinar, S. Rand, A. Klein, D. Maiman, and L.T. Muftuler, Changes in perfusion and diffusion in the endplate regions of degenerating intervertebral discs: A DCE-MRI study, Eur. Spine J. 24(11), 2458–2467 (2015),
https://doi.org/10.1007/s00586-015-4172-y
[30] D. Kurouski, R.P. Van Duyne, and I.K. Lednev, Exploring the structure and formation mechanism of amyloid fibrils by Raman spectroscopy: a review, Analyst 140(15), 4967–4980 (2015),
https://doi.org/10.1039/C5AN00342C
[31] S. Arya, A. Kumari, V. Dalal, M. Bhattacharya, and S. Mukhopadhyay, Appearance of annular ringlike intermediates during amyloid fibril formation from human serum albumin, Phys. Chem. Chem. Phys. 17, 22862–22871 (2015),
https://doi.org/10.1039/C5CP03782D
[32] C. Ladefoged, O. Fedders, and O.F. Petersen, Amyloid in intervertebral discs: A histopathological investigation of surgical material from 100 consecutive operations on herniated discs, Ann. Rheum. Dis. 45(3), 239–243 (1986),
https://doi.org/10.1136/ard.45.3.239
[33] R. Dacosta, H. Andersson, and B. Wilson, Molecular fluorescence excitation–emission matrices relevant to tissue spectroscopy, Photochem. Photobiol. 78(4), 384–392 (2003),
https://doi.org/10.1562/0031-8655(2003)0780384MFEMRT2.0.CO2
[34] A.C. Croce and G. Bottiroli, Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis, Eur. J. Histochem. 58(4), 320–337 (2014),
https://doi.org/10.4081/ejh.2014.2461