Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue

Abstract

Objective

Vocal fold scarring, a condition defined by increased collagen content, is challenging to treat without a method of noninvasively assessing vocal fold structure in vivo. The goal of this study was to observe the effects of vocal fold collagen content on optical coherence tomography imaging to develop a quantifiable marker of disease.

Study Design

Excised specimen study.

Setting

Massachusetts Eye and Ear Infirmary.

Subjects and Methods

Porcine vocal folds were injected with collagenase to remove collagen from the lamina propria. Optical coherence tomography imaging was performed preinjection and at 0, 45, 90, and 180 minutes postinjection. Mean pixel intensity (or image brightness) was extracted from images of collagenase- and control-treated hemilarynges. Texture analysis of the lamina propria at each injection site was performed to extract image contrast. Two-factor repeated measure analysis of variance and t tests were used to determine statistical significance. Picrosirius red staining was performed to confirm collagenase activity.

Results

Mean pixel intensity was higher at injection sites of collagenase-treated vocal folds than control vocal folds (P < .0001). Fold change in image contrast was significantly increased in collagenase-treated vocal folds than control vocal folds (P = .002). Picrosirius red staining in control specimens revealed collagen fibrils most prominent in the subepithelium and above the thyroarytenoid muscle. Specimens treated with collagenase exhibited a loss of these structures.

Conclusion

Collagen removal from vocal fold tissue increases image brightness of underlying structures. This inverse relationship may be useful in treating vocal fold scarring in patients.

Keywords

optical coherence tomography vocal fold scarring collagen

Get full access to this article

View all access options for this article.

References

Fujimoto

Brezinski

Tearney

. Optical biopsy and imaging using optical coherence tomography. Nat Med. 1995;1:970-972.

Huang

Swanson

Lin

. Optical coherence tomography. Science. 1991;254:178-1181.

Vignali

Solinas

Emanuele

Research and clinical applications of optical coherence tomography in invasive cardiology: a review. Curr Cardiol Rev. 2014;10:369-376.

Kirtane

Wagh

MS.

Endoscopic optical coherence tomography: advances in gastrointestinal imaging. Gastro Res Pract. 2014;2014:376367.

Sattler

Kastle

Welzel

Optical coherence tomography in dermatology. J Biomed Opt. 2013;18:061224.

Dhawan

D’Alessandro

Optical imaging modalities for biomedical applications. IEEE Rev Biomed Eng. 2010;3:69-92.

McLaughlin

Scolaro

Robbins

Saunders

Jacques

Sampson

DD.

Mapping tissue optical attenuation to identify cancer using optical coherence tomography. Med Image Comput Comput Assist Interv. 2009;12:657-664.

Wong

Jackson

Guo

. In vivo optical coherence tomography of the human larynx: normative and benign pathology in 82 patients. Laryngoscope. 2005;115:1904-1911.

Burns

Kim

deBoer

Anderson

Zeitels

SM.

Polarization-sensitive optical coherence tomography imaging of benign and malignant laryngeal lesions: an in vivo study. Otolaryngol Head Neck Surg. 2011;145:91-99.

10.

Beboujja

Garcia

Beaudette

. Intraoperative imaging of pediatric vocal fold lesions using optical coherence tomography. J Biomed Opt. 2016;21:1-10.

11.

Armstrong

Ridgway

Vokes

. Optical coherence tomography of laryngeal cancer. Laryngoscope. 2006;116:1107-1113.

12.

Garcia

Benboujja

Beaudette

. Using attenuation coefficients from optical coherence tomography as markers of vocal fold maturation. Laryngoscope. 2016;126:E218-E223.

13.

Burns

Kim

Kobler

deBoer

Lopez-Guerra

Zeitels

SM.

Real-time tracking of vocal fold injections with optical coherence tomography. Laryngoscope. 2009;119:2182-2186.

14.

Torkian

Guo

Jahng

. Noninvasive measurement of ablation crater size and thermal injury after CO₂ laser in the vocal cord with optical coherence tomography. Otolaryngol Head Neck Surg. 2006;134:86-91.

15.

Hirano

Kurita

Nakashima

. Growth, development, and ageing of human vocal folds. In: Bless

Abbes

eds. Vocal Fold Physiology Contemporary Research and Clinical Issues. San Diego, CA: College-Hill Press; 1983:23-43.

16.

Sato

Hirano

Nakashima

Age-related changes of collagenous fibers in the human vocal fold mucosa. Ann Otol Rhinol Laryngol. 2002;111:15-20.

17.

Buhler

Sennes

Tsuji

. Collagen type I, collagen type III, and versican in vocal fold lamina propria. Arch Otolaryngol Head Neck Surg. 2011;137:604-608.

18.

Titze

IR.

Normal vibration frequencies of the vocal ligament. J Acoust Soc Am. 2004;115:2264-2269.

19.

Buhler

Sennes

Mauad

. Collagen fiber and versican distribution within the lamina propria of fetal vocal folds. Laryngoscope. 2008;118:371-374.

20.

Hartnick

Rehbar

Prasad

Development and maturation of the pediatric human vocal fold lamina propria. Laryngoscope. 2005;115:4-15.

21.

Prades

Dumollard

Duband . Lamina propria of the human vocal fold: histomorphometric study of collagen fibers. Surg Radiol Anat. 2010;32:377-382.

22.

de Melo

ECM

Lemos

Filho

JAX

. Distribution of collagen in the lamina propria of the human vocal fold. Laryngoscope. 2003;113:2187-2191.

23.

Hahn

Kobler

Starcher

. Quantitative and comparative studies of the vocal fold extracellular matrix I: elastic fibers and hyaluronic acid. Ann Otol Rhinol Laryngol. 2006;115:156-164.

24.

Hahn

Kobler

Zeitels

. Quantitative and comparative studies of the vocal fold extracellular matrix II: collagen. Ann Otol Rhinol Laryngol. 2006;115:225-232.

25.

Butler

Hammond

Gray

SD.

Gender-related differences of hyaluronic acid distribution in the human vocal fold. Laryngoscope. 2001;111:907-911.

26.

Garrett

Coleman

Reinsich

Comparative histology and vibration of the vocal folds: implications for experimental studies in microlaryngeal surgery. Laryngoscope. 2000;110:814-824.

27.

Infusino

Ojha

Maurer

. The utility of histopathology in identifying structural differences among layers of the lamina propria. Int J Pediatr Otorhinolaryngol. 2013;77:1651-1654.

28.

Miri

AK.

Mechanical characterization of vocal fold tissue: a review study. J Voice. 2014;28:657-667.

29.

Graupp

Bachna-Rotter

Gerstenberger

. The unsolved chapter of vocal fold scars and how tissue engineering could help us solve the problem [published online June 25, 2015]. Eur Arch Otorhinolaryngol.

30.

Heris

Miri

Ghattamaneni

. Microstructural and mechanical characterization of scarred vocal folds. J Biomech. 2015;48:708-711.

31.

Welham

Montequin

Tateya

. A rat excised larynx model of vocal fold scar. J Speech Lang Hear Res. 2009;52:1008-1020.

32.

Rousseau

Hirano

Chan

. Characterization of chronic vocal fold scarring in a rabbit model. J Voice. 2003;18:116-124.

33.

Rousseau

Hirano

Scheidt

. Characterization of vocal fold scarring in a canine model. Laryngoscope. 2003;113:620-627.

34.

Hansen

Thibeault

SL.

Current understanding and review of the literature: vocal fold scarring. J Voice. 2006;20:110-120.

35.

Hhirano

Minamiguchi

Yamashita

. Histologic characterization of human scarred vocal folds. J Voice. 2009;23:399-407.

36.

Babalola

Mamalis

Lev-Tov

. Optical coherence tomography (OCT) of collagen in normal skin and skin fibrosis. Arch Dermatol Res. 2014;306:1-9.

37.

Abignano

Aydin

Castillo-Gallego

. Virtual skin biopsy by optical coherence tomography: the first quantitative imaging biomarker for scleroderma. Ann Rheum Dis. 2013;72:1845-1851.

38.

Knipper

Willenborg

Brinckmann

. Interleukin-4 receptor α signaling in myeloid cells controls collagen fibril assembly in skin repair. Immunity. 2015;43:803-816.

39.

Jayaraman

Jiang

Potsaid

. Design and performance of broadly tunable, narrow line-width, high repetition rate 1310nm VCSELs for swept source optical coherence tomography. Proc SPIE. 2012;8726:1-11.

40.

Tsai

Potsaid

Tao

. Ultrahigh speed endoscopic optical coherence tomography using micromotor imaging catheter and VCSEL technology. Biomed Opt Exp. 2013;4:1119-1132.

41.

Junqueira

LCU

Bignolas

Rentani

. Picrosirius staining plus polarization microscopy: a specific method for collagen detection in tissue sections. Histochem J. 1979;11:447-455.

42.

Stark

Kuhn

The properties of molecular fragments obtained on treating calfskin collagen with collagenase from Clostridium histolyticum. Eur J Biochem. 1968;6:534-541.

43.

Mookhtiar

Van Wart

HE.

Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix Suppl. 1992;1:116-126.

44.

Miri

Tripathy

Mongeau

Wiseman

Nonlinear laser scanning microscopy of human vocal folds. Laryngoscope. 2012;122:356-363.

45.

Heris

Miri

Ghattamaneni

. Microstructural and mechanical characterization of scarred vocal folds. J Biomech. 2015;48:708-711.

46.

Hirano

Current treatment of vocal fold scarring. Curr Opin Otolaryngol Head Neck Surg. 2005;13:143-147.

47.

Lim

Choi

Lee

. Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury. PLOS One. 2013;8:e54256.

48.

Mizuta

Hirano

Ohno

. Restoration of scarred vocal folds using 5 amino acid-deleted type hepatocyte growth factor. Laryngoscope. 2014;124:81-86.

49.

Hurst

Badalamente

Hentz

. Injectable collagenase clostridium histolyticum for Dupuytren’s contracture. NEJM. 2009;361:968-979.

50.

Levine

Cuzin

Mark

. Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie’s disease: a phase 3 open-label study. J Sex Med. 2015;12:248-258.