Nerve autofluorescence in near-ultraviolet light markedly enhances nerve visualization in vivo.

Autofluorescence Near-ultraviolet light Nerve Nerve-sparing surgery Spectroscopy

Journal

Surgical endoscopy
ISSN: 1432-2218
Titre abrégé: Surg Endosc
Pays: Germany
ID NLM: 8806653

Informations de publication

Date de publication:
03 2022
Historique:
received: 10 11 2020
accepted: 28 03 2021
pubmed: 10 4 2021
medline: 4 3 2022
entrez: 9 4 2021
Statut: ppublish

Résumé

During surgery, surgeons must accurately localize nerves to avoid injuring them. Recently, we have discovered that nerves fluoresce in near-ultraviolet light (NUV) light. The aims of the current study were to determine the extent to which nerves fluoresce more brightly than background and vascular structures in NUV light, and identify the NUV intensity at which nerves are most distinguishable from other tissues. We exposed sciatic nerves within the posterior thigh in five 250-300 gm Wistar rats, then observed them at four different NUV intensity levels: 20%, 35%, 50%, and 100%. Brightness of fluorescence was measured by fluorescence spectroscopy, quantified as a fluorescence score using Image-J software, and statistically compared between nerves, background, and both an artery and vein by unpaired Student's t tests with Bonferroni adjustment to accommodate multiple comparisons. Sensitivity, specificity, and accuracy were calculated for each NUV intensity. At 20, 35, 50, and 100% NUV intensity, fluorescence scores for nerves versus background tissues were 117.4 versus 40.0, 225.8 versus 88.0, 250.6 versus 121.4, and 252.8 versus 169.4, respectively (all p < 0.001). Fluorescence scores plateaued at 50% NUV intensity for nerves, but continued to rise for background. At 35%, 50%, and 100% NUV intensity, a fluorescence score of 200 was 100% sensitive, specific, and accurate identifying nerves. At 100 NUV intensity, artery and vein scores were 61.8 and 60.0, both dramatically lower than for nerves (p < 0.001). At all NUV intensities ≥ 35%, a fluorescence score of 200 is 100% accurate distinguishing nerves from other anatomical structures in vivo.

Sections du résumé

BACKGROUND
During surgery, surgeons must accurately localize nerves to avoid injuring them. Recently, we have discovered that nerves fluoresce in near-ultraviolet light (NUV) light. The aims of the current study were to determine the extent to which nerves fluoresce more brightly than background and vascular structures in NUV light, and identify the NUV intensity at which nerves are most distinguishable from other tissues.
METHODS
We exposed sciatic nerves within the posterior thigh in five 250-300 gm Wistar rats, then observed them at four different NUV intensity levels: 20%, 35%, 50%, and 100%. Brightness of fluorescence was measured by fluorescence spectroscopy, quantified as a fluorescence score using Image-J software, and statistically compared between nerves, background, and both an artery and vein by unpaired Student's t tests with Bonferroni adjustment to accommodate multiple comparisons. Sensitivity, specificity, and accuracy were calculated for each NUV intensity.
RESULTS
At 20, 35, 50, and 100% NUV intensity, fluorescence scores for nerves versus background tissues were 117.4 versus 40.0, 225.8 versus 88.0, 250.6 versus 121.4, and 252.8 versus 169.4, respectively (all p < 0.001). Fluorescence scores plateaued at 50% NUV intensity for nerves, but continued to rise for background. At 35%, 50%, and 100% NUV intensity, a fluorescence score of 200 was 100% sensitive, specific, and accurate identifying nerves. At 100 NUV intensity, artery and vein scores were 61.8 and 60.0, both dramatically lower than for nerves (p < 0.001).
CONCLUSIONS
At all NUV intensities ≥ 35%, a fluorescence score of 200 is 100% accurate distinguishing nerves from other anatomical structures in vivo.

Identifiants

pubmed: 33835251
doi: 10.1007/s00464-021-08484-0
pii: 10.1007/s00464-021-08484-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1999-2005

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Ciaramitaro P, Mondelli M, Logullo F et al (2010) Traumatic peripheral nerve injuries: epidemiological findings, neuropathic pain and quality of life in 158 patients. J Peripher Nerv Syst 15:120–127
doi: 10.1111/j.1529-8027.2010.00260.x
Kretschmer T, Antoniadis G, Braun V et al (2001) Evaluation of iatrogenic lesions in 722 surgically treated cases of peripheral nerve trauma. J Neurosurg 94:905–912
doi: 10.3171/jns.2001.94.6.0905
Szwedowicz P, Osuch-Wójcikiewicz E, Bruzgielewicz A et al (2011) Complications of parotid surgery for pleomorphic adenomas. Otolaryngol Pol 65(5 Suppl):46–52
doi: 10.1016/S0030-6657(11)70708-9
Bergauer B, Knipfer C, Amann A et al (2015) Does laser surgery interfere with optical nerve identification in maxillofacial hard and soft tissue? An experimental ex vivo study. Sensors 15:25416–25432
doi: 10.3390/s151025416
Walsh EM, Cole D, Tipirneni KE et al (2019) Fluorescence imaging of nerves during surgery. Ann Surg 270:69–76
doi: 10.1097/SLA.0000000000003130
Gandhe RU, Bhave CP (2018) Intraoperative magnetic resonance imaging for neurosurgery: an anaesthesiologist’s challenge. Indian J Anaesth 62:411–417
pubmed: 29962521 pmcid: 6004746
Jolesz FA (2005) Future perspectives for intraoperative MRI. Neurosurg Clin N Am 16:201–213
doi: 10.1016/j.nec.2004.07.011
Hingorani DV, Whitney MA, Friedman B et al (2018) Nerve-targeted probes for fluorescence-guided intraoperative imaging. Theranostics 8:4226–4237
doi: 10.7150/thno.23084
Reinhart MB, Huntington CR, Blair LJ et al (2016) Indocyanine green: historical context, current applications, and future considerations. Surg Innov 23:166–175
doi: 10.1177/1553350615604053
Amouroux M, Diaz-Ayil G, Blondel WC et al (2009) Classification of ultraviolet irradiated mouse skin histological stages by bimodal spectroscopy: multiple excitation autofluorescence and diffuse reflectance. J Biomed Opt 14:014011
doi: 10.1117/1.3077194
Breslin TM, Xu F, Palmer GM et al (2004) Autofluorescence and diffuse reflectance properties of malignant and benign breast tissues. Ann Surg Oncol 11:65–70
doi: 10.1007/BF02524348
de Veld DC, Skurichina M, Witjes MJ et al (2005) Autofluorescence and diffuse reflectance spectroscopy for oral oncology. Lasers Surg Med 36:356–364
doi: 10.1002/lsm.20122
Palmer GM, Zhu C, Breslin TM et al (2003) Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003). IEEE Trans Biomed Eng 50:1233–1242
doi: 10.1109/TBME.2003.818488
Shao X, Zheng W, Huang Z (2010) Polarized near-infrared autofluorescence imaging combined with near-infrared diffuse reflectance imaging for improving colonic cancer detection. Opt Express 218:24293–24300
doi: 10.1364/OE.18.024293
Zhu C, Chen S, Chui CH-K et al (2016) Early detection and differentiation of venous and arterial occlusion in skin flaps using visible diffuse reflectance spectroscopy and autofluorescence spectroscopy. Biomed Opt Express 7:11
Abbaci M, De Leeuw F, Breuskin I et al (2018) Parathyroid gland management using optical technologies during thyroidectomy or parathyroidectomy: a systematic review. Oral Oncol 87:186–196
doi: 10.1016/j.oraloncology.2018.11.011
Dip F, Falco J, Verna S et al (2019) Randomized controlled trial comparing white light with near-infrared autofluorescence for parathyroid gland identification during total thyroidectomy. J Am Coll Surg 228:744–751
doi: 10.1016/j.jamcollsurg.2018.12.044
Dip F, Rene A, Mariano S et al (2021) Nerve spectroscopy: understanding peripheral nerve autofluorescence through photodynamics. Surg Endosc. https://doi.org/10.1007/s00464-020-08227-7
doi: 10.1007/s00464-020-08227-7 pubmed: 34694489
Marcelissen TA, Den Hollander PP, Tuytten TR et al (2016) Incidence of iatrogenic ureteral injury during open and laparoscopic colorectal surgery: a single center experience and review of the literature. Surg Laparosc Endosc Percutan Tech 26:513–515
doi: 10.1097/SLE.0000000000000335
Berci G, Hunter J, Morgenstern L et al (2013) Laparoscopic cholecystectomy: first, do no harm; second, take care of bile duct stones. Surg Endosc 27:1051–1054
doi: 10.1007/s00464-012-2767-5
Yellinek S, Krizzuk D, J JN, et al (2018) Ureteral injury during colorectal surgery: two case reports and a literature review. J Anus Rectum Colon 2:71–76
doi: 10.23922/jarc.2017-052
Dip F, LoMenzo E, Sarotto L et al (2019) Randomized trial of near-infrared incisionless fluorescent cholangiography. Ann Surg 270:8
doi: 10.1097/SLA.0000000000003178
Falco J, Dip F, Quadri P et al (2016) Cutting edge in thyroid surgery: autofluorescence of parathyroid glands. J Am Coll Surg 2223:374–380
doi: 10.1016/j.jamcollsurg.2016.04.049
Kose E, Rudin AV, Kahramangil B et al (2020) Autofluorescence imaging of parathyroid glands: an assessment of potential indications. Surgery 67:173–179
doi: 10.1016/j.surg.2019.04.072
Rudin AV, Berber E (2019) Impact of fluorescence and autofluorescence on surgical strategy in benign and malignant neck endocrine diseases. Best Pract Res Clin Endocrinol Metab 1:101311
doi: 10.1016/j.beem.2019.101311
Bochenek K, Aebisher D, Międzybrodzka A et al (2019) Methods for bladder cancer diagnosis: the role of autofluorescence and photodynamic diagnosis. Photodiagn Photodyn Ther 27:8
doi: 10.1016/j.pdpdt.2019.05.036
Renkoski T, Hatch K, Utzinger U (2012) Wide-field spectral imaging of human ovary autofluorescence and oncologic diagnosis via previously collected probe data. J Biomed Opt 17:036003
doi: 10.1117/1.JBO.17.3.036003
Banda HK, Shah GK, Blinder KJ (2019) Applications of fundus autofluorescence and widefield angiography in clinical practice. Can J Ophthalmol 54:11–19
doi: 10.1016/j.jcjo.2018.10.003
Prentice AI (1965) Bone autofluorescence and mineral content. Nature 206:1167
doi: 10.1038/2061167a0
Prentice AI (1967) Autofluorescence of bone tissues. J Clin Pathol 20:717–719
doi: 10.1136/jcp.20.5.717
Wan L, Qin G, Yan W et al (2019) Skin autofluorescence is associated with diabetic peripheral neuropathy in Chinese patients with type 2 diabetes: a cross-sectional study. Genet Test Mol Biomarkers 23:387–392
doi: 10.1089/gtmb.2018.0328
Castro-e-Silva O, Sankarankutty AK, Correa RB et al (2008) Autofluorescence spectroscopy in liver transplantation: preliminary results from a pilot clinical study. Transplant Proc 40:722–725
doi: 10.1016/j.transproceed.2008.03.005
Stelzle F, Rohde M, Riemann M et al (2017) Autofluorescence spectroscopy for nerve-sparing laser surgery of the head and neck-the influence of laser-tissue interaction. Lasers Med Sci 32:1289–1300
doi: 10.1007/s10103-017-2240-8
Cotero VE, Siclovan T, Zhang R et al (2012) Intraoperative fluorescence imaging of peripheral and central nerves through a myelin-selective contrast agent. Mol Imaging Biol 14:708–717
doi: 10.1007/s11307-012-0555-1
Gibbs-Strauss SL, Nasr KA, Fish KM et al (2011) Nerve-highlighting fluorescent contrast agents for image-guided surgery. Mol Imaging 10(2):91–101
doi: 10.2310/7290.2010.00026
Gray D, Kim E, Cotero V et al (2012) compact fluorescence and white light imaging system for intraoperative visualization of nerves. Proc SPIE Int Soc Opt Eng 8207:10
pmcid: 3877310
de Melo GM, Cervantes O, Covolan L et al (2016) Facial nerve identification with fluorescent dye in rats. Acta Cir Bras 31(2):92–102
doi: 10.1590/S0102-865020160020000003
Hussain T, Nguyen LT, Whitney M et al (2016) Improved facial nerve identification during parotidectomy with fluorescently labeled peptide. Laryngoscope 126:2711–2717
doi: 10.1002/lary.26057
Whitney MA, Crisp JL, Nguyen LT et al (2011) Fluorescent peptides highlight peripheral nerves during surgery in mice. Nat Biotechnol 29:352–356
doi: 10.1038/nbt.1764

Auteurs

Fernando Dip (F)

Instituto Argentino de Diagnóstico y Tratamiento, Universidad de Buenos Aires, Buenos Aires, Argentina.
Cleveland Clinic Florida, Weston, FL, 33325, USA.

Pedro Bregoli (P)

Instituto Argentino de Diagnóstico y Tratamiento, Universidad de Buenos Aires, Buenos Aires, Argentina.

Jorge Falco (J)

Instituto Argentino de Diagnóstico y Tratamiento, Universidad de Buenos Aires, Buenos Aires, Argentina.

Kevin P White (KP)

ScienceRight Research Consulting, London, ON, Canada.

Raúl J Rosenthal (RJ)

Cleveland Clinic Florida, Weston, FL, 33325, USA. rosentr@ccf.org.
Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd., Weston, FL, 33331, USA. rosentr@ccf.org.

Articles similaires

Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell
Animals TOR Serine-Threonine Kinases Colorectal Neoplasms Colitis Mice
Animals Tail Swine Behavior, Animal Animal Husbandry

Classifications MeSH