Handheld multiphoton and pinhole-free reflectance confocal microscopy enables noninvasive, real-time cross-sectional imaging in skin.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 10 2024
30 10 2024
Historique:
received:
01
08
2024
accepted:
17
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
Biopsy-based histology has been the foundation of disease diagnosis and management for over a century. A long-sought goal in dermatology is the development of an imaging modality with sufficient resolution and compositional detail to noninvasively interrogate skin histology in vivo. Here, we describe a system that achieves this goal using cross-sectionally scanned, multimodal microscopy (cross-modal). Cross-modal combines multiphoton and reflectance confocal microscopy into one compact system with coordinated three-axis scanning that preserves optical resolution in cross-section. A custom pinhole-free mechanism employing finite-infinite conjugates further simplifies and stabilizes confocal alignment. Evaluated in participants ages 9-81 and Fitzpatrick skin types (FST) 1-5, cross-modal images revealed histological details analogous to those obtained from traditional biopsied tissue. We observed dermal elastosis in sun-damaged skin, elevated melanin in pigmented skin, basaloid nests in basal cell carcinoma, and elongated rete ridges in seborrheic keratosis, supporting cross-modal's potential to deliver histological insights noninvasively.
Identifiants
pubmed: 39478114
doi: 10.1038/s41598-024-76908-7
pii: 10.1038/s41598-024-76908-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
26129Informations de copyright
© 2024. The Author(s).
Références
Jaklitsch, E. et al. Clinical utility of an AI-powered, handheld elastic scattering spectroscopy device on the diagnosis and management of skin cancer by primary care physicians. J. Prim. Care Community Health. https://doi.org/10.1177/21501319231205979 (2023).
doi: 10.1177/21501319231205979
pubmed: 37933569
pmcid: 10631325
Esteva, A. et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature. https://doi.org/10.1038/nature21056 (2017).
doi: 10.1038/nature21056
pubmed: 28658222
pmcid: 8382232
Reiter, O. et al. The diagnostic accuracy of dermoscopy for basal cell carcinoma: A systematic review and meta-analysis. J. Am. Acad. Dermatol. 80, 1380–1388 (2019).
doi: 10.1016/j.jaad.2018.12.026
pubmed: 30582991
di Ferrante Ruffano, L. et al. Optical coherence tomography for diagnosing skin cancer in adults. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD013189 (2018).
doi: 10.1002/14651858.CD013189
Caroline, G. et al. In vivo evaluation of skin of children with LC-OCT: An objective assessment. J. Eur. Acad. Dermatol. Venereol. https://doi.org/10.1111/JDV.19163 (2023).
doi: 10.1111/JDV.19163
Rajadhyaksha, M., Marghoob, A., Rossi, A., Halpern, A. & Nehal, K. Reflectance confocal microscopy of skin in vivo: From bench to bedside. Lasers Surg. Med. 49, 1–23 (2017).
doi: 10.1002/lsm.22600
Ruini, C., Schuh, S., Sattler, E. & Welzel, J. Line-field confocal optical coherence tomography—Practical applications in dermatology and comparison with established imaging methods. Skin Res. Technol. 27, 340–352 (2021).
doi: 10.1111/srt.12949
pubmed: 33085784
Chen, K. J., Han, Y., Wang, Z. Y. & Cui, Y. Submicron resolution techniques: Multiphoton microscopy in skin disease. Exp. Dermatol. 32, 1613–1623 (2023).
doi: 10.1111/exd.14899
pubmed: 37522747
Gambichler, T., Pljakic, A. & Schmitz, L. Recent advances in clinical application of optical coherence tomography of human skin. Clin Cosmet. Investig. Dermatol. 8, 345–354 (2015).
doi: 10.2147/CCID.S69119
pubmed: 26185462
pmcid: 4501682
Levine, A. & Markowitz, O. Introduction to reflectance confocal microscopy and its use in clinical practice. JAAD Case Rep. https://doi.org/10.1016/j.jdcr.2018.09.019 (2018).
doi: 10.1016/j.jdcr.2018.09.019
pubmed: 30456275
pmcid: 6232695
Dinnes, J. et al. Reflectance confocal microscopy for diagnosing cutaneous melanoma in adults. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD013190 (2018).
doi: 10.1002/14651858.CD013190
pubmed: 30521691
pmcid: 6517294
Dinnes, J. et al. Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD013191 (2018).
doi: 10.1002/14651858.CD013191
pubmed: 30521691
pmcid: 6517294
Agozzino, M., Gonzalez, S. & Ardigò, M. Reflectance confocal microscopy for inflammatory skin diseases. Actas Dermo-Sifiliográficas (English Edition) 107, 631–639 (2016).
doi: 10.1016/j.adengl.2016.01.030
Levine, A. & Markowitz, O. In vivo reflectance confocal microscopy. Cutis 99, 399–402 (2017).
pubmed: 28686758
Razi, S. et al. Line-field confocal optical coherence tomography for the diagnosis of skin tumors: A systematic review and meta-analysis. Diagnostics 14, 1522 (2024).
doi: 10.3390/diagnostics14141522
pubmed: 39061659
pmcid: 11276068
Zipfel, W. R., Williams, R. M. & Webb, W. W. Nonlinear magic: multiphoton microscopy in the biosciences. Nat. Biotechnol. 21, 1369–1377 (2003).
doi: 10.1038/nbt899
pubmed: 14595365
Schenke-Layland, K., Riemann, I., Damour, O., Stock, U. A. & König, K. Two-photon microscopes and in vivo multiphoton tomographs—Powerful diagnostic tools for tissue engineering and drug delivery. Adv. Drug Deliv. Rev. 58, 878–896 (2006).
doi: 10.1016/j.addr.2006.07.004
pubmed: 17011064
Balu, M. et al. In vivo multiphoton microscopy of basal cell carcinoma. JAMA Dermatol. https://doi.org/10.1001/jamadermatol.2015.0453 (2015).
doi: 10.1001/jamadermatol.2015.0453
pubmed: 25909650
pmcid: 4607557
Seidenari, S. et al. Diagnosis of BCC by multiphoton laser tomography. Skin Res. Technol. https://doi.org/10.1111/j.1600-0846.2012.00643.x (2012).
doi: 10.1111/j.1600-0846.2012.00643.x
pubmed: 23279266
Yew, E., Rowlands, C. & So, P. T. Application of multiphoton microscopy in dermatological studies: A mini-review. J. Innov. Opt. Health Sci. 7, 1330010 (2014).
doi: 10.1142/S1793545813300103
pubmed: 25075226
pmcid: 4112132
König, K. Clinical multiphoton tomography. J. Biophotonics 1, 13–23 (2008).
doi: 10.1002/jbio.200710022
pubmed: 19343631
König, K. et al. Clinical two-photon microendoscopy. Microsc. Res. Tech. 70, 398–402 (2007).
doi: 10.1002/jemt.20445
pubmed: 17393493
Malik, A. N. et al. The use of handheld ultrasound devices in emergency medicine. Technol. Med. https://doi.org/10.1007/s40138-021-00229-6/Published (2021).
doi: 10.1007/s40138-021-00229-6/Published
Dunn, A. K., Wallace, V. P., Coleno, M., Berns, M. W. & Tromberg, B. J. Influence of optical properties on two-photon fluorescence imaging in turbid samples. Appl. Opt. https://doi.org/10.1364/AO.39.001194 (2000).
doi: 10.1364/AO.39.001194
pubmed: 18338003
Palero, J. A. et al. Spectrally resolved multiphoton imaging of in vivo and excised mouse skin tissues. Biophys. J. 93, 992–1007 (2007).
doi: 10.1529/biophysj.106.099457
pubmed: 17449667
pmcid: 1913153
Chen, G., Lui, H. & Zeng, H. Image segmentation for integrated multiphoton microscopy and reflectance confocal microscopy imaging of human skin in vivo. Quant. Imaging Med. Surg. https://doi.org/10.3978/j.issn.2223-4292.2014.11.02 (2015).
doi: 10.3978/j.issn.2223-4292.2014.11.02
pubmed: 26807369
pmcid: 4700236
Wang, H. et al. Perfectly registered multiphoton and reflectance confocal video rate imaging of in vivo human skin. J. Biophotonics 6, 305–309 (2013).
doi: 10.1002/jbio.201200067
pubmed: 23418008
Sanchez, G. N. et al. In vivo imaging of human sarcomere twitch dynamics in individual motor units. Neuron 88, 1109–1120 (2015).
doi: 10.1016/j.neuron.2015.11.022
pubmed: 26687220
pmcid: 5920519
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9(7), 676–682 (2012).
doi: 10.1038/nmeth.2019
pubmed: 22743772
Koehler, M. J., König, K., Elsner, P., Bückle, R. & Kaatz, M. In vivo assessment of human skin aging by multiphoton laser scanning tomography. Opt. Lett. 180, 2879 (2006).
doi: 10.1364/OL.31.002879
Pena, A. M. et al. In vivo multiphoton multiparametric 3D quantification of human skin aging on forearm and face. Sci. Rep. https://doi.org/10.1038/s41598-022-18657-z (2022).
doi: 10.1038/s41598-022-18657-z
pubmed: 36494395
pmcid: 9734164
Dubois, A. et al. Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors. J. Biomed. Opt. 23, 1 (2018).
doi: 10.1117/1.JBO.23.10.106007
pubmed: 30353716
Atak, M. F. et al. Confocal microscopy for diagnosis and management of cutaneous malignancies: Clinical impacts and innovation. Diagnostics 13, 854 (2023).
doi: 10.3390/diagnostics13050854
pubmed: 36899999
pmcid: 10001140