title: Confocal microscopy with strip mosaicing for rapid imaging over large areas of excised tissue.
abstract: Confocal mosaicing microscopy is a developing technology platform for imaging tumor margins directly in freshly excised tissue, without the processing required for conventional pathology. Previously, mosaicing on 12-×-12  mm² of excised skin tissue from Mohs surgery and detection of basal cell carcinoma margins was demonstrated in 9 min. Last year, we reported the feasibility of a faster approach called "strip mosaicing," which was demonstrated on a 10-×-10  mm² of tissue in 3 min. Here we describe further advances in instrumentation, software, and speed. A mechanism was also developed to flatten tissue in order to enable consistent and repeatable acquisition of images over large areas. We demonstrate mosaicing on 10-×-10  mm² of skin tissue with 1-μm lateral resolution in 90 s. A 2.5-×-3.5  cm² piece of breast tissue was scanned with 0.8-μm lateral resolution in 13 min. Rapid mosaicing of confocal images on large areas of fresh tissue potentially offers a means to perform pathology at the bedside. Imaging of tumor margins with strip mosaicing confocal microscopy may serve as an adjunct to conventional (frozen or fixed) pathology for guiding surgery.
authors: Memorial Sloan-Kettering Cancer Center, Research Engineering Laboratory, New York, New York 10065, USA. abeytuns@mskcc.org
authors: Sanjee
authors: S
authors: Abeytunge
authors: Yongbiao
authors: Y
authors: Li
authors: Bjorg
authors: B
authors: Larson
authors: Gary
authors: G
authors: Peterson
authors: Emily
authors: E
authors: Seltzer
authors: Ricardo
authors: R
authors: Toledo-Crow
authors: Milind
authors: M
authors: Rajadhyaksha
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000175:diagnosis / Q000601:surgery; D002280:Basal Cell Carcinoma / Q000175:diagnosis* / Q000601:surgery*; D004867:Equipment Design; D005260:Female; D006652:Histological Techniques / Q000295:instrumentation / Q000379:methods; D006801:Humans; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods*; D015580:Mohs Surgery / Q000295:instrumentation / Q000379:methods; D055620:Optical Phenomena; D010340:Pathology, Surgical / Q000295:instrumentation / Q000379:methods / Q000706:statistics & numerical data; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000601:surgery*
references: Br J Dermatol. 2010 Dec;163(6):1218-28
references: 20874785
references: J Pathol Inform. 2011;2:S8
references: 22811964
references: J Microsc. 2011 Dec;244(3):320-4
references: 21950542
references: J Biomed Opt. 2008 Sep-Oct;13(5):054001
references: 19021381
references: J Pathol Inform. 2011;2:28
references: 21773059
references: J Microsc. 2011 Jul;243(1):103-10
references: 21348869
references: J Biomed Opt. 2007 Sep-Oct;12(5):051901
references: 17994884
references: Gastrointest Endosc. 2011 Nov;74(5):992-1000
references: 21944314
references: Gastrointest Endosc. 2010 Jan;71(1):35-43
references: 19922916
references: J Biomed Opt. 2005 Jan-Feb;10(1):14011
references: 15847592
references: Med Image Comput Comput Assist Interv. 2005;8(Pt 1):753-60
references: 16685914
references: Biomed Opt Express. 2012 Oct 1;3(10):2428-35
references: 23082285
references: Cancer Prev Res (Phila). 2012 Nov;5(11):1280-90
references: 22961775
references: Lasers Surg Med. 2007 Oct;39(9):696-705
references: 17960751
references: Gastrointest Endosc. 2007 Nov;66(5):1001-7
references: 17767932
references: Front Neuroanat. 2011 Mar 07;5:17
references: 21629828
references: Arch Pathol Lab Med. 2012 May;136(5):517-26
references: 22540300
references: J Microsc. 2012 Oct;248(1):6-22
references: 22900940
references: Br J Dermatol. 2009 Jun;160(6):1242-50
references: 19416248
references: IEEE Trans Biomed Eng. 2012 Feb;59(2):531-41
references: 22084042
references: J Microsc. 2006 May;222(Pt 2):76-84
references: 16774516
references: IEEE Trans Biomed Eng. 2011 Jan;58(1):159-71
references: 20934939
references: Dermatol Surg. 2012 Sep;38(9):1548-51
references: 22823541
references: J Microsc. 2009 Jan;233(1):149-59
references: 19196421
references: Nat Methods. 2010 Apr;7(4):303-5
references: 20228814
references: BMC Ear Nose Throat Disord. 2006 Feb 17;6:2
references: 16503981
references: J Biomed Opt. 2009 May-Jun;14(3):034012
references: 19566305
references: J Microsc. 2008 Sep;231(3):408-18
references: 18754995
references: J Invest Dermatol. 2001 Nov;117(5):1137-43
references: 11710924
references: J Biomed Opt. 2007 May-Jun;12(3):034027
references: 17614735
references: J Biomed Opt. 2009 May-Jun;14(3):034050
references: 19566342
references: Stud Health Technol Inform. 2007;125:304-9
references: 17377290
references: J Biomed Opt. 2011 May;16(5):050504
references: 21639560
references: PLoS One. 2012;7(9):e43460
references: 22984428
references: Br J Dermatol. 2012 Oct;167(4):828-36
references: 22676506
references: J Biomed Opt. 2012 Jan;17(1):016006
references: 22352656
references: Med Image Anal. 2006 Oct;10(5):673-92
references: 16887375
references: J Microsc. 2006 Nov;224(Pt 2):158-65
references: 17204063
references: J Biomed Opt. 2011 Jul;16(7):076008
references: 21806269
references: Ann Surg Oncol. 2008 May;15(5):1271-2
references: 18320287