Advance Advances in Optical s in Optical Cohere Coherence nce Tom Tomograph ography 26/08/2015 Prof. Martin J. Leahy Chair of Applied Physics, NUI Galway Scientific Director, NBIP Ireland National University of Ireland, Galway
Microcirculation Imaging Techniques – TOMI lab • Laser Doppler perfusion imaging (LDPI) • Laser speckle contrast imaging (LSCI) • Tissue viability imaging (TiVi) PAT • Optical coherence tomography (OCT) • Photoacoustic Imaging (PAI) LDPI cmOCT TiVi
Optica Optical l Coherenc Coherence e Tomograp Tomography hy B-Scan A-line Courtesy of Johannes de Boer
OCT OCT: : optical an optical analogue of alogue of pulsed pulsed-wave wave ultr ultrasound asound J. Fujimoto, 2008
cmOCT of the thumb for a 5x5x3 mm region Sweat ducts Sub-surface Fingerprint Rising Capillary Loops Microcirculation Map Zam et al., 2013. J. Biophoton. 6 (9) , 663-667. McNamara et al., 2014, J. Biomed. Opt. 18 (12), 126008
Principle of cmOCT 200 µm embedded capillary tube with flowing fluid Excised section of Pig Skin
cmOCT of the thumb for a 5x5x3 mm region Sweat ducts Sub-surface Fingerprint Rising Capillary Loops Microcirculation Map Zam et al., 2013. J. Biophoton. 6 (9) , 663-667. McNamara et al., 2014, J. Biomed. Opt. 18 (12), 126008
cmOCT cmOCT Enfield, J. 2011 Biomedical Optics Express 2 (5) 1184-1193. Jonathan et al. 2011 J. Biophotonics 4 (5) • Correlation mapping OCT • 8 sequential frames • 2-D correlation map average correlation value for a square grid measuring 7x7
Imaging Domains Standard US fMRI 1000 Ultrasound High frequency US LDPI 100 LSPI Resolution ( m m) TiVi DOT 10 Optical Coherence Tomography Confocal 1 Microscopy 1 10 100 Sampling depth (mm)
Label-free Imaging Domains 1000 LDPI 100 LSPI Resolution ( m m) TiVi 10 1 Sampling depth (mm) 1 10 100
National University of Ireland, Galway
Mobile platfor Mobile platform Nokia J. Biophotonics 4 (5) 293-296.
Spectral signature of Haemoglobin code:http://tomi.nuigalway.ie/resources.html
Label-free Imaging Domains 1000 LDPI 100 LSPI Resolution ( m m) TiVi 10 1 Super-resolution Microscopy Sampling depth (mm) 1 10 100
Nanostructural sensitivity at depth 1000 1000 Structural Sensitivity 100 100 Resolution ( m m) ( m m) 10 10 1 1 Sampling depth (mm) 1 10 100 Alexandrov et al. 2014 Nanoscale , 6 , 3545-3549
Structural size is encoded in the spectrum as scattering potential
Accessible bandwidth of spatial frequencies in OCT. q OCT z , 1/mm ks z a 1500 K ks 0 K = k ( s – s 0 ) 1000 1250 nm 𝐺 𝒔 = 1 2 𝑜 2 𝒔 − 1 1280 nm 4𝜌 𝑙 0 1310 nm 1340 nm 1 500 = iK r 3 1370 nm F r F(K) e d K 3 π) 2 ( 𝑤 𝑨 = 𝑜(𝑑𝑝𝑡 q + 𝑑𝑝𝑡 a ) r , 1/mm 0 𝑤 𝑨 = 2𝑜 q = 0 , a = 0 -1000 0 1000 500 -500 Each wavelength corresponds to one particular axial spatial frequency (SESF approach). FDOCT signal represents complex amplitudes of the high axial spatial frequencies. Alexandrov et al. 2014 Nanoscale , 6 , 3545-3549
Spectral domain OCT setup RM LASER PC L4 L5 SLD PC FC Wavelength 1300 nm, OC spectral range 83 nm L2 PC Y-Scan X-Scan DG L1 L3 COMP Resolution CCD 30 m m x 30 m m x 12 m m Alexandrov et al. 2014 Nanoscale , 6 , 3545-3549
Sticky tape under pressure by PZT Illumination beam PZT Glass slide 30 nm Scattering Sticky tape 10 layers 0 nm Metal plate Alexandrov et al. Nanoscale , 6 , 3545-3549
OCT image of rat eye
Structural changes within the rat eye via dehydration t1+ 0.02s t1 H z , nm H z , nm 680 680 655 655 630 630
nsOCT images of collagen H z ,nm Correlation 670 1 0.5 650 0 630 -0.5 c a b d H z ,nm Correlation 670 1 0.5 650 0 630 -0.5 e f g h a,e – conventional OCT images of 3 days and 7 days collagen correspondingly, b,f – corresponding nsOCT images as maps of the dominant structure, c,g – nsOCT images as maps of the level of correlation with known structure, and d,h – light sheet microscopy images. Alexandrov et al. Nanoscale , 6 , 3545-3549
srSESF superresolution approach Alexandrov S.A., McGrath, J., Subhash H., Boccafoschi F., Giannini C. and Leahy M, 2015. Novel approach for label free super-resolution imaging in far field. Nature Scientific Reports (accepted).
Nanosphere aggregates, diameter 400 nm reflection configuration Wide field microscopy Scanning srSESF microscopy NA=0.9 microscopy NA=0.5 visible light NA=0.5 = 1230-1370 nm R 370 nm = 1230-1370 nm 1.0 0.85 0.7 White Bar = 2 0.9 µm 0.87 0.85 1 m m x 1 m m Alexandrov S.A., McGrath, J., Subhash H., Boccafoschi F., Giannini C. and Leahy M, 2015. Novel approach for label free super-resolution imaging in far field. Nature Scientific Reports (accepted).
Optical Coherence Tomography Optical Coherence Tomography OCT uses low coherence interferometry to produce a two Reference arm or three dimensional image of SLD optical scattering from internal tissue microstructures. 90/10 OCT can provide both micro x-y scanner structural and functional Sample arm information with high resolution and sensitivity High resolution (2-15 µm ) Detector Axial Depth 3D imaging in scattering tissue (2-3 mm) Non invasive – “Optical Biopsy” National University of Ireland, Galway
Commer Commercially cially available available OCT OCT systems systems Cirrus HD-OCT ILUMIEN Conventional clinic-scale OCT instruments, priced from € 45,000 to € 120,000, over were Skintell commercialized early in the last decade for use by ophthalmologists, dermatologist, cardiac surgeons National University of Ireland, Galway
Compact imaging Compact imaging solution solution with with MR MR-OCT OCT MR-OCT features Small form factor: About the size of a computer DVD read/write head Robust, cost-effective design: Virtually solid state, typical of handheld devices Low-operating power requirements Flexible “free space” optical architecture National University of Ireland, Galway
CD CD ROM ROM Pickup Unit Pickup Unit Voice coil & Lens Cost 10$!!! Beam Splitter Detector Lens Grating Laser National University of Ireland, Galway
Replacing Replacing CD CD ROM ROM Pickup Pickup Unit Unit with with MR MR-OCT OCT Sample Lens Cost 10$!!! Lens Voice coil Beam Detector Lens Splitter SLD National University of Ireland, Galway
Multiple Reference Optical Multiple Reference Optical Coherence Coherence Tomography Tomography (MR (MR-OCT) OCT) MR-OCT is similar to PD conventional TD-OCT, except a L4 partial mirror is placed very Order of Reflection 1 2 3 4 5 6 7 close to the reference mirror. L1 L2 BS SLD The partial mirror causes the light to be reflected back and PM RM forth multiple times between the M1 L3 partial mirror and the reference VC mirror. Each reflection between the partial and reference mirrors is delayed by the round trip time between the two mirrors. National University of Ireland, Galway
Summary • In vivo / Ex vivo • Scattering or non-scattering tissue? • Depth versus resolution • Speed – frames per second – motion? • Functional – flow, oxygenation, i) ii) iii) molecular sensitivity Swe at • Sub-resolution duc ts content/activity Sub- Rising Microcir surface Capillary culation • Fit for purpose Fingerpri Loops Map iv) nt
NBIPI: Tissue Optics and Microcirculation Imaging Facility TOMI I Team: m: Alumni ni: Prof. Martin Leahy Dr Jim O’Doherty , Snr. PET Physicist, Prof. Steve Jacques (adjunct) King’s Hospital London Prof. Valery Tuchin (adjunct) Dr Neil Clancy, Research Fellow Dr Paul McNamara Imperial College London Dr Hrebesh Subhash Dr Joey Enfield, Senior Java Developer, Fexco Dr Sergey Alexandrov Dr David Connolly, Assistant Professor, Dr Shiju Joseph University of Aalborg Dr Brian Kelleher, Lecturer, DCU Aedan Breathnach Dr Anne-Marie Henihan, Research Fellow, UL Dennis Warncke Gillian Lynch Dr Emmanuel Pican, Lecturer,CIT Kate Lawlor Cerine Lal Dr Marie-Louise O’Connell, Medical Devices, Olga Zhernovaya Sean O’Gorman Irish Medicines Board Susan McElligott James Mc Grath Roshan Dsouza Collab abora rators rs: Haroon Zafar Fujifilm-VisualSonics, Inc. Dr Sheeona Gorman, RCSI Covidien, Inc. St. Jude Medical, Inc. Compact Imaging , Inc. Wheelsbridge AB
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