Advance Advances in Optical s in Optical Cohere Coherence nce - - PowerPoint PPT Presentation

Advance Advances in Optical s in Optical Cohere Coherence nce Tom Tomograph

• graphy

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)
• Optical coherence tomography (OCT)
• Photoacoustic Imaging (PAI)

LDPI TiVi cmOCT PAT

A-line B-Scan

Optica Optical l Coherenc Coherence e Tomograp Tomography hy

Courtesy of Johannes de Boer

OCT OCT: : optical an

• ptical analogue of

alogue of pulsed pulsed-wave wave ultr ultrasound asound

• J. Fujimoto, 2008

Rising Capillary Loops Sub-surface Fingerprint Sweat ducts Microcirculation Map

cmOCT of the thumb for a 5x5x3 mm region

Zam et al., 2013. J. Biophoton. 6 (9) , 663-667. McNamara et al., 2014, J. Biomed. Opt. 18 (12), 126008

Principle of cmOCT

Excised section of Pig Skin 200 µm embedded capillary tube with flowing fluid

Rising Capillary Loops Sub-surface Fingerprint Sweat ducts Microcirculation Map

cmOCT of the thumb for a 5x5x3 mm region

Zam et al., 2013. J. Biophoton. 6 (9) , 663-667. McNamara et al., 2014, J. Biomed. Opt. 18 (12), 126008

• Correlation mapping

OCT

• 8 sequential frames
• 2-D correlation map

average correlation value for a square grid measuring 7x7

Jonathan et al. 2011 J. Biophotonics 4 (5) Enfield, J. 2011 Biomedical Optics Express 2 (5) 1184-1193.

cmOCT cmOCT

Imaging Domains

1 10 1000 1 10 100

Sampling depth (mm)

100

Resolution (mm)

Optical Coherence Tomography Standard US High frequency US LDPI TiVi Ultrasound LSPI Confocal Microscopy DOT fMRI

Label-free Imaging Domains

1 10 100

Sampling depth (mm)

1 10 1000 100

Resolution (mm)

LDPI TiVi LSPI

National University of Ireland, Galway

Nokia

Mobile Mobile platfor platform

• J. Biophotonics 4 (5) 293-296.

Spectral signature of Haemoglobin

code:http://tomi.nuigalway.ie/resources.html

Label-free Imaging Domains

1 10 100

Sampling depth (mm)

1 10 1000 100

Resolution (mm)

LDPI TiVi LSPI Super-resolution Microscopy

Nanostructural sensitivity at depth

1 10 1000 100

Structural Sensitivity (mm)

1 10 100

Sampling depth (mm)

1 10 1000 100

Resolution (mm) 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 = 0, a = 0 𝑤𝑨 = 2𝑜 

Each wavelength corresponds to one particular axial spatial frequency (SESF approach). FDOCT signal represents complex amplitudes of the high axial spatial frequencies.

K = k(s – s0) K a q ks ks0

𝑤𝑨 = 𝑜(𝑑𝑝𝑡q + 𝑑𝑝𝑡a) 

1500 1000 500 z, 1/mm r, 1/mm

• 500

500

• 1000

1000

1280 nm 1310 nm 1340 nm 1370 nm 1250 nm

OCT

z

𝐺 𝒔 = 1 4𝜌 𝑙0

2 𝑜2 𝒔 − 1

 

K d e F(K) π) ( r F

r iK 3 3

2 1





=

Alexandrov et al. 2014 Nanoscale, 6, 3545-3549

PC

LASER

SLD PC L1 CCD COMP DG FC X-Scan Y-Scan PC OC L5 L3 L4 L2 RM

Spectral domain OCT setup

Resolution 30 mm x 30 mm x 12 mm Wavelength 1300 nm, spectral range 83 nm Alexandrov et al. 2014 Nanoscale, 6, 3545-3549

Sticky tape under pressure by PZT

PZT Scattering Sticky tape 10 layers Glass slide Illumination beam Metal plate 30 nm 0 nm Alexandrov et al. Nanoscale, 6, 3545-3549

OCT image of rat eye

Structural changes within the rat eye via dehydration

t1+ 0.02s t1 630 Hz, nm 680 655 630 Hz, nm 680 655

Hz,nm

630 650 670

a e b d c f

Correlation

1

• 0.5

0.5

Hz,nm

630 650 670

Correlation

1

• 0.5

0.5

h g

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.

nsOCT images of collagen

Alexandrov et al. Nanoscale, 6, 3545-3549

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).

srSESF superresolution approach

Wide field microscopy NA=0.9 visible light R  370 nm Scanning microscopy NA=0.5 = 1230-1370 nm srSESF microscopy NA=0.5 = 1230-1370 nm

0.85 0.9 0.87 0.7 1.0 0.85

1 mm x 1 mm

White Bar = 2 µm

Nanosphere aggregates, diameter 400 nm reflection configuration

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

• r three dimensional image of
• ptical scattering from internal

tissue microstructures.

• OCT can provide both micro

structural and functional information with high resolution and sensitivity

• High resolution (2-15 µm )
• 3D imaging in scattering

tissue (2-3 mm)

• Non invasive – “Optical

Biopsy”

Reference arm Sample arm 90/10 x-y scanner Detector

SLD

Axial Depth

National University of Ireland, Galway

Commer Commercially cially available available OCT OCT systems systems

Conventional clinic-scale OCT instruments, priced from €45,000 to

• ver

€120,000, were commercialized early in the last decade for use by

• phthalmologists,

dermatologist, cardiac surgeons

ILUMIEN Cirrus HD-OCT Skintell

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”
• ptical architecture

National University of Ireland, Galway

CD CD ROM ROM Pickup Unit Pickup Unit

Grating Laser Beam Splitter Lens Voice coil & Lens Detector

National University of Ireland, Galway

Cost 10$!!!

Replacing Replacing CD CD ROM ROM Pickup Pickup Unit Unit with with MR MR-OCT OCT

Detector SLD Beam Splitter Lens Lens Voice coil

National University of Ireland, Galway

Lens

Cost 10$!!!

Sample

Multiple Multiple Reference Optical Reference Optical Coherence Coherence Tomography Tomography (MR (MR-OCT) OCT)

National University of Ireland, Galway

• MR-OCT

is similar to conventional TD-OCT, except a partial mirror is placed very close to the reference mirror.

• The partial mirror causes the

light to be reflected back and forth multiple times between the partial mirror and the reference mirror.

• Each reflection between the

partial and reference mirrors is delayed by the round trip time between the two mirrors.

PM RM PD BS

1 2 3 4 5 6 7

Order of Reflection VC L1 L2 L4 L3 M1

SLD

Summary

• In vivo / Ex vivo
• Scattering or non-scattering

tissue?

• Depth versus resolution
• Speed – frames per second –

motion?

• Functional – flow, oxygenation,

molecular sensitivity

• Sub-resolution

content/activity

• Fit for purpose

Rising Capillary Loops Sub- surface Fingerpri nt Swe at duc ts Microcir culation Map i) ii) iii) iv)

NBIPI: Tissue Optics and Microcirculation Imaging Facility

TOMI I Team: m:

• Prof. Martin Leahy
• Prof. Steve Jacques (adjunct)
• Prof. Valery Tuchin (adjunct)

Dr Paul McNamara Dr Hrebesh Subhash Dr Sergey Alexandrov Dr Shiju Joseph Aedan Breathnach Dennis Warncke Gillian Lynch Kate Lawlor Cerine Lal Olga Zhernovaya Sean O’Gorman Susan McElligott James Mc Grath Roshan Dsouza Haroon Zafar Dr Sheeona Gorman, RCSI Alumni ni: Dr Jim O’Doherty, Snr. PET Physicist, King’s Hospital London Dr Neil Clancy, Research Fellow Imperial College London Dr Joey Enfield, Senior Java Developer, Fexco Dr David Connolly, Assistant Professor, University of Aalborg Dr Brian Kelleher, Lecturer, DCU Dr Anne-Marie Henihan, Research Fellow, UL Dr Emmanuel Pican, Lecturer,CIT Dr Marie-Louise O’Connell, Medical Devices, Irish Medicines Board Collab abora rators rs: Fujifilm-VisualSonics, Inc. Covidien, Inc.

• St. Jude Medical, Inc.

Compact Imaging , Inc. Wheelsbridge AB