Wolfgang Drexler, Rainer Leitgeb

http://www.meduniwien.ac.at/zmpbmt

Clinical Multimodal Optical Imaging

Acknowledgements

Financial support Medical University Vienna (MUW)

FFG COHESION (848588) FFG 3D PAT INTRAOP (BRIDGE)

FAMOS (FP7 ICT, 317744) BiopsyPen (FP7 ICT, 611132)

OCTChip (H2020, ICT 688173) MIB (H2020, HEALTH 667933)

FWF SFB (SFB-F68) FWF(P26687-N25)

FBI (H2020, ITN 721766) ESOTRAC (H2020, ICT 732729)

MOON (H2020, ICT 732969) Leitgeb / Drexler Lab (November 2017)

MIB-H2020.eu

Innovationtransforminghealthcare

GlobalMarketforMedicalImagingTechnologies

Pogue,SPIEProfessional,January2018

Optical64%

$73billion

Radiological36%$40billion

+Mobile/HomeHealth$20-40billion+largegrowth

W. Drexler, A.F. Fercher, C.K. Hitzenberger, R.A. Leitgeb – January 2016

Pioneers in Optical Coherence Tomography (OCT)

…..…since the late 1980’s

Optical Coherence Tomography“Non-invasive, high resolution optical analogue to ultrasound”

Micrometer Resolution (≈ 1 µm)

High Speed Imaging (up to 600 million A-scans/s)

Contrast enhanced OCT(polarisation, phase,..)

Depth resolved functional OCT (blood flow, physiology,..)

Multi-modal OCT (fluorescent, PAT/PAM, MPM,

CARS,….)

Adaptive Optics Enhanced Ophthalmic DiagnosisAO Fundus Camera

2D, cellular

M. Paques INSERM, Paris, France

Drusen

Cones

Vessel wall

AO SLO (split detector)2D, cellular, contrast

Shelley Mo et al Submitted 2016.

Dubra et al. BOE 2 (7), 2011)

AO SLO FA

Rods and Cones

Microangiography

AO OCT3D, cellular

3D Cone Morphology

3D Cellular Resolution

Michael Pircher

Matthias Salas

U. Schmidt-ErfurthAndreas Pollreisz

Sonja Karst

Julia Hafner Adrian Reumüller

Lorenz Wassermann Marion Funk

Philipp Roberts Markus Ritter

Universitätsklinik für

Augenheilkunde und Optometrie

Label-free OCT Widefield MicroangiographyData recorded in 7 sec 1.7 MHz A-scan rate

50 deg widefield 2000 x 5000 pixe

collaboration with R. Huber, LMU Munich

Rainer Leitgeb

Jesse Schallek, PhD Assistant Professor of Ophthalmology

Flaum Eye Institute, University of Rochester

�8Coordinator: Rainer Leitgeb (MUW)

Rainer Leitgeb

Ryan Santosa Matthias Salas

Hybrid Photoacoustic / OCT in Chicken Embryos EDD 3.5

PAT

A V

E

PAAs

DAo

VVs

SS-OCT

VVs

A

E

B

OCT / PATPAT

M. Liu, B. Maurer, W. J. Weninger, W. Drexler et al., Biomed Opt Express. 2014, BOE

Mengyang Liu

Wolfgang Weninger Zentrum für

Anatomie und Zellbiologie

Mengyang Liu

10Center for Medical Physics and Biomedical Engineering

Mobile PAT/OCT/OCTA for Clinics

Mengyang Liu

Zhe Chen

Harald Kittler, Universitätsklinik f. Dermatologie

Christoph Sinz, Universitätsklinik f. Dermatologie

Quantitative PAT/OCT Elastography 11J. Schmid (Drexler Lab, ZMPBMT/ CSC

University of Vienna)

Funding: This project has received funding from the FWF Grant No. P26687: Interdisciplinary Coupled Physics Imaging

SFB - Tomography across the scales - F6801-N36

Quantitative Multimodal PAT/OCT Elastography

Researcher: Academic cooperations:

Introduction: Quantitative Elastography is a medical imaging modality that maps the biomechanical parameters of tissues. This is motivated by the fact that the stiffness of tissue gives information about its pathological state. The main contrast in an OCT (Optical Coherence Tomography) image are the different scattering properties of a tissue. PAT (Photoacoustic Tomography) makes the absorption visible. We utilize this complementary nature of the two modalities to get a better displacement field and a better quantitative estimate of the stiffness.

Insight Photonic Solutions, Inc.

Industrial cooperations:

Otmar Scherzer (Head of Computational Science Center – University of Vienna)

Julian Schmid Procedure

1. Samples with different E-Moduli are prepared from Agarose and Silicone.

2. Samples are imaged before and after compression by a multi-modal PAT, OCT System

3. A displacement map is derived using Optical Flow code and both modalities.

4. The stiffness is recovered from the flow field and can be compared to the ground truth.

www.mib-h2020.eu

Innolas Semiconductor

Peter Ellbau Leonidas Mindrinos Ekaterina Sherina

Lisa Krainz

Tri-Modality OCT/ MPT / Doppler-OCT C. Blatter, R. Leitgeb; J. Weingast, M. Binder, H. Pehamerger, W. Drexler

TPEFSHG

Dermatoscopy En face OCT

3D OCT

Cross-sectional OCT

Doppler OCT

HistologyBCC

forehand,74 yrs. male, skin type III

Rainer Leitgeb

Industrial cooperations: GRINTECH Jena Blazejewski Medi-TechInsight Photonic Solutions, Inc

Multi-modal endoscope 13Wurster, Placzek (Drexler Lab, ZMPBMT)

Funding:

This project has received funding from the European Union’s Horizon 2020 research contract number 667933.

Multimodal OCT/Raman/Photoacoustic Endoscope for Bladder Cancer Detection

Researcher:

Academic partners: IMTEK FreiburgHelmholtz Zentrum MünchenTechnical University of Denmark Leibniz IPHT, Jena A. Ellerbee Bowden, Standford Univ.

Motivation: Increasing number of people are diagnosed with cancer. New tools to provide an early diagnosis are needed!

Current status:

Fabian Placzek

Physics, M.Sc.

www.mib-h2020.eu

Source: G. W. Dy et al., “Global Burden of Urologic Cancers, 1990–2013,” European Urology, vol. 71, no. 3, pp. 437–446, Mar. 2017.

A first endoscope design for OCT has been developed and is currently tested on bladder phantom and biopsies. The final endoscope can by used in combination with a cystoscope.

Approach: Combine different imaging modalities to perform in vivo endoscopic imaging to gain morphologic but also functional information of the tissue.

Optical coherence tomography

à staging

Raman, photoacoustic imaging

à gradingLara Wurster

Biomedical Engineering, M.Sc.

Diagnoses Deaths

173864

401174

130838

263307

19901990 2013

2013

Shahrokh Shariat, A. Haitel,

N. Garstka, Universitätsklinik

für Urologie

E LP

M

MIB-H2020.eu

Innovationtransforminghealthcare

Bladder phantomBladder biopsy

MIB-H2020.eu

Innovationtransforminghealthcare

Multi-modal endoscope 14Qian Li (Drexler Lab, ZMPBMT)

Funding:

This project has received funding from the European Union’s Horizon 2020 research contract number 732720.

Multimodal OCT Endoscope for Early Esophageal Cancer DetectionResearcher: Academic partners:

Helmholtz Zentrum MünchenTechnical University of Denmark

Motivation:

More than 450.000 people are diagnosed with esophageal cancer each year worldwide and ~400.000 die annually from the disease. The high mortality rate is attributed to the late detection of the disease. The current white-light endoscopy is not sensitive to detecting early disease. This also lowers the accuracy of tissue sampling in the subsequent biopsies.

Current status:

Cooperations:

SONAXIS S.A. Rayfos Ltd. Amplitude-Systèmes Statice Ascenion GmbH

Qian Li

Biomedical Engineering, M.Sc.

https://www.esotrac2020.eu/

Source: 1. Ferlay, J., et al. European Journal of Cancer, 2013. 2. Fitzgerald, R.C., et al. Gut, 2014.

Suitable OCT and PAT technologies for esophageal imaging have been developed and under test. The first multi-modal endoscope is designed and in production.

Approach: In vivo endoscopic esophageal imaging combining optical coherence tomography (OCT) and photoacoustic tomography (PAT). The novel multi-modal endoscopy provides depth-resolved, three-dimensional images of surface and subsurface esophageal precancerous/cancerous features.

Circumferential three-dimensional imaging of the esophagus is realized by a multi-modal capsule probe swallowed by the patient.

Clinical partners: Medical Research Council Cancer Unit, University of Cambridge

E LP

M

Photoacoustic tomography

à Deep physiological imaging

Optical coherence tomography

à Morphological imaging

Current OCT system setup for imaging ex vivo esophagus samples at the benchside.

Photoacoustic laparoscopy 15S. Preißer (Drexler Lab, ZMPBMT)

Funding:

This project has received funding from the Austrian Research Promotion Agency Bridge research contract number 855797.

Intraoperative Photoacoustic Laparoscopic imaging probeResearcher:

There is a high demand for endoscopic imaging methods allowing:

− the reliable detection of the border between cancerous and healthy tissue: intraoperative detection of incomplete resection.

− the intraoperative thickness detection of endometrium tissue for an optimized resection planning in endometriose surgery.

Current status:

Industrial and partners:

XARION Laser Acoustics

Richard Wolf

Stefan Preißer

Physics, PhD

Biomedical Engineering, M.Sc.

A new optical ultrasound pressure sensor for PA signal detection was designed and tested by scanning an anesthetized zebrafish larva .

Approach: Perform in vivo endoscopic imaging with a developed PA probe to gain information on the vessel thickness and density in order to help the physician to differentiate between pathological and healthy tissue.

René Wenzl Gynaecology

E LP

Stefan.preisser@meduniwien.ac.at https://www.ffg.at/en/bridge

Motivation:

Photoacoustic (PA) imaging

Imaging depth >1 mm with optical contrast Well suited for vessel visualization

Is sensitive to optical absorption differences

A first endoscopic design for PA imaging has been developed and the optical and acoustic performance tested.

Shahrokh Shariat Urology

Multimodal surgical microscope 16M. T. Erkkilä (Drexler Lab, ZMPBMT)

Funding:

This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 721766.

Hybrid OCT/PpIX Fluorescence Enabled Surgical MicroscopeResearcher:

Carl Zeiss Meditec AG

Clinical relevance: In glioblastoma surgery an extent of resection (EOR) of 100 % prolongs the median survival from 15.2 to 9.8 months compared to EOR < 100 %.

Current status:

Industry:

Starna Scientific Ltd.

Georg Widhalm (Univ.-Klinik f. Neurochirurgie)

Thomas Roetzer (Neuropathologie)

Yifan Jian (GPU/OCT expert) SFU Vancouver, Canada

Mikael T. Erkkilä

Physics, M.Sc. (FSU Jena, TU Dresden)

mikael.erkkilae@meduniwien.ac.at www.fbi-itn.eu

Source: Li et al. (2016, J. Neurosurgery)

The assistant port of a Carl Zeiss surgical microscope was removed and fitted with a custom designed scanner head for real time volumetric OCT using a 1.3 µm akinetic laser.

Approach: Using enhanced optical imaging to visualize cancerous tissue and to guide the surgeon towards a greater EOR.

A camera based system is attached to the extension port to allow 5-ALA induced PpIX fluorescence excitation (405 nm) and detection.

Imaging on ex vivo human glioma biopsies approved

Optical coherence tomography

à Retrieve tissue scattering properties

Enhanced PpIX fluorescence imaging

à Detect invisible PpIX at lower concentrations

SWPCARS

beamexpander

M1

M1

BS

pBS

pBS

M1

M1

HWP

QWP

BS

sample

objective

M1

M1

SWBS

SWBS

flipperM1

M1

BS

HWP

OCT

M1

camera

lens

grating

telescopebeam dump

M1Ti:SMosaik

M1

SWPMPT

M. Andreana, A. Unterhuber, T. Kamali. W. Drexler

VerdiV5

Ti:sapph80MHz

Timedelayline

PCF-basedStokesgen.

Blocksofglass

Label-free Molecular Imaging CARS/SHG/THG/OCT

Ryan Santosa

Angelika Unterhuber

Marco Andreana

Jeremias PülsDaniela Bovenkamp

Ophthalmic OCT on a Chip

Laser Source

PIC Fabrication

PIC Design Electronics

Optics

Packaging Clinical Translation

Elisabet Rank

Handheld OCT System for Dermatology • Monitoring and diagnostic of Non-Melanoma Skin Cancer • Improved clinical workflow integration • Promote widespread adoption in clinical practice

Compact, Low-cost and Reliable OCT engine • Based on Silicon-On-Insulator (SOI) photonic technology • Akinetic axial scanning, MEMS lateral scanner, battery driven • Ultra-low propagation (0.15 dB/cm) and coupling (0.7 dB) lossesUltra-low propagation (0.15 dB/cm) and coupling (0.7 dB) losses

”OCT in the hands of everyone”

8cm

”Worldwide smallest

OCT”

19.5 mm

1.1 mm

Harald Kittler

Elisabet Rank

2nd edition (June 2015) – 84 chapters – 2600 color pages - 3rd edition in preparation

> 350.000 chapter downloads

> 4300 books sold

/ downloaded