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Quantitative multimodal spectral optoacoustic and speed-of-sound imaging for multimodal handheld diagnostic ultrasound

Applicant Frenz Martin
Number 179038
Funding scheme Project funding (Div. I-III)
Research institution Institut für angewandte Physik Universität Bern
Institution of higher education University of Berne - BE
Main discipline Other disciplines of Physics
Start/End 01.06.2018 - 31.05.2022
Approved amount 526'369.00
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All Disciplines (2)

Discipline
Other disciplines of Physics
Biomedical Engineering

Keywords (6)

reflection mode; photoacoustic imaging; medical diagnosis; quantitative imaging; functional imaging; blood oxygen saturation

Lay Summary (German)

Lead
Die medizinische Bildgebung gewinnt bei der Diagnose von Krankheiten zunehmend an Bedeutung. Da sich viele Krankheitsbilder nicht alleine durch strukturelle Veränderungen im Körper manifestieren, sucht die moderne Wissenschaft nach Methoden, die sowohl Informationen über die Struktur, als auch über Körperfunktionen liefern. Ein wichtiger Faktor bei der Beurteilung des Gesundheitszustandes ist die Bestimmung der Blutsauerstoffsättigung in Gefässen. Eine weitere Anforderung an die Bildgebung ist, dass sie flexibel, unkompliziert und mobil eingesetzt werden kann. Um diese Anforderungen zu realisieren sollen die Grundlagen geschaffen werden, um ein multimodales, multifunktionelles Bildgebungssystem basierend auf einem Ultraschallgerät realisieren zu können.
Lay summary

Inhalt und Ziel des Forschungsprojektes:

Das Ziel dieses Forschungsprojektes ist es den klassischen Ultraschall mit neuen quantitativen Diagnosemöglichkeiten wie optoakustische Bildgebung und Schallgeschwindigkeitsmessungen zu ergänzen, die in der Lage sind, zum einen die Blutsättigung in einzelnen Gefässen mit hoher Auflösung und Präzision zu bestimmen, als auch durch Messung der lokalen Schallgeschwindigkeiten im Gewebe aberrationsfreie Bilder zu liefern, bzw. Gewebe zu charakterisieren. Zu diesem Zweck werden wir die spektrale abhängige Abschwächung von Licht im Gewebe und unerwünschte Ultraschallreflexionen experimentell bestimmen und Methoden entwickeln um diese zu kompensieren.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojektes:

Unsere Arbeiten werden vollkommen neue diagnostische Möglichkeiten z.B. in der Brusttumorerkennung oder bei Lebererkrankungen eröffnen und stellen somit einen weiteren Schritt in Richtung „personalized“ Medizin dar. Die Kombination von Optoakustik, Schallgeschwindigkeitsmessungen und Ultraschall wird neue Massstäbe in der diagnostischen Bildgebung setzen.

Direct link to Lay Summary Last update: 09.05.2018

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Reliability assessment for blood oxygen saturation levels measured with optoacoustic imaging
Ulrich Leonie, Held Kai Gerrit, Jaeger Michael, Frenz Martin, Akarçay Hidayet Günhan (2020), Reliability assessment for blood oxygen saturation levels measured with optoacoustic imaging, in Journal of Biomedical Optics, 25(04), 046005-1-046005-15.
Quantitative comparison of frequency-domain and delay-and-sum optoacoustic image reconstruction including the effect of coherence factor weighting
Spadin Florentin, Jaeger Michael, Nuster Robert, Subochev Pavel, Frenz Martin (2020), Quantitative comparison of frequency-domain and delay-and-sum optoacoustic image reconstruction including the effect of coherence factor weighting, in Photoacoustics, 17, 100149-100149.
Toolbox for In Vivo Imaging of Host–Parasite Interactions at Multiple Scales
De Niz Mariana, Spadin Florentin, Marti Matthias, Stein Jens V., Frenz Martin, Frischknecht Friedrich (2019), Toolbox for In Vivo Imaging of Host–Parasite Interactions at Multiple Scales, in Trends in Parasitology, 35(3), 193-212.
Receive Beam-Steering and Clutter Reduction for Imaging the Speed-of-Sound Inside the Carotid Artery
Kuriakose Maju, Muller Jan-Willem, Stähli Patrick, Frenz Martin, Jaeger Michael (2018), Receive Beam-Steering and Clutter Reduction for Imaging the Speed-of-Sound Inside the Carotid Artery, in Journal of Imaging, 4(12), 145-145.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
OSA Biophotonics Congress: Biomedical Optics Talk given at a conference A metric to estimate the reliability of absolute oxygen saturation levels in quantitative optoacoustic imaging 21.04.2020 An OSA virtual meeting, United States of America Ulrich Leonie; Frenz Martin;
BMPN annual meeting 2019, Bern Poster On the importance of assessing the reliability of blood oxygen saturation levels determined with optoacoustic imaging 10.12.2019 Bern, Switzerland Ulrich Leonie; Frenz Martin;
BMPN annual meeting 2019, Bern Talk given at a conference Quantitative handheld optoacoustic imaging: a novel multimodal diagnostic device? 10.12.2019 Bern, Switzerland Ulrich Leonie; Frenz Martin;
BMPN annual meeting 2019, Bern Poster Frequency-Domain Reconstruction and Coherence Factor Weighting in Optoacoustic Microscopy 10.12.2019 Bern, Switzerland Frenz Martin; Ulrich Leonie;
IEEE International Ultrasonics Symposium 2019 Poster Diffraction-limited spatial resolution in synthetic focus time-of-flight ray ultrasound tomography 08.10.2019 Glasgow, Great Britain and Northern Ireland Frenz Martin;
IEEE International Ultrasonic Symposium 2019 Talk given at a conference Reflection-mode speed-of-sound imaging using soft-prior limits 08.10.2019 Glasgow, Great Britain and Northern Ireland Frenz Martin;
Excite Symposium 2019 / Multi-Scale Optoacoustic Imaging - from Theory to Clinical Practice Talk given at a conference Quantitative handheld optoacoustic imaging: problems and possible solutions 07.09.2019 Zurich, Switzerland Frenz Martin;
International Congress on Ultrasonics (ICU) 2019 Talk given at a conference Soft-prior regularization for improved speed-of-sound imaging in cute 03.09.2019 Bruges, Belgium Frenz Martin;
Topical Problems of Biophotonics- TPB2019 Talk given at a conference Steps toward an epi-style multimodal quantitative optoacoustic imaging device 29.07.2019 Nizhny Novgorod, Russia Frenz Martin;
SPIE Photonics West, BIOS Poster Quantitative optoacoustic imaging with multiple-irradiation sensing: models and methods to image oxygen saturation levels in arteries and veins 02.02.2019 San Francisco, United States of America Frenz Martin; Ulrich Leonie;
SPIE Photonics West, BIOS Poster Spectral correction for handheld optoacoustic imaging by means of near‐infrared optical tomography in reflection mode 02.02.2019 San Francisco, United States of America Frenz Martin; Ulrich Leonie;
BMPN annual meeting 2018, EMPA Poster Optoacoustic multiple irradiation sensing for the determination of blood oxygen saturation levels: an in vivo feasibility study 11.12.2018 St. Gallen, Switzerland Frenz Martin; Bramer Grace; Ulrich Leonie;
BMPN annual meeting, EMPA Poster Receive angle steering and clutter reduction for imaging the speed-of-sound inside large blood vessels 11.12.2018 St. Gallen, Switzerland Frenz Martin;
BMPN annual meeting 2018, EMPA Poster Receive angle steering and clutter reduction for imaging the speed-of-sound inside large blood vessels 11.12.2018 St. Gallen, Switzerland Frenz Martin;
IEEE International Ultrasonics Symposium Poster Receive beam steering for dynamic image reconstruction of speed of sound in biological organs using computed ultrasound tomography in echo mode 22.10.2018 Kobe, Japan Frenz Martin;
Physics Kolloquium Rostock Individual talk Optoacoustic imaging - possibilities and limitations 27.07.2018 Rostock, Germany Frenz Martin;


Awards

Title Year
Best presentation at the annual meeting of the Biomedical Photonic Network with the title "On the importance of assessing the reliability of blood oxygenation saturation levels determined with optoacoustic imaging" 2019

Associated projects

Number Title Start Funding scheme
144443 Combined deep optoacoustics and ultrasound for quantitative multimodal imaging of the human body 01.01.2013 Project funding (Div. I-III)

Abstract

Modern clinical practise relies on imaging for diagnosis and patient-tailored therapy. Ultrasound (US) is one of the most prevalent modalities, because its portability, safety (devoid of ionising radiation), real time display and a comparably low price make it favourable for bed-side care, GP office and emergency units. On the downside, grey-scale US often suffers from non-specific contrast and must then be complemented by e.g. X-ray, CT or MRI provoking additional health care costs. With the goal to pair the advantages of US with competitive diagnostic power, research is directed towards novel ultrasound-based techniques that yield complementing diagnostic information in a single, multimodal device. Over the past two decades we considerably contributed to the development of optoacoustic (OA) imaging. OA allows the display of optical absorption contrast of e.g. blood vessels with the spatial resolution of US, based on detection of thermoelastically generated ultrasound when irradiating the tissue with pulsed laser light. Spectral analysis of the OA signal as a function of optical wavelength can complement conventional US with functional information of local blood oxygen saturation when combined in a single handheld probe. To enable clinical combined OA and US imaging, we have focused on pushing the limits of contrast and imaging depth. To reduce clutter noise - the most important limitation to deep OA imaging - we in collaboration with partners from the UK and the Netherlands have developed displacement-compensated averaging (DCA), localised vibration tagging (LOVIT) and photoacoustic-guided focused ultrasound (PAFUSion). Besides clutter, acoustic aberrations - caused by an inhomogeneous speed-of-sound (SoS) - degrade spatial resolution. To solve this problem, we have developed computed ultrasound tomography in echo mode (CUTE) that allows reconstructing the spatial distribution of SoS using pulse-echo US. Knowledge of SoS in turn allows aberration correction and thus diffraction-limited resolution both in US and OA. In addition, CUTE has great diagnostic potential because an image of SoS reflects tissue composition and thus can reveal disease progression. Within the proposed project, we want to achieve the next ground-breaking and very important step: Enable quantitative imaging of blood oxygen saturation and tissue composition, which can be integrated with real-time handheld US in a single multimodal device. The subsequent translation of our scientific results to clinics will have a significant impact on existing diagnostic chains, and open a large variety of new diagnostic possibilities. Whereas the basic feasibility of spectral OA imaging of blood oxygen has already been demonstrated, quantitative imaging is still challenging due to the a priori unknown spectral optical attenuation inside tissue. The situation becomes even more aggravated with limited-bandwidth limited-aperture handheld probes where a reconstruction of the absolute optical absorption coefficient becomes impossible. Therefore, quantitative imaging using handheld probes is considered as extremely challenging throughout the community. We want to break this limit, starting from the multiple-irradiation sensing (MIS) technique: The skin surface is scanned with a small irradiation spot. The OA signal amplitudes of blood vessels as function of irradiation position serve as intrinsic fluence detectors that allow a reconstruction of the tissue’s attenuating properties and thus provide the missing link to quantitative OA imaging of blood oxygen saturation SO2. In spite of the limitations of handheld probes, the SO2 can be calculated from the ratio of optical absorption between different wavelengths as opposed to absolute values, and we have already demonstrated the promise of this technique in phantoms as well as in volunteer results. Yet, these studies were so far limited to simple geometries and media/tissues with uniform optical background properties. Significant development is therefore still required to bridge the gap to quantitative imaging independent of anatomy. We will achieve this goal by developing - via validation in realistic phantom studies - semi-empirical light propagation models and reconstruction techniques that tweak the trade-off between real-time capability and accuracy. We will then integrate and optimise our technique in a setup that allows fast multiple-irradiation scanning integrated in a handheld probe. In addition, to strengthen combined OA and US with additional diagnostic value, we want to develop CUTE towards quantitative imaging of SoS indicating tissue composition and disease stage. So far, quantitative results were limited to layered phantoms and tissues - showing the promise for liver diagnosis - but inconsistencies in more complicated structures revealed incompleteness in our understanding of the image generation process. In addition, reconstruction artefacts so far limited the robust detection of small structures. Within the proposed project, we want to achieve a clinically demanded contrast resolution and accuracy independent of anatomy, suitable to aid a clinical diagnosis of e.g. liver disease or breast cancer and therapy monitoring. For this purpose, we will develop and verify a novel physical model of the image generation process that also incorporates ultrasound refraction. In addition we want to understand and ultimately reduce various sources of artefacts. Thereby, a special focus will be put on developing techniques to compensate for the influence of ultrasound reverberations.
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