15th European Molecular Imaging Meeting
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Ultrasound & Opto-Acoustic Technologies

Session chair: Jan Laufer (Halle, Germany); Steven Machtaler (Saskatchewan, Canada)
 
Shortcut: PS 24
Date: Friday, 28 August, 2020, 10:00 a.m. - 11:30 a.m.
Session type: Parallel Session

Contents

Abstract/Video opens by clicking at the talk title.

10:00 a.m. PS 24-01

Introductory Lecture

Andre C. Stiel1

1 HelmholtzZentrum München, Neuherberg, Germany

 
10:18 a.m. PS 24-02

Interstitial-illumination photoacoustic imaging for device guidance and monitoring of radiofrequency ablation of the liver

Hindrik Kruit1, Srirang Manohar1, Francis Kalloor Joseph1, 2, Elina Rascevska3

1 University of Twente, Multi-Modality-Medical Imaging, Enschede, Netherlands
2 University of Twente, Biomedical Photonic Imaging, Enschede, Netherlands
3 Lawson Health Research Institute, The University of Western Ontario, Imaging Program, London, Canada

Introduction

Unresectable liver tumors are preferably treated with radiofrequency ablation (RFA) [1]. However, there is a high local recurrence rate because of incomplete ablation often due to misplacement of the RFA device, or not accounting for the heat sink effect of blood vessels [2].
The optical property differences between metals [3], blood, native and ablated tissue [4] imply that photoacoustic (PA) imaging can image the RFA device, blood vessels and the ablation zone. We report on PA imaging using interstitial-illumination intended for percutaneous RFA-device guidance and monitoring of ablation.

Methods

Our developed annular fiber probe (AFP), allows the insertion of the RFA needle through its lumen at the proximal side. The distal end has optical fibers arranged in an annular shape for illumination inside tissue. The clinical RFA needle deploys multiple electrodes (tines) at its distal end. An ultrasound transducer is used to measure the PA signal (Fig. 1.).
Three experiments are conducted: First, to determine light propagation from the AFP, the signal from an optical absorber in a mixture of intralipid and India Ink is measured. Second, visualizing the lateral extent to which the tines can be deployed while still visible in the field-of-view of the transducer, and thus still be guided with PA imaging. Third, to measure differences in PA response of native and ablated bovine liver tissue.

Results/Discussion

Measuring light propagation from the AFP, showed that the penetration depth is 10mm with half of the PA intensity remaining, having an absorption and reduced scattering coefficient of 0.5 cm-1 and 10 cm-1  in the liquid phantom mimicking bovine liver tissue at 700nm. This shows potential to use PA imaging with the AFP, to visualize the tines with at least 10mm deployment.
Figure 2A shows tines in ex-vivo breast chicken tissue with PA imaging at 700nm, having a contrast to noise ratio (CNR) of 8.2± 0.3 with the background, while for the US image this was 1.1± 0.2. Figure 2B shows the combined PA-US image, showing improved visibility for locating the tines compared to US alone. Longer wavelengths should increase the penetration depth for imaging wider tine deployment.
Figure 2C shows preliminary results of a PA image showing the ablated boundary in bovine liver tissue at 700nm, topped with a layer of chicken tissue. We will explore other wavelengths for PA ablation imaging.

Conclusions

We showed improved visibility of tines in combined PA-US imaging than in US imaging alone, and demonstrated visualization of the ablation boundary. Interstitial-PA imaging has the potential to increase targeting accuracy in RFA procedures, and further to visualize the ablation region. In our coming experiments, we intent to use longer wavelengths in tissue to achieve greater penetration depths and better visibility of the ablated region.

Acknowledgment

This work is funded by a joint grant from the Netherlands Organisation for Scientific Research (NWO), the Netherlands Organisation for Health Research and Development (ZonMw) and the Department of Biotechnology (Government of India) under the program Medical Devices for Affordable Health (MDAH) as Project Imaging Needles (Grant Number 116310008). Authors acknowledge contributions of Vinay Parameshwarappa and Luuk Dappers in the initial studies.

References
[1] P. L. Pereira, "Actual role of radiofrequency ablation of liver metastases," European Radiology, vol. 17, no. 8, pp. 2062-2070, 2007.
[2] E.Tanis, J.W.Spliethoff, D.J.Evers, G.C.Langhout, P.Snaebjornsson, W.Prevoo, B.H.W.Hendriks and T.J.M.Ruers, "Real-time in vivo assessment of radiofrequency ablation of human colorectal liver metastases using diffuse reflectance spectroscopy," European Journal of Surgical Oncology, vol. 42, no. 2, pp. 251-259, 2016.
[3]  J. L. Su, R. R. Bouchard, A. B. Karpiouk, J. D. Hazle and S. Y. Emelianov, "Photoacoustic imaging of prostate brachytherapy seeds," Biomedical Optics Express, vol. 2, no. 8, pp. 2243-2254, 2011.
[4] R. Nachabé, D. J. Evers, B. H. W. Hendriks, G. W. Lucassen, M. v. d. Voort, J. Wesseling and T. J. M. Ruers, "Effect of bile absorption coefficients on the estimation of liver tissue optical properties and related implications in discriminating healthy and tumorous samples," Biomedical Optics Express, vol. 2, no. 3, pp. 600-614, 2011.
Figure 1. Experimental setup of the annular fiber probe.
(left) Near-infrared laser light from an OPO system is coupled into the AFP using a fiber bundle. At the distal end, tissue is illuminated and the RFA device can be inserted.  An ultrasound transducer picks up the photoacoustic signals additionally to normal B-mode US imaging. Tissue is held into a tank which has a grounding pad for the RFA device. (Right) Depiction of the arrangement of the fibers on the distal end of the probe and the needle insertion shaft on the proximal side.
Figure 2. Photoacoustic imaging under 700nm interstitial-illumination with the annular fiber probe.
A) PA image of the tines in ex-vivo chicken-breast tissue. B) Combined PA-US image of the tines in the same setup. C) Combined PA-US image of ex-vivo bovine liver tissue. The red circle shows the ablated liver region. The arrow indicates the ablation boundary. Chicken tissue was placed on top of the liver tissue to mimic the skin
Keywords: Interstitial-illumination, photoacoustics, ultrasound, liver, radiofrequency ablation
10:30 a.m. PS 24-03

Development of a polymer-in-oil tissue-mimicking material with tuneable optical and acoustic characteristics for technical validation of photoacoustic imaging systems

Lina Hacker1, 2, Aoife Ivory3, James Joseph1, 2, Bajram Zeqiri3, Srinath Rajagopal3, Sarah E. Bohndiek1, 2

1 University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, United Kingdom
2 University of Cambridge, Department of Physics, Cavendish Laboratory, Cambridge, United Kingdom
3 University of Cambridge, National Physical Laboratory, Teddington, United Kingdom

Introduction

International efforts at standardising photoacoustic imaging (PAI) measurements demand a stable, highly reproducible physical phantom to enable routine quality control as well as robust performance evaluation for comparison of different PAI instruments. To address this need, an optimised low-cost polymer-in-oil tissue mimicking material has been developed which is easy and fast to produce and in which all constituents have defined CAS numbers and are readily available from commercial chemistry suppliers.

Methods

The base material consisted of mineral oil, polymer and stabiliser. Oil-based inks and titanium dioxide (TiO2) were used to provide optical absorption and scattering, respectively. The acoustic and optical properties were optimised using various combinations and ratios of the constituents. The attenuation and speed of sound were measured using a substitution-method through-transmission acoustic characterisation system (Fig.1A, National Physical Laboratory, UK). The optical properties were measured using a double-integrating sphere setup (Fig.1B, Cambridge, UK). Furthermore, a longitudinal study of the acoustic and optical properties was performed in order to assess the long-term stability of the materials. The mechanical, thermal and photo-stability properties were also studied.

Results/Discussion

By adjusting polymer type and ratio of the base material (Fig.2A), the speed of sound (c) could be tuned in a biologically relevant range of 1450±0.48 ms-1 to 1494±0.18 m/s-1 (at 5 MHz, Fig.2B) and the acoustic attenuation (αω) in a range of 0.63±0.04  dB/cm/MHz  to 1.59±0.02 dB/cm/MHz (n=4 measurements; Fig. 2C). The base material was characterized by low intrinsic optical properties, which could be adapted as needed by the addition of Nigrosin and TiO2 (Fig. 2D). Adjustment of the optical properties did not show any impact on the acoustic characteristics. The recipe proved to be highly reproducible (for n=3: optical absorption coefficient µa(532 nm): standard deviation s=0.001 mm-1, reduced scattering coefficient µs’(532 nm): s= 0.0153 mm-1, c(5 MHz): s= 0.533 ms-1, αω(5 MHz)= 0.090 dB/cm) and showed good thermal stability in the relevant working range up to 40°C. The acoustic and optical properties were found to be stable over a time frame of two months so far.

Conclusions

The presented materials represent good candidates for a standardised PAI phantom due to their: ease of manufacture; stability in terms of mechanical, thermal, optical and acoustic properties; low cost; and the ability to tune biologically relevant optical and acoustic properties. Further work will establish the interlaboratory repeatability of the material fabrication with the aim of establishing a standard phantom method for PAI techniques.

AcknowledgmentThe project was funded by a studentship from the National Physical Laboratory, Teddington, UK.
Figure 1: Setup of the acoustic characterization system and double-integrating sphere system.
The setup of the acoustic characterization system (A) for determination of the acoustic properties, and the setup of the double-integrating sphere system (B) for the evaluation of the optical properties is shown.
Figure 2: Fabrication of tissue-mimicking materials with tuneable optical and acoustic properties.

A) The fabrication process includes weighing of the components (1), sonication of TiO2 in mineral oil (2), heating of the polymer-in-oil mixture (3), vacuuming (optional) and curing (4). The tunability of the acoustic attenuation coefficient (B) and phase velocity (C) by variation of the material-specific polymer concentration, as well as the tunability of the reduced scattering coefficient (D) by addition of TiO2 is shown for one of the fabricated materials (mean±SEM, n=4 measurements; error bars within symbols).

Keywords: phantom, Photoacoustic imaging, tissue-mimicking material, polymer-in-oil material, technical validation
10:42 a.m. PS 24-04

Analytical precision optoacoustic spectrometer

Juan Pablo Fuenzalida Werner1, Yuanhui Huang1, Kanuj Mishra1, Vasilis Ntziachristos1, Andriy Chmyrov1, Andre C. Stiel1

1 Helmholtz zentrum münchen, IBMI, Oberschleißheim, Germany

Introduction

Despite the advances in optoacoustic (OA) imaging, there is no detailed understanding of OA signal generation of its contrast agents. To close this gap, we developed a multi-modal laser spectrometer (MLS) to simultaneous measure OA, absorbance, and fluorescence. Dyes, for example, show high energy shoulder with more OA efficiency than their monomeric transition. Additionally, proteins have favored OA signal generation from the neutral/zwitterionic chromophores. Finally, OA-spectra shed light on the general photophysics of proteins and dyes, e.g. photo-switching behavior unobserved so far.

Methods

Illumination, power control, recording of OA signals and absorption measurements are laid out as described in1 and show in Fig 1a. The raw signal is computed in the following steps (Fig. 1b): 1. ‘Filt. Hilbert’ - take absolute maximum OA signal values (OAS) for each wavelength from filtered Hilbert transform of raw signal to have smooth spectra that is immune to thermal noise in acquisition devices.  2. ‘- Dark’ – subtract the filtered Hilbert transform of raw signal with that of a noise signal that is acquired with no light. 3. ‘Pulse Fl.’ - divide OAS of sample by that of ink to reduce the influence of laser pulse-to-pulse fluctuation.. 4. ‘- Ink Spect.’ - multiply the spectra with absorbance spectra of ink to recover the sample spectra.  5. ‘- Coloring’ – correct for ink laser coloring.

Results/Discussion

The OA and absorption spectra of NiCl2, which show total conversion of absorbed photons to OA signal2. The resulting spectrum has 1.5% STD (bottom red curve in Fig. 1b), and an R2 of 0.9986 relative to the absorbance spectra of NiCl2 (blue spectra in Fig. 1b). The benefit of such a precise spectral measurement becomes apparent when measuring substance that does not show such clear photophysics. For example, the transgene label tdTomato, HcRed or the dye CW800. As evident in figure 1c, tdTomato shows a 20 nm red-shifted OA spectrum with strong evidence of ground stated depopulation in its excitation spectrum. CW800 (Fig 1d) shows a non-fluorescence dimer transition with higher OA capacity than the monomer. Finally, we found out that HcRed under pulsed illumination photo converts to a strong photoacoustic emitter (1e and 1f). Thus, time domain-based imaging of HcRed becomes possible.

Conclusions

It is essential to understand how different molecular states contribute to the generation of OA signals, e.g. to engineer effects like photo-switching, aggregation or changes in the Grüneisen parameter. We believe that measuring reliable and reproducible OA will contribute to solid data for OA contrast agents and endogenous reference compounds.
-JPFW and YH contributed equally to this work.

AcknowledgmentThis work was supported by the Federal Ministry of Education and Research, Photonic Science Germany, Tech2See-13N12624, 13N12623. The work of K.M. and A.C.S. was supported by the Deutsche Forschungsgemeinschaft (STI 656/1-1).
References
[1] Paul Vetschera, Kanuj Mishra, Juan Pablo Fuenzalida-Werner, Andriy Chmyrov, Vasilis Ntziachristos, Andre C. Stiel, Characterization of Reversibly Switchable Fluorescent Proteins in Optoacoustic Imaging, Anal. Chem. 2018, 90, 17, 10527-10535
[2] Laufer, J.; Zhang, E.; Beard, P. Evaluation of Absorbing Chromophores Used in Tissue Phantoms for Quantitative Photoacoustic Spectroscopy and Imaging. IEEE J. Sel. Top. Quantum Electron. 2010, 16 (3), 600–607.
Figure 1
(a) Setup diagram. (b) Improvement in optoacoustic spectrum of NiCl2 brought by each of the correction steps. Normalized optoacoustic signal (OAS), absorption, emission and excitation spectra for  (c) tdTomato, (d) IRDye 800CW, (e) HcRed. (f)Optoacoustic signal kinetic for HcRed illuminated with 565nm and 590nm light. 
Keywords: Optoacoustic, spectroscopy, Dyes, Proteins
10:54 a.m. PS 24-05

Aptamer-functionalized microbubbles: Ultrasound molecular imaging using an anti-P-selectin aptamer for imaging acute bowel inflammation.

Una Goncin1, Ronald Geyer2, Steven Machtaler1

1 University of Saskatchewan, Department of Medical Imaging, College of Medicine, Saskatoon, Canada
2 University of Saskatchewan, Department of Pathology and Laboratory Medicine, College of Medicine, Saskatoon, Canada

Introduction

Aptamers are oligonucleotides that bind with high affinity and specificity to a range of targets. There are two limitations to their use in molecular imaging: they are quickly degraded by nucleases and rapidly filtrated via the kidneys. Ultrasound molecular imaging (US-MI) uses targeted microbubbles (MBs) that bind vascular disease markers 4-10 mins after injection, allowing for rapid detection. Our goal is to combine strengths of aptamers and MBs to create a targeted MB to P-selectin (a vascular inflammatory marker) and use it to image inflammation in a murine model of acute bowel colitis.

Methods

MBs were produced by sonicating a perfluorobutane-sparged solution containing solubilized phospholipids including DSPE-PEG2000-DBCO. MBs were incubated with either a fluorescent P-selectin-aptamer (P-Ap) (5’-azide-P-Ap-3’-Cy3) or non-fluorescent (5’-azide-P-Ap) for 15 min at 37°C, placed on ice for 5 min, and washed via centrifugation. Acute colitis was induced through rectal administration of TNBS in 5 of 8 mice. Mice were imaged using a preclinical ultrasound system following i.v. bolus of 1x108 MBs. MBs circulated for 4 min before the US-MI signal was collected. Each mouse received a bolus of both non-targeted and P-Ap-MBs separated by 20 min. Following imaging, bowels were excised and harvested for histology. Images were analyzed using VEVOCQ.

Results/Discussion

Successful labeling of MBs with P-Ap-Cy3 was verified with confocal microscopy (Figure 1A). There was a low US-MI signal detected using both non-targeted (0.4 ± 0.3 a.u.) and P-Ap-MBs (0.6 ± 0.8 a.u.) in control (no inflammation) mice. There was a significant increase in the US-MI signal in mice with acute colitis using the P-Ap-MBs (13.5 ± 8.1 a.u.)  in comparison to non-targeted MBs (3.2 ± 2.2 a.u.)(Figure 1B & C). US-MI signals correlated well to H&E histology (Figure 1D).

Conclusions

We constructed a targeted MB to P-selectin using an aptamer, which generated a detectable US-MI signal in mice with acute colitis. This approach for constructing quick, cost-efficient targeted MBs may represent a new generation of US-MI contrast agents that can be clinically translated.

Ultrasound molecular imaging (US-MI) using P-selectin aptamer for imaging acute bowel inflammation.
A) Schematic of perfluorobutane-filled lipid shelled MBs and successful labelling with fluorescent P-selectin aptamer (P-Ap; red). B) US imaging with non-targeted (left) and P-Ap targeted (right) MBs in control (bottom) and acute colitis mice (top) (B-mode: left; US-MI signal: right; green ROI highlights cross section of bowel). C) Bar graph (mean ± standard deviation) of US-MI signal using non-targeted and P-Ap targeted MBs in control (n=3) and acute colitis mice (n=5). D) H&E staining of bowels for control (left) and acute colitis mice (right; note large infiltration of immune cells).
Keywords: aptamer, P-selectin, inflammation, ultrasound, ultrasound molecular imaging
11:06 a.m. PS 24-06

Delivery of liposomal nanomedicines across the blood brain barrier in mice using rapid short pulses (RaSP) of focused ultrasound

Aishwarya Mishra1, 2, Sophie Morse2, James Choi2, Rafael T.M. de Rosales1

1 King's College London, School of Biomedical Engineering and Imaging Sciences, London, United Kingdom
2 Imperial College London, Department of Bioengineering, London, United Kingdom

Introduction

Focused ultrasound (FUS) in combination with microbubbles has been shown to open the blood-brain barrier (BBB) increasing drug delivery, being quite effective for small-molecule drugs1. Recently, RaSP FUS has been used to safely deliver dextran and AuNPs (25 nm)2,3 to the brain. Liposomal nanomedicines (ca. 100 nm) are excellent drug delivery systems, but suffer from inability to cross the BBB. In this study, we test the ability of RaSP to successfully and safely increase the delivery of liposomes in the brain in vivo, compared to conventional ms-long ultrasound sequences.

Methods

DiD-PEGylated liposomes (DPLs) were synthesized by co-incubation of DiD dye and PEG liposomes for 2 hrs/37oC. The DPLs were purified using size exclusion chromatography and characterized using fluorescence/DLS. Thirty-six female wild-type mice underwent FUS after injections of Sonovue® microbubbles and DPLs. The left hippocampus of 18 mice was exposed to low-energy short pulses (1 MHz, 5 cycles, MPapk-neg= 0.4 and 0.6) of US emitted at a rapid rate (1.25 kHz) in bursts (0.5 Hz) and another 18 mice were exposed to standard long pulses (10 ms, 0.5 Hz). Mice were sacrificed at 0 hr (n=16) or 2 hr (n=16) after US treatment. The delivered drug dose was quantified using normalized optical density (NOD) measurements and tissue damage/RBC extravasation assessed by H&E staining.

Results/Discussion

The DPLs synthesized by insertion of dye (dye concentration of 2.1±0.5 µg/mL) did not modify size, zeta potential and PDIs of the original PEG liposomes (Fig 1A). DPLs were stable in human serum for at least 48 h (Fig 1B).  The long pulses with 0.6 MPa show an uptake of DPLs with fluorescence signal concentrated around the blood vessels. The delivery with RaSP sequences shows more diffused delivery and larger spread from vessels. Regions of interest around the left (US) and right (control) hippocampus were selected. The NOD analysis shows comparable DPL delivery in brains with long pulse and RaSP sequence sonication at 0.6 MPa. However, no delivery is observed with RaSP sequence sonication at the lower 0.4 MPa pressure. No RBC extravasation is observed in H&E staining of the target (RaSP FUS 0.6 MPa) and the control (no US) regions of the brain.

Conclusions

Long ultrasound pulses at 0.6 MPa pressure show localised extravasation of fluorescent liposomes into the brain. However, previous studies have shown this delivery to be invasive and damaging to brain vasculature4. Delivery of DPLs (~100 nm) with RaSP sequences shows promise at 0.6 MPa with a diffused delivery and larger spread. In addition, it appears to not result in vasculature damage. Further tests will allow us to confirm these observations.

AcknowledgmentFunding: EPSRC, King's College London and Imperial College London
References
[1] Snipstad, S. et al. Sonopermeation to improve drug delivery to tumors: from fundamental understanding to clinical translation. Expert Opinion on Drug Delivery 15, 1249–1261 (2018)
[2] Morse, S. V. et al. Rapid Short-pulse Ultrasound Delivers Drugs Uniformly across the Murine Blood-Brain Barrier with Negligible Disruption. Radiology 181625 (2019). doi:10.1148/radiol.2019181625
[3] Chan, T. G., Morse, S. V., Copping, M. J., Choi, J. J. & Vilar, R. Targeted Delivery of DNA-Au Nanoparticles across the Blood-Brain Barrier Using Focused Ultrasound. ChemMedChem 13, 1311–1314 (2018).
[4] Baseri, B., Choi, J. J., Tung, Y. S. & Konofagou, E. E. Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: A short-term study. Ultrasound Med. Biol. 36, 1445–1459 (2010).
Figure 1. Characterization of DiD-PEGylated liposomes and focussed ultrasound sonication setup
(A) Structure of DPLs; (B) Comparison of properties of synthesized DPLs with PEGylated liposomes; (C) Serum stability of DPLs over 48 hours; (D) SEC HPLC UV and fluorescence elution profile; (E) Rapid short pulse overlayed and compared from conventional long pulse ms sequence; (F) Experimental setup for focused ultrasound-mediated BBB disruption. Microbubbles are injected intravenously, followed by DiD-liposomes2; (G) The left thalamus is sonicated using ultrasound pulses as seen in black circled region; (H) Timeline of the FUS experiment from animal preparation to imaging of brain slices.
Figure 2. Imaging of brain slices for assessment of fluorescence uptake and tissue damage
(A) Representative fluorescence images of the left thalamus from the delivery of DPLs across the BBB using focused ultrasound for long pulses 0.6 MPa (left) and RaSP 0.6 MPa (right) both with a 2 h wait post sonication (inset: control region: right thalamus); (B) NOD calculated for sonicated animal groups: RaSP at 0.6 MPa sonicated subjects shows comparable delivery to long pulses sonicated subjects and no delivery is observed for brains sonicated with RaSP at 0.4 MPa; (C) Assessment of safety by H&E staining of sonicated (RaSP-0.6 MPa) and control (no US) regions showing no RBC extravasation.
Keywords: Focussed ultrasound, RaSP, BBB, liposomes, non-invasive
11:18 a.m. PS 24-07

INDUSTRY TALK (FUJIFILM VisualSonics)Photoacoustic hypoxia mapping of vital peripheral organs after myocardial infarction in mice

Helene David2, 1, Aurore Ughetto2, 1, Philippe Gaudard2, 1, Maelle Plawecki3, Nitchawat Paiyabhroma1, Pascal Colson2, Sylvain Richard1, Pierre Sicard1

1 INSERM, CNRS, Université de Montpellier, PHYMEDEXP, Montpellier, France
2 Arnaud de Villeneuve Hospital, CHU Montpellier, Department of Anesthesiology and Critical Care Medicine,, Montpellier, France
3 CHU Lapeyronie, Département de biochimie, Montpellier, France

Content

Introduction: Early alterations of microvascular blood flow after myocardial infarction (MI) may participate in the development of multiple organ failure. The aim of this study was to determine the relevance of photoacoustic (PA) imaging to detect an early alteration in oxygen saturation (sO2) in peripheral organs after MI in mice.

Methods and results: MI was produced by permanent ligation of the left anterior descending artery (n=42) versus sham (n=22) BALB/c mice and followed-up for 7 days post-MI. High-resolution ultrasound (Vevo3100) allowed to assess persistent left ventricular (LV) dysfunction after MI. PA imaging (Vevo LAZR-X) was operated to measure kinetics of sO2 in the LV anterior wall using PA-EKV mode, brain, kidney and liver after MI. A strong correlation was established between LV sO2 and longitudinal anterior myocardial strain measured the first day (r=-0.44, p<0.0001, n=64). Photoacoustic mapping showed a 10-15% (p<0.05) decrease in sO2 level in cerebral, renal and hepatic tissues both at 4h and 1 day post-MI compared to sham animals. Despite permanent and persistent cardiac dysfunction, the peripheral organs sO2 level was normalized after 7 days. In addition, the kinetics of ASAT and creatinine were correlated (r=-0.97; p<0.0001, n=9; r=-0.81, p<0.01, n=9) to a specific tissue sO2 level at 4h.

Conclusions: Post-MI heart failure generates transient and moderate hypoxia of peripheral organs in mice. PA imaging enabled early detection of multi-organ sO2 desaturation. The sO2 organs mapping is an accurate marker to identify real time microcirculation alteration.

Acknowledgment

This work was supported by grants from INSERM (S.R), Université de Montpellier/Muse (PS), Franco-Thai Scholarship (NP) and by a grant from the Fondation Leducq (RETP).

Keywords: Myocardial infarction, cardiogenic shock, hypoxia, photoacoustic imaging.