High resolution near-field thermoacoustic sensing and imaging

• Applicant: Professor Dr. Vasilis Ntziachristos
• Subject Area: Medical Physics, Biomedical Technology
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 214937490

Final Report Abstract

This project aimed to build fundamental knowledge on previously undocumented near-field thermoacoustic (NFT) technology for the development of a new sensing modality that can advance our understanding on the mechanisms and usage of electromagnetic absorption at the sub-cellular, cellular and tissue level. Near-field technology leads to mesoscopic (30-200 micron) and to ultra-high (<5-10 micron) imaging resolution, which can 1) directly measure electro-magnetic (EM) energy deposition and effects in cells and tissues, 2) resolve dielectric properties and effects within cells/cellular compartments and tissues and 3) study intrinsic high resolution tissue contrast or extrinsically administered (para-) magnetic and (semi-) conductive particles used as contrast agents. Aim of this project was the development of 1) hybrid NFT and fluorescence microscopy and 2) a tissue imaging NFT system coupled with conventional ultrasound imaging. In accordance to that we developed 1) a hybrid NFT fluorescence microscope using an open transmission line with oil as radio frequency (RF) energy couplant and 2) a handheld scanner with simultaneous NFT and Ultrasound detector. We investigated their resolution limit and penetration depth and implemented the Synthetic Aperture Focusing Technique (SAFT), as an algorithm to obtain high quality images. We independently studied the electro-acoustic and magneto-acoustic contrast mechanisms for both modalities. Furthermore this project aimed to research the following three application areas: 1) the direct measurement of EM depositions at the cellular and sub-cellular level and the observation of possible biological effects, using fluorescent tags, 2) the generation of methods to experimentally measure EM energy deposition and dielectric properties in tissues in high resolution and 3) the development of a portable sensing and imaging modality for medical applications in particular in bed-side or point of care applications. In this regard we could show micrometer scale distribution variations in electrical conductivity resulting in RF absorption contrast in single cells. Furthermore we measured electrical conductivity absorption from brain, heart/vascular in NFT, from both wild-type and casper zebrafish and measured fluorescent proteins such as GCaMP6s in zebrafish. We performed phantom, postmortem and in-vivo measurements of different animal tissues and discovered that muscle and blood give strong NFT contrast, confirming the clinical potential on these new modalities and building the foundation for their application in clinical settings.

Publications

• Hybrid multiphoton and optoacoustic microscope. Opt Lett 2014; 39(7): 1819-22
  Tserevelakis GJ, Soliman D, Omar M, Ntziachristos V
  
• Sensitive interferometric detection of ultrasound for minimally invasive clinical imaging applications. Laser & Photonics Reviews 2014; 8(3): 450-7
  Rosenthal A, Kellnberger S, Bozhko D, et al.
  
• Ultrawideband reflection-mode optoacoustic mesoscopy. Opt Lett 2014; 39(13): 3911-4
  Omar M, Soliman D, Gateau J, Ntziachristos V
  
• Combining microscopy with mesoscopy using optical and optoacoustic label-free modes. Sci Rep 2015; 12902-1
  Soliman D, Tserevelakis GJ, Omar M, Ntziachristos V
  
• Pushing the optical imaging limits of cancer with multi-frequency-band raster-scan optoacoustic mesoscopy (RSOM). Neoplasia 2015; 17(2): 208-14
  Omar M, Schwarz M, Soliman D, Symvoulidis P, Ntziachristos V
  
• Magnetoacoustic Sensing of Magnetic Nanoparticles 2016; Phys Rev Lett 116
  Kellnberger S, Rosenthal A, Myklatun A, Westmeyer GG, Sergiadis G, and Ntziachristos V
  
• A method and apparatus for determining an energy deposition of an ion beam. Google Patents; 2017
  Dollinger G, Parodi K, Assmann W, Ntziachristos V, Kellnberger S
  
• Electrolytic conductivity-related radiofrequency heating of aqueous suspensions of nanoparticles for biomedicine. Phys Chem Chem Phys 2017; 19(18): 11510-7
  Tamarov K, Gongalsky M, Osminkina L, et al.
  
• Blood vessel imaging using radiofrequency-induced second harmonic acoustic response. Sci Rep 2018; 8(1): 15522
  Huang Y, Kellnberger S, Sergiadis G, Ntziachristos V
  
• Looking at sound: optoacoustics with all-optical ultrasound detection. Light: Science & Applications 2018; 7(1): 53
  Wissmeyer G, Pleitez MA, Rosenthal A, Ntziachristos V
  
• Optoacoustic microscopy at multiple discrete frequencies. Light: Science & Applications 2018; 7(1): 109
  Kellnberger S, Soliman D, Tserevelakis GJ, et al.