title: Ultrasound modulated optical tomography contrast enhancement with non-linear oscillation of microbubbles.
abstract: BACKGROUND
  Ultrasound modulated optical tomography (USMOT) is an imaging technique used to provide optical functional information inside highly scattering biological tissue. One of the challenges facing this technique is the low image contrast.
  
  
  METHODS
  A contrast enhancement imaging technique based on the non-linear oscillation of microbubbles is demonstrated to improve image contrast. The ultrasound modulated signal was detected using a laser pulse based speckle contrast detection system. Better understanding of the effects of microbubbles on the optical signals was achieved through simultaneous measurement of the ultrasound scattered by the microbubbles.
  
  
  RESULTS
  The length of the laser pulse was found to affect the system response of the speckle contrast method with shorter pulses suppressing the fundamental ultrasound modulated optical signal. Using this property, image contrast can be enhanced by detection of the higher harmonic ultrasound modulated optical signals due to nonlinear oscillation and destruction of the microbubbles. Experimental investigations were carried out to demonstrate a doubling in contrast by imaging a scattering phantom containing an embedded silicone tube with microbubbles flowing through it.
  
  
  CONCLUSIONS
  The contrast enhancement in USMOT resulting from the use of ultrasound microbubbles has been demonstrated. Destruction of the microbubbles was shown to be the dominant effect leading to contrast improvement as shown by simultaneously detecting the ultrasound and speckle contrast signals. Line scans of a microbubble filled silicone tube embedded in a scattering phantom demonstrated experimentally the significant image contrast improvement that can be achieved using microbubbles and demonstrates the potential as a future clinical imaging tool.
authors.affiliation: 1 Electrical Systems and Optics Research Division, Faculty of Engineering, University of Nottingham, Nottingham, NG7 2RD, UK ; 2 Department of Electrical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA ; 3 Institute of Biophysics, Imaging and Optical Sciences, University of Nottingham, UK.
authors.forename: Haowen
authors.initials: H
authors.lastname: Ruan
authors.affiliation: 1 Electrical Systems and Optics Research Division, Faculty of Engineering, University of Nottingham, Nottingham, NG7 2RD, UK ; 2 Department of Electrical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA ; 3 Institute of Biophysics, Imaging and Optical Sciences, University of Nottingham, UK.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Mather
authors.affiliation: 1 Electrical Systems and Optics Research Division, Faculty of Engineering, University of Nottingham, Nottingham, NG7 2RD, UK ; 2 Department of Electrical Engineering, California Institute of Technology, 1200 E California Boulevard, Pasadena, California 91125, USA ; 3 Institute of Biophysics, Imaging and Optical Sciences, University of Nottingham, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Morgan
keywords: Ultrasound modulated optical tomography (USMOT); harmonic imaging; microbubbles; optical scattering; ultrasound