1. Opto-Acoustic Imaging Peter E. Andersen Optics and Fluid Dynamics Department Risø National Laboratory Roskilde, Denmark E-mail peter.andersen@risoe.dk

2. P.E. Andersen [BIOP], Feb. 2, 2000 Outline ! Tissue optics – optical properties, – light propagation in highly scattering media. ! Photoacoustic imaging – generation, propagation, and detection of stress waves, – imaging systems and clinical potential.

3. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics ! Optically tissue may be characterized by its – scattering, refractive index, and absorption. ! The scattering arises from – cell membranes, cell nuclei, capillary walls, hair follicles, etc. ! The absorption arises from – visible and NIR wavelengths (400 nm - 800 nm); >hemoglobin and melanin, – IR wavelengths; >water and molecular vibrational/rotational states.

4. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics

5. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics

6. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics ! Single particle – light scattering by a single particle is characterized by its scattering cross section [m 2 ] and phase function p(  ), – using Mie theory the scattering may be deter- mined knowing; >the size parameter (perimeter compared to wavelength), >refractive index ratio between particle and media.

7. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics ! Turbid media – tissue is a (huge) collection of scattering particles; >various sizes and shapes, – light propagation cannot be described as single scattering, – models taking into account multiple scattering must be applied.

8. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics ! Modeling light propagation in tissue – transport theory (or the diffusion approximation); >known from heat transfer (Boltzman’s equation), – extended Huygens-Fresnel principle, – Monte Carlo simulations. ! Optical properties (macroscopic) – absorption coefficient  a [m -1 ], – scattering coefficient  s [m -1 ], – asymmetry parameter g or phase function p(  ), – refractive indices.

9. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics ! Light propagation (Monte Carlo simulation) Incident light Ballistic component “Snake” component Diffuse reflectance Absorption Diffuse transmittance

10. P.E. Andersen [BIOP], Feb. 2, 2000 Tissue optics ! References – Light scattering; >C. Bohren and D. Huffman, Absorption and scattering of light by small particles, J. Wiley & Sons, New York, 1983, – Multiple scattering; >A. Ishimaru, Wave propagation and scattering in random media I & II, Academic Press, New York, 1978, >R. F. Lutomirski and H. T. Yura, Appl. Opt. 7, 1652 (1971), – Tissue optics; >A. J. Welch and M. J. C. van Gemert (eds.), Optical- Thermal response of laser-irradiated tissue, Plenum Press, New York, 1995.

11. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Thermoelastic stress and generation of stress waves Absorber Short laser pulse Stress wave (acoustic wave) Thermoelastic stress

12. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Stress waves – thermoelastic stress is generated due to the absorption of a short laser pulse, – knowing the optical, mechanical, and thermal properties of the absorber, the amplitude and shape of the stress wave may be calculated, – vice versa, measuring the amplitude and shape of the stress wave may provide e.g. the optical properties of the absorber, – stress confinement; >duration of the irradiating laser pulse must be smaller than the time for the acoustic wave to traverse the optically heated volume.

13. P.E. Andersen [BIOP], Feb. 2, 2000 – the stress building up inside the absorbing target is  :Grüneisen parameter (0.11 for water at room temperature)  :radiant exposure (from laser)  a :optical absorption coefficient Photoacoustic imaging ! Stress waves (cont’d) – stress confinement (mathematically); c:speed of sound D:Min{optical penetration, laser beam diameter, slab}

14. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Example: estimation of  T and  P – Grüneisen parameter:0.11 @ room temp. – absorption coefficient  a :20 cm -1 – radiant exposure  : 16 mJ/(  0.2 2 cm 2 ) =127 mJ/ cm 2 >beam diameter 4 mm >pulse energy 16 mJ – temperature change: (  a  )/(  c v ) = 0.63 °C >density  1 g/cm 3 and specific heat c v 4 J/(g K) – Pressure change:2.6 bar

15. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Stress waves (cont’d) – the radiant exposure  depends on the optical properties of the tissue being probed, and found using “tissue optics”, – the thermoelastic stress couples into the surrounding medium, – the resulting stress wave may then be calculated from the acoustic wave equation, – diffraction and rarefaction effects may have to be included.

16. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Detection – microphone (hydrophone), – piezoelectric transducers, – all-optical method(s) based on interferometry.

17. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Suggested reading – Stress waves in liquids and gases (review); >M. W. Sigrist, J. Appl. Phys. 60, R83 (1986), – Determination of optical properties from stress waves; >A. A. Oraevsky et al., Proc. SPIE 1882, 86 (1993), – Optical transducer; >G. Paltauf and H. Schmidt-Kloiber, J. Appl. Phys. 82, 1525 (1997), – All-optical detection; >S. L. Jacques et al., Proc. SPIE 3254, 307 (1998), >P. E. Andersen et al., Proc. SPIE 3601 (1999).

18. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Three-dimensional imaging – system built at Dept. of Applied Optics, University of Twente, NL; >C. G. Hoelen et al., Opt. Lett. 23, 648 (1998). ! Key figures: – laser; 8 ns pulses, 10 Hz rep. rate, – spatial resolution 10  m, – acquisition time: >2 hours(!).

19. P.E. Andersen [BIOP], Feb. 2, 2000 Photoacoustic imaging ! Imaging tissue (in vitro) – many source-detector pairs, – back-propagation algorithm. ! Experiment – 6 mm chicken breast tissue, – two nylon capillaries (inner diameter 280  m) filled with whole blood, – placed at 2 and 4 mm depth, – spatial resolution 10  m, – acquisition time: from minutes to hours.

20. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! Motivation for the study – to investigate the photoacoustic imaging method with respect to the all-optical detection scheme, – the all-optical detection scheme facilitates non- contact compact, highly sensitive probing of the stress wave.

21. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! The setup – a HeNe laser as the source, – a beam splitter, – a Wollaston prism and a lens; >to form two co-aligned beams, >these two components determine the beam separation, – the focus of the lens should be as close as possible to the object (surface) of investigation to insure optimum system performance. ! The reflected light – collected through the lens and sent to the detector by passing the beam splitter.

22. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! The all-optical detection scheme (top view)

23. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! The setup may be operated in – transmission mode, – reflection mode. ! The irradiating laser is a pulsed Nd:YAG source – pulse duration 5 ns, – pulse energy 16 mJ @ 532 nm or 30 mJ @ 1064 nm, – 10 Hz pulse repetition rate, – spot size 4 mm at the object. ! Optical detection – beam separation of 9 mm.

24. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! Figures-of-merit – minimum signal: 10-30 mbar (measured, not optimized), – linear dynamic range: 0.03 - 33 bar (measured). ! Advantages – high common-mode rejection ratio, – non-contact procedure, – compact and robust, when integrated into a single HOE. ! Disadvantages – high performance requires a free, smooth surface, e.g. water.

25. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! The tissue phantom – the tissue sample is chicken breast samples of various thickness, – the absorbing object is silicon rubber dyed with India ink, – various shapes; >circular disk, >rectangular box. Nd:YAG Absorber Tissue Water HeNe beams 632 nm 532 nm Translation

26. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! The “peak” at edge – depends on sample thickness, – pronounced with thin sample, – primarily due to changes in the stress wave shape. ! Broadening of the image profile – due to a combination of scattering of the illuminating beam and attenuation of the stress wave.

27. P.E. Andersen [BIOP], Feb. 2, 2000 All-optical detection scheme ! Comparison – all-optical method (not optimized); >minimum signal level:10-30 mbar, >linear dynamic range:0.03-33 bar, – piezo-electric transducers; >minimum signal level:20-40 mbar, >linear dynamic range:0.04-6* bar, [from Oraevsky et al., Appl. Opt. 36, 402 (1997)]. * probably larger

28. P.E. Andersen [BIOP], Feb. 2, 2000 Summary ! Opto-acoustic is a feasible method for imaging in human tissue ! All-optical detection is advantageous due to – high sensitivity, – non-contact procedure. ! Applications – imaging of breast cancers, – in vivo concentration measurements.