chapter  11
Combined Photoacoustic and Ultrasound Imaging of Metal Nanoparticles in vivo
Pages 26

The field of nanotechnology is poised to revolutionize medical imaging. As discussed in the previous chapters, nanoparticles can be detected in vivo through myriad techniques. Here we introduce another technique, photoacoustic imaging, that combines the advantages of optical and ultrasound imaging methods, resulting in the ability to detect metal nanoparticles deep in tissue in comparison with pure optical techniques. The benefits of employing combined photoacoustic and ultrasound imaging are discussed along with examples of fabrication, functionalization, and in vivo imaging of gold and silver nanoparticles. 11.1 INTRODUCTIONPhotoacoustic imaging is an emerging technique on the precipice of reaching the clinic. The basics and history of photoacoustic imaging are presented in this section along with the benefits of combining it with the well-known and characterized ultrasound system. Furthermore, metal nanoparticles are introduced and the plasmon resonance properties of nanoparticles that enable their use as photoacoustic contrast agents are explained. Nanoimaging Edited by Beth Goins and William Phillips Copyright © 2011 by Pan Stanford Publishing Pte. Ltd. www.panstanford.com

11.1.1 History of Photoacoustic ImagingThe photoacoustic (and, in general, thermoacoustic) effect refers to the conversion of light (electromagnetic energy) to thermal and then acoustic energy. This phenomenon was first discovered in the late 19th century by Alexander Graham Bell. In 1880, Bell patented the “photophone,” a device that could produce sound when incident light striking the surface of a solid object was rapidly interrupted, typically on the order of kilohertz. Bell correctly conjectured that the resulting acoustic signal was dependent on the composition of the sample, and thus caused by the absorption of light [6]. However, it was over 100 years before Bowen et al. recognized the potential of applying the same phenomena for imaging of soft tissues in the body [9]. In the mid 1990s, Beard et al. [5] constructed an optical fiber photoacoustic-photothermal imaging probe, while Kruger et al. and Oraevsky et al. developed 3D tomographic imaging techniques for clinical applications [30, 48]. Through the work of Wang et al. and others, photoacoustic imaging has continued to enjoy a steady wave of advances as a noninvasive imaging modality that is capable of providing both morphological and functional information for various applications ranging from cardiovascular applications to tissue engineering and cancer [16, 27, 34, 42, 54, 58, 70]. 11.1.2 Photoacoustic Imaging Basics

Figure 11.1 Depiction of the photoacoustic effect.Obtaining a photoacoustic image can be simplified to a four-step process. First, the tissue of interest is illuminated with a short laser pulse, on the order of several nanoseconds. Next, the deposition of this energy in the tissue causes localized heating followed by rapid thermal expansion and the generation of

acoustic pressure transients. Finally, acoustic waves, detected with an ultrasound transducer, are digitally processed to form an image of the spatial distribution of tissue optical absorption (Fig. 11.1). 11.1.2.1 Photoacoustic pressure generationThe governing equations of photoacoustics are derived from the linearized equations of fluid dynamics for an isotropic, homogeneous, inviscid fluid as well as the heat transfer equation, which relates the change of thermal energy to the change of electromagnetic radiation [28, 32]. The absorbed energy density from a laser source, Eabs (J/m3), causes a localized increase in temperature, DT (K), giving rise to a pressure transient, DP (Pa), in the tissue volume given by [48]

BcEP T H CpC

β β µ γ γ

   ∆  ∆      (11.1)where γ (Pa-4) is the thermodynamic coefficient of isothermal compressibility,

β  (K-1) is the thermal coefficient of volume expansion, ρ  (kg/m3) is the density of the medium, Cv and Cp (J/kg×K) are the heat capacities at constant volume and pressure, respectively, and cs (m/s) is the speed of sound in the medium. Eabs is the product of the laser fluence H (J/m2) and the absorption coefficient of the medium μa(m-1). The expression (βcs2/Cp) represents the Grüneisen parameter G, which is the dimensionless, temperature-dependent factor representing the fraction of thermal energy converted into mechanical stress, yielding the simplified expression

(11.2) Equation (11.2) is valid only in the case when the stress confinement condition is met, that is, when the heat diffusion time (τD) is significantly shorter than the stress relaxation time (τSR), i.e., the time for the acoustic waves to propagate through the irradiated volume. This condition limits the duration of the laser pulse (τL), implying that it must also be much shorter than the stress relaxation time. When the stress confinement condition is met, the input laser energy generates photoacoustic pressure with the greatest efficiency.