Gold nanoparticles targeting epidermal growth factor receptor via antibody conjugation undergo molecular specific aggregation when they bind to receptors on cell surfaces, leading to a red shift in their plasmon resonance frequency. Capitalizing on this effect, we demonstrate the efficacy of the molecular specific photoacoustic imaging technique using subcutaneous tumor-mimicking gelatin implants in ex-vivo mouse tissue. The results of our study suggest that highly selective and sensitive detection of cancer cells is possible using multiwavelength photoacoustic imaging and molecular specific gold nanoparticles.The developments in the fields of nanotechnology and molecular biology provide a promising platform for detection of cancer at an asymptomatic stage. Bioconjugated nano contrast agents together with imaging techniques can satisfy the compelling need to reliably detect, diagnose and characterize cancer at an early stage. [1][2][3][4][5][6][7] Recently, gold nanoparticles (Au NPs) have gained popularity as nano-sized contrast agents 2,6,[8][9][10][11][12][13][14] for their well-developed bioconjugation protocols, 11,[15][16][17] biocompatibility 18,19 and ease of tuning the optical properties. [20][21][22] Immunotargeted gold nanoparticles have been used to enhance contrast in optical imaging techniques. 6,9,13,14 However, the penetration depth achievable with high resolution optical imaging techniques is limited to a few millimeters. Optical techniques utilizing incoherent light extend the penetration depth to several centimeters while spatial resolution is severely sacrificed. Therefore, an in vivo imaging technique that is sensitive in detecting Au NPs and capable of imaging deep lying structures is desired. Photoacoustic imaging [23][24][25] is a technique that can provide penetration depth on the order of centimeters if near-infrared (NIR) laser light is used. In the photoacoustic phenomenon, 26 electromagnetic energy in the form of light is absorbed and subsequently an acoustic wave is emitted. Using a wideband ultrasound detector the acoustic waves can be detected and spatially resolved to provide an image of the optical absorption properties of the internal tissue structure. [23][24][25] Gold nanoparticles have been used as contrast agents in photoacoustic imaging because of their unique optical absorption properties. 8,10,[27][28][29][30][31] Using three-dimensional (3D) tissue models, we previously demonstrated that highly selective detection of cancer could be achieved using molecular targeted gold nanoparticles and combined photoacoustic and ultrasound imaging. 8,32 In particular, the contrast in the photoacoustic images was attributed to the epidermal growth factor receptor (EGFR) 33,34 leading to plasmon resonance coupling between adjacent gold particles and a red-shift in their absorbance spectra 6,8,9,14 while the nontargeted or isolated gold nanoparticles have absorbance peak at around 520 nm. 8,35,36 In this paper, we demonstrate the efficacy of multiwavelength photoacoustic imagin...

To detect macrophages in atherosclerotic plaques, plasmonic gold nanoparticles are introduced as a contrast agent for intravascular photoacoustic imaging. The phantom and ex vivo tissue studies show that the individual spherical nanoparticles, resonant at 530 nm wavelength, produce a weak photoacoustic signal at 680 nm wavelength while photoacoustic signal from nanoparticles internalized by macrophages is very strong due to the plasmon resonance coupling effect. These results suggest that intravascular photoacoustic imaging can assess the macrophage-mediated aggregation of nanoparticles and therefore identify the presence and the location of nanoparticles associated with macrophage-rich atherosclerotic plaques.

Intravascular photoacoustic (IVPA) imaging can characterize atherosclerotic plaque composition on the basis of the optical absorption contrast between different tissue types. Given the high optical absorption of lipid at 1720 nm wavelength, an atherosclerotic rabbit aorta was imaged at this wavelength ex vivo using an integrated intravascular ultrasound (IVUS) and IVPA imaging catheter in the presence of luminal blood. Strong optical absorption of lipid combined with low background signal from other tissues provides a high-contrast, depth-resolved IVPA image of lipid. The ability to image lipid at a single wavelength without removing luminal blood suggests that in vivo detection of lipid in atherosclerotic plaques using combined IVUS/IVPA imaging is possible.

Intravascular photoacoustic (IVPA) imaging is a catheter-based, minimally invasive, imaging modality capable of providing high-resolution optical absorption map of the arterial wall. Integrated with intravascular ultrasound (IVUS) imaging, combined IVPA and IVUS imaging can be used to detect and characterize atherosclerotic plaques building up in the inner lining of an artery. In this paper, we present and discuss various representative applications of combined IVPA/IVUS imaging of atherosclerosis, including assessment of the composition of atherosclerotic plaques, imaging of macrophages within the plaques, and molecular imaging of biomarkers associated with formation and development of plaques. In addition, imaging of coronary artery stents using IVPA and IVUS imaging is demonstrated. Furthermore, the design of an integrated IVUS/IVPA imaging catheter needed for in vivo clinical applications is discussed.

Atherosclerosis is characterized by formation and development of the plaques in the inner layer of the vessel wall. To detect and characterize atherosclerotic plaques, we previously introduced the combined intravascular ultrasound ͑IVUS͒ and intravascular photoacoustic ͑IVPA͒ imaging capable of assessing plaque morphology and composition. The utility of IVUS/IVPA imaging has been demonstrated by imaging tissue-mimicking phantoms and ex vivo arterial samples using laboratory prototype of the imaging system. However, the clinical realization of a IVUS/IVPA imaging requires an integrated intravascular imaging catheter. In this paper, two designs of IVUS/IVPA imaging catheters-side fire fiber-based and mirror-based catheters-are reported. A commercially available IVUS imaging catheter was utilized for both pulse-echo ultrasound imaging and detection of photoacoustic transients. Laser pulses were delivered by custom-designed fiber-based optical systems. The optical fiber and IVUS imaging catheter were combined into a single device. Both designs were tested and compared using point targets and tissue-mimicking phantoms. The results indicate applicability of the proposed catheters for clinical use.