No abstract

Presently, clinicians routinely apply ultrasound endoscopy in a variety of interventional procedures which provide treatment solutions for diseased organs. Ultrasound endoscopy not only produces high resolution images, it is also safe for clinical use and broadly applicable. However, for soft tissue imaging, its mechanical wave-based image contrast fundamentally limits its ability to provide physiologically-specific functional information. By contrast, photoacoustic endoscopy possesses a unique combination of functional optical contrast and high spatial resolution at clinically-relevant depths, ideal for soft tissue imaging. With these attributes, photoacoustic endoscopy can overcome the current limitations of ultrasound endoscopy. Moreover, the benefits of photoacoustic imaging do not come at the expense of existing ultrasound functions; photoacoustic endoscopy systems are inherently compatible with ultrasound imaging, enabling multi-modality imaging with complementary contrast. Here, we present simultaneous photoacoustic and ultrasonic dual-mode endoscopy and demonstrate its ability to image internal organs in vivo, illustrating its potential clinical application.

Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bio-conjugated with [Nle 4 ,D-Phe 7 ]-α-melanocytestimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bio-conjugated AuNCs enhanced contrast ~300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS). KeywordsPhotoacoustic tomography; gold nanocages; melanoma; bio-conjugation; molecular imagingThe 10-year survival rate of early-stage cutaneous melanoma patients is very high (~99%), but the rate drops to 40% after nodal metastases. 1,2 Thick melanomas (>4 mm) are typically associated with a high risk of nodal and distant metastases. Highly sensitive molecular imaging techniques including positron emission tomography (PET) and optical imaging have been developed for detecting early-stage melanomas. [3][4][5] However, PET requires on the use of radio-labeling materials, which can cause potential hazards to patients. Moreover, it suffers from low spatial resolution and high cost due to the need of additional anatomical information from magnetic resonance imaging (MRI) and/or X-ray computed tomography (CT). Since optical imaging uses nonionizing radiation and is cost-effective, it has received much attention in molecular imaging. 6 However, conventional optical imaging tools are often limited by either shallow penetration depth (<1 mm) 7 Besides early detection, accurate delineation of the margins of a melanoma can significantly improve surgical removal of the primary tumor. High-frequency ultrasound has been applied preoperatively for this purpose, 9 but it cannot effectively resolve the margins of a melanoma and does not infiltrate cells. Additionally, accurate staging (describing cancer metastasis, typically with numbers I to IV) of patients after nodal metastases is important for treatment planning. 10 Again, the current technique based on sentinel lymph node biopsy is ionizing and intraoperative, and thus poses postoperative complications. These limitations of the current techniques suggest a strong need for a single, highly sensitive, safe, economical, noninvasive, and high-resolution imaging technique with nonradioactive contrast agents in early diagnosis of malignant melanomas, image-guided resection of melanoma boundaries, and accurate staging of melanoma patients.PAT is a hybrid biomedical imaging modality that offers both strong optical absorption contrast...

Hydrodynamic pattern formation (PF) and dewetting resulting from pulsed laser induced melting of nanoscopic metal films have been used to create spatially ordered metal nanoparticle arrays with monomodal size distribution on SiO 2 /Si substrates. PF was investigated for film thickness h ≤ 7 nm < laser absorption depth ∼ 11 nm and different sets of laser parameters, including energy density E and the irradiation time, as measured by the number of pulses n. PF was only observed to occur for E ≥ E m , where E m denotes the h-dependent threshold energy required to melt the film. Even at such small length scales, theoretical predictions for E m obtained from a continuumlevel lumped parameter heat transfer model for the film temperature, coupled with the 1-D transient heat equation for the substrate phase, were consistent with experimental observations provided that the thickness dependence of the reflectivity of the metal-substrate bilayer was incorporated into the analysis. The model also predicted that perturbations in h would result in intrinsic thermal gradients ∂T /∂h whose magnitude and sign depend on h, with ∂T /∂h > 0 for h < h c and ∂T /∂h < 0 for h > h c ≈ 9 nm. For the thickness range investigated here, the resulting thermocapillary effect was minimal since the thermal diffusion time τ H ≤ the pulse time. Consequently, the spacing between the nanoparticles and the particle diameter were found to increase as h 2 and h 5/3 respectively, which is consistent with the predictions of the thin film hydrodynamic (TFH) dewetting theory. PF was characterized by the appearance of discrete holes followed by bicontinuous or cellular patterns which finally consolidated into nanoparticles via capillary flow rather than via Rayleigh-like instabilities reported for low temperature dewetting of viscous liquids. This difference is attributed to the high capillary velocities of the liquid metal arising from its relatively large interfacial tension and low viscosity as well as the smaller length scales of the liquid bridges in the experiments. The predicted liquid phase lifetime τ L was between 2 − 15 ns, which is much smaller than the dewetting time τ D ≥ 25 ns as predicted by the linear TFH theory. Therefore, dewetting required the application of multiple pulses. During the early stages of dewetting, the ripening rate, as measured by the rate of change of characteristic ordering length with respect to n, increased linearly with E due to the linear increase in τ L with increasing E as predicted by the thermal model. The final nanoparticle spacing was robust, independent of E and n, and only dependent on h due to the relatively weak temperature dependence of the thermophysical properties of the metal (Co). These results suggest