Widefield and high-resolution reflectance imaging of gold and silver nanospheres.

Metallic nanoparticles have unique optical properties that can be exploited for molecular imaging in tissue. Image contrast depends on the nature of the particles, properties of the target tissue, and the imaging system. Maximizing image contrast for a particular application requires an understanding of the interplay of these factors. We demonstrate an approach that integrates the use of reflectance spectroscopy and imaging of particles in water and various tissue phantoms to evaluate the expected image contrast. We illustrate the application of this methodology for gold and silver nanospheres targeted against a biomarker expressed in epithelial tissue; predictions of contrast properties using diffuse reflectance spectroscopy were compared with widefield and high-resolution images of labeled tissue phantoms. The results show that the predicted image contrast based on spectroscopy agrees well with widefield and high-resolution imaging, and illustrate that gold and silver nanospheres at subnanomolar concentration are sufficient to produce contrast in both imaging modes. However, the effective contrast achieved with a particular type of nanoparticle can differ dramatically depending on the imaging modality. The ability to predict and optimize image contrast properties is a crucial step in the effective use of these nanomaterials for biomedical imaging applications.

Wearable near-infrared optical probe for continuous monitoring during breast cancer neoadjuvant chemotherapy infusions.

We present a new continuous-wave wearable diffuse optical probe aimed at investigating the hemodynamic response of locally advanced breast cancer patients during neoadjuvant chemotherapy infusions. The system consists of a flexible printed circuit board that supports an array of six dual wavelength surface-mount LED and photodiode pairs. The probe is encased in a soft silicone housing that conforms to natural breast shape. Probe performance was evaluated using tissue-simulating phantoms and in vivo normal volunteer measurements. High SNR (71 dB), low source-detector crosstalk ( ? 60 ?? dB ), high measurement precision (0.17%), and good thermal stability (0.22% V rms / ° C ) were achieved in phantom studies. A cuff occlusion experiment was performed on the forearm of a healthy volunteer to demonstrate the ability to track rapid hemodynamic changes. Proof-of-principle normal volunteer measurements were taken to demonstrate the ability to collect continuous in vivo breast measurements. This wearable probe is a first of its kind tool to explore prognostic hemodynamic changes during chemotherapy in breast cancer patients.

Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging.

We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a crosscorrelation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

Metal-based nanorods as molecule-specific contrast agents for reflectance imaging in 3D tissues.

Anisotropic metal-based nanomaterials have been proposed as potential contrast agents due to their strong surface plasmon resonance. We evaluated the contrast properties of gold, silver, and gold-silver hybrid nanorods for molecular imaging applications in three-dimensional biological samples. We used diffuse reflectance spectroscopy to predict the contrast properties of different types of nanorods embedded in biological model systems of increasing complexity. The predicted contrast properties were then validated using wide-field and high-resolution imaging. Results demonstrated that silver nanorods yield images with higher positive-contrast than gold nanorods; however, it is more difficult to synthesize silver nanorods which are homogeneous in shape and size. Gold-silver hybrid nanorods combine the homogeneous synthesis of gold nanorods with the higher scattering properties of silver nanorods. The spectroscopic and imaging results demonstrated that the image contrast properties that can be achieved with anisotropic nanomaterials depend strongly on the material composition, mode of imaging, presence of targeting molecules, and the biological environment. We also found that gold, silver, and gold-silver hybrid nanorods are stable and biocompatible sources of positive and absorptive contrast for use in reflectance molecular imaging and are promising for future clinical translation.