Raiyan T. Zaman

In Vivo Detection of Gold Nanoshells in Tumors Using Diffuse Optical Spectroscopy

This study demonstrates the use of diffuse optical spectroscopy (DOS) for the noninvasive measurement of gold nanoshell concentrations in tumors of live mice. We measured the diffuse optical spectra (500-800 nm) using an optical fiber probe placed in contact with the tissue surface. We performed in vitro studies on tissue phantoms illustrating an accurate measurement of gold-silica nanoshell concentration within 12.6% of the known concentration. In vivo studies were performed on a mouse xenograft tumor model. DOS spectra were measured at preinjection, immediately postinjection, 1 and 24 h postinjection times, and the nanoshell concentrations were verified using neutron activation analysis.

Fiber-Optic System for Dual-Modality Imaging of Glucose Probes 18F-FDG and 6-NBDG in Atherosclerotic Plaques

Background Atherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD)–the leading cause of death in the United States. Thus, the ultimate goal of this research is to advance our understanding of human CAD by improving the characterization of metabolically active vulnerable plaques within the coronary arteries using a novel catheter-based imaging system. The aims of this study include (1) developing a novel fiber-optic imaging system with a scintillator to detect both 18F and fluorescent glucose probes, and (2) validating the system on ex vivo murine plaques. Methods A novel design implements a flexible fiber-optic catheter consisting of both a radio-luminescence and a fluorescence imaging system to detect radionuclide 18F-fluorodeoxyglucose (18F-FDG) and the fluorescent analog 6-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-6-Deoxyglucose (6-NBDG), respectively. Murine macrophage-rich atherosclerotic carotid plaques were imaged ex vivo after intravenous delivery of 18F-FDG or 6-NBDG. Confirmatory optical imaging by IVIS-200 and autoradiography were also performed. Results Our fiber-optic imaging system successfully visualized both 18F-FDG and 6-NBDG probes in atherosclerotic plaques. For 18F-FDG, the ligated left carotid arteries (LCs) exhibited 4.9-fold higher radioluminescence signal intensity compared to the non-ligated right carotid arteries (RCs) (2.6×104±1.4×103 vs. 5.4×103±1.3×103 A.U., P = 0.008). Similarly, for 6-NBDG, the ligated LCs emitted 4.3-fold brighter fluorescent signals than the control RCs (1.6×102±2.7×101 vs. 3.8×101±5.9 A.U., P = 0.002). The higher uptake of both 18F-FDG and 6-NBDG in ligated LCs were confirmed with the IVIS-200 system. Autoradiography further verified the higher uptake of 18F-FDG by the LCs. Conclusions This novel fiber-optic imaging system was sensitive to both radionuclide and fluorescent glucose probes taken up by murine atherosclerotic plaques. In addition, 6-NBDG is a promising novel fluorescent probe for detecting macrophage-rich atherosclerotic plaques.

Changes in morphology and optical properties of sclera and choroidal layers due to hyperosmotic agent

Light scattering in the normally white sclera prevents diagnostic imaging or delivery of a focused laser beam to a target in the underlying choroid layer. In this study, we examine optical clearing of the sclera and changes in blood flow resulting from the application of glycerol to the sclera of rabbits. Recovery dynamics are monitored after the application of saline. The speed of clearing for injection delivery is compared to the direct application of glycerol through an incision in the conjunctiva. Although, the same volume of glycerol was applied, the sclera cleared much faster (5 to 10 s) with the topical application of glycerol compared to the injection method (3 min). In addition, the direct topical application of glycerol spreads over a larger area in the sclera than the latter method. A diffuse optical spectroscopy system provided spectral analysis of the remitted light every two minutes during clearing and rehydration. Comparison of measurements to those obtained from phantoms with various absorption and scattering properties provided estimates of the absorption coefficient and reduced scattering coefficient of rabbit eye tissue.

Variation of fluorescence in tissue with temperature.

Previous studies demonstrated a decrease in fluorescence intensity as tissue temperature increased. In vitro samples were increased from room temperature and in vivo canine liver from body temperature. This study investigated variations in fluorescence intensity with temperatures starting at 14°C and compared in vivo and in vitro results for consistency.

Perfusion in Hamster Skin Treated With Glycerol

The objective of this article is to quantify the effect of hyper‐osmotic agent (glycerol) on blood velocity in hamster skin blood vessels measured with a dynamic imaging technique, laser speckle contrast imaging (LSCI).

Micro-patterned drug delivery device for light-activated drug release.

The primary goal of this study was the fabrication, long‐term stability, and measured release of a marker dye from a micro‐patterned drug delivery device using (i) mechanical puncture and (ii) photodisruption with an ophthalmic Nd:YAG laser.

Scintillating Balloon-Enabled Fiber-Optic System for Radionuclide Imaging of Atherosclerotic Plaques

Atherosclerosis underlies coronary artery disease, the leading cause of death in the United States and worldwide. Detection of coronary plaque inflammation remains challenging. In this study, we developed a scintillating balloon-enabled fiber-optic radionuclide imaging (SBRI) system to improve the sensitivity and resolution of plaque imaging using 18F-FDG, a marker of vascular inflammation, and tested it in a murine model. Methods: The fiber-optic system uses a Complementary Metal-Oxide Silicon (CMOS) camera with a distal ferrule terminated with a wide-angle lens. The novelty of this system is a scintillating balloon in the front of the wide-angle lens to image light from the decay of 18F-FDG emission signal. To identify the optimal scintillating materials with respect to resolution, we calculated the modulation transfer function of yttrium–aluminum–garnet doped with cerium, anthracene, and calcium fluoride doped with europium (CaF2:Eu) phosphors using an edge pattern and a thin-line optical phantom. The scintillating balloon was then fabricated from 10 mL of silicone RTV catalyst mixed with 1 mL of base and 50 mg of CaF2:Eu per mL. The addition of a lutetium oxyorthosilicate scintillating crystal (500 μm thick) to the balloon was also investigated. The SBRI system was tested in a murine atherosclerosis model: carotid-ligated mice (n = 5) were injected with 18F-FDG, followed by ex vivo imaging of the macrophage-rich carotid plaques and nonligated controls. Confirmatory imaging of carotid plaques and controls was also performed by an external optical imaging system and autoradiography. Results: Analyses of the different phosphors showed that CaF2:Eu enabled the best resolution of 1.2 μm. The SBRI system detected almost a 4-fold-higher radioluminescence signal from the ligated left carotid artery than the nonligated right carotid: 1.63 × 102 ± 4.01 × 101 vs. 4.21 × 101 ± 2.09 × 100 (photon counts), P = 0.006. We found no significant benefit to adding a scintillating crystal to the balloon: 1.65 × 102 ± 4.07 × 101 vs. 4.44 × 101 ± 2.17 × 100 (photon counts), P = 0.005. Both external optical imaging and autoradiography confirmed the high signal from the 18F-FDG in carotid plaques versus controls. Conclusion: This SBRI system provides high-resolution and sensitive detection of 18F-FDG uptake by murine atherosclerotic plaques.

Porcine skin ED50 damage thresholds for 1214 nm laser irradiation

A series of experiments were conducted in vivo on porcine skin to determine the ED50 damage thresholds for 1214 nm continuous wave laser irradiation. These results provide new information for refinement of Maximum Permissible Exposure (MPE). The study employed exposure durations of 1 sec, 3 sec, and 10 seconds with nominal spot diameters of 6 mm, 8 mm and 10 mm and as a function of laser power. The effect of each irradiation was evaluated acutely, one hour after exposure, and 24 hours post exposure. Probit analysis was conducted to estimate the dose for 50% probability of laser-induced damage (ED50); Damage was defined as persistent redness at the site of irradiation for the pig skin after 24 hours. The results indicated that Maximum Permissible Exposure (MPE) limits should be lowered for the laser beam diameters larger than 6 mm.

Measuring Gold Nanoparticle Concentrations In Tissue Using Diffuse Optical Spectroscopy

We developed diffuse optical spectroscopy (DOS) to non-invasively measure gold nanoparticle concentrations within tissue. We demonstrate DOSs accuracy to quantify nanoparticle concentrations using tissue phantoms and an in vivo murine model.

Enhancement of light in tissue using hyper-osmotic agents

Optical changes in skin blood flow due to the presence of glycerol were measured from a two-dimensional map of blood flow in skin blood vessels with a dynamic imaging technique using laser speckle. In this study a dorsal skin-flap window was implanted on the hamster skin with and without a hyper-osmotic agent i.e. glycerol. The hyper-osmotic drug was delivered to the skin through the open dermal end of the window model. A two-dimensional map of blood flow in skin blood vessels were obtained with very high spatial and temporal resolution by imaging the speckle pattern with a CCD camera. Preliminary studies demonstrated that hyper-osmotic agents such as glycerol not only make tissue temporarily translucent, but also reduce blood flow. The blood perfusion was measured every 3 minutes up to 36-60 minutes after diffusion of anhydrous glycerol. Small capillaries blood flow reduced significantly within 3-9 minutes. Perfusion rate in lager blood vessels i.e. all arteries and some veins decreased (speckle contrasts increased from 0.0115 to 0.384) over time. However, the blood flow in some veins reduced significantly in 36 minutes. After 24 hours the blood perfusion further reduced in capillaries. However, the blood flow increased in larger blood vessels in 24 hours compared to an hour after application of glycerol. For further investigation the speckle contrast measurement were verified with color Doppler optical coherence tomography.