Search

We have engineered hybrid nanostructures derived from erythrocytes, which can be doped with various near infrared (NIR) organic chromophores, including the FDA-approved indocyanine green (ICG). We refer to these vesicles as NIR erythrocyte-mimicking transducers (NETs), as they are capable of generating heat, reactive oxygen species (ROS) or emit fluorescence light. We present preliminary results that demonstrate the effectiveness of NETs for fluorescence imaging and photodynamic therapeutic destruction of breast cancer cells, upon photo-excitation using NIR light. These hybrid nanostructures present a promising platform with theranostic capability for future biomedical clinical applications.

A quantitative comparison has been performed between two commercial near-infrared (NIR) vein-viewing systems which are designed to supplement the clinician’s traditional skills in locating veins by means of visualization and palpation. The AccuVein AV300 and Novarix IV-eye real-time imaging systems employ very different imaging geometries; the former generates an image from reflected NIR light produced by a beam scanned across the surface, while the latter illuminates the viewed region at four points on the periphery and records the resulting distribution of diffusely transmitted light. The comparison involved measuring the contrast produced by absorbing rods (simulated blood vessels) in a cylindrical phantom with tissue-like optical properties, and the contrast of superficial blood vessels in the arms of healthy volunteers. The locations and sizes of the blood vessels were independently verified using a clinical ultrasound imaging system. The phantom measurements suggested that the AV300 displays the most superficial vessels with greater contrast, but the IV-eye is able to detect vessels when they are at a depth up to 2 mm greater than the limit observed for the AV300. The results for thirty healthy volunteers also indicated that the AV300 typically displays vessels with higher overall contrast, but the effectiveness of the IV-eye at visualizing deeper vessels was even more pronounced, with a maximum depth several millimeters greater than that achieved by the AV300, and more than ten times as many vessels observed at depths below 4 mm.

Background: Prior research indicates the epidermal pigment layer of human skin (Melanin) has a significant absorption coefficient in the near infra-red (NIR) region; hence attenuation of light in vivo is a potential confounder for NIR spectroscopy (NIRS). A NIRS method developed for transcutaneous evaluation of bladder function is being investigated as a means of improving the burden of bladder disease in sub-Saharan Africa. This required development of a simple wireless NIRS device suitable for use as a screening tool in patients with pigmented skin where the NIR light emitted would penetrate through the epidermal pigment layer and return in sufficient quantity to provide effective monitoring. Methods: Two healthy subjects, one with pigmented skin and one with fair skin, were monitored as they voided spontaneously using the prototype transcutaneous NIRS device positioned over the bladder. The device was a self-contained wireless unit with light emitting diodes (wavelengths 760 and 850 nanometres) and interoptode distance of 4cm. The raw optical data were transmitted to a laptop where graphs of chromophore change were generated with proprietary software and compared between the subjects and with prior data from asymptomatic subjects. Results: Serial monitoring was successful in both subjects. Voiding volumes varied between 350 and 380 cc. In each subject the patterns of chromophore change, trend and magnitude of change were similar and matched the physiologic increase in total and oxygenated hemoglobin recognized to occur in normal bladder contraction during voiding. Conclusions: Skin pigmentation does not compromise the ability of transcutaneous NIRS to interrogate physiologic change in the bladder during bladder contraction in healthy subjects.

Paget’s disease of bone affects about 1 to 3 percent of people over 40 years of age in the United States. The disease is characterized by an increase in the rate of bone remodeling due to excessive osteoclast activity; therefore patients with Paget’s disease can develop severe bone deformities. Pagetoid bones are large, fragile and prone to fractures. A hallmark of Paget’s disease of bone is a marked increase in vascularization in bones. The fingerprint determinants of vascularization are deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2), which are the key chromophores in the NIR “tissue optical window” from 700nm to 1200nm. We have designed a Bone Optical Analyzer which utilizes optical spectroscopy imaging to non-invasively measure the changes of Hb and HbO2, thus enabling early diagnosis and monitoring of disease progression in these patients. Using inverse imaging algorithms, based on the diffusion equation, 2D and 3D maps of the bone’s internal structure can be reconstructed. The use of NIR light will allow for repeated studies on patients with Paget’s disease quickly, safely, inexpensively and without the risks associated with standard procedures. The model will be tested on bone tissue phantoms which mimic the scattering properties of human bone. This work will be the foundation for the future use of this device in vivo.

Nanoshells are a new class of optically tunable nanoparticles composed of a dielectric core (silica) coated with an ultrathin metallic layer (gold). Since nanoshells are roughly one million times more efficient at converting NIR light into heat than conventional dyes when exposed to NIR light, they can generate sufficient heat to induce cell death. Macrophages are frequently found in and around glioblastomas in both experimental animals and patient biopsies. Inflammatory cells loaded with nanoparticles could therefore be used to target tumors.

The anti-EGFR antibody, cetuximab, was labeled with IRDye 800CW fluorescent dye and conjugated to gold nanorods (GNR). GNR with aspect ratio of ~ 4 and plasmon resonance peak at ~785 nm were fabricated for use in these experiments. The IRDye:cetuximab:nanorod conjugate treatment with NIR light selectively heated the GNR and was sufficient to treat cancers. Excitation induced fluorescence of the IRDye 800CW enabling real-time imaging. We characterized and optimized the parameters for the conjugation of the GNR to cetuximab to facilitate active targeting of the nanorods to the site of the tumor. This combination of selective targeting, imaging, and photothermal treating of malignant cells is a viable approach for a variety of squamous cell carcinomas.

NIR light scattering from ex vivo porcine cardiac tissue was investigated to understand how imaging or point measurement approaches may assist development of methods for tissue depth assessment. Our results indicate an increase of average image intensity as thickness increases up to approximately 2 mm. In a dual fiber spectroscopy configuration, sensitivity up to approximately 3 mm with an increase to 6 mm when spectral ratio between selected wavelengths was obtained. Preliminary Monte Carlo results provided reasonable fit to the experimental data.

Though sinusitis is a significant health problem, it remains a challenging diagnosis for many physicians mainly because of its vague, non-specific symptomology. As such, physicians must often rely on x-rays and CT, which are not only costly but also expose the patient to ionizing radiation. As an alternative to these methods of diagnosis, our laboratory constructed a near infrared (NIR) transillumination system to image the paranasal maxillary sinuses. In contrast to the more conventional form of transillumination, which uses visible light, NIR transillumination uses light with a longer wavelength which is less attenuated by soft tissues, allowing increased signal intensity and tissue penetration. Our NIR transillumination system is low-cost, consisting of a light source containing two series of light emitting diodes, which give off light at wavelengths of 810 nm and 850 nm, and a charge coupled device (CCD) camera sensitive to NIR light. The light source is simply placed in the patient’s mouth and the resultant image created by the transmittance of NIR light is captured with the CCD camera via notebook PC. Using this NIR transillumination system, we imaged the paranasal maxillary sinuses of both healthy patients (n=5) and patients with sinus disease (n=12) and compared the resultant findings with conventional CT scans. We found that air and fluid/tissue-filled spaces can be reasonably distinguished by their differing NIR opacities. Based on these findings, we believe NIR transillumination of the paranasal sinuses may provide a simple, safe, and cost effective modality in the diagnosis and management of sinus disease.

Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

pH electrodes have been used during open heart surgery to ensure adequate delivery of blood and oxygen to the myocardium during the surgical procedure. The electrodes are cumbersome and suffer from motion artifacts. Near infrared spectroscopy was evaluated as a noninvasive method of measuring myocardial pH during regional ischemia in seven beating dog hearts. Two pH microelectrodes were implanted in the distribution area of the left anterior descending (LAD) coronary artery. The LAD was occluded to stop the myocardial blood flow and to initialize regional ischemia. Ischemia was maintained for 20 minutes before the LAD was released to resume blood flow. A fiber-optic probe was used to collect the reflected NIR light over the spectral region of 575 nm to 1100 nm from the heart muscle. Partial least-squares multivariate calibration technique was applied to relate the myocardial pH changes to the NIR spectral changes in the region of 700 to 1100 nm. Calibration models based on data collected on each individual dog heart had an average of 7 factors with an R2 of 0.84. The standard error of prediction (SEP) averaged 0.09 pH units for a mean pH change of 0.73 pH units, adequate for monitoring pH changes during cardiac surgery.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.