Yury Budansky

Deep optical imaging of tissue using the second and third near-infrared spectral windows.

Abstract. Light at wavelengths in the near-infrared (NIR) region allows for deep penetration and minimal absorption through high scattering tissue media. NIR light has been conventionally used through the first NIR optical tissue window with wavelengths from 650 to 950 nm. Longer NIR wavelengths had been overlooked due to major water absorption peaks and a lack of NIR-CCD detectors. The second NIR spectral window from 1100 to 1350 nm and a new spectral window from 1600 to 1870 nm, known as the third NIR optical window, were investigated. Optical attenuation measurements from thin tissue slices of normal and malignant breast and prostate tissues, pig brain, and chicken tissue were obtained in the spectral range from 400 to 2500 nm. Optical images of chicken tissue overlying three black wires were also obtained using the second and third spectral windows. Due to a reduction in scattering and minimal absorption, longer attenuation lengths and clearer optical images could be seen in the second and third NIR optical windows compared to the conventional first NIR optical window. A possible fourth optical window centered at 2200 nm was noted.

Near infrared photonic finger imager for prostate cancer screening.

A portable rectal near infrared (NIR) scanning polarization imaging unit with an optical fiber-based rectal probe, designated as a Photonic Finger (PF), was designed, developed, built and tested. PF was used to image and locate the three dimensional (3D) positions of abnormal prostate tissue embedded inside normal prostate tissue. An inverse image reconstruction algorithm, namely Optical Tomography using Independent Component Analysis (OPTICA) was developed to unmix the signal from targets (cancerous tissue) embedded in a turbid media (normal tissue) in the backscattering imaging geometry. The Photonic Finger combined with OPTICA was ex vivo tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded inside large pieces of normal tissue. This new developed instrument, Photonic Finger, may provide an alternative imaging technique, which is accurate, of high spatial resolution and non-or-less invasive for prostate cancers screening.

Optical spectral fingerprints of tissues from patients with different breast cancer histologies using a novel fluorescence spectroscopic device.

The fluorescence of paired human breast malignant and normal tissue samples was investigated using a novel fluorescence spectroscopic (S3-LED) ratiometer unit with no moving parts. This device can measure the emission spectra of key native organic biomolecules such as tryptophan, tyrosine, collagen and elastin within tissues by using LED (light emitting diode) excitation sources coupled to an optical fiber. With this device, the spectral profiles of 11 paired breast cancerous and normal samples from 11 patients with breast carcinoma were obtained. In each of the 11 cases, marked increases in the tryptophan levels were found in the breast carcinoma samples when compared to the normal breast tissues. In the breast cancer samples, there were also consistently higher ratios of the 340 to 440 nm and the 340 to 460 nm intensity peaks after 280 nm excitation, likely representing an increased tryptophan to NADH ratio in the breast cancer samples. This difference was seen in the spectral profiles of the breast cancer patients regardless of whether they were HER2 positive or negative or hormone receptor positive or negative, and was found regardless of meno-pausal status, histology, stage, or tumor grade.

Aorta and Skin Tissues Welded by Near-Infrared Cr4+:YAG Laser

OBJECTIVE The aim of our study was to explore the wavelength dependence of welding efficacy. Ex vivo samples of human and porcine aorta and skin tissues were investigated using a tunable Cr(4+):yttrium aluminum garnet (YAG) laser. BACKGROUND DATA Tissue welding is possible using laser light in the NIR spectral range. Collagen bonding in the tissue induced by thermal, photothermal, and photochemical reactions-or a combination of all of these-is thought to be responsible for tissue welding. Laser tissue welding (LTW) has gained success in the laboratory using animal models. Transition from laboratory to clinical application requires the optimization of welding parameters. MATERIALS AND METHODS A near-infrared (NIR) Cr(4+):YAG laser was used to weld ex vivo samples of human and porcine aorta and skin at wavelengths from 1430 to 1470 nm. Welding efficacy was monitored by measuring the tensile strength of the welded tissue and the extent of collateral tissue damage. Tensile strengths were measured using a digital force gauge. Changes in tissue morphology were evaluated using optical and scanning electron microscope (SEM). Fluorescence imaging of the welded areas was also used to evaluate molecular changes following tissue welding. RESULTS Full-thickness tissue bonding was observed with porcine aorta samples. No collateral damage of the aorta samples was observed. Tissue denaturation was observed with human aorta, human skin, and porcine skin samples. The optimum tensile strength for porcine and human aorta was 1.33 +/- 0.15 and 1.13 +/- 0.27 kg/cm2, respectively, at 1460 nm, while that for porcine and human skin was 0.94 +/- 0.15 and 1.05 +/- 0.19 kg/cm2, respectively, achieved at 1455 nm. The weld strength as a function of wavelength demonstrated a correlation with the absorption spectrum of water. Fluorescence imaging of welded aorta and skin demonstrated no significant changes in collagen and elastin emission at the weld site. CONCLUSION The observation that welding strength as a function of wavelength follows the absorption bands of water suggests that absorption of light by water plays a significant role in laser tissue welding.

Differences in fluorescence profiles from breast cancer tissues due to changes in relative tryptophan content via energy transfer: tryptophan content correlates with histologic grade and tumor size but not with lymph node metastases

Abstract. The correlation between histologic grade, an increasingly important measure of prognosis for patients with breast cancer, and tryptophan levels from tissues of 15 breast carcinoma patients was investigated. Changes in the relative content of key native organic biomolecule tryptophan were seen from the fluorescence spectra of cancerous and paired normal tissues with excitation wavelengths of 280 and 300 nm. Due to a large spectral overlap and matching excitation–emission spectra, fluorescence resonance energy transfer from tryptophan-donor to reduced nicotinamide adenine dinucleotides-acceptor was noted. We used the ratios of fluorescence intensities at their spectral emission peaks, or spectral fingerprint peaks, at 340, 440, and 460 nm. Higher ratios correlated strongly with high histologic grade, while lower-grade tumors had low ratios. Large tumor size also correlated with high ratios, while the number of lymph node metastases, a major factor in staging, was not correlated with tryptophan levels. High histologic grade correlates strongly with increased content of tryptophan in breast cancer tissues and suggests that measurement of tryptophan content may be useful as a part of the evaluation of these patients.

Third therapeutic spectral window for deep tissue imaging

Light at wavelengths in the visible and near-infrared (NIR) regions (650 nm – 1,350 nm) is used in numerous medical applications. The NIR region between 650 nm and 950 nm, known as the first optical window, allows for deeper depth penetration in tissue than in the visible region due to a reduction in absorption. There also exists a second NIR optical window with wavelengths from 1,100 nm to 1,350 nm. Longer wavelengths above 1,350 nm were ignored due to major water absorption and lack of 2D photodetectors. In this study, a new therapeutic spectral window with wavelengths between 1,600 nm and 1,870 nm is reported. This third optical window can be used for imaging more deeply into tissue due to a reduction in scattering. In this paper, light attenuation from 400 nm to 2,000 nm, including all three optical windows, was measured. 200 micron slices of normal and benign prostate and breast tissues were studied. The total attenuation lengths (lt) of light were obtained. The attenuation length of malignant and normal tissue in the third optical window was larger than in the first and second therapeutic windows. Optical images of chicken tissue over three black wires were also obtained using the third optical window.

A novel approach to Paget's disease diagnosis and monitoring using near-infrared absorption spectroscopy

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.

Near-infrared supercontinuum laser beam source in the second and third near-infrared optical windows used to image more deeply through thick tissue as compared with images from a lamp source

With the use of longer near-infrared (NIR) wavelengths, image quality can be increased due to less scattering (described by the inverse wavelength power dependence 1/λ(n) where n ≥ 1 ) and minimal absorption from water molecules. Longer NIR windows, known as the second (1100 nm to 1350 nm) and third (1600 to 1870 nm) NIR windows are utilized to penetrate more deeply into tissue media and produce high-quality images. An NIR supercontinuum (SC) laser light source, with wavelengths in the second and third NIR optical windows to image tissue provides ballistic imaging of tissue. The SC ballistic beam can penetrate depths of up to 10 mm through tissue.

Deep tissue imaging of microfracture and non-displaced fracture of bone using the second and third near-infrared therapeutic windows

Near-infrared (NIR) light in the wavelengths of 700 nm to 2,000 nm has three NIR optical, or therapeutic, windows, which allow for deeper depth penetration in scattering tissue media. Microfractures secondary to repetitive stress, particularly in the lower extremities, are an important problem for military recruits and athletes. They also frequently occur in the elderly, or in patients taking bisphosphonates or denosumab. Microfractures can be early predictors of a major bone fracture. Using the second and third NIR therapeutic windows, we investigated the results from images of chicken bone and human tibial bone with microfractures and non-displaced fractures with and without overlying tissues of various thicknesses. Images of bone with microfractures and non-displaced fractures with tissue show scattering photons in the third NIR window with wavelengths between 1,650 nm and 1,870 nm are diminished and absorption is increased slightly from and second NIR windows. Results from images of fractured bones show the attenuation length of light through tissue in the third optical window to be larger than in the second therapeutic window. Use of these windows may aid in the detection of bone microfractures, and thus reduce the incidence of major bone fracture in susceptible groups.

Optical biopsy fiber-based fluorescence spectroscopy instrumentation

Native fluorescence spectroscopy of biomolecules has emerged as a new modality to the medical community in characterizing the various physiological conditions of tissues. In the past several years, many groups have been working to introduce the spectroscopic methods to diagnose cancer. Researchers have successfully used native fluorescence to distinguish cancerous from normal tissue samples in rat and human tissue. We have developed three generations of instruments, called the CD-scan, CD-ratiometer and CD-map, to allow the medical community to use optics for diagnosing tissue. Using ultraviolet excitation and emission spectral measurements on both normal and cancerous tissue of the breast, gynecology, colon, and aerodigestive tract can be separated. For example, from emission intensities at 340 nm to 440 nm (300 nm excitation), a statistically consistent difference between malignant tissue and normal or benign tissue is observed. In order to utilize optical biopsy techniques in a clinical setting, the CD-scan instrument was developed, which allows for rapid and reliable in-vitro and in-vivo florescence measurements of the aerodigestive tract with high accuracy. The instrumentation employs high sensitivity detection techniques which allows for lamp excitation, small diameter optical fiber probes; the higher spatial resolution afforded by the small diameter probes can increase the ability to detect smaller tumors. The fiber optic probes allow for usage in the aerodigestive tract, cervix and colon. Needle based fiber probes have been developed for in-vivo detection of breast cancer.