Rami Nachabe

Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600 nm

We demonstrate a method to estimate the concentrations of water and lipid in scattering media such as biological tissues with diffuse optical spectra acquired over the range of 900 to 1600 nm. Estimations were performed by fitting the spectra to a model of light propagation in scattering media derived from diffusion theory. To validate the method, spectra were acquired from tissue phantoms consisting of lipid and water emulsions and swine tissues ex vivo with a two-fiber probe.

Estimation of biological chromophores using diffuse optical spectroscopy: Benefit of extending the UV-VIS wavelength range to include 1000 to 1600 nm

With an optical fiber probe, we acquired spectra from swine tissue between 500 and 1600 nm by combining a silicon and an InGaAs spectrometer. The concentrations of the biological chromophores were estimated by fitting a mathematical model derived from diffusion theory. The advantage of our technique relative to those presented in previous studies is that we extended the commonly-used wavelength ranges of 500 and 1000 nm to include the range of 1000 to 1600 nm, where additional water and lipid absorption features exist. Hence, a more accurate estimation of these two chromophores is expected when spectra are fitted between 500 and 1600 nm than between 500 and 1000 nm. When extending the UV-VIS wavelength range, the estimated total amount of chromophores approached 100% of the total as present in the probed volume. The confidence levels of the water and lipid related parameters increases by a factor of four.

Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods

We report on the use of diffuse optical spectroscopy analysis of breast spectra acquired in the wavelength range from 500 to 1600 nm with a fiber optic probe. A total of 102 ex vivo samples of five different breast tissue types, namely adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ from 52 patients were measured. A model deriving from the diffusion theory was applied to the measured spectra in order to extract clinically relevant parameters such as blood, water, lipid, and collagen volume fractions, β-carotene concentration, average vessels radius, reduced scattering amplitude, Mie slope, and Mie-to-total scattering fraction. Based on a classification and regression tree algorithm applied to the derived parameters, a sensitivity-specificity of 98%-99%, 84%-95%, 81%-98%, 91%-95%, and 83%-99% were obtained for discrimination of adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in situ, respectively; and a multiple classes overall diagnostic performance of 94%. Sensitivity-specificity values obtained for discriminating malignant from nonmalignant tissue were compared to existing reported studies by applying the different classification methods that were used in each of these studies. Furthermore, in these reported studies, either lipid or β-carotene was considered as adipose tissue precursors. We estimate both chromophore concentrations and demonstrate that lipid is a better discriminator for adipose tissue than β-carotene.

Effect of bile absorption coefficients on the estimation of liver tissue optical properties and related implications in discriminating healthy and tumorous samples

We investigated differences between healthy tissue and metastatic tumor from ex vivo human partial liver resections using diffuse optical spectroscopy with a fiber optic probe. We extracted various physiological and morphological parameters from the spectra. During evaluation of the residual between the measurements and a fit model based on diffusion theory, we found that bile is an additional chromophore absorbing in the visible wavelength range that was missing in our model. Consistency of the residual with the absorption spectrum of bile was noticed. An accurate measurement of the absorption coefficient of bile from various human bile samples was performed and implemented into the fit model. Having the absorption coefficient of bile as a priori knowledge in the model showed a clear improvement in terms of reducing the fitting discrepancies. The addition of this chromophore yields significantly different estimates of the amount of blood. Furthermore, the estimated bile volume fraction and reduced scattering amplitude turned out to be two main relevant discriminators between normal and metastatic liver tissues.

Improved identification of peripheral lung tumors by using diffuse reflectance and fluorescence spectroscopy

INTRODUCTION A significant number of transthoracic diagnostic biopsy procedures for lung lesions show indeterminate results. Such failures are potentially due to inadequate recognition of vital tumor tissue. The objective of this study was to evaluate whether optical spectroscopy at the tip of a biopsy needle device can improve the accuracy of transthoracic lung biopsies. METHODS Ex vivo optical measurements were performed on lung tissue from 13 patients who underwent either lobectomy or segmental resection for primary non-small cell lung cancer or pulmonary metastases from various origins. From Diffuse Reflectance Spectroscopy (DRS) and Fluorescence Spectroscopy (FS) measurements, different parameters were derived such as tissue composition as well as physiological and metabolic characteristics. Subsequently, a classification and regression trees (CART) algorithm was used to classify the type of tissue based on the derived parameters. Histology analysis was used as gold standard to report sensitivity and specificity of the tissue classification based on the present optical method. RESULTS Collective analysis of all DRS measurements showed an overall discrimination between lung parenchyma and tumor tissue with a sensitivity and specificity of 98 and 86%, respectively. When the data were analyzed per individual patient, eliminating inter-patient variation, 100% sensitivity and specificity was achieved. Furthermore, based on FS parameters, necrotic and non-necrotic tumor tissue could be distinguished with 91% sensitivity and specificity. CONCLUSION This study demonstrates that DRS provides accurate diagnosis of malignant lung lesions, whereas FS enables identification of necrotic tissue. When both optical techniques are combined within a biopsy device, the diagnostic performance and the quality of transthoracic biopsies could significantly be enhanced.

Epidural needle with embedded optical fibers for spectroscopic differentiation of tissue: ex vivo feasibility study

Epidural injection is commonly used to provide intraoperative anesthesia, postoperative and obstetric analgesia, and to treat acute radicular pain. Identification of the epidural space is typically carried out using the loss of resistance (LOR) technique, but the usefulness of this technique is limited by false LOR and the inability to reliably detect intravascular or subarachnoid needle placement. In this study, we present a novel epidural needle that allows for the acquisition of optical reflectance spectra from tissue close to the beveled surface. This needle has optical fibers embedded in the cannula that deliver and receive light. With two spectrometers, light received from tissue is resolved across the wavelength range of 500 to 1600 nm. To determine the feasibility of optical tissue differentiation, spectra were acquired from porcine tissues during a post mortem laminectomy. The spectra were processed with an algorithm that derives estimates of the hemoglobin and lipid concentrations. The results of this study suggest that the optical epidural needle has the potential to improve the accuracy of epidural space identification.

Chromophore based analyses of steady-state diffuse reflectance spectroscopy: current status and perspectives for clinical adoption

Diffuse reflectance spectroscopy is a rapidly growing technology in the biophotonics community where it has shown promise in its ability to classify different tissues. In the steady-state domain a wide spectrum of clinical applications is supported with this technology ranging from diagnostic to guided interventions. Diffuse reflectance spectra provide a wealth of information about tissue composition; however, extracting biologically relevant information from the spectra in terms of chromophores may be more useful to gain acceptance into the clinical community. The chromophores that absorb light in the visible and near infrared wavelengths can provide information about tissue composition. The key characteristics of these chromophores and their relevance in different organs and clinical applications is the focus of this review, along with translating their use to the clinic.

Identification of the epidural space with optical spectroscopy: an in vivo swine study.

Background:Accurate identification of the epidural space is critical for safe and effective epidural anesthesia or treatment of acute lumbar radicular pain with epidural steroid injections. The loss-of-resistance technique is commonly used, but it is known to be unreliable. Even when it is performed in conjunction with two-dimensional fluoroscopic guidance, determining when the needle tip enters the epidural space can be challenging. In this swine study, we investigated whether the epidural space can be identified with optical spectroscopy, using a custom needle with optical fibers integrated into the cannula. Methods:Insertion of the needle tip into the epidural space was performed with midline and paramedian approaches in a swine. In each insertion, optical spectra were acquired at different insertion depths, and anatomical localization of the needle was determined by three-dimensional imaging with rotational C-arm computed tomography. Optical spectra that included both visible and near-infrared wavelength ranges were processed to derive estimates of the blood and lipid volume fractions. Results:In all insertions, the transition of the needle tip to the epidural space from an adjacent tissue structure (interspinous ligament or the ligamentum flavum) was found to be associated with an increase in the lipid volume fraction. These increases, which ranged from 1.6- to 3.0-fold, were statistically significant (P = 0.0020). Lipid fractions obtained from the epidural space were 1.9- to 20-fold higher than those obtained from muscle (P = 0.0013). Accidental penetration of an epidural vein during one insertion coincided with a high blood volume fraction. Conclusions:The spectroscopic information obtained with the optical spinal needle is complementary to fluoroscopic images, and it could potentially allow for reliable identification of the epidural space during needle placement.

Diffuse reflectance spectroscopy: a new guidance tool for improvement of biopsy procedures in lung malignancies

BACKGROUND A significant number of percutaneous intrathoracic biopsy procedures result in indeterminate cytologic or histologic diagnosis in clinical practice. Diffuse reflectance spectroscopy (DRS) is an optical technique that can distinguish different tissue types on a microscopic level. DRS may improve needle localization accuracy during biopsy procedures. The objective of this study was to assess the ability of DRS to enhance diagnosis of malignant disease in human lung tissue. METHODS Ex vivo analysis with a DRS system was performed on lung tissue from 10 patients after pulmonary resection for malignant disease. Tissue spectra measured from 500 to 1600 nm were analyzed using 2 analysis methods; a model-based analysis that derives clinical and optical properties from the measurements and a partial least-squares discriminant analysis (PLS-DA) that classifies measured spectra with respect to the histologic nature of the measured tissue. RESULTS Sensitivity and specificity for discrimination of tumor from normal lung tissue were 89% and 79%, respectively, based on the model-based analysis. Overall accuracy was 84%. The PLS-DA analysis yielded a sensitivity of 78%, a specificity of 86%, and an overall accuracy of 81%. CONCLUSIONS The presented results demonstrate that DRS has the potential to enhance diagnostic accuracy in minimally invasive biopsy procedures in the lungs in combination with conventional imaging techniques.

Significant Dose Reduction for Pediatric Digital Subtraction Angiography Without Impairing Image Quality: Preclinical Study in a Piglet Model

OBJECTIVE The purpose of this study was to validate the hypothesis that image quality of digital subtraction angiography (DSA) in pediatrics is not impaired when using a low-dose acquisition protocol. MATERIALS AND METHODS Three piglets corresponding to common pediatric population sizes were used. DSA was performed in the aorta and renal, hepatic, and superior mesenteric arteries using both the commonly used reference standard and novel radiographic imaging noise reduction technologies to ensure pairwise radiation dose and image quality comparison. The air kerma per frame at the interventional reference point for each DSA acquisition was collected as a radiation dose measure, and image quality was evaluated by five interventional radiologists in a randomized blinded fashion using a 5-point scale. RESULTS The mean air kerma (± SD) at the interventional reference point with the novel x-ray imaging noise reduction technology was significantly lower (1.1 ± 0.8 mGy/frame) than with the reference technology (4.2 ± 3.0 mGy/frame, p = 0.005). However, image quality was statistically similar, with average scores of 3.2 ± 0.4 and 3.1 ± 0.5 for the novel and reference technologies, respectively (p = 0.934); interrater absolute agreement was 0.77. CONCLUSION The DSA radiation dose for pediatrics can be reduced by a factor of four with a novel x-ray imaging noise reduction technology without deterioration of image quality.