Biomedical subjects

V Ntziachristos

Publications and source records attributed to V Ntziachristos.

11 recordsLinked to original sources

PubMed2001

Kirchhoff approximation for diffusive waves.

Quantitative measurements of diffuse media, in spectroscopic or imaging mode, rely on the generation of appropriate forward solutions, independently of the inversion scheme employed. For complex boundaries, the use of numerical methods is generally preferred due to implementation simplicity, but usually results in great computational needs, especially in three dimensions. Analytical expressions are available, but are limited to simple geometries such as a diffusive slab, a sphere or a cylinder. An analytical approximation, the Kirchhoff approximation, also called the tangent-plane method is presented for the case of diffuse light. Using this approximation, analytical solutions of the diffusion equation for arbitrary boundaries and volumes can be derived. Also, computation time is minimized since no matrix inversion is involved. The accuracy of this approximation is evaluated on comparison with results from a rigorous numerical technique calculated for an arbitrary geometry. Performance of the approximation as a function of the optical properties and the size of the medium is examined and it is demonstrated that the computation time of the direct scattering model is reduced at least by two orders of magnitude.

Journal Article↗

PubMed2001

[Progress in optical imaging].

Different optical imaging technologies have significantly progressed over the last years. Besides advances in imaging techniques and image reconstruction, new "smart" optical contrast agents have been developed which can be used to detect molecular targets (such as endogenous enzymes) in vivo. The combination of novel imaging technologies coupled with smart agents bears great diagnostic potential both clinically and experimentally. This overview outlines the basic principles of optical imaging and summarizes the current state of the art.

Animals↗

PubMed2001

Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument.

The frequency-domain multiple-distance (FDMD) method is capable of measuring the absolute absorption and reduced scattering coefficients of optically turbid media. Absolute measurement of absorption at two near-infrared (NIR) wavelengths makes possible the quantitation of tissue haemoglobin concentration and tissue haemoglobin oxygen-saturation (StO2). However, errors are introduced by the uncertainties of background absorption and the dissimilarities between real tissues and the simplified mathematical model on which these measurements are based. An FDMD-based tissue instrument has been used for the monitoring of tissue haemoglobin concentration and oxygenation in the brain of newborn piglets during periods of hypoxia and hyperoxia. These tissue haemoglobin saturation values were compared with arterial saturation (SaO2) and venous saturation (SvO2) measured by blood gas analyses. A linear correlation was observed between StO2 and the average of SaO2 and SvO2. However, StO2 is not equal to any fixed weighted average of SaO2 and SvO2 unless we introduce an effective background tissue absorption. The magnitude of the background absorption was about 0.08 cm(-1) at 758 nm and 0.06 cm(-1) at 830 nm, and it was nearly consistent between piglets. The origin of this 'effective' background absorption may be real, an artefact caused by the application of a simplified model to a complex sample, or a combination of factors.

Animals↗

PubMed2001

Diffuse optical tomography of highly heterogeneous media.

We investigate the performance of diffuse optical tomography to image highly heterogeneous media, such as breast tissue, as a function of background heterogeneity. To model the background heterogeneity, we have employed the functional information derived from Gadolinium-enhanced magnetic resonance images of the breast. We demonstrate that overall image quality and quantification accuracy worsens as the background heterogeneity increases. Furthermore we confirm the appearance of characteristic artifacts at the boundaries that scale with background heterogeneity. These artifacts are very similar to the ones seen in clinical examinations and can be misinterpreted as actual objects if not accounted for. To eliminate the artifacts and improve the overall image reconstruction, we apply a data-correction algorithm that yields superior reconstruction results and is virtually independent of the degree of the background heterogeneity.

Algorithms↗

PubMed2001

Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy.

We assess typical systematic experimental errors involved in a time-resolved measurement as applied to NIR diffuse optical spectroscopy and investigate their effect on the quantification accuracy of the absorption and the reduced scattering coefficient. We demonstrate that common systematic experimental uncertainties may lead to quantification errors of 10% or more, even when excellent signal to noise ratio conditions exist and accurate photon propagation models are employed. We further demonstrate that the accuracy of the calculation depends nonlinearly on the optical properties of the medium measured. High scattering and low absorbing media can be quantified more accurately than media with low scattering or high absorption using measurements of the same signal to noise ratio. We further discuss curve-shape fitting schemes that aid in improving the quantification accuracy in the presence of experimental errors. Finally, we identify uncertainties that set quantification accuracy limits and we find temporal resolution as the ultimate limiting factor in the quantification accuracy achieved. Our findings suggest that temporal resolution of the order of 10 ps is necessary for quantifying the absorption and reduced scattering coefficient of diffuse media with accuracy better than 5% using curve fitting methods. In that sense this analysis can be used in time-resolved system design and in predicting the expected errors given the technology selected for time-resolved measurements.

Biophysical Phenomena↗

PubMed2001

Recovery of optical parameters in multiple-layered diffusive media: theory and experiments.

Diffuse photon density waves have lately been used both to characterize diffusive media and to locate and characterize hidden objects, such as tumors, in soft tissue. In practice, most biological media of medical interest consist of various layers with different optical properties, such as the fat layer in the breast or the different layers present in the skin. Also, most experimental setups consist of a multilayered system, where the medium to be characterized (i.e., the patient's organ) is usually bounded by optically diffusive plates. Incorrect modeling of interfaces may induce errors comparable to the weak signals obtained from tumors embedded deep in highly heterogeneous tissue and lead to significant reconstruction artifacts. To provide a means to analyze the data acquired in these configurations, the basic expressions for the reflection and transmission coefficients for diffusive-diffusive and diffusive-nondiffusive interfaces are presented. A comparison is made between a diffusive slab and an ordinary dielectric slab, thus establishing the limiting distance between the two interfaces of the slab for multiple reflections between them to be considered important. A rigorous formulation for multiple-layered (M-layered) diffusive media is put forward, and a method for solving any M-layered medium is shown. The theory presented is used to characterize a two-layered medium from transmission measurements, showing that the coefficients of scattering, mu'(s) , and absorption, mu(a) , are retrieved with great accuracy. Finally, we demonstrate the simultaneous retrieval of both mu;(s) and mu(a).

Diffusion↗

PubMed2000

Probing physiology and molecular function using optical imaging: applications to breast cancer.

The present review addresses the capacity of optical imaging to resolve functional and molecular characteristics of breast cancer. We focus on recent developments in optical imaging that allow three-dimensional reconstruction of optical signatures in the human breast using diffuse optical tomography (DOT). These technologic advances allow the noninvasive, in vivo imaging and quantification of oxygenated and deoxygenated hemoglobin and of contrast agents that target the physiologic and molecular functions of tumors. Hence, malignancy differentiation can be based on a novel set of functional features that are complementary to current radiologic imaging methods. These features could enhance diagnostic accuracy, lower the current state-of-the-art detection limits, and play a vital role in therapeutic strategy and monitoring.

Breast Neoplasms↗

PubMed2000

Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement.

We present quantitative optical images of human breast in vivo. The images were obtained by using near-infrared diffuse optical tomography (DOT) after the administration of indocyanine green (ICG) for contrast enhancement. The optical examination was performed concurrently with a magnetic resonance imaging (MRI) exam on patients scheduled for excisional biopsy or surgery so that accurate image coregistration and histopathological information of the suspicious lesions was available. The ICG-enhanced optical images coregistered accurately with Gadolinium-enhanced magnetic resonance images validating the ability of DOT to image breast tissue. In contrast to simple transillumination, we found that DOT provides for localization and quantification of exogenous tissue chromophore concentrations. Additionally our use of ICG, an albumin bound absorbing dye in plasma, demonstrates the potential to differentiate disease based on the quantified enhancement of suspicious lesions.

Aged↗

PubMed2000

Oximetry based on diffuse photon density wave differentials.

The quantification of tissue optical properties for calculating blood saturation and hemoglobin concentration using measurements of diffuse photon density waves at some distance away from an intensity-modulated light source, generally requires the determination of the amplitude and phase of this light source. This determination may become a severe impediment for measurements performed in the clinical environment. In this work we extend a self-calibrating methodology developed for constant wave and modulation depth-phase measurements, to include amplitude and phase measurements of diffuse photon density waves. The method uses amplitude and phase changes of intensity modulated light, under the assumption of known index of refraction and invariant reduced scattering coefficient mu's, to quantify the absorption coefficient mu(a) without requiring initial amplitude and phase knowledge. Quantification of the mu(a) at selected time points during a measurement can then be employed to calibrate numerical solutions of the diffusion equation and compute the mu(a) for the remaining time points of the experiment. It is shown that the method is quite insensitive to the knowledge of the exact mu's value so that an assumption on the average mu's value for the tissue measured may be employed. The sensitivity of calculating blood saturation and hemoglobin concentration, as a function of the deviation of the mu's used in the calculation versus the real mu's value is investigated using simulated data. It is also demonstrated that the saturation calculation is especially insensitive to the mu's guess. The performance of the method to quantify blood oxygen saturation and the concentrations of oxy- and deoxy-hemoglobin is examined with experimental measurements at two wavelengths on specially constructed blood model phantoms. To validate the method the measurements are monitored by a time-resolved spectrometer. The method is shown to be accurate to within +/-5% in calculating blood saturation and to within +/-10% in calculating hemoglobin concentration compared to the results obtained with the time-resolved spectrometer and the expected theoretical values.

Algorithms↗

PubMed2000

Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization.

We have synthesized a group of glucamine and gluosamine-substituted cyanine dyes structurally related to indocyanine green (ICG) and have characterized these compounds with regard to their potential as contrast agents for biomedical optical imaging. The compounds reported herein exhibit increased hydrophilicity and less plasma protein binding (< 50%), and are thus expected to have different pharmacokinetic properties compared with ICG. Furthermore, we measured enhanced fluorescence quantum yields (7-15%) in a physiological environment with respect to ICG. For the derivative with the highest hydrophilicity (5a) the efflux from tumor and normal tissue was monitored by intensity-modulated diffuse optical spectroscopy after intravenous injection into tumor-bearing rats. In comparison with ICG, 5a exhibited a considerably enhanced tissue-efflux half-life (73 min versus less than 10 min for ICG in tumor tissue), a two-fold higher initial tissue absorption coefficient compared to ICG, and finally, it generated an elevated tumor-to-tissue concentration gradient up to 1 h after injection. In conclusion, compounds such as 5a are promising contrast agents for optical imaging, and could facilitate highly sensitive and specific detection of breast cancer or other malignancies by utilizing mechanisms similar to contrast-enhanced magnetic resonance imaging or computerized tomography.

Animals↗

PubMed1997

Dipolar resonance frequency shifts in 1H MR spectra of skeletal muscle: confirmation in rats at 4.7 T in vivo and observation of changes postmortem.

Non-isotropic contributions to 1H MR spectra from human skeletal muscle in vivo have recently been observed in the 0- to 5-ppm region. One pair of peaks has been identified to be subject to dipolar couplings. The corresponding changes in resonance frequency are related to the orientation of muscle fibers with respect to the external magnetic field and are analogous to the behavior of small molecules dissolved in liquid crystals. Image-guided localized spectroscopy based on the STEAM method has been applied to verify these phenomena in rat skeletal muscle in vivo and to investigate the effect postmortem. Residual dipolar couplings and anisotropic contributions to 1H MR spectra of skeletal muscle have been confirmed in animals and at a higher field strength--albeit with a slightly different spectral pattern compared to the human study. The most prominent dipolar doublet due to creatine and/or phosphocreatine vanishes postmortem with a rate similar to the disappearance of phosphocreatine, and is no longer observable 2 h postmortem.

Animals↗