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Biomedical subjects

Subhadra Srinivasan

Publications and source records attributed to Subhadra Srinivasan.

10 recordsLinked to original sources

Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography.

Magnetic resonance (MR)-guided near-infrared spectral tomography was developed and used to image adipose and fibroglandular breast tissue of 11 normal female subjects, recruited under an institutional review board-approved protocol. Images of hemoglobin, oxygen saturation, water fraction, and subcellular scattering were reconstructed and show that fibroglandular fractions of both blood and water are higher than in adipose tissue. Variation in adipose and fibroglandular tissue composition between individuals was not significantly different across the scattered and dense breast categories. Combined MR and near-infrared tomography provides fundamental molecular information about these tissue types with resolution governed by MR T1 images.

Adipose Tissue↗

In vivo hemoglobin and water concentrations, oxygen saturation, and scattering estimates from near-infrared breast tomography using spectral reconstruction.

RATIONALE AND OBJECTIVES: Near-infrared (NIR) imaging has its niche in quantifying and characterizing functional changes in tissue relating to vascularity and metabolic status. Here, NIR tomography was applied to study mammographically normal breast tissue in vivo by evaluating relationships between functional parameters so obtained to clinical representers in an effort to understand factors influencing tissue compositional changes. MATERIALS AND METHODS: A new spectral reconstruction method that is considered to provide the most accurate estimates of hemoglobin level, oxygen saturation, water fraction, scattering power, and amplitude was used to assess healthy breast tissue imaged in vivo by means of NIR tomography. The approach directly recovers functional parameters with inherent inclusion of spectral behavior enforced through the incorporation of a priori model assumptions. Sixty subjects were imaged by using a frequency-domain instrument followed by spectral image reconstruction and statistical analysis for significant correlations. RESULTS: The new analysis shows statistically significant inverse correlations between body mass index and breast total hemoglobin and water fractions. Water fraction also correlated inversely with age and separated certain categories of breast density. Average scatter power was indicative of breast radiographic density composition, whereas scatter amplitude varied inversely with breast diameter. Total hemoglobin correlated with water fraction, whereas water correlated with scatter power. CONCLUSION: The changes observed here are attributable to volume fraction alterations and provide some of the most comprehensive data on breast composition variations with demographic factors.

Adult↗

Video-rate near-infrared optical tomography using spectrally encoded parallel light delivery.

A novel parallel source implementation approach to near-infrared tomography is demonstrated through spectral encoding of the light delivery. This new technique allows many sources to be input into the tissue at the same time, and a high-resolution spectrometer is used to spatially spread out the signals from each spectrally encoded source. The parallel sampling of all sources at all detection locations renders rapid imaging. Acquisition of complete tomographic data sets at a video rate of 35 frames/s is achieved for imaging of a 6.35 mm diameter inclusion with an absorption coefficient of 0.01 mm(-1) and a reduced scattering coefficient of 1.5 mm(-1) that is moving along a circular path inside a 1% Intralipid solution.

Computer Systems↗

Spectral priors improve near-infrared diffuse tomography more than spatial priors.

We compare the benefits of spatial and spectral priors in near-infrared diffuse tomography image reconstruction. Although previous studies that incorporated anatomical spatial priors have shown improvement in algorithm convergence and resolution, our results indicate that functional parameter quantification by this approach can be suboptimal. The incorporation of a priori spectral information significantly improves the accuracy observed in recovered images. Specifically, phantom results show that the maximum total hemoglobin concentration ([Hb(T)]) in a region of heterogeneity reached 91% of the true value compared to 63% using spatial priors. The combination of both priors produced results accurate to 98% of the true [Hb(T)]. When both spatial and spectral priors were applied in a healthy volunteer, glandular tissue showed a higher [Hb(T)], water fraction, and scattering power compared to adipose tissue.

Algorithms↗

Spectrally constrained chromophore and scattering near-infrared tomography provides quantitative and robust reconstruction.

A multispectral direct chromophore and scattering reconstruction technique has been implemented for near-infrared frequency-domain tomography in recovering images of total hemoglobin, oxygen saturation, water, and scatter parameters. The method applies the spectral constraint of the chromophores and scattering spectra directly in the reconstruction algorithm, thereby reducing the parameter space of the inversion process. This new method was validated by use of simulated and experimental data, and results show better robustness and stability in the presence of higher levels of noise. The method suppresses artifacts, especially those significant in water and scatter power images, and reduces cross talk between chromophore and scatter parameters. Variation in scattering was followed by this spectral approach successfully in experimental data from 90-mm-diameter cylindrical phantoms, and results show linear variation in scatter amplitude and reduced scattering coefficient (micro(s)'), with total hemoglobin, oxygen saturation, and water remaining constant and quantitatively accurate. Similar experiments were carried out for varying oxygen saturation and total hemoglobin. Accurate quantification was obtained with a mean error of 7.7% for oxygen saturation and 6.2% for total hemoglobin, with minimal cross talk between different parameters.

Algorithms↗

Near-infrared characterization of breast tumors in vivo using spectrally-constrained reconstruction.

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six cases were malignant (infiltrating ductal carcinomas) and showed higher hemoglobin (34-86% increase), a reduction in oxygen saturation, an increase in water content as well as scatter changes relative to surrounding normal tissue. Three of six cases were benign, two of which were diagnosed with fibrocystic disease and showed a dominant contrast in water, consistent with fluid filled cysts. Scatter amplitude was the main source of contrast in the volunteer with the benign condition fibrosis, which typically contains denser collagen tissue. The changes monitored correspond to physiological changes associated with angiogenesis, hypoxia and cell proliferation anticipated in cancers. These changes represent potential diagnostic indicators, which can be assessed to characterize breast tumors.

Adult↗

Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography.

Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic density. Total hemoglobin concentration correlated inversely to body mass index, likely because lower body mass indicates proportionately less fat and more glandular tissue, and glandular tissue contains greater vascularity, hence, more total hemoglobin. Optical scattering was correlated to breast diameter, subject age, and radiographic density. In the radiographic density, fatty breasts had low scattering power and extremely dense breasts had higher values. This observation is consistent with low attenuation of conventional x-rays with fat and higher attenuation in glandular tissues. Optically, fatty tissues have large scatterers leading to a low scattering power, whereas glandular or fibrous tissues have more cellular and collagen-based structures that lead to high scattering power. The study presents correlative data supporting the hypothesis that optical measurements of absorption and scattering can provide physiologically relevant information about breast tissue composition. These breast constituents vary significantly between individuals and can be altered because of changes in breast physiology or pathological state.

Adult↗

Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes.

Near-infrared imaging was used to quantify typical values of hemoglobin concentration, oxygen saturation, water fraction, scattering power, and scattering amplitude within the breast tissue of volunteer subjects. A systematic study of the menstrual variations in these parameters was carried out by measuring a group of seven premenopausal normal women (aged 41 to 47 years) in the follicular (days 7 to 14 of the cycle) and secretory phases (days 21 to 28) of the cycle, for two complete menstrual cycles. An average increase in hemoglobin concentration of 2.6 microM or 13% of the background breast values was observed in the secretory phase relative to the follicular phase (p<0.0001), but no other average near-infrared parameter changes were significant. While repeatable and systematic changes were observed in all parameters for individual subjects, large intersubject variations were present in all parameters. In a survey of thirty-nine normal subjects, the total hemoglobin varied from 9 to 45 microM, with a systematic correlation observed between total hemoglobin concentration and breast radiographic density. Scattering power and scattering amplitude were also correlated with radiographic density, but oxygen saturation and water fraction were not. Images of breast lesions indicate that total hemoglobin-based contrast can be up to 200% relative to the background in the same breast. Yet, since the background hemoglobin values vary considerably among breasts, the maximum hemoglobin concentrations observed in cancer tumors may vary considerably as well. In light of these observations, it may be important to use hemoglobin contrast values relative to the background for a given breast, rather than absolute hemoglobin contrast when trying to compare the features of breast lesions among subjects.

Adult↗

Improved quantification of small objects in near-infrared diffuse optical tomography.

Diffuse optical tomography allows quantification of hemoglobin, oxygen saturation, and water in tissue, and the fidelity in this quantification is dependent on the accuracy of optical properties determined during image reconstruction. In this study, a three-step algorithm is proposed and validated that uses the standard Newton minimization with Levenberg-Marquardt regularization as the first step. The second step is a modification to the existing algorithm using a two-parameter regularization to allow lower damping in a region of interest as compared to background. This second stage allows the recovery of the actual size of an inclusion. A region-based reconstruction is the final third step, which uses the estimated size and position information from step 2 to yield quantitatively accurate average values for the optical parameters. The algorithm is tested on simulated and experimental data and is found to be insensitive to object contrast and position. The percentage error between the true and the average recovered value for the absorption coefficient in test images is reduced from 47 to 27% for a 10-mm inclusion, from 38 to 13% for a 15-mm anomaly, and from 28 to 5.5% for a 20-mm heterogeneity. Simulated data with absorbing and scattering heterogeneities of 15 mm diam located in different positions show recovery with less than 15% error in absorption and 6% error in reduced scattering coefficients. The algorithm is successfully applied to clinical data from a subject with a breast abnormality to yield quantitatively increased absorption coefficients, which enhances the contrast to 3.8 compared to 1.23 previously.

Algorithms↗

Image reconstruction of effective Mie scattering parameters of breast tissue in vivo with near-infrared tomography.

A method for image reconstruction of the effective size and number density of scattering particles is discussed within the context of interpreting near-infrared (NIR) tomography images of breast tissue. An approach to use Mie theory to estimate the effective scattering parameters is examined and applied, given some assumptions about the index of refraction change expected in lipid membrane-bound scatterers. When using a limited number of NIR wavelengths in the reduced scattering spectra, the parameter extraction technique is limited to representing a continuous distribution of scatterer sizes, which is modeled as a simple exponentially decreasing distribution function. In this paper, image formation of effective scatterer size and number density is presented based on the estimation method. The method was evaluated with Intralipid phantom studies to demonstrate particle size estimation to within 9% of the expected value. Then the method was used in NIR patient images, and it indicates that for a cancer tumor, the effective scatterer size is smaller than the background breast values and the effective number density is higher. In contrast, for benign tumor patients, there is not a significant difference in effective scatterer size or number density between tumor and normal tissues. The method was used to interpret magnetic resonance imaging-coupled NIR images of adipose and fibroglandular tissues, and it indicated that the fibroglandular tissue has smaller effective scatterer size and larger effective number density than the adipose tissue does.

Algorithms↗