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Biomedical subjects

Shudong Jiang

Publications and source records attributed to Shudong Jiang.

At least 19 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↗

Spectrally resolved bioluminescence optical tomography.

Spectrally resolved bioluminescence optical tomography is an approach to recover images of luciferase activity within a volume using multiwavelength emission data from internal bioluminescence sources. The underlying problem of uniqueness associated with nonspectrally resolved intensity-based bioluminescence tomography is highlighted. Reconstructed images of bioluminescence are presented by using as input both simulated and real multiwavelength data from a tissue-simulating phantom. The location of the internal bioluminescence is obtained with 1 mm accuracy. Further, the amplitude of the reconstructed source is proportional to the actual bioluminescence intensity.

Imaging, Three-Dimensional↗

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↗

Breast deformation modelling for image reconstruction in near infrared optical tomography.

Near infrared tomography (NIR) is a novel imaging technique that can be used to reconstruct tissue optical properties from measurements of light propagation through tissue. More specifically NIR measurements over a range of wavelengths can be used to obtain internal images of physiologic parameters and these images can be used to detect and characterize breast tumour. To obtain good NIR measurements, it is essential to have good contact between the optical fibres and the breast which in-turn results in the deformation of the breast due to the soft plasticity of the tissue. In this work, a tissue deformation model of the female breast is presented that will account for the altered shape of the breast during clinical NIR measurements. Using a deformed model of a breast, simulated NIR data were generated and used to reconstruct images of tissue absorption and reduced scatter using several assumptions about the imaging domain. Using either a circular or irregular 2D geometry for image reconstruction produces good localization of the absorbing anomaly, but it leads to degradation of the image quality. By modifying the assumptions about the imaging domain to a 3D conical model, with the correct diameter at the plane of NIR measurement, significantly improves the quality of reconstructed images and helps reduce image artefacts. Finally, assuming a non-deformed breast shape for image reconstruction is shown to lead to poor quality images since the geometry of the breast is greatly altered, whereas using the correct deformed geometry produces the best images.

Algorithms↗

Automated region detection based on the contrast-to-noise ratio in near-infrared tomography.

The contrast-to-noise ratio (CNR) was used to determine the detectability of objects within reconstructed images from diffuse near-infrared tomography. It was concluded that there was a maximal value of CNR near the location of an object within the image and that the size of the true region could be estimated from the CNR. Experimental and simulation studies led to the conclusion that objects can be automatically detected with CNR analysis and that our current system has a spatial resolution limit near 4 mm and a contrast resolution limit near 1.4. A new linear convolution method of CNR calculation was developed for automated region of interest (ROI) detection.

Artifacts↗

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↗

In vivo near-infrared spectral detection of pressure-induced changes in breast tissue.

A diffuse near-infrared tomography system was used to measure dynamic changes in the absolute optical properties of the human breast that were induced through pressure applied to the tissue surface. Results from five subjects show that absorption and scattering coefficients changed measurably when pressure was increased and that these relative changes correlated with the subjects' body-mass index, indicating that the effect depends on tissue composition. Fitting the absolute absorption and scattering coefficients at six wavelengths to the molar absorption spectra of the three predominant chromophores revealed that both the average total hemoglobin and oxygen saturation increased by 10%, while water concentration decreased by more than 12%. These changes indicate that the pressure-induced variation is likely due to water displacement and vascular volume increase in the region being imaged, for mild application of pressure to the breast. These results suggest that the pressure applied during optical measurements of tissue may alter the tissue physiology, and care should be taken to factor this effect into the design of optical medical instrumentation. In addition, the technique provides a unique approach to measuring tissue elastic changes in vivo in the female breast and may offer a new method for dynamic contrast imaging based on elasto-optical measurements.

Adult↗

Quantitative analysis of near-infrared tomography: sensitivity to the tissue-simulating precalibration phantom.

A near-infrared (NIR) imaging system is evaluated as a diagnostic clinical tool to image total hemoglobin concentration and oxygen saturation within tissue. Calibration of this type of system requires measurement of the response at each detector and source location from a homogeneous tissue-simulating phantom. The effect of using calibration phantoms of varying composition, size, and optical properties is examined to determine how it affects the overall image accuracy. All of the calibration phantoms investigated result in accurate reconstruction of absorbing heterogeneities due to increased blood concentration with less than 4% standard deviation. Images from a patient with a biopsy-confirmed ductal carcinoma are also evaluated and found to be insensitive to the choice of calibration object, with only 1% variation between images generated with different calibration objects. The tumor total hemoglobin contrast is approximately 240% higher than the average total hemoglobin concentration in contralateral breast. Soft calibration phantoms, which mimic the elastic properties of human breast tissue, are also considered and found to diminish positioning errors in the fibers relative to the actual breast exam, thereby reducing the artifacts in the periphery of the reconstructed image.

Aged↗

Comparisons of three alternative breast modalities in a common phantom imaging experiment.

Four model-based imaging systems are currently being developed for breast cancer detection at Dartmouth College. A potential advantage of multimodality imaging is the prospect of combining information collected from each system to provide a more complete diagnostic tool that covers the full range of the patient and pathology spectra. In this paper it is shown through common phantom experiments on three of these imaging systems that it was possible to correlate different types of image information to potentially improve the reliability of tumor detection. Imaging experiments were conducted with common phantoms which mimic both dielectric and optical properties of the human breast. Cross modality comparison was investigated through a statistical study based on the repeated data sets of reconstructed parameters for each modality. The system standard error between all methods was generally less than 10% and the correlation coefficient across modalities ranged from 0.68 to 0.91. Future work includes the minimization of bias (artifacts) on the periphery of electrical impedance spectroscopy images to improve cross modality correlation and implementation of the multimodality diagnosis for breast cancer detection.

Breast Neoplasms↗

Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part I--Theory and simulations.

Near-infrared (NIR) diffuse tomography is an emerging method for imaging the interior of tissues to quantify concentrations of hemoglobin and exogenous chromophores non-invasively in vivo. It often exploits an optical diffusion model-based image reconstruction algorithm to estimate spatial property values from measurements of the light flux at the surface of the tissue. In this study, mean-squared error (MSE) over the image is used to evaluate methods for regularizing the ill-posed inverse image reconstruction problem in NIR tomography. Estimates of image bias and image standard deviation were calculated based upon 100 repeated reconstructions of a test image with randomly distributed noise added to the light flux measurements. It was observed that the bias error dominates at high regularization parameter values while variance dominates as the algorithm is allowed to approach the optimal solution. This optimum does not necessarily correspond to the minimum projection error solution, but typically requires further iteration with a decreasing regularization parameter to reach the lowest image error. Increasing measurement noise causes a need to constrain the minimum regularization parameter to higher values in order to achieve a minimum in the overall image MSE.

Computer Simulation↗

Statistical analysis of nonlinearly reconstructed near-infrared tomographic images: Part II--Experimental interpretation.

Image error analysis of a diffuse near-infrared tomography (NIR) system has been carried out on simulated data using a statistical approach described in Part I of this paper (Pogue et al., 2002). The methodology is used here with experimental data acquired on phantoms with a prototype imaging system intended for characterizing breast tissue. Results show that imaging performance is not limited by random measurement error, but rather by calibration issues. The image error over the entire field of view is generally not minimized when an accurate homogeneous estimate of the phantom properties is available; however, local image error over a target region of interest (ROI) is reduced. The image reconstruction process which includes a Levenberg-Marquardt style regularization provides good minimization of the objective function, yet its reduction is not always correlated with an overall image error decrease. Minimization of the bias in an ROI which contains localized changes in the optical properties can be achieved through five to nine iterations of the algorithm. Precalibration of the algorithm through statistical evaluation of phantom studies may provide a better measure of the image accuracy than that implied by minimization of the standard objective function.

Breast↗

Multispectral near-infrared tomography: a case study in compensating for water and lipid content in hemoglobin imaging of the breast.

Images of hemoglobin concentration and oxygen saturation are presented from multispectral near-infrared tomographic measurements in the breast of a woman with an invasive cancer. Images of the absorption coefficient and reduced scattering coefficient are recovered from the measured data using a finite element reconstruction algorithm based on the frequency-domain diffusion equation. Three methods of recovering the hemoglobin concentration and oxygen saturation images are presented which compensate for water and lipid absorption in different ways: (1) an assumed bulk content of water and lipids is used, (2) four chromophores are imaged, and (3) scattering power data are applied to deduce water and lipid images. In all three cases, a large increase in the hemoglobin concentration (3:1) is observed at the location of the cancer while a maximum of 15% difference is observed in the hemoglobin images between each of these methods for water and lipid compensation.

Aged↗

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↗