KEYWORDS: Luminescence, Finite element methods, 3D modeling, 3D image processing, Diffusion, Samarium, Tissues, Natural surfaces, Animal model studies, 3D acquisition
A boundary element method with dual reciprocity method (BEM-DRM) was used to model fluorescence in tissue using
coupled diffusion equations in 3D. This method eliminates the need for node connectivity in a volume mesh of arbitrary
shapes, requiring instead, a surface mesh with interior points to model the fluorescence source in 3D. Results using
BEM-DRM show agreement with data from open source finite-element based software package NIRFAST7 with mean
error difference of 0.08 for optimally chosen support parameter for radial basis functions used.
KEYWORDS: Natural surfaces, Near infrared, Tissues, 3D modeling, Diffusion, Chemical elements, Image segmentation, Open source software, Near infrared spectroscopy, Tissue optics
NIRFAST is open source software for near infrared (NIR) imaging using finite element method for modeling light
diffusion tissue. Recently, we integrated an add-on to NIRFAST based on boundary-element method (BEM) solution to
the diffusion equation. This toolbox requires only surface discretization of the imaging domain as opposed to volume
meshing, geared towards 3D NIR spectroscopy. The software is
Matlab-based and provides a framework for surface
meshing, forward model, reconstruction and data and solution visualization capabilities as well as ability to run in
parallel environments using OpenMP standard. This was validated in simulations, experiments and applied to in-vivo
clinical data and was made open-source for the near infrared imaging community.
A near-infrared (NIR) tomography system with spectral-encoded sources at two wavelength bands was built to quantify
the temporal contrast at 20 Hz bandwidth, while imaging breast tissue. The NIR system was integrated with a magnetic
resonance (MR) machine through a custom breast coil interface, and both NIR data and MR images were acquired
simultaneously. MR images provided breast tissue structural information for NIR reconstruction. Acquisition of finger
pulse oximeter (PO) plethysmogram was synchronized with the NIR system in the experiment to offer a frequency-locked
reference. The recovered absorption coefficients of the breast at two wavelengths showed identical temporal
frequency as the PO output, proving this multi-modality design can recover the small pulsatile variation of absorption
property in breast tissue related to the heartbeat. And it also showed the system's ability on novel contrast imaging of
fast flow signals in deep tissue.
KEYWORDS: Breast, Tissues, Tissue optics, Magnetic resonance imaging, Near infrared, Tumors, In vivo imaging, Image segmentation, Near infrared spectroscopy, Natural surfaces
We demonstrate quantitative functional imaging using image-guided near-infrared spectroscopy (IG-NIRS) implemented with the boundary element method (BEM) for reconstructing 3-D optical property estimates in breast tissue in vivo. A multimodality MRI-NIR system was used to collect measurements of light reflectance from breast tissue. The BEM was used to model light propagation in 3-D based only on surface discretization in order to reconstruct quantitative values of total hemoglobin (HbT), oxygen saturation, water, and scatter. The technique was validated in experimental measurements from heterogeneous breast-shaped phantoms with known values and applied to a total of seven subjects comprising six healthy individuals and one participant with cancer imaged at two time points during neoadjuvant chemotherapy. Using experimental measurements from a heterogeneous breast phantom, BEM for IG-NIRS produced accurate values for HbT in the inclusion with a <3% error. Healthy breast tissues showed higher HbT and water in fibroglandular tissue than in adipose tissue. In a subject with cancer, the tumor showed higher HbT compared to the background. HbT in the tumor was reduced by 9 µM during treatment. We conclude that 3-D MRI-NIRS with BEM provides quantitative and functional characterization of breast tissue in vivo through measurement of hemoglobin content. The method provides potentially complementary information to DCE-MRI for tumor characterization.
An approach to quantitatively image targeted-agent binding rate in vivo is demonstrated with dual-probe injection of both targeted and nontargeted fluorescent dyes. Images of a binding rate constant are created that reveal lower than expected uptake of epidermal growth factor in an orthotopic xenograft pancreas tumor (2.3×10−5 s−1), as compared to the normal pancreas (3.4×10−5 s−1). This approach allows noninvasive assessment of tumor receptor targeting in vivo to determine the expected contrast, spatial localization, and efficacy in therapeutic agent delivery.
Verteporfin photodynamic therapy (PDT) is a promising adjuvant therapy for pancreas cancer and investigations for its use are currently underway in both orthotopic xenograft mouse models and in human clinical trials. The mouse models have been studied extensively using magnetic resonance (MR) imaging as a measure of surrogate response to verteporfin PDT and it was found that tumor lines with different levels of aggression respond with varying levels to PDT. MR imaging was successful in determining the necrotic volume caused by PDT but there was difficultly in distinguishing
inflamed tissues and regions of surviving tumor. In order to understand the molecular changes within the tumor immediately post-PDT we propose the implementation of MR-guided fluorescence molecular tomography (FMT) in conjunction with an exogenously administered fluorescently labeled epidermal growth factor (EGF-IRDye800CW, LI-COR Biosciences). We have previously shown that MR-guided FMT is feasible in the mouse abdomen when multiple
regions of fluorescence are considered from contributing internal organs. In this case the highly aggressive AsPC-1 (+EGFR) orthotopic tumor was implanted in SCID mice, interstitial verteporfin PDT (1mg/kg, 20J/cm) was performed when the tumor reached ~60mm3 and both tumor volume and EGF binding were followed with MR-guided FMT.
Delivery of therapeutic agents to solid tumors is challenging, and the issues that govern this can be distilled down into
parameters which allow computational modeling. In this paper, the basic rate equations and diffusion kernel for the time
and space modeling of delivery are developed, along with an analytical solution to this equation. The model is then used
to compare delivery of Avastin antibody relative to delivery encapsulated in a nanocell delivery vehicle. The key factors
are the plasma clearance or excretion rates, and the binding, or not, as it transports into the tumor tissue. A reduction in
the plasma clearance rate inherently increases available delivery over time, and additionally the reduction in binding
from antibody to nanocell allows higher penetration into the tumor at the longer circulation times.
Over the last several decades little progress has been made in the therapy and treatment monitoring of pancreas
adenocarcinoma, a devastating and aggressive form of cancer that has a 5-year patient survival rate of 3%. Currently,
investigations for the use of interstitial Verteporfin photodynamic therapy (PDT) are being undertaken in both orthotopic
xenograft mouse models and in human clinical trials. In the mouse models, magnetic resonance (MR) imaging has been
used as a measure of surrogate response to Verteporfin PDT; however, MR imaging alone lacks the molecular
information required to assess the metabolic function and growth rates of the tumor immediately after treatment. We
propose the implementation of MR-guided fluorescence tomography in conjunction with a fluorescently labeled (IR-Dye
800 CW, LI-COR) epidermal growth factor (EGF) as a molecular measure of surrogate response. To demonstrate the
effectiveness of MR-guided diffuse fluorescence tomography for molecular imaging, we have used the AsPC-1
(+EGFR) human pancreatic adenocarcinoma in an orthotopic mouse model. EGF IRDye 800CW was injected 48 hours
prior to imaging. MR image sequences were collected simultaneously with the fluorescence data using a MR-coupled
diffuse optical tomography system. Image reconstruction was performed multiple times with varying abdominal organ
segmentation in order to obtain a optimal tomographic image. It is shown that diffuse fluorescence tomography of the
orthotopic pancreas model is feasible, with consideration of confounding fluorescence signals from the multiple organs
and tissues surrounding the pancreas. MR-guided diffuse fluorescence tomography will be used to monitor EGF
response after photodynamic therapy. Additionally, it provide the opportunity to individualize subsequent therapies
based on response to PDT as well as to evaluate the success of combination therapies, such as PDT with chemotherapy,
antibody therapy or even radiation.
Using extracted spectral features is proposed to reconstruct video-rate optical-properties images. Compared
with reconstruction through time-sequence data, the results through spectral features are exempt from noise
affection, and are able to differentiate hemodynamic conditions in a single heart-beat cycle.
Tomographic imaging of a glioma tumor with endogenous fluorescence is demonstrated using a noncontact single-photon counting fan-beam acquisition system interfaced with microCT imaging. The fluorescence from protoporphyrin IX (PpIX) was found to be detectable, and allowed imaging of the tumor from within the cranium, even though the tumor presence was not visible in the microCT image. The combination of single-photon counting detection and normalized fluorescence to transmission detection at each channel allowed robust imaging of the signal. This demonstrated use of endogenous fluorescence stimulation from aminolevulinic acid (ALA) and provides the first in vivo demonstration of deep tissue tomographic imaging with protoporphyrin IX.
It is well known that diffuse optical tomography (DOT) has limited spatial resolution, and sufficient contrast recovery is
limited to lesions greater than ~6 mm[1]. However, with the addition of multimodality methods that combine high
spatial resolution imaging, such as MRI, it has been shown that quantification and feature recovery improves[2].
However, it is not known how well MRg-DOS will perform with characterizing small lesions in 3D. These limits need
to be established in order to determine the practical limitations of optical imaging.
This paper investigates the contrast resolution limits of 3 dimensional MRg-DOS. Short irregular inclusions of various
diameters are added to a homogeneous background. Two case studies are presented which represent these limiting
situations.
Image-guided near infrared spectroscopy (IG-NIRS) can provide high-resolution vascular, metabolic and molecular
characterization of localized tissue volumes in-vivo. The approach for IG-NIRS uses hybrid systems where the spatial
anatomical structure of tissue obtained from standard imaging modalities (such as MRI) is combined with tissue
information from diffuse optical imaging spectroscopy. There is need to optimize these hybrid systems for large-scale
clinical trials anticipated in the near future in order to evaluate the feasibility of this technology across a larger
population. However, existing computational methods such as the finite element method mesh arbitrary image volumes,
which inhibit automation, especially with large numbers of datasets. Circumventing this issue, a boundary element
method (BEM) for IG-NIRS systems in 3-D is presented here using only surface rendering and discretization. The
process of surface creation and meshing is faster, more reliable, and is easily generated automatically as compared to full
volume meshing. The proposed method has been implemented here for multi-spectral non-invasive characterization of
tissue. In phantom experiments, 3-D spectral BEM-based spectroscopy recovered the oxygen dissociation curve with
mean error of 6.6% and tracked variation in total hemoglobin linearly.
Fluorescence molecular tomography (FMT) has the potential to become a powerful quantitative research tool for pre-clinical
applications such as evaluating the efficacy of experimental drugs. In this paper, we show how a time-domain
FMT/microCT instrument can in principle be used to monitor volumetric fluorescence intensity over time for low
fluorophore concentration levels. The experimental results we present relate to Protoporphyrin IX which has a quantum
efficiency as much as two orders of magnitude lower compared to more conventional extrinsic dyes used for molecular
imaging (e.g., Alexa Fluor dyes, Cyanine dyes). Our results highlight the high sensitivity of the single photon counting
technology on which the optical system we have built is based. In conjunction with this system we have developed a
diffuse optical fluorescence reconstruction technique that is robust and shown here to perform adequately even in cases
when the contribution of noise to the data is important. Related to this, we show that the regularization scheme we have
developed is reliable even for low fluorophore concentration values and that no adjustment of the regularization
parameter needs to be made for different levels of noise. This generic reconstruction approach insures that images
reconstructed from data sets acquired at different times and for different fluorescence levels can be compared on an
equal footing.
Near-infrared (NIR) region-based spectroscopy is examined for accuracy with spectral recovery using frequency domain data at a discrete number of wavelengths, as compared to that with broadband continuous wave data. Data with more wavelengths in the frequency domain always produce superior quantitative spectroscopy results with reduced noise and error in the chromophore concentrations. Performance of the algorithm in the situation of doing region-guided spectroscopy within the MRI is also considered, and the issue of false positive prior regions being identified is examined to see the effect of added wavelengths. The results indicate that broadband frequency domain data are required for maximal accuracy. A broadband frequency domain experimental system was used to validate the predictions, using a mode-locked Ti:sapphire laser for the source between 690- and 850-nm wavelengths. The 80-MHz pulsed signal is heterodyned with photomultiplier tube detection, to lower frequency for data acquisition. Tissue-phantom experiments with known hemoglobin absorption and tissue-like scatter values are used to validate the system, using measurements every 10 nm. More wavelengths clearly provide superior quantification of total hemoglobin values. The system and algorithms developed here should provide an optimal way to quantify regions with the goal of image-guided breast tissue spectroscopy within the MRI.
Raman spectroscopic diffuse tomographic imaging has been demonstrated for the first time. It provides a noninvasive, label-free modality to image the chemical composition of human and animal tissue and other turbid media. This technique has been applied to image the composition of bone tissue within an intact section of a canine limb. Spatially distributed 785-nm laser excitation was employed to prevent thermal damage to the tissue. Diffuse emission tomography reconstruction was used, and the location that was recovered has been confirmed by micro-computed tomography (micro-CT) images.
We report tomographic reconstruction of objects located several millimeters below the surface of highly scattering
media. For this purpose we adapted proven software developed for fluorescence tomography with and without the use of
spatial priors1. For this first demonstration we acquired Raman spectra using an existing ring/disk fiber optic probe with
fifty collection fibers2. Several illumination ring diameters were employed to generate multiple angles of incidence.
Tomographic reconstruction from Raman scatter was tested using a 9.5 mm diameter Teflon® sphere embedded in a gel
of agarose and 1% Intralipid. Blind reconstruction of the sphere using the 732 cm-1 C-F stretch yielded an accurate shape
but an inaccurate depth. Using the known shape and position of the object as spatial priors, a more accurate
reconstruction was obtained. We also demonstrated a reconstruction of the tibial diaphysis of an intact canine hind limb
using spatial priors generated from micro-computed tomography. In this first demonstration of Raman tomography in
animal tissue, the P-O stretch of the bone mineral at 958 cm-1 was used for the reconstruction. An accurate shape and
depth were recovered.
Advanced imaging systems and theoretical models have been developed to quantify fluorescence, and this theoretical
framework involves numerical-based solutions of a set of coupled diffusion equations. One key to advancing this
modality is the extension of the imaging into realistic tissue geometries, which can be dynamically updated from data
from other high resolution modalities. Here we explore the quantification of fluorescence in a three-dimensional
(3-D) mouse phantom tagged with heterogeneous optical properties. A finite element model for the diffusion equation
was used to approximate light propagation along with Newton's method for image reconstruction, to recover 3-D
images of fluorescent yield. Using measurements generated on a brain tumor in a mouse with 2% noise, our results
show that only 11.4% of the expected fluorescent yield could be recovered without any prior knowledge about the
spatial structure of the domain. Using a parameter reduction scheme based upon prior spatial information of the location
and size of the tumor, 100% of the expected value could be estimated. These preliminary results indicate that image
guided fluorescence spectroscopy has the ability to provide accurate fluorescence recovery, whereas diffuse imaging
based recovery is limited in the ability to quantify.
Incorporating near infrared (NIR) diffuse optical tomography into magnetic resonance imaging (MRI) increases the
value of MR breast cancer imaging because it adds functional imaging of hemoglobin, oxygen saturation, water, lipid
content, and scattering parameters, properties that infer tissue health. Reconstruction algorithms that incorporate MR into
a diffusive modality accrue unavoidable errors from improper tissue segmentation of the MR image, which create
inaccuracies in the structural prior. This paper focuses on identifying the most accurate reconstruction approach based on
imperfect prior knowledge of tissue boundaries. Specifically, it focuses on how unavoidable segmentation errors of
different breast densities affect edge-constraining reconstruction methods to determine the correct approach. Results
show that these reconstruction methods all retain the improperly defined edges, but are quantitatively accurate even
when the anatomical boundaries mismatch the optical boundaries by as much as 50%. The most accurate approach is one
where the problem has been reduced to the least number of unknowns, and the edges are constrained through
regularization.
NIR tomography has advanced considerably over the past decade. The historical developments which have led to creation of NIR tomography have largely resulted in systems which were optimized for signal accuracy and high numbers of point measurements, rather than speed of acquisition. One of the key technological designs limiting the acquisition speed is the requirement that the source light be delivered sequentially or through frequency encoding of the time signal. The approach presented here provides a method to introduce all sources and all detectors simultaneously with no moving parts and retaining the dynamic range of the detector, by separating the signals spatially prior to detection. This is achieved by spectral wavelength encoding of the sources, which allows many sources to be input into the tissue at the same time, followed by spectral-decoding of all detection channels in parallel using a spectrometer and CCD detector. A data acquisition speed of 35Hz frame rate has been achieved with this configuration. The described system features 8 sources at an overall 785nm center band and 8 detectors evenly deployed in a 27mm array designed for imaging with small animal tissues. This paper discusses the design, instrumentation of the system, and the imaging characteristics.
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.
This paper presents the design, instrumentation, and performance of a rapid imaging near-infrared diffuse optical tomography system that is capable of collecting tomographic measurements at 35 frames per second. The video-rate tomographic data acquisition is achieved by spectral wavelength encoding of the sources, which allows many
sources to be input into the tissue at the same time, followed by spectral-decoding of all detection channels in parallel using a spectrometer and CCD detector. The combination of spectral-decoding of the source lights horizontally in a spectrometer and spatial-separation of the detector positions vertically at the entrance slit provides continuous data for the entire set of source-detector pairs. A data acquisition speed of 35Hz frame rate was achieved with the use of the CCD operating in frame-transfer mode. The described system features 8 sources at an overall 785nm center band with average of 1.25nm spacing in wavelength and 8 detectors evenly deployed in a 27mm array designed for imaging with small animal tissues. The system's imaging characteristics as well as examples of capturing transient changes of absorption in the dynamic phantom are presented.
Hybrid NIR-MRI imaging has been used in a clinical breast imaging system to characterize breast tissue properties. The multi-spectral, frequency-domain tomography system operates inside a clinical scanner via long silica-glass optical fiber bundles and using a non-magnetic fiber-patient interface attached to a high resolution MR breast coil. Sixteen fiber bundles are positioned around the circumference of the female breast yielding 240 measurements of light transmission (amplitude and phase) at six optical wavelengths from 660-850nm through up to 12 cm of tissue. From optical measurements, we use a Newton-type algorithm to reconstruct images of tissue optical properties (absorption and scattering), and physiological tissue features such as oxy-hemoglobin [Hb-O2], deoxy-hemoglobin concentrations [Hb-R], water concentration [water], scattering amplitude, and scattering power. We are exploring the synergistic benefits of a combined NIR-MRI data set, specifically the ways in which MRI (i.e. high spatial resolution) can be used to enhance NIR (i.e. high contrast resolution) image reconstruction. A priori knowledge can be applied to image reconstruction in the form of spatial and spectral constraints to improve spatial resolution, contrast, and quantitative accuracy of NIR images. In vivo results suggest that this combined system can accurately quantify contrast between the properties of tissues present in the breast (i.e. adipose and fibroglandular) regardless of their varied and complex spatial organization. For a group of healthy female volunteers, we observe greater contrast between the properties of adipose and glandular tissues when we use MR-guidance than when we do not, and values of total hemoglobin and water content are more consistent with what is physiologically expected.
A multi-spectral direct chromophore and scattering reconstruction for frequency domain NIR tomography has been implemented using constraints of the known molar spectra of the chromophores and a Mie theory approximation for scattering. This was tested in a tumor-simulating phantom containing an inclusion with higher hemoglobin, lower oxygenation and contrast in scatter. The recovered images were quantitatively accurate and showed substantial improvement over existing methods; and in addition, showed robust results tested for up to 5% noise in amplitude and phase measurements. When applied to a clinical subject with fibrocystic disease, the tumor was visible in hemoglobin and water, but no decrease in oxygenation was observed, making oxygen saturation, a potential diagnostic indicator.
While near-infrared tomography has advanced considerably over the past decade, key technological designs still limit what can be achieved, especially in terms of imaging acquisition speed. One of these fundamental limitations is the requirement that the source light be delivered sequentially or through frequency encoding of the time signal. Sequential delivery inherently limits the speed at which images can be acquired. Modulation frequency-dependent encoding of the sources solves the problem by allowing sources near the same location to be turned on simultaneously, thereby improving the speed for acquisition, but suffers from dynamic range problems. In this study, we demonstrate an alternative parallel source implementation approach which uses spectral wavelength encoding of the source. This new technique allows many sources to be input into the tissue at the same time, as long as the spectrally encoded signals can be decoded at the output. To test the implementation of this approach, 8 single-mode laser diodes of wavelengths distributed within a narrow range of 10 nm are used, and the lights are all input into tissue phantom simultaneously. On the detection side, a high-resolution spectrometer is used to spatially spread out the signals to facilitate parallel detection of the signal from each spectrally-encoded source. This robust approach allows rapid parallel sampling of all sources at all detection locations. The implementation of this technique in a NIR tomography application is examined, and the preliminary results of video-rate imaging at 30 Hz is presented.
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.
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 µM 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 µM, 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.
Near-infrared imaging can be used in humans to characterize changes in breast tumor tissue by imaging total hemoglobin and water concentrations as well as oxygen saturation. In order to improve our understanding of these changes, we need to carefully quantify the range of variation possible in normal tissues for these parameters. In this study, the effect of the subject’s menstrual cycle was examined by imaging their breast at the follicular (7-14 days of the cycle) and secretory phases (21-28 days of the cycle), using our NIR tomographic system. In this system, a three layer patient interface is used to measure 3 planes along the breast from chest wall towards the nipple at 1cm increments. Seven volunteers in their 40s were observed for 2 menstrual cycles and all of these volunteers recently had normal mammograms (ACR 1) with heterogeneously dense breast composition. The results show that average total hemoglobin in the breast increased in many subjects between 0 to 15% from the follicular phase to secretory phase. Oxygen saturation and water concentration changes between these 2 parts of the cycle were between −6.5% to 12% for saturation and between −33% to 28% for water concentration. While the data averaged between subjects showed no significant change existed between phases, it was clear that individual subjects did exhibit changes in composition which were consistent from cycle to cycle. Understanding what leads to this heterogeneity between subjects will be an important factor in utilizing these measurements in clinical practice.
Near Infrared diffuse optical tomography was used to measure the molar absorption spectra for de-oxyhemoglobin, oxyhemoglobin and water through phantom experiments. The measured spectra compensate for any systemic errors and errors arising from model-based estimation of concentrations of these chromophores, and show reasonable agreement with existing literature values. The spectra were validated by phantom experiments to obtain the oxygen dissociation curve. Variation of the partial pressure of oxygen in solution yielded results consistent with theory of mean error of 7.6% in estimation of oxygen saturation, and accurate within 5% in estimation of hemoglobin.
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