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Imaging complex structures with diffuse light

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We use diffuse optical tomography to quantitatively reconstruct images of complex phantoms with millimeter sized features located centimeters deep within a highly-scattering medium. A non-contact instrument was employed to collect large data sets consisting of greater than 10(7) source-detector pairs. Images were reconstructed using a fast image reconstruction algorithm based on an analytic solution to the inverse scattering problem for diffuse light.
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Imaging complex structures with diffuse light
Soren D. Konecky1, George Y. Panasyuk2, Kijoon Lee1,3, Vadim Markel2,4, Arjun G.
Yodh1, and John C. Schotland2
1 Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104-6396
2 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6396
3 Division of Bioengineering, Nanyang Technological University, Singapore 637457
4 Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104-6396
Abstract
We use diffuse optical tomography to quantitatively reconstruct images of complex phantoms with
millimeter sized features located centimeters deep within a highly-scattering medium. A non-contact
instrument was employed to collect large data sets consisting of greater than 107 source-detector
pairs. Images were reconstructed using a fast image reconstruction algorithm based on an analytic
solution to the inverse scattering problem for diffuse light.
1. Introduction
The study of light propagation in highly scattering random media such as clouds, paint and
tissue is of fundamental interest and considerable applied importance [1]. Novel physical
effects such as the dynamic correlations of speckle patterns and weak localization arise from
coherent effects in multiple scattering. Incoherent effects are also of interest and have lead to
new experimental tools to probe the structure of highly-scattering media. One such technique,
known as diffuse optical tomography (DOT), uses highly scattered near-infrared light to image
biological tissue and provide functional information about physiological parameters such as
blood volume and oxygenation [2–4]. Current clinical applications of DOT include breast
imaging [5–12] and functional brain mapping [13–21].
In an optically-thick medium such as the human breast, multiple scattering of light creates a
fundamental obstruction to the direct formation of images. DOT overcomes this problem to
some extent by solving an appropriate inverse problem, usually based on the diffusion equation,
wherein the optical properties of a highly-scattering medium are reconstructed from boundary
measurements. Since such inverse scattering problems are severely ill-posed [3], the resultant
image quality in DOT is expected to be poor; typical images resemble structureless ‘blobs’.
As a result many accept that anatomically accurate DOT images cannot be reconstructed.
Accordingly, the emphasis in DOT has been on functional imaging, and on multi-modality
imaging, in which simultaneously acquired MRI or CT images are used to provide anatomical
detail [4].
It has been suggested that the relatively low quality of images in DOT can be improved by the
use of large data sets [22–26]. Moreover, data sets of approximately 10 8 measurements may
be readily acquired with non-contact DOT systems [27–29]. For example, Turner et al. have
shown that simple shapes can be imaged in an experiment using an optically-thin sample by
Correspondence to: Soren D. Konecky (Email: E-mail: skonecky@physics.upenn.edu).
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Published in final edited form as:
Opt Express. 2008 March 31; 16(7): 5048–5060.
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employing time gating of early-arriving photons [27]. However, this approach uses photons
that travel ballistically through the sample and is therefore not useful in optically thick tissues
such as breast and brain.
In this contribution, we demonstrate for the first time that three-dimensional, quantitative
images of the interior of such an optically thick medium, with millimeter scale complex
structure, can be acquired using DOT. The reconstructed images exhibit spatially-resolved
features that are much smaller than the overall size of the sample and are obtained by utilizing
large data sets and fast image reconstruction algorithms developed in earlier work [23–26,30,
31]. Our findings have important implications for biomedical applications, since we achieve
image quality and spatial resolution sufficient for visualization of anatomical detail.
We have applied fast reconstruction methods to DOT imaging in previous work [29]. However,
in that work we imaged a sample with very strong absorption and a simple geometrical structure
(i.e. two perfectly absorbing balls). This choice did not allow us to explore the full potential
of large data sets and is of limited relevance to conditions encountered in tissue. The
experimental reconstructions obtained in Ref. [29] appeared as spherical inhomogeneities
correctly positioned in space, but slightly larger than the actual balls. Thus the detection and
localization of targets was shown, but neither the ability to reconstruct the shapes of spatially
extended objects nor the ability to image objects with more biologically realistic absorption
contrast was demonstrated. To overcome these limitations, in the present work we have
reconstructed images of several objects that have complex structure and have optical properties
comparable to those of tissue. Experiments with these objects immersed in an optically-thick
medium reveal that DOT is capable of producing quantitative images of complex structures
with spatially-resolved features on the sub-centimeter scale. This level of detail and the spatial
resolution achieved in our experiment are expected to significantly enhance the practical utility
of DOT, especially for localization and demarcation of breast tumors. We have quantified the
maximum attainable resolution with the current experimental system, and we have
demonstrated the effects of sampling on image quality. The effect of noise on the practical
limits of diffuse optical experimental resolution was also characterized.
2. Methods
2.1. Instrumentation
The experimental apparatus consisted of a continuous-wave diode laser (Model TC40, SDL
Inc., San Jose, CA) operating at 785 nm and coupled via a 100 μm multi-mode fiber to a pair
of galvanometer-controlled mirrors (Innovations in Optics, Woburn, MA). The mirrors raster
scanned the beam (on a 35 × 35 rectangular grid with 4 mm step size) over a 13.6 × 13.6
cm2 square on one side of an imaging tank containing a target. For each laser beam position,
the light transmitted through the tank was collected by a f=25 mm F/0.95 lens and focused on
a front-illuminated thermoelectric-cooled 16-bit CCD array (DV887ECS-UV, Andor
Technology, Belfast, Ireland). A 20 × 20 cm2 square area of the opposite surface was mapped
onto a square grid of 512 × 512 CCD pixels; this corresponds to a grid of detectors with 0.4
mm step. The signal recorded by each CCD pixel for a given source beam position defined an
independent measurement. The total size of the data set recorded in a single experiment was
(35 × 512)2 3 × 108. Somewhat smaller subsets of the data were used for image reconstruction.
The imaging tank had an inner thickness L = 6 cm, and was filled with a mixture of water, a
highly scattering fat emulsion (Liposyn III, 30%, Abbott Laboratories, Chicago, IL), and India
ink (Black India 4415, Sanford, Bellwood, IL). The absorption and the reduced scattering
coefficients of the mixture at 786 nm were μa = 0.05 cm1 and , respectively. The
transport mean free path was . The diffuse wave number (i.e. the
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inverse characteristic length over which the diffuse waves decay exponentially) was
. The tank thickness was therefore much larger than *, and thus the
experiments were carried out in the diffusion regime. In addition k dL 6.6, and thus the
transmitted light was substantially attenuated. These parameters are typical of human breast
tissues in the NIR spectral region.
2.2. Targets
Targets were made of a mixture of silicone rubber (RTV-12, General Electric, Waterford, NY),
titanium dioxide (T-8141, Sigma-Aldrich, St. Louis, MO), and carbon black (Raven 5000 Ultra
Powder II, Columbian Chemicals Co., Marietta, GA) [32]. The ingredients were mixed in a
proportion such that the reduced scattering coefficient of the targets was approximately
matched to that in the surrounding fluid while the absorption coefficient μa was four times
larger. Targets were made in the shape of letters (3 cm tall, 2 cm wide, 5 mm thick with
individual components 3 mm in width), and bars (6 cm tall, 5 mm thick, with widths of 7-9
mm).
Titration experiments were performed using an 18 mm tall clear plastic cylinder with a diameter
of 17 mm and 1 mm thick walls. It was positioned in the center of the tank. Laboratory tubing
(outer diameter 2 mm) was used to flow fluid through the cylinder. During the first scan, the
cylinder contained matching fluid identical to the fluid in the tank. Twelve titrations were then
performed in which the ratio of ink concentration in the cylinder to that in the tank gave an
expected absorption contrast ranging from 2:1 to 64:1.
2.3. Theoretical background
We use the diffusion approximation to the radiative transport equation [1,33] to model the
propagation of multiply-scattered light. The approximation is valid if . This condition
was satisfied everywhere in the experimental medium. In the diffusion approximation, the
electromagnetic energy density u(r) inside the medium obeys the diffusion equation
(1)
Here the diffusion coefficient, c is the average speed of light in the
medium and S is the power density of the source. The diffusion equation (1) is supplemented
by the boundary condition
(2)
where is the extrapolation distance [33,34]. In the same limit that is required for validity of
the diffusion approximation, . Thus, if the reduced scattering coefficient is the
same inside the target and the surrounding medium, we have D D(0) = const. In this case, the
goal of DOT is to reconstruct μa(r) from a set of boundary measurements of u(r), assuming
D(0) is known. We, however, do not imply that reconstruction of is not possible or not
important in general. As was discussed in references [30,31], simultaneous reconstruction of
μa and is possible with the use of either time-resolved or frequency resolved measurements.
The fast image reconstruction method described in Section 2.4 can easily be generalized to the
case of heterogeneous [30,31].
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In our experiments, light entered the tank at the point rs = (ρs,zs). The CCD camera measured
the intensity of the beam exiting through the opposite surface at the point rd = (ρd,zd). Here
the z-axis is perpendicular to the slab, and |zd zs| = L is the slab thickness, while ρs and ρd
are the two-dimensional radius-vectors characterizing the transverse coordinates of the source
and detector, respectively. The measured intensity in such an experiment, I(rd,rs), is
mathematically related to the Green's function of the diffusion equation (1), G(rd,rs), by I
(rd,rs) = CdCsG(rd,rs). Here Cd and Cs are coupling constants which depend, in particular, on
the extrapolation distance , the transport mean free path * (see Refs. [30, 31]), and on other
factors; these constants can be excluded from consideration as shown below. Note that for two
arbitrary spatial arguments r and r which may be either on the surface or inside the medium,
G(r,r) can be found from the equation
(3)
and the boundary conditions (2). We next decompose the absorption coefficient μa(r) as
. where is the constant value of the absorption coefficient in the fluid
while δμa(r) represents a spatial fluctuation due to the target. Then the Green's function satisfies
the Dyson equation
(4)
where the integral is taken over the volume of the sample and G0 is the Green's function in the
reference medium with . G0 satisfies Eq. (3) with the substitution and can
be found analytically in an infinite slab [30]. The left-hand side of Eq. (4) is directly measurable
but G(r,rs), which appears in the right-hand side, can not be measured since the point r lies
inside the medium. Since G depends on δμa, the right-hand side of (4) is, generally, a nonlinear
functional of the latter. Several approximate linearization methods can be used to transform
Eq. (4) to an equation which is linear in δμa. We have used the first Rytov approximation,
according to which, the right-hand side in (4) is replaced by the expression
Note that this expression coincides with the right-hand side of (4) to leading order in δμa. We
then define the data function as
(5)
where T(rd,rs) I(rd,rs)/I0(rd,rs) is the experimentally measurable transmission function. Here
I0(rd,rs) is the result of a measurement in a reference homogeneous medium with δμa = 0. We
then obtain the following linear integral equation:
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(6)
The kernel Γ(rd,rs;r) = G0(rd,r)G0(r,rs) is known analytically and the right-hand side
ϕ
(rd,rs) is measured experimentally. Note that we have used the fact that I(rd,rs)/I0(rd,rs) = G
(rd,rs)/G0(rd,rs) to eliminate the coupling constants Cd and Cs. Equations (5) and (6) are the
main equations of linearized DOT. The method we have used for inverting (6) is briefly
described below.
2.4. Inversion formula
The image reconstruction method used by us is based on the translational symmetry of the slab
geometry. The latter allows one to write G0 as
(7)
where the explicit expressions for g(q;z,z) are given in Ref. [30]. Note, both g(q;z,z) and
G0(ρ,z;ρ′, z) are real for continuous-wave measurements. We substitute this plane-wave
decomposition of G0 into (6) and take a four-dimensional Fourier transform with respect to
the source and detector transverse coordinates to obtain
(8)
where the Fourier-transforms are defined as
(9)
(10)
With the change of variables qd = q + p, qs = p, we can now re-write (8) as
(11)
where and κ(q,p;z) = cg(q + p;zs,z)g(p;z,zd).
Thus, the problem has been reduced to inverting a set of linear one-dimensional integral
equations with known kernels κ(q,p;z). We do so for a discrete set of samples of the Fourier
variable q and then use the inverse Fourier transform to obtain δμa(ρ,z). Note that Eq. (11) is
inverted for each sample of q by utilizing multiple discrete values of p. To this end, we construct
analytically the pseudoinverse to the linear integral operator of the left-hand side of (11). The
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mathematical details of this construction are given in Ref. [30]. Computing δμa(ρ,z) by the
inverse Fourier transform accounting for sampling and truncation of real-space data is
discussed in Refs. [25,31]. In Ref. [31], we have considered symmetry-based image
reconstruction algorithms from a more general point of view and a number of special cases
have been derived, including the specific modality used in this paper (Section 3.C.1, “Fourier
tomography”).
The computational complexity of the image reconstruction algorithm described in this section
is , where Nq is the number of discrete values of the vector q, while Np is the number
of discrete values of p used to invert each one-dimensional equation (11). This is the
computational cost of inverting the integral operator only. To this one should add the cost of
Fourier-transforming the real-space data function and computing ψ(q,p). With the use of the
fast Fourier transform, the latter scales as . If the same amount of data and the same
grid of voxels is used with a purely algebraic image reconstruction method, the computational
cost of matrix inversion scales as O((NqNp)3). In the above estimate, we have assumed that the
number of measurements is equal to the number of voxels. We thus see that the fast image
reconstruction methods exploit the block structure of the linear operator that couples the data
to the unknown function. Instead of inverting a large matrix of size NqNp, these methods require
inversion of Nq matrices of the size Np each, thus gaining a factor of in computation time.
We note that reconstructions which utilized data sets of up to 107 source-detector pairs required
less than one minute of CPU time on a 1.3GHz workstation.
2.5. Simulated data
Simulated data functions for a point absorber were generated within the linear approximation
by representing δμa(r) as a delta-function. Data for infinite lattices of sources and detectors
was computed directly in the Fourier domain using (8). For finite lattices we computed G0
numerically using (7) and substituted the result into (9); in the latter formula, summation over
real space variables was truncated.
We then added noise to the data function generated for the finite lattice as follows. We expect
the standard deviation due to shot noise for repeated measurements of a single source detector
pair to be equal to the square root of the mean number of detected photo-electrons
. Propogating the error to the data function defined in equation (5) we get
to first order . We scaled both the simulated data function
and the simulated reference intensity I0 to have the same maximum values as were
experimentally measured. The resulting data function with shot noise was then
(12)
Here R is a random variable with a Gaussian distribution and a variance of one. We note that
since I0
ϕ
, the shot noise depends primarily on the reference intensity, not on the data
function itself. In order to simulate the effect of read noise and dark current, we determined
the stardard deviation σbg of a background image taken with the light source blocked. This
error was propagated as , and the resulting data function was calculated according
to (12).
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3. Experimental results
For the reconstructions shown in Fig. 1, the target was constructed of silicone rubber and shaped
in the form of the letters “DOT” and “PENN”. In the first experiment, we placed the letters
“DOT” one centimeter from the source plane and the letters “PENN” one centimeter from the
detector plane, directly behind the “DOT” letters. The reconstruction is shown in Fig. 1(b).
The letters are clearly visible. Note that the central slice from the middle of the tank is empty,
as expected. In a second experiment we placed the letters “DOT” in the center of the tank (the
letters “PENN” were not present) three centimeters from source and detector planes. The
reconstruction is shown in Fig. 1(c). The letters are clearly reconstructed.
In Fig. 2 we show the data used to reconstruct the images. Only data corresponding to a single
source beam position is shown. For each reconstruction we show, from left to right, the
reference intensity I0 when the target is not present (scattering fluid only), the intensity I when
the target is present, and the Rytov data,
ϕ
= log(I/I0), which is used in the reconstruction
algorithm (see Methods). Note that the letters cannot be identified by simply inspecting images
of the transmitted light. Structure is visible in the Rytov data when the letters “PENN” are close
to the detector plane (Fig. 2(a)). However, when the letters “DOT” are in the center of the tank
(Fig. 2(b)) their shape is completely blurred.
In order to quantify the transverse resolution of the reconstructed images, we prepared several
bar targets from the same material described above. The bars were 7 mm to 9 mm thick and
placed consecutively (one at a time) in the center of the slab. Fig. 3(a) shows the corresponding
reconstructions. As the bar widths decrease, the modulation depth between bars decreases. As
can be seen, all but the 7 mm bar target are well resolved. Fig. 3(b) shows reconstructions for
two experiments in which the 7 mm bar target was positioned 1 cm from the source and detector
planes, respectively. The bars in this figure are well resolved and the images are smoother and
have fewer artifacts. As can be expected, the image is better resolved when the target is closer
to the detector plane. This is because the detectors are sampled on a finer grid than the sources.
Experiments were also performed with bar targets having an absorption contrast of 2:1. The
resulting images were very similar to those acquired with a 4:1 absorption contrast bar targets,
but they contained less contrast and more noise.
The images in Fig. 3 were reconstructed using approximately 107 measurements. The effect
of changing the size of the data set was investigated by sampling the detectors on a grid with
a step size of 2 mm, five times larger than the minimum experimentally available detector
spacing. We found that increasing the number of detectors up to the experimentally available
maximum did not improve image quality. That is, reconstructions performed using 2 mm
source separations or with a denser sampling of CCD pixels were visually indistinguishable
from those in Fig. 3. However, decreasing the number of data points does result in poorer
image quality, as is illustrated in Fig. 4. From left to right, three separate reconstructions of the
8 mm bar target are shown. The data for these reconstructions were taken from a single
experiment with the target positioned in the center of the tank. All reconstruction parameters
are kept constant, except for the number of measurements used. The reconstruction on the left
uses 8 × 106 measurements with sources and detectors sampled with 4 mm and 2 mm steps,
respectively. In the center reconstruction, we use 4 mm spacing for both the sources and
detectors, which corresponds to 2 × 106 data points. In the reconstruction on the right, the
sampling is 8 mm for sources and 4 mm for detectors, or, approximately, 5 × 105 data points.
It can be seen that as the number of measurements decreases, image artifacts become more
prominent and resolution is lost. We note that the optimal number measurements for a given
experiment will vary depending on factors such as experimental geometry and noise level. For
example, smaller/larger data sets would be optimal if the reconstruction field of view was
smaller/larger.
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To investigate the capability for quantitative reconstruction of the absorption coefficient, we
have performed a titration experiment. A clear plastic cylinder was positioned in the center of
the tank, and laboratory tubing was used to flow fluid through the cylinder. During the first
scan, the cylinder contained scattering fluid identical to the fluid in the tank. Twelve titrations
were then performed in which the ratio of ink concentration in the cylinder, to that in the tank,
gave an expected absorption contrast ranging from 2:1 to 64:1. The absorption contrast, i.e.,
the ratio of the absorption coefficient in the cylinder to that in the surrounding fluid, was taken
from the corresponding reconstructed value for a single voxel located inside the cylinder. This
voxel was chosen to be the voxel with the maximum reconstructed value of the absorption
coefficient for the tenth titration. In Fig. 5, the reconstructed contrast is plotted against
the expected contrast. It can be seen that the absorption is quantitatively reconstructed with a
linear dependence on ink concentration over nearly a decade in absorption contrast. Deviation
from linearity occurs at higher concentrations, as expected.
4. Discussion
4.1. Transverse resolution and Fourier analysis of data
Factors that limit the ability to achieve even greater spatial resolution include the finite size of
the source and detector grids, the shot noise in the measured light, the noise in the CCD array
(a combination of dark current and read noise), and systematic errors. The latter are errors of
the model. In particular, the light transmitted through the tank is described by the diffusion
equation only approximately. There are also systematic errors associated with non-ideal optics
(diffraction, multiple reflections on the lens and tank surfaces). Finally, there are systematic
errors associated with the nonlinearity of the inverse problem of DOT.
To better understand the dependence of transverse spatial resolution on the factors listed above,
we performed the following analysis. Let all inhomogeneities be confined in a thin slice of the
medium parallel to the slab, z0 h/2 < z < z0 + h/2, where h is small. We seek to reconstruct
the deviation of the absorption coefficient in this slice, δμa(ρ,z0), from the respective value in
the surrounding fluid, as a function of the transverse variable ρ = (x,y). The formula (11) derived
in the Methods Section becomes in this case
Here ψ(q,p) is the measurable data function, κ(q,p) is known analytically (see Methods for
precise definitions of ψ and κ), and δμa(q,z0) is the transverse Fourier transform of δμa(ρ,z0)
with respect to ρ. The real-space function δμa(ρ,z0) is obtained by inverse Fourier
transformation, namely,
The choice of p in the above formula is arbitrary since the problem is overdetermined (we use
four-dimensional data to reconstruct a two-dimensional function); it is sufficient to choose p
= 0. We then use the data function ψ(q,0) for reconstruction. The latter is taken from experiment
and contains noise. It is important to note that the “ideal” data function is rapidly
(exponentially) decreasing with |q|. However, the experimental noise is approximately white,
i.e., the amplitude of its Fourier transform is approximately constant in the range of |q| which
is of interest. In image reconstruction, integration in the above formula is over a disc |q| <
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qmax such that outside of this disc, the signal-to-noise ratio in ψ(q,0) becomes smaller than
unity. It then follows that the minimum spatial feature that can be resolved has a characteristic
transverse dimension of Δx π/qmax.
A few comments on the above analysis are necessary. First, if the target is not confined to a
thin slice, the transverse resolution can only be lower than the estimate π/qmax. Second, one
can attempt to use additional degrees of freedom (i.e., N distinct values of p) to improve the
resolution. This approach, however, is not expected to yield a significant improvement since
the noise amplitude decreases no faster than , while the function ψ(q,p) decreases
exponentially with |q|.
To illustrate the above resolution estimate, we plot in Fig. 6 the power spectrum of the data for
a point absorber located in the center of the tank. The data function ψ(q,0) is in this case
cylindrically symmetric and we can write ψ(q,0) = Ψ(q), where q = |q|. The five curves shown
in Fig. 6 contain (i) simulated ideal data corresponding to infinitely large and dense grids of
noiseless sources and detectors, (ii) simulated data (without noise) for the finite grids of sources
and detectors that were used in the experiments, (iii) simulated data for the finite grids with
background noise added (i.e. Gaussian distributed noise with a variance equal to the variance
of the detected signal when the laser is off), (iv) simulated data for the finite grid with shot
noise added (i.e. Gaussian distributed noise with a variance equal to the number of photo-
electrons detected experimentally), and (v) data from an experiment with a small (4 mm) highly
absorbing target in the tank (see Methods for details of the simulations). The early onset of
noise in the simulated data with shot noise, suggests the latter is the limiting factor in our
experiments. We thus conclude that the other errors discussed above (e.g. the finite numbers
of sources and detectors, CCD noise, errors in the diffusion model, non-ideal optics, and non-
linearity) do not play a significant role in limiting image resolution. We see that noise begins
to dominate the data at qmax/π 0.1 mm1. This corresponds to a spatial resolution of 1 cm.
For objects closer to the surface, the power spectrum decays more slowly. For example, for a
point absorber located 1 cm from the surface, shot noise begins to dominate the data at qmax/
π 0.25 mm1, which corresponds to a spatial resolution of 4 mm.
4.2. Titration experiments
The saturation effect seen in Fig. 5 can be explained as follows. When the absorption of the
target is very high, most of the light is absorbed as soon as it enters the target and almost no
light reaches its interior; the absorption coefficient of the interior can be arbitrarily changed
with no significant effect on the measured signal. This is a manifestation of the nonlinearity
of the inverse problem of DOT. Note that the onset of nonlinearity in Fig. 5 occurs at absorber
concentrations which are well beyond the range of contrast encountered in biological tissues.
We finally note that the nonlinearity becomes stronger when the absorbing target becomes
larger, as less and less light can penetrate the interior.
5. Conclusion
We have obtained high quality, quantitatively accurate, reconstructed images of complex
structures deeply embedded in highly-scattering media. This result was achieved by using both
a non-contact scanner capable of collecting large amounts of data and a fast image
reconstruction algorithm capable of utilizing this data. We expect that these techniques will
greatly improve the utility of diffuse optical methods in biomedical imaging.
Acknowledgments
This research was supported, in part, by the NIH grants R01-CA75124, R01-EB-002109, NTROI 1U54CA105480,
P41RR02305, R21EB004524, R01-EB-004832 and by the NSF under grants DMS-0554100 and EEC-0615857.
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Fig. 1.
Slices from three dimensional image reconstructions of the relative absorption coefficient
for targets suspended in a 6 cm thick slab filled with highly scattering fluid. The
three slices shown for each reconstruction correspond to depths of 1 cm (left), 3 cm (middle),
and 5 cm (right) from the source plane. The field of view in each slice is 16 cm × 16 cm. The
quantity plotted is (a) Schematics of the positions of the letters during the experiments.
Left: The target consists of letters “DOT” and “PENN”, suspended 1 cm and 5 cm from the
source plane, respectively. Right: The target consists only of the letters “DOT” suspended 3
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cm from the source plane, i.e., in the center of the slab. (b) Reconstructed image of the letters
“DOT” and “PENN” (c) Reconstructed image of the letters “DOT”.
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Fig. 2.
Representative CCD data for the image reconstructions shown in Fig. 1. Each image
corresponds to the measured light intensity for a single source beam position. The left column
shows the reference intensity I0 when the target is not present (scattering fluid only). The middle
column shows the intensity I when the target is present. The right column shows the Rytov
data,
ϕ
= log(I/I0), which is used in the reconstruction algorithm. (a) The target consists of
the letters “DOT” and “PENN” (b) The target consists of the letters “DOT” only
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Fig. 3.
Reconstructed images of bar targets. Only slices drawn at the depth of the actual target are
shown. (a) 7 mm to 9 mm bar targets located in the center of the tank. Here d denotes the width
of the individual bars in the targets. (b) The 7 mm bar target located 1 cm from the source (left)
and detector (right) planes.
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Fig. 4.
Images of the 8 mm bar target from a single experiment. All reconstruction parameters are held
fixed except for the number of measurements used. From left to right, correspond to N = 8 ×
106, 2 × 106, and 5 × 105 measurements were used for the reconstruction.
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Fig. 5.
Reconstructed contrast of the absorption coefficient between the cylinder and the tank
vs. the expected contrast.
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Fig. 6.
Power spectra of the data function |Ψ(q)|2 (defined in the text) for a small absorber located in
the center of the tank. The different curves correspond to simulated ideal data, simulated data
from finite grids of sources and detectors, simulated data with background noise, simulated
data with shot noise, and to experimental data, as indicated.
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... [δD(r )∇u 0 (r ) · ∇G(r, r ) + δµ a (r )u 0 (r )G(r, r )] dr . (55) In the following analysis we assume that D 0 is constant in Ω, as it is customary done in CW-DOT applications (see, e.g., papers [37,101] for examples of such a simplification which is customarily applied when a fast computation is required). Hence a reduced version of Equation (55) can be considered. ...
... Materials for which the total distance a photon has propagated through the material L * are said to be in the diffusive regime [13,14]. The task of reconstructing images in the highly diffusive regime is nontrivial since the problem is ill-posed [15][16][17][18], although computational strategies have successfully improved the condition of the inverse problem [19][20][21][22][23][24][25][26][27][28][29] and enabled imaging through >80 * [30]. In relatively thin materials <10 * , there is a significant probability of detecting, at very early times, ballistic photons that are transmitted without any scattering events and which preserve spatial information [31][32][33][34][35][36][37]. ...
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... DOS measures oxy-haemoglobin and deoxy-haemoglobin concentrations, and has been successfully employed for the assessment of tissue haemodynamics [13][14][15][16][17][18][19][20][21] in clinical problems, such as breast cancer diagnosis and therapy monitoring 19,22 , brain function 23 and injury monitoring 17 . In most of these applications, however, reflected light penetration is limited to less than 2 cm below the surface 24,25 . The new instrumentation and algorithms that we report here provide improvements in methodology needed to measure the oxygen haemodynamics of the anterior placenta amidst intervening heterogeneous tissue layers. ...
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Direct assessment of blood oxygenation in the human placenta can provide information about placental function. However, the monitoring of placental oxygenation involves invasive sampling or imaging techniques that are poorly suited for bedside use. Here we show that placental oxygen haemodynamics can be non-invasively probed in real time and up to 4.2 cm below the body surface via concurrent frequency-domain diffuse optical spectroscopy and ultrasound imaging. We developed a multimodal instrument to facilitate the assessment of the properties of the anterior placenta by leveraging image-reconstruction algorithms that integrate ultrasound information about the morphology of tissue layers with optical information on haemodynamics. In a pilot investigation involving placentas with normal function (15 women) or abnormal function (9 women) from pregnancies in the third trimester, we found no significant differences in baseline haemoglobin properties, but statistically significant differences in the haemodynamic responses to maternal hyperoxia. Our findings suggest that the non-invasive monitoring of placental oxygenation may aid the early detection of placenta-related adverse pregnancy outcomes and maternal vascular malperfusion.
... The photon flux, Φ within the medium is described by the photon diffusion equation [46][47][48][49][50][51]: ...
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The ability to image through turbid media, such as organic tissues, is a highly attractive prospect for biological and medical imaging. This is challenging, however, due to the highly scattering properties of tissues which scramble the image information. The earliest photons that arrive at the detector are often associated with ballistic transmission, whilst the later photons are associated with complex paths due to multiple independent scattering events and are therefore typically considered to be detrimental to the final image formation process. In this work, we report on the importance of these highly diffuse, “late” photons for computational time-of-flight diffuse optical imaging. In thick scattering materials, >80 transport mean free paths, we provide evidence that including late photons in the inverse retrieval enhances the image reconstruction quality. We also show that the late photons alone have sufficient information to retrieve images of a similar quality to early photon gated data. This result emphasises the importance in the strongly diffusive regime of fully time-resolved imaging techniques.
... Diffuse optical tomography [1][2][3][4][5] can probe non-invasively deep into scattering medium like biological tissues and provides quantitative measurement of the optical absorption and scattering properties. Though extensively employed both in the pre-clinical research and clinical imaging, it is plagued with a poor spatial resolution due to the ill-posed inversion of photon transport in the diffusive regime. ...
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Diffuse optical tomography (DOT) is well known to be ill-posed and suffers from a poor resolution. While time domain DOT can bolster the resolution by time-gating to extract weakly scattering photons, it is often confronted by an inferior signal to noise ratio and a low measurement density. This is particularly problematic for non-contact DOT imaging of non-planar objects, which faces an inherent tradeoff between the light collection efficiency and depth of field. We present here ultrafast contour imaging, a method that enables efficient light collection over curved surfaces with a dense spatiotemporal sampling of diffused light, allowing DOT imaging in the object’s native geometry with an improved resolution. We demonstrated our approach with both phantom and small animal imaging results. ©2020 Optical Society of America
... Diffuse optical tomography (DOT) reconstructs objects within thick scattering media by modeling the diffusion of light from illumination sources to detectors placed around the scattering volume 27,28 . While conventional CMOS detectors have been used for DOT 29,30 , time-resolved detection 2,31-36 is promising because it enables direct measurement of the path lengths of scattered photons. ...
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Optical imaging techniques, such as light detection and ranging (LiDAR), are essential tools in remote sensing, robotic vision, and autonomous driving. However, the presence of scattering places fundamental limits on our ability to image through fog, rain, dust, or the atmosphere. Conventional approaches for imaging through scattering media operate at microscopic scales or require a priori knowledge of the target location for 3D imaging. We introduce a technique that co-designs single-photon avalanche diodes, ultra-fast pulsed lasers, and a new inverse method to capture 3D shape through scattering media. We demonstrate acquisition of shape and position for objects hidden behind a thick diffuser (≈6 transport mean free paths) at macroscopic scales. Our technique, confocal diffuse tomography, may be of considerable value to the aforementioned applications.
... The photon flux, Φ within the medium is described by the photon diffusion equation [43][44][45][46][47][48]: ...
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The ability to image through turbid media such as organic tissues, is a highly attractive prospect for biological and medical imaging. This is challenging however, due to the highly scattering properties of tissues which scramble the image information. The earliest photons that arrive at the detector are often associated with ballistic transmission, whilst the later photons are associated with complex paths due to multiple independent scattering events and are therefore typically considered to be detrimental to the final image formation process. In this work we report on the importance of these highly diffuse, "late" photons for computational time-of-flight diffuse optical imaging. In thick scattering materials, >80 transport mean free paths, we provide evidence that including late photons in the inverse retrieval enhances the image reconstruction quality. We also show that the late photons alone have sufficient information to retrieve images of a similar quality to early photon gated data. This result emphasises the importance in the strongly diffusive regime discussed here, of fully time-resolved imaging techniques.
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Background Functional near-infrared spectroscopy (fNIRS) is a suitable tool for recording brain function in pediatric or challenging populations. As with other neuroimaging techniques, the scientific community is engaged in an evolving debate regarding the most adequate methods for performing fNIRS data analyses. New method We introduce LIONirs, a neuroinformatics toolbox for fNIRS data analysis, designed to follow two main goals: (1) flexibility, to explore several methods in parallel and verify results using 3D visualization; (2) simplicity, to apply a defined processing pipeline to a large dataset of subjects by using the MATLAB Batch System. Results Within the graphical user interfaces (DisplayGUI), the user can reject noisy intervals and correct artifacts, while visualizing the topographical projection of the data onto the 3D head representation. Data decomposition methods are available for the identification of relevant signatures, such as brain responses or artifacts. Multimodal data recorded simultaneously to fNIRS, such as physiology, electroencephalography or audio-video, can be visualized using the DisplayGUI. The toolbox includes several functions that allow one to read, preprocess, and analyze fNIRS data, including task-based and functional connectivity measures. Comparison with existing methods Several good neuroinformatics tools for fNIRS data analysis are currently available. None of them emphasize multimodal visualization of the data throughout the preprocessing steps and multidimensional decomposition, which are essential for understanding challenging data. Furthermore, LIONirs provides compatibility and complementarity with other existing tools by supporting common data format. Conclusions LIONirs offers a flexible platform for basic and advanced fNIRS data analysis, shown through real experimental examples. Highlights The LIONirs toolbox is designed for fNIRS data inspection and visualization. Methods are integrated for isolation of relevant activity and correction of artifacts. Multimodal auxiliary, EEG or audio-video are visualized alongside the fNIRS data. Task-based and functional connectivity measure analysis tools are available. The code structure allows to automated and standardized analysis of large data set. Graphical abstract
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Optical methods offer a range of spectoscopies useful for characterization of a wide variety of samples. The optical spectroscopies are rigorous, and work well in simple, homogenous, optically thin samples. Unfortunately many practical materials are not so simple. Human tissues, for example, are highly scattering media. Light penetration in tissues is limited, and generally the effects of tissue absorption and internal motion must be separated from the effects of tissue scattering. Nevertheless, the use of light to investigate the human body interior has grown enormously in recent years, in part as a result in advances in our fundamental understanding about light transport in highly scattering materials, and in part as a result of technological innovations in optics [1]. Using examples from my laboratory I will discuss the basic physical ideas that underly diffusing light probes, as well as some of their applications. [1] See for example, Spectroscopy and Imaging with Diffusing Light (Arjun Yodh and Britton Chance), Physics Today, Volume 48, No. 3, 34-40 (1995).
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