This work investigates a forward model associated with intra-lumenal detection of acoustic signal originated from
transient thermal-expansion of the tissue. The work is specific to intra-lumenal thermo-acoustic tomography (TAT)
which detects the contrast of tissue dielectric properties with ultrasonic resolution, but it is also extendable to intralumenal
photo-acoustic tomography (PAT) which detects the contrast of light absorption properties of tissue with
ultrasound resolution. Exact closed-form frequency-domain or time-domain forward model of thermally-induced
acoustic signal have been studied rigorously for planar geometry and two other geometries, including cylindrical and
spherical geometries both of which is specific to external-imaging, i.e. breast or brain imaging using an externally-deployed
applicator. This work extends the existing studies to the specific geometry of internal or intra-lumenal imaging,
i.e., prostate imaging by an endo-rectally deployed applicator. In this intra-lumenal imaging geometry, both the source
that excites the transient thermal-expansion of the tissue and the acoustic transducer that acquires the thermally-induced
acoustic signal are assumed enclosed by the tissue and on the surface of a long cylindrical applicator. The Green's
function of the frequency-domain thermo-acoustic equation in spherical coordinates is expanded to cylindrical
coordinates associated with intra-lumenal geometry. Inverse Fourier transform is then applied to obtain a time-domain
solution of the thermo-acoustic pressure wave for intra-lumenal geometry. Further employment of the boundary
condition to the "convex" applicator-tissue interface would render an exact forward solution toward accurate
reconstruction for intra-lumenal thermally-induced acoustic imaging.
We predict the phenomenon of "spiral-planar equivalence" for steady-state photon diffusion associated with a cylindrical
applicator. Recently we have derived a unified theory of steady-state photon diffusion in a homogenous medium
bounded either externally (referred to as a concave geometry) or internally (referred to as a convex geometry) by an
infinitely long circular cylindrical applicator [JOSAA, 27(3): 648-662 (2010)]. Despite the idealization of the geometry
by assuming an infinite length of the applicator, the analytic prediction withholds the quantitative examinations based on
experimental measurements, and finite-element solution of photon diffusion. An interesting finding is that the decay of
photon fluence in a concave boundary is smaller in the azimuth direction but greater along the longitudinal direction, in
comparison with that in a semi-infinite geometry along a straight line, for the same line-of-sight distance between the
source and the detector. Conversely, the decay of photon fluence in a convex boundary is greater in the azimuth direction
but smaller along the longitudinal direction, in comparison with that in a semi-infinite geometry along a straight line, for
the same line-of-sight source-detector distance. These findings suggest that on the cylindrical applicator interface there
should exist a spiral direction (oblique to both the azimuthal and longitudinal directions), along which the rate of photon
fluence decay follows that along a straight line on a planar semi-infinite interface---which is called the "spiral-planar
equivalence". The "spiral-planar equivalence" is derivable analytically, and subject to quantitative evaluations.
Validating the "spiral-planar equivalence" not only enriches the understanding of photon diffusion in cylindricalinterface
geometry, but also provides unique semi-infinite-based imaging application in trans-lumenal diffuse optical
sensing. The "spiral-planar equivalence" may be applicable to time-resolved photon-diffusion.
Needle-based core-biopsy to locate prostate cancer relies heavily upon trans-rectal
ultrasound (TRUS) imaging guidance. Ultrasonographic findings of classic hypoechoic
peripheral zone lesions have a low specificity of ~28%, a low positive predictive value of ~29%,
and an overall accuracy of ~43%, in prostate cancer diagnosis. The prevalence of isoechoic or
nearly invisible prostate cancers on ultrasonography ranges from 25 to 42%. As a result, TRUS
is useful and convenient to direct the needle trajectory following a systematic biopsy sampling
template rather than to target only the potentially malignant lesion for focal-biopsy. To address
this deficiency in the first-line of prostate cancer imaging, a trans-rectal ultrasound-coupled
spectral tomography (TRUST) approach is being developed to non-invasively resolve the likely
optical signatures of prostate malignancy. The approach has evolved from using one NIR
wavelength to two NIR bands, and recently to three bands of NIR spectrum information. The
concept has been evaluated on one normal canine prostate and three dogs with implanted prostate
tumor developed as a model. The initial results implementing TRUST on the canine prostate
tumor model includes: (1) quantifying substantially increased total hemoglobin concentration
over the time-course of imaging in a rapidly growing prostate tumor; (2) confirming hypoxia in a
prostatic cystic lesion; and (3) imaging hypoxic changes of a necrotic prostate tumor. Despite
these interesting results, intensive technologic development is necessary for translating the
approach to benefiting clinical practice, wherein the ultimate utility is not possibly to eliminate
needle-biopsy but to perform focal-biopsy that is only necessary to confirm the cancer, as well as
to monitor and predict treatment responses.
Different optical spectral characteristics were observed in a necrotic transmissible venereal tumor
(TVT) and a cystic lesion in the same canine prostate by triple-wavelength trans-rectal optical
tomography under trans-rectal ultrasound (TRUS) guidance. The NIR imager acquiring at 705nm,
785nm and 808nm was used to quantify both the total hemoglobin concentration (HbT) and oxygen
saturation (StO2) in the prostate. The TVT tumor in the canine prostate as a model of prostate cancer
was induced in a 7-year old, 27 kg dog. A 2 mL suspension of 2.5x106 cells/mL of homogenized
TVT cells recovered from an in vivo subcutaneously propagated TVT tumor in an NOD/SCID
mouse were injected in the cranial aspect of the right lobe of the canine prostate. The left lobe of the
prostate had a cystic lesion present before TVT inoculation. After the TVT homogenate injection,
the prostate was monitored weekly over a 9-week period, using trans-rectal NIR and TRUS in grey-scale
and Doppler. A TVT mass within the right lobe developed a necrotic center during the later
stages of this study, as the mass presented with substantially increased [HbT] in the periphery, with
an area of reduced StO2 less than the area of the mass itself shown on ultrasonography. Conversely,
the cystic lesion presented with slightly increased [HbT] in the periphery of the lesion shown on
ultrasound with oxygen-reduction inside and in the periphery of the lesion. There was no detectable
change of blood flow on Doppler US in the periphery of the cystic lesion. The slightly increased
[HbT] in the periphery of the cystic lesion was correlated with intra-lesional hemorrhage upon
histopathologic examination.
In vivo trans-rectal near-infrared (NIR) optical tomography was performed concurrently with, albeit reconstructed without spatial a prior of, trans-rectal ultrasound (US) on transmissible venereal tumor (TVT) developed as a model in the canine pelvic canal. Studies were taken longitudinally at prior to, 14 days after, and 35 days after the TVT injection. As the tumor grew, the nodules became increasingly hyperabsorptive and moderately hyperscattering on NIR. The regions of strong NIR contrast, especially on absorption images, correlated well with those of US hypoechoic masses indicative of tumors. Combining the information of trans-rectal NIR and US detected the tumor more accurately than did the US alone at 14 days postinjection.
An approach of hierarchically implementing the spatial prior information in trans-rectal optical
tomography is introduced. Trans-rectal optical imaging of the prostate deals with photon propagation
through the rectum wall, the peri-prostate tissue and the prostate. Reconstructing a lesion in the prostate
is challenging due to the structural complexity as well as the optical heterogeneity. Incorporating spatial
"hard" a priori information available from complementary imaging modalities such as trans-rectal
ultrasound could in principle improve the accuracy of trans-rectal optical tomography reconstruction.
However, the reconstruction is potentially subject to the local-minimum sensitivity if the values of all
regional optical properties are to be initialized simultaneously. We propose a hierarchical spatial prior
approach for trans-rectal optical tomography reconstruction. Instead of assigning the initial values to all
sub-regions at once, a region is initially assumed homogenous, and the reconstructed optical properties
are used as the initial guess for the region as a background when a sub-region is included in the next step.
This approach translates to a 3-step iteration routine whereby the first step reconstructs the entire imaging
volume as a single region, the second step uses these results as the initial guess of peri-prostate tissue to
reconstruct the prostate and the rectum wall, and the third step assigns the updated results as the initial
values of 3 existing regions to reconstruct a lesion inside the prostate. This approach, validated by
simulation and applied to experimental measurements, is more reliable in global convergence, robust in
imaging of single or multiple targets, and accurate for the recovering of optical properties.
In vivo trans-rectal near-infrared (NIR) optical tomography is conducted on a tumor-bearing canine prostate
with the assistance of trans-rectal ultrasound (TRUS). The canine prostate tumor model is made possible by a unique
round cell neoplasm of dogs, transmissible venereal tumor (TVT) that can be transferred from dog to dog regardless of
histocompatibility. A characterized TVT cell line was homogenized and passed twice in subcutaneous tissue of
NOD/SCID mice. Following the second passage, the tumor was recovered, homogenized and then inoculated by
ultrasound guidance into the prostate gland of a healthy dog. The dog was then imaged with a combined trans-rectal NIR
and TRUS imager using an integrated trans-rectal NIR/US applicator. The image was taken by NIR and US modalities
concurrently, both in sagittal view. The trans-rectal NIR imager is a continuous-wave system that illuminates 7 source
channels sequentially by a fiber switch to deliver sufficient light power to the relatively more absorbing prostate tissue
and samples 7 detection channels simultaneously by a gated intensified high-resolution CCD camera. This work tests the
feasibility of detecting prostate tumor by trans-rectal NIR optical tomography and the benefit of augmenting TRUS with
trans-rectal NIR imaging.
The geometry of trans-lumenal diffuse optical measurement is considerably different from that of externally applied
diffuse optical imaging. In externally-applied diffuse optical imaging of breast, brain, etc, an analytic solution to
the diffusion equation for a planar semi-infinite medium is often applied. This solution works accurately for planar
applicator and is a good approximation for a ring applicator of considerable size. In trans-lumenal diffuse optical
imaging of internal organs like the prostate, the applicator likely should have a convex surface profile for interfacing
with a typically circular cross-section of the lumen. The influence of this convex applicator shape upon the photon
transport is expected to cause a deviation from the solution predicted by a semi-infinite planar boundary. This
interference, if available, is particularly relevant to the axial geometry in trans-lumenal diffuse optical imaging. This
work investigates the analytic solution of continuous-wave photon diffusion equation for axial imaging when a
cylindrical trans-lumenal applicator is used. The Green's function of the photon diffusion equation in an infinite medium
geometry is expanded in cylindrical coordinates, and an image-source method is utilized to derive the analytic solution
for circular concave & circular convex boundary profiles based on extrapolated boundary condition. Numerical
evaluations are conducted to examine the effect of the circular boundary. Empirical solution potentially useful for
calibrating the photon remission data in a circular boundary is also derived. The numerical evaluation results and the
empirical solution are subject to validation against Monte Carlo simulations and experimental measurements.
The trans-rectal implementation of NIR optical tomography makes it possible to assess functional status like hemoglobin
concentration and oxygen saturation in prostate non-invasively. Trans-rectal NIR tomography may provide tissue-specific
functional contrast that is potentially valuable for differentiation of cancerous lesions from normal tissues. Such
information will help to determine if a prostate biopsy is needed or can be excluded for an otherwise ambiguous lesion.
The relatively low spatial resolution due to the diffuse light detection in trans-rectal NIR tomography, however, limits
the accuracy of localizing a suspicious tissue volume. Trans-rectal ultrasound (TRUS) is the clinical standard for guiding
the positioning of biopsy needle owing to its resolution and convenience; nevertheless, TRUS lacks the pathognomic
specificity to guide biopsy to only the suspicious lesions. The combination of trans-rectal NIR tomography with TRUS
could potentially give better differentiation of cancerous tissue from normal background and to accurately localize the
cancer-suspicious contrast obtained from NIR tomography. This paper will demonstrate the design and initial evaluation
of a trans-rectal NIR tomography probe that can conveniently integrate with a commercial TRUS transducer. The transrectal
NIR tomography obtained from this probe is concurrent with TRUS at matching sagittal imaging plane. This
design provides the flexibility of simple correlation of trans-rectal NIR with TRUS, and using TRUS anatomic
information as spatial prior for NIR image reconstruction.
Near-infrared optical tomography is an interesting technique of imaging with high blood-based contrast. Unfortunately non-invasive NIR tomographic imaging has been restricted to specific organs like breast that can be transilluminated externally. In this paper, we demonstrate that near-infrared (NIR) optical tomography can be employed at the endoscope-scale, and implemented at a rapid sampling speed that allows translation to in vivo use. A spread-spectral-encoding technique based on a broadband light source is combined with light delivery by linear-to-circular fiber bundle, to provide endoscopic probing of multiple source/detector fibers for tomographic imaging as well as parallel sampling of all source-detector pairs for rapid data acquisition. Endoscopic NIR tomography is demonstrated by use of a 12mm diameter probe housing 8 sources and 8 detectors at 8 Hz frame rate. Transrectal NIR optical tomography by use of tissue specimen is also presented. This novel approach provides the key feasibility studies to allow this blood-based contrast imaging technology to be tried in cancer detection of internal organs via endoscopic interrogation.
Endoscopic near-infrared (NIR) optical tomography is a novel approach that allows the blood-based high intrinsic
optical contrast to be imaged for the detection of cancer in internal organs. In endoscopic NIR tomography, the imaging
array is arranged within the interior of the medium as opposed to the exterior as seen in conventional NIR tomography
approaches. The source illuminates outward from the circular NIR probe, and the detector collects the diffused light
from the medium surrounding the NIR probe. This new imaging geometry may involve forward and inverse approaches
that are significantly different from those used in conventional NIR tomography. The implementation of a hollow-centered
forward mesh within the context of conventional NIR tomography reconstruction has already led to the first
demonstration of endoscopic NIR optical tomography. This paper presents some fundamental computational aspects
regarding the performance and sensitivity of this endoscopic NIR tomography configuration. The NIRFAST modeling
and image reconstruction package developed for conventional circular NIR geometry is used for endoscopic NIR
tomography, and initial quantitative analysis has been conducted to investigate the "effective" imaging depth, required
mesh resolution, and limit in contrast resolution, among other parameters. This study will define the performance
expected and may provide insights into hardware requirements needed for revision of NIRFAST for the endoscopic NIR
tomography geometry.
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