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High-resolution imaging diagnosis of
human fetal membrane by
three-dimensional optical coherence
tomography
Hugang Ren
Cecilia Avila
Cynthia Kaplan
Yingtian Pan
Journal of Biomedical Optics 16(11), 116006 (November 2011)
High-resolution imaging diagnosis of human fetal
membrane by three-dimensional optical coherence
tomography
Hugang Ren,aCecilia Avila,bCynthia Kaplan,cand Yingtian Pana
aStony Brook University, Department of Biomedical Engineering, Stony Brook, New York 11794
bStony Brook University, Department of Obstetrics, Gynecology, and Reproductive Medicine,
Stony Brook, New York 11794
cStony Brook University, Department of Pathology, Stony Brook, New York 11794
Abstract. Microscopic chorionic pseudocyst (MCP) arising in the chorion leave of the human fetal membrane
(FM) is a clinical precursor for preeclampsia which may progress to fatal medical conditions (e.g., abortion) if left
untreated. To examine the utility of three-dimensional (3D) optical coherence tomography (OCT) for noninvasive
delineation of the morphology of human fetal membranes and early clinical detection of MCP, 60 human FM
specimens were acquired from 10 different subjects undergoing term cesarean delivery for an ex vivo feasibility
study. Our results showed that OCT was able to identify the four-layer architectures of human FMs consisting of
high-scattering decidua vera (DV, average thickness dDV ≈92 ±38 μm), low-scattering chorion and trophoblast
(CT, dCT ≈150 ±67 μm), high-scattering subepithelial amnion (A, dA≈95 ±36 μm), and low-scattering epithe-
lium (E, dE≈29 ±8μm). Importantly, 3D OCT was able to instantaneously detect MCPs (low scattering due to
edema, fluid buildup, vasodilatation) and track (staging) their thicknesses dMCP ranging from 24 to 615 μm. It was
also shown that high-frequency ultrasound was able to compliment OCT for detecting more advanced thicker
MCPs (e.g., dMCP>615 μm) because of its increased imaging depth. C
2011 Society of Photo-Optical Instrumentation Engineers
(SPIE). [DOI: 10.1117/1.3646530]
Keywords: optical coherence tomography; high-frequency ultrasound; fetal membrane; microscopic chorionic pseudocyst; preeclamp-
sia.
Paper 11142RRR received Mar. 22, 2011; revised manuscript received Sep. 12, 2011; accepted for publication Sep. 15, 2011; published
online Oct. 26, 2011.
1 Introduction
Preeclampsia is a medical disorder associated with increased
blood pressure and proteinuria during pregnancy or postpartum
period.1It persists as a major cause of maternal and fetal mortal-
ity and morbidity in the United States and worldwide, affecting
5% to 8% of all pregnancies.2Preeclampsia may progress to
eclampsia, which is potentially a fatal medical condition, thus
rendering it crucial for clinical management.3Current diagno-
sis of preeclampsia mainly relies on clinical observation of the
symptoms and other unspecific tests4(e.g., over 140/90 blood
pressure or 300 mg protein in urine). However, these methods
become effective only when preeclampsia develops to advanced
stages. At that moment, the only treatment option is abortion
or early delivery, which may lead to various medical compli-
cations to both the preterm newborn and the pregnant woman.
Preeclampsia is a complicated syndrome that may exhibit differ-
ent symptoms and no definite causative factors are found to be
responsible for the disease.5Therefore, studies on specific fea-
tures that have significant correlations with preeclampsia would
be of great interest for providing an earlier, more accurate, and
objective clinical diagnosis.
A recent study on fetal membranes (FMs) revealed that mi-
croscopic chorionic pseudocysts (MCP) arising in the chorion
Address all correspondence to: Yingtian Pan, State University of New York at
Stony Brook, Department of Biomedical Engineering, Bioengineering Building,
Room G17, Stony Brook, New York 11794-5281. Tel: (631) 632-1519 (Office),
(631) 632-1750 (Lab); Fax: (631) 632-2322; Email: yingtian.pan@sunysb.edu.
leave of the FMs were found to be strongly associated with
preeclampsia (p≤0.001).6,7Although the results were based
on an ex vivo FM specimen study and artifacts induced by patho-
logical preparation (e.g., formalin fixation) could potentially be
misinterpreted as MCP due to their similar appearances, the
interesting finding that correlates MCP with preeclampsia may
provide a new perspective in clinical prediction of preeclampsia.
In this respect, an endoscopic imaging technique that enables in-
stantaneous, noninvasive, or minimally invasive “optical biopsy”
would be of high clinical relevance in the diagnosis of patho-
logical conditions of pregnancy such as preeclampsia.
Among several emerging biomedical imaging techniques,
optical coherence tomography (OCT) has shown great promise
for noninvasive or minimally invasive optical biopsy of various
subsurface tissue owing to its high resolution (e.g., 1 to 12 μm),
intermediate imaging depth (e.g., 1 to 3 mm), and high detection
sensitivity (e.g., over 100 dB dynamic range). Recent techno-
logical advances have enabled real-time two-dimensional (2D)
and three-dimensional (3D) OCT imaging, Doppler OCT for
functional subsurface blood flow imaging, ultrahigh-resolution
OCT for subcellular imaging, and endoscopic OCT for noninva-
sive imaging of various internal organs.8–10 Meanwhile, preclin-
ical and clinical studies have demonstrated the utility of OCT
in delineating morphological details of biological tissues (e.g.,
skin, oral cavity, esophagus, colon, bladder, and cervix),11–13
and thus the potential for detecting cancers in these organs.
1083-3668/2011/16(11)/116006/6/$25.00 C
2011 SPIE
Journal of Biomedical Optics November 2011 rVol. 16(11)116006-1
Ren et al.: High-resolution imaging diagnosis of human fetal membrane...
While our recent human study showed the clinical feasibility
of our endoscopic OCT to significantly enhance early bladder
cancer diagnosis,10 here we present a pilot feasibility study on
fresh human fetal membrane specimens from normal controls
and from patients with MCP to explore the potential of OCT
for early detection of pathological changes, which might serve
in the prediction of preeclampsia or other diseases associated
with pregnancy. We compare the image results of OCT and
high-frequency ultrasound (HFUS) with the corresponding his-
tological counterparts (clinical standard), so that the utility and
potential limitations of OCT for high-resolution delineation of
the morphology of human FMs and identification of pathologi-
cal changes can be examined.
2 Materials and Methods
2.1 Sample Preparation
A 3D OCT imaging examination was performed on 60 human
FM specimens. These specimens were acquired from 10 dif-
ferent subjects undergoing term cesarean delivery. For each
subject, 6 samples were obtained from different sectors of the
FMs, e.g., 4 from the posterior and anterior uterine wall and
2 near the cervix. The fresh human specimens were preserved in
0.9% saline, rinsed, stretched uniformly to the thickness closely
mimicking the anatomic architecture of FMs in vivo,andthen
mounted on a custom φ20 mm ring holder placed in a modi-
fied ringer’s buffer solution (37◦C, pH 7.4) to undergo ex vivo
imaging evaluations. All of the human specimen studies were
approved by the Stony Brook University Institutional Review
Board and with patients’ prior informed consents.
2.2 3D OCT
Figure 1depicts the schematic of the spectral-domain OCT
(SDOCT) used to acquire all of the 3D images of the FM
specimens in this study. The 3D OCT engine was upgraded
from a high-speed 2D SDOCT setup previously reported,10 in
which a pigtailed broadband laser at central wavelength of λ
=1310 nm and with a spectral bandwidth of λ =90 nm (i.e.,
coherence length Lc≈8.5 μm) was used to illuminate a fiber
optic Michelson interferometer. Green light from a laser diode
Fig. 1 A sketch of the 3D OCT setup. BBS: broadband source; GLD:
green diode laser; FC: fiber optic coupler; PC: polarization controller;
CM: collimator; M: mirror; G: grating; LC: linear InGaAs camera; S:
specimen (fetal membrane); X-S, Y-S: X,Yaxes of the 2D servo scanner;
L1–L3: lenses.
(λ=532 nm) was coupled into the fiber optic system for visual
guidance of OCT scans. In the reference arm, a prism pair (e.g.,
using adjustable BK7 and fused silica wedge prisms) were used
for dispersion compensation and a stationary retroreflective mir-
ror was used to match the pathlength with the sample arm. The
sample arm was connected to a handheld stereoscope in which
light exiting the monomode fiber was collimated, scanned later-
ally by 2D servo mirrors (x-yscanners), and then focused by a
near-infrared objective lens (f40 mm/NA 0.12) onto the surface
of the FM specimen under examination. Light from both refer-
ence and sample arms was recombined in the detection fiber and
connected to a spectrometer in which the spectral interferograph
was detected by a line InGaAs camera (1024×1 pixels, up to
47 kHz line rate) and interfaced via Camlink with a workstation
for 2D and 3D image acquisition and reconstruction. Recent
system development in detection optics and image acquisition
and control resulted in enhanced axial and lateral resolutions
(∼9μm), large field of view (FOV: 5 ×5×2.5 mm3)athigh
dynamic range (>110 dB), and fast frame rate (8 to 47 fps).
2.3 Imaging Examination
With the FMs properly stretched and the maternal side fac-
ing upwards to mimic in vivo endoscopic imaging diagnosis, a
number of 2D OCT prescans across the entire specimen were
performed first to quickly locate the regions of interest (ROI).
For each ROI, sequential OCT scans were performed within
60 s to acquire a 3D OCT image over a cubic volume of 5 ×5
×2.5 mm3and displayed in pseudo color to enhance visualiza-
tion. By visual guidance with a green laser, the enface FOV for
each 3D OCT image was landmarked to align the subsequent
scans for 3D HFUS imaging,14 which was acquired for some
thickened specimens with advanced preeclampsia. 3D HFUS
scans were performed using a miniature 40 MHz probe with
an axial resolution of ∼40 μm (Vevo 770, Visualsonics Inc.,
Toronto, Canada). OCT delineates the morphological details
(e.g., layers) of human FMs according to their backscattering
differences. For simplicity, tissue backscattering was expressed
by back reflectance, defined as the measured OCT intensity nor-
malized to that of the top layer (i.e., decidua vera). Quantitative
computer segmentation of FMs in both 2D and 3D OCT images
was performed based on intensity gradient by adapting the algo-
rithm previously reported,12 and the average thickness (d)and
back reflectance (r) of each layer were then analyzed. After the
imaging study, the specimens were preserved in 10% formalin
fixative together with the ring holders to avoid artifacts such
as tissue deformation for hematoxylin and eosin (H&E) stained
histological examination. A double blind histologic evaluation
was independently performed by a clinical pathologist later to
compare with the prior OCT and HFUS identifications and di-
agnoses. The data were presented as mean ±s.t.d.
3Results
Previous studies have demonstrated the utility of OCT to enable
high-resolution delineation of the morphological features of
biological tissues (e.g., urinary bladder) based on their backscat-
tering differences that attribute to the structural properties.
Figure 2exemplifies a typical cross-sectional 2D OCT image
[Fig. 2(a)] of a normal FM acquired from the maternal side
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Ren et al.: High-resolution imaging diagnosis of human fetal membrane...
Fig. 2 2D images of a normal human fetal membrane. (a) cross-
sectional OCT image; (b) corresponding H&E stained histology. DV:
decidua vera (dDV ≈92 ±38 μm), CT: chorion and trophoblast (dCT
≈150 ±67 μm, rCT/DV =0.51 ±0.17), A: subepithelial amnion (dA
≈95 ±36 μm, rA/DV =0.84 ±0.45), and E: epithelium (dE≈29
±8μm, rE/DV =0.44 ±0.20).
and the corresponding H&E stained histological evaluation
[Fig. 2(b)]. OCT was able to identify the four layers of the
FMs according to their backscattering differences. For instance,
the outermost layer, decidua vera (DV) was relatively thin
(dDV ≈92 ±38 μm), heterogeneous, and high scattering.
The underlying chorion and trophoblast (CT) layer was thick
(dCT ≈150 ±67 μm) and relatively low scattering (rCT/DV
=0.51 ±0.17) possibly due to its loose structure and high
interstitial fluid content. The subepithelial amnion (A) layer
was slightly thinner (dA≈95 ±36 μm) than the CT layer
and was high scattering (rA/DV =0.84 ±0.45) resulting from
subepithelial connective tissue. The innermost epithelium
(E) was very thin (dE≈29 ±8μm or less, with 1 to 2 cell
depths), uniform, and low scattering (rE/DV =0.44 ±0.20). It
is noteworthy that the thicknesses of the intermediate amnion
(A) and chorion (CT) layers and the FMs might vary with
the trimester of pregnancy, the extent of tissue stretching, and
the location of OCT scans, which might result in large error
margins. Overall, the OCT identifications of the four layers
within the FMs correlated well with the counterparts in the
corresponding histological image [Fig. 2(b)] except detachment
of amnion in some specimens, which is a common artifact
induced by tissue fixation during histological processing.
In addition to the 2D OCT presented in Fig. 2,3DOCT
image, e.g., by rendering 350 slices of sequential 2D cross-
sectional OCT images, may provide improved image fidelity
and more affirmative identifications of morphological features.
For example, Fig. 3summarizes the results of normal human
FMs in which Fig. 3(e) shows a pie-cut graph of the 3D OCT
image and Fig. 3(f) illustrates a 2D OCT slice with the four layers
of the FMs automatically segmented based on their backscat-
tering differences. Figures 3(a)–3(d) show the 3D images of the
segmented 4 layers sequentially from DV and CT to A and E
layers. Compared with 2D OCT in Fig. 2,3DOCTinFig.3,
owing to its improved spatial correlation (along the y-axis), pro-
vides enhanced image quality, which may permit more detailed
analysis to characterize the architectural features of individual
layers.
In this pilot human specimen study, not only normal human
FMs but also potential pathological human FM specimens were
examined to evaluate the utility of OCT for noninvasive and
high-resolution imaging diagnosis of FM diseases (e.g., MCP).
Figure 4shows 2D OCT image [Fig. 4(a)]ofanFMsample
with MCP which was characterized by dark holes (low backre-
flection) with thickness of dMCP ≈320 μm between A and CT
layers. The low-scattering characteristics of MCP (dark holes
with rMCP/DV =0.17 ±0.06) were caused by fluid buildup (i.e.,
edema) within the lesions. Figure 4(b) represents the corre-
sponding H&E histology which correlated well with the OCT
identifications of the 4 layers and the cysts (MCP) within the CT
and A layers except that the lesions (dMCP ≈400 μm) appeared
larger than those (dMCP ≈320 μm) in OCT image [Fig. 4(a)].
This discrepancy likely resulted from the artifacts induced by
tissue fixation and histological processing.
Similarly, Fig. 5shows the results of 3D OCT of a human
FM specimen with “early stage” MCP progression. Despite
the fact that the surface image appeared normal, the segmented
3D OCT images revealed early, minor detachment (dMCP
≈80 μm, rMCP/DV =0.14) within the CT and A layers, resulting
in drastically increased inhomogeneity within the CT layer
[Fig. 5(c)]. Interestingly, the innermost epithelial layer E
Fig. 3 3D image of a normal human FM. (a)–(d) 3D OCT images of the segmented DV, CT, A, and E layers; (e) 3D OCT image of the entire human
FMs; (f) 2D OCT image to illustrate the automatic segmentation procedure based on the backscattering differences of each layer; (g) corresponding
H&E histology of OCT image in (f).
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Ren et al.: High-resolution imaging diagnosis of human fetal membrane...
Fig. 4 2D image of a human FM specimen with MCP. (a) 2D OCT im-
age; (b) corresponding H&E histology. The MCP lesions characterized
by OCT as dark holes correlated with the cysts in histology. The thick-
ness of MCP lesions in OCT (dMCP ≈320 μm) matched the histological
counterpart (dMCP ≈400 μm).
[Fig. 5(a)] also became less uniform than the normal coun-
terpart in Fig. 3(a), which could be associated with the
inflammatory reactions of MCP. By detecting the size progres-
sion of MCP lesions, OCT was potentially capable of providing
noninvasive evaluation (i.e., “staging”) of MCP development
and severity, in particular by 3D image segmentation to provide
quantitative assessments of cyst depth (e.g., dMCP ≈80 μmin
Fig. 5,dMCP ≈320 μminFig.4) and the resultant inhomogene-
ity which was associated with fluid buildup, vasodilation, local
microhemorrhage, macrophage, and mast cell accumulations.
It should be noted that although the corresponding histological
image in Fig. 5(g) correlated favorably with the OCT delin-
eations, the artifacts induced by tissue fixation complicated the
identification of MCP (cysts) from distortion (fall off) of CT
and A layers, which might compromise the utility of histology
for affirmative staging of MCP growth and spreading.
Figure 6compares three human FM specimens to show
the capability of OCT to assess the growth of MCP lesions.
Fig. 5 3D OCT image of a human FM with MCP. (a)–(d) 3D OCT images of the segmented DV, CT, A, and E layers. (e) 3D OCT image of the intact
human FMs with MCP; (f) segmented 2D OCT image to illustrate automatic segmentation based on their backscattering differences; (g) corresponding
histology of the OCT image in (f). The CT and E layers were more heterogeneous than the previous normal specimen in Fig. 3.
Fig. 6 OCT images of human FM specimens with different-size MCP lesions compared with the corresponding H&E stained histological images.
(a), (c), and (e) 2D OCT images with the MCPs automatically segmented as landmarked by green dashed circles. The thicknesses of MCPs were dMCP
≈60 μm(a),dMCP ≈150 μm(c),anddMCP ≈265 μm (e), respectively. The percentage areas of MCP, i.e., the ratios of the area of MCPs against
the entire FM cross-section were 3.7% (a), 25.6% (c), and 28.3% (e). (b), (d), (f) The corresponding histological images. The thicknesses of MCPs
were dMCP ≈53 μm(b),dMCP ≈141 μm (d), and dMCP ≈251 μm (f), which correlated with the OCT measurements despite artifacts such as tissue
detachment induced by histological process.
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Ren et al.: High-resolution imaging diagnosis of human fetal membrane...
Fig. 7 3D HFUS image of a human FM with thick MCP. (a) 3D HFUS
image; (b) a slice of 2D HFUS from image (a); (c) corresponding 2D
OCT image. Despite the lower spatial resolution, HFUS was able to
penetrate the entirety of the thicker FMs while the image depth of OCT
was limited to layer DV or top CT.
Although the thickness of MCP (dMCP) may vary with the
point of measurement, the increase of MCP lesions could be
differentiated by their mean thickness. OCT measurement of
dMCP ≈60 μm, rMCP/DV =0.13 for the small MCP lesion in
Fig. 6(a) correlated with the histological evaluation dMCP
≈53 μminFig.6(b); the two large lesions dMCP
≈150 μm, rMCP/DV =0.18 [Fig. 6(c)] and, dmcp =265,
rmcp/dv =0.19 [Fig. 6(e)] measured by OCT [Fig. 6(c)]
were correlated favorably with the corresponding histological
measures, dMCP ≈141 μminFig.6(d) and dMCP ≈251 μmin
Fig. 6(f), respectively. Alternatively, the percentage area of MCP
lesion, i.e., SMCP(%) =SMCP /SFM (SMCP and SFM are the cross-
sectional areas of the PCM lesions and FMs) can be employed;
the results of OCT measures were 3.7%, 25.6%, and 28.3% for
Figs. 6(a),6(c),and6(e), respectively. In addition, we calculated
the statistical result of the average thickness of MCP based on
32 lesions. The result showed that the MCP detectable by OCT
varied from dMCP =24 μmtodMCP =615 μm with a mean thick-
ness of 160 μm and a median thickness of 120 μm. These results
suggest that endoscopic OCT could potentially be deployed
to instantaneously diagnose MCPs and quantitatively evaluate
(i.e., stage) their progress as well as the treatment effects. It is
noteworthy from the histological images in Figs. 6(b),6(d),and
6(f) that distortion and other artifacts (e.g., formalin infiltration)
might compromise the evaluation of histological specimens.
The limited imaging depth of OCT (e.g., ∼1 to 3 mm) may
potentially restrict its utility in the diagnosis and assessment
of later-stage severe MCP lesions. For instance, for a few FM
specimens (e.g., different locations on the FMs) with a thick DV
layer (e.g., 2 to 4 mm) from the maternal side, OCT was unable
to fully delineate the layered structures of the FMs, in partic-
ular, the innermost epithelium (E). In cases like this, HFUS
might compliment OCT to overcome the imaging-depth limi-
tation. To examine the feasibility, additional 3D HFUS scans
following OCT imaging were performed using a miniature
40 MHz probe. Figure 7exemplifies a 3D HFUS image of hu-
man FMs. The results show that because of lower resolution than
OCT, the boundaries between the layers (e.g., DV, CT, and A)
in HFUS images [Figs. 7(a) and 7(b)] were not as well defined
than the counterparts in Figs. 2–5and were unable to resolve
the innermost epithelial layer (e.g., dE<30 μm). Nevertheless,
the increased imaging depth of HFUS allowed it to visualize
the full-thickness architecture of the thickened FMs. Interest-
ingly, despite drastically reduced image contrast, HFUS was
still able to detect the embedded intermediate-size MCP lesion.
In contrast, due to markedly thicker (dEV>1 mm) DV layer and
drastically increased heterogeneity in this FM specimen, OCT
was unable to delineate the underlying layers within the FMs.
4 Discussions and Conclusions
Early diagnosis of preeclampsia, crucial to effective therapeutic
treatment, remains a clinical challenge due to the multifactorial
nature of this disease.4,5A previous study revealed that MCP
originating from the chorion leave (involving mostly CT and A
layers) of the FMs was demonstrated to be closely related to
preeclampsia (p≤0.001),6thus early diagnosis and evaluation
of the progression of MCP could be of great clinical relevance.
Current diagnosis is based on ex vivo histopathologic exami-
nation of the excised tissue specimens, whose clinical value is
restricted by its invasive and destructive natures. Moreover, little
has been studied about potential pathological misinterpretation
of MCP as a result of artifacts induced by tissue fixation and
processing.
In contrast, noninvasive early diagnosis of MCP could
potentially benefit the treatment. Current medical imaging
techniques such as MRI and ultrasound may provide limited
diagnostic values because of their insufficient spatial resolution
and other technical imperfections (e.g., potential radiation
hazard to the fetus). OCT is an emerging optical imaging
modality that, if integrated with endoscopy, permits noninvasive
cross-sectional 2D and 3D imaging of biological tissue at high
spatial resolutions (e.g., 1 to 10 μm) and over intermediate
depths (e.g., 1 to 3 mm). Previous preclinical studies validated
the capability of OCT for delineating the morphological details
of various biological tissues such as oral cavity, bladder, esoph-
agus, and cervix.11–13 More interestingly, recent in vivo clinical
studies clearly demonstrated the utility of our endoscopic OCT
technique in significantly enhancing current clinical approach
(i.e., white-light cystoscopy) for noninvasive diagnosis of early
bladder cancer. Technically, the areas of fetal membranes prone
to preeclamptic changes can potentially be imaged in vivo using
our newly developed miniature (e.g., φ2 mm) flexible OCT
catheter during intrauterine examination. We have presented a
preliminary study based on human tissue specimens, including
both normal control and diseased FMs. Results in Figs. 2and
3show that OCT was capable of delineating the morphological
details of normal human FMs as the four layers (e.g., DV, CT,
A, and E) based on their backscattering differences (e.g., rCT/DV
=0.51 ±0.17; rA/DV =0.84 ±0.45; rE/DV =0.44 ±0.20).
Results in Figs. 4and 5further demonstrate the utility of OCT
to affirmatively detect the MCP lesions (cysts) in the CT layer
of human FMs based on their drastically reduced backscattering
(e.g., rMCP/DV =0.17 ±0.06). More importantly, by applying
post-image processing techniques (e.g., image segmentation and
registration) to the original 3D OCT image dataset, OCT mor-
phometric placental analysis could potentially be implemented
to provide quantitative, accurate evaluation of MCP progress
(i.e., staging of MCP), which is essential to potentially monitor
the preeclampsia development and to evaluate treatment effects.
Our initial study using HFUS suggests that despite its limited
spatial resolution to delineate layered structures in FMs, HFUS
could be a complimentary method to detect large MCP lesions in
markedly thickened FMs where a deeper penetration is needed.
However, in order to further justify the utility and potential
limitations of OCT and HFUS in the diagnosis of preeclampsia,
Journal of Biomedical Optics November 2011 rVol. 16(11)116006-5
Ren et al.: High-resolution imaging diagnosis of human fetal membrane...
further detailed and more quantitative studies should be per-
formed in the future, in particular, in vivo imaging evaluations.
In summary, we performed an in vitro study on fresh human
FM specimens to examine the efficacy and limitations of OCT
for future noninvasive or minimally invasive hysteroscopic OCT
imaging of fetal membranes. Results presented above show that
the high resolution and 3D imaging capability of OCT enabled
delineation of morphological details of human FMs (e.g., DV,
CT, A, and E layers) based on their backscattering differences,
which correlated well with the corresponding histological eval-
uations. Additionally, OCT was able to identify early MCPs
and accurately measure the size of these lesions. Further histo-
morphometric and immunohistochemical studies are needed to
characterize the heterogeneity increases in these layers with the
presence of different cell types and their accumulations so that
more specific diagnosis of the severity and progress of MCP
can be predicted. In addition, more in vivo animal and human
studies will be required to fully examine the efficacy, technical
feasibility, and safety of OCT hysteroscopy, as well as HFUS
for potential future clinical application to minimally invasive
diagnosis of MCP and staging their progress.
Acknowledgments
We acknowledge Jarrett Santorellim, BS at Stony Brook Univer-
sity for participating in this study (handling fetal membrane sam-
ples). This work was supported in part by NIH Grant Nos. 2R01-
DK059265 (YP), 1RC-1DA028534 (CD, YP), 1R21-DA032228
(YP) and Fusion Award.
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