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Multimodality microscopy and micro-Raman spectroscopy for in vivo skin characterization and diagnosis Wang, Hequn
Abstract
Accurate and early diagnosis of skin diseases will improve clinical outcomes. Visual inspection alone has limited diagnostic accuracy, while biopsy followed by histopathology examination is invasive and time-consuming. The objective is to design and develop a multimodal optical instrument that provides biochemical and morphological information on human skin in vivo. Raman spectroscopy (RS) is capable of providing biochemical information of tissues. Reflectance confocal microscopy (RCM), which generates micron-level resolution images with capability of optical sectioning, can provide refractive-index-based morphological information of the skin. Multiphoton microscopy (MPM) could simultaneously provide biochemistry-based morphological information from two-photon fluorescence (TPF) and second-harmonic-generation (SHG) images. The thesis hypothesis is that a multimodality instrument combining RS, RCM, and MPM could be developed and provide complementary information in real-time for in vivo skin evaluation and aiding non-invasive diagnosis. A confocal Raman spectroscopy system was initially developed and tested in a study on in vivo mouse skin. Spectral biomarkers (899 and 1325-1330 cm-¹) were found to differentiate tumor-bearing skin from normal skin. A RCM system was then integrated with the spectroscopy system to guide spectral measurements. Noninvasive morphological and biochemical analysis was performed on ex vivo and in vivo human skin. The system was further enhanced by adding an MPM module that can image cellular structures with TPF signals from keratin, NADH, and melanin, as well as image elastic and colla ii gen fibers via TPF and SHG signals, respectively. The finalized system was utilized to noninvasively measure a cherry angioma lesion and its surrounding structures on the skin of a volunteer. Confocal Raman spectra from various regions-of-interest acquired under the guidance of MPM and RCM imaging showed different spectral patterns for blood vessels, keratinocytes, and dermal fibers. The system was also successfully used to perform imaging directed two-photon absorption based photothermolysis on ex vivo mouse skin. All the results showed positive evidence, well supporting the overall hypothesis. The developed multimodality system, capable of acquiring co-registered RCM, TPF and SHG images simultaneously at video-rate, and performing image-guided region-of-interest Raman spectral measurements of human skin in vivo, is a powerful tool for non-invasive skin evaluation and diagnosis.
Item Metadata
Title |
Multimodality microscopy and micro-Raman spectroscopy for in vivo skin characterization and diagnosis
|
Creator | |
Publisher |
University of British Columbia
|
Date Issued |
2013
|
Description |
Accurate
and
early
diagnosis
of
skin
diseases
will
improve
clinical
outcomes.
Visual
inspection
alone
has
limited
diagnostic
accuracy,
while
biopsy
followed
by
histopathology
examination
is
invasive
and
time-consuming.
The
objective
is
to
design
and
develop
a
multimodal
optical
instrument
that
provides
biochemical
and
morphological
information
on
human
skin
in
vivo.
Raman
spectroscopy
(RS)
is
capable
of
providing
biochemical
information
of
tissues.
Reflectance
confocal
microscopy
(RCM),
which
generates
micron-level
resolution
images
with
capability
of
optical
sectioning,
can
provide
refractive-index-based
morphological
information
of
the
skin.
Multiphoton
microscopy
(MPM)
could
simultaneously
provide
biochemistry-based
morphological
information
from
two-photon
fluorescence
(TPF)
and
second-harmonic-generation
(SHG)
images.
The
thesis
hypothesis
is
that
a
multimodality
instrument
combining
RS,
RCM,
and
MPM
could
be
developed
and
provide
complementary
information
in
real-time
for
in
vivo
skin
evaluation
and
aiding
non-invasive
diagnosis.
A
confocal
Raman
spectroscopy
system
was
initially
developed
and
tested
in
a
study
on
in
vivo
mouse
skin.
Spectral
biomarkers
(899
and
1325-1330
cm-¹)
were
found
to
differentiate
tumor-bearing
skin
from
normal
skin.
A
RCM
system
was
then
integrated
with
the
spectroscopy
system
to
guide
spectral
measurements.
Noninvasive
morphological
and
biochemical
analysis
was
performed
on
ex
vivo
and
in
vivo
human
skin.
The
system
was
further
enhanced
by
adding
an
MPM
module
that
can
image
cellular
structures
with
TPF
signals
from
keratin,
NADH,
and
melanin,
as
well
as
image
elastic
and
colla
ii
gen
fibers
via
TPF
and
SHG
signals,
respectively.
The
finalized
system
was
utilized
to
noninvasively
measure
a
cherry
angioma
lesion
and
its
surrounding
structures
on
the
skin
of
a
volunteer.
Confocal
Raman
spectra
from
various
regions-of-interest
acquired
under
the
guidance
of
MPM
and
RCM
imaging
showed
different
spectral
patterns
for
blood
vessels,
keratinocytes,
and
dermal
fibers.
The
system
was
also
successfully
used
to
perform
imaging
directed
two-photon
absorption
based
photothermolysis
on
ex
vivo
mouse
skin.
All
the
results
showed
positive
evidence,
well
supporting
the
overall
hypothesis.
The
developed
multimodality
system,
capable
of
acquiring
co-registered
RCM,
TPF
and
SHG
images
simultaneously
at
video-rate,
and
performing
image-guided
region-of-interest
Raman
spectral
measurements
of
human
skin
in
vivo,
is
a
powerful
tool
for
non-invasive
skin
evaluation
and
diagnosis.
|
Genre | |
Type | |
Language |
eng
|
Date Available |
2013-10-31
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
|
DOI |
10.14288/1.0073699
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Graduation Date |
2013-05
|
Campus | |
Scholarly Level |
Graduate
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International