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Inexpensive diffuse reflectance spectroscopy system for measuring changes in tissue optical properties

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The measurement of changes in blood volume in tissue is important for monitoring the effects of a wide range of therapeutic interventions, from radiation therapy to skin-flap transplants. Many systems available for purchase are either expensive or difficult to use, limiting their utility in the clinical setting. A low-cost system, capable of measuring changes in tissue blood volume via diffuse reflectance spectroscopy is presented. The system consists of an integrating sphere coupled via optical fibers to a broadband light source and a spectrometer. Validation data are presented to illustrate the accuracy and reproducibility of the system. The validity and utility of this in vivo system were demonstrated in a skin blanching/reddening experiment using epinephrine and lidocaine, and in a study measuring the severity of radiation-induced erythema during radiation therapy. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE)
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Inexpensive diffuse reflectance
spectroscopy system for measuring
changes in tissue optical properties
Diana L. Glennie
Joseph E. Hayward
Daniel E. McKee
Thomas J. Farrell
Inexpensive diffuse reflectance spectroscopy system
for measuring changes in tissue optical properties
Diana L. Glennie,a,*Joseph E. Hayward,a,b Daniel E. McKee,cand Thomas J. Farrella,b
aMcMaster University, Department of Medical Physics and Applied Radiation Sciences, 1280 Main Street West, Hamilton,
Ontario L8S 4L8, Canada
bJuravinski Cancer Centre, Department of Medical Physics, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada
cMcMaster University, Department of Surgery, Division of Plastic and Reconstructive Surgery, 1280 Main Street West, Hamilton,
Ontario L8S 4L8, Canada
Abstract. The measurement of changes in blood volume in tissue is important for monitoring the effects of a
wide range of therapeutic interventions, from radiation therapy to skin-flap transplants. Many systems available
for purchase are either expensive or difficult to use, limiting their utility in the clinical setting. A low-cost system,
capable of measuring changes in tissue blood volume via diffuse reflectance spectroscopy is presented. The
system consists of an integrating sphere coupled via optical fibers to a broadband light source and a spectrom-
eter. Validation data are presented to illustrate the accuracy and reproducibility of the system. The validity and
utility of this in vivo system were demonstrated in a skin blanching/reddening experiment using epinephrine and
lidocaine, and in a study measuring the severity of radiation-induced erythema during radiation therapy. ©2014
Society of Photo-Optical Instrumentation Engineers (SPIE) [DOI: 10.1117/1.JBO.19.10.105005]
Keywords: integrating sphere; tissue optics; chromophores; erythema; diffuse reflectance spectroscopy; visible light.
Paper 130855SSR received Nov. 29, 2013; revised manuscript received Jan. 31, 2014; accepted for publication Feb. 3, 2014; pub-
lished online Oct. 7, 2014.
1 Introduction
The ability to quantify changes in the concentration of chromo-
phores in the skin (particularly oxy- and deoxy-hemoglobin)
in vivo and in real time has many applications in healthcare.
For example, a complication of radiation therapy is radiation-
induced erythema, which, if not monitored closely, can progress
to painful moist desquamation.14In photodynamic therapy, tis-
sue oxygenation can be used to indicate treatment efficacy5
since oxygen is required for the activation of the cytotoxic pho-
tochemicals.6,7Finally, in plastic surgery, proper blood flow is
integral for the success of free tissue transplants and is used to
indicate whether or not a return to the operating room is
necessary.8
Several methods have been validated for measuring skin red-
ness. In increasing complexity and accuracy they are visual
assessment (with or without a color chart), colorimetry/photog-
raphy, and spectroscopy.9Although the visual assessment tech-
nique,10 is the most common, it is qualitative in nature. Due to its
subjective nature and the nonlinearity of human vision, it is
highly prone to interobserver as well as intraobserver varia-
tions.11 The subjectivity of this method can be minimized by
the introduction of color charts; however, a very large number
of color shades would be required to best account for the effect
of pigmentation on the perceived redness. Despite these difficul-
ties, visual assessment remains the gold standard for measuring
skin redness.12,13
Digital photography is usually approached as a two-dimen-
sional implementation of colorimetry. In colorimetry, the color
is quantified using a set of three specifically tuned color sensors
(usually RGB) that represent the color using a standard color
map, such as the L*a*b* system from the International
Commission on Illumination (CIE).14 Colorimetry (and digital
photography) is made extremely difficult by the necessity to cal-
ibrate and standardize the results to allow for intermeasurement
comparison (between days or between individuals).15 Following
correct calibration, both methods are capable of detecting
changes in blood and oxygen saturation but, since the relation-
ship between the measured data and skin redness is not fully
characterized, they are only capable of indicating whether the
skin is more or less red in comparison to previous or baseline
measurements.1619
Spectroscopy-based methods, such as reflectance spectros-
copy and hyperspectral imaging, are the most complex of the
methods used for measuring skin color.2024 Spectroscopy pro-
vides quantitative data across a range of wavelengths, allowing
for different parameters to be extracted from its measurements,
depending on the scope of the investigation and the apparatus
used. User-friendly commercial models capable of monitoring
relative erythema and tissue oxygen saturation are expensive
and use single-use detection probes. For example, the
T-Stat®(Spectros, Portola Valley, California) costs approxi-
mately $25,000 US.25 Cheaper models are less user-friendly
and mostly only provide a single value for oxygen saturation.
As a result, these systems are primarily used by highly trained
investigators at research institutions and are rarely utilized in a
typical clinical setting where they could be used routinely and
would prove most beneficial.
In order to facilitate the translation of spectroscopy systems
from the research laboratory to the routine clinical setting for the
use on human skin in vivo, an economic integrating sphere-
based diffuse reflectance spectroscopy (DRS) unit was devel-
oped and characterized. The system designs and specifications
will be outlined. To illustrate the validity and utility of the
assembled system, the results of two ongoing clinical studies
*Address all correspondence to: Diana L. Glennie, E-mail: glennid@mcmaster
.ca 0091-3286/2014/$25.00 © 2014 SPIE
Journal of Biomedical Optics 105005-1 October 2014 Vol. 19(10)
Journal of Biomedical Optics 19(10), 105005 (October 2014)
measuring erythema under different conditions will be
presented.
2 Design of the Total DRS System
Simply, the total DRS system consists of a white light source
coupled to an integrating sphere via an optical fiber. A second
detection optical fiber directs the reflected light to a spectrom-
eter. The spectrometer is controlled by a computer on which the
required processing software was installed. A schematic of
the system design is shown in Fig. 1. A detailed description
of the selection of each component is presented below.
2.1 Light Source
Oxy- and deoxy-hemoglobin have spectral absorption features
within the visible light range.26,27 Therefore, a light source
encompassing this range, without any narrow bandwidth spec-
tral excitation features, is required. In addition, a stable output
over the measurement period (minutes to hours) is required for
proper reflectance calculation. An Oriel 77501 Radiometric
Fiber Optic Source (Newport, Irvine, California) was chosen
with a 100 W quartz tungsten halogen lamp to produce a highly
stable output within the visible-NIR wavelength range that can
be easily coupled to an optical fiber. It also has an adjustable iris
to allow for output optimization.
2.2 Spectrometer and Optical Fibers
The spectrometer must be capable of detecting light with high
sensitivity across the visible spectrum. It must also have suffi-
cient spectral resolution to allow for the differentiation between
the spectral features of oxy- and deoxy-hemoglobin (<13 nm for
oxy-hemoglobin). An ideal spectrometer would also be small
for ease of portability.
The S2000 Miniature Fiber Optic Spectrometer from Ocean
Optics (Dunedin, Florida) was chosen for this system. It has a
wavelength range of 340 to 1000 nm and a dynamic range of
2000 for a single scan. The 2048-element linear CCD-array
results in a pixel width of approximately 0.35 nm and the inte-
gration time can range from 3 ms to 60 s. Its small size
(<150-mm cube) allows for easy transportation between clinical
sites.
The fiber optic connector specifications for the Ocean Optics
spectrometer are for an SMA 905 to single-strand 0.22 NA opti-
cal fiber. The optical fiber acts in place of a slit in the spectrom-
eters hardware. A relatively large fiber core of 400 μm was
chosen to maximize light collection. This resulted in spectral
resolution of 10 nm as determined from the measurement of
a mercuryargon calibration source (HG-1 Mercury Argon
Calibration Source, Ocean Optics, Dunedin, Florida). The effect
of this spectral resolution on the reflectance spectrum analysis is
described in Sec. 4.2. The final criterion for the fibers was high
transmission in the visible spectrum. Two such fibers, with a
wavelength range between 400 and 2200 nm, were purchased
from Thorlabs (Newton, New Jersey).
2.3 Integrating Sphere
The size of the integrating sphere is dictated by its use to mea-
sure light reflectance from human skin. As such, the integrating
sphere should be relatively small (on the order of 5 to 10 cm in
diameter) so that it can fit onto the various curves of the human
body. A small sphere would also be easier to maneuver and keep
stationary, resulting in more stable measurements.
The size of the measurement port of the sphere should be
sufficiently large that local inhomogeneities in the measurement
area (such as small freckles or hairs) do not overwhelm the
result, but should result in the spheres port fraction (the
ratio of the total port area to the total internal surface area of
the sphere) falling between 2% and 5%.28 For the range of
sphere sizes suggested above, the port diameter would fall
somewhere within 1.5 to 5 cm.
The sphere should also have a high internal reflectance
(greater than 94%) and produce a uniform light field at the meas-
urement port.2931 If the input light is directly incident on the
detection port, the sphere should include a baffle, blocking
this path. For spheres of the size used in this experiment, baffles
should be avoided when possible as they disrupt the internal sur-
face of the sphere, reducing the uniformity of the illumination
within the sphere.
The integrating sphere was made from a cube of Spectralon®
(Labsphere®, North Sutton, New Hampshire) with side lengths
of 2 in. (50.8 mm). The cube was bisected and a hemispherical
cavity was machined into both halves using a 1¼ in. (31.75 mm)
ball-end mill. The bottom of one of these halves was milled
down, creating a port measuring 15.2 mm in diameter. The
parts were assembled to form the sphere and holes were drilled
through the center of the unmilled half as well as through one
side at the junction to accommodate SMA 905 connectors which
would become the detection and illumination ports, respectively
(see Fig. 2).
2.4 Implementation Costs
The specifications for each individual component have some
flexibility; therefore, a DRS system can be built within a
wide range of costs while still achieving the same measurement
results.
In choosing the light source, it is only important that it covers
the desired wavelength range and be stable to within 1%.
Although a uniform spectral output is ideal to keep the signal
uncertainty relatively constant, it is not necessary. A quartz tung-
sten halogen lamp provides smooth spectral features and high
output powers; however, a less expensive alternative would
be a white LED. These provide excellent illumination and
Fig. 1 A schematic of the measurement system (not to scale). The
light source is connected to the side port of the integrating sphere.
Light collected through the overhead port is detected by the spectrom-
eter and processed by the laptop.
Journal of Biomedical Optics 105005-2 October 2014 Vol. 19(10)
Glennie et al.: Inexpensive diffuse reflectance spectroscopy system for measuring changes.. .
are relatively stable, although they do have an emission peak in
the blue region (465 nm).
Integrating spheres can be purchased from an optical device
supplier; however, spheres can be built for costs as low as $100
US by obtaining a suitable block of Spectralon. Since the sphere
is not being used for radiometric purposes, it can deviate from an
ideal integrating sphere and still provides an accurate reflectance
measurement. Spheres can also be constructed by vacuum form-
ing plastic styrene about a spherical mold and coating the inside
with barium sulfate paint.32
The most expensive piece of equipment component is the
spectrometer, and its price will depend on the detection sensi-
tivity and grating size. The average cost for a common fiber-
based spectrometer is around $2000 US. Although not recom-
mended, spectrometers can also be built cheaply if necessary.33
The computer must be able to interface with the spectrometer
and run the necessary software. Therefore, an inexpensive net-
book or laptop will be sufficient. Optical fibers are uniformly
priced in the market and will contribute very little to the total
cost of the system.
A list of itemized expenses is shown in Table 1, assuming
new materials were required. For comparison, a hand-held col-
orimeter is available for $6000 US from Derma Spectrometer
(MIC Global, London, United Kingdom).
3 Procedure and Performance
3.1 Integrating Sphere Configuration
The optical fibers are connected to the integrating sphere follow-
ing a d0 deg (diffuse illumination/direct detection) geometry
such that the input light is first incident on the sphere wall before
encountering the tissue surface and the output fiber is directly
across from the measurement port (as shown in Fig. 1). In this
geometry, the sample is more uniformly illuminated compared
with a 0 deg dgeometry due to the multiple reflections of the
light prior to exiting the sphere at the tissue. In addition, since
the illumination is diffuse rather than normally incident, the pen-
etration of light is more superficial due to the oblique entrance
angle (average 55 deg). Thus, a greater percentage of spectro-
scopic information originates from the upper layers of skin
where the chromophores of interest are located. Due to the
small size of this integrating sphere, a baffle was not used.
The geometry and the detector fiber acceptance angle
(0.22 NA) allowed only light that was specularly or diffusely
reflected from the tissue surface to be collected.
3.2 Calculating Spectral Reflectance
The spectral reflectance of a tissue sample was normalized by
dividing the spectral count rate with the detection port on the
tissue, StðλÞ, by the spectral count rate from a highly reflecting
standard, SnormðλÞ. Both of these were adjusted by subtracting
the background signal rate, SbgðλÞ, so that the modified total
diffuse reflectance, R
mðλÞ, is given by
R
mðλÞ¼ StðλÞSbgðλÞ
SnormðλÞSbg ðλÞ. (1)
Normalizing to a reflectance standard eliminates the need to
correct the measured signal rate for the system spectral response.
A 99% reflectance standard (SRS-99-010, Labsphere, North
Sutton, New Hampshire) was used as the normalization standard
while a 2% reflectance standard (SRS-02-010, Labsphere, North
Sutton, New Hampshire) was used for the background. The 2%
standard was used instead of directing the detection port into a
dark room in order to avoid changes in ambient lighting condi-
tions, should the system be used in different locations which
would affect the calculated reflectance. This substitution did
not affect the accuracy or precision of the measurement. If
reflectance standards are not available, a piece of thick, matte
black cloth may be substituted for the 2% standard, and a
piece of high diffusely reflective material such as a piece of
Spectralon or a flat surface coated with barium sulfate may
be substituted.
For each spectral count rate measurement, the integration
time was set such that the maximum intensity was approxi-
mately 90% of the dynamic range. This allowed for optimal pre-
cision while ensuring that the signal would not saturate. Five
measurements were averaged to further reduce the noise. The
averaged measurements were converted into a count rate by
dividing by the integration times.
Fig. 2 A cross-sectional diagram of the integrating sphere. The block
of Spectralon®used to make the sphere is bisected before processing
and then reattached to form the sphere.
Table 1 Cost estimates for the DRS system. Listed prices are based
on the purchase of new material.
Component
Pricing (USD)
Low High
Light source $100 $500
Integrating sphere $100 $1500
Spectrometer $500 $3000
Computer $250 $500
Connection cables $100 $200
Total $1050 $5700
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3.3 Sphere Preparation
The measurement port of the integrating sphere was covered
with a sheet of occlusive dressing (Tegadermfilm, 3M
Health Care, St. Paul, Minnesota) in order to prevent dirt and
other material from contaminating the inside of the sphere. A
new sheet was applied for each patient before any measurements
to ensure sterility. The dressing was left on for the normalization
and background measurements and, therefore, did not modify
the resulting reflectance. Reflectance measurements were per-
formed on calibrated diffuse reflectance standards ranging
from 2% to 99% (RSS-08-010, Labsphere, North Sutton,
New Hampshire) with the dressing in place and removed.
Both sets of measurements showed no measurable difference.
3.4 Correcting for Single Beam Substitution Error
Single beam integrating spheres used for reflectance spectros-
copy suffer from single beam substitution error34,35 due to the
decrease of the total flux within the sphere when the normali-
zation plate is replaced with the sample. This can be corrected
using Eq. (2). The parameters (a,b,c), as a function of wave-
length, were determined empirically by measuring the calibrated
reflectance standards described in the previous section and
developing a relationship between the measured and calibrated
reflectances (represented by R
mand Rm, respectively), based on
the fraction of reflected light. If reflectance standards are not
available, Intralipid(Baxter, Deerfield, Illinois) and India
ink liquid phantoms can be used as they have well-characterized
extinction coefficients.36,37
Rm¼aR
mþb
R
mþc. (2)
These data were fit using a nonlinear least-squares algorithm
at each of the wavelengths. A typical fit for a single wavelength
is shown in Fig. 3. This correction was applied to the modified
total diffuse reflectance, resulting in a corrected total diffuse
reflectance (Rm). A set of colored diffuse reflectance standards
(CSS-04-010, Labsphere, North Sutton, New Hampshire) were
measured and, following correction, the measured reflectance
was within 0.01 of the calibrated reflectance specified by the
supplier (Fig. 4).
3.5 Reflectance Measurement Reproducibility
The reproducibility of the system was tested using the green
reflectance standard (SCS-GN-010) because it had reflectance
similar to human skin and spectral features in the same region
as hemoglobin. Reflectance was measured every day for 30 days
and the standard deviation across the 500 to 700 nm spectral
region never exceeded 1%. As expected, it varied with the
spectral reflectance of the reflectance standard (i.e., the
uncertainty was lower when the reflectance/signal was higher).
Reproducibility measurements were also performed on human
skin and they had a similar result.
4 Experimental Validation
4.1 Study Overviews
In order to demonstrate the use and validity of the DRS system,
sample data from two ongoing erythema studies are presented.
In the first study, erythema and skin blanching were induced via
subcutaneous injection of lidocaine (a vasodilator and anes-
thetic) with or without epinephrine (a vasoconstrictor) over
the deltoid muscles of volunteersupper arms. The aim of
this study was to determine the time to maximal effect of
injected epinephrine. In the second study, serial skin reflectance
measurements were taken on head and neck cancer patients
undergoing intensity-modulated radiation therapy (IMRT).
The goal of this study was earlier detection of radiation-induced
erythema compared with visual assessment methods. Both
studies received Hamilton Health Sciences Research Ethics
approval.
4.2 Erythema Index Analysis
The measured reflectance spectra were processed using the
Dawson erythema index (EI).38 This model was chosen because
of its wide acceptance and use (over 280 citations to date),39 as
well as its straight-forward calculation method. Briefly, the EI is
the area under the curve of the log of the inverse reflectance
spectrum between 510 and 610 nm (encompassing the absorp-
tion features of oxy- and deoxy-hemoglobin). The influence of
melanin in the EI can be approximately corrected using reflec-
tance data between 650 and 700 nm (EIc). For serial measure-
ments on an individual, a relative erythema index (EIr) can also
0.0
0.2
0.4
0.6
0.8
1.0
0.0 0.2 0.4 0.6 0.8 1.0
Calibrated reflectance ( cal)
Measured reflectance ( m*)
R
R
Fig. 3 The integrating sphere calibration curve at 600 nm. The fitted
function corrects the measured reflectance for single-beam substitu-
tion error. The dots are the calibrated and measured reflectance pairs
and the dashed line is the fit to these data.
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
500 550 600 650 700
Reflectance
Wavelength (nm)
Fig. 4 The measured (symbols) and calibrated (lines) reflectance
spectra for a set of four colored diffuse reflectance standards: red
(), yellow (), green (), and blue (). Correction for the single-
beam substitution error brought the measured reflectance values to
within 0.01 of the calibrated reflectance specified by the supplier.
Journal of Biomedical Optics 105005-4 October 2014 Vol. 19(10)
Glennie et al.: Inexpensive diffuse reflectance spectroscopy system for measuring changes.. .
be calculated. Simply, a baseline EIcis obtained either at time
zero or at a nearby reference location. This is subtracted from
EIcvalues measured at later time points such that, in the absence
of changes in hemoglobin, EIrwould be zero.
The 10 nm FWHM spectral resolution of the system has
the effect of broadening spectral features in the measured reflec-
tance. Although this would be problematic for narrow features,
the absorption features in the hemoglobin spectra are very broad
and were not strongly affected. To verify the effect on the EI,
spectra derived from the literature40 were convolved with a
10 nm FWHM Gaussian function and the EI calculated before
and after. Small differences in the calculated EI were noted (data
not shown), however changes in EI with respect to an increase or
decrease in hemoglobin were insensitive to the spectrometers
spectral resolution.
4.3 Study Results
In the first study, the reflectance was measured serially for 2 h
following the injection of lidocaine (with or without epineph-
rine) and the measurements were processed to calculate the
EIras a function of time. A time course for one volunteer is
shown in Fig. 5along with the reflectance spectra at specific
time points. For both injections, there was a rapid increase in
the EIrindicating an increase in the hemoglobin content. The
combined lidocaine and epinephrine injection then decreased
to a minimum EIrof approximately 16 at the 22 min mark
indicating a reduction in hemoglobin content. An analysis of
the EIrfor all subjects indicated that the maximum epineph-
rine-induced blanching occurred approximately 25 min follow-
ing injection, after which surgical incision may commence.41
In the second study, the reflectance was measured daily over
the course of the patientshead and neck IMRT treatments.
During this study, it was necessary to have multiple investigators
operate the DRS system. This requirement illustrated the ease
of training associated with the system, as all investigators
were capable of properly using the system following a short
15 min tutorial. Greater variation was observed in the daily mea-
surements compared with the short-term measurements of the
first study (see Fig. 6). The EIrwas not calculated because
the baseline consisted of a single measurement. The variation
is the result of daily changes such as time of day and patient
temperature.42 An increase in EIcwas observed over the course
of the 35 days. Erythema was first visually diagnosed on day 18
of treatment. This study is ongoing.
5 Discussion
This paper illustrates two clinical applications of a DRS system.
These results demonstrate that a low-cost spectroscopy system is
capable of measuring spectral changes in reflectance due to
changes in the concentration of hemoglobin. These changes
were quantified using the Dawson EI. The system is easy to
operate and yields valuable clinical data with little training
required. The system described here may be found to have a
wide range of clinical assessment roles, which would make it
an even more useful tool for health care practitioners.
However, since the system collects a full spectrum, it is capable
of generating much more valuable information than just a single
EI value. For example, correcting for background chromophores
is only approximate and any changes over the measurement
period could register as incorrect increases or decreases in
skin redness. An alternative modeling approach using a spec-
trally constrained diffuse reflectance model to fit the measured
reflectance spectrum with concentrations of the major tissue
chromophores may be advantageous. This will allow for the
detection of skin color changes in reference to their responsible
chromophore, but would require the measured spectrum to be
extremely accurate and precise.
One of the limitations of this spectroscopy system is that the
signal is normalized using a highly scattering Spectralon®stan-
dard. In comparison, human skin is much less scattering and
therefore the true reflectance is under-represented due to scatter-
ing losses. These scattering losses are not large but, since they
0 20 40 60 80 100 120
Time (min)
(a)
Lidocaine
Lidocaine + epinephrine
500 525 550 575 600 625 650 675 700
Wavelength (nm
)
(b)
Baseline
Lidocaine
Lidocanie + epinephrine
-20
-10
0
10
20
30
40
50
60
Relative erythema index (a.u)
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0.55
0.60
Reflectance
Fig. 5 (a) A sample time course for one volunteer in the study involv-
ing lidocaine and epinephrine. (b) Full reflectance spectra from before
injection (), 1 min following the injection of lidocaine alone (Δ), and
26 min following the injection of lidocaine and epinephrine ().
80
100
120
140
160
180
200
220
180 5 10 15 20 25 30 35
Corrected erythema index (a.u)
Treatment progress (days)
Fig. 6 Corrected erythema index for a head and neck IMRT cancer
patient. Daily measurements were taken over the course of treatment.
Erythema was not visually noted until day 18.
Journal of Biomedical Optics 105005-5 October 2014 Vol. 19(10)
Glennie et al.: Inexpensive diffuse reflectance spectroscopy system for measuring changes.. .
vary with the tissue optical properties, they would need to be
accounted for in a spectrally dependent model.
This paper presents a low-cost, user-friendly DRS system for
measurement of changes in skin hemoglobin concentration. The
performance of the system was characterized in terms of wave-
length accuracy and measurement stability, uncertainty, and
reproducibility. The validity and utility of the system were dem-
onstrated through a skin reddening/blanching experiment and a
radiation-induced erythema study, followed by analysis with a
simple erythema model. Further uses of the system have yet to
be investigated.
Acknowledgments
The authors would like to thank Kevin R. Diamond and Gabriel
A. Devenyi for their assistance in the preparation of this paper.
This work was financially supported by the Natural Sciences
and Engineering Research Council of Canada.
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Journal of Biomedical Optics 105005-6 October 2014 Vol. 19(10)
Glennie et al.: Inexpensive diffuse reflectance spectroscopy system for measuring changes.. .
... Each EMW band has an exposure threshold or 'minimal erythema dose' (MED) [6]; if reached, skin erythema is directly induced [7]. In addition to EMW exposure, physical pressure [8], skin ulceration [9,10], application of cosmetic and medical topical agents, and electrical stimulation [11][12][13][14] are all external stimuli of skin erythema. Over and above, burns induce erythema around resultant scars [15]. ...
... For instance, a recent study proved that IS-DRS system can be built with low costs while being efficient and simple to construct as shown in Fig. 3 [14]. The same setup was used in a clinical study to detect the temporal development of skin erythema via computing the erythema index. ...
... The study displayed the computed erythema indices based on the measurement of the daily skin diffuse reflectance in cancer patients. Based on the computed erythema index, DRS was able to detect the patients' skin color change earlier than visual assessment, however, both techniques were done synchronously [14]. In addition, the acquired DRS data were able to quantify skin erythema via estimating the apparent concentrations of skin chromophores during radiation treatment [14]. ...
Article
Abstract Background Skin erythema may present due to many causes. One of the common causes is prolonged exposure to sun rays. Other than sun exposure, skin erythema is an accompanying sign of dermatological diseases such as acne, psoriasis, melasma, post inflammatory hyperpigmentation, fever, as well as exposure to specific electromagnetic wave bands. Methods Quantifying skin erythema in patients enables the dermatologist to assess the patient’s skin health. Therefore, quantitative assessment of skin erythema was the target of several studies. The clinical standard for erythema evaluation is visual assessment. However, the former standard has some imperfections. For instance, it is subjective, and unqualified for precise color information exchange. To overcome these shortcomings, the past three decades witnessed various methodologies that aimed to achieve erythema objective assessment, such as diffuse reflectance spectroscopy (DRS), and both optical and non-optical systems. Discussion This review article revises the studies published in the past three decades where the performance, the mathematical tactics for computation, and the limited capabilities of erythema assessment techniques for cutaneous diseases are discussed. In particular, the current achievements and limitations of the current techniques in erythema assessment are presented. Conclusion The profits and development trends of optical and non-optical methods are displayed to provide the researcher with awareness into the present technological advances and its potential for dermatological diseases research. Keywords Skin pigments; Erythema assessment; Dermatological diseases; Skin inflammation; Optical diagnosis
... An intriguing example of MED is the transient flush erythema which takes place rapidly in people with fair skin, in the summer upon exposure to sunlight [10]. In addition to EMW exposure, physical pressure [11], skin ulceration [12], [13], application of cosmetic/medical topical agents, and electrical stimulation [14]- [17] are all external stimuli of skin erythema. Over and above, burns induce erythema around resultant scars [18]. ...
... Figure 5 displays the computed erythema indices in the study, based on the measurement of the daily skin diffuse reflectances in cancer patients. Based on the computed erythema index, DRS was able to detect the patients' skin color change earlier than visual assessment, however, both techniques were done synchronously [17]. Over and above, the acquired DRS data were able to quantify skin erythema via estimating the apparent concentrations of skin chromophores during radiation treatment [17]. ...
... Based on the computed erythema index, DRS was able to detect the patients' skin color change earlier than visual assessment, however, both techniques were done synchronously [17]. Over and above, the acquired DRS data were able to quantify skin erythema via estimating the apparent concentrations of skin chromophores during radiation treatment [17]. In sum, the simple and affordable IS-DRS system succeeded to properly detect and precisely quantify radiation dermatitis during cancer treatment before visual detection by radiotherapists was possible. ...
... treatment plan, unless attentively monitored and precisely addressed (13). Erythema is not only accompanying radiation therapy treatment, but also photodynamic therapy and plastic surgery. ...
... This interest fueled the innovation of precise techniques for quantifying erythema. From most to least complex, the techniques are: spectroscopy, colorimetry/ photography, and visual assessment (VA) (13). VA is still the current gold standard for erythema assessment in dermatology clinics (14,15). ...
Conference Paper
Full-text available
Surveillance and assessment of radiation-induced erythema is an important aspect of managing skin toxicity in radiation therapy treated patients. Upon receiving the early fractions of radiation, an inflammatory response and vascular dilation takes place due to damage of basal cells in the skin’s epidermal layer. This process of skin reddening known as erythema. The gold standard used for assessing and grading erythema is visual assessment (VA) by an experienced clinician/ radiotherapist using toxicity scoring tools. This method is limited by the assessor’s experience, vision acuity, and the subjectivity of qualitative scores. An alternative optical technique to VA, is diffuse reflectance spectroscopy (DRS). A comparison between both techniques performance in detecting radiation therapy-induced erythema is demonstrated in this pilot study. The results evidenced that DRS is capable of detecting skin erythema before an expert eye could do so.
... Until now(?), visual assessment by a dermatologist [3], [4]is the gold standard for diagnosising and evaluating the treatment of skin diseases [1], [2],. However, visual assessment was criticized in many studies to be subjective, qualitative, temporally inconsistent, and invasive [5]- [10]. ...
... Within optical techniques, there are two main approaches for skin assessment: diffuse reflectance spectroscopic (DRS) measurements and color imaging. The spectroscopic-based-approach is well-known for detecting the spectral signature of the skin's signs with highly precise, inexpensive equipment [4]. Hence, it aids the dermatologist in differentiating between visibly similar skin conditions. ...
Conference Paper
Full-text available
The incessant innovations of hyperspectral imaging (HSI) and data mining algorithms create necessity for developing reliable means of assessment and comparison. In medical applications of HSI, for instance, one of such means is tissue-equivalent phantoms. These phantoms are designed to mimic the spectral behavior of real living tissues. In this work, gel-based-phantoms were prepared with adjusted ingredients. The gel phantom's ingredients include India ink and Intralipid to provide absorption and scattering, respectively. Unlike visual assessment and photography, HSI was successful in identifying the various phantoms based on their spectral signature. In conclusion, we introduce a simple method of evaluating the performance of newly developed optical imaging techniques including HSI via affordable, inexpensive, and easy-to-make phantoms.
... En este trabajo se utilizó la aproximación propuesta por Glennie et Al. [323] para determinar el Indice del Eritema de Dawson a partir de mediciones de DRS. Este parámetro se calcula como elárea bajo la curva del negativo del logaritmo base 10 del espectro de la reflectancia difusa (conocido como la absorbancia aparente y expresado por la ecuación 4.6 en un rango de 650 − 700nm, y de igual forma que para el indice de melanina, descartando las contribuciones de la deoxy-Hb y la oxy-Hb. ...
... However, visual assessment is far from ideal, since it is subjective and strongly dependent on observer experience and human factors including visual acuity. Two assessment techniques, Diffuse reflectance spectroscopy (DRS) [30][31][32] and digital imaging [33][34][35] were studied as objective alternatives to VA. Yet, both were found unsatisfactory by clinicians. ...
Article
Skin cancer (SC) is a widely spread disease in the USA, Canada, and Australia. Skin cancer patients are mostly of advanced age and therefore more likely to be treated with radiation therapy as many are comorbid and not surgical candidates. However, radiation therapy has side effects, which may range from skin erythema to skin necrosis. As erythema is the early evidence of exposure to radiation, monitoring erythema is important to prevent more severe reactions. Visual assessment (VA) is the gold standard for evaluating erythema. Nevertheless, VA is not ideal, since it depends on the observer’s experience and skills. Digital photography and hyperspectral imaging (HSI) are optical techniques that provide an opportunity for objective assessment of erythema. Erythema indices were computed from the spectral data using Dawson’s technique. The Dawson relative erythema index proved to be highly correlated (97.1%) with clinical visual assessment scores. In addition, on the 7th session of radiation therapy, the relative erythema index differentiates with 99% significance between irradiated and non-radiated skin regions. In this study, HSI is compared to digital photography for skin erythema statistical classification.
... For that reason, melanin effect needs to be compensated in erythema index computation. For melanin correction factor, reflectance data at two wavelengths (650&700 nm) is used to compute Dawson melanin index (DMI) [40]. The former wavelengths were selected because melanin spectral absorbance is proportional to its concentration at these two spectral points, as well as the low absorbance of the hemoglobin in this spectral region [39]. ...
Preprint
Full-text available
Skin cancer (SC) is a widely spread type of cancer in USA, Canada, and Australia. Patients, in the senior age, of skin cancer is usually referred to radiation therapy, rather than surgery due to old age complications, for treatment. However, radiation therapy induces side effects that may vary between tissue necrosis down to skin erythema. As erythema is the primary evidence of skin health perturbation due to radiation exposure, it needs to be precisely assessed. Visual assessment (VA) is the gold standard for erythema evaluation. Nevertheless, VA is anything but ideal, due to being dependent on experience and varying human sensations. Hyperspectral imaging (HSI), far from human dependency, is an optical technique that provides an opportunity for objective investigation of erythema. HSI spectral data permitted the computation of erythema indices using Dawson's technique. Dawson relative erythema index proved to be highly correlated (97.1%) to clinically visual score in monitoring skin erythema. In addition, on the 7 th session of radiation therapy, relative erythema index differentiates with 99% significance between irradiated and non-radiated skin regions. In this study, HSI is compared to digital photography for skin erythema statistical classification.
... Diffuse reflectance spectroscopy (DRS) is a non-invasive method which can be used to quantify volumetric total hemoglobin concentration (THC), tissue oxygen saturation (StO 2 ), and tissue scattering at or within accessible tissue sites [1][2][3][4][5][6][7][8][9][10]. This technique has been adapted for studies of tumor perfusion and response to therapy, since THC and StO 2 can be used to differentiate therapeutic responders from non-responders over the course of treatment [11][12][13]. ...
Article
Diffuse reflectance spectroscopy (DRS) has been used in murine studies to quantify tumor perfusion and therapeutic response. These studies frequently use inhaled isoflurane anesthesia, which depresses the respiration rate and results in the desaturation of arterial oxygen saturation, potentially affecting tissue physiological parameters. However, there have been no controlled studies quantifying the effect of isoflurane anesthesia on DRS-derived physiological parameters of murine tissue. The goal of this study was to perform DRS on Balb/c mouse (n = 10) tissue under various anesthesia conditions to quantify effects on tissue physiological parameters, including total hemoglobin concentration, tissue oxygen saturation, oxyhemoglobin and reduced scattering coefficient. Two independent variables were manipulated including metabolic gas type (pure oxygen vs. medical air) and isoflurane concentration (1.5 to 4.0%). The 1.5% isoflurane and 1 L/min oxygen condition most closely mimicked a no-anesthesia condition with oxyhemoglobin concentration within 89% ± 19% of control. The time-dependent effects of isoflurane anesthesia were tested, revealing that anesthetic induction with 4.0% isoflurane can affect DRS-derived physiological parameters up to 20 minutes post-induction. Finally, spectroscopy with and without isoflurane anesthesia was compared for colon tumor Balb/c-CT26 allografts (n = 5) as a representative model of subcutaneous murine tumor allografts. Overall, isoflurane anesthesia yielded experimentally-induced depressed oxyhemoglobin, and this depression was both concentration and time dependent. Investigators should understand the dynamic effects of isoflurane on tissue physiological parameters measured by DRS. These results may guide investigators in eliminating, limiting, or managing anesthesia-induced physiological changes in DRS studies in mouse models. © 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.
Article
Skin erythema may present due to many causes. One of the common causes is prolonged exposure to sunrays. Other than sun exposure, skin erythema is an accompanying sign of dermatologic diseases, such as psoriasis and acne. Quantifying skin erythema in patients enables the dermatologist to assess the patient's skin health. Quantitative assessment of skin erythema has been the target of several studies. The clinical standard for erythema evaluation is visual assessment; however, the former standard has some imperfections. For instance, it is subjective, and unqualified for precise color information exchange. To overcome these shortcomings, the past three decades has witnessed various methodologies that aimed to achieve erythema objective assessment, such as diffuse reflectance spectroscopy (DRS), and both optical and non-optical systems. This review appraises the studies published in the past three decades, where the performance, the mathematical tactics for computation, and the limited capabilities of erythema assessment techniques for cutaneous diseases are discussed. The current achievements and limitations of the current techniques in erythema assessment are presented. The profits and development trends of optical and non-optical methods are displayed to provide the researcher with awareness into the present technological advances and its potential for dermatological diseases research.
Article
Full-text available
A survey of the literature is presented that provides an analysis of the optical properties of human skin, with particular regard to their applications in medicine. Included is a description of the primary interactions of light with skin and how these are commonly estimated using radiative transfer theory (RTT). This is followed by analysis of measured RTT coefficients available in the literature. Orders of magnitude differences are found within published absorption and reduced-scattering coefficients. Causes for these discrepancies are discussed in detail, including contrasts between data acquired in vitro and in vivo. An analysis of the phase functions applied in skin optics, along with the remaining optical coefficients (anisotropy factors and refractive indices) is also included. The survey concludes that further work in the field is necessary to establish a definitive range of realistic coefficients for clinically normal skin.
Chapter
This chapter discusses the techniques of measurement of reflectance and diffuse transmittance where it is associated with diffuse reflectance in a technique called “transflectance.” “Reflectance spectroscopy” concerns the measurement of four distinct types of materials and their interaction with light. Specular materials reflect the predominant amount of radiation at an angle equal and opposite to the incident radiation. Diffusely reflective materials scatter light over a wide range of angles with the perfectly diffuse (or Lambertian) scatterer exhibiting a cosine response to the incident radiation. Gonioapparent materials have both a specular and a diffuse component (as do most materials) but these substances have particular scattering components only at certain angles of incidence or collection because of particulate inclusions within the materials. The chapter discusses transflectance to cover those materials that both diffusely reflect and diffusely transmit incident radiation. Relative reflectance requires the use of a reference mirror to produce accurate measurements. Absolute specular measurements do not require a reference mirror but instead use various optical techniques to bring the reflected beam to a detector. Both of these measurements have their advantages and pitfalls that must be considered in choosing the measurement technique.
Article
The erythema resulting from the minimal erythema dose (MED) test is subjectively assessed. The evaluator visually grades erythema on an ordinal scale. Both intra- and interobserver variation have been found for this erythema assessment. We wanted to examine if objective measurements could be used to confirm the subjective finding. One hundred two ultraviolet radiation (UVR)-exposed skin sites on the backs of 17 healthy volunteers were assessed. Erythema was visually graded according to a 5-point scale [0, (+), 1+, 2+, 3+] and objectively measured by a skin reflectance meter. Skin water content was objectively measured by tissue dielectric constant measurements. The relationship between subjective assessments and objective measurements of erythema was found to be linear (R(2) = 0.482, P < 0.0001). A positive correlation was found between subjective assessments of erythema and objective measurements of water content (Spearman's Rho = 0.414, P < 0.0001). Water content in categories 2+ and 3+ of the subjective erythema assessments differed significantly from the lesser categories (P < 0.0001). A linear relationship was found between the objective measurements of erythema and water content (R(2) = 0.241, P < 0.0001). Objective measurements of skin erythema and water content after UV exposure were in good agreement with the subjective assessments of erythema, but showed considerable interpersonal variation.
Article
When light is diffusely reflected from tissue containing a dye, such as a photosensitizer, with a known absorption spectrum, the changes in the reflectance spectrum caused by the presence of the dye can be identified and correlated with the dye concentration. A feasibility study' of this method for the noninvasive determination of the concentration of photosensitizers in tissue found, however, that the changes in reflectance also depended on the optical properties of the tissue. In this study we propose a simple model of light propagation which allows quantitative prediction of the sensitivity of the method. The optical absorption and scattering coefficients required as input for the model are obtained from two ancillary noninvasive measurements: the total diffuse reflectance and the spatial variation of the local diffuse reflectance. Experiments performed using tissue-simulating phantoms suggest that the simple model, when combined with the ancillary measurements, allows absolute calibration of the method to within 20%.
Article
White light spectroscopy non-invasively measures hemoglobin saturation at the capillary level rendering an end-organ measurement of perfusion. We hypothesized this technology could be used after microvascular surgery to allow for early detection of ischemia and thrombosis. The Spectros T-Stat monitoring device, which utilizes white light spectroscopy, was compared with traditional flap monitoring techniques including pencil Doppler and clinical exam. Data were prospectively collected and analyzed. Results from 31 flaps revealed a normal capillary hemoglobin saturation of 40-75% with increase in saturation during the early postoperative period. One flap required return to the operating room 12 hours after microvascular anastomosis. The T-stat system recorded an acute decrease in saturation from ∼50% to less than 30% 50 min prior to identification by clinical exam. Prompt treatment resulted in flap salvage. The Spectros T-Stat monitor may be a useful adjunct for free flap monitoring providing continuous, accurate perfusion assessment postoperatively. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.
Article
Background: The time until maximal cutaneous vasoconstriction after injection of lidocaine with epinephrine is often given in textbooks and multiple choice examinations as 7 to 10 minutes. However, in our experience, there is significantly less cutaneous bleeding if one waits considerably longer than 7 to 10 minutes after injection of local anesthesia with epinephrine for most procedures on human skin. Methods: This was a prospective, randomized, triple-blind study where 12 volunteers were injected simultaneously in each arm with either 1% lidocaine with epinephrine (study group) or 1% plain lidocaine (control group), after which the relative hemoglobin concentration of the underlying skin and soft tissues was measured over time using spectroscopy. Results: In the epinephrine group, the mean time at which the lowest cutaneous hemoglobin level was obtained was 25.9 minutes (95 percent CI, 25.9 ± 5.1 minutes). This was significantly longer than the historical literature values of 7 to 10 minutes for maximum vasoconstriction after injection. Mean hemoglobin index values at every time measurement after postinjection minute 1 were significantly different between the study group and the control group, with use of a two-tailed paired t test (p < 0.01). Conclusions: If optimal visualization is desired, the ideal time for the surgeon to begin the incision should be 25 minutes after injection of local anesthetic with epinephrine. It takes considerably longer than 7 to 10 minutes for a new local equilibrium to be obtained in relation to hemoglobin quantity.
Article
Skin erythema has been widely used as a diagnostic parameter in dermatology. This study describes a methodology for real-time measurement of skin erythema variation induced by negative compression. This study developed an optical measurement probe, which includes a RGB color sensor that translates in the vertical direction, with the magnitude of vertical translation dependening on the amount of skin deformation. Real-time measurement of erythema variation as a function of both negative compression and time was performed in vivo on 10 measurement sites located on the back of each of 12 volunteers who participated in this study. Negative compression was sequentially applied from -30 to -80  kPa and continuously at a constant magnitude (-80  kPa) condition. The results showed that skin erythema was uniformly induced at the measurement sites and linearly increased as a function of both negative compression and time. A wide range of individual variation was noted for skin erythema, which may be due to variations in anisotropic skin properties between volunteers. This study demonstrated the clinical feasibility of a novel optical device for skin erythema measurement. Future studies are needed to investigate the clinical applications of this device.
Article
This paper demonstrates the high potential of a web camera to be utilized as a low-cost multichannel fiber-optic spectrometer suitable for either educational or quality-control purposes in small and medium enterprises. The key idea is to arrange N input optical fibers in a line and position an external dispersive element to separate incoming optical beams into their associated spectral components in a two-dimensional (2D) space. With a commercial web camera, each set of the spectral components is imaged through a plastic lens onto the 2D image sensor of the web camera. For the demonstration, a five-channel webcam-based fiber-optic spectrometer is implemented where each channel is calibrated by selected reference light sources. The constructed spectrometer can perform wavelength analysis of the spectral irradiance in the range of 400 to 655 nm. Experimental results also show that peak operating wavelengths of five light-emitting diodes and a laser pointer can be determined with a wavelength measurement error of less than 10.5 nm. The total cost of the webcam-based five-channel fiber-optic spectrometer is only approximately US$92.50 and effectively performs to the desired results.