We have developed a high-bandwidth frequency-domain photon migration (FDPM) instrument which is capable of noninvasively determining the optical properties of biological tissues in near-real-time. This portable, inexpensive, diode-based instrument is unique in the sense that we employ direct diode laser modulation and avalanche photodiode detection. Diffusion models were used to extract the optical properties (absorption and transport scattering coefficients)of tissue-simulating solutions.from the 300 kHz to I GHz photon density wave data

Anderson, Eric R.

Haskell, Richard C.

Madsen, Steen J.

Tromberg, Bruce J.

English

Scholarship@Claremont

Claremont CollegesScholarship @ ClaremontAll HMC Faculty Publications and Research HMC Faculty Scholarship5-30-1995A High-Bandwidth Frequency-Domain PhotonMigration Instrument for Clinical UseSteen J. MadsenUniversity of Nevada, Las VegasEric R. AndersonUniversity of California - IrvineRichard C. HaskellHarvey Mudd CollegeBruce J. TrombergUniversity of California - IrvineThis Conference Proceeding is brought to you for free and open access by the HMC Faculty Scholarship at Scholarship @ Claremont. It has beenaccepted for inclusion in All HMC Faculty Publications and Research by an authorized administrator of Scholarship @ Claremont. For moreinformation, please contact scholarship@cuc.claremont.edu.Recommended CitationMadsen, Steen J., Eric R. Anderson, Richard C. Haskell, and Bruce J. Tromberg. "A high-bandwidth frequency-domain photonmigration instrument for clinical use." Proceedings of SPIE: Optical tomography, photon migration, and spectroscopy of tissue andmodel media: theory, human studies, and instrumentation. Vol. 2389, (1995): 257-263. DOI: 10.1117/12.209976A High-Bandwidth Frequency-Domain Photon Migration Instrument for Clinical UseSteen1.Madsen'', EricR. Anderson'', Richard C. HaskeUb andBruce1. Tromberg''(a) BeckmanLaserInstituteandMedical Clinic, University of California, Irvine, CA92715(b) Harvey MuddCollege, Claremont, CA 91711ABSlRACTWe have developed a high-bandwidth frequency-domain photon migration (FDPM) instrumentwhich is capable of noninvasively determining the opticalproperties of biological tissues in near-real-time.This portable, inexpensive, diode-based instrument is uniquein the sensethat we employ directdiode lasermodulation andavalanche photodiode detection.Diffusion models were used to extract the optical properties (absorption and transport scatteringcoefficients)of tissue-simulating solutions.from the 300 kHz to I GHzphotondensity wavedata.Keywords: frequency-domain photon migration, optical properties, diode laser. network analyzer,avalanche photodiode2. INTRODUCTIONKnowledge of the optical properties of biological tissues is vital in therapeutic and diagnosticapplications involving the use of lasers and other light sources. For example, in therapeutic applications,such as PhotodynamicTherapy (PDT), the optical properties are required in order to determine the lightdistribution in pathological and normal tissues1. In diagnostic applications, light can be used to obtaininformationabout structure and function. For example, differences in theopticalproperties between normaland pathological tissues may be exploited for imaging purposes. In addition, temporal changes may beindicative of metabollic changes. To be clinically useful, the optical properties should be determinednoninvasively. Thismay be accomplished usingfrequency-domain photonmigration (FDPM).In FDPM the intensity of light incident on a material, such as biological tissue, is modulated athigh frequency (106 - 109 Hz), and the diffusely reflected or transmitted signal is monitored by a phase-senstitivedetector. It has been shownthatthe modulated wavepropagates through multipe-scattering media,such as biological tissue, as diffuse photon density waves with a coherent front2-4. Since density wavedispersion depends on the optical properties of the material probed, the absorption (/.La) and transport0-8194-1736-X/95/$6.00 SPJE Vo/. 2389/257scattering (Jl's) coefficients can be determined by fitting the measured frequency- and distance- dependentbehavior to analytical expressions derived from diffusion theory't.A number of modulation-detection techniques have been developed for FDPM. The most generalinvolves modulation of the light source (arc lamp or laser) using a Pockels cell and cross-correlationdetection using conventional photomultiplier tubes5. However, due to its limited bandwidth (200 - 300MHz), this technique may be insufficient for determining the optical properties of most biological tissues.For example, FDPM measurements on human uterine tissue indicate that frequencies in excess of 350 MHzare required for reliable determination of Jla and Jl's in a single measurementv, This bandwidth limitationcan be overcome by use of the high harmonic content of pulsed mode-locked lasers and sensitive, fastphotodetectors. Although such systems are ill suited to the clinic due to their cost and complexity, theypermit recording of photon density wave dispersion with sufficient temporal resolution for optical propertiesto be calculated in a single measurement.In this work we describe a relatively simple, inexpensive diode-based FDPM system operating innear real time between 300 kHz and 1 GHz which allows rapid determination of the optical properties ofbiological tissues from a single multifrequency measurement.3. INSTRUMENTATIONA schematic overview of the system is shown in Figure 1. A novel feature of the system is thevector network analyzer (Hewlett-Packard Model 8753C), which measures reflection and transmissioncharacteristics of devices and networks by applying a known swept signal and measuring the responses. Theanalyzer's built-in synthesized source produces a swept rf signal (300 kHz - 1 GHz) which is superimposedupon the direct current of a diode laser by means of a bias tee (Picosecond Pulse Labs Model 5575A). Asmall fraction of the rf is split off and used as a reference signal. The direct current is obtained from astabilized current source (ILX Lightwave Model LDC-3742) which also provides thermoelectric coolingcontrol for the laser diode. A directional coupler prevents reflections at the laser diode from reaching thenetwork analyzer. An rf switch allows for the incorporation of up to four different diodes in the system.Two laser diodes are used in the present configuration: a AIGaInP O. = 674 nm) and a GaAIAs (A. = 811nm) both obtained from SDL, Inc. All measurements described in this work were performed using theAIGaInP diode. The laser is usually biased at 50 rnA above lasing threshold (210 rnA) and 14 dBm of RFpower is applied. However, since no impedance matching of the laser diode to the 50 ohm source impedancewas performed, the actual ac optical power is much less than 14 dBm. The diode laser output is focusedthrough a grin lens and coupled into a 100 um gradient-index multimode fiber. Typically, optical powersranging from 20 - 40 mW are coupled into the sample.258/ SPIE Vol. 2389Network AnalyzerRFout Ret inFigure 1. Schematic of the frequency-domain photon migration instument.The optical signal is collected with a 600 11m step-index multimode fiber and transimtted to ahigh-gain (4 x 103) avalanche photodiode (APD; New Focus Inc., Model 1651) biased at 15 V. The deoutput of the APD is monitored with a picoammeter (Keithley Model 485). Acquisiton times of photon-density-wave phase and amplitude over the entire 300 kHz to 1 GHz frequency spectrum are variable anddepend primarily on intermediate frequency bandwidth and signal averaging parameters. Reasonable signalscan be collected on the order of seconds. Shorter acquisition times can be realized by constraining themeasurement bandwidth.4. RESULTS AND DISCUSSIONThe source modulation at low and high frequency is illustrated in Figure 2 for a dc bias setting of254 rrtA, There is some distortion of the sinusoidal waveform at high frequency which is due to thedynamic behavior of the semiconductor laser under strong modulation7. The distortions become morepronounced as the de bias approaches threshold. In practical terms, we were able to compensate for smallwaveform distortions by acquiring sample and reference data under identical conditions.SPIE Vol. 2389 I 259•100 MHz•1000 MHzh'!FoJi~"~ ~~ .,~,, ,••••,, , ..• 10 :i" A'., • I 'I' ", I I,'j' • " I'. " 1-- ,. -to , ,• ....,.. ,. •, .,' ~ .: f. ,1 ,",· 'to. 01 ' ..:, ,- -, ," . :,"',., I'J ," ,, '~ '\ ~/''IJ •~.. t' :; 'It: ,.'.V'I ,Figure 2. Source modulation at a dc bias of 254 rnA and a) 100 MHz and b) 1000 MHz. The vertical scatesin a) and b) are 100 and 50 mY/div. respectively. The corresponding horizontal scales are 10 and 1 ns/div,respectively.The ability of the system to determine the optical properties of tissue-simulating solutions wastested using 2% Intralipid (Kabivitrum Inc., Clayton, NC) and 1 ug/ml of nickel tetrasulfonatedphthlocyanine (NiSPC; Midcentury, Posen, II). The concentrations oflntralipid and NiSPC were chosen tocorrespond to the optical properties of typical tissues. Measurements were performed in two geometries:infinite and semi-infinite (Fig. 3). In the case of the infinite geometry, the source and detector fibers werecentered and placed at a depth of approximately 10 cm in a 4 L cylindrical beaker containing 3.5 L of theliquid solution. For the semi-infinite measurements, the source and detector fibers were positioned at thesurface of the solution. In both cases, reference and signal measurements were made at source-detectorseparations of 5 and 12 mm (effective separation =7 mm). The propagation of light in the tissue-simulating solutions was analyzed using diffusion theory. Appropriate diffusion models were fit to theinfinite4 and semi-infinite8 data using a nonlinear least-squares fitting routine, based on a Marquardt-Levenberg algorithm.260 ISPIE Vol. 238910080-...:f 60"t:l'-'~v.l~ 40.=~2000 200 400 600Freq. (MHz)800 1000Figure 3. Phase vs, frequency responsefor 2% Intralipid and 1 ~g/ml NiSPC tissue-simulating solutions oftwo geometries. In both cases, the effective source-detector separation was 7.0 mm. The curves representbest fits to the data.Figure 3 shows the phase vs. frequency plots in the two geometries. Each data set was acquired inapproximately 14 s. As expected, the phase is lower in the semi-infinite case due to tha fact that onlyphotons propagating in the plane below the fibers contribute to the signal. The plots demonstrate thatreliable phase data can be obtainedin tissue-simulating solutions at frequencies up to 800MHz. The actualand fitted optical properties are summarized in Table 1. The fitted absorption and transport scatteringcoefficientsare in good agreement with the actual values. In the case of the transportscattering coefficient.the actual value is determined fromMie theory9.Table 1. Summary of fittedand actualoptical propertiesJ.La (mm-!)Ws (mm-!)Semi-infinite0.00871.86Infinite0.01082.65Actual valuesom -0.0132.0 - 2.5In general, we have been able to obtain reliable phase information up to 800 MHz at source-detector separations up to 18 mm in tissue-simulating solutions (Ila= 0.01 mm-1, ~'s = 2.0 mml). RapidSPIE Vol. 2389 f 261attenuation of the ac signal component limits the bandwidth of the instrument at greater distances. Atpresent, the overall system bandwidth is detector limited. The APD has a 3 dB rolloff at 1 GHz, however,the response of the detector falls by 1.5 dB at 800 MHz at the high gain settings used in these experiments.Modifications to the present system should improve the signal-to-noise ratio and allowmeasurements up to the 1 GHz APD limit. These modifications include: (1) improving the optical couplingonto the small-area (200 urn dia.) detector, (2) improving the optical coupling between the laser diode andfiber, (3) improving source modulation characteristics by placing a low inductance resistor in series with thelaser diode so the overall impedance is matched to the 50 ohm rf output, (4) increasing the sourcemodulation depth (especially at high frequencies) by amplifying the network analyzer rf output, and (5)combining phase data with the ac and dc amplitude information to calculate optical properties.5. CONCLUSIONSWe have developed a high-bandwidth FDPM instrument, which employs direct diode modulationand APD detection at multiple modulation frequencies up to 1 GHz. Access to 1 GHz multifrequency phaseand amplitude information permits rapid, noninvasive characterization of the optical properties of mostcommonly encountered tissues in a single measurement. With the incorporation of additional wavelengthdiodes the system will be capable of monitoring various physiological parameters, including oxygenated anddeoxygenated hemoglobin levels, drug concentration, blood volume changes, tissue hydration status, andtissue scattering properties. Since the instrument is compact, it can easily be transported to operating roomsand bedridden patient, such as neonates in intensive care. These features suggest that portable FDPM devicescan be constructed to provide high-bandwidth information for a variety of applications in tissue diagnosticsand imaging.6. ACKNOWLEDGMENTSThe authors wish to thank Ray Golish and Fabio Rojas for developing the computer programmes.We also thank Lars Svaasand for many useful discussions. This research was supported by the WhitakerFoundation (WFl6493), the National Institutes of Health (R29GM50958), and Beckman Instruments, Inc.In addition, we acknowledge Beckman Laser Institute program support from the Office of Naval Research(N00014-91-0134), the Department of Energy (DE-FG--3-91-ER61227), and the National Institutes ofHealth (5P4IRR01192-15).262/ SPIE Vol. 23897. REFERENCES1. B.C. Wilson and M. S. Patterson, Phys, Med. Biol., 31, 327-360, 1986.2. J. Fishkin, E. Gratton, M. 1. vandeVen and W. W. Mantulin, Proc. Soc. Photo-Opt. lnstrum.Eng., 1431, 122, 1991.3. M. A. O'Leary, D.A. Boas, B.C. Chance and A. G. Yodh, Phys. Rev. Lett., 69, 2658, 1992.4. B. J. Tromberg, L. O. Svaasand, T.-T. Tsay and R. C. Haskell,Appl. Opt., 32, 607, 1993.5. J. R. Lakowicz, Principles of Fluorescence Spectroscopy, Plenum, New York, 1983.6. S. J. Madsen, P. Wyss, L. O. Svaasand, R. C. Haskell, Y. Tadir and B. J. Tromberg, Phys,Med. Biol., 39, 1191, 1994.7. W. 1. Way, 1. Lightwave Technol., LT-5, 305, 1987.8. R. C. Haskell, L. O. Svaasand, T.-T. Tsay, T.-C. Feng, M. S. McAdams and B. 1. Tromberg,J. Opt. Soc. Am. A, 11 (10),2727, 1994.\9. H. J. Van Staveren, C. J. M. Moes, J. van Marle, S. A. Prahl and M. J. C. vanGemert, Appl.Opt. 30, 4507, 1991.SPIE Vol. 2389/263

A High-Bandwidth Frequency-Domain Photon Migration Instrument for Clinical Use

Keck Graduate Institute

Claremont Colleges
Scholarship @ Claremont
All HMC Faculty Publications and Research HMC Faculty Scholarship
5-30-1995
A High-Bandwidth Frequency-Domain Photon
Migration Instrument for Clinical Use
Steen J. Madsen
University of Nevada, Las Vegas
Eric R. Anderson
University of California - Irvine
Richard C. Haskell
Harvey Mudd College
Bruce J. Tromberg
University of California - Irvine
This Conference Proceeding is brought to you for free and open access by the HMC Faculty Scholarship at Scholarship @ Claremont. It has been
accepted for inclusion in All HMC Faculty Publications and Research by an authorized administrator of Scholarship @ Claremont. For more
information, please contact scholarship@cuc.claremont.edu.
Recommended Citation
Madsen, Steen J., Eric R. Anderson, Richard C. Haskell, and Bruce J. Tromberg. "A high-bandwidth frequency-domain photon
migration instrument for clinical use." Proceedings of SPIE: Optical tomography, photon migration, and spectroscopy of tissue and
model media: theory, human studies, and instrumentation. Vol. 2389, (1995): 257-263. DOI: 10.1117/12.209976
A High-Bandwidth Frequency-Domain Photon Migration Instrument for Clinical Use
Steen1.Madsen'', EricR. Anderson'', Richard C. HaskeUb andBruce1. Tromberg''
(a) BeckmanLaserInstituteandMedical Clinic, University of California, Irvine, CA92715
(b) Harvey MuddCollege, Claremont, CA 91711
ABSlRACT
We have developed a high-bandwidth frequency-domain photon migration (FDPM) instrument
which is capable of noninvasively determining the opticalproperties of biological tissues in near-real-time.
This portable, inexpensive, diode-based instrument is uniquein the sensethat we employ directdiode laser
modulation andavalanche photodiode detection.
Diffusion models were used to extract the optical properties (absorption and transport scattering
coefficients)of tissue-simulating solutions.from the 300 kHz to I GHzphotondensity wavedata.
Keywords: frequency-domain photon migration, optical properties, diode laser. network analyzer,
avalanche photodiode
2. INTRODUCTION
Knowledge of the optical properties of biological tissues is vital in therapeutic and diagnostic
applications involving the use of lasers and other light sources. For example, in therapeutic applications,
such as PhotodynamicTherapy (PDT), the optical properties are required in order to determine the light
distribution in pathological and normal tissues1. In diagnostic applications, light can be used to obtain
informationabout structure and function. For example, differences in theopticalproperties between normal
and pathological tissues may be exploited for imaging purposes. In addition, temporal changes may be
indicative of metabollic changes. To be clinically useful, the optical properties should be determined
noninvasively. Thismay be accomplished usingfrequency-domain photonmigration (FDPM).
In FDPM the intensity of light incident on a material, such as biological tissue, is modulated at
high frequency (106 - 109 Hz), and the diffusely reflected or transmitted signal is monitored by a phase-
senstitivedetector. It has been shownthatthe modulated wavepropagates through multipe-scattering media,
such as biological tissue, as diffuse photon density waves with a coherent front2-4. Since density wave
dispersion depends on the optical properties of the material probed, the absorption (/.La) and transport
0-8194-1736-X/95/$6.00 SPJE Vo/. 2389/257
scattering (Jl's) coefficients can be determined by fitting the measured frequency- and distance- dependent
behavior to analytical expressions derived from diffusion theory't.
A number of modulation-detection techniques have been developed for FDPM. The most general
involves modulation of the light source (arc lamp or laser) using a Pockels cell and cross-correlation
detection using conventional photomultiplier tubes5. However, due to its limited bandwidth (200 - 300
MHz), this technique may be insufficient for determining the optical properties of most biological tissues.
For example, FDPM measurements on human uterine tissue indicate that frequencies in excess of 350 MHz
are required for reliable determination of Jla and Jl's in a single measurementv, This bandwidth limitation
can be overcome by use of the high harmonic content of pulsed mode-locked lasers and sensitive, fast
photodetectors. Although such systems are ill suited to the clinic due to their cost and complexity, they
permit recording of photon density wave dispersion with sufficient temporal resolution for optical properties
to be calculated in a single measurement.
In this work we describe a relatively simple, inexpensive diode-based FDPM system operating in
near real time between 300 kHz and 1 GHz which allows rapid determination of the optical properties of
biological tissues from a single multifrequency measurement.
3. INSTRUMENTATION
A schematic overview of the system is shown in Figure 1. A novel feature of the system is the
vector network analyzer (Hewlett-Packard Model 8753C), which measures reflection and transmission
characteristics of devices and networks by applying a known swept signal and measuring the responses. The
analyzer's built-in synthesized source produces a swept rf signal (300 kHz - 1 GHz) which is superimposed
upon the direct current of a diode laser by means of a bias tee (Picosecond Pulse Labs Model 5575A). A
small fraction of the rf is split off and used as a reference signal. The direct current is obtained from a
stabilized current source (ILX Lightwave Model LDC-3742) which also provides thermoelectric cooling
control for the laser diode. A directional coupler prevents reflections at the laser diode from reaching the
network analyzer. An rf switch allows for the incorporation of up to four different diodes in the system.
Two laser diodes are used in the present configuration: a AIGaInP O. = 674 nm) and a GaAIAs (A. = 811
nm) both obtained from SDL, Inc. All measurements described in this work were performed using the
AIGaInP diode. The laser is usually biased at 50 rnA above lasing threshold (210 rnA) and 14 dBm of RF
power is applied. However, since no impedance matching of the laser diode to the 50 ohm source impedance
was performed, the actual ac optical power is much less than 14 dBm. The diode laser output is focused
through a grin lens and coupled into a 100 um gradient-index multimode fiber. Typically, optical powers
ranging from 20 - 40 mW are coupled into the sample.
258/ SPIE Vol. 2389
Network Analyzer
RFout Ret in
Figure 1. Schematic of the frequency-domain photon migration instument.
The optical signal is collected with a 600 11m step-index multimode fiber and transimtted to a
high-gain (4 x 103) avalanche photodiode (APD; New Focus Inc., Model 1651) biased at 15 V. The de
output of the APD is monitored with a picoammeter (Keithley Model 485). Acquisiton times of photon-
density-wave phase and amplitude over the entire 300 kHz to 1 GHz frequency spectrum are variable and
depend primarily on intermediate frequency bandwidth and signal averaging parameters. Reasonable signals
can be collected on the order of seconds. Shorter acquisition times can be realized by constraining the
measurement bandwidth.
4. RESULTS AND DISCUSSION
The source modulation at low and high frequency is illustrated in Figure 2 for a dc bias setting of
254 rrtA, There is some distortion of the sinusoidal waveform at high frequency which is due to the
dynamic behavior of the semiconductor laser under strong modulation7. The distortions become more
pronounced as the de bias approaches threshold. In practical terms, we were able to compensate for small
waveform distortions by acquiring sample and reference data under identical conditions.
SPIE Vol. 2389 I 259
•100 MHz
•
1000 MHz
h'!
FoJi~
"~ ~~ .,~,, ,
••••
,
, , ..
• 10 :i" A'., • I 'I' ", I I,
'j' • " I'. " 1-- ,. -to , ,• ....,.. ,. •
, .,' ~ .: f. ,1 ,
"
,
· '
to. 01 ' ..:, ,
- -, ," . :,
"'
,
., I
'J ," ,
, '~ '\ ~/'
'IJ •~.. t' :; 'I
t: ,
.'.
V'
I ,
Figure 2. Source modulation at a dc bias of 254 rnA and a) 100 MHz and b) 1000 MHz. The vertical scates
in a) and b) are 100 and 50 mY/div. respectively. The corresponding horizontal scales are 10 and 1 ns/div,
respectively.
The ability of the system to determine the optical properties of tissue-simulating solutions was
tested using 2% Intralipid (Kabivitrum Inc., Clayton, NC) and 1 ug/ml of nickel tetrasulfonated
phthlocyanine (NiSPC; Midcentury, Posen, II). The concentrations oflntralipid and NiSPC were chosen to
correspond to the optical properties of typical tissues. Measurements were performed in two geometries:
infinite and semi-infinite (Fig. 3). In the case of the infinite geometry, the source and detector fibers were
centered and placed at a depth of approximately 10 cm in a 4 L cylindrical beaker containing 3.5 L of the
liquid solution. For the semi-infinite measurements, the source and detector fibers were positioned at the
surface of the solution. In both cases, reference and signal measurements were made at source-detector
separations of 5 and 12 mm (effective separation =7 mm). The propagation of light in the tissue-
simulating solutions was analyzed using diffusion theory. Appropriate diffusion models were fit to the
infinite4 and semi-infinite8 data using a nonlinear least-squares fitting routine, based on a Marquardt-
Levenberg algorithm.
260 ISPIE Vol. 2389
100
80
-..
.
:f 60
"t:l
'-'
~
v.l
~ 40.=
~
20
0
0 200 400 600
Freq. (MHz)
800 1000
Figure 3. Phase vs, frequency responsefor 2% Intralipid and 1 ~g/ml NiSPC tissue-simulating solutions of
two geometries. In both cases, the effective source-detector separation was 7.0 mm. The curves represent
best fits to the data.
Figure 3 shows the phase vs. frequency plots in the two geometries. Each data set was acquired in
approximately 14 s. As expected, the phase is lower in the semi-infinite case due to tha fact that only
photons propagating in the plane below the fibers contribute to the signal. The plots demonstrate that
reliable phase data can be obtainedin tissue-simulating solutions at frequencies up to 800MHz. The actual
and fitted optical properties are summarized in Table 1. The fitted absorption and transport scattering
coefficientsare in good agreement with the actual values. In the case of the transportscattering coefficient.
the actual value is determined fromMie theory9.
Table 1. Summary of fittedand actualoptical properties
J.La (mm-!)
Ws (mm-!)
Semi-infinite
0.0087
1.86
Infinite
0.0108
2.65
Actual values
om -0.013
2.0 - 2.5
In general, we have been able to obtain reliable phase information up to 800 MHz at source-
detector separations up to 18 mm in tissue-simulating solutions (Ila= 0.01 mm-1, ~'s = 2.0 mml). Rapid
SPIE Vol. 2389 f 261
attenuation of the ac signal component limits the bandwidth of the instrument at greater distances. At
present, the overall system bandwidth is detector limited. The APD has a 3 dB rolloff at 1 GHz, however,
the response of the detector falls by 1.5 dB at 800 MHz at the high gain settings used in these experiments.
Modifications to the present system should improve the signal-to-noise ratio and allow
measurements up to the 1 GHz APD limit. These modifications include: (1) improving the optical coupling
onto the small-area (200 urn dia.) detector, (2) improving the optical coupling between the laser diode and
fiber, (3) improving source modulation characteristics by placing a low inductance resistor in series with the
laser diode so the overall impedance is matched to the 50 ohm rf output, (4) increasing the source
modulation depth (especially at high frequencies) by amplifying the network analyzer rf output, and (5)
combining phase data with the ac and dc amplitude information to calculate optical properties.
5. CONCLUSIONS
We have developed a high-bandwidth FDPM instrument, which employs direct diode modulation
and APD detection at multiple modulation frequencies up to 1 GHz. Access to 1 GHz multifrequency phase
and amplitude information permits rapid, noninvasive characterization of the optical properties of most
commonly encountered tissues in a single measurement. With the incorporation of additional wavelength
diodes the system will be capable of monitoring various physiological parameters, including oxygenated and
deoxygenated hemoglobin levels, drug concentration, blood volume changes, tissue hydration status, and
tissue scattering properties. Since the instrument is compact, it can easily be transported to operating rooms
and bedridden patient, such as neonates in intensive care. These features suggest that portable FDPM devices
can be constructed to provide high-bandwidth information for a variety of applications in tissue diagnostics
and imaging.
6. ACKNOWLEDGMENTS
The authors wish to thank Ray Golish and Fabio Rojas for developing the computer programmes.
We also thank Lars Svaasand for many useful discussions. This research was supported by the Whitaker
Foundation (WFl6493), the National Institutes of Health (R29GM50958), and Beckman Instruments, Inc.
In addition, we acknowledge Beckman Laser Institute program support from the Office of Naval Research
(N00014-91-0134), the Department of Energy (DE-FG--3-91-ER61227), and the National Institutes of
Health (5P4IRR01192-15).
262/ SPIE Vol. 2389
7. REFERENCES
1. B.C. Wilson and M. S. Patterson, Phys, Med. Biol., 31, 327-360, 1986.
2. J. Fishkin, E. Gratton, M. 1. vandeVen and W. W. Mantulin, Proc. Soc. Photo-Opt. lnstrum.
Eng., 1431, 122, 1991.
3. M. A. O'Leary, D.A. Boas, B.C. Chance and A. G. Yodh, Phys. Rev. Lett., 69, 2658, 1992.
4. B. J. Tromberg, L. O. Svaasand, T.-T. Tsay and R. C. Haskell,Appl. Opt., 32, 607, 1993.
5. J. R. Lakowicz, Principles of Fluorescence Spectroscopy, Plenum, New York, 1983.
6. S. J. Madsen, P. Wyss, L. O. Svaasand, R. C. Haskell, Y. Tadir and B. J. Tromberg, Phys,
Med. Biol., 39, 1191, 1994.
7. W. 1. Way, 1. Lightwave Technol., LT-5, 305, 1987.
8. R. C. Haskell, L. O. Svaasand, T.-T. Tsay, T.-C. Feng, M. S. McAdams and B. 1. Tromberg,
J. Opt. Soc. Am. A, 11 (10),2727, 1994.\
9. H. J. Van Staveren, C. J. M. Moes, J. van Marle, S. A. Prahl and M. J. C. vanGemert, Appl.
Opt. 30, 4507, 1991.
SPIE Vol. 2389/263


We have developed a high-bandwidth frequency-domain photon migration (FDPM) instrument which capable of noninvasively determining the optical properties of biological tissues in near-real-time. This portable, inexpensive, diode-based instrument is unique in the sense that we employ direct diode laser modulation avalanche photodiode detection. Diffusion models were used to extract the optical properties (absorption and transport scattering coefficients) of tissue-simulating solution from the 300 kHz to 1 GHz photon density wave data

Madsen, Sten

Anderson, Eric R

Haskell, Richard C

Tromberg, Bruce J

eScholarship - University of California

High-bandwidth frequency-domain photon migration instrument for clinical use

https://scholarship.claremont.edu/cgi/viewcontent.cgi?article=1300&amp;context=hmc_fac_pub

A High-Bandwidth Frequency-Domain Photon Migration Instrument for Clinical Use

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Keck Graduate Institute

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