A setup for pulsed-laser Doppler flowmetry ~LDF! measurements has been built and tested. Measurements were carried out comparing continuous-wave and pulsed LDF. With pulsed LDF a higher peak power can be injected into the tissue without exceeding the safety limits. This enables a much larger spacing between the locations of illumination and detection. Thus, the penetration depth, and thus the measurement volume, can be enlarged using the pulsed-LDF method. This method will allow, e.g., monitoring of the cerebral perfusion

de Mul F. F. M.

Dopheide D.

Erwin Hondebrink

Frits F. M. de Mul

Jentink H. W.

Kolinko V. G.

Lohwasser R.

Olkkonen H.

René A. Bolt

Roy G. M. Kolkman

Soelkner G.

Wiendelt Steenbergen

Kolkman, R.G.M.

Hondebrink, Erwin

Bolt, R.A.

Steenbergen, Wiendelt

de Mul, F.F.M.

University of Twente Research Information

REVIEW OF SCIENTIFIC INSTRUMENTS VOLUME 72, NUMBER 11 NOVEMBER 2001Pulsed-laser Doppler flowmetry provides basis for deep perfusion probingRoy G. M. Kolkman,a) Erwin Hondebrink, René A. Bolt, Wiendelt Steenbergen,and Frits F. M. de MulDepartment of Applied Physics, University of Twente, P.O. Box 217, NL-7500 AE Enschede, the Netherlands~Received 14 March 2001; accepted for publication 14 August 2001!A setup for pulsed-laser Doppler flowmetry~LDF! measurements has been built and tested.Measurements were carried out comparing continuous-wave and pulsed LDF. With pulsed LDF ahigher peak power can be injected into the tissue without exceeding the safety limits. This enablesa much larger spacing between the locations of illumination and detection. Thus, the penetrationdepth, and thus the measurement volume, can be enlarged using the pulsed-LDF method. Thismethod will allow, e.g., monitoring of the cerebral perfusion. ©2001 American Institute ofPhysics. @DOI: 10.1063/1.1409566#ticaDhlieaermrttodphelinwrmneuanonredtheoneenFlesalriodyco-rort-theth.m,er-umthetor:erforI. INTRODUCTIONLaser Doppler flowmetry~LDF! provides a method fornoninvasive measurement of the perfusion of tissue. Thesue is illuminated with a cw laser source and the backstered light from the tissue is then detected and analyzed.to scattering of the light at moving red blood cells, this liggets a frequency shift, which causes the detector signafluctuate due to interference. These fluctuations containformation about the perfusion. Bonner and Nossal1 haveshown that the first-order moment of the power spectral dsity of these signals is proportional to the root-mean-squvelocities of the red blood cells:E0`vS~v!dv;A^n2&. ~1!Perfusion deep under the tissue surface can in principlemeasured with laser Doppler flowmetry by placing the fibfor illumination and detection at a sufficient distance froeach other. However, due to the strong attenuation offlected light, laser powers would be needed which exceedsafety limits. Soelkner and co-workers2,3 have shown that itis possible to perform laser Doppler measurements updepth of 30 mm with 120 mW cw light in a tissue-like heaphantom. However, the high power needed prevented apcation on real tissue.A way to increase the power without exceeding tsafety limit is by pulsing the laser source and pulse sampthe Doppler signal. By using short pulses, a high peak pocan be achieved with a low average power. For long-temonitoring of the perfusion the average power determithe maximum allowable power for skin illumination.The developed pulsed-LDF method expressly makesof the high peak power by sampling the peak signals,thus enables noninvasive monitoring of deep perfusiOther pulsed-4 or modulated-5 LDF methods do not makeuse of the higher peak power, but use the average powedetermine the blood flow. Applications of the developa!Electronic mail: r.g.m.kolkman@tn.utwente.nl4240034-6748/2001/72(11)/4242/3/$18.00Downloaded 01 Jun 2004 to 130.89.26.124. Redistribution subject to AIs-t-uetton-n-rebese-heali-gerssed.topulsed-LDF method include noninvasive measurement ofbrain perfusion as well as monitoring of the perfusithroughorgans~e.g., kidney!.To test the proposed LDF method a test setup has bconstructed using a pulsed-laser diode.II. METHODWith tissue perfusion the typical frequency range of LDis 0–20 kHz, corresponding with characteristic time scaup from 50 ms. These times are much larger than typiccoherence times of the laser, which implies that each peof the Doppler signal will contain information from mancoherence times. Then, it does not matter whether thoseherence times were directly adjacent to each other~as is thecase with cw! or had intermittent time periods~as withpulsed LDF!. Following this line, the pulsed-laser Dopplemethod has been designed.The minimum pulse durationtpulse is limited by themaximum path-length differencel max, which can occur inthe measurement volume: photons traveling along the shest path length should have the opportunity to interfere atdetector with photons traveling along the longest path lengThe minimum pulse duration can be estimated bytpulse.l maxc/n, ~2!with n the refractive index of tissue andc the speed of lightin vacuum.Assuming a maximum path-length difference of 50 cwhich holds for nearly all practical cases, and51.33 givesa minimum pulse duration of 2.2 ns. Furthermore, the cohence length of the laser has to be larger than the maximpath-length difference to make photons traveling alongshortest and longest path-length interfering at the detecl coh. l max.As laser diodes are often used6–8 as a light source inLDF instruments, for this pulsed-LDF method also a lasdiode has been used, which fulfills the mentioned criteriathe pulsed light source.2 © 2001 American Institute of PhysicsP license or copyright, see http://rsi.aip.org/rsi/copyright.jspne-eperrihooisulsetoForplee, anticigs.sed-thetheh ist.e4243Rev. Sci. Instrum., Vol. 72, No. 11, November 2001 Pulsed-laser Doppler deep perfusion flowmetryThe LDF time signals are collected by sampling with aanalog-to-digital AD card. A sample is taken during the timthe laser is ‘‘on.’’ The laser is switched off for the time between two adjacent sample points~Fig. 1!. The averagepowerPavg during the LDF measurement is equal to the timratio of the pulse widthtpulse and the repetition timet repetitiontimes the peak pulse powerPpeak:Pavg5tpulset repetitionPpeak. ~3!The basic setup is shown in Fig. 2. A pulse generator~Hameg8035! is used to modulate the laser diode driver~ThorlabsLDC 500! and provides the trigger for the AD card~NationalInstruments AT-MIO-16XE-50!. The light pulses of thesingle-mode laser diode~Hitachi HL6501MG! are transmit-ted via an optical fiber~step index, NA50.23 and core di-ameter 400mm! to the sample. The backscattered and Dopler shifted light is transmitted through the same type of fibto a photodiode~BPW 34!. In this study the pulse generatodelivers pulses of 16ms with a repetition rate of 15 kHz. Byusing the laser pulse as a trigger for the AD card, a measument is recorded only when the laser is on. In this way itsimulated that the LDF signal is generated by a cw ligsource with a power equal to the peak pulse power. Or,other words: the light source is switched off between twadjacent samples of the AD card. Using a sample-and-hFIG. 1. Schematic representation of time scheme pulsed-LDF measuremFIG. 2. Pulsed-LDF setup.Downloaded 01 Jun 2004 to 130.89.26.124. Redistribution subject to AI-re-stinldcircuit, the AD card does not notice that the light sourceswitched off and measures a power equal to the peak ppower.A Labview program is used to collect the signals andcalculate the power spectrum of the detected signals.each spectrum 1000 data points are collected at a samrate, determined by the pulse generator~15 kHz!. To reducethe noise, several spectra can be averaged. As a samplINTRALIPID™ ~IL ! suspension is used~IL 10%!. As the fatparticles are in Brownian motion~‘‘flow’’ !, the photons willbe Doppler shifted. A white nylon block is used as a sta~‘‘no-flow’’ ! scattering object~no Doppler shifted photons!.III. RESULTSResults of phantom measurements are presented in F3 and 4. Figure 3 gives the spectra measured with the pulLDF method of a static scattering object~white nylon block,no flow! and a dynamic scattering object~ uvet with IL 10%,flow, by Brownian motion!. The nylon block has similarscattering and absorption properties as the IL 10%. Also,spectrum of the background is shown. The spectrum ofIL sample shows the expected Doppler broadening, whicnot present in the spectrum of the static scattering objecnt.FIG. 3. Pulsed-LDF spectra Intralipid-10%, nylon, and dark.FIG. 4. LDF spectra Intralipid-10%, cw compared with pulsed LDF.P license or copyright, see http://rsi.aip.org/rsi/copyright.jspouharaeedthga, aesr tfoethrrioin-theinl toure-thetra-i-onh isd iser toherurceam-n.ncytet 40theDFellda-d.H.dse,nd4244 Rev. Sci. Instrum., Vol. 72, No. 11, November 2001 Kolkman et al.Comparison of pulsed and cw LDF has been carriedby comparing the phantom data results of pulsed LDF witpeak pulse power of 20 mW to cw LDF with a power equto the peak pulse power and a power equal to the avepulsed power: 4.7 mW~Fig. 4!. The time ratio of repetitiontime and length of the pulses was 4.2.Figure 4 shows that the pulsed-LDF method giveshigher LDF signal than the cw method with the same avage power. If the power of the cw LDF method is increaswith a factor equal to the time ratio~4.2!, to the peak powerof the pulsed-LDF method, both measurements result insame signal levels.An in vivo experiment on a thumb of a volunteer, usinthe pulsed-LDF method, with and without an occlusion hbeen performed. The spectra are recorded before, duringafter the occlusion.Figure 5 shows that during the occlusion there are lhigh frequencies present in the spectrum. Some time afteocclusion, the spectrum is about equal to the spectrum beocclusion.IV. DISCUSSIONFigure 3 proves that the pulsed-LDF method indemeasures LDF signals. The LDF spectrum only showsexpected Doppler broadening when a measurement is caout on a sample with flow~cuvet filled with IL 10%!. ThisDoppler broadening is not present in the no-flow situat~nylon block!.FIG. 5. In vivo, pulsed-LDF spectra of thumb volunteer, before, during, aafter occlusion.Downloaded 01 Jun 2004 to 130.89.26.124. Redistribution subject to AItalgear-,esndsheredeiednFurthermore, it is obvious~Fig. 4! that the proposedpulsed-LDF method makes use of the high peak powerstead of the lower average power. Figure 4 shows thatpulsed-LDF method gives the same Doppler-signal levelsthe spectrum as the cw LDF method with a power equathe peak pulse power. This proves that the pulsed measment offers the expected results, using the peak power ofpulses.Standard cw laser Doppler instruments have a penetion depth up to a few millimeters. This is suitable for montoring of the microcirculation. To obtain a larger penetratidepth, the distance of the fibers must be increased, whicpossible when the proposed pulsed-laser Doppler methoused.Other published pulsed-4 or modulated-5 LDF methodsdo not use the high peak power, but use the average powmeasure LDF signals. As the peak power can be much higthan the average power, the separation between the soand detector fiber can be increased, resulting in a larger spling volume, containing information about deep perfusioThe expected Doppler shifts in tissue cover a frequerange from 0 to 20 kHz. This implies that the repetition raof the pulsed-laser Doppler instrument should be at leaskHz to avoid aliasing. If short pulses~;50 ns! together withthis repetition rate are used, a peak power of 500 timesaverage power can be achieved.Possible applications of the proposed pulsed-Lmethod include the monitoring of cerebral perfusion as was monitoring of perfusionthroughorgans~e.g., kidney!.ACKNOWLEDGMENTThis research was sponsored by the Technology Fountion STW of the Netherlands~Grant No. TTN.4661!.1R. F. Bonner and R. Nossal, Appl. Opt.20, 2097~1981!.2G. Soelkner, G. Mitic, and R. Lohwasser, Appl. Opt.36, 5647~1997!.3R. Lohwasser and G. Soelkner, Appl. Opt.38, 2128~1999!.4V. G. Kolinko, F. F. M. de Mul, J. Greve, and A. V. Priezzhev, J. BiomeOpt. 3, 187 ~1998!.5H. Olkkonen, Proc. SPIE1922, 219 ~1992!.6D. Dopheide, H. Pfeifer, M. Faber, and G. Taux, J. Laser Appl.1, 40~1989!.7H. W. Jentink, J. A. J. van Beurden, M. A. Helsdingen, F. F. M. de Mul,E. Suichies, J. G. Aarnoudse, and J. Greve, J. Phys. E20, 1281~1987!.8F. F. M. de Mul, J. van Spijker, D. van der Plas, J. Greve, J. G. Aarnouand T. M. Smits, Appl. Opt.23, 2970~1984!.P license or copyright, see http://rsi.aip.org/rsi/copyright.jsp

Pulsed-laser Doppler flowmetry provides basis for deep perfusion probing

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