Medical ultrasound with simultaneous dual-band near infrared diffusive light imaging and co-registration

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1 Medicl ultrsound with simultneous dul-bnd ner infrred diffusive light imging nd co-registrtion Quing Zhu Electricl nd Computer Engineering Deprtment University of Connecticut Storrs, CT 6269 Nn Gung Chen Electricl nd Computer Engineering Deprtment University of Connecticut Storrs, CT 6269 Puyun Guo Electricl nd Computer Engineering Deprtment University of Connecticut Storrs, CT 6269 Abstrct - Recently, we hve constructed novel combined imger suitble for simultneous ultrsound nd ner infrred (NIR) diffusive light imging nd coregistrtion. The imger consists of combined hndheld probe, designed for imging of humn brest, nd the ssocited electronics for dt cquisition. A twodimensionl ultrsound rry is deployed t the center of the combined probe nd 12 dul wvelength lser source fibers (78 nm nd 83 nm) nd 8 opticl detector fibers re deployed t the periphery. Preliminry clinicl results hve indicted tht simultneously displying opticl contrst nd ultrsound morphology structures of the lesions cn significntly improve brest cncer detection nd dignosis. Experimentl results with phntoms hve shown tht high-resolution functionl NIR imging cn be chieved with the guidnce of priori trget locliztion provided by co-registered ultrsound. With the combined probe, fusion of coregistered ultrsound nd NIR imges is fesible nd its potentil in cncer dignosis will be explored in the future. Keywords: Medicl Imging, Co-registrtion, Ultrsound imging, Opticl diffused light imging. 1 Introduction Medicl ultrsound is used extensively for differentition of cysts from solid lesions in brest exmintions nd it is routinely used in conjunction with mmmogrphy. Ultrsound cn detect brest lesions few mm in size [1]. However, its specificity in brest cncer detection is not high s result of overlpping chrcteristics of benign nd mlignnt lesions [2-3]. Figures 1 nd 2 give exmples of medicl ultrsound brest imging. Figure 1 shows gry scle ultrsound imge of plpble lump in 85 yer-old womn. The horizontl nd verticl xes correspond to lterl dimension nd propgtion depth, respectively. Skin surfce is t the top of the imge. Numericl vlues on both xes re imge pixel numbers. The ultrsound shows n irregulr poorly defined hypoechoic mss (pointed by the big white rrow) with chrcteristic mlignnt fetures. The dignosis ws highly suspicious for mlignncy nd biopsy reveled tht the lesion ws infiltrting ductl crcinom. Figure 2 shows gry-scle scn of plpble mss in 27 yers old womn. The imge revels 14 mm mcrolobulted solid mss (pointed by the white rrow) with irregulr mrgins. The mss center is locted t pproximtely 1.2 cm depth. These findings were suspicious, nd ultrsound guided core biopsy ws recommended. Biopsy yielded benign fibrodenom. These two exmples show tht ultrsound specificity in dignosis is not high which results in mny norml biopsies. Opticl imging bsed on diffusive ner- infrred (NIR) light hs the gret potentil to differentite tumors from norml brest tissues through determintion of tissue prmeters, such s blood volume, blood O 2 sturtion, tissue light scttering, wter concentrtion, nd the concentrtion nd lifetime of exogenous contrst gents

2 [4-5]. As shown in Figure 3, the deoxyhemoglobin hs much higher bsorption coefficient t ~78 nm thn tht of oxyhemoglobin. This difference cn be used to chrcterize tumor oxygen sttus when dul wvelengh mesurments re mde t 78 nm nd the isosbestic wvelength t 83 nm. nd 2, respectively. Due to the incresed oxygen consumption of mlignnt cncers, the deoxyhemoglobin concentrtion in generl is high in mlignnt cncers. By compring Figures 4 nd 5, we cn see tht the mlignnt cncer shown in Figure 1 hs significnt deoxy content, while the benign one shown in Figure 2 does not hve significnt deoxy content..3 Absorption Fctor (cm -1 ) OxyHb DeoxyHb Wter Wvelength (nm) KSR 99 Figure 1. A 85 yer-old womn with plpble lump. Ultrsound shows n irregulr poorly defined hypoechoic mss with chrcteristic mlignnt fetures. Biopsy reveled tht the lesion ws infiltrting ductl crcinom. Figure 2. Ultrsound imge of 27 yer-old womn with plpble left brest mss of ~1.4 cm in size. The imge revels mcrolobulted mss with irregulr mrgins. These findings re suspicious. Biopsy yielded benign fibrodenom. As potentil dignostic tool, however, NIR diffusive light imging suffers from low sptil resolution nd lesion loction uncertinties due to intense light scttering in tissue. Figures 4 nd 5 show the corresponding NIR deoxyhemoglobin mps of Figures 1 Figure 3. In vitro bsorption spectr of hemoglobin nd wter, showing spectrl window in tissue in the NIR window. The window is brought bout by first decrese in blood (oxy - nd deoxyhemoglobin) bsorption nd then n increse in wter bsorption with incresing wvelength. While the NIR provides more functionl prmeters for cncer dignosis, its resolution is disppointing. As one cn see in Figure 4, the sptil distribution of the NIR deoxy mp well exceeds cncer size which is ~1 cm in dimeter. The fundmentl problem results from the fct tht the diffusive photons generlly experience hundreds nd thousnds scttering events, nd tht they tke rndom pths from source to detector. This is quite different from imging techniques using X-ry, which hs very week interctions with humn bodies. Consequently, most photons cn go through directly, while few portions re bsorbed nd few re scttered once. Imge reconstruction lgorithms developed for X-ry CT re too simple to tret photon density wves. Diffusive light probes widespred region insted of providing informtion long stright line. Multiple mesurements re lwys correlted s result of overlpping of probed regions. Therefore, incresing the totl number of mesurements does not necessrily provide more independent informtion for imge reconstruction. In generl, the inverse imge reconstruction is underdetermined nd ill-posed. Our group hs introduced novel hybrid imging method tht combines the complementry fetures of

3 ultrsound nd ner-infrred diffusive light imging [6-9]. The hybrid imging obtins co-registered ultrsound nd NIR diffusive light imges through simultneous deployment of n ultrsound rry nd NIR source detector fibers on the sme probe. Co-registrtion permits joint evlution of coustic nd opticl properties of brest lesions, nd enbles the use of lesion morphology provided by high-resolution ultrsound to improve the lesion opticl property estimte. With the priori knowledge of lesion loction nd shpe provided by co-registered ultrsound, NIR imging reconstruction cn be loclized within specified three-dimensionl (3-D) regions. As result, the reconstruction is over-determined becuse the totl number of unknown opticl properties is reduced significntly. In ddition, the reconstruction is less sensitive to noise becuse the convergence cn be chieved with smll number of itertions. 2. Methods The clinicl use of the combined dignosis relies on the co-registrtion of both ultrsound nd NIR sensors t the probe level. Conventionl ultrsound pulse echo imging requires n imging trnsducer be locted on top of the trget, while NIR diffusive light imging is fesible when the opticl source nd detector fibers re distributed t the periphery of the ultrsound trnsducer. Figure 6 () shows probe configurtion nd (b) is the picture of the combined probe. A 1.75D ultrsound rry cpble of ner 3-D imging is locted in the middle of the combined probe. Our 12 dulwvelength lser diode source fibers nd 8 Photo Multiplier Tube (PMT) detector fibers re distributed t the periphery of the ultrsound trnsducer. Simultneous ultrsound nd NIR imging cn be chieved with this combined probe. Y Z O X () Figure 4. Corresponding deoxyhemoglobin mp of Figure 1. Significnt chnge of deoxy ws found in this mlignnt lesion. The dimension of the imge is 1 cm by 1 cm. (b) Figure 6. () Schemtic of combined probe. The centrl rectngulr slot llows ultrsound rry to ccess tissues underneth the probe. Circulr holes re used to hold opticl fibers. Smll ones re for light sources, while big ones re for detectors. (b) Picuture of our combined probe with NIR sensors deployed t the periphery nd n ultrsound rry locted in the middle of the probe. Figure 5. Opticl deoxyhemoglobin mp of Figure 2. No significnt chnge in deoxy ws found in this benign lesion.

4 3. Results We hve conducted serious phntom experiments to evlute the performnce of the combined imging. Figure 7() is the ultrsound B-scn imge of smll emulted lesion (6 mm in dimeter) of low opticl contrst (bsorption coefficient µ =.1 cm -1 ) locted 2.5 cm deep into the opticl scttering medium (reduced ' scttering coefficient µ = cm -1 ). The verticl xis is s 6 the propgtion direction nd the horiztl xis is the lterl dimension. Figure 7(b) is the ultrsound C-scn or sptil imge of the trget co-registered with NIR imges shown in Figure 7 (c) nd (d). Without ultrsound imge guidnce shown in (b), the µ imge shown in Figure 7(c) does not converge nd two trgets pper t wrong loctions. With the ultrsound guidnce shown in (b), the trget shown in Figure 7(d) ppers t the correct loction nd the estimted µ is 86% of the true vlue. These preliminry results re very encourging nd suggest tht hybrid imging method hs gret potentil to improve erly detection by combining high sptil resolution of ultrsound nd high contrst of opticl imging. () (b) Y (cm) Y (cm) X (cm) (c ) X (cm) (d) Figure 7. Ultrsound nd opticl imges of smll (6mm in dimeter) emulted tumor of low opticl contrst µ =.1cm -1 ) imbedded in the opticl scttering medium ( ' (reduced scttering coefficient is µ s = 6 cm -1 ). () Ultrsound imge obtined in x-z scn, where x is the lterl direction nd z is the propgtion direction). The trget is slightly echogenic nd clerly seen. (b) C-scn or sptil x-y imge of the ultrsound co-registered with NIR imges shown in (c) nd (d). The horizontl size of the imge is 3 cm nd the verticl size is 1.7 cm. The size is scled to the sme s in (c) nd (d). (c) Reconstructed opticl bsorption imge µ without ultrsound guidnce. The smll trget should pper t the center loction of the imge, however, two trgets pper t wrong loctions. (d) With the guidnce of coregistered ultrsound shown in (b), the reconstructed trget ppers t correction loction nd the reconstructed vlue is the true vlue. µ =.86 cm -1 which is 86% of

5 Figure 8 shows exmples of two trget cses. In generl, it is very difficult to chrcterize two trgets bsed on NIR only if the trgets re locted closer to ech other nd contrst is similr to ech other. We used two geometriclly identicl trgets tht were pproximtely 1 cm 3 cubes. The ultrsound imges resulted in very good estimtions of trget geometries (Figure 8() nd (b)). The centers of the two trgets re bout 2 cm prt. For co-registered NIR imging, two different combintions of trgets were dopted. The first ws pir of equl-bsorbing cubes with the bsorption coefficient being.65 cm -1 (Figure 8 (c)). The second ws composed of one of.65 cm -1, nd nother of.1 cm -1 (Figure 8(d)). The true vlues nd reconstructed vlues re compred in Tble 1. With the ultrsound guidnce, the reconstructed vlues re very close to true vlues. () X( m m) X( m m) (c ) (d) Z(mm) X(mm) (b) Figure 8. () Ultrsound imge of one of the two trgets in y-z plne. Y is the lterl dimension nd z is the propgtion dimension. (b) Ultrsound imge of the two trgets in Y-X plne. Both re sptil dimensions. (c) NIR imge of two equl opticl-contrst trgets reconstructed with ultrsound guidnce. The reconstructed opticl bsorption coefficients re very close to true vlues (see Tble 1). (d) NIR imge of one low nd one high opticl-contrst trgets reconstructed with ultrsound guidnce. The recosntructed vlues re very close to true vlues. 4. Summry Simultneous ultrsound nd NIR imging hs shown promising results in providing complementry informtion to cncer detection nd ccurtely chrcterizing the tumor opticl properties. This method hs gret clinicl potentil for improving the cncer detection nd dignosis. With the co-xil probe configurtion, co-registered ultrsound nd opticl imges cn be obtined nd imge fusion is fesible. The methods of imge fusion nd the interprettions of fused imges require further study.

6 Acknowledgments We would like to thnk the following for their funding support: the Stte of Connecticut, DOD ARMY Brest Cncer Progrm (DAMD , DAMD ). Reference : 1. T. A, Stvros, D. Thickmn, C. Rpp, Solid brest nodules: use of sonogrphy to distinguish between benign nd mlignnt lesions, Rdiology 196, (1995). 2. E. A. Sickles, R.A. Filly, P. W. Cllen, Benign brest lesions: ultrsound detection nd dignosis, Rdiology 151, (1984). Tble 1. Reconstructed bsorption coefficients from phntom experiments Combintion 1 Combintion 2 Trget 1 Trget 2 Trget 1 Trget 2 Rel vlue (cm -1 ) Reconstructed vlue(cm -1 ) V. P. Jckson, The role of US in brest imging, Rdiology 177, (199). 4. B. Tromberg, N. shh, R. Lnning, A. Cerussi, J. Espinoz, T. Phm, L. Svsnd nd J. Butler, Non- Invsive in vivo chrcteriztion of brest tumors using photon migrtion spectroscopy, Neoplsi 2, 26-4 (2). 5. A. Yo dh nd B. Chnce, Spectroscopy nd imging with diffusing light, Physics Tody, 48 (3): 34-4 (1995). 6. Q. Zhu, T. Dunrn, M. Holboke, V. Ntzichristos nd A. Yodh, Imger tht combines ner infrred diffusive light nd ultrsound, Opt. Lett., 24(15), (1999) Q. Zhu, E. Connt nd B. Chnce, Opticl imging s n djunct to sonogrph in differentiting benign from mlignnt brest lesions, Journl of Biomedicl Optics 5(2), (2). 9. Q. Zhu, NG. Chen, DQ, Pio, PY. Guo nd XH. Ding, Design of ner infrred imging probe with the ssistnce of ultrsound locliztion, Appl. Opt. July No.4 (21). 1. NG. Chen, PY. Guo, SK.Yn, DQ. Pio nd Q. Zhu, Simultneous ner infrred diffusive light nd ultrsound imging, Appl. Opt. Accepted (My 21).