We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors

Transcription

1 We are InechOpen, he world s leading publisher of Open Access books Buil by scieniss, for scieniss 4, , M Open access books available Inernaional auhors and ediors Downloads Our auhors are among he 154 Counries delivered o TOP 1% mos cied scieniss 12.2% Conribuors from op 500 universiies Selecion of our books indexed in he Book Ciaion Index in Web of Science Core Collecion (BKCI) Ineresed in publishing wih us? Conac book.deparmen@inechopen.com Numbers displayed above are based on laes daa colleced. For more informaion visi

2 23 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles Yasuoshi Ishihara 1, Tsuyoshi Kuwabara 2 and Naoki Wadamori 2 1 Meiji Universiy, 2 Nagaoka Universiy of Technology Japan 1. Inroducion The enhanced permeaion and reenion (EPR) effec (Masumura & Maeda, 1986) caused by he leakage of inernally adminisered nanoparicles from blood vessels and heir accumulaion in cancerous issues can be used o diagnose cancer. Gleich and Weizenecker proposed he magneic paricle imaging (MPI) approach (Gleich & Weizenecker, 2005), whereby he posiions of hese magneic nanoparicles (MNPs) accumulaed in cancerous issue can be deeced by applying a local alernaing magneic field from a source posiioned ouside he body. In basic MPI, he local magneic field disribuion is scanned o encode he spaial informaion, and he magneizaion signal wih odd-order harmonics is deeced from MNPs inside a seleced region when an alernaing magneic field is applied o he MNPs. Furhermore, a fas daa acquisiion mehod by scanning spaial daa along wih a Lissajous rajecory was proposed (Gleich e al., 2008; Knopp e al., 2009), and real ime image-daa acquisiion was achieved (Weizenecker e al., 2009). However, inerference from he magneizaion signal generaed from he MNPs ouside he seleced region degraded he image resoluion and signal sensiiviy (signal-o-noise raio). We proposed an image reconsrucion mehod for reducing hese inerference signals mainly generaed by even harmonics, and a correcion mehod o suppress he inerference signals (Kusayama & Ishihara, 2007; 2009; Ishihara & Kusayama, 2009). This was achieved by aking ino accoun he difference beween he sauraed waveform of he magneizaion signal deeced from he MNPs ouside he seleced region and ha deeced from he MNPs inside he region. We performed numerical analyses o prove ha he image resoluion in he molecular imaging echnique can be improved by using our proposed image reconsrucion mehod, which is based on he abovemenioned ideas. Furhermore, a fundamenal sysem was consruced and he numerical analyses were experimenally validaed using MNPs wih diameers of nm. The deecion sensiiviy and he resoluion were improved by he use of mehods in he case of locally disribued MNPs. However, a reconsruced image wih he correc disribuion of MNPs may no be obained when he MNPs are disribued coninuously. This is because he abovemenioned proposed mehod acs as an inense high-pass filer agains he reconsruced image (Ishihara & Kusayama, 2011).

3 494 Elecromagneic Waves These problems in MPI originae from he characerisics of he MNPs and he imperfec disribuion of he magneic field applied o he MNPs, as discussed laer. Gleich and Weizenecker concenraed on he fac ha he observaional daa overlapped he sysem funcion reflecing he characerisics of he MNP and he applied magneic field disribuion, and proposed an image reconsrucion mehod for improving image qualiy (Gleich & Weizenecker, 2005). The abovemenioned mehod involved performing an inverse marix operaion (such as singular value decomposiion; SVD) (Weizenecker e al., 2007) or an ieraive operaion (algebraic reconsrucion echnique; ART) (Weizenecker e al., 2009) on he obained daa. However, when an image marix becomes large, he use of his mehod o reconsruc images, which is based on a marix operaion, may resul in he reconsruced images being underspecified. Here, we propose a new image reconsrucion mehod wih higher image resoluion and signal inensiy. Our mehod is based on informaion regarding he correlaion beween he observed signal and a sysem funcion, and i does no use he inverse-marix mehod. 2. Principle 2.1 Magneizaion response generaed by a MNP The saic magneizaion (M) of a MNP exposed o a magneic field is described well by he Langevin heory of paramagneism, which is defined in equaion (1). mµ 0H 1 M = Ms coh kt mµ B 0H kt B (1) where M s is he sauraion magneizaion of a MNP, μ 0 is he magneic permeabiliy of 3 vacuum, m is he magneic momen of a paricle m= πd M s 6, H is he applied field, k B is Bolzmann s consan, and T is he absolue emperaure (Vekas e al., 2000). A magneizaion response wih higher-order harmonics corresponding o he nonlinear magneizaion properies of he MNP is generaed when an alernaing magneic field is applied o a MNP (Fig. 1, [A]). However, such harmonics are no generaed when a local saic magneic field ha is srong enough o saurae he magneizaion of he MNPs is applied (Fig. 1, [B]). The harmonics can be exraced by Fourier ransformaion of he deeced signals; herefore, he posiions of he MNPs can be idenified and imaged by scanning he local disribuion of a magneic field which has approximaely zero srengh in he desired region (he field-free poin, FFP) and is srong enough o saurae he magneizaion in regions oher han he FFP (Gleich & Weizenecker, 2005). 2.2 Fundamenal MPI sysem A fundamenal MPI model is shown in Fig. 2. A magneic field disribuion wih very high field srengh ha surrounds he seleced region, in conras o having a firs-order gradien a he cener, is achieved by applying a DC curren I DC o wo ses of Maxwell coil pairs. Thus, an FFP is formed a he cener of hese coils (Fig. 2 ). The posiion of his FFP is scanned by applying an offse DC curren o each coil (Fig. 2 (c)). The MNPs generae a magneizaion response because of he alernaing magneic field creaed by he AC curren I AC in he Maxwell coil pair consising of he op and boom coils. The response is deeced as an elecromoive force induced by he receiver coil according o Faraday's law.

4 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles 495 M Magneizaion response Magneizaion characerisics of nanoparicle H Fourier ransform Offse field Alernaing magneic field f 0 2f 0 3f 0 4f 0 5f 0 6f 0 7f 0 f [A] Wihou offse field [B] Wih offse field Fig. 1. Principle of MPI. MPI is based on he nonlinear magneizaion properies of MNPs. When an alernaing magneic field wih a frequency f 0 is applied o MNPs placed in a region where he saic magneic field srengh is almos zero (FFP) [A], he MNPs generae a magneizaion response wih odd-order harmonics. In conras, very few magneizaion responses are deeced from MNPs placed in a region where he magneic field is srong enough o saurae heir magneizaion [B]. I DC + I AC Magneic field [a.u.] I DC FOV Receiver coil I DC z y x I DC -I AC (c) Fig. 2. Fundamenal MPI model and generaed magneic field. Each Maxwell coil pair produces a magneic field gradien along each axis. An FFP is formed a he cener of he field of view (FOV), as shown in, when he DC currens applied o each coil are equal. The posiion of his FFP can be scanned by adjusing he raio of currens applied o each coil (c). An alernaing magneizaion response is generaed when an AC curren is applied o he Maxwell coil pair consising of he op and boom coils. This response from he MNPs is recorded using a receiver coil.

5 496 Elecromagneic Waves 2.3 Concep of image reconsrucion by convenional mehod As menioned above, in MPI, image reconsrucion is performed using he magneizaion response waveform deeced while scanning he FFP. In his approach, he shape of he FFP (he magneic field disribuion) applied o he MNPs has a significan influence on he resoluion of he reconsruced image. For example, if he formed FFP is spaially localized by a seep magneic field disribuion as shown in Fig. 3, image resoluion comparable o he size of he FFP could be obained. However, he local characerisics of he magneic field disribuion formed wih he usual magne are limied and imperfec (Fig. 3). Moreover, he magneizing properies (sauraion characerisics) of he MNP also affec he spaial resoluion. Tha is, he finie gradien of he magneizaion curve limis he spaial resoluion (Fig. 4). Under he influence of hese wo facors, an addiional signal appears from he MNPs ha are ouside he boundary of he FFP, and inerferes wih he signal generaed from he MNPs inside he FFP. This is shown in Fig. 5. When MNPs exis only in he cener of he FOV, a signal is deeced ideally only in he posiion of he desired FFP (FFP-a, shown in Fig. 5). However, when he gradien of he magneic field disribuion which forms he FFP is genly-sloping, or when he gradien of he magneizaion curve of a MNP is finie, a signal is also deeced from MNPs ha are in a locaion oher han he desired FFP (e. g., FFP-b, shown in Fig. 5). Therefore, he convenional MPI image reconsrucion mehod uses ha he frequency specrum of a magneizaion response waveform would ideally consis only of odd harmonic componens when he FFP is scanned a he poin where he MNPs are locaed. Hence, when he FFP is in he wo-dimensional plane (x-z plane) of y = 0 on Fig. 2, he signal srengh in he reconsruced image is expressed by he following equaion. N h Uxz (, ) = V xz,, 2n + 1 ( ) (2) n= 1 U(x, z): reconsruced disribuion in x-z plane V[x, z, n]: n-h harmonic conained in he waveform a each FFP (x, z) N h : maximum harmonic order for reconsrucion However, because he ampliude is minue for he higher-order componens, he informaion included in he higher-order componens is no sufficienly uilized. Moreover, i is difficul o remove he inerference caused by he imperfecion of he wo abovemenioned facors using his mehod only, resuling in he appearance of a blur and an arifac in he reconsruced image. In addiion, from he MPI viewpoin, a larger MNP diameer is preferable according o he magneizaion properies expressed in equaion (1) (Yavuz e al., 2006), because a comparaively small alernaing magneic field is sufficien. On he oher hand, because ens of nm is an effecive disance for acquiring he EPR effec, a srong alernaing magneic field is required. This means ha he influence of he abovemenioned inerference signal becomes large. Therefore, a mehod ha successfully suppresses arifacs and improves deecion sensiiviy is indispensable. 3. Proposed mehods For ypical MPI image-reconsrucion, Weizenecker e al. (2009) proposed a mehod ha performs an inverse-marix operaion on he obained daa by scanning he FFP along wih a

6 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles 497 Ideal field disribuion Zero field Magneic field Insufficien field srengh Sufficien field srengh Fig. 3. Influence of FFP imperfecion (magneic field disribuion). Ideal FFP: The magneic field srengh is almos zero only in he area seleced for acquiring a signal, in conras o sufficien magneizaion of MNP o reach sauraion in oher regions. Acually formed FFP: he magneic field disribuion generaed wih Maxell coil pairs has a murky FPP boundary. Ideal magneizaion M H No ideal magneizaion M H Fig. 4. Influence of imperfecion in he MNP s magneizing properies. Ideal magneizaion (sauraion) propery: when an alernaing magneic field is superimposed on an offse magneic field, he AC componen is no conained in he magneizaion response of he MNP. No ideal magneizaion (sauraion) propery: he AC componen conained in he magneizaion response of he MNP is affeced by he offse magneic field srengh superimposed on an alernaing magneic field.

7 498 Elecromagneic Waves MNP 1 mm FFP-b FFP-a FOV Magneizaion response [a.u.] 1.2 FFP-a 0.8 FFP-b Time [ms] Specrum inensiy [a.u.] FFP-a FFP-b n h order harmonics (c) (d) Fig. 5. Harmonic componens deeced a each FFP. A magneizaion response composed of only odd harmonics is deeced from he MNPs a he cener of he FFP (FFP-a). Because he local magneic field disribuion ha forms he FFP does no have a seep gradien, a magneizaion response wih even harmonics is also deeced a a poin where he FFP is a a cerain disance from he MNPs (FFP-b). Lissajous rajecory wihin he FOV, and delivered srong resuls. However, wih his mehod, when he image size becomes large, a huge operaion is needed, which raises concerns regarding he sabiliy of he reconsruced image. In his chaper, in order o reduce he image arifac and blurring, we firs inroduce he proposed mehod, and explain is efficiency and he problems i raises. Then, we propose an image reconsrucion mehod ha has excellen sabiliy, image resoluion, and deecion sensiiviy wihou performing inverse-marix operaions. 3.1 Adjusing he harmonic componens As explained in Fig. 5, in addiion o he odd harmonics, considerable even harmonics are also deeced in he signal when he FFP is se a a cerain disance from a MNP owing o imperfecions in he magneic field disribuion ha forms he FFP. Alhough convenional MPI is reconsruced using only he odd harmonics based on equaion (2), in he image reconsrucion mehod proposed in his sudy, he odd harmonics are used, whereas he even harmonics are reduced, as defined in equaion (3) (Kusayama & Ishihara, 2009). If he magneic field disribuion, which is formed as an FFP, and he magneic characerisics of he MNP are known, he necessary componens of he odd harmonics and he unnecessary componen of he even harmonics can be deermined. As a resul, as shown in Fig. 6, he odd harmonics can be emphasized, and he even harmonics can be reduced.

8 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles 499 N h α( 2n+ 1) β( 2n Uxz (,) = { V xz,,2 ( n+ 1 ) e Vxz,,2 ( n) ke ) } (3) n= 1 U(x, z): correced disribuion in x-z plane V[x, z, n]: n-h harmonics conained in he waveform a each FFP (x, z) N h : maximum harmonic order for reconsrucion α, β: weighing facors for harmonics k: arbirary consans Fig. 6. Adjusmen of harmonic componens deeced a each FFP. The odd harmonics were lef unchanged and he even harmonics were reduced, in conras o convenional image reconsrucion mehods. 3.2 Differeniaing he waveforms obained from inside and ouside he FFP Even if we use he mehod based on equaion (3), he image resoluion degrades because of he inerference of he magneizaion signals generaed from several MNPs locaed ouside he FFP boundary. For example, he signals generaed from he MNPs locaed ouside he FFP, as shown in Fig. 7, may be composed of odd harmonics similar o hose obained from he MNPs placed inside he FFP. Because he effec of such inerferences canno be suppressed by he abovemenioned procedure alone, he image arifac appears in he reconsruced image (Fig. 7 (d)), degrading he image resoluion. Here, a big difference is noiced when he waveforms generaed from he MNPs inside he FFP region are compared wih he inerfering waveforms from ouside he FFP region (Fig. 7 ). To disinguish beween he inerference signals, firs, he offse componen of he deeced signal is correced and normalizaion is performed. Second, he correlaion beween he correced waveform and a waveform (sysem funcion) ha is generaed from a MNP a each FFP is evaluaed. These processes are expressed in equaion (4), and Fig. 8. Finally, his difference in waveforms is defined in erms of he correcion facor, and suppression of unnecessary inerference signals is aemped by muliplying heir facors wih he daa deermined from equaion (3). C Ns 1 i 1 w n wn wmean c = 1 Ns i n= 0 w max wmax wmean N s : number of sampling poins w n, w i n: sampled inerference and ideal waveform daa w max, w i max: maximum value of each waveform w mean : mean value of inerference waveform c a : arbirary consan c a (4)

9 500 Elecromagneic Waves MNP 1 mm FFP FOV Magneizaion response [a.u.] Inerference signal Ideal signal Time [ms] Specrum inensiy [a.u.] n h order harmonics (c) Inerference signal Ideal signal (d) Fig. 7. Inerference signal deeced from regions ouside he FFP. Because he magneizaion response generaed from he MNPs placed ouside he FFP consiss of odd harmonics a he FFP in he halfway poin beween MNPs, his inerference canno be eliminaed by correcion on he basis of he ype of harmonics. w mean M Inerference waveform: w n Shif and normalizaion 0 Ideal waveform: w i n Fig. 8. Disinguishing he inerference signal by using he correlaion coefficien. In order o remove he inerference of he magneizaion signals, he following is performed: (1) correcion of he offse componen, (2) normalizaion of he waveform, (3) calculaion of correlaion coefficien, and (4) muliplicaion of correlaion coefficien.

10 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles Correlaing wih he sysem funcion The mehod proposed above is exremely effecive in reducing blurring and arifacs in images, as will be shown laer. However, his mehod emphasizes he signal from he isolaed signal source ha exiss a he cener of each FFP, and assumes ha he signal generaed from ha circumference is an unnecessary inerference. This is a problem when adjacen signal sources (MNPs) exis, as he inrinsic signal generaed from hese sources is recognized as an unnecessary inerference o each oher. In order o overcome his unexpeced effec, a mehod of reconsrucing he exac spaial disribuion of MNPs is proposed. Using he same mehod proposed by Weizenecker e al. (2009), he waveform generaed from a MNP a each FFP is measured as a sysem funcion, bu he correlaion beween his sysem funcion and a waveform generaed by he unknown MNPs disribuion a each FFP is calculaed wihou any inverse marix operaion. More specifically, he esimaion of he MNPs disribuion is based on he correlaion beween he observed signal S(x, z) from he unknown MNPs disribuion and he sysem funcion (i.e., poin-spread funcion) G(i, j; x, z), which is a space-varian sysem deermined by he ineracion of he magneic field and he MNPs disribuion. As shown in Fig. 9, his sysem funcion can be deermined by measuring he waveforms a FFP poins of (x, z) when a MNP is se a each poin (i, j) wihin he FOV, and by connecing all hese measured waveforms as one-dimensional daa, which is sequenially arranged in an array of rows and columns (i, j). Consequenly, he MNP disribuion in he x-z plane is reconsruced using equaion (5). J I Uxz (, ) = SxzGij (, ) (, ; xz, ) (5) j= 1i= 1 Fig. 9. Calculaion of correlaion coefficiens: he sysem funcion G(i, j; x, z) is defined as a space-varian sysem. I can be deermined by measuring he waveforms a FFP poins (x, z) when a MNP is se a each poin (i, j) wihin he FOV. The MNP disribuion is calculaed by correlaion wih S(x, z), which is he waveform measured by each FFP of (x, z) and arranged in a one-dimensional array. 4. Numerical simulaion 4.1 Simulaion mehods In order o examine he validiy of he proposed mehod using he higher harmonic componens appropriaely, a numerical analysis using he sysem model shown in Fig. 2

11 502 Elecromagneic Waves was conduced. In his examinaion, wo Maxell coil pairs (diameer: 50 mm, opposie disance: 50 mm) and a receiver coil (diameer: 16 mm, number of urns: 200) were used, and he FOV was se as 9 9 mm 2 wih a marix size of A magneic field disribuion wih a gradien magneic field of abou 5 T/m formed in he z direcion a he MNPs wih a paricle diameer of 20 nm was applied as an FFP using his Maxell coil pair. In addiion, an alernaing magneic field of 20 mt was applied in he same direcion. 4.2 Simulaion resuls Figure 10 shows he reconsruced images of he MNP placed a he cener of he FOV using he convenional mehod wih equaion (2) and he proposed mehod based on equaion (3). The magneic field was disribued over he region where he MNPs were posiioned owing o he influence of he FFP formed as a resul of he imperfecion of he local magneic field disribuion. Therefore, because he alernaing magneic field was applied only in he z- direcion, image blurring was observed paricularly along he z-direcion in he image reconsruced using he convenional mehod (Fig. 10). On he oher hand, such image blurring was reduced by suppressing he even harmonics on he basis of equaion (3) and by using opimized parameers (N h = 7, α = 0.19, β = 0.12, k = 1.39) (Fig. 10). Furhermore, i was confirmed ha a drasic reducion in he image arifac compared o he convenional mehod could be achieved by using he proposed mehod shown in Fig. 11 by differeniaing beween he inerference of he signal from he MNPs placed ouside and inside he region on he basis of equaion (4) using he opimized parameers (c a = 10). Alhough his proposed mehod enables us o improve image resoluion by suppressing he inerference signal due o he even harmonic componens generaed from he MNPs and also o improve he sensiiviy by emphasizing he odd harmonic componens, he ouer par of he reconsruced image was weighed excessively, as in a high-pass-filer effec. For example, he perimeer region is emphasized when he MNPs indicae coninuous disribuion, as shown in Fig. 12 while here are fewer blurring and arifacs compared wih he convenional mehod shown in Figs. 10 and 11 when he MNPs are separaed. MNP MNP [a.u.] 1.0 Original z 1 mm 1 mm x Fig. 10. Improvemen of image resoluion by adjusing he harmonic componens based on equaion (3). Overall image blurring due o he imperfecion of he local magneic field disribuion formed as FFP is observed on he image reconsruced by he convenional mehod. The spread of he disribuion along he z-direcion was suppressed by using he proposed mehod wih equaion (3).

12 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles 503 MNPs MNP [a.u.] 1.0 Original z 1 mm 1 mm x Fig. 11. Improvemen of image resoluion by suppressing he inerference signals on he basis of equaion (4). When using he convenional mehod, an image arifac was formed a he FFP beween he nanoparicles placed symmerically on eiher side of he FFP. Wih he proposed mehod, his image arifac was eliminaed, and he spread of he field disribuion in he z-direcion was suppressed on he basis of equaion (4). Consequenly, he efficiency of he reconsrucion mehod based on he newly proposed equaion (5) was evaluaed. Figure 13 illusraed he reconsruced resuls for he original image (Fig. 13) using he convenional mehod (Fig. 13), he mehod based on equaions (3) and (4) (Fig. 13(c)), and he mehod based on equaion (5) (Fig. 13(d)). Wih he convenional mehod, he reconsruced disribuion was spread around he region where he MNPs were acually posiioned, and an image arifac was observed. On he oher hand, wih he reconsrucion mehod based on equaion (5), alhough some image blurring is observed in he peripheral par of he image, a more exac reconsrucion image wih fewer arifacs is obained, compared o oher mehods. Furhermore, i is confirmed from Fig. 14, which shows he profile of he cenral secion of hese images, ha he sensiiviy of his mehod based on equaion (5) was high abou 20% compared wih oher mehods. MNP [a.u.] 1.0 Fig. 12. The reconsrucion resul for a coninuous disribuion of MNP. The ouer par of he reconsruced image is excessively emphasized, as in he effec of a high pass image filer.

13 504 Elecromagneic Waves (c) (d) Fig. 13. Reconsrucion resuls of each mehod. Original image. Wih he convenional mehod, significan image blurring and an arifac appear. (c) Wih he proposed mehod based on equaions (3) and (4); alhough he image is less blurred, he edges are emphasized excessively. (d) Wih he proposed mehod based on equaion (5); alhough he image is somewha blurred, he original image is reconsruced more accuraely han wih he oher mehods. 1.2 siy 1 n e 0.8 in e d0.6 liz a0.4 r m o N0.2 0 Original Convenional Proposed-1 Proposed X-marix Fig. 14. Profile of a reconsruced image. The proposed mehod based on equaion (5) reconsrucs he MNP disribuion more accuraely han he oher mehods. In addiion, his mehod has excellen sensiiviy. 5. Experimen 5.1 Maerials and mehods In order o confirm he validiy of he proposed mehods and numerical compuaion, he influence of he inerference originaing from he magneizaion response waveform generaed ouside he arge region was esimaed by a fundamenal experimen. The prooype Maxell coil pair (diameer: 180 mm, number of urns: 285 each, and opposie disance: mm) (Toyojiki indusry Co. Ld., Niiza, Japan) used for he experimen is shown in Fig Deecing magneizaion response When an alernaing magneic field was applied, he higher harmonic componen conained in he magneizaion response deeced from he MNPs was evaluaed, and he validiy of he numerical analysis was confirmed. In his experimen, an alernaing magneic field wih

14 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles 505 an ampliude of abou 90 mt was generaed in he cener of he coil by applying an alernaing curren (frequency of 35 Hz, and ampliude 10.6 A) in he same direcion o each coil. As a measuring objec, a 2.0-g dry paricle of iron oxide (nominal diameer of 10 nm), which has polar surface properies (EMG1500, Ferroec Corp., Chiba, Japan)) was enclosed in he conainer, as shown in Fig. 15. The magneizaion response waveform generaed from he MNPs a he cener of he Maxwell pair coil was deeced using a receiver coil (diameer: 35 mm, number of urns: 40) which surrounds he phanoms. Here, in order o reduce a nonlinear error, inrinsic o he sysem, which originaes from imperfecions in he power supplies and he Maxell coil pair, difference processing beween he signals observed wih and wihou he exisence of he measuring objec was carried ou. Field of view 30 mm - 50 mm 10 mm Fig. 15. Experimenal modules for signal deecion. A Maxwell coil pair (diameer: 180 mm, urns: 285 each, disance beween coils: mm) was used in he z-direcion for generaion of an FFP and an alernaing magneic field. The magneizaion response from he dry paricle of iron oxide enclosed wihin he conainer (c) was deeced by a receiver coil (diameer: 35 mm, urns: 40). (c) Differeniaing he waveforms obained from inside and ouside of he FFP Nex, i was evaluaed by he experimen ha he inerference of he magneizaion response signal generaed from MNPs ouside an FFP can be decreased wih he proposed mehod based on equaions (3) and (4). In his experimen, an alernaing magneic field wih an ampliude of abou 20 mt was generaed in he cener of he coil by applying an alernaing curren (frequency of 80 Hz, and ampliude 4.7 A) in he same direcion o each coil. A he same ime, a direc curren of 9.4 A was applied o each coil in he opposie direcion and a gradien magneic field of abou 1.2 T/m was generaed, and as a resul, an FFP was generaed around he cener of he coil gap. A 0.5-cc hydrophilic colloidal soluion of superparamagneic iron oxide (concenraion abou 500 mm/lier), which is coaed wih carboxydexran (Ferucarboran, Fujifilm RI Pharma Co., Ld., Tokyo, Japan), enclosed in he conainer shown in Fig. 16 (c) was used as a phanom. The magneizaion response waveform generaed from he MNPs a he cener of he Maxwell coil pair was deeced using a receiver coil (diameer: 35 mm, number of urns: 40) (Fig. 16 ) ha surrounds he phanoms. In order o correspond o he numerical analysis (Fig. 11), he wo phanoms were coaxially arranged, 20 mm apar, beween he opposie coils (Fig. 16 ).

15 506 Elecromagneic Waves The FFP was se a he cener beween he coils, a an equal disance from he phanoms, and he magneizaion response waveform generaed from he phanoms was deeced using he receiver coil (diameer: 23 mm, number of urns: 400) ha surrounded he phanoms. The ideal waveforms (he sysem funcion) were deermined by arranging a phanom a he cener beween he coils and measuring he signal, in order o calculae he correlaion wih he deeced signal. 50 mm FFP 10 mm Phanom Receive coil Fig. 16. Experimenal modules for evaluaion of he signal inerference. The magneizaion signal from he MNPs (MRI conras agen: Ferucarboran) (c), which are placed in wo conainers in order o reproduce he condiions of numerical analysis, was observed using a receiver coil (diameer: 23 mm, urns: 400). 10 mm (c) 5.2 Experimenal resuls Deecing magneizaion response Figure 17 shows he elecromoive force induced by he receiver coil when applying he alernaing magneic field o he MNPs. By inegraing over his elecromoive force wave, he magneizaion response waveform of he paricles was obained (Fig. 17 ) and is shown in Fig. 17 (c) wih he resul of he Fourier ransform. These experimenal resuls confirmed ha he mehod of our numerical analysis is accurae Deecing magneizaion response The magneizaion response waveform deeced by he receiver coil and he ideal waveforms are shown in Fig. 18. The influence of inerference is refleced in he deeced magneizaion response waveform, and a similar wave shape o ha shown in Fig. 7 was observed. In order o confirm ha he inerference of he magneizaion response waveform generaed ouside he FFP region can be suppressed by using he proposed mehod, he convenional mehod based on equaion (2) and he proposed mehod based on equaions (3) and (4) were applied o he magneizaion response waveform obained in he experimen. Here, he correcion coefficiens used in equaions (3) and (4) were deermined based on he characerisics of he ideal waveforms (N h = 7, α = 0.10, β = 5, k = 1.22, c a = 5.0). The signal srengh reconsruced by each mehod is shown in Fig. 18 (c). For he convenional mehod, he signal srengh, which reflecs he inerference of he magneizaion response waveform generaed from ouside he FFP, (which corresponds o

16 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles 507 he inerference signal deeced a he cener of he Maxwell coil pair) was abou 79.0% of he ideal waveform signal. On he oher hand, i was confirmed ha his inerference signal can be suppressed o abou 9.0% by our proposed mehod based on equaions (3) and (4). The resuls of his fundamenal experimen were well in agreemen wih he resuls of he numerical analysis, confirming he efficiency of he proposed mehods and he compuaional process. Induced elecromoive force [a.u.] Experimenal Simulaed Magneizaion response [a.u.] Experimenal Simulaed Time [ms] Time [ms] 1.0 Experimenal Simulaed Specrum inensiy [a.u.] N-h order harmonics (c) Fig. 17. Deeced signal from MNPs. The signal from he MNPs is deeced as elecromoive force induced by he receiver coil. A magneizaion response is obained by inegraing his signal, and he harmonics are compued by he Fourier ransform of his response (c).

17 508 Elecromagneic Waves Magneizaion response [a.u.] Inerference Ideal Specrum inensiy [a.u.] Inerference Ideal Time [ms] N-h order harmonics Inerference Ideal Signal inensiy [a.u.] Convenional (c) Proposed Fig. 18. Suppression effec of inerference signal. I is confirmed ha by using he proposed mehod, he inerference signal deeced from he cener of he Maxwell coil can be suppressed o less han 9.0% (c). 6. Conclusion In MPI, inerference of he magneizaion signal generaed from he MNPs ouside he boundary of an FFP due o he nonlinear responses, resuls in degradaion of he signal sensiiviy. Alhough we proposed an image reconsrucion mehod ha suppresses he inerference componen while emphasizing he signal componen using he propery of he higher harmonic componens generaed from he MNPs, he perimeer of he reconsruced image was over-emphasized due o he high-pass-filer effec when using his mehod. We herefore proposed a new mehod based on he correlaion informaion beween he observed signal and a sysem funcion, and performed a numerical analysis. As a resul, he image blurring was sill visible, bu we clearly showed ha he deecion sensiiviy can be improved wihou he inverse-marix operaion used by he convenional image reconsrucion mehod. In addiion, alhough such proposed mehods and numerical

18 Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles 509 analyses could be demonsraed by a basic experimen, he reconsrucion of an image by means of a phanom experimen should be evaluaed in he fuure. 7. Acknowledgemens This sudy was suppored by a Gran in Aid for Scienific Research (B), , 2008 from he Japan Sociey for he Promoion of Science (JSPS). 8. References Gleich, B. & Weizenecker, J. (2005). Tomographic imaging using he nonlinear response of magneic paricles. Naure, Vol. 435, No. 7046, Jun. 2005, , Gleich, B.; Weizenecker, J., & Borger, J. (2008). Experimenal resuls on fas 2D-encoded magneic paricle imaging. Phys. Med. Biol., Vol. 53, No. 6, Mar. 2008, N81 N84, Ishihara, Y. & Kusayama, Y. (2009). Resoluion improvemen of he molecular imaging echnique based on magneic nanoparicles. Proceedings of SPIE Medical Imaging 2009, pp I I.8, , Orlando, USA, Feb Ishihara, Y. & Kusayama, Y. (2011). Sensiiviy improvemen of a molecular imaging echnique based on magneic nanoparicles. Proceedings of SPIE Medical Imaging 2011, Orlando, USA, Feb (in press). Knopp, T.; Biederer, S., Sael, T., Weizenecker, J., Gleich. B, Borger, J. & Buzug, T. M. (2009). Trajecory analysis for magneic paricle imaging. Phys. Med. Biol., Vol. 54, No. 2, Jan. 2009, , Kusayama, Y. & Ishihara, Y. (2007). A preliminary sudy on he molecular imaging device using magneic nanoparicles. Technical Repor of IEICE, MBE, Vol. 107, No. 218, Sep. 2007, 15 18, Kusayama Y. & Ishihara, Y. (2009). High-resoluion image reconsrucion mehod on he molecular imaging using magneic nanoparicles. IEICE Trans. D, Vol. J92 D, No. 9, Sep. 2009, , Masumura, Y. & Maeda, H. (1986). A new concep for macromolecular herapeuics in cancer chemoherapy: mechanism of umoriropic accumulaion of proeins and he aniumor agen smancs. Cancer Res., Vol. 46, No. 12, Dec. 1986, , Vekas, L.; Rasa, M. & Bica, D. (2000). Physical properies of magneic fluids and nanoparicles from magneic and magneo-rheological measuremens. J. Colloid Inerface Sci., Vol. 231, No. 2, Nov. 2000, , Weizenecker, J.; Borger, J. & Gleich, B. (2007). A simulaion sudy on he resoluion and sensiiviy of magneic paricle imaging. Phys. Med. Biol., Vol. 52, No. 21, Nov. 2007, , Weizenecker, J.; Gleich, B., Rahmer, J., Dahnke, H. & Borger, J. (2009). Three-dimensional real-ime in vivo magneic paricle imaging. Phys. Med. Biol., Vol. 54, No. 5, Mar. 2009, L1 L10,

19 510 Elecromagneic Waves Yavuz, C. T.; Mayo, J. T., Yu, W. W., Prakash, A., Falkner, J. C., Yean, S., Cong, L., Shipley, H. J., Kan, A., Tomson, M., Naelson, D. & Colvin, V. L. (2006). Low-field magneic separaion of monodisperse Fe 3 O 4 nanocrysals. Science, Vol. 314, No. 5801, Nov. 2006, ,

20 Elecromagneic Waves Edied by Prof. Vialiy Zhurbenko ISBN Hard cover, 510 pages Publisher InTech Published online 21, June, 2011 Published in prin ediion June, 2011 This book is dedicaed o various aspecs of elecromagneic wave heory and is applicaions in science and echnology. The covered opics include he fundamenal physics of elecromagneic waves, heory of elecromagneic wave propagaion and scaering, mehods of compuaional analysis, maerial characerizaion, elecromagneic properies of plasma, analysis and applicaions of periodic srucures and waveguide componens, and finally, he biological effecs and medical applicaions of elecromagneic fields. How o reference In order o correcly reference his scholarly work, feel free o copy and pase he following: Yasuoshi Ishihara, Tsuyoshi Kuwabara and Naoki Wadamori (2011). Image Resoluion and Sensiiviy Improvemens of a Molecular Imaging Technique Based on Magneic Nanoparicles, Elecromagneic Waves, Prof. Vialiy Zhurbenko (Ed.), ISBN: , InTech, Available from: hp:///books/elecromagneic-waves/image-resoluion-and-sensiiviy-improvemens-of-amolecular-imaging-echnique-based-on-magneic-nan InTech Europe Universiy Campus STeP Ri Slavka Krauzeka 83/A Rijeka, Croaia Phone: +385 (51) Fax: +385 (51) InTech China Uni 405, Office Block, Hoel Equaorial Shanghai No.65, Yan An Road (Wes), Shanghai, , China Phone: Fax:

21 2011 The Auhor(s). Licensee InechOpen. This chaper is disribued under he erms of he Creaive Commons Aribuion-NonCommercial- ShareAlike-3.0 License, which permis use, disribuion and reproducion for non-commercial purposes, provided he original is properly cied and derivaive works building on his conen are disribued under he same license.