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nced Imaging Resannedy Krieger Insti

duction: Currentlyfication by MRI serparts is that theynce. Consequently

nging compounds erred within a giveounds with such ra

with an increase EST studies. Frequer. Using spectroscting these out usinm of this study wa

rial & Methods: Tof n label-transfer ve 90x/90-x RF pulse fresh z-magneting multiple modul

ng efficiency. In coding on the frequencribed (Eq. 2) by

on of EuDOTA-(glthird a 4% agaroseed by a fast spin-ewas acquired by v

tion (0 ppm) (7) aer of LTMs = 0, 10signal without LTM

. FLEX FIDs (LTEST solution mixets & Discussions: LEX FIDs and spespectrum (green

ncy Δωso1 of 18,00(0 ppm) due to thedrop due to MT insolute water (18,0

araCEST agent; bEST agent but notdue to a shorter Ton of number of LT4 mM for agarose z-axis after the evousion: The first im

ed separation of Mvivo imaging of paence: 1. J. Zhou, 31, 2009. 4. J.I. Fr7. J. Cavanagh, et

PTR s = x s ⋅

Imaging parChien-Yua

arch Center, Univeitute, Baltimore, M

Hopkins Univers

y, there is an incresuch as temperatuy can be engineerey, saturation pulses

can be used whien time frame, resuapid exchange rate

in conventional muency labeled exccopy, it has been shng FLEX time domas to implement theThe FLEX approac

modules (LTMs)lses is applied, in zation is present fles during the prepontrast to CEST, ncy difference beta free induction d

ly)-4, a second the

e solution as a conecho acquisition wvarying tevol from and keep high effi00, 300, 500, 700,Ms.

TM=500) and corred with agarose: bl

ectra in the three sline) of the short

00Hz and generatee limited excitation the first 20-30 μ000 Hz) and free wblack: free water).t in the agarose-on

T1w and a potential TMs according to phantoms (Fig. 2bolution time, whicmages from FLEX

MT and exchange taraCEST agents. et al., PNMRS, 4

riedman., et al., JAal., in Protein NM

⋅ λs ⋅ (1 − e− kex, s ⋅

raCEST Agenn Lin1,2, Nirbhay Nersity of Texas Sou

Maryland, United Ssity, Baltimore, Ma

easing effort underure, glucose, pH, ed to have large cs can be applied wile still adhering tulting in an increaes (kex ~ 104 s-1) remagnetization tran

change transfer (FLhown that FLEX a

main analysis (5,6)e FLEX techniquech has been descri. Within each LTMbetween which ch

for the solute protoparation time. Thewhich detects the

tween the offset fredecay (FID). Thresame paraCEST s

ntrol. All MRI datith a TR of 5 s, a T1μs to 196 μs usi

ficiency for labelin, 1000, and 1500.

responding Fourielue FID). Fig. 2. FL

samples are shownT2* component o

ed a peak at 50 ppmon of bulk water. Iμs, followed by a mwater (38,000 Hz) . FLEX-MRI obtanly sample. The mincrease in partialthe FLEX theory

b). The concentratih accumulates whX-MRI experimentransfer effects in

48: 109-136, 2006ACS, 132:1813-18

MRS: principle and

texch )⋅ e{−1+ (

i=1

n∑

nts Using FreqN Yadav2,3, S. Jamuthwestern MedicaStates, 3Division ofaryland, United Sta

rway to design parnitric oxide, and

chemical shift difwell away from theto the slow exchaase of transfer effiequires a high B1 lnsfer (MT) effectsLEX) (4) is a newallows detection o. This presents the

e on preclinical MRibed in detail prev

M, exchangeable shemical shift evolons at the start of

e PTR can be exprdecrease of water

equency (o1) of thee phantoms in trisolution mixed witta were acquired aTE of 8.65 ms, a Fing time intervalsng paraCEST agenSignal differences

er-transform spectrLEX-MRI (LTM=

n in Fig.1. The rapof the semi-solid Mm (red line). NoticIn the combined samore gradual decacomponents, the f

ained by pixel-bymismatch of signall saturation of the (Eqs.1,2), we deteion underestimatioen applying multip

nts on a paraCESTthe time domain a

. 2. A.D. Sherry e15, 2010. 5. C.Y. practice, 912, 200

i−1) / n} tprep / T1w

quency Labeledmes Ratnakar1, A. Dal Center, Dallas, f MR Research, Ruates, 4University of

ramagnetic chemic

d enzyme activityfferences (Δω >10e water resonance,ange limit (kex < iciency as expresslevel to achieve ats in biological tis

w approach that def rapidly exchangi

e potential for imagRI systems and to viously (4-6). Briesolute protons are flution of the exchaeach LTM, allowessed as Eq. 1, whr signal, FLEX mehe 90x excitation ps buffer (pH=7) wth 4% agarose in oat 37°C on a Vari

FOV of 1.5 cm, a sof 5 μs (dwell tim

nts (50 ppm). Thes with respect to th

ra in three differe=500) and calculate

pid initial decay inMT effect. The wce that the 50 ppmample (paraCESTay. Using time dofitted FLEX spect

y-pixel time domal magnitude betwewater pool due to

ermined the concenon is probably dueple LTMs. T agent solution aand provided quan

et al., Annu Rev BLin, et al., Procee

07.

w [1]

d Exchange TDean Sherry1,4, andTexas, United Staussell H. Morgan Dof Texas at Dallas,

cal exchange satur(1-3). The main

0 ppm) between th, thus avoiding offΔω) necessary fo

sed by the proton tt least partial RF

ssues, which, despetects exchanginging water moleculging the distributioevaluate the possi

efly, the pulse sequfrequency labeledangeable protons

wing multiple oppohere χs is the fracteasures modulatio

pulse and the solutwere prepared for order to generate Mian 9.4T MRI systslice thickness of 5me). The o1 of lae other parameterhe average water

ent phantoms (Aged concentration i

n the FLEX FID owater signal modulm resonance in the T agent mixed withomain analysis wittrum could be sepaain fitting (Fig. 2aeen the pure solutio MT exchange brntration of the par

e to exchange trans

at physiologic temntitative concentra

Biomed Eng, 10: edings of 19th ISM

Iw = PTRs ⋅ e

−

s∑

Transfer (FLEd Peter C. M. van

ates, 2F.M. Kirby CDept. of Radiology, Dallas, Texas, Un

ration transfer (pabenefit of paraC

he resonances of f-resonance saturaor CEST. This alltransfer ratio (PTRsaturation before

pite the large Δω,protons using frees kex >10,000s-1 won of functional paibility for imaginguence contains a p

d and transferred tooccurs over a peri

ortunities to transftional concentratioon in the water sigte resonance (Δωso

MRI acquisition. MT effect similar tem. FLEX image5 mm, and a matrixabeling pulse = 95rs for FLEX data signal after decay

garose only: greenimage of paraCEST

of the agarose phalation in the paraCFLEX spectrum (

h agarose), the FLth the prior knowlarated into three sa) shows the paraion (2.9%) and so

roadening. FortunaraCEST agent to bsfer of additional d

mperature and pH ation images. Thes

391-411, 2008. 3.MRM, 709, 2011. 6

−(kex,s +1 /T2s* )⋅tevol ⋅

EX) MRI Zijl2,3

Center for Functiongy and Radiologica

United States

araCEST) agents fCEST agents over

the exchanging pation of bulk waterlows for more satR). However, deteexchange occurs. can still complicquency transfer in

without interferencaraCEST agents in of paraCEST agen

preparation time (to water. In the labiod, tevol. Signal am

fer labeled protonson of the solute (s)gnal as a function o1). The effect on th

One contained ato that observed i

es were measured bx size of 64 *64 m

5 ppm was calculaacquisition were:

y were normalized

n FID; paraCEST T agent.

antom correspondsCEST agent soluti(red line) is much

LEX FID (blue lineedge (Eq.2) aboutignal components aCEST signal in polution mixed withately, by fitting thebe identical, 6.6 mMdephased signal th

are presented. Thse findings demon

. S. Aime, et al., A6. van Zijl et al., M

cos( Δω sol ⋅ tevol )[2]

nal Brain Imagingal Science, Johns

for biological targer their diamagnetipools and the water. In addition, fasteturated spins to bection of paraCESUnfortunately, thi

cate the analysis instead of saturatioce of MT effects bn biological tissuesnts. tprep) consisting of eling part, a pair omplification occurs to the water whe) protons and λs thof tevol in a mannehe water signal ca10 mM paraCES

in biological tissueby multiple LTMs

mm. The FLEX FIDated to avoid wate

texch = 400 μs anwith respect to th

solution: red FID

s to the broad banion modulated at larger than the free) indicates a rapit frequencies of th(green: MT effec

phantoms with thh agarose (1.5%) ie FLEX signal as M for pure solutio

hat was not returne

he FLEX approacnstrate the potentia

Acc Chem Res, 42MRM, 65:927-948

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et ic er er be T is n n y s.

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2: 8,

3379Proc. Intl. Soc. Mag. Reson. Med. 20 (2012)