New geeneration hybbrid FMT/M RI system used to assess β ... · lowing tracer adm rid FMT/MR wa...

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1 Ins Intro of FM provid struct used f our gr the ca amylo amylo Mate 94/30 in the diame single the be rails r supply was e glass filters respec accom to def Two 2 the he the ta differ matrix from epi-flu surfac regist regist Resul of cer anima both i dye b (Fig.2 Discu a tran visual confir absorp Ackn constr J Neu New ge stitute for Biomed duction: Fluores MT is photon sca ding quantitative ural, physiologic for improvement roup and proof-of amera. These iss oid plaque load in oid in vivo [2]. Th rials and Metho 0 Biospec (Bruker e magnet’s isocen eter, which was fo et lens (f=1000mm eam across the ob rigidly fixed at bo y, a custom-made enclosed in a ligh lens (V-4301, FL s (Semrock, Roch ctively. For refer mmodate optical m flect the incomin 24-month old AP ead and placed on ail vein. FMT m rent sequences we x size = 200x200 a 4.7x4.7cm 2 RO uorescence imag ce height map, w ration. Signals fr ered surface was lts: The quality o rebral amyloid an als 20 and 180 mi in wt and tg mice inding to plaques 2 green inlets). ussion: A new gen nsgenic model for lized using FMT, rmed using ex viv ption), which wil nowledgments: T ruction of the FM urol, 2007 eneration hyb Katerina dical Engineering Gree scence molecular attering and atten molecular inform cal and metabolic of FMT reconstr f-principle has be sues have been ad n APP23 mice, a he technical detai ods: Description r BioSpin MRI, E nter. Fluorescence ocused on the sam m, Melles Griot, bject’s surface, a oth ends of the ma e transceiver surf ht-tight custom-m L=2.1mm BFL=5 hester, USA) wit rence white light measurements in ng laser beam. In PP23 mice (tg) an n the heated anim measurements wer ere performed in- 0, 8 averages) wit OI on the head usi ing and histology which was interpo rom anatomical l used in FMT rec of both MR and op ngiopathy [3], wer inutes post) allow e (Fig.2). The dec s. Three hours fol neration of a hyb r cerebral amyloid , while MRI revea vo analyses. In a ll be used as prior This work was fin MT/MRI system. R brid FMT/M a Dikaiou 1 , Floria g, University and ece, 3 University o tomography (FM nuation by tissue, mation with stabl information on a ructions. A first g een demonstrated ddressed in a rede transgenic mode ils of the system a of FMT/MRI sy Ettlingen, German e excitation consi mple with a nume Bensheim, Germ scan head (Scanl agnet to ensure m face coil (20x24m made PPSU housin 5.6mm, Marshall th peak waveleng t images of the both reflection an vivo experimen nd two age-match mal platform. The re performed at -between the FMT th 29 axial slices ing a 8x14 source y. Data processi olated to match t landmarks on the construction. Prog ptical images wa re detected on on wed estimation of cay constant was s llowing tracer adm brid FMT/MR wa dosis. In 22 mont aled microbleeds next step, structu r information for nancially supporte References: [1] S Fig.1 MRI system us an Stuker 1 , Jan K d ETH Zurich, Zur of Zurich, Institute MT) allows mappi which limits lig le imaging agents a single platform generation free-b d in a subcutaneou esigned system, w el of Alzheimer’s and the results of ystem: The exper ny) small animal sted of a 670nm erical aperture-m many) and two coa lab, Puchheim, G mechanical stabili mm) for MR excit ng including a fil Electronics, CA gths 660nm and sample, an electr nd transmission m nts: All in vivo ex ed control litterm eir temperature w every 20 minute T measurements ( of 0.7mm thickn e excitation grid. ing: The 2D RAR the optical image e skull were inter gramming and vis s good (SNR=22 ne tg animal with the local fluorop slower for tg ((b = ministration, sign s presented, featu hs old APP23 mi indicative of vas ural information d the FMT reconst ed by the EU FP7 Stuker et al., IEEE sed to assess β Klohs 1 , Andreas E rich, Zurich, Swi e of Pharmacolog ing of the spatial ght penetration to s at a relatively l for pre-clinical a beam FMT/MRI u us tumor model [ which was used f disease. FMT da f the in vivo FMT erimental setup co MR system oper continuous wave matched collimatio ated highly reflec Germany) was use ity and reproducib tation/detection a lter wheel, a mec A, USA), yielding 720nm were use roluminescent m mode, three coate xperiments were mates (wt) were an was held stable at es for three hour (Fig.1 inlets). A r ness was acquired After 3 hours, th RE data were sm e pixel dimension ractively selected sualization was d and 568, respect MRI (Fig.2 gray phore concentratio = -0.0014) than f nificant residual F uring technical im ice, significant A scular pathology. derived from MR tructions. 7 FMT/XCT proje E Trans Med Ima β-amyloid pla lmer 1 , Jorge Ripo tzerland, 2 Institut gy and Toxicolog l distribution of fl o a few centimete ow cost. The com applications. Mor using a avalanche 1]. This system w for the first time ata were collected /MRI study are p onsisted of an FM rating at 400 MHz e laser (Coherent on lens (Thorlabs ctive front surfac ed. The detection ble positioning. It and a 256x256 C chanical filter swi g a 55x55mm 2 FO ed for measureme membrane (Distrel ed front surface m carried out in str nesthetized using 32C. At time t= rs. Each FMT m reference 2D RA d for each animal he animals were s moothed and segm ns. The height m d to compute an done in Matlab (T tively). Cerebral m y inlet). Reconstru on in vivo which for wt animals (b FMT intensity wa mprovements. Pro OI987 binding in Wildtype mice d RI data will be use ect. We acknowle ag, 2011 [2] Hint Fig.2 aque load on oll 1,2 , and Markus te for Electronic S gy, Zurich, Switze luorescently label ers. FMT may be mbination of FMT reover, the structu e diode array for was limited by the in a neuroimagin d using the dye A resented here. MT excitation mo z, and of an optic Inc., California, U , Munich, Germa e mirrors (Thorla module (Fig.1) w t comprised a hea MOS detection a itching mechanism OV at a focal dist ents at the AOI98 lec, Switzerland) mirrors (Edmund O rict adherence wi g 2% isoflurane in 0, AOI987 (0.1m easurement laste ARE sequence (TE l. The optical sign acrificed and bra mented. Isosurfac map and the optic affine transform The Mathworks, In microbleeds, a ch uction of FMT da displayed an exp = -0.0043), indic as observed ex viv oof-of-concept fo ndicative of cereb displayed no patho ed to generate map edge the contribut ersteiner et al., N APP23 mice s Rudin 1,3 Structure and La erland led compounds. T e considered the T with MRI has ural information p photon detection e small array size ng study with the AOI987, known t odule located at th cal/MR sample de USA) generating any), an anti-refle abs, Munich, Ger was designed to s ated animal platfo array (CSEM, Sw m and a miniatur tance of 400mm. 87 excitation and ) was fixed on th Optics, Karlsruhe with the Swiss law n an oxygen/air ( mg/kg, 0.01mg/m ed 12 minutes. M E/TR = 5ms/383m gnal at 680nm and ains extracted for ces were determin cal white light im mation between th nc.). haracteristic featu ata (Fig.3, showin ponential decay up cating a slower dy vo in tg mice, but or hybrid imaging bral β-amyloid de hology. The in viv aps of optical prop ution of M. Kuepf Nat Biotech, 2005 in vivo ser – FORTH, Cr The principal lim optical analog o the potential to p provided by MR n has been describ e, FOV and low S e goal to estimate o bind to aggrega he entrance of a B etection module l a laser beam of 0 ectance coated sp rmany). For scann slide on two carb orm with anesthe witzerland). The d re anti-reflection High quality ban d emission wave he housing botto e, Germany), wer w for animal prot 1:4) mixture, sha ml) was administer MR measurement ms, FOV = 2.2x2 d 720 nm was co ex vivo validatio ned to compute t mage were used f he two images. T ure observed indic ng one pair of tg/ pon tracer injectio ye washout in tg d not in wt animal g was established eposition could be vo findings have b perties (scattering fer in the mechan 5 [3] Jellinger et a Fig. rete, mitation f PET, provide can be bed by SNR of e the β- ated β- Bruker located 0.5mm herical ning of bon-rod sia gas detector coated ndpass length, om. To re used tection. aved on red via ts with .1cm2, llected on with the top for co- The co- cative /wt on due to ls using e been g and ical al., Eur .3 2757 Proc. Intl. Soc. Mag. Reson. Med. 20 (2012)

Transcript of New geeneration hybbrid FMT/M RI system used to assess β ... · lowing tracer adm rid FMT/MR wa...

Page 1: New geeneration hybbrid FMT/M RI system used to assess β ... · lowing tracer adm rid FMT/MR wa osis. In 22 mont led microbleeds next step, structu information for ancially supporte

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Discua tranvisualconfirabsorpAcknconstrJ Neu

New ge

stitute for Biomed

duction: FluoresMT is photon scading quantitative ural, physiologicfor improvement roup and proof-ofamera. These issoid plaque load inoid in vivo [2]. Thrials and Metho

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enclosed in a lighlens (V-4301, FL

s (Semrock, Rochctively. For refer

mmodate optical mflect the incomin24-month old APead and placed onail vein. FMT mrent sequences wex size = 200x200a 4.7x4.7cm2 ROuorescence imagce height map, wration. Signals frered surface was lts: The quality orebral amyloid anals 20 and 180 miin wt and tg miceinding to plaques2 green inlets).

ussion: A new gennsgenic model forlized using FMT,rmed using ex vivption), which wil

nowledgments: Truction of the FM

urol, 2007

eneration hybKaterina

dical EngineeringGree

scence molecular attering and atten

molecular informcal and metabolic

of FMT reconstrf-principle has be

sues have been adn APP23 mice, a he technical detaiods: Description r BioSpin MRI, E

nter. Fluorescencefocused on the samm, Melles Griot, bject’s surface, a oth ends of the mae transceiver surf

ht-tight custom-mL=2.1mm BFL=5hester, USA) witrence white lightmeasurements in

ng laser beam. InPP23 mice (tg) ann the heated anim

measurements werere performed in-0, 8 averages) witOI on the head usi

ing and histologywhich was interporom anatomical lused in FMT rec

of both MR and opngiopathy [3], werinutes post) allow

e (Fig.2). The decs. Three hours fol

neration of a hybr cerebral amyloid, while MRI reveavo analyses. In a ll be used as prior

This work was finMT/MRI system. R

brid FMT/Ma Dikaiou1, Floriag, University andece, 3University of

tomography (FMnuation by tissue,mation with stablinformation on a

ructions. A first geen demonstratedddressed in a redetransgenic mode

ils of the system aof FMT/MRI sy

Ettlingen, Germane excitation consimple with a numeBensheim, Germscan head (Scanlagnet to ensure mface coil (20x24m

made PPSU housin5.6mm, Marshall th peak wavelengt images of the both reflection an vivo experimen

nd two age-matchmal platform. There performed at -between the FMTth 29 axial slices ing a 8x14 sourcey. Data processiolated to match tlandmarks on theconstruction. Progptical images ware detected on on

wed estimation ofcay constant was sllowing tracer adm

brid FMT/MR wadosis. In 22 montaled microbleedsnext step, structur information for

nancially supporteReferences: [1] S

Fig.1

MRI system usan Stuker1, Jan K

d ETH Zurich, Zurof Zurich, Institute

MT) allows mappiwhich limits lig

le imaging agentsa single platformgeneration free-b

d in a subcutaneouesigned system, wel of Alzheimer’s and the results of ystem: The experny) small animal sted of a 670nm erical aperture-m

many) and two coalab, Puchheim, G

mechanical stabilimm) for MR excitng including a filElectronics, CA

gths 660nm and sample, an electrnd transmission m

nts: All in vivo exed control litterm

eir temperature wevery 20 minuteT measurements (of 0.7mm thickn

e excitation grid. ing: The 2D RARthe optical imagee skull were intergramming and viss good (SNR=22

ne tg animal with f the local fluoropslower for tg ((b =ministration, sign

s presented, featuths old APP23 mi indicative of vas

ural information dthe FMT reconst

ed by the EU FP7Stuker et al., IEEE

sed to assess βKlohs1, Andreas E

rich, Zurich, Swite of Pharmacolog

ing of the spatial

ght penetration tos at a relatively lfor pre-clinical a

beam FMT/MRI uus tumor model [which was used f disease. FMT da

f the in vivo FMTerimental setup co

MR system opercontinuous wave

matched collimatioated highly reflec

Germany) was useity and reproducibtation/detection alter wheel, a mec

A, USA), yielding720nm were useroluminescent mmode, three coatexperiments were

mates (wt) were anwas held stable at es for three hour(Fig.1 inlets). A rness was acquiredAfter 3 hours, thRE data were sme pixel dimensionractively selectedsualization was d and 568, respectMRI (Fig.2 gray

phore concentratio= -0.0014) than f

nificant residual F

uring technical imice, significant Ascular pathology. derived from MRtructions. 7 FMT/XCT projeE Trans Med Ima

β-amyloid plalmer1, Jorge Ripotzerland, 2Institutgy and Toxicolog

l distribution of flo a few centimeteow cost. The comapplications. Morusing a avalanche1]. This system wfor the first timeata were collected/MRI study are ponsisted of an FMrating at 400 MHze laser (Coherent on lens (Thorlabsctive front surfaced. The detection ble positioning. It

and a 256x256 Cchanical filter swig a 55x55mm2 FOed for measureme

membrane (Distreled front surface mcarried out in str

nesthetized using32C. At time t=

rs. Each FMT mreference 2D RAd for each animalhe animals were smoothed and segmns. The height md to compute an

done in Matlab (Ttively). Cerebral m

y inlet). Reconstruon in vivo which for wt animals (b FMT intensity wa

mprovements. ProOI987 binding inWildtype mice d

RI data will be use

ect. We acknowleag, 2011 [2] Hint

Fig.2

aque load on oll1,2, and Markuste for Electronic Sgy, Zurich, Switze

luorescently labelers. FMT may bembination of FMTreover, the structue diode array for was limited by thein a neuroimagind using the dye Aresented here.

MT excitation moz, and of an opticInc., California, U, Munich, Germae mirrors (Thorlamodule (Fig.1) w

t comprised a heaMOS detection aitching mechanismOV at a focal distents at the AOI98lec, Switzerland)

mirrors (Edmund Orict adherence wi

g 2% isoflurane in0, AOI987 (0.1measurement laste

ARE sequence (TEl. The optical signacrificed and bra

mented. Isosurfacmap and the optic

affine transformThe Mathworks, Inmicrobleeds, a chuction of FMT dadisplayed an exp= -0.0043), indic

as observed ex viv

oof-of-concept fondicative of cerebdisplayed no pathoed to generate map

edge the contributersteiner et al., N

APP23 mices Rudin1,3 Structure and La

erland

led compounds. Te considered the T with MRI has ural information pphoton detection

e small array sizeng study with theAOI987, known t

odule located at thcal/MR sample deUSA) generatingany), an anti-refleabs, Munich, Gerwas designed to sated animal platfoarray (CSEM, Swm and a miniaturtance of 400mm.87 excitation and) was fixed on thOptics, Karlsruhe

with the Swiss lawn an oxygen/air (mg/kg, 0.01mg/med 12 minutes. ME/TR = 5ms/383mgnal at 680nm andains extracted for ces were determincal white light im

mation between thnc.).

haracteristic featuata (Fig.3, showin

ponential decay upcating a slower dyvo in tg mice, but

or hybrid imagingbral β-amyloid dehology. The in vivaps of optical prop

ution of M. KuepfNat Biotech, 2005

in vivo

ser – FORTH, Cr

The principal limoptical analog othe potential to pprovided by MR n has been describe, FOV and low Se goal to estimateto bind to aggrega

he entrance of a Betection module l a laser beam of 0

ectance coated sprmany). For scannslide on two carborm with anesthe

witzerland). The dre anti-reflection High quality band emission wavehe housing bottoe, Germany), wer

w for animal prot1:4) mixture, sha

ml) was administerMR measurementms, FOV = 2.2x2d 720 nm was coex vivo validationed to compute t

mage were used fhe two images. T

ure observed indicng one pair of tg/pon tracer injectioye washout in tg dnot in wt animal

g was established eposition could bevo findings have bperties (scattering

fer in the mechan5 [3] Jellinger et a

Fig.

rete,

mitation f PET,

provide can be bed by

SNR of e the β-ated β-

Bruker located 0.5mm herical ning of

bon-rod sia gas

detector coated ndpass length,

om. To re used tection. aved on red via ts with .1cm2, llected

on with the top for co-

The co-

cative /wt on due to ls

using

e been g and

ical al., Eur

.3

2757Proc. Intl. Soc. Mag. Reson. Med. 20 (2012)