Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia

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1 Mgn Reson Med Sci 2017; 16; doi: /mrms.mp Pulished Online: July 12, 2016 MAJOR PAPER Gd-sed Contrst Enhncement of the Perivsculr Spces in the Bsl Gngli Shinji Ngnw *, Toshiki Nkne, Hisshi Kwi, nd Toshiki Tok Purpose: In textooks, the perivsculr spce (PVS) is descried s non-enhncing fter the intrvenous dministrtion of gdolinium-sed contrst gent (IV-GBCA). We noticed tht the PVS sometimes hs high signl intensity (SI) on hevily T 2 -weighted 3D-FLAIR (ht 2 -FL) imges otined 4 h fter IV-GBCA. The purpose of this study ws to retrospectively evlute the contrst enhncement of the PVS. Mterils nd Methods: In 8 helthy sujects nd 19 ptients with suspected endolymphtic hydrops, mgnetic resonnce cisternogrphy (MRC) nd ht 2 -FL imges were otined efore nd 4 h fter single dose of IV-GBCA. No sujects hd renl insufficiency. On xil MRC t the level of the nterior commissure (AC)-posterior commissure (PC) line, 1 cm circulr regions of interest (ROIs) were drwn centering on the PVS in the ilterl sl gngli nd thlmi. Three-millimeter dimeter ROIs were set in the cererospinl fluid (CSF) of the ilterl mient cistern. The ROIs on MRC were copied onto the ht 2 -FL imges nd the SI ws mesured. The SI rtio (SIR) ws defined s SIR PVS = SI of PVS/SI of the thlmi, nd SIR CSF = SI of CSF/SI of the thlmi. The verge of the ilterl vlues ws used for the clcultion. The SIR CSF, SIR PVS, nd SI of the thlmi were compred etween efore nd 4 h fter IV-GBCA. Results: The SIR ws from 1.02 ± 0.37 to 2.65 ± 0.82 in the CSF (P < 0.01) nd from 1.20 ± 0.35 to 2.13 ± 1.23 in the PVS t 4 h fter IV-GBCA (P < 0.01). The SI of the thlmi showed no significnt difference. Conclusion: The enhncement of the PVS t 4 h fter IV-GBCA ws confirmed even in sujects without renl insufficiency. It is possile tht the GBCA in the lood vessels might hve permeted into the cererospinl fluid (CSF) spce nd the PVS. This might e first step in the imging evlution of the glymphtic system (wste clernce system) of the rin. Keywords: mgnetic resonnce imging, perivsculr spce, gdolinium, glymphtic system Introduction In textooks, the perivsculr spce (PVS) is descried s non-enhncing fter the intrvenous dministrtion of gdolinium-sed contrst gent (IV-GBCA). 1 The PVS exists throughout the rin, ut is most frequently seen in the inferior third of the sl gngli ner the nterior commissure (AC). 1 We routinely performed mgnetic resonnce (MR) imging for the ssessment of endolymphtic hydrops 4 h fter single dose of IV-GBCA. 2 7 We noticed occsionlly Deprtment of Rdiology, Ngoy University Grdute School of Medicine 65 Tsurumi-cho, Shouw-ku, Ngoy, Aichi , Jpn *Corresponding uthor, Phone: , Fx: , E-mil: ngnw@med.ngoy-u.c.jp 2016 Jpnese Society for Mgnetic Resonnce in Medicine This work is licensed under Cretive Commons Attriution-NonCommercil- NoDerivtives Interntionl License. Received: April 05, 2016 Accepted: My 17, 2016 tht the PVS would hve high signl intensity (SI) on hevily T 2 -weighted 3D-FLAIR (ht 2 -FL) imges otined 4 h fter single dose of IV-GBCA. ht 2 -FL imging hs een utilized s sensitive technique to detect very low concentrtions of GBCA in fluid. 4,8,9 The slight enhncement of the cererospinl fluid (CSF) on ht 2 -FL imges cquired 4 h fter single dose of IV-GBCA hd een reported in helthy sujects with norml renl function 10 ; however, the enhncement of the PVS in helthy sujects hs not een reported previously. The enhncement of the PVS, though, hs een reported in ptient with renl insufficiency. 11 The PVS represents n entrnce point to the glymphtic system, recently discovered mcroscopic wste clernce system of the rin. 12,13 The purpose of this study ws to retrospectively evlute the contrst enhncement of the PVS oth prior to nd 4 h fter single dose of IV-GBCA in sujects who underwent MR imging. Mgnetic Resonnce in Medicl Sciences Vol. 16, No. 1 61

2 S. Ngnw et l. Mterils nd Methods In 8 helthy men (ges: 29 53) nd 19 ptients with suspected endolymphtic hydrops (7 men, 12 women; ges: 27 75), MR cisternogrphy (MRC), nd ht 2 -FL imges were otined on 3T scnner (Mgnetom Verio, Siemens Helthcre, Erlngen, Germny) prior to nd 4 h fter single dose of IV-GBCA. No sujects hd renl insufficiency. The 8 volunteers nd 7 of the ptients received IV-GBCA of 0.1 mmol/kg ody weight or 0.2 ml/kg ody weight using Gdoteridol (Gd-HP-DO3A: ProHnce, Eisi, Tokyo, Jpn) nd the other 12 ptients received the sme mount of IV-GBCA using Gdodimide (Gd-DTPA-BMA: Omni scn, Diichi-Snkyo, Tokyo, Jpn). In this study, we defined renl insufficiency s the history of proteinuri within 3 months or the estimted glomerulr filtrtion rte (egfr) <60 ml/min/1.73 m 2. All MR scns were performed using 32-chnnel rry hed coil nd GRAPPA (ccelertion fctor of 2). The slice thickness, field of view, mtrix size, nd slice position were identicl in oth the MRC nd ht 2 -FL imges. The voxel size ws mm 3. All sequences utilize frequency selective ft suppression pre-pulse. Further detils of the MR prmeters re listed in Tle 1. On the xil MRC prllel to the AC-posterior commissure (PC) line, 1 cm circulr region of interest (ROI) ws drwn nd centered on the PVS ilterlly in oth the sl gngli nd in the center of the thlmi for signl reference. The PVS ws defined s smll, shrply delineted structures with CSF-like intensity on the MRC tht followed the course of the perforting rteries. If CSF-like signl re of 3 mm or ove ws found, coronl reformtting ws performed to exclude the CSF contining lcunes y checking the shpe (Fig. 1). 14 The circulr 1 cm dimeter ROI for the PVS in sl gngli ws plced ccording to the instructions given elow. Select the highest xil MRC slice tht contins oth the AC nd PC. Drw the verticl line long the center of the interhemispheric fissure (line V on Fig. 2). Drw the horizontl line perpendiculr to line V through the AC (line H on Fig. 2). Drw n ROI (ROI 1 on Fig. 2) posterior to line H contcting the nterior edge of the circle. The distnce etween the contcting point nd midline (Line 2 on Fig. 2) should e mm. The ROI should e plced to cover s mny PVS s possile on the MRC. If the VRS is not cler on the MRC, distnce of 27.5 mm should e employed. Then, the ROIs were copied onto the ht 2 -FL imge nd the SI of the ROI ws mesured (Fig. 2). The circulr ROIs of 1 cm dimeter were plced in the ilterl thlmi on the sme slice s the PVS t 1 cm lterl to the midline. The 3 mm dimeter ROIs were set within the ilterl CSF spces of the mient cistern, voiding the vessels. Then, the ROIs were copied onto the ht 2 -FL imge nd the SI of the ROI ws mesured. We chose the mient cistern for the signl mesurement of CSF ccording to the previous study. 10 In mient cistern, the pprent signl decrese of Tle 1. Pulse sequence prmeters Scn time (min:s) Numer of excittions Mtrix size Field of view (mm) Echo trin length Numer of slices Pixel size (mm) Section thickness/ gp (mm) Flip ngle (degree) Inversion time (ms) Echo time (ms) Repetition time (ms) Type Sequence nme 1/ :13 90/initil 180 decrese to constnt NA SPACE with restore pulse MR cisternogrphy 1/ :21 90/initil 180 decrese to constnt SPACE with inversion pulse Hevily T 2 -weighted 3D-FLAIR MR, mgenetic resonnce; NA, not pplied; SPACE, smpling perfection with ppliction-optimized contrsts using different flip ngle evolutions 62 Mgnetic Resonnce in Medicl Sciences

3 Enhncement of Perivsculr Spces CSF due to flow ws not seen on MRC, nd the significnt contrst enhncement ws detected on HF in the previous volunteers study. The significnt enhncement in lterl ventricle ws not detected in tht study. 10 One experienced neurordiologist plced the ROIs on the MRC. The SI rtio (SIR) ws defined s: SIR PVS = SI of PVS/SI of the thlmi, nd SIR CSF = SI of CSF/SI of the thlmi. The verge of the ilterl vlues ws used for the clcultion. The signl enhncement rtio (SER) of the PVS ws given s SER = SIR of the post-contrst dministrtion/sir of the precontrst dministrtion. The SIR CSF, SIR PVS, nd SI of the thlmi were compred prior to nd 4 h post IV-GBCA using Student s t-test. The SER of the volunteers nd ptients were compred using Mnn-Whitney s test. We set 5% s significnce level for the sttisticl test. Fig 1. Coronl reformtting is performed to differentite lrge perivsculr spce (PVS) from the cererospinl fluid (CSF)- contining lcunes. On coronl reformtted imge, the PVS (rrows) shows typicl shpe following perforting vessels without surrounding gliosis. For the helthy volunteers scns, the medicl ethics committee of our institution pproved the study nd written informed consent ws otined from ll volunteers. For the ptients retrospective study, the medicl ethics committee of our institution pproved this retrospective study with wiver of written informed consent from the ptients. Results In ll 27 sujects, the men SIR CSF from 1.02 ± 0.37 to 2.65 ± 0.82 fter the IV-GBCA dministrtion (P < 0.01) nd the men SIR PVS from 1.20 ± 0.35 to 2.13 ± 1.23 fter IV-GBCA (P < 0.01) (Figs. 3, 4). No significnt difference ws found etween the SI of the thlmi prior to nd 4 h fter IV-GBCA. When limited to the 8 volunteers nd 7 ptients who received IV-GBCA y Gdoteridol, the men SIR CSF from 0.91 ± 0.32 to 2.35 ± 0.72 fter the IV-GBCA dministrtion (P < 0.01) nd the men SIR PVS from 1.00 ± 0.16 to 1.38 ± 0.14 fter IV-GBCA (P < 0.01). When limited to the 12 ptients who received IV-GBCA y Gdodimide, the men SIR CSF from 1.15 ± 0.11 to 3.03 ± 0.22 fter the IV-GBCA dministrtion (P < 0.01) nd the men SIR PVS from 1.46 ± 0.10 to 3.07 ± 0.37 fter IV-GBCA (P < 0.01). The SER of the PVS nd the SER of the CSF showed no significnt difference etween the 8 volunteers nd 19 ptients. When limited to the Gdoteridol group, the SER of the PVS nd the SER of the CSF showed no significnt difference etween the 8 volunteers nd 7 ptients. Among the ptients who received IV-GBCA y Gdodimide nd tht y Gdoteridol, there ws no significnt difference in the SER of the PVS or the SER of the CSF. Discussion In this study, the enhncement of the PVS nd CSF ws confirmed even in sujects without renl insufficiency. The high Fig 2. Exmple of region of interest (ROI) plcement. On mgnetic resonnce cisternogrphy (MRC) () t the nterior commissure (AC)-posterior commissure (PC) slice, horizontl line (line H) ws drwn through the AC verticl to the midline (line V). A 1 cm dimeter ROI ws drwn just posterior to line H (circle 1). The distnce from midline (length of line 2) ws cm. The ROI ws plced to include s much of the perivsculr spce (PVS) s possile. If the PVS is not cler on MRC, line 2 ws plced t 2.75 cm. Then, the ROI ws copied onto the ht 2 -FL imge (). Fig 3. The signl intensity rtio (SIR) distriution in ll 27 sujects. () The SIR of the perivsculr spce ws t 4 h fter intrvenous dministrtion of gdolinium-sed contrst gent (IV-GBCA). () The SIR of the cererospinl fluid (CSF) ws t 4 h fter IV-GBCA. Vol. 16, No. 1 63

4 S. Ngnw et l. c Fig 4. A 71-yer-old womn with suspected endolymphtic hydrops. On mgnetic resonnce cisternogrphy (MRC) (), there is much perivsculr spce (PVS) in the ilterl sl gngli (rrows). On pre-contrst hevily T 2 -weighted FLAIR (ht 2 -FL) imge, the PVS hs low-signl intensity (). On post-contrst ht 2 -FL imges (c), the PVS hs n incresed signl intensity (rrows). The cererospinl fluid (CSF) lso hs incresed signl. Note tht some of the PVS hs higher signl thn the CSF. sensitivity of the ht 2 -FL imge to low concentrtion of GBCA in fluid llowed the detection of the slightest enhncement of the PVS in sujects without renl insufficiency. 4,8 It hs een reported tht GBCA injected intrtheclly enters into the PVS nd rin prenchym. 15 In this study, it is speculted tht the IV-GBCA entered into the PVS from the CSF. In the previous helthy volunteer study, the timing of enhncement is erlier in the optic nerve sheth, Meckel s cve round trigeminl nerve, nd the fundus of the internl uditory cnl round the seventh nd eighth crnil nerves thn in the CSF of the mient cistern. 10 These findings suggested tht GBCM permeted from the peripherl prt of the crnil nerve or nerve sheth to CSF, even in the sujects with intct lood rin rrier. On the other hnd, some of the PVS signls were visully higher thn tht of the CSF t 4 h fter IV-GBCA (Fig. 4). Simple penetrtion of the CSF into the interstitil fluid of the PVS cnnot explin this more intensely incresed PVS signl. This suggests tht the PVS hs n ctive mechnism such s the sorption of wter in the PVS or the secretion of gdolinium into the PVS. This ctive function of the PVS might e investigted using MR imging in the future. A signl decrese of CSF due to flow cnnot e completely ruled out; however, the CSF signl of mient cistern on MRC ws quite high s inner er fluid. Therefore, the flow effect in mient cistern might e quite smll. Most reports regrding the glymphtic system re descriing the PVS round rtery t the entry site of CSF to the glymphtic system 12 ; however, one report is descriing the PVS round the rtery s oth the entry nd outlet. 16 If the PVS round perforting rtery cts lso s n outlet, more intense enhncement of PVS thn CSF seems to e resonle. The MR scns t most time points should e performed in the future to revel the precise kinetics of GBCA in the rin. The PVS in nother region of the rin should lso e investigted. The glymphtic system is reported to e ctive during sleep 17 ; thus, the sleep condition should e controlled during the investigtion of the glymphtic system. The findings of this study suggest tht the lood CSF rrier nd the CSF interstitil fluid (IF) rrier might e lekier thn the lood rin rrier. The deposition of gdolinium in the rin prenchym such s in the dentte nucleus nd glous pllidus is recent hot topic in the field of MR imging. 18,19 Intct gdolinium- cheltes might penetrte the rin prenchym through the CSF nd PVS (i.e., the glymphtic system). Recently, severl reports hve suggested tht the PVS is prt of the rin lymphtic system (glymphtic system) through which the interstitil solutes re clered from the rin 12,13,20,21 It hs een demonstrted tht rteril pulstion drives the surchnoid CSF flow into the PVS, clering solule proteins such s myloid et (Aβ) from the rin. 20,21 The wstes re wshed out of rin from peri-venous spces to CSF spce. Dysfunction of the PVS pthwys thus my led to n enlrged PVS, incresed Aβ deposition, nd susequent neuronl dysfunction nd loss, which clerly would hve profound implictions for Alzheimer s disese. 21 In the niml study, n intrthecl injection of gdolinium ws utilized to investigte glymphtic function y nlyzing the CSF-ISF exchnge cross the rin. 20 The results of this study might open the door to n exmintion of the glymphtic system in humns y cliniclly fesile method using MR imging nd IV-GBCA. Conclusion The enhncement of the PVS t 4 h fter single dose of IV- GBCA ws confirmed in humn sujects without renl insufficiency. This might represent the first steps using MR imging to evlute the glymphtic system in humns. References 1. Osorn AG. Nonneoplstic cysts, 1st ed. In: Osorn AG, ed. Osorn s rin: imging, pthology, nd ntomy. Alton: Amirsys, 2013; Ngnw S, Kwi H, Iked M, Sone M, Nkshim T. Imging of endolymphtic hydrops in 10 minutes: new strtegy to reduce scn time to one third. Mgn Reson Med Sci 2015; 14: Mgnetic Resonnce in Medicl Sciences

5 Enhncement of Perivsculr Spces 3. Ngnw S, Nkshim T. Visuliztion of endolymphtic hydrops with MR imging in ptients with Ménière s disese nd relted pthologies: current sttus of its methods nd clinicl significnce. Jpn J Rdiol 2014; 32: Ngnw S, Ymzki M, Kwi H, Bokur K, Sone M, Nkshim T. Visuliztion of endolymphtic hydrops in Ménière s disese with single-dose intrvenous gdo liniumsed contrst medi using hevily T2-weighted 3D-FLAIR. Mgn Reson Med Sci 2010; 9: Ngnw S, Ymzki M, Kwi H, Bokur K, Sone M, Nkshim T. Imging of endolymphtic nd perilymphtic fluid fter intrvenous dministrtion of single-dose gdodimide. Mgn Reson Med Sci 2012; 11: Ngnw S, Ymzki M, Kwi H, Bokur K, Sone M, Nkshim T. Visuliztion of endolymphtic hydrops in Ménière s disese fter single-dose intrvenous gdoliniumsed contrst medium: timing of optiml enhncement. Mgn Reson Med Sci 2012; 11: Ngnw S, Ymzki M, Kwi H, Bokur K, Sone M, Nkshim T. Visuliztion of endolymphtic hydrops in Ménière s disese fter intrvenous dministrtion of single-dose gdodimide t 1.5T. Mgn Reson Med Sci 2013; 12: Ngnw S, Kwi H, Sone M, Nkshim T. Incresed sensitivity to low concentrtion gdolinium contrst y optimized hevily T 2 -weighted 3D-FLAIR to visulize endolymphtic spce. Mgn Reson Med Sci 2010; 9: Ngnw S. The technicl nd clinicl fetures of 3D- FLAIR in neuroimging. Mgn Reson Med Sci 2015; 14: Ngnw S, Suzuki K, Ymzki M, Skuri Y. Seril scns in helthy volunteers following intrvenous dministrtion of gdoteridol: time course of contrst enhncement in vrious crnil fluid spces. Mgn Reson Med Sci 2014; 13: Knmll US, Boyko OB. Gdolinium diffusion into oritl vitreous nd queous humor, perivsculr spce, nd ventricles in ptients with chronic renl disese. AJR Am J Roentgenol 2002; 179: Jessen NA, Munk AS, Lundgrd I, Nedergrd M. The glymphtic system: eginner s guide. Neurochem Res 2015; 40: Kyrtsos CR, Brs JS. Modeling the role of the glymphtic pthwy nd cererl lood vessel properties in Alzheimer s disese pthogenesis. Plos One 2015; 10:e Wrdlw JM, Smith EE, Biessels GJ, et l. Neuro imging stndrds for reserch into smll vessel disese nd its contriution to geing nd neurodegenertion. Lncet Neurol 2013; 12: Li L, Go FQ, Zhng B, Luo BN, Yng ZY, Zho J. Overdosge of intrthecl gdolinium nd neurologicl response. Clin Rdiol 2008; 63: Bkker EN, Bcski BJ, Arel-Ornth M, et l. Lym phtic clernce of the rin: perivsculr, prvsculr nd significnce for neurodegenertive diseses. Cell Mol Neuroiol 2016; 36: Berezuk C, Rmirez J, Go F, et l. Virchow Roin spces: correltions with polysomnogrphy-derived sleep prmeters. Sleep 2015; 38: Knd T, Fukusto T, Mtsud M, et l. Gdolinium-sed contrst gent ccumultes in the rin even in sujects without severe renl dysfunction: evlution of utopsy rin specimens with inductively coupled plsm mss spectroscopy. Rdiology 2015; 276: McDonld RJ, McDonld JS, Kllmes DF, et l. Intrcrnil gdolinium deposition fter contrst- enhnced MR imging. Rdiology 2015; 275: Iliff JJ, Lee H, Yu M, et l. Brin-wide pthwy for wste clernce cptured y contrst-enhnced MRI. J Clin Invest 2013; 123: Zong XP, Prk SH, Shen DG, Lin WL. Visuliztion of perivsculr spces in the humn rin t 7 T: sequence optimiztion nd morphology chrcteriztion. Neuroimge 2016; 125: Vol. 16, No. 1 65