Him ORIGINAL CONTRIBUTION Comparison of MRI and CT for Detection of Acute Intracerebral Hemorrhage Ghekea S, Kidwell, MD. Julio A. Chalela, MD Jelirey L. Saver, MD yy Starkinan, MD Michael D. Hill, MD Andrew M. De Tawre Marie T Mlison E. Teary, MD ret Dremel MD, PhD MD) Andre Fredieu, MD ‘Shuichi Suzuki, MD, PhD. J Pablo V MD Mustaph Joseph Haymore, MIS, ACNP John K. Lynch, DO, MPH. Context. Noncontast computed tomography (CT) the standard bran imaging study forthe inal evaluation of patents With acute stroke symptoms. Multimodal mag” netic resonance imaging (MRI has ben proposed a an altemaiv to CT inthe emet= fenoystakeseting Howeve the acca of MRI eve to CT forthe detection ypetacute intracerebral hemorrhage has not been demonstrated. Objective To compare the accuracy of MRI and CT fr detection of acute intace- rebral hemorthage in patients presenting with acute focl stroke symptoms Design, Setting, and Patients A prospective, multicenter study was performed at2 Hroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, ind), between October 2000 and February 2003. Patients presenting with focal stoke symptoms within 6 hours of onset underwent brain MARI Tallowed by non- contast Ct Main Outcome Measures Acute intracerebral hemonhage and ay intracerebral hemorchage diagnosed on gradient recalled echo (GRE) MRI and CT scans by acon- sensus of blinded readers Results The study was stopped eal, aftr 200 patients were envlled, when it be- came apparent at the ime of an unplanned interim analysis that MRL was detecting cases of hemorthagicansformation nt detected by CT. Forth dagnosisof any her orthage, MRI was postive inpatients with CT postive in 29 (Pe=-001). For the d= anos of acute hemorthage, Mil and CT were equivalent 06% concordance). Acute hemorthage was diagnosed in25 patents on both MAI and CT. In other patents, acute hemorrhage Was present on MII but not on the coresponding CT-—each of these 4 cases wa interpreted as hemorrhagic vansformation ofan chemi infarct. In 3 patients, replons interpreted as acute hemorrhage on CT were interpreted aschonic hemorhage on MA. Int patient, subarachnoid hemorrhage was Gaghosed on CT Bul not on MRL In 49 patents, chronic hemorrhage, most often mirobleeds, Was vsulzed on MRI but not on Cr. Conclusion MRimay be as accurate as CT forthe detection of acutehemothage in patients presenting with acute focal stoke symptoms and fs more acute than CT forthe detection of chronic intracerebral hemorrhage snug aaos2328n 1890 wacom Tica Davis, MSN, RN Steven Warach, MD, PAD. (ONCONTRAST COMPUTED TO- ography (CT) hasbeen the standard imaging modality for the initial evaluation of patients presenting with acute stroke symptoms.'* The primary diagnosticad- vantage of CT in the hyperacute phase (© to 6 hours) is its ability to rule out ‘See also p 1883 and Patient Page. (©2004 American Medical Assoc ton, Al rights reserved. (Reprinted) AMA, Oe Author Aflitions UCLA Soke Center rs Kiwel,_Univesty of Calgary, Calgary, Alberta (Or HD Saver, Staenan Alger, Teme Oviagse Freie, agree Radiology Departmen Waren G_ Magi: Staub apd Viana) Deparment ot Newelngy Oe son Clea Center, Natona Institutes of Heh ‘wel Save, StamanTremwel Ovagle, Fedeu, Bethesda Ma (Drs 8utman Pao and Age) D: and Sux) Depart ofemergncy Medic (Orion of Ske and Vascular Neurology, et ae Stak), Deparent of Radology (OsFreeu, Sur Deaconess Meal Center, oso, Mas (Or Lea 1, andVilabana), Aansor-Lveace ran Map” Spas Newly Cente, Fort Sih, vk (Or Te fing Center (r Age), UCLA Medeal Centr LosAn- wel RayalMlboume Hospal, Vicor Ausala (r ss, Calt Nana nstutecNeursogl Deore Dav) Department ot Neuroogy. Emory Unversty Sd rok, Nabonal ists of Heath Bethea, Alara, Ga (Dr Ezedne: Center fr Newoscenee fd (De Chall Butman, Ptronae, Latour, Bar, Sees Washington ent op Takara Par, Dun, Toad, Lynch nd Viarach and Ms Luby, and Md Wr yma). Davi Cagay Stake rogram. Deparment Cini-Cavesponding Author Chaba, Kiel MD, Wash CaiNewrordentes, UnwersyoFCagey, FootlsHor- ington Rosa Ceter Soke Centr 100 ng St Pla, Calgary, Abeta Des land Demch Dee NW, East Bg Room 6126, Washngon, OC 20010, FartmentsofMedicne/Conmunty Heath Sciences, (cadwelul ed), 5 1823 Downloaded From: http:/Jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/4948/ on 05/01/2017MIRTVS CT FOR HEMORRHAGE DETECTION Figure 1. Acste ntraparenchyral Hlemators imagee With Computed Tomography ane ith Magnetic Resonance Imaging Computed Tomography Magnetic Resonance aging (GRE) ‘ramp of acateinvapaenchymalhenstoma inaged tt hour 4 minutes rom symptom ose wih com puted omegraphy (A whstearowhead) apd at | hut 12 minutes Fo symptom onset with magne fsa Farce imaging gradient eal echo (GRE] image, back aroeadh, the presence of hemorrhage. Accurate carly detection of blood is crucial since ahistory of intracerebral hemorthage is 4 contraindication to the use of throm- bolyticagents. However, a major disad- vantage of conventional CT within the first few hours of symptom onset is its limited sensitivity for identifying early cevidence of cerebral ischemia, Conversely, multimodal magnetic resonance imaging (MRD, including dif- fusion-weighted imaging (DWD, has excellent capacity to delineate the pres- cence, size, location, and extent of by peracute ischemia,” but unproven reli- ability in identifying early parenchymal hemorrhage. The advent of thrombo- Iytic therapy and other interventional therapies for acute ischemic stroke has led to increasing interest in using MRL to select and stratify candidates for reat- ments.* Currently, many stroke cen- ters obtain both CT and MRI in the ini- Uial evaluation of patients with stroke, The use of both modalities is time- consuming and expensive While conventional T1- and T2-weighted MRI pulse sequences are sensitive for the detection of subacute and chronic blood, they are less sensi- live to parenchymal hemorrhage dur- 1824 JAMA, Ocols No. 15 (Reprinted {ng the initial 6 hours after strokesymp- tomonset. A growing body of data have suggested that hyperacute parenchy- smal blood ean be accurately detected using gradient recalled echo (GRE) pulse sequences that are sensitive to static magnetic field inhomogeneity (ie, T2*-sensitive).** These sequences detect the paramagnetic effects of deoxyhemoglobin and methemoglo- bin. The hyperacute lesion on GRE/ 12" typically consists ofacore of! geneous signal intensity, reflecting the ‘most recently extravasated blood that ‘may still contain significant amounts of diamagnetic oxyhemoglobin, sur rounded by arim of hypointensity, sig- nifying parenchymal blood that has had lume to become more fully deoxygen- ated and paramagnetic (FiGURE 1).""" We undertook a prospective com- parison study of MRI vs CT in a large cohort of patients with acute stroke to establish that GRE MRI sequences are sensitive to acute hemorrhage. METHODS: Patients and Settings The Hemorrhage and Early MRI Evalu- ation (HEME) study was performed at 2academic stroke centers (UCLA Medi- Downloaded From: http:/Jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/4948/ on 05/01/2017 ceal Center and National Institutes of Health [NIH] Stroke Center at Subur- bban Hospital, Bethesda, Md). Initially 2 additional ce involved but subsequently discontinued participa- tion in the study because of inadequate sat enrollment. Patients present- ing with focal stroke symptoms within 6 hours of onset were screened for e1 rollment. Only symptomatic patients with a definite last known well time when initial imaging took place were e sible. Patients were excluded if any of the following were present: coms; pace- maker o other contraindication to MRI; symptoms suggestive of subarachnoid hemorrhage (SAH); inability to obtain MRI within © hours from last known well time; initiation of thrombolytic therapy, anticoagulants, o antithrombotic in- vestigational drug prior to completion of both imaging studies; oF cardiores- pitatory instability precluding MRI Site participation in the study was contingent upon the site's current rou- Line clinical practice of obtaining MRL followed by CT for patients with po- tential acute stroke, The institutional review board (IRB) at each site gave ap- proval to prospectively collect and ana- Iyze clinical and imaging data with iden- tying information removed. ALUCLA, the IRB waived consent; at Suburban Hospital, the study was performed un- der an IRB approved natural history of stroke protocol in which waiver was permitted in individual cases if waiver ‘of consent could not be obtained, ravenous antithrombotics oF Imaging Techniques All patients underwent MRI followed by CT. Imaging time goals were completion of both MRI and CT within (90 minutes of presentation to the emer- gency department, with no more than 30 minutes between the end of MRL and, the start of CT. Each site was required to keep a monthly log ofall patients pre senting within 6 hours of stroke symp- om onset to ensure that at least 50% ofall fully eligible patients were being enrolled. To qualily for enrollment, both GRE and DWI had to be completed, (©2004 American Medical Association, AU rights reservedAll MRis were performed on 1.5-T scanners equipped with echo-planar im- aging capability: UCLA, Siemens Vi- sion (Siemens Medical System, Iselin, Np:and Suburban Hospital, GE Signa scanner (General Electric Medical Sys- tems, Milwaukee, Wis). Computed to- mographie scans were performed on 1 of the following fourth-generation scanners: Somatom Plus scanner (Si mens), High Speed Advantage scan- nner (General Electric), or Lightspeed. scanner (General Electric). Images were acquired following the orbito-meatal plane with 5 mm thickness for the en- lire examination. Both scanners used the following pulse sequence param- ters: slice thickness, 7 mm (GRE and DWH) repetition time (TR), 800 ms (GRE); flip angle 30° (GRE): acquist- tion matrix, 256% 102 (GRE) and 128X128 (DWH). Pulse parameters at UCLA and at Suburban Hospital, re- spectively, were: lield of view, 24 em and 22.em (GRE and DW); echo ume (TE), 20 msand 15 ms (GRE); TR, 6000 ms and 60000 ms (DWI) (20 con- Liguouss slices, interleaved, and co- localized); and TE, 100 ms and 72 ms wn. ‘Outcome Measures A panel of 4 readers (2 neuroradiolo- aglsts and 2 stroke neurologists) inde- pendently evaluated each scan blinded to the clinical information and all pa- lient identifiers. None of the 4 readers ‘was involved in the elinial care or evalu- ation ofthe enrolled patients. Before pe forming study interpretations, the read cers were given examples (compiled from an independent data set) of each hem- corthage ype to ensure consistency of in- lerpretation toa common standard. In- lerpretations for each imaging modality (CT vs MRD) for a single patient were performed on different days to avoid reader recognition of recall of findings Irom the other modality. The order of presentation of the films was random- ized and differed for each modality. The following data were recorded by each, reader for each scan: hemorthage pre cent or absent; if hemorthage present, hemorthage age (acute or chronic), (©2004 American Medical Assoc MRI VS CT FOR HEMORRHAGE DETECTION ‘Table 1 cine Character of HEME Cofort ‘ge, ean fanghy TEE Sex, No. fe] women 20 5) Tine to MA, radian Tange” Za TS (28 INTO OREO Tine to CT, mesan fa ‘SAS min {66min te oh2O Mm Basaine NFSST soo, median FaABE) 80 Fraldecharge dagnoss, No. (=) "ACS, 169 845) Festa racer hero ZEB, Bath 7) type(e) (cubarachnoid subdural, epi _terpretation was reached by group con- diva, intraventricular, intaparenchy-sensus discussion. Final hospital tnaD) location ordeal subcortical white discharge diagnosis incorporating all tnatter, basal ganglia, brainstem, cer- available lineal laboratory, and imag. chelhise,thalamus),and umber (single ing data was made atthe time of dis- or multiple). For MRI interpretations, charge by the attending physician readers had access to DWI bo, tace DW $1000, and GRE images. Statistical Analysis, Tntraperenchytnal hemorshage was Theprimaty objective ofthe study was further classified as hematoma, hemor to compare the accuracy of MRI vs CT Hlugic tanaformation, ot microbleed. forthe detection of acute hemorthage Microbleeds were defined as rounded, Secondary objectives were to compare puncute, homogenous hypoiniensi~ the accuracy of MRI vs CT for any hem ties generally les than 05cm in size orrhage (acute or chronic) and for within the parenchyma, visualized on chronic hemorrhage alone GRE MRI scans, and thought to repre-__Initial sample size calculations as- sent regions of chronic hemosiderin sumed that CT was 100% accurate for deposition."" Hemorthagie transfor. hemorrhage and sought to demon- ration (petechial hemorrhage) was de- strate that MRI was also 100% accu- fined as a region of hyperdensity (CT) rate. In this noninferiority design, the or hypointensity (GRE MRD) occurring sample size required to narrow the di withinanacute,subscule,orchtonicis ference in the 95% confidence interval chemic lesion. Chronic hematoma was (CI) between MRI and CT to less than. defined asaslivlike region of hypoden- 5% was exact concordance between sity (CT) oF hypointensity (GRE MRI) MRI and CT on 55 hemorrhages. The thought wobedue to hemosiderin depo- selected software was Microsoft Ex- sition from a remote hematoma. Com- cel, using binomial theory. Thea priori puted tomographic acute hemorthage confidence level is 95%; however, ana volumes were subsequently calculated priori significance level is unavailable (by CS.K) usinga volumetric imaging since we are making a confidence analysis program, bound, not significance testing Wunanimousagreement regarding the In early 2003, an unplanned interim presence and acuity of hemorrhage on analysis was performed when prelim- an individual scan was not achieved by nary results of a complementary study cach of the 4 readers, the interpretation became available." During the interim, ofthe majority ofeaders wasused asthe analysis, it became apparent that MRI was final imaging diagnosis, In evenly dis- detecting acute hemorthages not vist tuibuted disagreements (2vs2), final in- alized on CT and, therefore, the initial mn. All ights reserved. (Reprinted) JAMA, Oxi 20,2004 Not 292, No, 1S 895 Downloaded From: http:/Jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/4948/ on 05/01/2017MRI VS CT FOR HEMORRHAGE DETECTION sample size, based on the assumption of using CT as the criterion standard, was not valid. Accordingly, the primary analysis plan was changed to bidire Uuonal comparison of CT vs MRI with: ‘uit assuming that one technique was in- herently acriterion standard, Inaddition, at this juncture, the study was stopped carly alter 200 patients were enrolled, as the investigators believed it would be i= portant to expedite, complete, and re- port the analysts of these patients be- ‘cause ofthe potential major impact the Lindings could have on current acute stroke management. Interrater reliability was calculated. for paired observers of both CT and MRI interpretations using the kappa (4) statistic. The MeNemar test for paired proportions was used to determine if fone imaging modality diagnosed hem- corrhage more frequently than the other. RESULTS Between October 2000 and February 2003, 391 consecutive patients presen ing with focal stroke symptoms within 6 hours of onset were screened for en- rollment in the study and a total of 200 patients were enrolled. Reasons for ex ‘Table 2. MRI vs CT Panel Results oer: Ray Remomhage ‘uate ee Mae 1 128] oo Aeutahemarhage Mee % 4 Mae 4167] >99 (Chron hemorhoge Ma 0 82 Ma ova] 1929 Downloaded From: http:/Jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/4948/ on 05/01/2017MRI VS CT FOR HEMORRHAGE DETECTION sented genuine acute hemorrhage. We also specifically excluded any patient ‘with symptoms suggestive of SAH. Al- though prior studies have suggested that both GRE MRI and fluid-attenuated in- version recovery images may be accu- rate in identifying subarachnoid blood, this will need to be prospectively con firmed in a future study." Because net- ther CT nor MRI ean exclude SAH with, 100% reliability, the clinician should purstie an extensive evaluation in any patient with whom SAH is contem- plated, including CT as well as lumbar puncture if CT is negative. Interreader reliability (« statistic) for detection of hemorthage was better for CT than for MRI Thisislikely due osev- eral factors, including less experience of the readers in interpreting actte MRI for |hemorthageand diferencesin the intrin- sic conspicuity ofhemorrhageappearanice on CT and MRI Therefore, .comprehen- sive educational program should be un- dertaken at any institution choosing to perform only MRI and not CT for the evaluation of acute stroke patients Recent reports have indicated wide- spread availabilty ofadvanced MRI tech- niques in the United States for the evalt- ation of patients with acute stroke.” However, concerns have been raised re- garding the logistical aspects of acquit- ing multimodal MRL in the acute stroke selling, particularly with regard to im- age acquisition times (and potential de- lays in initiating thrombolytic therapy). Based on our overall experience, the comprehensive MRI stroke protocol we used generally takes 10 to 15 minutes, Anabbreviated protocol, including DWI, GRE, and perfusion weighted imaging (PWD, takes less than 5 minutesand still provides substantially more informa- tion than a nonconteast CT. ‘Ourstudy may have implications for the imaging evaluation of patients with, acute stroke symptoms. Our findings support priorstudies suggesting that MRL isasaccurateas CT for the detection of hyperacute hemorthage."” One impor- tant caveat is that with simall hemor rhages, blood that appears as acute on. CT may appearas chronic on GRE MRL and anoncontrast CT may be required 4820 JAMA October 20,2004 Vol 292, No 15 Reprinted toconfirm the diagnosis in these cases, (Our study suggests that GRE MRI may beable todetect regions of hemorrhagic uansformation of an acute ischemic strokenotevidenton CT, Ourstudycon- firms the superiority of MRI for detec Lon of chronic hemorthage, particularly microbleeds, The roleof these findings inthe decision-making process for treat- ‘ment of patients who are candidates for thrombolytic therapy is currently un- known, Due to its advantages in delin- cating ischemic pathophysiology, in combination with the findings suggest- ing equivalency to CT fordetecting acute hemorrhage, MRI may be acceptable as the sole imaging technique for acute strokeat centers with expertise in int preting these findings. ‘Autor Contibutions: Or Kwel ba ful acces to ‘tthe ata he study an takes ul esponsb iy for teintegnty of he data and the aearcy of the dat nay, ‘Stuy conept and design: Kidwel, Chl, Saver, Stanan Warach, ‘Acguston of dt: wel, Chala, Save Stakan, Hil Demehuk,Pavoras, Ager Latour, Sag, Ley, “remedial Free, usu vlan, Daves, Dan Tek zene Haymore Lynch, Dav Waach ‘Analyssandintepreation of dat Kiel, Cae, Saver Butman, Patronas, Alger, Latour, Luby, ‘iaanca, Davis, arch Drang of he manuscript Kiwel, Chall, Feu, Davi Warach, aver Cita reson a he manus fr mpartant ints ‘etal cantnt Keel, Chala Soe, tana. Demat utman Patoas Agr Lalor Luby Bae, Leary, Teme, Ovb.gee, Sanuk, Vialanca Das, Dur Ted zene Haya Lynch, Dave Wack ‘Sets ana ee, Cale Sve iby, Wah (bvained funn: Kael, Saver, Warach, ‘Adniisatve tecnico matral sapere Kowa, Sever staoman, Hil Alger, Latou Luby, Leary, Fred, Dav, Tod, Haymore, Wars ‘Stuy sprain: Kdwel Chai, tarean, Ba Eszeddne, Warah Fuing/Support: This study was supported party the Divtionoflnvamaral Research Nationa tte ‘tNerogea Deere and Soke NDS ard ras fram the Armencan Heat Asotin (0170033N, OF Kel AMA Wester Sats Ailatelowsho Award DrLeaiy) and NINDS (23 NS 088, Oe Kel NS 535#50/E3 002087, Dr Alger K24NS 02082. Dr Sve). Dr las supoted in pat by te Her & Stoke Feundaton of Abeta NVVTINU andthe Canaan Stes for Heath Resse Role a the Sponco: The study se whol designed ‘candid, analyzed, ndepored by tears th ‘uta put rom ndstal sponse. ‘Ragonledgment We woudike toacknowledgethe Invaluable Stance proved by Paice Lal 3A, ‘ek Hyneman. Esa Lands 8, and Sarah Hiton, BS forthe completo of ths poet. TaN 4. Bode, Adams HP I aan We a. Guide ees forthe management of spontaneous ivacate brajnemonhage. Stake. 199530905915. 3 adame Pe Adams ect al Ces for Downloaded From: http:/Jamanetwork.com/pdfaccess.ashx?url=/data/journals/jama/4948/ on 05/01/2017 theca management of patie ith ischeic stoke, ‘Shove 2008.2 1036-1028, 3 Sarg AE, Waracns Magtcresonanee imaging ot Zee sroke I Crs lod low hess 120.1885 a 4 Aes GW. Expanding the wind or tomb IYecharoy nsedestout ote 1985502250.2257, 3 esaman A ata Buon eta MR em ihage anew sppeach AINE Am ered! 1385 CE conn ncn ty eco as Comet ie Chee ees count ans Sate Ur aoe ets bids se a te terior a ey nt min Se Sikeadol Pas oTe Ia Te ee eae na ne Site aa i scare a EEN permet Sretsrate eeae Srepcioiie ora bee moons etme bee TE coat cenea tere Pes arene he et Ee oat aati IES wma a SOS t=" an 2 eee et tres come ease EE Ey Ee ae hee aE ra 1B. NINDS PAStoke Group Tse pasminogenac thatrforace chore sk ng Mad. 95535 se 1387 20. Hemer M. Ngrogonian N. Catton of ‘sucepby-weghed magngioceesioleasesmen- Srove 200835 1969 1908, 21 Chaka A Kang OW, WaraehS. Mute cerebral flebleds/Neurrmaging 2004 15457, Ba Fant rang Lan MakVC Wang. Ce ‘eb merbleed cask tatoo subeeuer in Cebraleroaasanongatetth aie che te aove Soke 2008949240. 233. Wong Chan, Lal, Gao Lam W Asn fomaterscroblegr sas ator for sprinted Inhesebalnemortages Newly 200350511513, 2a Wesranntt MaerTeousyl Medee Hamar GF, ucknann#Detcton of hyperacute bach ‘noi hemaage ofthe brandy ng metres ‘cena Nurs Soe e 25 Sigel ASS ayer Subaornadspce seas: Racoigy. 1996208617422, 26. che Wins 1, Hoggard etal Dele {onofstnachned naemenhage wih magrelereso. ‘ance Neue Neos Pycnaty 200-7 Soot 27 nbecindDS, Yang CK. Sy) Balai 8, Neuro Inagngotertralizhemaincinal pace ea ‘ke Soca435, 2B Rand S, Gort Pa, Scmneck M4, Kim 0, Moote CG Leurares Aste sotzcze nln Sooke 2003, Sees, (©2004 American Medical Association, All rights reserved.