Quantification of hyperdense middle cerebral artery sign by multidetector computed tomography (MDCT)

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1 Neurordiology Updte rticle Quntifiction of hyperdense middle cererl rtery sign y multidetector computed tomogrphy (MDCT) Frncisco Meli, Jvier Vllejos, Cludi Álvrez, Crlos Cpuñy, Ptrici Crrscos Resumen Ojetivos. Otener un cuntificción solut y reltiv de l densidd en el signo de l rteri cererl medi (ACM) con el fin de logrr un vlor ojetivo pr el dignóstico temprno de isquemi cererl gud con TCMD. Mteriles y Métodos. Se incluyeron 40 pcientes, 20 con sospech de isquemi cererl gud (edd medi 73,4 ños) y 20 pcientes controles (edd medi 71,2 ños, p=0,63), que se relizron TC cererl con un equipo de 64 fils de detectores. L cuntificción solut se relizó midiendo l densidd en UH en el segmento de l ACM visulmente de myor densidd. Tmién se midió l densidd en el mismo segmento de l ACM contrlterl pr clculr l diferenci entre ms rteris (cuntificción reltiv). Resultdos. En pcientes csos, l densidd medi de l ACM fectd (62,5 UH, IC 99%: 46,2-78,7) fue myor que l de l ACM contrlterl (39,3 UH, IC 99%: 33,3-45,3) (p=0,0004) y tmién fue myor en comprción con l ACM en pcientes controles (44,7 UH, IC 99%: 37,4-52) (p=0,0045). En l cuntificción reltiv, l diferenci medi entre l densidd de l ACM fectd y l de ACM contrlterl en los pcientes csos fue de 23,2 UH (IC 95%: 11,7-34,7), mientrs que, en pcientes controles, l diferenci medi entre l densidd de l ACM derech y l ACM izquierd fue 5,2 UH (IC 95%: 2,4-8,4) (diferenci: 17,8 UH, p=0,0032, IC 95%: 6,8-28,8). Conclusión. Mostrmos diferencis significtivs (soluts y reltivs) en l densidd de l ACM en pcientes con sospech de isquemi cererl gud en comprción con sujetos normles. Plrs clve. Accidente cerero vsculr. Arteri cererl medi. Tomogrfí computd multidetector. Astrct Quntifiction of hyperdense middle cererl rtery sign y multidetector computed tomogrphy (MDCT). Purposes. To otin solute nd reltive quntifiction vlues of density in the middle cererl rtery (MCA) sign, in order to otin n ojective vlue for n erly dignosis of cute ischemic stroke using MDCT. Mteril nd Methods. Forty dult ptients, 20 with suspected dignosis of cute ischemic stroke (men ge: 73.4 yers) nd 20 controls (men ge: 71.2 yers, p=0.63), underwent rin CT scns with 64-row multi-detector scnner (Brillince 64; Philips Medicl Systems). Asolute quntittive nlysis ws ssessed y trcking tissue density of the MCA segment using region of interests. For reltive quntifiction, density in the sme segment of the contr-lterl MCA ws mesured to clculte the difference etween oth rteries. Results. In cses, men density of ffected MCA (62.5 HU, 99% CI: ) ws greter thn tht of the contr-lterl MCA segments (39.3 HU, 99% CI: ) (p<0.0004) nd lso greter thn tht of controls (44.7 HU, 99% CI: ) (p=0.0045). In reltive quntifiction, the men difference etween density of the ffected MCA nd tht of contr-lterl MCA in cses ws 23.2 HU (95% CI: ), while in controls the men difference etween the right MCA density nd the left MCA density ws 5.2 HU (95% CI: ) (difference: 17.8 HU, p = , 95% CI: ). Conclusion. We showed significnt (reltive nd solute) differences in MCA density in ptients with suspected cute ischemic stroke s compred to norml sujects. Keywords. Middle cererl rtery. Multidetector computed tomogrphy. Stroke. INTRODUCTION Computed tomogrphy (CT) nd mgnetic resonnce imging (MRI) ply centrl role in the mngement of cute stroke. CT perfusion, diffusionweighted imging, nd perfusion MRI my help to improve identifiction of ptients who re cndidtes for thromolytic therpy (1,2). However, ecuse of etter vilility, ese of use nd short exmintion time, CT is still --nd is likely to remin--the method of choice in the initil differentil dignosis of stroke. During the first hours of n cute stroke, CT findings my e sutle or even undetectle, even when lrge territory is involved. However, mny signs hve een descried s mrkers of erly cute stroke on CT: 1) sl gngli hypodensity, 2) hypottenution of the insulr rion, 3) effcement of convexity sulci, nd 4) the hyperdense middle cererl rtery Deprtmento de Tomogrfí Computd y Resonnci Mgnétic de Dignóstico Mipú. Av. Mipú CP B1602ABQ. Vicente López, Buenos Aires Argentin. Correspondenci: Dr. Jvier Vllejos - [email protected] Reciido: ferero 2011; ceptdo: octure 2011 Received: ferero 2011; ccepted: octoer 2011 SAR-FAARDIT RAR - Volumen 75 - Número Págin 1

2 Quntifiction of hyperdense middle cererl rtery sign Fig. 1: () Brin MDCT xil imge of 68-yer-old mle ptient showing right MCA hyperdensity. () Zoomed-in imge showing solute quntifiction of density of oth MCAs y single pixel ROI. The difference etween the ffected MCA nd the contrlterl MCA is 16 HU. Fig. 2: () Brin MDCT xil imge of 69-yer-old femle ptient showing oth MCAs with norml density. () Zoomed-in imge showing similr ttenution vlues in oth MCAs. sign (HMCAS) (3-5). In recent yers, recognition of the erly signs of stroke hs ecome more importnt with the dvent of systemic thromolytic therpy (6). Incresed ttenution of the middle cererl rtery (MCA) ws first descried in the erly 1980s, corresponding to the presence of n occlusive thromus within the involved vessel (7). This finding hs een oserved within 90 minutes of symptom onset (8). In ddition, some uthors hve reported tht the presence of this sign hs n independent prognostic vlue in terms of susequent moridity nd mortlity (4,5). Some uthors hve reported tht the specificity of HMCAS in identifying MCA occlusion pproches 100%, wheres its sensitivity is lower (4,5). However, flse positives hve een noted in ptients with high hemtocrit or clcified therosclerotic disese. Furthermore, with the new multidetector CT scnners, reduction of prtil volume effects hs een chieved due to thinner slice thickness. This determines n pprent reltive vsculr hyperdensity. Págin 2 RAR - Volumen 75 - Número

3 Frncisco Meli et l. Fig. 3: Box plot showing quntifiction of the middle cererl rtery sign on the ffected side versus the contrlterl MCA. Fig.4: Box plot showing the reltion in the quntifiction of the middle cererl rtery sign on the ffected MCA in cses versus controls. Fig. 5: Brin MDCT xil imge in 72-yerold femle ptient with left-sided fcil, rm nd leg motor deficit. Density mesurements were performed on MCAs, nd significnt difference ws found. Fig. 6: Brin MDCT performed in 62 yerold femle ptient with clinicl symptoms indictive of stroke. Axil imge shows hyperdensity of the left MCA (rrow). Fig. 7: Sixty-seven yer-old mle ptient with left-sided motor deficit. Brin MDCT ws performed 3 hours fter the onset of symptoms. Axil imge shows hyperdensity of the right MCA (rrow) s the only indictive sign of ischemic stroke. The im of this study is to otin solute nd reltive quntifiction vlues of density in the middle cererl rtery (MCA) sign, in order to otin n ojective vlue for n erly dignosis of cute ischemic stroke using multidetector CT. MATERIALS AND METHODS The project ws pproved y the Institutionl Review Bord. A prospective study ws performed, from Novemer 2007 to Mrch 2010, in 32 ptients who underwent rin CT scn on the sme dy s stroke ws cliniclly suspected. Twelve ptients with intrprenchyml hemtom on CT were excluded. Of the remining 20 ptients, 16 (80%) were mles nd 4 (20%) were femles. The men ge in this group ws 73.4 yers (rnge 60-82). We lso reviewed selected studies of 20 ptients with n ge rnge etween 60 nd 80 yers who ttended our site to hve rin CT scn performed for other resons during the sme period. In this control group, 12 ptients (60%) were mles nd 8 (40%) were femles, nd the men ge ws 71.2 yers (rnge 62-79). All ptients underwent non-contrst rin CT scns with 64-row multidetector scnner (Brillince 64; Philips Medicl Systems, Clevelnd, OH). The following technicl prmeters were used for dt cquisition: collimtion, 64? mm; 2-mm reconstruction slice thickness; tle increment, 1 mm; mtrix, 512 x 512; pitch 0.45; 140 kv; 300 ma; gntry rottion time, 0.75 sec. The ffected side ws defined s the one where the HMCAS ws sujectively oserved. Asolute quntifiction ws performed y mesuring vsculr ttenution in HU on xil CT slices using one-pixel regions of interests (ROIs) in the visully MCA s densest segment. Using the sme methodology, density ws lso mesured in the sme segment of the contrlterl MCA (not ffected). For reltive quntifiction, density in the sme segment of the contrlterl MCA ws mesured to clculte the difference etween oth rteries (Fig. 1). In controls, density mesure- RAR - Volumen 75 - Número Págin 3

4 Quntifiction of hyperdense middle cererl rtery sign Fig. 8: Progression of ischemic stroke in 71-yer old ptient. () Brin MDCT performed 6 hours fter the onset of symptoms. Coronl reconstruction shows hyperdensity of the left MCA nd sutle hypodensity of ipsilterl sl gngli. () Follow-up MDCT performed 24 hours fter the onset of symptoms, showing persistent left MCA sign nd extensive re of infrction in the MCA territory. Fig. 9: Brin MDCT, xil slice in 64-yer-old ptient. Sylvin cisterns re nrrow nd impir proper identifiction of the MCA. In these cses, n incresed slice thickness improves visuliztion of the right HMCAS (rrow). Fig. 10: Seventy-yer-old ptient with right motor deficit nd left HMCAS on rin MDCT. For tortuous vessel courses, mximum intensity projection (MIP) reconstructions llow more pprent visuliztion of the sign. ments were tken from n ritrry portion of the M1 segment of the MCAs on oth sides, with the im of otining n solute nd reltive quntifiction of ttenution (Fig. 2). All mesurements were mde y two oservers with different levels of experience, neurordiologist (F.M.) nd third-yer resident in Rdiology (C.A.). Sttisticl nlyses were performed using Student s t test to clculte differences etween groups, when the study vrile showed norml distriution. Differences with p vlues < 0.05 were considered sttisticlly significnt. Interoserver vriility in mesurements of MCA ttenution ws ssessed y clculting the Spermn s correltion coefficient nd the greement intervl y the Blnd-Altmn method. Págin 4 RAR - Volumen 75 - Número

5 Frncisco Meli et l. Fig. 11: Seventy-four yer-old femle ptient with dysrthri of 6 hours durtion. () Density of MCAs does not visully pper to e incresed on rin MDCT. () When solute quntifiction of the right MCA is performed, density is effectively 45 HU, which cn e oserved in norml ptients. However, when compring the right MCA density with tht of the left MCA, the difference is 20 HU. This suggests positive sign on the right side. The ptient experienced n infrction in the territory of the right MCA. Fig. 12: Differentil dignosis: fifty-two yer old ptient with high hemtocrit. () Hyperdensity of oth MCAs on CT scn. () Quntifiction revels similr density on oth sides, with no evidence of significnt difference. RESULTS There were no significnt differences (p = 0.63) in ge etween the group of cses with suspected stroke (men 73.4 yers; rnge 60-82) nd controls (men 71.2 yers; rnge 62-79). When solute quntifiction ws performed, in cses, the men density of the ffected MCA ws 62.5 HU (99% CI: 46.2 to 78.7), while tht of the helthy contrlterl MCA ws 39.3 HU (99% CI: 33.3 to 45.3), with significnt difference of 23.2 HU (p<0.0004) (Fig. 3). The men density of MCAs in controls ws 44.7 HU (99% CI: 37.4 to 52), significntly lower thn the density of the ffected MCA in cses, with difference of 17.8 HU (p = ) (Fig. 4). In reltive quntifiction, the men difference etween density of the ffected MCA nd tht of contrlterl MCA in cses (Fig. 5) ws 23.2 HU (95% CI: 11.7 to 34.7), while in controls the men difference etween the right MCA density nd the left MCA density ws 5.2 HU (95% CI: 2.4 to 8.4). The difference etween cses nd controls ws significnt with p vlue = (95% CI: 6.8 to 28.8). In the ssessment of interoserver vriility, the coefficient of correltion ws r=0.87 with 95% limits of greement etween -8.4 to 6.3 HU. RAR - Volumen 75 - Número Págin 5

6 Quntifiction of hyperdense middle cererl rtery sign Fig. 13: Differentil dignosis: theromtous plques. () Seventy-yer-old ptient with hyperdensity of the left MCA on CT scn. An ssessment of the vessel on the orthogonl plne y multiplnr reconstruction llows visuliztion of eccentric hyperdensity of lumen (rrow), which is typicl of clcified therom plques. () A 75-yer-old ptient with right MAC MCA hyperdensity on CT scn. In the orthogonl plne, hyperdensity involves the whole vessel lumen (rrow), which is indictive of vsculr thromus. This differentil dignosis cnnot e mde only y density mesurement, s there re firous theromtous plques tht re usully less thn 100 HU nd vsculr thromi of over 100 HU, which indictes n overlp of ttenution vlues nd the impossiility of determining cut-off vlue. Págin 6 RAR - Volumen 75 - Número

7 Frncisco Meli et l. DISCUSSION According to the literture, the HMCAS is oserved in 30% of ptients experiencing vsculr event in the territory of the MCA (9,10). In most studies, this sign is qulittively reported, nd no HU vlues re mentioned. However, Koo et l (6) found s positive vlue ove 43 HU in ttenution of the ffected MCA. Schuknecht et l (11) susequently focused on the sme issue, ut did not report comprtive vlues etween oth MCAs. Recently, Aul-Ksim et l (2) considered MCA ttenution ove 50 HU nd MCA rtio (ffected MCA/ helthy MCA) ove 1.4 s cut-off vlues defining the limit etween the presence nd sence of HMCAS. After performing densitometric mesurements, we otined significnt difference when compring HU vlues in the ffected MCA in ptients with cute stroke to those in the contrlterl MCA nd in controls (Figs. 6 nd 7). Aul-Ksim et l (2) reported ojective nd sujective findings in cses of cute stroke with HMCAS. The vlues they found in 39 ptients were slightly lower on the ffected side (60.5 HU) thn ours (62.5 HU). When using the ffected MCA / helthy MCA density rtio, the men vlue ws 1.5. In our cses, the men difference etween density of the ffected MCA nd tht of the helthy MCA ws 23.2 HU, while in controls the difference ws only 5.2 HU. To our knowledge, this is the first report of quntittive ssessment of the HMCAS in prospective series of ptients, evluted with multidetector CT scnner, with results tht re in generl greement with those otined y Aul-Ksim et l. Other uthors emphsize tht the presence of HMCAS hs prognostic vlue in the evlution of ptients fter thromolysis (4,5,12). Khritonov et l (13) oserved in 1905 ptients tht HMCAS disppered fter IV thromolysis in hlf of cses, nd these ptients hd much etter prognosis thn those with persistent HMCAS on CT scns (Fig. 8). Therefore, given the existence of n lterntive tretment pproch with good results, evidence cretes the need for relile method to ccurtely detect this sign. Even though it is well-known tht erly signs of rin ischemi on CT scn re less pprent (compring to diffusion-weighted MRI) nd require trining for proper identifiction, Wrdlow et l (14) stted tht the oserver s experience is not the min fctor to ensure n ccurte dignosis (Figs. 9 nd 10). Identifiction of which signs re most importnt to e recognized nd the clrifiction of their definition re the two fctors with mjor implictions for dignostic ccurcy. In our study, vsculr density ws evluted nd quntified y two oservers with different levels of experience in neurordiologicl imging ( senior physicin nd resident) nd high degree of correltion nd greement ws chieved. Therefore, sed on the therpeutic nd prognostic implictions of this sign, its identifiction y physicins with little experience is of prmount importnce, s mny of these ptients re seen t emergency deprtments y junior physicins nd/or residents. Most of the times, they perform rin CT scn in ptients with cute ischemic stroke. Quntittive ssessment would provide ojective dt to support visul inspection, not mtter how ccurte nd detiled visul inspection might e (Fig. 11). A comined qulittive nd quntittive ssessment mkes it possile to rule out other differentil dignoses tht could led to flse positive HMCAS, such s high hemtocrit or clcified therosclerotic plques. In the first cse, incresed density is generlized nd oth middle cererl rteries often show high ttenution (Fig. 12). In the presence of theromtous disese, clcified plques re usully eccentric. This is etter pprecited on multiplnr reconstructions orthogonl to the mjor xis of the vessel involved (Fig. 13). Limittions to our study include the smll smple size, lthough the interoserver correltion ws very good. However, we included group of controls with no vsculr involvement, which provides further informtion nd mkes results stronger. An dditionl limittion is the inclusion of ptients with different times of progression on the sme dy of the cererovsculr event. The greement etween the few studies on quntittive ssessment of HMCAS reported in the literture nd our findings is promising. Hyperdense MCA my e ojectively detected y multidetector CT y mesuring MCA density nd compring it with tht of the helthy contrlterl MCA. We think tht the incorportion of routine reding of CT scns in this group of ptients t emergency deprtments with sujective nd ojective (quntifiction) ssessments would further increse the finl outcome ccurcy nd precision nd provide the clinicl neurologist with necessry rdiologicl dt to mke decision on the therpeutic pproch. References 1. Wrdlw JM, Mielke O. 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8 Quntifiction of hyperdense middle cererl rtery sign Hyperdense Middle Cererl Artery Sign? Cererovsculr diseses 2000; 10: Gcs G, Fox AJ, Brnett HJM, Vinuel F. CT visuliztion of intrcrnil rteril thromoemolism. Stroke 1983; 14: Tomsick T, Brott T, Brsn W, Broderick J, Hley EC, Spiler J, et l. Prognostic vlue of the hyperdense middle cererl rtery sign nd stroke scle score efore ultrerly thromolytic therpy. AJNR Am J Neurordiol 1996; 17: Mnelfe C, Lrrue V, von Kummer R, Bozzo L, Ringle P, Bstinello S, et l. Assocition of hyperdense middle cererl rtery sign with clinicl outcome in ptients treted with tissue plsminogen ctivtor. Stroke 1999; 30: Bstinello S, Pierllini A, Colonnese C, Brughitt G, Angeloni U, Antonelli M, et l. Hyperdense middle cererl rtery CT sign: comprison with ngiogrphy in the cute phse of ischemic suprtentoril infrction. Neurordiology 1991; 33: Schuknecht B, Rtzk M, Hofmnn E. The "dense rtery sign"--mjor cererl rtery thromoemolism demonstrted y computed tomogrphy. Neurordiology 1990; 32: Zorzon M, Msè G, Pozzi-Mucelli F, Antonutti L, Ion L, Czzto G. Incresed density in the middle cererl rtery y nonenhnced computed tomogrphy: Prognostic vlue in cute cererl infrction. Eur Neurol 1993; 33: Khritonov T, Ahmed N, Thorén M, Wrdlw JM, von Kummer R, Glhn J, et l. Hyperdense middle cererl rtery sign on dmission CT scn--prognostic significnce for ischemic stroke ptients treted with intrvenous thromolysis in the sfe implementtion of thromolysis in Stroke Interntionl Stroke Thromolysis Register. Cererovsc Dis 2009; 27: Wrdlw JM, Dormn PJ, Lewis SC, Sndercock PA. Cn stroke physicins nd neurordiologists identify signs of erly cererl infrction on CT? J Neurol Neurosurg Psychitry 1999; 67: Págin 8 RAR - Volumen 75 - Número