Sensitivity of Computer Assisted Radionuclide Angiography in Transient Ischemic Attack and Prolonged Reversible Ischemic Neurological Deficit
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1 Sesitivity of Computer Assisted Radiouclide Agiography i Trasiet Ischemic Attack ad Prologed Reversible Ischemic Neurological Deficit 829 Compariso with Fidigs i Radiographic Agiography ad Trasmissio Computerized Axial Tomography UDALRICH BUELL, M.D., KARL F. SCHEID, M.D., WOLFGANG LANKSCH, M.D., EDUARD KLEINHANS, M.D., VOLKHARD ULBERT, M.D., ULRIKE REGER, M.D., MANFRED RATH, M.D., AND ERNST A. MOSER, M.D. SUMMARY Computer assisted radiouclide agiography (CARNA) with "Tc-DTPA was employed to study 143 patiets with trasiet lscbemic attacks () ad 79 patiets with prologed reversible ischemic eurologic deficit (PRIND). The results of CARNA were compared with fidigs from radiographic agiography (RGA) i 173 patiets ad withfidigsi trasmissio computerized axial tomography (T-CAT) i 154 patiets. I patiets with, CARNA showed a hemispherical perfusio deficit i 74.8%, ad with PRIND 873%. This deficit, determied as the relative differece betwee the ivolved ad the o-ivolved hemisphere, was sigificatly (p < ) greater I PRIND (mius 23%) tha i (mius 17%). Sesitivity of CARNA was idepedet of the iterval from ictus to examiatio for more tha 4 moths. RGA i TLA revealed true positives i 82.0%, i PRIND it was 89.5%. T-CAT was positive i i oly 16.8% but i PRIND it was 64.4%. Combied sesitivities i (92.4%) ad i PRIND (94.0%) were highest with the combiatio of CARNA ad RGA. However, i PRIND the combiatio of o-ivasive methods (CARNA ad T-CAT) revealed 93.2% positive fidigs. Combiatios of these evaluatio methods may be used to detect cerebrovascular disease i patiets with such dysfuctio. Stroke, Vol 12, No 6, 1981 RADIONUCLIDE agiography (RNA) with Tc- pertechetate or wm Tc-DTPA is the first compoet of cerebral serial scitigraphy (CSS) ad the secod is static imagig. CSS yields useful results i both the detectio ad idetificatio of itra-craial tumors 1 as well as i the detectio ad localizatio of craial vascular disease. 1 Itra-craial vascular disease i static uclear images is reflected by itra-craial accumulatio of Tc at the site of a disrupted blood brai barrier. Sice such accumulatio occurs maily i completed stroke, less severe chages of itra-cerebral perfusio may be detected exclusively by employig RNA, evaluated either by visual 1 " 4 or by computerized aalysis.*" 7 Computer assisted radiouclide agiography (CARNA) was employed i patiets with trasiet ischemic attacks () or prologed reversible ischemic eurologic deficit (PRIND) to establish the sesitivity of CARNA i detectig ad quatifyig chages of cerebral perfusio. Results of CARNA were compared with fidigs from trasmissio computerized axial tomography (T-CAT) ad with fidigs from craial radiographic agiography (RGA) to obtai data o the combied sesitivities of these methods. From the Departmets of Radiology, Neurosurgery, ad Neurology, Uiversity of Muich, Kliikum Grosshader, Muich, Federal Republic of Germay. Reprits: Dr. Buell, Dept. Radiology, Uiversity of Muich, Kliikum Grosshader, 8000 Muich 70, Federal Republic of Germay. Material ad Methods A total of 222 patiets were studied. Of these, 143 had ad 79 had PRIND. The patiets were further divided accordig to the iterval of time which had elapsed betwee ictus ad examiatio. Patiets icluded i the preset study were ot iitially examied to compare results of CARNA, T-CAT ad RGA, ad all 3 methods were ot employed i every patiet. Selectio of patiets for T-CAT ad RGA was made by eurologists ad eurosurgeos accordig to the patiet's cliical presetatio ad to the scheme used i this hospital.' For 22 moths, patiets with ad PRIND who had CARNA ( = 222) were used to assemble availablefidigs,icludig T- CAT ( = 154) ad RGA ( = 173) results. Radiouclide images were obtaied with a Ohio- Nuclear Series ON 110 gamma camera. A bolus of 370 MBq (10 mci) of Mm Tc-DTPA was ijected rapidly ito a atecubital vei by acceleratig the tracer with 10 ml of salie. Polaroid photographs recorded the total couts accumulated over a 3-sec period with the patiet i upright positio i either aterior or posterior projectio. Data were trasferred to a o-lie computer system (CINE 200, Itertechique) at a rate of 2.5 frames per sec for 40 sec for subsequet computer-assisted aalysis. Static images were made to exclude itracraial tumor. Time radioactivity curves were derived from 2 regios of iterest, each icludig oe hemisphere. These regios were defied by a computer program as described." This was desiged to defie the cotours of
2 830 STROKE VOL 12, No 6, NOVEMBER-DECEMBER cts Relative Perfusio (F/F') 1981 Efficiecy Curve 1 Curve 2 ormal (mea* 2 SO) ( = 112 ) 1.00 t 0.12 FIGURE 2. Schematic time radioactivity curves derived from the hemispherical regios of iterest. Relative perfusio efficiecy is computed by dividig the areas F (white) by F (hatched). Values smaller tha 0.88 or greater tha 1.12 or if values are expressed as differece from 1.00 values greater tha 0.12 are desigated as "pathologic." 1. Regios of iterest, each icludig oe hemisphere, as defied by a computer program. FIGURE the ier calvarium ad to exclude the sagittal sius ad the base of the skull (fig. 1). From the curves, a right to left hemisphere ratio was computed by dividig the areas F by F' as illustrated i figure 2. This ratio is called a relative perfusio efficiecy with a ormal value of ± 0.12 (mea ± 2 SD) but 1.00 ± 0.12 is used i these calculatios.* The ratio is expressed as the differece from Thus, differeces greater tha 0.12 were desigated "pathologic." Reproducibility of CARNA was tested by evaluatig the iter-observer variability (2 observers) i 102 patiets. The paired determiatio for the F/F' ratio correlated well (r = 0.97). The mea value of differeces was with a stadard error of Oe hudred ad fifty-four of 222 patiets were examied by T-CAT. Of these, 95 had ad 59 had PRIND. T-CAT studies were made with a EMI CT 1010 scaer usig a stadard techique. I selected patiets, if T-CAT was performed from the 8th to the 28th day after ictus ad if the pre-cotrast sca was ormal, additioal scas were obtaied followig the itraveous ijectio of 60% sodium diatrizoate, 1 ml/kg. Scas were evaluated accordig to published criteria.2' "" Tumors, abscesses, cogeital ad posttraumatic lesios were excluded by history, cliical status, T-CAT appearace ad experiece. T-CAT evaluatio was used to defie whether a patiet had regios of altered desity correspodig to itracerebral vascular disease ("true positives") i the cliically affected hemisphere. Biplae radiographic agiography, usig the Seldiger techique, was performed i 106 patiets with ad 67 patiets with PRIND. Morphology of lesios see was evaluated oly with respect to a lumial arrowig of a artery sice RGA fidigs were used oly to defie whether a patiet had craial vascular disease (true positives) or ot. The evaluatio icluded determiatio of steosis or occlusio of the commo carotid artery, iteral carotid artery ad of the mai cerebral arteries or their braches. If vascular lesios were foud o both sides, oly those sides with the higher degree of steosis were evaluated (i.e., if steosis ad occlusio occurred, oly the occlusio is listed i "results"). The cliical diagosis of a or PRIND was established as described by Schmiedek et al.10 Wheever the eurologic deficit lasted loger tha 24 hours but the bega to clear, it was desigated as prologed (PRIND). Patiets with complaied of episodes of temporary focal cerebral dysfuctio which cleared completely withi 24 hours. I 10 patiets with ad i 9 with PRIND, the cliical symptoms occurred repeatedly ad they were ot icluded i the group of patiets which was desiged to illustrate the sesitivity of CARNA i relatio to the iterval betwee ictus ad examiatio. Physicias iterpretig CARNA, T-CAT ad RGA studies kew the patiet's cliical presetatio but were ot iformed of the results of the other examiatios.
3 SENSITIVITY OF CARNA IN AND PRWD/Buell et al. 831 Results Sesitivity of CARNA i correlatio with the cliical fidigs (, PRIND) is give i table 1. I patiets with (fig. 1) it was 74.8%. I patiets with PRIND, it was foud to be 87.3%. Statistical compariso of these 2 percetages, based o the cofidece limits for the biomial distributio, revealed a sigificat differece o the basis ofp < If ad PRIND patiets were take as oe group, sesitivity was 79.3%. Relative perfusio efficiecy decreased for the ivolved hemisphere. If this parameter was expressed as the differece from 1.00, it icreased from to PRIND (table 1). Studet's /-test for upaired data revealed a sigificat differece (table 1). Table 2 reflects sesitivities of CARNA i ad PRIND depedig o the period of time which had elapsed from ictus to examiatio (1 week to more tha 12 weeks). Sice sub-groups are relatively small, o statistical compariso was made. I ad i PRIND, o cosiderable decrease was detected withi the periods of time studied. The sesitivity of CARNA was idepedet of the iterval from ictus to examiatio. I, the sesitivity of T-CAT (table 3) was sigificatly (p < 0.01) less tha that of CARNA (16.8% vs 72.6%). I PRIND, the differece was smaller (64.4% vs 83.1%). Combied sesitivity was 82.5% which was sigificatly higher (p < 0.01) tha the sesitivity of T-CAT aloe (35.1%). RGA revealed steoses (> 50% lumial diameter) of the iteral carotid arteries i 39 patiets of the group (fig. 3) ad i 18 patiets with PRIND. The artery was occluded i 40 ad i 30 PRIND patiets. The commo carotid artery was occluded i 3 patiets with PRIND. Steosis of the middle cerebral artery was foud i 5 patiets with ad i 2 TABLE 1 Sesitivity of CARNA i ad PRIND PRIND Total Positive fidigs p<0.01 patiets with PRIND. Occlusio of the middle cerebral artery was foud i 3 ad i 7 patiets with PRIND. These 147 patiets with agiographically cofirmed lesios accout for the 84.9% sesitivity of RGA i the group of patiets with ad PRIND (table 4). If ad PRIND were evaluated separately, RGA was positive i 82.0% with ad i 89.5% with PRIND. CARNA i these groups revealed 76.4% true positives i ad 82.1% i PRIND. Noe of the differeces was sigificat. However, combied sesitivities were higher (table 4). If ad PRIND patiets formed oe group, combied sesitivity (93.1%) was sigificatly higher (p < 0.01) tha that of either method. To evaluate which method (T-CAT or RGA) provided more iformatio to CARNA with combied evaluatio, results from tables 3 ad 4 were compared. I, T-CAT added 3.2%, RGA 16.0%. The differece was sigificat (p < 0.01). I PRIND, additive iformatio from either method was early the same, resultig i a sesitivity of about 94% by either combiatio. Coversely, CARNA added 10.4% sesitivity to RGA i (p < 0.01) ad 4.5% i PRIND. Discussio To determie the sesitivity of a o-ivasive procedure i cerebrovascular disease, results of such procedure ca be related to a) cliical or to b) morphological fidigs. Cliicalfidigsiclude completed stroke (severe eurological deficits of log duratio), PRIND ad. Morphological fidigs were obtaied by craial radiographic agiography (RGA) or by T-CAT. T-CAT ca show itra-craial vascular territories damaged by cerebral ifarctio. 1 - e ~ 1 * Such areas are of lower desity tha ormal. They ehace with cotrast medium ad "To-compouds " l7 if the Sesitivity 74.8% 87.3% 79.3% Differece from 1.00* (mea ± 3D) ± ±0.123 (p < )t 'Results of relative perfusio efficiecy. A differece greater tha 0.12 U "pathologic" (correspodig to 1.00 ± 0.12 by F/F, Le., mea ± 2 3D i 112 ormals). TStudet's t-teat for upaired data. TABLE 2 Sesitivity of CARNA i ad PRIND Correlated with Iterval from Ictus to Examiatio Time after ictus 1-7 days 8-14 days days 5-8 weeks 8-12 weeks more tha 12 weeks Positive fidigs Sesitivity 82% 70% 69% 70% 72% 81% PRIND Positive fidigs Sesitivity 75% 79% 78% 100% 77% 91%
4 832 STROKE VOL 12, No 6, NOVEMBER-DECEMBER 1981 TABLE 3 Sesitivity (%) of CARNA ad TCA T i ad PRIND PRTND CARNA+ 69 (72.6%) 49 (83.1%) -^ (1(11 T-CAT + 16 (16.8%) 38 (64.4%) CARNA, T-CAT + (combied) 72 (75.8%) 55 (93.2%) Total + positive fldigi. : subgroups from table (76.6%) 54 (35.1%) 127 (82.5%) TABLE 4 Sesitivity (%) of CARNA ad Radiographic Agiography (RGA) i ad PRIND PRIND Total + positive fidigs. : subgroups from table 1. CARNA + RGA (76.4%) 87 (82.0%) (82.1%) 136 (78.6%) 60 (89.5%) 147 (84.9%) -p < p < CARNA, RGA + (combied) 98 (92.4%) 63 (94.0%) 161 (93,1%) blood-brai barrier is disrupted or if eovascularity develops without such a barrier. 18 This occurs from about the 8th through the 28th day after ictus ad is maily correlated with severe eurologic defects. Circumscribed atrophy (fig. 3) occurs i some patiets with chroic, dimiished perfusio. 1 ' Agiographically (RGA) detected steosis or occlusio of the carotid artery are reported to be frequetly associated with pathological T-CAT fidigs (cerebral atrophy or areas of ifarctio) " ie I patiets with completed stroke, T-CAT ad cerebral serial scitigraphy both provide useful additioal iformatio.'- ia Thus, either o-ivasive method may be used to defie correctly the situatio of such patiets. I patiets with reversible ischemic cerebral dysfuctio, T-CAT was foud to be less accurate. 2 ' "" " The results of the preset study reveal a sesitivity of T-CAT i PRIND of 64.4% ad i of 16.8% (table 3, fig. 3). Therefore, especially i, morphological defects i the affected hemisphere are a rare fidig usig T-CAT, despite the detectio of steosis or occlusio of the iteral carotid artery i 75% of the patiets i the preset study. CARNA revealed a hemispherical perfusio "deficit" i 74.8% of the patiets ad i 79.3% of all patiets ( ad PRIND) (table 1). To iterpret correctly the "perfusio deficits" described by CARNA, it must be emphasized that CARNA as a method usig the iitial tracer distributio ("wash i") withi a give time to compare global hemispherical flow values does ot differetiate delay from deficit. Delayed "wash i" almost always is associated with a perfusio "deficit" or reductio (fig. 2). The results of the preset study reveal that this ca be observed eve for 50% steoses of the carotid artery (i.e., 75% reductio of cross sectio) (fig. 3), which is believed to be the level of steosis related to margial hemodyamic sigificace. 4 I such patiets the iitial uptake i the respective hemisphere was delayed i compariso to the cotralateral oe (fig. 3). By employig the ratio F/F' (fig. 2), a sigificat differece from ormal values was foud betwee the extet of reduced (ad/or delayed) hemispherical perfusio i ad PRIND (table 1). I PRIND, perfusio of the ivolved hemisphere was reduced by 23% as compared to the cotralateral oe. I, it was dimiished by 17%. CARNA reveals ot oly positives or egatives but provides semiquatitative data o perfusio differeces, closely correlated to the patiet's cliical state. CARNA caot differetiate betwee hemodyamically relevat chages i oly oe or i those occurrig i both hemispheres simultaeously. However, bilateral alteratios rarely cause precisely idetical chages i "wash i."'-' Radiographic agiography (RGA) was positive i 82.0% of the patiets with (table 4). This sesitivity is similar to that published by others."- ai Although sesitivity of CARNA (76.4%) was ot much less, RGA additioally provides iformatio o morphological appearace ad localizatio of defects i the craial vasculature ad is, i cotrast to CARNA, diagostic i vertebrobasilar ischemic symptoms. 91 Agiography is a ivasive procedure which is ot employed as a screeig method i every patiet with a history of ad PRIND. I, combied sesitivity of CARNA ad RGA (92.4%) was sigificatly higher tha the sesitivity of RGA (82.0%) (Table 4), which suggests that 10.4% of the patiets with were correctly idetified oly by the uclear method. Similar fidigs have bee reported by Britto et al., M employig a special form of computer assisted measuremet of regioal cerebral blood flow ad by Schmiedek et al. 10 usig ivasive rcbf determiatio with iu xeo. There was o importat loss i sesitivity of CARNA by a icreasig iterval from ictus to examiatio (table 2). Thus, there is o restrictio o
5 SENSITIVITY OF CARNA IN AND PRIND/flue// et al. FIGURE year-old male with right sided trasiet ischemic attack 10 days prior to the examiatio. A) Radiouclide agiogram shows delayed perfusio of the left hemisphere (arrow). B) Time radioactivity curves reveal delay of left-sided hemispherical perfusio (arrow). Q (right to left hemisphere) = 1.17, i.e. 17% "deficit" or 0.17 differece to 1.00 (see table 1 adfig.2). (A ad B = CARNA.) C) T-CA T (without cotrast ehacemet) shows borderlie wideig of vetricular bodies ad cerebral suld ad oticeable wideig of the left Sylviafissure (arrow) the latter idicatig chroically dimiished perfusio. D) Craial radiographic agiograms (sequece) show irregularities of the left iteral carotid artery ad a 50% steosis of the supraclioid portio. The origi of the iteral carotid artery was ormal.
6 834 STROKE VOL 12, No 6, NOVEMBER-DECEMBER 1981 employig CARNA up to 4 moths after ictus. This result illustrates that a delayed ad/or reduced hemispheric "wash i" (perfusio) may be foud eve if eurological symptoms have cleared. A ca occur as a focal reductio of perfusio (e.g., by emboli) withi a permaetly chaged hemispheric perfusio. The latter was detected i 74.8% of such patiets by CARNA (table 1). CARNA may be the preferred o-ivasive procedure because it detects ad quatifies disorders of vascular supply i patiets with ad PRIND. Doppler soography ca provide excellet iformatio if a alteratio i the extracraial vasculature causes cerebral dysfuctio. 7 - ** u Whe itra-craial chages are resposible, this o-ivasive method fails. 7 ' u If o computer assistace is used to evaluate craial radiouclide agiography, results are cosiderably less accurate. 4 ' l * Specificity of CARNA is 84.6%. 7 If CARNA is egative (25.2% i ; 12.7% i PRIND), a further method must be employed to cofirm the craial vascular origi of a attack which may be RGA for ad T-CAT for PRIND. This diagostic sequece leads to 92.4% detectio of positives i ad to 93.2% positives i PRIND. Refereces 1. Buell U, Niedorf HP, Kazer E et al: Computerized trasaxial tomography ad cerebral serial scitigraphy i itracraial tumors rates of detectio ad tumor-type idetificatio: cocise commuicatio. J Nucl Med 19: 476, Buell U, Kazer E, Rath M et al: Sesitivity of computed tomography ad serial scitigraphy i cerebrovascular disease. Radiology 131: 393, Foo D, Herickso F: Radiouclide cerebral blood flow ad carotid agiogram. Correlatio i iteral carotid artery disease. Stroke 8: 39, Armas R, Kirkwood JR, Zubi S: The posterior cerebral radiouclide agiogram for the detectio of carotid artery disease. Cli Nucl Med 6: 19, Rath M, Buell U, Wiesbauer A et al: Multi-parameter evaluatio of cerebral perfusio curves i cerebrovascular disease. Results of computer-assisted radiouclide agiography. Nucl Med 18: 111, Kleihas E, Berger H, Buell U et al: Automatic recogitio of hemisphere-borderlies i cerebral radiouclide agiography. Nucl Med 18: 232, Buell U, Leschem D, Rath M et al: Radiouclide agiography ad Doppler soography to detect patiets with cerebrovascular disease. A correlatio with radiographic agiography. Stroke 11: 452, Buell U, Kazer E: Trasmissio computerized tomography ad serial scitigraphy i itracraial tumors: what is the desirable state of the art? (lett.) J Nucl Med 20: 806, Brahme FJ: CT diagosis of cerebrovascular disorders a review. Comput Tomogr 2: 173, Schmiedek P, Laksch W, Olteau-Nerbe V et al: Combied use of regioal cerebral blood flow measuremet ad computerized tomography for the diagosis of cerebral ischemia. I Schmiedek P, Gratzl O, Spetzler RF (eds) Microsurgery for Stroke. New York, Spriger, 1977, Chap 8, pp Lewis SE, Hickey DC, Parkey RW: Radiouclide brai imagig its role ad relatio to CT scaig. Comput Tomogr 2: 115, Lee KF, Chambers RA, Diamod C et al: Evaluatio of cerebral ifarctio by computed tomography with special emphasis o microifarctio. Neuroradiology 16: 156, Radd EW, Moseley IF: Carotid artery occlusio ad computed tomography. A cliicoradiological study. Neuroradiology 17: 7, Ruggiero G, Fiizio FS, Nuzzo G et al: CT ad arteriography i cerebral ischemia. A prelimiary ote. Neuroradiology 16: 168, Sager WD, Ladurer G: Klassifikatio ud Verlauf des Hirifarktes im Computertomogramm. Fortschr Roetgestr 131: 470, Wodarz R, Ratzka M, Grosse D: Watershed ifarctios a special type of ifarctio i cases with carotid artery steosis or occlusio verified by CT ad agiography. Fortschr Roetgestr 134: 128, BergstrSm M, Ericso K: Compartmet aalysis of cotrast ehacemet i brai ifarctios. J Comp Asst Tomogr 3:234, DiChiro G, Timis EL, Joes AE et al: Radiouclide scaig ad microagiography of evolvig ad completed brai ifarctio. A correlative study i mokeys. Neurology (Mieap) 24: 418, Waxma A, Siegel E, Brachma M et al: Compariso of oivasive methods i the evaluatio of patiets with cerebral vascular isufficiecy sydromes: the importace of Xeo quatitative techiques (abstr). Cli Nucl Med (Suppl) 5: 61, Marti-Vilalta JL, Lopez-Pousa S, Grau JM et al: Trasiet ischemic attacks. Retrospective study of 150 cases of ischemic ifarct i the territory of the middle cerebral artery. Stroke 10: 259, Thurma DJ, Millika CH: Cliical pheomea ad their correlatio to agiographic fidigs i cerebrovascular disease. Stroke 12: 54, Britto KE, Nimmo CC, Jarritt PH et al: Cerebrovascular disorder: assessmet with radiouclides. I Besser GM (ed) Advaced Medicie. Lodo, Pitma Medical, 1977, Vol 13, pp Bares RW, Russell HE, Boe GE et al: Doppler cerebrovascular examiatio: improved results with refiemets i techique. Stroke 8: 468, Crummy AB, Zwiebel WJ, Barriga P et al: Doppler evaluatio of extracraial cerebrovascular disease. Am J Roetgeol 132: 91, 1979
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