Ellen G. Hoeffner, MDIan Case, BS, RT(CT)Rajan Jain, MDSachin K. Gujar, MDGaurang V. Shah, MDJohn P. Deveikis, MDRuth C. Carlos, MDB. Gregory Thompson, MDMark R. Harrigan, MDSuresh K. Mukherji, MD

Index terms:Brain, CT, 13.12111, 13.12113,

13.12115Brain, infarction, 13.78Brain, ischemia, 13.721, 13.762,

13.767Brain, perfusionReview

Published online before print10.1148/radiol.2313021488

Radiology 2004; 231:632–644

Abbreviations:ACA � anterior cerebral arteryCBF � cerebral blood flowCBV � cerebral blood volumeMCA � middle cerebral arteryMTT � mean transit timePS � permeability surface product

areaROI � region of interestSAH � subarachnoid hemorrhage

1 From the Departments of Radiology(E.G.H., I.C., R.J., S.K.G., G.V.S., J.P.D.,R.C.C., S.K.M.) and Neurosurgery (B.G.T.,M.R.H.), University of Michigan HealthSystem, 1500 E Medical Center Dr, Uni-versity Hospital B2 A209, Ann Arbor, MI48109. Received November 14, 2002; re-vision requested January 17, 2003; revi-sion received March 21; accepted May 1.Address correspondence to E.G.H.(e-mail: hoeffner@umich.edu).© RSNA, 2004

Cerebral Perfusion CT:Technique and ClinicalApplications1

Perfusion computed tomography (CT) is a relatively new technique that allows rapidqualitative and quantitative evaluation of cerebral perfusion by generating maps ofcerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time(MTT). The technique is based on the central volume principle (CBF � CBV/MTT)and requires the use of commercially available software employing complex decon-volution algorithms to produce the perfusion maps. Some controversies exist re-garding this technique, including which artery to use as input vessel, the accuracyof quantitative results, and the reproducibility of results. Despite these controversies,perfusion CT has been found to be useful for noninvasive diagnosis of cerebralischemia and infarction and for evaluation of vasospasm after subarachnoid hem-orrhage. Perfusion CT has also been used for assessment of cerebrovascular reserveby using acetazolamide challenge in patients with intracranial vascular stenoses whoare potential candidates for bypass surgery or neuroendovascular treatment, for theevaluation of patients undergoing temporary balloon occlusion to assess collateralflow and cerebrovascular reserve, and for the assessment of microvascular perme-ability in patients with intracranial neoplasms. This article is a review of the tech-nique, clinical applications, and controversies surrounding perfusion CT.© RSNA, 2004

The advent of thrombolytic therapy for acute nonhemorrhagic stroke has intensified theneed for a rapid readily available technique to help identify and quantify the presence andextent of a perfusion deficit (1–3). Magnetic resonance (MR) perfusion, xenon computedtomography (CT), positron emission tomography (PET), and single photon emissioncomputed tomography (SPECT) have all been used to evaluate cerebral perfusion but arehampered by limited availability, cost, and/or patient tolerance (2). Perfusion CT wasintroduced as a means to rapidly and easily evaluate cerebral perfusion in patients pre-senting with acute stroke symptoms, most of whom would already undergo unenhancedhead CT to exclude acute hemorrhage (2,4). Perfusion CT can be performed quickly withany standard spiral CT scanner, and the perfusion maps can be generated in a short timeat a workstation equipped with the appropriate software. At our institution, the techniquehas been extended for evaluation of cerebrovascular reserve with acetazolamide challengein patients with stenotic lesions who are potential candidates for bypass surgery orneuroendovascular treatment, for evaluation of collateral flow and cerebrovascular reservein patients undergoing temporary balloon occlusion (5), and for evaluation of patientswith possible vasospasm after subarachnoid hemorrhage (SAH). This technique can also beapplied in patients with neoplasms to measure the permeability surface product area (PS)(6–8).

TECHNIQUE

The theory behind this technique is the central volume principle, which relates cerebralblood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in thefollowing equation: CBF � CBV/MTT. Perfusion studies are obtained by monitoring thefirst pass of an iodinated contrast agent bolus through the cerebral vasculature. There is alinear relationship between contrast agent concentration and attenuation, with the con-trast agent causing a transient increase in attenuation proportional to the amount of

Review

632

Ra

dio

logy

contrast agent in a given region. Contrastagent time-concentration curves are gen-erated in an arterial region of interest(ROI), a venous ROI, and in each pixel.Deconvolution of arterial and tissue en-hancement curves, a complex math-ematic process, gives the MTT. CBV iscalculated as the area under the curve ina parenchymal pixel divided by the areaunder the curve in an arterial pixel. Thecentral volume equation can then besolved for CBF (2,4,9).

Perfusion CT scans are obtained at ourinstitution by using a multi–detector rowscanner (Lightspeed; GE Medical Systems,Milwaukee, Wis). After unenhanced CT ofthe whole brain, four adjacent 5-mm-thicksections are selected starting at the level ofthe basal ganglia. At this level, all threesupratentorial vascular territories are visu-alized. Fifty milliliters of a nonionic con-trast agent (300 mg of iodine per milliliter)is injected at a rate of 4 mL/sec. At 5 sec-onds after initiation of the injection, a cine(continuous) scan is initiated with the fol-lowing technique: 80 kVp, 190–200 mA,4 � 5-mm sections, 1-second per rotationfor a duration of 50 seconds. If 370 mg ofiodine per milliliter is used, a volume of 40mL is given at a rate of 4 mL/sec with ascan duration of 45 seconds. The injectionrates with the deconvolution technique aremuch lower than those of other CT perfu-sion techniques, such as the maximal-slope model, and thus are more practical

and tolerable for patients (9,10). Theselower injection rates do not represent adisadvantage because the deconvolutionanalysis compares the arterial input time-attenuation curve with that of the tissue tocontrol for bolus dispersion (10). Perfusionmaps of good quantitative quality havebeen obtained in humans with injectionrates as low as 1.5 mL/sec (4,10).

The 1-second images are reformatted at0.5-second intervals, and the 5-mm sec-tions are reformatted into two 10-mm-thick sections. The scans are obtained at5 mm rather than 10 mm to lessen beam-hardening artifacts in the brain. The re-formatted 10-mm-thick sections providea better signal-to-noise ratio than do the5-mm-thick sections and improved (0.5-

Figure 1. (a) Transverse CT image obtained during contrast agent administration and (b) time-concentration curves in a healthy adult volunteer. (a) A branch of the anterior cerebral artery(ACA) is chosen as the input artery (white arrow) and the torcular herophili is chosen as the inputvein (black arrow). (b) Time-concentration curves are generated for the input artery (green line)and vein (red line).

Figure 2. Transverse CT perfusion maps in a healthy adult volunteer show normal perfusion. Various color ramps, selected according to userpreference, are used to display the (a) CBF, (b) CBV, and (c) MTT maps.

Volume 231 � Number 3 Perfusion CT: Technique and Clinical Applications � 633

Ra

dio

logy

Figure 3. Transverse (a) CT image and(b) CBF map in a healthy adult volunteer, withcircular ROIs (in purple) in place. IdenticalROIs appear on CBV and MTT maps (notshown).

Figure 4. Acute infarction in a 76-year-oldwoman who was unresponsive. (a) Initialtransverse head CT image shows subtle hy-poattenuation (arrows) in left insula, tempo-ral lobe, and frontal lobe. (b) Transverse CBFmap shows decreased CBF (arrows) in left ACAand anterior MCA territories, with quantita-tive values as low as 11 mL/100 g/min.(c) Transverse CBV map shows decreased CBV(arrows). (d) Transverse MTT map showsslightly elevated MTT (arrows). Changes areconsistent with infarction. (e) Follow-uptransverse CT image shows large infarct (ar-rows) in left ACA and MCA territories.

634 � Radiology � June 2004 Hoeffner et al

Ra

dio

logy

second cine interval) temporal resolu-tion. The overall effective dose requiredfor dynamic CT (2.0–3.4 mSv) is onlyslightly higher than that required for rou-tine head CT (1.5–2.5 mSv). This doseequivalent is less than the dose equiva-lent obtained with PET or SPECT and iscomparable to that of a single-level xe-non CT examination (4,11–13).

CT perfusion data are analyzed at an im-aging workstation (Advantage Windows;GE Medical Systems) equipped with com-mercially available software (CT Perfusion;GE Medical Systems). Post–image-collec-tion processing involves placement of free-hand drawn ROIs in an input artery and aninput vein, for which contrast-enhance-ment curves are generated (Fig 1). The ACAor middle cerebral artery (MCA) can be se-lected as the input artery. A large venousstructure such as the torcular herophili ischosen as the input vein. Since the inputartery is usually smaller than the inputvein, the venous ROI serves to correct forvolume averaging in the arterial ROI. Thevenous ROI may also affect the signal-to-noise ratio, with the peak enhancementvalue of the venous ROI correlating signif-icantly with the signal-to-noise ratio ofCBF and CBV maps (14). The software thengenerates color-coded CBF, CBV, and MTTmaps (Fig 2).

ROIs can be placed in the brain paren-chyma to yield quantitative data. We typ-ically place six circular ROIs along the pe-riphery of each hemisphere (Fig 3). Thismethod was chosen, with input from ourneurosurgery colleagues, to approximatethe ROIs used with xenon CT. A similartechnique has been used for perfusion-weighted MR and SPECT imaging of thebrain (15).

CLINICAL INDICATIONS

Acute Stroke

Conventional unenhanced head CT isstill the primary imaging modality usedto evaluate patients presenting withstroke symptoms, to help exclude intra-cranial hemorrhage and detect signs ofbrain ischemia (2). Detection of earlyischemic changes, such as parenchymalhypoattenuation and/or sulcal efface-ment, is important for stratifying pa-tients who may benefit from thrombo-lytic therapy (2,3). Thrombolytic therapyhas been reported to be most beneficialin patients with cytotoxic edema involv-ing 33% or less of the MCA territory. It isalso important to identify patients whowill not benefit from thrombolytic ther-apy: namely, those with conventional CT

findings of cytotoxic edema involvinggreater than 33% of the MCA territory.The findings of cerebral ischemia or in-farction, however, can be subtle or ab-sent. It has been suggested that evalua-tion of brain perfusion may help in theselection of patients for thrombolytictherapy by allowing identification ofthose patients with potentially salvage-able tissue that is at risk for infarction(the ischemic penumbra) from thosewith extensive infarct (11). Other tech-niques to measure cerebral perfusion,such as xenon CT, SPECT, PET, and per-fusion-weighted MR imaging, are limited

by patient tolerance, availability, andlack of quantitative results (2).

Evaluation of acute stroke is one of themain indications for perfusion CT, withthe goal of distinguishing infarcted tissuefrom the penumbra (2,4,9). The latter tis-sue may be salvageable with the admin-istration of thrombolytic agents, whileirreversibly damaged tissue will not ben-efit from reperfusion and may be at in-creased risk of hemorrhage after throm-bolytic therapy (2,3). It is hypothesizedthat tissue at risk of infarction will havedecreased CBF, normal or elevated CBVsecondary to activation of cerebral auto-

Figure 5. Ischemia without infarction in a 47-year-old woman with severe right internal carotidartery stenosis and episodes of left arm numbness. (a) Transverse perfusion CT map showsdecreased CBF (arrows) in right ACA and MCA territories, with quantitative values as low as 21mL/100 g/min. (b) CBV and (c) MTT are both elevated (arrows) on transverse perfusion maps.Changes are consistent with reversible ischemia. CBV is elevated due to cerebral autoregulatorymechanisms, with vasodilatation in response to decreased perfusion. (d) Follow-up transverse CTimage obtained 8 months later shows no evidence of cortical infarction.

Volume 231 � Number 3 Perfusion CT: Technique and Clinical Applications � 635

Ra

dio

logy

regulatory mechanisms, and elevatedMTT, while infarcted tissue will have de-creased CBF and CBV with elevated MTT(4,9) (Figs 4, 5).

In a recent retrospective study, East-wood et al (16) demonstrated a statisti-cally significant difference in CBF, CBV,and MTT in the symptomatic hemi-sphere, compared with those values inthe contralateral hemisphere, in patientspresenting with acute MCA stroke. Thefollowing thresholds for ischemia werechosen: CBF of 0–10 mL/100 g/min, CBVof 0–1.5 mL/100 g, and MTT of greaterthan 6 seconds. They found that the ex-tent of regional abnormalities on the per-fusion maps was greatest with MTT, fol-lowed by CBF and CBV. Thus, MTT mapsmay be the most sensitive indicators ofstroke, with changes in CBF and CBV be-ing more specific for distinguishing isch-emia from infarction. In the same study,25% of the patients with acute stroke hadno abnormality on the CBV map, whichmay make this a less accurate indicator inthe discrimination between the penum-bra and infarcted tissue. These resultscorrelated with those of an experimentalrabbit model of ischemia in which perfu-sion CT findings and postmortem tissuespecimens were compared (17). In thatstudy, MTT maps were the most sensi-tive, particularly with regard to detectionof early stages of minor ischemia, whileCBF maps showed the best correlationbetween critical ischemia and postmor-

tem evaluation results. CBV maps were ofonly moderate diagnostic value. Thus, itmay be best to evaluate the CBF and MTTmaps for abnormalities first and, if abnor-malities are present, to use the CBV mapto try to elucidate the underlying patho-physiology (ischemia vs infarct), keepingin mind that CBV may be normal even incases of infarction.

However, in a prospective study in whichpatients with acute ischemic stroke wereevaluated, Wintermark et al (11) reportedthat they were able to distinguish infarctfrom penumbra by defining ischemic tis-sue (infarct plus penumbra) as cerebralpixels with a greater than 34% decreasein CBF relative to clinically normal areasin the cerebral hemispheres. Within thisischemic area, a CBV threshold of 2.5mL/100 g was selected, with higher andlower values representing penumbra andinfarct, respectively. Using these criteria,Wintermark et al showed a significantcorrelation between penumbra size oninitial perfusion CT images and clinicalimprovement as measured with the Na-tional Institutes of Health Stroke Scale inpatients with arterial recanalization (ei-ther spontaneous or due to thrombolytictherapy). They also reported a close cor-relation between infarct size on perfusionCT images obtained at admission and in-farct size on delayed diffusion-weightedMR images in patients undergoing recana-lization, likely reflecting recovery of the pen-umbra. In addition, in patients without

recanalization there was a close correla-tion between the combined infarct andpenumbra on the initial perfusion CT im-ages and the final infarct size on delayeddiffusion-weighted MR images, due toevolution of the penumbra toward in-farction.

Quantitatively, reversible paralysis hasbeen demonstrated to occur in monkeysat CBF values of less than 20–23 mL/100g/min, with a transition to irreversible in-farction at a CBF of less than 10–12 mL/100 g/min (4,9,18,19). This transition fromischemia to infarction depends not onlyon CBF values but also on the duration ofthe diminution in blood flow, with theinfarction threshold increasing over timeto 17–18 mL/100 g/min (18–20). Increas-ing severity and duration of ischemialead to increasingly severe histologicdamage (19). It has been suggested thatthe upper threshold reflects failure ofnormal electric activity and the lowerthreshold reflects energy and ion pumpfailures, with the potentially salvageablepenumbra being between these two lev-els (20,21). Cessation of electric activityin baboons and cats has been demon-strated at CBF values of 18 mL/100 g/minand 15 mL/100 g/min, respectively, withion pump failure occurring in the ba-boon at a CBF threshold of 10 mL/100g/min (20). In humans undergoing ca-rotid endarterectomy, flattening of theelectroencephalogram occurs at CBF val-ues of less than 16–18 mL/100 g/min(20,22).

By using PET to measure CBF in pa-tients with MCA ischemia or infarction,the minimum averaged gray and whitematter CBF to maintain cerebral functionwas 19 mL/100 g/min or greater, whilethe minimum CBF to preserve tissue via-bility was 15 mL/100 g/min. There was,however, substantial overlap in CBF val-ues between infarcted areas and viabletissue (22). Touho and Karasawa (23), us-ing xenon CT in patients with anteriorcirculation ischemia, showed that CBFgreater than 19 mL/100 g/min did notresult in cortical infarction even if recan-alization did not occur. Below this level,progressively lower CBF values resultedin cortical infarction at progressivelyshorter time intervals, with CBF valuesless than 9 mL/100 g/min invariably re-sulting in infarction. In another studywith xenon CT (24), mixed cortical grayand white matter regions with CBF lessthan 6 mL/100 g/min were destined forinfarction.

Evaluation and clinical application ofsuch threshold determinations is compli-cated by being carried out in different

Figure 6. Known right common carotid artery occlusion in a 52-year-old man with 3-weekhistory of amaurosis fugax, left-sided weakness and numbness, and left-sided facial droop.(a) Transverse perfusion CT image obtained before acetazolamide challenge shows decreased CBF(arrows) in right ACA and MCA territories. CBV and MTT maps (not shown) revealed elevation ofboth CBV and MTT. Changes are compatible with reversible ischemia. (b) After acetazolamideinjection, there is steal phenomenon in right ACA and MCA territories. Transverse CBF mapshows CBF decreased (arrows) from baseline values, indicating hemodynamic stress and tissue athigh risk of infarction.

636 � Radiology � June 2004 Hoeffner et al

Ra

dio

logy

species under variable conditions andwith differing methods of flow measure-ment (25). Despite these difficulties, it isevident that the penumbra lies within anarrow range of perfusion and is depen-dent on small changes in perfusion pres-sure (26). Factors other than depth andduration of ischemia may also play a rolein the viability of the penumbra, includ-ing selective vulnerability of specific neu-ronal populations, antecedent glucosestores, and physiologic conditions duringresuscitation (22,27).

Areas of hypoattenuation on unen-hanced head CT scans in the study byEastwood et al (16) had a mean CBF valueof 13.1 mL/110 g/min � 8.4 (SD), whichcorrelates well with previously reportedvalues for xenon CT and PET results inpatients with MCA stroke. In a small se-ries comparing quantitative CBF valuesderived from xenon CT and perfusion CTdata (28), there was good correlation be-tween these two methods. Quantitativeresults can vary depending on the choiceof input artery and the placement of ROIs(28,29).

Further studies are necessary to clarifythese results and to compare perfusionCT with other methods of measuring ce-rebral perfusion (16,28). However, theseearly results show that perfusion CT mayenable prediction of which patients willbenefit from thrombolysis on the basis ofthe size of the penumbra and determina-tion of the final infarct size in patientswith and patients without recanaliza-tion.

Cerebrovascular Reserve

In patients with known chronic cere-bral ischemia related to underlying ste-notic lesions, it is necessary to distin-guish tissue in need of increased CBF(tissue under hemodynamic stress) fromtissue with decreased CBF due to de-creased metabolic demand (30). Hemo-dynamic stress can be evaluated by usinga tolerance test such as acetazolamide(Diamox; Wyeth, Marietta, Pa) adminis-tration in conjunction with quantitativemeasurement of CBF. Although the exactmechanism of action is uncertain, acet-azolamide normally causes vasodilata-tion of cerebral arterioles and an increasein CBF (30). Patients with hemodynamicstress, however, are already maximallyvasodilated due to the utilization of cere-bral autoregulatory mechanisms in re-sponse to decreased perfusion pressureand cannot respond further to acetazol-amide. These patients are considered tobe at increased risk of stroke and may

benefit from interventions to increaseCBF (30–32).

Xenon CT, PET, SPECT, transcranialDoppler sonography, and perfusion-weighted MR imaging have all been usedto evaluate cerebrovascular reserve withthe acetazolamide test (33–35). With xe-non CT to measure CBF, an increase of20%–40% over baseline is normal, an in-crease of less than 5% over baseline isindicative of relative hemodynamic in-sufficiency, and a decrease of 5% orgreater from baseline (steal phenome-non) indicates tissue at higher risk of

stroke (35,36). Perfusion CT in conjunc-tion with acetazolamide challenge mayhelp to identify such patients (29). Acet-azolamide is generally well tolerated. Themost common side effects are circumoralnumbness, paresthesias, and headache. Acase of reversible ischemia has been re-ported with the use of acetazolamide(32,37).

At our institution, patients undergo aroutine perfusion CT examination. Sub-sequently, 1,000 mg of acetazolamide isgiven intravenously, followed 20 min-utes later by another perfusion CT exam-

Figure 7. Transverse perfusion CT maps in a 65-year-old man with progressive worsening of lefthand and foot numbness and clumsiness. Angiogram (not shown) revealed severe stenosis ofprecavernous right internal carotid artery. (a) Decreased CBF (arrows) is shown in right ACA andMCA territories before acetazolamide challenge. CBV was normal to elevated and MTT waselevated (not shown). (b) After acetazolamide injection, CBF map reveals decrease (arrows) in CBFvalues from baseline in right ACA and MCA territories, consistent with steal phenomenon.(c) After angioplasty and stent placement, repeat pre–acetazolamide challenge perfusion CTshows more symmetric CBF between the two hemispheres. CBV and MTT were also moresymmetric (not shown). (d) After acetazolamide injection, CBF map now shows augmentation offlow in both hemispheres, with flow increased over that of baseline.

Volume 231 � Number 3 Perfusion CT: Technique and Clinical Applications � 637

Ra

dio

logy

ination (Fig 6). Whether the same quan-titative values can be used for perfusionCT that have been used for xenon CT isyet to be determined in prospective stud-ies comparing the two techniques. Thequantitative results potentially availablewith perfusion CT may be an advantageover qualitative techniques such asSPECT and perfusion-weighted MR imag-ing (31). The ability to measure CBV andMTT may also be an added advantage ofperfusion CT. This technique can also be

used to evaluate the efficacy of revascu-larization procedures (32) (Fig 7).

Temporary Balloon Occlusion

Temporary balloon occlusion is per-formed in patients in whom arterial sac-rifice or prolonged temporary occlusionis considered as part of the surgical orendovascular therapy (38,39). Temporaryballoon occlusion in conjunction with aquantitative analysis of CBF can help

identify patients who will not toleratepermanent occlusion despite clinicallypassing the temporary balloon occlusiontest (38,39). Patients who have clinicallypassed the temporary balloon occlusiontest but who have CBF of less than 30mL/100 g/min as measured with xenonCT had a 56% incidence of temporary orpermanent neurologic deficit, whilethose with a CBF of greater than 30 mL/100 g/min had a stroke incidence of 7%(40). The use of an absolute CBF value ofless than 30 mL/100 g/min as a criterionfor the success or failure of temporaryballoon occlusion was corroborated in anoutcome study in which intracarotid in-jection of xenon 133 was used to measureCBF (41). The use of acetazolamide chal-lenge during temporary balloon occlu-sion may help identify patients who arealready maximally vasodilated in re-sponse to the balloon occlusion aloneand cannot vasodilate further in re-sponse to the acetazolamide. In suchcases, CBF may be maintained during theocclusion by exhausting autoregulatoryreserves (42). The goal is to identify pa-tients who clinically pass temporary bal-loon occlusion but have low CBF or ab-normal response to acetazolamide whomay not tolerate sacrifice or prolongedocclusion. Xenon CT, transcranial Dopp-ler sonography, SPECT, PET, and perfu-sion-weighted MR imaging have all beenused to evaluate cerebral perfusion dur-ing temporary balloon occlusion (38,43).

At our institution, patients undergoangiography and balloon occlusion, dur-ing which time they are clinically evalu-ated for 30 minutes. Patients who passthe clinical portion of the examinationare brought to the CT suite with the bal-loon in place. A perfusion CT scan is ob-tained with the balloon inflated andagain with the balloon deflated. The bal-loon is reinflated, 1,000 mg of acetazol-amide is injected intravenously, and afinal perfusion CT scan is obtained.

As with assessment of cerebrovascularreserve, it is unclear whether the samequantitative parameters can be used forperfusion CT as have been used for xe-non CT. Initial results from our institu-tion indicate that asymmetry of flow be-tween the two hemispheres and responseto acetazolamide challenge may be a bet-ter indicator than a CBF value of less than30 mL/100 g/min (5) (Figs 8, 9). One pa-tient with flow of 17–23 mL/100 g/min inwatershed areas ipsilateral to balloon oc-clusion but with normal response to ac-etazolamide underwent successful per-manent occlusion without stoke (5).

Figure 8. Images in a 45-year-old man with recent onset of left-sided headache and retro-orbitalpain. CT, MR, and angiographic images (not shown) indicated giant left supraclinoid carotidaneurysm. Temporary balloon occlusion was performed to determine if patient could tolerateembolization of the aneurysm and sacrifice of the left internal carotid artery. Perfusion CT wasperformed as part of the evaluation. (a) Transverse CT image obtained during perfusion CT showslarge enhancing aneurysm (arrows) in left frontal region. (b) Transverse perfusion CT map withballoon inflated in left internal carotid artery shows relatively symmetric CBF throughout bothhemispheres except in area corresponding to the aneurysm. (c) Transverse CBF map with balloondeflated again demonstrates symmetric CBF except in area of aneurysm (arrows). (d) Withballoon inflated after acetazolamide injection, transverse CBF map shows normal augmentationof flow in both hemispheres except in area corresponding to aneurysm. Patient did well aftertreatment of aneurysm, with no neurologic deficit.

638 � Radiology � June 2004 Hoeffner et al

Ra

dio

logy

However, further investigation is war-ranted.

Vasospasm

Vasospasm is a frequent complicationin the early clinical course after aneurys-mal SAH (12). Angiographic evidence ofvasospasm is present in 60%–80% of pa-tients with SAH, with approximately32% of patients becoming symptomatic(44–46). In approximately 50% of cases,vasospasm is manifested by the onset of aneurologic deficit related to ischemia,with progression to infarction occurringin approximately half of the symptom-atic cases (44). In addition, it is estimatedthat among patients with aneurysmalSAH who reach neurosurgical referral

centers, 7% will be severely disabled and7% will die as a result of vasospasm(46,47). Measurement of CBF can be use-ful in identifying patients at risk for ce-rebral ischemia by guiding therapeuticdecisions and monitoring response totherapy (13,48–51). Various methodshave been employed to measure cerebralperfusion, including PET, SPECT, xenonCT, and transcranial Doppler sonogra-phy. The latter has been the most widelyused, but it is operator dependent, can-not quantify CBF at the tissue level, andmay not be specific enough by itself toguide therapy (13,50). Studies with xe-non CT have indicated that patients areat risk of ischemia or infarction if CBFdecreases below 18–20 mL/100 g/min,while a PET study found CBF values of lessthan 12 mL/100 g/min to be a good pre-dictor of subsequent infarction (13,48,51).

Perfusion CT has been used to monitorcerebral perfusion after SAH. Nabavi et al(13) reported that patients with delayedinfarct after SAH, presumably due to va-sospasm, had a lower mean CBF valuethan did patients with early or no infarct.Minimal CBF and CBV values occurredboth 1–3 and 10–17 days after SAH, andmean CBF and CBV were significantlylower in patients with moderate to severe

vasospasm, compared with those withabsent to mild vasospasm. While theirmean CBF, CBV, and MTT results weresimilar to those reported in studies withPET and xenon CT to assess patients afterSAH, Nabavi et al could not define aclear-cut threshold for cerebral infarct byusing perfusion CT. They attributed thisto the use of relatively large ROIs, whichresulted in volume averaging with nor-mal and ischemic tissue. Further investi-gation may lead to the definition of aperfusion CT ischemic threshold in pa-tients with aneurysmal SAH. In addition,the ability to assess CBV and MTT mayhelp in understanding the impairment ofautoregulation that is believed to occurin some patients after SAH (13) (Fig 10).

Tumors

Tumors are inherently associated withincreased angiogenic activity and neo-vascularization that results in increasedblood volume and hyperpermeability re-lated to the immature vessels (6,7,52–54).Results of previous studies (52,53) haveindicated that microvascular permeabil-ity increases with increasing biologic ag-gressiveness of tumors, while a reductionin permeability in response to antiangio-

Figure 9. Images in a 33-year-old man with history of medullary thyroid cancer and metastasisto right cavernous sinus with right cavernous sinus syndrome. Perfusion CT was performed inconjunction with temporary balloon occlusion to determine if patient could tolerate rightcarotid sacrifice as part of aggressive skull base excision of metastases. (a) Transverse perfusionCT map with balloon inflated before acetazolamide challenge shows globally low CBF in bothhemispheres (quantitative values, 13–29 mL/100 g/min) but with asymmetrically lower flow inmuch of right hemisphere. There was corresponding increased CBV and MTT in the righthemisphere (not shown). (b) Transverse CBF map with balloon deflated shows that CBF is moresymmetric but still globally low. (c) Transverse CBF map obtained with balloon inflated afteracetazolamide injection shows multiple areas of steal. Because of these findings, patient under-went superficial temporal artery–to-MCA bypass before resection of metastases. (d) Transversediffusion-weighted MR image (b � 1,000 sec/mm2) obtained after surgery shows graft hasbecome occluded and patient has developed right MCA stroke (arrows).

Volume 231 � Number 3 Perfusion CT: Technique and Clinical Applications � 639

Ra

dio

logy

genic therapy correlates with decreasedtumor growth. Results of initial studies(52,53) in which CBV and PS, a measureof microvascular permeability, were ob-tained with dynamic contrast agent–en-hanced MR imaging indicates PS to bepredictive of pathologic grade and to cor-relate with tumor mitotic activity.

Subsequently, dynamic contrast-en-hanced CT has been investigated in ani-mal models of brain tumors and used inhuman brain tumors to quantify CBF,CBV, and PS (6,8,12). The technique ismodified from that used in cerebral isch-emia to account for the extravasation ofcontrast material from the intravascularspace to the extravascular space acrossthe impaired blood-brain barrier and toallow measurement of PS (12). These cal-culations can be performed with com-mercially available software (CT Perfu-

sion 2; GE Medical Systems). CBF, CBV,and PS were all higher in the tumor andin peritumoral areas than in normal tis-sue in animal models (12). Initial resultsobtained with this technique in humansrevealed variable elevations in CBF andCBV in the tumor and a more conspicu-ous increase in PS (6,7). In addition, theelevated PS was evident only in the tu-mor and not in the surrounding tissues(6,7). CT may prove to be advantageousover MR imaging in the assessment oftumor angiogenesis, given the linear re-lationship between contrast agent con-centration and attenuation changes, thelack of sensitivity to flow, the high spatialresolution, and the absence of suscepti-bility artifacts (7). However, the exposureto ionizing radiation, the potential foradverse reaction to the contrast agent,and the limited anatomic coverage are

limitations of CT, compared with MR, forevaluation of the microvasculature (7).

We have also used perfusion CT toevaluate squamous cell carcinomas of thehead and neck (Fig 11). Initial results re-vealed elevated PS, CBF, and CBV and alower MTT in the primary tumor site,compared with those values in normalstructures; however, further investiga-tion is still necessary. This technique mayprovide a way to noninvasively measuretumor malignancy, guide biopsies to themost malignant portion of the tumor,and assess response to treatment (6,7,53).

CONTROVERSIES

Although quantitative values can be ac-quired with perfusion CT, the accuracy ofthe flow values obtained has not been

Figure 10. Images in a 56-year-old womanwith left hemiparesis 5 days after SAH and 1day after clipping of posterior communicatingartery aneurysm. (a) Transverse perfusion CTimage reveals decreased CBF in bilateral ACAterritories (arrows), with quantitative valuesof 7 and 17 mL/100 g/min on the right andleft, respectively. (b, c) There is correspondingdecrease in (b) CBV (arrows) and slight in-crease in (c) MTT (arrows) on transverse per-fusion maps, findings that are of concern forinfarction. (d) Subsequent oblique view fromright internal carotid angiogram shows severespasm involving ACAs (arrows). (e) Despiteangioplasty, follow-up transverse diffusion-weighted MR image (b � 1,000 sec/mm2)demonstrates restricted diffusion in ACA ter-ritories (arrows) corresponding to changes onperfusion CT images.

640 � Radiology � June 2004 Hoeffner et al

Ra

dio

logy

fully validated. It has not been deter-mined if normal and disease thresholdsas measured with PET or xenon CT can beapplied in perfusion CT. Perfusion CTuses an intravascular tracer to measureintravascular CBF, which likely reflects adifferent physiologic mechanism thanthat of PET and xenon CT, which employa diffusible tracer (55). The authors ofone study (28) in which perfusion CT wascompared with xenon CT in a small het-erogeneous group of patients concludedthat in regions excluding major vessels(Fig 12), quantitative results with perfu-sion CT are in agreement with those ofxenon CT. The mean CBF value obtainedin the basal ganglia by using perfusionCT in a group of control patients in an-other study (16) was greater than thatreported in the literature for the basalganglia when PET was used and for thecortical gray matter when xenon CT wasused. However, authors of a different

study (2) reported systematically low val-ues for CBF as measured with perfusionCT, compared with the values reportedfor xenon CT, while CBV values obtainedwith perfusion CT were in good agree-ment with CBV values obtained by usingMR techniques.

Further studies comparing perfusionCT with more established methods ofmeasuring cerebral perfusion are neededto fully validate the quantitative value ofthis technique (2,16). Other than exclu-sion of areas that contain major bloodvessel branches, there are no standard-ized techniques or guidelines for placingROIs on the perfusion maps, which maymake comparing results between differ-ent investigators difficult. Larger ROIsmay result in greater volume averaging ofgray and white matter and, thus, lowerquantitative values for CBF, comparedwith the results obtained when smallerROIs centered in the cortex are used.

Uncertainties also exist regarding howthe quantitative values should be calcu-lated. The choice of input artery clearlyplays a role, with different quantitativeresults depending on the artery chosen(Fig 13). It is probably more accurate touse an input artery from the normal side,although further investigation is stillnecessary (29). In some clinical situa-tions, the normal side may not be knownat the time of the examination or theremay be bilateral or diffuse disease, as isoften the case with atherosclerosis or va-sospasm. In animal and human studies,extracranial arteries have been used asthe arterial input (4,13,17). The animalstudies showed highly significant corre-lates for CBF, CBV, and MTT values cal-culated with extracranial artery and in-ternal carotid artery inputs (4). In humanstudies, there was good correlation be-tween perfusion CT–derived data withthe radial artery and other clinical and

Figure 11. Aggressive tumor involvingtongue base on the left side in a 59-year-oldman. (a) Transverse CT image from perfusionscan. ROIs are placed in the following struc-tures: 1 � carotid artery, 2 � jugular vein, 3 �tongue base cancer, 4 � normal contralateralgenioglossus/geniohyoid complex, 5 � ipsi-lateral genioglossus/geniohyoid complex, 6 �sternocleidomastoid muscle, 7 � paraspinalmuscle. (b) Transverse PS map shows in-creased permeability within tumor (arrows),compared with PS of surrounding tissue.(c) Transverse blood volume map shows in-creased volume within tumor (arrows), com-pared with that of adjacent tissue. (d) Trans-verse blood flow map shows increased flowwithin tumor (arrows), compared with that ofsurrounding tissue. (e) Transverse MTT mapshows decreased MTT (arrows), comparedwith that of adjacent normal structures.

Volume 231 � Number 3 Perfusion CT: Technique and Clinical Applications � 641

Ra

dio

logy

neuroradiologic findings (4,13). With theradial artery as the arterial input, how-ever, the use of a specially designedholder for the patient’s forearm was nec-essary (4,13). We are currently investigat-ing the superficial temporal artery as thearterial input in cases of bilateral or dif-fuse disease; however, one drawback isthat this artery may not always be iden-tifiable. The size of the arterial ROI mayalso affect results (55).

The reproducibility of perfusion CThas also not been fully validated. Soft-ware to analyze the perfusion CT data iscommercially available and relativelyeasy to use, although training is required.The amount of training necessary to cre-

ate reliable perfusion maps is not known(55). Results of an initial investigation(56) indicate that the findings are repro-ducible between different operators. Thisstudy used experienced radiologist inves-tigators to create the perfusion maps. Thereproducibility between experienced andinexperienced radiologists, between radi-ologists and technologists, or betweenthe same radiologist or technologist ondifferent days has not been evaluated(55).

Another limitation of perfusion CT isits restricted anatomic coverage. A tog-gling-table technique has been describedthat allows coverage at two distinct tablepositions (57). While this does allow

greater coverage, it is at the expense oftemporal resolution (5 seconds). Alterna-tively, if an abnormality is clinically sus-pected distant from the level of the basalganglia, such as in the posterior fossa, theexamination can be tailored to the sus-pected area (Fig 14).

In summary, perfusion CT is clearly aviable alternative to other modalitiesused to measure cerebral perfusion. Thistechnique is fast and available for moststandard spiral CT scanners equippedwith the appropriate software. PerfusionCT can be used to assess not only patientswith acute stroke but also a wide range ofpatients with other cerebrovascular dis-eases. It may also be helpful in the diag-

Figure 12. (a–c) Because fewer major vessel branches (from a to c) are included in the ROI on transverse CBF maps, CBF values decrease.

Figure 13. Depending on the choice of input artery, (a) ACA, (b) right MCA, or (c) left MCA, the quantitative values for CBF vary, as seen ontransverse CBF maps.

642 � Radiology � June 2004 Hoeffner et al

Ra

dio

logy

nosis and subsequent treatment responsein patients with a variety of tumors. Fur-ther investigations are necessary to deter-mine the accuracy, reliability, and repro-ducibility of the quantitative results.

References1. Tissue plasminogen activator for acute

ischemic stroke. The National Institute ofNeurological Disorders and Stroke rt-PAStroke Study Group. N Engl J Med 1995;333:1581–1587.

2. Koenig M, Klotz E, Luka B, Venderink DJ,Spittler JF, Heuser L. Perfusion CT of thebrain: diagnostic approach for early de-tection of ischemic stroke. Radiology1998; 209:85–93.

3. Von Kummer R, Allen KL, Holle R, et al.Acute stroke: usefulness of early CT find-ings before thrombolytic therapy. Radiol-ogy 1997; 205:327–333.

4. Nabavi DG, Cenic A, Craen RA, et al. CTassessment of cerebral perfusion: experi-mental validation and initial clinical ex-perience. Radiology 1999; 213:141–149.

5. Jain R, Hoeffner EG, Deveikis J, HarriganM, Thompson GB, Mukherji SK. PerfusionCT evaluation in carotid balloon test oc-clusion with acetazolamide challengetest: feasibility. Radiology 2004; 231:000–000.

6. Roberts HC, Roberts TP, Lee TY, DillonWP. Dynamic contrast-enhanced CT ofhuman brain tumors: quantitative assess-ment of blood volume, blood flow andmicrovascular permeability—report oftwo cases. AJNR Am J Neuroradiol 2002;23:828–832.

7. Roberts HC, Roberts TP, Lee TY, DillonWP. Dynamic contrast-enhanced com-puted tomography (CT) for quantitativeassessment of microvascular permeabilityin human brain tumors. Acad Radiol2002; 9(suppl 2):S364–S367.

8. Bondestam S, Halavaara JT, JaaskelainenJE, Kinnunen JJ, Hamberg LM. PerfusionCT of the brain in the assessment of flowalterations during brachytherapy of me-ningioma. Acta Radiol 1999; 40:469–473.

9. Wintermark M, Maeder P, Thiran JP,Schnyder P, Meuli R. Quantitative assess-ment of regional cerebral blood flow byperfusion CT studies at low injectionrates: a critical review of the underlyingtheoretical models. Eur Radiol 2001; 11:1220–1230.

10. Eastwood JD, Provenzale JM, Hurwitz LM,Lee TY. Practical injection-rate CT perfu-sion imaging: deconvolution-derived he-modynamics in a case of stroke. Neurora-diology 2001; 43:223–226.

11. Wintermark M, Reichhart M, Thiran JP,et al. Prognostic accuracy of cerebralblood flow measurement by perfusioncomputed tomography, at the time ofemergency room admission, in acutestroke patients. Ann Neurol 2002; 51:417–432.

12. Cenic A, Nabavi DG, Craen RA, Gelb AW,Lee TY. A CT method to measure hemo-dynamics in brain tumors: validation andapplication of cerebral blood flow maps.AJNR Am J Neuroradiol 2000; 21:462–470.

13. Nabavi DG, LeBlanc LM, Baxter B, et al.Monitoring cerebral perfusion after sub-

arachnoid hemorrhage using CT. Neuro-radiology 2001; 43:7–16.

14. Eastwood JD, Loving VA, DeLong DM.Assessment of the influence of variablesrelated to arterial and venous input func-tions and CT perfusion image signal-to-noise value: importance of the venousoutflow curve (abstr). Radiology 2002;225(P):280.

15. Kikuchi K, Murase K, Miki H, et al. Mea-surement of cerebral hemodynamics withperfusion-weighted MR imaging: com-parison with pre- and post-acetazolamide133Xe-SPECT in occlusive carotid disease.AJNR Am J Neuroradiol 2001; 22:248–254.

16. Eastwood JD, Lev MH, Azhari T, et al. CTperfusion scanning with deconvolutionanalysis: pilot study in patients with

acute middle cerebral artery stroke. Radi-ology 2002; 222:227–236.

17. Nabavi DG, Cenic A, Henderson S, GelbAW, Lee TY. Perfusion mapping usingcomputed tomography allows accurateprediction of cerebral infarction in exper-imental brain ischemia. Stroke 2001; 32:175–183.

18. Jones TH, Morawetz RB, Crowell RM, etal. Thresholds of focal cerebral ischemiain awake monkeys. J Neurosurg 1981; 54:773–782.

19. Marcoux FW, Morawetz RB, Crowell RM,DeGirolami U, Halsey JH. Differential re-gional vulnerability in transient focal ce-rebral ischemia. Stroke 1982; 13:339–346.

20. Astrup J, Siesjo BK, Symon L. Thresholds

Figure 14. Images in a 72-year-old man who became confused and developed left-sided ataxiaduring hepatic angiography. Suspicion of a posterior fossa pathologic condition lead to perfusionCT performed through the level of the cerebellum. (a–c) Transverse perfusion CT maps show(a) decreased CBF (arrows), (b) decreased CBV (arrows), and (c) increased MTT (arrows) in medialleft cerebellum. (d) Transverse diffusion-weighted MR image (b � 1,000 sec/mm2) shows corre-sponding area of restricted diffusion (arrows).

Volume 231 � Number 3 Perfusion CT: Technique and Clinical Applications � 643

Ra

dio

logy

in cerebral ischemia: the ischemic pen-umbra. Stroke 1981; 12:723–725.

21. Hakim AM. The cerebral ischemic pen-umbra. Can J Neurol Sci 1987; 14:557–559.

22. Powers WJ, Grubb RL, Darriet D, RaichleME. Cerebral blood flow and cerebralmetabolic rate of oxygen requirementsfor cerebral function and viability in hu-mans. J Cereb Blood Flow Metab 1985;5:600–608.

23. Touho H, Karasawa JH. Evaluation oftime-dependent thresholds of cerebralblood flow and transit time during theacute stages of cerebral embolism: a ret-rospective study. Surg Neurol 1996; 46:135–146.

24. Kaufmann AM, Firlik AD, Fukui MB,Wechsler LR, Jungries CA, Yonas H. Isch-emic core and penumbra in humanstroke. Stroke 1999; 30:93–99.

25. Hossmann KA. Viability thresholds andthe penumbra of focal ischemia. AnnNeurol 1994; 36:557–565.

26. Ginsberg MD. Adventures in the patho-physiology of brain ischemia: penumbra,gene expression, neuroprotection. Stroke2003; 34:214–223.

27. Hossmann KA. Neuronal survival and re-vival during and after cerebral ischemia.Am J Emerg Med 1983; 1:191–197.

28. Wintermark M, Thiran JP, Maeder P,Schnyder P, Meuli R. Simultaneous mea-surement of regional cerebral blood flowby perfusion CT and stable xenon CT: avalidation study. AJNR Am J Neuroradiol2001; 22:905–914.

29. Lee T, Lev MH, Eastwood JD, ProvenzaleJM, Azhari T, Herzau MA. Effect of choiceof artery in the measurement of cerebralblood flow in stroke by CT perfusion (ab-str). Radiology 2001; 221(P):481.

30. Nariai T, Suzuki R, Hirakawa K, MaeharaT, Ishii K, Senda M. Vascular reserve inchronic cerebral ischemia measured bythe acetazolamide challenge test: com-parison with positron emission tomogra-phy. AJNR Am J Neuroradiol 1995; 16:563–570.

31. Yonas H, Pindzola RR, Meltzer CC, SasserH. Qualitative versus quantitative assess-ment of cerebrovascular reserves. Neuro-surgery 1998; 42:1005–1010.

32. Eastwood JD, Alexander MJ, Petrella JR,Provenzale JM. Dynamic CT perfusionimaging with acetazolamide challengefor the preprocedural evaluation of a pa-tient with symptomatic middle cerebralartery occlusive disease. AJNR Am J Neu-roradiol 2002; 23:285–287.

33. Hirano T, Minematsu K, Hasegawa Y,Tanaka Y, Hayashida K, Yamaguchi T. Ac-etazolamide reactivity on 123I-IMP singlephoton emission computed tomogra-phy in patients with major cerebral ar-tery occlusive disease: correlation with

positron emission tomography parame-ters. J Cereb Blood Flow Metab 1994;14:763–770.

34. Detre JA, Samuels OA, Alsop DC, Gonza-lea-At JB, Kasner SE, Raps EC. Noninva-sive magnetic resonance imaging evalua-tion of cerebral blood flow withacetazolamide challenge in patients withcerebrovascular stenosis. J Magn ResonImaging 1999; 10:870–875.

35. Webster MW, Makaroun MS, Steed DL,Smith HA, Johnson DW, Yonas H. Com-promised cerebral blood flow reactivity isa predictor of stroke in patients withsymptomatic carotid artery occlusive dis-ease. J Vasc Surg 1995; 21:338–345.

36. Yonas H, Smith HA, Durham SR, Pen-theny SL, Johnson DW. Increased strokerisk predicted by compromised cerebralblood flow reactivity. J Neurosurg 1993;79:483–489.

37. Komiyama M, Nishikawa M, Yasui T,Sakamoto H. Reversible pontine ischemiacaused by acetazolamide challenge. AJNRAm J Neuroradiol 1997; 18:1782–1784.

38. Mathis JM, Barr JD, Horton JA. Therapeu-tic occlusion of major vessels, test occlu-sion and techniques. Neurosurg Clin NAm 1994; 5:393–401.

39. Mathis JM, Barr JD, Jungreis CA, et al.Temporary balloon occlusion of the in-ternal carotid artery: experience in 500cases. AJNR Am J Neuroradiol 1995; 16:749–754.

40. Sen C, Laligam N. Direct vein reconstruc-tion of the cavernous, petrous and uppercervical internal carotid artery: lessonslearned from 30 cases. Neurosurgery 1992;30:732–743.

41. Marshall RS, Lazar RM, Young WL, et al.Clinical utility of quantitative cerebralblood flow measurements during internalcarotid artery test occlusions. Neurosur-gery 2002; 50:996–1005.

42. Okudaira Y, Arai H, Sato K. Cerebralblood flow alteration by acetazolamideduring carotid balloon occlusion. Stroke1996; 27:617–621.

43. Michel E, Liu H, Remley KB, et al. Perfu-sion MR neuroimaging in patients under-going balloon test occlusion of the inter-nal carotid artery. AJNR Am J Neuroradiol2001; 22:1590–1596.

44. Mayberg MR, Batjer HH, Dacey R, et al.Guidelines for the management of aneu-rysmal subarachnoid hemorrhage: specialreport—a statement for healthcare pro-fessionals from a special writing group ofthe Stroke Council, American Heart Asso-ciation. Circulation 1994; 90:2592–2605.

45. Griffiths PD, Wilkinson ID, Mitchell P, etal. Multimodality MR imaging depictionof hemodynamic changes and cerebralischemia in subarachnoid hemorrhage.AJNR Am J Neuroradiol 2001; 22:1690–1697.

46. Awad IA, Carter P, Spetzler RF, Medina M,Williams FW. Clinical vasospasm aftersubarachnoid hemorrhage: response tohypervolemic hemodilution and arterialhypertension. Stroke 1987; 18:365–372.

47. Kassell NF, Sasaki T, Colohan AR, NazarG. Cerebral vasospasm following aneu-rysmal subarachnoid hemorrhage. Stroke1985; 16:562–572.

48. Yonas H, Sekhar L, Johnson DW, Gur D.Determination of irreversible ischemia byxenon-enhanced computed tomographicmonitoring of cerebral blood flow in pa-tients with symptomatic vasospasm.Neurosurgery 1989; 24:368–372.

49. Lewis DH, Eskridge JM, Newell DW, et al.Brain SPECT and the effect of cerebralangioplasty in delayed ischemia due tovasospasm. J Nucl Med 1992; 33:1789–1796.

50. Clyde BL, Resnick DK, Yonas H, SmithHA, Kaufmann AM. The relationship ofblood velocity as measured by transcra-nial Doppler ultrasonography to cerebralblood flow an determined by stable xe-non computed tomographic studies afteraneurysmal subarachnoid hemorrhage.Neurosurgery 1996; 38:896–905.

51. Firlik AD, Kaufmann AM, Jungreis CA,Yonas H. Effect of transluminal angioplastyon cerebral blood flow in the managementof symptomatic vasospasm following aneu-rysmal subarachnoid hemorrhage. J Neuro-surg 1997; 86:830–839.

52. Roberts HC, Roberts TP, Brasch RC, Dil-lon WP. Quantitative measurement ofmicrovascular permeability in humanbrain tumors achieved using dynamiccontrast-enhanced MR imaging: correla-tion with histologic grade. AJNR Am JNeuroradiol 2000; 21:891–899.

53. Roberts HC, Roberts TP, Ley S, Dillon WP,Brasch RC. Quantitative estimation ofmicrovascular permeability in humanbrain tumors: correlation of dynamic Gd-DTPA-enhanced MR imaging with his-topathologic grading. Acad Radiol 2002;9(suppl 1):S151–S155.

54. Padhani AR, Neeman M. Challenges forimaging angiogenesis. Br J Radiol 2001;74:886–890.

55. Roberts HC, Roberts TP, Dillon WP. CTperfusion flow assessment: “up and com-ing” or “off and running”? AJNR Am JNeuroradiol 2001; 22:1018–1019.

56. Sanelli PC, Eastwood JD, Lee T, Azhari T,Chueng RT, Lev MH. CT perfusion imag-ing of acute stroke: variability in quanti-fication of perfusion parameters (abstr).Radiology 2001; 221(P):394.

57. Roberts HC, Roberts TP, Smith WS, LeeTJ, Fischbean NJ, Dillon WP. Multisec-tion dynamic CT perfusion for acute ce-rebral ischemia: the “toggling-table”technique. AJNR Am J Neuroradiol 2001;22:1077–1080.

644 � Radiology � June 2004 Hoeffner et al

Ra

dio

logy