andrew w. asimos, md how can we use advanced neuroimaging in the ed to optimize treatment options...

Andrew W. Asimos, MD

How Can We Use Advanced How Can We Use Advanced Neuroimaging in the ED to Neuroimaging in the ED to

Optimize Treatment Options Optimize Treatment Options for Acute Stroke Patients?for Acute Stroke Patients?


Andrew Asimos, MDAndrew Asimos, MDDirector of Emergency Stroke CareDirector of Emergency Stroke Care

Carolinas Medical CenterCarolinas Medical CenterCharlotte, NCCharlotte, NC

Adjunct Associate Professor Adjunct Associate Professor Department of Emergency MedicineDepartment of Emergency Medicine

University of North Carolina School of University of North Carolina School of Medicine at Chapel HillMedicine at Chapel Hill


Attending PhysicianAttending PhysicianEmergency MedicineEmergency Medicine

Carolinas Medical CenterCarolinas Medical CenterDepartment of Emergency MedicineDepartment of Emergency Medicine

Charlotte, NCCharlotte, NC

Andrew Asimos, MD, FACEP

DisclosureDisclosure

• None related to the content of this None related to the content of this presentationpresentation


Session ObjectivesSession Objectives• Acknowledge latest guidelines and systematic Acknowledge latest guidelines and systematic

review related to advanced neuroimagingreview related to advanced neuroimaging• Review important unenhanced CT conceptsReview important unenhanced CT concepts• Review CTA/CTP concepts and supporting dataReview CTA/CTP concepts and supporting data• Overview of latest MRI dataOverview of latest MRI data


Clinical QuestionsClinical Questions

• What is the goal of initial neuroimaging for presumed acute stroke patients?

• How can CTP/CTA or MRI/MRA be utilized•To optimize the use of IV tPA and the triage of ED stroke patients for advanced IR therapeutics?

•To detect the site of the vascular occlusion, and CTP (DWI/PWI) the size of the ischemic penumbra and the infarct core?

•To maximize the potential benefit and minimize risk when using IV tPA in ED stroke patients?


Clinical QuestionsClinical Questions

• What are perfusion scans, what do they demonstrate, and how are they interpreted?

• What software or technology is necessary for advanced neuroimaging?

• How can these capabilities be developed at my hospital?

• What usage of these advanced diagnostics is the standard of care in 2007?


Case:Case:Patient presenting within 3 hour windowPatient presenting within 3 hour window

• 50 yo male50 yo male• CT less than 2 hours CT less than 2 hours

within symptom onsetwithin symptom onset• Awake, alert, dysarthricAwake, alert, dysarthric• Fixed right sided gazeFixed right sided gaze• Left sided weaknessLeft sided weakness



BF BV TTPInitial


Case:Case:“Wake up” Stroke“Wake up” Stroke

0735 at outside hospital


Case:Case: “Wake up” Stroke “Wake up” Stroke


Case:Case: “Wake up” Stroke “Wake up” Stroke

1030 at stroke center


Impact of Neuroimaging on Impact of Neuroimaging on Decision MakingDecision Making

• Both art and science to treatment Both art and science to treatment decision making for acute strokedecision making for acute stroke

• Lots of non-imaging related factors Lots of non-imaging related factors increase SICH risk after treatment with increase SICH risk after treatment with tPAtPA

• Average EM physician cannot keep up Average EM physician cannot keep up with advances in neuroradiologic with advances in neuroradiologic technology and literature regarding its technology and literature regarding its impact on decision makingimpact on decision making

• Guidelines cannot keep upGuidelines cannot keep up


Essential Imaging QuestionsEssential Imaging Questions• Is there hemorrhage?Is there hemorrhage?• Are findings consistent with acute Are findings consistent with acute

ischemic stroke?ischemic stroke?• Can this imaging modality’s results add Can this imaging modality’s results add

to my risk/benefit analysis?to my risk/benefit analysis?• Is there large vessel occlusion?Is there large vessel occlusion?• Is there “irreversibly” infarcted core?Is there “irreversibly” infarcted core?• Is there “salvageable” penumbra?Is there “salvageable” penumbra?• Are other findings present that should be Are other findings present that should be

consideredconsidered• MicrobleedsMicrobleeds• LeukoaraiosisLeukoaraiosis


The Four P’s of Acute Stroke The Four P’s of Acute Stroke ImagingImaging

PParenchymaarenchyma Assess early signs of acute stroke, rule Assess early signs of acute stroke, rule out hemorrhageout hemorrhage

PPipesipes Assess intracranial and extracranial Assess intracranial and extracranial circulation for evidence of circulation for evidence of intravascular thrombusintravascular thrombus

PPerfusionerfusion Assess cerebral blood flow, blood Assess cerebral blood flow, blood volume, and mean transit timevolume, and mean transit time

PPenumbraenumbra Assess tissue at risk of dying if Assess tissue at risk of dying if ischemia continuesischemia continues

Rowley HA et al. Am J Neuroradiol 2001;22:599-601.


2007 Imaging Guidelines2007 Imaging Guidelines

Adams HP et al. Stroke 2007;38:1655-1711.


Systematic Review of DWI/PWI Mismatch and Systematic Review of DWI/PWI Mismatch and Thrombolysis in Acute StrokeThrombolysis in Acute Stroke


Class I RecommendationsClass I Recommendations• Imaging of the brain is recommended before Imaging of the brain is recommended before

initiating any specific therapy to treat acute initiating any specific therapy to treat acute ischemic strokeischemic stroke

• In most instances, CT will provide the information In most instances, CT will provide the information to make decisions about emergency managementto make decisions about emergency management

• The brain imaging study should be interpreted by The brain imaging study should be interpreted by a physician with expertise in reading CT or MRI a physician with expertise in reading CT or MRI studies of the brainstudies of the brain

• Some findings on CT, including the presence of a Some findings on CT, including the presence of a dense artery sign, are associated with poor dense artery sign, are associated with poor outcomes after strokeoutcomes after stroke

• Multimodal CT and MRI may provide additional Multimodal CT and MRI may provide additional information that will improve diagnosis of information that will improve diagnosis of ischemic strokeischemic stroke



Unenhanced CT:Unenhanced CT:Beyond HemorrhageBeyond Hemorrhage


Unenhanced CT:Unenhanced CT:HDMCA SignHDMCA Sign

• Overall poor prognosis if HDMCA Overall poor prognosis if HDMCA sign on CTsign on CT

• Limited data suggest IV-t-PA Limited data suggest IV-t-PA ineffective in treating acute stroke ineffective in treating acute stroke in the setting of HDMCA signin the setting of HDMCA sign

Somford DM et al. Radiology 2002;223:667–671.Barber PA et al. Stroke 2001;32:84–88.


From the 2007 GuidelinesFrom the 2007 Guidelines

“Several studies have suggested that perfusion CT may be able to

differentiate thresholds of reversible and irreversible ischemia and thus

identify the ischemic penumbra.114,115”

Klotz E et al. Eur J Radiol 1999; 30: 170–184.Wintermark M et al. Ann Neurol 2002; 51: 417–432.


Class II RecommendationsClass II Recommendations• Data are insufficient to state that, with Data are insufficient to state that, with

the exception of hemorrhage, any the exception of hemorrhage, any specific CT finding (including evidence of specific CT finding (including evidence of ischemia affecting more than one third of ischemia affecting more than one third of a cerebral hemisphere) should preclude a cerebral hemisphere) should preclude treatment with rtPA within 3 hours of treatment with rtPA within 3 hours of onset of strokeonset of stroke

• Vascular imaging is necessary as a Vascular imaging is necessary as a preliminary step for intra-arterial preliminary step for intra-arterial administration of pharmacological administration of pharmacological agents, surgical procedures, or agents, surgical procedures, or endovascular interventionsendovascular interventions



Unenhanced CT:Unenhanced CT:ASPECTS SystemASPECTS System


ASPECTS ExampleASPECTS Example


ASPECTS Score andASPECTS Score andFunctional OutcomeFunctional Outcome

Weir NU et al. Neurology 2006;67(3):516-8.


Usefulness of ASPECTS Score at Predicting Usefulness of ASPECTS Score at Predicting Outcome of Individual PatientsOutcome of Individual Patients

Weir NU et al. Neurology 2006;67(3):516-8.


ASPECTS Score Applied to tPA ASPECTS Score Applied to tPA Treated PatientsTreated Patients

• Used ECASS II DatabaseUsed ECASS II Database• 788 baseline CT scans788 baseline CT scans• 6 hour treatment window6 hour treatment window

Dzialowski I et al. Stroke 2006:37(4):973-8.


90 Day Outcome by ASPECTS > 790 Day Outcome by ASPECTS > 7

Dzialowski I et al. Stroke 2006:37(4):973-8.


Class III RecommendationsClass III Recommendations

• Emergency treatment of stroke Emergency treatment of stroke should not be delayed in order to should not be delayed in order to obtain multimodal imaging studiesobtain multimodal imaging studies

• Vascular imaging should not delay Vascular imaging should not delay treatment of patients whose treatment of patients whose symptoms started <3 hours ago and symptoms started <3 hours ago and who have acute ischemic strokewho have acute ischemic stroke



Therapeutic WindowTherapeutic Window

• Time from ictus used for theoretical Time from ictus used for theoretical and practical reasonsand practical reasons

• Increasingly will rely on imaging Increasingly will rely on imaging studies to determine tissue studies to determine tissue salvageability and clot burdensalvageability and clot burden


Good Collateral Flow will Buy Good Collateral Flow will Buy you Some Time and Brainyou Some Time and Brain


Advanced CT Imaging for Acute Stroke:Advanced CT Imaging for Acute Stroke:CTP versus MRICTP versus MRI

Parameters Definition of Penumbra

Advantages Limitations

CT Perfusion

CBF, CBV, MTT, TTP

MTT threshold at 145%

•Combined with plain CT•Available•Fast

•Limited brain coverage•Poorly sensitive to posterior circulation•Iodonated contrast

DWI-PWI MRI

CBF, CBV, MTT, TTP, ADC

Relative TTP (or MTT) delay >45s and normal DWI

•Sensitive•No radiation

•Limited availability•Patient cooperation required•Frequent contraindications

Muir KW et al. Lancet Neurology 2006; 5:755-768


MRI/MRA in Acute MCA Ischemic Stroke MRI/MRA in Acute MCA Ischemic Stroke Treated Successfully with t-PATreated Successfully with t-PA


MRI/MRA in Acute MCA Ischemic Stroke MRI/MRA in Acute MCA Ischemic Stroke Not Treated with t-PANot Treated with t-PA


CT Perfusion TerminologyCT Perfusion Terminology

Blood FlowBlood Flow Blood VolumeBlood Volume Mean Transit TimeMean Transit Timeoror

Time to PeakTime to Peak


DefinitionsDefinitions

PerfusionPerfusion The steady-state delivery of blood to The steady-state delivery of blood to cerebral tissue through the capillariescerebral tissue through the capillaries

CBFCBF(Cerebral Blood Flow)(Cerebral Blood Flow)

Volume flow rate of blood through the Volume flow rate of blood through the cerebral vasculature per unit timecerebral vasculature per unit time

CBVCBV(Cerebral Blood Volume)(Cerebral Blood Volume)

Amount of blood in a given amount of Amount of blood in a given amount of tissue at any timetissue at any time

MTTMTT(Mean Transit Time)(Mean Transit Time)

Average time it takes for blood to Average time it takes for blood to traverse from the arterial to the traverse from the arterial to the venous side of the cerebral venous side of the cerebral vasculaturevasculature


Changes in Cerebral Vascular Physiology Changes in Cerebral Vascular Physiology with Worsening Circulatory Impairmentwith Worsening Circulatory Impairment

CBFCBF CBVCBV MTTMTT

Salvageable Salvageable PenumbraPenumbra

↓↓ ↔↔↑↑

↑↑

↓ ↓↓ ↓ ↓↓ ↑↑IrretrievableIrretrievable

InfarctInfarct↓↓ ↓↓ ↑ ↑

↑↑


Relationship between CBV, CBF, Relationship between CBV, CBF, and MTTand MTT

MTT= CBV/CBFMTT= CBV/CBF

Blood FlowBlood Flow Blood VolumeBlood Volume Mean Transit TimeMean Transit Timeoror

Time to PeakTime to Peak


Example of the Progression of Example of the Progression of Advanced ImagesAdvanced Images


Pure PenumbraPure Penumbra

Parsons MW et al. Neurology 2007;68(10):730-6.


Core Infarct and PenumbraCore Infarct and Penumbra



Largely Completed InfarctionLargely Completed Infarction



Are CTP Techniques Ready for Are CTP Techniques Ready for Prime Time?Prime Time?

• CTP more accurate than CTP more accurate than unenhanced CT for detecting stroke unenhanced CT for detecting stroke and determining the extent of strokeand determining the extent of stroke

• Possible to distinguish penumbra Possible to distinguish penumbra from infarcted tissuefrom infarcted tissue

• Correlation between PCT/CTA and Correlation between PCT/CTA and MRI is excellentMRI is excellent

• Already used in DIAS and DEDASAlready used in DIAS and DEDAS

Wintermark M et al. Am J Neuroradiol 2005;26(1):104-12.Wintermark M et al. Stroke 2006;37:979-985.Wintermark M et al. Neurology 2007;68(9):694-697.


Important Remaining CTP Important Remaining CTP QuestionsQuestions

• What is the interrater reliability of visual What is the interrater reliability of visual estimation of lesion volumes?estimation of lesion volumes?

• Is that variability clinically important?Is that variability clinically important?

• Can computerization automate Can computerization automate measurement of absolute perfusion measurement of absolute perfusion thresholds and lesion volume in a thresholds and lesion volume in a clinically meaningful way?clinically meaningful way?

• Will the current perfusion thresholds for Will the current perfusion thresholds for penumbra and infarct be maintained with penumbra and infarct be maintained with rigorous future testing?rigorous future testing?


Relative MTT is the Best CTP Parameter Relative MTT is the Best CTP Parameter

for Identifying Penumbrafor Identifying Penumbra

Wintermark M et al. Stroke 2006;37:979-985


Absolute CBV is the Best CTP Absolute CBV is the Best CTP Parameter for Identifying InfarctParameter for Identifying Infarct

Wintermark M et al. Stroke 2006;37:979-985


DEFUSE StudyDEFUSE Study

• Prospective pilot study (n=74)Prospective pilot study (n=74)• Patients treated with IV tPA 3-6 hours Patients treated with IV tPA 3-6 hours

after symptom onsetafter symptom onset• Goal to identify MRI patterns that predict Goal to identify MRI patterns that predict

the clinical response to early reperfusionthe clinical response to early reperfusion

Albers GW et al. Ann Neurol 2006:60(5):508-17.


Key Results of theKey Results of theDEFUSE STUDYDEFUSE STUDY

• Target Mismatch patternTarget Mismatch pattern• Identifies patients who appear to benefit Identifies patients who appear to benefit

substantially from early reperfusionsubstantially from early reperfusion

• Malignant MRI patternMalignant MRI pattern• Predicts severe ICH following reperfusionPredicts severe ICH following reperfusion

• Small DWI and PWI lesionsSmall DWI and PWI lesions• Associated with favorable outcomesAssociated with favorable outcomes



Target Mismatch PatternTarget Mismatch Pattern



Malignant Mismatch PatternMalignant Mismatch Pattern



Case Conclusion:Case Conclusion:Patient presenting within 3 hour windowPatient presenting within 3 hour window

BF BV TTP 3 day fuInitial


Case Conclusion:Case Conclusion: “Wake up” Stroke “Wake up” Stroke


Proposed Imaging AlgorithmProposed Imaging Algorithm


ConclusionsConclusions• Advanced neuroimaging techniques will make

symptom onset time increasingly obsolete•Wake up stroke•Onset time unclear

• Application of visual estimation of penumbral volumes versus automated measurement requires further study

• These techniques can•Distinguish penumbra from infarct•Will drive acute stroke care therapeutic decisions in the future


Questions?Questions?

www.FERNE.org

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andrew w. asimos, md how can we use advanced neuroimaging in the ed to optimize treatment options...

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