Acute Ischemic Stroke Imaging Ronald L. Wolf, MD, PhD Associate Professor of Radiology
Title of First Slide of Substance An Illustrative Case 2
Disclosures No financial disclosures Off-label uses of some products (e.g., bolus gadolinium perfusion) Some MR perfusion images created for display/educational purposes using PMA image analysis software (copyright owner: Kohsuke Kudo) provided by ASIST-JAPAN) or RAPID software for academic or research purposes and cannot be used for clinical evaluation. 3
Acute Ischemic Stroke (AIS) Imaging The basics Advanced imaging options Perfusion imaging in practice, yes or no? 4
Stroke Lay term for sudden loss of neurologic function ( brain attack ) Two major categories Ischemic (80-85%) Hemorrhagic (10-15%) Third largest cause of mortality, leading cause of morbidity in the US 5
Treatment Options Approved treatment IV tpa: infarct < 3 (4.5) hours Mechanical: Merci > Penumbra > Solitaire, Trevo (stent retrievers) <6 hours Off label IV tpa after 3 (4.5) hours, IA tpa < 6 hours (longer for basilar occlusion) Greatest benefit Low thrombus burden/small vessel, good collaterals, lack of extended infarct 6
TICI Grade Assessment of EVT technical outcome Modified thrombolysis in cerebral infarction (TICI) grade Grade 0: no antegrade perfusion Grade 1: perfusion past initial obstruction but limited distal branch filling with little or slow distal perfusion Grade 2: 2a: perfusion of < 50% of vascular distribution of occluded artery 2b: perfusion of 50% of vascular distribution of the occluded artery Grade 3: full perfusion with filling of all distal branches Grade 2b/3: better clinical outcome than 2a mrs 0-2: 49 vs 34% D/C home: 41 vs 17% Marks et al. JNIS 2014 Jayaraman et al. AJNR 2013 7
Goals: Diagnostic Imaging in AIS At minimum: Exclude hemorrhage (and obvious non-stroke disorders) usually NECT, MRI if possible Evaluate location and extent of infarct/edema (e.g., > 1/3 MCA territory?) NECT or better DWI 8
Not AIS 9
Not AIS Chorea - Toxoplasmosis Pt. 1 Pt. 2 HA, MS - PRES Chorea - Toxoplasmosis HA, MS - PRES 10
Acute Aphasia, 2 hours from onset 11
Determinants of Outcome Symptom severity NIHSS>10 poor prognosis without successful treatment NIHSS<5 favorable Infarct core size > 70-100 ml less favorable Arteries involved Basilar, proximal MCA, ICA less favorable Small branch, presence of collaterals favorable Treatment/recanalization Score (NIHSS) Stroke Severity 0 No Symptoms 0-4 Minor 5-15 Moderate 16-20 Moderate to Severe 21-42 Severe 12
Outcome: ASPECTS Alberta Stroke Program Early CT Score (ASPECTS) 10 point topographic CT score Quantify/score early ischemic changes ASPECTS 7 poor functional outcome and symptomatic hemorrhage Barber et al, Lancet 2000; 355; 1670 Hill et al, AJNR 2006; 27:1612 Hill et al. AJNR 2006 13
Outcome: ASPECTS M1 C L I IC M2 M3 M4 M6 M5 ASPECTS = 2 (10-8) 14
Outcome: ASPECTS C L IC M1 I M2 M4 M5 M3 M6 15
Outcome: BASIS Boston Acute Stroke Imaging Scale (BASIS) Proximal occlusion on CTA or MRA (ICA, M1, M2, and/or basilar) major stroke (BASIS +) If no proximal occlusion, evaluation parenchyma with MR or CT ASPECTS 7 = major stroke (BASIS +) Others are minor stroke (BASIS -) 205 AIS patients, 16 with IV± IA tpa 149 minor, 56 major stroke Majority of BASIS + with poor outcome (death or discharge to rehab facility vs. discharge home) Torres-Mozqueda et al, AJNR 2008; 29: 1111 Fig. from González RG et al, PLoS One. 2012; 7(1): e30352 16
What next? LMCA syndrome, onset unclear RMCA syndrome, 6 hours out s/p IV rtpa 17
Goals: Diagnostic Imaging in AIS At minimum: Exclude hemorrhage (and obvious non-stroke disorders) Evaluate location and extent of infarct/edema (e.g., > 1/3 MCA territory?) Maximize benefit/risk - tissue clock : Accurate assessment of 4 P s Parenchyma, Pipes, Perfusion, Penumbra Target patients who will benefit most from treatment Extend treatment window Minimize risk Rowley, AJNR 2001; 22: 599 18
Acute Ischemic Syndrome The basics Advanced imaging options Parenchyma Pipes Perfusion Penumbra Perfusion imaging in practice, yes or no? 19
Parenchyma: CTA-SI ASPECTS Left MCA syndrome 20
Parenchyma: DWI DWI is the optimal method if feasible Only minimal reversibility for acute ischemic infarct Large DWI insult (>70mL) unfavorable with or without recanalization Small DWI insult more favorable, and with target perfusion mismatch more likely to benefit from recanalization 21
Parenchyma: DWI/FLAIR Mismatch DWI minutes FLAIR hours DWI+, FLAIR- For < 4.5 hr from symptoms Sens 62%, NPV 54% Spec 78%, PPV 83% Thomalla et al, Lancet Neurol 2011 22
Infarct Patterns Embolic Embolic with fragmentation Small vessel Internal Watershed Watershed Vasculitis CP arrest HSV 1 23
Stroke? Left gaze preference, left sided weakness 24
Stroke? Left gaze preference, left sided weakness 25
Right Hemiparesis: Stroke? DWI FLAIR 26
Acute Ischemic Syndrome The basics Advanced imaging options Parenchyma Pipes Perfusion Penumbra Perfusion imaging in practice, yes or no? 27
Lateral Medullary (Wallenberg) Syndrome FLAIR DWI ADC 28
Pipes: MR Angiography Left vertebral artery dissection/occlusion 2D TOF MRA MIP 2D TOF MRA source images 29
Pipes: CT Angiography Left vertebral artery dissection/occlusion CTA: slab-mip 30
Pipes: Collaterals 31
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Pipes: Collaterals, HVS on FLAIR Sluggish flow in poorly developed collaterals 33
Elderly Male, Collapsed, Locked In 34
Basilar Artery Occlusion DWI 3D TOF MRA 35
On Presentation 36
Vasculitis Right anterior circulation 37
3 Days Later 38
Watershed Infarct Traumatic Carotid Dissection 39
Carotid Dissection 40
Acute Ischemic Syndrome The basics Advanced imaging options Parenchyma Pipes Perfusion Penumbra Perfusion imaging in practice, yes or no? 41
Perfusion/Penumbra: AIS at 6 Hours Status post IV rtpa 42
Perfusion/Penumbra: AIS at 6 Hours Status post IV rtpa: occluded RICA and distal MCA, ACA branches 43
Perfusion/Penumbra: AIS at 6 Hours CTP: large infarct, small mismatch rcbf < 30% rcbv 40% TTP 5-6s Tmax > 5s 44
Perfusion/Penumbra: AIS at 8 Hours 45
Perfusion/Penumbra: AIS at 8 Hours Diffusion perfusion mismatch (penumbra) 46
Left MCA Occlusion 47
Acute Ischemic Syndrome The basics Advanced imaging options Parenchyma Pipes Perfusion Penumbra Perfusion imaging in practice, yes or no? 48
Perfusion and Penumbra Fig. from González RG JMRI 2012; 36: 252 González RG JMRI 2012; 36: 252 49
Penumbra Imaging IA rtpa and/or mechanical lysis better recanalization than IV rtpa alone Early recanalization associated with improved outcomes prior to irreversible injury Diffusion alone or perfusion/penumbra? 50
Perfusion Imaging in AIS Accurately assess dead vs. salvageable? Acute MCA occlusive disease (hours) Chronic MCA occlusive disease (days, weeks, months) 51
Value of Perfusion Imaging in AIS Stroke 2009; 40: 3646 Stroke 2010; 41: E25 52
Perfusion in AIS: Against Major strokes Most important is rapid ID of occlusion (CTA, MRA) and size of infarct (DWI) Core and penumbra not independent Collaterals link the two Minor strokes or TIA DWI small or none Mild symptoms, small vessel occlusion or partial compensation? Greater value PWI in this setting González RG JMRI 2012;36:259 53
Perfusion in AIS: For 54
Tissue Clock and Target Mismatch Dead versus salvageable DEFUSE 2 Target mismatch PWI(T max >6s)/DWI 1.8 DWI < 70mL PWI(T max >10s) < 100mL Mismatch volume > 15mL Target mismatch patients more favorable response with reperfusion OR 8.8 for favorable clinical response with reperfusion in target mismatch group OR 0.2 in no target mismatch group Lansberg et al, Lancet Neurology 2012; 11: 860 55
LMCA Syndrome, 6 hrs, NIHSS 30 56
LMCA Syndrome, 6 hrs, NIHSS 30 57
LMCA Syndrome, 6 hrs, NIHSS 30 CBF CBV MTT Tmax PMA image analysis software, provided by ASIST-JAPAN) 58
LMCA Syndrome, 6 hrs, NIHSS 30 Penumbra (pre) Penumbra (post) post DSA CT 59
NINDS tpa Trials IV r-tpa vs. placebo within 3 hours First proven/approved stroke treatment Neurologic recovery better with tpa (30% more likely to have minimal or no disability) Hemorrhage more likely (6.4% tpa vs. 0.6% placebo) Mortality similar at 3 months (17% tpa vs. 21% placebo) Limitations 22% present within 3 hours, and only 4% get tpa 51% ineligible (mild severity, med/surg history, etc) Sustained recanalization in only 13% Hemorrhage risk NEJM 1995; 333: 1581 60
Acute Stroke Imaging after 2014 Prior to 2014 R-tPA only proven effective treatment for acute ischemic stroke After MR CLEAN ESCAPE EXTEND-IA SWIFT PRIME REVASCAT 61
Acute Stroke Imaging: Recent Trials 62
Where are we going? 6-16 hours Perfusion imaging 63
2015 AHA/ASA Updated EVT Guidelines Eligible patients should get IV tpa even if EVT considered (Class I, Level A) Should receive EVT with stent retriever if meeting following criteria (Class I, Level A) Pre-stroke mrs 0 to 1 IV tpa within 4.5 hours ICA/M1 occlusion Age at least 18 years NIHSS score at least 6 ASPECTS at least 6 Treatment initiated within 6 hours of onset Powers et al. Stroke 2015 64
2015 AHA/ASA Updated EVT Guidelines TICI 2b/3 reperfusion as early as possible (Class I; Level of Evidence A), preferably within 6 hrs of onset (Class I; Level of Evidence B-R) Effectiveness of EVT initiated >6hrs of onset uncertain. Additional data needed. (Class IIb; Level of Evidence C) EVT, if completed within 6 hrs of onset, for selected pts with contraindication to IV TPA is reasonable. Additional data needed. (Class IIa; Level of Evidence C) EVT is reasonable for M2/M3, ACA, basilar, PCA in selected pts if initiated within 6 hrs of onset. Additional data needed. (Class IIb; Level of Evidence C) Powers et al. Stroke 2015 65
Conclusions: AIS Imaging Need to: Exclude hemorrhage (and obvious non-stroke disorders) Evaluate location and extent of infarct/edema (e.g., > 1/3 MCA territory?) Want to address 4 P s : Parenchymal injury, Pipes, Perfusion, Penumbra Rationale is to improve safety, target patients who will benefit most from treatment (e.g., with tpa), extend treatment window Comments Email: ronald.wolf@uphs.upenn.edu 66
Protocols Tissue Clock, not Ticking Clock Emergent MRI (~12min) DWI Fast FLAIR GRE Add-ons PWI (~1min) Fast 3D TOF of COW (< 5 min) 3D CE MRA Head and Neck (~1min) Emergent CT/CTA/CTP ~10-15 minutes Full MRI (~45min) Routine brain with/without contrast GRE DWI and PWI MRA 3D TOF of head 2D TOF neck 3D CE MRA neck Option: fat sat T1 neck 67
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