Jan BogaertRadiology & Medical Imaging Research Centre

Working Group on Magnetic ResonanceLoutraki, Greece February 17-19, 2011

No-Reflow Phenomenon

Back in History

From Bench to Bedside

Mechanisms responsible for No-Reflow

Niccoli G et al. J Am Coll Cardiol 2009;54:281-292

Ischemia Time

Ischemia Time – No-Reflow

Francone M et al. J Am Coll Cardiol 2009;54:2145-53

Infarct Size

Diagnosis of No-Reflow

• Coronary angiography (TIMI flow grade – Myocardial Blush Grade)

• ECG (STR 1h after PPCI)

• Myocardial contrast echocardiography (MCE)

• Cardiac MRI

MR Sequence Arsenal

• Morphology (T1w-SE MRI / cine MRI)

• Myocardial edema (T2w-STIR-SE MRI)

• Cardiac function – Systolic (cine MRI / tagging)– Diastolic function: (VENC cine MRI)

• Myocardial perfusion imaging (MPI)

• Tissue Characterization– late or delayed (gadolinium) enhancement– T2* sequences

• Flow & Motion imaging – b-SSFP cine MRI– velocity-encoded cine MRI

• Vessel (coronary artery imaging)– b-SSFP 3D MR(C)A– contrast-enhanced 3D MR(C)A

MRI Approach

J Am Coll Cardiol 2008;52:181-189

• extensive infarct with low EF LV (28%)• day 3 post-infarct

No-Reflow Phenomenon

• increases with the duration of ischemia time (TARANTINI et al. 2005; FRANCONE et al. 2009)

• is related to more severe myocardial damage (BOGAERT et al. 2007)

• ….. together with other parameters such as intramyocardial hemorrhage (GANAME et al. 2009; MATHER et al. 2010).

• and is independently associated with lack of functional recovery, adverse ventricular remodeling and worse patient outcome (ITO et al. 1992; ITO et al. 1996; WU et al. 1998a; ROGERS et al. 1999; KRAMER et al. 2000; GERBER et al. 2000; TAYLOR et al. 2004; HOMBACH et al. 2005; BAKS et al. 2006; FUNARO et al. 2009; NIJVELDT et al. 2008; ORN et al. 2009)

Therapeutic Approaches

Conclusions

• shift from open coronary artery to open microvessel theory

• microvascular obstruction is frequently present in both STEMI and non- STEMI infarcts

• contrast-enhanced MRI probably the best technique => detection of MVO can be seen as a “free bonus” in infarct imaging– first pass perfusion– early ceMRI – late ceMRI

• unresolved issues are exact timing post contrast administration and post PCI

• novel strategies are targeted toward reduction of microvascular damage

Coronary artery disease – related pathology

• angor/angina pectoris– stable– Unstable

• myocardial infarction– non-STEMI– STEMI

• ischemia-related heart failure

• sudden cardiac death

myocardialischemiaimaging

myocardialinfarct

imaging

heart failure

imaging

Imaging in Ischemic Heart Disease

“functionality”(inducible ischemia)

CA anatomy(stenosis detection/exclusion)

consequencesof CA disease

stress perfusionstress functionCTCA / MRCA infarct/viability

Myocardial Ischemia Imaging

• Morphology (T1w-SE MRI / cine MRI)

• Myocardial edema (T2w-STIR-SE MRI)

• Cardiac function– Systolic (cine MRI / tagging)– Diastolic function: (VENC cine MRI)

• Myocardial perfusion imaging (MPI)

• Tissue Characterization– late or delayed (gadolinium) enhancement– T2* sequences

• Flow & Motion imaging – b-SSFP cine MRI– velocity-encoded cine MRI

• Vessel (coronary artery imaging)– b-SSFP 3D MR(C)A– contrast-enhanced 3D MR(C)A

Coronary occlusion 20 min. 60 min. 3hrs. >3-6hrs.

LV

Normal myocardium

Myocardium at risk

Necrosis

Reversible injury Irreversible injury

Reperfusion

Consequences of ischemia/reperfusion

• Stunning• Preconditioning• Tissue viability(no necrosis)

• Subendocardial necrosis(salvage of outer layers)

• Necrosis extends intomidmyocardium, subepicardium

• Near transmural infarction (no salvage oftissue but may lead to negative LV remodeling)

LV

Transmural Wave Front of Necrosis

Each 30 min increase in time-to-treatment resulted ina 21-24% risk increase in transmurality (Thiele et al. Eur Heart J 2007;28:1433)

Myocardial Infarct Imaging

• Morphology (T1w-SE MRI / cine MRI)

• Myocardial edema (T2w-STIR-SE MRI)

• Cardiac function– Systolic (cine MRI / tagging)– Diastolic function: (VENC cine MRI)

• Myocardial perfusion imaging (MPI)

• Tissue Characterization– late or delayed (gadolinium) enhancement– T2* sequences

• Flow & Motion imaging – b-SSFP cine MRI– velocity-encoded cine MRI

• Vessel (coronary artery imaging)– b-SSFP 3D MR(C)A– contrast-enhanced 3D MR(C)A

Myocardial Edema

T2w-STIR MRI (triple IR sequence)

200020009393

myocardiumblood

Non-selective +Selective 180° pulse pair Readout

Mz Data acquisition

fat

Selective 180°Inversion pulse

ECG

TI1 TI2

‘edema-weighted MRI’

relaxation times in ‘infarcted’ myocardium are different from that in normal myocardium (related to increase in free water) (Mc.Namara et al. Circulation 71: 717, 1985)

Francone M et al. J Am Coll Cardiol 2009

Wright J et al. J Am Coll Cardiol Cardiovascular Imaging

Role of Edema Imaging

• increased (free) water content => hyperintense appearance• abnormalities occur very early and persist > 1 week• reflect : area-at-risk (overestimation of true necrotic area)(Dymarkowski et al. Invest. Radiol 2003)

• myocardial salvage (ratio LGE / AAR)– decreases with increasing time to reperfusion (Francone M et al JACC in press)

– reflect ST segment resolution – LV remodeling (Masci PG et al JACCi in press)

• useful to differentiate between acute – chronic infarcts

• findings are non-specific – not necessarily reflect myocardial necrosis (e.g. myocarditis)

• adjacent slow moving/stagnant blood: hyperintense

Aborted Myocardial Infarction

Necrosis / Fibrosis Imaging

• prolonged coronary occlusion leads to irreversible myocardial damage (necrosis)

• infarct healing and scar formation• paramagnetic contrast agents (gadolinium) enhance necrotic / fibrotic

myocardium• new sequences allow improved differentation between normal and

abnormal myocardium

timetime

contrastinjection

infarctedinfarcted myocardiummyocardium

ischemicischemic myocardiummyocardium

firstfirst--passpass delayed delayed enhancementenhancement

bloodblood poolpool

nono--reflowreflow--zonezone

normal normal myocardiummyocardium

33’’ 77’’

1010’’ 2525’’

Contrast-Enhanced Inversion Recovery MRI

Mz

Mxy

180

TI or inversion time

null point (tissue specific)

scarred myocardium

normalmyocardium

Simonetti et al. Radiology 2001Delayed (Contrast) Enhancement (DE / DCE) MRILate (Gadolinium) Enhancement (LE/LGE) MRI

Patterns of enhancement

• 1) subendocardial enhancement• 2) uniform, diffuse (ie transmural) enhancement• 3) centrally dark areas in reperfused infarcts• 4) doughnut pattern in occlusive infarcts

enhancement patterns - reflect infarct severity- related to peak serum enzyme levels- regional functional parameters- prognostically important (3)(4)=> infarct expansion / LV remodeling /

worser outcome

• 5) hemorrhagic infarction• 6) myocardial edema without infarction

(aborted infarction)

de Roos et al. Radiology 1989

(1) Subendocardial (2) Transmural

(3) No-Reflow (4) Occlusive

Post-Reperfusion Myocardial Hemorrhage

Microvascular Obstruction

• lack of reperfusion at tissue level– severe edema compressing intramural vessels or– extensive myocardial necrosis and – microcirculatory damage in center of a large infarction

• no-reflow zone may increase (x 3-fold) first 2d reperfusion (Rochitte et al. Circulation 1998)

– progressive microvascular and myocardial injury after reperfusion• area of no-reflow is a better predictor of LV remodeling than infarct size

(Gerber et al. Circulation 2000)

• MVO independent predictor of adverse remodeling and patient outcome (Hombach et al. Eur Heart J 2006)

3 minutes 20 minutes

Acute phase FU (4 months)

Noninvasive Gold for Infarct Imaging ?

A. Wagner et al. Lancet 2003

necrosis as small as 1g can be detected with CE-IR-MRI <=> 10 g with SPECT

Ibrahim T et al. J Am Coll Cardiol 2007;49:208

CE-IR MRI is superior to SPECT in detecting myocardial necrosisafter reperfused AMI because MRI detects small infarcts that were missed by SPECT independent of the infarct location

Infarct Imaging

– area-at-risk– myocardial necrosis

• location (perfusion territory)• circumferential and transmural extent• tissue characteristics

– microvascular obstruction– postreperfusion myocardial hemorrhage

– impact on regional and global ventricular function– associated findings – complications

• valve regurgitation (papillary muscle necrosis – ventricular dilation)• thrombus formation• myocardial rupture• pericardial inflammation

– baseline exam to evaluate• infarct healing• (adverse) LV remodeling

comprehensive MRI exam in acute MI

LCx Infarction

Infarct Healing – Ventricular Remodeling

Jugdutt B Circulation 2003;108:1395

Integration of DSMRI in Cardiac MRI Protocol

ScoutViews

FunctionalImaging at Rest

Delayed EnhancementMRI

DSMRIlow-dose

DSMRIhigh-dose

Viability

Ischemia