my conflicts of interest are€¦ · wilke n et al. mrm 1993 • qualitative (eyeballing) •...

MY CONFLICTS OF INTEREST ARE

Grant support, Siemens Medical Solutions

Consultant, GlaxoSmithKline

Advanced Angioplasty 2007

MRI in Ischemic Heart Disease

Stefan Neubauer, MD FRCP FACC Professor of Cardiovascular Medicine

Department of Cardiovascular Medicine University of Oxford

John Radcliffe Hospital Oxford UK

Imaging in Ischemic Heart Disease

•  Chest X-ray

•  Echocardiography

•  Nuclear scintigraphy

•  Catheterisation Resolution

Information Radiation

Invasiveness •  Cardiac MRI

The Comprehensive Cardiac MR (CMR) Examination

•  Cardiac and great vessel anatomy

•  Cardiac volumes and mass

•  Global and regional contractile function

•  Regional myocardial tissue perfusion

•  Regional myocardial tissue characteristics:

Viability, oedema, inflammation, fibrosis, metabolism

•  Coronary artery lumen, wall anatomy, blood flow

Goal: <30 min acquisition, <10 min post-processing

1. What CMR has to offer 2. CMR research in PCI

Comprehensive CMR Study

•  High resolution anatomy

•  Global / regional function

•  Regional perfusion

•  Viability/Oedema/Fibrosis

•  Coronary Angiography

Horizontal long axis Vertical long axis

Cardiac Function: True-FISP MRI

Jane Francis, MR technologist, University of Oxford Centre for Clinical MR Research

Short axis Stack of short axes

+10mm +20mm +30mm +40mm

+50mm +60mm +70mm +80mm +90mm

Base

Apex

Simpson’s Rule

HLA cine Pre-vs. post-surgery MRI

pre post Norm EDV (ml) 1423 167 77-195 EF (%) 3 54 56-78

Selvanayagam J et al, Circulation 2003

Tissue Phase Mapping Regional Tissue Contractility

3D Velocities: Radial, circumferential, longitudinal

Petersen S et al, Radiology 2005

Dobutamine-Stress MR: 4-Chamber

rest 20 µg

40 µg 30 µg

Nagel E et al, Circulation 1999

Influence of image quality

0102030405060708090

100

good / very good moderate

sensitivity (DSE)specificity (DSE)sensitivity (DSMR)specificity (DSMR)

E. Nagel, Z Kardiol 1999



•  Regional perfusion - GdDTPA




<10s

Perfusion

10-20 min

Infarct

[Gd]

time

“First pass” study: Time-intensity curves

Normal

Ischemia/Infarct

LV Blood pool

Myocardial Perfusion - Quantification

Wilke N et al. MRM 1993

•  Qualitative (eyeballing)

•  Semi-quantification (upslope)

→ perfusion reserve

•  Absolute quantification (ml/min x g)

Rest and stress perfusion (i.v. Adenosine 140µg/kg x min)

Regional Myocardial Perfusion

•  n=84

•  Prevalence of CAD 51%

•  Sensitivity 88%

•  Specificity 90%

•  Diagnostic accuracy 89%

Nagel E el al. Circulation 2003

Wolff SD et al, Circulation 2004 Giang TH et al, Eur Heart J 2004

MR IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial) A phase III multicenter, multivendor trial comparing perfusion cardiac magnetic resonance versus single photon emission computed tomography for the detection of coronary artery disease. J. Schwitter, 1 C. Wacker, 2 N. Wilke, 3

N. Al-Saadi, 4 N. Hoebel, 5 T. Simor 6

1 Zurich, Switzerland, 2 Würzburg, Germany, 3 Gainesville/Jacksonville, US 4 Berlin Germany, 5 Munich, Germany, GEHC, 6 Pecs, Hungary

•  33 centres, 1.5 Tesla, 465 patients •  Patients with chest pain undergoing coronary angiography •  CAD defined as >50% diameter stenosis in at least one vessel with at

least 2mm diameter

CardioVascular MR Center Zurich

0

0.25

0.5

0.75

1

0 0.25 0.5 0.75 1 1-Specificity

MR-IMPACT II 33 Centers – Multivendor: Dose 0.075 mmol/kg Gd-DTPA-BMA

*

Sens

itivi

ty


SPECT all n=465 AUC: 0.65±0.03 P=0.0004

Perfusion-CMR n=465 AUC: 0.75±0.02

gated-SPECT n=277 AUC: 0.69±0.03 P=0.018 ungated-SPECT n=188 AUC: 0.63±0.04 P=0.023 P=ns vs Gated

0

0.25

0.5

0.75

1

0 0.25 0.5 0.75 1 1-Specificity

MR-IMPACT II - MVD 33 Centers – Multivendor: Dose 0.075 mmol/kg Gd-DTPA-BMA

Sens

itivi

ty


SPECT all n=339 AUC: 0.72±0.03 P=0.003

Perfusion-CMR n=339 AUC: 0.80±0.03

gated-SPECT n=188 AUC: 0.75±0.04 P=0.040 ungated-SPECT n=140 AUC: 0.69±0.05 P=0.049 P=ns vs Gated 1-3 VD SPECT

MR-IMPACT II It is the largest multicenter MR/SPECT trial performed so far using 99mTc-tracers and ECG-gating (33 centers, 465 patients) It shows:

§  Perfusion-CMR (at 0.075 mmol/kg Gd-DTPA- BMA) is superior to SPECT for the detection of coronary artery disease

§  Perfusion-CMR is a short and safe test, is sensitive and specific, and can be recommended as an alternative for SPECT imaging in experienced centers


Comparison of 3T vs. 1.5T CMR Perfusion 3T Stress 1.5T Stress

•  61 patients (age 64±8 years)

•  Referred for diagnostic CA for investigation of exertional CP

•  Stress/rest perfusion CMR at both 1.5T (Sonata) and 3T (Trio) on same day

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Sens

itivi

ty

3 T AUC: 0.89±0.05

1.5 T AUC: 0.70±0.08

p < 0.05

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Sens

itivi

ty

3 T AUC: 0.89±0.05

1.5 T AUC: 0.70±0.08

p < 0.05

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Sens

itivi

ty

3 T AUC: 0.95±0.03

1.5 T AUC: 0.82±0.06

p < 0.05

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Sens

itivi

ty

3 T AUC: 0.95±0.03

1.5 T AUC: 0.82±0.06

p < 0.05

MVD SVD

3T provided a significant increase in SNR (17±6 vs. 11±2; p<0.01) compared to 1.5T

Cheng A et al, JACC in press

Delayed Enhancement MRI

•  10 – 20 min post Gd DTPA

•  Inversion recovery FLASH or True-FISP

•  “Bright is dead”

•  Normal, stunned, hibernating

myocardium is dark

Kim R et al, Circulation 1999

Kim R et al, NEJM 2001

Delayed Enhancement MRI In vivo infarct imaging

LV Function: cine MRI Myocardial Viability: DE-MRI

Superior to SPECT for the detection of sub-endocardial infarction Wagner et al Lancet 361:378

Example: Acute Antero-Septal Infarction

Relationship between transmural extent of HE before bypass surgery and likelihood of increased contractility after surgery

Transmural Extent of Hyperenhancement (%)

Impr

oved

con

trac

tility

(%)

0

20

40

60

80

100

All Dysfunctional Segments

Selvanayagam J et al Circulation 2004

Example: Viable vs. non-viable myocardium

Baseline Cine

Del. Enhancement

6 Months Cine

Delayed Enhancement Phenomenon

Acute Myocarditis

HCM: Fibrosis

Not specific for ischemic injury

M. Friedrich et al S. Petersen et al McCrohon et al Circulation 2003

DCM: Fibrosis

Imaging of Myocardial Oedema

Aletras et al Circulation 2006

Salvaged myocardium = Area at risk (T2w)– Area of necrosis (DE)

90 min occlusion reperfusion Microspheres: AAR TTC staining: AON

MR Coronary Angiography: Fundamental challenges

•  Small structures (1-4mm diameter)

•  Need 3 D resolution

•  Move rapidly with cardiac cycle

and respiration (RCA by ~ 10cm)

Spatial resolution Temporal resolution

Cardiac cath 0.3 x 0.3 mm 8 ms (shutter speed)

CT Coronary Angiography

Spatial resolution Temporal resolution 0.4 x 0.4 x 0.4 mm 120 ms

Achenbach S, Erlangen University

MR Coronary Angiography

Spatial resolution Temporal resolution 0.6 x 0.6 x 0.6 mm minutes (navigator)

Sakuma H, Matsusaka Central Hospital, Mie, Japan

Future of Coronary MRA

•  “Luminography”

•  Vessel wall: Qualitative/quantitative analysis of atherosclerotic plaque

•  Vessel function: Flow, flow velocity, distensibility

A vascular “one-stop-shop”

Wiesmann F et al Circulation 2003

0 200 400 600 800 1000

250

300

350

400

450

500

550

cros

s se

ctio

nal a

rea

(mm

2 )

time within cardiac cycle (ms)

area AA area PDA area DDA

Distensibility = (Amax – Amin)/Amin * (Pmax – Pmin)

CMR research in patients undergoing PCI

●  CMR: New level of understanding of the

interrelations amongst coronary stenosis, myocardial blood flow, function and irreversible injury

1. Use of CMR in monitoring injury from revascularisation procedures

2. Blood flow in hibernating myocardium

With A. Banning, K. Channon, J. Selvanayagam

Use of CMR in monitoring injury from revascularisation procedures

Questions

●  Occurrence and location of peri-procedural myocardial necrosis

in complex PCI?

●  Relationship between magnitude of troponin rise to the volume

of myocardial tissue loss?

●  Mechanisms of irreversible myocardial tissue injury?

New HE-8.5g; Trop I 4.8

48 consecutive patients undergoing complex PCI all received aspirin, clopidogrel and abciximab

24hr Pre and 24 hr Post PCI MRI; pre and 24 hr troponin I

Selvanayagam JB et al, Circulation 2005

●  2-vessel PCI ●  Stent length >30mm

●  Treated segment involved at least one side branch >20mm

●  Chronic total occlusion

Complex PCI

Irreversible myocardial injury

New Hyperenhancement •  14/48 (29%) patients

4

8

n = 14 n = 48

5% of LV Mass

1.7 % of LV Mass

New

Hyp

eren

hanc

emen

t (gr

ams)

Selvanayagam JB et al Circulation 2005

Correlation of cTnI rise with new myocardial hyperenhancement

3

8

13

18 N

ew H

yper

enha

ncem

ent (

gram

s)

2 5 8 Troponin rise at 24 hrs (ųg/L)

r= 0.84

p<0.001

0

n = 48


Relationship Between Plaque Volume and Occurrence and Location of Peri-Procedural Myocardial Necrosis Following PCI

New HE •  15/64 (23%) vessels

2

4

n = 8 n = 7 New

Hyp

eren

hanc

emen

t (gr

ams)

p = 0.6

Distal Adjacent

Porto I et al, Circulation 2006

Example: Pre PCI

Angiogram IVUS DE-CMR


Example: Post PCI

Angiogram IVUS DE-CMR


Plaque Volume vs. Location of Peri-Procedural Myocardial Necrosis

} * } * } * } *

*p<0.001

No HE Distal Adjacent No HE Distal Adjacent


Blood flow in hibernating myocardium

●  Impairment in perfusion reserve is well recognized in myocardium supplied by significantly diseased coronary arteries (CAD)

●  However, it is unknown whether resting blood flow is abnormal in such myocardium

●  Studies to date mainly using PET have produced conflicting results

Background

Methods 27 patients undergoing percutaneous coronary intervention (PCI) ●  one/ two vessel CAD (>85% stenosis by QCA) ●  at least one dysfunctional segment

Cine & Rest

Perfusion DE CMR

PCI Cine

Rest Perfusion

DE CMR

Cine CMR

9 months 24h 24h

CMR Perfusion: Absolute quantification of blood flow

95% stenosis of proximal LAD


Blood flow in hibernating segments

•  No delayed enhancement

•  Significant recovery of function at 9 months


Segments with

Mean corrected

MBF pre-PCI

* **

* **

p < 0.001 p < 0.0001

NS

Selvanayagam JB et al Circulation 2005

Relationship between transmural scar and baseline/post- PCI blood flow

•  Troponin elevation 24 hr post PCI represents new

myocardial injury •  Both impairment of side branches and distal embolisation of

plaque material contribute to myocardial necrosis during PCI

•  Resting myocardial blood flow is reduced in hibernating myocardium

Summary of Oxford PCI research studies

Clinical CMR Techniques on the Horizon •  Regional strain (tissue phase mapping)

•  Non-contrast perfusion (ASL)

•  Oxygenation (BOLD)

•  23Na-Imaging

•  Metabolism (MRS)

•  7 Tesla

•  Molecular Imaging

Selvanayagam J et al, works in progress

Robson M et al Works in Progress

PCr

γ- !α- !β-ATP

2,3-DPG

PDE

! 5 !0 !-5 !-10 !-15 !-20 ppm

Non-invasive imaging tool

MRI in Ischemic Heart Disease

Multi-parametric phenotyping

Clinical studies of patients with IHD

Diagnostic Cardiology

Acknowledgments

OCMR Joseph Selvanayagam, Ranjit Arnold, Adrian Cheng

Collaborators Adrian Banning Keith Channon Michael Jerosch-Herold Italo Porto William van Gaal

Funding British Heart Foundation Medical Research Council The Wellcome Trust Siemens Medical Solutions

Myocardial Viability: Clinical Relevance

Schelbert H et al, Seminars in Nuclear Medicine 2002

Pagano et al, J Thorac Cardiovasc Surgery 1998

Cardiac Function: MR vs. Echo

•  ~10 x higher contrast

•  ~10 x more accurate

•  True 3D

•  Independent of geometric assumptions

•  Any plane

•  Right ventricular planes (ARVC)

•  Independent of acoustic window

•  Unlimited field of view

•  Part of one-stop-shop

•  Availability

•  Cost

•  5% claustrophobic

•  MR contraindications:

- Pacemaker

- Ocular foreign bodies etc.

+ -

Myocardial Perfusion: MR vs. Nuclear

•  Much higher spatial resolution

•  Transmural extent

•  Radiation free

•  Fast (15 minutes)


•  Prognostic data missing!

•  Quantification

•  Data processing

+ ?

Myocardial ViabilityThe Clinical Problem:

Akinetic myocardium,supplied by stenosed coronary artery

Viable= Stunning, Hibernation

Non-viable= Scar

Revascularisation(PTCA, CABG)

No Revascularisation

Myocardial Viability: MRI > Echo or Nuclear

•  Specific contrast for non-viable tissue

•  Highest resolution (2 g detectable), quantification in g

•  Transmural aspect of viability

•  Radiation-free

•  No need to stress the heart

•  One contrast agent bolus for both perfusion and viability


Quantification of Global Myocardial Function

COMass EF EDV ESVl/ming % ml ml

LV 6.6±1.4112±27 69±6 150±31 47±15

RV ---38±8 61±6 173±39 69±22

Hudsmith et al, JCMR 2005 n = 108

Comparative Sample Sizes, Echo vs CMR

Change Echo CMR

LV EDV 8.3 mL 250 46 (18%)

LV ESV 5.5 mL 250 34 (14%)

LV EF 2.3% 250 50 (20%)

LV Mass 12.7 g 250 8 (3%)

Power 80%, P<0.05

Otterstad, Froeland, St John Sutton, Holme. Eur Heart J 1997

Bellenger, Davies, Francis, Marcus, Pennell. JCMR 2000

DSE DSMR p sensitivity 74.3% 88.7% < 0.05

specificity 69.8% 85.7% < 0.05

+ prediction value 81.0% 91.3% < 0.05

- prediction value 61.1% 78.3% < 0.05 accuracy 72.7% 86.0% < 0.005

E. Nagel, Circulation 1999;99:763-770

Methods ●  The diagnostic coronary angiogram was used to define affected

myocardial segments

●  Wall motion was assessed visually:

normal 1; hypokinetic 2; akinetic 3; dyskinetic 4.

●  In each slice, MBF was determined for 8 myocardial sectors in ml/min/g by deconvolution of signal intensity curves with an arterial input function measured in the LV blood pool

Jerosch-Herold, M. et. al JMRI 2004

Results Coronary lesion severity was 80-95% stenosis by quantitative coronary angiography

Mean MBF normalized by rate pressure product (‘corrected MBF’) was 1.2+/-0.3 in segments without significant coronary stenosis and 0.7 +/-0.2 in segments with coronary stenosis pre PCI (z=23.9, p<0.001)

Early post procedure, the MBF was 1.2+/-0.2 in revascularised segments, and 1.3+/-0.2 in non-diseased segments

Methods

Prep

3 Min Adeno

0.14mg/ /kg/min

LE Imaging

BH BH

25‘

MR Study and Monitoring:


–2 to 0h Vit Signs

12-ECG

1-1.5 h Vit S

12-ECG

24 h Vit S Phys

12-ECG Lab AE

1 h Vit S

12-ECG

- 36h to 0 h History

Phys. Exam Symptoms Preg Test Blood Lab

≤4 weeks: QCA

≤4 weeks: SPECT

≤4 weeks: QCA

≤4 weeks: SPECT

0.075 mmol/kg Gd-DTPA-BMA

0.075 mmol/kg Gd-DTPA-BMA

Vital signs (HR, BP, O2 sat, etc)

~1.5h

72 h AE 10‘

SPECT stress perfusion 99mTc: Sestamibi, Teboroxime, Tetrofosmin

SPECT Study: gated-SPECT (ungated-SPECT allowed if clinical routine)

Multi-Vendor 1-Day Protocol permitted

Preparation

Adeno 0.14mg/ /kg/min

Stress Rest


Methods

Identical to stress perfusion 99mTc: Sestamibi, Teboroxime, Tetrofosmin

•  Physics complex

•  Nuclear spin

•  External magnetic field

•  RF waves -> FID

MR (NMR) - Nuclear Magnetic Resonance

•  Magnetic field gradient

•  MR image contrast: - Spin density - Relaxation (T1, T2) - Flow - Pulse sequence

Nature 1973; 242:190-191

my conflicts of interest are€¦ · wilke n et al. mrm 1993 • qualitative (eyeballing) •...

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