Vulnerable Plaque: Pathologists View Signal Quantification · Marcelo Andia, KCL and PUC Quantification of Contrast Uptake RF Gy Gx Signal Signal RF Gy Gx T2* Cartesian Radial T2*

1

MR Imaging of Atherosclerosis

René M. Botnar, PhD Chair of Cardiovascular Imaging Division of Imaging Sciences and Biomedical Engineering King’s College London

Atherothrombosis

Adapted from Choudhury et al. Nat Rev Drug Discov. 2004

Biomarkers*in*Atherosclerosis*

albumin

Vulnerable Plaque: Pathologists View

A) Pathogenesis of atherosclerosis. Falk E et al. J Am Coll Cardiol 2006; 47:C7-12 B) The popcorn plaques. Jagat Narula & H William Strauss. Nature Medicine 13, 532 - 534 (2007)

A)# B)#

Signal Quantification

Pulse#sequences#can#be##designed#to#allow#

quan3fy*3ssue*T1,*T2*and*T2**relaxa3on*3mes*

T1#and#T2*#mapping#allows*quan3fica3on*of*contrast*agents*based*on*their*T1*and**T2**values*

*

N AQ N AQ N AQ N AQ

S S S

t

Mz

S Saturation pulse N Navigator AQ SSFP acquisition

1/T1 = 1/T10 + r1 * [Gd]

Mz(t) = M0 – M0•exp(-t/T1)

Heart rate independent!

T1 Mapping: Saturation Recovery

raw data

subject #1 #2 #3 #4 mean ± SD

T1pre[ms] 737 737 737 737 n/a

T1post[ms] 366 377 354 316 353 ± 27

c [µMol] 92 86 98 121 99 ± 15

T1 T1w

RV LV

RVOT

1500 ms

60 ms

LAD

60 ms 60 ms

T1 T1 1500 ms 1500 ms T1 maps T1w BB image

Quantification of Contrast Uptake

2

AQ

t

Mz

T1 Mapping: Inversion Recovery

AQ AQ AQ AQ AQ AQ AQ IR IR

M0*

M0

-M0*

1/T1 = 1/T10 + r1 * [Gd]

Estimation of Relaxivity

0"

50"

100"

150"

200"

250"

0.2" 1" 1.8" 2.6" 3.4" 4.2" 5" 5.8" 6.6" 7.4" 8.2" 9" 9.8"

R1#[1

/s]#

contrast#agent#concentra0on#[Gd]#

Relaxa0on#rate#vs.#Gd#concentra0on#

r1"="5/s"

r1"="10/s"

r1"="20/s"

R1 = R10 + r1 * [Gd]

r1 = ΔR1 / [ΔGd]

R1 = R10 + r1 * [Gd] R1 = 1/T1

Marcelo Andia, KCL and PUC

Quantification of Contrast Uptake

RF

Gy

Gx

Signal Signal

RF

Gy

Gx T2*

Cartesian Radial

T2*

T2* Quantification

signal = A*e-n*TE/T2* n = echo number TEn = n-th echo time A = Mz * cos (alpha)

T2* Quantification

signal = A*e-n*TE/T2* n = echo number TEn = n-th echo time A = Mz * cos (alpha)

1T2*

= 1T2

+ 1T2'

1T2'

= 1γ ⋅ ΔB

R2* = R20* + r2* ⋅[Gd]

R2* = 1T2*

A ⋅e−n⋅ TE

T 2*

T2* Quantification

y = 3.1234x - 97.831 R² = 0.96109

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

20 30 40 50 60 70 80

% Y

ello

w s

tain

(Red

Cel

ls)

Thrombus Average R2* value [Hz]

y = 7.3238ln(x) + 10.314 R² = 0.94163

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

45.0

0 5 10 15 20 25 30

Ave

rage

T2*

Thr

ombu

s Va

lue

[ms]

Days after Venous Thrombosis

3

Tissue Characterization

Pulse#sequences#can#be#designed#to#allow#differen3ate*between*3ssues*based*on*their*T1*and*T2*relaxa3on*3mes*

T1w,#T2w#and#PDw#MRI#allows*enhancing*or**suppressing*3ssues*based**on*their*T1,*T2*or*proton**density*values*

*

Imaging Sciences Interdisciplinary

Medical Imaging Group BLACK BLOOD T1W IMAGING

� �� $

ECG

Mid$diastole+

NAV

3D TSE or TFE TE = shortest Fa

tSat

Dua

l-IR

prepulses+ imaging+ECG triggered: TR = every heart beat Non triggered: every TR= 300-500ms

iMSD

E

QIR


Medical Imaging Group DUAL-INVERSION T1W IMAGING

� �� $

ECG

Mid$diastole+

3D TSE TE = shortest Fa

tSat


RF

180° 180°

Gz

Dual-IR Black Blood Imaging

��

ECG

Mid$diastole+


tSat

RF

180° 180°

Gz

Intraplaque Hemorrhage

Mz

1

-1

α α α α α

black blood

180° 180°


Medical Imaging Group QUADRUPLE INVERSION

� �� $

ECG

Mid$diastole+


tSat


RF

180° 180°

Gz

RF

180° 180°

Gz

TI1 TI2

QIR Black Blood Imaging

Post contrast: fibrous cap enhancement

��

ECG

Mid$diastole+


tSat

RF

180° 180°

Gz

180° 180°

Mz

nsIR Acquisition

TI1

nsIR

TI2

4

iMSDE Based Black Blood Imaging

Wang J et al. PLoS ONE 6(10): e26567.

Φ(r0, t) = γ ⋅r0 ⋅G ⋅ t

Φ(v, t) = γ ⋅v ⋅G ⋅ t2

Static spins:

Moving spins:

B1(t)

90°

G(t)

Φ(t)

static

moving

S(t)

Comparison– Dual-IR vs. iMSDE

Dual$IR+ iMSDE+

iMSDE+coronary+wall+

1. Wang J et al. PLoS ONE 6(10): e26567.


Medical Imaging Group T2W IMAGING

� �� $

ECG

Mid$diastole+

NAV

3D TSE TE = 50-80ms Fa

tSat

Dua

l-IR

prepulses+ imaging+ECG triggered: TR = every 2nd heart beat Non triggered: every TR= 2000-3000ms

iMSD

E

QIR


Medical Imaging Group PDW IMAGING

� �� $

ECG

Mid$diastole+

NAV


tSat

Dua

l-IR

prepulses+ imaging+ECG triggered: TR = every 2nd heart beat Non triggered: every TR= 2000-3000ms

iMSD

E

QIR

T1w, T2w, PDw and TOF Images

iMSDE+

Figure 4

* * *

* *

TOF T1W CE-T1W

PDW T2W

Contrast Enhanced Imaging

Pulse#sequences#can#be#designed#to#visualize#contrast*agents*based*on*their*T1*or*T2*shortening*effects*

#Inversion#recovery#or#DCEFMRI#

allows*enhancing*3ssues*with*gadolinium*uptake*while**suppressing*3ssues**without*contrast*uptake*based*on*their*T1*relaxa3on*3me*values*

*

5


Medical Imaging Group INVERSION RECOVERY (T1W)

� �� $

ECG

Mid$diastole+

NAV

3D TFE Fa

tSat

IR

prepulses+ imaging+

Inversion Recovery Imaging (T1w)

DE-MRI Fusion HE EvG

Control

4 weeks HFD

8 weeks HFD

12 weeks HFD

Treatment

a Inversion delay

ECG Inversion delay

trigger delay

Mz

1

-1

α α α α α

background tissue

180° Gd

blood

DE-MRI

Intraplaque Hemorrhage Imaging

DE-MRI

Kawasaki*T*et*al.*JACC*Imaging.*2009*Oei*ML*et*al.*Eur*Radiol.*2010

CTA CTA MRA

DE-MRI DE-MRI


Medical Imaging Group DCE-MRI

B1(t)

Gx(t)

S(t)

α

Gz(t)

Gy(t)

2D GRE 2D GRE

B1(t)

Gx(t)

S(t)

α

Gz(t)

Gy(t)

10-30s

5-10ms

DCE-MRI Images

Figure 8

Lumen/Wall Identification on

T1W image

Registration / Filtering of DCE-MRI

Automated Processing of

DCE-MRI

Registration of Lumen

Boundary

Blood CurveExtraction

Kinetic Modeling

Optimization of Outer Wall Boundary Average

Ktrans

Ct(t): tissue Gd concentration Cp(t): plasma Gd concentration

Non Contrast Angiography

Spin#Labeling#or#T2prep#allows*enhancing*or**suppressing*3ssues*based**on*their*T1,*T2*values*

*

6

180x° Non

Selective

Adiabatic Pulse

TI 1 TI 2

RR

Trigger Delay

nsIR sIR AQ NNR NS

180x°

Selective

Rest Slab

180x° Non

Selective

Adiabatic Pulse

180x°

Navigator

Restore

nsIR

��Mz

nsIR Acquisition

TI1

nsIR

TI2

180x° Non

Selective

Adiabatic Pulse

TI 1 TI 2

RR

Trigger Delay

nsIR sIR AQ NNR NS

180x°

Selective

Rest Slab

180x° Non

Selective

Adiabatic Pulse

180x°

Navigator

Restore

nsIR

�� Mz

nsIR sIR Acquisition

TI1

nsIR

TI2

180x° Non

Selective

Adiabatic Pulse

TI 1 TI 2

RR

Trigger Delay

nsIR sIR AQ NNR NS

180x°

Selective

Rest Slab

180x° Non

Selective

Adiabatic Pulse

180x°

Navigator

Restore

nsIR

Mz

nsIR sIR Acquisition

TI1

nsIR

TI2

Contrast Enhancement

T1 [ms] T2 [ms] f0 [Hz] flow

Blood 1200 250 0 yes

Muscle 850 50 0 no

Fat 250 100 220 no

Contrast Enhancement

!  T2 Prepulse

x

y z

90 -90 180 RF 180 180 180

TE

time

1)  Brittain JH, et al., Magn Reson Med. 33:689-696 (1995). 2)  Botnar RM, et al.: Circulation. 99(24):3139-3148 (1999).

muscle

blood

7

T2prep 90 -90 180 RF 180 180 180

TE

time

T2prep OFF T2prep ON

ECG

3D GRE Nav T2prep

TE1

Gp

Gr

DAQ

Gs

RF

dTE

TR

B)

C)

D)

E)

A)

Water/Fat Coronary Imaging

S0 = (W + F) ⋅eiΦ0 S1 = (W − F) ⋅eiΦ ⋅eiΦ0

W = 0.5 ⋅ S0 + S1

F = 0.5 ⋅ S0 − S1In phase Out of phase

Nehrke K. et al. Radiology


Medical Imaging Group

Respiratory Motion Correction

End expiration

End inspiration

3D NAV

2D Self-Navigation

��

Motion Correction

Henningsson M et al. MRM 2011

a a

a a

i jj jz z e θ⋅ ⋅= ⋅

2a

a

aFOVπθ ⋅Δ=

a a a→ +Δ

1 2 5 7 (a) (b) (c) (d)

(e) (f) (g) (h)

��#��!� ��$��%��

Henningsson M et al. MRM 2011

2D Self-Navigation

8

Coronary Lumen Sequence

Li D et al. Radiology. 1996 Botnar RM et al. Circulation. 1999 Stuber M et al. JACC. 1999

Coronary Wall Sequence

Inversion!

Dual Inversion!

Spin Echo!


Medical Imaging Group VESSEL WALL MRI

� �� $

ECG

Mid$diastole+

NAV

3D Spiral

FatS

at

Local+Inversion+(black+blood)+

180° 180°

RF

Gx

Gy

kx

ky

Coronary Vessel Wall Imaging Double Inversion Radial Sequence

3D radial

Katoh M et al. J Magn Reson Imaging. 2006;23(5):757-62.

Courtesy: Marcelo Andia MD MSc and Markus Henningsson MSc

iT2prep Vessel Wall Imaging (T2prep on / off)

�� !�

�"�! ��!��&��!��'��"�! ��!��

blood Tissue

L1

L2

L3

4f 4g

4h 4i

4j

LCA

RCA

Ao

1 cm

0.00

0.20

0.40

0.60

0.80

1.00

No

rmal

ized

Sig

nal

Inte

nsi

ty

0.00

0.20

0.40

0.60

0.80

1.00

No

rmal

ized

Sig

nal

Inte

nsi

ty

0.00

0.20

0.40

0.60

0.80

1.00

No

rmal

ized

Sig

nal

Inte

nsi

ty

L1 L2 L3

9

Conclusions*

•  MRI provides many contrast weightings that allow imaging

•  vessel lumen

•  vessel wall (morphology)

•  vessel wall vascularity (DCE-MRI)

•  vessel wall biology (CE-MRI)

•  advanced motion correction " coronary lumen and vessel imaging

Thank You! •  King’s College London

•  Alkystis Phinikaridou, PhD •  Marcus Makowski, MD •  Alberto Smith, PhD •  Reza Razavi, MD •  Phil Blower PhD •  Tobias Schaeffter, PhD •  Eike Nagel, MD •  Marcelo Andia MD MSc •  Sarah Peel, MSc •  Markus Henningsson, MSc •  Ajay Shah, MD •  Michael Marber, MD •  Alice Warley, PhD •  Friederike Cuello, PhD •  Andrea Wiethoff, PhD •  Boris Bigalke, MD •  Andreas Indermuehle, MD •  Britta Butzbach, MD •  Rafa Torres, PhD •  Andreas Protti, PhD •  …

•  BIDMC, Harvard, Boston –  Warren Manning, MD –  Dana Peters, PhD –  Reza Nezafat, PhD

•  TUM München –  Christian von Bary, MD –  Tareq Ibrahim, MD –  Anne Preissel, VMD –  Silvia Schachoff, RT –  Albert Schoemig, MD –  Markus Schwaiger, MD

•  Charité, Berlin –  Matthias Taupitz, MD

•  Lantheus Medical Imaging –  Simon Robinson, PhD –  Joel Lazewatsky, PhD –  David Onthank, PhD –  Richard Cesati, PhD

Vulnerable Plaque: Pathologists View Signal Quantification · Marcelo Andia, KCL and PUC Quantification of Contrast Uptake RF Gy Gx Signal Signal RF Gy Gx T2* Cartesian Radial T2*

Documents