Dynamic Contrast Enhanced MRI

Sungheon Gene Kim, PhD NYUSOM/Radiology/CBI

Dynamic Contrast Enhanced MRI

Normal and tumor vasculature

(Dreher et al., JNCI, 2006, 98 (5):335-‐344)

• The Gd-‐induced dipole dipole interactions with the surrounding water molecules lead to shortening of T1 (broadening of the spectral lines, positive contrast in T1 weighted image).

• The Gd-‐complex also induce susceptibility effects, as a result of the magnetic field gradient between the contrast agents in the blood vessels and the surrounding tissue, that lead to shortening of T2 or T2* (negative contrast).

• Generic name: Gadopentetate dimeglumine,

• Chemical compound: Gadolinium-‐diethylenetriaminepentaacetic acid

•  Introduced in 1981, as the first paramagnetic MRI contrast agent. The used metal ion Gd3+ (Gadolinium) is toxic, and therefore bound in the renally excreted DTPA chelate, a very stable complex.

Gd-‐DTPA

1.  T1 weighted DCE-‐MRI •  Contrast kinetic models •  Practical examples •  Arterial input fuction •  Other things to consider

2.  T2 weighted DCE-‐MRI •  DSC-‐MRI

Contents

Example of DCE-‐MRI T1w-DCE-MRI

(TR=5 ms, TE=4 ms, FA=20 deg, 2.5 s/frame, 10 min)

(Kim et al, JMRI 2007)

Bolus tracking T1w-DCE-MRI

Analysis of DCE-‐MRI Data

(Poptani et al, NMR Biomed, 2003)

S0 : Average of 24 (60 s) precontrast images

Si : Signal intensity

Intensity based measures •  Max slope •  Peak enh. •  Peak time •  Washout slope •  Initial area under the curve (IAUC)

(Noworolski et al, J Magn Reson Img, 2003)

T1w-DCE-MRI

Physiologically relevant parameters

(Taylor et al, J Magn Reson Img, 1999)

T1w-DCE-MRI

EES Extravascular Extracellular Space F Capillary flow P Permeability of capillary wall S Surface area of capillaries E Extraction ratio Ca [Gd] in arterial blood Ce [Gd] in EES Cv [Gd] in veneous blood

Compartmental Model T1w-DCE-MRI

Cp(t) C1(t) K1

K2

Plasma to tissue transfer Parameter Rate constant K1 Rate K1Cp(t)

Tissue to plasma transfer Parameter Rate constant K2 Rate K2C1(t)

Intracellular space (vi)

EES (ve)

At equilibrium,

Volume fraction of EES

Tofts & Kermode Model (Tofts and Kermode, MRM 17:357-67, 1991)

T1w-DCE-MRI

The plasma curve is assumed a bi-exponential decay:

where a1, a2, m1 and m2 are determined empirically.

where

General Kinetic Model T1w-DCE-MRI

Cp(t)

Ct(t) Ktrans

Kep ve

JMRI (1999)

T1w-DCE-MRI

Exercise #1

A N2

Spoiled gradient echo sequence (TE = 4 ms, TR = 5 ms, FA = 20 deg)

Find Ktrans, ve and kep of the tumor ROI N2.

T1w-DCE-MRI Exercise #1

MRI signal to Gd concentration

r1 ~ 5.0 mmol-1sec-1 at 3T

(Liu et al, ISMRM 2005)

Signal from spoiled gradient echo sequence :

Signal enhancement :

If pre-contrast T1 (R1o) is available, S(t) can be converted to Ct(t) .

T1w-DCE-MRI

Exercise #1

A

N2

Spoiled gradient echo sequence (TE = 4 ms, TR = 5 ms, FA = 20 deg)

Find Ktrans, ve and kep of the tumor ROI N2.


Curve fitting

Ktrans = 0.42 min-1

ve = 0.47

Cp(t)

Ct(t) Ktrans

Kep ve


Effect of Ktrans

Ktrans = 0.1 – 1.0 min-1

ve = 0.47

Cp(t)

Ct(t) Ktrans

Kep ve


Effect of ve Ktrans = 0.42 min-1

ve = 0.1 – 0.8

Cp(t)

Ct(t) Ktrans

Kep ve


Can we do better?

Ktrans = 0.42 min-1

ve = 0.47

Cp(t)

Ct(t) Ktrans

Kep ve

GKM with vascular compartment T1w-DCE-MRI

Intracellular space (vi) EES (ve)

Vascular space (vp)

Ktrans = 0.42 min-1

ve = 0.47 vp = 0.001

T1w-DCE-MRI

Delay and Dispersion

(Gabrys et al, 2005) where

(Calamante et al, 2000)

?

?

α=1-5

α=1-5


Extended GKM with AIF dispersion

Ktrans = 0.21 min-1

ve = 0.30 vp = 0.17 α = 7 s (fixed)

Ktrans = 0.42 min-1

ve = 0.47 vp = 0.001

T1w-DCE-MRI

Extraction in capillary bed

Artery

Capillaries

Vein

CA

CV

f

Permeability-Surface area product (PS)

Renkin-Crone model

T1w-DCE-MRI

Ktrans=F(f, PS)

0.2

0.2

0.2 0.2 0.2

0.4

0.40.4 0.4

0.6

0.6

0.6 0.6

0.8

0.8

0.8

1

1

1.2

PS (/min)

Fp (/

min

)Ktrans Map

0.5 1 1.5 2

0.5

1

1.5

2

PS limited

Flow limited

T1w-DCE-MRI

More modeling….

Figure 8 from Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability S P Sourbron and D L Buckley 2012 Phys. Med. Biol. 57 R1 doi:10.1088/0031-9155/57/2/R1

Adiabatic approximation to the TH (AATH, St Lawrence and Lee 1998)

(Sangren and Sheppard, 1953)

(Johnson and Wilson, 1966)

AATH model T1w-DCE-MRI

Ktrans = 0.18 min-1

ve = 0.29 PS = 0.19 min-1

Fp = 1.42 min-1

Tc = 8 s vp = 0.19 α = 7 s

(Taylor et al, J Magn Reson Img, 1999)

Underlying Assumptions T1w-DCE-MRI

1.  Compartments with the instantly well-mixed CA

2.  No CA flux between adjacent EES compartments

3.  Linear inter-compartment flux

4.  Time invariant parameters

5.  Arterial Cp Capillary Cp

6.  Fast exchange of all mobile protons within the tissue

(Dreher et al., JNCI, 2006, 98 (5):335-‐344)

•  Human Squamous Cell Carcinoma (FaDu)

•  BALB/C nu/nu mouse

•  Dorsal skin fold window chamber

•  Red: Rhodamine-labeled 2-MDa dextran

•  Green: dextrans with lower molecular weights (3.3, 10, 40, and 70 kDa)

Tumor micro-‐vascular environment T1w-DCE-MRI

(Dreher et al., JNCI, 2006, 98 (5):335-‐344)

T1w-DCE-MRI

Diffusion of macromolecules

Diffusion of contrast agent

Pellerin et al, MRM 58:1124-1134 (2007)

Diffusion-perfusion (DP) model

T1w-DCE-MRI

Underlying Assumptions T1w-DCE-MRI

1.  Compartments with the instantly well-mixed CA

2.  No CA flux between adjacent EES compartments

3.  Linear inter-compartment flux

4.  Time invariant parameters

5.  Arterial Cp Capillary Cp

6.  Fast exchange of all mobile protons within the tissue

R1 vs. [Gd]

(Landis et al., MRM 42:467-478, 1999; Wedeking et al. MRI 10:97-108)

T1w-DCE-MRI

(Liu et al, ISMRM 2005)

Transcytolemmal Water Exchange

τi

R1i

R1o

•  When [Ct] ~ 0, Water exchange effect not visible to NMR measurement. Fast eXchange Limit (FXL)

•  As [Ct] increases, Water exchange effect becomes visible to NMR measurement. Bi-exp. longitudinal relaxation

Shortening T1

Intracellular space

Extracellular space

T1w-DCE-MRI

Bolus Enhanced Relaxation Overview (BOLERO)/ Shutter-‐Speed Analysis

Bloch-McConnell two-site exchange model

FXR (Fast eXchange Regime)

τI : Mean intracellular water lifetime po : volume fraction of tissue water in EES R1i : intracellular rate constant without exchange R1o : extracellular pre-CR rate constant r1 : extracellular CR relaxivity

SXR (Slow eXchange Regime)

(Landis et al., MRM 42:467-478, 1999)

T1w-DCE-MRI

Application to Breast Cancer

(Huang et al., Radiology 261:394-403, 2011)

T1w-DCE-MRI


2.  T2 weighted DCE-‐MRI •  DSC-‐MRI

Contents

Susceptibility Contrast T2w-DCE-MRI

(Tofts et al., Quantitative MRI of the Brain)

The magnetic field in a sample depends on the strength of magnet and the susceptibility constant of the sample.

Tissue χ = -10-5 ~ -10-6 diamagnetic substance Gd χ = ~ 3.2 x10-7/mM paramagnetic substance

The magnetic field within 1mM solution of Gd in 1.5T (64 MHz) will have approximately a 20 Hz shift in resonance frequency relative to undoped water.

Susceptibility

(Barbier et al., JMRI 13:496-520, 2001)

T2w-DCE-MRI

T2/T2*-‐weighed DCE-‐MRI T2w-DCE-MRI

(Tofts et al., Quantitative MRI of the Brain)

(uL/g)

Cerebral Blood Volume (CBV)


T2w-DCE-MRI

(uLg-1s-1)

Cerebral Blood Flow (CBF)


T2w-DCE-MRI

(From Table 1 and 2)

Tissue rMTT (s)

Human brain 5.0 Baboon 4.2 Rat brain, cortical parietal surface 1.4 Rat brain, whole brain 1.5

Mean Transit Time (MTT)


T2w-DCE-MRI

Kinetic Model Analysis T2w-DCE-MRI

Gradient-‐Echo Experiments: R2* Changes

• At the long echo times and at a high concentration of contrast agent:

• Sensitive to both macro- and microvasculature.


T2w-DCE-MRI

Spin-‐Echo Experiments: R2 Changes

•  Diffusion effects become more visible.

•  With large vessels, each diffusing water molecule experiences an approximately constant field gradient, which can be refocused.

•  For small vessels, a diffusing water molecule experiences a whole range of magnetic fields resulting in the averaging of phase differences.


T2w-DCE-MRI


2.  T2 weighted DCE-‐MRI •  Susceptibility contrast •  CBV, CBF, MTT •  GE vs. SE

Summary

Dynamic Contrast Enhanced MRI

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