Dynamic Contrast Enhance (DCE)-MRI€¦ · Dynamic Contrast Enhance (DCE)-MRI Prof. Dr. Zöllner I...

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Prof. Dr. Zöllner I Slide 29I 11/21/2018

Dynamic Contrast Enhance (DCE)-MRI

� contrast enhancement in ASL: labeling of blood (endogenous)

� for this technique: usage of a exogenous contras agent

� typically based on gadolinium molecules packed inside a chelate to be nontoxic and inert

� interact with surrounding protons

� alter relaxation times (T1, T2*) locally

� increase in signal intensity

� Combined with fast repeated imagingallows for tracking the tracer‘s movement

Cao et al. J. Mater. Chem. B, 2017



� typical molecules of CAs

Cao et al. J. Mater. Chem. B, 2017

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� image acquisition requirements

� heavily T1 weighted images /T2* weighted (for DSC)

� fast repeated imaging to sample the signal change over time (upto 1s)

� respective SNR / resolution

� various appraoches and sequences

� low flip angle GRE sequences (e.g. FLASH) or EPI readout (DSC)

� parallel imaging technology

� underampling scheme

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� radial sampling



� key hole techniques

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� K-t Blast / Sense


Quantification of Perfusion

� so far, learned about the imaging techiques

� what about quantification of perfusion ?

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� General Theory of Tracer Kinetics

� CT(t): the tracer concentration in the tissue of interest defined as the quantity of indicators relative the tissue volume in mol. This quantity is directly measurable.

� λ: the dimensionless volume of distribution, i.e. the fraction of tissue accessible to the tracer. Mostly expressed in ml/100 ml. λ is also referred to as blood-tissue partition coefficient.

� CA(t): the tracer concentration within its volume of distribution in mol, i.e. the arterial tracer concentration. By definition it is: CA(t) = CT (t)/ λ.

� f: the perfusion or clearance in 1/min.



� Tracer

� freely-diffusible: distributed throughout the entire tissue volume→ λ ≈1

� intravascular : restricted to remain in the vasculature→ λ refects the blood volume

� neither destroyed nor created within the physiological system, its mass is conserved

freely-diffusible intravascular

λ λ

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� Exchange of tracer

� rate of change of the CT (t) of a tissue with i inlets and o outlets is given by thedifference between total influx and outflux

� link between inlet and outlet flux given by the time that elapses during the tracer's passage through the tissue voxel

� probability distribution function h of transit times

Sourbron, S. P., & Buckley, D. L. NMR in Biomedicine 2013



� Exchange of tracer

� hi(t) is the fraction of the tracer that flew into the tissue through inlet i at t = 0 and already left it at the time t

� residue function ri(t) describes the fraction of the same tracer that is still present in the tissue at the time t

� reformulated

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� Rewriting of general influx – outflux equation

� denotes the convolution, integrating this

CA(t) CT(t)



� Ri(t) is the residue function of the inlet i that is the fraction of particles entering through i with a transit time >t

� properties

� positive,

� decreasing

� of unit area

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Quantification ASL - General Kinetic Model

� General Kinetic Model by Buxton et al.:

� c(t): the delivery function represents the normalized arterial concentration of magnetization arriving in the imaged voxel at the time t

� r(t; t0): the residue function is the amount of tagged water that entered the voxel at time t0 and still remains at time t

� m(t; t0): the magnetization relaxation function gives the fraction of the original longitudinal magnetization of tagged blood carried by the water molecules that arrived at time t0 that remains at t0.


Quantification ASL - General Kinetic Model

� after the inversion pulse:

� magnetization difference M is 2M0;A,

� M0;A is the equilibrium magnetization of arterial blood.

� tracer concentration CA(t) is then given by 2M0;Am(t)c(t)

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Quantification ASL - Standard Kinetic Model

� analytical solution to the General Kinetic Model

� assumption

� uniform plug flow

� complete and instantaneous extraction of labeled water after its arrival in the tissue.

� no labeled blood arrives in the tissue before a transit delay ∆t

� the label initially decays with the longitudinal relaxation time T1;A of arterial blood

� after arrival in the tissue decays with T1;T, the longitudinal relaxation rate of the tissue



� α is label efficiency, T is bolus length

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� solution for PASL



� solution for PASL

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Example of ASL (A,B) and DCE-MRI (C,D)


Quantification of DCE-MRI

� based on the “tracer-dilution" theory

� two types of approaches can be distinguished� model free� model the physiology of the underlying tissue, e.g.

multi-compartment models

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Quantification of DCE-MRI – Model free

� model-free analysis no assumptions on the interior structure of the underlying tissue are made

� tissue sample is assumed to have a single inlet through which arterial blood is delivered

� tissue-characteristic impulse response function I(t) = f r(t)

� I(t) calculated by deconvolution of CT(t) with CA(t)

since r(o)=1


Quantification of DCE-MRI – Compartment models

� model based approach always tries to incorporate knowledge about the underlying tissue

� one or more compartments

� between compartments a flow exists that exchanges the tracer between them

� extravasation flow can be unidirectional or bidirectional

� >20 years ago Larsson, Tofts, Brix and colleagues published their first approaches to the quantitative assessment of DCE-MRI data for measuring BBB permeability


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� estimated parameters



Quantification of DCE-MRI: Volumes and flows

� 2 independent parameters as a fraction of the total tissue volume:

� plasma volume vp

� interstitial volume ve.

� vp + ve ≤ 1

� 2 independent parameters; rate at which the indicator enters the compartments:

� plasma flow Fp

� permeability–surface area product PS

� perfusion parameters : Fp , vp

� permeability parameters: PS, ve

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Quantification of DCE-MRI: Mean Transit Times

� single mean transit time can be associated with each subspace and with each inlet to the space

� combined extracellular space consisting of plasma and interstitium

� interstitium mean transit time Te is

� plasma mean transit time Tp is


Quantification of DCE-MRI: Transfer constants

� critical measure of tissue function is the rate at which nutrients are delivered to the interstitial space

� volume transfer constant Ktrans

� number of indicator particles delivered to the interstitium, per unit of time, tissue volume and arterial plasma concentration

� kep rate constant between interstitium and plasma

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Quantification of Perfusion – 1-compartment model

� plasma space is modelled as a single compartment

� mass balance:

� compartment is defined as a well-mixed space, i.e. a region

� concentration is spatially uniform within the volume of distribution

� Or space where the diffusion of indicator is very high, so that any concentration differences are immediately levelled out.

� concentration co(t) at any outlet o must equal the uniform concentration c(t).

� mass conservation for a compartment depends on c(t) and the inlet concentrations alone



� plasma space is modelled as a single compartment

� mass balance:

� leads to


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� extraction fraction of a compartment is then

� leads to




� important in understanding tissue and tumor haemodynamics

� interplay of perfusion (Fp) and microvascular function

� measure blood volume (Vp) and capillary permeability surface area product separately from Fp


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� 2-compartment exchange model (2CXM)

plasma compartment

interstitial compartment



� solution of the couple differential equation (impulse responsefunction):

� bi-exponential

� amplitudes and rate constants (Ai,Bi) are functions of the parameters{Fp,vp,PS,ve}

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Example of signal curve, fit and

calculated parametric maps

Soubron et al. Invest Radiol 2008



� today various approaches exist

Sourbron, & Buckley. (2013).. NMR in Biomedicine

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Quantification of DCE-MRI - Tools

� software for perfusion anaylsis exists

� RocketShip, firevoxel, dcmri, UMMPerfusion, dcmri.lj, PMI, …

Zöllner et al., BMC Medical Imaging 2016


Perfusion Imaging - Applications

brain

heart

kidney

lung

liver

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Applications - Brain

� Stroke

� Brain tumors

T2w DWI CBV

T1w, ce CBV fusion

Petrella et al., Am J Roentgenol 2000


Applications - Body

� oncology

Türkbey et al. Diagn Interv Radiol. 2010 , Chang et al. JMRI 2012

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Applications - Body

� oncology

Gaa, et al., Scientific Reports 2017


Applications - Body

� lung function

Weidner et al., European Radiology, 2014

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Applications - Body

� kidney function

Zöllner et al., BMC Medical Imaging 2016


Summary

� Perfusion MRI allows non invasive imaging/ measurementof the perfusion at tissue level

� insights into function of organ/ tissue� two technqiues for imaging perfusion

� ASL and DCE/DSC-MRI� difference in use of contrast agent type to visualize the

perfusion� quantification of the perfusion

� ASL: analytical solution of the signal equations -> Buxton model

� DCE: model based (compartment models) or modelfree anaylsis (deconvolution)

Dynamic Contrast Enhance (DCE)-MRI€¦ · Dynamic Contrast Enhance (DCE)-MRI Prof. Dr. Zöllner I...

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