Dynamic Contrast Enhance (DCE)-MRI€¦ · Dynamic Contrast Enhance (DCE)-MRI Prof. Dr. Zöllner I...
Transcript of 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
Prof. Dr. Zöllner I Slide 30I 11/21/2018
Dynamic Contrast Enhance (DCE)-MRI
� typical molecules of CAs
Cao et al. J. Mater. Chem. B, 2017
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Prof. Dr. Zöllner I Slide 31I 11/21/2018
Dynamic Contrast Enhance (DCE)-MRI
Prof. Dr. Zöllner I Slide 32I 11/21/2018
Dynamic Contrast Enhance (DCE)-MRI
� 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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Prof. Dr. Zöllner I Slide 33I 11/21/2018
Dynamic Contrast Enhance (DCE)-MRI
� radial sampling
Prof. Dr. Zöllner I Slide 34I 11/21/2018
Dynamic Contrast Enhance (DCE)-MRI
� key hole techniques
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Prof. Dr. Zöllner I Slide 35I 11/21/2018
Dynamic Contrast Enhance (DCE)-MRI
� K-t Blast / Sense
Prof. Dr. Zöllner I Slide 36I 11/21/2018
Quantification of Perfusion
� so far, learned about the imaging techiques
� what about quantification of perfusion ?
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Prof. Dr. Zöllner I Slide 37I 11/21/2018
Quantification of Perfusion
� 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.
Prof. Dr. Zöllner I Slide 38I 11/21/2018
Quantification of Perfusion
� 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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Prof. Dr. Zöllner I Slide 39I 11/21/2018
Quantification of Perfusion
� 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
Prof. Dr. Zöllner I Slide 40I 11/21/2018
Quantification of Perfusion
� 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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Prof. Dr. Zöllner I Slide 41I 11/21/2018
Quantification of Perfusion
� Rewriting of general influx – outflux equation
� denotes the convolution, integrating this
CA(t) CT(t)
Prof. Dr. Zöllner I Slide 42I 11/21/2018
Quantification of Perfusion
� 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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Prof. Dr. Zöllner I Slide 43I 11/21/2018
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.
Prof. Dr. Zöllner I Slide 44I 11/21/2018
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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Prof. Dr. Zöllner I Slide 45I 11/21/2018
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
Prof. Dr. Zöllner I Slide 46I 11/21/2018
Quantification ASL - Standard Kinetic Model
� α is label efficiency, T is bolus length
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Prof. Dr. Zöllner I Slide 47I 11/21/2018
Quantification ASL - Standard Kinetic Model
� solution for PASL
Prof. Dr. Zöllner I Slide 48I 11/21/2018
Quantification ASL - Standard Kinetic Model
� solution for PASL
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Prof. Dr. Zöllner I Slide 49I 11/21/2018
Quantification ASL - Standard Kinetic Model
Example of ASL (A,B) and DCE-MRI (C,D)
Prof. Dr. Zöllner I Slide 50I 11/21/2018
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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Prof. Dr. Zöllner I Slide 51I 11/21/2018
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
Prof. Dr. Zöllner I Slide 52I 11/21/2018
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
Sourbron, S. P., & Buckley, D. L. NMR in Biomedicine 2013
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Prof. Dr. Zöllner I Slide 53I 11/21/2018
Quantification of DCE-MRI
� estimated parameters
Sourbron, S. P., & Buckley, D. L. NMR in Biomedicine 2013
Prof. Dr. Zöllner I Slide 54I 11/21/2018
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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Prof. Dr. Zöllner I Slide 55I 11/21/2018
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
Prof. Dr. Zöllner I Slide 56I 11/21/2018
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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Prof. Dr. Zöllner I Slide 57I 11/21/2018
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
Prof. Dr. Zöllner I Slide 58I 11/21/2018
Quantification of Perfusion – 1-compartment model
� plasma space is modelled as a single compartment
� mass balance:
� leads to
Sourbron, S. P., & Buckley, D. L. NMR in Biomedicine 2013
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Prof. Dr. Zöllner I Slide 59I 11/21/2018
Quantification of Perfusion – 1-compartment model
� extraction fraction of a compartment is then
� leads to
Sourbron, S. P., & Buckley, D. L. NMR in Biomedicine 2013
Prof. Dr. Zöllner I Slide 60I 11/21/2018
Quantification of DCE-MRI – Compartment models
� 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
Sourbron, S. P., & Buckley, D. L. NMR in Biomedicine 2013
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Prof. Dr. Zöllner I Slide 61I 11/21/2018
Quantification of DCE-MRI – Compartment models
� 2-compartment exchange model (2CXM)
plasma compartment
interstitial compartment
Prof. Dr. Zöllner I Slide 62I 11/21/2018
Quantification of DCE-MRI – Compartment models
� 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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Prof. Dr. Zöllner I Slide 63I 11/21/2018
Quantification of DCE-MRI – Compartment models
Example of signal curve, fit and
calculated parametric maps
Soubron et al. Invest Radiol 2008
Prof. Dr. Zöllner I Slide 64I 11/21/2018
Quantification of DCE-MRI
� today various approaches exist
Sourbron, & Buckley. (2013).. NMR in Biomedicine
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Prof. Dr. Zöllner I Slide 65I 11/21/2018
Quantification of DCE-MRI - Tools
� software for perfusion anaylsis exists
� RocketShip, firevoxel, dcmri, UMMPerfusion, dcmri.lj, PMI, …
Zöllner et al., BMC Medical Imaging 2016
Prof. Dr. Zöllner I Slide 66I 11/21/2018
Perfusion Imaging - Applications
brain
heart
kidney
lung
liver
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Prof. Dr. Zöllner I Slide 67I 11/21/2018
Applications - Brain
� Stroke
� Brain tumors
T2w DWI CBV
T1w, ce CBV fusion
Petrella et al., Am J Roentgenol 2000
Prof. Dr. Zöllner I Slide 68I 11/21/2018
Applications - Body
� oncology
Türkbey et al. Diagn Interv Radiol. 2010 , Chang et al. JMRI 2012
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Prof. Dr. Zöllner I Slide 69I 11/21/2018
Applications - Body
� oncology
Gaa, et al., Scientific Reports 2017
Prof. Dr. Zöllner I Slide 70I 11/21/2018
Applications - Body
� lung function
Weidner et al., European Radiology, 2014
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Prof. Dr. Zöllner I Slide 71I 11/21/2018
Applications - Body
� kidney function
Zöllner et al., BMC Medical Imaging 2016
Prof. Dr. Zöllner I Slide 72I 11/21/2018
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)