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 (T 1, T 2* ) locally increase in signal intensity Combined with fast repeated imaging allows for tracking the tracer s movement Cao et al. J. Mater. Chem. B, 2017 Prof. Dr. Zöllner I Slide 28I 10/30/2018 Dynamic Contrast Enhance (DCE)-MRI typical molecules of CAs Cao et al. J. Mater. Chem. B, 2017 Prof. Dr. Zöllner I Slide 29I 10/30/2018 1
Dynamic Contrast Enhance (DCE)-MRI Prof. Dr. Zöllner I Slide 30I 10/30/2018 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 (up to 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 Prof. Dr. Zöllner I Slide 31I 10/30/2018 2
Dynamic Contrast Enhance (DCE)-MRI radial sampling Prof. Dr. Zöllner I Slide 32I 10/30/2018 Dynamic Contrast Enhance (DCE)-MRI key hole techniques Prof. Dr. Zöllner I Slide 33I 10/30/2018 3
Dynamic Contrast Enhance (DCE)-MRI K-t Blast / Sense Prof. Dr. Zöllner I Slide 34I 10/30/2018 Quantification of Perfusion so far, learned about the imaging techiques what about quantification of perfusion? Prof. Dr. Zöllner I Slide 35I 10/30/2018 4
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 36I 10/30/2018 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 λ λ freely-diffusible intravascular Prof. Dr. Zöllner I Slide 37I 10/30/2018 5
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 the difference 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 38I 10/30/2018 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 Prof. Dr. Zöllner I Slide 39I 10/30/2018 6
Quantification of Perfusion Rewriting of general influx outflux equation denotes the convolution, integrating this C A (t) C T (t) Prof. Dr. Zöllner I Slide 40I 10/30/2018 Quantification of Perfusion R i (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 Prof. Dr. Zöllner I Slide 41I 10/30/2018 7
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 42I 10/30/2018 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 C A (t) is then given by 2M 0;A m(t)c(t) Prof. Dr. Zöllner I Slide 43I 10/30/2018 8
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 44I 10/30/2018 Quantification ASL - Standard Kinetic Model α is label efficiency, T is bolus length Prof. Dr. Zöllner I Slide 45I 10/30/2018 9
Quantification ASL - Standard Kinetic Model solution for PASL Prof. Dr. Zöllner I Slide 46I 10/30/2018 Quantification ASL - Standard Kinetic Model solution for PASL Prof. Dr. Zöllner I Slide 47I 10/30/2018 10
Quantification ASL - Standard Kinetic Model Example of ASL (A,B) and DCE-MRI (C,D) Prof. Dr. Zöllner I Slide 48I 10/30/2018 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 Prof. Dr. Zöllner I Slide 49I 10/30/2018 11
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 C T (t) with C A (t) since r(o)=1 Prof. Dr. Zöllner I Slide 50I 10/30/2018 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 Prof. Dr. Zöllner I Slide 51I 10/30/2018 12
Quantification of DCE-MRI estimated parameters Prof. Dr. Zöllner I Slide 52I 10/30/2018 Quantification of DCE-MRI: Volumes and flows 2 independent parameters as a fraction of the total tissue volume: plasma volume vp interstitial volume ve. v p + v e 1 2 independent parameters; rate at which the indicator enters the compartments: plasma flow F p permeability surface area product PS perfusion parameters : F p, v p permeability parameters: PS, v e Prof. Dr. Zöllner I Slide 53I 10/30/2018 13
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 T p is Prof. Dr. Zöllner I Slide 54I 10/30/2018 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 K trans 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 Prof. Dr. Zöllner I Slide 55I 10/30/2018 14
Quantification of Perfusion 1-compartment model plasma space is modelled as a single compartment mass balance: leads to Prof. Dr. Zöllner I Slide 56I 10/30/2018 Quantification of Perfusion 1-compartment model extraction fraction of a compartment is then leads to Prof. Dr. Zöllner I Slide 57I 10/30/2018 15
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 Prof. Dr. Zöllner I Slide 58I 10/30/2018 Quantification of DCE-MRI Compartment models 2-compartment exchange model (2CXM) Prof. Dr. Zöllner I Slide 59I 10/30/2018 16
Quantification of DCE-MRI Compartment models 2-compartment exchange model (2CXM) Prof. Dr. Zöllner I Slide 60I 10/30/2018 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 61I 10/30/2018 17
Quantification of DCE-MRI today various approaches exist Sourbron, & Buckley. (2013).. NMR in Biomedicine Prof. Dr. Zöllner I Slide 62I 10/30/2018 Perfusion Imaging - Applications brain lung heart liver kidney Prof. Dr. Zöllner I Slide 63I 10/30/2018 18
Applications - Brain Stroke Brain tumors T2w DWI CBV T1w, ce CBV fusion Petrellaet al., Am J Roentgenol 2000 Prof. Dr. Zöllner I Slide 64I 10/30/2018 Applications - Body oncology Türkbey et al. Diagn Interv Radiol. 2010, Chang et al. JMRI 2012 Prof. Dr. Zöllner I Slide 65I 10/30/2018 19