Perfusion MRI: Technical Aspects 장건호 경희대학교영상의학과
Objectives 관류영상방법의원리를이해. 1. DCE perfusion MRI 2. DSC perfusion MRI 3. ASL perfusion MRI 관류영상방법의최신동향을이해.
Contents Perfusion( 관류 ) MRI Exogenous Dynamic Contrast Enhanced (DCE, bolus passage) Dynamic Susceptibility Contrast (DSC, bolus tracking) Endogenous Arterial spin labeling (ASL)
Abbreviations BBB: blood- brain barrier SI: signal intensity T1W: T1- weighted (T1WI, imaging) T2*W: T2*- weighted (T2*WI, imaging) EPI: echo planar imaging EES: extravascular- extracullular space AIF: Arterial input function
Terminologies and Units CBV: Cerebral Blood Volume 4 ml blood/100g tissue CBF: Cerebral Blood Flow 50 ml blood/100g tissue/minute Time related factors T0: Arriving Time (sec) MTT: Mean Transit Time (5 sec) TTP: Time- to- Peak (sec) K trans : Transfer constant, permeability factor 1/minute
1. DCE Perfusion MRI Exogenous Sequences 2D Dynamic T1W MRI 3D Dynamic T1W MRI Applications Breast Prostate Pelvic Muscle Brain
DCE Perfusion MRI Short TR Short TE Small flip angle Long scan time Output Factors Initial slope, T0, Time to peak, Area under curve (AUC, blood volume or CBV ) EES (Ve) volume, Ktrans
GD- DTPA 조영제 In the normal brain, the BBB keeps GD inside the blood capillaries; it cannot reach the brain tissue outside the capillaries. The blood volume in the normal brain is small (about 2-4%), and no signal enhancement is seen. In MS or tumors, the capillary wall (endothelium) is damaged, GD can escape into the relatively large EES. GD is a contrast agent which decreases the value of T1, and hence increases the SI in a T1W sequence. In the EES there can be enough GD to reduce T1 and hence increase signal.
DCE Signal- to- Time Curve The time to peak and peak enhancement vary according to the kind of lesion. Parameters have been used to characterize GD enhancement: Initial slope Time to peak Area under curve (AUC)
Pharmacokinetic Compartmental Model T1 depends on GD concentration. Be often used by an in- vitro value for relaxivity. Be ignored in intravascular tracer. The T1 of the tissue before injection of GD must be known in order to calculate CBF. T1 maps
Two- compartment parmacokinetic model The driving parameters in this model are: PS: the permeability surface area product of the endothelium, Ktrans Ve: the fractional size of the EES (0<Ve<1) AIF: the time course of blood plasma GD concentration CA: the dose or tracer of injected GD
Other New Parameters in DCE Two parameters PS and ve characterize the biology of the situation. rate constant : kep=ps/ ve (Brix model) What does Ktrans signify? In a limited permeability situation (ex, MS) Ktrans=PS (flow>>ps)= Limited permeability model Acute MS lesions: Ktrans=0.050/ min and ve=21% Chronic MS lesions: Ktrans=0.013/ min and ve=49% In a limited flow situation (ex, tumor): Ktrans=flow (flow<<ps)=pwi perfusion imaging Often mixed PS and flow- weighting Hard to interpret Larger contrast agents have lower PS, so can give limited permeability behavior in tumors. Hence measure flow and PS separately.
Generalization to Permeability ( K trans ) In tumors PS is higher than in MS, and often CBF is insufficient to maintain the local plasma concentration at the arterial level. Thus GD uptake may reflect flow not permeability. From: A. G. Sorensen MD @ MGH
CBF Calculation in DCE T1W DCE gives CBF under conditions of: Low PS (i.e. flow- limited) and Blood plasma volume (vp) not too big (IV tracer not modeled well).
Example
Current Issues of DCE Imaging Protocol: temporal vs spatial resolution 3D Fast GE T1W sequence TR<7 msec, TE<1.5 msec, FA=30 AIF can be ideally measured with MRI Hard to get a slice, Partial volume errors Good temporal resolution needed Signal nonlinear with high GD concentrations Modeling: IV tracer: incomplete exchange of intravascular and extravascular water reduces the visibility of IV GD. Distributed system (tissue homogeneity model better?)
2. DSC Perfusion MRI Exogenous Sequences 2D Gradient- echo T2*W MRI 2D Echo- planar imaging (EPI) T2*W MRI 3D T2*W MRI Application Brain
DSC Perfusion MRI Long TE (35 msec) Intermediate TR (2 sec) High flip angle (90 degree) Short scan time Factors CBV, CBF, MTT, T0, TTP
DSC or T2*W PWI pmri Common outputs: CBF, CBV, MTT, Peak height, Percent signal recovery 조영제의주입으로 Susceptibility( 자화감수성 ) 이증가하며, T2* 신호가감소하게됨. 이감소를시간에따른 T2* relaxivity contrast 변화 ( R2*) 로나타내게됨. 영상은 EPI sequence 를이용하여얻게되고한 volume 을얻는데약 1.5-2 초정도가소요된다.
Signal intensities
Change in MRI signal due to passage of contrast agent Figure from Cerebral MR Perfusion. Sorensen and Reimer A. Pre-injection baseline B. Contrast arrival C. Peak signal change D. Recirculation E. Post-injection baseline A. Arrival time B. Maximum contrast concentration C. Full-width at half maximum
CBF measurement in DSC C m ( t) = CBF AIF( t) R( t) unknown known [Ostergaard et al. 1996] C m C m (t) : measured concentration curve in tissue CBF : Cerebral Blood Flow [ml/100g/min] AIF (t) : Arterial Input function R (t) : Residue function ( g / ml) 1 ( t) = ρ CBF( ml /100g / min) (min/ sec) AIF( t) R( t) k 60 H
Example of MCA- AIF AIF: 정량적인 flow을얻기위해서는 brain- feeding artery 에서조영제농도의변화를알아야됨
Deconvolution Deconvolution 을위한최초발표된 singular value decomposition (SVD) 방법 : 낮은 SNR 와 residue function 에대해독립적이기때문에사용이편리 조영제의 delay에의존도가커서여러다른방법이최근에개발되고있음 최근개발된 Deconvolution 방법 : modified SVS Fourier method 및 maximum- likelihood expectation maximization (MLEM)
Current Issues I Data presentations First fitting for each voxel and then average ROI First average ROI and then fitting. Flow quantifications Linear relationship: 조영제의농도와 R2* 의변화가선형관계 실제로는비선형적 (quadratic relation) 관계임. Phase를이용한 flow quantification: 조영제의자화감수성에따른혈관내 magnetic field가변화하여선형적인 Phase 변화를유발 이 phase 변화에기초를둔조영제의변화를이용한 flow quantification이개발되고있음.
Current Issues II AIF and Partial Volume Effect (PVE) GE 영상에서는 voxel 크기가커서 PVE의문제가발생 Artery가 main magnetic field에 parallel 평행인경우 : artery 내부의신호만이변화하게되며 partial volume에의한 voxel 내의총신호는 blood와주위 tissue 의합. 따라서 PVE 를어렵지만수정할수가있음. Artery가 main magnetic field와 non- parallel 경우 AIF를 MCA나 local AIR algorithms 을사용할경우에발생하고 조영제로인해 vessel 이외의 tissue 도신호가변화 voxel 내의신호는 vessel의직경, vessel 에대한 voxel 의위치, main magnetic field 에대한 vessel 의각도및 voxel의위치에따라변화 partial volume effect 를보완하기가매우힘들다. 최근에는 local AIF 방법이개발되고있는데이경우는한개의 AIF가아닌각각의 voxel에대한 AIF 값을이용.
Current Issues III Data Corrections Hematocrit 양의차이의보정 : 주입된조영제는 intravascular 와 extracellular space 에만작용 큰혈관과작은혈관사이에 Hematocrit 양의차이가존재하여이를보정해야함 각각의환자에대해측정하기가불편하여일정상수로처리 Dispersion 에대한 flow 값의오차가발생 Local AIF 방법에의하여수정될수있음 최적의 bolus profile 을얻기위해서는 4-5 ml/sec 로조영제를주입 약 20 gauge 의 IV line 을이용하는것이좋음
Output Maps
3. ASL Perfusion MRI Endogenous Sequences 2D Proton- density weighted EPI MRI 3D Proton- density weighted EPI MRI Applications Brain Heart Kidney Muscle
ASL Perfusion MRI Long TR (3 sec) Short TE (shortest) High flip angle (90 degree) Long scan time with multiple averaging Factors CBF, (T0, TTP, CBV)
ASL pmri Common output: CBF ASL perfusion 영상 : RF 펄스를이용하여 arterial blood 의 longitudinal magnetization 를변화시켜얻는방법 blood 의 T1 relaxation 시간이영상의질을좌우 Control or Reference 영상 : blood 는자화없이영상 Labeled or Tagged 영상 : blood를자화시킨후에영상 PWI = Control - Labeled ASL 방법 : pulsed ASL (PASL) continuous ASL (CASL) velocity selective ASL(VS- ASL) Vascular Territory Imaging (VTI)
Development issues static tissue 의기여도를최소한도로줄이고 blood labeling 효과를최대한도로높이기위함 Static tissue의기여로 flow 량의계산에오차가발생하는데그주된이유중의하나가 magnetization transfer (MT) effect에의한것임
PASL vs CASL PASL 방법 : 짧은시간동안 blood 를 labeling 하는방법 기존에사용되고있는일반 MRI 장비로사용이가능 예 : FAIR, PICORE, EPISTAR, UNFAIR, EST, TITL, DIPLOMA 및 IDOL CASL 방법 : 긴시간동안 flow driven adiabatic inversion 에의해 blood 를 labeling 하는방법 특별한하드웨어의지원이필요 PASL 방법에비하여어려움 SNR이높은것이장점 pseudo- CASL이개발 기존의 CASL에서사용되는 continuous RF irradiation 부분을연속적인 discrete RF 펄스로대처 기존 CASL에서사용되는 continuous gradient 부분을연속적인 discrete gradient 펄스로대처 이로인해 RF 펄스의공명영역이증가하여 MT effect를약 20% 줄었으며 SNR을높이고특별하드웨어없이일반장비에서도사용가능 임상연구에사용하는데는한계가있음.
DIOLOMA ASL pmri Labeling or Tagging Scan Control or Reference Scan Jahng et al. Magn Reson Med 2003
Principle of ASL Blood is tagged at inferior using inversion pulse. Tagged blood is flowing into capillary sites of brain with relaxing T 1b of blood. Tagged blood exchanges into brain tissues from capillary vessel with relaxing T 1t of tissue. Some of tagged blood is also flowing out in venous vein.
Principle Sequence for ASL Perfusion Double Inversion with Proximal Labeling both tag and control images: DIPLOMA Label Control Saturation For Bolus Imaging By EPI TIME
Why High Field ASL? Advantages Higher SNR Longer blood T1 Limitations Physiological noise Susceptibility effects Wang et al MRM 2002
CBF by Evaluating Kinetics of Perfusion Voxel T 1blood Blood T 1tissue ATT T ex M 0_blood Time
Complicated Kinetics of Perfusion M 0_blood T 1blood Voxel Macromolecular pool Blood T 1tissue ATT T ex Back flow Gradients of Blood Concentration Time
Dynamics of ASL pmri Labeled water flows into capillaries and exchanges with tissue water Perfusion Signa al ATT Tex T1blood; T1tissue Li et al, Magn Reson Med 2005 Time
VS- ASL 뇌졸증환자와같은 cerebrovascular diseases 환자의경우 labeled blood 가영상영역으로흐르는시간이각각다르며 blood T1 값보다시간이길게될수있음 VSASL 방법 : blood 의최저속도를기준으로 (cutoff velocity Vc) 설정 그이상의혈류에대해서만 labeling 하는방법 spatial selection 은없으며일정시간 TI 후에피의속도가 Vc 이하인것만 (decelerated blood only) 영상을얻는방법 venous blood 의 acceleration 효과때문에 venous blood 의기여도를줄일수있음.
Vascular Territory Imaging (VTI) Cerebrovascular disease 환자에서 stenotic vessel 들이여러개있을경우 carotid endarterectomy, stenting, 혹은 bypass 등의 intervention 시술을수행할경우에유용하게사용될수있음. VTI 영상법은 PASL 방법을이용하여일부 feeding artery 만을 labeling 하는방법임.
CBF and BOLD and CMRO2 ASL 영상법을이용하는경우 oxygen metabolism (CMRO2) 을얻을수있음 동시에 CBF와 BOLD 영상을얻고이를바탕으로 CMRO2을구할수있음 Dual- echo method: 1st echo=asl 2nd echo=bold CMRO2 Single- echo method: addition=bold subtraction=cbf CMRO2
Whole Brain ASL Perfusion MRI at 4T Imaging Parameters: 2.4mm x 2.4mm; 3mm slices with 0.75mm gap; TR/TE=4200/11ms, 120 averages; 8 min
Acknowledgements 대한자기공명의과학회 경희대학교부속동서신의학병원영상의학과 보건복지부보건의료기술진흥사업의지원 (A062284).