Arterial Spin Labeling (ASL)

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1 Arterial Spin Labeling (ASL) Imaging Seminars Series Stony Brook University, Health Science Center Stony Brook, NY - December 11 th, 2012 Francesca Zanderigo, PhD

2 Layout BASIC PRINCIPLES ACQUISITION SEQUENCES QUANTIFICATION APPLICATIONS

3 BASIC PRINCIPLES ACQUISITION SEQUENCES QUANTIFICATION APPLICATIONS

4 The MRI s family MRI ANATOMICAL PERFUSION DIFFUSION fmri ENDOGENOUS EXOGENOUS SPECTROSCOPY AGENT AGENT ASL GADOLINIUM BOLD DSC-MRI DCE-MRI ASL

5 Arterial Spin Labeling (ASL) ASL is: a technique to measure (brain) perfusion totally non-invasive - labeled or tagged water molecules as endogenous tracer attractive to both clinical & research - it can be repeated on the same subject many times without limitations considered one of the most demanding disciplines within MRI

6 Perfusion Perfusion is an important biological function - oxygen & nutritional substances are delivered to the tissue through the blood flow

7 The basic idea behind ASL TWO IMAGES TAGGED IMAGE: arterial blood is magnetized A minus CONTROL IMAGE: arterial blood is NOT magnetized B The difference between the two images is related to the perfusion Perfusion can be calculated from the difference image

8 The basic idea behind ASL TAGGED IMAGE CONTROL IMAGE T1 - = T1 PERFUSION WEIGHTED

9 BASIC PRINCIPLES ACQUISITION SEQUENCES QUANTIFICATION APPLICATIONS

10 3-phases sequences LABELING POST- LABELING READ-OUT

11 Labeling LABELING POST- LABELING READ-OUT Application of the impulses necessary to magnetize the blood Continuous ASL (CASL): for a fixed amount of time (1-5 s), all the blood flowing through a given plane is labeled Pulsed ASL (PASL): all the blood in a given volume is labeled by using a quick impulse (10-50 ms) Pseudo-continuous (pcasl): a train of quick impulses with very small volumes simulates a CASL labeling

12 Labeling: CASL The blood is labeled when it flows through a given plane, the inversion plane TAGGED IMAGE CONTROL IMAGE ACQUIRED SLIDE ACQUIRED SLIDE INVERSION PLANE UNLABELED BLOOD LABELED BLOOD UNLABELED TISSUE UNLABELED BLOOD LABELED BLOOD UNLABELED TISSUE

13 Labeling: CASL TAGGED IMAGE CONTROL IMAGE Arterial component: different magnetizations (red & green) it shows up in the difference image Tissue: same magnetization (black) it is eliminated in the difference image

14 Labeling: PASL EPISTAR BASE DIPLOMA QUASAR PICORE STAR- HASTE PULSAR FAIR FAIRER UNFAIR TILT

15 Labeling LABELING POST- LABELING READ-OUT CASL/pCASL PASL SNR high low labeling time long short acquisition time long short 3D N/Y Y

16 Post-labeling LABELING POST- LABELING READ-OUT Application of impulses to improve the SNR or help the quantification NO BACKGROUND SUPPRESSION Background suppression Saturation impulses Q2TIPS/QUIPSS II BLOOD %+!,)'# TISSUE &'(()*"# signal due to tissue > signal due to blood: variations in the tissue between tagged & control!"#$%### affect the difference BACKGROUND SUPPRESSION BLOOD %+!,)'# TISSUE &'(()*"#!"#$%### $%### Background suppression reduces the tissue impact on the variability of the difference image

17 Read-out LABELING POST- LABELING READ-OUT Read-out is the image/signal acquisition/collection EPI HASTE 3D-GRASE bssfp acquisition multi-slice single-slice 3D single-slice whole brain partial partial Y N SNR low medium high medium widely adopted - good for flexible - sensitive to gold-standard - abdominal used for both blood flow - sensitive to air imaging abdominal & mostly used for artifacts (e.g., lungs) brain imaging abdominal imaging

18 Read-out: EPI CONTROL IMAGE DIFFERENCE IMAGE Zaharchuk et al., MRM 41: , 1999 CASL - readout EPI; FOV 40x24 cm; voxel size (3.1 x 3.75 x 7 mm 3 ); labeling time 3.3 s

19 Read-out: 3D-GRASE DIFFERENCE IMAGE Günter, MRM 56(3): 671-6, 2006 single-shot 3D-GRASE read-out; TI 1750 ms; acquisition time 28 s

20 Read-out: bssfp TAGGED IMAGE CONTROL IMAGE DIFFERENCE IMAGE Grossman et al., JMRI 29(6): , 2009 PASL (FAIR) - bssfp readout; TI = 1200 ms, acquisition time 2.5 min, voxel size (1 x 1 x 8 mm 3 )

21 BASIC PRINCIPLES ACQUISITION SEQUENCES QUANTIFICATION APPLICATIONS

22 The importance of quantification To be useful in clinical investigations, the information collected by the camera - the pictures of the distribution of labeled H 2 O blood molecules in the brain - must be translated into numbers that relate to well-defined biologic entities. Short of a validated quantitative analysis, the information is of little value for clinical investigations. To quantify, a model is often applied to the measured data Laruelle et al., Molecular Imaging and Biology 5(6): , 2003

23 What is a model? MODEL = a representation that includes only some relevant aspects of reality REALITY = a biological/physiological system, whose complexity and (indirect) measurements issues (e.g., in vivo) make the use of models appealing MATHEMATICAL MODEL = set of mathematical equations describing the relationships existing between the variables of the real system Answers for X Answers from M X SYSTEM M MODEL Questions about X Questions about M To DESCRIBE - QUANTIFY - INTERPRET - PREDICT

24 The ASL signal time for the tracer to reach the volume of interest (VOI) the tracer is entering the VOI the tracer is exiting the VOI & decades due to longitudinal T1 relaxation Dynamic of the difference signal (control-tagged)

25 The ASL signal The difference signal is: related to the perfusion (f), but NOT a direct measurement of the perfusion influenced by many factors besides f, such as tissue T1, blood T1, capillary permeability, arrival time, inversion efficiency etc.

26 Mono-compartment model for ASL M : tissue magnetization T1 : blood & tissue T1 f : perfusion m a : arterial magnetization m v : venous magnetization The model gives an equation, which describes how the magnetization changes over time in the VOI Alsop & Detre, JCBF&Met 16: , 1996

27 Matching model & data real data obtained via 1.5T Parkes & Tofts, MRM 48: 27-41, 2002

28 Bi-compartment model for ASL Parkes & Tofts, MRM 48: 27-41, 2002

29 Mono- vs. bi-compartment compromise between good description of the data & complexity of the model Parkes & Tofts, MRM 48: 27-41, 2002

30 Buxton model general (includes previous models) - based on the tracers kinetic theory (similarly to PET) fraction of labeled blood remaining in the time t (residue function) arterial concentration of labeled blood entering the VOI (input function) VOI fraction of original magnetization remaining in the time t (magnetization loss function) account for deviations/confounding effects by specifying (measuring or estimating) the proper shape for these three functions QUASAR - deconvolution Buxton et al., MRM 40: , 1998

31 QUANTIFICATION Petersen et al., Non-invasive measurement of perfusion: a critical review of arterial spin labelling techniques - Review article, The British Journal of Radiology, 79: , 2006

32 BASIC PRINCIPLES ACQUISITION SEQUENCES QUANTIFICATION APPLICATIONS

33 Perfusion studies Different pathologies (e.g., tumors) modify the tissue metabolism: perfusion studies can highlight areas affected by the pathology & its evolution T1 anatomical - post-contrast T2 anatomical FAIR Noguchi et al., AJNR A0903: 1-6, 2008

34 Vascularized areas studies Idea: to selectively label the blood only in a major artery to obtain a map of the areas perfused by that artery (2 coils protocol, 2D RF impulses, inversion volume with tissue suppression) selective magnetization of just one carotid (CASL) difference control difference control Zaharchuk et al., MRM 41: , 1999

35 Vascularized areas studies ICA right ICA left basal artery (inversion volume with tissue suppression) Günter et al., MRM 56(3): 671-6, 2006

36 ASL as an alternative to angiography ICA left VA right (standard) TOF angiography ASL angiography ICA right Okell et al., MRM 64: 430-8, 2010 VA left

37 ASL as functional imaging metabolism use & demand of oxygen CBF neuronal activation causes an increase in the metabolism perfusion locally increases in the activation area by using ASL to quantify perfusion, it is possible to measure the neuronal activation

38 ASL as functional imaging signal in the primary (M1) & supplementary (SMA) motor cortex during finger-tapping ASL fmri BOLD fmri Obata et al., Neuroimage 21(1): , 2004

39 ASL as functional imaging (acquisition during bilateral finger-tapping with a 30 sec stimulus) BOLD fmri ASL fmri Wang et al., MRM 49: , 2003

40 ASL & fmri Borogovac & Asllani, Arterial Spin Labeling (ASL) fmri: Advantages, Theoretical Constrains and Experimental Challenges in Neurosciences - Review article, International Journal of Biomedical Imaging, Article ID , 2012 ASL & APPLICATIONS Detre et al., Applications of Arterial Spin Labeled MRI in the Brain - Review article, JMRI 35: , 2012 ASL as a biomarker of pharmacological actions ASL in neuropsychiatry ASL & PET

41 ASL: a few take home messages ASL is non-invasive & has no side effects (e.g., pediatric studies) ASL has low SNR & needs careful modeling for absolute perfusion quantification ASL needs no hypothesis on the blood-brain barrier ASL does not need exogenous tracers or arterial or venous blood sampling ASL is attractive for longitudinal CBF studies in healthy & diseased individuals (e.g., marker of metabolism): QUASAR test-retest study* QUASAR *Petersen et al., NeuroImage 49: , 2010

42 Acknowledgment: Denis Peruzzo, PhD - Department of Computer Science, University of Verona, Italy (for very helpful material & conversations, as always, & everlasting collaboration) THANK YOU FOR YOUR ATTENTION! :-)

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