Arterial Spin Labelling Neuroradiological Clinical Practice Xavier Golay, Ph.D. Chair, MR Neurophysics and Translational Neuroscience UCL Institute of Neurology Queen Square, London Disclosure • Part of the work presented here was done in collaboration with Philips Medical Systems (now Philips Healthcare) Layout • Introduction and Definitions • Differences between DSC and ASL • Clinical ASL Examples -Atherosclerotic Diseases -Stroke -AVMs -Pediatrics -Dementia -Tumours • Conclusions Definitions • The Cerebral Perfusion can be defined as the steady state delivery rate of blood to the tissue capillary bed • The main parameter measured is the Cerebral Blood Flow (CBF), which is the rate of delivery of blood to the capillary bed • Its measurement relies on the Indicator Dilution Theory Quantitative Perfusion Measurement Kety-Schmidt Method (1945) N2O MRI-based Perfusion Imaging • Free-diffusible Tracers (2H, 19F, 17O, 129Xe) • Arterial Spin Labeling (ASL) - Continuous ASL - Pulsed ASL • Dynamic Susceptibility Contrast (DSC) Perfusion Imaging (Gd-based) Theoretical Differences arteries/arterioles Gadolinium Labeled Water capillaries venules/veins Theoretical Differences • Gadolinium is an intravascular tracer (at least without disruption of BBB) - Assessment of the complete vascular compartment size (I.e. Cerebral Blood Volume or CBV) is possible • ASL can be considered as a free diffusible tracer - Assessment of the complete vascular compartment size (CBV) is NOT possible Arterial Spin Labeling Basics Control M Label Tracer = Labeled Magnetization Pulsed Arterial Spin Labeling • Pulsed Arterial Spin Labeling -STAR (Signal Targeting by Alternating Radio-frequency pulses) Label: 180° Edelman & Chen. MRM 40(6): 800 (1998) Golay et al., MRM, 53:15 (2005) Pulsed Arterial Spin Labeling • Pulsed Arterial Spin Labeling -STAR (Signal Targeting by Alternating Radio-frequency pulses) Control: 180° + 180° Edelman & Chen. MRM 40(6): 800 (1998) Golay et al., MRM, 53:15 (2005) ASL: Model-Free CBF quantification Tissue signal Arterial signal Tissue response t M (t ) 2 M 0,b f c( ) r (t ) m(t 0 Meier & Zierler, J Appl Physiol, 6:731(1954) CT: Gobbel et al, Phys Med Biol, 39:1133(1994) MRI: Ostergaard et al, MRM, 36:715(1996) ASL: Buxton et al., MRM, 40:383(1998) )d ASL: Model-Free Perfusion Imaging 50 350 650 950 1250 Non crushed data Crushed data (Venc = 3cm/s) Arterial Input Function Petersen et al., MRM, 55: 219 (2006) 1550 1850 2150 2450 [ms] ASL: Model-Free Perfusion Imaging • Deconvolution: -SVD or other regularization method -Circular SVD* chosen here -Maximum of Residue function equals the perfusion! Max = CBF = 75 ml/min/100g Model ! *Ona Wu, MRM, 50:164(2003) ASL Parametric Maps Reason: Left Cortical CVA & Hypertension ASL Parametric Maps ASL Parametric Maps: CBF 70 ml/min/100g 0 ASL Parametric Maps: aBV / CBVa 3 ml/100g 0 Advantages of DSC over ASL • Very robust method to depict perfusion deficits in numerous diseases • Rapid (~1min) • Uses standard sequences (GRE/SE-EPI) • High SNR • Capable of measuring delays in arrival times of several seconds • Automated processing available Advantages of ASL over DSC • Does not require contrast (NFS, children, …) • Can be repeated (while Gd is dose-limited) • Provides absolute quantification of CBF • Has a better temporal resolution • Can be made insensitive to large vessel artifacts • Can be combined with selective excitation Atherosclerotic Diseases “Borderzone sign” on ASL • In patients with normal PWI, more information may be available with ASL • 43% show bilateral dropout of ASL signal in watershed regions • Serpiginous high ASL in cortical sulci • “Borderzone sign” • Additional imaging findings related to slow flow. – Collaterals, aneurysms, fistulas Slide courtesy of G. Zaharchuk Normal Mild Moderate Severe Zaharchuk et al. Radiology 2009 Identification of Pathological Status in a Patient with Carotid Stenosis Uchihashi et al, ISMRM 09 Comparison of CBF values obtained by ASL & SPECT in Patients with Carotid Stenosis Uchihashi et al, ISMRM 09 Comparison of CBF values obtained by ASL & SPECT in Patients with Carotid Stenosis Uchihashi et al, ISMRM 09 Territorial (or selective) ASL Selective labeling: Left ICA Hendrikse et al. Stroke 35 (2004) Territorial ASL Selective labeling: Right ICA Hendrikse et al. Stroke 35 (2004) Territorial ASL Selective labeling: Vertebral arteries (POST) Hendrikse et al. Stroke 35 (2004) ASL: Labeling T-ASL Hendrikse et al. Stroke 35 (2004) Patient with left ICA Occlusion TASL vs. DSA Chng et al. Stroke 39 (2008) TASL vs. DSA Chng et al. Stroke 39 (2008) TASL vs. DSA • Significant Contingency between RPI & DSA (V=0.53, C=0.67, p<0.0001) • “Substantial Agreement” between methods when compared using a weighted kappa test (k=0.70 flow, k=0.72 collaterals) Chng et al. Stroke 39 (2008) Stroke Singapore Stroke study: Scan Protocol • T2W + DWI • 3D TOF MRA • Two ASL scan - Global perfusion (non-selective, label all vessels at the same time) - Territorial perfusion (selectively label individual vascular territory) • Dynamic Susceptibility Contrast - Single dose (2 ml/kg Gadolinium) - Power Injector 5/ml/s Patient 1: Complete work-up Hendrikse et al. Stroke, in press (2009) Patient 2: Complete work-up DWI PWI (CBF) PWI (MTT) ASL (CBF) ASL (AT) ASL (TASL) ASL versus PWI ASL (left) / PWI (right) Non-affected hemisphere (N=87) ASL versus PWI ASL-CBF vs. PWI-CBF (Ratio = ipsi/cont.) Within infarct (>8cc) (>20cc) r=0.55, p=0.0015 Peripheral (8mm) r=0.54, p=0.0014 Preliminary Conclusion on Singapore Stroke Study • Success rate: 91.7% in 160 patients • Changed classification in 11% of patients with cortical / borderzone infarcts • Added perfusion information in stroke - Risk management of large vessel disease • DSC and ASL provide similar, yet complimentary information Hendrikse et al, Stroke 40 (2009) Clinical evaluation Stroke patient Slide courtesy from M. Guenther ASL can visualize collateral flow 74 year-old man with right facial droop Serpiginous high ASL signal surrounding the infarct represents slow flow in collateral vessels Bolus PWI Tmax ASL without vessel suppression ASL with vessel suppression Slide courtesy from G. Zaharchuk Arterio-Venous Malformations 49 F, known AVM T2 ASL CBF PWI CBF Slide courtesy from G. Zaharchuk 4D-MRA & selective ASL 45 y/o patient, grade II AVM, 2 feeding arteries AVM left ICA left ICA Functional crossfilling documented by selective ASL Slide courtesy from W. Willinek Paediatrics CASL: Sickle Cell Patient 250 ml/min/100g 255 ml/min/100g 0 ml/min/100g K. Oguz, et al. Radiology (2003) 0 ml/min/100g CASL: Sickle Cell Patient 2 255 ml/min/100g 0 ml/min/100g K. Oguz, et al. Radiology (2003) Sickle Cell : Results K. Oguz, et al. Radiology (2003) Dementia and Aging ASL application Age dependency of perfusion 15 years 56 years ASL CBF GREDSC rCBF Slide courtesy from M. Guenther Warmuth, C; Günther, M; Zimmer, C.: Radiology 2003, Vol. 228, pp. 523-532 Alzheimer’s Disease Patient Collaboration with Dr. Christopher Chen, NUS, Singapore Vascular Dementia Patient Collaboration with Dr. Christopher Chen, NUS, Singapore ASL in Dementia (Chinese population) Brain Perfusion Reduction (Normal vs. Demented) Mak et al. ISMRM (2010) ASL in Dementia Brain Perfusion Reduction (Normal vs. Demented) Mild Cognitive Impairment Johnson et al. Radiology, 234:851–859 (2005) Alzheimer’s Disease Tumours Cerebral blood flow and perfusion Comparison DCE-ASL 67y, female, brain metatasis, before and after radiotherapy T2w T1w ASL DSC before after Slide courtesy from M. Guenther M.-A.Weber, A. Kroll, M.Günther et al, Radiologe 2004 · 44:164–173 Cerebral blood flow and perfusion Comparison DCE-ASL 59y, female, meningioma Slide courtesy from M. Guenther ASL DSC T1w T2w M.-A.Weber, A. Kroll, M.Günther et al, Radiologe 2004 · 44:164–173 Pathologies • Routine clinical work ASL • Pharmacological Studies ASL • Stroke DSC / ASL • Carotid Artery Stenosis / TIA DSC / ASL • Moya-Moya DSC / ASL • Dementia ASL • Brain Tumors: ASL / DCE - Primary brain lesions (Gliomas, etc…) - Meningiomas - Metastases • Children ASL Conclusions • In the last years, ASL managed to catch-up with DSC -Recognition of Arterial Transit Time Artifacts -Providing Quantification (CBF, aBV, ATT) • DSC is still the preferred method in pathologies involving very large arterial delays (Moya-moya, Carotid stenosis, …) • ASL is an add-on in patients where no perfusion measurement was present (dementia, epilepsy, …) • ASL should be the method of choice in pediatrics and renal failure patients Acknowledgments • Slides: Yoshito Uchihashi, Greg Zaharchuk, Winfried Willinek, Matthias Guenther • Staff from NNI: Esben Petersen, Lynn Ho, Ivan Zimine, Tchoyoson Lim, Yih Yian Sitoh, Francis Hui • National Medical Research Council (NMRC), Singapore, NMRC/0919/2004 • Singhealth Foundation, Singapore, NHGARPR/04012 • Philips Medical Systems ASL Network www.asl-network.org/