Arterial Spin Labeling in Body MR

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1 Arterial Spin Labeling in Body MR Neil M. Rofsky, MD FACR, FISMRM, FSCBTMR Department of Radiology and Advanced Imaging Research Center

2 None Disclosures

3 Acknowledgements Ananth J. Madhuranthakam, Ph.D. David Alsop, Ph.D. Ivan Pedrosa, M.D.

4 Why Perfusion? Perfusion refers to the delivery of O 2 and nutrients to Lssue by means of blood flow Classically measured using a diffusible tracer that can exchange between the vascular compartment and Lssue and is quanlfied in Lssue- specific units of ml/g /min

5 Perfusion

6 PharmacokineLc modeling Blood flow K trans K ep k ep = K ve trans With contrast we can only measure the mean value of tumor components assumplons of exchanges are used to derive QuanLtaLve Results

7 Tumor Perfusion, Permeability Microvessels of cancer High density Hyperpermeability Permeability Perfusion Diffusion

8 Background: DCE Long history of ullizalon Based on firm theories & models Data acquisilon w/ basic pulse sequences Has been used in a variety of cancers

9 DCE MRI: Pi^alls Safety/tolerance NSF, allergy Protocol HarmonizaLon ExecuLon of sequences: not = All Gd agents are not = Ionic, non- ionic Blood Hct/ Arterial input Broad applicability of model assumplons? Tumor heterogeneity KineLcs best assessed w/ high temp/low spalal resolulon

10 Arterial Spin Labeling QuanLtaLve method for assessing perfusion No contrast media Blood H 2 0 is magnelcally labeled Labeled blood flows to Lssue of interest

11 ASL Schematic Spatially Selective Inversion Arterial Inflow Inverted Spins T1 Tissue Venous Outflow At 3T: slower decay rate of labeled blood

12 ASL SubtracLon Experiment Control Image Labeled Image Imaged Slice Inversion Labeling (a negalve signal)

13 ConLnuous vs. Pulsed ASL 2 broad labeling strategies ConLnuous ASL has higher signal to noise ralo as the spins are inverted for a longer period of Lme and closer to the anatomy CompaLble with a short RF coil, magnet, gradient ConLnuous Labeling Pulsed Labeling

14 ConLnuous vs. Pulsed ASL at 3 Tesla Wang et al. Radiology 2005

15 ASL in Neurological ApplicaLons Robust In widespread research use Validated in animals Validated in humans w/ PET Commercially available *Dai W et. al. MRM 2008; 60: CBF in a 60 yo pt with bx proven glioblastoma, 3 Tesla, 5 min

16 Blood Flow Monitoring of Experimental AnLangiogenic Tx in Glioma (Grade III Oligodendroglioma) Pre 4 wks 10 wks 16 wks 24 wks 30 wks c/o David Alsop, PhD, BIDMC

17 Fenchel M et. al. Radiology 2006; 238: Wu WC et. al. Radiology 2011; 261: ASL outside Neurological ApplicaLons High flow physiology/pathophysiology is best evaluated Measures renal perfusion w/o external contrast agent injeclon Advantageous for pts with compromised renal fxn

18 Pulsed ASL (PASL) Flow AlternaLng Inversion Recovery (FAIR)* Combined with True- FISP (or b- FFE) acquisilon # *Kim SG MRM 1995; 34: # MarLrosian P MRM 2004; 51: Fenchel M et. al. Radiology 2006; 238: 1013

19 Pseudo ConLnuous ASL (pcasl) pcasl has relalvely high labeling efficiency* pcasl is amenable to background suppression #, and readily quanlfiable Unique resp triggering strategies have been developed for prolonged data acquisilons *Dai W et. al. Magn Reson Med 2008; 60: # Robson PM et. al. Magn Reson Med 2009; 61:

20 4.1s 3.0 s Pulse Sequence FOCI Inversion Non-selective Pulse Saturation pulses Inversion Pulses (imaging region) pseudo-casl 1.5 s TR = 6 s Superior Saturation Pulses SShTSE 0 s before imaging 1.5 seconds long labeling 1.5 seconds long post- label delay Label image is with inversion Control image is without inversion Robson PM et. al. Magn Reson Med 2009; 61:

21 2D Perfusion in Normal Volunteer Control Image = Perfusion Difference Image Label Image - Perfusion difference image shows clear corlco- medullary differenlalon

22 2D Perfusion Comparison = Gd DCE series shows clear corlco- medullary differenlalon Perfusion difference image shows clear corlco- medullary differenlalon

23 2D Perfusion in Normal Volunteer Perfusion Difference Image Perfusion Map ml/100g/min Perfusion can also be quanlfied using magnelzalon (M0) image

24 Significance of Background Suppression No Background Suppression # Robson PM et. al. MRM 2009; 61: 1374

25 ASL Renal BF Test- Retest Results (Repeatability) Renal blood flow (w/in slice) Mean 355 (128 intersubj SD) ml/min/ 100g Within scan test retest SD 5.03% One week test retest SD 13.3% Baseline Study One Week Study Robson et al. Magn Reson Med 2009 Scan 1 Scan 2 Scan 1

26 2D Perfusion in PaLent Volunteer Scan Lme: 3min, 18 sec Perfusion Difference Image 2D T 2 - weighted image Perfusion Map ml/100g/min Pt with clear cell RCC shows heterogeneous tumor perfusion

27 2D Perfusion in PaLent Volunteer Perfusion 2D T 2 - weighted Difference image Image Perfusion Map ml/100g/min Pt with clear cell RCC exhibilng high perfusion with a dark fibrolc band in the middle, confirmed on pathology

28 Arterial Spin Labeling MRI: Clinical ImplimentaLon in the Body Magnetic fields alter signal from inflowing arterial blood No injection required! Multiple acquisitions Measures blood flow with MRI High spatial resolution No ionizing radiation

29 Spin Labeling Images tumor tumor tumor muscle

30 72 MetastaLc RCC treated with PTK 787, targets VEGF tyrosine kinase receptor

31 ASL Monitoring of AnL VEGF Receptor Therapy in RCC! Size changes not meaningful!

32 Early changes at 1 mo in blood flow and tumor size vs. delay of dz progression after initiation of the tx. de Bazelaire C, et al. Clin Cancer Res 2008;14: by American Association for Cancer Research

33 Hx: Rt nephrectomy, New LT RC; egfr = Min growth Cont growth é size No size change sig é perf sig é perf ê perf ~ no perf ASL MRI Pedrosa, et al. Eur Radiol 2012 Feb;22(2): RT 4/08 & 6/08

34 3D AcquisiLon 2D acquisilon = single slice, 16 pairs of label/control in ~ 3 min 3D TSE??? Protocol includes slices of 3 mm in ~ 4 min FOCI Inversion Pulse Saturation pulses (imaging region) Non-selective Inversion Pulses Superior Saturation Pulses pseudo-casl 3D TSE

35 3D Perfusion Diff Image in Nl Volunteer Coronal 2D Coronal 3D Sagival Reformat Axial Reformat

36 3D Perfusion in PaLent Volunteer Sagival 3D AcquisiLon Coronal Reformat High perfusion Invasive T 2 - Weighted Image Post- Contrast Surgical Excision AcquisiLon Arterial Delayed Perfusion difference image in the nalve sagival orientalon Low perfusion Clear cell renal cell carcinoma showing high perfusion in the superior localon of the kidney (outline) R01 CA

37 T2 HF ASL Invasive LF Arterial Invasive Delayed HF #1 HF #2 Invasive LF 9 Post-contrast Ivan Pedrosa M.D. NIH RO1 (1R01CA )

38 Low Flow More hyalinized Ivan Pedrosa M.D., UTSW NIH RO1 (1R01CA ) High Flow #1 Classic clear cell More trabeculated ASL 012 Invasive HF 2

39 Conclusions ASL can provide absolute perfusion quanlficalon without confounding vascular permeability Allows non- invasive assessment of tumors with high accuracy Can be used repeatedly without the administralon of exogenous contrast agent Can be extended to other tumors Fibroids, Lung Ca, Sarcomas

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