Arterial Spin Labeling in Body MRI

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

2 Disclosures None Acknowledgements Ananth J. Madhuranthakam, Ph.D. David Alsop, Ph.D. Ivan Pedrosa, M.D.

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

4 Perfusion is tracer determined

5 Pharmacokinetic modeling Blood flow v K trans K ep v e k ep K ve trans With contrast we can only measure the mean value of tumor components assumptions of exchanges are used to derive Quantitative Results

6 Pharmacokinetic modeling Microvessels of cancer High density Hyperpermeability Blood flow K trans K ep k ep K ve trans With contrast we can only measure the mean value of tumor components assumptions of exchanges are used to derive Quantitative Results

7 Background: DCE Long history of utilization Based on firm theories & models Uses basic pulse sequences Used in a variety of cancers

8 DCE MRI: Pitfalls Safety/tolerance NSF, allergy Protocol Harmonization Sequences: not = Gd agents are not = Ionic, non-ionic Blood Hct/ Arterial input Broad applicability of model assumptions? Tumor heterogeneity Kinetics best assessed w/ high temp/low spatial resolution

9 Arterial Spin Labeling No contrast media; no tracer accumulation Blood H 2 0 is magnetically labeled Labeled blood flows to tissue of interest Quantitative method for assessing perfusion

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

11 ASL Subtraction Experiment Control Image Labeled Image Imaged Slice Inversion Labeling (a negative signal)

12 ASL in Neurological Applications Robust Validated in animals & humans 60 yo w/ bx proven glioblastoma, 3 Tesla, 5 min Commercially available *Dai W et. al. MRM 2008; 60:

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

14 ASL outside Neurological Applications Best for high flow physiology/pathophysiology Measures tissue perfusion w/o exogenous contrast material Advantageous for pts with compromised renal fxn Fenchel M et. al. Radiology 2006; 238: Wu WC et. al. Radiology 2011; 261:

15 Pulsed ASL (PASL) Flow Alternating Inversion Recovery (FAIR)* Combined with True-FISP (or b-ffe) acquisition # *Kim SG MRM 1995; 34: # Martirosian P MRM 2004; 51: Fenchel M et. al. Radiology 2006; 238: 1013

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

17 Pulse Sequence FOCI Inversion Non-selective Pulse Saturation pulses Inversion Pulses (imaging region) pseudo-casl 4.1s 3.0 s 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 Robson PM et. al. Magn Reson Med 2009; 61:

18 2D Perfusion in Normal Volunteer Control Image = Perfusion Difference Image Label Image - Perfusion difference image shows clear cortico-medullary differentiation

19 Background Suppression No Background Suppression # Robson PM et. al. MRM 2009; 61: 1374

20 ASL Renal BF Test-Retest Results (Repeatability) Baseline Study 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% Scan 1 Scan 2 One Week Study Robson et al. Magn Reson Med 2009

21 ml/100g/min 2D Perfusion in Patient Scan time: 3min, 18 sec 2D T 2 -weighted image Perfusion Difference Image Perfusion Map Clear cell RCC shows heterogeneous tumor perfusion

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

23 72 Metastatic RCC treated with PTK 787, targets VEGF tyrosine kinase receptor

24 ASL Monitoring of Anti VEGF Receptor Therapy in RCC Size changes not meaningful

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

26 3D ASL 2D acq = single slice, in ~ 3 min; 16 pairs of label/control 3D acq = 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

27 3D Perfusion Diff Image in Nl Volunteer Coronal 2D Coronal 3D Sagittal Reformat Axial Reformat

28 3D Perfusion in Patient Volunteer Sagittal 3D Acquisition Coronal Reformat High perfusion Invasive T 2 -Weighted Post-Contrast Surgical Excision Acquisition Image Arterial Delayed Perfusion difference image in the native sagittal orientation Low perfusion Clear cell renal cell carcinoma showing high perfusion in the superior location of the kidney (outline) R01 CA

29 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

30 Heterogeneous Perfusion in High Grade ccrcc T2 ASL K trans Kep Gross High Flow Low Flow CD31 IHC Zhang et al. Clin Genitourin Cancer. 2015

31 Conclusions ASL provides absolute perfusion quantification non-invasive assessment of tumors high accuracy & reproducibility Can be used repeatedly no exogenous contrast agent no ionizing radiation Can be extended to other tumors Fibroids, Lung Ca, Sarcomas

32 Results: Dynamic Inflow Visualization MIP views of 8-slice image for each time point (total 12 min scan time) 200 ms 400 ms 600 ms 800 ms 1000 ms Labeling in the common carotid artery 1500 ms 2000 ms 2500 ms 3000 ms Symmetric filling Healthy volunteer ~1 sec to fill ACA/MCA branches above CoW and basilar artery below CoW ~2 sec to fill the extra-cranial arteries 8a

33 Quantitative MRI vascular measures vs MVD MVD = Microvessel density on CD31 IHC Zhang et al. Clin Genitourin Cancer. 2015

34 THANK YOU

35 6 Results: 3D Imaging - Cerebral Vasculature MIP of 64 slice-encode 10-min scan Labeling in the common carotid artery Excellent depiction of vessels Coronal View Rotated Interpolated Reformat

36 7 Results: 3D Imaging - Cerebral Vasculature Multiple view planes of vasculature Single projection acquisition Flexibility afforded by subtraction and BGS MIP views of multiple 8 slice-encode images in 2-min scan Single projection image acquired in less than 10 seconds

37 Results: Dynamic Inflow Visualization MIP views of 8-slice image for each time point (2 min per time point) Labeling in the common carotid artery Labeling duration before imaging: between 200 ms and 3000 ms 8 Symmetric Filling Healthy volunteer ~1 sec to fill ACA/MCA branches above CoW and basilar artery below CoW ~2 sec to fill the extracranial arteries

38 9 Results: Vessel Selectivity MIP views of 8-slice image (2 min scan time) Labeling in left and right ICAs Excellent contra-lateral suppression

39 10 Results: Vessel Selectivity MIP views of 8-slice image (2 min scan time) Labeling in right ECA, vertebral artery ECA and cerebellar branches separated Residual labeling in ICA Sufficient selectivity to identify collateral flow

40 Results: Dynamic Inflow Visualization MIP views of 8-slice image for each time point (total 12 min scan time) Labeling Duration before imaging: between 200 ms and 3000 ms Labeling in the common carotid artery 200 ms 400 ms 600 ms 800 ms 1000 ms 1500 ms 2000 ms 2500 ms 3000 ms Symmetric filling Healthy volunteer ~1 sec to fill ACA/MCA branches above CoW and basilar artery below CoW 8a

41 New Slides for Neil Full refocusing (180deg) suppresses ghosting 8-slice encodes, 1.5 min scan, 180 flip angle, 2 sec labelling duration

42 New Slides for Neil Normal variation left ICA feeds both ACA branches 8-slice encodes, ~2 min scan, 180 flip angle, 2 sec labelling duration

43 New Slides for Neil 8-slice encodes, ~2 min scan, 180 flip angle, 2 sec labelling duration Nl variation LT ICA feeds both ACA branches

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