Contrast-Enhanced MRI for Tissue Perfusion
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1 Contrast-Enhanced MRI for Tissue Perfusion Hsiao-Wen Chung ( 鍾孝文 ), Ph.D., Professor Dept. Electrical Engineering, National Taiwan Univ. Dept. Radiology, Tri-Service General Hospital 1 of 95
2 Perfusion MRI with Gd I have to assume that you are familiar with T1 contrast agents in MRI (Gd- DTPA or the like) although I never taught relaxation mechanism & contrast agent 2 of 95
3 What Is Perfusion? Microcirculation, blood flow... Not angiography though Capillary blood flow at tissue site Exchange of nutrients/wastes 3 of 95
4 Meaning of Perfusion? 4 of 95
5 To See Capillary Flow Capillary diameter : mm Current imaging does not see (resolution limitation) Meaningless to see single capillary Overall evaluation of nutrient exchange at tissue site 5 of 95
6 Perfusion & Tracer Tracer kinetics Inject tracer into blood vessel Often intravenous injection Blood flow extrapolated by following the tracer 6 of 95
7 Tracer Distribution (a Time Function) wash-in wash-out? 7 of 95
8 What Does Curve Tell? No obvious change in signal: ischemia, upstream occlusion Large change: abnormal blood volume Slow wash-in: upstream narrowing (stenosis), collateral flow Slow wash-out: tortuous vessels, increased permeability 8 of 95
9 Tracer concentration Perfusion from Tracer-Time Curve Normal tissue Low blood volume Long transit time Two typical types of ischemia Time 9 of 95
10 Perfusion Maps Get time curve for every pixel Calculate blood volume, transit time, blood flow for every pixel Map perfusion parameters back to form new images 10 of 95
11 Tracer concentration Perfusion from Tracer-Time Curve area ~ blood volume width ~ transit time height ~ blood flow Time Fairly close although not too accurate 11 of 95
12 Distribution of Cerebral Blood Volume Siemens Vision+ 1.5T 0.2 mm/kg Gd-DTPA EPI (TR=1000, TE=60) 128x128, 3 slices Bright means more blood Allows rapid lesion/normal comparison 12 of 95
13 Distribution of Mean Transit Time Siemens Vision+ 1.5T 0.2 mm/kg Gd-DTPA EPI (TR=1000, TE=60) 128x128, 3 slices Bright means slower passage Allows rapid lesion/normal comparison 13 of 95
14 Typical Perfusion Imaging (Not necessarily MRI) Intravenous tracer injection Dynamic image scanning Calculate perfusion parameters Form parameter images 14 of 95
15 Perfusion MRI Contrast + dynamic scan T1-weighted T2*-weighted Arterial spin labeling 15 of 95
16 Perfusion MRI Contrast + dynamic scan T1-weighted T2*-weighted Arterial spin labeling 16 of 95
17 Ha! Too Simple! Intravenous Gd-DTPA injection T1WI scanned many times Gd flows in brightened, flows out darkened not that straightforward though 17 of 95
18 Capillary Permeability Contrast has relatively large chelate that may not enter tissue rapidly In the case of low blood volume fraction, T1 enhancement very small 18 of 95
19 What Is Chelate Then? Molecule that surrounds the heavy metal ion Isolate toxicity Avoid heavy metal poisoning 19 of 95
20 Gd-DTPA (Magnevist) Structure Safe and still effective in enhancing relaxation 20 of 95
21 Some FDA Approved Gd Chelates Gd-DTPA (Magnevist) Gd-DOTA (Dotarem) Gd-DTPA-BMA (Omniscan) Gd-HP-DO3A (Prohance) Still large compared capillary permeability 21 of 95
22 Diffusible Tracer DTPA capillary wall DTPA DTPA DTPA capillary capillary wall But not completely freely diffusible 22 of 95
23 T1 Effect Restricted within Capillaries image voxel tissue capillaries Low volume fraction small T1 enhancement 23 of 95
24 Capillary Permeability Contrast has relatively large chelate that may not enter tissue rapidly In the case of low blood volume fraction, T1 enhancement very small 24 of 95
25 Solution Extend image scan to permit multiple (actually many) circulations Contrast gradually enters/leaves tissue T1WI continuously follow for ~10 min Scan & injection do not need to be fast 25 of 95
26 Example: Breast Malignant tumor often contains highly permeable neovasculature Called angiogenesis Perfusion MRI uses wash-in & washout information for tumor malignancy 26 of 95
27 Normal vs. Tumor Signal-Time Curves min min 27 of 95
28 Parameter Calculation Brix model (1991) Signal-time curve consists of 3 major parameters Blood volume, exchange rate, (kidney) excretion rate 28 of 95
29 Brix Perfusion Model (1991) Assumption: exchange rate in equilibrium 29 of 95
30 No Mean Transit Time Very long dynamic scan used How fast contrast agent passes the tissue cannot be examined Equilibrium phase 30 of 95
31 Clinical Applications Brain tissue with disrupted BBB Pituitary gland Femoral head, hip joint Breast imaging 31 of 95
32 That s Low Blood Volume What about high blood volume fraction? Example: lung Almost all air & capillaries (alveoli) Blood the only MR signal source Obvious signal change during first-pass 32 of 95
33 But T1WI Scan Time Gradient echo: tens of seconds Spin echo: some minutes One circulation: ~22 sec T1WI often too slow for first-pass 33 of 95
34 First-Pass T1 Perfusion Only for specific tissue (lung) New fast-scan T1WI technique Limited slice coverage Rapid (bolus) contrast injection 34 of 95
35 Lung Perfusion MRI Example wash-in 25 wash-out Pre-contrast 5 0 2nd pass Post-contrast of 95
36 Parameter Calculation Gamma-variate function Signal-time curve consists of 2 major parameters Blood volume, mean transit time 36 of 95
37 Tracer concentration Perfusion from Tracer-Time Curve area ~ blood volume width ~ transit time height ~ blood flow Time Fairly close although not too accurate 37 of 95
38 Perfusion Parameters Blood volume = integration of (area under) first-pass curve Mean transit time = normalized first-moment (centroid) 38 of 95
39 Tracer concentration Plus Variations in Arrival Time Time Most normal perfusion curves are like this 39 of 95
40 No Permeability Very short time in first-pass transit little contrast leakage First-pass: sec Complete circulation: ~22 sec 40 of 95
41 Diffusible Tracer DTPA capillary wall DTPA DTPA DTPA capillary capillary wall But not completely freely diffusible 41 of 95
42 About Injection Speed Ideal vs. nonideal bolus injection 42 of 95
43 Tracer concentration Mean Transit Time from the Curve Fast wash-in? Fast upstream? Slow wash-in? Slow upstream? Time Gd in upstream + tissue both considered 43 of 95
44 Gd Signal-Time Curve Upstream & tissue combined De-convolution to obtain pure tissue perfusion (complicated) Like x = z/y from xy = z 44 of 95
45 Clinical Applications Tumor angiogenesis Pulmonary stenosis Pulmonary embolism Other lung perfusion evaluation 45 of 95
46 Healthy Male Lung Perfusion rmtt rpbv 46 of 95
47 Lung Cancer rmtt rpbv 47 of 95
48 Pulmonary Stenosis rmtt rpbv 48 of 95
49 Note: Lung MRI Lung MRI itself is challenging Low proton density, short T2 Sequence with TE < 1 ms needed Shown are research examples 49 of 95
50 Note: First-Pass Gd Contrast (& blood) just passes the tissue capillaries Don t know if enters tissue Blood flow unequal to perfusion 50 of 95
51 Another Example: Liver Malignant tumor: recruit vessels in hepatic artery territory Blood from portal vein fine Dynamic Gd imaging for hepatic arterial & portal venous phases 51 of 95
52 Hepatocellular Carcinoma MRI Pre Gd Arterial phase Portal venous phase VIBE MIP 52 of 95
53 Note: Perfusion? Fast dynamic imaging doesn t show blood perfuse into tissue Sometimes just properly called dynamic contrast-enhanced MRI 53 of 95
54 Perfusion MRI Contrast + dynamic scan T1-weighted T2*-weighted Arterial spin labeling 54 of 95
55 Intravascular Contrast Contrast simply does not leave low-volume-fraction capillaries Brain (blood-brain barrier) Use first-pass T2* perfusion MRI 55 of 95
56 Diffusible & Non-diffusible Tracer capillary wall DTPA DTPA DTPA DTPA capillary capillary wall Contrast agent completely non-diffusible 56 of 95
57 T1 Effect Restricted within Capillaries image voxel tissue capillaries Low volume fraction small T1 enhancement 57 of 95
58 2 Effects of Gd Contrast T1: shortened bright on T1WI Within vessel, small range T2*: shortened dark on T2*WI Near vessel, wide range 58 of 95
59 Unpaired Electron of Gd Distorts Bo Bo H 2 O Larmor freq altered for nearby protons 59 of 95
60 MR Contrast Agents Gd: paramagnetic agent Shorten T1 (with Gd presence) Distorts Bo homogeneity (wherever close to Gd) 60 of 95
61 Range of T1 Influence capillary Confined within capillaries with intact BBB 61 of 95
62 Range of T2* Influence capillary range of Bo alteration About 62% water molecules affected 62 of 95
63 T2* Perfusion MRI Use paramagnetic susceptibility of Gd to distort Bo & shorten T2* Dynamic susceptibility-contrast perfusion-weighted MRI 63 of 95
64 T2*WI in Brain Perfusion Ideal first-pass perfusion MRI Fast scan + T2* weighting EPI 6+ slices each second Bolus Gd injection 64 of 95
65 Signal Changes as a Function of Time 5 sec 6 sec 7 sec 8 sec 65 of 95
66 Signal Changes as a Function of Time 9 sec 11 sec 13 sec 15 sec 66 of 95
67 Signal Changes as a Function of Time 17 sec 19 sec 21 sec 23 sec 67 of 95
68 Signal Changes as a Function of Time 5 sec 11 sec 17 sec 23 sec 68 of 95
69 Signal intensity Wash-in & Wash-out of T2*WI Curve Time Signal drops when Gd arrives 69 of 95
70 Parameter Calculation Gamma-variate function Same as first-pass T1 Blood volume, mean transit time After conversion from T2* to [Gd] 70 of 95
71 Signal intensity Wash-in & Wash-out of T2*WI Curve Time Signal drops when Gd arrives 71 of 95
72 Tracer concentration Perfusion from Tracer-Time Curve area ~ blood volume width ~ transit time height ~ blood flow Time Fairly close although not too accurate 72 of 95
73 Perfusion Parameters Blood volume = integration of (area under) first-pass curve Mean transit time = normalized first-moment (centroid) Same as first-pass T1 73 of 95
74 Tracer concentration Plus Variations in Arrival Time Time Most normal perfusion curves are like this 74 of 95
75 Parameter Names rcbv = cerebral blood volume rmtt = mean transit time rcbf = cerebral blood flow r for relative 75 of 95
76 Why Only Relative? Inter-subject comparison not allowed 76 of 95
77 Intra-Subject Perfusion Map Depiction rcbv rmtt rcbf 77 of 95
78 T2* Brain Perfusion MRI Good sensitivity 30 ~ 60% signal change First-pass suffices short scan Routinely used clinically 78 of 95
79 Clinical Applications Ischemic stroke Infarct, therapeutic decision Brain tumor Angiogenesis, biopsy guide 79 of 95
80 Perfusion MRI for Ischemic Stroke Angio CT T1+Gd 80 of 95
81 Perfusion MRI for Ischemic Stroke DWI (b=1000) ADC map 81 of 95
82 Perfusion MRI for Ischemic Stroke rmtt map rcbv map 82 of 95
83 Ischemic Stroke Diffusion negative: cytotoxic edema not commenced yet Likely reversible process Large CBV + long MTT: collateral 83 of 95
84 Diagnosis Affects Therapy 5-hr onset 13 hr after IA rtpa rmtt rmtt rcbv rcbv 84 of 95
85 Perfusion MRI for Glioma T2 FLAIR rcbv map 85 of 95
86 Perfusion MRI for Glioma F/U at 7 months F/U at 1 year 86 of 95
87 Note: DSC Perfusion MRI Also first-pass transit only Contrast (& blood) just passes the tissue capillaries Blood flow unequal to perfusion 87 of 95
88 Note: Abnormal Curves Signal drop without returning to baseline? Gd does not flow out?? Tortuous vessels? Permeable vessels? Microvascular structure? Still under debate & investigation 88 of 95
89 Perfusion MRI for Glioma T1WI + Gd rcbv map 89 of 95
90 Contrast concentration (arbitrary units) Gd Concentration-Time Curve lesion normal Time after bolus arrival (seconds) Likely reflect tortuous neovasculature 90 of 95
91 Gd Perfusion MRI Contrast + dynamic scan T1-weighted equilibrium phase T1-weighted first-pass T2*-weighted first-pass 91 of 95
92 Which Method to Use? Depends on tissue capillary characteristics Brain T2*WI used routinely Not necessarily for other tissues 92 of 95
93 Perfusion MRI Contrast + dynamic scan T1-weighted T2*-weighted Arterial spin labeling 93 of 95
94 Perfusion MRI with ASL Arterial spin labeling RF pulse to label the blood No injection needed We ll leave it for other semesters! 94 of 95
95 Contrast-Enhanced MRI for Tissue Perfusion Hsiao-Wen Chung ( 鍾孝文 ), Ph.D., Professor Dept. Electrical Engineering, National Taiwan Univ. Dept. Radiology, Tri-Service General Hospital 95 of 95
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