Contrast-Enhanced MR Perfusion Imaging - University of Wisconsin ...

RSNA Chicago Dec 2, 2008
Contrast-Enhanced
MR Perfusion Imaging
Howard A. Rowley, M.D.
University of Wisconsin, Madison
hrowley@uwhealth.org
Learning Objectives
Principles of dynamic CE-MR perfusion
Pathophysiology of perfusion – stroke & tumors
Stroke trials: Perfusion-Diffusion mismatch
Perfusion protocols for tumors
Perfusion Overview
• Per · fyu' zhun: the flow of blood per unit mass of tissue
• Methods
–Intravascular tracers
• Gadolinium contrast (DSC-MRI and DCE-MRI)
• Iodinated contrast (CT perfusion)
–Diffusable tracers
• 99m Tc-HMPAO (SPECT) H
15
2 O (PET)
• Magnetized blood H 2 O protons (ASL-MRI)
• Applications
– Stroke
– Tumors
Basis
Contrast
SNR
Flow
Volume
Transit
Coverage
Brain Perfusion Techniques
DSC
Dynamic
Susceptibility
Contrast
T2*
Gd
+++
+
+
++
+++
DCE
Dynamic
Contrast
Enhancement
T1
Gd
++
-
++
++
Permeability
+
ASL
Arterial
Spin
Labeling
Spin Tag
-
+
++
-
-
+++
CTP
CT
Perfusion
Density
Iodine
++
++
++
++
+
Ischemic Stroke Treatment – 2008
• IV tissue plasminogen activator (tPA)
– Only FDA-approved acute stroke drug
– 3 hour treatment window
• MERCI - Concentric clot retrieval device
– Rescue therapy - approved 2004
– Device approval (not outcomes-based)
• Off label approaches
– IV tPA after 3 hours
– IV-IA tPA sequential strategies
– IA tPA, clot angioplasty / fragmentation
– Ultrasound-assisted tPA lysis
–Imaging-based selection
Courtesy of
Chelsea Kidwell, MD
Pathophysiology of Ischemic Stroke
Cerebral Blood Flow Thresholds
CBF 100
90
ml /
100 gm / 80
min
70
60
50
40
30
20
10
Normal
Hypoperfusion
Modified from W.T.Yuh and others
Oligemia
Ischemia
Penumbra
Infarction
100
90
80
70
60
50
40
30
20
10
Pathophysiology of Ischemic Injury:
Duration and Degree of ↓ CBF
CBF
ml /
100g /
min
25
20
15
10
5
0
Normal neuronal function
Reversible injury
(penumbra)
Infarction
1 Time (hrs) 2
MCA infarct:
1.9 million
neurons die
per minute!
J Saver
Stroke 2006

Overview: CT and MR Perfusion Methods
Inject Scan Model Parameter Maps
Overview: CT and MR Perfusion Methods
Inject Scan Model Parameter Maps
CT
I
CT
I
MTT CBV
CBF
MR
Gd
MR
Gd
Key Perfusion Parameters
• Cerebral Blood Flow (CBF)
– Delivery of blood to tissue / unit time
– Units: ml / 100g brain / min
• Cerebral Blood Volume (CBV)
– Measure of autoregulation
– Units: ml / 100 g brain
• Mean Transit Time (MTT)
– Average time to flow thru
capillaries (artery → vein)
– Units: seconds
CBF = CBV
MTT
Central Volume
Principle
Ischemia: Hemodynamics & Perfusion
• ↑ Collateral flow → ↑ MTT
• Vasodilatation → ↑ CBV (until CPP ↓)
• End result: ↓ CBF
Central
volume
theory
MTT
CBF =
CBV
MTT
CBV
CBF
Ischemia: Hemodynamics & Perfusion
Perfusion Modeling
• ↑ Collateral flow → ↑ MTT
• Vasodilatation → ↑ CBV (until CPP ↓)
• End result: ↓ CBF
MTT
CBV
CBF
Central
volume
theory
CBF =
CBV
MTT
Zaharchuk, G. AJNR 2007; 28: 1850-1858

Perfusion and Traffic Jams…
• Long transit times MTT
• Collateral routes CBV
• Variable net effect CBF
Penumbral Imaging
Perfusion-Diffusion Mismatch
DWI
MTT
Penumbra = Target for Intervention
Clinical Trials - PWI/DWI Mismatch
• DIAS, DEDAS, DIAS-2 (Hacke)
– 3-9 hours, Desmoteplase vs placebo
• DEFUSE (Wechsler)
– 3-6 hours, open label IV tPA
• EPITHET (Davis)
– 3-6 hours, IV tPA vs placebo
– Selected by CT, but all get PWI/DWI
– MR at 3-5 days and 90 days
– Unique design: is the PWI/DWI concept valid?
• MR RESCUE (Kidwell)
– 0-8 hours
– MERCI retrieval vs medical therapy
Desmoteplase Trials: DEDAS / DIAS
Dose Escalation study of Desmoteplase in Acute ischemic Stroke
Desmoteplase In Acute ischemic Stroke
Trial Overview:
Double blind, randomized, placebo controlled trials
IV delivery, 3-9 hour time window
Plasminogen activator – from vampire bat saliva
Selection based on PWI-DWI Mismatch
MRI Inclusion:
PWI defect at least 2 cm AND ~20% larger than DWI
PWI should be obvious, even visible on raw images
MRI Exclusion:
DWI > 1/3 MCA
MRA: ICA occlusion
DIAS Results: Hacke et al
Stroke 2005; 36:66-73
DEDAS Results: Furlan et al
Stroke 2006; 37:1227-1231
BATS
Diffusion-Perfusion Mismatch
Treatment Triage
%
80
70
60
50
40
Desmoteplase – DIAS Results
Hacke et al, Stroke 2005; 36:66-73
46.7 46.7
71.4
60
49.3
38.7
102 patients
3-9 hours
IV DSPA
PWI > DWI
30
20
10
0
23.1
13
19.2 22.2
62.5 90 125 Total Placebo
Desmoteplase dose (μg/kg) vs placebo
Reperfusion
Favorable
Outcome

DEFUSE Trial
Mismatch associated
with good outcomes following reperfusion
Before tPA
NIHSS 16
Albers et al Ann Neurol 60: 508-517, 517, 2006
Key Results of the DEFUSE Study
• Target Mismatch pattern (42%)
identifies patients who appear to benefit
substantially from early reperfusion
3 cc
65 cc ↓ M2 Flow
• Malignant MRI pattern (8%) predicts
severe ICH following reperfusion
4.5 hrs
After tPA
NIHSS 5
• Small DWI and PWI lesions (26%)
are associated with favorable outcomes
6 cc 0 cc Improved
Albers et al Ann Neurol 60: 508-517, 517, 2006
MR Rescue - Penumbral Pattern:
Recanalization, Good Outcome
Pre
Post
Baseline NIHSS 11 Left MCA Occlusion, TIMI 2
Recanalization at 5 hrs 50 mins, Day 90 mRS 1
MR RESCUE data courtesy of Chelsea Kidwell
EPITHET Results
• EPI Thrombolysis Evaluation Trial
• 101 patients, 3-6 hrs IV tPA vs placebo
• Selected by CT, but all got PWI/DWI
• MR at 3-5 days and 90 days
• Results (ISC 2008)
• 83% had penumbral pattern (Tmax >2 sec)
• Mean infarct growth: 1.24 tPA vs 1.78 placebo
• If mismatch present, tPA ↑ reperfusion
• All trends favor PWI-DWI selection
• EXTEND mismatch trial being planned: 3-9 hrs
Davis et al Lancet Neurology 2008; 7:299-309
PWI-DWI selection better than basic CT
Schellinger et al Stroke 2007; 38:2640-2645
1210 patients 5 centers IV tPA
CT

Stroke MR Alters Therapy Plan in 26%
CT Perfusion Mismatch = DWI/PWI Mismatch
Wintermark et al Neurology 2007; 68:694-697 and Stroke 2006; 37:979-985
Mismatch Criteria
MR CT
PWI ↑ MTT
DWI ↓ CBV
PCT
CTA
Perfusion CT ‘Mismatch’: ↑ MTT >145% = penumbra ↓ CBV < 2 ml/100gm = core
DWI PWI MRA
Heidenreich et al Acta Radiologica 2008; 49:550-557
10 Minute Acute Stroke Protocol
Physiologic stroke triage: occlusion site, PWI-DWI mismatch
Ischemic Penumbra
Value of Dynamic Perfusion Metrics
FrFSE 1:03
DWI 0:40
FSPGR 0:36
CBV
CBF - bc
CBF - ASL
TRICKS 0:54
PWI 1:12
Automated processing
FMT CBV CBF
FMT Tmax MTT
Glioma: Perfusion Shows ↑CBV
CBV & Permeability Predict Tumor Grade
T2*
T2*
based
CBV
Grade 2
Fibrillary
astrocytoma
K fp
T1
based
ROI
T2* vs time
Grade 3
Anaplastic
astrocytoma
T2*
Effect
T1
Effect
Grade 4
Glioblastoma
multiforme
CBV
T1+
MTT
Patankar et al AJNR 2005; 26:2455-2465

↑ CBV Predicts Glioma Transformation
Post Radiation Necrosis : Low CBV
Baseline 6 months 18 months
Danchaivijitr et al Radiology 2008; 247: 170-178
CBV Estimation in Tumors
Gadolinium Preload Reduces Model Dependence
UTI CTI GV PBSI MSD NEI
Metastatic Breast Carcinoma (HER-2 +)
Without preload
CT-
MTT
CBF
With preload
Paulson and Schmainda Radiology 2008; 249:601
CT+ CBV Permeability
Elevated Permeability in Acute Ischemic Stroke
Perfusion Summary
CT
CTA
MTT
CBF
1
2
3
1
2
3
CBV
KPS
1
2
3
1
2
3
• Perfusion Methods
–Dynamic Susceptibility Contrast – T2*
–Dynamic Contrast Enhancement – T1
–Arterial Spin Labeling - Tag
• Key Parameters
–Cerebral Blood Flow
–Cerebral Blood Volume
–Mean Transit Time
• Applications
–Stroke and Tumors