Assessment of Renal Fibrosis Using Magnetization Transfer MRI...©2011 MFMER | slide-1 Assessment of...
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©2011 MFMER | slide-1 Assessment of Renal Fibrosis Using Magnetization Transfer MRI Lilach O. Lerman, MD, PhD Division of Nephrology and Hypertension Mayo Clinic, Rochester, MN
Transcript of Assessment of Renal Fibrosis Using Magnetization Transfer MRI...©2011 MFMER | slide-1 Assessment of...
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©2011 MFMER | slide-1
Assessment of Renal Fibrosis
Using Magnetization Transfer MRI
Lilach O. Lerman, MD, PhD Division of Nephrology and Hypertension Mayo Clinic, Rochester, MN
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©2011 MFMER | slide-2
Development of Renal fibrosis • Consistent predictor of an irreversible loss of renal
function • Accumulation of extracellular matrix is a common
denominator of progressive fibrosis • macromolecules like fibronectin, collagens type I, III, and
IV, elastin, thrombospondin, vitronectin, laminin, proteoglycans, glycoproteins
• A noninvasive, direct, specific method is needed • improve early diagnosis and gauge progression of renal
injury or success of therapy
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©2011 MFMER | slide-3
Magnetization transfer imaging (MTI) • Molecular MRI based on co-
existence of 2 tissue proton pools: 1. Observable, free water pool
(freedom to perfuse / diffuse) 2. Invisible, restricted water pool
(bound to local molecules).
• An off-resonance MT can render restricted molecules ‘visible’
• Longitudinal magnetization of restricted water molecules is saturated using a selective radio-frequency (RF) pulse
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Evaluation of MTI contrast
• Due to their saturation, exchanged molecules do not participate in the MR signal of the free water pool - a detectable decrease in free water signal at the readout - proportional to restricted pool size and exchange rate
• In scar tissue collagen is the main target macromolecule
• Optimal MTI parameters depend on - Collagen type - Tissue type - Magnetic field
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Experimental Validation
7T and 16.4T: • Ex vivo: excised mouse kidneys • In vitro: collagen phantom • In vivo: unilateral murine renal artery stenosis (RAS) • Longitudinal: at 2, 4, & 6 wks of unilateral murine RAS 3T: • In vitro: collagen phantom • In vivo: unilateral swine RAS • In vivo: prediction/detection of reversal of swine RAS
• Hypothesis: MTI can detect renal fibrosis - correlate with kidney function and oxygenation
in renovascular disease
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MTR Maps of Murine RAS Kidneys
Baseline MT-Weighted MTR Map
1.0
0.8
0.6
0.4
0.2 0
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©2011 MFMER | slide-7
1.0
0.8
0.6
0.4
0.2 0
STK Sham
Trichrome Sirius Red under Polarized Light MTR Map
Fibrosis Necrosis Pelvis
MTI for Fibrosis Measurement in Murine RAS
• Jiang K, et al… Lerman LO. Radiology: 160566, 2016.
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Baseline 2 Weeks 4 Weeks 6 Weeks 0
1.0
0.2
0.4
0.6
0.8
Fibrosis Necrosis Edema MTI vs. BOLD-MRI
MTI
BOLD
Jiang K, et al… Lerman LO. Radiology: 160566, 2016.
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3.0 Tesla MRI
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©2011 MFMER | slide-10
MTI with Moderate and Severe RAS
Jiang K, et al. Invest Radiol 52: 686-692, 2017
50#
60#
70#
80#
90#
1# 2# 3# 4# 5# 6# 7# 8# 9# 10# 11# 12# 13# 14# 15# 16#
MTR
#(%)#
Cortex ############Medulla##############################Cortex####################Medulla#1000#Hz# # # ###############600#Hz#
0#
1.4#
1000#Hz#
600#Hz#
Control# Moderate#Stenosis#a" Severe#Stenosis#
b"P=0.001"
P
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Correlation between MTR and Renal Fibrosis
Control ARAS y = 1.14x + 67.28
r = 0.75 P
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©2011 MFMER | slide-12
0.5
0.55
0.6
0.65
0.7
0.75
0.8
Baseline 50% 75% 100% Recovery
MTR
0.6
0.65
0.7
0.75
0.8
0.85
0.9
Baseline 50% 75% 100% Recovery
MTR
MTI: Hemodynamic Stability
Baseline 50% 75% 100% Recovery
• STK cortical MTR largely stable over a range of RBF • slight drop at recovery
• A transient decrease in CLK MTR, due to increased fluid?
0
1.4
STK CLK
* *
* * *P
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MTI in Predicting Renal Recovery
• Pigs studied after 6 wks of RAS and again 4 wks after PTRA• ΔMTR correlates well with renal ΔGFRn
y = -127.5x + 0.2 r = 0.75
P = 0.072
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-5
0
5
10
-0.04 -0.02 0.00 0.02 0.04 0.06
ΔG
FRn (
ml/1
00m
l/min
)
ΔMTR
y = -135.6x - 1.6 r = 0.87
P = 0.028
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-0.06 -0.04 -0.02 0.00 0.02 0.04
ΔG
FRn (
ml/1
00m
l/min
) ΔMTR
Cortex Medulla
• Jiang K, et al. In Progress
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Quantitative MT (qMT)
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0
2
4
6
1
f (%
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Control RAS
Control (n=5) RAS (n=8)
In Vivo qMT at 16.4T: Renal Cortex
P=0.021 y = 0.12x + 4.01
r = 0.88 P
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-100
100Hz
0
1.5
1.0
3.0sB0 Map B1 Map T1 Map
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CLK STK CLK STK
f (%
)
Cortex Medulla
CLK STK
qMT Fitting Bound Pool Fraction f
Feasibility of qMT in Swine Kidney at 3.0 T
• Jiang K, et al. In Progress
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©2011 MFMER | slide-17
Conclusions: MTI for Detection of Kidney Fibrosis • In vivo MTR (16.4T, 7T, 3T) correlates well with
renal fibrosis determined by histology May allow detection/monitoring of renal disease
• May allow quantitative reproducible measures • Need to establish sensitivity and specificity;
application to other models • Cost, availability, contraindications, vendor
dependence, application in human subjects?
