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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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©2011 MFMER | slide-4
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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©2011 MFMER | slide-5
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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©2011 MFMER | slide-6
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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©2011 MFMER | slide-8
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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©2011 MFMER | slide-9
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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©2011 MFMER | slide-11
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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©2011 MFMER | slide-13
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
-10
-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
-10
-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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©2011 MFMER | slide-14
Quantitative MT (qMT)
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©2011 MFMER | slide-15
0
2
4
6
1
f (%
)
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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©2011 MFMER | slide-16
-100
100Hz
0
1.5
1.0
3.0sB0 Map B1 Map T1 Map
0
2
4
6
8
10
12
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?
