ADVANCES IN LIVER MRI - Creative Group, Inc.

2014-10-27
RECENT ADVANCES
ADVANCES IN LIVER MRI
QUANTITATIVE
LIVER IMAGING
DYNAMIC
CONTRAST
TECHNIQUES
DR. KARTIK S. JHAVERI , MD
DIRECTOR , ABDOMINAL MRI
[email protected]
LIVER
SPECIFIC
CONTRAST
AGENTS
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1
RECENT ADVANCES
QUANTITATIVE
LIVER IMAGING
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DIFFUSE LIVER DISEASE
 Diffuse Liver disease can be challenging to
diagnose, quantitate and monitor
 Diagnosis
 Severity
Treatment Decisions
 Prognosis
 Newer Therapies Need Efficacy evaluation
 Anatomical MRI has limitations
 Quantitative Liver MRI Biomarkers !
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QUANTITATIVE MRI BIOMARKERS
QUANTITATIVE MRI BIOMARKERS
FAT
FAT
FIBROSIS
FIBROSIS
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IRON
IRON
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Fatty Liver Disease(FLD)
QUANTITATIVE MRI BIOMARKERS
Steatosis is characterized by lipid vacuoles within hepatocytes
FAT
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NAFLD / NASH
NAFLD/NASH
Non-Alcoholic Fatty liver Disease/Steatohepatitis
 SteatosisSteatohepatitisFibrosis
 NASH accounts for nearly 25% of all
NAFLD diagnoses
 Cirrhosis develops in 20-30% of NASH
patients
 Hepatocellular carcinoma develops at a
rate of 2.6% per year
Current Diagnosis and Monitoring
 Liver Biopsy: Invasive
 Risks associated with invasive procedure
 Only small portion of the liver is sampled
 Only one time point is sample
 Treatment is monitored by serum biomarkers (LFTs)
which are neither sensitive nor specific
 By 2020, NASH cirrhosis is predicted
to be the leading indication for liver
transplantation in the United States
As new drugs for NAFLD are being developed, the need for a simple and safe diagnostic
test is growing.
CHEMICAL SHIFT MR
Liver MRI Techniques
Most accurate imaging modality for liver fat estimation
 Signal Fat Fraction
 Chemical Shift Imaging
 MR Spectroscopy
 Frequency Selective Imaging (T2)
 Proton Density Fat fraction
Multiecho Low Flip Angle GRE
SI
TE
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CHEMICAL SHIFT
CHEMICAL SHIFT
IP
SI
SI
OP
TE
OP
TE
MRI
IP
MRI
OP
IP
OP
IP
OP
1.5T 0
2.2
4.4
6.6
8.8
11
3T
1.3
2.6
3.9
5.2
6.5
0
IP
OP
IP
OP
IP
OP
1.5T 0
2.2
4.4
6.6
8.8
11
3T
1.3
2.6
3.9
5.2
6.5
0
MRI
MRI
IP
OP
IP
OP
IP
OP
1.5T 0
2.2
4.4
6.6
8.8
11
3T
1.3
2.6
3.9
5.2
6.5
0
OP >> IP
IP
OP
IP
OP
IP
OP
1.5T 0
2.2
4.4
6.6
8.8
11
3T
1.3
2.6
3.9
5.2
6.5
0
IP >> OP
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Chemical Shift Imaging (In/Out Phase )
Fat Quantification
T1 IP
• Normal liver: similar signal on IP and OP
• Fatty liver: Dec. signal on OP images
SI IP – SI OP
~Liver Fat percentage = ---------------- X 100
SI IP
T1 OP
SOP
F+W
>15% Drop
High FA(>60-90) Detection
Low FA (<10) Quantification
MR Spectroscopy
 Direct measurement of the chemical
composition of tissue based on the frequency
composition of the signal arising from the
voxel of interest
 water peak: 4.7 ppm
 CH2 peak: 1.3 ppm
 STEAM/PRESS
F
FF =
SIP
Fat signal fraction confounded by T1 bias and T2*
MR Spectroscopy
Spectral Quantification:
•
Single voxel proton MRS
 Total hepatic triglyceride
concentration (HTGC)
Longo et al. JMRI 1995.
Szczepaniak et al. Am J Physiol Endocrinol Metab August 2004
% HTGC
=
Area under Total Lipid (TL)
peaks
(Between 0.9 to 3 ppm)
---------------------------------------------TL + Water
Illustration of normal spectra in a healthy control as compared
to the raised lipid peak in mild and severe fatty infiltration.
Disadvantages
 Sampling errors- 1 voxel
 Quality ~ Uniformity of the magnetic field
 Susceptibility effects -organ boundaries or
foreign bodies
 Shimming often required-Time
 Skilled operator to correctly perform the
examination, process the data, and interpret the
results.
 Data analysis is complex
Multi-Echo Low FA GRE
 Corrects for T2*/T2, T1 effects, spectral fat
modelling,eddy currents etc
 Fast: Single breath-hold sequence
 Simple: Technically less challenging than
spectroscopy.
Yokoo et al. Radiology. 2009 Apr;251(1):67-76.
Ishizaka et al. Magn Reson Med Sci. 2011;10(1):41-8.
Meisamy S,et al Radiology 2011;258:767–775.
 Addressed by Newer MRS Modifications
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Multi-Echo Low FA GRE
Multi-Echo Low FA GRE
(Proton Density)
Fat Fraction Map: 21.4%
TE=1.15
TE= 2.30
TE=3.45
TE=4.60
Low FA
Multiecho 3-6
MRI PULSE SEQUENCE PACKAGE
 Screening Dixon
 Multi-Echo Dixon VIBE
 HISTO (Hi Speed T2 Corrected MR
Spectro)
MRI PULSE SEQ WORKFLOW
Inline
Report*
SCREENING
DIXON
Clinical Report:
• 13.79% Fat
• 38.45 s-1 R2water
HISTO*
(MR
SPECT)
Inline
Report*
Multiecho
Dixon
VIBE
Clinical Report:
• e.g.13.02% Fat
• e.g. 54,39 s-1 R2*
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POTENTIAL APPLICATIONS
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*The product is currently under development; is not for sale in the U.S. and other countries. Its future availability cannot
be guaranteed.
LIVER DONOR STEATOSIS
Liver Donor Evaluation
(NA)FLD Clinic – Monitoring Tool
Bariatric Surgery-Pre,Post
Clinical Research / Drug Trials
Donor Steatosis Screening
Mild – OK
Moderate - ?
Severe- Rejected
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LIVER STEATOSIS
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LIVER STEATOSIS
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Liver Fibrosis
QUANTITATIVE MRI BIOMARKERS
FIBROSIS
• Excessive accumulation of extracellular
matrix proteins including collagen
• Can result in cirrhosis, liver failure, portal
hypertension requiring liver transplantation.
• Need to assess severity
- Hep. Surveillance
- Antiviral therapy in Hep B,C ?
• Accurate estimation difficult clinically
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Liver Fibrosis-Biopsy
Liver Fibrosis-Staging
•
• Gold (reference) standard for diagnosis &
severity
• ~ 1 / 50,000 of the liver (sampling error)
• specimen of ≥15 mm required for accuracy
(20–25 mm)
• 6–8 complete portal tracts (≥11)
• Small biopsies misleading for fibrosis
• Especially to stage NASH & HCV
• Invasive, Morbidity, Cost
METAVIR
STAGING
F0 normal collagen
•
F1 collagen expansion
•
F2 collagen extension
•
F3 bridging
•
F4 cirrhosis
Standish et al. Gut 2006
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Faria et al.RadioGraphics 2009
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What is MR Elastography ?
Liver Fibrosis Estimation
• Noninvasive measure of tissue stiffness
 Blood tests: Fibrotest, APRI(AST-Plt)
 US – Fibroscan (Transient Elastography)
 MR Elastography
 MR Diffusion, Perfusion
• Generation and transmission of mechanical shear
waves(low frequency – 60HZ) into body
• Phase contrast MRI sequence images the
resulting micron level tissue displacements
• Mathematical technique converts this data into
maps of tissue stiffness
 MR Gadolinium
• Normal liver stiffness ~2-2.5 kPa
MR Elastography-Set Up
MR Elastography – Images
Hardware and Software:
 Active and passive drivers*
 One sequence and protocols
 Sequence: 2D gradient-echo
with motion-encoding gradients
(MEG)
 20-30s per slice
0
4
8
Relative Shear Stiffness
MR Elastography examination set-up
Active Driver
Passive Driver and Body 18
Slide Courtesy: Siemens
Wave image
Elastogram
 Obtained by the application of
mechanical waves
 While measuring with a motionsensitive MR sequence
 Calculated from the wave image
 Providing reliable data about
tissue stiffness
Slide Courtesy: Siemens
MR Elastography -Data
Liver Fibrosis ?
“MRE is an accurate, noninvasive method of staging hepatic
fibrosis a and can replace liver biopsy for monitoring patients”
Performance of Magnetic Resonance Elastography and Diffusion-Weighted Imaging for the Staging of
Hepatic Fibrosis: A Meta-Analysis .Wang et al. HEPATOLOGY, Vol. 56, No. 1, 2012
Fibrosis
Score
F0
F1
F2
F3
F4
Sensitivity/Specificity
Wang
Chen
Kim
91/97%
92/95%
90/87%
Rustogi
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95/87%
94/73%
100/92%
85/88%
Rustogi et al. J Magn Reson Imaging. 2012 Jan 13.
Chen et al. Radiology. 2011 Jun;259(3):749-56
Kim et al. J Magn Reson Imaging. 2011 Nov;34(5):1110-6
Wang et al. AJR Am J Roentgenol. 2011 Mar;196(3):553-61
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MRE LIMITATIONS
US VS MR ELASTOGRAPHY
US
MR
 Small sample area
 Technical success,
repeatability variations
 Obesity, steatosis,ascites
 Young Modulus
 1D
 Accuracy ?
 Cheaper, Clinic
 Entire Liver
 Technical success better,
consistency
 Not affected
 Shear Modulus
 2D/3D
 Superior results
 Expensive
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 F0 vs F1 vs F2 (F1/F2 VS F3,F4 )
 NASH VS F1/F2,(F3/F4 IN NASH)
 Co-existent Iron ( Spin Echo MRE)
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QUANTITATIVE MRI BIOMARKERS
Hepatic Iron Overload
 Primary Hemochromatosis
-Genetic,
iron absorption
-Liver(hepatocytes), pancreas, heart
-Spleen NOT affected.
-Cirrhosis, HCC
IRON
• Secondary Hemochromatosis
-Transfusion, hemolytic anemias
-Spleen, Liver(Kupfer), Panc, Heart
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Hepatic Iron Overload
Out Phase
In Phase
Why Measure Liver Iron
Concentration (LIC) ?
 LIC predicts body iron stores
 Changes in LIC ~changes in body iron with chelation
therapy - calculate iron balance
 LIC predicts risk of complications
 Se. ferritin and transferrin saturation -Not
consistent/reliable
 MRI accurate- replaces liver biopsy
Chemical Shift MR Imaging
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 Normal Liver Fe < 36 µmol Fe/g;
 Iron overload Fe > 80 µmol Fe/g
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LIC Estimation
Signal Intensity Ratio- T2*
 Gandon Technique(Lancet 2004;363:357–362)
Signal Intensity Ratio - T2*,T2
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Relaxometry – T2 or R2(1/T2),T2*
GRE
Multiecho, Multiflip angle
SI Ratio -Liver and Paraspinal Muscle
ROI-large,same slice,avoid large vessels ,
artifacts
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Signal Intensity Ratio- T2*
Signal Intensity Ratio- T2*
GRE "T1" sequence GRE "PD" sequence GRE "T2" sequence
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GRE "T2+" sequence GRE "T2++" sequence
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RELAXOMETRY- R2
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www.radio.univ-rennes1.fr
RELAXOMETRY- R2
St Pierre et al (Blood 2005;105:855–861)
Ferriscan (www.resonancehealth.com/resonance/ferriscan)
Regulatory Approval - FDA,HC
Multiecho Spin Echo Pulse sequence
10-15min
Image Transfer to external server
LIC report within 48hours
~$300
TE6
TE9
FERRISCAN,9,12,15,18
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TE 12
TE 15
TE 18
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LIC Methods- Comparison
R2 Transverse Relaxation Times
SI RATIO-T2*
St Pierre et al. Blood. 2005;105:855.
Nonoverload
R2
(s-1)
79
500
66
400
50
300
26
200
13
100
0
0
0
233
80
160
240
320
400
80
160
240
320
400
Transverse relaxation rate R2 (s-1)
 Accurate for low and
moderate overload
 Callibrated for specific
scanner
 Good for detection,
inadequate for
quantification
 Easier to implement
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Thalassemia
major
155
RELAXOMETRY- R2
 Accurate across entire
clinical range of overload
 Validated for different
scanners and sites
 Accurate and Precise
quantification for guiding
therapy
 Involves additional cost
116
77
R2 (s-1)
0
0
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CAIPIRINHA
RECENT ADVANCES
Controlled Aliasing In Parallel Imaging Results In
Higher Acceleration
DYNAMIC
CONTRAST
TECHNIQUES
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CAIPIRINHA
CAIPIRINHA
•Reduced Aliasing
•Higher SNR
•Higher R factors
Reduce BH
Excellent IQ
1mm,12s,Matrix 320 x256
Phase Encoding Offsets =
Reduce Aliasing Artifacts
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CAIPIRINHA VIBE
without CAIPI
25.2 sec
CAIPI x 4
7.3 sec
CAIPIRINHA VIBE
CAIPI x 5,
5.9 sec
3D VIBE FatSat, matrix 256,
SL 3 mm, 261 x 380 mm
Courtesy Siemens
DYNAMIC IMAGING
TWIST-VIBE
Free-breathing, dynamic contrast-enhanced body imaging.
1mm,12s,Matrix 320 x256
DYNAMIC IMAGING
Hard to hit right
arterial phase
.
RADIAL-VIBE(STAR-VIBE)
Free-breathing, Non-dynamic contrast-enhanced body imaging.
Courtesy Siemens
TWIST-VIBE
TWIST-VIBE
Time Resolved Imaging With Interleaved Stochastic Trajectories
Courtesy Siemens
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FREE BREATHING MULTI-ARTERIAL PHASES, NO FLORO TRIGGER
*This product may not be commercially available in countries outside U.S., future availability cannot be guaranteed.
.
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RECENT ADVANCES
STAR-VIBE (RADIAL-VIBE)
2 year old patient with hepatoblastoma**
Conventional
LIVER
SPECIFIC
CONTRAST
AGENTS
StarVIBE*
10 year old patient
StarVIBE*
Conventional
Courtesy Siemens
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CLASSIFICATION
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CONTRAST ENHANCED LIVER MRI
Extracellular Gd-Based Contrast Agents (GBCA)
Extracellular
(ECCA)
Liver Specific
(HBCA)
Limitations of EBCA
Detection
• Dynamic phase imaging improves detection and
characterization of lesions
• Difficulties remain in detection of small hypovascular
lesions(Metastasis)
 Difficulties remain in characterization of hypervascular
lesions and HCC
LIVER SPECIFIC CONTRAST AGENTS
DUAL CAPABILITY
Characterization
Dynamic phase
Liver
Uptake in Hepatocytes
Selective increase of SI
Lesion
DYNAMIC PHASE - LIKE ECCM
HEPATOCYTE PHASE - BILIARY EXCRETION
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Gd-EOB-DTPA (Primovist)
CLINICAL APPLICATION
LIVER
Increase Lesion
Detection
 1st Gd based contrast agent approved specifically
for LIVER (in adults) by FDA & HC in North America
 “Focal Liver Lesion- Detection and Characterization”
 Lipophilic Ethoxybenzyl Group(EOB) – Hepatocyte
Characterize
Hypervascular lesions
Metastases
FNH vs Adenoma
Hypervascular
Met. vs FNH
HCC ?
? Biliary
? Liver Function
MUTIHANCE VS PRIMOVIST
LIVER SPECIFIC CONTRAST AGENTS
MULTIHANCE
Gd-BOPTA
PRIMOVIST
Gd-EOB-DTPA
MULTIHANCE
Gd-BOPTA
PRIMOVIST
Gd-EOB-DTPA
TYPE
Ionic Linear
Ionic Linear
TYPE
Ionic Linear
Ionic Linear
DOSE
0.1mmol/kg
0.025mmol/kg
DOSE
0.1mmol/kg
0.025mmol/kg
RELAXIVITY(relative)
BILIARY EXCRETION
Higher
Lower
RELAXIVITY(relative)
Higher
Lower
4%
50%
BILIARY EXCRETION
4%
50%
HEPATOBILIARY
PHASE
Late & Short
(1-2hr)
Early & Prolonged
(10min-hours)
HEPATOBILIARY
PHASE
Late & Short
(1-2hr)
Early & Prolonged
(10min-hours)
FDA APPROVAL
CNS
Adults and
Children(>2yrs)
LIVER
Adults
FDA APPROVAL
CNS
LIVER
Bolus Rate and Arterial Phase
MUTIHANCE VS PRIMOVIST
DYNAMIC PHASE - ARTERIAL ENHANCEMENT
2 ml/s
MULTIHANCE
PRIMOVIST
78
1ml/s
Haradome et al. JMRI 2010
Chung S-H et al JMRI 2010
Schmid-Tannwald et al .Acta Radiol 2012
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ARTERIAL PHASE ARTIFACT
ARTERIAL PHASE ARTIFACT
ACUTE
TRANSIENT
DYSPNOEA ?
ART
PRE
14% - Gd-EOB-DTPA
5% - Gd-BOPTA
Dose ?
Flow Rate ?
2ml/s > 1-2ml/s
AJR 2014 Oct
ARTERIAL
DELAYED
PVP
DEL
80
HEPATOBILIARY PHASE
BOLUS TRIGGER - ARTERIAL TIMING
AXIAL
CORONAL
15-20min
10min Post Injection
Van Kessel CS et al Eur Radiol 2012
SAGITTAL
3D GRE(VIBE)
2.5mm
1 ml /s
82
FLIP ANGLE (1.5T)
HEPATOBILIARY PHASE
HI RESOLUTION In 2014 !
12
20
25
1.5 T
CAIPIRHNA
30
35
40
3D RT-IR-GRE
84
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2014-10-27
Gd-DTPA MRI PROTOCOL
MR Protocol Optimization
Automated injection: 1 ml /s (vs 2 ml/s)
Use bolus detection: Fluoro Triggering or other
Unenhanced
T1
Use saline chaser of 20ml @ 1-2 ml/sec
T2
DWI
Gd DTPA
(2 ml/s)
Dynamic
Gd
Sequential K space Ordering versus Centric in 3D T1 GRE
Use Higher Flip Angle 25-30 for HB Phase
If serum bilirubin >1.8 mg/dl(>160umol/L), MELD >11,Child C : Poor
HB phase enhancement
TOTAL TABLE / SLOT TIME 20-30 Min
LIVER METASTASES
Gd-EOB-DTPA MRI PROTOCOL
10 min HC
Phase
Unenhanced
T1
T2
DWI
Gd-EOBDTPA
(1 ml/s)
20
Dynamic
min HC
Phase
Gd
TOTAL TABLE / SLOT TIME 30-45 Min
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Increase Lesion Detection
NEUROENDOCRINE TUMOR
COLORECTAL CARCINOMA
Increase Lesion Detection
NEUROENDOCRINE TUMOR
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SURGICAL PLAN - LOCATION
Increase Lesion Detection
NEUROENDOCRINE TUMOR
92
Characterize Hypervascular Lesions
Characterize Hypervascular Lesions
ADENOMA
FNH
LIVER SPECIFIC MR CONTRAST EXAM
Grazioli L. Radiology 2005; 236:166-77.
Giovanoli O. AJR Am J Roentgenol 2008; 190:W290-3.
Grazioli L .Radiology 2012;262:520-29
Purysko AJR 2012;198:115–123
 FNH
 HCA
 Benign Hyperplastic
Nodule/Mass
 Vascular Malformation
 Bile Ducts
 No Complications
 Conservative RX
 Benign Neoplasm




OC,Steriods
No bile ducts
Hemorrhage,Malignt
Surgical Resection
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FNH
95
HCC : Gd-EOB-DTPA
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LIVER DONOR EVLAUATION
SUMMARY
• Quantitative Liver MRI - Fat ,Fibrosis, Iron
- Replace Liver Biopsy ?
• Dynamic Fast Imaging (CAIPIRINHA)
-Increase Temporal Resolution(Multi Arterial)
- Free Breathing Dynamic(Poor BH,Children)
- High Resolution T1 VIBE(1mm , 320 x224)
 Liver Specific Contrast
- Technique Optimization
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OFF-LABEL USE
98
- Liver Metastases Surgical plan, FNH vs Adenoma
ACKNOWLEDGEMENTS
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Dr.Sunil Sugurulaxman, Siemens Canada
Nancy Talbot - MRI Supervisor, UHN
Karen Bodolai -MRI Technical Specialist
MRI Technologists Team, UHN
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