Richard L. Ehman, M.D.Richard L. Ehman, M.D.

SCBT·MR Annual CourseOctober 26, 2011

SCBT·MR Annual CourseOctober 26, 2011

MR Elastography:

Assessment of Diffuse Liver Disease

MR Elastography:

Assessment of Diffuse Liver Disease

The Mayo Clinic and the presenter have patent rights and a relevant financial interest.

The Mayo Clinic and the presenter have patent rights and a relevant financial interest.

Disclosure:Disclosure:

Compliant with oversight by the Mayo Clinic Conflict of Interest Review Board.Compliant with oversight by the Mayo Clinic Conflict of Interest Review Board.

Assurance:Assurance:

www.softnono.com

Importance of Chronic Liver Disease, Fibrosis, CirrhosisImportance of Chronic Liver Importance of Chronic Liver Disease, Fibrosis, CirrhosisDisease, Fibrosis, Cirrhosis

•• A leading cause of death worldA leading cause of death world--wide wide

•• Increasing prevalence of conditions that Increasing prevalence of conditions that cause hepatic fibrosiscause hepatic fibrosis•• Hepatitis C Hepatitis C -- 170 M people globally170 M people globally•• Hepatitis BHepatitis B•• Obesity / Fatty liver diseaseObesity / Fatty liver disease

•• Fibrosis can be reversed, if diagnosed Fibrosis can be reversed, if diagnosed early and treatedearly and treated

Progression of Liver DiseaseProgression of Liver Disease

Liver BiopsyStandard Diagnostic Procedure to rule-out Fibrosis

Liver BiopsyStandard Diagnostic Procedure to rule-out Fibrosis

• Risk of Complications

• Potential Sampling Errors

• Subjective Histology Grading

• Risk of Complications

• Potential Sampling Errors

• Subjective Histology Grading

NormalNormal FibrosisFibrosis

ReversibleSilent

ReversibleSilent

CirrhosisCirrhosis

IrreversibleHigh mortality

IrreversibleHigh mortality

Noninvasive TestsNoninvasive Tests

• Serum Biomarkers

• Direct and Indirect

• Conventional Imaging

• MRI, US, CT

• US Elastography

• Fibroscan

• ARFI

• MRI Techniques

• Contrast enhanced

• Diffusion-weighted

• MR Elastography

MR ElastographyMR Elastography

2.5cm2.5cm

ConventionalMR Image

ConventionalMR Image

Tissue-simulating gel phantom with

stiff inclusions

3. Inversion3. Inversion

800 40Shear Stiffness (kPa)Shear Stiffness (kPa)

ElastogramElastogram

1. Driver1. Driver(30-500 Hz)(30-500 Hz)

2. MRE Sequence2. MRE Sequence

-10

Wave ImagesWave Images

0 +10Displacement (m)Displacement (m)

Acoustic Driver System for MREAcoustic Driver System for MREAcoustic Driver System for MRE

MREAbdominal Driver

MREAbdominal Driver

MREVibration Source

MREVibration Source

Elastogram

Sh

ear

Sti

ffn

ess

(kP

a)S

hea

r S

tiff

nes

s (k

Pa)

0

10

4

6

8

2

MR Elastography:adds ~ 5 min

(15 second scan)

MR Elastography:adds ~ 5 min

(15 second scan)

Conventional MRIexam of Abdomen:

~ 45 min

Conventional MRIexam of Abdomen:

~ 45 min

2.1 kPa Normal

Shear Stiffness (kPa)Shear Stiffness (kPa)0 102 4 6 8

Liver FibrosisLiver FibrosisLiver FibrosisBiopsy:Stage F2Biopsy:Stage F2

3.5 kPa

Biopsy:Stage F1Biopsy:Stage F1

3.1kPa

Biopsy:Stage F3Biopsy:Stage F3

4.8 kPa

Biopsy:Stage F4Biopsy:Stage F4

10.8 kPa

2.1 kPa

Normal

MRE-Assessed Liver Stiffness

(5.31, 6.24)2.265.78944

(3.92, 4.73)1.934.32893

(3.32, 4.04)1.523.68702

(2.81, 3.21)0.873.01761

(2.59, 2.96)0.972.771090

95% CIStd Dev

MeanNo.Fibrosis Stage

438 patients with biopsy < 1 year

0

2

4

6

8

10

Mea

n L

iver

Sti

ffn

ess

(kP

a)

0 1 2 3 4Fibrosis Stage

Normal

Normal F1

F4F2

Shear Stiffness (kPa)0 84 62

F0

F3

Sensitivity and Specificity of MRE for Hepatic Fibrosis• Rouviere O, Yin M, Dresner MA, et al. MR elastography of the liver: preliminary results.

Radiology. 2006;240:440-448.

• Huwart L, Peeters F, Sinkus R, et al. Liver fibrosis: non-invasive assessment with MR elastography. NMR Biomed. 2006;19:173-179.

• Yin M, Woollard J, Wang X, et al. Quantitative assessment of hepatic fibrosis in an animal model with magnetic resonance elastography. Mag Reson Med. 2007;58:346-353.

• Salameh N, Peeters F, Sinkus R, et al. Hepatic viscoelastic parameters measured with MR elastography. 2007;26:956-962.

• Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5:1207-1213.

• Huwart L, Sempoux C, Salameh N, et al. Liver fibrosis: Noninvasive assessment with MR elastography versus aspartate aminotransferase-to-platelet ratio index. Radiology. 2007;245:458-466.

• Huwart L, Salameh N, ter Beek L, et al. MR elastography of liver fibrosis: preliminary results comparing spin-echo and echo-planar imaging. Eur Radiol. 2008;18:2535-2541.

• Huwart L, Sempoux C, Vicaut E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135:32-40.

• Salameh N, Larrat B, Abarca-Quinones J, et al. Early detection of steatohepatitis in fatty rat liver by using MR elastography. Radiology. 2009;253:90-97.

• Asbauch P, Klatt D, Schlosser B, et al. Viscoelasticity-based staging of hepatic fibrosis with multifrequency MR elastography. Radiology. 2010;257:80-86.

Comparability to Transient Ultrasound Elastography• Oudry J, Chen J, Glaser KJ, et al. Cross-validation of magnetic resonance

elastography and ultrasound-based transient elastography: a preliminary phantom study. J Magn Reson Imaging. 2009;30:1145-50.

Reproducibility• Hines CD, Bley TA, Lindstrom MJ, Reeder SB. Repeatability of magnetic

resonance elastography for quantification of hepatic stiffness. J Magn ResonImaging. 2010;31:725-731.

• Motosugi U, Ichikawa T, Sano K, et al. Magnetic resonance elastography of the liver: preliminary results and estimation of inter-rater reliability. Jpn J Radiol. 2010;28:623-627.

• Hines CD, Lindstrom MJ, Varma AK, Reeder SB. Effects of postprandial state and mesenteric blood flow on the repeatability of MR elastography in asymptomatic subjects. J Magn Reson Imaging. 2011;33:239-244.

• Shire NJ, Yin M, Chen J, et al. Test-Retest Reproducibility of Magnetic Resonance Elastography for Non-Invasive Liver Fibrosis Assessment in Hepatitis C. Submitted.

Safety• Ehman EC, Rossman PJ, Kruse SA, Sahakian AV, Glaser KJ. Vibration safety

limits for magnetic resonance elastography. Phys Med Biol. 2008;53:925-935.

0.5

0.6

0.7

0.8

0.9

1.0

F≥1 F≥2 F≥3 F≥4

Fibrosis StageFibrosis StageFibrosis Stage

Huwart L et al. Gastroenterology 235 (2008) – 141 Patients Huwart L et al. Gastroenterology 235 (2008) – 141 Patients

UTEUTEUTE

MREMREMRE

Diagnostic Performance: APRI, UTE, & MREDiagnostic Performance: APRI, UTE, & MREDiagnostic Performance: APRI, UTE, & MRE

100% Correct100% Correct100% Correct

WorthlessWorthlessWorthless

Area underROC CurveArea underArea underROC CurveROC Curve

APRIAPRIAPRI

AST to platelet

ratio index

AST to AST to platelet platelet

ratio ratio indexindex

TechnicalSuccess

TechnicalSuccess

94%94%94%

84%84%84%

• Biopsy : No fibrosis• Biopsy : No fibrosisShear Stiffness (kPa)

80 4

2.3

41 yo Patient – Fatty Liver Disease 41 41 yoyo Patient Patient –– Fatty Liver Disease Fatty Liver Disease

• Biopsy : Stg. 3 fibrosis• Biopsy : Stg. 3 fibrosisShear Stiffness (kPa)

80 4

7.5

69 69 yoyo Patient Patient -- Fatty Liver Disease Fatty Liver Disease

Steatosis Does Not Affect Liver StiffnessSteatosisSteatosis Does Not Affect Liver StiffnessDoes Not Affect Liver Stiffness

Liv

er S

tiff

nes

s (k

Pa)

Liv

er S

tiff

nes

s (k

Pa)

Liv

er S

tiff

nes

s (k

Pa)

22

44

66

88

1010

1212

1414

00 55 1010 1515 2020 2525

Fat / Water RatioFat / Water RatioFat / Water Ratio

0.680.68

NormalNormal

Stage 0Stage 0

Stage 1Stage 1

Stage 2Stage 2

Stage 3Stage 3

Stage 4Stage 4

Liv

er P

atie

nt

Liv

er P

atie

nt

How Early Can MRE Demonstrate NASH in Patients with Fatty Liver Disease?

How Early Can MRE Demonstrate NASH in How Early Can MRE Demonstrate NASH in Patients with Fatty Liver Disease?Patients with Fatty Liver Disease?

Liver stiffness measurement (kPa)

Liver biopsy findings

cp484 cp765cp685 cp910 cp478 cp958

InflammGrade 0 0 1 1 2 1

Fibrosis Stage 0 0 0 0 4 4

MR Elastograms

2.02 2.05 4.38 3.59 10.24 7.52

Detection of Detection of SteatohepatitisSteatohepatitisbeforebefore the onset of Fibrosisthe onset of Fibrosis

• Biopsy: Not performedShear Stiffness (kPa)

80 4

11.7

55 55 yoyo Patient Patient –– Chronic Hepatitis C Chronic Hepatitis C

• Biopsy : Stg. 4 fibrosisShear Stiffness (kPa)

80 4

6.0

59 59 yoyo Patient Patient –– Alcohol Alcohol

76 76 yoyo Patient Patient -- AlcoholAlcoholShear Stiffness (kPa)

80 4

5.5

3.4

Abstinent

9 months later

47 47 yoyo female with Autoimmune Hepatitisfemale with Autoimmune Hepatitis

8/14/07 6/18/09

Mean Liver Stiffness: 4.0 kPa

Liver Biopsy Score = F0Liver Biopsy Score = F2Mean Liver Stiffness: 2.9 kPa

Sh

ear

Sti

ffn

ess

(kP

a)80

4

MR ElastographyMR MR ElastographyElastography

•• Emerging as a reliable nonEmerging as a reliable non--invasive invasive method for diagnosing hepatic fibrosismethod for diagnosing hepatic fibrosis

•• Safer, less expensive, and less affected Safer, less expensive, and less affected by sampling error than liver biopsyby sampling error than liver biopsy

•• Other potential applications (heart, lung, Other potential applications (heart, lung, pancreas, breast) are being exploredpancreas, breast) are being explored