Imaging Cartilage using MR with a focus on knee osteoarthritis

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Imaging Cartilage using MR-- with a focus on
knee osteoarthritis
Advanced MSK Imaging Seminar Series

• Xiaojuan Li, PhD,
• MQIR, Dept. of Radiology, UCSF
• BioE297, Oct 21, 2005

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OUTLINE

• Overview of MRI and knee structure
• Imaging cartilage morphology
• qualitatively
• quantitatively
• Imaging cartilage biochemistry
• T2 mapping
• dGEMRIC
• Sodium imaging
• T1rho mapping

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Knee Joint Model
www.emedx.com
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MR Imaging
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Knee MRI
Femur
Biceps femoris muscle
Femoral cartilage
Lateral meniscus Anterior horn
Lateral meniscus Posterior horn
Tibial cartilage
Gastrocnemius muscle
Fibula
Tibia
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Knee MRI
Patellar cartilage
Anterior cruciate ligament
Patellar Ligament
Posterior cruciate ligament
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T2 relaxation

• Loss of phase coherence due to
• Molecular interactions
• Inhomogeneity of B0
• 1/T2 1/T2 1/T2inhomo

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T1 Relaxation
z
M0

y
x
Energy change btw spins and surroundings T1 time
depends on tissue composition, structure and
surroundings
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Cartilage Imaging

• Radiography provides in-direct imaging of
  cartilage.

• MR can image cartilage directly with good
  contrast to tissues around.

• High-resolution MR imaging can quantify
  morphologic changes in cartilage.

• Detecting biochemical or functional changes in
  cartilage is desirable.

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Imaging Cartilage Morphology
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T1-weighted Images
Spin Echo Image
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T1-weighted SPGR Images
SPGR-fs
Axial
Sagittal
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PD and T2-weighted images
Proton Density-weighted
T2-weighted
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Correlation With arthroscopy
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3 Tesla Imaging
1.5 T
3 T
1.5 T
3 T
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3 Tesla Imaging
3 T
1.5 T
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High Field MR Imaging
4.7 T, T2-weighted
Foster et. al., OA and cartilage, 1999
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Osteoarthritis (OA)

• Prevalent disease characterized primarily by
  cartilage degeneration
• In the US Today More than 20 million 80 people
  older than 75 years - radiographic evidence
• Debilitating disease leading to joint
  replacement 64.8 billion
• Early diagnosis of OA remains elusive.

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MR findings in Osteoarthritis

• More accurate -- quantitative analysis
• Earlier -- biochemical or functional changes in
  addition to morphological changes

Link et al., Radiology 2003
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Quantitative Image Analysis

• Articular Cartilage Volume
• Articular Cartilage Thickness
• Focal Cartilage Lesions

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Visualization
2D
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Cartilage morphology
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Focal Defect Quantitation
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Imaging Cartilage Biochemistry
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Cartilage Biochemical changes in OA

• Loosening or thinning of collagen network
• Increase of water
• Loss of proteoglycan
• More loss of PG
• Loss of water
• Further damage to Collagen network
• Cartilage thinning to nearly completely destroyed

http//bidmc.harvard.edu/
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T2 relaxation time mapping

• Slow molecular motion of cartilage water protons
  and ECM structure influence spin-spin relaxation
  (T2)
• T2 is dominated by anisotropic motion of water
  molecules in a fibrous collagen network
• Increase of water, damage to collagen network --gt
  increase of T2

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T2 vs. Histology (Toluidine Blue)
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T2 Z-score Image Examples
Normal
Mild OA
Severe OA
Z (T2-mean)/SD
Dunn et al, Radiology 2004
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Cartilage T2
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dGEMRIC

• Delayed gadolinium (Gd)-enhanced proton MRI of
  cartilage
• Proteoglycan (PG), or glycosaminoglycans (GAG)
  highly negative charged and Gd-DTPA also negative
  charged
• Loss of PG --gt increase of Gd-DTPA concentration
  --gt shorter T1 --gt increase of MR signal

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dGEMRIC
Bone
Cartilage
dGEMRIC
Bashir et al, MRM 1999
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Limitation of dGEMRIC

• Need injection of Gd-DPTA
• Joint exercise and long delay are needed after Gd
  injection for penetration of the contrast agent
  into cartilage
• Long time of T1 mapping

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Sodium Imaging of Cartilage

• Proteoglycan is a highly negative charged protein
  aggregate --gt fixed charge density (FCD) of
  cartilage
• This negative charge attracts sodium ions around
• Loss of PG --gt loss of sodium signal

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In Vivo Sodium Imaging
Healthy volunteer
Symptomatic Subject
Loss of sodium reflecting PG loss
Reddy et. al.
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Limitation of Sodium Imaging

• Inherently low sensitivity of sodium signal
• Special hardware requirements
• May have more applications with ultra-high field
  strength, such as 7T

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T1rho relaxation time mapping

• Spin-lattice relaxation in rotation frame
• T1rho can probe slow slow motion interactions
  between motionally restricted water molecules and
  their local macromolecular environment
• Increase of water, loss of PG --gt increase of
  T1rho

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Why T1rho?

• Approximately T1 at very low field --gt low
  frequency information --gt specific to changes in
  marcomolecues
• Different relaxation mechanism with T2
• T2 dipolar interaction, dominated by collagen
  network
• T1rho may dominated by NH-OH changes btw PG and
  water, therefore dominated by PG loss
• No need for contrast agent injection, neither
  special hardware requirement

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Spin-locking Technique
TSL Time of spin-locking, normally ranging
0-200ms FSL Spin-locking frequency, defining
strength of spin-lock, ranging from a few
hundreds to a few thousands Hz
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T1rho Fitting
S
(ms)
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40
60
80
TSL
T1rho-weighted images and fitted T1rho map
(TSL10,20,,90,100ms)
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In vivo T1rho in healthy volunteers
T1rho-weighted images at varying TSLs
TSL20ms
TSL40ms
TSL60ms
TSL80ms
High-res T1-weighted image
Reconstructed T1rho map
Reproducibility (n4) Coefficient of Variation
4.8
T1rho53.414.4 ms
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In vivo T1rho Spatial Variation
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T1rho in controls vs. OA
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T1rho vs. T2 values
Effect size mean1-mean2/pooled SD
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Acknowledgments

• MQIR/CMFI, Department of Radiology, UCSF
• Sharmila Majumdar, PhD
• Thomas Link, MD
• David Newitt, PhD
• Catherine Phan, MD
• Roland Krug, PhD
• Jan Bauer, MD
• Sandra Shefelbine, PhD
• Galateia Kazakia, PhD
• Julio Carballido-Gamio, PhD
• Tim Dunn
• Banerjee, Suchandrima
• Gabby Blumenkrantz
• Ben Hyun
• Kayvan Keshari
• Andrew Burghardt
• Jesus Lozano
• Darwin Castillo

Thank you for your attention!