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Where are we with Molecular Imaging The Molecular Imaging System

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Where are we with Molecular Imaging The Molecular Imaging System Powered By Docstoc
					                                                                                         The Molecular Imaging System
                                                                                                      Ligaments
                                                                                                                                   Synovium

                                             Where are we with                                                     Bone

                                             Molecular Imaging?                                                                            Meniscus




                                          Bernard J. Dardzinski, Ph.D.                                                                                  Cartilage
                             Sr. Director, Imaging
                Bone, Respiratory, Immunology, Endocrinology
                            Merck, West Point, PA
           Adjunct Professor of Radiology, University of Pennsylvania

3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                         Molecular Imaging?
          • What molecules?
          • Cartilage Composition
          • Cartilage Imaging
                    –     T2 Mapping
                    –     T1ρ Mapping
                    –     dGEMRIC
                    –     Diffusion-Weighted Imaging/Mapping
                    –     Sodium
          • Analysis
          • Summary

3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                             Molecular Imaging?




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                    1
                               Composition of Cartilage




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                      3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   http://www.bidmc.org/Research/Departments/Radiology/Laboratories/Cartilage.aspx




              Histologic Zones of Articular Cartilage                                                                                                                    Spatial Variation in the Solid and
                                                                                                                                                                                   Fluid Phase
                                 Gliding Zone                                                                                                                                                 90                                                                         35




                                                                                                                                                                                                                                                                                Solid Content (%)
                                                                                                                                                                         Fluid Content (%)


                                                                                                                                                                                              85                                                                         30


                Transitional Zone                                                                                                                                                             80                                                                         25


                                  Radial Zone                                                                                                                                                 75                                                                         20

      Zone of Calcified Cartilage
                                                                                                                                                                                              70                                                                         15
                                                                            Subchondral Bone
                                                                                                                                                                                                   0           20               40          60         80        100

                                                               Orientation of                                                                                                                Normalized distance from subchondral bone
                                                               Collagen Fibrils
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                      3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                   Cartilage Imaging                                                                                                                                         MR
                                                                                                                                                                                                          Parameter
  Healthy                         Minor Collagen       Major Structural          Complete
                                                                                                                                                                                                                                                 Collagen
  Cartilage                 PG       Changes Localized    Defects Gross Volume Cartilage Loss                                                                                                                              T2                  Water Content
                          Depletion            Lesions                Changes
                                                                                                                                                                                                                                                Orientation
                                onset of symptoms                            pain, swelling                 loss of function                                                                                                                   Proteoglycan
                                                                                                                                                                                                                      T1ρ
                                                                                                                                                                                                                                                Collagen??
                                            Molecular Imaging

                                                        T2 MRI
                                                                                           Conventional MRI                                                                                                dGEMRIC                               Proteoglycan
                                                       T1ρ MRI
                                                     Diffusion MR
                                                      dGEMRIC
                                                                                                            Radiography                                                                                                                          Tortuosity,
                                                     Sodium MRI
                                                                                                                                                                                                                     ADC                      Diffusivity, Fiber
                                                                                                                                                                                                                                                 Orientation

3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009      Adapted from www.mmrrcc.upenn.edu/highlights/Knee_Sampler.ppt   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                                                                                                             2
                                                                                                                                                                          More Exotic
                                                                                                                 • Synovial Inflammation
                                                                                                                                     – DCE-MRI
                                                                                                                                     – Subchondral fluid dynamics in a model of osteoarthritis: use of dynamic
                                                                                                                                       contrast-enhanced magnetic resonance imaging.
                                                           MR                                                                               • Lee JH, Dyke JP, Ballon D, Ciombor DM, Rosenwasser MP, Aaron RK.
                                                                                                                                            • Osteoarthritis Cartilage. 2009 Apr 17. [Epub ahead of print]
                                                       Parameter                                                                     – Post Contrast MRI
                                                                                                                                     – Magnetic resonance imaging in osteoarthritis: which method best
                                                         Signal                                                                        reflects synovial membrane inflammation? Correlations with clinical,
                                                                            Proteoglycan                                               macroscopic and microscopic features.
                                                        Intensity                                                                           • Loeuille D, Rat AC, Goebel JC, Champigneulle J, Blum A, Netter P, Gillet P,
                                                                                                                                              Chary-Valckenaere I.
                                                                                                                                            • Osteoarthritis Cartilage. 2009 Mar 24. [Epub ahead of print]
                                                                                                                                     – USPIO
                                                                                                                                     – FDG-PET
                                                                                                                                     – Folate
                                                                                                                 • Optical Probes


3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                  Signal Intensity


                                                                                                                                                                                           M0                                     T2
                                                                   T2 Mapping




                                                                                                                                             9                                       TE (ms)                                                   99
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                       T2 vs. Distance from
                    T2 Maps of Normal Cartilage
                                                                                                                                                        Subchondral Bone
                                                                                                                                            80
                                                                                       T2 (ms)
                                                                                                                                            70
                                                                                           1 - 20
                                                                                                                                            60
                                                                                                                                T2 (msec)




                                                                                           21 - 30
                                                                                           31 - 40
                                                                                                                                            50
                                                                                           41 - 50
                                                                                           51 - 60                                          40
                                                                                           61 - 70
                                                                                           71 - 80                                          30
                                                                                           81 - 110                                         20
                                                                                           111 - 140
                                                                                                                                                 0.1     0.2            0.3        0.4   0.5       0.6        0.7         0.8        0.9         1
                                                                                           141 - 255
                                                                                                                                                          Normalized Distance from Subchondral Bone


                                                                                                                                                                                         Dardzinski, et al., Spatial variation of T2 in human articular cartilage,
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                       Radiology, 1997.




                                                                                                                                                                                                                                                                     3
                                                                                                                                                                                          34 yo Subject with Superficial
                                                                                                                                                                                                   Fibrillation
                                                                                                                   T2 (ms)
                                                                                                                          1 - 20
                                                                                                                          21 - 30                                                                                                                      T2 Profile
                                                                                                                          31 - 40
                                                                                                                                                                                                                                   80
                                                                                                                          41 - 50                                                                                                  75
                                                                                                                                                                                                                                   70
                                                                                                                          51 - 60                                                                                                  65

                                                                                                                          61 - 70                                                                                                  60

                                                                                                                                                                           T2 Map




                                                                                                                                                                                                                         T2 (ms)
                                                                                                                                                                                                                                   55
                                                                                                                          71 - 80                                                                                                  50
                                                                                                                                                                                                                                   45
                                                                                                                          81 - 110
                                                                                                                                                                                                                                   40
                                                                                                                                                                                                                                                                            Superficial Zone
                                                                                                                          111 - 140                                                                                                35
                                                                                                                                                                                                                                   30
                                                                                                                          141 - 255
                                   Normal                                        Symptomatic                                                                                                                                             0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

                                                                                                                                                                                                                                            Normalized Distance from Subchondral Bone



3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                            T2 Maps                                                                                   Variation in T2 As a Function of Age

                                                                                                            T2 (ms)                                                                                   Young Adult
                                                                                                                                                                                           80
                                                                                                                 1 - 20                                                                               Adult
                                                                                                                 21 - 30
                                                                                                                                                                                                      Mature Adult
                                                                                                                                                                                           60
                                                                                                                                                               T2 (msec)



                                          Young Adult                                                            31 - 40
                                                                                                                  41 - 50
                                                                                                                  51 - 60
                                                                                                                  61 - 70                                                                  40
                                                                                Adult                             71 - 80
                                                                                                                  81 - 110
                                                                                                                  111 - 140                                                                20
                                                                                                                  141 - 255                                                                     0.0            0.2                 0.4           0.6            0.8             1.0
                                             Mature Adult
                                                                                                                                                                                                                     Normalized Distance
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                 Mosher, Dardzinski, and Smith, Radiology, 214, 2000.




In Vivo Proximal Interphalangeal Joint T2 Mapping
                                                                                                                                                                                          PIP Average T2 (n = 5)
                                                                                                                                                                                           75
                                                                                                                                                                 Mean Cartilage T2 (ms)




                                                                                                                                                                                           70

                                                                                                               256 ms                                                                      65

                                                                                                                                                                                           60

                                                                                                                                                                                           55

                                                                                                                                                                                           50
                                                                                                               85 ms
                                                                                                                                                                                           45

                                                                                                               0 ms                                                                        40

                                                                                                                                                                                           35
                                                                                                                                                                                                      0.0          0.2             0.4         0.6        0.8         1.0
                                                                                                                                                                                                         Normalized Distance From Bone
      39 x 39 x 1000 μm                                                          Lazovic-Stojkovic J, Mosher TJ, Smith HE, Yang QX,
                                                                                 Dardzinski BJ, Smith MB.
                                                                                                                                                                                                                                             Lazovic-Stojkovic J, Mosher TJ, Smith HE, Yang QX,
                                                                                                                                                                                                                                             Dardzinski BJ, Smith MB.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009        Radiology. 2004 Oct;233(1):292-6. Epub 2004 Aug 18.   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                             Radiology. 2004 Oct;233(1):292-6. Epub 2004 Aug 18.




                                                                                                                                                                                                                                                                                                        4
                       T2 Mapping in the Shoulder
          • T2 mapping of articular cartilage of
            glenohumeral joint with routine MRI
            correlation-initial experience.
                    – Maizlin ZV, Clement JJ, Patola WB, Fenton
                      DM, Gillies JH, Vos PM, Jacobson JA.
                    – HSS J. 2009 Feb;5(1):61-6. Epub 2009 Jan
                      22.




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                      Cartilage Repair
          • Ability of dGEMRIC and T2 mapping to
            evaluate cartilage repair after
            microfracture: a goat study.
                    – Watanabe A, Boesch C, Anderson SE, Walter
                      B, Mainil Varlet P.
                    – Osteoarthritis Cartilage. 2009 Apr 17. [Epub
                      ahead of print]
                                                                                                                              Figure 4
                                                                                                                              The difference in T2 between that measured at 0, 30, 55, and
                                                                                                                              90 degrees relative to B0 in each superficial and deep layer
                                                                                                                              of repair tissue and native cartilage. The bar indicates the
                                                                                                                              standard error of the mean.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                 Cartilage Repair and Damage
                                                                                                          • T2 mapping and dGEMRIC after autologous chondrocyte
                                                                                                            implantation with a fibrin-based scaffold in the knee: Preliminary
                                                                                                            results.
                                                                                                                    – Domayer SE, Welsch GH, Nehrer S, Chiari C, Dorotka R, Szomolanyi
                                                                                                                      P, Mamisch TC, Yayon A, Trattnig S.
                                                                                                                    – Eur J Radiol. 2009 Jan 19. [Epub ahead of print
                                                                                                          • Quantitative T2 mapping during follow-up after matrix-associated
                                                                                                            autologous chondrocyte transplantation (MACT): Full-thickness and
                                                                                                            zonal evaluation to visualize the maturation of cartilage repair tissue.
                                                                                                                    – Welsch GH, Mamisch TC, Marlovits S, Glaser C, Friedrich K, Hennig
                                                                                                                      FF, Salomonowitz E, Trattnig S.
                                                                                                                    – J Orthop Res. 2009 Jan 9. [Epub ahead of print]
                                                                                                          • Can T2 relaxation values and color maps be used to detect chondral
                                                                                                            damage utilizing subchondral bone marrow edema as a marker?
                                                                                                                    – Bining HJ, Santos R, Andrews G, Forster BB.
             Figure 5
                                                                                                                    – Skeletal Radiol. 2009 May;38(5):459-65. Epub 2008 Dec 17.
             T2-calculated map of the cartilage specimen measured at 0 (A), 30 (B), 55 (C),
             and 90 (D) degrees relative to B0. No obvious dependence of T2 on the angles
             relative to B0 was observed in repair tissue (arrows), while clear dependence of
3rd
             T2 on the angles relative to B0 was observed in adjacent native cartilage
      International Workshop on Osteoarthritis Imaging, May 13 -16 ,2009
                                                             th   th                            3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                             5
                                                                   T2 Mapping                                                                                             T2 Posters @ this Meeting
                                                                                                                                                •               #13 – Same Day T1ρ, T2, and dGEMRIC measures of cartilage post-acl
          • Sensitive to                                                                                                                                        injury
                                                                                                                                                                       – Pedersen, et al.
                    – Hydration – collagen concentration                                                                                        •               #16 – Voxel based assessment of disease progression in articular cartilage
                                                                                                                                                                with T2 follow-up examinations: getting new diagnostic information for free
                    – Orientation                                                                                                                                      – Raya, et al.
                                                                                                                                                •               #17 – Reproducibility of knee cartilage T2 measures across different
          • Newly available pulse sequences and                                                                                                                 vendors’ 3.0T scanners
            software on MRI scanners with color T2                                                                                              •
                                                                                                                                                                       – Balamoody, et al.
                                                                                                                                                                19 – A comparison of methods to measure T2 decay times
            map generation                                                                                                                                             – Riek, et al.
                                                                                                                                                •               #20 – Effect of knee alignment on T2 relaxation time of articular cartilage
          • Relatively rapid acquisition                                                                                                        •
                                                                                                                                                                       – Ojala, et al.
                                                                                                                                                                #21 – Long-term and short-term reproducibility of T2 relaxation time in
          • SNR and resolution trade offs                                                                                                                       human knee cartilage
                                                                                                                                                                       – Lammentausta, et al.

          • Biomechanical, aging changes

3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                             3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                    Signal Intensity


                                                                                                                                                                                                                      M0      T1ρ
                                                                            T1ρ (rho)




                                                                                                                                                                            0      10                               40         80
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                             3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   TSL (ms)




                Rapid 3D molecular imaging (< 10 min)
                                                                                                            T1ρ (ms)                                                            T1ρ and the Meniscus
                                                                                                                                                • T1rho relaxation time of the meniscus and
                                                                                                                                                  its relationship with T1rho of adjacent
                                                                                                                                                  cartilage in knees with acute ACL injuries
        0.7 x 0.7 x 3 mm3
        32 Slices per view
                                                                                                                                                  at 3 T.
        TA = 10 min
                                                                                                                                                                       – Bolbos RI, Link TM, Ma CB, Majumdar S, Li
                                                                                                                                                                         X.
                                                                                                                                                                       – Osteoarthritis Cartilage. 2009 Jan;17(1):12-8.
                                                                                                                                                                         Epub 2008 Jul 7.


3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009          www.mmrrcc.upenn.edu/highlights/Knee_Sampler.ppt   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                                              6
                                                                            Bolbos RI, Link TM, Ma CB, Majumdar S, Li X.                                                                                                 Bolbos RI, Link TM, Ma CB, Majumdar S, Li X.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   Osteoarthritis Cartilage. 2009 Jan;17(1):12-8. Epub 2008   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009         Osteoarthritis Cartilage. 2009 Jan;17(1):12-8. Epub 2008
                                                                            J l7                                                                                                                                         J l7




                                                             Other Studies                                                                                                                                         T1ρ
          • In vivo T1rho quantitative assessment of knee cartilage after anterior
            cruciate ligament injury using 3 Tesla magnetic resonance imaging.                                                                   •      Similar to T2 relaxation
                    – Bolbos RI, Ma CB, Link TM, Majumdar S, Li X.
                    – Invest Radiol. 2008 Nov;43(11):782-8.                                                                                      •      Probe molecular fluctuations in kHz range
          • Quantitative assessment of bone marrow edema-like lesion and
            overlying cartilage in knees with osteoarthritis and anterior cruciate                                                               •      Wider dynamic range in cartilage defects
            ligament tear using MR imaging and spectroscopic imaging at 3
            Tesla.                                                                                                                               •      Special pulse sequences needed
                    – Li X, Ma BC, Bolbos RI, Stahl R, Lozano J, Zuo J, Lin K, Link TM,
                      Safran M, Majumdar S.                                                                                                      •      SAR
                    – J Magn Reson Imaging. 2008 Aug;28(2):453-61.
          • Meniscal measurements of T1rho and T2 at MR imaging in healthy                                                                       •      B1 field inhomogeneities
            subjects and patients with osteoarthritis.
                    – Rauscher I, Stahl R, Cheng J, Li X, Huber MB, Luke A, Majumdar S,                                                          •      Mensical as well as cartilage
                      Link TM.
                    – Radiology. 2008 Nov;249(2):591-600.                                                                                        •      R1ρ correlates with PG

3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                      T1ρ Posters @ this Meeting
          • #13 – Same Day T1ρ, T2, and dGEMRIC
            measures of cartilage post-acl injury
                    – Pedersen, et al.                                                                                                                                                                        dGEMRIC




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                                                                                    7
                                                                                                                                                            Proteoglycans in Articular Cartilage

                                                                                                                                                                                                                             +
              Signal Intensity




                                                                                                                                                                                                                                            +
                                                                                                                                                                                                                             –
                                                                                                                                                                                                                             —      – +                                     + Na+
                                                                                                                                                                                                                                    –                                        – Gd-DTPA2-
                                                                                                                                                                                                                                        –
                                                                                                                                                                                                                                                                             – GAG
                                                                                                                                                                                                                                –
                                                                                                                                                                                                                             + –
                                                                                 M0                                        T1                                                                                                 –

                                       50                                                                                  1650
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009
                                                                            TI (ms)                                                              3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                          Bashir, Gray, Burstein, MRM 1996




                 Excised Human Articular Cartilage
                                                                                                                               1mM Gd-DTPA2-                                                                  Hip Dysplasia
                                                                                       MR image, TI = 2.5 sec



                                                                                       MR image, TI = 0.25 sec


                                                                                       [GAG], T1 map



                                                                                       H&E staining (structure)                                                                           dGEMRIC image of the asymptomatic
                                                                                                                                                                                          (left) and symptomatic (right) hip in the
                                                                                                                                                                                          same individual.
                                                                                       Toluidine Blue staining (GAG)
                                                                                                                                                                                          The symptomatic hip has lower GAG
                                                                                                                                                                                          concentration.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                    Bashir, Gray, Hartke, Burstein, MRM 1999            3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                      http://radiology.bidmc.harvard.edu/research/cartilage/research/glyco/invivo-app2.html




                                                             Other Studies                                                                                                                                              dGEMRIC
          •               Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage: Clinical Associations
                          in Obese Adults.
                                 –   Anandacoomarasamy A, Giuffre BM, Leibman S, Caterson ID, Smith GS, Fransen M, Sambrook PN, March
                                                                                                                                                           • Measure of GAG concentration
                                     LM.

          •
                                 –   J Rheumatol. 2009 Apr 15. [Epub ahead of print]
                          Reproducibility of imaging human knee cartilage by delayed gadolinium-enhanced MRI of                                            • T1 post Gd maps
                          cartilage (dGEMRIC) at 1.5 Tesla.
                                 –
                                 –
                                     Multanen J, Rauvala E, Lammentausta E, Ojala R, Kiviranta I, Häkkinen A, Nieminen MT, Heinonen A.
                                     Osteoarthritis Cartilage. 2009 May;17(5):559-64. Epub 2008 Dec 10.                                                    • Lower dGEMRIC index – lower T1 – lower
          •               Relationship between cartilage glycosaminoglycan content (assessed with dGEMRIC) and OA
                          risk factors in meniscectomized patients.
                                 –   Ericsson YB, Tjörnstrand J, Tiderius CJ, Dahlberg LE.
                                                                                                                                                             GAG concentration
                                 –   Osteoarthritis Cartilage. 2009 May;17(5):565-70. Epub 2008 Oct 29.
          •               In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis
                          using multi-parametric MRI.                                                                                                      • Intravenous Gd-DTPA2- injection
                                 –   Juras V, Bittsansky M, Majdisova Z, Szomolanyi P, Sulzbacher I, Gäbler S, Stampfl J, Schüller G, Trattnig


          •
                                 –
                                     S.
                                     J Magn Reson. 2009 Mar;197(1):40-7. Epub 2008 Dec 8
                          Radiographic and patient factors associated with pre-radiographic osteoarthritis in hip dysplasia.
                                                                                                                                                           • Move joint for 10 minutes, image 30-90
                                 –
                                 –
                                     Jessel RH, Zurakowski D, Zilkens C, Burstein D, Gray ML, Kim YJ.
                                     J Bone Joint Surg Am. 2009 May;91(5):1120-9.
                                                                                                                                                             min post injection
                                                                                                                                                           • Sensitive to physiological state

3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                        3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                                                                                                                                        8
                        T2, T1 Relaxation Mapping                                                             dGEMRIC Posters @ this Meeting
                           of Articular Cartilage
                                                                                                          • #13 – Same Day T1ρ, T2, and dGEMRIC measures of
                                                                                                            cartilage post-acl injury
            • T2:                                                                                                             – Pedersen, et al.
                      – Water changes in articular                                                        • #14 – Effects of weight loss on articular cartilage
                        cartilage (collagen matrix)                                                         proteoglycan content utilizing dGEMRIC at 3T
                                                                                                                              – Anandacoomarasamy, et al.
            • T1:                                                                                         • #22 – Depth-wise temporal dynamics of Gd-DTPA2- in
                                                                                                            femoral articular cartilage
                      – Proteoglycan integrity                                                                                – Lammentausta, et al.
                                                                                                          • #23 – Delayed gadolinium enhanced MRI of meniscus:
                                                                                                            differences in OA
                                                                                                                              – Li, et al.


3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                             Diffusion Imaging
                                                                                                           Signal Intensity


                                                                                                                                                                                M0            ADC
                        Apparent Diffusion Coefficient
                                   (ADC)




                                                                                                                                  0                                                           500
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   b-value (s/mm2)




          Multimodal approach in the use of clinical scoring, morphological MRI and
          biochemical T2-mapping and diffusion-weighted imaging in their ability to assess
          differences between cartilage repair tissue after microfracture therapy and matrix-
          associated autologous chondrocyte transplantation: a pilot study.
                                                                                                                                                   Diffusion Imaging
                    – Welsch GH, Trattnig S, Domayer S, Marlovits S, White LM, Mamisch
                      TC.                                                                                 • Low T2 makes acquisition difficult
                    – Osteoarthritis Cartilage. 2009 Apr 17. [Epub ahead of print]
                                                                                                          • Long acquisition time for multiple b-values

                                          DWI                               T2 Map




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                    9
                                                                                                                                          Proteoglycans in Articular Cartilage

                                                                                                                                                                                                           +
                                                                                                                                                                                                                                 +
                                                                 Sodium MRI                                                                                                                                 —                  +                     + Na+
                                                                                                                                                                                                                       –
                                                                                                                                                                                                                             –
                                                                                                                                                                                                                                                     – GAG
                                                                                                                                                                                                                  –
                                                                                                                                                                                                             +




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                      3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                        Bashir, Gray, Burstein, MRM 1996




                                                                             Borthakur A, Mellon E, Niyogi S, Witschey W,
                                                                             Kneeland JB, Reddy R.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009    NMR Biomed. 2006 Nov;19(7):781-821. Review        3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   http://www.nibib.nih.gov/nibib/Image/Eadvances/Feb07/Gold_technology_image.jpg




          Sodium imaging of osteoarthritis
     Detection of molecular loss in cartilage




                                                                                                                                                                                                                                       Borthakur A, Mellon E, Niyogi S, Witschey W,
                                                                                                                                                                                                                                       Kneeland JB, Reddy R.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   www.mmrrcc.upenn.edu/highlights/Knee_Sampler.ppt   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                               NMR Biomed. 2006 Nov;19(7):781-821. Review




                                                                                                                                                                                                                                                                                            10
          • Clean demarcation of cartilage tissue
            23Na by inversion recovery.
                    – Rong P, Regatte RR, Jerschow A.
                    – J Magn Reson. 2008 Aug;193(2):207-9. Epub
                      2008 May 1.




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                            3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                           Sodium Imaging
                                                                                                               •      Naturally occurring in cartilage
                                                                                                               •      Low background concentration
                                                                                                               •      Requires special hardware
                                                                                                               •      Low SNR
                                                                                                               •      Low resolution
                                                                                                               •      7T+



3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                            3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                           Reviews of Molecular MRI
          •      Comparison of quantitative imaging of cartilage for osteoarthritis: T2, T1rho,
                 dGEMRIC and contrast-enhanced computed tomography.
                    –     Taylor C, Carballido-Gamio J, Majumdar S, Li X.
                    –     Magn Reson Imaging. 2009 Mar 6. [Epub ahead of print
          •      MR imaging of cartilage and its repair in the knee - a review.


          •
                    –
                    –
                          Trattnig S, Domayer S, Welsch GW, Mosher T, Eckstein F.
                          Eur Radiol. 2009 Mar 13. [Epub ahead of print]
                 Tracking longitudinal changes in knee degeneration and repair.
                                                                                                                       Parameter (T2) Map Analysis
                    –     Burstein D.
                    –     J Bone Joint Surg Am. 2009 Feb;91 Suppl 1:51-3
          •      Toward imaging biomarkers for glycosaminoglycans.
                    –     Gray ML.
                    –     J Bone Joint Surg Am. 2009 Feb;91 Suppl 1:44-9.
          •      New techniques in articular cartilage imaging.
                    –     Potter HG, Black BR, Chong le R.
                    –     Clin Sports Med. 2009 Jan;28(1):77-94. Review
          •      Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.
                    –     Borthakur A, Mellon E, Niyogi S, Witschey W, Kneeland JB, Reddy R.
                    –     NMR Biomed. 2006 Nov;19(7):781-821. Review




3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                            3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                 11
                                                                                                                                                                             Group Composite Map
                                                                                                                                                                          Verb Generation Task, N=158




                                                                                 Dardzinski BJ, Mosher TJ, Li S, Van Slyke MA, Smith MB.                                                                                   Talairach J, Tournoux P (1988). Co-planar stereotaxic atlas of the
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009        Radiology. 1997 Nov;205(2):546-50.                        3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009       human brain. Thieme, New York.




                                                Application of MRI to                                                                                                         Generating the Warped
                                                 population studies                                                                                                              Cartilage Image
          • Motivation: Application of MRI parametric
                                                                                                                                                                                                                                                              bone
            mapping to population studies and
            therapeutic clinical trials                                                                                                                                                                                                                Articular surface

          • Problem: How can information contained                                                                                                                             T2 map                                                          Warped Cartilage
            within MR images be reduced for
            statistical analysis without loss of                                                                                                                                                                                                                 T2 (ms)
                                                                                                                                                                                                                                                                      1 - 20
            important spatial information?                                                                                                                                                                                                                            21 - 30
                                                                                                                                                                                                                                                                      31 - 40
                                                                                                                                                                                                                                                                      41 - 50
                                                                                                                                                                                                                                                                      51 - 60
                                                                                                                                                                                                                                                                      61 - 70
                                                                                                                                                                                                                                                                      71 - 80

                                                                                                                                                                                                                       Generate ROI                                   81 - 110
                                                                                                                                                                                                                                                                      111 - 140
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                  3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                  141 - 255




         Results: Asymptomatic Reference Population                                                                                                     Case Study: 42 year-old Male
            Subject                                T2 Map                   Warped T2 Map
                                                                                                                                                       Subject with Anterior Knee Pain
                     1
                                                                                                                                                                       Standard T2 Map                                                          Intra z-score
                     2                                                                                        Population
                                                                                                               Average

                     3


                     4


                     5
                                                                                                                                                                                                                       Warped T2 Map
                     6
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                  3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                                                                                                12
       Potential Methods of Comparison                                                                                                                                        Comparing Bulk T2 Value with
          with Reference Population                                                                                                                                              Reference Population
                                                                                                                                                                         • Patient: 45 msec ± 13
                                                                                                                                                                           msec
          •      Subjective scoring by expert readers                                                                                                                    • Reference
          •      Bulk T2 value                                                                                                                                             Population: 45 msec                                                          140



          •      Cartilage T2 profiles                                                                                                                                     ± 13 msec                                                                    120

                                                                                                                                                                                                                                                        100



          •      Warped cartilage T2 maps                                                                                                                                                                                                                80




                                                                                                                                                                                                                                               Number
                                                                                                                                                                                                                                                         60
                                                                                                                                                                                                                                                                                          x = 45 msec
                                                                                                                                                                                                                                                                                          σ = 45 msec
                                                                                                                                                                                                                                                         40

                                                                                                                                                                                                                                                         20

                                                                                                                                                                                                                                                          0
                                                                                                                                                                                                                                                              10   20   30    40     50   60    70      80
                                                                                                                                                                                                                                                                             T2 (msec)



                                                                                                                                                               Conclusion: No statistically significant difference
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                                      3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




       Comparing Average Cartilage T2                                                                                                                                                Comparison with Reference
       Profile with Reference Population                                                                                                                                                    Population
                                                                                        80


                                                                                        70                                                                                                      Patient                                                        Reference
                                                                                        60
                                                                            T2 (msec)




                                                                                        50


                                                                                        40


                                                                                        30                                                                                                                                                                                         > +2.0 s.d.
                                                                                        20
                                                                                             0.0   0.1   0.2   0.3   0.4   0.5   0.6   0.7   0.8   0.9   1.0
                                                                                                                                                                                                                                           Z-score                                 > - 2.0 s.d.
                                                                                                                Normalized Distance

                                                                                                                                                                                     Conclusion: Focal area of statistically
Conclusion: No statistically significant difference                                                                                                                                  significant increased T2 (1% of total area)
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                                      3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                      Comparison with Reference                                                                                                                                                                  Cartilage Warping
                     Reference
                                                                                                                                                                         • Objective inter-subject comparison of
                                      Patient                                                Z-score                       % > +2.0 s.d                                    cartilage parametric maps
                                                                                                                                   0.55                                  • Retain important spatial information
                                                                                                                                   1.05                                  • More sensitive to focal regional differences
                                                                                                                                   0.40
                                                                                                                                                                           than bulk T2 values, or cartilage profiles
                                                                                                                                                                         • Limited by distortion at cartilage
                                                                                                                                   1.55
                                                                                                                                                                           boundaries
                                                                                                                                   0.15
                                                                                                                                                                         • Characterize large populations for clinical
                                                                                                                                   4.20                                    trials
                                                                                                                                   2.25
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                                      3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                                                                                                             13
                                                                                                                                                                                                                    Baseline                 Follow Up
                                                     New Techniques
                                                                                                                                                                        Intra
                                                                                                                                                                       Subject
          • New techniques for cartilage magnetic
            resonance imaging relaxation time
            analysis: texture analysis of flattened
            cartilage and localized intra- and inter-                                                                                                                   Inter
                                                                                                                                                                       Subject
            subject comparisons.
                    – Carballido-Gamio J, Link TM, Majumdar S.
                    – Magn Reson Med. 2008 Jun;59(6):1472-7.



                                                                                                                                                                                                                                                    Carballido-Gamio J, Link TM, Majumdar S.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                                                                   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009               Magn Reson Med. 2008 Jun;59(6):1472-7.




                                                                                                                                                                                                 Voxel base techniques
                                                                                                                                                                      • Voxel-based
                                                                                                                                                                        reproducibility of T2
                                                                                                                                                                        relaxation time in patellar
                                                                                                                                                                        cartilage at 1.5 T with a
                                                                                                                                                                        new validated 3D rigid
                                                                                                                                                                        registration algorithm.
                                                                                                                                                                                – Raya JG, Horng A, Dietrich
                                                                                                                                                                                  O, Weber J, Dinges J,
                                                                                                                                                                                  Mützel E, Reiser MF,
                                                                                                                                                                                  Glaser C.
                                                                                                                                                                                – MAGMA. 2009 Apr 1.
                                                                                                                                                                                  [Epub ahead of print


                                                                                                            Carballido-Gamio J, Link TM, Majumdar S.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009                                   Magn Reson Med. 2008 Jun;59(6):1472-7.          3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                   Vendor Platforms                                                                                                                                                                     Analysis
                                                                                                                                                                      •      Inherent spatial variation
                                                                                                                                                                      •      Registration for longitudinal studies
                                                                                                                                                                      •      Intra- and Inter- subject comparisons
                                                                                                                                                                      •      Reproducibility and disease state
                                                                                                                                                                      •      Sequence parameters, TEs and TIs
                                                                                                                                                                      •      Coverage vs. time
                        Siemens Syngo MapIt ®                                                                 GE Cartigram®
          provides the Inline calculation of parametric maps for the T1, T2
          and T2* properties of the imaged tissue and the necessary
          measurements.

3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   http://www.gehealthcare.com/euen/mri/products/signa-hdx-3t/image_gal_msk.html   3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                                                                                               14
                                        Sequence and Analysis
                                                                                                                                         Changes in OA
                                        Posters @ this Meeting
          • #17 – Reproducibility of knee cartilage T2 measures                           • T2
            across different vendors’ 3.0T scanners                                                 – Heterogeneous
                    – Balamoody, et al.                                                             – ↑ - Loss of anisotropy w/ early damage
          • 19 – A comparison of methods to measure T2 decay                              • T1ρ
            times                                                                                   – Increased
                    – Riek, et al.
                                                                                                    – Increased dynamic range than T2
          • #24 – Fast 3D T1 mapping for dGEMRIC by variable flip
            angle approach: need for B1 correction                                        • dGEMRIC
                    – Manuel, et al.                                                                – Sensitive to GAG
          • #25 – Accuracy of T1 fitting for pharmacokinetic analysis                               – Decrease in index before morphological changes??
            of contrast enhanced knee MR                                                  • Sodium
                    – de Bruin, et al.                                                              – Direct imaging correlation w/loss of PGs


3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                       Complimentary Techniques
          • Spatial distribution and relationship of T1ρ                        Healthy Control
            and T2 relaxation times in knee cartilage
            with osteoarthritis.
                                                                                                                                              T1ρ                    T2
                    – Li X, Pai A, Blumenkrantz G, Carballido-
                      Gamio J, Link T, Ma B, Ries M, Majumdar S.
                    – Magn Reson Med. 2009 Mar 24. [Epub ahead                       OA Subject
                      of print



                                                                                                                                                            Li X, Pai A, Blumenkrantz G, Carballido-Gamio J, Link T,
                                                                                                                                                            Ma B, Ries M, Majumdar S.
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009   Magn Reson Med. 2009 Mar 24. [Epub ahead of print]




                                                                  Conclusions
                                                                                                                               Cartilage
          • Technical and application development continues – T2
            and dGEMRIC widely used
          • Take advantage of T2 mapping from OAI                                                                                Menisci

          • New analysis techniques are needed                                                                                      Bone
          • What is the predictive value?
          • Have we addressed reproducibility adequately?                                                                     Synovium
          • Have we addressed natural progression?
          • T2 and dGEMRIC/T1ρ measures are complimentary
          • Larger T1ρ studies                                                                                               Ligaments
          • Use in limited ways to select subjects?



3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009       3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




                                                                                                                                                                                                                       15
3rd International Workshop on Osteoarthritis Imaging, May 13 th-16th,2009




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