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MRI-based
MRI based Monitoring Tools for
       Iron Chelation


      Pairash Saiviroonporn Ph D
              Saiviroonporn, Ph.D.


      Radiology Department
Faculty of Medicine Siriraj Hospital
F   l    f M di i Si i j H i l
        Mahidol Universityy
Topics


* Introduction
   * Benefit
   * Concept
   * Implementation
       p
* T2* measurement at Siriraj Hospital
* Asia-Pacific Network for T2 measurement
                           T2*
MR Applications Related to Iron

 Qualitative
   * S
     Susceptibility Detection
            tibilit D t ti
       * Abnormal Vein: Deoxy Hemoglobin
       * Cerebral Micro bleeds: Hemosiderin
       * Activation of Neuron: Oxy/Deoxy Hemoglobin
   * Superparamagnetic Iron Oxide particle (SPIO)
       * In vivo Tracking of Stem Cell


Q
 Quantitative
      i i
   * Iron Concentration Measurement
MR Applications Related to Iron

  Susceptibility Detection (Abnormal Vein: Deoxy Hemoglobin)




           T1 Post-Contrast                       SWI

Images courtesy of Daniel Kido, MD, Loma Linda University, Loma Linda, CA
MR Applications Related to Iron
* Susceptibility Detection (Cerebral Micro Bleeds)




                    T2          T2*
               Stroke. 2002;33:1536-1540.
MR Applications Related to Iron

Susceptibility Detection (Activation of Neuron: Oxy/Deoxy Hemoglobin)


    Finger Tapping           Verbal Fluency         Checker board
MR Applications Related to Iron

      * In vivo Tracking of Stem Cell




  Figure 4 Test of positive-contrast imaging in vivo. A short-axis section of porcine myocardium
  injected with superparamagnetic-iron-oxide-labeled embryonic stem cells is shown. (A) Gradient-
  echo images show voids at each injection site of 1 million labeled cells (B) The off resonance
                                                                        cells.          off-resonance
  projection at –800 Hz clearly shows the four injections of labeled cells as regions of bright signal
  (arrow). Permission obtained from John Wiley & Sons © Cunningham CH et al. (2005) Magn Reson
  Med 53: 999–1005.


NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE OCTOBER 2006 VOL 3 NO 10
MR Applications Related to Iron
* Iron Concentration Measurement




   TE1            TE4              TE8     T2* map




   TE1            TE4              TE8      LIC map
MRI

           Hardware


            Software



 SE         GREASE          GRE

PD,T1,T2
PD T1 T2   PD,T1,T2+T2
           PD T1 T2+T2*   PD,T1,T2
                          PD T1 T2*
MR Applications Related to Iron
* Susceptibility Detection (Cerebral Micro Bleeds)




                    T2          T2*
               Stroke. 2002;33:1536-1540.
Black Blood T2* Images (Qualitative)


Normal




Mild




Severe



          PD (TE1)      T2*(TE4)   Heavily T2*(TE8)
T2 and T2* Variables

  - T2 (R2) and T2* (R2*) Relaxation Time

                   1/T2*=1/T2+1/T2´
                     R2*=R2+R2´

     Note: R2*=1000/T2*; T2 in msec and R2 in Hz

T2´  local magnet inhomogeneity
such as from patient (stored iron in myocardium) or
MR machine (main magnetic field inhomogeneity)

     Higher Iron Concentration  Lower T2*
       g
                                Higher R2*

    N t Iron Concentration  R2* or (1/ T2*)
    Note: I  C     t ti
T2* Measurement

Relative signal intensity at
  e ve s g         e s y
    each TE was fit to                               Low Iron
                                                     Concentration
a monoexponetial function:


  S( )
  S(TE) = A.exp(-TE/T2*)
           .e p(   /   )
        = A.exp(-TE*R2*)



                                                TE

                          High Iron Concentration
Black Blood T2* Images and maps (Quantitative)


Normal



Marginal




Mild




Severe


             TE1       TE4      TE8       T2* map   msec
LIC=2.5 (normal [ < 3] )   4.3 (mild [ 3-7 ] )




                                                    mg/g dry
                                                      / d
                                                    weight
8.7 (moderate [ 7-15] )    22.7 (severe [ > 15] )
Cardiac T2* Analysis : CMRtools (Brompton)
CHLA’s Software (Pixel-wised)




                                Can
                                C report on
                                          t
                                - Mean of ROI
                                - Median of ROI
Siriraj Iron Analysis (SIA) Software (Pixel-wised)
Comparison of T2* and T2 Iron Measurement

T2* (sensitive but not
    (se s ve bu o        T2 (less se s ve bu good
                            ( ess sensitive but
for heavily overload)       for heavily overload)




     1-Kg Scale                20-Kg Scale
Comparison of T2* and T2 Iron Measurement




T. He, et al. MRM 2009;61:501-6.   CJ Brewer, et al. JMRI 2009;29:357-64.
Cardiac T2* and T2 Measurements:
                    Case#1 - No Iron Overload




         TE1
           1                       TE2              TE4
                                                      4
T2* Sequence: T. He, et al. JMRI 2007;25:1205-9.          msec
T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
Cardiac T2* and T2 Measurements:
                 Case#2 - Moderate Iron Overload




         TE1
           1                       TE2              TE4
                                                      4
T2* Sequence: T. He, et al. JMRI 2007;25:1205-9.          msec
T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
Cardiac T2* and T2 Measurements:
                  Case#3 - Severe Iron Overload




         TE1                       TE2              TE4
T2* Sequence: T. He, et al. JMRI 2007;25:1205-9.
                                                          msec
T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
Liver T2* and T2 Measurements:
                     Case#1 - No Iron Overload




         TE1                       TE3                  TE6
T2* Sequence: CJ. Brewer, et al. JMRI 2009;29:357-64.         msec
T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
Liver T2* and T2 Measurements:
                   Case#2 - Severe Iron Overload




         TE1                       TE3                  TE6
T2* Sequence: CJ. Brewer, et al. JMRI 2009;29:357-64.         msec
T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
Liver T2* and T2 Measurements:
                Case#3 - Very Severe Iron Overload
                            y




         TE1                       TE3                  TE6
T2* Sequence: CJ. Brewer, et al. JMRI 2009;29:357-64.         msec
T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
SIA Software
SIA Software: Time Series Report
SIA Software: Case#1 – Good Response




t=0 mo    t=7 mo     t=22 mo   t=0 mo   t=7 mo        t=22 mo
                   msec                          mg/g dw
                                                  gg
SIA Software: Case#1 – Not Good Response




t=0 mo   t=7 mo     t=22 mo   t=0 mo   t=7 mo        t=22 mo
                  msec                          mg/g dw
                                                 gg
Acknowledgements
                  g
Department Faculty of Medicine Siriraj Hospital
  - Her Majesty Cardiac Center
  - Diagnostic Division, Radiology Department
  - Haematology/Oncology Division, Department of
  Pediatrics
  -Thalassemia Center

Philips Medical Systems

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MRI-based Monitoring Tools for Iron Chelation

  • 1. MRI-based MRI based Monitoring Tools for Iron Chelation Pairash Saiviroonporn Ph D Saiviroonporn, Ph.D. Radiology Department Faculty of Medicine Siriraj Hospital F l f M di i Si i j H i l Mahidol Universityy
  • 2. Topics * Introduction * Benefit * Concept * Implementation p * T2* measurement at Siriraj Hospital * Asia-Pacific Network for T2 measurement T2*
  • 3. MR Applications Related to Iron  Qualitative * S Susceptibility Detection tibilit D t ti * Abnormal Vein: Deoxy Hemoglobin * Cerebral Micro bleeds: Hemosiderin * Activation of Neuron: Oxy/Deoxy Hemoglobin * Superparamagnetic Iron Oxide particle (SPIO) * In vivo Tracking of Stem Cell Q Quantitative i i * Iron Concentration Measurement
  • 4. MR Applications Related to Iron Susceptibility Detection (Abnormal Vein: Deoxy Hemoglobin) T1 Post-Contrast SWI Images courtesy of Daniel Kido, MD, Loma Linda University, Loma Linda, CA
  • 5. MR Applications Related to Iron * Susceptibility Detection (Cerebral Micro Bleeds) T2 T2* Stroke. 2002;33:1536-1540.
  • 6. MR Applications Related to Iron Susceptibility Detection (Activation of Neuron: Oxy/Deoxy Hemoglobin) Finger Tapping Verbal Fluency Checker board
  • 7. MR Applications Related to Iron * In vivo Tracking of Stem Cell Figure 4 Test of positive-contrast imaging in vivo. A short-axis section of porcine myocardium injected with superparamagnetic-iron-oxide-labeled embryonic stem cells is shown. (A) Gradient- echo images show voids at each injection site of 1 million labeled cells (B) The off resonance cells. off-resonance projection at –800 Hz clearly shows the four injections of labeled cells as regions of bright signal (arrow). Permission obtained from John Wiley & Sons © Cunningham CH et al. (2005) Magn Reson Med 53: 999–1005. NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE OCTOBER 2006 VOL 3 NO 10
  • 8. MR Applications Related to Iron * Iron Concentration Measurement TE1 TE4 TE8 T2* map TE1 TE4 TE8 LIC map
  • 9. MRI Hardware Software SE GREASE GRE PD,T1,T2 PD T1 T2 PD,T1,T2+T2 PD T1 T2+T2* PD,T1,T2 PD T1 T2*
  • 10. MR Applications Related to Iron * Susceptibility Detection (Cerebral Micro Bleeds) T2 T2* Stroke. 2002;33:1536-1540.
  • 11. Black Blood T2* Images (Qualitative) Normal Mild Severe PD (TE1) T2*(TE4) Heavily T2*(TE8)
  • 12. T2 and T2* Variables - T2 (R2) and T2* (R2*) Relaxation Time 1/T2*=1/T2+1/T2´ R2*=R2+R2´ Note: R2*=1000/T2*; T2 in msec and R2 in Hz T2´  local magnet inhomogeneity such as from patient (stored iron in myocardium) or MR machine (main magnetic field inhomogeneity) Higher Iron Concentration  Lower T2* g  Higher R2* N t Iron Concentration  R2* or (1/ T2*) Note: I C t ti
  • 13. T2* Measurement Relative signal intensity at e ve s g e s y each TE was fit to Low Iron Concentration a monoexponetial function: S( ) S(TE) = A.exp(-TE/T2*) .e p( / ) = A.exp(-TE*R2*) TE High Iron Concentration
  • 14. Black Blood T2* Images and maps (Quantitative) Normal Marginal Mild Severe TE1 TE4 TE8 T2* map msec
  • 15. LIC=2.5 (normal [ < 3] ) 4.3 (mild [ 3-7 ] ) mg/g dry / d weight 8.7 (moderate [ 7-15] ) 22.7 (severe [ > 15] )
  • 16. Cardiac T2* Analysis : CMRtools (Brompton)
  • 17. CHLA’s Software (Pixel-wised) Can C report on t - Mean of ROI - Median of ROI
  • 18. Siriraj Iron Analysis (SIA) Software (Pixel-wised)
  • 19. Comparison of T2* and T2 Iron Measurement T2* (sensitive but not (se s ve bu o T2 (less se s ve bu good ( ess sensitive but for heavily overload) for heavily overload) 1-Kg Scale 20-Kg Scale
  • 20. Comparison of T2* and T2 Iron Measurement T. He, et al. MRM 2009;61:501-6. CJ Brewer, et al. JMRI 2009;29:357-64.
  • 21. Cardiac T2* and T2 Measurements: Case#1 - No Iron Overload TE1 1 TE2 TE4 4 T2* Sequence: T. He, et al. JMRI 2007;25:1205-9. msec T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
  • 22. Cardiac T2* and T2 Measurements: Case#2 - Moderate Iron Overload TE1 1 TE2 TE4 4 T2* Sequence: T. He, et al. JMRI 2007;25:1205-9. msec T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
  • 23. Cardiac T2* and T2 Measurements: Case#3 - Severe Iron Overload TE1 TE2 TE4 T2* Sequence: T. He, et al. JMRI 2007;25:1205-9. msec T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
  • 24. Liver T2* and T2 Measurements: Case#1 - No Iron Overload TE1 TE3 TE6 T2* Sequence: CJ. Brewer, et al. JMRI 2009;29:357-64. msec T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
  • 25. Liver T2* and T2 Measurements: Case#2 - Severe Iron Overload TE1 TE3 TE6 T2* Sequence: CJ. Brewer, et al. JMRI 2009;29:357-64. msec T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
  • 26. Liver T2* and T2 Measurements: Case#3 - Very Severe Iron Overload y TE1 TE3 TE6 T2* Sequence: CJ. Brewer, et al. JMRI 2009;29:357-64. msec T2 Sequence: H. Guo, et al. JMRI 2009;30:394-400.
  • 28. SIA Software: Time Series Report
  • 29. SIA Software: Case#1 – Good Response t=0 mo t=7 mo t=22 mo t=0 mo t=7 mo t=22 mo msec mg/g dw gg
  • 30. SIA Software: Case#1 – Not Good Response t=0 mo t=7 mo t=22 mo t=0 mo t=7 mo t=22 mo msec mg/g dw gg
  • 31. Acknowledgements g Department Faculty of Medicine Siriraj Hospital - Her Majesty Cardiac Center - Diagnostic Division, Radiology Department - Haematology/Oncology Division, Department of Pediatrics -Thalassemia Center Philips Medical Systems