1. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 1 Declaration of Conflict of Interest or Relationship Speaker Name: Paul Tofts I have no conflicts of interest to disclose with regard to the subject matter of this presentation.

2. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 2 Methods for quantitative relaxation parameter mapping: measuring T 1 and T 2 Paul Tofts PhD Chair in Imaging Physics Brighton and Sussex Medical School, UK Download this from http://www.paul-tofts-phd.org.uk/talks see also : qmri.org http://www.paul-tofts-phd.org.uk/talksqmri.org

3. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 3 Why measure relaxation times? T 1 needed for K trans measurement in DCE MRI T 1 needed for quantitative MT analysis T 1 and T 2 demonstrate subtle damage in normal-appearing white matter

4. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 4

5. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 5 overview Principles of T 1 measurement Principles of T 2 measurement B 1 effects Quality assurance Measurements on a clinical scanner Image analysis

6. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 6 T 1 measurement Bloch eqn: Steady state solution: Repeated θ pulses; M z just before a pulse

7. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 7 T 1 measurement: 1. saturation recovery Spin echo; repeated 90 o pulses 2 (or more) TRs gives T 1 short and long TRs (TR 2T1) Needs good 90 o pulse (need Mz(0+)=0) Slow (compared to gradient echo GE)

8. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 8 T 1 measurement: 2. spoilt gradient echo gradient echo; repeated θ pulses 2 (or more) FAs gives T 1 (nb FA=θ) Small and large θ (θ θ E : T 1 w; θ E = Ernst angle) Needs accurate θ pulses (more later) Fast (can be 3D) Inaccuracies (at short TR): Incomplete spoiling Relaxation during pulse

9. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 9 T 1 measurement: 3. inversion recovery repeated [180 o, TI, 90 o, readout, TR-TI] NB any TR arbitrary FAs: Fix TR, vary TI Gives ACCURATE T 1 (any TR, any FA) This is gold standard, used in spectroscopy MRI in spectroscopy mode (small uniform sample; long TR) Slow; interleaving slices

10. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 10 T 1 measurement: 4. specialist methods There are a number of specialist methods (see e.g. Gowland 2003), which differ quite substantially from the conventional methods described above include Look-Locker, DESPOT, DESPOT2, and TAPIR often very fast, and sometimes can function in the presence of B 1 errors (although at the expense of worse SNR) may be vulnerable to off- resonance effects usually require intimate access to the MR imager to implement the sequences Gowland PA, Stevenson VL. T1: the Longitudinal Relaxation Time (chapter 5). In: Paul Tofts, editor. Quantitative MRI of the brain: measuring changes caused by disease. Chichester: John Wiley, 2003: 111-141.

11. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 11 T 2 measurement Bloch eqn: Steady state solution: Needs TR-TE>>T 1 (or else variable recovery after 180 o pulse) If FAs inaccurate, T 2 estimate is still ACCURATE

12. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 12 T 2 measurement: 2. multi-echo Tempting to acquire >1 echo in 1 shot E.g. dual echo or FSE Selective 180 o pulse is imperfect Slice thinning Even in a long T 2 substance (e.g. pure water T 2 >2s) echoes decay with each refocusing Simple QA on T 2 accuracy Gold standard is: repeated single echo long TR few slices

13. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 13 Hippocampal T 2 in epilepsy Conventional multi- slice dual spin echo TE=30,120ms Figure 2 Unilateral focal anterior hippocampal sclerosis. The quantitative data show a left anterior involvement which was missed by visual inspection.

14. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 14 T 2 measurement: 3. multiple-T 2 s There is no such thing as T 2 In real biological tissue the transverse magnetisation almost always decays with several T 2 values 3 distinct compartments in brain Myelin water (10-50ms) Intra-cellular + extra-cellular (70ms) CSF (>1s) estimated (mono-exponential) T 2 value depends on TE values chosen e.g. 4ms range (white matter T 2 ~80ms) Whittall KP, MacKay AL, et al. In vivo measurement of T2 distributions and water contents in normal human brain. Magn Reson Med 1997;37:34-43.

15. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 15 B 1 effects and FA errors Many RT measurement methods rely on accurate FA sources of FA error Scanner prescan procedure Slice selection (in 2D sequence) Dielectric resonance Worse at 3T Transmit coil nonuniformity Body coil better than head coil Solutions Use FA-insensitive methods Map FA Dowell NG, Tofts PS. Fast, accurate, and precise mapping of the RF field in vivo using the 180 degrees signal null. Magn Reson Med 2007;58:622-630.

16. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 16 FA errors and slice selection Selective 90 o pulse gives reasonable profile at correct B 1 value Poor profile at incorrect B 1 Effective FA varies across slice Out-of-phase component

17. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 17 Quality assurance for RT mapping Needs specific tests Distinct from e.g. resolution, SNR tests Phantoms (test objects) Healthy controls Convenient to scan+- Well characterised (measure accuracy) +- need temperature control?Yes (2-3% / o C)+ realism-+ Manufacture/purchase-+

18. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 18 Accuracy and reproducibility Accuracy Closeness to truth Important for multi-centre studies Small systematic errors are acceptable in typical (well-designed) cross-sectional and serial studies Reproducibility Test-retest Bland-Altmann analysis from pairs of measurements Instrumental variance usually sets limit to smallest biological change that can be measured determines power of a study Improved reproducibility gives smaller studies faster, cheaper Tofts PS, Collins DJ. Multicentre imaging measurements for oncology and in the brain. (in press) 2009.http:www.paul-tofts- phd.org.uk/CV/reprints/multicentre-2009.pdfwww.paul-tofts- phd.org.uk/CV/reprints/multicentre-2009.pdf

19. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 19 Cross-sectional study Normal tissue value = 100 sd_normal = 3 disease effect = 5 perfect instrument * : sd << sd_normal sd << 3 Serial study: perfect instrument sd << sd_within subject sd << 1 * An instrument which is so precise that it does not introduce any significant variation to the existing biological variation

20. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 20 Measurement using a clinical MR imager Implementation not straightforward Commercial sequences for RT are undeveloped Speed; accuracy; B 1 errors Home-made sequence needs research agreement Literature Not much! cf MT, DTI, MRS, K trans, volume … Scope for research

21. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 21 Measurement using a clinical MR imager – T 1 Spoilt Gradient Echo Brain: 3D; 1.5 x 1.5 x 1.5 in 10 minutes Body: multi-slice; breath-hold? B 1 and FA nonuniformity Body coil; nonuniformity fixed for a given subject Fast Inversion Recovery IR-prepared SPGR ; IR-EPI (MP-RAGE) Accurate (fixed readout; short readout, long TR) Typical 3% accuracy in 10 min Single slice, long time is gold standard Slow; limited coverage

22. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 22 Measurement using a clinical MR imager – T 2 Spin echo Multi-slice (2D) Beware slice cross-talk Dual echo Single echo more accurate but slower Faster readout with RARE (multiple phase encodes per shot) FSE, turbo SE Multiple-T 2 analysis No commercial software

23. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 23 Image analysis for relaxation time measurement Region of interest Test a specific location (prior information and hypothesis) biased Histogram Whole brain; unbiased good for diffuse disease in Normal Appearing Tissue Voxel-Based Morphometry VBM Unbiased testing of many locations Each location can be correlated with external score (clinical, genetic, proteomic, cognitive) Texture dirty white matter tissue often becomes more heterogeneous in disease

24. Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 24 More… http://www.paul-tofts-phd.org.uk/talks This talk (presentation and document) Multicentre measurements 2009 (in press) qmri.org Out of print (2 nd hand market £130 $288 $512) E-book ~ £110 through university library Book updates planned on website ISMRM list serve Standards in Quantitative MR http://ismrm.org/sqmr/sqmrrules.htm Haacke et al 2009 E-book