Paul Tofts ISMRM Hawaii 2009 - measuring T1 and T2 1 Declaration of Conflict of Interest or...

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 ofthis presentation.


Methods for quantitative relaxation parameter mapping:

measuring T1 and T2

Paul Tofts PhDChair 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/talks

http://qmri.org/


Why measure relaxation times?

• T1 needed for Ktrans measurement in DCE MRI

• T1 needed for quantitative MT analysis

• T1 and T2 demonstrate subtle damage in ‘normal-appearing’ white matter


overview

• Principles of T1 measurement

• Principles of T2 measurement

• B1 effects

• Quality assurance

• Measurements on a clinical scanner

• Image analysis


T1 measurement

• Bloch eqn:

• Steady state solution:

Repeated θ pulses; Mz just before a pulse

1

)()(

T

tMM

dt

tdM zoz

1

1

/

/

0 cos1

1)0(

TTR

TTR

z e

eMM


T1 measurement: 1. saturation recovery

• Spin echo; repeated 90o pulses

• 2 (or more) TR’s gives T1

short and long TR’s (TR<0.5T1, TR>2T1) Needs good 90o pulse (need Mz(0+)=0) Slow (compared to gradient echo GE)

)1()( 1/0

TTRxy eMtM


T1 measurement: 2. spoilt gradient echo

• gradient echo; repeated θ pulses

• 2 (or more) FA’s gives T1 (nb FA=θ) Small and large θ

• (θ<θE: PDw; θ>θE: T1w; θE= Ernst angle) Needs accurate θ pulses (more later) Fast (can be 3D) Inaccuracies (at short TR):

• Incomplete spoiling• Relaxation during pulse

sincos1

1)(

1

1

/

/

0 TTR

TTR

xy e

eMtM


T1 measurement: 3. inversion recovery

• repeated [180o, TI, 90o , readout, TR-TI]

NB any TR

• arbitrary FA’s:

Fix TR, vary TI

Gives ACCURATE T1 (any TR, any FA)• This is gold standard, used in spectroscopy• MRI in ‘spectroscopy mode’ (small uniform sample; long TR)• Slow; interleaving slices

)21()2( 11 //0

TTRTTIz eeMM

1/):2( TTIz BeATIM

1

11

/21

/1

/1

0 coscos1

cos)cos1(1)2(

TTR

TTRTTI

z e

eeMM


T1 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 B1 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.


T2 measurement

• Bloch eqn:

• Steady state solution:

Needs TR-TE>>T1 (or else variable recovery after 180o pulse)

• If FA’s inaccurate,

T2 estimate is still ACCURATE

2

)()(

T

tM

dt

tdM xyxy

21 //0 )1(),( TTETTR

xy eeMTETRM

2/)( TTExy AeTEM


T2 measurement: 2. multi-echo

• Tempting to acquire >1 echo in 1 shot E.g. dual echo or FSE

• Selective 180o pulse is imperfect Slice thinning

• Even in a long T2 substance (e.g. pure water T2>2s) echoes decay with each refocusing

Simple QA on T2 accuracy

• Gold standard is: repeated single echo

long TR

few slices


Hippocampal T2 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.


T2 measurement: 3. multiple-T2 s• There is no such thing as T2

• In real biological tissue the transverse magnetisation almost always decays with several T2 values

• 3 distinct compartments in brain Myelin water (10-50ms)

Intra-cellular + extra-cellular (70ms)

CSF (>1s)

• estimated (mono-exponential) T2 value depends on TE values chosen

e.g. 4ms range (white matter T2~80ms)

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.


B1 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.


FA errorsand slice selection

Selective 90o pulse gives reasonable profile at correct B1 value

Poor profile at incorrect B1

Effective FA varies across slice

Out-of-phase component


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% / oC) +

realism - +

Manufacture/purchase - +


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.pdf

http://www.paul-tofts-phd.org.uk/CV/reprints/multicentre-2009.pdf


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

Power calculation (G*Power3) effect=5; sd_norm=3; sd_disease=4.25; alpha=0.05; P=0.80; 2-tailed; N1=N2

0

20

40

60

80

100

120

140

160

0 2 4 6 8 10 12

sd_instrument

sample size


Measurement using a clinical MR imager

• Implementation not straightforward Commercial sequences for RT are undeveloped

• Speed; accuracy; B1 errors

Home-made sequence needs research agreement

• Literature Not much!

• cf MT, DTI, MRS, Ktrans, volume …

Scope for research


Measurement using a clinical MR imager – T1 • Spoilt Gradient Echo

Brain: 3D; 1.5 x 1.5 x 1.5 in 10 minutes Body: multi-slice; breath-hold? B1 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


Measurement using a clinical MR imager – T2 • 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-T2 analysis No commercial software


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


More…

• http://www.paul-tofts-phd.org.uk/talks This talk (presentation and document) Multicentre measurements 2009 (in press)

• qmri.org Out of print (2nd 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 2009E-book

http://www.paul-tofts-phd.org.uk/talks

http://qmri.org/

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