Synopsis
Dynamic contrast enhanced MRI (DCE-MRI) allows quantitative
assessment of tumour status. The addition of a relaxation rate (R1) measurement following the dynamic acquisition in
DCE-MRI studies allows the uncertainty in the conversion from signal intensity
(S) to R1 to be assessed. In this work the effect of errors in
flip angle and pre-contrast signal estimation on the S(t) to R1(t) conversion were evaluated. Results indicated
that uncertainty in the measurement of Spre had greater effect than realistic flip angle variations on
the S(t) to R1(t)
conversion, and that the error was tissue dependent. Background and Aims
Dynamic
contrast enhanced magnetic resonance imaging (DCE-MRI) allows quantitative
assessment of tumour status, based on angiogenesis, and has shown much promise
in clinical oncology
1. Accurate measurement of contrast agent concentration in vivo is required to obtain useful
pharmacokinetic parameter estimates from tracer kinetic modelling. However,
inaccuracies in concentration measurement are thought to be associated with
inaccurate pre-contrast T
1 measurement, errors in the applied flip
angle (α) during the dynamic acquisition and incorrect pre contrast signal (S
pre)
estimation. For this investigation the relaxation rate (R
1), a
precursor to concentration, was investigated. The Bookend Method
2 allows one
to assess the agreement between the R
1 measured at the end of the
dynamic acquisition (R
1postDCE) and that measured using an
additional post-contrast R
1 measurement (R
1postIRTFE),
following the dynamic acquisition. The percentage difference in these R
1
measurements is the R
1 error. The aim of this investigation was to
quantify R
1 error in the peripheral zone (PZ) and central gland (CG)
of the prostate and internal obturator muscle (IOM).
Methods
13
prostate cancer patients were imaged at 1.5 T (Achieva, Philips Medical
Systems, Best, The Netherlands) using the cardiac coil. An imaging volume of 400
x 400 x 100 mm was acquired. The MR examination began with high resolution T
2w
imaging (TSE, TR/TE=4800/120 ms, matrix 560 x 560 x 20), subsequent images were
acquired with matrix 176x176x20 (overcontiguous slices) and SENSE factor 2.5 in
the PE (LR) direction. An inversion-recovery turbo field echo (IRTFE) sequence
was used to measure T
1 (TR/TE/α=2.38/0.77 ms/12°, ETL=51, TI = 64,
250, 1000, 2500, 3900 ms), followed by DCE-MRI images (turbo field echo
TR/TE/α=2.47/0.86 ms/30°, temporal resolution 1.2 s for 260 time points)
acquired during injection of 0.2 ml/kg Dotarem at 2 ml/s followed by a saline
chaser. Data analysis was performed using Matlab. Regions of interest (ROIs)
were drawn over the CG, PZ and IOM on a T
2w image slice through the
centre of the prostate. ROIs were then down sampled to the resolution of the
pre and post contrast IRTFE and DCE data sets. T
1 was estimated from
fitting to the IRTFE data and signal intensity vs time curves were converted to
R
1 vs time curves. The R
1 error was then estimated for each
region on a pixelwise basis. Simulations were then performed to determine the
effect of errors in applied α and S
pre estimation on R
1
error. A realistic range of flip
angle variations was determined from flip angle maps obtained in a volunteer.
Results
Median
R
1 errors (95% confidence intervals) of 15% (4.8 – 22%), 2.8% (-3.6
– 9.2%) and -3.2% (-6.7 – 0.2%) were measured in the CG, PZ and IOM
respectively. Figure 1 shows an example of the median R
1 vs time
data obtained in the CG. Correcting for α error in the realistic range of the
applied α (α ± 10%) did not allow the median R
1 errors to reach 0%.
The errors in S
pre which would produce a median R
1 error
of 0% were -15% (-22 - -4%), -6% (-8 – 2%) and 4% (1 – 7%) for CG, PZ and IOM
respectively. Figure 2.a shows an R
1 error map over prostate showing
more negative R
1 error in PZ and tumour than surrounding tissue,
with the tumour extent shown in the T
2w image in figure 2.b.
Discussion
R
1
error was thought to be related to errors in the applied α, estimation of S
pre
and contrast agent washout between R
1postDCE and the R
1postIRTFE
measurements. Simulation results showed that uncertainty in S
pre had
greater effect on R
1 error than realistic α error. Therefore,
improvements in S
pre estimation could provide more accurate
concentration measurements, improving the pharmacokinetic parameter estimates
obtained from tracer kinetic modelling. S
pre estimates could be
improved by ensuring that pre-steady state signal does not contribute to S
pre
estimation. Future work could focus on; comparing R
1 error in
healthy and cancerous tissue, quantifying the effect of R
1 error on
pharmacokinetic parameter estimates, identifying the sampling period required
to improve S
pre estimation.
This is the first time to our knowledge that the Bookend Method has been
used to quantify the effect of different parameters, e.g. applied α and S
pre
estimation, on the accuracy of R
1 (and hence contrast agent concentration) measurements.
Conclusion
Errors
exist in the measurement of R
1 in DCE-MRI. S
pre estimates
appear to have greater effect on R
1 error than realistic α error.
Extra care should be taken when measuring S
pre, especially if
performing analysis on a voxelwise basis.
Acknowledgements
WMIC Radiographers
Magnetic Resonance Imaging Facility Grant for funding
Ananya Choudhury
Andrew McPartlin
References
[1]
Padhani, Dynamic contrast-enhanced MRI in
clinical oncology: current status and future directions. J Magn Reson
Imaging, 2002. 16(4): p. 407-22.
[2] Cron et al, Accurate and rapid quantitative dynamic contrast-enhanced breast MR
imaging using spoiled gradient-recalled echoes and bookend T(1) measurements.
Magn Reson Med, 1999. 42(4): p. 746-53.