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Rapid High-Resolution T1 Mapping by

Variable Flip Angles: Accurate and Precise
Measurements in the Presence of
Radiofrequency Field Inhomogeneity

Hai‐Ling Margaret Cheng and Graham A. Wright

Version Post-print/accepted manuscript

Citation Cheng, H.‐L.M. and Wright, G.A. (2006), Rapid high‐

(published version) resolution T1 mapping by variable flip angles: Accurate and precise
measurements in the presence of radiofrequency field inhomogeneity.
Magn. Reson. Med., 55: 566-574. doi:10.1002/mrm.20791

Publisher’s Statement This is the peer reviewed version of the following article: Cheng, H.‐
L.M. and Wright, G.A. (2006), Rapid high‐resolution T1 mapping by
variable flip angles: Accurate and precise measurements in the presence
of radiofrequency field inhomogeneity. Magn. Reson. Med., 55: 566-
574. doi:10.1002/mrm.20791, which has been published in final form at
https://doi.org/10.1002/mrm.20791. This article may be used for non-
commercial purposes in accordance with Wiley Terms and Conditions
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 tapraid5/z3t-mrm/z3t-mrm/z3t00206/z3t2425d06a gockleyj S#9 12/14/05 13:49 Art: 05-8050 Input-sl
Rapid High-Resolution T1 Mapping by Variable Flip
Angles: Accurate and Precise Measurements in the
Presence of Radiofrequency Field Inhomogeneity
Hai-Ling Margaret Cheng1,2* and Graham A Wright3,4
Rapid 3D mapping of T1 relaxation times is valuable in diverse
clinical applications. Recently, the variable flip angle (VFA)
spoiled gradient recalled echo approach was shown to be a
practical alternative to conventional methods, providing better
precision and speed. However, the method is known to be
sensitive to transmit field (B1!) inhomogeneity and can result in
significant systematic errors in T1 estimates, especially at high
field strengths. The main challenge is to improve the accuracy
of the VFA approach without sacrificing speed. In this article,
the VFA method was optimized for both accuracy and precision
by considering the influence of imperfect transmit fields, noise
bias, and selection of flip angles. An analytic solution was
developed for systematic B1!-induced T1 errors and allows
simple correction of T1 measurements acquired with any imag-
ing parameters. A noise threshold was also identified and pro-
vided a guideline for avoiding T1 biases. Finally, it was shown
that three flip angles were the most efficient for maintaining
accuracy and high precision over large ranges of T1. A rapid B1!
mapping sequence was employed in all phantom experiments
and high-field in vivo brain scans. Experimental results con-
firmed the theory and validated the accuracy of the proposed
method. Magn Reson Med 55:000 – 000, 2006. © 2006 Wiley-
Liss, Inc.
Key words: T1 mapping; fast volumetric imaging; high-field MRI;
quantitative MRI
Rapid and accurate measurement of the longitudinal, or
T1, relaxation time has long challenged MRI scientists but
remains an important goal because of its clinical relevance
across a diverse range of applications. Many of these ap-
plications, however, including dynamic contrast-en-
hanced studies of cancer, perfusion studies of muscle,
diagnosis of neurologic disorders such as multiple sclero-
sis and epilepsy, and enhanced tissue discrimination for
image-guided procedures, require low-noise, high-resolu-
tion mapping over a large volume. These requirements
cannot be achieved in a clinically acceptable time frame
(!30 min) using conventional methods of inversion- or
saturation-recovery (1–3). An alternative method (4) in-
volves determining T1 from a set of two or more spoiled
1
Department of Diagnostic Imaging & The Research Institute, The Hospital for
Sick Children, Toronto, Canada.
2
Department of Medical Imaging, University of Toronto, Toronto, Canada.
3
Sunnybrook and Women’s College Health Sciences Centre, Toronto, Can-
ada.
4
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
*Correspondence to: Hai-Ling Margaret Cheng, Department of Diagnostic
Imaging, The Hospital for Sick Children, 555 University Avenue, Toronto,
Ontario M5G 1X8, Canada. E-mail: hai-ling.cheng@sickkids.ca
Received 26 August 2005; revised 20 October 2005; accepted 31 October
2005
DOI 10.1002/mrm.20791
Published online in Wiley InterScience (www.interscience.wiley.com).
© 2006 Wiley-Liss, Inc.
Magnetic Resonance in Medicine 55:000 – 000 (2006)
gradient recalled-echo (SPGR) images acquired with var-
ied flip angles. Advantages of this approach include low
power deposition compared to spin echo techniques and
low spatial distortion compared to rapid echo planar im-
aging. Most importantly, the accuracy has been shown to
be similar to that achieved with conventional and acceler-
ated techniques but with a significant reduction in imaging
time (5,6).
A dominant source of error in the variable flip angle
(VFA) approach is inaccurate knowledge of the flip angles
due to transmit field B1" inhomogeneity. Although the
impact on T1 accuracy is known (7,8), correction of mea-
sured T1 has been reported in only a few studies (9,10),
mainly due to the complexity and long scan time require-
ments of mapping the B1" field. A second source of sys-
tematic error is noise-induced bias. The effect on T1 mea-
surements is generally subtle and may be the reason it has
not, to our knowledge, been previously reported. However,
these errors can be appreciable below a certain signal-to-
noise (SNR) threshold, particularly with multiple angles,
and one must identify and image at a suitable SNR level to
ensure accurate measurements. Another consideration un-
related to T1 accuracy is optimizing the efficiency (preci-
sion per unit time) over the desired T1 range. Recent (6,11)
and past (5) efforts on optimizing the VFA method have
investigated the influence of flip angles, using efficiency as
the performance metric—accuracy was not explicitly con-
sidered. They concluded that dual angles were best for
achieving the highest efficiency over a narrow T1 range,
while multiple angles (11) achieved the most uniform
efficiency over a wide T1 range. Ideally, we seek an angle
set that will yield the highest and most uniform precision
across large T1 ranges while maintaining accuracy.
In the present work, we describe a set of methods for
accurate and precise 3D T1 mapping across a large T1 range
(50 –3000 ms) in less than 15 s per slice. We first develop
an analytical expression for systematic T1 biases in the
presence of inaccurate flip angles. This yields a calibration
curve that, together with a rapid method for mapping B1"
field variations, is used to correct T1 measurements ac-
quired with any choice of flip angles and repetition time
(TR). Accuracy is further ensured by maintaining suffi-
cient SNR. Furthermore, we show that a multiple-angle
approach based on three angles achieves higher and more
consistent precision across a large T1 range, compared to
dual angles, and avoids the potential for noise-related
biases when imaging with an even larger angle set. Numer-
ical simulations are performed to assess the validity of the
analytic expressions. The feasibility and accuracy of the
technique are demonstrated in phantom studies. Finally,
1
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2 Cheng and Wright

T1 measurements in brains of healthy human volunteers at

3 T are presented.

THEORY
The SPGR steady-state signal amplitude Si acquired at a
flip angle $i is a function of the longitudinal relaxation
time T1, repetition time TR, and equilibrium magnetiza-
tion M0 (12),

1%E1
Si #M0sin$i , [1]
1%cos$i E1 C
O
where E1 # exp(%TR/T1). By acquiring signal at different L
flip angles, the T1 can be determined first by transforming O
Eq [1]. into the linear form Yi # mXi " b,
R
FIG. 1. T1 estimation from linear regression on low and high angle
Si Si data points, aL and aH. Noise bias shifts data points to new locations
#E "M0(1%E1), [2]
sin$i 1 tan$i (crosses) in the directions indicated (arrows). The result is a fitted
line that overestimates (dashed) or underestimates (dotted) the true
and then extracting T1 from the slope m # E1 as follows slope (solid), leading to errors in T1.
(5,6):

T1#%TR/ln(m).
We now derive the systematic error in the T1 estimate due
to inaccurate angles. Assuming that the angle error (d$) is
small, we can calculate to first order the error propagated
into T1:
[3] tion of T1. This undesired influence of noise bias can be
reduced by placing greater emphasis on high SNR points
through weighted least-squares analysis. However, signals
collected at more than two angles need to be acquired.
The precision, or uncertainty (T1, in the T1 measure-
ment is another important performance indicator and
stems from propagation of random noise into the T1 cal-

!
N culation (see derivation in Appendix B). The precision
&T1 &T1 &T1 &T1
dT1# d$ " d$ ". . ." d$ # d$ . [4] normalized for a constant scan time is often used to com-
&$1 1 &$2 2 &$N N &$i i pare the relative merits of different T1-mapping strategies
i#1
(1). This metric, known as the efficiency, essentially de-
Following the derivation shown in Appendix A, we obtain scribes the T1-to-noise ratio (T1NR), or T1/(T1, per square
an expression for the T1 error due to inaccurate flip angles, root of the total imaging time Tseq (6). In this article, we
define a relative efficiency, )

!
N
%T12 exp(TR/T1) d$i
dT1# [Y (X ! X)"Xi (1"tan2$i ) ) " *T1/(T1)/ #Tseq+T1NR/ #TR ! NEX ! N. [7]
TR ! N(X2%X2) tan$i i i
i#1

' (Yi ! Y%2exp(%TR/T1)(Xi ! X))] [5] MATERIALS AND METHODS

where N is the number of flip angles, Xi # Si/tan ai,Yi #
Si/sin ai, and X! ,Y
! are mean values.
Random noise in the signal can also introduce system-
F1 atic T1 errors, as illustrated conceptually in Fig. 1. In the
absence of noise, signal acquired at two angles, aLand aH,
are transformed according to Eq [2]., and the exact T1 can
be extracted from the slope of the fitted (solid) line. In the
presence of noise ((), the measured magnitude signal is
larger than the true value A due to noise threshold and is
approximately (13)
MAVE " #A2"(2.
Graphically, data at aL and aH shift in the direction of the
arrows (Fig. 1). Depending on whether noise bias affects
the low or high angle signal, the fitted slope (dashed line)
increases or decreases, resulting in over- or underestima-
Choice of Flip Angles
Achieving the best precision for the T1 range of interest
requires judicious selection of flip angles, but the selection
process remains complex, particularly for multiple angles.
However, a couple of key results from previous work on
this topic (5,6,11,14,15) serve as useful guidelines. When
imaging for a single T1, precision can be optimized using
two “ideal” angles, defined as those whose signals are 71%
of the Ernst angle signal (6). Multiple angles are preferred
when imaging over a large T1 range, especially T1 ,
2000 ms, to achieve more uniform but lower precision
(11).
[6] In this study, we attempted to find the smallest angle set
that provided the high precision possible only with dual
angle imaging but across a large T1 range. Sets were cre-
ated on the premise that appropriate combinations of ideal
angles tuned to different T1’s may increase the range of
precise measurements. The simplest solution combined
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Accurate and Precise VFA T1 Mapping
two pairs of ideal angles, each tuned to the minimum or
maximum T1 of interest. For example, for a TR # 5 ms, a
four-angle set [2,3,9,19] (in degrees) was formed from ideal
angles, [3,19] and [2,9], tuned to 500 and 2500 ms, respec-
tively. The actual T1 values to which angles were tuned
were adjusted, and more ideal angle pairs were incorpo-
rated, to assess the effect on the precision profile. In any
set, similar values may be combined to reduce the number
of angles. For example, a three-angle set can be derived
from four angles, as the smaller two angles are often within
1 point of each other and only one need to be retained. Ten
angles optimized for TR # 5 ms from a genetic algorithm
(11) were also evaluated, consisting of the set 10$ '
[2,3,4,5,7,9,11,14,17,22]. Although our straightforward
strategy of combining appropriate ideal angles was not as
sophisticated as these other approaches for multiple angle
selection, we showed that comparable precision profiles
could be achieved.
Simulation Studies
Numerical simulations were performed to verify our the-
oretical models and study the influence of flip angles,
systematic angle biases, and noise on accuracy and preci-
sion. The range T1 # 50 –3000 ms was considered. Estima-
tion of T1 began with signal generation (Eq. [1]) using the
chosen angles, TR # 5 ms, and M0 # 1000. Gaussian-
distributed, complex-valued random noise (zero mean,
( # M0/SNR) was added prior to data averaging, where
SNR is the maximum signal-to-noise per pixel for an image
acquired with $ # 90° and TR , 6 ' T1. The SNR level was
varied from 150 to 1000 to study noise-related biases.
Furthermore, a fixed imaging time of 15 s or less per slice
for a 256 ' 256 matrix was considered for a clinical set-
ting. This time constraint, together with SNR # 250, was
used to evaluate different angle sets, where more SNR gain
through averaging of multiple signal acquisitions was pos-
sible for smaller sets. T1 was then determined through a
weighted least-squares regression on Eq. [2], with weights
proportional to signal. The process was repeated 10000
times to obtain a mean estimate (T! 1) and SD ((T1).
To study the influence of inaccurate flip angles, errors
were introduced such that true angle values varied be-
tween 50 and 130% of the nominal. Simulations were
performed as outlined above, using true angles for signal
generation and nominal angles for estimating T1.
Transmit Field B1" Imaging
The transmit field B1" of a volume coil is generally quite
uniform. However, substantial inhomogeneity may arise
when using separate transmit/receive coil systems or
when imaging at field strengths above 1.5 T. An accurate
approach to account for these variations is to map the B1"
field distribution using a double-angle method (16,17).
Standard spin echo (SE) acquisitions are the most robust,
as they are insensitive to B0 variations, but are impractical
in the clinic due to long scan times. Rapid B1" mapping
has recently been demonstrated using a SE segmented-EPI
sequence (18). Similar to conventional SE techniques, sig-
nal is acquired at excitation angles of 60 and 120° for
maximum sensitivity to small variations in B1". However,
3
because of sensitivity to B0 offsets, SE-EPI B1" maps need
to be corrected by normalizing against SE measurements.
For simplicity, we assume a pure B0offset, which does not
affect the RF distribution. We have found that the speed
advantage of SE-EPI can be retained by determining the
normalization factor off-line, from calibration scans per-
formed on a phantom.
The sequences employed were: SE-EPI, 8 shots, TE #
18 ms, bandwidth (BW) # 250 kHz; SE % TE # 10 ms,
BW # 15.6 kHz. Common parameters are TR # 4000 ms,
128 ' 128 matrix, slice thickness (SL) # 4 mm, 60 and
120° excitation angles, 120 and 240° refocusing angles.
Phantom Studies
Quantitative T1 imaging was performed on a 1.5 T MRI
system (Signa Excite TwinSpeed, GE Healthcare, Milwau-
kee, WI, USA) using an eight-channel receive-only head
array coil (MRI Devices). Eight phantoms, one containing
water and seven doped with NC100150 (Nycomed Amer-
sham), spanning an approximate T1 range of 50 to
3000 ms, were used to test the accuracy of our proposed
method. A cylindrical phantom (12 cm diameter, 20 cm
length) filled with distilled water and 3.33 g/liter NiCl and
1.4 g/liter NaCl was also used to assess the accuracy of our
B1" measurements. Transmit B1" maps were acquired as
described above. Data for T1 maps were acquired with a 3D
fast SPGR sequence: TR/TE # 4.4/1.1 ms, 256 ' 256 ' 28
matrix, FOV # 20 cm, SL # 5 mm, BW # 31.25 kHz. Flip
angles and number of signal averages (NEX) were chosen
to match those used in simulations, using 6 NEX for twin
angles, 4 NEX for three angles, and so on. Systematic angle
offsets were also introduced to study the effects of RF
pulse imperfection on T1 evaluation. The potential for
noise bias at lower SNR was assessed by reducing the slice
thickness to 1 mm. Reference T1 values were measured
using single-shot fast SE inversion-recovery (SSFSE-IR):
TR/TE # 5000/32.4 ms, 256 ' 256 matrix, FOV # 20 cm,
SL # 5 mm, BW # 31.25 kHz, and TI # [50, 100, 150, 250,
500, 750, 1000, 1500, 2000, 2500, 3000, 3500, 4000] ms.
Pixel-by-pixel T1 maps were calculated and then cor-
rected for the measured B1" field nonuniformity using Eq.
[5] for calibration. The mean and SD of T1 were computed
within each phantom to yield measures of accuracy and
precision, respectively.
In Vivo Studies
For final evaluation, brains of two volunteers were imaged
on a 3.0 T MRI system (GE Signa Excite Eclipse) using an
eight-channel receive-only head array coil (MRI Devices).
T1 maps were acquired with 3D fast SPGR, with all param-
eters the same as at 1.5 T with the following exceptions:
FOV # 24 cm, TR/TE # 6.1/1.5 ms, NEX # 1. This resulted
in a total scan time of 2 min 24 s for three angle acquisi-
tions over 28 slices. In vivo B1" maps were acquired using
SE-EPI in under 2 min, while calibration scans were taken
off-line on a phantom (15 cm diameter, 28 cm length).
Pixel-by-pixel T1 maps, corrected for B1" variation, were
then generated.
 tapraid5/z3t-mrm/z3t-mrm/z3t00206/z3t2425d06a gockleyj S#9 12/14/05 13:49 Art: 05-8050 Input-sl
4 Cheng and Wright
FIG. 2. T1 bias due to inaccurate flip angle $ (B1" error). Simulated
measurements of T1 relative to true value in the absence of random
signal noise show a significant offset dependent only on the relative
error in $ (thick line). Results are shown for various combinations of
flip angles and TR, averaged over T1 # 50 –3000 ms. Theoretical
predictions (thin line) based on Eq. (5) provide a good approximation
when relative errors in $ are within 15%.
RESULTS
Simulation Results
Inaccurate flip angles were a dominant source of error in
T1 estimation. T1 measurements were calculated in the
absence of signal noise for a range of angle offsets, and the
measured value relative to true T1 was averaged across T1
# 50 –3000 ms for each angle offset. This was repeated for
different combinations of $ and TR. The results are shown
F2 in Fig. 2 (thick line). The various solutions are difficult to
distinguish due to close agreement. Theoretical predic-
tions based on Eq. [5] are also shown (thin line). The key
observation is that the relative T1 error is constant for any
T1 and depends only on the angle offset. When the true
angle is within 15% of the nominal, the analytic solution
is a useful approximation of the error contracted in T1. In
this range, the relative T1 error is twice the relative angle
error. Whether the calibration curve or the analytic ap-
proximation was used, correction was easily achieved and
was accurate for any combination of $ and TR, requiring
only knowledge of angle variations.
F3 Noise-induced systematic T1 error is illustrated in Fig. 3
for sets of 2, 3, and 10 flip angles at various SNR levels.
The exact nature of the bias depended on the specific angle
values, but several observations can be made. Dual angles
generally suffered from biases at T1 values outside the
target range even when SNR is high. With 3 angles, better
accuracy was achieved over the entire T1 range. However,
biases were again elevated in increasing the angle set to 10.
This may be due to a preferential increase in the fitted
slope (Fig. 1) arising from the presence of more noisy data
points. At a threshold of SNR # 350, the T1 error was
within 2%, except for the range T1 , 1250 ms when the
dual angles were used.
The efficiency performance of various flip angles is pre-
sented in Fig. 4a. Dual angles tuned to 500, 1000, and F4
2500 ms demonstrated the highest efficiency at the respec-
tive T1’s. Note that in these dual-angle profiles, equal or
better efficiency was achieved down to roughly 20% of the
T1 to which they are tuned. However, efficiencies were
poor either at low or high T1 values, due to placement of
angles in the low signal portion of the signal-versus-$
curve. The use of multiple angles overcame this problem
and maintained consistently high efficiencies. Efficiency
profiles of the 3- and 4-angle sets were comparable to the
10-angle combination optimized through a genetic algo-
rithm (11), but the selection was much simpler, based on
combining dual-angle pairs tuned to 500 and 2500 ms.
Moreover, for an SNR # 250 before signal averaging and
constant scan time, greater T1 bias was seen with larger
angle sets (Fig. 4b). Three flip angles appeared to be opti-
mal, providing consistently high efficiencies with minimal
noise bias.
Phantom Results
Phantom experiments validated our analytic expression
for correcting T1 errors due to inaccurate flip angles and
confirmed our angle selection for optimizing accuracy and
efficiency. Figure 5a shows a B1" map acquired in a cylin- F5
drical phantom, which was used to correct T1 values ac-
quired with three angles. A cross-section taken centrally
through the cylinder, averaged over 10 rows, showed that
corrected T1 values (117.0 - 2.86 ms) agreed closely with
reference SSFSE-IR measurements (116.8 - 2.07 ms) (Fig.
5b). However, the VFA method was three times faster than
the accelerated version of a standard SE-IR sequence. T1
maps before and after B1" correction are also shown (Fig.
5c and d).
The accuracy of our technique for correcting B1"-related
T1 errors across a wide T1 range is shown in Fig. 6a. F6
Noise-related bias was not significant as sufficient SNR
was maintained. Although B1" variations were small,
within 6%, the accuracy of T1 measurements improved
after B1" correction. Furthermore, consistent results were
obtained for different combinations of angles and TR,
thereby confirming that the correction method is indepen-
dent of imaging parameters. In Fig. 6b, additional offsets of
10 and 20% were introduced into the nominal flip angles
FIG. 3. T1 bias due to noise. Simulated T1
measurements relative to true T1 at various
SNR levels for TR # 5 ms and flip angles of
(a) [2,14], (b) [2,9,19], and (c) 10 % $ (see
text). Measurements are mean values ob-
tained from 10000 random trials.
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Accurate and Precise VFA T1 Mapping 5

FIG. 4. Flip angles for optimal performance over a wide T1 range. (a) Efficiency measurements from 10000 simulation trials show that
multiple angles maintain consistent efficiencies across the entire T1 range. Dual angles fail at either low or high T1 values. (b) Accuracy is
best ensured using fewer angles. An SNR # 250 prior to signal averaging and TR # 5 ms were used. Dual-angle acquisitions were averaged
six times, three angles averaged four times, and so on to maintain comparable total scan time.

to test further the accuracy of our correction method and
illustrate the errors incurred in uncorrected T1 estimates.
Efficiencies obtained in phantoms followed the trends
predicted from simulations, with the three-angle set pro-
viding the highest and most uniform efficiency overall.
F7 Figure 7 shows that both multiple-angle schemes (3 and 10
angles) offered comparable efficiencies, while perfor-
mance was degraded either at low or high T1 when dual
angles were used.
Noise-induced bias predicted from simulations was con-
F8 firmed in vitro. Figure 8 shows that greater bias was ob-
served when the slice thickness was reduced from 5 mm
(SNR . 300) to 1 mm (SNR . 60), progressively worsening
with an increased number of angles. Dual angles were even
more susceptible to noise-related errors, even for 5-mm
slices, outside a limited T1 range.
In Vivo Results
F9 Figure 9 shows B1" maps and corresponding T1 maps
obtained at 3.0 T. Note that T1 values in the corrected
images were more balanced within a slice and among
different slices. Furthermore, measured T1 values agreed
with those reported in the literature (see Table 1). T1
DISCUSSION
The variable flip angle method allows rapid T1 quantifica-
tion with better precision and accuracy than conventional
approaches and was recently shown to be capable of gen-
erating rapid 3D T1 maps in a clinical setting (6,7). The
value of quantitative imaging spans numerous clinical ap-
plications, from quantifying vascular properties in dy-
namic contrast studies to improved characterization of
neurologic diseases. T1 maps offer the advantage of remov-
ing confounding influences of T2 effects, proton density,
and coil sensitivity on T1-weighted images. Unfortunately,
these advantages have remained largely unexplored in the
clinic, since T1 mapping is not part of routine assessment.
However, the combination of speed, volume, and high
resolution possible with the VFA approach has made it a
practical alternative. In fact, recent studies of breast (19)
and brain (20) tumors have been reported using this ap-

FIG. 5. Correction of T1 map acquired in

phantom at 1.5 T using the VFA approach
($ # [2,9,19], 4 NEX). (a) Transmit field map.
(b) Cross-section taken centrally through
uncorrected (dotted line) and corrected
(solid line) T1 maps compared to reference
SSFSE-IR measurements (thick line). (c) Un-
corrected and (d) corrected T1 maps. All T1
values are in milliseconds.
 tapraid5/z3t-mrm/z3t-mrm/z3t00206/z3t2425d06a gockleyj S#9 12/14/05 13:49 Art: 05-8050 Input-sl
6 Cheng and Wright
proach. With its growing popularity in the clinic, it is
important to understand the limitations as well as the
conditions under which accurate measurements are pos-
sible.
The total scan time required for 3D T1 mapping depends
on the specific clinical target. For brain imaging, large
volume coverage with high spatial resolution may require
128 slices of 1 mm thickness. Unilateral breast imaging
may require as few as 28 slices. Regardless of the applica-
tion, it is crucial to maintain the highest SNR possible due
to the sensitivity of the VFA approach to noise-related
errors. Accuracy and short scan times are best ensured
with high-resolution coils and, if possible, imaging with
larger voxels. An additional problem of B1" field-related
errors is encountered when imaging at field strengths
higher than 1.5 T, and correcting this error imposes more
demands on scan time. In this work, we obtained in under
4 min a full 3D T1 map of the brain in vivo, with 1 ' 1 '
5 mm3 resolution, calibrated for B1" variations, using an
eight-channel head array coil on a 3.0 T system.
The first contribution of this work is an analytic solution
(Eq. [5[) for the systematic error in T1 measurements due to
inaccurate flip angles. Inaccurate angles can arise from two
sources: slice profile errors, which are minimized using 3D
sequences, and B1" inhomogeneity. The latter problem is
exacerbated at higher field strengths and needs to be cor-
rected (16). Even some coil configurations at 1.5 T require
FIG. 7. Efficiencies achieved in phantoms over T1 # 50 –3000 ms.
Three angles offer an efficiency profile comparable to a 10-angle
acquisition and is significantly more uniform compared to any dual
angle acquisition.
FIG. 6. Accuracy of corrected T1 measure-
ments in phantoms over T1 # 50 –3000 ms.
(a) Correction scheme is accurate and inde-
pendent of parameter settings. (b) Errors in
T1 measurements are significant when ad-
ditional offsets of 10 and 20% are intro-
duced into the flip angles. Corrected results
correspond closely to reference values.
correction, as 25% deviations have been reported in cer-
tain regions of a breast coil (19). Our results indicated that
the relative T1 error is significant and is approximately
twice the relative angle error for B1" variations under
15%. However, we have shown that correction requires
only knowledge of the B1" error and was accurate for T1
maps acquired with any choice of angles and TR.
The second contribution is a better understanding of the
SNR threshold necessary to achieve accurate T1 measure-
ments. An SNR . 350 (for $ # 90° and TR , 6 ' T1) was
shown to reduce T1 biases to less than 2% for the angle sets
studied. Three angles were better than dual angles, as
weighted least-squares regression could be implemented
to reduce the influence of noisy data points. Three angles
were also better than 10 optimized angles for two reasons:
the presence of fewer data points to experience noise bias,
even at the same SNR; and more time was available for
signal averaging to further improve SNR. Inadequate noise
reduction results in characteristic biases in our T1 mea-
surements, best evidenced in Fig. 3c. Here, the same set of
10 angles are positioned mainly in the low angle portion of
the signal-versus-$ curve for small T1 measurements, but
mainly in the high angle portion for large T1. When noise
dominates, the fitted slope of Eq. [2] preferentially in-
creases or decreases, respectively (see Fig. 1). The average
tendency was to overestimate small T1 values and under-
estimate large T1 values (Fig. 3c).
C
O
L
O
R
FIG. 8. T1 bias in low SNR phantom experiments. Reduced SNR
through thinner slices (5 mm, black; 1 mm, red) results in undesired
T1 bias. This bias is more severe with larger angle sets. However,
even with 5-mm slices, bias is evident for dual angles beyond a
limited T1 range.
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Accurate and Precise VFA T1 Mapping
C
O
L
O
R
FIG. 9. In vivo brain 3D T1 map-
ping at 3.0 T. (a) Transmit field
maps. (b) Uncorrected and (c)
corrected T1 maps acquired with
three flip angles ($ # [2,9,19], 1
NEX).
Finally, we offered a simple and practical method for
choosing flip angles to achieve accurate and precise T1
measurements. In contrast to most papers on this topic
(5,6,11), which optimize the precision per unit time, we
also considered accuracy. Another distinction was that our
focus was not to devise a systematic method for determin-
ing optimal angles. Instead, we provided a set of guide-
lines based on validated results from theory and experi-
ments. Once the T1 range of interest has been determined,
ideal angles tuned to the maximum T1 and at least five
times the minimum T1 are calculated. We found that tun-
ing to this lower T1 threshold was sufficient, as the effi-
ciency profile peaks over an even lower T1 range. In fact,
tuning to the minimum T1 value resulted in poorer preci-
sion overall. This process yields a four-angle set, and only
one of the two smallest angles needs to be retained. The
addition of more angles tuned to intermediate T1 values
may not offer better efficiency and can potentially cause
bias if SNR is insufficient.
Practical demonstration of our technique was given in
full-brain T1 mapping at 3 T. Total scan time was under
4 min, including correction for B1" inhomogeneity. At this
field strength, RF miscalibration was significant. The field
distribution was asymmetrical (Fig. 9a), resulting in low-
ered T1 values in the right frontal and diametrically oppo-
site regions (Fig. 9b). Corrected T1 maps showed improved
symmetry within a slice and consistency among slices
(Fig. 9c). Our measurements agreed well with literature
values, especially for white matter. Greater variability ex-
ists in reported gray matter T1’s, possibly due to the diffi-
culty of isolating gray matter regions without partial vol-
TABLE 1
T1 Values Measured in White and Gray Matter at 3.0 T in Two Healthy Volunteers
Volunteer 1
White matter 1084 - 79
Gray matter 1703 - 53
Note. Mean - SD averaged across 20 anatomical regions in six consecutive 5-mm slices were obtained for both white (frontal, parietal, and
occipital regions) and gray matters (frontal, parasagittal, insular, parietal, and occipital regions).
7
ume effects from white matter or cerebral spinal fluid. An
additional challenge with long T1 species, such as gray
matter, is that accuracy is more dependent on experimen-
tal conditions. With conventional inversion- or saturation-
recovery methods, which are used in Refs. (24,25), often
parameters adopted are optimized for measuring T1’s in a
lower range and/or TRs chosen are too short to allow
sufficient recovery of magnetization. These factors repre-
sent a potential source of T1 underestimation reported in
the literature for gray matter. In our approach, these
sources of biases are accounted for, which may explain
higher T1 measurements compared to those reported by
Ethofer et al. (24) and Wansapura et al. (25). In fact, our
values agree with those of Stanisz et al. (23), who also
considered details related to T1 accuracy.
In addition to the choice of flip angles, noise threshold-
ing, and B1" inhomogeneity, other factors can influence
the accuracy of the VFA technique. Off-resonance effects
may become problematic at low bandwidths, but this is
not generally a concern for the short TRs employed. An-
other important but subtle criterion for accuracy is that the
equilibrium condition of Eq. [1]) must be satisfied (14).
Failure to drive the spin system to equilibrium prior to
data sampling can occur if the number of pulses prior to
data acquisition is inadequate, which is more likely in
tissues with very long T1 relaxation times. T1 mapping
techniques based on signal detection during the recovery
to equilibrium may circumvent this possible source of
error (3,21). Comparing the merit of VFA imaging against
other rapid sequences is a topic of future studies.
T1 (ms)
Volunteer 2 Literature
1087 - 49 1084 - 45 (23)
1110 - 45 (24)
832 - 10 (25)
1732 - 70 1820 - 114 (23)
1470 - 50 (24)
1331 - 13 (25)
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8 Cheng and Wright

A major component of this work required that accu- Each term in Eq. [A2] will now be derived. The first term
rate B1" maps of the transmit field be acquired rapidly to is obtained from Eq. [3]:
preserve the time advantage of the VFA T1 mapping
approach. The SE-EPI sequence we adopted (18) is sig- &T1 T12
nificantly faster than traditional SE imaging and offers " exp(TR/T1). [A3]
&m TR
comparable accuracy. However, the off-resonance offset
needs to be determined and accounted for. We have
found this calibration can be performed in a phantom as Next, the definitions of Xi and Yi given in Eq. [2] are used
a separate step to avoid additional scan time in vivo. to find the two partial terms:
Errors in the calibration will propagate into our correc-
tion of T1. Sequences that are insensitive to off-reso-
nance effects will obviate the need for off-line calibra-
&Yi &
# & '
Si
&$i &$i sin$i
#%Yi /tan$i [A4]
tion and need to be developed. Another possible source

& '
of error is slice profile effects. Slice-selective pulses &Xi & Si
were used to obtain the transmit field maps, while the T1 # #%Xi (tan$i "1/tan$i ). [A5]
&$i &$i tan$i
sequence was non-slice-selective. To ensure high accu-
racy in the correction, the pulses for both sequences
should match. Since slice profile effects due to finite RF The last two partial terms in Eq. [A2] are determined from
pulses are not corrected by field mapping, differences the definition of the slope m, which follows a least-squares
between 2D and 3D acquisitions, if significant, will af- regression (22):
fect the accuracy of our T1 correction.
In conclusion, the results of this study suggest that XY ! XY
accurate and rapid 3D T1 mapping can be achieved with m# 2 . [A6]
X %X2
the VFA approach across a wide range of T1’s encoun-
tered in various clinical problems. Analytic and exper-
imental results demonstrate significant sensitivity to Equation [A6], together with the definition for the operator
1 N
transmit field B1" (i.e., flip angles) errors, resulting in Z! " ! Z , are used to find the last two partial terms:
N i#1 i
relative T1 errors that are approximately twice the rela-
tive angle error and are independent of imaging param-
eters. This bias must be corrected, especially when im- &m !
Xi ! X
# [A7]
aging at field strengths higher than 1.5 T or using spe- &Yi N(X2%X2)
cialized coils with significant inhomogeneity. We have
proposed a method that retains the speed efficiency of
&m 1
VFA by using a rapid B1" mapping method and a simple " ! %2exp(%TR/T1)(Xi ! X
[Y ! Y ! )]. [A8]
calibration curve to correct for these errors. Further- &Xi N(X2%X2) i
more, we have identified an SNR threshold and have
shown that imaging with three flip angles, tuned to the Combining these expressions for partial derivatives into
cover the T1 range of interest, ensures the best use of Eqs. [A1] and [A2] gives the final formula in Eq. [5].
scan time to achieve accurate and precise measurements APPENDIX B
across a large T1 range. Our T1 values were accurate and The precision in T1 can be determined by deriving the
agreed closely with standard inversion-recovery mea- variance (T12 due to random errors in the signal. We begin
surements. Further validation was obtained from in vivo with the formula for noise propagation (22):
brain results at 3 Tesla, with T1 measurements in agree-
ment with literature values.
!$%
N
APPENDIX A &T1 2
( T12# (i2 , [A9]
In deriving the equation for the systematic error in T1 due &Si
i#1
to errors in flip angles d$i, we begin with a first-order
approximation:
where (i is the noise level for the image acquired using flip
angle $i. Assuming that (i is independent of flip angle and

! is equal to (, it can be factored outside the summation

N
&T1 &T1 &T1 &T1
dT1 " d$ " d$ ". . . " d$ " d$i . sign:
&$1 1 &$2 2 &$N N &$i
i#1

!$ %
[A1] N
&T1 2
( T1 2#(2 . [A10]
&Si
The T1 estimated depends on the signal Si through the i#1

ordinates and slope defined in Eq. [2]. Using the chain

rule, the dependence of T1 on flip angles $i can be obtained The partial derivative can be expanded according to the
as follows: chain rule:

" " $
&T1 &T1 &m &T1 &m &Yi &m &Xi
"
&$i &m &$i &m &Yi &$i &Xi &$i
. % [A2] # " # $
&T1 &T1 &m &T1 &m &Yi &m &Xi
&Si &m &Si &m &Yi &Si &Xi &Si
. % [A11]
 tapraid5/z3t-mrm/z3t-mrm/z3t00206/z3t2425d06a gockleyj S#9 12/14/05 13:49 Art: 05-8050 Input-sl

Accurate and Precise VFA T1 Mapping 9

Each term in Eq. [A11] can be derived in a similar fashion 7. Deoni SC, Peters TM, Rutt BK. High-resolution T1 and T2 mapping of
as was done in Appendix A. Equations [A3], [A7], and [A8] the brain in a clinically acceptable time with DESPOT1 and DESPOT2.
Magn Reson Med 2005;53:237–241.
still hold, while the remaining two partial derivatives are 8. Kay I, Henkelman RM. Practical implementation and optimization of
given by one-shot T1 imaging. Magn Reson Med 1991;22:414 – 424.
9. Venkatesan R, Lin W, Haacke EM. Accurate determination of spin-
&Xi
"
&
& '
Si
&Si &Si tan$i
" 1/tan$i [A12]
density and T1 in the presence of RF-field inhomogeneities and flip-
angle miscalibration. Magn Reson Med 1998;40:592– 602.
10. Parker GJ, Barker GJ, Tofts PS. Accurate multislice gradient echo T(1)
measurement in the presence of non-ideal RF pulse shape and RF field
&Yi & Si nonuniformity. Magn Reson Med 2001;45:838 – 845.
" [ ] " 1/sin$i . [A13] 11. Deoni SC, Peters TM, Rutt BK. Determination of optimal angles for
&Si &Si sin$i variable nutation proton magnetic spin-lattice, T1, and spin-spin, T2,
relaxation times measurement. Magn Reson Med 2004;51:194 –199.
These expressions are combined into Eqs. [A10] and [A11] 12. Zur Y, Stokar S, Bendel P. An analysis of fast imaging sequences with
steady-state transverse magnetization refocusing. Magn Reson Med
to yield
1988;6:175–193.
13. Henkelman RM. Measurement of signal intensities in the presence of
(2T14exp(2TR/T1) noise in MR images. Med Phys 1985;12:232–233.
( T12# 2 2 2 2 14. Homer J, Beevers MS. Driver-equilibrium single-pulse observation of
M0TR N (X %X2)2 T1 relaxation. A re-evaluation of a rapid “new” method for determining
NMR spin-lattice relaxation times. J Magn Reson 1985;63:287–297.

!& '
N
! Yi ! Y
Xi ! X !) 2
! %2exp(%TR/T1)(Xi ! X
$ # . [A14]
sin$i tan$i
i#1
ACKNOWLEDGMENTS
The authors thank Eric Han (Applied Science Laboratory
West, GE Healthcare, Menlo Park, CA, USA) for helpful
advice on pulse sequence manipulation.
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