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Echo-Planar Imaging

F Schmitt, Siemens Healthcare, Erlangen, Germany


ã 2015 Elsevier Inc. All rights reserved.

Historical Development of Echo-Planar Imaging Ogawa described the blood oxygenation level dependent
(BOLD) effect in 1990 and proposed to apply it for measuring
Echo-planar imaging (EPI), was invented by Sir Peter Mansfield brain function after activation (Ogawa et al., 1990). His first
in 1977 (Mansfield, 1977) long time before major companies mouse imaging data were acquired by using a conventional
invested in the development of clinical magnetic resonance gradient-recalled echo (GRE) imaging sequence at a vertical
imaging (MRI), which started in honest in 1983. Peter Mansfield bore 7 T magnet. In Boston, at the MGH, John Belliveau
received the Nobel Prize in 2003 for his contribution in the (Belliveau et al., 1991) performed the first contrast enhanced
development of MRI and EPI in particular. His research group (CE) human in vivo functional MRI experiment using EPI.
in Nottingham focussed on the technical challenges of image While Belliveau focussed on CE methods, Ken Kwong per-
formation under bipolar gradients. In the late 1980s it eventually formed the first susceptibility weighted EPI-GRE based
reached the state to be used for abdominal and cardiac imaging human in vivo experiment in 1991 (Kwong, 2012).
(Howseman et al., 1988) and eventually also for neuro-imaging After initial animal experiments, Seiji Ogawa and Kamil
(Stehling et al., 1991). Ugurbil succeeded with human in vivo fMRI on a 4 T scanner
In the mid 1980s Ian Pykett and Richard Rzedzian, both in Kamil Ugurbil’s MRI lab in Minneapolis in 1991 (Ogawa
being trained in Sir Peter Mansfield’s lab, founded Advanced et al., 1992). Their initial experiments were based on a conven-
NMR (ANMR) which used a 2 T magnet for its EPI development. tional T1 weighted two dimensional (2D) GRE technique, called
In 1987 they published the first in vivo human body imaging FISP imaging (Oppelt et al., 1986). They later moved to EPI also.
using EPI (Pykett and Rzedzian, 1987). ANMR provided the first Besides MGH, other groups also recognized that EPI was
commercially available EPI-only scanner. It was installed at the important for fMRI and focussed their efforts on this technol-
Massachusetts General Hospital’s (MGH) research center in ogy. In 1991, Peter Bandettini and Eric Wong build their own
Charlestown, MA, USA in 1990. An existing General Electric EPI gradient coil (Bandettini, 2011) and produced their first
Signa 1.5 T scanner was retrofitted with the ANMR Instascan™ fMRI results in fall 1991. In the end, when they published their
console and EPI capable gradients driven in a resonance circuit work in 1992, it was in fact the first published paper on human
(Cohen and Weiskoff, 1991). At Siemens EPI activities started in in vivo BOLD fMRI (Bandettini et al., 1992).
1987, with the first imaging results in March 1988 (Schmitt, About the same time Bob Turner, an early fellow of Sir Peter
et al., 1988a,b). However, the results from MGH running an Mansfield in Nottingham, skilled in knowledge about EPI and
ANMR EPI scanner spurred the efforts at the other major ven- gradient coil design built his own z-gradient coil, capable of
dors significantly. This effort resulted in the first EPI scanner performing EPI for fMRI at NIH. He first used it for diffusion
installed in a clinical environment at the Beth Israel Hospital weighted imaging, but realized after the MGH results have
(BIH) in Boston under Bob Edelman’s guidance in summer been shown that its use for fMRI is essential. His results were
1992 (Edelman et al., 1994b; Schmitt et al., 1993). published in 1993 (Turner et al., 1993).
As EPI is the fastest MRI technique, the early EPI scanners In Bob Shulman’s lab at Yale, Andrew Blamire developed
were primarily dedicated to explore applications in the body his version of EPI on a 2.1 T whole body scanner running a
and heart to freeze the motion. Other body organs also have Bruker Biospec NMR console. His results have been shown at
been explored, such as liver and kidney imaging (Müller et al., the ISMRM 1992 in Berlin (Blamire et al., 1992).
1994) and even cardiac diffusion (Edelman et al., 1994a,b) has In the mid 1980s Le Bihan et al. realized that diffusion con-
been tried out. However, it soon turned out that the suscepti- trast can be utilized for viewing neurological pathologies in
bility effects at the heart-lung tissue interface or the air in the tumors (Le Bihan et al., 1986). About at the time of the raise of
bowels were too severe to make this a valuable and acceptable EPI driven fMRI it was also discovered that the combination of
clinical tool for general whole body applications. While the diffusion weighting with EPI as data acquisition module has great
MGH primarily focussed on EPI for perfusion and succeeding potential for clinical neurological examinations for the detection
to neuro-functional MRI (fMRI), eventually the BIH scanner of early onset of stroke (Moseley et al., 1990; Warach et al., 1992).
was successfully used for early stroke imaging and therefore Eventually ANMR was bought by GE which sold about 20
opened the door to important clinical use. of these scanners before GE started its own EPI development.
The discovery that MRI is feasible to see signal changes By mid-1990 EPI was introduced with their new generation
when performing visual tasks was key to the dissemination of scanners by all the major MRI vendors and now is a technique
EPI as a method on clinical scanners for the use in neuro- available in many facets on every MRI platform, ranging from
science. Therefore, I describe in short the key events which full size whole body human scanners with field strength’s from
are important for understanding the role of EPI in functional 0.5 T up to 11.7 T to animal scanners at field strength up to
MRI and its technology development. 16 T and higher.
That blood changes its tranverse relaxation time depending For further reading on the history of EPI I suggest (Cohen &
on oxygenation was shown by Thullborn et al. (1982). Seiji Schmitt, 2013; Mansfield, 2013; Ordidge, 1999).

Brain Mapping: An Encyclopedic Reference http://dx.doi.org/10.1016/B978-0-12-397025-1.00006-3 53


54 INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging

Pulse Sequences Transform (2D FT) of the acquired 2D k-space data (com-
monly called raw data).
The MR signal generation and reception is quite complex and will The maximum signal can be expressed as
not be described in this article. Pulse sequences are the essence of
Sðt ¼ TEÞ ¼ So eTE=T2* [2]
an MRI machine, as it allows acquiring the data required to
calculate images of the organ on scope. For better understanding with So describing the MR signal without T2* relaxation. While
MR imaging methods see Mark Haacke’s book on Physical princi- for T2* the following relation holds
ples and sequence design of MRI (Haacke et al., 1999a).
1 1
Below, a brief walk from the most basic MR pulse sequence, ¼ þ gDBo [3]
the GRE sequence, to the various EPI sequences is given. All T2* T2
common neuroscience and clinical neurology-related single with DBo describing the magnetic flux changes across the voxel
shot EPI sequences are described. caused by magnetic susceptibility differences of the adjacent
tissue (for fMRI this is the BOLD induced susceptibility effect).
T2* decay is happening asymmetrically across the k-space data
The Basic GRE Pulse Sequence line.
For MR angiographic applications, for example, TE and TR
Conventional MR imaging is based on the interaction of the are kept as short as possible, while for measuring the best
magnetic moment of proton spins (in water) with static and BOLD signal for fMRI one needs to prolong TE quite substan-
dynamic electromagnetic fields. A strong magnet is needed to tially specific to the field strength of the magnet used. It is
create a net polarization of spins which can then be excited with generally established that for 1.5, 3, and 7 T TEs of 40, 30,
RF pulses and hence generates the MR signal. Pulsed gradients and 20 ms are used, respectively, while the repetition time TR is
(see a typical GRE pulse sequence in Figure 1) are used for slice on the order of seconds to avoid or minimize T1 weighting.
selection (SS) and spatial image encoding. The direction of the Assuming a matrix size of N ¼ 64, which was typically used for
three axis gradients are commonly referred to as SS, phase fMRI in the early days, total scan times per image (i.e., slice) are
encoding (PC), and read out (RO) gradient orientation. For SS on the order of 2–5 min for a stack of slices covering the brain
an RF-pulse is played out simultaneously with the SS gradient volume of interest. This takes much too long for performing
pulse. The RF-pulse amplitude is commonly expressed with the useful fMRI experiments. But it can be and was used in the early
so-called excitation flip-angle. If only a single excitation pulse times of fMRI as no other faster method like EPI was available
gets applied, a flip angle of 90 always generates the strongest (see above in the history section).
MR signal. When driven in steady state, that is, repetitive, the
flip-angle required optimizing contrast and signal-to-noise-ratio
(SNR) for specific applications is lower (10–20 ) (Ernst &
EPI Pulse Sequences
Anderson, 1966). This GRE imaging method is also called fast
low angle shot imaging and was invented in 1986 by Haase et al. Many variants of EPI are possible providing T1, T2, T2*, and
(1986). diffusion weighting. Image acquisition is possible in single shot
The gradient echo formation is best explained with the and multi shot (i.e., segmented EPI). Here we describe all
k-space method. For deeper understanding of the k-space relevant single shot EPI techniques only. For better understand-
terminology we suggest (Haacke et al., 1999b). The definition ing of the segmented techniques we suggest (Wielopolski et al.,
of k-space is given in eqn [1] below 1998). Spiral EPI described by Ahn et al. (1986) which is as fast
ðt as EPI is not described in this article. Contrary to EPI which
kðt Þ ¼ g Gðt Þdt [1] mostly uses a rectilinear k-space grid, spiral echo-planar sam-
0
ples the k-space on a spiral trajectory (non rectilinear grid). This
where G(t) defines the time dependent gradient pulse and g the technique is used by some fMRI researcher. For further reading
gyromagnetic ratio (g ¼ 42.578 MHz T1). In graphical terms, on this we suggest (Meyer, 1998) as it has not fully made it into
the condition of a gradient echo is achieved when the area the fMRI.
under the (negative polarity) pre-phasing lobe of the RO gra- EPI uses a single shot pulsing scheme, meaning that all k-
dient is balanced by the accumulated area under the (positive space data needed to reconstruct a final image gets acquired
polarity) RO gradient pulse. For clarity reasons these two sec- after a single excitation pulse. In contrast to this GRE imaging
tions are shown shaded in Figure 1. Usually, this coincides uses multiple shots to acquire the corresponding image data.
with the time when the maximum signal is detected and is The key to the EPI sequence is the periodic RO gradient pulse
called echo time (TE). While the SS and read-out gradient pulse train shown in Figure 2. All k-space data lines are acquired
remain constant during the entire imaging process for a 2D under this long RO pulse train. K-space traversal is in meander
imaging experiment, conventional MRI employs a so-called like fashion as shown in Figure 2. The resulting MR image is
phase encoding step. After each repetition time (TR) one computed by performing a 2D FT similar to the above
(k-space) data line is acquired and the PC gradient is changing described GRE image reconstruction, but some extra steps of
a bit, by stepping in incremental steps of dGPC ¼ 2GPC/N from pre-processing of the k-space data are required. In particular k-
GPC to þGPC, where N is the matrix size. Total scan time is space resampling, phase corrections and time reversal of every
therefore N times TR, while TR is defined application specific. other data line are required in order to fill the k-space properly.
K-space traversal is line by line as shown in Figure 1. The Due to its alternating acquisition under positive and negative
image is then calculated by a two dimensional Fourier gradient lobes, EPI is very vulnerable to the so-called Nyquist
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 55

a
RF

Raw data Image data


GSS

GPC 2D FT

GRO
K-space Image space
RO →
PC 1 ………………………
2 ………………………
e−t/T2* ………………………

.
. ………………………
.
………………………
Signal
.
………………………
………………………
. ………………………
t
. ………………………
TE . ………………………
TR . ………………………
. ………………………
. ………………………
N ………………………
1……………………..………N
(a) K-space trajectory

Figure 1 (a) GRE sequence. Left column: GRE-2D pulse sequence. Note: Condition for a GRE is highlighted in shaded areas of GRO pulse train.
Middle column: typical magnitude raw-data set (above) and rectilinear k-space trajectory (below). Right column: resulting image. (b) 7 T T2* weighted
high-resolution GRE images (1024  1024 matrix size). Left: magnitude image, right: phase image. Note the contrast variations in the phase image
across the optical radiation fiber bundles (see arrows).

EPI-GRE Sequence
or N/2-ghosting artifact which creates double/ghost images Figure 2 shows the most basic EPI sequence, that is, the
shifted by half the matrix size N and wrapped around in PC EPI-GRE type which is used for BOLD imaging. The image
direction. For further reading on EPI image reconstruction we is acquired after a single RF-pulse excitation. Shape and
suggest (Schmitt et al., 1998). amplitude of PC and the RO gradient pulses are kept
90˚

RF

GSS
RO


PC 1 ……………………
N…………………………………………….…...………1

↓ 2
……………………
N+1 …………………………………………………….2N

. ……………………
GPC PC blips
. ……………………
. ……………………
.
……………………
……………………
Phase Correction EPI Readout . ……………………
. ……………………
GRO . ……………………
. ……………………
. ……………………
. ……………………
N ……………………
Signal e–t/T2* 1……………………..………N
K-space trajectory

(a) TE

Figure 2 (a) 2D EPI-GRE sequence. Left column: EPI-GRE sequence. MR signal is T2* weighted as indicated in signal trace. Right column: K-space
trajectory is meander like starting from upper right to lower left. Advance in PC direction is generated by little blips in PC direction. (b) Typical 2D
EPI-GRE images through brain taken on a 3 Thead-only MRI system. Scan parameters: Single shot EPI; TE/TR ¼ 3000/50 ms; 128  128 matrix size;
48 slices at 3 mm voxel size.
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 57

constant during the acquisition of the entire image. What is magnet field strength. T2* decay is asymmetric around the
established with the PC table in a regular GRE sequence is echo center at TE. To optimize for strongest BOLD effects the
accomplished by small gradient pulses (so-called blips) TE needs to be adjusted accordingly, as described previously. In
during the zero crossings of the periodically oscillating RO the RO gradient axis, an extra pulsing scheme, the phase cor-
gradient pulse train. Typically trapezoidal or sinusoidal rection section, is introduced before the actual EPI readout.
pulse shapes are applied. Although sinusoidal RO gradient Data acquired under these pulses are used for image recon-
pulses have dominated the early times of EPI (Cohen et al., struction, to align the trace of echoes and fit the k-space
1991; Mansfield et al., 1991; Schmitt et al., 1989), these smoothly before performing the final image reconstruction
days, they are neglected entirely and trapezoidal pulses are via Fourier Transformation. A more detailed description of
only used. For simplicity we therefore stick to trapezoidal the phase corrections for EPI is presented in (Schmitt and
pulses in all the graphical representations of sequences. Wielopolski, 1998).
Under each half wave of the RO pulse train, a single k- For fMRI a multi slice scheme covering the brain area of
space data line is acquired. Hence scan time is significantly interest is repeated over and over again until the activation
shorter, that is, for N ¼ 64 and a typical basic frequency of paradigm is finished. Often 500 volumes are acquired resulting
1 kHz (corresponding to 500 ms per half wave) a total RO in a total BOLD scan time on the order of 10–20 min.
period of 32 ms is achieved. By considering a few millisec-
onds for the SS the total scan time per slice is below 40 ms,
EPI-SE Sequence Type
in case no acceleration methods such as half Fourier imag-
ing (Haacke et al., 1991; Margosian et al., 1986) or parallel While the EPI-GRE sequence is highly sensitive to the BOLD
receive, pRX, methods (see succeeding text) are applied. To effect from large venous vessels, it however, can mimic acti-
cover the entire brain with 3 mm thick slices the resulting vation away from functionally active gray matter (GM) (Olman
TR is typically on the order of 3–5 s and therefore the total et al., 2007). Also, sometimes fMRI experiments request to
scan time is also on the order of 3–5 s. separate the BOLD effect of small from large venous vessels at
Figure 2 resembles a susceptibility weighted 2D multi slice higher resolution. For this case a so-called Hahn spin-echo
EPI-GRE sequence which is widely used across different (HSE) (Hahn, 1950) excitation scheme is applied (see Figure 3).

180°
90°

RF

GSS RO →
1 ……………………
1…………………………………………….…...………N

PC 2 ……………………
2N …………………………………………………….N+1

……………………

.
GPC
PC blips
. ……………………
.
……………………
……………………
. ……………………
. ……………………
. ……………………
GRO . ……………………
t
. ……………………
. ……………………
. ……………………
N ……………………
e–t/T2
K-space trajectory

e–|t|/T2*

t
t t
TE
(a)

Figure 3 (a) 2D EPI-SE sequence. Left column: EPI-SE sequence. MR signal is T2 weighted as indicated in signal trace. T2* weighting still exists, but is
very minor and occurs only earlier and later to TE. Right column: K-space trajectory is meander like starting from upper left to lower right. Note the
difference in k-space traversal due to 180 HSE refocussing pulse.
(Continued)
58 INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging

Figure 3 cont’d (b-g) Anatomical and functional images from one volunteer taken at 9.4 Tesla. High-resolution anatomical GRE images (b) and (c)
clearly show the veins in both the magnitude and phase representation, respectively. SE-EPI (d) and GRE-EPI (e) have been acquired with 1 mm3
voxel size and show clear activation of the motor and somatosensory cortex (color overlay). Zoomed images of the activation, registered to the
high-resolution anatomical data, are shown in (f) and (g). The locations of the veins are overlaid in blue. The color bar shows the z-score and scaling is
equal in whole brain and zoomed images. Images with permission from MRM and courtesy of Budde, J., Shajan, G., Zaitsev, M., Scheffler, K., &
Pohmann, R. (2014). Functional MRI in human subjects with gradient-echo and spin-echo EPI at 9.4 T. Magnetic Resonance in Medicine, 71, 209–218.
Max Planck Institute Tübingen.

A HSE is created with a 90 -t-180 -t-TE RF pulse train. At TE Perfusion Imaging Using EPI
the susceptibility contrast is zero and the signal is purely T2
Two types of imaging methods using EPI are available for
weighted and can be expressed as
qualitative and quantitative perfusion measurement in the
Sðt ¼ TEÞ ¼ So eTE=T2 [4] brain. A T2* based CE method using Gadolinium compounds,
such as Gd-DTPA, is commonly used for qualitative evaluation
Susceptibility/T2* weighting is much smaller and is present of perfusion in tumors or stroke. Quantitative blood flow
only before and after TE and therefore affects the higher spatial imaging can be performed with a T1 based method called
frequency raw-data lines only, as being indicated in Figure 3. arterial spin labeling (ASL).
Overall the effects of susceptibility weighting are considered
very small and this technique therefore is better suited for high
resolution fMRI at ultra-high magnetic fields such as 7 T and Dynamic susceptibility contrast perfusion imaging using EPI
above (Budde et al., 2014; Yacoub et al., 2005). Gadolinium bolus imaging is used for qualitative perfusion in
The EPI-HSE excitation scheme is also the basis for diffu- stroke and tumors. To employ this before, during and after
sion imaging. See succeeding text. bolus injection of a Gadolinium compound, the entire brain is
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 59

repetitively scanned with a multi slice GRE-EPI sequence (b.t. As T1B prolongs with increasing magnetic field, longer data
w. this is the method which was used by Jack Belliveau in his acquisition times after the tagging pulses can be utilized and
first CE based fMRI experiment). Sometimes an SE-EPI the overall ASL SNR increases with increasing field strength.
sequence is used to highlight effects of smaller vessels (see This technique can be applied to achieve quantitative blood
preceding text). TEs are ranging between 30 and 50 ms and flow measurements or even for fMRI of brain activation. Figure 5
50 and 80 ms for a GRE-EPI and SE-EPI acquisition respec- shows a principle ASL sequence. Here an EPI-SE version is shown.
tively. TR is typically kept below 2 s in order to allow sufficient A faster method is using an EPI-GRE sequence module as the basic
time points by covering the entire brain. Total acquisition time acquisition scheme. A tagging slap (inversion) is excited in the
is on the order of 90–120 s. Contrast dose is typically neck region followed by an EPI data acquisition covering the entire
0.1–0.2 mmol kg1. brain. Figure 6 shows a functional MRI finger tapping comparison
On the order of 100 time points are scanned. The time course of BOLD and ASL, acquired at 7 T. The same areas of the cortex are
of selected voxels in a region of interest, that is, tumor or stroke activated and demonstrated with both techniques.
lesion, can be used to calculate specific maps reflecting the
physiological state of lesion. Typical maps are relative cerebral
blood volume, relative mean transit time, time to peak, etc. Diffusion Weighted Imaging Using EPI
Arterial input function, information is requested (time course
The mostly used pulse sequence scheme for diffusion weighting
of a selected arterial vessel) for calculating these maps.
imaging (DWI) is the so-called Stejskal–Tanner scheme (Stejskal
Figure 4 shows the basic time course and the achieved
and Tanner, 1965) which uses an EPI-SE sequence as the basic
image contrast during a DSC imaging experiment with admin-
imaging module. Additional to the EPI-SE pulse scheme strong
istered Gadolinium bolus.
diffusion weighting gradient pulses are placed symmetrically
around the 180 refocussing pulse (see Figure 7). The signal at
ASL for quantitative perfusion using EPI echo-time TE with existing diffusion weighting can therefore be
MR Imaging can be sensitized to inflowing spins of blood if expressed as
these spins have different magnetization state compared to that
of stationary tissue. The technique to achieve this is called DSðt ¼ TE;bÞ ¼ So eTE=T2 ebD [6]
arterial spin labeling introduced by Detre et al. (1992) as con- D describes the tissue dependent diffusion coefficient and b the
tinuous ASL, refined by Edelman and Chen (1998) as EPISTAR strength of the diffusion weighting, described in the simplest
and Wong et al. (1997, 1998) as PICORE and QUIPSS. The form of rectangular diffusion lobes shown in Figure 7 as
inflowing blood exchanges with the tissue water and therefore  
changes the tissue magnetization. Based on this effect quantita- d
b ¼ g2 G2 d2  D  [7]
tive perfusion weighted images can be generated by subtracting 3
labeled and unlabeled inflowing blood signal images. The
Clinical diffusion sequences for exploring early stroke, for
strength of the ASL signal changes, DS, as a function of time
example, use b-weighting of 1000 s mm2. A series of different
and is also dependent on T1 of blood, T1B. It can described as
b-weighting for a stroke case is shown in Figure 8. It is obvious
 t that the diffusion contrast peaks at about 1000s mm2. which in
DSðt Þ≺B0 e T1B [5] fact is commonly used in clinical routine stroke scanning.
Signal

500

450

400

350

300

250
0 10 20 30 40
Time point

0s 1.5 s 3s 4.5 s 6s 7.5 s 9s 10.5 s 12 s 13.5 s

Figure 4 T2* weighted perfusion time curve. Images shown in insert show the actual time stamps from the bolus arrival until 13.5 s after bolus.
60 INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging

Inversion 180° HSE-180°


90°
t
RF

TI TE

GSS

GPC
Imaging
slices

Inversion
slab
GRO

Figure 5 2D EPI-ASL sequence. Typically a thick slab in the neck region is inverted and after a wait time of TI an EPI-SE sequence is used to acquire the
flow sensitive MR signal.

most general form of diffusion weighting (and processing)


called diffusion spectrum imaging (DSI) or high angular
resolution diffusion imaging (Tuch et al., 1999; Figure 9),
is applied. The latter employs significantly stronger b-weight-
ing, typically 5000–15 000 s mm2. Conventional clinical
scanners therefore only achieve rather long echo-times
(over 100 ms) for those highly b-weighted scans.
Diffusion imaging is starving for SNR as the MR signal
decays very rapidly with increasing b-value, very strong gradi-
ents are therefore needed to achieve short echo-times. Experi-
mental gradient systems performing in such a range have been
developed for the NIH Blueprint for Neuroscience Research
called Human Connectome Project (see ‘Relevant Websites’)
Figure 6 Motor task ASL experiment (left) and its corresponding (Kimmlingen et al., 2012).
BOLD fMRI experiment (right) taken at 7 T. Both acquisitions show Figure 10 demonstrates what can be accomplished with
activation in the right motor sensory area. Images courtesy Lawrence L. very high b-values at short TE. At b-values of
Wald. b ¼ 10 000 s mm2 still MR signal is visible, not visible at
longer TE. It is also obvious that a better fiber detection is
possible with those high b-weighted at shorter TE (Wedeen et
al., 2012).
In general, the diffusion coefficient is not a scalar quan-
tity but will exhibit a directional dependence. For example,
water molecules can move rather freely along axonal fibers,
but are restricted in their motion perpendicular to fiber axis. Other EPI Sequence Variants Interesting for NeuroScience
Thus, a tensor model is commonly applied which sets the Some sequence types which are kind off forgotten and are not
stage for advanced processing techniques like fiber tracking. necessarily included in clinical scanners are worth mentioning
It requires a modification of the pulse sequence such that as they may provide interesting contrast for particular neuro-
diffusion lobes are applied in all three gradient directions science questions.
and vary in amplitude. Diffusion tensor imaging is one
variant of DWI, allowing to track neuronal fibers. It has
one caveat though; crossing fibers in a single voxel are Inversion recovery-EPI-GRE and Inversion recovery-EPI-SE
beyond the scope of the model and thus cannot be resolved T1 contrast is not easily possible with EPI. Standard T1 GRE
(Tournier et al., 2013). To overcome this uncertainty the sequences use a low flip GRE sequence with as short as
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 61

180°
90°
t
RF

TE

GSS

GDiff

GPC

d d
D

GRO

Figure 7 2D EPI-Diffusion weighted imaging sequence applying the Steijskal–Tanner diffusion pulsing scheme. The basic sequence is an EPI-SE
sequence with strong diffusion sensitizing gradient lobes (GDiff) between 90 –180 pulse and 180 -RO module. These gradient lobes can vary in
amplitude and direction depending on the DTI pulsing scheme. On clinical scanners (Gmax 45 mT m1) with b1000 this pulsing scheme results in
echo-times of about 80–100 ms.

possible TR. As the EPI RO train is rather long that method


b values does not work well for EPI as the TR would be too long and
s mm−2 additionally there is always a strong T2 and T2* weighting
involved. Instead, similar to the MPRAGE sequence (Mugler
35
& Brookman, 1991) an inversion recovery (IR) 180 pulse is
applied to invert the Mz magnetization. After a certain wait
time, TI, the regular EPI GRE (see Figure A2(a)) or SE (see
141 Figure A2(b)) pulse scheme is applied. TI is usually set to
null specific tissue type T1, such as fat, WM or, GM. In
principle, form a series of different TI’s one can calculate a
318 T1 image (Ordidge, Gibbs, Chapman, Stehling, & Mansfield,
1990). Figure A2(c) shows a mid-slice series of TI ranging
from 0 to 3800 ms. A TI of about 1200 ms provides great
GR/WM contrast. This TI, for example, can be best used to
565
overlay fMRI activation maps as the image distortion can be
adjusted the same as for the BOLD sequence, i.e., no mis-
alignment between the BOLD and the anatomical scans is
883 present.

EPI-GRE-SE
1271 As mentioned above EPI-GRE used for BOLD is very sensitive
to larger venous vessels, while EPI-SE is more sensitive to
smaller vessels. Normally when exploring these two excitation
Figure 8 2D multi slice EPI diffusion weighted scanning in patient with methods they are applied consecutively. It can, however, be
a stroke in left MCA. Left column shows the b-weighting. Common combined in one pulse sequence as shown in Figure A3. First
clinical practice uses a b-value of 1000 s mm2. Images courtesy Steven the T2* weighted GRE signal is acquired and after a 180
Warach, Bob Edelman, BIH. inversion pulse the T2 (and weakly T2*) weighted HSE signal
180°
90°
t
RF

TE

GSS

GPC

GRO

Figure 9 2D EPI-DSI sequence with diffusion encoding in three directions. Due to the typically very high b-weightings used in DSI long echo-times in
the excess of 100 ms is resulting. This method is therefore better used in very high performing gradient systems (Gmax > 100 mT m1).

b = 10 000 s mm−2, 1.5mm isotropic resolution diffusion weighed images (single direction)

Gmax = 40 mT m−1 100 mT m−1 300 mT m−1

bmax = 10 000 s mm−2 10 000 s mm−2 10 000 s mm−2 15 000 s mm−2

Gmax = 40 mT m−1 100 mT m−1 200 mT m−1 300 mT m−1

Figure 10 Upper row: Diffusion weighted images (single direction) acquired at Gmax ¼ 40 mT m1, 100 mT m1 and 300 mTm1 with
b ¼ 10,000 s mm2 and 1.5 mm isotropic resolution. Corresponding TE is 120, 80, 50 ms, respectively. i.e. with increasing available maximum
gradient strength shorter echo times are achieved and hence SNR of the diffusion weighted scans is significantly improved. Data acquired with the 64
channel brain array. Lower row: Effect of gradient strength on diffusion MRI of path crossings. DSI with peak gradients Gmax 40, 100, 200, and
300 mT m1, with mixing time adjusted for constant bmax 10 000 s mm2 are shown in panels 1–3 (from left to right), and bmax 15 000 in panel 4. As
noted, TE’s are minimized for each Gmax. The total number of path solutions identified within the Superior longitudinal fasciculus (SLF; horizontal
green, at center) increases by about 50% from the conventional (40 mT m1) to ultra-high gradient levels. Crossing pathways increase more
dramatically, their count increases by 2–3x from conventional to intermediate gradient performance (100 mT m1), and an additional 2–3x gain from
intermediate to the ultra-high gradients (100 vs 300 mT m1). Images courtesy V. Wedeen and L.L. Wald, MGH Martinos Center.
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 63

is acquired (Schmitt et al., 1988b). However, due to the long distortions. These methods need extra scans in order to correct
EPI RO train, a long TE is expected for the SE acquisition, for static (Jezzard & Balaban, 1995) and dynamic (van Gelde-
which results in a low SNR. This method therefore is better ren, de Zwart, & Stareweicz, 2007; Visser, Poser, Bart, & Zwiers,
suited for ultra high field imaging at 7 T and above. 2012) B0 deterioration. An image example using a similar
(static) technique (Zaitsev, Hennig, & Speck, 2004) is shown
in Figure 11(c). Acquisition parameters are the same as shown
EPI Limitations and Caveats for Figure A2(c). Most recently, methods have been proposed
Magnetic Susceptibility and Its Effect on Image Quality to compensate for dynamic B0 variations.

Human tissue has certain magnetic properties which become


relevant when exposed to an external magnetic field, H 0 , pro- Acquisition Speed is Limited by Physiological Effects due
duced by the magnet coil winding. In general it can increase or to Peripheral Nerve Stimulation
decrease the magnetic field (the flux) inside the human tissue,
When gradients are switched with high amplitudes and slew-
depending on its magnetic properties i.e., dia, para od ferro
rates physiological side effects, such as peripheral nerve
magnetic tissue. For further reading on magnetic susceptibility
stimulation (PNS) can occur. This effect was first reported
we suggest (Ernst & Anderson, 1966). The relation between the
when applying EPI sequences in humans, causing muscle
magnetic flux, B 0 , (the effective field the tissue is exposed to)
twitching at the location of the strongest exposed field
and the external field H 0 is describe with eqn [8]
(Figure 13; Budinger et al., 1991; Cohen et al., 1989; Fischer
B 0 ¼ m0 ð1 þ wÞH 0 [8] et al., 1989). One way to mitigate this effect is by shortening
the linearity volume as shown in Figure 13. Head gradients
show the highest PNS thresholds as the gradient field extend is
m and x describe the magnetic permeability and susceptibility typically very short (covering the head/brain only).
(see also Ernst & Anderson, 1966) In general, the PNS threshold expressed in gradient
Considering a tissue interface with susceptibility w1 and w2 a strength, GTH, is a linear function of the rise time, TRise, when
local field inhomogeneity periodic gradient pulses are applied, such as it is used in EPI.
DB0 ¼ ðw1  w2 ÞB0 [9] Sinusoidal and trapezoidal pulse trains result in slightly differ-
ent slopes of the threshold curves as shown in Figure 14 left,
is caused, which results in local image distortion, Dx, and but still preserve the linear relation of GTH  TRise (Irnich,
phase differences, DF, as shown in eqns [10] and [11] below. 1993). Interesting to note is the fact that after a certain number
of periods (16 cycles) the thresholds reach a minimum
DB0
Dx ¼ [10] (Figure 14, right) (Schmitt et al., 1998).
G
Safe operation is guaranteed by implementing PNS safety
Significant image artifacts arise due to these local inhomo- monitors who basically resemble the linear relation of Figure 14
geneities. For further reading we suggest (Lüdeke et al., 1985). and avoid PNS by staying below this linear threshold curve.
For EPI sequences the relevant gradient axis is the very low
strength equivalent PC gradient. Therefore severe distortions
can be seen in regions of strong susceptibility changes, such as Quality Assurance and Temporal Stability
the eye and nasal sinus. Change of the polarity of the PC
gradient is changing the distortion behavior significantly, that fMRI exams using EPI-BOLD acquisition is a highly repetitive
is, it can either stretch or squeeze those regions (see Figure 11). process, that is, the same stack of slices covering the brain is
This leaves room to optimize EPI accordingly to minimize repeated over and over again to follow the excitation paradigm.
distortion effects. Hence time points of each voxel are created and analyzed along
Signal voids due to phase cancelation caused by intra-voxel the time axis. Ideally one assumes that everything works per-
signal dephasing is also a common susceptibility-related issue fectly and no extra noise from the MRI machinery or subject
with EPI, described with eqn [11] itself is introduced. However, this is not the case. Both, the MRI
scanner and the human brain introduce statistical and systema-
DFgDB0 t [11] tical changes which need to be considered.
During scanning of the long lasting EPI acquisitions the
Especially the nasal sinus regions, the top of frontal lobe gradient system may heats up and expands. That can cause a
and the region close to the ear canals are prone to signal voids frequency drift (f0(t)) as the paradigm progresses. As an
when using EPI. The appearance of gross signal void suscepti- effect a thermal drift in the temporal BOLD signal is visible
bility effects in echo-planar images is demonstrated with vary- which may render an fMRI experiment useless if not coun-
ing slice thickness (Figure 12(a)) and TEs (Figure 12(b)). ter acted (similar to what can be seen in Figure 15(b) top
Obviously these are effects which limit the usability of EPI, left). To solve this the calibration scan (see Figure 2) is used
when not counter acted. Thin slices and reasonable short TE is to extract the frequency drift f0(t) and shift the image
helpful. Applying in-plane acceleration methods, as described according to its f0 drift. Also, imperfections in shim, gradi-
later in this chapter, is also helping. An example of distortion ents and RF electronic may cause sudden changes in the
minimization is shown in Figure 11(b). Acceleration beyond BOLD signal which are virtually impossible to compensate.
R ¼ 2 helps to reduce these uncertainties. Also, there are This was a common problem of the early days of fMRI and
correction methods known to reduce the susceptibility-caused now is more or less fixed through careful engineering of the
64 INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging

RO →
PC

(a)

Figure 11 (a) Susceptibility artefacts. Distortion in eyes and nasal sinus. Polarity of PC gradient is inverted between left and right image, causing
stretching and squeezing of the eyes and nasal sinus region, respectively. (b) 1 mm resolution diffusion-weighted images showing improvement in
frontal lobe susceptibility distortion as acceleration is increased beyond R ¼ 2. Images acquired at 3 T with a 32ch head coil. Data courtesy of L.L. Wald,
MGH Martinos Center. (c) Distortion correction of EPI images via PSF deconvolution. EPI-GRE acquisition taken at 7 T with a 32RX head coil.
Slice thickness 1.4 mm; #slices ¼ 10; in plane resolution 1.41.4 mm2; FOV 224224; Matrix 160160; Partial Fourier 6/8; GRAPPA factor 3;
TR/TE ¼ 5000/25 ms.
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging
21 ms 30 ms 40 ms 50 ms 60 ms
(b)

Figure 12 (a) Susceptibility artefacts. Through-plane signal void as a function of slice thickness. The thicker the slice the more severe the signal voids. Image courtesy Lawrence L. Wald, MGH. (b) Susceptibility
artefacts. In-plane signal void as a function of echo time TE. The longer TE the more the signal voids are pronounced. Therefore BOLD fMRI is a balance between the desired BOLD signal effect and the
accompanying susceptibility aretfacts. Image courtesy Lawrence L. Wald, MGH.

65
66 INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging

B
Bmax

zS zL z

FOVS
Z-gradient
FOVL

Figure 13 Peripheral nerve stimulation in relation to short and long gradients illustrated with a z-gradient. PNS occur at location of strongest magnetic
flux exposure.
GTh(TRise)

GTh(#pulse)
~30%

TRise 1 N #periods
Figure 14 PNS threshold gradient amplitudes as a function of gradient pulse rise time G ¼ fct(T ) for sinusoidal and trapezoidal pulse trains (left).
Th Rise

When increasing the numbers of pulses per pulse train, threshold reduces by about 30% and reach a stable value at about 16 periods.

entire gradient chain. However, care must be taken in order Accelerated EPI
to understand the fidelity of the MRI scanner in use for
fMRI. As the BOLD signal is on the order of a few percent, EPI is the fastest MRI pulse sequence existing. However, accel-
overall the temporal stability requirements for performing eration is still advantageous for a variety of reasons. One
good fMRI should not exceed 0.5% peak–peak with thermal reason for accelerating is to minimize susceptibility artefacts,
drift compensated. that is, distortion and signal voids, as described above. Another
Clinical MRI exams are less vulnerable to these fluctuations reason is data throughput, that is, how many slices per seconds
compared to fMRI scans. Therefore, a daily quality assurance can be acquired. This is generally achieved by using knowledge
(QA) procedure is helpful to determine the status of an MRI of the spatial extend of the RF coil profiles of multi-channel
scanner when used for fMRI. The evaluation procedure was receive coils which are common these days. All major vendors
introduced by Robert Weisskoff in 1996 (Weisskoff, 1996) and offer head RX coils with up to 32 RX channels for clinical
is now considered the gold standard for performing quality scanners now. Experimental coils have been proposed and
assurance for fMRI. introduced offering up to 128 RX channels allowing even
It is important to note that the brain itself creates physio- further accelerations in MR imaging (Keil and Wald, 2013;
logical noise which appears in the temporal behavior of the Wiggins et al., 2009).
BOLD signal. This was carefully investigated over the last Acceleration schemes are basically differentiated by
decade and can be best understood by reading the publications methods which accelerate the scan time per image (i.e., in-
of Triantafyllou, Wald et al. (Triantafyllou et al., 2005, 2011) plane) or by accelerating the scan time per stack of slices (i.e.,
which describe these phenomena over a range of field strength through-plane). Here we briefly describe these two basic
of 1.5, 3, and 7 T. To demonstrate the relation of machine methods, as they are interwoven into the EPI acquisition.
noise and physiological noise see Figure 15. It shows temporal
fMRI signals of white matter (WM), gray matter (GM), and
cerebral spinal fluid (CSF) as well as from a small phantom
In-Plane Acceleration
attached to the skull. It is obvious that the MRI machine noise,
taken from the phantom, should be smaller than the physio- The general terminology for accelerated MR imaging is parallel
logical noise. imaging, abbreviated as pRX. These methods have been
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 67

WM

CSF

PH

GM

(a)

1640 1135
Phantom 1130 CSF
1630
1125
Mean signal over ROI
Mean signal over ROI

1120
1620
1115
1610 1110
1105
1600
1100
1095
1590 Stability(*)~ 0.5% peak–peak Stability ~ 1.8% peak–peak
(*) after detrending 1090
1580 1085
0 50 100 150 200 250 300 0 50 100 150 200 250 300
Time points Time points

840 910
WM GM
835 905
Mean signal over ROI

Mean signal over ROI

830 900

825 895

820 890

815 Stability ~ 0.7% peak–peak 885 Stability ~ 1.1% peak–peak

810 880
0 50 100 150 200 250 300 0 50 100 150 200 250 300
(b) Time points Time points
Figure 15 (a) Cross sectional EPI-BOLD scan with adjacent phantom to the right taken on a 3T head scanner. Red boxes show 77 pixel
ROIs to be evaluated (see below). Scan parameter are TE ¼ 20 ms, TR ¼ 2000 ms, matrix size is 6464. (b) Time course evaluation of ROIs
(shown in red in Figure 15 (a)) do reflect MRI scanner noise and physiological noise of an fMRI experiment. Data courtesy of C. Triantafilou
and L. L. Wald, MGH.
68 INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging

invented at the turn of the last millennium. Pruessmann et al. Gmax ¼ SImax [13]
(1999) proposed the SENSE method, followed by Sodickson
(2000) who introduced SMASH. The GRAPPA method was with S describing the sensitivity of the gradient coil expressed
announced by Griswold et al. (2002) and later refined as in units of gradient strength per current, that is, mT m1 A1
CAIPIRHINA (Breuer et al., 2005). Of these techniques and Imax the current needed to achieve Gmax
SENSE and GRAPPA are the most commonly used for fMRI. (b) how fast one can switch a gradient pulse from zero to
In-plane acceleration for EPI shortens the RO pulse train. Extra maximum gradient strength, commonly expressed as slew rate
calibration data need to be acquired to calculate the de- (SR) measured in units of gradient strength per second, that is,
convolution kernel for the SENSE/GRAPPA pRX reconstruc- T m1 s1.
tion. In-plane SENSE and GRAPPA have the major drawback dG Gmax
that with increasing acceleration signal loss and structured SR ¼ ¼ [14]
dt T Rise
noise appears, rendering very high acceleration useless. SNR
relates to acceleration R as described in eqn [12], while g Other aspects of importance are
describes the geometry factor, which is coil geometry depen- (c) how long one can pulse the gradients before they over
dent, and SNRo describes the intrinsic SNR without heat. This is generally expressed in something called gradient
acceleration power duty cycle (DC) expressed in (%)
ð t2
SNR 0
SNRaccel ¼ pffiffiffi [12] Gðt Þ2 dt
g R
DCðt1 ; t2 Þ ¼ 2t1  100% [15]
Gref ðt2  t1 Þ
With current RF coil technology acceleration of up to four
times can work reliably. This is very RF coil performance (d) the gradient linearity over a certain volume of interest
dependent also. which defines the geometric imaging fidelity, that is, if the
images is distorted and how much. Ideally the gradient field
should be perfectly linear and can then be described for a
Through-Plane Acceleration z-gradient as
Through-plane acceleration has been developed over the recent
Bz ðzÞ ¼ Gz [16]
3–5 years and is making very promising advances. These
methods are based on a technique called multi band (MB). Note: for MR imaging only the z-component of the magnet
While the MB method exists since the early 2000s (Larkman field is important.
et al., 2001) it recently has been refined to allow very high MRI gradient performance was very meager at the begin-
acceleration rates (Feinberg et al., 2010; Moeller et al., 2010). ning of MRI (around 1983) compared to these days. Gradient
Simultaneous multi slice (SMS) in combination with EPI is strength of 1 mT m1 at a SR of 1 T s1 m1 or even lower was
based on blipped CAIPHRINHA and provides excellent common, while today state of the art whole body scanners of
through-plane acceleration (Setsompop et al., 2012). The real all major vendors provide at least 40 mT m1 at SRs of
advantage of not losing SNR with increasing acceleration, as it 200 T m1 s1. EPI strongly benefits from this increase in per-
happens with the in-plane methods, is very helpful to maintain formance. In fact, it was EPI which has driven the specification
high SNR with high accelerations. Through-plane acceleration to these current levels. Another driver for higher gradient spec-
allows high temporal resolution resting state fMRI (rsfMRI) as ification is EPI based diffusion weighted imaging. Based on
it shortens the scan time per stack of slices below a second (see such requests dedicated whole body gradient systems are now
Figure 16). in use providing 300 mT m1 at SR 200 T m1 s1, two orders
For high resolution DSI with very long scan times of of magnitude stronger than the first commercial scanners pro-
30 min or longer are normal if no acceleration is applied. vided (Kimmlingen et al., 2012).
Combining in-plane and through-plane acceleration helps The key components of a gradient system are the gradient
to shorten scan time significantly (Setsompop et al., 2013). amplifier and the gradient coil. Gradient amplifiers can be
Figure 17 shows results of this technique taken at a 7 T envisioned as very strong audio amplifiers providing high
scanner. Fifteen-fold acceleration is achieved by applying output voltages and current in order to drive the specific pulses
threefold in-plane (using GRAPPA) with fivefold through- through the gradient coil. Electric circuits are characterized by
plane SMS acceleration. its resistance (measured in O; 1 O ¼ 1 V A1) and inductance
(measured in milli Henry, mH; 1 H ¼ Vs/A). The relations
below (eqns [17] and [18]) describe the requirement for volt-
age and current for driving a trapezoidal gradient pulse
Appendix
Technology Development of EPI Capable Gradient Systems dI
U ¼ L þ RI [17]
The key specifications of a gradient system is shown in dt
Figure A1 and is characterized by With U describing the voltage needed to drive a current change
(a) the maximum achievable gradient amplitude, Gmax, (dI/dt) in a gradient coil of inductance L and resistance R
measured in magnetic flux variation per meter, that is, (Ohm’s law). Maximum voltage and current for reaching
mT m1, which is usually expressed as Gmax at the shortest possible TRise is then expressed as.
(a) (b)

INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging


(c) (d)

Figure 16 Multiband through-plane acceleration applied to resting state fMRI at 3 T by using a 32 channel RX head coil. TE ¼ 30 ms and 1.6 mm isotropic voxel resolution. (a) Standard fMRI protocol-no
acceleration, TR ¼ 6.7 s, flip angle ¼ 90 . (b) MultiBand 6 acceleration, PE3, 6/8 PF, TR 6.7 ms, flip angle <90 . (c) MultiBand 6 acceleration, PE3, 6/8 PF, TR 1.1 ms, flip angle <90 . (d) 2 mm isotropic voxels.
MultiBand 6 acceleration, PE3, 7/8 PF, TR 0.74 ms, flip angle <90 . Images courtesy E. Yacoub, K. Ugurbil, D. Feinberg et al. CMRR, Minneapolis.

69
70 INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging

Figure 17 In-plane (GRAPPA) and through-plane (SMS) acceleration combined results acquired on a 7 T system by using a 32 channel RX
head coil: In total a R¼15-fold acceleration is achieved. Rin-plane¼3, Rthrough-plane¼5. Images courtesy K. Setsompop & J. Polmeni, MGH Martinos
Center.

G(t)

Gmax

Gmax= S ⋅ I max
t
TRise
I(t)

Imax

dI ( t)
t V(t) = I(t)⋅R−L⋅
dt
V(t)
V max

I max
V max = I max ⋅ R + L ⋅
TRise
t

Figure A1 Grad-pulse characteristics and specifications.

Gmax current required is on the order of 2000 V and 600–900 A,


U max ¼ LS þ RImax [18]
T Rise respectively. This is strongly depending on the gradient coil
Modern gradient coils have inductance and resistance of about design, resulting in lower or higher currents and voltages. For
1 mH and 100 mO, respectively. Sensitivity is on the order of further reading on understanding gradient systems we suggest
0.05 mT m1 A1. Thus the maximum output voltage and Schmitt (2009).
INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 71

Inversion 180°
90°

RF

GSS

GPC

GRO

0
+Mz
Magnetization Mz MR signal
Mz/signal e−t/T2*
1−e−t/T1

0
−Mz
TNULL
TI TE
(a)
Inversion 180° 180°
90°

RF

GSS

GPC

GRO

0
+Mz
Magnetization Mz MR signal
Mz/signal e−t/T2
1−e−t/T1

0
–Mz
TNULL
(b) TI TE

Figure A2 (a) 2D Inversion recovery with EPI-GRE data acquisition sequence. (b) 2D Inversion recovery with EPI-SE data acquisition sequence.
(Continued)
Figure A2 cont’d (c) Typical image acquired with a 2D inversion recovery with EPI-GRE data acquisition sequence. Note the different TI causes
different contrast between GM and WM.

180°
90°

RF

GSS

GPC

GRO

e–t/T2*
e–t/T2

e–(t–TEHSE)/T2*

TEGRE

TEHSE

Figure A3 GRE and SE double acquisition EPI sequence.


INTRODUCTION TO ACQUISITION METHODS | Echo-Planar Imaging 73

Acknowledgments Echo-Planar Imaging


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The author is grateful to T. Feiweier for reading and correcting Stehling, M. K., Turner, R., & Mansfield, P. (1991). Echo-planar imaging: Magnetic
the manuscript and to H. Meyer for helping with sequence resonance imaging in a fraction of a second. Science, 254, 43–50.
diagrams. I also deeply appreciate receiving the imaging data Pykett, I. L., & Rzedzian, R. R. (1987). Instant images of the body by magnetic
of K. Ugurbil, L.L. Wald, V. Wedeen, E. Yakoub, C. Triantafyl- resonance. Magnetic Resonance in Medicine, 5, 563–571.
Mansfield, P., Harvey, P. R., & Coxon, R. J. (1991). Multi-mode resonant gradient coil
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