Susceptibility-Weighted Imaging: Technical Aspects and Clinical Applications, Part 1
Susceptibility-Weighted Imaging: Technical Aspects and Clinical Applications, Part 1
PHYSICS REVIEW
as a means to measure susceptibility in clinical MR imaging. would still need to be adopted in a broad clinical environment
In 1997, we developed a means to remove most of the un- and then executed as a standard “neuroprotocol” on a clinical
wanted phase artifacts and keep just the local phase of inter- platform. Once the latter step has taken place, the method
est.1 This set the stage for discovering other aspects of suscep- should eventually be adopted by the radiology community as a
tibility imaging and even hinted at the future direction of whole and become part and parcel of conventional educa-
susceptibility mapping.26 We began to see different types of tional courses offered at radiology meetings for accreditation.
contrast in the SWI filtered phase images for different diseases. Only then could we say that a method is fully incorporated
To make the information more accessible to radiologists, into the international radiology routine.
though phase and magnitude images separately are also criti- In this review, we summarize the motivation behind SWI, the
cal pieces of information, we combined the phase and the concepts that led to its discovery, the optimal parameters to use,
magnitude information and thus created a new susceptibility- and the interpretation of the SWI processed data and phase im-
weighted magnitude image, which today is referred to as ages; and we conclude by discussing the technology in use today,
SWI.22 This new pair of images (the SWI filtered phase data the postprocessing, and future directions of SWI research.
and the merged SWI magnitude data) is now available on at MR imaging has already an overabundance of different ap-
least 1 major manufacturer’s systems (Siemens Medical Sys- proaches for investigational anatomic, functional, and meta-
tems), though it took almost 10 years to see the actual imple- bolic imaging. Each method focuses on a new issue, such as the
mentation of this approach in a clinical setting around the delivery of blood to the tissue in perfusion-weighted imaging
world. or molecular motion along a fiber track in diffusion tensor
Many technical developments take years to leave the re- imaging. The susceptibility information is an adjunct to what
search environment and become part of standard radiology is available with conventional spin density, T1-, and T2-
applications. This has been true for perfusion imaging, diffu- weighted imaging methods. SWI offers information about any
tissue that has a different susceptibility than its surrounding
From the Departments of Radiology (E.M.H., Y.-C.N.C.), Biomedical Engineering (E.M.H., structures such as deoxygenated blood, hemosiderin, ferritin,
J.N., Y.-C.N.C.), and Neurosurgery (S.M.), Wayne State University, Detroit, Mich; Karmanos and calcium. There are numerous neurologic disorders that
Cancer Institute (S.M.), Detroit, Mich; and Department of Biomedical Engineering (Z.W.), can benefit dramatically from a very sensitive method that
McMaster University, Hamilton, Ontario, Canada.
monitors the amount of iron in the brain, whether in the form
This work was supported in part by the National Institutes of Health grant NIH R01 NHLBI
62983-04 and Siemens Medical Systems.
of deoxyhemoglobin, ferritin, or hemosiderin. Such diseases
Please address correspondence to E. Mark Haacke, PhD, Wayne State University, Detroit,
and conditions include, but are not limited to, aging, multiple
MI; e-mail: [email protected] sclerosis (MS), stroke, trauma, vascular malformations, and
Indicates open access to non-subscribers at www.ajnr.org
tumors. There is no doubt that as SWI becomes more broadly
accepted, we will see many new applications develop because
DOI 10.3174/ajnr.A1400 of the astute observations of clinical researchers and the wide
Gradient-Echo Imaging
Historically, data were first collected with a free induction de-
cay.64,65 The concept of a spin-echo was invented only when it
was seen that local field inhomogeneities had caused dramatic
signal intensity loss. For some time, the spin-echo approach was
the mainstay of clinical MR imaging for resistive machines.66 Not
long after the appearance of superconducting systems on the
market, gradient-echo imaging67-69 came back to life because the
field uniformity in these systems was markedly better (and has
continued to improve during the last 20 years). People quickly
realized that they could eliminate most artifacts in magnitude
images by running the gradient-echo scans with short TEs in se-
quences like magnetization-preparation rapid acquisition of gra-
dient echo.70 This high-bandwidth sequence had little distortion
Fig 1. Gradient-echo sequence design. Ts refers to the sampling time interval. The gradient
and offered excellent T1 contrast (and presented a good method pulses are designed to give first-order flow compensation. SS indicates the slice-select
to collect T1-weighted data even at 3T). Longer TEs were used in gradient; PE, the phase-encoding gradient; ADC, analog-to-digital conversion.
2D gradient-echo imaging but with fairly thick sections, usually 3
or 4 mm. The TEs were often chosen to be 15, 20, or rarely 25 2) 共 兲 ⫽ m()exp(⫺i␥⌬BTE),
ms because of the signal-intensity loss associated with rapid
where ⌬B represents the local field deviation caused by iron,
phase changes across a voxel. Imaging with longer TEs,
for example, and ␥ is the gyromagnetic constant, which is
while maintaining image quality, was only possible with 3D
equal to 2 䡠 42.58 MHz/T for protons. This can be rewritten
gradient-echo imaging. Once this was recognized and res-
as
olutions on the order of ⱕ1 mm3 were realized with a suf-
ficient signal intensity–to-noise ratio (SNR), the ability to 3) 共 兲 ⫽ m()exp(⫺i␥g⌬BoTE),
look at hidden information in phase data became possi-
ble.57,71 Thus, the stage to study susceptibility effects was set where g is a geometric factor, ⌬ is the difference of the local
in the mid 1990s, and the first article on SWI was published magnetic susceptibility of the tissue of interest from its sur-
in 1997.1 To appreciate the basic elements of SWI, we must roundings, and B0 is the field strength. Starting with the Lar-
first review the basic gradient-echo sequence design on mor equation
which it is based. 4) ⫽ ␥ B o,
In MR imaging, it is necessary to create some transverse mag-
netization first.72 This can be accomplished by using a transmit the expression for phase is
coil to produce a radio-frequency (rf) pulse which tips the longi-
5) ⫽ t.
tudinal magnetization (Mo) partially or completely into the
transverse plane. The rf pulse is applied at the Larmor frequency, The change in phase between 2 tissues after a period of time,
⫽ ␥Bo. If Mo is rotated an angle about the x-axis, it will create TE, can then be written as
a component along y that will be picked up by a receiver coil. The
data are then encoded in both the phase- and partition-encoding ⌬ ⫽ ⌬ TE,
directions (y and z, respectively, for a transverse acquisition), where
while a dephasing gradient is applied in the readout direction.
The read gradient is then turned on and the data are sampled. ⌬ ⫽ ␥ ⌬B and ⌬B ⫽ g⌬Bo
After this, the remnant signal intensity is further dephased, and rf so that
spoiling is applied by varying the axis about which the rf is applied
so that no transverse magnetization remains before the next rf 6) ⌬ ⫽ ⫺ ␥ ⌬BTE
pulse. All this is shown pictorially in Fig 1. The magnitude signal-
intensity response for this rf-spoiled short-TR gradient-echo se- 7) ⌬ ⫽ ⫺ ␥ g⌬BoTE.
quence is given by All of ⌬B, ⌬, and, therefore, ⌬ are dependent on the local
1) m() ⫽ osin exp(⫺TE/T2*)⫻ tissue susceptibility.
Table 1: Tissue parameters used to simulate the T1-weighted derestimate the amount of Fe by a factor of 5). The suscepti-
images shown in Fig 2 bilities of most biologic tissues73 tend to be ⬍10⫺4. However,
all forms of iron may not be visible with MR imaging if ⌬ ⫽
GM WM CSF
0 for that substance. This can happen if the iron is shielded by
Spin density % 80 65 100
1.5T 1000 ms 650 ms 4000 ms
other elements such as oxygen. For a more detailed descrip-
3T 1283 ms 838 ms 4000 ms tion of the different forms of magnetism see Schenck73 and
Note:—GM indicates gray matter; WM, white matter; CSF, cerebrospinal fluid. CSF is
Saini et al.74
taken to have 100% water content.
Geometry Effects
9) H ⫽ B / o ⫺ M The induced magnetization (owing to its susceptibility) in an
and is the magnetic susceptibility relating M and H. We can object within a uniform external magnetic field distorts the
also write uniform field outside the object. The spatial distribution of
this deviation in the external applied field is a function of the
10) B ⫽ H, geometry of the object.75 The local field deviation inside and
around an object is of interest because it gives rise to local
where ⫽ or is the permeability, o is the permeability in
phase differences in MR imaging. When discussing the effects
vacuum, r is the relative permeability, and H the magnetic
of geometry on local field variations, we usually neglect the
field (B is the induced magnetic field). Using the relative per-
background field and assume that ⬍⬍ 1. For a cylinder mak-
meability as
ing an angle to the main field, the effect on the field inside the
11) r ⫽ 1 ⫹ , cylinder is given by
we find 14) ⌬B in ⫽ ⌬Bo(3cos2 ⫺ 1)/6 ⫹ eBo/3,
12) M ⫽ B/o/(1 ⫹ ). which includes the Lorentzian sphere term. We have used
⌬ ⫽ i ⫺ e. Here, i and e are the susceptibilities inside and
For linear materials with ⬍⬍ 1, we find outside the cylinder, respectively. Generally, when we are
looking at changes in local tissue fields, the final term eBo / 3
13) M ⫽ B/o,
no longer plays a role because it is a common constant both
and it becomes clear that the induced magnetization is directly inside and outside the object. If we write
proportional to the main field and the magnetic susceptibility.
15) ⌬Bin ⫽ gin⌬Bo,
Each tissue or substance behaves somewhat differently in a
magnetic field. For the purposes of this review, we shall con- we have
sider only diamagnetic and paramagnetic substances. Dia-
16) gin ⫽ (3cos2 ⫺ 1)/6.
magnetic substances have ⬍ 0. For example, calcium in the
body tends to be in the form of calcium phosphates such as For blood vessels in particular, we have
Ca3(PO)4 and is diamagnetic. On the other hand, paramag-
17) ⌬Bin ⫽ ⌬doBo(3cos2 ⫺ 1)/6,
netic substances (ie, most iron-based materials or tissues) have
⬎ 0. For example, deoxygenated blood has ⌬ ⬇ 0.45 ppm where
in SI units, relative to surrounding tissue. Moreover, iron-
18) ⌬ do ⫽ 4A(0.18ppm)Hct(1 ⫺ Y).
containing proteins, like ferritin and hemosiderin, tend to
have varying susceptibilities depending on the amount of se- Here, A is a constant to be determined by the absolute suscep-
questered iron within the protein. Typically, on the basis of tibility of blood in vivo, Hct is the hematocrit, and Y is the
phase measurements from 75 subjects,62 approximately a oxygen saturation. Practically, the choice of A depends on the
⌬ ⫽ 0.21 ppm in SI units with respect to CSF, corresponds to value of Y in vivo: with A ⫽ 1, then Y ⫽ 0.55,1 whereas with
60 g of iron (Fe) per gram of tissue (although this may un- A ⫽ 1.5, then Y ⫽ 0.70.76,77
The field outside is more complicated and is given by Creating Susceptibility-Weighted Filtered-Phase Images
First, an HP filter is applied to remove the low-spatial fre-
19) ⌬B out ⫽ ⌬doBosin2cos(2⌽)a2/(2r2), quency components of the background field. This is usually
done by using a 64 ⫻ 64 low-pass filter divided into the orig-
where a is the radius of the blood vessel, which is assumed as a inal phase image (eg, an image with a matrix size of 512 ⫻ 512)
long cylinder intercepting an angle with the main field, r is to create an HP-filter effect. The end result is the HP filter.
the distance perpendicularly from the axis of the cylinder to Specifically, the HP-filtered image is obtained by taking the
the position, and ⌽ is the angle between the vector r and the original image (r), truncating it to the central n ⫻ n complex
projection of the main field direction onto a plane perpendic- image n(r), creating an image by zero-filling the elements
ular to the axis of the vessel. The constant term, eBo / 3, has outside the central n ⫻ n elements, and then complex dividing
been dropped in equation 19. (r) by n(r) to obtain a new image,60
For more complicated structures, the expressions for mag-
netic field variations around the object are not so straightfor- 22) ⬘共r兲 ⫽ (r)/n(r),
ward. The key point is that susceptibility differences between 2
adjacent structures lead to a spatial field deviation within and which has most of the bothersome parts of the terms
around them, which is a function of their geometries. Follow- ⌬Bglobal geometry ⫹ ⌬Bmain field removed (Fig 3).
ing equation 6, this field deviation in turn leads to local phase Once we have a pristine phase image with the background
changes in the MR phase images. However, phase images con- field changes removed, the door is open to differentiate one
tain information about all magnetic fields, microscopic and type of tissue from another, depending on their susceptibili-
macroscopic. The former may be from small amounts of local ties. This may be particularly useful at high field because the T1
iron deposits, for example, whereas the latter consists of field difference between tissues begins to decrease, but any changes
changes caused by the geometry of the object, such as air/tissue in susceptibility remain the same. Figure 4 shows an example
interface effects, and by inhomogeneities in the main magnetic of a T1-weighted image compared with the gradient-echo
field. With all these properties brought together, the phase magnitude and phase data. Here we see that the gray matter,
should be written as especially in the motor cortex area—the central sulcus—is
clearly delineated in the phase image because of its iron con-
20) ⫽ ⫺ ␥ 共⌬B local geometry ⫹ ⌬B cs ⫹ ⌬B global geometry tent. Figure 5 shows an example of a phase image in the
midbrain.
⫹ ⌬B main field 兲TE.
All these terms are a function of the spatial location. The first Marrying Magnitude and Phase Images to Create
term contains the local field changes of interest. The second Magnitude SWI Data
term represents a chemical shift effect and causes changes of Although HP-filtered phase images themselves are quite illus-
the form trative of the susceptibility contrast, they are influenced by
both the intratissue phase (from ⌬Bin) and the associated extra-
21) ⌬Bcs ⫽ ⫺B0, tissue phase (from ⌬Bout), which can impair the differentia-
tion of adjacent tissues with different susceptibilities. Hence,
where represents the chemical shift. The difference between the “phase mask” is designed to enhance the contrast in the
chemical shift and the first term in equation 20 is that chemical original magnitude image by suppressing pixels having certain
shift has no geometry dependence but is more of a point field phase values. Magnitude and phase data are brought together
change.75 The last 2 terms create artifacts and are not our in- as a final magnitude SWI dataset by multiplying a phase mask
terest. They tend to have a low spatial-frequency dependence image into the original magnitude image.22
(the phase varies slowly over the image) and, for this reason, The phase mask is designed to be a number between zero
can be removed with a high-pass (HP) filter.60 and 1. When there are no phase characteristics that we want to
Fig 5. A, HP-filtered phase image in the midbrain acquired at 4T with TE ⫽ 15 ms. B, India ink-stained cadaver brain section showing a strong correspondence to variations in signal intensity
as seen with SWI HP-filtered phase.
enhance, the phase mask is set to 1. Otherwise, the phase mask a phase of 0.1 or causes ⬍25% reduction in visibility in
is designed to suppress the signal intensity in areas where the either case, suggesting that m ⫽ 4 is a good compromise if one
phase takes on certain values. For example, if the phase of is limited to just 1 representative SWI dataset. Of course, m
interest is negative, the mask is designed as can be varied to produce a series of SWI data that can be used
in a diagnosis. After this processing, the data are often viewed
23) f(x) ⫽ [ ⫹ (x)]/ for ⫺ ⬍ (x) ⬍ 0 by using a minimum intensity projection (mIP) over ⱖ4 im-
⫽ 1 otherwise, ages. Clinically, 4 sections are the current common display,
though showing a projection over 10 sections can be useful to
where (x) is the phase at location x. The phase mask can be visualize a larger coverage of the venous drainage system in a
applied any number of times to the original magnitude image given area. Figure 8 shows projection data over the original
(x) to create a new image, magnitude images and the SWI processed images. One can
also present the data as a sliding mIP, which means that one
24) ⬙共 x兲 ⫽ fm(x)(x)
starts with the original series of images and mIPs over 4, moves
with a different contrast. The number of phase mask multipli- to the next original image and mIP over 4 again so that a series
cations is chosen to optimize the contrast-to-noise ratio of the of 64 images now becomes a series of 61 mIP images.
SWI image. This mathematical masking process is illustrated Furthermore, combining phase and magnitude informa-
in Fig 6 and with a specific example from a 1.5T dataset shown tion ensures the detectability of signal-intensity changes com-
in Fig 7. ing from both T2 and susceptibility differences between tis-
A simple mathematical model can be built to estimate the sues. The existence of a phase difference does not necessarily
value of m (from Equation 24).30 The number of multiplica- lead to a T2* effect (uniform phase causes no T2⬘ decay), so
tions needed for a phase ⱖ0.3 is ⱕ4. For a phase ⬍0.3, a these 2 sources of information complement each other. Also,
value of m ⱖ 4 should be used. However, choosing m ⫽ 4 for suppressing the veins fully helps to create a clear distinction
Fig 8. mIP data over the original magnitude images (A) and over the processed SWI images (B ). The mIP is carried out over 7 sections (representing a 14-mm slab thickness). The images
were collected at 3T. There is a dropout of signal intensity in the frontal part of the brain, but otherwise the vessel visibility is much improved in B. In the future, this frontal dropout
should not be a problem when the air/tissue geometries are corrected (Fig 9).
SNR increases, so a sacrifice of some SNR (because the image is one of the most robust sequences in MR imaging and con-
quality at 1.5T is already good enough clinically) to obtain not tinues to show its advantages at high field where images appear
only faster coverage but also higher resolution of the whole brain much more uniform than spin-echo images. SWI, for exam-
coverage at 3T can be easily tolerated. With parallel imaging at 3T, ple, uses flip angles much smaller than 90°, and because the
whole-brain coverage by using SWI can be obtained in as short as SAR varies as the square of the flip angles, SWI has a much
4 minutes. Figure 10 shows the phase behavior as a function of smaller power deposition than spin-echo sequences. As dis-
field strength, given that equation 25 is obeyed. As expected, it is cussed previously, phase can be kept invariant as a function of
difficult to differentiate field strengths except for the fact that the field strength by appropriately adjusting the TE. On the other
SNR is higher for the 3T image than the 1.5T image. Otherwise, hand, phase information from local structures does not
the phase images should have the same contrast. strongly depend on local rf inhomogeneities. These 2 proper-
The advent of very high fields such as 7T and above offers ties suggest that the SWI filtered-phase images can play a role
unprecedented resolution and SNR in imaging the brain. in comparing subject data across field strengths. High-field
However, there are concerns about field homogeneity and images are shown in Figs 11 and 12 (for recommended imag-
high specific absorption rates (SAR). Gradient-echo imaging ing parameters at different field strengths, see Table 2). From
Fig 10. A and B, Phase images, keeping the product BoTE constant. A phase image acquired at 1.5T (A) and the same subject at 3T (B ) show the same overall contrast but with a better
SNR. The gray/white matter contrast in these images comes from the increased MR-visible iron content in the gray matter, giving it an appearance similar to a T1-weighted scan.
tify iron or follow changes in iron deposition with time, to Conversely, choosing a lower flip angle tends to highlight
follow the resolution of cerebral hemorrhages in patients with the spin attenuation and makes CSF a bit brighter than gray
trauma, or to monitor the development of microbleeds in pa- matter or white matter to regain some contrast. The former
tients with dementia. In the future, phase will likely also be choice of, for example, 20° at 1.5T is the most popular. After
used to quantify oxygen saturation in major veins. Because the processing, the SWI takes advantage of the high iron content
original phase data have been filtered, we often refer to the new in gray matter and begins to recreate gray matter/white matter
phase images as the SWI-filtered phase images. contrast. The phase image has a lot of resemblance to a T1-
The third component used in interpreting SWI is the final weighted image. This gets carried over to the SWI. At the end,
processed SWI. These data have taken full advantage of T2* to better delineate the nature of the vascular content, we per-
signal-intensity losses in the magnitude image and iron in- form an MIP of the SWIs, usually over 4 adjacent images, to
creases in the phase images to highlight both types of contrast create an effective 8-mm-thick section. These mIP images
in a single image. At this point, these images show many “black present a great tool for visualizing vessel connectivity and mi-
holes,” most often representing the cross-sections of small crobleed locations with respect to the vasculature and other
veins. How can we discriminate between these cross-sections structures in the brain.
and microbleeds? The best way to check for vessel connectivity
is to take an mIP over a number of sections (most often 4). Future Directions
This is similar to using a maximum intensity projection (MIP) To date, SWI has had most of its clinical applications in the
to see arteries in MR angiography (MRA). A point of interest neuroimaging arena (this will be covered in Part 2 to be pub-
here is that the MIP of SWI data can be taken as well. The lished in a later issue).81 Many of the ideas relating to iron
resulting image, which is simply an SWI version of an MRA, is quantification remain to be validated in animal models and
not so impressive at 1.5T; but at 3T, this MRA begins to ap- further tested longitudinally in patients. Technical develop-
proach the quality of a conventional MRA.53 ments such as creating susceptibility maps that remove all
A key point of practical interest is the orientation used for phase artifacts are a particularly exciting direction.78,82 This
SWI. This is invariably transverse for a number of reasons. The would open the door to being able to use SWI in the spine, for
foremost reason is that the phase of veins perpendicular to the example. Other developing applications include imaging car-
main field is, in theory, opposite to that of those parallel to the tilage, imaging calcium in atherosclerosis, imaging breast, and
main field, with the latter showing a negative phase and the liver hemochromatosis.
former, a positive phase (equation 17). However, with an in-
plane resolution to section-thickness aspect ratio of 2:4, the
Acknowledgments
phase outside the small veins contributes more than the phase
The authors would like to thank Charbel Habib for manage-
inside, reversing the phase behavior so that all veins show a
ment of all images and Alexander Boikov for reviewing the
negative phase.30 This reversal of phase behavior makes the
manuscript.
processing much easier because only a single negative phase
mask needs to be used in the transverse orientation and this
makes the visualization of the veins in the SWI-processed im- References
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