Dr. Auger is a third-year resident in diagnostic imaging at
Rhode Island Hospital, Providence, Rhode Island, and will begin a
year as a chief resident in July 2001. She received her MD from
Brown University in 1997, and will enter an oncoradiology
fellowship at Dana-Farber Cancer Institute in Boston, Massachusetts
Signal intensity in proton magnetic resonance imaging (MRI)
depends on several factors including the local environment of a
proton, density of protons in a tissue, and the sequence of
radiofrequency (RF) and gradient pulses used to generate the
magnetic resonance signal. The local environment of a proton
affects relaxation, that is, the rate of return to equilibrium of
proton magnetization after perturbation by a RF pulse. At
equilibrium, net proton magnetization is in the longitudinal axis.
With an applied RF pulse, longitudinal magnetization decreases and
there is some magnetization in the transverse plane. The
longitudinal and transverse components of proton magnetization then
return to equilibrium with different time constants. Longitudinal
magnetization recovers at a rate determined by the average T1
relaxation time of the tissue. Tissues with short T1 recover a
greater portion of their longitudinal magnetization within a given
time period, and tend to have a higher signal intensity than
tissues with a longer T1. After an RF pulse, transverse
magnetization de-creases because of spin-spin relaxation, or
dephasing, and is described by the T2 relaxation time.
In MRI, differences in tissue relaxation can be translated into
differences in image contrast. Each tissue has unique T1 and T2
relaxation times that are affected by both the internal biochemical
environment as well as the external environment. Internal factors
that affect proton relaxation include motion, chemical shift, and
blood flow. External factors include external field strength,
magnetic field inhomogeneity, and the use of exogenous contrast
agents. For example, T1 relaxation time varies with magnetic field
strength (Larmor frequency) to a much greater degree than does T2
relaxation time, to such an extent that T2 is often considered to
be independent of field strength.
Magnetic resonance contrast material
Magnetic resonance (MR) contrast agents act by enhancing T1
and/or T2 relaxation rates for a given tissue type in a particular
environment. Materials can be distinguished based on their inherent
magnetic properties. Paramagnetic agents are materials that have no
intrinsic magnetic field, but, when placed within an external
field, can augment that field by alignment of its dipoles. Examples
of paramagnetic materials are copper, iron, and manganese.
Superparamagnetic materials are small particles that can act as
single magnetic domains. A collection of these particles, when
placed within an external magnetic field, enhance that field to a
greater degree than do paramagnetic materials.
The affinity of a material for magnetization is termed
susceptibility, with the magnitude and vector of the induced
magnetic field dependent on the characteristics of the material.
Relaxivity is a term used to describe the energy exchange that
occurs when excited protons in water molecules return to a state of
equilibrium more quickly when within the sphere of influence of
Selective enhancement may be based on differences in
biodistribution and residence times of the contrast agent within a
particular tissue. This allows a very small amount of contrast
material to affect a large number of protons. Compared to iodinated
contrast media doses, MR contrast doses are relatively small.
The most commonly used intravenous (IV) MR contrast media are
agents that enhance T1 relaxation times. All have metal ions that
contain one or more unpaired electrons. These metal ions are either
part of a metal-chelate compound, such as gadolinium
diethylenetriamine pentaacetic acid (DTPA) or are contained within
a macromolecular ligand. When T1 contrast agents are used, tissue
water diffuses into the sphere of influence of the metal ion and
the relaxed water is then exchanged with bulk tissue water,
resulting in a rapid relaxation of tissue water in the vicinity of
the contrast agent. In this way, a very small amount of contrast
agent can exert a large influence on tissue longitudinal
Other T1 contrast media use manganese as the metal ion, usually
chelated with dipyridoxylethylenediamine diacetate bisphosphate
(DPDP). This complex is specific for hepatocellular uptake.
Gadolinium DTPA (GdDTPA) is the most commonly used IV T1
contrast agent. GdDTPA is the meglumine salt of diethylenetriamine
pentaacetic acid, and acts by enhancing the relaxation rates of
protons in its vicinity, having its greatest effect on T1
relaxation time. The usual dosage is 0.1 mmol/kg. GdDTPA is
excreted primarily by glomerular filtration, and has a half-life of
90 minutes. Excretion is slower in patients with renal failure, but
this does not increase the incidence of adverse side effects as
there is no associated nephrotoxicity. The incidence of minor side
effects is 1.5% with the most commonly reported effects being
headache, symptoms at the injection site, and nausea. Death is rare
with a reported incidence of 1 in 2,500,000.
T2 contrast agents are iron oxides and other materials that can
form tiny particles called nanoparticles measuring 10
meters (1 nanometer [nm]). These nanoparticles share electron
fields, and produce large magnetic fields in the MR scanner magnet.
Superparamagnetic agents have greater magnetic moment than
paramagnetic agents, and their biodistribution is affected by
particle characteristics including material, crystalline symmetry,
core size, and coating.
A particle smaller than 15 nm can act as a single magnetic
domain, and can create a large magnetic gradient that produces
local field inhomogeneity. Diffusion of water protons through these
gradients results in rapid dephasing of spin, and leads to a
relative shortening of T2 relaxation times. Surface coatings affect
biodistribution, a well-known feature of scintigraphic agents. It
is possible to target agents to specific body tissues as a result.
Superparamagnetic agents have a powerful effect on the relaxation
times of targeted tissues, making it possible to use only small
amounts. This is beneficial from a toxicity standpoint.
The inherent toxicity of native metal ions necessitates careful
chelation. Gadolinium chelates have been used since the 1980s, and
the adverse reaction rate has been reported in the 3% range.
Most reactions are categorized as minor; however anaphylactoid,
severe asthmatic, and even fatal reactions have been reported.
There is no appreciable difference in the incidence of adverse
reactions among the four approved gadolinium agents currently in
use (gadopentetate meglumine, gadoteridol, gadodiamide, and
The incidence of adverse reactions is somewhat higher with the
single manganese chelate (7% to 17%) and the larger ferumoxide
particles (15%) than with gadolinium agents.
In the United States, IV administration of contrast agents is not
approved for use in children under 2 years of age; however,
off-label use of contrast is common in these children.
In European countries, approval for use of IV contrast in children
under 2 years of age is more common, and there is no reported
increase in incidence of adverse reactions in the younger pediatric
Extracellular magnetic agents are excreted in breast milk, and
cross the placenta and are excreted by the fetal kidneys. These
agents are therefore category C, not proven safe for use in
pregnant or lactating women. They can be used in patients with
diminished renal function as they are partially dialyzable,
however, agents designed for the hepatobiliary and
reticuloendothelial systems have an intracellular biodistribution
and as such can be considered to be of greater potential harm.
Newer applications of contrast-enhanced MRI in
Cardiac and vascular anomalies
--Many congenital anomalies of the heart and great vessels require
early detection and surgical repair in the neonatal period.
Abnormal development of the aortic arch and the great vessels can
result in a variety of symptoms related to extrinsic pressure or
shunt vascularity. Arch anomalies can also be largely asymptomatic.
Obviously, the more symptomatic lesions are detected earlier in
An aberrant right subclavian artery is the most common arch
anomaly, occurring when the proximal part of the right fourth
embryonic vascular arch is absorbed rather than the distal part.
The aberrant right subclavian artery runs posteriorly from the
descending thoracic aorta on its path to the right arm, passing
behind the esophagus and causing a typical indentation. This
anomaly is usually asymptomatic and may be an incidental finding on
a barium swallow esophagram.
A right-sided aortic arch occurs when the distal fourth arch is
absorbed on the left instead of on the right (figure 1). This may
result in mirror image or non-mirror image reversal of the great
vessel origins. A right arch can be asymptomatic, but is commonly
associated with tetralogy of Fallot and truncus arteriosus.
The more symptomatic anomalies typically result from vascular
rings formed around the trachea and esophagus. These are seen with
a double aortic arch (figure 2) formed when there is no absorption
of any part of the embryonic fourth vascular arch. The right arch
causes compression posteriorly on the esophagus as it passes behind
to join the left arch. Both left and right arches cause lateral
indentation of the trachea and esophagus. The descending aorta is
usually left sided, but can be right sided with a retroesophageal
left arch. A constricting ring can also be formed with a
right-sided aortic arch and a left-sided patent ductus arteriosus
or ligamentum arteriosum, causing indentations on the esophagus and
trachea similar to those seen with a double arch.
Obstructive aortic anomalies can be divided into diffuse or
localized narrowing of the aorta. Diffuse narrowing is usually
associated with some degree of arch hypoplasia, formerly known as
preductal coarctation, in the region of the aortic isthmus. In
severe cases, this may result in complete interruption of the arch
and is frequently associated with devastating congenital cardiac
A localized juxtaductal or postductal coarctation (figure 3) can be
seen as an isolated anomaly, but is also associated with bicuspid
aortic valve (85%), aberrant subclavian arteries, ventricular
septal defects, patent ductus arteriosus, berry aneurysms of the
circle of Willis, and Turner's syndrome. Overall fetal development
is usually normal with an isolated juxtaductal coarct because of
blood flow through the widely patent ductus arteriosus. As the
ductus closes off, the changing blood flow patterns can cause left
ventricular failure and symptoms of aortic stenosis. Uncorrected
coarcts can cause development of collateral circulation with
typical rib notching in later life; in the neonatal period,
collaterals have not yet developed.
Surgical repair of congenital vascular anomalies is done as
early as possible to prevent strain on the developing
cardiovascular system. Presurgical planning is almost as important
as the surgery itself. A reliable noninvasive method of mapping is
required for optimum pediatric patient care. Studies have shown
that 3D gadolinium- enhanced MR angiography (MRA) using the
double-dose "FASTCARD" technique is a safe and effective adjunct to
MRI of the thoracic aorta
--Aortic imaging studies provide anatomic information for the
surgeon as well as an indication of the functional effects of a
vascular lesion on hemodynamics. Current vascular MRI techniques
are considered more accurate than echocardiography in the depiction
of the aortic arch and the descending thoracic aorta.
Compared with conventional catheter aortography, MRA is appealing
because it is noninvasive and requires neither iodinated contrast
nor ionizing radiation. Sedation is still usually required for
children under the age of 5 years, but older children are usually
able to remain still for the required image acquisition time. Body
coils are generally used for optimum signal-to-noise ratio, but in
infants and small children a head coil may provide even better
resolution. Electrocardiographic gating can be used to acquire
images at a particular point in the cardiac cycle, and respiratory
compensation may be applied as needed.
Three types of MRA are currently in use: black blood, bright
blood non-contrast-enhanced, and bright blood contrast-enhanced
techniques. The simplest sequence is a T1-weighted spin echo
acquisition that produces a static "black blood" image from the
flow voids within vessels. Slab thickness in children is usually 3
to 5 mm. Transaxial, sagittal oblique, and coronal oblique planar
images provide views equivalent to the standard conventional
angiographic positions, allowing ease of interpretation.
The second type of MRA is a gradient refocused echo technique
that provides a dynamic "bright blood" image secondary to
flow-related enhancement. In these images, the signal intensity is
roughly equivalent to the blood flow velocity. MRA can be performed
using phase contrast or time-of-flight sequences. Phase contrast
techniques are generally not used in the chest secondary to
degradation by cardiac and respiratory motion artifact.
Gadolinium contrast-enhanced MRA has been used to better
delineate complex anatomy prior to surgery, especially in lesions
which disrupt the normal blood flow. Gadolinium-enhanced 3D
time-of-flight images are acquired as slabs in the sagittal and
coronal planes, and post-processed into 3D volumes. These volumes
can then be rotated in space and viewed from multiple angles.
Breath hold time-of-flight images provide im-proved signal-to-noise
ratio, in-creased resolution, and decreased image acquisition time,
but are not always practical in the pediatric population without
the use of general anesthesia.
--Musculoskeletal injuries in children can adversely influence
future growth and development of normal bone. A "simple" fracture
that would be easily treated in an adult may have serious
implications in a skeletally immature individual. Careful imaging
plays a major role in the accurate assessment of injury and the
subsequent treatment plan.
MRI has become a mainstay of pediatric musculoskeletal imaging,
with its superior depiction of marrow spaces, joints, soft tissues
and its ability to aid in the accurate characterization of tumors.
Contrast-enhanced MRI is being used to better evaluate
cartilaginous and synovial injury. Physeal injuries, growth plate
fractures, and any cause of ischemia to the growth plate have
important implications for future growth arrest, and consequently
need careful imaging evaluation. These changes can be seen in
developmental dysplasia of the hip (DDH), proximal focal femoral
dysplasia (PFFD), hemimelias, acute fractures, chronic trauma, and
infection. The use of gadolinium contrast has allowed early
identification of Legg-Calvé-Perthes disease, infection, and
ischemia due to physeal injury.
Synovial overgrowth, the hallmark of juvenile rheumatoid arthritis
(JRA), can be easily delineated using contrast-enhanced MRI
techniques. The affinity of gadolinium contrast agents for synovium
permits diagnosis of JRA before bony erosions have occurred (figure
In a Swiss study by Weishaupt et al,
dynamic MRI of Legg-Calvé Perthes disease in the pediatric hip was
found to be as effective as arthrography in the evaluation of the
articular surfaces. The MRI must be performed on an open magnet to
allow for changes in hip position. Dynamic MRI was noninvasive, did
not use ionizing radiation, and, in this study, did not require
Intravenously administered gadolinium contrast medium
concentrates in synovial joint fluid, and the relative enhancement
can be increased with moderate exercise.
This arthrogram effect can be utilized in patients who will not
tolerate an intra-articular injection. The synovium itself can be
seen to enhance following IV administration of gadolinium contrast
In a study performed at Children's Hospital in Boston,
gadolinium contrast-enhanced MRI was performed following reduction
and spica casting of dysplastic hips.
Hip position and physeal vascularity were adequately demonstrated.
This technique may aid in predicting response to conservative
treatment and the need for surgical intervention in developmental
dysplasia of the hip.
MRI techniques are attractive for use in the pediatric patient
population mainly due to the lack of ionizing radiation. In the
United States, most gadolinium contrast agents are approved for IV
use in the over
2-year-old age group, but "off-label" applications are frequently
utilized in children under 2 years of age. Pediatric approval in
European countries has been less stringent with no increase in
reported adverse reactions. New techniques utilizing gadolinium
contrast are improving diagnosis of congenital vascular anomalies,
making surgical planning easier, and obviating the need for
invasive angiographic examinations. Applications of
contrast-enhanced MR techniques in the musculoskeletal system are
improving prognostic predictions in the management of
Legg-Calvé-Perthes disease, JRA, and developmental dysplasia of the
hip. Continued development of sophisticated imaging sequences will
provide faster and better examinations in the pediatric patient
The author wishes to thank Dr. Glen Tung for his review of this
manuscript; Drs. Michael Wallach, Diego Jaramillo, and Ramiro
Hernandez for assistance with images; and Nathan Goldshlag for