Magnetic resonance imaging (MRI) of the breast continues to evolve with the potential to allow earlier and more accurate detection of breast cancer. While mammography and ultrasound remain the primary modalities for breast imaging, MRI is increasingly being used in a variety of situations. MRI offers several advantages over the conventional breast imaging modalities. Neither mammography nor ultrasound has the high soft-tissue contrast or thin-section and multiplanar capabilities of MRI. Additionally, MRI provides a pathophysiologic view of breast lesions by evaluating the contrast-enhancement characteristics. These capabilities, if properly harnessed, may ultimately allow breast MRI to play a significant role in reducing the morbidity and mortality associated with breast cancer.
Dr. Ingle is chief resident in Diagnostic Radiology at
the University of Tennessee at Memphis. He graduated with honors
from William Jewell College and Oxford University in 1993, and
received his DO from the University of Osteopathic Medicine and
Health Sciences in Des Moines, IA. Dr. Ingle plans a fellowship
in musculoskeletal imaging at Indiana University beginning July
Breast cancer accounts for one out of every three cancers
diagnosed in women in the United States, with approximately 175,000
new cases and nearly 43,000 deaths annually. Only lung cancer
accounts for more cancer deaths in women.
With these sobering numbers in mind, emphasis remains on early
detection, diagnosis, and staging of breast cancer, with the goal
of improving survival and treatment options.
It is generally accepted that the widespread use of routine
screening mammography has played a key role in improving detection
and survival. Beginning in 1989, the number of breast cancer deaths
and rates have continued to decline at an average of 1.8% per year.
One study from Malmo, Sweden reported a 43% decrease in the death
rate from breast cancer in that city since the introduction of
Although screening mammography has had a tremendous impact on
overall outcomes, the false-negative rate reportedly ranges from 8%
with some studies suggesting that as many as 25% of breast cancers
may be missed on screening mammography.
Several recent studies have found MRI to be much more sensitive
than mammography for detecting breast cancer.
Four of these studies also found MRI to be more sensitive than
mammography in defining tumor extent (figures 1 and 2) with
reported sensitivities of 100% vs. 33%,
85% vs. 32%,
98% vs. 55%,
and 96% vs. 44%,
Contrast-enhanced MRI has very high sensitivity for detecting
invasive breast cancer--approaching 90% to 100%
--and can detect mammographically and clinically occult breast
cancers (figure 3).
One advantage of contrast-enhanced MRI over conventional imaging is
the ability to depict malignant changes caused by tumor
Tumor angiogenesis (the induction of new capillary vessels in
response to specific mediators produced by tumor cells) is crucial
to the development of various tumors, including breast cancer. Such
neovascularity is one of the most important characteristics
distinguishing breast cancer from benign processes.
In fact, the presence of intratumoral, marginal, and peritumoral
vascularity on MRI as an indicator of malignancy has been shown to
have a positive predictive value of 95%, 87%, and 92% respectively.
Angiogenesis has also been shown to correlate with tumor
In conjunction with angiogenesis, the contrast-enhancement
characteristics and patterns can be used to distinguish benign and
malignant lesions. Malignant tissues tend to enhance earlier than
benign lesions or normal glandular tissue, with a stronger and
faster increase in signal intensity.
Breast malignancies demonstrate early enhancement after contrast
administration due to a preferential accumulation of gadolinium
(figure 4). This shortens the T1 relaxation of water protons,
thereby yielding brighter signal intensity on the T1-weighted
An altered or increased vascularity in breast cancers relative to
benign or normal breast tissue is the likely reason for this
stronger and earlier enhancement.
One method of increasing both the sensitivity and specificity of
breast MRI is assessment of enhancement kinetics and the signal
intensity time course. This is accomplished by placing a region of
interest (ROI) in the most enhancing part of the lesion with a
subsequent plot on a time-signal intensity curve.
A relative increase in signal of 80% or more in the first post-
contrast minute is a sign of malignancy, while lesion with values
less than 80% are usually benign.
Several studies have shown added specificity by evaluating the
intermediate and late post-contrast periods.
Based on these studies, three enhancement patterns have been
described: type I demonstrates steady enhancement; type II
demonstrates plateau of signal intensity; and type III demonstrates
washout of signal intensity.
Studies by Kuhl et al
and Kinkel et al
have shown that the contrast washout time-signal intensity curve is
extremely useful in differentiating benign and malignant lesions. A
washout pattern is characterized by an initial upstroke, after
which enhancement is abruptly cut off, followed by a signal
intensity decrease (washout) in the intermediate post-contrast
period. Kuhl et al
showed an 87% likelihood of malignancy with a washout pattern and
Kinkel et al
reported an 85% likelihood. In comparison, a steady time-signal
intensity curve, characterized by continued increase over the
entire dynamic period, appeared in 94% of benign lesions in one
and in 95% in the other.
Kuhl et al
found the signal intensity time course to be substantially more
specific in identifying breast cancer than enhancement rate alone,
with an improved specificity of 83% vs. 37%, respectively.
Integration of both morphologic features depicted on breast MRI
and the dynamic enhancement characteristics are needed to optimize
the diagnostic capability of breast MRI.
This is evidenced by the fact that approximately 10% of
malignancies--including lobular, medullary, and some ductal
carcinomas, as well as metastases--will enhance slowly this is a
pattern typically seen in benign lesions.
In these instances, morphology may be critical to making the
correct diagnosis. Lesions with irregular, ill-defined or
spiculated borders (figure 5); peripheral enhancement; and ductal
enhancement are suggestive of malignancy.
Morphologic features suggestive of benign disease include: smooth
or lobulated borders, lack of contrast enhancement, non-enhancing
internal septations, and patchy parenchymal enhancement.
Nunes et al
found these characteristics to be highly predictive of benign
disease. Lesions with smooth borders demonstrated a 100% negative
predictive value (NPV), while lobulated borders had an 87% NPV.
Additionally, they demonstrated that the presence of spiculated
borders had an 88% positive predictive value (PPV) for malignancy.
Combining the morphologic features and dynamic enhancement
characteristics has led to the following proposed diagnostic
criteria: any lesion with spiculated margins, regardless of
enhancement pattern, or lesions with lobulated margins that
demonstrate washout are considered malignant. Lesions without
spiculated margins or washout are considered benign.
Using these criteria, Kinkel et al
reported a NPV of 96% and PPV of 97%.
Despite some general agreement among radiologists regarding the
importance of both morphologic features and dynamic enhancement
characteristics, no standard interpretation guidelines have been
Most published diagnostic criteria have involved site-specific
software programs or unique MR sequences.
One reason for the lack of a general consensus regarding
interpretation criteria is that considerable overlap exists between
the enhancement characteristics of benign and malignant lesions,
with specificities ranging from 37% to 97%.
Benign lesions such as fibroadenomas, fibrocystic changes, radial
scars, mastitis, atypical ductal hyperplasia, and lobular neoplasia
have been shown to enhance similar to malignant lesions.
Normal breast tissue has also demonstrated variable enhancement
during different phases of the menstrual cycle,
however, this can be minimized by imaging during the second week of
The recent studies by Kuhl et al
and Kinkel et al
address many of the issues that have prevented the acceptance of
more standard interpretation guidelines. Their work incorporates
both lesion morphology and time course kinetics, which optimizes
the discriminatory capability of breast MRI. Although the overall
study populations have been small, it appears that the principles
remain valid. The enhancement kinetics as represented by the
time-signal intensity curves differ significantly among benign and
malignant lesions. This shows great promise for enabling breast MRI
to have both high sensitivity and specificity.
Much of the reason for the lack of consensus regarding
diagnostic criteria for breast lesion evaluation has stemmed from
different image acquisition protocols emphasizing either
high-spatial-resolution images or dynamic breast MRI.
These two concepts involve the competing demands of adequate
spatial and temporal resolution. High-spatial-resolution techniques
place emphasis on morphologic features, such as margins and
internal characteristics, while sacrificing some temporal
In comparison, contrast-enhanced dynamic MRI emphasizes the
enhancement characteristics and involves high-temporal resolution
of approximately one minute or less.
Since both types of information have been shown to be useful,
integrating both the kinetic and morphologic information through an
acceptable imaging technique seems logical. The recent work of
Kinkel et al
provides an example of one such technique combining the morphologic
and semi-dynamic data by acquiring three-high-spatial-resolution MR
Just as no formal interpretation guidelines exist, standardized
imaging protocols have not yet been developed either. Part of the
reason for this is the fact that nearly all of the early and
current work has occurred primarily in a research setting. The work
of Kuhl et al
and Kinkel et al
combining both high-temporal and spatial resolution, is such an
example. A wide range of protocols exist based on the different
hardware and software available, clinical indications, desired
results, clinical experience,
type of breast coil, magnetic field strength, and imaging
Despite this variability, some agreement does exist regarding
general imaging techniques. It is agreed that the signal from fat
should be removed because enhancing lesions may become isointense
to fat after gadolinium contrast administration and therefore may
This can be accomplished by either post-processing image
subtraction or by different fat suppression techniques.
One pitfall to post-processing image subtraction is that there can
be no patient motion between the pre-contrast and post-contrast
The rotating delivery of excitation off resonance (RODEO) sequence
is an example of a fat suppression technique combined with
magnetization transfer and T1 weighting in an efficient
non-selective three-dimensional acquisition.
Radiofrequency spoiling is used to depict lesions with a high fluid
content. This helps to distinguish cysts from enhancing masses,
which produce opposite signals. Masses are hypointense on
pre-contrast and hyperintense on post-contrast RODEO MR images,
while cysts are hyperintense on pre-contrast and hypointense on
With this technique, Harms et al
demonstrated a nearly 100% negative predictive value for
malignancy, with only 3 false negatives in more than 3,000
Currently, most MRI protocols use two- and three-dimensional
T1-weighted gradient echo techniques for dynamic breast imaging
over 6 to10 minutes after bolus injection of gadolinium-based
contrast agents. A T2-weighted sequence is also performed to depict
cysts or cystic lesions. One of the more recent techniques being
investigated involves fast T2*-weighted perfusion imaging, which
uses susceptibility-mediated perfusion imaging of the breast to
distinguish between benign and malignant tumors. The individual
sequence patterns and imaging protocols vary according to the
manufacturer. High magnetic fields and strong gradients are
recommended. Also, breast coils with compression devices help
reduce motion artifacts, thus improving subtraction images.
While breast cancer remains one of the most devastating diseases
in women's health, advances and experience in MRI of the breast
hold great promise for allowing earlier and more accurate detection
of breast cancer. In turn, it is hoped, this will provide more
favorable and effective treatment op-tions. MRI of the breast has
the ability to detect both clinically and mammographically occult
malignancies. It also has a very high sensitivity and specificity
for breast cancer detection. Perhaps just as important, it has a
negative predictive value of malignancy approaching 100%.
Tremendous advances have been made in the past 10 years in
breast MRI, including improved MRI units, breast coils, imaging
sequences, clinical experience, and the introduction of
contrast-enhanced imaging. Future directions of breast MRI are
focused on developing additional imaging sequences, new contrast
agents, and MRI needle localization-biopsy systems.
I wish to thank Dr. Waleed Qaisi for his valuable support in
preparing this manuscript. I also would like to thank Dr. Steven
Harms for allowing the generous use of images.