interpretation of breast mri: correlation of kinetic and

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*Corresponding author, Phone:＋81-3-3433-1111, Fax: ＋81-3-3431-1775, E-mail: tozaki＠mtf.biglobe.ne.jp

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Magnetic Resonance in Medical Sciences, Vol. 3, No. 4, p. 189–197, 2004

REVIEW

Interpretation of Breast MRI: Correlation of Kinetic and MorphologicalParameters with Pathological Findings

Mitsuhiro TOZAKI*

Department of Radiology, The Jikei University School of Medicine3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105–8461, Japan

(Received January 17, 2005; Accepted February 2, 2005)

Breast MRI (magnetic resonance imaging) has emerged as a highly sensitive modalityfor imaging of breast tumors. DiŠerences in MR enhancement characteristics betweenbenign and malignant lesions are believed to re‰ect diŠerences in vascularity, vesselpermeability, and extracellular diŠusion space. However, interpretation of breast MRIremains a challenging task. Precise MR-pathologic correlations may also lead to animproved understanding of the histological heterogeneity of breast cancers and deˆnitionsof diagnostic criteria.

Keywords: breast neoplasm, MR imaging, interpretation, contrast enhancement kinetics,tissue characterization

Introduction

With the introduction of MR contrast agents,advances in surface coil technology, and develop-ment of new imaging protocols, MRI of the breasthas emerged as the most sensitive modality forbreast tumors. Breast MRI has been found to be94z–99z accurate for the detection of breastcancer.1–6 However, no standardized guidelinesexist for performing and interpreting breast MRI.1

The lack of standardized interpretation criteria iscaused by diŠerences in image acquisition protocolsthat range from dynamic study to high spatialresolution imaging.

The purpose of this review is to explain thevarious techniques of breast MRI, the internationalterminology of MR ˆndings, and current interpre-tation models, with particular emphasis on histo-pathologic correlations.

Historical Overview

The use of gadolinium dimeglumine as an MRcontrast agent was introduced in Europe about 15years ago. Following the introduction of thiscontrast agent, several diŠerent approaches havebeen developed for breast MRI.

Heywang et al.2 were the ˆrst to use gadolinium

dimeglumine for MRI of the breast. They reportedstrong contrast enhancement of breast cancers,whereas the normal parenchyma exhibited onlyweak enhancement. Imaging was performed withlimited temporal and spatial resolution.

Kaiser et al.3 ˆrst reported dynamic breast MRI,a modality designed to track rapid changes in signalintensity. With this method, both breasts areimaged at the highest possible temporal resolution(60 s). Because rapid imaging is necessary, post-processing image subtraction (``passive'' fat sup-pression) is used to suppress signals from fattytissue.

In contrast to this dynamic study protocol,Harms et al.4 reported a static breast MRI tech-nique designed to analyze morphologic details.With this method, a single breast is imaged at ahigh spatial resolution. Because temporal resolu-tion is not the main focus of this method, a three-dimensional gradient echo sequence with ``active''fat suppression is used.

Dynamic breast MRI, popular in Europe, at-tempts to distinguish between benign and malig-nant lesions according to enhancement kinetics ata high temporal resolution. Static breast MRI, pop-ular in the U.S.A., attempts to achieve the samegoal by evaluating the morphologic features at ahigh spatial resolution. Until recently, the severetechnical constraints of MR units have made itnecessary to choose either temporal or spatial res-olution. In Japan, a preference for either dynamic

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Table. ACR BI-RADS-MRI lexicon classiˆcation form

A. FocusWFoci (tiny spot of enhancement,º5 mm)B. Mass

ShapeRound, Oval, Lobular, Irregular

MarginSmooth, Irregular, Spiculated

Mass EnhancementHomogeneous, Heterogeneous, Rim enhancement,Dark internal septation, Enhancing internal septation, Central enhancement

C. Non- Mass-Like EnhancementDistribution Modiˆers

Focal area, Linear, Ductal,Segmental, Regional, Multiple regions, DiŠuse

Internal EnhancementHomogeneousHeterogeneousStippled, punctateClumpedReticular, dendritic

D. Symmetirc or Asymmetric (bilateral scans only)E. Other FindingsF. Kinetic Curve Assessment

Intial rise (slow, medium, rapid)Delayed phase (persistent, plateau, washout)

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or static studies has not been established. Onereason for this uncertainty is that the purposeof performing a breast MRI in Japan diŠers fromthat in Europe or the United States. In Japan,ultrasonography is widely used to distinguish be-tween benign and malignant lesions; breast MRIis usually performed to evaluate the extent of breastcancer after a histological conˆrmation of malig-nancy has been made. In this situation, static imag-ing may be more suitable than dynamic MRI.

However, Orel et al.1 predicted that both highspatial and high temporal resolution images mightultimately dominate MRI protocols for the breast.Recently, the development of new imaging pro-tocols has enabled high spatial and high temporalresolution images to be obtained simultaneously.One of the representative sequences is a three-dimensional fat-suppressed gradient-recalled echotechnique with volumetric interpolation, ˆrstdescribed by Rofsky et al.7 The VIBE (volumetricinterpolated breath-hold examination) sequencethus introduced allows high-spatial-resolutionimages with near-isotropic voxels. This sequenceis thought to be a promising method for detectingthe extent of breast cancer and evaluating lesioncharacteristics.8–10

Typical MR Findings for Breast Lesions (basedon BI-RADS-MRI)

Lesion identiˆcation following MRI of the breastdepends on contrast enhancement within the breastafter intravenous injection of a contrast material.DiŠerences in MR enhancement characteristicsbetween benign and malignant lesions are believedto rely on diŠerences in vascularity, vessel perme-ability, and extracellular diŠusion space. Over thepast 15 years, substantial research eŠorts have beenmade to identify the most signiˆcant features fordiagnosing breast cancer with MRI.

The recently published BI-RADS (Breast Imag-ing Reporting and Data System)11 produced by theAmerican College of Radiology included the ˆrstedition of an MRI lexicon. The BI-RADS MRIlexicon classiˆcation for breast lesions is summa-rized in Table.

Analysis of Lesion Morphologic FeaturesFirst, lesion conˆguration is determined. It is

classiˆed as being a focal mass enhancement(space-occupying lesion) or non-mass-like enhance-ment.12 Non-mass-like enhancement includeslinear, ductal, regional, segmental, and diŠuseenhancement.

Second, if a focal mass enhancement is present,

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its shape and margin should be evaluated. Lesionshape is classiêd as follows: round, oval, lobular,and irregular. Mass margins are smooth, irregular,or spiculated. To analyze these morphologic detailsof enhancing mass, high spatial resolution imagesare required. However, it is di‹cult to diŠerentiatemass shapes from mass margins.13

Analysis of Enhancement KineticsIt is evident that analysis of enhancement

kinetics requires a good temporal resolution(approximately 1–2 min per dynamic scan). Ifdynamic study was performed without `àctive'' fatsuppression, lesion enhancement kinetics should beevaluated in both subtracted and non-subtractedimages.

First, enhancement rates should be quantiêd bydetermining an ROI (region of interest) for themost intensely enhancing area.11 The signalintensity in the ROI is then plotted over time.To account for diŠerences in baseline tissue T1

relaxation times, enhancement is calculated as asignal intensity increase relative to baseline values.3

Enhancement rates＝[(SIpost－SIpre)WSIpre]×100 (z)

SIpre＝baseline signal intensity and SIpost＝signalintensity after contrast injection

An increase in relative signal intensity occurringin a certain period of time, usually the ˆrst post-contrast minute, is referred to as enhancement rate(or wash-in rate). The rationale for calculating theenhancement rate is based on the observation thatmalignant lesions tend to have higher enhancementvelocities than benign ones.3

Second, timeWsignal intensity curves (TIC)should be evaluated. There are three general typesof curves that rely less on the absolute value of theenhancement than on the shape of the enhancementcurve.14 A ``persistent'' curve shows continuousenhancement increasing with time in its delayedphase. A ``plateau'' curve reaches a maximumsignal intensity approximately 2 to 3 min after in-jection, and the signal intensity remains constant atthis level. A ``washout'' curve shows decreasingsignal intensity after peak enhancement has beenreached for about 2 to 3 min. As a general rule,11

many benign lesions follow ``persistent'' curves,and many malignant lesions follow ``washout''curves. A ``plateau'' curve can be seen with bothbenign and malignant lesions.

However, quantitative analysis by ROI-basedsignal intensity measurements is somewhat complexand may be time-consuming. Recently, enhance-ment kinetics have been visually assessed by

comparing the signal intensity of the early anddelayed dynamic images.15 By deˆnition, anydecline in signal intensity is considered a``washout'' enhancement pattern. ``Plateau'' en-hancement is considered to be stabilized enhance-ment without a change in signal intensity. ``Per-sistent'' (or ``progressive'') enhancement is consi-dered to be an increase in signal intensity through-out the dynamic period. In many cases, the visualassessment of enhancement kinetics is considereduseful.

Analysis of Internal Enhancement Based on Dy-namic Studies

The internal enhancement characteristics ofbreast lesions must be further evaluated. In previ-ous reports,11–13 the internal enhancement charac-teristics have been characterized as homogeneous,heterogeneous, rim enhancement (ring-like en-hancement or peripheral enhancement), dark inter-nal septations (nonenhancing dark septations), en-hancing internal septations, or central enhance-ment. However, recent static MRI protocols canalso be performed as dynamic studies with varioustemporal resolutions. Thus, internal enhancementshould also be analyzed for dynamic series (e.g.,rim enhancement during delayed phases).

In addition to internal enhancement, the borderof the lesion is changed in comparison with thedynamic series; this is called ``blooming sign.''16

Blooming sign describes a lesion with initiallysharply shaped borders 1 min after bolus injectionthat become unsharp 7 min after injection, withthe lesion fast enhancing during the ˆrst 2 minafter injection. Blooming sign might be a helpfuladditional diagnostic tool with high speciˆcity(85.3z).16

Interpretation of Focal Mass Enhancement

Interpretation Model Based on Morphologic Fea-tures

Nunes et al.17,18 reported an interpretation modelusing logistic regression methods based on morpho-logic features of focal mass enhancement. Thismodel uses a post-contrast high spatial resolutionimage (static breast MRI). The lesion was ˆrstinterpreted by considering the margin of the lesion,followed by the presence or absence of internalseptations and the degree of enhancement at 2–4min after contrast injection. This model demon-strated a sensitivity of 96z and a speciˆcity of79z.

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Fig. 1. Diagnostic criteria comprising a combination of kinetic and morpho-logic characteristics published by Kinkel15

Fig. 2. Interpretation model of focal breast masses, combining kinetic pattern and morphologiccharacteristics with high-spatial-resolution MR imaging. Benign terminal nodes are shaded. PPVwas 98z (49W50).

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Fig. 3. Invasive ductal carcinoma (scirrhous carcinoma)A: A coronal MR image showing an enhancing mass with a spiculated margin in the early phaseB: A coronal MR image showing a persistent pattern in the lesionC: A histological section showing marked intratumor ˆbrosis and degeneration in the central zone


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Interpretation Model Based on Kinetic and Mor-phological Parameters

Recently, diagnostic criteria comprising a combi-nation of kinetic and morphologic characteristicshave been reported.15,19–21 Only two studies usinglogistic regression methods proposed interpretationmodels that concentrate on the interpretation offocal mass enhancement.15,21

The ˆrst published model used two post-contrasthigh spatial resolution images acquired at 2 min30 s and 7 min 30 s.15 A three-dimensional sagittalfat-suppressed T1-weighted fast gradient-recalledecho sequence was used (slice thickness, 2.0 mm;acquisition time, 5 min). In this study, the malig-nancy threshold that classiˆed a speciˆc margin asmalignant depended on the presence or absence ofwashout enhancement at 7 min 30 s after contrastinjection (Fig. 1). This model demonstrated a sen-sitivity of 97z and a speciˆcity of 96z (n＝57).

The second model used two post-contrast highspatial resolution images acquired at 1 min and 4min.21 A three-dimensional coronal fat-suppressedVIBE sequence was used (slice thickness, 1.2 mm;acquisition time, 35 s). In this study, lesion inter-pretation was obtained by ˆrst considering theshapeWmargin of the lesion, followed by the

presence or absence of washout enhancement andenhancing internal septations (Fig. 2). This modeldemonstrated a sensitivity of 100z and a speciˆcityof 93z (n＝63).

Breast MR Features of Focal Masses:Histopathologic Correlations

MR-pathologic correlations between ˆndings forfocal breast masses have been demonstrated withthe following interpretation model (Figs. 1, 2).15,21

Kuhl et al.14 reported that the washout patternwas frequently observed in malignant lesions (57z;58W101), whereas it was rarely observed in benignlesions (5z; 9W165). Because the washout pattern isa strong indicator of malignancy, it was ˆrstemphasized in the interpretation model publishedby Kinkel.15 The most common characteristic ofbreast cancers without a washout pattern was aspiculated margin. The histological characteristicsof this type of breast cancer tend to show promi-nent intratumor ˆbrosis, degeneration, and spicu-lated margins. Many of these breast cancers arecalled ``scirrhous carcinoma'' in Japanese classiˆ-cations (Fig. 3). However, breast cancers that donot exhibit a washout pattern do not necessarily

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Fig. 4. Mucinous carcinomaA: A coronal MR image showing a peripheral enhancing mass with smoothmargin in the early phaseB: A coronal MR image showing a persistent pattern in the lesionC: A histological section showing isolated or clusters of carcinoma cells ‰oatingin the mucus lakes

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have spiculated margins (Fig. 4). The most sig-niˆcant limitation of this interpretation model isthat some malignant lesions may be classiˆed asbelonging to category 3.

The recently published interpretation model wasbased on morphologic features of focal massenhancement.21 Lesion interpretation ˆrst consid-ered the lesion shapeWmargin classiˆed as follows:smooth (smoothWround or smoothWoval), lobulat-ed (lobular shape), irregular (irregular margin orirregular shape), and spiculated (spiculatedmargin). The frequencies of the above-mentionedshapeWmargin classiˆcations in benign (29z, 64z,7z, and 0z, respectively) and malignant (0z,10z, 47z, and 43z, respectively) lesions weresimilar to those reported by Nunes et al.18 in a studyexamining 274 focal masses (benign: 27z, 60z,7z, and 5z, respectively; malignant: 1z, 7z,39z, and 53z, respectively). In this study, the

most common characteristic of breast cancerswith a lobulated conˆguration was visual washout(80z), whereas a negative washout pattern wasfrequent in lobulated benign lesions (78z).Positive visual washout is thought be a useful toolfor diŠerentiating benign and malignant lobulatedlesions.

Regarding the internal enhancement characteris-tics, rim enhancement has been considered sugges-tive of malignancy.5,22 Buadu et al.23 reporteddiŠerent patterns of rim enhancement, concludingthat early rim enhancement with progression to thecenter was fairly speciˆc for carcinomas. Incontrast, almost 30z of the benign lesions reportedby Wedegartner et al.19 exhibited a positive rimenhancement. Kuwada et al.24 reported that``delayed rim enhancement'' following centralwashout was considered a speciˆc ˆnding of breastcancer. Delayed rim enhancement was well cor-

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Fig. 5. Invasive ductal carcinomaA: A coronal MR image showing a homogeneous enhancing mass with irregular margin in the earlyphaseB: A coronal MR image showing delayed rim enhancement (arrows) following the central washoutC: The histological section shows marginal ˆbrosis (arrows), corresponding to delayed rim enhance-ment on MRI.

Fig. 6. Invasive ductal carcinomaA: A transverse MPR image showing a lobulated enhancing mass in the early phaseB: A transverse MPR image showing a washout pattern, rim enhancement, and enhancing internalseptations


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related with marginal ˆbrosis (Fig. 5). We reportedthat enhancing internal septations followingwashout were useful in diŠerential diagnosis inlobulated breast lesions.21 ``Enhancing septations''were well correlated with histological ˆbrousstroma (Fig. 6). High-spatial-resolution imageswith near-isotropic voxels obtained with a VIBEsequence are useful for evaluating lesion charac-teristics. Enhancing septations and delayed rimenhancement following washout are thought to bespeciˆc to lobulated malignant lesions.

Some cases of mucinous carcinoma show lobu-

lated margins, progressive kinetics, and a very highsignal intensity in T2-weighted images, in contrastto other histological types of invasive ductalcarcinoma.25 In contrast, a very high signal masswith lobulation and internal septation in T2-weight-ed images re‰ects the intrinsic growth patterns ofˆbroadenomas.26 Isomoto et al.27 reported thatstrongly hyperintense masses with dark internalseptations in T2-weighted images were thought torepresent benign lesions, such as ˆbroadenoma,phyllodes tumor, or ˆbrocystic disease. Theseˆndings appear to be useful for diŠerentiating

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Fig. 7. Mucinous carcinomaA T2-weighted MR image showing a stronglyhyperintense mass without dark internalseptations

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between mucinous carcinoma and ˆbroadenoma(Fig. 7).

Conclusion

Recently, the American College of Radiology(BI-RADS-MRI) issued a standardized breast MRIlexicon.11 However, the interpretation of breastMRI ˆndings remains a challenging task. An idealinterpretation model incorporating a standardizedbreast MRI lexicon for lesion descriptions wouldassist surgeons in managing enhanced lesions.Precise MR-pathologic correlations may also leadto an improved understanding of the histologicalheterogeneity of breast cancers and deˆnitions ofdiagnostic criteria.

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Dynamic MR imaging of the breast. Analysis ofkinetic and morphologic diagnostic criteria. ActaRadiol 2003; 44:379–386.

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interpretation of breast mri: correlation of kinetic and

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