MR MAMOGRAPHY

A Norouzi MDFellowship of CT scan, MRI &

Interventional Radiology

Breast cancer is the most common malignant neoplasm in female population.

The complexity of early breast carcinoma diagnostics is conditioned by the variability of the breast structure during life, as well as cyclic, hormone conditioned changes.

Today, the most important and the most widely applied radiological modality is mammography, which value has been proved by many studies.

The basic lack of the mammography is the impossibility of lesion demarcation in dense breast with well-preserved fibrograndular tissue, as well as with diffuse fibrocystic changes.

Further on, the sensitivity and specificity of the mammography is limited by the fact that early malignancy often shows non-characteristic image.

The evaluation of post-therapeutic breast also falls into the group of the changes where the mammography does not demonstrate satisfactory results.

Up-to-date diagnostic algorithm also includes the breast evaluation by ultrasound (US) with the probes of 7.5 and 10 MHz that provide for high tissue resolution.

The main role of ultrasound application is the differentiation of palpable changes, as well as the differentiation solid vs. cystic lesions, where the specificity is 98%.

The evaluation of secretory breast, the suspected rupture of silicon implant, as well as the detection of the tumour within radiographically dense breast with positive familiar history, fall into the group of relative indications.

Except for the visualisation capabilities, the application of US is exceptionally significant in interventional procedures.

Today this diagnostic modality is widely accepted in aspiration of cysts, in core biopsy, and ductography.

Magnetic resonance (MR) currently presents the most up-to-date visualization modality.

Its basic technical possibilities: multiplanarity, tissue resolutionbiological noninvasiveness,

unambiguously make MR the most sensitive and the most specific radiological method for evaluation of the majority of organism regions.

The breast was one of the first organs studied with magnetic resonance imaging (MRI) for the detection of cancer, albeit initially in vitro. 

The breast was also the first organ in which the detection of invasive tumor neovascularity was highlighted through the application of rapid serial imaging after an injection of contrast agent.

Since then, numerous developments and refinements have improved the diagnostic performance of breast MRI. The technical developments that revolutionized breast MRI and propelled it into its current importance as an adjunct technique for the evaluation of breast disease include the following:

The development of the first intravenous (IV) contrast medium for MRI, gadolinium dimeglumine

The development of rapid GRE pulse sequences sensitive to contrast enhancement

The development of high-field-strength magnets (>1 T) that enabled spectral fat-suppression techniques

The development of dedicated breast coils for bilateral or independent breast imaging

The exploitation of new methods of k-space filling to increase speed and resolution

The development of computerized, automated techniques for contrast enhancement and architectural feature analysis of large image datasets

The development of MRI-guided breast biopsy and localization methods

WHY BREAST MRI

Limitations of Conventional Breast Assessment

Conventional breast assessment includes the combination of screen-film radiographic mammography, high-resolution breast US, and clinical breast examination.

This tried-and-true method forms the foundation of modern strategies for breast cancer detection.

The results of this assessment also serve as the final arbiter for the use of breast biopsy in breast screening programs worldwide.

Despite the usefulness of this approach, almost every breast radiologist is familiar with cases in which conventional assessment fails to depict a breast malignancy accurately, as in 1 of the following scenarios:

Palpable lesion without a focal imaging correlate So-called interval cancers that are missed or are

not visible on initial images Understaging of the extent of the lesion or

multifocality in the same or opposite breast Patient presenting with distant or axillary breast

cancer metastasis, with no breast lesion found on mammograms or sonograms

Chest wall invasion that is not detected Inaccurate clinical assessment of large tumors

that are treated with neoadjuvant chemotherapy

In short, in a significant minority of patients, breast malignancy will not be adequately assessed with conventional imaging and physical examination.

In each of the scenarios above, MRM has been shown to be a sensitive and effective method of detecting, diagnosing, and staging intramammary breast malignancy, even when conventional imaging results have been negative.

The use of MRM may change the clinical management in these situations if unexpected abnormalities are detected.

In nonfatty breasts, US and MR imaging were more sensitive than mammography for invasive cancer, but both MR imaging and US involved risk of overestimation of tumor extent.

The sensitivity of mammography to the index cancer ranges from 63% to 98% and has been reported to be as low as 30%–48% in dense breasts .

Several groups have evaluated the preoperative use of supplemental magnetic resonance (MR) imaging , ultrasonography (US) , or both after mammography and clinical breast examination to assess the extent of disease within the breast(s).

Across these series, a change in management in 11%–15% of patients resulted from additional imaging after mammography; 27%–34% of breasts had additional malignant foci not seen mammographically

Increased breast density has been shown to increase the risk of breast cancer from 2.2- to fivefold when breasts with densest grades are compared with fatty breasts .

The combination of decreased mammographic sensitivity and increased prevalence of cancer in denser breasts has prompted interest in the investigation of supplemental screening with US or even MR imaging.

Contrast-enhanced MR imaging of the female breast has been reported to have a sensitivity of 93-100% in the detection of malignancy.

Its specificity, however, ranges between 29% and 73%, depending on technique and patient selection.

In a study, Weinstein et al concluded that the addition of MRI to mammography in patients with a high risk of breast cancer has the greatest potential to detect additional, mammographically occult cancers.

The investigators prospectively compared breast cancer detection of digital mammography (DM), whole-breast US (WBUS), and contrast-enhanced MRI in a high-risk screening population that previously screened negative when film screen mammography (FSM) was used.

In the study, The overall cancer yield on a per-patient basis was 3.0% (18 of 609 patients). The cancer yield by modality was 1.0% for FSM (6 of 597 women), 1.2% for DM (7 of 569 women), 0.53% for WBUS (3 of 567 women), and 2.1% for MRI (12 of 571 women). Of the 20 cancers detected, some were detected only on 1 imaging modality (FSM, 1; DM, 3; WBUS, 1; MRI, 8)

Advantages of Using MRM

The numerous advantages of MRM over conventional breast imaging for the detection of malignancy have become apparent with increasing clinical experience. These advantages include the following: No ionizing radiation All imaging planes possible Capability of imaging the entire breast volume and chest wall Superb 3-dimensional (3D) lesion mapping with techniques such as

maximum intensity projection (MIP) slab 3D reconstruction, as shown in the first image below.

Greater than 90% sensitivity to invasive carcinoma Detection of occult, multifocal, or residual malignancy Accurate size estimation for invasive carcinoma Good spatial resolution Ability to image regional lymph nodes (though accurate staging

remains problematic)

Disadvantages of Magnetic Resonance Mammography

The widespread use of MRM for the detection breast malignancy also has a number of disadvantages. These are as follows: High equipment costs High examination cost Limited scanner availability Need for the injection of a contrast agent No standard technique Poor throughput compared with that of US or mammography Large number of images Long learning curve for interpretation False positive enhancement in some benign tissues (limited specificity) Variable enhancement of in situ carcinoma An incidence of slowly or poorly enhancing invasive carcinomas of

about 5%

Prerequisites for the performance of MRI

MRM is a highly specialized diagnostic technique that complements clinical assessment and conventional imaging with mammography and US. It does not replace these techniques except in certain unusual situations. In general, MRM should not be performed without conventional imaging first.

MRM is best performed in a multidisciplinary setting with access to additional breast imaging, as well as close collaboration between the surgeon, radiologist, and pathologist.

Role of MRM in mammographic examination

MRM is used as an adjunct to conventional mammographic assessment because, unless significant neoangiogenesis is present as well, it is inconsistent in the diagnosis of ductal carcinoma in situ (DCIS).

This finding is typically seen in high-nuclear-grade DCIS.

In some cases, DCIS has only weak enhancement that is indistinguishable from that of benign breast tissue.

Ongoing studies are addressing the benefits of using MRM in conjunction with conventional imaging for surveillance screening in women who are known to be at high risk, either because they have the gene for breast cancer

(BRCA), because they have an extremely strong family

history of breast and/or ovarian cancer in a first-degree relative,

or because they have undergone prior radiation therapy in the chest wall (eg, those with Hodgkin disease).

To date, these studies have shown that MRM can depict small, invasive breast cancers before they become apparent on sonograms or mammograms.

However, the cost of MRM is high, and the low specificity means that women with suspect findings usually have to undergo multiple scans and MRI-guided breast biopsies.

It remains to be seen whether MRM has any impact on survival and mortality.

Diagnostic approaches

The increasing use of MRM has inevitably been accompanied by incidental enhancing abnormalities, which typically were not detected on earlier, conventional images.

These apparent lesions may represent normal or dysplastic tissues, cyclic hormonal changes, benign tumors, or even unexpected malignant foci.

If the enhancement rate, intensity, or pattern is suspicious, the nature of such foci must be clarified so that a cancer is not missed.

Three strategies are commonly used to diagnose these lesions: performing MRI-guided repeat US, repeating the MRM examination at another

suitable time, or performing MRI-guided needle biopsy.

MRI-Guided Ultrasonography

High-resolution US of the suspect region of the breast should be the first method used, because it is rapid and can be performed immediately after the MR examination.

MRM is used to guide the examination to determine the size, shape, and position of the suspect lesion.

Using this technique, the present authors and others have found malignancies previously missed with routine US, particularly in cases with multifocal or occult malignancies.

Sometimes, such lesions are subtle. They may even appear benign on sonograms, being

confidently detected only because the operator was aware of the existence of the lesion.

If an MRI-guided sonogram depicts the same lesion that the MRM does, US-guided needle biopsy and/or localization of the lesion for excision can then be routinely performed.

However, even when the examination is performed with care and by experienced operators, MRI-guided US can still fail to depict a tumor, possibly because of its size, location, or US characteristics.

Indications for Performing MRM

The high cost and limited availability of MRM, as well as the difficulties inherent in performing and interpreting the studies, require careful recommendations for its use.

The following are commonly agreed-upon and useful indications for performing MRM:

Absolute indications for MR mammography are:

1- The evaluation of post-therapeutic breast with breast conserving surgical therapy (with or without radiotherapy) and evaluation of suspicious relapse in the zone of extensive scar.It is necessary to emphasise that such an

examination may be validly performed only after 9-12 months after the surgery and 15-18 months after the radiotherapy

2-The evaluation of silicon implant means the analysis of the implant integrity, as well as the potential detection of the malignity behind and around the implant.

3- The monitoring of neoadjuvant chemotherapy

Relative indications for MR mammography are:

1-Dense breast, i.e. the breast with mammographically dense fibrograndular tissue that masks the potential malignancy, as well as with extensive fibrocystic changes.

2- In pre-surgery preparation in order to exclude multicentricity and bilateralism, MRM, according to the majority of authors, is the most sensitive method.

3-Complicated findings where there is a discrepancy between clinical and radiological finding;

4-CUP (carcinoma unknown primary), i.e. with axillary metastatic illness potentially resulting from the breast and with non-defined clinical/radiological finding.

Detection of occult breast carcinoma in a patient with carcinoma in an axillary lymph node

Evaluation of suspected multifocal or bilateral tumor Evaluation of invasive lobular carcinoma (ILC), which has a

high incidence of multifocality Evaluation of suspected, extensive, high-grade intraductal

carcinoma Characterization of an indeterminate lesion after a full

assessment with mammography, ultrasonography (US), and physical examination

Detection of recurrent breast cancer Detection of occult primary breast carcinoma in the presence

of metastatic adenocarcinoma of unknown origin Monitoring of the response to neoadjuvant chemotherapy

It is important to emphasise that in particular cases MR mammography provides no information:During pregnancy and lactation due to

expressive hormonal stimulation and increased consecutive vascular permeability, the diffuse postcontrast enhancement of glandular parenchyma disables the valid discrimination of possible pathological changes;

Hormone substitutive therapy has the same, above-mentioned effect ;

Inflammatory process of malignant or non-malignant etiology also enhances all involved structures in diffusive postcontrast manner and also masks potential malignant process;

Detected microcalcifications are not the indication for MR mammography because they correlate with DCIS in high percentage, for which MRM shows relatively low sensitivity; in such cases there is the indication of biopsies, which is more specific and cheaper as well.

Contraindications to Performing MRM

In a number of situations, MRM is essentially contraindicated, usually because of physical constraints that prevent adequate patient positioning.

These constraints include the following:Patient's inability to lie proneMarked kyphosis or kyphoscoliosisMarked obesityExtremely large breastsSevere claustrophobiaInability to use contrast material

IMAGING PROTOCOL

The protocol of breast screening includes the use of special surface coil, where the patient is in prone position.

Namely, contrast application is necessary and the dynamic study is mandatory, i.e. the monitoring of contrast dynamics within the respectively repeated time intervals.

The function of the paramagnetic contrast is to: Mark the lesion which is not visualised before

contrast administration; Mark the lesion from the healthy parenchyma;Place emphasis on the type of signal intensity

increase after contrast administration; Create dynamic and functional study in the

region of interest.

The biological basis of the contrast presentation in the malignant lesions is the consequence of the presence of neoangiogenesis, the phenomenon that is typical for invasive tumours.

The presence of newly-created pathological capillary network is correlated with increased pathological vascularity, vascular permeability, as well as with the increase of interstitium in the malignant tumour (in comparison with the benign one) and the consecutive increase of the paramagnetic increase in the region of interest.

Literature data show the fact that majority of invasive carcinomas behave according to this type, providing fast and intensive postcontrast intensification, and on the basis of such approach, very high sensitivity and specificity are achieved, which ranges, according to different authors, from 86% to 100% and from 51% to 100%, respectively.

LESION ANALYSIS

Lesion analysis is based on :Postcontrast focal/diffuse enhancementCentrifugal (benign) vs centripetal

(malignant) enhancementDynamics of postcontrast enhancement

○ Two types of the curve demonstrate all malignant changes: the plateau type and wash out type.

Lesion contoursInternal structure

Three basic curve shapes have been described by Kuhl and co-investigators[25] :

Type I is slowly enhancing in which gradual steady enhancement occurs over about 5 minutes. This has been further classified into type Ia, which is slow, linearly progressive enhancement, and Ib, which is slow enhancement with a late plateau that produces a bowlike curve.

Type II is a plateau with early strong enhancement (1-2 min) and a subsequent plateau phase. This is suspicious and often indicates malignancy.

Type III is washout with early strong enhancement (1-2 min) and a subsequent decline in enhancement. This produces a characteristic peak that some investigators have dubbed the cancer corner. This enhancement curve is strongly associated with malignancy.

Benign curve

Malignant curve

MRM Characteristics Associated With Differential Diagnosis

If early rapid enhancement due to neovascularity were unique to malignant tissues, MRM would be the standard in clinical practice today.

Unfortunately, such enhancement is not specific, and several benign conditions may enhance in a fashion similar to cancer.

Conversely, a small percentage of malignancies either enhance identically to benign breast parenchyma, or rarely, they do not enhance at all.

Nonmalignant pathologies that may mimic malignant enhancement include the following:

Cyclical parenchymal enhancement Fibroadenoma Sclerosing adenosis Florid epithelial hyperplasia Lobular carcinoma in situ Infection Fat necrosis Posttreatment scarring and/or granulation tissue Intraductal papilloma Juvenile papillomatosis Radial scar and/or complex sclerosing lesion Silicone granuloma

Low-grade DCIS is a common malignancy that may show benign-type enhancement.

Uncommon malignancies that may show benign-type enhancement include the following:

High-grade DCIS Highly scirrhous invasive ductal carcinoma (IDC) Invasive lobular carcinoma Mucinous carcinoma Papillary carcinoma Tubular carcinoma

Post-Radiation Therapy Changes on MRI Scans

In the first 9-12 months after radiation therapy, a diffuse increase in capillary permeability occurs.

This change initially causes marked parenchymal enhancement that later becomes patchy.

In most women, this enhancement gradually declines after 18 months because of fibrosis.

As a result, normal tissues have minimal enhancement, and any enhancing lesion on this background is suggestive of a recurrent tumor, which may appear nodular with carcinoma recurrence or may appear linear with DCIS.

Some patients may nevertheless benefit from MRM soon after surgery and radiation therapy if the presence of residual disease is strongly suspected.

Although diffuse parenchymal enhancement is of little diagnostic value, the demonstration of typically malignant enhancement in a focal lesion should prompt repeat excision.

Post chemotherapy Changes on MRI Scans

MRM has been used successfully before, during, and after neoadjuvant chemotherapy to assess the preoperative tumor response in advanced local malignancy.

Typically, such monitoring is performed by means of clinical palpation of the size of the tumor.

However, this method can be highly inaccurate. For example, a good tumor response with necrosis and

fibrosis may occur with only a slight reduction in the clinical size of a tumor.

A clinical complete response may result in no enhancement or residual neovascularity visible on MRMs. In the latter case, this indicates residual viable tumor with a high degree of reliability.

Chemotherapy does not produce the initial edema response seen with radiation therapy, and parenchymal enhancement becomes bland soon after the administration of contrast material; this characteristic also helps in the differentiation of normal tissues from malignant tissues.

Invasive ductal carcinoma

Fibroadenoma in a 47-year-old patient

solitary bilateral enhancing masses proved to be bilateral grade III IDC at US-guided core biopsy

Bilateral MLO mammograms show dense parenchyma with no discrete abnormality. Palpable mass in lower left breast is marked with radiopaque marker

Radial sonogram obtained in 6 o’clock position in left breast demonstrates at least five discrete hypoechoic irregular masses suspicious for cancer. US-guided core biopsy was performed for palpable largest mass and a second mass 3 cm superior to it , both proving to be ILC.

sagittal MIP of subtracted MR image obtained 90 seconds after contrast agent injection , with biopsied masses indicated by arrowheads. Patient opted for mastectomy. Only the two cored masses proved to be ILC. Remainder were lobular carcinoma in situ

Images in 46-year-old woman with nonpalpable 5-mm tubular carcinoma in left breast seen only at MR imaging