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Magnetic Resonance Imaging of the Breast: Current Practice and Future Developments
MAGNETIC RESONANCE IMAGING
.BHOFUJD3FTPOBODF*NBHJOHPGUIF#SFBTU $VSSFOU1SBDUJDFBOE'VUVSF%FWFMPQNFOUT Joanne Muldoon, M.R.T. (R.) (M.R.) MRI Clinical Coordinator and Research Liaison, St. Michaelʼs Hospital, Toronto, ON
AB S T RA C T
RÉSUMÉ
ver the past decade, there has been a dramatic increase in the use of magnetic resonance imaging (MRI) of the breast. MRI has proven to be a key tool in the detection and diagnosis of breast cancer and it plays a very important role in the evaluation of response to therapy. Breast MRI is highly sensitive and is able to detect lesions, which are occult on mammography and ultrasound. With the introduction of contrast agents, advances in surface coil technology and focused work in optimal scan protocols, breast MRI has continued to evolve as a valuable adjunctive breast imaging tool. This review will give a summary of current criteria and techniques that may be used in the detection, diagnosis and excision of breast lesions.
O
n a assisté, au cours de la dernière décennie, à une impressionnante montée de lʼutilisation de lʼimagerie du sein par résonance magnétique. Lʼimagerie par résonance magnétique (IRM) sʼest avérée un outil majeur pour le dépistage et le diagnostic du cancer du sein et elle joue un rôle critique dans lʼévaluation des résultats de la thérapie. LʼIRM du sein est particulièrement précise et permet de découvrir des lésions invisibles à la mammographie et à lʼéchographie. Grâce à lʼintroduction des agents de contraste, des progrès de la technologie de la bobine de surface et des travaux portant sur les protocoles de scintillographie optimale, lʼIRM du sein a poursuivi son évolution pour devenir un outil auxiliaire précieux de lʼimagerie du sein. Cet examen présente un résumé des critères actuels et des techniques à utiliser pour le dépistage, le diagnostic et lʼablation des lésions du sein.
INTRODUCTION
current techniques in interventional procedures and future trends for breast MR imaging.
MRI has proven to be a very versatile imaging technique in the detection of breast cancer. Although conventional imaging such as ultrasound and mammography are still considered to be the primary breast imaging modalities, MRI provides many unique advantages as a supplemental imaging method. MRI provides exquisite soft tissue contrast and its superior differentiation of fat and water makes it ideal for breast imaging. Another advantage of MRI is its ability to image the breast in fine sections, dynamically and in multiple planes, thereby providing four-dimensional information. Since the introduction of contrast agents such as Gadolinium (Gd- DTPA), dynamic contrast enhanced MRI is considered to be the most sensitive imaging technique in the evaluation of breast cancer.1 Contrast enhanced MRI (CEMRI) of the breast has the unique ability to provide both morphological and functional information to assist in the differential diagnosis of conventionally questionable lesions.2 Developments have been made in surface coil technology and in imaging protocols, resulting in a significant improvement in both spatial resolution and temporal resolution. Despite the technical advances, there are many unresolved issues in contrast enhanced breast MRI, including low specificity and the lack of a defined standard technique for both imaging and image interpretation.3,4 This paper will discuss the application of breast MRI, a typical breast MRI protocol, diagnostic criteria and analysis. It will also examine
• Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005
O
BREAST MR IMAGING INDICATIONS Due to the relatively low specificity and also the fact that MRI is a complex and relatively expensive examination, MRI should be used on strict indications only. The following indications for MRI of the breast seem to be widely accepted. 1)
Preoperative Staging MRI has been proven to be successful in the detection of cancers that are occult on both mammography and ultrasound. Based on these results, CEMRI for breast could be used as an additional imaging technique to identify the extent of cancer before treatment planning. It is a useful tool for patients with a known breast cancer in the detection of multicentric or contralateral disease. These indications would change patient management in the decision to have a lumpectomy vs. a mastectomy.5
2)
Recurrence MRI is useful in distinguishing scar vs. carcinoma in patients who have undergone breast conservation therapy. It is recommended that imaging be performed at least one year after treatment due to high false positive rates caused by early tissue changes in the post surgical and post radiated breast.6
3)
Inconclusive conventional imaging findings MRI can be a very useful problem-solving tool when breast cancer is suspected but a diagnosis cannot be made with mammography, ultrasound or physical exam.6
4)
High-risk screening MRI is the most sensitive modality for the breast surveillance of BRCA1 and BRCA2 mutation carriers. These patients have an 80-90% lifetime risk of being diagnosed with breast cancer at a younger age. Intensive screening commences at 25-30 years. MRI may be helpful for these women because the technology is effective in dense breast tissue and most young women have dense breasts. Investigators in Europe and at Sunnybrook and Womenʼs Hospital in Toronto, have found MRI to have superior sensitivity compared to mammography and ultrasound in screening detection.1
5)
Implant integrity Known complications for breast implants include capsular contracture and implant rupture. MR imaging appears to be the most accurate method for evaluating implant integrity. MRI is also recommended as a diagnostic tool for known or suspected cancer in women with breast implants.6
6)
Neo-Adjuvant Chemotherapy MRI can document tumour response to chemotherapy, both with regards to size and tumour perfusion.6
BREAST MRI PROTOCOL Exam Scheduling Breast imaging of premenopausal women should be scheduled during the second week of her menstrual cycle, as to minimize contrast enhancement related to cyclical hormonal variations. Women on hormone replacement therapy should be advised to stop taking the hormones a couple of months before MR imaging if possible. Magnets and Surface Coils MRI of the breast should always be performed at high field strength (1.0T-1.5T) imaging systems. This will accommodate the best temporal and spatial resolution, as well as giving optimal separation between fat and water peaks. A dedicated breast surface coil should be used for imaging (Figure 1 and 2). Coil design will vary by manufacturer, but should allow for the breast to be imaged in its natural dependent state. Some coil designs consists of mild compression of the breast in the medial-lateral direction between two plates, each of which contain a phased array coil (Figure 2). The advantages to this design over conventional breast coils is that with the breast positioned closer to the surface coils, there is a substantial increase in signal to noise ratio.
Utilizing compression during the exam will reduce the dimension of the breast in the medial-lateral direction, thus reducing the number of slices required in sagittal imaging. Compression is also important in stabilizing the breast in a natural configuration for MR-guided interventions. Many advances have been made in coil development with parallel imaging capabilities, allowing for bilateral imaging in the sagittal direction.
Figure 1: Example of an “open” phased array breast coil.
Figure 2: Example of a “closed” phased array breast coil. Patient Positioning Positioning of the breast for an exam is as important for MRI as mammography. The patient lies prone face down on a special doughnut-shaped face pillow, or if such luxuries are not available, the patient can lie with the head turned sideways on a conventional pillow. Optimal positioning for a breast MRI is with the patient lying with both arms at their sides to allow full coverage of the entire breast and axilla. If this is not achievable due to patient size, condition or I.V. access, the patient can be positioned with one or both arms raised by their head. The breast should be pulled away from the chest wall and placed in the center of the coil with the nipple centered. Markers, such as vitamin E capsules, should be placed over the nipples and any palpable abnormalities. Optimizing the positioning is important to allow for reproducibility between follow-up studies and for correlating lesion location with conventional imaging. An intravenous line should be started before the patient lies in the coil. The technologist should emphasize to the patient the importance of avoiding coughing, wiggling or any other large motions during or in between scans. Instruct the patient to practice shallow, steady breathing during the exam to minimize any respiratory motion artifact.
Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005 •
MRI Technique There is no gold standard. Depending on hardware and software capabilities, there are a wide variety of techniques used at different imaging centers. However, several general principles should be adhered to in any breast MR protocol. High spatial resolution scans are very important for the detection of small lesions and providing fine anatomical detail. Typically, in-plane resolution (pixel size) of approximately 1mm and through-plane resolution (slice thickness) < 2-3mm is optimal. Temporal resolution is also an important factor in any breast MR protocol for evaluating the different stages of contrast enhancement. The minimum temporal resolution per dynamic enhanced scan should be < 2 minutes. These dynamic techniques are designed to study enhancement kinetics after contrast agent administration. With rapid imaging, enhancing lesions can be identified before the enhancement of normal glandular tissue, which shows more delayed enhancement. Early enhancement occurs approximately two to four minutes after the administration of contrast media, whereas late or delayed enhancement tends to occur approximately ten minutes post-contrast. Gradient-echo sequences, both 2D and 3D are used during dynamic scanning due to the faster scan times, offer inherently better T1 contrast and are much more sensitive to the T1 shortening effects of gadolinium chelates than spin echo sequences.4 A very short TR, TE and relatively low excitation angle are necessary for rapid acquisition times. T1-weighted images can provide excellent visual separation of adipose tissue from glandular tissue.7 Fat saturation techniques are necessary to distinguish enhancing lesions from background fatty tissue. T2 weighted (long TR, long TE) fast spin echo images with fat saturation provides very useful information in the depiction of cysts, necrosis, hemorrhage, and some fibroadenomas.7 Fat saturation (“fat sat”) can be achieved by a variety of methods, each with its own challenges. The use of chemical or spectral pre-saturation techniques is most commonly used. This technique takes advantage of the frequency separation between fat and water. A chemically selective RF pulse selectively saturates the signal arising from fat based on its resonant frequency relationship to water. At 1.5T, the difference in frequencies is approximately 220 Hz. Fat suppression can also be achieved by means of post processing image subtraction (passive fat suppression). Identical imaging parameters before and after the administration of contrast are required. Subtracted images will yield the difference in signal intensity between the unenhanced and enhanced images, directly proportional to the degree of enhancement.
• Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005
Two advantages of image subtraction are minimized acquisition times, because inversion recovery and saturation pulses are not used, and insensitivity to magnetic field inhomogeneity. The major disadvantages of image subtraction are decreased signal-to-noise ratio and sensitivity to patient motion, which can result in misregistration.4 Inversion recovery sequences offers the ability to selectively suppress signal based on the T1 times of specific tissues and may also be used as a fat suppression technique. Whenever a pulse sequence without spectrally selective fat suppression is used, the echo time must be chosen to avoid opposed phase imaging, since with opposed phase imaging enhancement of small lesions may be obscured. Unilateral vs. Bilateral Exam The decision to perform unilateral vs. bilateral imaging is dependent on hardware and software capabilities and radiologist preference. The innovation of parallel imaging has improved breast imaging dramatically, allowing bilateral breasts to be imaged in the sagittal plane with the same spatial resolution as a unilateral study. Some scanners may not have current upgrades with parallel imaging capabilities, which leaves the radiologist with the decision of performing either unilateral imaging in the sagittal plane or bilateral imaging in the axial plane. Both techniques have pros and cons. The advantage to performing unilateral sagittal images is the small field of view that can be achieved, thus increasing spatial resolution. Sagittal imaging is also very complimentary to mammography. The disadvantages to unilateral imaging include the patient being required to have two appointments and two separate injections of contrast. This can be both costly to the department as well as inconvenient for the patient. Bilateral imaging in the axial plane can be done in one patient visit and one injection but requires the use of a large field of view, which can decrease spatial resolution, and fat suppression techniques may be more difficult at a large field of view. With parallel imaging, a 3D volume encompasses both breasts in a sagittal acquisition while maintaining a smaller field of view. The technologist is able to shim over each breast individually for better fat suppression and the decreased scan times associated with parallel imaging improve temporal resolution during dynamic imaging while maintaining high spatial resolution.8 Pulse Sequences Protocols and pulse sequences will vary between imaging centers. Again, there is no standard technique when it comes to breast MR imaging. For example, the technique used at Sunnybrook and Womenʼs College Health Sciences Center in Toronto, Ontario includes: (1) a 3 plane localizer scan; (2) a bilateral sagittal FSE T2W with fat saturation; (3) bilateral sagittal T1W 3D Spoiled gradient echo (SPGR) is performed pre-contrast to assure proper coverage of anatomy. A rapid bolus injection of 0.1 mmol/L/kg gadolinium is administered
and after a forty second delay, four subsequent scans with identical scan parameters as the pre-contrast scan are performed, image acquisition time < 2 min, section thickness 2-3mm without gap, matrix 256 x 192, FOV 18-20cm (Figure 3). This 3D dynamic acquisition employs an elliptic-centric kspace trajectory allowing imaging to be much more rapid as opposed to the conventional rectilinear trajectory commonly used in conventional spin echo and gradient echo techniques. Lastly, post-imaging subtraction of enhanced-unenhanced images for each breast is performed after imaging is completed. This technique will subtract all background tissue and only demonstrate areas of enhancement and is done for each phase of dynamic imaging.6
a
b
c
Figure 3: High-resolution sagittal 3D SPGR with fat saturation images demonstrating (a) DCIS and (b) DCIS and IDC (c) DCIS after i.v. injection of gadolinium.
Post-processing of 3D volume acquisitions is a valuable tool to assist in image interpretation and surgical planning. 3D images can be reformatted into alternate imaging planes providing a more realistic 3D view and maximum intensity projections (MIPs) can demonstrate lesion vascularity.
IMAGE INTERPRETATION
Morphology and Kinetic Analysis In breast MRI, lesions are usually identified because they enhance after i.v. injection of contrast. There are two major approaches to differentiate benign from malignant lesions: (1) evaluation of lesion morphology or appearance. (2) Evaluation of enhancement kinetics or patterns of contrast enhancement.10 If a mass or focal enhancement is present, its shape and borders should be evaluated as well as its internal architecture. Lesion morphologies that suggest malignancy include speculated or irregular borders, peripheral enhancement (rim enhancement) and ductal enhancement. Lesion morphologies that suggest a benign lesion include smooth or lobulated borders, non-enhancing internal septations (fibroadenoma), patchy parenchymal enhancement and no enhancement.10 In order to analyze subtle morphological details of enhancing lesions, maximum spatial resolution is required. If a lesion is suspicious based on morphology, it requires tissue sampling. Evaluation of enhancement kinetics is demonstrated by a time-signal intensity curve. There are three types of curves when attempting to distinguish benign from malignant lesions: Type I:
Steady enhancement where a persistent increase in signal intensity is present after 2 minutes.
Type II:
Plateau, where the maximum signal intensity is achieved in 2 minutes and remains constant.
Type III:
Washout, where the maximum achieved signal is demonstrated by 2 minutes and decreases with time.
Malignant lesions tend to demonstrate a Type III curve and benign lesions demonstrate a Type I curve11 (Figure 4).
Breast MR Lexicon A proposed MR lexicon is being developed to standardize MRI reporting and to help establish terms describing breast lesion morphology and enhancement. Specific terms for important features essential for cancer diagnosis could then be described and compared using the wide range of available MR hardware and software. The lexicon is being developed by a group of international breast MR experts and its design is based on the BI-RADS lexicon used in mammography. This lexicon will help improve specificity of breast MR by standardizing terminology for breast reporting, including recommendations for reporting clinical history, technical parameters, descriptions for general breast composition, morphologic and kinetic characteristics of mass lesions or regions of abnormal enhancement, and overall impression and management recommendations.9
Figure 4: MR Enhancement Kinetics
Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005 •
For a good evaluation of enhancement kinetics, at least four post-contrast sequences should be performed. This allows for the evaluation of initial early contrast enhancement as well as the later phases, often showing the washout phenomenon in malignant lesions. Lesion enhancement kinetics should be evaluated on both the subtracted and non-subtracted images and throughout the entire dynamic series. To quantify a lesionʼs enhancement, a region of interest (ROI) is manually placed over the area in which earliest enhancement occurs. Unfortunately, locally increased vascularity is not specific to malignant tissues. Some tumours such as invasive lobular and ductal carcinoma in situ (DCIS) may demonstrate variable angiogenic activity (slow, progressive enhancement) making diagnosis based on enhancement rates difficult.11
a b Figure 5: (a) & (b) Seven channel phased array breast coil (MRI Devices) with interventional capabilities.
MRI GUIDED BREAST BIOPSY Sensitivity of contrast enhanced MRI is very high, reported as 94-100%, but a major limitation is its relatively low specificity (37-97%).12 With an imaging modality that is highly sensitive but not highly specific, tissue sampling is required to differentiate between false-positive benign enhancing lesions and true-positive carcinomas. Because MRI detected abnormalities often are not visible with conventional imaging methods and are not palpable, MR-guided interventions are required. Investigators have reported clinical experience with MRI-guided needle localization for surgical excision and percutaneous biopsy using fine needle, automated core needle or vacuum-assisted biopsy probe. MRI-guided breast biopsies pose many challenges, some of which include the requirement for specific MRI-compatible equipment, the need to remove the patient from the magnet in between imaging to perform the biopsy, decreasing lesion conspicuity during the procedure (“vanishing” target), needle artifact obscuring the lesion site and lack of a standard localization technique. A dedicated biopsy compression device with a grid-localizing system is required to accurately perform interventions in the MR (Figures 5 and 6). MRI-guided vacuum assisted biopsy (VAB) is a new technique that is gaining popularity because it allows rapid acquisition of multiple specimens and is a safe and accurate alternative to surgery and to existing MRI-guided needle biopsy methods13. After the biopsy is performed, a clip is deployed into the tissue cavity to serve as a marker for future imaging studies (Figure 7). Because this is a new and costly technique, it is currently only being practiced at research institutes in Canada, such as Sunnybrook and Womenʼs College Health Sciences Centre in Toronto.
• Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005
a b Figure 6: (a) & (b) Eight Channel phased array breast imaging system (Sentinelle Medical Inc.) with interventional capabilities
a b c Figure 7: (a) Enhancing lesion; (b) Post VAB and (c) Axial post VAB demonstrating hematoma and clip placement at biopsy site.
CURRENT DEVELOPMENTS MR Spectroscopy (MRS) is a valuable tool to assist in lesion characterization and diagnosis when used in combination with MRI. Cancerous lesions will demonstrate elevated choline levels from increased cellular proliferation. Single voxel spectroscopy cannot aid in the detection of suspicious lesions, however it can play an important role in the characterization of suspicious lesions thus improving specificity. Further development in multivoxel spectroscopic methods, referred to as chemical shift imaging (CSI), may help to improve the sensitivity of choline detection, however this technique is still in the research phase.14 Magnetic resonance elastography (MRE) is a phase-contrastbased MR imaging technique, using mechanical waves to evaluate the elasticity properties of tissues. MRE is a new and promising technique demonstrating high elasticity values in malignant lesions and lowest elasticity values in normal breast parenchyma and fatty tissues. Further research is needed to evaluate the potential applications in breast diagnosis.15 MR/US co-registration is a novel technique, which combines the sensitivity of contrast enhanced MRI with the realtime guidance capabilities of ultrasound. A quick contrast enhanced study is performed in the MRI until the lesion is visualized. The patient is then removed from the magnet and with the aid of optical tracking and software visualization system, the radiologist can visualize the MR-detected lesion under ultrasound. With further development, this technique can potentially aid in the improvement of biopsy guidance or minimally invasive treatment of lesions.16,17
Previously, Joanne worked as MR research technologist at Sunnybrook and Womenʼs Hospital in Toronto where she gained experience in interventional breast MRI. She was the 2005 Co-chair for the Eastern Canada Regional Educational Seminar in Toronto organized by the Section of MR Technologists (www.ismrm.org).
REFERENCES 1.
Warner E, Plewes D, Hill K, Causer P, Zubovits J, Jong R, et al. Surveillance of BRCA1 and BRCA2 Mutation Carriers with Magnetic Resonance Imaging, Ultrasound, Mammography and Clinical Breast Examination. JAMA 2005;293:931.
2.
Kuhl CK. MRI of breast tumours. Eur.Radiol 2000;10:46-58.
3.
Goscin CP, Berman CG. Magnetic Resonance Imaging of the Breast. Cancer Control 2001;8(5):399-406.
4.
Orel SG, Schnall MD. MR Imaging of the Breast for the Staging of Breast Cancer. Radiology 2001;220:13-30.
5.
Kinkel K. MR Imaging: Breast Cancer Staging and Screening. Seminars in Surgical Oncology 2001;20:187-196.
6.
Causer P. Breast Imaging. SMRT 12th Annual Meeting Syllabus May 2003:71-79.
7.
Jacobs MA, Barker P, Bluemke D, Maranto C, et al. Benign and Malignant Breast Lesions: Diagnosis with Multiparametric MR Imaging. Radiology 2003;229:225-232.
8.
Friedman PD, Swaminathan SV, Smith R. Sense Imaging of the Breast. AJR 2005;184:448-451.
9.
Ikeda DM, Hylton NM, Kinkel K, Hochman M, Kuhl C, Kaiser WA, Weinreb JC, Smazal SF, Degani H, Viehweg P, Barclay J, Schnall MD. Development, standardization, and testing of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging studies. Journal of Magnetic Resonance Imaging 2001;13(6):889895.
10.
Goscin CP, Berman C, Clark R. Magnetic Resonance Imaging of the Breast. Cancer Control 2001;8(5):399-406.
11.
Kuhl CK. Differential Diagnosis in Dynamic Contrast-Enhanced MR Imaging of The Breast. Available at: www.star-program.de/data--starprogram/upload/star_abstracts_304_KUHL-1.pdf
12.
Liberman L, Morris E, Lee MJ-Y, Kaplan J, LaTrenta L, Menell J, Abramson A, Dashnaw S, Ballon D, Dershaw D. Breast Lesions Detected on MR Imaging: Features and Positive Predictive Value. AJR 2002;179:171-178.
13.
Liberman L, Morris E, Dershaw D, Thornton C, Van Zee K, Tan L. Fast MRI-Guided Vacuum-Assisted Breast Biopsy: Initial Experience. AJR 2003;181:1283-1293.
14.
Cecil K, Schnall MD, Seigelman E, Lenkinski R. The evaluation of human breast lesions with magnetic resonance imaging and proton magnetic resonance spectroscopy. Breast Cancer Research and Treatment 2001;68:45-54.
15.
Wiberg MK. Magnetic Resonance Imaging in Breast Diagnosis. Fredagen den 22 november 2002, kl. 9.00. Föreläsningssalen M63, Huddinge Universitetssjukhus.
16.
Piron CA, Causer P, Jong R, Shumak R, Plewes DB. A Hybrid Breast Biopsy System Combining Ultrasound and MRI. IEEE Transactions on Medical Imaging, September 2003;22(9).
17.
Muldoon J, Piron CA, Sela G, Causer P, Jong R, Kucharczyk W, Plewes DB. MR-Targeted Ultrasound of Breast Lesions. SMRT 14th Annual Meeting Syllabus, May 2005.
CONCLUSION MR imaging is emerging as the most promising adjunctive imaging modality for breast cancer detection to date. Advantages of MRI compared with conventional imaging techniques include superior evaluation of the extent and multifocality of cancer when staging patients, enhanced detection of recurrence, better evaluation of the augmented breast and improved screening for high-risk women. Although contrast enhanced MRI of the breast is a sensitive method for detecting breast cancer, its variable specificity is a major limitation. Work continues to define the technical requirements for optimal imaging, criteria for image interpretation, development of accurate MR-guided localization and biopsy systems, and cost-effectiveness. These improvements and advancements will result in an expanded role for MRI in womenʼs imaging providing clinicians with the tools needed to better diagnose and manage breast disease. About the Author: Joanne Muldoon graduated from the Red River College MRI/Spectroscopy Technologist Program and is currently working at St. Michaelʼs Hospital in Toronto, Ontario where she is the Clinical Coordinator for MRI.
Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005 •
.BHOFUJD3FTPOBODF*NBHJOHPGUIF#SFBTU $VSSFOU1SBDUJDFBOE'VUVSF%FWFMPQNFOUT Joanne Muldoon, M.R.T. (R.) (M.R.) MRI Clinical Coordinator and Research Liaison, St. Michaelʼs Hospital, Toronto, ON
AB S T RA C T
RÉSUMÉ
ver the past decade, there has been a dramatic increase in the use of magnetic resonance imaging (MRI) of the breast. MRI has proven to be a key tool in the detection and diagnosis of breast cancer and it plays a very important role in the evaluation of response to therapy. Breast MRI is highly sensitive and is able to detect lesions, which are occult on mammography and ultrasound. With the introduction of contrast agents, advances in surface coil technology and focused work in optimal scan protocols, breast MRI has continued to evolve as a valuable adjunctive breast imaging tool. This review will give a summary of current criteria and techniques that may be used in the detection, diagnosis and excision of breast lesions.
O
n a assisté, au cours de la dernière décennie, à une impressionnante montée de lʼutilisation de lʼimagerie du sein par résonance magnétique. Lʼimagerie par résonance magnétique (IRM) sʼest avérée un outil majeur pour le dépistage et le diagnostic du cancer du sein et elle joue un rôle critique dans lʼévaluation des résultats de la thérapie. LʼIRM du sein est particulièrement précise et permet de découvrir des lésions invisibles à la mammographie et à lʼéchographie. Grâce à lʼintroduction des agents de contraste, des progrès de la technologie de la bobine de surface et des travaux portant sur les protocoles de scintillographie optimale, lʼIRM du sein a poursuivi son évolution pour devenir un outil auxiliaire précieux de lʼimagerie du sein. Cet examen présente un résumé des critères actuels et des techniques à utiliser pour le dépistage, le diagnostic et lʼablation des lésions du sein.
INTRODUCTION
current techniques in interventional procedures and future trends for breast MR imaging.
MRI has proven to be a very versatile imaging technique in the detection of breast cancer. Although conventional imaging such as ultrasound and mammography are still considered to be the primary breast imaging modalities, MRI provides many unique advantages as a supplemental imaging method. MRI provides exquisite soft tissue contrast and its superior differentiation of fat and water makes it ideal for breast imaging. Another advantage of MRI is its ability to image the breast in fine sections, dynamically and in multiple planes, thereby providing four-dimensional information. Since the introduction of contrast agents such as Gadolinium (Gd- DTPA), dynamic contrast enhanced MRI is considered to be the most sensitive imaging technique in the evaluation of breast cancer.1 Contrast enhanced MRI (CEMRI) of the breast has the unique ability to provide both morphological and functional information to assist in the differential diagnosis of conventionally questionable lesions.2 Developments have been made in surface coil technology and in imaging protocols, resulting in a significant improvement in both spatial resolution and temporal resolution. Despite the technical advances, there are many unresolved issues in contrast enhanced breast MRI, including low specificity and the lack of a defined standard technique for both imaging and image interpretation.3,4 This paper will discuss the application of breast MRI, a typical breast MRI protocol, diagnostic criteria and analysis. It will also examine
• Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005
O
BREAST MR IMAGING INDICATIONS Due to the relatively low specificity and also the fact that MRI is a complex and relatively expensive examination, MRI should be used on strict indications only. The following indications for MRI of the breast seem to be widely accepted. 1)
Preoperative Staging MRI has been proven to be successful in the detection of cancers that are occult on both mammography and ultrasound. Based on these results, CEMRI for breast could be used as an additional imaging technique to identify the extent of cancer before treatment planning. It is a useful tool for patients with a known breast cancer in the detection of multicentric or contralateral disease. These indications would change patient management in the decision to have a lumpectomy vs. a mastectomy.5
2)
Recurrence MRI is useful in distinguishing scar vs. carcinoma in patients who have undergone breast conservation therapy. It is recommended that imaging be performed at least one year after treatment due to high false positive rates caused by early tissue changes in the post surgical and post radiated breast.6
3)
Inconclusive conventional imaging findings MRI can be a very useful problem-solving tool when breast cancer is suspected but a diagnosis cannot be made with mammography, ultrasound or physical exam.6
4)
High-risk screening MRI is the most sensitive modality for the breast surveillance of BRCA1 and BRCA2 mutation carriers. These patients have an 80-90% lifetime risk of being diagnosed with breast cancer at a younger age. Intensive screening commences at 25-30 years. MRI may be helpful for these women because the technology is effective in dense breast tissue and most young women have dense breasts. Investigators in Europe and at Sunnybrook and Womenʼs Hospital in Toronto, have found MRI to have superior sensitivity compared to mammography and ultrasound in screening detection.1
5)
Implant integrity Known complications for breast implants include capsular contracture and implant rupture. MR imaging appears to be the most accurate method for evaluating implant integrity. MRI is also recommended as a diagnostic tool for known or suspected cancer in women with breast implants.6
6)
Neo-Adjuvant Chemotherapy MRI can document tumour response to chemotherapy, both with regards to size and tumour perfusion.6
BREAST MRI PROTOCOL Exam Scheduling Breast imaging of premenopausal women should be scheduled during the second week of her menstrual cycle, as to minimize contrast enhancement related to cyclical hormonal variations. Women on hormone replacement therapy should be advised to stop taking the hormones a couple of months before MR imaging if possible. Magnets and Surface Coils MRI of the breast should always be performed at high field strength (1.0T-1.5T) imaging systems. This will accommodate the best temporal and spatial resolution, as well as giving optimal separation between fat and water peaks. A dedicated breast surface coil should be used for imaging (Figure 1 and 2). Coil design will vary by manufacturer, but should allow for the breast to be imaged in its natural dependent state. Some coil designs consists of mild compression of the breast in the medial-lateral direction between two plates, each of which contain a phased array coil (Figure 2). The advantages to this design over conventional breast coils is that with the breast positioned closer to the surface coils, there is a substantial increase in signal to noise ratio.
Utilizing compression during the exam will reduce the dimension of the breast in the medial-lateral direction, thus reducing the number of slices required in sagittal imaging. Compression is also important in stabilizing the breast in a natural configuration for MR-guided interventions. Many advances have been made in coil development with parallel imaging capabilities, allowing for bilateral imaging in the sagittal direction.
Figure 1: Example of an “open” phased array breast coil.
Figure 2: Example of a “closed” phased array breast coil. Patient Positioning Positioning of the breast for an exam is as important for MRI as mammography. The patient lies prone face down on a special doughnut-shaped face pillow, or if such luxuries are not available, the patient can lie with the head turned sideways on a conventional pillow. Optimal positioning for a breast MRI is with the patient lying with both arms at their sides to allow full coverage of the entire breast and axilla. If this is not achievable due to patient size, condition or I.V. access, the patient can be positioned with one or both arms raised by their head. The breast should be pulled away from the chest wall and placed in the center of the coil with the nipple centered. Markers, such as vitamin E capsules, should be placed over the nipples and any palpable abnormalities. Optimizing the positioning is important to allow for reproducibility between follow-up studies and for correlating lesion location with conventional imaging. An intravenous line should be started before the patient lies in the coil. The technologist should emphasize to the patient the importance of avoiding coughing, wiggling or any other large motions during or in between scans. Instruct the patient to practice shallow, steady breathing during the exam to minimize any respiratory motion artifact.
Winter 2005 | The Canadian Journal of Medical Radiation Technology | Hiver 2005 •
MRI Technique There is no gold standard. Depending on hardware and software capabilities, there are a wide variety of techniques used at different imaging centers. However, several general principles should be adhered to in any breast MR protocol. High spatial resolution scans are very important for the detection of small lesions and providing fine anatomical detail. Typically, in-plane resolution (pixel size) of approximately 1mm and through-plane resolution (slice thickness) < 2-3mm is optimal. Temporal resolution is also an important factor in any breast MR protocol for evaluating the different stages of contrast enhancement. The minimum temporal resolution per dynamic enhanced scan should be < 2 minutes. These dynamic techniques are designed to study enhancement kinetics after contrast agent administration. With rapid imaging, enhancing lesions can be identified before the enhancement of normal glandular tissue, which shows more delayed enhancement. Early enhancement occurs approximately two to four minutes after the administration of contrast media, whereas late or delayed enhancement tends to occur approximately ten minutes post-contrast. Gradient-echo sequences, both 2D and 3D are used during dynamic scanning due to the faster scan times, offer inherently better T1 contrast and are much more sensitive to the T1 shortening effects of gadolinium chelates than spin echo sequences.4 A very short TR, TE and relatively low excitation angle are necessary for rapid acquisition times. T1-weighted images can provide excellent visual separation of adipose tissue from glandular tissue.7 Fat saturation techniques are necessary to distinguish enhancing lesions from background fatty tissue. T2 weighted (long TR, long TE) fast spin echo images with fat saturation provides very useful information in the depiction of cysts, necrosis, hemorrhage, and some fibroadenomas.7 Fat saturation (“fat sat”) can be achieved by a variety of methods, each with its own challenges. The use of chemical or spectral pre-saturation techniques is most commonly used. This technique takes advantage of the frequency separation between fat and water. A chemically selective RF pulse selectively saturates the signal arising from fat based on its resonant frequency relationship to water. At 1.5T, the difference in frequencies is approximately 220 Hz. Fat suppression can also be achieved by means of post processing image subtraction (passive fat suppression). Identical imaging parameters before and after the administration of contrast are required. Subtracted images will yield the difference in signal intensity between the unenhanced and enhanced images, directly proportional to the degree of enhancement.
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Two advantages of image subtraction are minimized acquisition times, because inversion recovery and saturation pulses are not used, and insensitivity to magnetic field inhomogeneity. The major disadvantages of image subtraction are decreased signal-to-noise ratio and sensitivity to patient motion, which can result in misregistration.4 Inversion recovery sequences offers the ability to selectively suppress signal based on the T1 times of specific tissues and may also be used as a fat suppression technique. Whenever a pulse sequence without spectrally selective fat suppression is used, the echo time must be chosen to avoid opposed phase imaging, since with opposed phase imaging enhancement of small lesions may be obscured. Unilateral vs. Bilateral Exam The decision to perform unilateral vs. bilateral imaging is dependent on hardware and software capabilities and radiologist preference. The innovation of parallel imaging has improved breast imaging dramatically, allowing bilateral breasts to be imaged in the sagittal plane with the same spatial resolution as a unilateral study. Some scanners may not have current upgrades with parallel imaging capabilities, which leaves the radiologist with the decision of performing either unilateral imaging in the sagittal plane or bilateral imaging in the axial plane. Both techniques have pros and cons. The advantage to performing unilateral sagittal images is the small field of view that can be achieved, thus increasing spatial resolution. Sagittal imaging is also very complimentary to mammography. The disadvantages to unilateral imaging include the patient being required to have two appointments and two separate injections of contrast. This can be both costly to the department as well as inconvenient for the patient. Bilateral imaging in the axial plane can be done in one patient visit and one injection but requires the use of a large field of view, which can decrease spatial resolution, and fat suppression techniques may be more difficult at a large field of view. With parallel imaging, a 3D volume encompasses both breasts in a sagittal acquisition while maintaining a smaller field of view. The technologist is able to shim over each breast individually for better fat suppression and the decreased scan times associated with parallel imaging improve temporal resolution during dynamic imaging while maintaining high spatial resolution.8 Pulse Sequences Protocols and pulse sequences will vary between imaging centers. Again, there is no standard technique when it comes to breast MR imaging. For example, the technique used at Sunnybrook and Womenʼs College Health Sciences Center in Toronto, Ontario includes: (1) a 3 plane localizer scan; (2) a bilateral sagittal FSE T2W with fat saturation; (3) bilateral sagittal T1W 3D Spoiled gradient echo (SPGR) is performed pre-contrast to assure proper coverage of anatomy. A rapid bolus injection of 0.1 mmol/L/kg gadolinium is administered
and after a forty second delay, four subsequent scans with identical scan parameters as the pre-contrast scan are performed, image acquisition time < 2 min, section thickness 2-3mm without gap, matrix 256 x 192, FOV 18-20cm (Figure 3). This 3D dynamic acquisition employs an elliptic-centric kspace trajectory allowing imaging to be much more rapid as opposed to the conventional rectilinear trajectory commonly used in conventional spin echo and gradient echo techniques. Lastly, post-imaging subtraction of enhanced-unenhanced images for each breast is performed after imaging is completed. This technique will subtract all background tissue and only demonstrate areas of enhancement and is done for each phase of dynamic imaging.6
a
b
c
Figure 3: High-resolution sagittal 3D SPGR with fat saturation images demonstrating (a) DCIS and (b) DCIS and IDC (c) DCIS after i.v. injection of gadolinium.
Post-processing of 3D volume acquisitions is a valuable tool to assist in image interpretation and surgical planning. 3D images can be reformatted into alternate imaging planes providing a more realistic 3D view and maximum intensity projections (MIPs) can demonstrate lesion vascularity.
IMAGE INTERPRETATION
Morphology and Kinetic Analysis In breast MRI, lesions are usually identified because they enhance after i.v. injection of contrast. There are two major approaches to differentiate benign from malignant lesions: (1) evaluation of lesion morphology or appearance. (2) Evaluation of enhancement kinetics or patterns of contrast enhancement.10 If a mass or focal enhancement is present, its shape and borders should be evaluated as well as its internal architecture. Lesion morphologies that suggest malignancy include speculated or irregular borders, peripheral enhancement (rim enhancement) and ductal enhancement. Lesion morphologies that suggest a benign lesion include smooth or lobulated borders, non-enhancing internal septations (fibroadenoma), patchy parenchymal enhancement and no enhancement.10 In order to analyze subtle morphological details of enhancing lesions, maximum spatial resolution is required. If a lesion is suspicious based on morphology, it requires tissue sampling. Evaluation of enhancement kinetics is demonstrated by a time-signal intensity curve. There are three types of curves when attempting to distinguish benign from malignant lesions: Type I:
Steady enhancement where a persistent increase in signal intensity is present after 2 minutes.
Type II:
Plateau, where the maximum signal intensity is achieved in 2 minutes and remains constant.
Type III:
Washout, where the maximum achieved signal is demonstrated by 2 minutes and decreases with time.
Malignant lesions tend to demonstrate a Type III curve and benign lesions demonstrate a Type I curve11 (Figure 4).
Breast MR Lexicon A proposed MR lexicon is being developed to standardize MRI reporting and to help establish terms describing breast lesion morphology and enhancement. Specific terms for important features essential for cancer diagnosis could then be described and compared using the wide range of available MR hardware and software. The lexicon is being developed by a group of international breast MR experts and its design is based on the BI-RADS lexicon used in mammography. This lexicon will help improve specificity of breast MR by standardizing terminology for breast reporting, including recommendations for reporting clinical history, technical parameters, descriptions for general breast composition, morphologic and kinetic characteristics of mass lesions or regions of abnormal enhancement, and overall impression and management recommendations.9
Figure 4: MR Enhancement Kinetics
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For a good evaluation of enhancement kinetics, at least four post-contrast sequences should be performed. This allows for the evaluation of initial early contrast enhancement as well as the later phases, often showing the washout phenomenon in malignant lesions. Lesion enhancement kinetics should be evaluated on both the subtracted and non-subtracted images and throughout the entire dynamic series. To quantify a lesionʼs enhancement, a region of interest (ROI) is manually placed over the area in which earliest enhancement occurs. Unfortunately, locally increased vascularity is not specific to malignant tissues. Some tumours such as invasive lobular and ductal carcinoma in situ (DCIS) may demonstrate variable angiogenic activity (slow, progressive enhancement) making diagnosis based on enhancement rates difficult.11
a b Figure 5: (a) & (b) Seven channel phased array breast coil (MRI Devices) with interventional capabilities.
MRI GUIDED BREAST BIOPSY Sensitivity of contrast enhanced MRI is very high, reported as 94-100%, but a major limitation is its relatively low specificity (37-97%).12 With an imaging modality that is highly sensitive but not highly specific, tissue sampling is required to differentiate between false-positive benign enhancing lesions and true-positive carcinomas. Because MRI detected abnormalities often are not visible with conventional imaging methods and are not palpable, MR-guided interventions are required. Investigators have reported clinical experience with MRI-guided needle localization for surgical excision and percutaneous biopsy using fine needle, automated core needle or vacuum-assisted biopsy probe. MRI-guided breast biopsies pose many challenges, some of which include the requirement for specific MRI-compatible equipment, the need to remove the patient from the magnet in between imaging to perform the biopsy, decreasing lesion conspicuity during the procedure (“vanishing” target), needle artifact obscuring the lesion site and lack of a standard localization technique. A dedicated biopsy compression device with a grid-localizing system is required to accurately perform interventions in the MR (Figures 5 and 6). MRI-guided vacuum assisted biopsy (VAB) is a new technique that is gaining popularity because it allows rapid acquisition of multiple specimens and is a safe and accurate alternative to surgery and to existing MRI-guided needle biopsy methods13. After the biopsy is performed, a clip is deployed into the tissue cavity to serve as a marker for future imaging studies (Figure 7). Because this is a new and costly technique, it is currently only being practiced at research institutes in Canada, such as Sunnybrook and Womenʼs College Health Sciences Centre in Toronto.
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a b Figure 6: (a) & (b) Eight Channel phased array breast imaging system (Sentinelle Medical Inc.) with interventional capabilities
a b c Figure 7: (a) Enhancing lesion; (b) Post VAB and (c) Axial post VAB demonstrating hematoma and clip placement at biopsy site.
CURRENT DEVELOPMENTS MR Spectroscopy (MRS) is a valuable tool to assist in lesion characterization and diagnosis when used in combination with MRI. Cancerous lesions will demonstrate elevated choline levels from increased cellular proliferation. Single voxel spectroscopy cannot aid in the detection of suspicious lesions, however it can play an important role in the characterization of suspicious lesions thus improving specificity. Further development in multivoxel spectroscopic methods, referred to as chemical shift imaging (CSI), may help to improve the sensitivity of choline detection, however this technique is still in the research phase.14 Magnetic resonance elastography (MRE) is a phase-contrastbased MR imaging technique, using mechanical waves to evaluate the elasticity properties of tissues. MRE is a new and promising technique demonstrating high elasticity values in malignant lesions and lowest elasticity values in normal breast parenchyma and fatty tissues. Further research is needed to evaluate the potential applications in breast diagnosis.15 MR/US co-registration is a novel technique, which combines the sensitivity of contrast enhanced MRI with the realtime guidance capabilities of ultrasound. A quick contrast enhanced study is performed in the MRI until the lesion is visualized. The patient is then removed from the magnet and with the aid of optical tracking and software visualization system, the radiologist can visualize the MR-detected lesion under ultrasound. With further development, this technique can potentially aid in the improvement of biopsy guidance or minimally invasive treatment of lesions.16,17
Previously, Joanne worked as MR research technologist at Sunnybrook and Womenʼs Hospital in Toronto where she gained experience in interventional breast MRI. She was the 2005 Co-chair for the Eastern Canada Regional Educational Seminar in Toronto organized by the Section of MR Technologists (www.ismrm.org).
REFERENCES 1.
Warner E, Plewes D, Hill K, Causer P, Zubovits J, Jong R, et al. Surveillance of BRCA1 and BRCA2 Mutation Carriers with Magnetic Resonance Imaging, Ultrasound, Mammography and Clinical Breast Examination. JAMA 2005;293:931.
2.
Kuhl CK. MRI of breast tumours. Eur.Radiol 2000;10:46-58.
3.
Goscin CP, Berman CG. Magnetic Resonance Imaging of the Breast. Cancer Control 2001;8(5):399-406.
4.
Orel SG, Schnall MD. MR Imaging of the Breast for the Staging of Breast Cancer. Radiology 2001;220:13-30.
5.
Kinkel K. MR Imaging: Breast Cancer Staging and Screening. Seminars in Surgical Oncology 2001;20:187-196.
6.
Causer P. Breast Imaging. SMRT 12th Annual Meeting Syllabus May 2003:71-79.
7.
Jacobs MA, Barker P, Bluemke D, Maranto C, et al. Benign and Malignant Breast Lesions: Diagnosis with Multiparametric MR Imaging. Radiology 2003;229:225-232.
8.
Friedman PD, Swaminathan SV, Smith R. Sense Imaging of the Breast. AJR 2005;184:448-451.
9.
Ikeda DM, Hylton NM, Kinkel K, Hochman M, Kuhl C, Kaiser WA, Weinreb JC, Smazal SF, Degani H, Viehweg P, Barclay J, Schnall MD. Development, standardization, and testing of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging studies. Journal of Magnetic Resonance Imaging 2001;13(6):889895.
10.
Goscin CP, Berman C, Clark R. Magnetic Resonance Imaging of the Breast. Cancer Control 2001;8(5):399-406.
11.
Kuhl CK. Differential Diagnosis in Dynamic Contrast-Enhanced MR Imaging of The Breast. Available at: www.star-program.de/data--starprogram/upload/star_abstracts_304_KUHL-1.pdf
12.
Liberman L, Morris E, Lee MJ-Y, Kaplan J, LaTrenta L, Menell J, Abramson A, Dashnaw S, Ballon D, Dershaw D. Breast Lesions Detected on MR Imaging: Features and Positive Predictive Value. AJR 2002;179:171-178.
13.
Liberman L, Morris E, Dershaw D, Thornton C, Van Zee K, Tan L. Fast MRI-Guided Vacuum-Assisted Breast Biopsy: Initial Experience. AJR 2003;181:1283-1293.
14.
Cecil K, Schnall MD, Seigelman E, Lenkinski R. The evaluation of human breast lesions with magnetic resonance imaging and proton magnetic resonance spectroscopy. Breast Cancer Research and Treatment 2001;68:45-54.
15.
Wiberg MK. Magnetic Resonance Imaging in Breast Diagnosis. Fredagen den 22 november 2002, kl. 9.00. Föreläsningssalen M63, Huddinge Universitetssjukhus.
16.
Piron CA, Causer P, Jong R, Shumak R, Plewes DB. A Hybrid Breast Biopsy System Combining Ultrasound and MRI. IEEE Transactions on Medical Imaging, September 2003;22(9).
17.
Muldoon J, Piron CA, Sela G, Causer P, Jong R, Kucharczyk W, Plewes DB. MR-Targeted Ultrasound of Breast Lesions. SMRT 14th Annual Meeting Syllabus, May 2005.
CONCLUSION MR imaging is emerging as the most promising adjunctive imaging modality for breast cancer detection to date. Advantages of MRI compared with conventional imaging techniques include superior evaluation of the extent and multifocality of cancer when staging patients, enhanced detection of recurrence, better evaluation of the augmented breast and improved screening for high-risk women. Although contrast enhanced MRI of the breast is a sensitive method for detecting breast cancer, its variable specificity is a major limitation. Work continues to define the technical requirements for optimal imaging, criteria for image interpretation, development of accurate MR-guided localization and biopsy systems, and cost-effectiveness. These improvements and advancements will result in an expanded role for MRI in womenʼs imaging providing clinicians with the tools needed to better diagnose and manage breast disease. About the Author: Joanne Muldoon graduated from the Red River College MRI/Spectroscopy Technologist Program and is currently working at St. Michaelʼs Hospital in Toronto, Ontario where she is the Clinical Coordinator for MRI.
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