Diffusion weighted magnetic resonance imaging of the breast: protocol optimization, interpretation, and clinical applications

Abstract

Diffusion-weighted magnetic resonance (MR) imaging (DWI) has shown promise for improving the positive predictive value of breast MR imaging for detection of breast cancer, evaluating tumor response to neoadjuvant chemotherapy, and as a noncontrast alternative to MR imaging in screening for breast cancer. However, data quality varies widely. Before implementing DWI into clinical practice, one must understand the pertinent technical considerations and current evidence regarding clinical applications of breast DWI. This article provides an overview of basic principles of DWI, optimization of breast DWI protocols, imaging features of benign and malignant breast lesions, promising clinical applications, and potential future directions.

Keywords: Apparent diffusion coefficient; Breast MR imaging; Breast cancer; Diffusion-weighted imaging; Neoadjuvant chemotherapy; Oncologic imaging; b-value.

Figure 1

Schematic comparing water diffusion in tissues with differing cellularity. The net distance (indicated by red dashed arrows) traveled by protons in the extracellular fluid during a specific time is much greater in regions of low cellularity (right) where random motion is not impeded by the presence of cellular membranes. In this way, the degree of water diffusion in biologic tissue is inversely correlated to the tissue cellularity and the integrity of cell membranes.

Figure 2

Pulse sequence diagram of a diffusion-weighted spin echo sequence based on a Stejskal-Tanner encoding scheme. Two precisely matched diffusion-sensitizing gradients are inserted before and after a 180° RF refocusing pulse. Important factors defining the degree of diffusion-sensitization are the gradient amplitude (G), duration (δ), and the time between the two sensitizing gradients (Δ).

Figure 3

Example images obtained with DWI scan. Shown are corresponding slices from A. S₀ with b=0 s/mm² (primarily T2-weighted). B. S_D with b=800 s/mm². C. ADC map. An invasive tumor (arrow) exhibits reduced diffusivity on DWI, appearing hyperintense on S_D (b=800 s/mm²) images (B) and hypointense on the ADC map (C).

Figure 4

Influence of diffusion weighting (b-value) on breast ADC measures. Data acquired in a single normal volunteer over a range of b-values. Data points represent the mean of bilateral ADC fibroglandular tissue measures at each b value. ADC generally decreases with increasing b value. Adapted from Magn Reson Imaging. 2010 Apr;28(3):320-8.

Figure 5

Effect of b-value on lesion conspicuity. The chosen b-value can greatly affect the resulting image contrast, as well as ADC. In this example, a malignant lesion (arrow) is best visualized at higher b-values. Low b-values may allow too much signal from normal tissue. At higher b-values, the SNR is decreased, but lesion contrast may be increased.

Figure 6

Example of a patient with low mammographic parenchymal breast density. A 60 year old female with a family history of breast cancer underwent breast MRI for high risk screening. A. MLO view mammogram demonstrating scattered fibroglandular densities in a normal breast. Axial MR images are shown at the level of the nipple. B. Post-contrast T1 weighted image shows sparse fibroglandular tissue. C. DWI b=0 s/mm² image where signal comes primarily from vessels and fibroglandular tissue. D. ADC map (mean ADC = 1.04 ×10⁻³mm²/sec for normal fibroglandular tissue).

Figure 7

Example of a high quality DWI study in a patient with a breast lesion. A. Enhancing lesion and regions of normal appearing fibroglandular and adipose tissue are readily distinguished on the post-contrast T1 weighted image. B. DWI b=0 s/mm² image demonstrates uniform, effective fat suppression with good SNR in fibroglandular tissue and no apparent artifacts or distortions. C. The lesion retains high signal on the b=800 s/mm² diffusion-weighted image due to restricted diffusion. Fat signal appears relatively brighter on the b=800 s/mm² image due to signal decrease of the fibroglandular tissue.

Figure 8

Common technical challenges of breast DWI. Illustrated in separate subjects are examples of A. Poor shimming causing poor fat suppression and detrimental chemical shift artifacts on DWI. B. Low SNR of b=0 s/mm² image due to long TE (100ms). C. Magnetic susceptibility artifact (arrows) causing distortion at air/tissue skin surface on DWI (right) in comparison with undistorted T1-weighted image (left). D. Another example of distortion at air/tissue skin surface (arrow) due to magnetic susceptibility differences (right) in comparison with undistorted T1-weighted image (left).

Figure 9

Spatial misregistration between images within a DWI sequence due to motion or eddy-current artifacts causes ADC inaccuracies. In this example, the lesion appears shifted in the DWIx b=600 s/mm² image (obtained with diffusion gradients applied in the x direction) with respect to the b=0 s/mm² image and other b=600 s/mm² images (obtained with gradients in the y and z directions) due to eddy current effects. This misalignment causes an artifactual increase in ADC (arrow).

Figure 10

Example of basic region of interest (ROI) approach for quantitation of ADC values. Lesions are typically first identified on contrast-enhanced DCE-MRI and then ROIs are defined on DWI images at the corresponding location (outlined in yellow). The ROI is propagated to the ADC map to calculate the mean pixel value. Examples given illustrate A. Large 37mm spiculated mass (with clip artifact) determined to be invasive ductal carcinoma. B. Small 9mm clumped nonmass enhancement determined to be DCIS. C. Large 67mm segmental, heterogeneous nonmass enhancement determined to be LCIS. D. Region of normal appearing fibroglandular breast tissue.

Figure 11

Malignant breast lesion. A 44 year old female with a family history of breast cancer presents for a high risk screening MRI. Mammogram 6 months earlier was negative. Axial 3T MR images are shown. An 11 mm irregular mass (arrow) with spiculated margins and heterogeneous internal enhancement is present in the central right breast, posterior depth. The mass demonstrates restricted diffusion. The diffusion characteristics and DCE-MRI images are suspicious. This mass was biopsied and was invasive ductal carcinoma. A. Post-contrast T1W subtraction MIP. B. Post-contrast T1W image. C. DWI b = 800 s/mm² image demonstrates a high signal intensity mass (arrow). D. ADC map demonstrates corresponding low values in the mass (mean ADC = 0.88 ×10⁻³ mm²/sec) (arrow).

Figure 12

Malignant breast lesion. A 42 year old female with history of invasive lobular cancer on the right, status post-mastectomy presents for high risk screening MRI. Mammogram performed the same day was negative. Axial 3T MR images are shown. An 11 mm lobular mass (arrow) with irregular margins and heterogeneous internal enhancement is present in the central left breast, mid depth. The mass demonstrates restricted diffusion. The diffusion characteristics and DCE-MRI images are suspicious. This mass was biopsied and was invasive lobular carcinoma. A. Post-contrast T1W subtraction MIP. B. Post-contrast T1W image. C. DWI b = 800 s/mm² image demonstrates a high signal intensity mass (arrow). D. ADC map demonstrates corresponding low values in the mass (mean ADC = 1.12 ×10⁻³ mm²/sec) (arrow)..

Figure 13

Noninvasive malignancy. A 58 year old female with a family history of breast cancer presents for a high risk screening MRI. Mammogram performed the same week was negative. Axial 3T MR images are shown. A 9 mm focal area of clumped non-mass enhancement (arrow) is present in the central left breast, anterior depth. The non-mass enhancement demonstrates restricted diffusion. The diffusion characteristics and DCE-MRI images are suspicious. The area was biopsied and was high grade DCIS. A. Post-contrast T1W subtraction MIP. B. Post-contrast T1W image. C. DWI b = 800 s/mm² image demonstrates an area of high signal intensity (arrow). D. ADC map demonstrates corresponding low values in the lesion (mean ADC = 1.12 ×10⁻³mm²/sec) (arrow).

Figure 14

Benign lesion. A 53 year old female BRCA1 carrier presented for a high risk screening MRI. Axial 3T MR images are shown. A 7 mm oval mass (arrow) with smooth margins and homogeneous enhancement is present in the central right breast, mid depth. The mass does not demonstrate restricted diffusion and has high T2 signal (not shown). Based on conventional MR imaging characteristics, the mass was assigned a benign (BI-RADS 2) assessment code instead of recommending an image guided biopsy. A. Post-contrast T1W subtraction MIP. B. Post-contrast T1W image. C. DWI b = 800 s/mm² image demonstrates a high signal intensity mass (arrow). D. ADC map demonstrates corresponding high values (mean ADC = 1.84 ×10⁻³mm²/sec) (arrow).

Figure 15

Study of 175 false positive lesions (recommended for biopsy based on DCE-MRI and determined to be benign). A. Box plots show median and range of ADCs for each subtype in the order of frequency. AD = adenosis, AM = apocrine metaplasia, DHU = usual ductal hyperplasia, FA = fibroadenoma, FC = fibrocystic change, FF = focal fibrosis, FM = fibromatosis, HE = hemangioma, IF = inflammation, LN = lymph node, LoN = lobular neoplasia (ALH, LCIS), NBT = normal breast tissue, PA = papilloma, PSH = pseudoangiomatous stromal hyperplasia. Dashed horizontal line indicates previously determined ADC diagnostic threshold of 1.81 × 10⁻³ mm²/s. High risk lesions (ADH, LoN), indicated by hashed pattern, were the most common non-malignant subtypes with ADC below threshold, overlapping with malignancies. B. Benign (non-high-risk) lesions (n = 147) showed significantly higher ADCs than high-risk lesions (n = 28) and malignant lesions (n = 31, from an earlier study). * = Significant difference from benign lesions, p < .0001. However, there were no differences in ADC between the high-risk and malignant lesion types (p = .1). Reprinted with permission Radiology 2012 Dec;265(3):696-706.

Figure 15

Study of 175 false positive lesions (recommended for biopsy based on DCE-MRI and determined to be benign). A. Box plots show median and range of ADCs for each subtype in the order of frequency. AD = adenosis, AM = apocrine metaplasia, DHU = usual ductal hyperplasia, FA = fibroadenoma, FC = fibrocystic change, FF = focal fibrosis, FM = fibromatosis, HE = hemangioma, IF = inflammation, LN = lymph node, LoN = lobular neoplasia (ALH, LCIS), NBT = normal breast tissue, PA = papilloma, PSH = pseudoangiomatous stromal hyperplasia. Dashed horizontal line indicates previously determined ADC diagnostic threshold of 1.81 × 10⁻³ mm²/s. High risk lesions (ADH, LoN), indicated by hashed pattern, were the most common non-malignant subtypes with ADC below threshold, overlapping with malignancies. B. Benign (non-high-risk) lesions (n = 147) showed significantly higher ADCs than high-risk lesions (n = 28) and malignant lesions (n = 31, from an earlier study). * = Significant difference from benign lesions, p < .0001. However, there were no differences in ADC between the high-risk and malignant lesion types (p = .1). Reprinted with permission Radiology 2012 Dec;265(3):696-706.

Figure 16

Benign lesion. A 51-year-old woman with a personal history of cancer in the right breast underwent breast MRI for high-risk screening. Axial MR images are shown, with insets indicating ROI for DWI quantitation. A 19-mm lobular mass (arrow) with smooth borders and heterogeneous enhancement is present in the left breast 27 mm from the nipple at middle depth and assigned a BI-RADS category 5. The lesion is a biopsy proven fibroadenoma. A. Post-contrast T1W subtraction image. B. Post-contrast T1W image: the lesion (arrow) shows 100% persistent delayed kinetics (blue). C. Axial T2W MR image. The lesion is hyperintense. D. DWI image demonstrates a high signal intensity mass. E. ADC map demonstrates corresponding high values (mean ADC = 2.11 × 10⁻³mm²/sec). F. Histologic examination. Hematoxylin-eosin stain; original magnification, ×20. Reprinted with permission Radiology 2012 Dec;265(3):696-706.

Figure 17

High risk lesion. A 61-year-old woman with personal history of right-breast DCIS underwent breast MRI for high-risk screening. Axial MR images are shown, with insets indicating ROI for DWI quantitation. A 13 mm lobular heterogeneously enhancing mass (arrow) with a smooth margin is present in the subareolar region of the left breast and is classified as BI-RADS category 4. The lesion is biopsy proven atypical ductal hyperplasia with intraductal papilloma. A. Post-contrast T1W subtraction image. B. Post-contrast T1W image: the lesion (arrow) shows mixed kinetics overall, 28% delayed persistent enhancement (blue), 34% delayed plateau (green), and 38% delayed washout (red). C. Axial T2W MR image. The lesion (arrow) is hypointense. D. DWI image demonstrates a high signal intensity mass (arrow). E. ADC map demonstrates corresponding low values (mean ADC = 1.06 × 10⁻³ mm²/sec) (arrow). F. Histologic examination. Hematoxylin-eosin stain; original magnification, ×200. Reprinted with permission Radiology 2012 Dec;265(3):696-706.

Figure 18

Cyst in a 53 year old female BRCA1 carrier who underwent a high risk screening MRI. Axial 3T MR images are shown. A 10 mm round mass (arrow) with smooth margins and rim enhancement is present in the central right breast, mid depth. The mass demonstrates restricted diffusion. If diffusion images were used alone, this mass would be suspicious. Correlation with DCE-MRI images demonstrates thin rim enhancement and high T2 signal, which allowed characterization as a benign proteinaceous cyst (BI-RADS 2). A. Post-contrast T1W image. B. Post-contrast T2W image. C. Post-contrast T1W subtraction image. D. DWI b = 800 s/mm² image demonstrates a high signal intensity mass (arrow). E. ADC map demonstrates corresponding low values (mean ADC = 0.48 ×10⁻³ mm²/sec) (arrow).

Figure 19

Hematoma in a 54 year old female who underwent a staging MRI for newly diagnosed cancer in the right breast. The patient had a left breast stereotactic biopsy 21 days ago that was benign and concordant. Axial 3T MR images are shown. A 7 mm round mass (arrow) with smooth margins and no enhancement is present in the central left breast, anterior depth. The mass demonstrates restricted diffusion. If diffusion images were used alone, this mass would be suspicious. Correlation with DCE-MRI images demonstrated no enhancement, high T2 signal, and high pre-contrast T1 signal, which allows characterization as a benign hematoma (BI-RADS 2). Incidentally noted is susceptibility artifact from a biopsy clip in the anterior aspect of the hematoma. A. Pre-contrast T1W image. B. Post-contrast T2W image. C. Post-contrast T1W subtraction image. D. DWI b = 800 s/mm² image demonstrates a high signal intensity mass (arrow). E. ADC map demonstrates corresponding low values (mean ADC = 0.28 ×10⁻³mm²/sec) (arrow).

Figure 20

Example of serial DWI tumor measures in a 48 year old female undergoing chemotherapy (cyclophosphamide/doxorubicin), for invasive ductal carcinoma. A. Pretreatment: the tumor is identified on DCE-MRI (left) and an ROI is drawn at the corresponding location of hyperintensity on the DWI b=800 s/mm² image (middle) and propagated to the ADC map (mean ADC = 1.09 ×10⁻³mm²/sec). B: Post 3 months of treatment: the same tumor region is measured, with the ROI adjusted for any change in size and shape of the lesion (mean ADC = 1.99 ×10⁻³mm²/sec). This subject exhibited a complete pathologic response at the end of neoadjuvant therapy.

Figure 21

Axillary metastasis. A 30 year old female underwent a staging MRI after newly diagnosed invasive ductal carcinoma in the left breast. Axial 3T MR images are shown. A 23 mm irregular mass (arrow) with smooth margins and homogeneous internal enhancement is present in the left axilla. The mass demonstrates restricted diffusion. The diffusion characteristics and DCE-MRI images are suspicious. This mass was biopsied and was metastatic carcinoma. A. Post-contrast T1W image. B. Post-contrast T1W subtraction image. C. DWI b = 800 s/mm² image demonstrates a high signal intensity mass (arrow). D. ADC map demonstrates corresponding low values (mean ADC = 0.98 ×10⁻³mm²/sec) (arrow).

Figure 22

Improved signal enables increased spatial resolution on diffusion weighted MRI at 3T when compared to 1.5T in a patient newly diagnosed with DCIS (arrow). There is improved anatomic detail for both the reference post-contrast T1-weighted image with fat saturation at 3T (B) and the DWI image at 3T (D) when compared to respective images at 1.5T (A, C). J Magn Reson Imaging. 2012 May;35(5):1222-6.

Figure 23

Reduced-field of view (rFOV) imaging can be used to improve spatial resolution and allow air-tissue interfaces to be excluded from the shim volume. This has been shown to reduce susceptibility induced artifacts and image distortion. In the example case, overall image quality was improved on T2 weighted (b = 0) and DW images for rFOV DWI compared to standard FOV. Singer L, et al. Acad Rad 2012; 19(5):526–534.