Role of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) in differentiating between benign and malignant breast lesions

ORIGINAL ARTICLE

Role of diffusion-weighted imaging (DWI)

and apparent diffusion coefficient (ADC)

in differentiating between benign and malignant

breast lesions

Wael Abdulghaffar

*

_{, Magdy M. Tag-Aldeen}

a

Medical Imaging Department, Mansoura University, Egypt

b

General Surgery Department, Al Noor Specialist Hospital, Holy Makah, Saudi Arabia

Received 18 August 2013; accepted 14 September 2013 Available online 9 October 2013

KEYWORDS

Diffusion-weighted imaging; Apparent diffusion coefficient; MRI breast

Abstract Objective: To assess the role of DWI and ADC in differentiating between benign and malignant breast lesions.

Materials and methods: 51 patients (age range 24–66 years; mean age 48 years) were included in our study. MRI was done using bilateral fat-suppressed T2- weighted fast spin-echo, STIR, axial T1-weighted fast spin-echo. DWI series were acquired using echo planar imaging pulse sequences incorporated with diffusion gradients and finally dynamic contrast enhancement study was done.

Results: Sixty three lesions were detected in 51 patients included in our study. Twenty one lesions were malignant, three lesions were intermediate and twenty two lesions were fibroadenoma accord-ing to the final histopathological study and seventeen lesions were breast cysts. A total of 21 lesions showed lower ADC values than benign lesions and were in the range of 0.76–1.29·10 3mm2/s and were diagnosed as malignant breast lesions. The sensitivity and specificity for DWI in the differen-tiating malignant from benign breast lesions were calculated and showed 95.4% and 97.5%, respec-tively.

Conclusion: DWI is easy to obtain in short scan time and easy to evaluate, and ADC values can differentiate between benign and malignant breast lesions with high sensitivity and specificity.

2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Radiology and Nuclear Medicine.

1. Introduction

Diffusion is the result of thermal fluctuations with a random pattern and this is often referred to as ‘‘Brownian motion’’. Diffusion-weighted imaging (DWI) is the primary modality that is used to evaluate acute cerebral infarction (1). DWI

* Corresponding author.

E-mail addresses: [email protected], [email protected]

(W. Abdulghaffar).

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has recently been widely used to evaluate other organs such as the ovaries, pancreas, prostate, liver and breast. Until now, there have been few reports published about using the DWI technique to detect and characterize breast tumors, and espe-cially malignant breast tumor(2–3).

Early reports on breast lesion interpretation by MRI relied entirely on lesion enhancement kinetics or lesion morphology

(4). But neither enhancement kinetics nor lesion morphology alone was sufficient for differential diagnosis and resulted in a poor specificity. Over the past decade, new MR techniques and interpretation strategies have been developed to increase the specificity and positive predictive value (PPV) of breast MRI. The most proposed strategy includes obtaining MR images of both high spatial and temporal resolution and ana-lyzing the morphologic and the kinetic features in combina-tion. In recent publications using this new interpretation technique, increased specificities are reported, ranging between 67% and 92%(4–5).

Use of diffusion-weighted (DW) imaging is another ap-proach that may improve MR imaging lesion characterization. DW imaging has the potential to yield physiologic information about the functional environment and movement of water in normal versus abnormal tissue. DW imaging is sensitive to changes in the micro-diffusion of water in the intracellular and extracellular spaces (6–7). Differences in the apparent diffusion coefficients (ADCs) of benign and malignant breast lesions have been reported(8). The ADCs of malignant breast lesions are usually lower than those of benign lesions, indicat-ing restricted water diffusion and increased cellularity. The ADCs of benign lesions are higher, reflecting normal cellular-ity and no restriction of water movement(9–10).

Diffusion-weighted imaging (DWI) was recently integrated into the standard breast MRI examination for this purpose

(11–19). It is a noninvasive technique that measures the ran-dom motion of free water protons and characterizes the tissues with a mechanism that is different from T1 and T2 relaxation. The motion of water protons in the tissue is affected by fluid viscosity, membrane permeability, blood flow, and cellularity of the tissue. For the quantification of this motion, apparent diffusion characteristic (ADC) values are used. Since 2002, many studies(11–18)have revealed the usefulness of DWI in differentiation of malignant from benign tumors of the breast. In these studies, sensitivity in the range of 80–96% and specificity in the range of 46–91% were reported. Recently Yabuuchi et al.(18)revealed 92% sensitivity and 86% specific-ity and Partridge et al.(20)revealed 10% improvement in the PPV with the addition of DWI to dynamic contrast-enhanced MRI (DCE-MRI) in the characterization of breast masses.

2. Objective

The aim of our study was to shed light on the role of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) for the assessment of breast lesions.

3. Materials and methods 3.1. Patients

Between February 2011 and February 2013, 51 patients (age range, 24–66 years; mean age, 48 years) with suspicious clinical

findings and positive diagnoses at mammography were included in our study. Patients were imaged using conventional MRI, DWI and DCE-MRI before biopsy of their breast tu-mors. Approval for the study was obtained from the local eth-ics committee in the Alnoor specialist hospital, in Holey Makkah. Written informed consent was obtained from all pa-tients before MRI. In all papa-tients, MRI was performed bilaterally.

3.2. MRI technique

MRI examinations were performed before biopsy (in solid breast lesions) and within the 2 weeks before surgery. Patients were examined in the prone position using a 1.5-T MRI scan-ner (Magnetom Espree, Siemens Healthcare) with a dedicated 4-channel phased array bilateral breast coil. Before administra-tion of contrast media, axial bilateral fat-suppressed T2-weighted fast spin-echo, axial STIR, axial T1-T2-weighted fast spin-echo and DWI series were acquired.

DW image was performed in axial slice orientation using echo planar imaging pulse sequences incorporating with diffu-sion gradients. DW EPI with fat suppresdiffu-sion was applied using TR/TE of about 8400/98 ms, FOV of 340·170 mm, matrix: 192·96 and a slice thickness of 4 mm. Spectral pre-saturation with inversion recovery (SPAIR) was used for fat suppression. An acceleration factor of two was applied using the general-ized auto-calibrating partially parallel acquisition (GRAPPA) of parallel imaging technique. Motion-probing gradients in three orthogonal orientations were applied with b values of 50, 400 and 800 using 3-scan trace calculation. Isotropic diffu-sion-weighted (trace) images were reconstructed for eachb va-lue. For quantitative analysis of the data acquired from DWI, ADC maps were automatically created using software pro-vided by the MRI system manufacturer (Syngo, Siemens Healthcare) using three b values (50, 400, and 800 s/mm2_).

We apply the DW sequences prior to the dynamic scan as the T1 relaxation due to the contrast agent will cause changes to the inversion of the tissue and thus can have a strong impact.

Finally, dynamic axial bilateral breast images of fat-sup-pressed high-resolution T1-weighted 3D fast gradient-echo images were sequentially acquired. Five measurements were acquired one before and four after the administration of contrast media. For the dynamic study, gadopentetate dimeglumine (Magnevist) was administered IV using a power injection at a dose of 0.1 mmol/kg of body weight at a flow rate of 2 mL/s, followed by flushing with 25 mL of saline. The parameters were as follows: TR/TE 4.2/1.6; flip angle 15; FOV 340·340 mm; matrix 512·410; thick-ness 0.9 mm; acquisitions 1; and acquisition time 110 s. SPAIR for fat suppression and a GRAPPA acceleration fac-tor of two for parallel imaging technique were also applied. DCE was done in 50 cases and contraindicated in one pa-tient with renal failure on hemodialysis with GFR less than 30 Ml/min.

4. Results

Sixty three lesions were detected in the 51 patients included in our study. Twenty one lesions were malignant, three lesions were intermediate and twenty two lesions were fibroadenoma

according to the final histopathological study and seventeen le-sions were breast cysts.

According to the ADC values (Table 1) thirty nine lesions were benign with 17 lesions were cysts (Fig. 1), and showed mean ADC values of 1.89 ± 0.31·10 3 mm2/s and ADC range of (1.75–2.56·10 3 mm2/s) and twenty two lesions were fibroadenomas (Fig. 2) and showed mean ADC values of 1.48 ± 0.33·10 3mm2/s and ADC range of 1.23– 1.67·10 3_mm2_/s.

In our study three lesions were intermediate (phylloides) le-sions (Fig. 3) and showed mean ADC values of 1.25 ± 0.15·10 3 mm2/s and ADC range of 1.15–1.45·10

3 mm2

/s and twenty one lesions were malignant lesions (Figs. 4 and 5) and showed mean ADC values of 0.93 ± 0.27·10

3

mm2/s and ADC range of 0.76–1.29·10 3mm2/s (See

Fig. 6).

A total of 21 lesions showed lower ADC values than benign lesions and were in the range of 0.76–1.29·10 3_mm2_{/s and}

were diagnosed as malignant breast lesions.

In our study, using a cutoff point 1.25·10 3 mm2_{/s, the}

sensitivity, and specificity for DWI in the differentiating malig-nant breast lesions from benign breast lesions obtained were

95.4% and 97.5%, respectively and total accuracy of about 96.7%.

5. Discussion

Breast MRI is the widely accepted diagnostic approach for evaluating the breast. To improve the sensitivity of detecting breast cancer, several diverse techniques are used for breast MRI(21). In particular, dynamic-enhanced MRI provides for evaluating multiple foci of carcinoma in the breast and it dis-plays extremely high sensitivity for identifying breast cancer. However, dynamic-enhanced breast MRI has some disadvan-tages such as being time-consuming and costly, the possible side effects of the contrast media and the relatively low specificity compared to mammography and ultrasonography(22–24).

Generally in biological tissues, microscopic motion in-cludes both the molecular diffusion of water and the blood microcirculation in the capillary network, and both diffusion and perfusion affect the ADC values. Because of the extent of micro-vessels in malignant breast tumor, the ADC value can be strongly affected by perfusion when the b value is small. A previous report insisted that b-values less than

Figure 1 A 46-year-old woman with small right breast fibroadenoma. (A) Axial post-contrast T1-weighted image shows small homogeneously enhancing right breast mass (white arrow). (B)STIRimage shows small high signal intensity mass. (C) The axial diffusion weighted image shows small slightly high-signal intensity mass. (D) ADC: the apparent diffusion coefficient value of the right breast tumor was 1.45·10 3_mm2_/s.

Table 1 Different ADC values for malignant, intermediate, and benign breast lesions.

Types of lesions No. of lesionsN= 63 ADC values (·10 3_mm2_/s)

Range of ADC Mean ADC

Malignant breast lesions 21 0.76–1.29 0.93 ± 0.27

Intermediate lesions (Phylloides) 3 1.15–1.45 1.25 ± 0.15

Fibroadenomas 22 1.23–1.67 1.48 ± 0.33

750 s/mm2 _{are most effective for detecting breast tumors}

(21). However, we used EPI with a b-value up to 800 s/ mm2_{so we could obtain diffusion effects without any}

signif-icant image distortion.

Benign breast tumor including breast cyst and fibroade-noma demonstrate high signal intensity on T2-weighted MR images; however, the signal intensity of benign tumors is

vari-able on diffusion-weighted images and may be influenced byb

value much more than the signal intensity of malignant tumors because of T2 shine-through. These benign tumors may dis-play high signal intensity on diffusion-weighted images ob-tained at lower b values; on diffusion-weighted images obtained at higher b values, these tumors become isointense and may not be identified(17,18).

Figure 2 A 43-year-old woman with left breast cyst. (A) Axial post-contrast T1-weighted image shows non enhancing left breast lesion (white arrow). (B)STIR image displays high signal intensity of the mass. (C) The axial diffusion weighted image shows high-signal intensity mass (Which may be due to shine through effect). (D) ADC: the apparent diffusion coefficient value of the left breast cyst was 1.96·10 3_mm2_/s.

Figure 3 A 47 year-old woman with large left breast phylloides tumor. (A) The axial post-contrast T1-weighted image shows markedly enhancing left breast mass (white arrow) and lobulated parts (white arrow heads). (B)STIRimage shows mixed signal intensity mass. (C) The axial diffusion weighted image shows mixed signal intensity mass. (D) ADC: the apparent diffusion coefficient value of the left breast tumor was 1.35·10 3_mm2_/s.

In our study, we have 3 cystic lesions of high signal intensity on DWI. The signal intensity of cysts remains high atbvalues of 800 s/mm2 or lower, which were used in our breast MR imaging. A simple cyst shows greatly reduced signal intensity on an image obtained at a bvalue of 1500 s/mm2 compared

with an image obtained at abvalue of 1000 s/mm2with the same window setting. However, a cyst with condensed or pro-teinaceous content sometimes has a high signal intensity, even at higherbvalues(25–27).

Figure 4 A 51 year-old woman with right breast ductal carcinoma. (A) Axial post-contrast T1-weighted image shows markedly enhancing right breast mass (white arrow). (B)STIRimage shows high signal intensity mass with speculation. (C) The axial diffusion weighted image shows high-signal intensity mass with speculation. (D) ADC: the apparent diffusion coefficient value of the right breast tumor was 0.83·10 3_mm2_/s.

Figure 5 A 63 year-old woman with left breast invasive ductal carcinoma. (A) The axial post-contrast T1-weighted image shows markedly enhancing left breast mass with speculation (white arrow). (B)STIRimage shows high signal intensity mass with speculation. (C) The axial diffusion weighted image shows high-signal intensity mass with speculation. (D) ADC: the apparent diffusion coefficient value of the left breast tumor was 1.15·10 3_mm2_/s.

A major diagnostic problem associated with phylloides tu-mors is that fine-needle aspiration cytology, or mammography, or US can not be used to differentiate fibroadenomas from phyllodes tumors. Fine-needle aspiration cytology may lead to the misdiagnosis of a benign phyllodes tumor as a fibroad-enoma. According to previous study results, either a hypoin-tense area on T2-weighted images or a low ADC area on diffusion-weighted images is suggestive of an interstitial hyper-cellular lesion. Therefore, MR imaging can be used to guide the selection of an appropriate biopsy site(28). In our study there is limitation in phylloides the assessment because diffu-sion-weighted MR imaging was performed in only 3 patients; therefore, the correlation between ADC and histologic grade may be weak.

Malignant breast masses usually have higher cellularity, the majority of invasive ductal carcinomas demonstrate higher sig-nal intensity and lower ADC values than do benign tumors and normal breast parenchyma on diffusion-weighted images. In addition, there is occasionally central hypointensity in IDCs, which is thought to represent necrosis or fibrosis. This appearance usually corresponds to the appearance on con-trast-enhanced T1-weighted MR images. High-resolution dif-fusion-weighted imaging can display the morphologic features of the tumor, which may be helpful for interpretation

(9,17,25,26). In our study, while calculating ADC values, we avoid including the central necrosis of the tumor, otherwise, the resulting ADC value will not be accurate and will not reli-ably reflect the physiologic environment of the tumor.

In our study the mean ADC value for benign breast lesions was 1.48 ± 0.33·10 3 mm2_{/s and ADC range was 1.23–}

1.67·10 3mm2/s and for malignant breast lesions, mean ADC value was 0.93 ± 0.27·10 3 mm2/s and ADC range was 0.76–1.29·10 3 mm2/s.

These values agreed with the previous studies(21,27,29–31)

regarding the mean ADC values in differentiating benign from malignant breast lesions.

In our study, the sensitivity, and specificity for DWI in the differentiating malignant breast lesions from benign breast le-sions were 95.4% and 97.5%, respectively. The sensitivity and specificity of diffusion WI in differentiating benign and

malig-nant breast lesion in our study is in agreement of previous studies(15,19,32)which showed the sensitivity and specificity of DWI in the differentiation between benign and malignant breast lesions were ranging from 81% to 97%, and from 80% to 100%, respectively.

6. Conclusion

In conclusion, DWI is easy to obtain in short scan time and easy to evaluate, and ADC values can differentiate between be-nign and malignant breast lesions with high sensitivity and specificity. DWI is problem solving sequence in patients with contraindication to contrast media. We add DWI sequence to the standard MRI examination of the breast before contrast study and according to the result of our study it is a promising sequence. However, more studies with larger populations are needed for more evaluation of DWI in breast lesions.

Conflict of interest

We have no conflict of interest to declare.

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