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Diagnostic Usefulness of Combination of Diffusion-weighted Imaging and T2WI, Including Apparent Diffusion Coefficient in Breast Lesions

Posted Apr 30, 2018 Updated Apr 10, 2023
By Keum Won Kim MD PhD , Cherie M. Kuzmiak DO , Young Joong Kim MD , Jae Young Seo MD , Hae Kyoung Jung MD , Mu-Sik Lee MD PhD
12 min read

Purpose

This study aimed to compare the diagnostic values of a combination of diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and to evaluate the correlation of DWI with the histologic grade in breast cancer.

Materials and Methods

This study evaluated a total of 169 breast lesions from 136 patients who underwent both DCE-MRI and DWI (b value, 1000s/mm 2 ). Morphologic and kinetic analyses for DCE-MRI were classified according to the Breast Imaging-Reporting and Data System. For the DWI-T2WI set, a DWI-T2WI score for lesion characterization that compared signal intensity of DWI and T2WI (benign: DWI-T2WI score of 1, 2; malignant: DWI-T2WI score of 3, 4, 5) was used. The diagnostic values of DCE-MRI, DWI-T2WI set, and combined assessment of DCE and DWI-T2WI were calculated.

Results

Of 169 breast lesions, 48 were benign and 121 were malignant (89 invasive ductal carcinoma, 24 ductal carcinoma in situ, 4 invasive lobular carcinoma, 4 mucinous carcinoma). The mean apparent diffusion coefficient (ADC) of invasive ductal carcinoma (0.92 ± 0.19 × 10 −3 mm 2 /s) and ductal carcinoma in situ (1.11 ± 0.13 × 10 −3 mm 2 /s) was significantly lower than the value seen in benign lesions (1.36 ± 0.22 × 10 −3 mm 2 /s). The specificity, positive predictive value (PPV), and accuracy of DWI-T2WI set and combined assessment of DCE and DWI-T2WI (specificity, 87.5% and 91.7%; PPV, 94.3% and 96.2%; accuracy, Az = 0.876 and 0.922) were significantly higher than those of the DCE-MRI (specificity, 45.8%; PPV, 81.7%; accuracy, Az = 0.854; P < .05). A low ADC value and the presence of rim enhancement were associated with a higher histologic grade cancer ( P < .05).

Conclusion

Combining DWI, T2WI, and ADC values provides increased accuracy for differentiation between benign and malignant lesions, compared with DCE-MRI. A lower ADC value was associated with a higher histologic grade cancer.

Introduction

Diffusion-weighted imaging (DWI) is currently being evaluated to increase the specificity of breast magnetic resonance imaging (MRI) . DWI is a noninvasive technique that uses the biological characteristics of Brownian movement of protons in water. High signal intensity (SI) on DWI and a low apparent diffusion coefficient (ADC) value are correlated with highly cellular tissue and decreased movement of molecules . When DWI is used, malignant breast lesions have higher SI than with T2-weighted imaging (T2WI) fast spin echo (FSE) MRI, and malignant breast lesions have low ADC values. Malignant breast lesions display lower SI on T2WI than benign lesions because of shorter T2 relaxation time . The high cellularity of cancer cell caused the restriction of Brownian motion in extracellular water molecules around cancer cells. In contrast, fluid in cysts consists of free water molecules and a higher ADC .

Multiple studies have evaluated DWI and ADC value for breast tumor and evaluated the diagnostic value of combined dynamic contrast-enhanced (DCE) MRI and DWI for breast cancer detection . The detectability on DWI was higher than T1WI or T2WI for breast tumor, and the mean ADC value of invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) were lower than benign breast lesions. Kul et al. revealed the combination of DWI and DCE-MRI has the potential to increase the specificity of breast MRI. Another study reported that combined DCE-MRI and DWI had superior diagnostic accuracy than either DCE-MRI or DWI alone for the diagnosis of breast cancer . However, those studies did not compare each SI between DWI and T2WI for characterization of the lesion. In addition, those studies did not compare the accuracy of DWI-T2WI combination with that of DCE-MRI. In those studies, T2WI and DCE-MRI were used as pilot images for localizing the lesion. Thus, the purpose of our study is to compare the diagnostic values of a combination of DWI and T2WI with DCE-MRI, and to investigate the correlation of DWI, including ADC value, with the histologic grade in breast cancer lesions.

Materials and Methods

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MRI Protocol

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TABLE 1

Protocols of Each Sequence of Breast MRI

Fat-suppressed Turbo Spin-echo (TSE-FS) T2WI Postcontrast T1WI Fast Field Echo (T1WI-FFE) DW Single-shot Echo-planar Imaging with Sensitivity Encoding (SENSE) TR/TE 4375/70 4.4/1.6 1835/57 Flip angle 90° 10° 90° Slices 30 270 30 Field of view 350 × 350 mm 340 × 340 mm 350 × 350 mm Matrix 528 × 512 512 × 510 116 × 115 Number of excitation (NEX) 1.0 1.0 2.0 SENSE 1.5 2.0 0 Section thickness 4 mm 1.5 mm 4 mm Intersection gap 0 0 0 Acquisition time 4 min 8 min 3 min b Value 0 and 1000 s/mm 2

DW, diffusion-weighted; MRI, magnetic resonance imaging; TR/TE, repetition time/echo time; T1WI, T1-weighted imaging; T2WI, T2-weighted imaging.

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DWI Acquisition and ADC Analysis

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Reader Study Analysis

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TABLE 2

Reader DWI-T2WI Score with Corresponding Probability of Malignancy and DWI Findings for Lesion Characterization

DWI-T2WI score 1 Definitely benign T2 high SI/DWI low SI DWI-T2WI score 2 Probably benign T2 high SI/DWI intermediate SI DWI-T2WI score 3 Possibly malignant T2 high SI/DWI high SI DWI-T2WI score 4 Probably malignant T2 intermediate SI/DWI high SI DWI-T2WI score 5 Definitely malignant T2 intermediate or low SI/DWI very high SI

DWI-T2WI, diffusion-weighted imaging and T2-weighted imaging; SI, signal intensity

Figure 1, Examples of breast lesions for reader diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) scores used for lesion characterization. (a) DWI-T2WI score 1 (definitely benign) showed high signal intensity (SI) on T2WI and low SI on DWI; (b) DWI-T2WI score 2 (probably benign) showed high SI on T2WI and intermediate SI on DWI; (c) DWI-T2WI score 3 (possibly malignant) showed high SI on T2WI and high SI on DWI; (d) DWI-T2WI score 4 (probably malignant) showed intermediate SI on T2WI and high SI on DWI; and (e) DWI-T2WI score 5 (definitely malignant) showed low SI on T2WI and very high SI on DWI.

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Statistical Analysis

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Results

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TABLE 3

Pathologic Result of Breast Lesions

Benign (n = 48) Malignancy (n = 121) 6 Fibroadenoma

12 Fibrocystic change

3 Columnar-cell changes

4 Phyllodes tumor

12 Intraductal papilloma

1 Tuberculous granulomatosis

1 Diabetes mellitus mastopathy

2 Sclerosing adenosis

7 Atypical ductal hyperplasia 88 IDC

24 DCIS

5 Invasive lobular carcinoma

4 Mucinous carcinoma

IDC, invasive ductal carcinoma; DCIS, ductal carcinoma in situ.

TABLE 4

Correlation of DWI-T2WI Scores with Histology of the Lesions

DWI-T2WI Score Benign (n = 48) Malignant (n = 121) Number of Lesions (n = 169)P Value \* Score 1: definitely benign 9 (18.7) 0 (0) 9 (5.3) .00 Score 2: probably benign 33 (6.9) 22 (18.2) 55 (32.5) Score 3: possibly malignant 2 (4.2) 23 (19.0) 25 (14.8) Score 4: probably malignant 3 (6.3) 37 (30.6) 40 (23.7) Score 5: definitely malignant 1 (2.1) 39 (32.2) 40 (23.7)

DWI-T2WI, diffusion-weighted imaging and T2-weighted imaging.

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TABLE 5

Comparison of Sensitivity, Specificity, PPV, and AUC of DCE-MRI, DWI-T2WI Set, and Combined Assessment of DCE and DWI-T2WI

Results DCE-MRI Set DWI-T2WI Set Combined Assessment of DCE and DWI-T2WI Sensitivity (%) 95.9 81.8 83.5 Specificity (%) 45.8 87.5 91.7 PPV (%) 81.7 94.2 96.2 AUC (95% CI) 0.854 (0.797–0.911) 0.876 (0.818–0.934) 0.922 (0.878–0.965)

AUC, area under the receiver operating characteristic curve; CI, confidence interval; DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging; DWI-T2WI, diffusion-weighted imaging and T2-weighted imaging; PPV, positive predictive value.

Figure 2, Composite receiver operating characteristic (ROC) curves. The ROC curves show reader confidence in the characterization of malignant breast tumors using the diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) set, the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) set, and combined assessment of MRI. The mean area under the ROC (Az) values are 0.922 (combined assessment of MRI), 0.876 (DWI-T2WI set), and 0.854 (DCE-MRI set) ( P < .05). FPF = false-positive fraction; TPF = true positive fraction.

Figure 3, A 33-year-old woman with a palpable mass in the left breast. Pathology confirmed a benign phyllodes tumor. (a) Precontrast axial T1-weighted fast field echo (FFE), (b) postcontrast T1-weighted FFE (3 minutes after gadobutrol injection); (c) kinetic curve; (d) T2-weighted turbo-spin echo (TSE) with fat suppression (T2 SPAIR); (e) axial diffusion-weighted imaging (DWI) single-shot echo-planar image (EPI); and (f) focus of restricted diffusion on the apparent diffusion coefficient (ADC) map (b value, 1000 s/mm 2 ). The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) set (a, b, c) shows a 2.5-cm circumscribed, heterogeneously enhancing, oval mass in the upper mid portion of the left breast with a kinetic curve of 2 (BI-RADS C4). The diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) set (d, e, f) shows a high signal intensity in the left breast mass on T2WI and an intermediate signal intensity (ADC value, 1.4 × 10 −3 mm 2s). Therefore, it was scored as DWI-T2WI 2, considered probably benign. The value of combined assessment of DCE and DWI-T2WI was 6 (sum of BI-RADS C4 and DWI-T2WI score 2), considered benign. Histopathology (g) showed leaf-like projections of stroma covered by epithelium, consistent with benign phyllodes tumor (hematoxylin and eosin [H&E] stain; × 40). DWI-T2WI sets with ADC values were more useful to diagnose benign tumor than the DCE-MRI set. BI-RADS, Breast Imaging-Reporting and Data System; SPAIR, spectral attenuated inversion recovery.

Figure 4, A 57-year-old woman with a right breast mass. Pathology demonstrated a high-grade invasive ductal carcinoma. (a) Precontrast axial T1-weighted FFE; (b) postcontrast subtraction image (by subtracting the precontrast images from the 3 minutes postcontrast images); (c) kinetic curve; (d) T2 SPAIR; (e) axial DWI single-shot EPI; (f) focus of restricted diffusion on the ADC map (b value, 1000 s/mm 2 ). The DCE-MRI set (a, b, c) shows a 1.0-cm circumscribed, round homogeneously enhancing mass in the subareolar area of the right breast with kinetic curve 2. Note, the diffuse skin thickening of the right breast (BI-RADS C4). The DWI-T2WI set (d, e, f) shows intermediate SI mass in the right breast on T2WI and marked high SI lesion on DWI (ADC value, 0.67 × 10 −3 mm 2s). Therefore, it was scored as DWI-T2WI 5, considered definitely malignant. The value of combined assessment of DCE-DWI-T2WI was 9 (sum of BI-RADS C4 and DWI-T2WI score 5), considered malignant. Histopathology (g) showed invasive ductal carcinoma with a high histologic grade. Nuclei showed marked variation in size and shape with mitoses (Bloom and Richardson grade 3; tubule formation, 3; nuclear pleomorphism, 3; mitoses, >10 HPF) (H&E stain, ×400). ADC, apparent diffusion coefficient; BI-RADS, Breast Imaging-Reporting and Data System; DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging; DWI-T2WI, diffusion-weighted imaging and T2-weighted imaging; EPI, echo-planar image; FFE, fast field echo; H&E, hematoxylin and eosin; HPF, high-power field; SI, signal intensity; SPAIR, spectral attenuated inversion recovery.

TABLE 6

Correlation of ADC Values with Histopathology and Histologic Grade of Breast Lesions

No. of Lesions

(n = 169) ADC (10 −3 mm 2 /s)

(Mean ± SD)P Value \* Benign 48 (28.4) 1.36 ± 0.22 .00 Malignant (DCIS + IDC) 121 (71.6) 0.96 ± 0.20 DCIS 24 (19.8) 1.11 ± 0.13 .00 IDC 88 (72.7) 0.89 ± 0.17 Mucinous carcinoma 4 (3.3) 1.42 ± 0.21 Invasive lobular carcinoma 5 (4.1) 1.16 ± 0.63 DCIS 24 (19.8) 1.11 ± 0.13 .00 IDC grade 1 11 (6.5) 1.04 ± 0.26 IDC grade 2 43 (25.4) 0.97 ± 0.21 IDC grade 3 43 (25.4) 0.84 ± 0.15

ADC, apparent diffusion coefficient; ANOVA, analysis of variance; DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; SD, standard deviation.

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Figure 5, A 58-year-old woman with a palpable left breast mass. Pathology confirmed a mucinous carcinoma. (a) Precontrast axial T1-weighted FFE; (b) postcontrast T1-weighted FFE (3-minute postcontrast dynamic series); (c) kinetic curve; (d) T2 SPAIR; (e) axial DWI single-shot EPI; (f) focus of restricted diffusion on the ADC map (b value, 1000 s/mm 2 ). The DCE-MRI set (a, b, c) showed a circumscribed heterogeneous enhancing, oval mass in the upper outer quadrant of the left breast, with a kinetic curve of 2 (BI-RADS 4). The DWI-T2WI set (d, e, f) showed a strong, high SI in the left breast mass on T2WI and a low SI on DWI, with a high ADC value (1.45 × 10 −3 mm 2s). Therefore, it was scored as DWI-T2WI score 2, considered probably benign. The value of combined assessment of DCE and DWI-T2WI was 6 (sum of BI-RADS C4 and DWI-T2WI score 2), considered benign. Histopathology (g) showed abundant mucin with tumor cells from mucinous carcinoma (H&E stain, ×100). Because of the high ADC value of mucinous carcinoma, we misdiagnosed this tumor by both the DWI-T2WI set and combined assessment of MRI. ADC, apparent diffusion coefficient; BI-RADS, Breast Imaging-Reporting and Data System; DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging; DWI-T2WI, diffusion-weighted imaging and T2-weighted imaging; EPI, echo-planar image; FFE, fast field echo; H&E, hematoxylin and eosin; HPF, high-power field; SI, signal intensity; MRI, magnetic resonance imaging; SPAIR, spectral attenuated inversion recovery.

Figure 6, Diagram of ADC values for benign and malignant lesions. Box plots show the median and interquartile ranges (25th and 75th percentiles) of the ADC value in benign lesion, DCIS, invasive ductal carcinoma grades 1, 2, and 3 lesions. The mean ADC value was 1.36 ± 0.22 −3 mm 2s for benign lesions and 0.96 ± 0.20 −3 mm 2s for malignant lesions; this difference was statistically significant. The mean ADC of ductal carcinoma in situ (1.11 ± 0.13 −3 mm 2s) was statistically higher than that of invasive ductal carcinoma (0.89 ± 0.17 −3 mm 2s) ( P < .05). The mean ADC value was significantly associated with histologic grade ( P < .05), which is the lowest in grade 3 (0.84 ± 0.15 −3 mm 2s). ADC, apparent diffusion coefficient; DCIS, ductal carcinoma in situ.

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Discussion

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Academic Radiology, Volume 25, Issue 5
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