Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI and conventional MRI

Magnetic Resonance Imaging xxx (2014) xxx–xxx

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Original contribution

Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI and conventional MRI Eun Jeong Kim a, Sung Hun Kim a,⁎, Bong Joo Kang a, Byung Gil Choi a, Byung Joo Song b, Jae Jeong Choi c a b c

Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea General Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea Department of Radiology, Dongtan St. Heart Hospital

a r t i c l e

i n f o

Article history: Received 27 April 2014 Accepted 21 July 2014 Available online xxxx Keywords: Breast neoplasms Lymphatic metastasis Diffusion magnetic resonance imaging Magnetic resonance imaging

a b s t r a c t Purposes: To evaluate the diagnostic value of diffusion-weighted MRI (DWI) and combination of conventional MRI and DWI to predict metastatic axillary lymph nodes in breast cancer. Materials and methods: Two hundred fifty-two breast cancer patients with 253 axillae were included. The morphological parameters on axial T2-weighted images without fat saturation and apparent diffusion coefficient (ADC) values were retrospectively analyzed. An independent t-test/chi-square test and receiver operating characteristics (ROC) curve analysis were used. Results: On conventional MRI, short and long axis length, maximal cortical thickness, relative T2 value, loss of fatty hilum (p b 0.001 for each), and eccentric cortical thickening (p b 0.003) were statistically significantly different between the metastatic and nonmetastatic groups. The short axis to long axis ratio was not a statistically significant parameter. The ADC value was significantly different between the 2 groups, with an AUC that was higher than that of conventional MR parameters (AUC, 0.815; threshold, ≤0.986 × 10–3 mm2/sec; sensitivity, 75.8%; specificity, 83.9%). Using the adopted thresholds for each parameter, a total number of findings suggesting malignancy of 4 or higher was determined as the threshold, with high specificity (90.1%). Conclusion: Using conventional MRI and DWI, we can evaluate the axilla in breast cancer with high specificity. © 2014 Elsevier Inc. All rights reserved.

1. Introduction The presence of a metastatic axillary lymph node is the most important factor in predicting the long-term survival of patients with breast cancer [1,2]. Axillary lymph node dissection (ALND) is the standard method of axillary staging for patients with palpable axillary lymph nodes or metastatic lymph nodes confirmed by methods such as ultrasound-guided fine-needle aspiration biopsy. Sentinel lymph node dissection (SLND) is a method of staging the axilla of patients with clinically negative axilla [3]. These methods may involve complications such as lymphedema, arm pain, infection, or seroma [4]. It is estimated that lymphedema occurs in 34% [4] of patients who undergo ALND and 7% [5] of patients who undergo SLNB. It would be beneficial to predict axillary lymph node status preoperatively for choosing less invasive method. Currently, the use of MRI for preoperative axillary staging is based on the measurement of dimensions and morphological features such ⁎ Corresponding author at: Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-Gu, Seoul 137–701, Korea. Tel.: +82 2 2258 1455; fax: +82 2 2258 1457. E-mail address: [email protected] (S.H. Kim).

as shape, cortical globular thickening, or enhancement patterns [6–12]. However, the criteria for detecting a metastatic axillary lymph node remain controversial [9,11,13,14]. In a systematic review of 3 studies evaluating the use of MR to detect metastatic axillary lymph nodes, the mean sensitivity was 88%, and the mean specificity was 73%; these studies examined size, morphological features, gadolinium enhancement, or a combination of these methods [15]. The lack of criteria for detecting axillary lymph node metastasis has prompted the evolution of functional and physiological assessments of the lymph nodes. Diffusion-weighted MRI (DWI) is a functional MR imaging technique that characterizes tissues by their water diffusion properties [16–18]. DWI and the apparent diffusion coefficient (ADC) value have been used to differentiate between benign and malignant breast lesions and to successfully determine tumor extension [19–21], and DWI is now the standard protocol for breast cancer evaluation. The ADC value has been used to diagnose metastatic lymph nodes in various regions, such as head and neck, uterine, and cervical cancers [17,22]. However, it is not clear if the ADC value is useful for detecting metastatic axillary lymph nodes. The purpose of this study was to determine if DWI is a reliable means of detecting the presence of a metastatic lymph node in breast

http://dx.doi.org/10.1016/j.mri.2014.07.001 0730-725X/© 2014 Elsevier Inc. All rights reserved.

Please cite this article as: Kim EJ, et al, Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI an..., Magn Reson Imaging (2014), http://dx.doi.org/10.1016/j.mri.2014.07.001

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E.J. Kim et al. / Magnetic Resonance Imaging xxx (2014) xxx–xxx

cancer patients. In addition, we aimed to determine the most effective combination of parameters for conventional MRI and DWI to detect metastatic axillary lymph nodes in breast cancer patient. 2. Materials and methods 2.1. Patients This retrospective study was approved by the institutional review board and ethical review committee of our institution. Between January 2012 and December 2012, 537 patients with histopathologically proven breast cancer underwent preoperative breast MRI including DWI at our institution. The following patients were excluded: 85 patients receiving neoadjuvant chemotherapy, 44 patients for whom axillary lymph nodes were not pathologically confirmed, 14 patients with a greater than 3-week interval between biopsy/operation and MRI, 76 patients who underwent MRI using a 1.5 T system (b value = 1000 sec/mm 2), 24 patients whose most suspicious lymph nodes existed outside the field of view (FOV) on DWI, 14 patients with no measurable axillary lymph nodes on T1-weighted images, 8 patients with unmeasurable small lymph nodes on DWI, 6 patients with a poor-quality DWI, and 13 patients whose most suspicious lymph node had a short-axis length of less than 4 mm in T1-weighted images. As a result, 252 patients (mean age 51.6 ± 10.9 years, range 28–82 years) with 253 axilla (1 patient had bilateral cancers) were included. The primary cancer types consisted of 173 invasive ductal carcinomas (IDC), 13 invasive lobular carcinomas, 44 ductal carcinomas in situ, 1 lobular carcinoma in situ, 4 combined IDCs and mucinous carcinomas, 7 microinvasive ductal carcinomas, 3 mucinous carcinomas, 1 mixed invasive ductal and lobular carcinoma, 2 metaplastic carcinomas, 3 invasive micropapillary carcinomas, 1 intraductal papillary carcinoma, and 1 invasive cribriform carcinoma. 2.2. MR protocol MR imaging was performed with the patient in a prone position using a dedicated bilateral breast surface coil. Images were obtained with a 3 T MRI system (Verio; Siemens Healthcare, Erlangen, Germany) using the following sequences: 1) an axial, turbo spin-echo T2-weighted imaging sequence with a TR/TE of 4530/93, a flip angle of 80°, 34 slices, an FOV of 320 mm, a matrix size of 576 × 403, 1 NEX, a slice thickness of 4 mm, and an acquisition time of 2 minutes, 28 seconds; 2) axial DWI with readout segment echo planar imaging (rs EPI) (b values of 0 and 750 s/mm 2, TR/TE 5600/ 55 ms, FOV 360 × 180 mm, matrix size 192 × 82, slice thickness of 4 mm, acquisition time of 2 minutes and 31 seconds, with 5 readout segments); ADC maps were calculated from the DW images automatically using MRI software; 3) pre- and postcontrast axial T1-weighted flash 3-dimensional VIBE sequences with a TR/TE of 4.4/1.7, a flip angle of 10°, a slice thickness of 1.2 mm, and an acquisition time of 1 minute. The images were obtained before and 10, 70, 130, 190, 250, and 310 seconds after an injection of Gd-DTPA (0.1 mmol/kg Gadovist; Bayer Schering Pharma, Berlin, Germany). 2.3. Image analysis Two radiologists with experience in breast MRI interpretation (KEJ: 1 year experience; KSH: 8 years experience) retrospectively reviewed the images in consensus. Although the readers were aware that the patients had histopathologically confirmed breast cancer, they were blinded to the clinical findings and histopathological diagnosis based on the analysis of the axillary lymph nodes. Mammography and ultrasound findings were not available.

The most suspicious lymph node on the axial T2-weighted images without fat saturation was chosen for analysis. A lymph node was considered suspicious if it had 1 of the following features: loss of fatty hilum, round shape, and eccentric cortical thickening [23–25]. If more than 2 suspicious lymph nodes were found in an axilla or no lymph node with mentioned suspicious finding, the largest lymph node in the short axis length was chosen for analysis. We determined several morphological characteristics of the node: the short and long axis length, the short axis-long axis ratio, the fatty hilum (presence or loss), the maximal cortical thickness, and the cortical thickening pattern. The cortical thickening pattern was categorized as none, concentric, or eccentric. Eccentric cortical thickening was defined when the cortical thickness was more than one-third of the short-axis length. When the lymph node had lost fatty hilum, the short-axis length was considered the maximal cortical thickness, and the cortical thickening type was not classified. The relative T2 value was obtained in the selected lymph node on the axial T2-weighted images without fat saturation. We placed the largest possible ROI circles within the identified lesion, avoiding the fatty hilar portion, margins or apparent necrotic portions on contrast-enhanced T1-weighted images. The ROI area was larger than 9 mm2, according to the lesion size. To obtain the relative T2 value, the ipsilateral pectoralis minor muscle was used as the reference site. An identical-sized ROI was placed on the ipsilateral pectoralis minor muscle. The relative T2 value was calculated as the T2 value lymph node/T2 value pectoralis minor muscle. The same lymph node was subsequently identified in the DWI. A polygonal shaped region-of-interest (ROI) covering the lymph node cortex was placed on ADC maps obtained with a b value of 750 sec/mm 2. The fatty hilar or marginal portion and apparent necrotic portions were avoided as comparing to contrast-enhanced T1-weighted images. The ROI area was larger than 10.46 mm 2, according to the lesion size. ADC values were calculated using built-in software. To reduce the effects of partial volume artifacts, the smallest lymph node size for the ADC calculation was set at a minimum axial diameter of 4 mm on T2-weighted images without fat saturation. 2.4. Histopathological analysis The patients' pathology reports were reviewed by 2 radiologists. Histopathological examinations were performed for all patients. An 18G core needle biopsy was performed for 90 axillae with suspicious US findings. Of the 59 metastatic lymph nodes that were found on core needle biopsy, 29 axillary node dissections were completed. A total of 20 patients underwent neoadjuvant therapy and interval ALND (in these cases, the core needle biopsy result was considered the pathological result). No further surgical procedure was performed for 10 of the patients because of distant metastasis and old age. Of the 31 axillae that were negative on core needle biopsy, 21 SLNDs and 6 SLNDs followed by ALND were completed. For 4 patients, no further surgical procedure was performed. For the 136 axillae not undergoing CNB, 133 SLNDs and 30 SLNDs followed by ALND were completed. The final pathological confirmation of the axillary node was obtained by axillary node dissection (n = 65), sentinel node biopsy (n = 154), and 18G core needle biopsy (n = 34). Surgical specimens and MRI images were not compared directly. 2.5. Statistical analysis Statistical analysis was performed using the Statistical Package for Social Sciences software (SPSS, Version 21.0). Continuous data (short axis length, long axis length, short axis-long axis ratio, maximal cortical thickness, T2 relative value, and ADC value) are

Please cite this article as: Kim EJ, et al, Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI an..., Magn Reson Imaging (2014), http://dx.doi.org/10.1016/j.mri.2014.07.001

E.J. Kim et al. / Magnetic Resonance Imaging xxx (2014) xxx–xxx

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expressed as the mean ± standard deviation. All measurements were normally distributed. The independent t-test was used to compare means between metastatic and nonmetastatic axillary lymph nodes. Categorical data (fatty hilum, cortical thickening type) were compared using the chi-square test. We considered a 2-sided p-value b 0.05 statistically significant. The parametric estimate of the area under the receiver operating characteristic (ROC) curve was used to compare the diagnostic ability of variables to differentiate the nonmetastatic and metastatic lymph nodes. The optimal cut-off value was determined according to the Youden index (J), and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. To improve the ability of breast MRI to predict metastatic lymph nodes, a scoring system was designed. Parameters with statistical significance were selected as criteria, and each criterion was scored as 0 (without a malignant feature) or 1 (with a malignant feature) according to the obtained optimal threshold (continuous data) or the presence of a feature suggesting malignancy (categorical data). The threshold total score, area under the curve (AUC), sensitivity, specificity, PPV, and NPV were calculated using ROC curve analysis. 3. Results Of the 253 axillae, 91 (36%) were metastatic, and 162 (64%) were non-metastatic upon pathologic analysis. The lymph node features on conventional MR and DWI are summarized in Table 1. Of the continuous parameters, short axis length, long axis length, maximal cortical thickness, relative T2, and ADC value showed statistically significant differences between the 2 groups (p b 0.001). The short axis–long axis ratio was not a significant factor for predicting a metastatic axillary lymph node. A total of 50 (53.8%) of 91 metastatic lymph nodes lost fatty hilum, while 153 (94.4%) of 162 non-metastatic lymph nodes had intact fatty hilum (p b 0.001). In addition, eccentric cortical thickening was found to be a statistically significant feature suggesting malignancy. In addition to the 50 metastatic lymph nodes with a loss of fatty hilum, 21 (41.2%) of the 51 metastatic lymph nodes and 31 (20.4%) of the 152 nonmetastatic lymph nodes showed eccentric cortical thickening (p b 0.003). The mean ADC value of the metastatic lymph nodes (0.910 ± 0.29 × 10 −3 mm 2/sec) was significantly lower than that of the nonmetastatic nodes (1.270 ± 0.32 × 10 −3 mm 2/sec). Based on the ROC curves (Fig. 1), the ADC value was the most discriminative

Table 1 Axillary lymph node features on conventional MR and DWI. Parameter Short axis length (mm) Non-metastatic Malignant Long axis length (mm) Non-metastatic Malignant Short axis-long axis ratio Non-metastatic Malignant Maximal cortical thickness (mm) Non-metastatic Malignant ADC value (×10−3 mm2/sec) Non-metastatic Malignant Relative T2 value Non-metastatic Malignant a

Mean

SDa

Range

7.059 10.058

3.200 4.732

4.0–33.8 4.4–24.7

12.136 16.367

5.325 7.792

5.0–41.4 5.9–41.5

0.615 0.652

0.169 0.190

0.243–1 0.282–1

3.389 7.950

3.090 5.906

1.0–33.8 1.2–24.7

1.270 0.910

0.321 0.298

0.635–2.195 0.384–1.309

2.023 2.589

0.845 1.066

0.68–5.43 1.07–5.87

p valueb b0.001

b0.001

0.123

b0.001

b0.001

b0.001

Standard deviation. p value reflects the difference in mean between metastatic lymph nodes and nonmetastatic lymph nodes. b

Fig. 1. ROC curves for the individual evaluated MRI parameters of the axillary lymph node and scoring system.

variable for predicting a metastatic node (AUC, 0.815; Fig. 2). An ADC value of 0.986 × 10 −3 mm 2/sec was determined as the threshold at which the Youden index reached its peak. At the determined threshold, the sensitivity, specificity, PPV, and NPV were 75.8 % (69/ 91), 83.9% (136/162), 72.6% (69/95), and 86.0% (136/158), respectively. Maximal cortical thickness was also a good predictor of a metastatic node, with a threshold value of 3.7 mm (AUC, 0.773; sensitivity, 72.5%; specificity, 74.1; PPV, 61.1%; NPV, 82.7%; Fig. 3). Short axis length, long axis length, and relative T2 value were followed by AUC. The threshold for each parameter and the sensitivity, specificity, PPV, and NPV at the adopted threshold are summarized in Table 2. And the sensitivity, specificity, PPV, and NPV of categorical MR parameters of lymph nodes are summarized in Table 3. A scoring system for predicting a metastatic lymph node based on features that were significantly correlated with metastatic lymph nodes was designed (Table 4). Characteristics that suggested metastatic lymph nodes were defined as follows: short axis length longer than 9 mm, long axis length longer than 11 mm, maximal cortical thickness longer than 4 mm, relative T2 value greater than 2, an ADC value of 0.986 × 10 −3 mm 2/s or lower, and abnormal shape (fatty hilum loss or eccentric cortical thickening). A total score of 4 or higher was the threshold score with a sensitivity of 60.0%, a specificity of 90.1%, a PPV of 77.1%, and an NPV of 79.8% (Figs. 4 and 5). The AUC for the designed scoring system was larger than that for each parameter individually (0.840; Fig. 1).

4. Discussion Our study demonstrated the diagnostic performance of DWI and conventional T1- and T2-weighted MRI for detecting metastatic axillary lymph nodes in breast cancer patients. Among several conventional MRI parameters, maximal cortical thickness was the most discriminative variable for predicting metastatic nodes (AUC, 0.737; threshold, 3.7 mm). Scaranelo et al. [26] also reported the significance of cortical thickness as the best diagnostic parameter.

Please cite this article as: Kim EJ, et al, Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI an..., Magn Reson Imaging (2014), http://dx.doi.org/10.1016/j.mri.2014.07.001

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Fig. 2. A 47-year-old woman with invasive ductal carcinoma in the right breast. SLND followed by ALND was performed, and axillary metastasis was confirmed. a) Axial T2-weighted MR images without fat saturation showed morphologic features suggesting a nonmetastatic lymph node, such as a short axis of 8 mm, a cortical thickness of 2.8 mm, or preserved fatty hilum, or concentric cortical thickening. And the relative T2 value (T2 value lymph node/T2 value pectoralis minor muscle) was 1.48., suggesting nonmetastatic node features. b) DWI (b = 750 sec/mm2) showed a high-signal-intensity lymph node. c) The ADC value was 0.575 × 10−3 mm2/sec on the ADC map. The short axis was 8 mm, the long axis was 13 mm, the cortical thickness was 2.8 mm, and concentric cortical thickening with preserved fatty hilum was observed. This morphologically benign-looking lymph node had a low ADC value (0.602 × 10−3 mm2/sec).

The dimensions of the lymph nodes differed between the metastatic group and the nonmetastatic group. The optimal threshold for short and long axis length was 9.3 mm and 11.3 mm, respectively. The short axis length threshold was longer than previously reported and had a higher specificity (89.5%). Ni He et al. [12] and Luciani et al. [27] recently reported 5.5 mm as a threshold length, but while that threshold was highly sensitive, it was not very specific. In contrast to what is generally believed, the short-long axis ratio is not higher in the metastatic node than in the nonmetastatic node. Luciani et al. [24] reported results similar to ours; however, other studies have reported that a significant difference in the short axis–long axis ratio [12,28].

These conflicting results may be obtained because some lymph nodes were partially affected by malignant cells without changing shape or because the lymph node was completely replaced by tumor cells with irregular shapes. These limitations emphasize the importance of functional imaging. Two descriptive parameters (loss of fatty hilum and eccentric cortical thickening) showed a statistically significant difference. In particular, loss of fatty hilum had the highest specificity (94.4%), which is very useful for excluding the presence of a metastatic lymph node. These results are similar to those of prior studies [24,25,28,29]. The relative T2 value is also significant, in agreement with previous reports [24,27].

Fig. 3. A 43-year-old woman with invasive ductal carcinoma in the right breast and metastatic lymph node confirmed by ALND. On axial T2-weighted image without fat saturation the most suspicious lymph node in the right axilla had a short axis of 6 mm and preserved fatty hilum. The cortical thickness was 4.5 mm, and the cortical thickening type was eccentric.

Please cite this article as: Kim EJ, et al, Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI an..., Magn Reson Imaging (2014), http://dx.doi.org/10.1016/j.mri.2014.07.001

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Table 2 Diagnostic performance of the continuous MR parameters of axillary lymph node and scoring system.

Short axis length(mm) Long axis length(mm) Shot axis-long axis ratio Maximal cortical thickness(mm) Relative T2 value ADC value (x 10−3 mm2/sec) Total scoreb

AUC

95% CI

p valuea

Threshold

Youden index

Se (%)

Sp (%)

PPV (%)

NPV (%)

0.730 0.677 0.561 0.773 0.666 0.815 0.840

0.671–0.784 0.616–0.734 0.497–0.623 0.716–0.823 0.604–0.724 0.762–0.861 0.789–0.883

b0.001 b0.001 0.116 b0.001 b0.001 b0.001 b0.001

N9.3 N11.3 N0.6947 N3.7 N2.0687 ≤0.986 N3

0.3676 0.3350 0.1577 0.4660 0.2814 0.5977 0.5250

47.3 73.6 47.3 72.5 67.0 75.8 60.0

89.5 59.9 68.5 74.1 61.1 83.9 90.1

71.7 50.8 47.2 61.1 48.8 72.6 77.1

75.1 80.1 67.9 82.7 76.5 86.0 79.8

AUC: area under the ROC curve Se: sensitivity Sp: specificity. PPV: positive predictive value NPV: negative predictive value. a ROC curve analysis for variables to differentiate the nonmetastatic and metastatic lymph nodes. b Calculated score according to Table 4.

Several features determined by conventional MRI are useful for detecting metastatic lymph nodes; however, criteria based on size and morphological features may be inaccurate. In one histological analysis of axillary lymph nodes in breast cancer, 13.7% of metastatic nodes had a short-axis length of 5 to 9 mm [30], and Goro et al. [28] reported 16 false-negative results for 17 normal-sized axillary lymph nodes on MRI. DWI may be a reasonable alternative that can be performed in the same session as a standard breast MRI and does not require the administration of contrast media. Low spatial resolution is a disadvantage of DWI. For improved resolution and reduced susceptibility artifacts, we use DWI with a readout segmented diffusion technique (RESOLVE) instead of conventional single-shot echo-planar imaging (SS-EPI). Our ROC curve analysis demonstrated the satisfactory diagnostic performance of the ADC value for differentiating metastatic from nonmetastatic lymph nodes; the ADC value performed even better than the parameters from conventional MRI. When an ADC value lower than 0.986 × 10−3 mm2/sec was used to determine metastatic lymph nodes, the sensitivity, specificity, PPV, and NPV were 75.8%, 83.9%, 72.6% and 86.0%, respectively. Our results for the ADC value are roughly similar to those of previous studies. In recent studies, DWI evaluated metastatic axillary lymph nodes with sensitivities ranging from 53.8% to 94.7% and specificities ranging from 65.8% to 93% using different ADC thresholds [6,9–12,31]. The reported ADC threshold ranged from 0.80 × 10−3 mm2/sec to 1.35 × 10−3 mm2/sec at b = 800 sec/mm2 [9,10,27,31] and from 1.04 × 10−3 mm 2/sec to 1.05 × 10 −3 mm2/sec

Table 3 Diagnostic parameters of categorical MR parameters of axillary lymph node.

Fatty hilum loss Cortical thickening type Abnormal shape (fatty hilum loss or eccentric cortical thickening)

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

46.2 41.2 67.3

94.4 79.6 74.9

82.3 66.6 59.8

75.7 80.1 80.1

at b = 1000 sec/mm2 [6,11], with some differences in MRI parameter settings. By contrast, Nakai et al. [32] and Heusner et al. [33] reported that the ADC value was not significant for predicting metastatic nodes. Identifying significant parameters and assigning scores to each of them enabled a better diagnostic yield than that obtainable from each parameter alone. Using the adopted optimal threshold for each parameter, the evaluated lymph nodes were used as a test set to determine an optimal threshold value for the number of findings suggesting malignancy of 4 or more. This final score threshold yielded good specificity (90.1%), indicating that SLND is sufficient for axilla containing lymph nodes with 3 or fewer suspicious findings. Unnecessary aggressive axillary dissection can therefore be avoided. There are some limitations of our study. First, we assumed the most suspicious lymph node on MRI was correlated with the final histopathological result. To reduce error, only the most suspicious lymph node was included, but we could not confidently confirm any correlation between imaging findings and pathology results. Second, lymph nodes with a short axis length of 4 mm or less were not included because of low spatial resolution on imaging and the difficulty of measuring several values. Third, enhancement kinetics, a potential parameter for detecting metastatic lymph nodes, were not evaluated in this study. There are divergent opinions about the enhancement kinetics of metastatic nodes [12,25]. Fourth, just two b values were used in the DWI, prohibiting the differentiation between perfusion effects and true diffusion, and between lesion and fatty tissue [34]. We tried to avoid fatty tissue when measuring ADC value by comparison with conventional MR images. In conclusion, this study demonstrates several significant parameters on conventional MR and DWI for predicting metastatic axillary lymph nodes in breast cancer patients: short-axis length, long-axis length, maximal cortical thickness, the presence of fatty hilum, cortical thickening pattern, relative T2 value, and ADC value. The ADC value of axillary nodes shows good diagnostic performance, with a threshold of 0.986 × 10 −3 mm 2/sec. This finding suggests that DWI should be included in clinical practice for evaluating axillary nodes in breast cancer patients. Using the final proposed scoring system, scores of 4 or higher suggest the presence of a metastatic node with high specificity. References

Table 4 Scoring system for the preoperative evaluation of axillary metastasis. Parameter

Score

Short axis length N 9 mm Long axis length N 11 mm Cortical thickness N 4 mm Relative T2 value N 2 ADC value ≤0.986 × 10−3 mm2/sec Fatty hilum loss or eccentric Total

1 1 1 1 1 1 6

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Please cite this article as: Kim EJ, et al, Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI an..., Magn Reson Imaging (2014), http://dx.doi.org/10.1016/j.mri.2014.07.001

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Fig. 4. A 40-year-old woman with DCIS in the right breast. a) On an axial T2-weighted image without fat saturation, a short axis length was 8 mm; a long axis length was 15 mm; a cortical thickness was 3.2 mm; the cortical thickening type was concentric; and the relative T2 value (T2 value lymph node/T2 value pectoralis minor muscle) was 2.2. b) DWI (b = 750 sec/mm2) showed a high-signal-intensity lymph node. c) The ADC value was 1.305 × 10−3 mm2/sec on the ADC map. Two features suggested a metastatic axillary lymph node: the long axis and the relative T2 value. Based on our scoring system, these factors suggest a nonmetastatic lymph node. No axillary metastasis was found in the ALND.

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Please cite this article as: Kim EJ, et al, Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI an..., Magn Reson Imaging (2014), http://dx.doi.org/10.1016/j.mri.2014.07.001

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Fig. 5. A 64-year-old woman with invasive ductal carcinoma in the right breast. a) On an axial T2-weighted image without fat saturation, lymph node showed a short axis of 7.3 mm, a long axis of 9 mm, and a cortical thickness of 7.3 mm. The relative T2 value (T2 value lymph node/T2 value pectoralis minor muscle) was 2.4. The fatty hilum was lost. b) DWI (b = 750 sec/mm2) showed a high-signal-intensity lymph node. c) The ADC value was 0.833 × 10−3 mm2/sec on the ADC map. Four features suggested a metastatic axillary lymph node: loss of fatty hilum, cortical thickness, relative T2 value, and ADC value. Taken together, these features suggest a metastatic lymph node according to our scoring system. ALND was performed, and 3 of 26 lymph nodes were pathologically metastatic. [31] Luo N, Su D, Jin G, Liu L, Zhu X, Xie D, et al. Apparent diffusion coefficient ratio between axillary lymph node with primary tumor to detect nodal metastasis in breast cancer patients. J Magn Reson Imaging 2013;38(4):824–8. [32] Nakai G, Matsuki M, Harada T, Tanigawa N, Yamada T, Barentsz J, et al. Evaluation of axillary lymph nodes by diffusion-weighted MRI using ultra small superparamagnetic iron oxide in patients with breast cancer: initial clinical experience. J Magn Reson Imaging 2011;34(3):557–62.

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Please cite this article as: Kim EJ, et al, Diagnostic value of breast MRI for predicting metastatic axillary lymph nodes in breast cancer patients: diffusion-weighted MRI an..., Magn Reson Imaging (2014), http://dx.doi.org/10.1016/j.mri.2014.07.001