Investigation of the optimal b-value to detect breast tumors with diffusion weighted imaging by 1.5-T MRI
© Tamura et al.; licensee BioMed Central Ltd. 2014
Received: 20 March 2014
Accepted: 20 March 2014
Published: 22 April 2014
Previous studies have reported that the signal attenuation of diffusion-weighted magnetic resonance imaging (DWI) for normal breast tissue and tumor were well fitted by a monoexponential and a biexponential function, respectively. The aim of this study was to investigate the optimal b-value to detect breast tumors from DWI signal attenuations.
Sixty-four subjects with breast cancer underwent DWI using six b-values up to 3500 s/mm2. The signal attenuations of normal breast and tumor were fitted by mono- and biexponential functions, respectively. The maximum contrast b-values were estimated and compared in terms of frequency.
In almost all cases, the contrast increased with a b-value from 0 to approximately 1500 s/mm2. For b > 1500 s/mm2, the contrast decreased. The highest contrast b-value in the range of 0 to 2500 s/mm2 most frequently was b = 1500 and the next most frequent was 1400 s/mm2. Comparing sensitivity and specificity between b = 700 and b = 1400 s/mm2, b =1400 s/mm2 was slightly superior.
Based on these results, DWI with a b-value of approximately 1400-1500 s/mm2 is recommended for optimizing breast tumor detectability.
where S0 and Sb are the signals without and with diffusion sensitizing gradients, respectively; b is the b-value, and D is the ADC . However, the application of Equation (1) for measuring diffusion in vivo is problematic. The actual signal attenuation of breast tumors is non-monoexponential ; therefore, calculated ADCs using different b-values are also different .
Comparing the sensitivity and specificity of ADC using b = 0–1000 s/mm2 with a 250 s/mm2 interval to perform 1.5-T MR imaging, Pereira et al.  reported that the ADC calculated from b = 0 and 750 s/mm2 was slightly better than other b-value combinations for distinguishing malignant from benign. In a similar study using 3.0 T MRI, Bogner et al.  reported that the combination of b = 50 and 850 s/mm2 was slightly better, and using b-values over 1000 s/mm2 could lead to overdiagnosis and was not appropriate. However, Ochi et al.  reported that ADC values calculated from b = 1500 s/mm2 were useful to improve the diagnostic accuracy for malignant tumors and benign lesions, especially for noninvasive ductal carcinoma (NIDC) versus fibrocystic changes, except in cases of ductal hyperplasia. These differing results suggest that the optimum b-value for calculating the ADC has not yet been agreed upon. Additionally, it is well known that there is overlap between the ADCs of malignant and benign neoplasms , and although ADC reflects cell density, it does not directly reflect the character of the malignancy [11, 19, 28]. Proliferative tumors, both benign and malignant, exhibit high signal in DWI .
Another aim of DWI is the detection of tumors in general [18, 22]. The optimum b-value for tumor detection has also not yet been agreed upon. There have been many recent studies of DWI using b-values > 1000 s/mm2 [3, 12, 21, 25–29]. Higher b-values are able to apply weightings to more restricted diffusion but also cause decreased signal-to-noise ratio (SNR). Thus, excessively higher b-values do not improved tumor detection. In our previous study, we analyzed the DWI signal attenuation of normal mammary gland and breast tumors using multiple b-values up to 3500 s/mm2 and demonstrated that normal breasts and malignant tumors were well fitted by a monoexponential and biexponential function, respectively . The aim of the current study is to investigate the optimum b-value to detect breast tumors, surveying multiple b-value DWI signal attenuations.
This study was approved by our center’s Institutional Review Board (Hiroshima Atomic Bomb Casualty IRB, Trial registry number, 5) and all patients gave their informed consent. The subjects included 62 females with a total of 64 breast cancers (mean age = 56.0 years, age range = 33–81 years, mean tumor size = 2.17 ± 1.48 cm) and 38 normal controls (mean age 55.4 years, age range = 35–78 years). All subjects underwent breast magnetic resonance imaging (MRI) including DWI with multiple b-values. All tumors were excised and the final diagnosis established on the basis of histopathological examination. According to the World Health Organization classification, the 64 breast tumors were comprised of noninvasive ductal carcinoma (NIDC; n = 9), invasive carcinoma (IDC; n = 49), tubulo-lobular carcinoma (n = 3), mucinous carcinoma (n = 2), and medullary carcinoma (n = 1).
Scan parameters of breast MRI study
128 × 114(256R)
4 m 40 s
256 × 198(256R)
1 m 58 s
256 × 198(256R)
1 m 27 s
352 × 334(512R)
70 s × 3
512 × 496(512R)
Prior to the clinical study, we determined DWI signal attenuation of 4% CuSo4-doped saline to confirm the linearity of the diffusion gradient with each b-values. The scan parameters were identical to those of the clinical study without b-values. The number of diffusion b-values was changed to sixteen from six with an interval of 233 s/mm2, thereby, scan time was extended to 35 min 20 s.
Regions of interest
Tumor and normal breast contrast
In each case, we investigated the maximum contrast b-value and counted the frequency of maximum contrast b-values in all cases.
Sensitivity and specificity of DWI
We evaluated the sensitivity and specificity using b = 700 and 1400 s/mm2 of DWI by three observers (TT, MS, and NK with 11, 10, and 9 years of expertise in breast MRI diagnosis, respectively). The subjects were a total of 100 cases including the 62 patients (64 breast cancers) and the additional 38 normal cases. A total of 200 images (400 breasts) were randomly sorted and evaluated the ability of tumor detection and localization. The results were compared using the chi-square test (95% confidence interval); a p value < 0.05 was considered significant.
Tumor and normal breast contrast
Derived parameters from the biexponential fitting in malignant tumors
0.717 ± 0.114
2.07 ± 0.319
0.179 ± 0.10
0.624 ± 0.125
2.08 ± 0.48
0.192 ± 0.09
0.673 ± 0.172
2.05 ± 0.32
0.203 ± 0.10
Sensitivity and specificity of DWI
The sensitivity and specificity of DWI using b = 700 and 1400 s/mm 2
b = 700
b = 1400
b = 700
b = 1400
In this study, we assessed the DWI signal attenuation of normal breasts and tumors up to b =3500 s/mm2 using multiple b-value DWI data, and calculated the maximum contrast between normal breast and tumor. The frequencies of the maximum contrast b-values between malignant tumor and normal breast were widely distributed within the range of b = 0 to b = 2500 s/mm2; the most frequent b-value was b = 1500 s/mm2 (16.9%, 11/65) and the next was b = 1400 s/mm2 (12.3%, 8/65) (Figure 5).
The tumor-to-normal breast contrast of almost all cases increased with a b-value from b = 0 to approximately 1500 s/mm2, and decreased with b > 1500 s/mm2 (Figure 4). Increasing the b-value caused the DWI signal to decrease and in almost all cases of normal breast, the signal declined until it reached the background noise level at around b = 1000–1500 s/mm2. In addition, for b ≥ 1500 s/mm2, normal breast signals were constant as the background and tumor signals were residual (Figure 3). Consequently, the maximum contrast b-values were of high frequency at approximately b = 1500 s/mm2.
Subsequently, we examined the sensitivity and specificity of DWI at b = 700 and 1400 s/mm2, which was where the maximum contrast was seen in only two cases and where the higher frequency was observed, respectively. This was done to confirm whether the tumor detectability could be evaluated or not by using the optimal b-value (Table 3). As a result, the mean sensitivity and specificity of the three observers of the b = 1400 s/mm2 data were slightly superior to those for b = 700 s/mm2. By comparing the sensitivity and specificity, unfortunately, there was no statistically significant difference (p = 0.504 for sensitivity, p = 0.197 for specificity). However, for DWI, the residual signal of normal breast tissue suppresses the conspicuity of tumor. The DWI at b = 1400 s/mm2, without residual signal from normal tissue, is more likely to detect tumor.
In a similar study using 6 b-values up to b = 3000 s/mm2 and a 3.0 T MRI, Takanaga et al.  reported that the maximum contrast b-value between tumor and normal breast tissue was 1500 s/mm2 and they concluded that the decline of b-values for normal-breast-to-background level is higher than 1.5 T, because the SNR of 3.0 T MRI is higher than that of 1.5 T. As a result, the highest contrast b-value for 3.0 T might be higher than that of 1.5 T. However, the b-value using 1.5 T MRI was the same in our study. Matsuoka et al.  reported that there was no significant difference for breast tumor ADCs between 1.5 T and 3.0 T. We consider that the DWI signal attenuation does not depend on the magnetic field strength; consequently, there was no difference between the maximum contrast b-values for 1.5 and 3.0 T.
There are some limitations in the present study. First, we reproduced the DWI signal decay using only 6 b-value images because of limitations in examination time, and less data may cause incorrect signal decay reproduction. As the decay of normal breast declines to the background noise level until the lower b-value, there were only two or three data points generated during decay. Thus, there is a possibility that accurate signal attenuation cannot be reproduced. Furthermore, the shape of decay is affected by the ROI’s position and shape. Because of the heterogeneity within the tumor, DWI signal attenuation is different depending on the ROI’s position and shape. In this study, we set the ROIs to include the entire area of the tumor, thus the contrast between tumor and normal tissue might be underestimated and the estimated maximum contrast b-value may differ from actual values. Even with the presence of the abovementioned uncertainties, we speculate that maximum contrast b-values exist around b = 1500 s/mm2 with high frequency.
As a result of this study, the optimum b-value to detect breast tumors depends on the case, and so we consider it to be impossible to determine a single optimal b-value. Generally, the b-value is selected to be less than 1000 s/mm2 in breast DWI, although we recommend the use of approximately b-1500 s/mm2 to improve the diagnostic performance. However, we do not recommend the use of high b-values greater than 1000 s/mm2 only, because there are some reports that the accuracy of ADC to distinguish malignant from benign tissue is greatest when using values of b < 1000 s/mm2 [26, 27]. Consequently, we recommend using a combination of b = 750–850 s/mm2 for calculating ADC and b = 1400–1500 s/mm2 for detecting tumors. Using multiple b-value DWI causes prolongation of the scan time and so it may not be suitable to perform these steps in the limited time available. Additionally, it is impossible to set multiple b-values with some vendors’ machines, and selecting different b-values can cause more change in the TE. Higher b-values cause decreased SNR because of diphase due to water molecule diffusion; prolongation of TE will be further conducive to this. Therefore, tumor detection might become difficult under such conditions. Thus, we hope that advancement of technology for employing multiple b-values will enable their use in all vendors’ machines in a shorter TE with higher SNR.
We evaluated the malignant tumor/normal mammary gland contrast of 1.5 T breast DWI using six b-values up to 3500 s/mm2 and investigated the optimal b-value to detect breast cancer. As a result, the maximum contrast b-value was distributed around b = 0 to 2500 s/mm2, and b = 1400 and 1500 s/mm2 were the most frequent. Comparing sensitivity and specificity between b = 700 and 1400 s/mm2, b = 1400 s/mm2 was slightly superior to b = 700 s/mm2. From these results, DWI with a b-value of 1400–1500 s/mm2 is recommended for improving breast tumor detectability. Given that there are some reports that b = 750–850 is suitable for distinguishing malignant from benign tissue using ADC, we recommend performing multiple b-value DWI combinations (b = 750–850 s/mm2 and 1400–1500 s/mm2) for breast DWI.
We would like to offer our special thanks to members of Department of breast surgery, Hiroshima University Hospital.
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