DW imaging involves the random motion of water molecules, which is detected as attenuation of the measured SI [
15]. The motion of water molecules is more restricted in tissues with a higher cellular density and associated with numerous intact cell membranes [
5,
12,
24]. Therefore, highly cellular areas will appear to be higher in SI on DW images. Our study demonstrates that breast lesions displayed mild to strong SI on DW images compared to surrounding breast parenchyma, and intensity of malignant lesions was generally higher than that of benign lesions. Mean conspicuity grades of malignant lesions were 4.44

±

0.97 at b

=

600

s/mm
2, 4.38

±

1.04 at b

=

800

s/mm
2 and 4.36

±

0.96 at b

=

1000

s/mm
2. Those of benign lesions were 2.56

±

1.38 at b

=

600

s/mm
2, 2.56

±

1.38 at b

=

800

s/mm
2 and 2.17

±

0.99 at b

=

1000

s/mm
2. There was a highly significant difference in the conspicuity between malignant and benign lesions (
P
<

0.0001). Most malignant lesions were circumscribed and displayed strong signals with definite margins on DW images. Margin characteristics, such as the appearance of being spiculated, could not be displayed on DW images for inferior spatial resolution and partial-volume effect. Most benign lesions displayed mild to moderate signal with indistinct or definite margins on DW images. However, DW imaging cannot detect all lesions detected by other conventional MRI. This has been described previously, with 6–37.5% of malignant breast lesions reportedly not visible on DW imaging [
25-
27]. One DCIS and 1 hyperplastic lesion presented as non-mass enhancement on contrast-enhanced imaging but were invisible on DW imaging in the study. One fibroma displayed significant hypointensity on both T
1WI and T
2WI, but it was not detected on DW imaging because the signal intensity was similar to background.
DW imaging also allows quantitative calculation of ADC for each pixel of the image and is displayed as a parametric map. ADC is measured by acquiring the MR signal at least twice, typically with (S
b) and without (S
0) diffusion weighting by the following formula: ADC

=

[In (S
0/S
b)]/b, where S
b and S
0 are the signal intensities on the DW imaging and the reference imaging without diffusion weighting, respectively [
28]. Areas of restricted diffusion in highly cellular areas show low ADC compared with less cellular areas that return higher ADC values. Malignant tumours are frequently more cellular than benign lesions from which they originate and, thus, appear to be of relatively low ADC levels on ADC maps. Furthermore, ADC of invasive tumours appears to be lower than that of carcinoma in situ [
5-
7,
9,
29-
31]. High-grade lesions with the highest cell proliferation rate would have the lowest ADC, which is still controversial [
12,
31-
33]. Our results are in good agreement with previously published results on breast ADC calculation. The mean ADCs of breast cancers were significantly lower than those of benign lesions with all
P values <0.001 at b values of 600, 800 and 1000

s/mm
2. However, for some malignant and benign lesions, there is overlap between ADC values. This is based both on our study and the studies of others. Based on pathological analysis, 1 invasive ductal carcinoma and 1 medullary carcinoma showed ADCs that were within the confidence interval for benign lesions because of lower cellular density. One plasma cell mastitis showed a very small ADC value, possibly because of an increase in macromolecule protein and phlogocyte infiltration. Therefore, detection and characterization of breast lesions based solely on DW imaging is not sufficiently accurate, and DW imaging cannot solely substitute for other MR methods. DW imaging can be a potential adjunct to conventional MRI in the differentiation between malignant and benign lesions for fast imaging without the use of a contrast agent.
The diffusion gradient factor, also known as the “b value”, is an important parameter of DW imaging and determined by the following formula: b

=

γ
2 G
2 δ
2(Δ – δ/3), where γ is the magnetogyric ratio, G is the gradient intensity, δ is the duration of the applied gradient, and Δ is the time interval between the paired gradients. A greater b value indicates a more severe phase dispersion of water molecules and a more reduced signal under the effect of gradient pulse on DW imaging [
15]. Our study demonstrates that the average SI
lesion and SI
normal decreased with increasing b values, and SI was more severely reduced in malignant than in benign lesions and normal parenchyma. Although SNR and CNR of lesions decreased significantly, the degree was not great enough to be visually identified on DW imaging with b value increasing from 600 to 1000

s/mm
2. Most malignant (33/38) and benign (10/13) lesions showed the same conspicuity grades on the three DW imaging. All of lesions detected on the DW imaging at b

=

600

s/mm
2 remained at significant level on the DW imaging at the higher b values although the SI of some lesions decreased with increasing b values. The conspicuity grades of breast lesions were not significantly different among the three b values (
P
=

0.072). Bogner et al. [
18] also compared CNR of breast lesions at different b values on DW imaging. They have found that mean CNR for malignant and benign tumours rose with increasing b values from 0 to 850

s/mm
2, but decreased with even higher b values from 850 to 1200

s/mm
2. The result of our study was not consistent with that of theirs. There are two considerable differences in materials and methods compared between our study and their study. First, we performed DW imaging at 1.5

T and they performed at 3.0

T. Second, CNR were calculated differently. We directly measured SD
noise in the anterior areas outside of breast [
34]. They calculated the standard deviation of intensities σ
lesion and σ
tissue in both volumes as SD
noise.
We also found that there were no significant differences for ADC calculation among the three b values (
P
=

0.436). The results are consistent with previously published data [
35]. Conversely, Peters et al. [
36] have found that ADC of breast lesions varied substantially with the choice of different b values. However, they used quite different b values at 0, 150, 499, and 1500

s/mm
2. ROC analysis revealed AUC of 0.858

±

0.075 at b

=

600

s/mm
2, 0.870

±

0.081 at b

=

800

s/mm
2 and 0.866

±

0.073 at b

=

1000

s/mm
2 for the differentiation between malignant and benign lesions. No statistical significances were seen among the three b values (
P
=

0.743). The result is in good with previously published data involving the degree of b values ranged from 150 to 1500

s/mm
2[
35,
36].
It is first to prospectively evaluate the influence of b values on both the display and ADC measurement of breast lesions on DW imaging at 1.5

T. So far, only one similar study performed using 3.0

T [
18]. Our results suggest that there were significant differences in morphologic pattern and signal strength between malignant and benign lesions (
P
<

0.0001). Most malignant lesions were circumscribed and displayed strong signals with definite margins on DW images. Most benign lesions displayed mild to moderate signal with indistinct or definite margins on DW images. Other studies also demonstrated that strong signal on DW images could be help to diagnose malignant lesions, which is especially meaningful for patients who can’t accept contrast agent [
37,
38]. The ductus or branch distribution and the sign of ring-shape were only seen on malignant lesions in our initial study. Many articles have investigated the performance of ADC in discriminating breast lesions. However, the pooled ADC of malignant and benign lesions and their diagnostic performance vary with pathophysiologic characteristics, MRI techniques, and diagnostic criteria for malignancy in the studies. We think that the appearance pattern on DW imaging has potential value for differentiating malignant and benign breast lesions. This hypothesis should be verified by more clinical investigations.
Our study has some limitations. First, ROIs to measure SI and ADC were set by the operators, which is subjective and that little is known about the reproducibility of measurements. We found that some breast lesions were heterogeneous on DW images and ADC maps. Most tumours, especially malignant, have heterogeneous microenvironments. By drawing an ROI around a tumour, the summary statistical value does not adequately reflect lesion characteristics [
15]. In order to reduce the measurement biases and avoid contamination of the data by adjacent structures, we used a fixed small size of ROI. We selected the hypointensity region of the heterogeneous lesions on ADC maps which was the highest cellular density area on histopathological specimens as ROI to avoid omitting a malignant component of any given lesion.
In addition, we combined the minimal b value of 0

mm
2/s and the maximum b values ranging from 600 to 1000

mm
2/s to calculate ADC. According to previously published articles, the use of multiple b values did not increase the precision of ADC measurements. Instead, it increased vulnerability of patient movement due to longer acquisition times [
35]. A study performed with a 3.0

T MR imager suggested that ADC determination and DW imaging quality was optimum with a combined b value of 50 and 850

s/mm
2[
18]. Therefore, further investigation is needed to estimate whether another minimum b value, other than 0

mm
2/s, can reduce the perfusion effect and T
2-shine through effect on DW imaging.