| Part I Diffusion-Weighted MRI of the Breast: Potential for Lesion Characterization and Parameter Selection Objective To evaluate the vary b value of diffusion-weighted (DW) MRI in distinguishing between benign and malignant breast lesions. Methods Three diffusion-weighted sequences were implemented with 500, 1000 and 2000 s/mm2 b-value respectively on 83 patients 95 breast lesions. All lesions confirmed by pathology. The apparent diffusion coefficient (ADC) values and signal intensity (SI) were recorded and compared between breast cancer, benign lesion, cyst and normal beast tissue in same b value DWI. The mean ADC value and mean SI of each type breast lesion in different b values were also analyzed. Results 1) For same breast lesions, the mean ADC value and mean SI declined with the b values increased. One-way ANOVA analysis appeared that the change trend of the different breast lesions mean ADC value and mean SI in different b values were consistent. The significant difference was found in mean ADC value of breast lesions at b values were 500, 1000, and 2000 s/mm2. F=16.019 (P<0.001), F=16.578, (P<0.001), and F=3.122 (P=0.049) respectively. The significant difference was also indicated in mean SI at these b values. F=30.409 (P<0.001), F=23.092 (P<0.001), and F=23.888 (P<0.001) respectively. The difference in the mean ADC value was significant between tow type lesions (cancer and benign lesion, cancer and cyst, cancer and normal breasttissue ...... ) at b values were 500 and 1000 s/mm2. But at 2000 s/mm2, thesignificant difference was only seen between the cancer and the benign lesions. 2) The one-sided upper limit of 95% permissible interval of malignant ADCs was used as a upper threshold, the following diagnostic indices included sensitivity, specificity, accuracy and negative predictive value were higher at 500 s/mm2, and these indices reduced with the b value elevate. The areas under ROC curves in 500 s/mm2 and 1000 s/mm2 ADCs were AZ500 = 0.775 ± 0.046 (P<0.001) and AZ1000 = 0.780 ±0.044 (P<0.001), indicating significant difference of the mean ADC value among the breast lesions. But AZ2000 = 0.620 ± 0.062 (P=0.056), which revealed no difference was indicated at 2000s/mm2 . 3) The mean SI and signal noise ratio were significant difference between DWI of 500 s/mm2 and other's b value DWI. The former was F=65.878 (P<0.001), and the latter F=1.355 (P<0.001). The difference of the DWI noise was not significant among the different b values. Conclusions DWIs, which b value was 500 s/mm2 and 1000 s/mm2, have the potential in diagnosis anddifferentiate the breast lesions.Part II Evaluation of Breast Cancer Extension With Diffusion-Weighted MRI Objective To investigate the feasibility with diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) value in detecting accuracy of the cancer extension. Methods We used DWI to obtain images of 59 lesions (57 patients) before surgical excision. The ADC values of vary breast cancer type were compared. The cancer extension was invested in the different b value ADC map, which represents the distribution of ADC values, according to the threshold values discussed in part I. The lesion extension confirmed in enhanced image and in DWI map was also compared. The tumor extension was determined by calculating two lines. Line one: the maximum diameter of lesion. Line two: perpendicular crossed the midpoint at line one. All measurement was compared with the pathologic specimen. Results 1) The mean ADC value of each cancer type in b at 500 and 1000 s/mm2 was as follows respectively: invasive ductal carcinoma (n=48), 1.305 ± 0.358×103 mm2/s and 1.099±0.300×10-3 mm2/s; medullary carcinoma (n=2), 1.340 ± 0.057 × 10-3 mm2/s and 1.140 ± 0.311 ×10-3mm2/s; ductal carcinoma in situ with small invasive foci (n=6), 1.557 ±0.354 ×10-3 mm2/s and 1.305 ± 0.208 × 10-3 mm2/s; mucinous carcinoma (n=3), 1.873 ± 0.365 × 10-3 mm2/s and 1.623 ± 0.327× 10-3 mm2/s. No significant differences were found between each type of breast cancer but between invasive ductal carcinoma and mucinous carcinoma at b was 500 s/mm2 (P=0.01) and 1000 s/mm2 (P=0.004). 2) Based on the upper threshold 1.5×10-0 mm2/s, 1.3×10-3 mm2/s at b was 500 s/mm2 and 1000 s/mm2 respectively, a near precise distribution of low ADC value on ADC maps was described as cancer extension. The measure results were compared to pathologic figures. We categorized the pattern of correlation into 3 groups: Group 1, where the area of low ADC values was almost the same the pathological tumor extension; Group 2 (overdiagnose), where the area of low ADC values was wider and more than 20% the area of tumor extension; Group 3 (false negative), where no low ADC value was observed. There were all no significant difference in Groups 1 and Group 3 between DWI at b was 500 s/mm2 and 1000 s/mm2 (X2=0.160, P=0.689; X2=0.172, P=0.679). There were 2lesions in Group 2, which were consistent in DWI of 500 s/mm2 and 1000 s/mm2. There were 14 lesions misdiagnose, including overdiagnose 2 lesions and false negative 12 lesions. The former were invasive ductal carcinoma with notable atypical ductal hyperplasia. The latter were ductal carcinoma in situ with small invasive foci (2), invasive ductal carcinoma with marked bleeding necrosis and/or collagen (4), mucinous carcinoma (3) and invasive ductal carcinoma (3). Eight lesions measured at DWI of 500 s/mm2 and 1000 s/mm2 were not consistent. Five lesions were diagnosed correctly at DWI of 500 s/mm , three of them were ductal carcinoma in situ with small invasive foci. 3) The extension of lesion on dynamic enhanced imaging measured at 4 minutes post enhancement, which was compared to the extension measured at same slice on DWI map. Pathologic figures were golden standard. The extension of 47(80%) lesions on enhanced images accorded with DWI. The abnormal area on DWI, which accorded with pathologic figures, was wider than the area on enhanced images in 8 lesions. Of them, 3 lesions were mucinous carcinoma (100%), and 5 lesions were grade 3 invasive ductal carcinoma (83%). Conclusions DWI and the ADC value have the potential in evaluating the cancer extension. For ductal carcinoma in situ with small invasive foci, the measurement was accurate in b value of 500 s/mm2. For invasive ductal carcinoma with marked bleeding necrosis and/or collagen, mucinous carcinoma and smaller ductal carcinoma in situ with microinvasive foci, ADC values usually appeared false negative. The mucinous carcinoma and grade 3 invasive ductal carcinoma extension evaluated on DWI map was better than on dynamic enhanced images.Part III Locally Advanced Breast Cancer Response to Neoadjuvant Chemotherapy: A Pilot study with Diffusion-Weighted MRIObjective To assess the feasibility of using diffusion-weighted MRI for pretreatment prediction and monitoring of tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Methods Response group and progression group were separated in 10 patients according to the change of tumor size after chemotherapy. Changes in ADC value and signal intensity (SI) of DWI were compared between two groups before therapy and after treatment.Pretreatment ADCs were calculated and compared with posttreatment changes in tumor volumes measured on enhanced MR images by using the Spearman correlation test. Results 1) The ADC and SI measured before therapy revealed no distinction between the response group and progression group (P>0.05) , and so did the ADC and SI measured after therapy. But the mean ADC value of the posttreatment was increased in response group. Contrarily, in the progression group, ADC value was decreased, which demonstrated clearly with the use of b value 1000 s/mm2 or 2000 s/mm2 diffusion-weighted MR imaging. 2) The posttreatment mean ADC value was increased in comparison with the pretreatment mean ADC value in the higher viable tumor regions (b=1000 s/mm2: 1.371±0.295 vs 1.195 ± 0.23) . Conversely, the posttreatment mean ADC value was reduced in lower viable tumor regions (b=1 000 s/mm2:1.312 ± 0.297 vs 1.632 ± 0.241). These features closely matched the histologic findings such as tumor cells metamorphosis and collagen and fibrosis formation. 3) The strong negative correlation was observed between ADC values, measured prior to treatment, and changes in tumor volumes after therapy, especially in b at 1000 s/mm2 (r = -0.802, P = 0.005) and 2000 s/mm2 (r = -0.745, P = 0.013) respectively. Conclusions Diffusion-weighted MR imaging has potential use for detection of response to neoadjuvant chemotherapy in locally advanced breast cancer and for predicting treatment outcome prior to initiation of therapy.
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