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Apparent Diffusion Coefficient in Invasive Ductal Breast Carcinoma: Correlation with Detailed Histologic Features and the Enhancement Ratio on Dynamic Contrast-Enhanced MR Images

Apparent Diffusion Coefficient in Invasive Ductal Breast Carcinoma: Correlation with Detailed... Hindawi Publishing Corporation Journal of Oncology Volume 2010, Article ID 821048, 6 pages doi:10.1155/2010/821048 Clinical Study Apparent Diffusion Coefficient in Invasive Ductal Breast Carcinoma: Correlation with Detailed Histologic Features and the Enhancement Ratio on Dynamic Contrast-Enhanced MR Images 1, 2 2, 3 1 1, 4 Roka Namoto Matsubayashi, Teruhiko Fujii, Kotaro Yasumori, Toru Muranaka, and Seiya Momosaki Department of Radiology, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Breast Care Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Department of Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Department of Pathology, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Correspondence should be addressed to Roka Namoto Matsubayashi, radmad311@yahoo.co.jp Received 27 April 2010; Accepted 15 July 2010 Academic Editor: Jorg ¨ Kleeff Copyright © 2010 Roka Namoto Matsubayashi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. To investigate the correlation of Apperent Diffusion Coefficient (ADC) values in invasive ductal breast carcinomas with detailed histologic features and enhancement ratios on dynamic contrast-enhanced MRI. Methods and Materials.Dynamic MR images and diffusion-weighted images (DWIs) of invasive ductal breast carcinomas were reviewed in 25 (26 lesions) women. In each patient, DWI, T2WI, T1WI, and dynamic images were obtained. The ADC values of the 26 carcinomas were calculated with b-factors of 0 and 1000 s/mm using echoplanar DWI. Correlations of the ADC values were examined on dynamic MRI with enhancement ratios (early to delayed phase: E/D ratio) and detailed histologic findings for each lesion, including cellular density, the size of cancer nests, and architectural features of the stroma (broad, narrow, and delicate) between cancer nests. Results.The −3 2 mean ADC was 0.915 ± 0.151 × 10 mm /sec. Cellular density was significantly correlated with ADC values (P = .0184) and E/D ratios (P = .0315). The ADC values were also significantly correlated to features of the stroma (broad to narrow, P = .0366). Conclusion. The findings suggest that DWIs reflect the growth patterns of carcinomas, including cellular density and architectural features of the stroma, and E/D ratios may also be closely correlated to cellular density. 1. Introduction have demonstrated a relationship between apparent diffusion coefficient (ADC) values and tumor cellular density. Diffusion-weighted (DW) imaging has become an important Typically, invasive ductal carcinoma shows early strong method for diagnosis of breast lesions. Recent studies [1– enhancement due to the expression of many angiogenic or 5] have shown the usefulness of DW imaging for detecting growth factors, including vascular endothelial growth factor breast tumors and distinguishing between malignant and (VEGF) and tumor neovascularity. Pathologically, invasive benign breast lesions. In many tumors, histologic differen- ductal breast carcinomas are comprised of cancer nests, tiation reflects the cellular density, and several studies [6–9] stromas between these nests, and some ductal components. 2 Journal of Oncology We have shown that histologic morphologic features such 2.3. Image Analysis as the size of the cancer nests, the width of the stroma, Interpretation of MR Images. Two of the authors (R. N. fibrosis, angiogenesis, and patterns of VEGF expression Matsubayashi and T. Fujii) interpreted the MR images. We affect enhancement patterns of breast carcinomas [10]. recorded the size, shape, and enhancement pattern of each Additionally, these histologic parameters are closely related lesion but did not use the ACR MRI BI-RADS classification. with growth patterns of breast carcinomas. The aim of the study was to investigate the histologic features that affect the ADC in invasive ductal breast Measurement of the ADC. Based on the DW images, we carcinomas. To our knowledge, correlations of ADC values measured the ADC values of 26 carcinomas. ADC values with enhancement patterns on dynamic contrast-enhanced were calculated with b-factors of 0 and 1000 s/mm using MR images and morphologic histologic features in invasive echoplanar DW images. A region of interest (ROI) of as large ductal breast carcinomas have not been reported previously. a size as possible was positioned over the tumor to avoid necrosis or scar (nonenhanced area) and artifacts, based on dynamic MR images (Figures 1(a) and 1(b)). Positioning of 2. Material and Methods the ROI of each lesion was performed by a radiologist (R. N. Matsubayashi). 2.1. Patients. Twenty-five consecutive women (26 lesions) When the lesions were ring-like on DW images, we (age 30–74 years old, mean 59.2 ± 10.9 years old) with positioned the ROI in the peripheral portion. The signal invasive ductal breast carcinoma who underwent partial intensities in the ROI corresponded to the two different b or total mastectomy after MR imaging at our institution values. between September 2005 and August 2006 were selected for examination. The lesion was initially detected by physical Enhancement Ratio on MR Images. The enhancement ratio examination, mammography, or ultrasonography. None of on dynamic contrast-enhanced MR images in the early the patients had undergone chemotherapy or large-core nee- (60 sec) to the delayed (300 sec) phase (E/D ratio) was dle biopsy for tissue sampling before the MR examination. calculated for each lesion. When the lesion showed rim enhancement, the E/D ratio was calculated at the peripheral 2.2. MR Imaging. MR imaging was performed using a 1.5T region. whole-body imager (Magnetom Symphony; Siemens AG, Erlangen, Germany). The affected side in each patient was 2.4. Histopathologic Analysis. Two of the authors (R. N. Mat- examined using a dedicated breast coil with the patient subayashi: who has degree of pathology and S. Momosaki: in the prone position. DW images were acquired using a general pathologist) performed the histopathologic analysis. multisection single-shot short tau inversion recovery (STIR) Evaluation of morphologic features was performed using echoplanar sequence in the transverse or sagittal plane. slices stained with hematoxylin-eosin. Cellular density, the Following DW imaging, fat-suppressed T2- and T1-weighted size of the cancer nests, and the architectural features of the and dynamic images were obtained. Subtraction images stroma between the cancer nests were examined (Figure 2). were produced from dynamic images for identification of To determine the cellular density, the number of nuclei of enhancement. The imaging parameters were as follows: DWI cancer cells in 10 high-power fields (x400) for each lesion (TR/TE/TI = 5400/80/180 msec, matrix = 50 × 128, slice was counted, and the mean value was recorded. To assess thickness (SL) = 5 mm, FOV = 131 × 300 mm, b factor = the size of cancer nests and architectural features of the 0 and 1000 s/mm , with a motion probing gradient (MPG) stroma, the major axis of 10 cancer nests and the width of applied along the X , Y,and Z axes), 2D fat-suppressed the stroma at 10 points were also measured for each lesion. T2-weighted turbo spin-echo pulse sequence (TR/TE = Based on the mean length of the major axis, the sizes of 4500/84 msec, matrix = 460 × 512, SL = 5 mm, field of the cancer nests were determined and classified as small view (FOV) = 200 × 200 mm), and a three-dimensional fat- (<40 μm), medium (40–100 μm), or large (>100 μm). The suppressed T1-weighted FLASH pulse sequence (TR/TE = mean width and morphology of the stroma between the 5.9/2.4 msec, matrix = 141 × 256, SL = 1.5 mm, FOV = 150 cancer nests were determined, and the stroma was classified × 220 mm). The latter sequence was performed before and as delicate (<10 μm), narrow (10–50 μm), or broad (>50 μm). during intravenous contrast enhancement with 0.1 mmol gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) per kilogram of body weight. A bolus of contrast 2.5. Statistical Analysis. Statistical comparisons were per- agent was injected intravenously using a dedicated infusion formed using Fisher’s protected least significant difference pump at a rate of 1 ml/s, followed by a 20-ml saline solution test or Spearman’s log rank test. The correlation of ADC flush. Sequential multisection, whole-breast images were values with the E/D ratio on dynamic contrast-enhanced obtained in the sagittal plane at 30-second intervals for 5 MR images was examined. ADC values were also compared minutes. In all patients, late sagittal T1-weighted (TR/TE = between groups, for which the status of each histologic 420/10 msec, matrix = 384 × 512, SL = 5 mm, FOV = 200 × parameter, size of cancer nests, and stroma features were 200 mm) and transverse T1-weighted (TR/TE = 420/10 msec, determined. A P-value of less than .05 was considered to be matrix = 384 × 512, SL = 5 mm, FOV = 131 × 300 mm) statistically significant. Data are expressed as means ± SD. images were obtained for the bilateral breasts. Statistical analysis was performed using StatView software. Journal of Oncology 3 Early image DW image Delayed image ADC map (a) Early image DW image Delayed image ADC map (b) Figure 1: MR images of representative cases. (a) Case 3: a 59-year-old woman with invasive carcinoma of the left breast. E/D ratio: 1.03, −3 2 ADC value 0.850 × 10 mm /s. A well-demarcated mass with strong enhancement is observed. The mass shows high intensity on DWI (b = −3 2 1000). (b) Case 13: a 72-year-old woman with invasive carcinoma in the right breast. E/D ratio: 0.90, ADC value 0.975 × 10 mm /s. A mass with early rim enhancement with delayed internal enhancement is shown. The mass shows high intensity on DWI (b = 1000). The central portion shows relatively low signal intensity than that in the periphery. The central area showing delayed enhancement may have abundant fibrous stroma. 4 Journal of Oncology (a) (b) (c) Figure 2: Cancer nests at invasive sites are classified based on the mean length of the major axis: small, medium, or large. Features of the stroma between the nests are classified as delicate, narrow, or broad (nests: asterisk, stroma: black arrows). (a) Nests: large, stroma: broad. (b) Nests: medium, stroma: delicate. (c) Nests: small, stroma: narrow. All sections are hematoxylin-eosin stained. P = .0366 show high angiogenesis, especially at invasive sites. The expression level of one of the angiogenic factors, VEGF, correlates with the histologic grade and a variety of clinical and prognostic factors [12–15]. Dynamic contrast-enhanced MR imaging has been used to evaluate the vascular supply to breast carcinomas. Invasive ductal breast carcinomas show 60 strong early enhancement with prolonged or reduced delayed enhancement in such imaging, and these enhancement patterns are closely correlated with histologic morphologic features [10]. DWI is a useful tool for diagnosis of cerebral infarcts and other intracranial lesions and has recently been used for diagnosis and detection of neoplasms in several organs. In many carcinomas, cellular density is higher in lesions of Broad Delicate Narrow higher grade, and DWI may reflect the carcinoma growth Figure 3: ADC values were significantly correlated with stroma pattern. DWI has also been used for body imaging, since features (broad to narrow, P = .0366). D: delicate, N: narrow, it allows clear detection of breast carcinomas and is helpful −3 B: broad. ADC: ×10 mm /s.S:small,M:medium, L: large, in determination of the extent of the carcinoma and in the D: delicate, N: narrow, B: broad, E/D: enhancement ratio of differentiation between malignant and benign lesions [1–5]. early/delayed phase. DWI is also used to calculate ADC values, which can reflect cellular density; thus, this technique provides a lot of useful information for treatment decisions. 3. Results Kuroki et al. [3] showed that diffusion in breast carci- noma is significantly lower than that in benign masses, and Clinical data, MR imaging and histologic features, ADCs, a significant difference in diffusion has been seen between and the E/D ratio on contrast-enhanced MR images for all invasive ductal carcinoma and pure or predominant non- patients are summarized in Table 1. The sizes of lesions were invasive ductal carcinoma. Several reports have also shown 0.8–3.5 cm (mean 1.9 ± 0.8 cm). The mean ADC value of a correlation between the stage of liver fibrosis and ADCs −3 2 the lesions was 0.915 ± 0.151 × 10 mm /s, and the mean [16, 17]. Since breast carcinoma often has fibrotic stroma, enhancement ratio was 0.962 ± 0.1. Cellular densities were we hypothesized that the degree of fibrosis might also be significantly correlated with ADC values (P = .0184) and reflected by the ADC. E/D ratios (P = .0315). ADC values were also significantly Both cellular density and histologic architectural varia- correlated with stroma features (broad to narrow, P = .0366) tion of cancer nests and stroma may be affected by the growth (Figure 3). There was no correlation between ADC values pattern, including the histologic grade of the individual and E/D ratios and the size of cancer nests. breast carcinoma. In the present study, enhancement ratios of breast carcinomas on dynamic MR images closely corre- lated with cellular density and the histologic, morphologic 4. Discussion features. These results suggest that both DW imaging and MR imaging is useful for diagnosis of breast carcinomas dynamic studies can provide detailed histological or bio- [11] and to assist in selection of appropriate treatment. logical information about the lesions. Prediction of growth Due to overexpression of growth factors, breast carcinomas patterns of tumors from imaging findings may be useful for Journal of Oncology 5 Table 1: Clinical data, MR imaging and histologic features, ADCs, and the E/D ratio on contrast-enhanced MR images. Case Number Age Tumor diameter (cm) Cellular density Size of nest Type of stroma E/D ADC 161 1.4 × 1.0 1038 M N 0.98 0.564 269 3.0 × 2.3 315 M N 0.96 0.830 359 1.6 × 0.9 527 L D 1.03 0.850 462 0.8 × 0.7 301 S B 1.02 0.940 560 2.8 × 2.6 324 S B 0.88 0.910 649 0.8 × 0.8 902 M D 1.10 0.863 730 1.5 × 1.3 428 S B 0.91 0.885 867 3.5 × 3.4 502 L B 0.92 0.718 958 2.0 × 1.6 766 M D 1.06 0.971 10 65 2.5 × 1.9 278 S B 0.84 1.118 11 45 1.7 × 1.3 336 M N 0.99 0.930 12 58 1.0 × 0.8 303 M N 0.96 0.858 13 72 2.3 × 2.0 211 M D 0.90 0.975 14 61 2.5 × 1.9 224 L N 0.76 1.218 15 67 2.0 × 1.7 504 L D 1.11 0.828 16 41 1.9 × 1.7 508 S N 0.92 0.837 17 73 0.9 × 0.8 856 M D 0.93 0.866 18 68 1.8 × 1.2 886 L B 0.99 0.874 19 69 2.5 × 1.7 566 L D 1.08 0.934 20 63 3.2 × 2.9 452 S B 0.84 0.865 21 63 2.2 × 1.5 621 S B 0.73 0.928 22 56 2.2 × 1.3 877 S N 0.97 0.835 23 74 1.2 × 0.8 456 L B 1.04 1.294 24 45 1.5 × 1.5 356 M N 0.97 0.879 25 45 1.3 × 0.8 776 S B 1.11 1.111 26 59 2.1 × 1.3 935 L N 1.02 0.840 planning treatment for breast carcinoma, and we suggest that our results demonstrate the potential for use of DWI in the a combination of these imaging techniques may become an assessment of treatment for invasive ductal carcinoma. important tool to evaluate the effectiveness of chemotherapy or irradiation for breast carcinoma. References The study is limited by the relatively small number of patients. Also, it was difficult to evaluate ADCs of tiny lesions [1] R. Woodhams, K. Matsunaga, S. Kan et al., “ADC mapping of on our DW images because the images were distorted in benign and malignant breast tumors,” MRMS,vol. 4, no.1,pp. 35–42, 2005. the breast periphery. Parallel imaging techniques including SENSE may be able to reduce these artifacts (including [2] E. Rubesova, A.-S. Grell, V. De Maertelaer, T. Metens, S.- L. Chao, and M. Lemort, “Quantitative diffusion imaging in motion artifacts) and shorten the scanning time. Addition- breast cancer: a clinical prospective study,” Journal of Magnetic ally, for the optimal measurement of ADC values, patients Resonance Imaging, vol. 24, no. 2, pp. 319–324, 2006. with prior large-core needle biopsy must be excluded because [3] Y. Kuroki, K. Nasu, S. Kuroki et al., “Diffusion-weighted imag- the blood may affect the ADC. And then, we consider that ing of breast cancer with the sensitivity encoding technique: the ROI must cover the enhancing area as large as possible analysis of the apparent diffusion coefficient value,” MRMS, avoiding necrosis or scar to correctly reflect the cellular vol. 3, no. 2, pp. 79–85, 2004. density of the tumor. [4] H. Lyng, O. Haraldseth, and E. K. Rofstad, “Measurement of cell density and necrotic fraction in human melanoma 5. Conclusion xenografts by diffusion weighted magnetic resonance imag- ing,” Magnetic Resonance in Medicine, vol. 43, no. 6, pp. 828– Despite the small number of cases, our findings suggest 836, 2000. that enhancement ratios on dynamic MR imaging reflect [5] N. H. G. M. Peters, K. L. Vincken, M. A. A. J. Van Den Bosch, P. the growth patterns of invasive ductal breast carcinomas, R. Luijten, W. P.Th. M. Mali, and L. W. Bartels, “Quantitative including the cellular density. The cellular density and diffusion weighted imaging for differentiation of benign and cancer stroma also appear to be closely correlated with malignant breast lesions: the influence of the choice of b- ADC values. Both DW imaging and dynamic studies provide values,” Journal of Magnetic Resonance Imaging, vol. 31, no. 5, detailed information about invasive breast carcinomas, and pp. 1100–1105, 2010. 6 Journal of Oncology [6] Y. Guo, Y.-Q. Cai, Z.-L. Cai et al., “Differentiation of clinically benign and malignant breast lesions using diffusion-weighted imaging,” Journal of Magnetic Resonance Imaging, vol. 16, no. 2, pp. 172–178, 2002. [7] A. W. Anderson, J. Xie, J. Pizzonia, R. A. Bronen, D. D. Spencer, and J. C. Gore, “Effects of cell volume fraction changes on apparent diffusion in human cells,” Magnetic Resonance Imaging, vol. 18, no. 6, pp. 689–695, 2000. [8] S. Naganawa, C. Sato, H. Kumada, T. Ishigaki, S. Miura, and O. Takizawa, “Apparent diffusion coefficient in cervical cancer of the uterus: comparison with the normal uterine cervix,” European Radiology, vol. 15, no. 1, pp. 71–78, 2005. [9] X.-J. Sun, X.-Y. Quan, F.-H. Huang, and Y.-K. Xu, “Quan- titative evaluation of diffusion-weighted magnetic resonance imaging of focal hepatic lesions,” World Journal of Gastroen- terology, vol. 11, no. 41, pp. 6535–6537, 2005. [10] R. Matsubayashi, Y. Matsuo, G. Edakuni, T. Satoh, O. Tokunaga, and S. Kudo, “Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors,” Radiology, vol. 217, no. 3, pp. 841–848, 2000. [11] N. H. G. M. Peters,I.H.M.Borel Rinkes,N.P.A.Zuithoff,W. P. T. M. Mali,K.G.M.Moons,and P. H. M. Peeters, “Meta- analysis of MR imaging in the diagnosis of breast lesions,” Radiology, vol. 246, no. 1, pp. 116–124, 2008. [12] L. F. Brown, B. Berse, R. W. Jackman et al., “Expression of vascular permeability factor (Vascular endothelial growth factor) and its receptors in breast cancer,” Human Pathology, vol. 26, no. 1, pp. 86–91, 1995. [13] K. Anan, T. Morisaki, M. Katano et al., “Vascular endothelial growth factor and platelet-derived growth factor are potential angiogenic and metastatic factors in human breast cancer,” Surgery, vol. 119, no. 3, pp. 333–339, 1996. [14] G. Gasparini, M. Toi, M. Gion et al., “Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma,” Journal of the National Cancer Institute, vol. 89, no. 2, pp. 139–147, 1997. [15] K. Engels, S. B. Fox, and A. L. Harris, “Angiogenesis as a bio- logic and prognostic indicator in human breast carcinoma,” EXS, vol. 79, pp. 113–156, 1997. [16] B. Taouli, A. J. Tolia, M. Losada et al., “Diffusion-weighted MRI for quantification of liver fibrosis: preliminary experi- ence,” American Journal of Roentgenology, vol. 189, no. 4, pp. 799–806, 2007. [17] M. Koinuma, I. Ohashi, K. Hanafusa, and H. Shibuya, “Apparent diffusion coefficient measurements with diffusion- weighted magnetic resonance imaging for evaluation of hepatic fibrosis,” Journal of Magnetic Resonance Imaging, vol. 22, no. 1, pp. 80–85, 2005. 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Apparent Diffusion Coefficient in Invasive Ductal Breast Carcinoma: Correlation with Detailed Histologic Features and the Enhancement Ratio on Dynamic Contrast-Enhanced MR Images

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Hindawi Publishing Corporation
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Copyright © 2010 Roka Namoto Matsubayashi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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10.1155/2010/821048
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Abstract

Hindawi Publishing Corporation Journal of Oncology Volume 2010, Article ID 821048, 6 pages doi:10.1155/2010/821048 Clinical Study Apparent Diffusion Coefficient in Invasive Ductal Breast Carcinoma: Correlation with Detailed Histologic Features and the Enhancement Ratio on Dynamic Contrast-Enhanced MR Images 1, 2 2, 3 1 1, 4 Roka Namoto Matsubayashi, Teruhiko Fujii, Kotaro Yasumori, Toru Muranaka, and Seiya Momosaki Department of Radiology, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Breast Care Center, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Department of Surgery, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Clinical Research Institute, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Department of Pathology, National Hospital Organization Kyushu Medical Center, 1-8-1 Jigyohama, Chuo-ku, Fukuoka 810-8563, Japan Correspondence should be addressed to Roka Namoto Matsubayashi, radmad311@yahoo.co.jp Received 27 April 2010; Accepted 15 July 2010 Academic Editor: Jorg ¨ Kleeff Copyright © 2010 Roka Namoto Matsubayashi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. To investigate the correlation of Apperent Diffusion Coefficient (ADC) values in invasive ductal breast carcinomas with detailed histologic features and enhancement ratios on dynamic contrast-enhanced MRI. Methods and Materials.Dynamic MR images and diffusion-weighted images (DWIs) of invasive ductal breast carcinomas were reviewed in 25 (26 lesions) women. In each patient, DWI, T2WI, T1WI, and dynamic images were obtained. The ADC values of the 26 carcinomas were calculated with b-factors of 0 and 1000 s/mm using echoplanar DWI. Correlations of the ADC values were examined on dynamic MRI with enhancement ratios (early to delayed phase: E/D ratio) and detailed histologic findings for each lesion, including cellular density, the size of cancer nests, and architectural features of the stroma (broad, narrow, and delicate) between cancer nests. Results.The −3 2 mean ADC was 0.915 ± 0.151 × 10 mm /sec. Cellular density was significantly correlated with ADC values (P = .0184) and E/D ratios (P = .0315). The ADC values were also significantly correlated to features of the stroma (broad to narrow, P = .0366). Conclusion. The findings suggest that DWIs reflect the growth patterns of carcinomas, including cellular density and architectural features of the stroma, and E/D ratios may also be closely correlated to cellular density. 1. Introduction have demonstrated a relationship between apparent diffusion coefficient (ADC) values and tumor cellular density. Diffusion-weighted (DW) imaging has become an important Typically, invasive ductal carcinoma shows early strong method for diagnosis of breast lesions. Recent studies [1– enhancement due to the expression of many angiogenic or 5] have shown the usefulness of DW imaging for detecting growth factors, including vascular endothelial growth factor breast tumors and distinguishing between malignant and (VEGF) and tumor neovascularity. Pathologically, invasive benign breast lesions. In many tumors, histologic differen- ductal breast carcinomas are comprised of cancer nests, tiation reflects the cellular density, and several studies [6–9] stromas between these nests, and some ductal components. 2 Journal of Oncology We have shown that histologic morphologic features such 2.3. Image Analysis as the size of the cancer nests, the width of the stroma, Interpretation of MR Images. Two of the authors (R. N. fibrosis, angiogenesis, and patterns of VEGF expression Matsubayashi and T. Fujii) interpreted the MR images. We affect enhancement patterns of breast carcinomas [10]. recorded the size, shape, and enhancement pattern of each Additionally, these histologic parameters are closely related lesion but did not use the ACR MRI BI-RADS classification. with growth patterns of breast carcinomas. The aim of the study was to investigate the histologic features that affect the ADC in invasive ductal breast Measurement of the ADC. Based on the DW images, we carcinomas. To our knowledge, correlations of ADC values measured the ADC values of 26 carcinomas. ADC values with enhancement patterns on dynamic contrast-enhanced were calculated with b-factors of 0 and 1000 s/mm using MR images and morphologic histologic features in invasive echoplanar DW images. A region of interest (ROI) of as large ductal breast carcinomas have not been reported previously. a size as possible was positioned over the tumor to avoid necrosis or scar (nonenhanced area) and artifacts, based on dynamic MR images (Figures 1(a) and 1(b)). Positioning of 2. Material and Methods the ROI of each lesion was performed by a radiologist (R. N. Matsubayashi). 2.1. Patients. Twenty-five consecutive women (26 lesions) When the lesions were ring-like on DW images, we (age 30–74 years old, mean 59.2 ± 10.9 years old) with positioned the ROI in the peripheral portion. The signal invasive ductal breast carcinoma who underwent partial intensities in the ROI corresponded to the two different b or total mastectomy after MR imaging at our institution values. between September 2005 and August 2006 were selected for examination. The lesion was initially detected by physical Enhancement Ratio on MR Images. The enhancement ratio examination, mammography, or ultrasonography. None of on dynamic contrast-enhanced MR images in the early the patients had undergone chemotherapy or large-core nee- (60 sec) to the delayed (300 sec) phase (E/D ratio) was dle biopsy for tissue sampling before the MR examination. calculated for each lesion. When the lesion showed rim enhancement, the E/D ratio was calculated at the peripheral 2.2. MR Imaging. MR imaging was performed using a 1.5T region. whole-body imager (Magnetom Symphony; Siemens AG, Erlangen, Germany). The affected side in each patient was 2.4. Histopathologic Analysis. Two of the authors (R. N. Mat- examined using a dedicated breast coil with the patient subayashi: who has degree of pathology and S. Momosaki: in the prone position. DW images were acquired using a general pathologist) performed the histopathologic analysis. multisection single-shot short tau inversion recovery (STIR) Evaluation of morphologic features was performed using echoplanar sequence in the transverse or sagittal plane. slices stained with hematoxylin-eosin. Cellular density, the Following DW imaging, fat-suppressed T2- and T1-weighted size of the cancer nests, and the architectural features of the and dynamic images were obtained. Subtraction images stroma between the cancer nests were examined (Figure 2). were produced from dynamic images for identification of To determine the cellular density, the number of nuclei of enhancement. The imaging parameters were as follows: DWI cancer cells in 10 high-power fields (x400) for each lesion (TR/TE/TI = 5400/80/180 msec, matrix = 50 × 128, slice was counted, and the mean value was recorded. To assess thickness (SL) = 5 mm, FOV = 131 × 300 mm, b factor = the size of cancer nests and architectural features of the 0 and 1000 s/mm , with a motion probing gradient (MPG) stroma, the major axis of 10 cancer nests and the width of applied along the X , Y,and Z axes), 2D fat-suppressed the stroma at 10 points were also measured for each lesion. T2-weighted turbo spin-echo pulse sequence (TR/TE = Based on the mean length of the major axis, the sizes of 4500/84 msec, matrix = 460 × 512, SL = 5 mm, field of the cancer nests were determined and classified as small view (FOV) = 200 × 200 mm), and a three-dimensional fat- (<40 μm), medium (40–100 μm), or large (>100 μm). The suppressed T1-weighted FLASH pulse sequence (TR/TE = mean width and morphology of the stroma between the 5.9/2.4 msec, matrix = 141 × 256, SL = 1.5 mm, FOV = 150 cancer nests were determined, and the stroma was classified × 220 mm). The latter sequence was performed before and as delicate (<10 μm), narrow (10–50 μm), or broad (>50 μm). during intravenous contrast enhancement with 0.1 mmol gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) per kilogram of body weight. A bolus of contrast 2.5. Statistical Analysis. Statistical comparisons were per- agent was injected intravenously using a dedicated infusion formed using Fisher’s protected least significant difference pump at a rate of 1 ml/s, followed by a 20-ml saline solution test or Spearman’s log rank test. The correlation of ADC flush. Sequential multisection, whole-breast images were values with the E/D ratio on dynamic contrast-enhanced obtained in the sagittal plane at 30-second intervals for 5 MR images was examined. ADC values were also compared minutes. In all patients, late sagittal T1-weighted (TR/TE = between groups, for which the status of each histologic 420/10 msec, matrix = 384 × 512, SL = 5 mm, FOV = 200 × parameter, size of cancer nests, and stroma features were 200 mm) and transverse T1-weighted (TR/TE = 420/10 msec, determined. A P-value of less than .05 was considered to be matrix = 384 × 512, SL = 5 mm, FOV = 131 × 300 mm) statistically significant. Data are expressed as means ± SD. images were obtained for the bilateral breasts. Statistical analysis was performed using StatView software. Journal of Oncology 3 Early image DW image Delayed image ADC map (a) Early image DW image Delayed image ADC map (b) Figure 1: MR images of representative cases. (a) Case 3: a 59-year-old woman with invasive carcinoma of the left breast. E/D ratio: 1.03, −3 2 ADC value 0.850 × 10 mm /s. A well-demarcated mass with strong enhancement is observed. The mass shows high intensity on DWI (b = −3 2 1000). (b) Case 13: a 72-year-old woman with invasive carcinoma in the right breast. E/D ratio: 0.90, ADC value 0.975 × 10 mm /s. A mass with early rim enhancement with delayed internal enhancement is shown. The mass shows high intensity on DWI (b = 1000). The central portion shows relatively low signal intensity than that in the periphery. The central area showing delayed enhancement may have abundant fibrous stroma. 4 Journal of Oncology (a) (b) (c) Figure 2: Cancer nests at invasive sites are classified based on the mean length of the major axis: small, medium, or large. Features of the stroma between the nests are classified as delicate, narrow, or broad (nests: asterisk, stroma: black arrows). (a) Nests: large, stroma: broad. (b) Nests: medium, stroma: delicate. (c) Nests: small, stroma: narrow. All sections are hematoxylin-eosin stained. P = .0366 show high angiogenesis, especially at invasive sites. The expression level of one of the angiogenic factors, VEGF, correlates with the histologic grade and a variety of clinical and prognostic factors [12–15]. Dynamic contrast-enhanced MR imaging has been used to evaluate the vascular supply to breast carcinomas. Invasive ductal breast carcinomas show 60 strong early enhancement with prolonged or reduced delayed enhancement in such imaging, and these enhancement patterns are closely correlated with histologic morphologic features [10]. DWI is a useful tool for diagnosis of cerebral infarcts and other intracranial lesions and has recently been used for diagnosis and detection of neoplasms in several organs. In many carcinomas, cellular density is higher in lesions of Broad Delicate Narrow higher grade, and DWI may reflect the carcinoma growth Figure 3: ADC values were significantly correlated with stroma pattern. DWI has also been used for body imaging, since features (broad to narrow, P = .0366). D: delicate, N: narrow, it allows clear detection of breast carcinomas and is helpful −3 B: broad. ADC: ×10 mm /s.S:small,M:medium, L: large, in determination of the extent of the carcinoma and in the D: delicate, N: narrow, B: broad, E/D: enhancement ratio of differentiation between malignant and benign lesions [1–5]. early/delayed phase. DWI is also used to calculate ADC values, which can reflect cellular density; thus, this technique provides a lot of useful information for treatment decisions. 3. Results Kuroki et al. [3] showed that diffusion in breast carci- noma is significantly lower than that in benign masses, and Clinical data, MR imaging and histologic features, ADCs, a significant difference in diffusion has been seen between and the E/D ratio on contrast-enhanced MR images for all invasive ductal carcinoma and pure or predominant non- patients are summarized in Table 1. The sizes of lesions were invasive ductal carcinoma. Several reports have also shown 0.8–3.5 cm (mean 1.9 ± 0.8 cm). The mean ADC value of a correlation between the stage of liver fibrosis and ADCs −3 2 the lesions was 0.915 ± 0.151 × 10 mm /s, and the mean [16, 17]. Since breast carcinoma often has fibrotic stroma, enhancement ratio was 0.962 ± 0.1. Cellular densities were we hypothesized that the degree of fibrosis might also be significantly correlated with ADC values (P = .0184) and reflected by the ADC. E/D ratios (P = .0315). ADC values were also significantly Both cellular density and histologic architectural varia- correlated with stroma features (broad to narrow, P = .0366) tion of cancer nests and stroma may be affected by the growth (Figure 3). There was no correlation between ADC values pattern, including the histologic grade of the individual and E/D ratios and the size of cancer nests. breast carcinoma. In the present study, enhancement ratios of breast carcinomas on dynamic MR images closely corre- lated with cellular density and the histologic, morphologic 4. Discussion features. These results suggest that both DW imaging and MR imaging is useful for diagnosis of breast carcinomas dynamic studies can provide detailed histological or bio- [11] and to assist in selection of appropriate treatment. logical information about the lesions. Prediction of growth Due to overexpression of growth factors, breast carcinomas patterns of tumors from imaging findings may be useful for Journal of Oncology 5 Table 1: Clinical data, MR imaging and histologic features, ADCs, and the E/D ratio on contrast-enhanced MR images. Case Number Age Tumor diameter (cm) Cellular density Size of nest Type of stroma E/D ADC 161 1.4 × 1.0 1038 M N 0.98 0.564 269 3.0 × 2.3 315 M N 0.96 0.830 359 1.6 × 0.9 527 L D 1.03 0.850 462 0.8 × 0.7 301 S B 1.02 0.940 560 2.8 × 2.6 324 S B 0.88 0.910 649 0.8 × 0.8 902 M D 1.10 0.863 730 1.5 × 1.3 428 S B 0.91 0.885 867 3.5 × 3.4 502 L B 0.92 0.718 958 2.0 × 1.6 766 M D 1.06 0.971 10 65 2.5 × 1.9 278 S B 0.84 1.118 11 45 1.7 × 1.3 336 M N 0.99 0.930 12 58 1.0 × 0.8 303 M N 0.96 0.858 13 72 2.3 × 2.0 211 M D 0.90 0.975 14 61 2.5 × 1.9 224 L N 0.76 1.218 15 67 2.0 × 1.7 504 L D 1.11 0.828 16 41 1.9 × 1.7 508 S N 0.92 0.837 17 73 0.9 × 0.8 856 M D 0.93 0.866 18 68 1.8 × 1.2 886 L B 0.99 0.874 19 69 2.5 × 1.7 566 L D 1.08 0.934 20 63 3.2 × 2.9 452 S B 0.84 0.865 21 63 2.2 × 1.5 621 S B 0.73 0.928 22 56 2.2 × 1.3 877 S N 0.97 0.835 23 74 1.2 × 0.8 456 L B 1.04 1.294 24 45 1.5 × 1.5 356 M N 0.97 0.879 25 45 1.3 × 0.8 776 S B 1.11 1.111 26 59 2.1 × 1.3 935 L N 1.02 0.840 planning treatment for breast carcinoma, and we suggest that our results demonstrate the potential for use of DWI in the a combination of these imaging techniques may become an assessment of treatment for invasive ductal carcinoma. important tool to evaluate the effectiveness of chemotherapy or irradiation for breast carcinoma. 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