Cancer Investigation, Early Online:1–6, 2015 ISSN: 0735-7907 print / 1532-4192 online C 2015 Informa Healthcare USA, Inc. Copyright DOI: 10.3109/07357907.2015.1019674
ORIGINAL ARTICLE
Diffusion Weighted Imaging and Apparent Diffusion Coefficient in 3 Tesla Magnetic Resonance Imaging of Breast Lesions Rocchina Caivano,1,a Antonio Villonio,1,a Felice D’ Antuono,1 Matilde Gioioso,1 Paola Rabasco,1 Giancarlo Iannelli,1 Alexis Zandolino,1 Antonella Lotumolo,1 Giuseppina Dinardo,1 Luca Macarini,2 Giuseppe Guglielmi,2 and Aldo Cammarota1
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IRCCS—CROB, Rionero in Vulture (Pz), Italy1 Radiology, University of Foggia, Foggia, Italy2 malignant breast lesions (10–19), with higher ADC values for benign lesions reflecting lower molecular movement and cellularity, and subsequently lower ADC values for malignant lesions. These studies have been mainly performed with 1.5 T MRI scanners. 3T MRI, with appropriate acquisition parameters, affords an higher signal-to-noise ratio (SNR) and therefore an improved spatial resolution (20). To our knowledge, few studies have been focused on breast DWI-MRI at 3T (21–26). The purpose of the present study is to evaluate the ability of DWI, and related ADC values, to improve the breast cancer diagnosis in a routine breast 3T MRI study. In particular, the study aims to classify ADC values according to histology either for benign or malignant lesions and to confirm previous results in a larger sample size.
Objective: To evaluate the utility of diffusion-weighted-imaging (DWI) and apparent-diffusion-coefficient (ADC) in a 3T magnetic-resonance-imaging (MRI) study of breast cancer. In particular, the study aims to classify ADC-values according to histology either for benign or malignant lesions. Methods: 110 Breast MRI with MRI-DWI sequences and quantitative evaluation of the ADC were retrospectively reviewed. Results obtained with MRI-DWI and with biopsy were analyzed and ADC values were compared to histological results. Results: MRI showed a 95.5% sensitivity and a 83.7% specificity. The mean ADC values of benign and malignant lesions were 2.06 ± 0.19 and 1.03 ± 0.07 mm2 /s, respectively (p < .05). Conclusions: DWI and ADC-values could help distinguishing malignant and benign breast masses. Keywords: Breast cancer, 3T magnetic resonance imaging, Diffusion weighted imaging, Apparent diffusion coefficient
MATERIALS AND METHODS Patients We retrospectively reviewed the cases of 110 women who underwent breast MRI, between August 2011 and November 2012 at our Institution, after an abnormality was found on clinical examination and/or mammographic/ultrasonographic examination. Patients mean age was 52 year (range 29–79). Inclusion criteria were as follow: (a) study including MRI-DWI sequences and quantitative evaluation of the ADC; (b) evidence of lesion in dynamicCE sequences as well as in DWI sequences; (c) lesion assessed for the first time and not previously treated with Chemotherapy or other medical therapy and/or surgery; (d) histological evaluation after MRI by means of large-gauge core biopsy performed by an experienced operator or analysis of surgical specimen after mastectomy or quadrantectomy (partial mastectomy); (e) lesions with a BI-RADS score of 4/5-suspicious abnormality or finding highly suggestive of malignancy. Every MRI has been performed before biopsy, generally within
INTRODUCTION Magnetic Resonance Imaging (MRI) has been established as a valuable addition to mammography and ultrasonography for the detection of malignant breast lesions. ContrastEnhanced technique (CE-MRI) is currently proven to be the most sensitive method for breast cancer diagnosis (1, 2). However, the moderately low specificity has led the research in MRI field to test new sequences to improve diagnostic accuracy (3, 4). The use of Diffusion Weighted Imaging (DWI) has shown the potential to improve the specificity and the diagnostic accuracy of breast MRI (5). DWI technique has been initially applied in the study of cerebrovascular disease, but in recent years interest is grown in many fields of oncology due to the swiftness in performance and the absence of contrast medium (6–9). Several studies have reported significant differences in Apparent Diffusion Coefficient (ADC) of benign and a
R. Caivano and A. Villonio authors have contributed equally to this work.
Correspondence to: Rocchina Caivano, I.R.C.C.S.—C.R.O.B., Via San Pio 1, 85028 Rionero in Vulture (Pz) Italy. e-mail: rocchina.caivano@ gmail.com Received 21 November 2013; accepted 08 February 2015.
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one month; MRI was performed before biopsy to evaluate the perfusion of the lesion and to demonstrate possible multicentricity/multifocality (we have a research protocol in our Institute). The minimum considered diameter was 5 mm even if we have obtained the best results studying lesions with a diameter upper to 10 mm because there was greater precision in the characterization and localization on the ADC map. Multifocal/multicentric lesions have been included: in these cases we have analyzed the diameter and the peculiarities of signal intensity of the main lesion (70% of the lesions is localized in the upper outer quadrant), neglecting the others. DWI was acquired after intravenous injection of Gadolinium. The study was approved by the ethical committee of our Institute.
MRI technique All examinations were performed with a 3T MRI system (Philips Intera Achieva, Best, Netherlands) equipped with gradients of amplitude and maximum slew rate of 80 mT/m and 200 mT/m/ms, respectively, and through the use of four channels surface breast-dedicated coil. After the intravenous line was set up, the patient was placed in a scanner laying in the prone position throughout the duration of the MRI study. MRI examination was performed with a standard protocol consisting in T2-turbo spin echo (TSE) weighted sequences, fat suppressed Short TI Inversion Recovery (STIR), T1-weighted sequences, axial DWI sequences and axial dynamic pre- and post-contrast T1-weighted high-resolution isotropic volume examination (THRIVE) sequences. The scanning parameters were as follows: Bilateral axial T2-TSE weighted images: repetition time (TR) 4740 ms, echo time (TE) 120 ms, field of view (FOV) AP 340 mm, RL 340 mm, FH 150 mm, slice thickness 3 mm, number of slices 50, interslice gap 0 mm, matrix 452×331. Bilateral axial T2WI-STIR: TR 11689 ms, TE 60 ms, inversion time (TI) 230 ms, FOV AP 340 mm, RL 340 mm, FH 150 mm, slice thickness 3 mm, number of slices 50, interslice gap 0 mm, matrix 272 × 219, refocusing angle 120◦ . Bilateral axial isotopic DWI–SSH Echo Planar Imaging (EPI): TR 10648 ms. TE 44 ms, FOV AP 340 mm, RL 340 mm, FH 144 mm, slice thickness 3 mm, number of slices 48, interslice gap 0 mm, matrix 172 × 170, EPI factor 89, SPectral Attenuated Inversion Recovery (SPAIR) TR 221.83 ms, b-factors 0, 750 mm2 /s.
E- THRIVE dynamic bilateral axial 3D T1-WI: TR 4.4 ms, TE 2.2 ms, FOV AP 340 mm, RL 340 mm, FH 150 mm, slice thickness volumetric, number of slices 150, matrix 172 × 170, flip angle 12◦ , SPAIR TR 255.87 ms, dynamic scan time 55 s. The sequence was obtained before and 0, 60, 120, 180, 240, 300 s after a rapid bolus injection of Gadolinum (Gadovist C 1 mmol/L, Bayer). DWI was acquired in 2 min and 39.7 s. The duration of the complete protocol was about 16 min. Image analysis All of the images were evaluated by a trained senior radiologist, 20 years experienced breast radiology, blinded to histopathological results. In order to give greater diagnostic precision, all the images, then, have been analyzed by a second breast radiologist, in consensus. The lesions localization and morphology were defined mainly by using the CE T1-weighted images, taken as reference to determine the site of the ADC measurements. According to literature (2, 27), malignant tumor was identified as a focal lesion with speculated margins, irregular shape, heterogeneous internal architecture and a fast and strong enhancement that peaks in the early post CE phase, typically 1–3 min (Figure 1a). DWI sequences instead show breast cancer as hyperintense with signal intensity increasing with cellularity (Figure 1b). Benign lesions appear as a round well-defined mass, smooth margins, homogenous internal architecture and variable enhancement that depends on sclerosis or fibrosis degree and typically persists until the late phase. DWI sequences show a variable signal intensity, strongly influenced by b-value compared to malignant lesions (10), so that benign tumors look as iso- or hypointense foci (Figure 2–3). Every ADC value was calculated on ADC map, automatically constructed by using software provided by MRI manufacturer (Philips Medical System) on the operating console with different gradient factors (b values of 0 and 750 s/ mm2 ) through the use of a region of interest (ROI). Suspicious lesions were identified previously in CE sequences and hence an oval ROI, with an area of about 13 mm2 , was placed on DWI images and then superimposed on the ADC map in correspondence of the lesion, making sure it was within the identified pathological area, slightly smaller than it. The ADC values were measured superimposing the ROI on the ADC map and generated automatically using the software Functool (Philips Best Netherlands). The radiologist calculated
Figure 1. (a) A focal mass with speculated margins, irregular shape, heterogeneous internal architecture, and a fast and strong enhancement that peaks in the early post CE phase. (b) DWI sequence (black in inverted image) showing breast cancer as hyperintense with signal intensity increasing with cellularity. This lesion is compatible with an infiltrant ductal carcinoma, mean ADC value of 0.98 ± 0.41. Cancer Investigation
3T MRI of Breast Lesions: DWI and ADC Values
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Figure 2. (a) A well-circumscribed with regular and defined margins, oval shape, homogeneous internal architecture, and none enhancement in the early post CE phase. (b) DWI sequence showing the benign lesion hypointense. This benign lesion is compatible with benign dysplastic fibroadenoma, mean ADC value of 1.57 ± 0.78.
the ADC value twice, with a change of location, and then the average value of these measurements was recorded, for each malignant or benign nodule, paying attention to exclude normal tissue and necrotic portion areas, to minimize any error in the calculation. The threshold value between malignant and benign lesions was 1.10 × 10−3 mm2 /s (12–14, 16). Subsequently, ADC values were compared to histological results. Results obtained with MRI and with biopsy were analyzed in terms of accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). In particular, the readers separately evaluated one image set with only dynamic series, one image set in which DWI acquisitions were considered to calculate ADC values and these values were used to obtain accuracy, sensitivity, specificity, PPV and NPV. Finally results of combined evaluation (dynamic and DWI acquisitions) were obtained using an image set with both dynamic and DWI series with a dedicated reading session. Statistical analysis All statistical analysis was performed with SPSS software, version 17.0 (SPSS Inc. Chicago, IL). The Student-t test was used to evaluate the significance for changes in ADC values, with set at p < .05. RESULTS Histological results revealed 43 benign lesions and 67 malignant diseases. Benign lesions were divided in 12 cysts, 15 fibrosis, 9 fibroadenomas, and 7 mastitis. Malignancies were divided in 55 infiltrant ductal carcinoma (IDC), 8 infiltrant
lobular carcinoma (ILC), and 4 tubular carcinoma. Findings of the dynamic post-contrast acquisitions (CE-MRI) suggested malignancy in 74 patients, while a benign condition was found in 36 patients (Table 1). The CE-MRI findings were true positive in 64 and true negative in 33 patients, while 10 benign conditions were misclassified as malignant and three cases of carcinoma were not diagnosed, thus showing 95.5% sensitivity and 76.7% specificity, with 86.5% PPV, 91.7% NPV and 88.2% accuracy (Table 2). Considering only DWI sequences, before the injection of gadolinium, a pathological restriction of signal has been seen in 67 patients, while a condition of benignity has been seen in 43 patients. Of the 67 patients in whom DWI alone was suggestive of neoplastic lesions, histology confirmed 52 (true positive), while diagnosed benign lesions in 15 (false positive). Of the 43 patients in whom DWI diagnosed a condition of benignity, histology confirmed the absence of cancer in 31 patients (true negative), but identified a condition of malignancy in 12 (false negative). Based on these results, DWI showed a 81.2% sensitivity and a 67.4% specificity, with 77.6% PPV, 72.1% NPV, and 75.4% accuracy (table 2). Considering CE data in combination with DWI signal attenuation (CE-MRI+DWI), MRI was suggestive of a neoplastic lesion in 71 patients, while it diagnosed benign lesions in 39 patients. Of the 71 patients in whom CE + DWI-MRI was suggestive of a neoplastic lesion, histology confirmed 64 (true positive), while diagnosed benign lesions in 7 (false positive). Of the 39 patients without suspicious findings for cancer, histology confirmed the absence of neoplastic lesions in 36 (true negative), but detected carcinoma in 3 (false negative) (Table 1). Based on these results, MRI showed a 95.5% sensitivity and
Figure 3. (a) A round lesion, characterized by linear and regular walls, with disomogenous internal architecture for the presence of simple fluid content areas mixed to corpuscolated-inflamed ones. This lesion has none enhancement in the early post CE phase. (b) Inverted DWI sequence showing this benign lesion as hypointense, with disomogenous internal architecture: it contains both liquid and particulate matter, such as partially inflamed cysts. This lesion is compatible with benign complex cyst, mean ADC value of 3.42 ± 1.04. C 2015 Informa Healthcare USA, Inc. Copyright
R. Caivano et al.
Table 1. Correlation between MRI and Biopsy Findings CE MRI Biopsy findings
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Negative Positive
DWI
Negative
Positive
Negative
Positive
Negative
Positive
33 3
10 64
31 12
15 52
36 3
7 64
a 83.7% specificity, with 90.1% PPV, 92.3% NPV and 90.9% accuracy (table 2). Table 3 summarizes the mean lesion dimensions and the ADC values derived from DWI sequences in terms of mean values and standard deviation (SD). The mean ADC values of benign and malignant lesions were 2.06 ± 0.19 and 1.03 ± 0.07 mm2 /s, respectively. The difference between them was statistically significant (p < .05). Subsequently, ADC values were classified according to histology either for benign or malignant lesions. Among benign lesions, cysts revealed a mean ADC value of 3.42 ± 1.04, fibrosis 1.56 ± 0.64, fibroadenomas 1.57 ± 0.78 and mastitis 0.81 ± 0.13. The difference between them was statistically significant (p < .05) for all the benign couples (cysts vs. fibrosis, cysts vs. fibroadenomas, cysts vs. mastitis, fibrosis vs. fibroadenomas, fibrosis vs. mastitis, and fibroadenomas vs. mastitis) except between fibrosis vs. fibroadenomas for which p > .05 was found. Among malignant lesions, IDC revealed a mean ADC value of 0.98 ± 0.41, ILC 1.30 ± 0.60 and tubular carcinoma 0.58 ± 0.23. Differences were statistically significant (p < .05) between all couples (IDC vs. tubular carcinoma, ILC vs. tubular carcinoma, and IDC vs. ILC). ADC values are reported also for all the different histology. We notice that cystic lesions have higher ADC value compared to fibroadenomas, fibrosis or mastitis; anyway the overall ADC quantification is not affected by their inclusion, there aren’t any changes in our results excluding cystic lesions. The only change, obviously, concerns the mean ADC value of benign lesions that, excluding cysts, is 1.32 ± 0.11 mm2 /s, still statistically different from that of malignant lesions (p < 0.05). DISCUSSION The results in this study demonstrate that quantitative assessment of ADC values can be a powerful help to distinguish malignant from benign breast lesions in breast MRI examination. In accordance with the latest published studies (2), the main indications to breast MRI are prosthesis evaluation, carcinoma with unknown primary tumor assessment, evaluation of response to neoadjuvant chemotherapy and preoperative staging in patients affected by cancer. Breast MRI
Table 2. Sensitivity Specificity, PPV, NPV, and Accuracy of MRI Sensitivity Specificity PPV NPV Accuracy
CE MRI+DWI
CE MRI
DWI
CE-MRI+DWI
95.50% 76.70% 86.50% 91.70% 88.20%
81.20% 67.40% 77.60% 72.10% 75.40%
95.50% 83.70% 90.10% 92.30% 90.90%
combined with mammography and clinical breast exam, has been shown to provide sensitivity of 99% for the preoperative assessment of the local extension of disease in patients with newly diagnosed breast cancer (28). Since 1997, when Englander et al (29) showed the possibility to apply DWI to the human breast, several studies have evaluated the role of DWI in breast cancer detection with 1.5 T MRI system and they demonstrated that DWI, and related ADC, is an important support to standard dynamic CE-MRI. In particular ADC value of malignant tumors is reduced in comparison to that of benign lesions and normal tissue (11) and absolute threshold of ADC values have been reported to differentiate benign and malignant lesions (12–14, 16–18), with values ranging from 0.92 × 10−3 mm2 / sec to 1.6 × 10−3 mm2 /sec. The sensitivity and specificity for ADC quantitative assessment with these cut-off values were included between 80% to 95% for sensitivity and 80% to 100% for specificity. These data are in agreement with our findings, even if our results have been obtained with a 3T scanner, as few other previous studies (21–23, 25). El Khouli et al (25) found as optimal absolute ADC cut-off 1.6 × 10−3 mm2 /sec; with use of normalized ADCs, cut-off value is 0.7 × 10−3 mm2 /sec with a 92% specificity. Lo (22) and Bogner (23) showed high values of sensitivity (90% and 91%) and specificity (96% and 94%) and threshold of ADC values of 1.21 × 10−3 mm2 /sec and 1.25 × 10−3 mm2 /sec, respectively. Matsuoka et al (21) compared 3T and 1.5T DWI by evaluating ADC and visibility of breast cancer, in the same patients, and concluded that there was no significant difference in the ADC values of small (≤ 10 mm) and large (≥ 10 mm) benign and malignant lesions between 3T and 1.5T field strengths. In terms of lesions visibility, small lesions were more clearly visible at 3T than at 1.5T, supposedly for higher spatial resolution. In our study, mean ADC values of malignant and benign breast lesions were statistically different (p < .05). In agreement with previous results, sensitivity and specificity were 95.5% and 83.7%, respectively. Specificity was higher using DWI in addition to CE-MRI (83.7% vs. 75.0%), in agreement with previous papers (18), but compared to other studies, the absolute value appears relatively low. This is probably due to the utilization of DWI sequences within a standard CE-MRI examination. The gadolinium injection before DWI, in fact, can modify the ADC, slightly decreasing the values respectively to those without CE, causing therefore a higher number of false positive cases (13, 14). Our false positive rate is affected also by seven cases of breast mastitis, the latter in agreement with other findings (18, 30), show a very low mean ADC values, similar to malignant tumors. The cause still isn’t clearly understood, but it is probably due to the high number Cancer Investigation
3T MRI of Breast Lesions: DWI and ADC Values
Table 3. ADC Mean Values and Relative Standard Deviation (SD) for Benign and Malignant Lesions ADC values
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Mean + SD benign lesions (43)
2.06 + 0.19
malignant lesions (67)
1.03 + 0.07
ADC values Histology cysts (12) fibrosis (15) fibroadenomas (9) mastitis (7) ICD (55) ICL (8) tubular carcinoma (4)
of viable inflammatory cells, rather than pus or protein content, within the lesion. Our findings reveal moreover that tubular carcinoma shows a lower ADC value compared to the other malignant lesions, even if this is not related to its prognosis: this latter in fact is favorable compared to ICD and ICL. This is probably due to its tubular gland structure which is relatively crowded. On the other hand, as widely expected, cysts show a higher ADC value compared to that of fibrosis and fibroadenomas (Table 3). Nonetheless these latter still have a higher ADC value compared to malignant lesions (p < .05). Finally we have to mention that, based on published data (24, 31) and previous tests on volunteers at our institution, we acquired DWI and ADC measured with b-values of 0 and 750 sec/mm2 . In fact Peters et al. (24) evaluated the influence of the choice of b-values on the ADC and on the diagnosis performance of DWI in breast lesions. Five combinations of different b-values (0, 150, 499, 1500 sec/ mm2 ) were used to calculate ADC for every lesion, demonstrating that the absolute ADC value varies substantially with the choice of different bvalues, but the diagnostic performance of quantitative DWI is not affected by the choice of different b-values. Several studies have evaluated the same parameter with a 1.5T magnet. In particular, Pereira et al (31) found that the use of multiple bvalues is not necessary because the use of only two ensures the same sensitivity, and that the combination of values 0 and 750 sec/mm2 shows a sensitivity slightly better than other combinations. Indeed, other studies conducted at 3T utilized different combination of b-values, respectively, 0 and 600 sec/mm2 (25) and 0 and 1000 sec/mm2 (22). Wisner et al. (32) found that the use of High Resolution Diffusion-Weighted Imaging with readout-segmented echo-planar sequences (RESOLVE) improve separation of malignant versus benign lesions compared to standard single shot echo-planar imaging (ss-EPI) on BI-RADS 4/5 lesions detected on 3T-MRI. The use of 3T-MRI, compared with 1.5 T scanner, determines a greater homogeneity and intensity of magnet field and therefore there is a significant increase in spatial and temporal resolution of the images and in the diagnostic performance and detection of breast lesions (33). Cai et al. (34) assessed that the combination of ADC and other multi-sided characteristics (Sum Variance, Entropy, Elongation, etc.) with 3T scanner can increase the capability of discriminating malignant and benign breast lesions, even under different imaging protocols. C 2015 Informa Healthcare USA, Inc. Copyright
Lesion dimension (mm)
Mean + SD
Mean + SD
3.42 ± 1.04 1.56 ± 0.64 1.57 ± 0.78 0.81 ± 0.13 0.98 ± 0.41 1.30 ± 0.60 0.58 ± 0.23
14.0 ± 6.6 12.1 ± 5.4 12.9 ± 5.7 12.0 ± 4.4 20.8 ± 10.9 18.8 ± 8.1 15.8 ± 6.4
The present study has some limitations. First of all, it is a retrospective study and our cohort population came entirely from the same institution. Second, many factors may affect ADC, such as menstrual cycle variation: ADC values tend to decrease in week 2 and to increase during week 4 (35). This has not been considered, because the patient performed the examination as soon as possible, for the urgency of clinical suspicion and the use of the DWI technique within the MRI standard protocol. Thirdly, our series does not include nonmass like lesions (fibrocystic disease, ductal carcinoma in situ and lobular carcinoma in situ); we did not study ‘nonmass like lesions’ because in our series of patients, unfortunately, there were not lesions with those characteristics; surely, if we had considered non mass like lesions we would have had an increase of specificity in differential diagnosis with other breast lesions, both malign and benign, although the interpretation of CE-MRI and the analysis of both DWI and ADC would have not been simple. Anyway we notice that characterization of suspicious breast microcalcifications is limited to the MRI (36), particularly the diagnosis of low grade ductal carcinoma in situ, which shows poor angiogenesis and can give false negative to MRI examination. Finally to generalize the use of ADC values as a possible alternative for histological assessment of lesions, our sample number for some type of lesions is too small. Therefore a wider spectrum of lesions is necessary to definitively assess the role of MRIDWI and related ADC values as a possible alternative for histological assessment of lesions. In conclusion, our study shows that the addition of DWI in a standard 3T CE-MRI protocol improves specificity and increases the diagnostic performance of MRI in breast cancer detection. ADC values could be well correlate with cellularity, furnishing an objective tool to distinguish malignant and benign masses. However, a larger study cohort and a wider spectrum of breast lesions are necessary to definitively evaluate the role of DWI in the daily clinical practice and its usefulness in the classification of lesions by calculating the relative ADC aiming, in the future, to be able to use these values to avoid the biopsy. At the moment, the role of MRI-DWI could be that of reducing the number of biopsy for benign incidental findings. DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
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18. Kul S, Cansu A, Alhan E, Dinc H, Gunes G, Reis A. Contribution of diffusion weighted imaging to Dynamic contrast-enhanced MRI in the characterization of breast tumors. AJR 2011;196:210–217. 19. Sonmez G, Cuce F, Mutlu H, Incedayi M, Ozturk E, Sildiroglu O, Velioglu M, Bashekim CC, Kizilkaya E. Value of diffusionweighted MRI in the differentiation of benign and malign breast lesions. Wien Klin Wochenschr 2011;123:655–661. 20. Kuhl CK, Tr¨aber F, Schild HH. Whole-body high-field-strength (3-T) MR Imaging in Clinical Practice. Part I. Technical considerations and clinical applications. Radiology 2008;246:675–696. 21. Matsuoka A, Minato M, Harada M, Kubo H, Bandou Y, Tangoku A, Nakano K, Nishitani H. Comparison of 3-and 1.5-tesla diffusion-weighted imaging in the visibility of breast cancer. Radiat Med 2008;26:15–20. 22. Lo GG, Ai V, Chan JK, Li KW, Cheung PS, Wong TT, Ma M, Lee R, Chien D. Diffusion-weighted magnetic resonance imaging of breast lesions: first experiences at 3 T. J Comput Assist Tomogr 2009;33:63–69. 23. Bogner W, Gruber S, Pinker K, Grabner G, Stadlbauer A, Weber M, Moser E, Helbich TH, Trattnig S. Diffusion-weighted MR for differentiation of breast lesions at 3 T: how does selection of diffusion protocols affect diagnosis? Radiology 2009;253:341–351. 24. Peters NH, Vincken KL, van den Bosch MA, Luijten PR, Mali WP, Bartels LW. Quantitative diffusion weighted imaging for differentiation of benign and malignant breast lesions: the influence of the choice of b-values. J Magn Reson Imaging 2010;31:1100–1105. 25. Ei Khouli RH, Jacobs MA, Mezban SD, Huang P, Kamel IR, Macura KJ, Bluemke DA. Diffusion-weighted imaging improves the diagnostic accuracy of conventional 3-T breast MR imaging. Radiology 2010;256:64–73. 26. Takanaga M, Hayashi N, Miyati T, Kawashima H, Hamaguchi T, Ohno N, Sanada S, Yamamoto T, Matsui O. Influence of b value on the measurement of contrast and apparent diffusion coefficient in 3 Tesla breast magnetic resonance imaging. Nihon Hoshasen Gijutsu Gakkai Zasshi 2012;68:201–208. 27. Kuhl CK. MRI of breast tumors. Eur Radiol 2000;10:46–58. 28. Berg WA, Gutierrez L, NessAiver MS, Carter WB, Bhargavan M, Lewis RS, Ioffe OB. Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 2004;233:830–849. 29. Englander SA, Ulu˘g AM, Brem R, Glickson JD, van Zijl PC. Diffusion imaging of human breast. NMR Biomed 1997;10:348–352. 30. Neubauer H, Platzer I, Mueller VR, Meyer T, Liese J, Koestler H, Hahn D, Beer M. Diffusion-weighted MRI of abscess formations in children and young adults. World J Pediatr 2012;8:229–234. 31. Pereira FP, Martins G, Figueiredo E, Domingues MN, Domingues RC, da Fonseca LM, Gasparetto EL. Assessment of breast lesions with diffusion-weighted MRI: comparing the use of different b values. AJR Am J Roentgenol 2009;193:1030–1035. 32. Wisner DJ, Rogers N, Deshpande VS, Newitt DN, Laub GA, Porter DA, Kornak J, Joe BN, Hylton NM. High resolution diffusionweighted imaging for the separation of benign from malignant BI-RADS 4/5 lesions found on breast MRI at 3 T. J Magn Reson Imaging 2014;40:674–681. 33. Rahbar H, Partridge SC, DeMartini WB, Thursten B, Lehman CD. Clinical and technical considerations for high quality breast MRI at 3T. J Magn Reson Imaging 2013;37:778–790. 34. Cai H, Liu L, Peng Y, Wu Y, Li L. Diagnostic assessment by dynamic contrast-enhanced and diffusion-weighted magnetic resonance in differentation of breast lesions under different imaging protocols. BMC Cancer 2014;14:366. 35. Partridge SC, McKinnon GC, Henry RG, Hylton NM. Menstrual cycle variation of apparent diffusion coefficients measured in the normal breast using MRI. J Magn Reson Imaging 2001;14:433–438. 36. Bazzocchi M, Zuiani C, Panizza P, Del Frate C, Soldano F, Isola M, Sardanelli F, Giuseppetti GM, Simonetti G, Lattanzio V, Del Maschio A. Contrast-enhanced breast MRI in patients with suspicious microcalcifications on mammography: results of a multi center trial. AJR Am J Roentgenol 2006;186:1723–1732. Cancer Investigation
ORIGINAL ARTICLE
Diffusion Weighted Imaging and Apparent Diffusion Coefficient in 3 Tesla Magnetic Resonance Imaging of Breast Lesions Rocchina Caivano,1,a Antonio Villonio,1,a Felice D’ Antuono,1 Matilde Gioioso,1 Paola Rabasco,1 Giancarlo Iannelli,1 Alexis Zandolino,1 Antonella Lotumolo,1 Giuseppina Dinardo,1 Luca Macarini,2 Giuseppe Guglielmi,2 and Aldo Cammarota1
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IRCCS—CROB, Rionero in Vulture (Pz), Italy1 Radiology, University of Foggia, Foggia, Italy2 malignant breast lesions (10–19), with higher ADC values for benign lesions reflecting lower molecular movement and cellularity, and subsequently lower ADC values for malignant lesions. These studies have been mainly performed with 1.5 T MRI scanners. 3T MRI, with appropriate acquisition parameters, affords an higher signal-to-noise ratio (SNR) and therefore an improved spatial resolution (20). To our knowledge, few studies have been focused on breast DWI-MRI at 3T (21–26). The purpose of the present study is to evaluate the ability of DWI, and related ADC values, to improve the breast cancer diagnosis in a routine breast 3T MRI study. In particular, the study aims to classify ADC values according to histology either for benign or malignant lesions and to confirm previous results in a larger sample size.
Objective: To evaluate the utility of diffusion-weighted-imaging (DWI) and apparent-diffusion-coefficient (ADC) in a 3T magnetic-resonance-imaging (MRI) study of breast cancer. In particular, the study aims to classify ADC-values according to histology either for benign or malignant lesions. Methods: 110 Breast MRI with MRI-DWI sequences and quantitative evaluation of the ADC were retrospectively reviewed. Results obtained with MRI-DWI and with biopsy were analyzed and ADC values were compared to histological results. Results: MRI showed a 95.5% sensitivity and a 83.7% specificity. The mean ADC values of benign and malignant lesions were 2.06 ± 0.19 and 1.03 ± 0.07 mm2 /s, respectively (p < .05). Conclusions: DWI and ADC-values could help distinguishing malignant and benign breast masses. Keywords: Breast cancer, 3T magnetic resonance imaging, Diffusion weighted imaging, Apparent diffusion coefficient
MATERIALS AND METHODS Patients We retrospectively reviewed the cases of 110 women who underwent breast MRI, between August 2011 and November 2012 at our Institution, after an abnormality was found on clinical examination and/or mammographic/ultrasonographic examination. Patients mean age was 52 year (range 29–79). Inclusion criteria were as follow: (a) study including MRI-DWI sequences and quantitative evaluation of the ADC; (b) evidence of lesion in dynamicCE sequences as well as in DWI sequences; (c) lesion assessed for the first time and not previously treated with Chemotherapy or other medical therapy and/or surgery; (d) histological evaluation after MRI by means of large-gauge core biopsy performed by an experienced operator or analysis of surgical specimen after mastectomy or quadrantectomy (partial mastectomy); (e) lesions with a BI-RADS score of 4/5-suspicious abnormality or finding highly suggestive of malignancy. Every MRI has been performed before biopsy, generally within
INTRODUCTION Magnetic Resonance Imaging (MRI) has been established as a valuable addition to mammography and ultrasonography for the detection of malignant breast lesions. ContrastEnhanced technique (CE-MRI) is currently proven to be the most sensitive method for breast cancer diagnosis (1, 2). However, the moderately low specificity has led the research in MRI field to test new sequences to improve diagnostic accuracy (3, 4). The use of Diffusion Weighted Imaging (DWI) has shown the potential to improve the specificity and the diagnostic accuracy of breast MRI (5). DWI technique has been initially applied in the study of cerebrovascular disease, but in recent years interest is grown in many fields of oncology due to the swiftness in performance and the absence of contrast medium (6–9). Several studies have reported significant differences in Apparent Diffusion Coefficient (ADC) of benign and a
R. Caivano and A. Villonio authors have contributed equally to this work.
Correspondence to: Rocchina Caivano, I.R.C.C.S.—C.R.O.B., Via San Pio 1, 85028 Rionero in Vulture (Pz) Italy. e-mail: rocchina.caivano@ gmail.com Received 21 November 2013; accepted 08 February 2015.
R. Caivano et al.
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one month; MRI was performed before biopsy to evaluate the perfusion of the lesion and to demonstrate possible multicentricity/multifocality (we have a research protocol in our Institute). The minimum considered diameter was 5 mm even if we have obtained the best results studying lesions with a diameter upper to 10 mm because there was greater precision in the characterization and localization on the ADC map. Multifocal/multicentric lesions have been included: in these cases we have analyzed the diameter and the peculiarities of signal intensity of the main lesion (70% of the lesions is localized in the upper outer quadrant), neglecting the others. DWI was acquired after intravenous injection of Gadolinium. The study was approved by the ethical committee of our Institute.
MRI technique All examinations were performed with a 3T MRI system (Philips Intera Achieva, Best, Netherlands) equipped with gradients of amplitude and maximum slew rate of 80 mT/m and 200 mT/m/ms, respectively, and through the use of four channels surface breast-dedicated coil. After the intravenous line was set up, the patient was placed in a scanner laying in the prone position throughout the duration of the MRI study. MRI examination was performed with a standard protocol consisting in T2-turbo spin echo (TSE) weighted sequences, fat suppressed Short TI Inversion Recovery (STIR), T1-weighted sequences, axial DWI sequences and axial dynamic pre- and post-contrast T1-weighted high-resolution isotropic volume examination (THRIVE) sequences. The scanning parameters were as follows: Bilateral axial T2-TSE weighted images: repetition time (TR) 4740 ms, echo time (TE) 120 ms, field of view (FOV) AP 340 mm, RL 340 mm, FH 150 mm, slice thickness 3 mm, number of slices 50, interslice gap 0 mm, matrix 452×331. Bilateral axial T2WI-STIR: TR 11689 ms, TE 60 ms, inversion time (TI) 230 ms, FOV AP 340 mm, RL 340 mm, FH 150 mm, slice thickness 3 mm, number of slices 50, interslice gap 0 mm, matrix 272 × 219, refocusing angle 120◦ . Bilateral axial isotopic DWI–SSH Echo Planar Imaging (EPI): TR 10648 ms. TE 44 ms, FOV AP 340 mm, RL 340 mm, FH 144 mm, slice thickness 3 mm, number of slices 48, interslice gap 0 mm, matrix 172 × 170, EPI factor 89, SPectral Attenuated Inversion Recovery (SPAIR) TR 221.83 ms, b-factors 0, 750 mm2 /s.
E- THRIVE dynamic bilateral axial 3D T1-WI: TR 4.4 ms, TE 2.2 ms, FOV AP 340 mm, RL 340 mm, FH 150 mm, slice thickness volumetric, number of slices 150, matrix 172 × 170, flip angle 12◦ , SPAIR TR 255.87 ms, dynamic scan time 55 s. The sequence was obtained before and 0, 60, 120, 180, 240, 300 s after a rapid bolus injection of Gadolinum (Gadovist C 1 mmol/L, Bayer). DWI was acquired in 2 min and 39.7 s. The duration of the complete protocol was about 16 min. Image analysis All of the images were evaluated by a trained senior radiologist, 20 years experienced breast radiology, blinded to histopathological results. In order to give greater diagnostic precision, all the images, then, have been analyzed by a second breast radiologist, in consensus. The lesions localization and morphology were defined mainly by using the CE T1-weighted images, taken as reference to determine the site of the ADC measurements. According to literature (2, 27), malignant tumor was identified as a focal lesion with speculated margins, irregular shape, heterogeneous internal architecture and a fast and strong enhancement that peaks in the early post CE phase, typically 1–3 min (Figure 1a). DWI sequences instead show breast cancer as hyperintense with signal intensity increasing with cellularity (Figure 1b). Benign lesions appear as a round well-defined mass, smooth margins, homogenous internal architecture and variable enhancement that depends on sclerosis or fibrosis degree and typically persists until the late phase. DWI sequences show a variable signal intensity, strongly influenced by b-value compared to malignant lesions (10), so that benign tumors look as iso- or hypointense foci (Figure 2–3). Every ADC value was calculated on ADC map, automatically constructed by using software provided by MRI manufacturer (Philips Medical System) on the operating console with different gradient factors (b values of 0 and 750 s/ mm2 ) through the use of a region of interest (ROI). Suspicious lesions were identified previously in CE sequences and hence an oval ROI, with an area of about 13 mm2 , was placed on DWI images and then superimposed on the ADC map in correspondence of the lesion, making sure it was within the identified pathological area, slightly smaller than it. The ADC values were measured superimposing the ROI on the ADC map and generated automatically using the software Functool (Philips Best Netherlands). The radiologist calculated
Figure 1. (a) A focal mass with speculated margins, irregular shape, heterogeneous internal architecture, and a fast and strong enhancement that peaks in the early post CE phase. (b) DWI sequence (black in inverted image) showing breast cancer as hyperintense with signal intensity increasing with cellularity. This lesion is compatible with an infiltrant ductal carcinoma, mean ADC value of 0.98 ± 0.41. Cancer Investigation
3T MRI of Breast Lesions: DWI and ADC Values
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Figure 2. (a) A well-circumscribed with regular and defined margins, oval shape, homogeneous internal architecture, and none enhancement in the early post CE phase. (b) DWI sequence showing the benign lesion hypointense. This benign lesion is compatible with benign dysplastic fibroadenoma, mean ADC value of 1.57 ± 0.78.
the ADC value twice, with a change of location, and then the average value of these measurements was recorded, for each malignant or benign nodule, paying attention to exclude normal tissue and necrotic portion areas, to minimize any error in the calculation. The threshold value between malignant and benign lesions was 1.10 × 10−3 mm2 /s (12–14, 16). Subsequently, ADC values were compared to histological results. Results obtained with MRI and with biopsy were analyzed in terms of accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). In particular, the readers separately evaluated one image set with only dynamic series, one image set in which DWI acquisitions were considered to calculate ADC values and these values were used to obtain accuracy, sensitivity, specificity, PPV and NPV. Finally results of combined evaluation (dynamic and DWI acquisitions) were obtained using an image set with both dynamic and DWI series with a dedicated reading session. Statistical analysis All statistical analysis was performed with SPSS software, version 17.0 (SPSS Inc. Chicago, IL). The Student-t test was used to evaluate the significance for changes in ADC values, with set at p < .05. RESULTS Histological results revealed 43 benign lesions and 67 malignant diseases. Benign lesions were divided in 12 cysts, 15 fibrosis, 9 fibroadenomas, and 7 mastitis. Malignancies were divided in 55 infiltrant ductal carcinoma (IDC), 8 infiltrant
lobular carcinoma (ILC), and 4 tubular carcinoma. Findings of the dynamic post-contrast acquisitions (CE-MRI) suggested malignancy in 74 patients, while a benign condition was found in 36 patients (Table 1). The CE-MRI findings were true positive in 64 and true negative in 33 patients, while 10 benign conditions were misclassified as malignant and three cases of carcinoma were not diagnosed, thus showing 95.5% sensitivity and 76.7% specificity, with 86.5% PPV, 91.7% NPV and 88.2% accuracy (Table 2). Considering only DWI sequences, before the injection of gadolinium, a pathological restriction of signal has been seen in 67 patients, while a condition of benignity has been seen in 43 patients. Of the 67 patients in whom DWI alone was suggestive of neoplastic lesions, histology confirmed 52 (true positive), while diagnosed benign lesions in 15 (false positive). Of the 43 patients in whom DWI diagnosed a condition of benignity, histology confirmed the absence of cancer in 31 patients (true negative), but identified a condition of malignancy in 12 (false negative). Based on these results, DWI showed a 81.2% sensitivity and a 67.4% specificity, with 77.6% PPV, 72.1% NPV, and 75.4% accuracy (table 2). Considering CE data in combination with DWI signal attenuation (CE-MRI+DWI), MRI was suggestive of a neoplastic lesion in 71 patients, while it diagnosed benign lesions in 39 patients. Of the 71 patients in whom CE + DWI-MRI was suggestive of a neoplastic lesion, histology confirmed 64 (true positive), while diagnosed benign lesions in 7 (false positive). Of the 39 patients without suspicious findings for cancer, histology confirmed the absence of neoplastic lesions in 36 (true negative), but detected carcinoma in 3 (false negative) (Table 1). Based on these results, MRI showed a 95.5% sensitivity and
Figure 3. (a) A round lesion, characterized by linear and regular walls, with disomogenous internal architecture for the presence of simple fluid content areas mixed to corpuscolated-inflamed ones. This lesion has none enhancement in the early post CE phase. (b) Inverted DWI sequence showing this benign lesion as hypointense, with disomogenous internal architecture: it contains both liquid and particulate matter, such as partially inflamed cysts. This lesion is compatible with benign complex cyst, mean ADC value of 3.42 ± 1.04. C 2015 Informa Healthcare USA, Inc. Copyright
R. Caivano et al.
Table 1. Correlation between MRI and Biopsy Findings CE MRI Biopsy findings
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Negative Positive
DWI
Negative
Positive
Negative
Positive
Negative
Positive
33 3
10 64
31 12
15 52
36 3
7 64
a 83.7% specificity, with 90.1% PPV, 92.3% NPV and 90.9% accuracy (table 2). Table 3 summarizes the mean lesion dimensions and the ADC values derived from DWI sequences in terms of mean values and standard deviation (SD). The mean ADC values of benign and malignant lesions were 2.06 ± 0.19 and 1.03 ± 0.07 mm2 /s, respectively. The difference between them was statistically significant (p < .05). Subsequently, ADC values were classified according to histology either for benign or malignant lesions. Among benign lesions, cysts revealed a mean ADC value of 3.42 ± 1.04, fibrosis 1.56 ± 0.64, fibroadenomas 1.57 ± 0.78 and mastitis 0.81 ± 0.13. The difference between them was statistically significant (p < .05) for all the benign couples (cysts vs. fibrosis, cysts vs. fibroadenomas, cysts vs. mastitis, fibrosis vs. fibroadenomas, fibrosis vs. mastitis, and fibroadenomas vs. mastitis) except between fibrosis vs. fibroadenomas for which p > .05 was found. Among malignant lesions, IDC revealed a mean ADC value of 0.98 ± 0.41, ILC 1.30 ± 0.60 and tubular carcinoma 0.58 ± 0.23. Differences were statistically significant (p < .05) between all couples (IDC vs. tubular carcinoma, ILC vs. tubular carcinoma, and IDC vs. ILC). ADC values are reported also for all the different histology. We notice that cystic lesions have higher ADC value compared to fibroadenomas, fibrosis or mastitis; anyway the overall ADC quantification is not affected by their inclusion, there aren’t any changes in our results excluding cystic lesions. The only change, obviously, concerns the mean ADC value of benign lesions that, excluding cysts, is 1.32 ± 0.11 mm2 /s, still statistically different from that of malignant lesions (p < 0.05). DISCUSSION The results in this study demonstrate that quantitative assessment of ADC values can be a powerful help to distinguish malignant from benign breast lesions in breast MRI examination. In accordance with the latest published studies (2), the main indications to breast MRI are prosthesis evaluation, carcinoma with unknown primary tumor assessment, evaluation of response to neoadjuvant chemotherapy and preoperative staging in patients affected by cancer. Breast MRI
Table 2. Sensitivity Specificity, PPV, NPV, and Accuracy of MRI Sensitivity Specificity PPV NPV Accuracy
CE MRI+DWI
CE MRI
DWI
CE-MRI+DWI
95.50% 76.70% 86.50% 91.70% 88.20%
81.20% 67.40% 77.60% 72.10% 75.40%
95.50% 83.70% 90.10% 92.30% 90.90%
combined with mammography and clinical breast exam, has been shown to provide sensitivity of 99% for the preoperative assessment of the local extension of disease in patients with newly diagnosed breast cancer (28). Since 1997, when Englander et al (29) showed the possibility to apply DWI to the human breast, several studies have evaluated the role of DWI in breast cancer detection with 1.5 T MRI system and they demonstrated that DWI, and related ADC, is an important support to standard dynamic CE-MRI. In particular ADC value of malignant tumors is reduced in comparison to that of benign lesions and normal tissue (11) and absolute threshold of ADC values have been reported to differentiate benign and malignant lesions (12–14, 16–18), with values ranging from 0.92 × 10−3 mm2 / sec to 1.6 × 10−3 mm2 /sec. The sensitivity and specificity for ADC quantitative assessment with these cut-off values were included between 80% to 95% for sensitivity and 80% to 100% for specificity. These data are in agreement with our findings, even if our results have been obtained with a 3T scanner, as few other previous studies (21–23, 25). El Khouli et al (25) found as optimal absolute ADC cut-off 1.6 × 10−3 mm2 /sec; with use of normalized ADCs, cut-off value is 0.7 × 10−3 mm2 /sec with a 92% specificity. Lo (22) and Bogner (23) showed high values of sensitivity (90% and 91%) and specificity (96% and 94%) and threshold of ADC values of 1.21 × 10−3 mm2 /sec and 1.25 × 10−3 mm2 /sec, respectively. Matsuoka et al (21) compared 3T and 1.5T DWI by evaluating ADC and visibility of breast cancer, in the same patients, and concluded that there was no significant difference in the ADC values of small (≤ 10 mm) and large (≥ 10 mm) benign and malignant lesions between 3T and 1.5T field strengths. In terms of lesions visibility, small lesions were more clearly visible at 3T than at 1.5T, supposedly for higher spatial resolution. In our study, mean ADC values of malignant and benign breast lesions were statistically different (p < .05). In agreement with previous results, sensitivity and specificity were 95.5% and 83.7%, respectively. Specificity was higher using DWI in addition to CE-MRI (83.7% vs. 75.0%), in agreement with previous papers (18), but compared to other studies, the absolute value appears relatively low. This is probably due to the utilization of DWI sequences within a standard CE-MRI examination. The gadolinium injection before DWI, in fact, can modify the ADC, slightly decreasing the values respectively to those without CE, causing therefore a higher number of false positive cases (13, 14). Our false positive rate is affected also by seven cases of breast mastitis, the latter in agreement with other findings (18, 30), show a very low mean ADC values, similar to malignant tumors. The cause still isn’t clearly understood, but it is probably due to the high number Cancer Investigation
3T MRI of Breast Lesions: DWI and ADC Values
Table 3. ADC Mean Values and Relative Standard Deviation (SD) for Benign and Malignant Lesions ADC values
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Mean + SD benign lesions (43)
2.06 + 0.19
malignant lesions (67)
1.03 + 0.07
ADC values Histology cysts (12) fibrosis (15) fibroadenomas (9) mastitis (7) ICD (55) ICL (8) tubular carcinoma (4)
of viable inflammatory cells, rather than pus or protein content, within the lesion. Our findings reveal moreover that tubular carcinoma shows a lower ADC value compared to the other malignant lesions, even if this is not related to its prognosis: this latter in fact is favorable compared to ICD and ICL. This is probably due to its tubular gland structure which is relatively crowded. On the other hand, as widely expected, cysts show a higher ADC value compared to that of fibrosis and fibroadenomas (Table 3). Nonetheless these latter still have a higher ADC value compared to malignant lesions (p < .05). Finally we have to mention that, based on published data (24, 31) and previous tests on volunteers at our institution, we acquired DWI and ADC measured with b-values of 0 and 750 sec/mm2 . In fact Peters et al. (24) evaluated the influence of the choice of b-values on the ADC and on the diagnosis performance of DWI in breast lesions. Five combinations of different b-values (0, 150, 499, 1500 sec/ mm2 ) were used to calculate ADC for every lesion, demonstrating that the absolute ADC value varies substantially with the choice of different bvalues, but the diagnostic performance of quantitative DWI is not affected by the choice of different b-values. Several studies have evaluated the same parameter with a 1.5T magnet. In particular, Pereira et al (31) found that the use of multiple bvalues is not necessary because the use of only two ensures the same sensitivity, and that the combination of values 0 and 750 sec/mm2 shows a sensitivity slightly better than other combinations. Indeed, other studies conducted at 3T utilized different combination of b-values, respectively, 0 and 600 sec/mm2 (25) and 0 and 1000 sec/mm2 (22). Wisner et al. (32) found that the use of High Resolution Diffusion-Weighted Imaging with readout-segmented echo-planar sequences (RESOLVE) improve separation of malignant versus benign lesions compared to standard single shot echo-planar imaging (ss-EPI) on BI-RADS 4/5 lesions detected on 3T-MRI. The use of 3T-MRI, compared with 1.5 T scanner, determines a greater homogeneity and intensity of magnet field and therefore there is a significant increase in spatial and temporal resolution of the images and in the diagnostic performance and detection of breast lesions (33). Cai et al. (34) assessed that the combination of ADC and other multi-sided characteristics (Sum Variance, Entropy, Elongation, etc.) with 3T scanner can increase the capability of discriminating malignant and benign breast lesions, even under different imaging protocols. C 2015 Informa Healthcare USA, Inc. Copyright
Lesion dimension (mm)
Mean + SD
Mean + SD
3.42 ± 1.04 1.56 ± 0.64 1.57 ± 0.78 0.81 ± 0.13 0.98 ± 0.41 1.30 ± 0.60 0.58 ± 0.23
14.0 ± 6.6 12.1 ± 5.4 12.9 ± 5.7 12.0 ± 4.4 20.8 ± 10.9 18.8 ± 8.1 15.8 ± 6.4
The present study has some limitations. First of all, it is a retrospective study and our cohort population came entirely from the same institution. Second, many factors may affect ADC, such as menstrual cycle variation: ADC values tend to decrease in week 2 and to increase during week 4 (35). This has not been considered, because the patient performed the examination as soon as possible, for the urgency of clinical suspicion and the use of the DWI technique within the MRI standard protocol. Thirdly, our series does not include nonmass like lesions (fibrocystic disease, ductal carcinoma in situ and lobular carcinoma in situ); we did not study ‘nonmass like lesions’ because in our series of patients, unfortunately, there were not lesions with those characteristics; surely, if we had considered non mass like lesions we would have had an increase of specificity in differential diagnosis with other breast lesions, both malign and benign, although the interpretation of CE-MRI and the analysis of both DWI and ADC would have not been simple. Anyway we notice that characterization of suspicious breast microcalcifications is limited to the MRI (36), particularly the diagnosis of low grade ductal carcinoma in situ, which shows poor angiogenesis and can give false negative to MRI examination. Finally to generalize the use of ADC values as a possible alternative for histological assessment of lesions, our sample number for some type of lesions is too small. Therefore a wider spectrum of lesions is necessary to definitively assess the role of MRIDWI and related ADC values as a possible alternative for histological assessment of lesions. In conclusion, our study shows that the addition of DWI in a standard 3T CE-MRI protocol improves specificity and increases the diagnostic performance of MRI in breast cancer detection. ADC values could be well correlate with cellularity, furnishing an objective tool to distinguish malignant and benign masses. However, a larger study cohort and a wider spectrum of breast lesions are necessary to definitively evaluate the role of DWI in the daily clinical practice and its usefulness in the classification of lesions by calculating the relative ADC aiming, in the future, to be able to use these values to avoid the biopsy. At the moment, the role of MRI-DWI could be that of reducing the number of biopsy for benign incidental findings. DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
R. Caivano et al.
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