Evaluation of Kinetic Entropy of Breast Masses Initially Found on MRI using Whole-lesion Curve Distribution Data: Comparison with the Standard Kinetic Analysis.

OBJECTIVES: To quantify kinetic heterogeneity of breast masses that were initially detected with dynamic contrast-enhanced MRI, using whole-lesion kinetic distribution data obtained from computer-aided evaluation (CAE), and to compare that with standard kinetic curve analysis. METHODS: Clinical MR images from 2006 to 2011 with breast masses initially detected with MRI were evaluated with CAE. The relative frequencies of six kinetic patterns (medium-persistent, medium-plateau, medium-washout, rapid-persistent, rapid-plateau, rapid-washout) within the entire lesion were used to calculate kinetic entropy (KE), a quantitative measure of enhancement pattern heterogeneity. Initial uptake (IU) and signal enhancement ratio (SER) were obtained from the most-suspicious kinetic curve. Mann-Whitney U test and ROC analysis were conducted for differentiation of malignant and benign masses. RESULTS: Forty benign and 37 malignant masses comprised the case set. IU and SER were not significantly different between malignant and benign masses, whereas KE was significantly greater for malignant than benign masses (p = 0.748, p = 0.083, and p < 0.0001, respectively). Areas under ROC curve for IU, SER, and KE were 0.479, 0.615, and 0.662, respectively. CONCLUSION: Quantification of kinetic heterogeneity of whole-lesion time-curve data with KE has the potential to improve differentiation of malignant from benign breast masses on breast MRI. KEY POINTS: • Kinetic heterogeneity can be quantified by computer-aided evaluation of breast MRI • Kinetic entropy was greater in malignant masses than benign masses • Kinetic entropy has the potential to improve differentiation of breast masses.

High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media.

The purpose of this study was to use high resolution three-dimensional (3D) magnetic resonance imaging (MRI) to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12-20 weeks (n=12), were used in this study. A 34G, 45° tip Hamilton needle with a 25µL Hamilton syringe was inserted into the tip of the nipple. Approximately 20-25µL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p<0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p<0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers.

T(2)∗ relaxation times of intraductal murine mammary cancer, invasive mammary cancer, and normal mammary gland.

PURPOSE: This study investigates the feasibility of T(2)∗ to be a diagnostic indicator of early breast cancer in a mouse model. T(2)∗ is sensitive to susceptibility effects due to local inhomogeneity of the magnetic field, e.g., caused by hemosiderin or deoxyhemoglobin. In these mouse models, unlike in patients, the characteristics of single mammary ducts containing pure intraductal cancer can be evaluated. METHODS: The C3(1)SV40Tag mouse model of breast cancer (n = 11) and normal FVB∕N mice (n = 6) were used to measure T(2)∗ of normal mammary gland tissue, intraepithelial neoplasia, invasive cancers, mammary lymph nodes, and muscle. MRI experiments were performed on a 9.4T animal scanner. High resolution (117 microns) axial 2D multislice gradient echo images with fat suppression were acquired first to identify inguinal mammary gland. Then a multislice multigradient echo pulse sequence with and without fat suppression were performed over the inguinal mammary gland. The modulus of a complex double exponential decay detected by the multigradient echo sequence was used to fit the absolute proton free induction decay averaged over a region of interest to determine the T(2)∗ of water and fat signals. RESULTS: The measured T(2)∗ values of tumor and muscle are similar (∼15 ms), and almost twice that of lymph nodes (∼8 ms). There was a statistically significant difference (p < 0.03) between T(2)∗ in normal mammary tissue (13.7 ± 2.9 ms) and intraductal cancers (11 ± 2.0 ms) when a fat suppression pulse was applied. CONCLUSIONS: These are the first reported T(2)∗ measurements from single mammary ducts. The results demonstrated that T(2)∗ measurements may have utility for identifying early pre-invasive cancers in mouse models. This may inspire similar research for patients using T(2)∗ for diagnostic imaging of early breast cancer.

Ductal carcinoma in situ: detection, diagnosis, and characterization with magnetic resonance imaging.

Ductal carcinoma in situ (DCIS) is a preinvasive malignancy that currently accounts for over 20% of newly diagnosed breast cancers in the US. This article reviews how clinical magnetic resonance imaging methods are being implemented for the detection, diagnosis and characterization of DCIS. Research strategies that are being pursued to help realize the full potential for magnetic resonance imaging to improve the outcomes of patients diagnosed with DCIS are discussed.

The diverse pathology and kinetics of mass, nonmass, and focus enhancement on MR imaging of the breast.

PURPOSE: To compare the pathology and kinetic characteristics of breast lesions with focus-, mass-, and nonmass-like enhancement. MATERIALS AND METHODS: A total of 852 MRI detected breast lesions in 697 patients were selected for an IRB approved review. Patients underwent dynamic contrast enhanced MRI using one pre- and three to six postcontrast T(1)-weighted images. The "type" of enhancement was classified as mass, nonmass, or focus, and kinetic curves quantified by the initial enhancement percentage (E(1)), time to peak enhancement (T(peak)), and signal enhancement ratio (SER). These kinetic parameters were compared between malignant and benign lesions within each morphologic type. RESULTS: A total of 552 lesions were classified as mass (396 malignant, 156 benign), 261 as nonmass (212 malignant, 49 benign), and 39 as focus (9 malignant, 30 benign). The most common pathology of malignant/benign lesions by morphology: for mass, invasive ductal carcinoma/fibroadenoma; for nonmass, ductal carcinoma in situ (DCIS)/fibrocystic change(FCC); for focus, DCIS/FCC. Benign mass lesions exhibited significantly lower E(1), longer T(peak), and lower SER compared with malignant mass lesions (P < 0.0001). Benign nonmass lesions exhibited only a lower SER compared with malignant nonmass lesions (P < 0.01). CONCLUSION: By considering the diverse pathology and kinetic characteristics of different lesion morphologies, diagnostic accuracy may be improved.

Normal parenchymal enhancement patterns in women undergoing MR screening of the breast.

OBJECTIVES: To characterize the kinetic and morphological presentation of normal breast tissue on DCE-MRI in a large cohort of asymptomatic women, and to relate these characteristics to breast tissue density. METHODS: 335 consecutive breast MR examinations in 229 asymptomatic women undergoing high-risk screening evaluations based on recommendations from the American Cancer Society including strong family history and genetic predisposition were selected for IRB-approved review (average age 49.2 ± 10.5 years). Breast tissue density was assessed on precontrast T2-weighted images. Parenchymal enhancement pattern (PEP) was qualitatively classified as minimal, homogeneous, heterogeneous or nodular. Quantitative analysis of parenchymal enhancement kinetics (PEK) was performed, including calculation of initial and peak enhancement percentages (E1, E(peak)), the time to peak enhancement (T ( peak )) and the signal enhancement ratio (SER). RESULTS: 41.8% of examinations were classified as minimal, 13.7% homogeneous, 23.9% heterogeneous and 21.2% nodular PEP. Women with heterogeneously or extremely dense breasts exhibited a higher proportion of nodular PEP (44.2% (27/61)) and significantly higher E1, and E(peak) (p < 0.003) compared with those with less dense breasts. CONCLUSIONS: Qualitative and quantitative parenchymal enhancement characteristics vary by breast tissue density. In future work, the association between image-derived MR features of the normal breast and breast cancer risk should be explored.

In vivo MRI of early stage mammary cancers and the normal mouse mammary gland.

Since the advent of screening mammography, approximately one-quarter of newly diagnosed breast cancers are at the earliest preinvasive stage of ductal carcinoma in situ (DCIS). Concomitant with this improvement in early detection has been a growing clinical concern that distinguishing aggressive from indolent DCIS is necessary to optimize patient management. Genetically engineered mouse models offer an appealing experimental framework in which to investigate factors that influence and predict progression of preinvasive neoplasias. Because of the small size of early stage carcinomas in mice, high-resolution imaging techniques are required to effectively observe longitudinal progression. The purpose of the present study was to evaluate the feasibility of MRI for assessment of in situ mammary neoplasias and early invasive mammary cancers that stochastically arise in mammary glands of C3(1) SV40 Tag transgenic mice. Additionally, images of normal mammary glands from wild-type FVB/N mice were acquired and compared with those from transgenic mice. Sixteen mice underwent MR examinations employing axial two-dimensional multi-slice gradient recalled echo scans (TR/TE =∼1000/5.5 ms) with fat suppression in a two-step process targeting both the upper and lower mammary glands. MRI successfully detected in situ and early invasive neoplasias in transgenic mice with high sensitivity and specificity. The average signal-to-noise ratio (SNR) of in situ lesions on fat-suppressed high-resolution T(1) -weighted images was 22.9, which was lower than that of invasive tumors, lymph nodes and muscle (average SNR of 29.5-34.9, p < 0.0001) but significantly higher than that of normal mammary tissue (average SNR = 5.5, p < 0.0001). Evaluation of wild-type mammary glands revealed no cancerous or benign lesions, and comparable image contrast characteristics (average SNR = 5.2) as compared with normal tissue areas of transgenic mice. This present study demonstrates that MRI is an excellent candidate for performing longitudinal assessment of early stage mammary cancer disease progression and response to therapy in the transgenic model system.

Computerized assessment of breast lesion malignancy using DCE-MRI robustness study on two independent clinical datasets from two manufacturers.

RATIONALE AND OBJECTIVES: To conduct a preclinical evaluation of the robustness of our computerized system for breast lesion characterization on two breast magnetic resonance imaging (MRI) databases that were acquired using scanners from two different manufacturers. MATERIALS AND METHODS: Two clinical breast MRI databases were acquired from a Siemens scanner and a GE scanner, which shared similar imaging protocols and retrospectively collected under an institutional review board-approved protocol. In our computerized analysis system, after a breast lesion is identified by the radiologist, the computer performs automatic lesion segmentation and feature extraction and outputs an estimated probability of malignancy. We used a Bayesian neural network with automatic relevance determination for joint feature selection and classification. To evaluate the robustness of our classification system, we first used Database 1 for feature selection and classifier training, and Database 2 to test the trained classifier. Then, we exchanged the two datasets and repeated the process. Area under the receiver operating characteristic curve (AUC) was used as a performance figure of merit in the task of distinguishing between malignant and benign lesions. RESULTS: We obtained an AUC of 0.85 (approximate 95% confidence interval [CI] 0.79-0.91) for (a) feature selection and classifier training using Database 1 and testing on Database 2; and an AUC of 0.90 (approximate 95% CI 0.84-0.96) for (b) feature selection and classifier training using Database 2 and testing on Database 1. We failed to observe statistical significance for the difference AUC of 0.05 between the two database conditions (P = .24; 95% confidence interval -0.03, 0.1). CONCLUSION: These results demonstrate the robustness of our computerized classification system in the task of distinguishing between malignant and benign breast lesions on dynamic contrast-enhanced (DCE) MRI images from two manufacturers. Our study showed the feasibility of developing a computerized classification system that is robust across different scanners.

Breast cancers not detected at MRI: review of false-negative lesions.

OBJECTIVE: The objective of our study was to determine the sensitivity of cancer detection at breast MRI using current imaging techniques and to evaluate the characteristics of lesions with false-negative examinations. MATERIALS AND METHODS: Two hundred seventeen patients with 222 newly diagnosed breast cancers or highly suspicious breast lesions that were subsequently shown to be malignant underwent breast MRI examinations for staging. Two breast imaging radiologists performed a consensus review of the breast MRI examinations. The absence of perceptible contrast enhancement at the expected site was considered to be a false-negative MRI. Histology of all lesions was reviewed by an experienced breast pathologist. RESULTS: Enhancement was observed in 213 (95.9%) of the 222 cancer lesions. Of the nine lesions without visible enhancement, two lesions were excluded because the entire tumor had been excised at percutaneous biopsy performed before the MRI examination and no residual tumor was noted on the final histology. The overall sensitivity of MRI for the known cancers was 96.8% (213/220); for invasive cancer, 98.3% (176/179); and for ductal carcinoma in situ, 90.2% (37/41). CONCLUSION: In a population of 220 sequentially diagnosed breast cancer lesions, we found seven (3.2%) MRI-occult cancers, fewer than seen in other published studies. Small tumor size and diffuse parenchymal enhancement were the principal reasons for these false-negative results. Although the overall sensitivity of cancer detection was high (96.8%), it should be emphasized that a negative MRI should not influence the management of a lesion that appears to be of concern on physical examination or on other imaging techniques.

Cancerous breast lesions on dynamic contrast-enhanced MR images: computerized characterization for image-based prognostic markers.

PURPOSE: To assess the performance of computer-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging kinetic and morphologic features in the differentiation of invasive versus noninvasive breast lesions and metastatic versus nonmetastatic breast lesions. MATERIALS AND METHODS: In this institutional review board-approved HIPAA-compliant study, in which the requirement for informed patient consent was waived, breast MR images were retrospectively collected. The images had been obtained with a 1.5-T MR unit by using a gadodiamide-enhanced T1-weighted spoiled gradient-recalled acquisition in the steady state sequence. The breast MR imaging database contained 132 benign, 71 ductal carcinoma in situ (DCIS), and 150 invasive ductal carcinoma (IDC) lesions. Fifty-four IDC lesions were associated with metastasis-positive lymph nodes (LNs), and 64 IDC lesions were associated with negative LNs. Lesion segmentation and extraction of morphologic and kinetic features were automatically performed by a laboratory-developed computer workstation. Features were first selected by using stepwise linear discriminant analysis and then merged by using Bayesian neural networks. Lesion classification performance was assessed with receiver operating characteristic analysis. RESULTS: Differentiation of DCIS from IDC lesions yielded an area under the receiver operating characteristic curve (AUC) of 0.83 +/- 0.03 (standard error). AUCs were 0.85 +/- 0.02 for differentiation between IDC and benign lesions and 0.79 +/- 0.03 for differentiation between DCIS and benign lesions. Differentiation between IDC lesions associated with positive LNs and IDC lesions associated with negative LNs yielded an AUC of 0.82 +/- 0.04. AUCs were 0.86 +/- 0.03 for differentiation between IDC lesions associated with positive LNs and benign lesions and 0.83 +/- 0.03 for differentiation between IDC lesions associated with negative LNs and benign lesions. CONCLUSION: Computer-aided diagnosis of breast DCE MR imaging-depicted lesions was extended from the task of discriminating between malignant and benign lesions to the prognostic tasks of distinguishing between noninvasive and invasive lesions and discriminating between metastatic and nonmetastatic lesions, yielding MR imaging-based prognostic markers. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090838/-/DC1.

Relating dose of contrast media administered to uptake and washout of malignant lesions on DCEMRI of the breast.

RATIONALE AND OBJECTIVES: To quantify the relationship between dose of contrast administered and contrast kinetics of malignant breast lesions. MATERIALS AND METHODS: A total of 108 patients with 120 malignant lesions were selected for an institutional review board-approved review. Dynamic magnetic resonance protocol: one pre- and three or five post-contrast (at a fixed volume of 20 mL of 0.5 M gadodiamide) images. Patients were stratified into groups based on dose of contrast administered, after calculation of body weight (kg): Dose Group 1, <0.122 mmol/kg; Dose Group 2, 0.123-0.155 mmol/kg; Dose Group, 3 > 0.155 mmol/kg. Analysis of kinetic curve shape was made according to the Breast Imaging Reporting and Data System lexicon. Several quantitative parameters were calculated including initial and peak enhancement percentage (E(1) and E(peak)). Linear regression was used to model the variation of kinetic parameters with dose. RESULTS: There was no difference found in the qualitative Breast Imaging Reporting and Data System descriptors of curve shape between the three dose groups. There was a trend for E(1) and E(peak) to increase from Dose Group 1 to Dose Group 3 in malignant lesions overall, as well as in invasive ductal carcinoma lesions separately. Each decrement/increment of 0.05 mmol/kg in dose yielded a decrease/increase of 78% and 97% in E(1) for in situ and invasive cancers, respectively. CONCLUSION: Contrast should be administered at fixed dose to achieve comparable levels of lesion uptake in women of different weights. Our results suggest that reducing the contrast administered to 0.05 mmol/kg, as has been suggested for patients at risk of developing nephrogenic systemic fibrosis, could substantially decrease the observed initial enhancement in some cancers.

Ductal carcinoma in situ: X-ray fluorescence microscopy and dynamic contrast-enhanced MR imaging reveals gadolinium uptake within neoplastic mammary ducts in a murine model.

PURPOSE: To combine dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with x-ray fluorescence microscopy (XFM) of mammary gland tissue samples from mice to identify the spatial distribution of gadolinium after intravenous injection. MATERIALS AND METHODS: C3(1) Sv-40 large T antigen transgenic mice (n = 23) were studied with institutional animal care and use committee approval. Twelve mice underwent DCE MR imaging after injection of gadodiamide, and gadolinium concentration-time curves were fit to a two-compartment pharmacokinetic model with the following parameters: transfer constant (K(trans)) and volume of extravascular extracellular space per unit volume of tissue (v(e)). Eleven mice received gadodiamide before XFM. These mice were sacrificed 2 minutes after injection, and frozen slices containing ducts distended with murine ductal carcinoma in situ (DCIS) were prepared for XFM. One mouse received saline and served as the control animal. Elemental gadolinium concentrations were measured in and around the ducts with DCIS. Hematoxylin-eosin-stained slices of mammary tissues were obtained after DCE MR imaging and XFM. RESULTS: Ducts containing DCIS were unambiguously identified on MR images. DCE MR imaging revealed gadolinium uptake along the length of ducts with DCIS, with an average K(trans) of 0.21 min(-1) +/- 0.14 (standard deviation) and an average v(e) of 0.40 +/- 0.16. XFM revealed gadolinium uptake inside ducts with DCIS, with an average concentration of 0.475 mmol/L +/- 0.380; the corresponding value for DCE MR imaging was 0.30 mmol/L +/- 0.13. CONCLUSION: These results provide insight into the physiologic basis of contrast enhancement of DCIS lesions on DCE MR images: Gadolinium penetrates and collects inside neoplastic ducts.

Magnetic resonance imaging of the natural history of in situ mammary neoplasia in transgenic mice: a pilot study.

INTRODUCTION: Because of the small size of in situ mammary cancers in mouse models, high-resolution imaging techniques are required to effectively observe how lesions develop, grow and progress over time. The purpose of this study was to use magnetic resonance (MR) imaging to track in vivo the transition from in situ neoplasia to invasive cancer in a transgenic mouse model of human cancer. METHODS: MR images of 12 female C3(1) SV40 Tag mice that develop mammary intraepithelial neoplasia (MIN) were obtained. MIN is believed to be similar to human ductal carcinoma in situ (DCIS) and is considered a precursor of invasive tumors. Images were serially obtained from 10-21 weeks of age at 2-3 week intervals. MIN lesions were identified based on their morphology on MR images. Lesions were followed over time and several lesion features were measured including volume, growth rate and morphology. For those MIN lesions that progressed to invasive cancer the progression time was measured. RESULTS: Overall, 21 MIN lesions were initially detected at an average initial volume of 0.3 +/- 0.2 mm3 with an average growth rate of -0.15 +/- 0.66 week-1. Even though all mice were inbred to express the SV40 Tag transgene in the mammary epithelium and expected to develop invasive carcinoma, the individual MIN lesions took vastly different progression paths: (i) 9 lesions progressed to invasive tumors with an average progression time of 4.6 +/- 1.9 weeks; (ii) 2 lesions regressed, i.e., were not detected on future images; and (iii) 5 were stable for over 8 weeks, and were demonstrated by a statistical model to represent indolent disease. CONCLUSIONS: To our knowledge, the results reported here are the first measurements of the timescale and characteristics of progression from in situ neoplasia to invasive carcinoma and provide image-based evidence that DCIS may be a non-obligate precursor lesion with highly variable outcomes. In addition, this study represents a first step towards developing methods of image acquisition for identifying radiological characteristics that might predict which in situ neoplasias will become invasive cancers and which are unlikely to progress.

Kinetic curves of malignant lesions are not consistent across MRI systems: need for improved standardization of breast dynamic contrast-enhanced MRI acquisition.

OBJECTIVE: The purpose of this study was to compare MRI kinetic curve data acquired with three systems in the evaluation of malignant lesions of the breast. MATERIALS AND METHODS: The cases of 601 patients with 682 breast lesions (185 benign, 497 malignant) were selected for review. The malignant lesions were classified as ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and other. The dynamic MRI protocol consisted of one unenhanced and three to seven contrast-enhanced images acquired with one of three imaging protocols and systems. An experienced radiologist analyzed the shapes of the kinetic curves according to the BI-RADS lexicon. Several quantitative kinetic parameters were calculated, and the kinetic parameters of malignant lesions were compared across the three systems. RESULTS: Imaging protocol and system 1 were used to image 304 malignant lesions (185 IDC, 62 DCIS); imaging protocol and system 2, 107 lesions (72 IDC, 21 DCIS); and imaging protocol and system 3, 86 lesions (64 IDC, 17 DCIS). Compared with those visualized with imaging protocols and systems 1 and 2, IDC lesions visualized with imaging protocol and system 3 had significantly less initial enhancement, longer time to peak enhancement, and a slower washout rate (p < 0.004). Only 47% of IDC lesions imaged with imaging protocol and system 3 exhibited washout type curves, compared with 75% and 74% of those imaged with imaging protocols and systems 2 and 1, respectively. The diagnostic accuracy of kinetic analysis was lowest for imaging protocol and system 3, but the difference was not statistically significant. CONCLUSION: The kinetic curve data on malignant lesions acquired with one system showed significantly lower initial contrast uptake and a different curve shape in comparison with data acquired with the other two systems. Differences in k-space sampling, T1 weighting, and magnetization transfer effects may be explanations for the difference.

Quantitative analysis of dynamic contrast enhanced MRI for assessment of bowel inflammation in Crohn's disease pilot study.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the feasibility of quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data in the detection of bowel inflammation in patients with Crohn's disease. MATERIALS AND METHODS: Eleven patients who underwent magnetic resonance enterography for known or suspected Crohn's disease and had colonoscopy or surgery within 4 weeks of imaging were included in this study. DCE-MRI data were acquired using a 1.5-T scanner with temporal resolution of 5 to 12 seconds for approximately 5 to 7 minutes. A two-compartment pharmacokinetic model was used to analyze the data to obtain the volume transfer constant (K(trans)) and the extravascular extracellular space (v(e)). Additionally, semiquantitative parameters were derived using an empirical mathematical model to fit the contrast concentration curves. Endoscopic, surgical, and pathologic results were compared to the MRI data. Receiver-operating characteristic analysis was performed to compare the diagnostic accuracy of the parameters in the task of distinguishing normal tissue from inflammation. RESULTS: A total of 51 bowel segments (19 with inflammation, 32 normal) were included in the analyses. Inflamed bowel segments had faster K(trans) values, larger v(e) values, increased contrast uptake, larger initial areas under the contrast concentration curve, and steeper initial enhancement slopes than normal bowel segments (P < .05). The areas under the receiver-operating characteristic curve for these parameters ranged from 0.70 to 0.86. CONCLUSION: These preliminary results demonstrate that the quantitative analysis of DCE-MRI data is possible for the assessment of bowel inflammation in patients with Crohn's disease. Future studies need be performed on larger numbers of patients to correlate the severity and type of inflammation with kinetic parameters.

Evaluation of computer-aided diagnosis on a large clinical full-field digital mammographic dataset.

RATIONALE AND OBJECTIVES: To convert and optimize our previously developed computerized analysis methods for use with images from full-field digital mammography (FFDM) for breast mass classification to aid in the diagnosis of breast cancer. MATERIALS AND METHODS: An institutional review board approved protocol was obtained, with waiver of consent for retrospective use of mammograms and pathology data. Seven hundred thirty-nine FFDM images, which contained 287 biopsy-proven breast mass lesions, of which 148 lesions were malignant and 139 lesions were benign, were retrospectively collected. Lesion margins were delineated by an expert breast radiologist and were used as the truth for lesion-segmentation evaluation. Our computerized image analysis method consisted of several steps: 1) identified lesions were automatically extracted from the parenchymal background using computerized segmentation methods; 2) a set of image characteristics (mathematic descriptors) were automatically extracted from image data of the lesions and surrounding tissues; and 3) selected features were merged into an estimate of the probability of malignancy using a Bayesian artificial neural network classifier. Performance of the analyses was evaluated at various stages of the conversion using receiver-operating characteristic analysis. RESULTS: An area under the curve value of 0.81 was obtained in the task of distinguishing between malignant and benign mass lesions in a round-robin by case evaluation on the entire FFDM dataset. We failed to show a statistically significant difference (P = .83) compared to results from our previous study in which the computerized classification was performed on digitized screen-film mammograms. CONCLUSIONS: Our computerized analysis methods developed on digitized screen-film mammography can be converted for use with FFDM. Results show that the computerized analysis methods for the diagnosis of breast mass lesions on FFDM are promising, and can potentially be used to aid clinicians in the diagnostic interpretation of FFDM.

DCEMRI of breast lesions: is kinetic analysis equally effective for both mass and nonmass-like enhancement?

To perform a pilot study investigating whether the sensitivity and specificity of kinetic parameters can be improved by considering mass and nonmass breast lesions separately. The contrast media uptake and washout kinetics in benign and malignant breast lesions were analyzed using an empirical mathematical model (EMM), and model parameters were compared in lesions with mass-like and nonmass-like enhancement characteristics. 34 benign and 78 malignant breast lesions were selected for review. Dynamic MR protocol: 1 pre and 5 postcontrast images acquired in the coronal plane using a 3D T1-weighted SPGR with 68 s timing resolution. An experienced radiologist classified the type of enhancement as mass, nonmass, or focus, according to the BI-RADS lexicon. The kinetic curve obtained from a radiologist-drawn region within the lesion was analyzed quantitatively using a three parameter EMM. Several kinetic parameters were then derived from the EMM parameters: the initial slope (Slope(ini)), curvature at the peak (kappa(peak)), time to peak (T(peak)), initial area under the curve at 30 s (iAUC30), and the signal enhancement ratio (SER). The BI-RADS classification of the lesions yielded: 70 mass lesions, 38 nonmass, 4 focus. For mass lesions, the contrast uptake rate (alpha), contrast washout rate (beta), iAUC30, SER, Slope(ini), T(peak) and kappa(peak) differed substantially between benign and malignant lesions, and after correcting for multiple tests of significance SER and T(peak) demonstrated significance (p < 0.007). For nonmass lesions, we did not find statistically significant differences in any of the parameters for benign vs. malignant lesions (p > 0.5). Kinetic parameters could distinguish benign and malignant mass lesions effectively, but were not quite as useful in discriminating benign from malignant nonmass lesions. If the results of this pilot study are validated in a larger trial, we expect that to maximize diagnostic utility, it will be better to classify lesion morphology as mass or nonmass-like enhancement prior to kinetic analysis.

High spectral and spatial resolution MRI of age-related changes in murine prostate.

The purpose of this work was to evaluate high-resolution echo-planar spectroscopic MRI of normal and precancerous prostatic changes in a transgenic mouse line. Simian virus large T-antigen transgenic male mice (N = 7, age = 34 +/- 3.7 weeks) with prostatic hyperplasia and intraepithelial neoplasia (PIN) were studied. High spectral and spatial resolution (HiSS) MRI of the water proton signal was compared to the free induction decay (FID) integral image and conventional gradient-echo and spin-echo imaging. Water peak-height images of the prostate produced from HiSS datasets showed improved contrast-to-noise ratio (CNR) (P < 0.03), and greater morphological detail (P < 0.004) based on texture analysis. Despite the high spectral resolution of the HiSS datasets, signal-to-noise ratio (SNR) compared favorably with that of the FID integral and conventional images. Lobular features in HiSS images of older mice were consistent with hyperplasia seen on histology. A partially deuterated water-filled catheter was inserted in the mouse rectum for susceptibility matching between the colon interior and exterior to minimize image artifacts. These preliminary results suggest that HiSS MRI provides detailed morphology of the murine prostate and can detect early changes associated with the development of cancer. HiSS MRI of patients may have similar advantages.

Differentiation between benign and malignant breast lesions detected by bilateral dynamic contrast-enhanced MRI: a sensitivity and specificity study.

The purpose of this study was to apply an empirical mathematical model (EMM) to kinetic data acquired under a clinical protocol to determine if the sensitivity and specificity can be improved compared with qualitative BI-RADS descriptors of kinetics. 3D DCE-MRI data from 100 patients with 34 benign and 79 malignant lesions were selected for review under an Institutional Review Board (IRB)-approved protocol. The sensitivity and specificity of the delayed phase classification were 91% and 18%, respectively. The EMM was able to accurately fit these curves. There was a statistically significant difference between benign and malignant lesions for several model parameters: the uptake rate, initial slope, signal enhancement ratio, and curvature at the peak enhancement (at most P=0.04). These results demonstrated that EMM analysis provided at least the diagnostic accuracy of the kinetic classifiers described in the BI-RADS lexicon, and offered a few key advantages. It can be used to standardize data from institutions with different dynamic protocols and can provide a more objective classification with continuous variables so that thresholds can be set to achieve desired sensitivity and specificity. This suggests that the EMM may be useful for analysis of routine clinical data.

Pure ductal carcinoma in situ: kinetic and morphologic MR characteristics compared with mammographic appearance and nuclear grade.

PURPOSE: To retrospectively compare the kinetic and morphologic characteristics of pure ductal carcinoma in situ (DCIS) lesions depicted on dynamic contrast material-enhanced magnetic resonance (MR) images with the nuclear grade and conventional mammographic appearance of these lesions. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was institutional review board approved, and informed patient consent was waived. Seventy-eight patients with 79 histologically proved pure DCIS lesions were selected. There were 17 low-nuclear-grade, 26 intermediate-nuclear-grade, 30 high-nuclear-grade, and six unclassified lesions. Sixty-five lesions were classified as fine pleomorphic, fine linear, or fine linear-branching calcifications (n = 31); amorphous or indistinct calcifications (n = 18); noncalcified mass (n = 10); or occult (n = 6) at conventional (x-ray) mammography. One experienced radiologist analyzed lesion morphology and kinetic curve shape according to the Breast Imaging Reporting and Data System lexicon. Initial enhancement percentage, time to peak enhancement (T(peak)), and signal enhancement ratio (a measure of washout) were calculated for each lesion. RESULTS: Of the 79 pure DCIS lesions, 20 (25%) exhibited enhancement plateau curves and 35 (44%) exhibited washout curves. The lesions with a masslike appearance on mammograms exhibited more suspicious kinetic characteristics (mean T(peak) approximately 2 minutes) than did the lesions with amorphous or indistinct calcifications (mean T(peak) = 4.4 minutes). There was no significant difference in enhancement kinetic properties across the nuclear grades. Lesion morphology was predominantly nonmass, with clumped or heterogeneous enhancement in a segmental or linear distribution. CONCLUSION: The pure DCIS lesions exhibited washout, plateau, and persistent enhancement curves. Enhancement kinetic characteristics varied with mammographic appearance but not with nuclear grade. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/245/3/684/DC1.