MRI-Based Kinetic Heterogeneity Evaluation in the Accurate Access of Axillary Lymph Node Status in Breast Cancer Using a Hybrid CNN-RNN Model.

BACKGROUND: Accurate evaluation of the axillary lymph node (ALN) status is needed for determining the treatment protocol for breast cancer (BC). The value of magnetic resonance imaging (MRI)-based tumor heterogeneity in assessing ALN metastasis in BC is unclear. PURPOSE: To assess the value of deep learning (DL)-derived kinetic heterogeneity parameters based on BC dynamic contrast-enhanced (DCE)-MRI to infer the ALN status. STUDY TYPE: Retrospective. SUBJECTS: 1256/539/153/115 patients in the training cohort, internal validation cohort, and external validation cohorts I and II, respectively. FIELD STRENGTH/SEQUENCE: 1.5 T/3.0 T, non-contrast T1-weighted spin-echo sequence imaging (T1WI), DCE-T1WI, and diffusion-weighted imaging. ASSESSMENT: Clinical pathological and MRI semantic features were obtained by reviewing histopathology and MRI reports. The segmentation of the tumor lesion on the first phase of T1WI DCE-MRI images was applied to other phases after registration. A DL architecture termed convolutional recurrent neural network (ConvRNN) was developed to generate the KHimage (kinetic heterogeneity of DCE-MRI image) score that indicated the ALN status in patients with BC. The model was trained and optimized on training and internal validation cohorts, tested on two external validation cohorts. We compared ConvRNN model with other 10 models and the subgroup analyses of tumor size, magnetic field strength, and molecular subtype were also evaluated. STATISTICAL TESTS: Chi-squared, Fisher's exact, Student's t, Mann-Whitney U tests, and receiver operating characteristics (ROC) analysis were performed. P < 0.05 was considered significant. RESULTS: The ConvRNN model achieved area under the curve (AUC) of 0.802 in the internal validation cohort and 0.785-0.806 in the external validation cohorts. The ConvRNN model could well evaluate the ALN status of the four molecular subtypes (AUC = 0.685-0.868). The patients with larger tumor sizes (>5 cm) were more susceptible to ALN metastasis with KHimage scores of 0.527-0.827. DATA CONCLUSION: A ConvRNN model outperformed traditional models for determining the ALN status in patients with BC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Feasibility analysis of magnetic resonance imaging-based radiomics features for preoperative prediction of nuclear grading of ductal carcinoma in situ.

Background: The nuclear grading of ductal carcinoma in situ (DCIS) affects its clinical risk. The aim of this study was to investigate the possibility of predicting the nuclear grading of DCIS, by magnetic resonance imaging (MRI)-based radiomics features. And to develop a nomogram combining radiomics features and MRI semantic features to explore the potential role of MRI radiomic features in the assessment of DCIS nuclear grading. Methods: A total of 156 patients (159 lesions) with DCIS and DCIS with microinvasive (DCIS-MI) were enrolled in this retrospective study, with 112 lesions included in the training cohort and 47 lesions included in the validation cohort. Radiomics features were extracted from Dynamic contrast-enhanced MRI (DCE-MRI) phases 1st and 5th. After feature selection, radiomics signature was constructed and radiomics score (Rad-score) was calculated. Multivariate analysis was used to identify MRI semantic features that were significantly associated with DCIS nuclear grading and combined with Rad-score to construct a Nomogram. Receiver operating characteristic curves were used to evaluate the predictive performance of Rad-score and Nomogram, and decision curve analysis (DCA) was used to evaluate the clinical utility. Results: In multivariate analyses of MRI semantic features, larger tumor size and heterogeneous enhancement pattern were significantly associated with high-nuclear grade DCIS (HNG DCIS). In the training cohort, Nomogram had an area under curve (AUC) of 0.879 and Rad-score had an AUC of 0.828. Similarly, in the independent validation cohort, Nomogram had an AUC value of 0.828 and Rad-score had an AUC of 0.772. In both the training and validation cohorts, Nomogram had a significantly higher AUC value than Rad-score (P<0.05). DCA confirmed that Nomogram had a higher net clinical benefit. Conclusions: MRI-based radiomic features can be used as potential biomarkers for assessing nuclear grading of DCIS. The nomogram constructed by radiomic features combined with semantic features is feasible in discriminating non-HNG and HNG DCIS.

Nomogram for Early Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Using Dynamic Contrast-enhanced and Diffusion-weighted MRI.

RATIONALE AND OBJECTIVES: The study investigated the potential of the combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging in predicting the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) after two cycles of NAC. MATERIALS AND METHODS: Eighty-seven patients with breast cancer who underwent MR examination before and after two cycles of NAC were enrolled. The patients were randomly assigned to a training cohort and a validation cohort (3:1 ratio). MRI parameters including tumor longest diameter, time-signal intensity curve, early enhanced ratio (E90), maximal enhanced ratio and ADC value were measured, and percentage change in MRI parameters were calculated. Univariate analysis and multivariate logistic regression analysis were used to evaluate independent predictors of pCR in the training cohort. The validation cohort was used to test the prediction model, and the nomogram was created based on the prediction model. RESULTS: This study demonstrated that the ADC value after two cycles of NAC (OR = 1.041, 95% CI (1.002, 1.081); p = 0.037), percentage decrease in E90 (OR = 0.927, 95% CI (0.881, 0.977); p =0.004) and percentage decrease in tumor size (OR = 0.948, 95% CI (0.909, 0.988); p = 0.011) were significantly important for independently predicting pCR. The prediction model yielded AUC of 0.939 and 0.944 in the training cohort and the validation cohort, respectively. CONCLUSION: The combined use of dynamic contrast-enhanced MRI and diffusion-weighted imaging could accurately predict pCR after two cycles of NAC. The prediction model and the nomogram had strong predictive value to NAC.

FOXF2 reprograms breast cancer cells into bone metastasis seeds.

Bone metastases occur in most advanced breast cancer patients and cause serious skeletal-related complications. The mechanisms by which bone metastasis seeds develop in primary tumors and specifically colonize the bone remain to be elucidated. Here, we show that forkhead box F2 (FOXF2) functions as a master transcription factor for reprogramming cancer cells into an osteomimetic phenotype by pleiotropic transactivation of the BMP4/SMAD1 signaling pathway and bone-related genes that are expressed at early stages of bone differentiation. The epithelial-to-osteomimicry transition regulated by FOXF2 confers a tendency on cancer cells to metastasize to bone which leads to osteolytic bone lesions. The BMP antagonist Noggin significantly inhibits FOXF2-driven osteolytic bone metastasis of breast cancer cells. Thus, targeting the FOXF2-BMP/SMAD axis might be a promising therapeutic strategy to manage bone metastasis. The role of FOXF2 in transactivating bone-related genes implies a biological function of FOXF2 in regulating bone development and remodeling.

ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGFß Signaling Pathway.

Bone metastasis affects more than 70% of advanced breast cancer patients, but the molecular mechanisms of this process remain unclear. Here, we present clinical and experimental evidence to clarify the role of the integrin ß-like 1 (ITGBL1) as a key contributor to bone metastasis of breast cancer. In an in vivo model system and in vitro experiments, ITGBL1 expression promoted formation of osteomimetic breast cancers, facilitating recruitment, residence, and growth of cancer cells in bone microenvironment along with osteoclast maturation there to form osteolytic lesions. Mechanistic investigations identified the TGFß signaling pathway as a downstream effector of ITGBL1 and the transcription factor Runx2 as an upstream activator of ITGBL1 expression. In support of these findings, we also found that ITGBL1 was an essential mediator of Runx2-induced bone metastasis of breast cancer. Overall, our results illuminate how bone metastasis occurs in breast cancer, and they provide functional evidence for new candidate biomarkers and therapeutic targets to identify risk, to prevent, and to treat this dismal feature of advanced breast cancer.

Analysis of mammographic breast density in a group of screening chinese women and breast cancer patients.

BACKGROUND: A dense breast not only reduces the sensitivity of mammography but also is a moderate independent risk factor for breast cancer. The percentage of Western women with fat breast tissue is higher aged 40 years or older. To a certain extent, mammography as a first choice of screening imaging method for Western women of this group is reasonable. Hitherto, the frequency and age distribution of mammographic breast density patterns among Chinese women had not been characterized. The purpose of this study was to investigate the frequency and age distribution of mammographic breast density patterns among a group of Chinese screening women and breast cancer patients in order to provide useful information for age-specific guidelines for breast cancer screening in Chinese women. METHODS: A retrospective review of a total of 3,394 screening women between August and December 2009 and 2,527 breast cancer patients between July 2011 and June 2012 was conducted. Descriptive analyses were used to examine the association between age and breast density. The significance of differences of breast density between the screening women and the breast cancer patients was examined using nonparametric tests. RESULTS: There was a significant inverse relationship between age and breast density overall (r=-0.37, p<0.01). Breast density of the breast cancer patients in the subgroups of 40-49 years old was greater compared with that of the screening women, the same in those aged 50-54 years and in those 55 years old or older, less than in the screening group. CONCLUSIONS: With regard to the Chinese women younger than 55 years old, the diagnostic efficiency of breast cancer screening imaging examinations may be potentially improved by combining screening mammography with ultrasound.

Differences between breast cancer patients younger and older than 40 years: mammographic findings.

OBJECTIVE: To compare the mammogarphic appearance between breast cancer patients aged <40 and ≥40 years. METHODS: Needle localization and biopsy of suspicious mammographic lesions identified 1,959 breast carcinomas in a single institution from Jun 2012 to Apr 2013. According to the age, we divided patients into two groups: <40 and ≥40 years old, and analyzed mammographic appearance separately. RESULTS: Young patients had 44.2% foci with calcification, but old patients only had 39.4% (P<0.001). In younger group, the ratios of cases according to mass density were 41.8% or higher, 58.2% equivalent and lower. In older group, the ratios were 55.5 % and 44.5%, respectively. There were statistical differences between high density and others (P<0.05). The ratios of cases according to mass margin were 13.9% circumscribed and microlobulated, 86.1% indistinct and spiculated in the younger group, as compared to 6.5% and 93.5%, respectively, in the older group (P<0.05). CONCLUSIONS: Mammographic findings differ between young and old patients with breast cancer, for example regarding mass density, mass margin and microcalcification ratios.

Correlation between mammograghic findings and clinical/ pathologic features in women with small invasive breast carcinomas.

BACKGROUND: To study the relationship between mammographic findings and clinical/pathologic features in women with 1-15mm sized invasive breast cancer. MATERIALS AND METHODS: We investigated a consecutive series of 134 cases diagnosed in Tianjin Medical University Cancer Institute and Hospital in 2007. Mammographic findings were classified into five groups as follows :1) stellate mass without calcification; 2) non-stellate mass without calcification; 3) intermediate suspicious calcification with or without associated mass; 4) higher probability malignant calcification with or without associated mass; 5) focal asymmetry/distortion without associated calcification. Associations between mammographic and clinical/pathological features (menopause status/family history/histologic grade/lymph node status and ER/PR/HER2 status) was analyzed through logistic regression and chi square tests. RESULTS: Compared to the stellate mass without calcification group, higher probability malignant calcification patients were associated significantly with a positive lymph node status, always presenting in patients who were non-menopausal and with a family history of carcinoma. CONCLUSIONS: Higher probability malignant calcifications with or without associated tumor masses are associated with clinical/pathologic features of poor prognosis.

Elastography for breast cancer diagnosis: a useful tool for small and BI-RADS 4 lesions.

The present study aimed at evaluating and comparing the diagnostic performance of B-mode ultrasound (US), elastography score (ES), and strain ratio (SR) for the differentiation of breast lesions. This retrospective study enrolled 431 lesions from 417 in-hospital patients. All patients were examined with both conventional ultrasound and elastography. Two experienced radiologists reviewed ultrasound and elasticity images. The histopathologic result obtained from ultrasound-guided core biopsy or operation excisions were used as the reference standard. Pathologic examination revealed 276 malignant lesions (64%) and 155 benign lesions (36%). A cut-off point of 4.15 (area under the curve, 0.891) allowed significant differentiation of malignant and benign lesions. ROC (receiver-operating characteristic) curves showed a higher value for combination of B-mode ultrasound and elastography for the diagnosis of breast lesions. Conventional ultrasound combined elastography showed high sensitivity, specificity, and accuracy for group II lesions (10mm

[Comparison of full-field digital mammography and digital breast tomosynthesis on assessment of the lesions in dense breast: a preliminary study].

OBJECTIVE: To compare the performance of full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in the assessment of the lesions in dense breast, and to estimate the difference in diagnosis of breast disease by FFDM images alone and FFDM plus DBT images. METHODS: According to the breast imaging reporting and data system (BIRADS), 134 patients were selected. The morphology of the lesions shown on FFDM and DBT were evaluated and compared, and the maximum diameter of the lesions was measured. At first, doctors made the diagnosis of a patient by reading FFDM only. Then they made another diagnosis by combining with DBT images of the same patient. The two diagnoses were compared and analyzed according to the pathology results. RESULTS: One hundred and thirty-four patients were included in this study, and all of them were confirmed by histology (65 benign cases, 69 malignant cases). DBT could show more details about the morphology of the lesions, including the border of the masses, spiculation and vessels. The numbers of those signs detected by DBT were 46, 30 and 3, respectively, while only 33 case with circumscribed masses and 14 cases with spiculation were detected by FFDM. Only the difference of spiculation in heterogeneously dense breast detected by DBT and FFDM was statistically significant (P < 0.05). Of the cases with calcifications, DBT images (reconstructed as a 1-mm-thick slice) showed calcifications superior to FFDM in 2 cases, equal to FFDM in 23 cases, and inferior to FFDM in 11 cases. The difference was statistically significant (P < 0.05). But when thickness was changed into 1 cm, the visibility of calcifications in those cases was equal between FFDM and DBT. The maximum diameter of lesions was 2.46 ± 1.64 cm in DBT image, and 2.58 ± 1.62 cm in FFDM image, with a significant difference (P < 0.05). Comparing with reading FFDM images only, the accuracy of FFDM combining with DBT was increased from 88.8% to 91.8%. For FFDM, the AUC of ROC was 0.887, while for DBT it was increased to 0.912, with a non-significant difference (P > 0.05). CONCLUSIONS: DBT is superior to FFDM in the morphological characterization and small calcification in the lesions in dense breast. Combining FFDM and DBT improves the accuracy of diagnosis, but the difference is not statistically significant.

Breast magnetic resonance imaging in patients with occult breast carcinoma: evaluation on feasibility and correlation with histopathological findings.

BACKGROUND: As an uncommon presentation, occult primary breast cancer remains a diagnostic and therapeutic challenge in clinical practice. This study aimed to retrospectively assess the feasibility of breast magnetic resonance imaging (MRI) in patients with malignant axillary lymphadenopathy and unknown primary malignancy, and correlation with histopathological characteristics. METHODS: A total of 35 women with occult breast carcinoma were evaluated with dynamic contrast-enhanced breast MRI. Whole seriate section was used in all cases. MRI performance was assessed and correlated with histopathological findings. RESULTS: Twenty-one of 35 patients were found to have primary breast carcinoma histologically. Twenty of the 21 patients had abnormal MR findings and 1 patient had a normal MRI study. Of the remaining 14 patients, 10 were negative on both MRI and surgery. Four had suspicious enhancement on MRI and no corresponding tumor was found. Lesions with mass enhancement were found in 55% (11/20) and ductual and segmental enhancement in 45%. The average diameter of the primary tumors was 15 mm. Invasive ductal carcinomas were found in 81% (17/21). One of 17 invasive ductual carcinomas was too small to be graded. Fourteen of the remaining 16 were classified as grade II and 2 as grade I. Thirty-two of the 35 patients had received estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 examinations and the 12 of 32 were triple-negative breast carcinoma. CONCLUSIONS: Mass lesions with small size and lesions with ductal or segment enhancement are common MRI features in patients with occult breast cancer. The dominant types of primary tumors are invasive ductal carcinoma with moderate histopathological grade. The rate of triple-negative breast carcinoma may be higher in occult breast cancer.

Evaluation of spectral selected press sequence in breast lesion characterization.

OBJECTIVE: To evaluate the role of 1H spetral selected point-resolved spectroscopy (SS-PRESS) sequence in distinguishing benign from malignant breast lesions by the malignancy marker of choline peak and to investigate the factors influencing the diagnosis. METHODS: A total of 131 patients (aged 24-83 years, average 44.8 years) were enrolled in this study. The examinations were performed on a 1. 5T scanner with four-channel phased array breast coil. Single-voxel proton magnetic resonance spectroscopy (1H MRS) was acquired by SS-PRESS sequence in these patients referred to surgical or biopsy consultation. RESULTS: Among these patients, 74 were proved to have breast carcinomas and 57 have benign lesions by histopathological examinations. Thirty-one elevated choline peaks were observed in these 74 confirmed malignant lesions, and 5 detectable choline peaks were demonstrated in the 57 benign lesions. The sensitivity and specificity of 1H SS-PRESS MRS were 41.9% and 91.2%, respectively. The main factors influencing the diagnosis were signal-to-noise ratio and pathological type. CONCLUSIONS: 1H SS-PRESS MRS can provide a noninvasive, biochemical measurement of metabolism and improve the specificity of breast magnetic resonance imaging. Choline peak in vivo is a specific but not sensitive marker of malignancy. Technique factors and histopathological characterization of lesions influence the detection rate.

Proton diffusion determination and dual structure model for nickel hydroxide based on potential step measurements on single spherical beads.

Potential step measurement is carried out on single beads of spherical nickel hydroxide to determine the proton diffusion coefficient (D) and concentration of the effective proton vacancies (C). The semi-infinite diffusion equation for the initial stage and the finite diffusion equation for the long-term of the current response to potential step are used for deducing the D and C values. The diffusion coefficients deduced from short and long-term current responses are in the order of magnitude 10(-7) and 10(-10) cm2 s(-1), respectively. The sum of the effective proton vacancy concentrations associated with the two D values comes out to be equal within experimental error to the effective proton vacancy concentration converted from the released electricity during discharge. A dual structure model is proposed to interpret the above-mentioned findings, featuring densely packed grains within which proton diffusion is slow and an inter-grain matrix where proton diffusion is fast. With this model the huge difference (about 6 orders of magnitude) in D values reported in the literature as well as the controversy of the dependence of diffusion coefficient on the state of charge can be largely rationalized. This dual structure model is supported by SEM and AFM observations.

[Value of MR imaging and MR angiography in the differential diagnosis of carotid space tumour].

OBJECTIVE: To determine the imaging features of magnetic resonance imaging (MRI) and 2D time of flight (TOF) MR angiography (MRA) and study the value in the differential diagnosis and surgical planning for carotid space tumors. METHODS: Twenty-six patients with suspected pulsatile carotid space mass were imaged by MRI and 2D TOF MRA from 1996 to 2003. Its characteristic findings were analyzed for lesion shape, margin, signal intensity, angle of common carotid bifurcation, and the relationship between the great vessels and carotid space mass. RESULTS: Of the 26 patients, 22 were verified histopathologically, including 15 carotid body tumors (1 patient had bilateral carotid body tumors), 4 carotid artery aneurysms, 3 schwannomas, and 1 metastatic carcinoma. The rest four patients had clinical pseudomasses proved by MRI and MRA as considerable dilated or tortuous carotid artery as compared with the contralateral one. Combined MRI and MRA assessment of carotid body tumors and carotid artery aneurysm yielded an accuracy of 100%. It was also revealed that the anatomy shown on the MRI and axial MRA source images was consistent with that found by surgery. CONCLUSION: MRI in combination with MRA is considered as non-invasive imaging technique for the evaluation of carotid space tumor showing superiority to other modalities in the differential diagnosis between vascular versus non-vascular tumours. This method may take the place of traumatic carotid angiography.