Research on DCE-MRI Images Based on Deep Transfer Learning in Breast Cancer Adjuvant Curative Effect Prediction.

Breast cancer is a serious threat to women's physical and mental health. In recent years, its incidence has been on the rise and it has become the top female malignant tumor in China. At present, adjuvant chemotherapy for breast cancer has become the standard mode of breast cancer treatment, but the response results usually need to be completed after the implementation of adjuvant chemotherapy, and the optimization of the treatment plan and the implementation of breast-conserving therapy need to be based on accurate estimation of the pathological response. Therefore, to predict the efficacy of adjuvant chemotherapy for breast cancer patients is to find a predictive method that is conducive to individualized choice of chemotherapy regimens. This article introduces the research of DCE-MRI images based on deep transfer learning in breast cancer adjuvant curative effect prediction. Deep transfer learning algorithms are used to process images, and then, the features of breast cancer after adjuvant chemotherapy are collected through image feature collection. Predictions are made, and the research results show that the accuracy of the prediction reaches 70%.

1. Introduction

In recent years, technology has brought people not only the changes in living environment and lifestyle, but also some health diseases. For example, breast cancer has now occupied the first place among female malignant tumors in the world and has become the main culprit in the soaring mortality rate of female tumor patients [1, 2]. Adjuvant chemotherapy (NAC) is clinically used as a standard treatment for LABC patients before surgery. In some cases, it is suitable for women with larger tumors in stages IIA and IIB who wish to undergo breast-conserving surgery. It can not only effectively reduce the tumor volume, but also better the primary tumor to be downgraded, and it can improve the disease-free and long-term survival rate of patients [3]. However, not all breast cancer patients are sensitive to NAC. If the efficacy of chemotherapy cannot be evaluated in a timely and effective manner, it may lead to unnecessary toxicity in nonresponsive patients [4]. In addition, if the NAC cannot be stopped at the right time, it will cause a certain degree of overtreatment, which will not only exhaust the patient's body and mind, but also increase the medical burden. Therefore, it is necessary to clarify whether the treatment plan being adopted is appropriate as soon as possible. If it is found to be slow to a certain chemotherapy drug, it is necessary to replace the appropriate and useful chemotherapeutic drug as soon as possible to avoid the ineffective use of systemic adjuvant therapy and provide a reliable basis for the choice of clinical treatment decision.

For breast cancer assisted evaluation, although pathological biopsy is the most accurate, evidence-based medicine shows that patients with malignant tumors should minimize the number of biopsies to prevent the spread and metastasis of cancer cells. Therefore, pathological examinations often occur before chemotherapy. After the operation and the later period of treatment, there is a lag effect to some extent [5, 6]. Although there are many noninvasive examinations in the audience, dynamic contrast-enhanced MRI (DCE-MRI) has the most potential for development. In recent years, DCE-MRI imaging technology relies on its advantage that dynamic contrast-enhanced MRI contains rich disease information. It has become the mainstream in the prediction and evaluation of the curative effect of neoadjuvant chemotherapy for breast cancer. The correlation between the information contained in DCE-MRI images and the curative effect of NAC has also become a research hotspot in the biomedical field [7, 8]. However, it has mostly been done around semiquantitative analysis in the past and cannot indirectly accurately show the exchange and penetration process of the contrast agent in the tumor. Quantitative dynamic enhanced magnetic resonance uses its multiparameter, multitime image, and hemodynamic angle to evaluate tumor microvessels. The advantages of perfusion and penetration function stand out. It is based on the rapid and uninterrupted scanning of T1 level, selecting appropriate pharmacokinetic models, measuring specific quantitative parameters, and achieving noninvasive analysis of the microscopic changes of tumor neovascularization in vivo. At present, the deep transfer learning method has been applied in many image detection and recognition processes and has achieved effective applications. Among them, the more prominent algorithm is the Convolutional Neural Network (CNN) [9]. Convolutional Neural Networks can automatically learn features of different depths in images, so we explored the use of CNN combined with patients' DCE-MRI images to predict the efficacy of breast cancer adjuvant chemotherapy.

The main content of this article is the study of DCE-MRI image based on deep transfer learning in breast cancer adjuvant curative effect prediction. Firstly, the deep transfer learning algorithm is applied to breast cancer image processing, and secondly, the curative effect of breast cancer adjuvant chemotherapy is adopted. For evaluation and research, and finally through the feature data collection of images before and after adjuvant chemotherapy for breast cancer, the accuracy of DCE-MRI images in predicting the adjuvant curative effect of breast cancer is obtained. The innovation of this article lies in the application of deep migration learning algorithms to image processing before and after adjuvant chemotherapy for breast cancer, which achieves good results in image processing, detection, and classification.

2. Related Works

The background analysis of breast cancer can describe the progress and status of the tumor, which is based on the segmentation of the entire breast based on MRI images. By using MRI image sequences to construct a pipeline for breast region segmentation, the possibility of automatic breast cancer diagnosis can be realized. Research on breast region segmentation based on traditional and deep learning methods has been carried out for several years, but for the following background analysis, most of the studies have not achieved satisfactory results. Sui D proposed a new method of whole breast region segmentation method based on U-net++ [10]. Compared with the most used medical image analysis model (traditional U-net model), it can achieve better results and get a better IOU instead of CNN model. His experiments show that U-net++ with deep supervision can achieve a higher IOU than the U-net model. But the accuracy rate is relatively low.

Lu proposed a new method of information extraction based on deep Convolutional Neural Networks and transfer learning [11]. First, he excluded linear features based on Deep Convolutional Neural Network (DCNN). Next, he introduced the transfer learning mechanism to use the feature extraction method learned from DCNN for information extraction [12, 13]. Finally, the information extraction results were completed through DTCLE and e-cognitive information extraction (ECLE) [14, 15]. The experimental results show that the overall accuracy of experimental images 1, 2, and 3 using the DTCLE method are 91.7%, 88.1%, and 88.2%, respectively, and the overall accuracy of ECLE is 90.7%, 90.5%, and 87.0%. The accuracy of DTCLE is the same as that of ECLE, and it is also superior to ECLE in terms of completeness and continuity [16]. But his method is more cumbersome. Nakamura J. proposed that granulocyte colony stimulating factor (G-CSF) is used as a neutrophil support therapy in breast cancer chemotherapy [17]. Common adverse events of G-CSF include bone pain, headache, and fatigue. His study reported that a 66-year-old woman who had undergone breast cancer surgery received adjuvant chemotherapy and prophylactically used polyethylene glycol filgrastim (peg-G) [18, 19]. The woman cured polyethylene glycol-G-related vasculitis 11 days after receiving the first polyethylene glycol-G treatment. His research showed that although various blood and culture tests are required to rule out other vasculitis syndromes and infections, women's symptoms disappear spontaneously, and no treatment is given except for discontinuing causal drugs [19, 20]. His research was only one aspect of research, and there are limitations.

3. Deep Transfer Learning Algorithms and Applications

3.1. Convolutional Neural Network Algorithm Based on Deep Transfer Learning

Deep learning methods have been widely used in many patterns recognition tasks and have achieved good results. Among them, the more prominent algorithm is the Convolutional Neural Network (CNN) algorithm. Generally, the input of CNN is image data, so the structure of CNN can be designed according to the characteristics of the image, so that it has higher efficiency and better performance than general structure neural network [21, 22]. The differences from general neural networks are as follows: different from the feature vectors used in general neural networks, the network layer of CNN has 4 different structural layers, which are convolutional layer, pooling layer, linear rectification layer, and fully connected layer. The following introduces the basic algorithm of Convolutional Neural Network. This article mainly introduces the loss function.

The loss function is that after a given hypothesis function, we can calculate the probability score of each category for each input data x, but the degree of difference between the obtained probability score and the category to which the actual x belongs is not intuitively [23]. This introduces the concept of loss function, which is used to measure the degree of difference between the predicted value of x and the real value y, and it can also be used to measure the parameters w, b of the predicted value of x in the hypothetical function. When the loss function is high, the current parameters W and b perform poorly, and when the loss function is low, it means that the current parameters W and b perform better. In mathematical principle, the loss function of softmax classifier can be obtained by maximum likelihood estimation [24, 25]. The specific derivation process is as follows:

err is called cross entropy, and J (W, (b) is the loss function; for good (W, (b) parameters, the loss function can be made to obtain a smaller value. The specific operation method is to achieve corresponding matrix norm F through the loss function Add regular term (W) [26, 27]. Therefore, the final and complete loss function formula is as follows:

λ is an actual number, and its function is to adjust the degree of influence of regularization on the loss function. The size of the λ value setting determines the degree of influence. The above is the derivation process of the loss function and the final expression formula.

3.2. Application of Convolutional Neural Network Algorithm in Medical Images

In recent years, with the rapid development of computer vision, machine vision, and other technologies, deep learning has achieved better results than human eye recognition in some areas of processing natural images, such as image classification and target detection and behavior recognition [28, 29]. The most representative algorithm in deep learning is Convolutional Neural Network (CNN). Data-driven CNN has achieved very good results in scientific research and engineering applications. In the field of natural images, Convolutional Neural Networks are widely used, such as image classification and object recognition, which have achieved good results and have received great attention from academia and industrial streets [30-33]. Therefore, some researchers have introduced CNN into the study of medical images, such as image segmentation in brain magnetic resonance images, detection of lung nodules in lung CT images, and detection and classification in breast tissue pathological images [34].

4. Deep Transfer Learning Algorithm Structure

4.1. Structure of the Convolutional Neural Network Algorithm Based on Deep Transfer Learning

This part of the content mainly introduces the different structural layers in CNN, including convolutional layer, pooling layer, linear rectification layer, and fully connected layer. The general structure of CNN is shown in Figure 1.

Figure 1

Schematic diagram of Convolutional Neural Network structure.

Convolutional layer: compared with the general neural network layer, the CNN network layer has two different characteristics. One is convolution based on the principle of sparse connection, and the other is weight sharing [35]. (1) Convolution: each neuron only needs to be connected to a small part of the input neuron. This puts forward the concept of the receptive field of the local connection range, also called the convolution kernel. Through the change of the position of the convolution kernel on the input image, the local area is mapped to the next layer of neurons; that is, these neurons are activated. (2) Weight sharing: the feature of an image appears in different areas of the image or there are multiple areas of the image. Therefore, the same features in these different positions share the same weight on the neuron, which can also be used to find the location of the same feature in the image. Through the above two methods, the amount of CNN parameters can be greatly reduced.

Pooling layer: the operation of the pooling layer is performed independently on each depth component, and the most common one is maximum convergence [36]. What is commonly used is that the size of each filter is 2∗2, the stride S = 2, and the Max operation is used in each local space. 75% of the information is discarded from the input information, and the output result is obtained. The principle is shown in Figure 2.

Figure 2

Schematic diagram of pooling layer operation.

Linear rectification layer and fully connected layer: the linear rectification layer has the same operation as the above loss function, which activates the elements one by one without changing the data dimension [37, 38]. After the convolutional layer operation is completed, the fully connected layer collects the feature maps output by the convolution, so that some redundant parameters are invalidated, which can prevent the model from overfitting.

4.2. Evaluation of the Efficacy of Adjuvant Chemotherapy for Breast Cancer

In the clinical treatment of breast cancer, with the promotion and popularization of adjuvant chemotherapy, it has become the standard treatment mode for locally advanced breast cancer. In clinical applications, if an accurate evaluation of the efficacy of neoadjuvant chemotherapy is made before surgery, it is helpful to timely discover intractable tumors that do not respond to treatment or only have a small response and adjust the chemotherapy regimen for breast cancer patients in real time to reduce the risk of failure. Necessary treatments and toxic side effects caused by chemotherapeutic drugs increase the possibility of complete pathological remission for patients and at the same time help select the timing of surgery and determine the patients who are suitable for breast-conserving treatment. Therefore, it is necessary to make an objective and accurate evaluation of the expected curative effect of breast cancer patients during adjuvant chemotherapy. The efficacy of adjuvant chemotherapy is generally evaluated in both clinical and pathological aspects. Clinical evaluation is generally based on changes in tumor number and tumor volume to evaluate the efficacy of chemotherapy. Oncologists from anticancer organizations around the world have formulated the WHO evaluation criteria for the efficacy of solid tumors. With the continuous improvement of the treatment level and tumor diagnosis, the evaluation criteria for the efficacy of solid tumors have also undergone several revisions. The cooperation has established the Response Evaluation Criteria in Solid Tumors (RECIST) that is currently recognized by the international tumor community. Target lesions refer to measurable lesions used for comparative evaluation of efficacy before and after treatment in the RECIST1.1 standard. The difference between the efficacy evaluation standard and the WHO standard is shown in Table 1.

Table 1

Efficacy evaluation criteria for two solid tumors.

Curative effect	WHO	RECIST
CR	The tumor disappeared completely	The tumor disappeared completely and remained for four weeks
PR	The total tumor area is reduced by more than or equal to 50%, maintained for four weeks	The target lesion is reduced by 30% and maintained for four weeks
SD	Change between PR and PD	Change between PR and PD
PD	The total tumor area increased by more than 25%	The total longest diameter of the target lesion increased by more than 25%

Pathological examination is the gold standard for diagnosing the efficacy of neoadjuvant chemotherapy. Compared with clinical evaluation, it has more important meaning for treatment guidance and prognostic judgment. However, it requires case puncture during surgery, which will cause problems for the patient. At the same time, the secondary injury has the problem of not timely evaluation results, also limiting its clinical application. This study was carried out based on clinical evaluation standards, and the gold standard of pathological examination was used as a reference. Figure 3 shows the comparison of complete remission images, Figure 4 shows the comparison of partial remission images, and Figure 5 shows the comparison of stable disease images.

Figure 3

CR image comparisons. (a) Before. (b) Rear.

Figure 4

PR image comparisons. (a) Before. (b) Rear.

Figure 5

SD image comparisons. (a) Before. (b) Rear.

4.3. Data Collection of the Breast DCE-MRI Imaging Experiment

4.3.1. DCE Data Format

According to the operating principle of DCE-MRI image acquisition, the image data is composed of four-dimensional data. By combining the absorption and release of intravenous contrast agent in the analyzed tissue, three-dimensional images of the tissue before and after the injection of the contrast agent are obtained (1 sequence before injection, T0 mask sequence; 5 sequences after injection, T1 ∼ T5 enhanced sequence), so the data structure of DCE-MRI images is four-dimensional, that is, three spatial dimensions plus one time dimension (enhanced information at different times). Usually, the four-dimensional data structure of breast DCE-MRI scan is shown in Figure 6, where the directions of X-axis, Y-axis, and Z-axis represent the three-dimensional structure of the image, and the T-axis represents the enhancement of the image before and after the injection of the contrast agent. DCE-MRI images reflect the internal structure and characteristics of the analyzed tissue through the above-mentioned methods, and the data studied in this article are obtained from these image data.

Figure 6

Schematic diagram of the four-dimensional data structure of breast DCE-MRI.

4.3.2. Overview of Experimental Data

The case data of this experiment was collected from data of 60 malignant breast cancer patients confirmed by surgical cases in a certain regional hospital during a certain period. All cases were female patients, ranging in age from 29 to 61 years, with an average age of 47.35 years. Among the 60 patients, the pathological diagnosis showed 30 cases of invasive ductal carcinoma, 22 cases of invasive carcinoma, 4 cases of intraductal carcinoma, and 4 cases of invasive poorly differentiated adenocarcinoma. All patients underwent DCE-MRI scans before and 2 cycles after chemotherapy. The clinicopathological information of breast cancer patients was listed, including age, menopause, tumor size, and cancer type. The specific results are shown in Table 2. These clinicopathological information characteristics are not significant in the effective group and the ineffective group (P < 0.05).

Table 2

Statistics of clinicopathological characteristics of effective and ineffective groups of breast cancer adjuvant chemotherapy.

Clinicopathological characteristics	Total	Effective	Invalid	P
Age≥40	45	37	8	0.35
Menopause	20	15	5	0.45
Swollen lymph nodes in the armpit	50	45	5	0.35
The largest diameter of the lesion before chemotherapy
<2 cm	3	3	0	1
2 cm–5 cm	17	14	3	1
>5 cm	40	30	10	0.75
Maximum diameter of lesion after chemotherapy
<2 cm	15	13	2	1
2 cm–5 cm	40	28	2	0.19
>5 cm	5	4	1	0.40
Cancer type
Invasive ductal carcinoma	30	25	5	0.75
Invasive carcinoma	19	15	4	1
Intraductal carcinoma	7	5	2	0.45
Invasive poorly differentiated carcinoma	4	3	1	1

The examination equipment used for DCE-MRI image acquisition is a dedicated breast phased array coil for acquisition. During the examination and scanning process, the patient lies prone on the rigid testing table with the hands flat on both sides of the body, and the breasts on both sides naturally droop and enter the breast phased array coil.

The object analyzed in this study is T1-weighted dynamic enhanced imaging (DCE-MRI), the scan sequence is l3d1, and the detection time of a dynamic enhanced MRI of the breast is about 15 to 18 minutes. The first sequence of the dynamic enhancement scan is the mask plain scan sequence. For the sequence scan, the mask sequence is scanned before the injection of the contrast agent. At the end of the sequence, the paramagnetic contrast agent is placed on the patient's arm at a dose of 0.2 mmol/kg. A high-pressure syringe is used to inject intravenously at an average flow rate of 4 ml/s. In the dynamic enhancement scan process, the scan sequence of 3-time phases is set, after 1 minute 20 seconds and 2 minutes 25 seconds, respectively, and the image acquisition work of the S1 sequence and the S2 sequence is performed, respectively. Starting from 5 minutes to 30 seconds after S2 imaging is completed, the MRI scanner will change the parameters to perform high-resolution sequence image acquisition of the breast. The reconstruction layer thickness of this mode is reduced to 0.8 mm. It is possible to obtain a more detailed breast image than the first three sequences, so that the doctor can make an accurate diagnosis. Figure 7 shows the acquisition time axis and sequence of the pan sweep sequence.

Figure 7

Enhanced sequence (S0, S1, and S3) acquisition time axis.

Since the three plain scan sequences use the same scan parameters, the image set specifications of each sequence are the same. Therefore, the data is stored as a four-dimensional matrix to facilitate subsequent research. Table 3 presents the specific parameters of each sequence of breast DCE-MRI images.

Table 3

Brief description of the impact data of each sequence of breast DCE-MRI.

	S0 sequence	S1 sequence	S2 sequence	S3 sequence
Scan time	0	1m20s	2m25s	7m55s
Number of images collected	144 sheets	144 sheets	144 sheets	144 sheets
Slice size	448∗448	448∗448	448∗448	448∗448

5. Imaging and Prediction Results of Breast Cancer Adjuvant Chemotherapy

5.1. DCE-MRI Imaging to Evaluate Imaging of Neoadjuvant Chemotherapy for Breast Cancer

Dynamic contrast-enhanced MRI (DCE-MRI) is the introduction of contrast agent, tracing the TIC curve of the area of interest. And then the paper selects the appropriate pharmacokinetic model analysis to measure various quantitative parameters reflecting the microcirculation state of tumor foci and the penetration of contrast agent, including volume transfer constant Ktrans, rate constant Kep, and extravascular extracellular space volume ratio etc. In fact, the contrast agent itself does not directly have biological characteristics, but the penetration effect tends to condense in the tissue area with high vascular permeability, thus presenting an enhancement effect. The degree of enhancement depends on the microvessel density, blood flow, and vascular permeability of the lesion. In the case of sexual conditions, DCE-MRI can indirectly capture this microscopic change by analyzing the corresponding quantitative parameters. Moreover, neovascularization is the key to the development of breast cancer, while neoadjuvant chemotherapy drugs focus on destroying the formed tumor blood vessels and antagonizing them. The tumor is about to generate new blood vessels. Therefore, DCE-MRI can objectively and indirectly evaluate the effect of chemotherapy drugs on the tumor.

5.2. The Results of Breast Cancer Adjuvant Chemotherapy Prediction Results

5.2.1. Research Plan

In the research process of this part, firstly, the correlation analysis of breast DCE-MRI image features before adjuvant chemotherapy and after adjuvant chemotherapy for 2 cycles was performed to screen out some features, and then CNN was used to further select the feature set, and then the support vector machine was used to analyze the final features. The feature set is used for classification prediction. The specific process is shown in Figure 8.

Figure 8

Experimental flowchart.

When distributing the training set and test set data, the case is the basic unit to separate, to avoid the images in the same case sequence from appearing in training and testing. The area under the experimenter's characteristic curve (AUC) is evaluated by the following formulas about specificity, accuracy, and sensitivity to evaluate the experimental prediction results. When evaluating the classification effect of a classifier, the formula for each evaluation index used is as follows:

Sensitivity:

Specificity:

Accuracy:

True positive rate:

False positive rate:

A set of sensitivity and specificity will change with the change of the decision threshold, so only using SEN and SPE can only evaluate the classification effect of a specific threshold. The ROC curve can obtain continuously varying sensitivity and specificity under different thresholds. The closer the AUC is to 1, the better the performance of the classifier is.

5.2.2. Classification of Feature Subsets Based on Deep Transfer Learning

In deep transfer learning, the trained model parameters are assigned to the convolutional layer of CNN. At the same time, the basic learning rate of transfer learning needs to be adjusted appropriately before training. First, initialize the parameters to the convolutional layer before and after chemotherapy, and then lower the learning rate to the minus 4th power of 10. Second, input the training data to the model for training. Finally, the actual test results are obtained.

It can be seen from Table 4 that the classification sensitivity of the 17-dimensional optimal feature set before chemotherapy reached 0.97, the specificity reached 0.85, the accuracy rate reached 0.93, and the AUC value reached 0.95, regardless of whether it was compared with other dimensional feature sets before chemotherapy or compared with the feature set after chemotherapy; its predictive ability is quite good. From the above table, it can also be found that the feature set before chemotherapy is better than the feature set after chemotherapy in predicting the efficacy of neoadjuvant chemotherapy. The breast imaging features after the neoadjuvant chemotherapy are less predictive than the imaging features before chemotherapy. This is consistent with our preliminary estimate; that is, the DCE-MRI imaging features of the breast before chemotherapy are used to predict the efficacy of adjuvant chemotherapy. In order to further explore the separability of a single feature in the optimal feature set, this study performed a classification evaluation on a single feature in the 17-dimensional optimal feature set. The specific results are shown in Table 5.

Table 4

Feature set classification.

Feature	Evaluation index SEN	SPE	ACC	AUC
23-dimensional feature set before chemotherapy	0.91	0.85	0.87	0.8
17-dimensional feature set before chemotherapy	O.97	0.85	0.93	0.95
11-dimensional feature set before chemotherapy	0.86	0.8	0.86	0.79
15-dimensional feature set after chemotherapy	0.83	0.3	0.75	0.54
13-dimensional feature set before chemotherapy	0.92	0.45	0.83	0.55
11-dimensional feature set before chemotherapy	0.9	0.4	0.81	0.54

Table 5

Classification performance evaluation of a single feature in the optimal feature set.

Feature name	Evaluation index SEN	SPE	ACC	AUC
Mean enhancement rate of normal side	0.65	0.89	0.66	0.71
Lesion side enhancement variance	0.89	0.1	0.85	0.74
Lesion volume	0.9	0.11	0.76	0.65
Lesion radius	0.65	0.1	0.53	0.85
Lesion surface area	0.9	0.1	0.78	0.67

According to Table 5, in the optimal feature set, the AUC value of the lesion radius reached 0.85, and the average enhancement rate of the normal side and the AUC value of the enhancement variance feature of the lesion side also reached above 0.7, indicating that the above features are in the prediction of chemotherapy efficacy (a certain degree of credibility). In the above table, the reason why the specificity of features is generally low may be that the two sets of data are unbalanced, which makes it impossible to accurately classify the small data set, resulting in particularly low classification specificity. By comparing the classification ability of breast imaging features before and after chemotherapy in the efficacy of adjuvant chemotherapy, the DCE-MRI imaging features of the breast before chemotherapy can predict the efficacy of adjuvant chemotherapy, and as the chemotherapy progresses, the imaging features predict the efficacy of chemotherapy. The contribution of capacity will be reduced. This shows that, in the prediction, features can provide additional valuable information for the prediction of chemotherapy efficacy and improve the clinical application value.

6. Conclusion

Based on the research of deep transfer learning algorithm, this paper first applies the deep transfer learning algorithm to the detection and classification of images. Secondly, it establishes the evaluation characteristics through the evaluation criteria of the curative effect and finally uses DCE-MRI to conduct breast cancer before and after chemotherapy. The image analysis finally reached an accurate prediction of the curative effect of adjuvant chemotherapy for breast cancer. The research in this article has achieved a certain effect in the prediction of adjuvant chemotherapy for breast cancer. It is helpful to the treatment plan of adjuvant chemotherapy for breast cancer. It also relieves certain trial and error for patients with adjuvant chemotherapy for breast cancer. The process has certain practical guiding significance.