Transfer Learning for Oral Cancer Detection using Microscopic Images
School of Bioengineering Sciences and Research, MIT ADT University(MIT ADT大学生物工程科学与研究学院);Department of Oral and Maxillofacial Pathology, Sinhgad Dental College and Hospital(辛加德牙科学院与医院口腔颌面病理学系);Department of Computer Science, Stony Brook University(石溪大学计算机科学系)
Rutwik Palaskar, Renu Vyas, Vilas Khedekar, Sangeeta Palaskar, Pranjal Sahu
Oral cancer has more than 83% survival rate if detected in its early stages, however, only 29% of cases are currently detected early. Deep learning techniques can detect patterns of oral cancer cells and can aid in its early detection. In this work, we present the first results of neural networks for oral cancer detection using microscopic images. We compare numerous state-of-the-art models via transfer learning approach and collect and release an augmented dataset of high-quality microscopic images of oral cancer. We present a comprehensive study of different models and report their performance on this type of data. Overall, we obtain a 10-15% absolute improvement with transfer learning methods compared to a simple Convolutional Neural Network baseline. Ablation studies show the added benefit of data augmentation techniques with finetuning for this task.
King Khalid University(哈立德国王大学);Taif University(塔伊夫大学)
Discovering oral cavity cancer (OCC) at an early stage is an effective way to increase patient survival rate. However, current initial screening process is done manually and is expensive for the average individual, especially in developing countries worldwide. This problem is further compounded due to the lack of specialists in such areas. Automating the initial screening process using artificial intelligence (AI) to detect pre-cancerous lesions can prove to be an effective and inexpensive technique that would allow patients to be triaged accordingly to receive appropriate clinical management.…
Uppsala University(乌普萨拉大学);Pathology and Cytology Dalarna, County Hospital Falun(法伦县医院达拉纳病理与细胞学);Clinical Research Center Dalarna, Uppsala University(乌普萨拉大学达拉纳临床研究中心)
The current medical standard for setting an oral cancer (OC) diagnosis is histological examination of a tissue sample from the oral cavity. This process is time consuming and more invasive than an alternative approach of acquiring a brush sample followed by cytological analysis. Skilled cytotechnologists are able to detect changes due to malignancy, however, to introduce this approach into clinical routine is associated with challenges such as a lack of experts and labour-intensive work. To design a trustworthy OC detection system that would assist cytotechnologists, we are interested in AI-ba…
Uncertainty-Aware Multimodal Fusion for Oral Lesion Classification
1 School of Medical Science \& Technology, IIT Kharagpur, India 2 Department of Electrical Engineering, IIT Kharagpur, India 3 Dr. B.C. Roy Multispeciality Medical Research Centre, IIT Kharagpur, India
Uppsala University(乌普萨拉大学);Karolinska Universitetsjukhuset(卡罗林斯卡大学医院)
Oral cancer incidence is rapidly increasing worldwide. The most important determinant factor in cancer survival is early diagnosis. To facilitate large scale screening, we propose a fully automated pipeline for oral cancer detection on whole slide cytology images. The pipeline consists of fully convolutional regression-based nucleus detection, followed by per-cell focus selection, and CNN based classification. Our novel focus selection step provides fast per-cell focus decisions at human-level accuracy. We demonstrate that the pipeline provides efficient cancer classification of whole slide cy…
Microscopic examination of tissues or histopathology is one of the diagnostic procedures for detecting colorectal cancer. The pathologist involved in such an examination usually identifies tissue type based on texture analysis, especially focusing on tumour-stroma ratio. In this work, we automate the task of tissue classification within colorectal cancer histology samples using deep transfer learning. We use discriminative fine-tuning with one-cycle-policy and apply structure-preserving colour normalization to boost our results. We also provide visual explanations of the deep neural network's …
A Hybrid Feature Fusion Deep Learning Framework for Leukemia Cancer Detection in Microscopic Blood Sample Using Gated Recurrent Unit and Uncertainty Quantification
Jagannath University(贾格纳特大学);Green University of Bangladesh(孟加拉国绿色大学)
Charles Sturt University(查尔斯特大学);Al Iraqia University(伊拉克大学);Western Sydney University(西悉尼大学);Kent Institute Australia(澳大利亚肯特学院);Asia Pacific International College(亚太国际学院);Worcester State University(伍斯特州立大学);University of Kurdistan Hewler(库尔德斯坦休勒大学);Greater Western Sydney Area Health Services(大西悉尼地区卫生服务局)
Background and Aim: Over-fitting issue has been the reason behind deep learning technology not being successfully implemented in oral cancer images classification. The aims of this research were reducing overfitting for accurately producing the required dimension reduction feature map through Deep Learning algorithm using Convolutional Neural Network. Methodology: The proposed system consists of Enhanced Convolutional Neural Network that uses an autoencoder technique to increase the efficiency of the feature extraction process and compresses information. In this technique, unpooling and deconv…
Friedrich-Alexander-Universität Erlangen-Nürnberg(埃尔朗根-纽伦堡大学);University Medical Center Hamburg-Eppendorf(汉堡-埃彭多夫大学医学中心);University Medical Center Erlangen(埃尔朗根大学医学中心);Friedrich-Schiller-Universität Jena(耶拿大学);University Medical Center Mainz(美因茨大学医学中心);Johannes Gutenberg-Universität Mainz(美因茨约翰内斯·古腾堡大学)
Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer of the oral epithelium. Despite their high impact on mortality, sufficient screening methods for early diagnosis of OSCC often lack accuracy and thus OSCCs are mostly diagnosed at a late stage. Early detection and accurate outline estimation of OSCCs would lead to a better curative outcome and an reduction in recurrence rates after surgical treatment. Confocal Laser Endomicroscopy (CLE) records sub-surface micro-anatomical images for in vivo cell structure analysis. Recent CLE studies showed great prospects for a reliable, real-tim…
The Epithelial Dysplasia (ED) is a tissue alteration commonly present in lesions preceding oral cancer, being its presence one of the most important factors in the progression toward carcinoma. This study proposes a method to design a low computational cost classification system to support the detection of dysplastic epithelia, contributing to reduce the variability of pathologist assessments. We employ a multilayer artificial neural network (MLP-ANN) and defining the regions of the epithelium to be assessed based on the knowledge of the pathologist. The performance of the proposed solution wa…
Histopathological image analysis is the gold standard to diagnose cancer. Carcinoma is a subtype of cancer that constitutes more than 80% of all cancer cases. Squamous cell carcinoma and adenocarcinoma are two major subtypes of carcinoma, diagnosed by microscopic study of biopsy slides. However, manual microscopic evaluation is a subjective and time-consuming process. Many researchers have reported methods to automate carcinoma detection and classification. The increasing use of artificial intelligence (AI) in the automation of carcinoma diagnosis also reveals a significant rise in the use of …
Explainable Multimodal Deep Learning Integrating Imaging and Clinical Data for Oral Potentially Malignant Disorder Detection
Wyant College of Optical Sciences, University of Arizona(亚利桑那大学怀恩特光学科学学院);Beckman Laser Institute & Medical Clinic, University of California Irvine(加州大学尔湾分校贝克曼激光研究所与医学诊所)
Computer-aided diagnosis (CAD) can be used as an important tool to aid and enhance pathologists' diagnostic decision-making. Deep learning techniques, such as convolutional neural networks (CNN) and fully convolutional networks (FCN), have been successfully applied in medical and biological research. Unfortunately, histological image segmentation is often constrained by the availability of labeled training data once labeling histological images for segmentation purposes is a highly-skilled, complex, and time-consuming task. This paper presents the hematoxylin and eosin (H&E) stained oral cavit…
A Cytology Dataset for Early Detection of Oral Squamous Cell Carcinoma
Indian Council of Medical Research-National Institute for Research in Digital Health & Data Science(印度医学研究理事会-数字健康与数据科学国家研究所);Koita Centre of Digital Health(数字健康中心);IIT Bombay(印度理工学院-博伊斯);Department of Electrical Engineering(电气工程系);Division of Non Communicable Diseases(非传染性疾病部门);Indian Council of Medical Research(印度医学研究理事会);Regional Institute of Medical Sciences(地区医学科学研究所);Department of Pathology(病理学系);Pt BD Sharma PGIMS(Pt BD Sharma PGIMS医院);Institute of Pathology(病理研究所);Madras Medical College(马德拉斯医学院);SMS Medical College Jaipur(杰伊普尔SMS医学院);Department of Otorhinolaryngology(耳鼻喉科系)
University of Ottawa(渥太华大学);Minai University(米尼亚大学)
In this paper we discuss a new method for detecting leukemia in microscopic blood smear images using deep neural networks to diagnose leukemia early in blood. leukemia is considered one of the most dangerous mortality causes for a human being, the traditional process of diagnosis of leukemia in blood is complex, costly, and time-consuming, so patients could not receive medical treatment on time; Computer vision classification technique using deep learning can overcome the problems of traditional analysis of blood smears, our system for leukemia detection provides 97.3 % accuracy in classifying…
Hamburg University of Technology(汉堡工业大学);University of Bonn(波恩大学);Klinikum Braunschweig(布伦瑞克医院);University Medical Center Hamburg-Eppendorf(汉堡-埃彭多夫大学医学中心)
Early detection of head and neck tumors is crucial for patient survival. Often, diagnoses are made based on endoscopic examination of the larynx followed by biopsy and histological analysis, leading to a high inter-observer variability due to subjective assessment. In this regard, early non-invasive diagnostics independent of the clinician would be a valuable tool. A recent study has shown that hyperspectral imaging (HSI) can be used for non-invasive detection of head and neck tumors, as precancerous or cancerous lesions show specific spectral signatures that distinguish them from healthy tiss…
A High Magnifications Histopathology Image Dataset for Oral Squamous Cell Carcinoma Diagnosis and Prognosis
School of Software Engineering, South China University of Technology(华南理工大学软件工程学院);Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University(中山大学口腔颌面外科医院);Mohamed Bin Zayed University of Artificial Intelligence(马尔代夫人工智能大学);School of Computer Science, University of Adelaide(阿德莱德大学计算机科学学院)
Sharif University of Technology(谢里夫理工大学);BmDeep Group(BmDeep研究组)
Multiple myeloma cancer is a type of blood cancer that happens when the growth of abnormal plasma cells becomes out of control in the bone marrow. There are various ways to diagnose multiple myeloma in bone marrow such as complete blood count test (CBC) or counting myeloma plasma cell in aspirate slide images using manual visualization or through image processing technique. In this work, an automatic deep learning method for the detection and segmentation of multiple myeloma plasma cell have been explored. To this end, a two-stage deep learning method is designed. In the first stage, the nucle…
Breast cancer has the highest mortality among cancers in women. Computer-aided pathology to analyze microscopic histopathology images for diagnosis with an increasing number of breast cancer patients can bring the cost and delays of diagnosis down. Deep learning in histopathology has attracted attention over the last decade of achieving state-of-the-art performance in classification and localization tasks. The convolutional neural network, a deep learning framework, provides remarkable results in tissue images analysis, but lacks in providing interpretation and reasoning behind the decisions. …
Northeastern University(东北大学);China Medical University(中国医科大学);University of Luebeck(吕贝克大学)
The gold standard for gastric cancer detection is gastric histopathological image analysis, but there are certain drawbacks in the existing histopathological detection and diagnosis. In this paper, based on the study of computer aided diagnosis system, graph based features are applied to gastric cancer histopathology microscopic image analysis, and a classifier is used to classify gastric cancer cells from benign cells. Firstly, image segmentation is performed, and after finding the region, cell nuclei are extracted using the k-means method, the minimum spanning tree (MST) is drawn, and graph …
Khulna University of Engineering & Technology(库尔纳工程技术大学);Bangabandhu Sheikh Mujibur Rahman Science & Technology University(班加班杜·谢赫·穆吉布·拉赫曼科技大学);Khulna University(库尔纳大学)
Acute Lymphoblastic Leukemia (ALL) is a blood cell cancer characterized by numerous immature lymphocytes. Even though automation in ALL prognosis is an essential aspect of cancer diagnosis, it is challenging due to the morphological correlation between malignant and normal cells. The traditional ALL classification strategy demands experienced pathologists to carefully read the cell images, which is arduous, time-consuming, and often suffers inter-observer variations. This article has automated the ALL detection task from microscopic cell images, employing deep Convolutional Neural Networks (CN…
Guilin University of Electronic Technology(桂林电子科技大学);Guangxi Key Laboratory of Image and Graphic Intelligent Processing(广西图像图形智能处理重点实验室);Ganzhou Municipal Hospital(赣州市立医院)
Mitosis detection is one of the challenging problems in computational pathology, and mitotic count is an important index of cancer grading for pathologists. However, current counts of mitotic nuclei rely on pathologists looking microscopically at the number of mitotic nuclei in hot spots, which is subjective and time-consuming. In this paper, we propose a two-stage cascaded network, named FoCasNet, for mitosis detection. In the first stage, a detection network named M_det is proposed to detect as many mitoses as possible. In the second stage, a classification network M_class is proposed to ref…
Jalpaiguri Government Engineering College(贾尔派古里政府工程学院)
Invasive ductal carcinoma (IDC), which is also sometimes known as the infiltrating ductal carcinoma, is the most regular form of breast cancer. It accounts for about 80% of all breast cancers. According to the American Cancer Society, more than 180,000 women in the United States are diagnosed with invasive breast cancer each year. The survival rate associated with this form of cancer is about 77% to 93% depending on the stage at which they are being diagnosed. The invasiveness and the frequency of the occurrence of these disease makes it one of the difficult cancers to be diagnosed. Our propos…
Deep Learning Algorithms for Early Diagnosis of Acute Lymphoblastic Leukemia
The American College of Greece(希腊美国学院);National & Kapodistrean University of Athens(雅典国立卡波季斯特里安大学);Biomedical Research Foundation, Academy of Athens(雅典科学院生物医学研究基金会)
An estimated 300,000 new cases of leukemia are diagnosed each year which is 2.8 percent of all new cancer cases and the prevalence is rising day by day. The most dangerous and deadly type of leukemia is acute lymphoblastic leukemia (ALL), which affects people of all age groups, including children and adults. In this study, we propose an automated system to detect various-shaped ALL blast cells from microscopic blood smears images using Deep Neural Networks (DNN). The system can detect multiple subtypes of ALL cells with an accuracy of 98 percent. Moreover, we have developed a telediagnosis sof…
School of Engineering, Nazarbayev University(纳扎尔巴耶夫大学工程学院)
The automated segmentation of cells in microscopic images is an open research problem that has important implications for studies of the developmental and cancer processes based on in vitro models. In this paper, we present the approach for segmentation of the DIC images of cultured cells using G-neighbor smoothing followed by Kauwahara filtering and local standard deviation approach for boundary detection. NIH FIJI/ImageJ tools are used to create the ground truth dataset. The results of this work indicate that detection of cell boundaries using segmentation approach even in the case of realis…
University of British Columbia(不列颠哥伦比亚大学);Vancouver General Hospital(温哥华综合医院);BC Cancer Research Center(不列颠哥伦比亚癌症研究中心)
Ovarian cancer is the most lethal cancer of the female reproductive organs. There are $5$ major histological subtypes of epithelial ovarian cancer, each with distinct morphological, genetic, and clinical features. Currently, these histotypes are determined by a pathologist's microscopic examination of tumor whole-slide images (WSI). This process has been hampered by poor inter-observer agreement (Cohen's kappa $0.54$-$0.67$). We utilized a \textit{two}-stage deep transfer learning algorithm based on convolutional neural networks (CNN) and progressive resizing for automatic classification of ep…
Microscopic histology image analysis is a cornerstone in early detection of breast cancer. However these images are very large and manual analysis is error prone and very time consuming. Thus automating this process is in high demand. We proposed a hierarchical system of convolutional neural networks (CNN) that classifies automatically patches of these images into four pathologies: normal, benign, in situ carcinoma and invasive carcinoma. We evaluated our system on the BACH challenge dataset of image-wise classification and a small dataset that we used to extend it. Using a train/test split of…
National Institute of Technology Karnataka(卡纳塔克邦国家理工学院);Melaka Manipal Medical College(马六甲马尼帕尔医学院);Manipal Academy of Higher Education(马尼帕尔高等教育学院)
In this paper, a semi-automatic annotation of bacteria genera and species from DIBaS dataset is implemented using clustering and thresholding algorithms. A Deep learning model is trained to achieve the semantic segmentation and classification of the bacteria species. Classification accuracy of 95% is achieved. Deep learning models find tremendous applications in biomedical image processing. Automatic segmentation of bacteria from gram-stained microscopic images is essential to diagnose respiratory and urinary tract infections, detect cancers, etc. Deep learning will aid the biologists to get r…
Friedrich-Alexander-Universität Erlangen-Nürnberg(埃尔朗根-纽伦堡弗里德里希-亚历山大大学);University Hospital Erlangen(埃尔朗根大学医院);University Medical Center Hamburg-Eppendorf(汉堡-埃彭多夫大学医学中心);Johannes Gutenberg-Universität Mainz(美因茨约翰内斯·古腾堡大学);University Medical Center Mainz(美因茨大学医学中心)
Deep learning technologies such as convolutional neural networks (CNN) provide powerful methods for image recognition and have recently been employed in the field of automated carcinoma detection in confocal laser endomicroscopy (CLE) images. CLE is a (sub-)surface microscopic imaging technique that reaches magnifications of up to 1000x and is thus suitable for in vivo structural tissue analysis. In this work, we aim to evaluate the prospects of a priorly developed deep learning-based algorithm targeted at the identification of oral squamous cell carcinoma with regard to its generalization to …
Karolinska Institutet(卡罗林斯卡学院);Tampere University(坦佩雷大学);Lund University(隆德大学);University of Turku(图尔库大学);Karolinska University Laboratory(卡罗林斯卡大学实验室)
Molecular phenotyping is central in cancer precision medicine, but remains costly and standard methods only provide a tumour average profile. Microscopic morphological patterns observable in histopathology sections from tumours are determined by the underlying molecular phenotype and associated with clinical factors. The relationship between morphology and molecular phenotype has a potential to be exploited for prediction of the molecular phenotype from the morphology visible in histopathology images. We report the first transcriptome-wide Expression-MOrphology (EMO) analysis in breast cancer,…
Friedrich-Alexander-Universität Erlangen-Nürnberg(埃尔朗根-纽伦堡弗里德里希-亚历山大大学);University Hospital Erlangen(埃尔朗根大学医院);University Medical Center Hamburg-Eppendorf(汉堡-埃彭多夫大学医学中心);Johannes Gutenberg-Universität Mainz(美因茨约翰内斯·古腾堡大学);University Medical Center Mainz(美因茨大学医学中心);Universität Regensburg(雷根斯堡大学)
Squamous Cell Carcinoma (SCC) is the most common cancer type of the epithelium and is often detected at a late stage. Besides invasive diagnosis of SCC by means of biopsy and histo-pathologic assessment, Confocal Laser Endomicroscopy (CLE) has emerged as noninvasive method that was successfully used to diagnose SCC in vivo. For interpretation of CLE images, however, extensive training is required, which limits its applicability and use in clinical practice of the method. To aid diagnosis of SCC in a broader scope, automatic detection methods have been proposed. This work compares two methods w…
Due to cellular heterogeneity, cell nuclei classification, segmentation, and detection from pathological images are challenging tasks. In the last few years, Deep Convolutional Neural Networks (DCNN) approaches have been shown state-of-the-art (SOTA) performance on histopathological imaging in different studies. In this work, we have proposed different advanced DCNN models and evaluated for nuclei classification, segmentation, and detection. First, the Densely Connected Recurrent Convolutional Network (DCRN) model is used for nuclei classification. Second, Recurrent Residual U-Net (R2U-Net) is…
Leukemia is a hematologic cancer which develops in blood tissue and triggers rapid production of immature and abnormal shaped white blood cells. Based on statistics it is found that the leukemia is one of the leading causes of death in men and women alike. Microscopic examination of blood sample or bone marrow smear is the most effective technique for diagnosis of leukemia. Pathologists analyze microscopic samples to make diagnostic assessments on the basis of characteristic cell features. Recently, computerized methods for cancer detection have been explored towards minimizing human intervent…
MicroMIL: Graph-Based Multiple Instance Learning for Context-Aware Diagnosis with Microscopic Images
Korea Advanced Institute of Science and Technology(韩国科学技术院);Institute of High Performance Computing(高性能计算研究所);Seegene Medical Foundation, Pathology Center(Seegene医学基金会病理中心)
East China Normal University(华东师范大学);School of Computer Science, East China Normal University(华东师范大学计算机科学学院)
Prostate cancer (PCa) is one of the most common cancers in men around the world. The most accurate method to evaluate lesion levels of PCa is microscopic inspection of stained biopsy tissue and estimate the Gleason score of tissue microarray (TMA) image by expert pathologists. However, it is time-consuming for pathologists to identify the cellular and glandular patterns for Gleason grading in large TMA images. We used Gleason2019 Challenge dataset to build a convolutional neural network (CNN) model to segment TMA images to regions of different Gleason grades and predict the Gleason score accor…
University of British Columbia(不列颠哥伦比亚大学);Eindhoven University of Technology(埃因霍温理工大学);Massachusetts General Hospital(马萨诸塞州综合医院);Harvard Medical School(哈佛医学院);BC Cancer Agency(不列颠哥伦比亚癌症机构)
Visual microscopic study of diseased tissue by pathologists has been the cornerstone for cancer diagnosis and prognostication for more than a century. Recently, deep learning methods have made significant advances in the analysis and classification of tissue images. However, there has been limited work on the utility of such models in generating histopathology images. These synthetic images have several applications in pathology including utilities in education, proficiency testing, privacy, and data sharing. Recently, diffusion probabilistic models were introduced to generate high quality ima…
Microsoft Research(微软研究院);Beihang University(北京航空航天大学)
Fine-grained classification of microscopic image data with limited samples is an open problem in computer vision and biomedical imaging. Deep learning based vision systems mostly deal with high number of low-resolution images, whereas subtle detail in biomedical images require higher resolution. To bridge this gap, we propose a simple yet effective deep network that performs two tasks simultaneously in an end-to-end manner. First, it utilises a gated attention module that can focus on multiple key instances at high resolution without extra annotations or region proposals. Second, the global st…
University of Edinburgh(爱丁堡大学);Heriot-Watt University(赫瑞-瓦特大学)
Autofluorescence lifetime images reveal unique characteristics of endogenous fluorescence in biological samples. Comprehensive understanding and clinical diagnosis rely on co-registration with the gold standard, histology images, which is extremely challenging due to the difference of both images. Here, we show an unsupervised image-to-image translation network that significantly improves the success of the co-registration using a conventional optimisation-based regression network, applicable to autofluorescence lifetime images at different emission wavelengths. A preliminary blind comparison …
University of Saskatchewan(萨斯喀彻温大学);University of Tulane(杜兰大学)
Automatic detection of leukemic B-lymphoblast cancer in microscopic images is very challenging due to the complicated nature of histopathological structures. To tackle this issue, an automatic and robust diagnostic system is required for early detection and treatment. In this paper, an automated deep learning-based method is proposed to distinguish between immature leukemic blasts and normal cells. The proposed deep learning based hybrid method, which is enriched by different data augmentation techniques, is able to extract high-level features from input images. Results demonstrate that the pr…
INESC TEC - Institute for Systems and Computer Engineering, Technology and Science(系统与计算机工程、技术与科学研究所);Faculty of Engineering of University of Porto(波尔图大学工程学院);Seek AI Limited(Seek AI有限公司);Icahn School of Medicine at Mount Sinai(西奈山伊坎医学院);The Mount Sinai Hospital(西奈山医院)
Breast cancer is the most common invasive cancer in women, affecting more than 10% of women worldwide. Microscopic analysis of a biopsy remains one of the most important methods to diagnose the type of breast cancer. This requires specialized analysis by pathologists, in a task that i) is highly time- and cost-consuming and ii) often leads to nonconsensual results. The relevance and potential of automatic classification algorithms using hematoxylin-eosin stained histopathological images has already been demonstrated, but the reported results are still sub-optimal for clinical use. With the goa…
Hunan University(湖南大学);University of Ontario Institute of Technology(安大略理工大学);York University(约克大学);Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine(上海中医药大学附属龙华医院)
Gastric cancer is the second leading cause of cancer-related deaths worldwide, and the major hurdle in biomedical image analysis is the determination of the cancer extent. This assignment has high clinical relevance and would generally require vast microscopic assessment by pathologists. Recent advances in deep learning have produced inspiring results on biomedical image segmentation, while its outcome is reliant on comprehensive annotation. This requires plenty of labor costs, for the ground truth must be annotated meticulously by pathologists. In this paper, a reiterative learning framework …