Deep learning analysis of coronary arteries in cardiac CT angiography for detection of patients requiring invasive coronary angiography
Image Sciences Institute, University Medical Center Utrecht（乌得勒支大学医学中心影像科学研究所）；University Medical Center Utrecht（乌得勒支大学医学中心）；Amsterdam University Medical Center（阿姆斯特丹大学医学中心）；Utrecht University（乌得勒支大学）
Majd Zreik, Robbert W. van Hamersvelt, Nadieh Khalili, Jelmer M. Wolterink, Michiel Voskuil, Max A. Viergever, Tim Leiner, Ivana Išgum
备注：
This work has been accepted to IEEE TMI for publication
In patients with obstructive coronary artery disease, the functional significance of a coronary artery stenosis needs to be determined to guide treatment. This is typically established through fractional flow reserve (FFR) measurement, performed during invasive coronary angiography (ICA). We present a method for automatic and non-invasive detection of patients requiring ICA, employing deep unsupervised analysis of complete coronary arteries in cardiac CT angiography (CCTA) images. We retrospectively collected CCTA scans of 187 patients, 137 of them underwent invasive FFR measurement in 192 different coronary arteries. These FFR measurements served as a reference standard for the functional significance of the coronary stenosis. The centerlines of the coronary arteries were extracted and used to reconstruct straightened multi-planar reformatted (MPR) volumes. To automatically identify arteries with functionally significant stenosis that require ICA, each MPR volume was encoded into a fixed number of encodings using two disjoint 3D and 1D convolutional autoencoders performing spatial and sequential encodings, respectively. Thereafter, these encodings were employed to classify arteries using a support vector machine classifier. The detection of coronary arteries requiring invasive evaluation, evaluated using repeated cross-validation experiments, resulted in an area under the receiver operating characteristic curve of $0.81 \pm 0.02$ on the artery-level, and $0.87 \pm 0.02$ on the patient-level. The results demonstrate the feasibility of automatic non-invasive detection of patients that require ICA and possibly subsequent coronary artery intervention. This could potentially reduce the number of patients that unnecessarily undergo ICA.
Tsinghua University（清华大学）；Anzhen Hospital, Capital Medical University（首都医科大学附属安贞医院）；Capital Medical University（首都医科大学）；The First Affiliated Hospital of Zhengzhou University（郑州大学第一附属医院）
Cardiac coronary angiography is a major technology to assist doctors during cardiac interventional surgeries. Under the exposure of X-ray radiation, doctors inject contrast agents through catheters to determine the position and status of coronary vessels in real time. To get a coronary angiography video with a high frame rate, the doctor needs to increase the exposure frequency and intensity of the X-ray. This will inevitably increase the X-ray harm to both patients and surgeons. In this work, we innovatively utilize a deep-learning based video interpolation algorithm to interpolate coronary a…
Image Sciences Institute, University Medical Center Utrecht（乌得勒支大学医学中心影像科学研究所）；University Medical Center Utrecht（乌得勒支大学医学中心）；Utrecht University（乌得勒支大学）；Amsterdam University Medical Center（阿姆斯特丹大学医学中心）
Treatment of patients with obstructive coronary artery disease is guided by the functional significance of a coronary artery stenosis. Fractional flow reserve (FFR), measured during invasive coronary angiography (ICA), is considered the gold standard to define the functional significance of a coronary stenosis. Here, we present a method for non-invasive detection of patients with functionally significant coronary artery stenosis, combining analysis of the coronary artery tree and the left ventricular (LV) myocardium in cardiac CT angiography (CCTA) images. We retrospectively collected CCTA sca…
Automatic extraction of coronary arteries using deep learning in invasive coronary angiograms
Zhengzhou University of Light Industry（郑州轻工业大学）；Michigan Technological University（密歇根理工大学）；The First Affiliated Hospital of Nanjing Medical University（南京医科大学第一附属医院）
Image Sciences Institute（影像科学研究所）；University Medical Center Utrecht（乌得勒支大学医学中心）；Department of Radiology（放射科）
Detection of coronary artery stenosis in coronary CT angiography (CCTA) requires highly personalized surface meshes enclosing the coronary lumen. In this work, we propose to use graph convolutional networks (GCNs) to predict the spatial location of vertices in a tubular surface mesh that segments the coronary artery lumen. Predictions for individual vertex locations are based on local image features as well as on features of neighboring vertices in the mesh graph. The method was trained and evaluated using the publicly available Coronary Artery Stenoses Detection and Quantification Evaluation …
Fudan University（复旦大学）；Shanghai East Hospital, Tongji University（同济大学附属东方医院）；Ruijin Hospital, Shanghai Jiao Tong University School of Medicine（上海交通大学医学院附属瑞金医院）
We proposed a novel unsupervised methodology named Disarranged Zone Learning (DZL) to automatically recognize stenosis in coronary angiography. The methodology firstly disarranges the frames in a video, secondly it generates an effective zone and lastly trains an encoder-decoder GRU model to learn the capability to recover disarranged frames. The breakthrough of our study is to discover and validate the Sequence Intensity (Recover Difficulty) is a measure of Coronary Artery Stenosis Status. Hence, the prediction accuracy of DZL is used as an approximator of coronary stenosis indicator. DZL is …
Coronary Heart Disease (CHD) is a leading cause of death in the modern world. The development of modern analytical tools for diagnostics and treatment of CHD is receiving substantial attention from the scientific community. Deep learning-based algorithms, such as segmentation networks and detectors, play an important role in assisting medical professionals by providing timely analysis of a patient's angiograms. This paper focuses on X-Ray Coronary Angiography (XCA), which is considered to be a "gold standard" in the diagnosis and treatment of CHD. First, we describe publicly available datasets…
CADICA: a new dataset for coronary artery disease detection by using invasive coronary angiography
University of Málaga（马拉加大学）；Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND（马拉加生物医学与纳米医学平台研究所-IBIMA BIONAND平台）；Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)（心血管疾病网络生物医学研究中心）；Instituto de Salud Carlos III (ISCIII)（卡洛斯三世卫生研究所）
Tsinghua University（清华大学）；Beijing Anzhen Hospital, Capital Medical University（首都医科大学附属北京安贞医院）；The First Affiliated Hospital of Zhengzhou University（郑州大学第一附属医院）
Coronary angiography is an indispensable assistive technique for cardiac interventional surgery. Segmentation and extraction of blood vessels from coronary angiography videos are very essential prerequisites for physicians to locate, assess and diagnose the plaques and stenosis in blood vessels. This article proposes a new video segmentation framework that can extract the clearest and most comprehensive coronary angiography images from a video sequence, thereby helping physicians to better observe the condition of blood vessels. This framework combines a 3D convolutional layer to extract spati…
DeepCA: Deep Learning-based 3D Coronary Artery Tree Reconstruction from Two 2D Non-simultaneous X-ray Angiography Projections
University of Oxford（牛津大学）；Institute of Biomedical Engineering（生物医学工程研究所）；Division of Cardiovascular Medicine（心血管医学部）；Radcliffe Department of Medicine（拉德克利夫医学系）；Oxford Acute Vascular Imaging Centre（牛津急性血管成像中心）
Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR)（新加坡科技研究局生物信息学研究所）；Hwa Chong Institution (College)（华侨中学（高中部））；National Heart Centre Singapore（新加坡国家心脏中心）；Duke-NUS Medical School（杜克-新加坡国立大学医学院）；School of Computing, National University of Singapore（新加坡国立大学计算学院）；Singapore Eye Research Institute (SERI)（新加坡眼科研究所）；Rehabilitation Research Institute of Singapore（新加坡康复研究所）；Institute of Bioengineering and Nanotechnology, A*STAR（新加坡科技研究局生物工程与纳米技术研究所）
The evaluation of obstructions (stenosis) in coronary arteries is currently done by a physician's visual assessment of coronary angiography video sequences. It is laborious, and can be susceptible to interobserver variation. Prior studies have attempted to automate this process, but few have demonstrated an integrated suite of algorithms for the end-to-end analysis of angiograms. We report an automated analysis pipeline based on deep learning to rapidly and objectively assess coronary angiograms, highlight coronary vessels of interest, and quantify potential stenosis. We propose a 3-stage auto…
Peking University（北京大学）；Peking University First Hospital（北京大学第一医院）；MGH/BWH Center for Clinical Data Science（麻省总医院/布莱根妇女医院临床数据科学中心）
Segmenting coronary arteries is challenging, as classic unsupervised methods fail to produce satisfactory results and modern supervised learning (deep learning) requires manual annotation which is often time-consuming and can some time be infeasible. To solve this problem, we propose a knowledge transfer based shape-consistent generative adversarial network (SC-GAN), which is an annotation-free approach that uses the knowledge from publicly available annotated fundus dataset to segment coronary arteries. The proposed network is trained in an end-to-end fashion, generating and segmenting synthe…
Michigan Technological University（密歇根理工大学）；University of Southern Mississippi（南密西西比大学）；Tulane University（杜兰大学）；Ochsner Medical Center（奥克斯纳医疗中心）
In stable coronary artery disease (CAD), reduction in mortality and/or myocardial infarction with revascularization over medical therapy has not been reliably achieved. Coronary arteries are usually extracted to perform stenosis detection. We aim to develop an automatic algorithm by deep learning to extract coronary arteries from ICAs.In this study, a multi-input and multi-scale (MIMS) U-Net with a two-stage recurrent training strategy was proposed for the automatic vessel segmentation. Incorporating features such as the Inception residual module with depth-wise separable convolutional layers,…
Coronary artery disease (CAD) has posed a leading threat to the lives of cardiovascular disease patients worldwide for a long time. Therefore, automated diagnosis of CAD has indispensable significance in clinical medicine. However, the complexity of coronary artery plaques that cause CAD makes the automatic detection of coronary artery stenosis in Coronary CT angiography (CCTA) a difficult task. In this paper, we propose a Transformer network (TR-Net) for the automatic detection of significant stenosis (i.e. luminal narrowing > 50%) while practically completing the computer-assisted diagnosis …
Queen Mary University of London（伦敦玛丽女王大学）；Barts Health NHS Trust（巴特国民保健信托基金会）
X-ray coronary angiography (XCA) is used to assess coronary artery disease and provides valuable information on lesion morphology and severity. However, XCA images are 2D and therefore limit visualisation of the vessel. 3D reconstruction of coronary vessels is possible using multiple views, however lumen border detection in current software is performed manually resulting in limited reproducibility and slow processing time. In this study we propose 3DAngioNet, a novel deep learning (DL) system that enables rapid 3D vessel mesh reconstruction using 2D XCA images from two views. Our approach lea…
NeRF-CA: Dynamic Reconstruction of X-ray Coronary Angiography with Extremely Sparse-views
Department of Mathematics & Computer Science, Eindhoven University of Technology（数学与计算机科学系，埃因霍温理工大学）；Philips Healthcare（飞利普医疗）；Department of Electrical Engineering, Eindhoven University of Technology（电子工程系，埃因霍温理工大学）；ASML（ASML公司）
Shanghai Jiao Tong University（上海交通大学）；Peking Union Medical College Hospital（北京协和医院）
The segmentation of coronary arteries by convolutional neural network is promising yet requires a large amount of labor-intensive manual annotations. Transferring knowledge from retinal vessels in widely-available public labeled fundus images (FIs) has a potential to reduce the annotation requirement for coronary artery segmentation in X-ray angiograms (XAs) due to their common tubular structures. However, it is challenged by the cross-anatomy domain shift due to the intrinsically different vesselness characteristics in different anatomical regions under even different imaging protocols. To so…
3DGR-CAR: Coronary artery reconstruction from ultra-sparse 2D X-ray views with a 3D Gaussians representation
School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC)（中国科学技术大学生命科学与医学部生物医学工程学院）；Center for Medical Imaging, Robotics, Analytic Computing & Learning (MIRACLE), Suzhou Institute for Advance Research, USTC（中国科学技术大学苏州研究院医学影像、机器人、分析计算与学习中心）
Vessel stenosis is a major risk factor in cardiovascular diseases (CVD). To analyze the degree of vessel stenosis for supporting the treatment management, extraction of coronary artery area from Computed Tomographic Angiography (CTA) is regarded as a key procedure. However, manual segmentation by cardiologists may be a time-consuming task, and present a significant inter-observer variation. Although various computer-aided approaches have been developed to support segmentation of coronary arteries in CTA, the results remain unreliable due to complex attenuation appearance of plaques, which are …
NerT-CA: Efficient Dynamic Reconstruction from Sparse-view X-ray Coronary Angiography
Department of Mathematics and Computer Science, Eindhoven University of Technology, Eindhoven, The Netherlands（数学与计算机科学系，埃因霍温理工大学，埃因霍温，荷兰）；Philips Healthcare, Best, The Netherlands（飞利浦医疗，贝斯特，荷兰）；Department of Electrical Engineering, Eindhoven University of Technology, The Netherlands（电子工程系，埃因霍温理工大学，荷兰）
DAMO Academy, Alibaba Group（阿里巴巴集团达摩院）；University of Wisconsin Madison（威斯康星大学麦迪逊分校）
Automated anatomical labeling plays a vital role in coronary artery disease diagnosing procedure. The main challenge in this problem is the large individual variability inherited in human anatomy. Existing methods usually rely on the position information and the prior knowledge of the topology of the coronary artery tree, which may lead to unsatisfactory performance when the main branches are confusing. Motivated by the wide application of the graph neural network in structured data, in this paper, we propose a conditional partial-residual graph convolutional network (CPR-GCN), which takes bot…
Instituto Superior Técnico（高等技术学院）；University of Lisbon（里斯本大学）；CCUL（里斯本大学中心学院）；Lisbon School of Medicine（里斯本医学院）
Coronary artery disease leading up to stenosis, the partial or total blocking of coronary arteries, is a severe condition that affects millions of patients each year. Automated identification and classification of stenosis severity from minimally invasive procedures would be of great clinical value, but existing methods do not match the accuracy of experienced cardiologists, due to the complexity of the task. Although a number of computational approaches for quantitative assessment of stenosis have been proposed to date, the performance of these methods is still far from the required levels fo…
Zhengzhou University of Light Industry（郑州轻工业大学）；University of Southern Mississippi（南密西西比大学）；Michigan Technological University（密歇根理工大学）；New York Presbyterian Queens Hospital（纽约长老会皇后医院）；The First Affiliated Hospital of Nanjing Medical University（南京医科大学第一附属医院）
Automatic identification of proper image frames at the end-diastolic (ED) and end-systolic (ES) frames during the review of invasive coronary angiograms (ICA) is important to assess blood flow during a cardiac cycle, reconstruct the 3D arterial anatomy from bi-planar views, and generate the complementary fusion map with myocardial images. The current identification method primarily relies on visual interpretation, making it not only time-consuming but also less reproducible. In this paper, we propose a new method to automatically identify angiographic image frames associated with the ED and ES…
The Ohio State University College of Medicine（俄亥俄州立大学医学院）
We propose a fully automated algorithm based on a deep learning framework enabling screening of a coronary computed tomography angiography (CCTA) examination for confident detection of the presence or absence of coronary artery atherosclerosis. The system starts with extracting the coronary arteries and their branches from CCTA datasets and representing them with multi-planar reformatted volumes; pre-processing and augmentation techniques are then applied to increase the robustness and generalization ability of the system. A 3-dimensional convolutional neural network (3D-CNN) is utilized to mo…
The University of Tokyo（东京大学）；RIKEN Center for Advanced Intelligence Project（理化学研究所先进智能项目中心）；Sakurabashi Watanabe Hospital（樱桥渡边医院）
Providing closed and well-connected boundaries of coronary artery is essential to assist cardiologists in the diagnosis of coronary artery disease (CAD). Recently, several deep learning-based methods have been proposed for boundary detection and segmentation in a medical image. However, when applied to coronary wall detection, they tend to produce disconnected and inaccurate boundaries. In this paper, we propose a novel boundary detection method for coronary arteries that focuses on the continuity and connectivity of the boundaries. In order to model the spatial continuity of consecutive image…
Korea Advanced Institute of Science and Technology（韩国科学技术院）；University of Ulsan College of Medicine（蔚山大学医学院）；Asan Medical Center（峨山医学中心）
In this paper, we proposed T-Net containing a small encoder-decoder inside the encoder-decoder structure (EDiED). T-Net overcomes the limitation that U-Net can only have a single set of the concatenate layer between encoder and decoder block. To be more precise, the U-Net symmetrically forms the concatenate layers, so the low-level feature of the encoder is connected to the latter part of the decoder, and the high-level feature is connected to the beginning of the decoder. T-Net arranges the pooling and up-sampling appropriately during the encoder process, and likewise during the decoding proc…
School of Computer Science and Technology, Anhui University（安徽大学计算机科学与技术学院）；National Heart & Lung Institute, Imperial College London（帝国理工学院国家心肺研究所）；Key Laboratory of Intelligent Computing and Signal Processing, Ministry of Education, Anhui University（安徽大学智能计算与信号处理教育部重点实验室）；Cardiovascular Research Centre, Royal Brompton Hospital（皇家布朗普顿医院心血管研究中心）；School of Biomedical Engineering, Sun Yat-Sen University（中山大学生物医学工程学院）；Western University（韦仕敦大学）
The quantification of the coronary artery stenosis is of significant clinical importance in coronary artery disease diagnosis and intervention treatment. It aims to quantify the morphological indices of the coronary artery lesions such as minimum lumen diameter, reference vessel diameter, lesion length, and these indices are the reference of the interventional stent placement. In this study, we propose a direct multiview quantitative coronary angiography (DMQCA) model as an automatic clinical tool to quantify the coronary artery stenosis from X-ray coronary angiography images. The proposed DMQ…
A Diffusion Model for Simulation Ready Coronary Anatomy with Morpho-skeletal Control
Institute of Medical Engineering, MIT（麻省理工学院医学工程研究所）；Brigham and Women's Hospital, Harvard（哈佛大学布莱尔妇女医院）；HeartFlow（HeartFlow公司）；Showa University（昭和大学）；OLV Aalst
Background. Percutaneous coronary intervention(PCI) in stable coronary artery disease(CAD) is commonly triggered by abnormal myocardial perfusion imaging(MPI). However, due to the possibilities of multivessel disease and variability of coronary artery perfusion distribution, opportunity exists to better align anatomic stenosis with perfusion abnormalities to improve revascularization decisions. This study aims to develop a 3D multi-modality fusion approach to assist decision-making for PCI. Methods. Coronary arteries from fluoroscopic angiography(FA) were reconstructed into 3D artery anatomy. …
Scaling up fine-grained intracranial vessel annotations in computed tomography angiography
Brigham and Women’s Hospital Harvard Medical School（哈佛医学院布莱尔妇女医院）；Khoury College of Computer Sciences Northeastern University（东北大学计算机科学学院）；Washington University in St. Louis（圣路易斯华盛顿大学）；Dana-Farber Cancer Institute Harvard Medical School（哈佛医学院丹娜-法伯癌症研究院）
CAD-RADS scoring of coronary CT angiography with Multi-Axis Vision Transformer: a clinically-inspired deep learning pipeline
University of Pavia（帕维亚大学）；Centro Cardiologico Monzino IRCCS（蒙齐诺心脏病学中心IRCCS）；University of Milan（米兰大学）；IRCCS Istituti Clinici Scientifici Maugeri（IRCCS莫杰里科学临床研究所）
School of Biomedical Engineering, Shanghai Jiao Tong University（上海交通大学生物医学工程学院）；School of Continuing Education, Shanghai Jiao Tong University（上海交通大学继续教育学院）；Shanghai Jiao Tong University Affiliated Sixth People’s Hospital（上海交通大学附属第六人民医院）；Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University（上海交通大学医学院附属仁济医院）；Center for Advanced Neuroimaging, University of California, Riverside（加州大学河滨分校高级神经影像中心）
Although robust PCA has been increasingly adopted to extract vessels from X-ray coronary angiography (XCA) images, challenging problems such as inefficient vessel-sparsity modelling, noisy and dynamic background artefacts, and high computational cost still remain unsolved. Therefore, we propose a novel robust PCA unrolling network with sparse feature selection for super-resolution XCA vessel imaging. Being embedded within a patch-wise spatiotemporal super-resolution framework that is built upon a pooling layer and a convolutional long short-term memory network, the proposed network can not onl…
The purpose of this study is to present a new semi-automated methodology for three-dimensional (3D) reconstruction of coronary arteries and their plaque morphology using Computed Tomography Angiography (CTA) images. The methodology is summarized in seven stages: pre-processing of the acquired CTA images, extraction of the vessel tree centerline, estimation of a weight function for lumen, outer wall and calcified plaque, lumen segmentation, outer wall segmentation, plaque detection, and finally 3D surfaces construction. The methodology was evaluated using both expert manual annotations and esti…
This study is to characterize reflectance profiles of retinal blood vessels in optical coherence tomography (OCT), and to validate these vascular features to guide artery-vein classification in OCT angiography (OCTA) of human retina. Depth-resolved OCT reveals unique features of retinal arteries and veins. Retinal arteries show hyper-reflective boundaries at both upper (inner side towards the vitreous) and lower (outer side towards the choroid) walls. In contrary, retinal veins reveal hyper-reflectivity at the upper boundary only. Uniform lumen intensity was observed in both small and large ar…
CardioSyntax: end-to-end SYNTAX score prediction -- dataset, benchmark and method
Sber AI Lab（Sber AI实验室）；Tyumen Cardiology Research Center（泰姆普斯心脏病学研究中心）；Tomsk National Research Medical Center of Russian Academy of Science（托木斯克俄罗斯科学院国家医学研究中心）
Case Western Reserve University（凯斯西储大学）；The Hashemite University（哈希姆大学）；University Hospitals Cleveland Medical Center（克利夫兰大学医院医学中心）；Florida Institute of Technology（佛罗里达理工学院）；University of South Florida（南佛罗里达大学）
BACKGROUND Careful evaluation of the risk of stent under-expansions before the intervention will aid treatment planning, including the application of a pre-stent plaque modification strategy. OBJECTIVES It remains challenging to achieve a proper stent expansion in the presence of severely calcified coronary lesions. Building on our work in deep learning segmentation, we created an automated machine learning approach that uses lesion attributes to predict stent under-expansion from pre-stent images, suggesting the need for plaque modification. METHODS Pre- and post-stent intravascular optical c…
ImageCAS: A Large-Scale Dataset and Benchmark for Coronary Artery Segmentation based on Computed Tomography Angiography Images
Guangdong University of Technology（广东工业大学）；Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences)（广东省人民医院（广东省医学科学院））；Southern Medical University（南方医科大学）；Missouri University of Science and Technology（密苏里科技大学）
Babol Noshirvani University of Technology（巴博勒努希尔瓦尼技术大学）；Italian Institute of Technology（意大利技术研究院）；Royan Institute for Stem Cell Biology and Technology（罗扬干细胞生物学与技术研究所）；Sharif University of Technology（谢里夫理工大学）
Prediction of the blood flow characteristics is of utmost importance for understanding the behavior of the blood arterial network, especially in the presence of vascular diseases such as stenosis. Computational fluid dynamics (CFD) has provided a powerful and efficient tool to determine these characteristics including the pressure and velocity fields within the network. Despite numerous studies in the field, the extremely high computational cost of CFD has led the researchers to develop new platforms including Machine Learning approaches that instead provide faster analyses at a much lower cos…
Hankuk University of Foreign Studies（韩国外国语大学）；Seoul National University Bundang Hospital（首尔大学盆唐医院）
The Coronary Artery Occlusion (CAO) acutely comes to human, and it highly threats the human's life. When CAO detected, Percutaneous Coronary Intervention (PCI) should be conducted timely. Before PCI, localizing the CAO is needed firstly, because the heart is covered with various arteries. We handle the three kinds of CAO in this paper and our purpose is not only localization of CAO but also improving the localizing performance via preprocessing method. We improve localization performance from a minimum of 0.150 to a maximum of 0.372 via our noise reduction and pulse extraction based method.
Multivessel Coronary Artery Segmentation and Stenosis Localisation using Ensemble Learning
Birmingham City University（伯明翰城市大学）；University of the West of England (UWE)（西英格兰大学）；Institute of Accounting and Administration, University of Aveiro（阿威罗大学会计与行政学院）；NUS High School of Math and Science（新加坡国立大学数学与科学高中）；Qatar University（卡塔尔大学）；Information Technology University（信息技术大学）；Bristol Heart Institute, University of Bristol（布里斯托大学布里斯托心脏研究所）
