심층신경망을 이용한 자동화된 치과 의료영상 분석

학위논문(박사) -- 서울대학교대학원 : 치과대학 치의과학과, 2021.8. 한중석.목 적: 치과 영역에서도 심층신경망(Deep Neural Network) 모델을 이용한 방사선사진에서의 임플란트 분류, 병소 위치 탐지 등의 연구들이 진행되었으나, 최근 개발된 키포인트 탐지(keypoint detection) 모델 또는 전체적 구획화(panoptic segmentation) 모델을 의료분야에 적용한 연구는 아직 미비하다. 본 연구의 목적은 치근단 방사선사진에서 키포인트 탐지를 이용해 임플란트 골 소실 정도를 파악하는 모델과 panoptic segmentation을 파노라마영상에 적용하여 다양한 구조물들을 구획화하는 모델을 학습시켜 진료에 보조적으로 활용되도록 만들어보고, 이 모델들의 추론결과를 평가해보는 것이다. 방 법: 객체 탐지 및 구획화에 있어 널리 연구된 합성곱 신경망 모델인 Mask-RCNN을 키포인트 탐지가 가능한 형태로 준비하여 치근단 방사선사진에서 임플란트의 top, apex, 그리고 bone level 지점을 좌우로 총 6지점 탐지하게끔 학습시킨 뒤, 학습에 사용되지 않은 시험 데이터셋을 대상으로 탐지시킨다. 키포인트 탐지 평가용 지표인 object keypoint similarity (OKS) 및 이를 이용한 average precision (AP) 값을 계산하고, 평균 OKS값을 통해 모델 및 치과의사의 결과를 비교한다. 또한, 탐지된 키포인트를 바탕으로 방사선사진상에서의 골 소실 정도를 수치화한다. Panoptic segmentation을 위해서는 기존의 벤치마크에서 우수한 성적을 거둔 신경망 모델인 Panoptic DeepLab을 파노라마영상에서 주요 구조물(상악동, 상악골, 하악관, 하악골, 자연치, 치료된 치아, 임플란트)을 구획화하도록 학습시킨 뒤, 시험 데이터셋에서의 구획화 결과에 panoptic / semantic / instance segmentation 각각의 평가지표들을 적용하고, 픽셀들의 정답(ground truth) 클래스와 모델이 추론한 클래스에 대한 confusion matrix를 계산한다. 결 과: OKS값을 기반으로 계산한 키포인트 탐지 AP는, 모든 OKS threshold에 대한 평균의 경우, 상악 임플란트에서는 0.761, 하악 임플란트에서는 0.786이었다. 평균 OKS는 모델이 0.8885, 치과의사가 0.9012로, 통계적으로 유의미한 차이가 없었다 (p = 0.41). 모델의 평균 OKS 값은 사람의 키포인트 어노테이션 정규분포상에서 상위 66.92% 수준이었다. 파노라마영상 구조물 구획화에서는, panoptic segmentation 평가지표인 panoptic quality 값의 경우 모든 클래스의 평균은 80.47이었으며, 치료된 치아가 57.13으로 가장 낮았고 하악관이 65.97로 두번째로 낮은 값을 보였다. Semantic segmentation 평가지표인 global한 Intersection over Union (IoU) 값은 모든 클래스 평균 0.795였으며, 하악관이 0.639로 가장 낮았고 치료된 치아가 0.656으로 두번째로 낮은 값을 보였다. Confusion matrix 계산 결과, ground truth 픽셀들 중 올바르게 추론된 픽셀들의 비율은 하악관이 0.802로 가장 낮았다. 개별 객체에 대한 IoU를 기반으로 계산한 Instance segmentation 평가지표인 AP값은, 모든 IoU threshold에 대한 평균의 경우, 치료된 치아가 0.316, 임플란트가 0.414, 자연치가 0.520이었다. 결 론: 키포인트 탐지 신경망 모델을 이용하여, 치근단 방사선사진에서 임플란트의 주요 지점을 사람과 다소 유사한 수준으로 탐지할 수 있었다. 또한, 탐지된 지점들을 기반으로 방사선사진상에서의 임플란트 주위 골 소실 비율 계산을 자동화할 수 있고, 이 값은 임플란트 주위염의 심도 분류에 사용될 수 있다. 파노라마 영상에서는 panoptic segmentation이 가능한 신경망 모델을 이용하여 상악동과 하악관을 포함한 주요 구조물들을 구획화할 수 있었다. 따라서, 이와 같이 각 작업에 맞는 심층신경망을 적절한 데이터로 학습시킨다면 진료 보조 수단으로 활용될 수 있다.Purpose: In dentistry, deep neural network models have been applied in areas such as implant classification or lesion detection in radiographs. However, few studies have applied the recently developed keypoint detection model or panoptic segmentation model to medical or dental images. The purpose of this study is to train two neural network models to be used as aids in clinical practice and evaluate them: a model to determine the extent of implant bone loss using keypoint detection in periapical radiographs and a model that segments various structures on panoramic radiographs using panoptic segmentation. Methods: Mask-RCNN, a widely studied convolutional neural network for object detection and instance segmentation, was constructed in a form that is capable of keypoint detection, and trained to detect six points of an implant in a periapical radiograph: left and right of the top, apex, and bone level. Next, a test dataset was used to evaluate the inference results. Object keypoint similarity (OKS), a metric to evaluate the keypoint detection task, and average precision (AP), based on the OKS values, were calculated. Furthermore, the results of the model and those arrived at by a dentist were compared using the mean OKS. Based on the detected keypoint, the peri-implant bone loss ratio was obtained from the radiograph. For panoptic segmentation, Panoptic DeepLab, a neural network model ranked high in the previous benchmark, was trained to segment key structures in panoramic radiographs: maxillary sinus, maxilla, mandibular canal, mandible, natural tooth, treated tooth, and dental implant. Then, each evaluation metric of panoptic, semantic, and instance segmentation was applied to the inference results of the test dataset. Finally, the confusion matrix for the ground truth class of pixels and the class inferred by the model was obtained. Results: The AP of keypoint detection for the average of all OKS thresholds was 0.761 for the upper implants and 0.786 for the lower implants. The mean OKS was 0.8885 for the model and 0.9012 for the dentist; thus, the difference was not statistically significant (p = 0.41). The mean OKS of the model was in the top 66.92% of the normal distribution of human keypoint annotations. In panoramic radiograph segmentation, the average panoptic quality (PQ) of all classes was 80.47. The treated teeth showed the lowest PQ of 57.13, and the mandibular canal showed the second lowest PQ of 65.97. The Intersection over Union (IoU) was 0.795 on average for all classes, where the mandibular canal showed the lowest IoU of 0.639, and the treated tooth showed the second lowest IoU of 0.656. In the confusion matrix, the proportion of correctly inferred pixels among the ground truth pixels was the lowest in the mandibular canal at 0.802. The AP, averaged for all IoU thresholds, was 0.316 for the treated tooth, 0.414 for the dental implant, and 0.520 for the normal tooth. Conclusion: Using the keypoint detection neural network model, it was possible to detect major landmarks around dental implants in periapical radiographs to a degree similar to that of human experts. In addition, it was possible to automate the calculation of the peri-implant bone loss ratio on periapical radiographs based on the detected keypoints, and this value could be used to classify the degree of peri-implantitis. In panoramic radiographs, the major structures including the maxillary sinus and the mandibular canal could be segmented using a neural network model capable of panoptic segmentation. Thus, if deep neural networks suitable for each task are trained using suitable datasets, the proposed approach can be used to assist dental clinicians.Chapter 1. Introduction 1 Chapter 2. Materials and methods 5 Chapter 3. Results 23 Chapter 4. Discussion 32 Chapter 5. Conclusions 45 Published papers related to this study 46 References 47 Abbreviations 52 Abstract in Korean 53 Acknowledgements 56박

Production of a Bacteria-like Particle Vaccine Targeting Rock Bream (Oplegnathus fasciatus) Iridovirus Using Nicotiana benthamiana

Viral diseases are extremely widespread infections that change constantly through mutations. To produce vaccines against viral diseases, transient expression systems are employed, and Nicotiana benthamiana (tobacco) plants are a rapidly expanding platform. In this study, we developed a recombinant protein vaccine targeting the major capsid protein (MCP) of iridovirus fused with the lysine motif (LysM) and coiled-coil domain of coronin 1 (ccCor1) for surface display using Lactococcus lactis. The protein was abundantly produced in N. benthamiana in its N-glycosylated form. Total soluble proteins isolated from infiltrated N. benthamiana leaves were treated sequentially with increasing ammonium sulfate solution, and recombinant MCP mainly precipitated at 40–60%. Additionally, affinity chromatography using Ni–NTA resin was applied for further purification. Native structure analysis using size exclusion chromatography showed that recombinant MCP existed in a large oligomeric form. A minimum OD600 value of 0.4 trichloroacetic acid (TCA)-treated L. lactis was required for efficient recombinant MCP display. Immunogenicity of recombinant MCP was assessed in a mouse model through enzyme-linked immunosorbent assay (ELISA) with serum-injected recombinant MCP-displaying L. lactis. In summary, we developed a plant-based recombinant vaccine production system combined with surface display on L. lactis.11Nsciescopuskc