Development of Optical Devices for Digital Medicine

Department of Biomedical EngineeringAdvances of technology have made a revolution that interconnects industrial devices and fuses the boundaries of digital, physical and biological spaces. These technologies such as cloud computing, 3D printing technology, big data, internet of things (IOT), artificial intelligence (AI), and maturity of system integrations have been improved every year, changing our daily life quickly in intelligent and convenient ways. In this days, these explosions of technology, changing the way we live and think, is referred to 4th industrial revolution. As we know, every industry is affected by the new waves of technologies, digitalization and connectivity, and the biomedical or medical field is no exception. Healthcare fields have benefited mostly from recent technical improvements, revolutionizing the medical systems in many terms in cost-effective ways. Particularly, ???digital medicine??? has been recently came into the limelight as one of the uprising fields. In digital medicine, traditional medical devices and diagnostic programs have become miniaturized, digitalized, and automated. As taking advantages of digital medicine, specific fields related to digital pathology, point-of-care (POC) diagnostics, and application of deep learning or machine learning technologies have shown the great potentials not only in biomedical academia but also in the revenues of their markets. It allows to connect devices, hospital equipment, and to accelerate efficiencies in health service such as diagnosis, and to reduce the cost of services. Moreover, interconnection between advanced technologies has been improved the access of healthcare to the places where hospital or medical services are limited. Furthermore, artificial intelligence has shown promising results related to disease screening especially using medical images. Although fields in digital medicine are prospering, still there are limitations that needs to be overcome in order to provide further advanced health services to patients in the various situations. In digital pathology, improvements of microscopic technologies, internets, and storage capabilities have reduced the time-consuming processes. The simple transformation of microscopic image to digital have successfully alternated many limitations in the analogue histopathology workflow to efficient and cost saving ways. However, tissue staining is currently referred as one of the bottleneck that makes workflow still lengthy, labor-intensive, and costly. In the POC diagnostic fields, various digitalized portable smartphone-based diagnostic devices have been introduced as alternatives to conventional medical services. These devices have provided the quality assurance of diagnostics by taking advantages of sharing, and quantitative analysis of digital information. However, most of these works have been focused on replacing diagnostic process which mostly done in laboratory settings. As medical imaging devices and trained clinicians or practitioners are limited, there are also high demands on clinical imaging-based diagnostics in developing countries. In this thesis, computational microscope using patterned NIR illumination was developed for label-free quantitative differential phase tissue imaging to bypass the staining process of the pathology workflow. This system overcame the limitations found in the conventional quantitative differential phase contrast in a LED array microscope, allowing to captured light scattering and absorbing specimen while maintaining weak object approximation. Moreover, portable endoscope system was developed integrating the additive production technologies (3D printing), ICT, and optics for POC diagnostics. This innovative POC endoscope demonstrated comparable imaging capability to that of commercialized clinical endoscope system. Furthermore, deep learning and machine learning models have been trained and applied to each devices, respectively. Generative adversarial network (GAN) was applied to our NIR-based QPI system to virtually stain the label-free QPI which look comparable to image that is captured from bright field microscope using labeled tissue. Lastly, POC automated cervical cancer screening system was developed utilizing smartphone-based endoscope system as well as training the machine learning algorithm. 3-5% of acetic acid was applied to the suspicious lesion and its reaction was captured before and after application using smartphone endoscope. This screening system enables to extract the features of cancers and informs the possibility of cancer from endoscopic images.clos

Quantitative Screening of Cervical Cancers for Low-Resource Settings: Pilot Study of Smartphone-Based Endoscopic Visual Inspection After Acetic Acid Using Machine Learning Techniques

Background: Approximately 90% of global cervical cancer (CC) is mostly found in low- and middle-income countries. In most cases, CC can be detected early through routine screening programs, including a cytology-based test. However, it is logistically difficult to offer this program in low-resource settings due to limited resources and infrastructure, and few trained experts. A visual inspection following the application of acetic acid (VIA) has been widely promoted and is routinely recommended as a viable form of CC screening in resource-constrained countries. Digital images of the cervix have been acquired during VIA procedure with better quality assurance and visualization, leading to higher diagnostic accuracy and reduction of the variability of detection rate. However, a colposcope is bulky, expensive, electricity-dependent, and needs routine maintenance, and to confirm the grade of abnormality through its images, a specialist must be present. Recently, smartphone-based imaging systems have made a significant impact on the practice of medicine by offering a cost-effective, rapid, and noninvasive method of evaluation. Furthermore, computer-aided analyses, including image processing-based methods and machine learning techniques, have also shown great potential for a high impact on medicinal evaluations

Lamellar keratoplasty using position-guided surgical needle and M-mode optical coherence tomography

Deep anterior lamellar keratoplasty (DALK) is an emerging surgical technique for the restoration of corneal clarity and vision acuity. The big-bubble technique in DALK surgery is the most essential procedure that includes the air injection through a thin syringe needle to separate the dysfunctional region of the cornea. Even though DALK is a well-known transplant method, it is still challenged to manipulate the needle inside the cornea under the surgical microscope, which varies its surgical yield. Here, we introduce the DALK protocol based on the position-guided needle and M-mode optical coherence tomography (OCT). Depth-resolved 26-gage needle was specially designed, fabricated by the stepwise transitional core fiber, and integrated with the swept source OCT system. Since our device is feasible to provide both the position information inside the cornea as well as air injection, it enables the accurate management of bubble formation during DALK. Our results show that real-time feedback of needle end position was intuitionally visualized and fast enough to adjust the location of the needle. Through our research, we realized that position-guided needle combined with M-mode OCT is a very efficient and promising surgical tool, which also to enhance the accuracy and stability of DALK

Smartphone-Based Endoscope System for Advanced Point-of-Care Diagnostics: Feasibility Study

Background: Endoscopic technique is often applied for the diagnosis of diseases affecting internal organs and image-guidance of surgical procedures. Although the endoscope has become an indispensable tool in the clinic, its utility has been limited to medical offices or operating rooms because of the large size of its ancillary devices. In addition, the basic design and imaging capability of the system have remained relatively unchanged for decades. Objective: The objective of this study was to develop a smartphone-based endoscope system capable of advanced endoscopic functionalities in a compact size and at an affordable cost and to demonstrate its feasibility of point-of-care through human subject imaging. Methods: We developed and designed to set up a smartphone-based endoscope system, incorporating a portable light source, relay-lens, custom adapter, and homebuilt Android app. We attached three different types of existing rigid or flexible endoscopic probes to our system and captured the endoscopic images using the homebuilt app. Both smartphone-based endoscope system and commercialized clinical endoscope system were utilized to compare the imaging quality and performance. Connecting the head-mounted display (HMD) wirelessly, the smartphone-based endoscope system could superimpose an endoscopic image to real-world view. Results: A total of 15 volunteers who were accepted into our study were captured using our smartphone-based endoscope system, as well as the commercialized clinical endoscope system. It was found that the imaging performance of our device had acceptable quality compared with that of the conventional endoscope system in the clinical setting. In addition, images captured from the HMD used in the smartphone-based endoscope system improved eye-hand coordination between the manipulating site and the smartphone screen, which in turn reduced spatial disorientation. Conclusions: The performance of our endoscope system was evaluated against a commercial system in routine otolaryngology examinations. We also demonstrated and evaluated the feasibility of conducting endoscopic procedures through a custom HMD

One Small Step for Generative AI, One Giant Leap for AGI: A Complete Survey on ChatGPT in AIGC Era

OpenAI has recently released GPT-4 (a.k.a. ChatGPT plus), which is demonstrated to be one small step for generative AI (GAI), but one giant leap for artificial general intelligence (AGI). Since its official release in November 2022, ChatGPT has quickly attracted numerous users with extensive media coverage. Such unprecedented attention has also motivated numerous researchers to investigate ChatGPT from various aspects. According to Google scholar, there are more than 500 articles with ChatGPT in their titles or mentioning it in their abstracts. Considering this, a review is urgently needed, and our work fills this gap. Overall, this work is the first to survey ChatGPT with a comprehensive review of its underlying technology, applications, and challenges. Moreover, we present an outlook on how ChatGPT might evolve to realize general-purpose AIGC (a.k.a. AI-generated content), which will be a significant milestone for the development of AGI.Comment: A Survey on ChatGPT and GPT-4, 29 pages. Feedback is appreciated ([email protected]

Duodenal Duplication Cysts of Ampulla of Vater Containing Stone

Duodenal duplication cysts are rare congenital malformations. Most symptomatic cases are diagnosed in children and usually present with obstructive findings or bleeding symptoms. Treatment traditionally involves surgical resection, which can be often difficult because of the close proximity of the cysts to the papilla and bilopancreatic confluence. Endoscopic therapy has been used as an alternative to open surgery in a few selected cases. We report a case with a duodenal duplication cyst containing a brown pigmented stone within the cystic lumen. He was visited because of sudden right upper quadrant abdominal pain. An abdominal computed tomography revealed the presence of a cyst with a stone, which was finally removed by endoscopic resection

NGL-1/LRRC4C Deletion Moderately Suppresses Hippocampal Excitatory Synapse Development and Function in an Input-Independent Manner

Netrin-G ligand-1 (NGL-1), also known as LRRC4C, is a postsynaptic densities (PSDs)-95-interacting postsynaptic adhesion molecule that interacts trans-synaptically with presynaptic netrin-G1. NGL-1 and its family member protein NGL-2 are thought to promote excitatory synapse development through largely non-overlapping neuronal pathways. While NGL-2 is critical for excitatory synapse development in specific dendritic segments of neurons in an input-specific manner, whether NGL-1 has similar functions is unclear. Here, we show that Lrrc4c deletion in male mice moderately suppresses excitatory synapse development and function, but surprisingly, does so in an input-independent manner. While NGL-1 is mainly detected in the stratum lacunosum moleculare (SLM) layer of the hippocampus relative to the stratum radiatum (SR) layer, NGL-1 deletion leads to decreases in the number of PSDs in both SLM and SR layers in the ventral hippocampus. In addition, both SLM and SR excitatory synapses display suppressed short-term synaptic plasticity in the ventral hippocampus. These morphological and functional changes are either absent or modest in the dorsal hippocampus. The input-independent synaptic changes induced by Lrrc4c deletion involve abnormal translocation of NGL-2 from the SR to SLM layer. These results suggest that Lrrc4c deletion moderately suppresses hippocampal excitatory synapse development and function in an input-independent manner

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field