The global transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in over 677 million infections and 6.88 million tragic deaths worldwide as of March 10th, 2023. During the pandemic, the ability to effectively combat SARS-CoV-2 had been hindered by the lack of rapid, reliable, and cost-effective testing platforms for readily screening patients, discerning incubation stages, and accounting for variants. The limited knowledge of the viral pathogenesis further hindered rapid diagnosis and long-term clinical management of this complex disease. While effective in the short term, measures such as social distancing and lockdowns have resulted in devastating economic loss, in addition to material and psychological hardships. Therefore, successfully reopening society during a pandemic depends on frequent, reliable testing, which can result in the timely isolation of highly infectious cases before they spread or become contagious. Viral loads, and consequently an individual's infectiousness, change throughout the progression of the illness.
These dynamics necessitate frequent testing to identify when an infected individual can safely interact with non-infected individuals. Thus, scalable, accurate, and rapid serial testing is a cornerstone of an effective pandemic response, a prerequisite for safely reopening society, and invaluable for early containment of epidemics. Given the significant challenges posed by the pandemic, the power of artificial intelligence (AI) can be harnessed to create new diagnostic methods and be used in conjunction with serial tests. With increasing utilization of at-home lateral flow immunoassay (LFIA) tests, the National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC) have consistently raised concerns about a potential underreporting of actual SARS-CoV-2-positive cases. When AI is paired with serial tests, it could instantly notify, automatically quantify, aid in real-time contact tracing, and assist in isolating infected individuals.
Moreover, the computer vision-assisted methodology can help objectively diagnose conditions, especially in cases where subjective LFIA tests are employed. Recent advances in the interdisciplinary scientific fields of machine learning and biomedical engineering support a unique opportunity to design AI-based strategies for pandemic preparation and response. Deep learning algorithms are transforming the interpretation and analysis of image data when used in conjunction with biomedical imaging modalities such as MRI, Xray, CT scans, confocal microscopes, etc. These advances have enabled researchers to carry out real-time viral infection diagnostics that were previously thought to be impossible. The objective of this thesis is to use SARS-CoV-2 as a model virus and investigate the potential of applying multi-class instance segmentation deep learning and other machine learning strategies to build pandemic preparedness for rapid, in-depth, and longitudinal diagnostic platforms. This thesis encompasses three research tasks: 1) computer vision-assisted rapid serial testing, 2) infected cell phenotyping, and 3) diagnosing the long-term consequences of infection (i.e., long-term COVID).
The objective of Task 1 is to leverage the power of AI, in conjunction with smartphones, to rapidly and simultaneously diagnose COVID-19 infections for millions of people across the globe. AI not only makes it possible for rapid and simultaneous screenings of millions but can also aid in the identification and contact tracing of individuals who may be carriers of the virus. The technology could be used, for example, in university settings to manage the entry of students into university buildings, ensuring that only students who test negative for the virus are allowed within campus premises, while students who test positive are placed in quarantine until they recover. The technology could also be used in settings where strict adherence to COVID-19 prevention protocols is compromised, for example, in an Emergency Room. This technology could also help with CDC’s concern on growing incidences of underreporting positive COVID-19 cases with growing utilization of at-home LFIA tests.
AI can address issues that arise from relying solely on the visual interpretation of LFIA tests to make accurate diagnoses.
One problem is that LFIA test results may be subjective or ambiguous, especially when the test line of the LFIA displays faint color, indicating a low analyte abundance. Therefore, reaching a decisive conclusion regarding the patient's diagnosis becomes challenging. Additionally, the inclusion of a secondary source for verifying the test results could potentially increase the test's cost, as it may require the purchase of complementary electronic gadgets. To address these issues, our innovation would be accurately calibrated with appropriate sensitivity markers, ensuring increased accuracy of the diagnostic test and rapid acquisition of test results from the simultaneous classification of millions of LFIA tests as either positive or negative. Furthermore, the designed network architecture can be utilized to detect other LFIA-based tests, such as early pregnancy detection, HIV LFIA detection, and LFIA-based detection of other viruses.
Such minute advances in machine learning and artificial intelligence can be leveraged on many different scales and at various levels to revolutionize the health sector. The motivating purpose of Task 2 is to design a highly accurate instance segmentation network architecture not only for the analysis of SARS-CoV-2 infected cells but also one that yields the highest possible segmentation accuracy for all applications in biomedical sciences. For example, the designed network architecture can be utilized to analyze macrophages, stem cells, and other types of cells.
Task 3 focuses on conducting studies that were previously considered computationally impossible. The invention will assist medical researchers and dentists in automatically calculating alveolar crest height (ACH) in teeth using over 500 dental Xrays. This will help determine if patients diagnosed with COVID-19 by a positive PCR test exhibited more alveolar bone loss and had greater bone loss in the two years preceding their COVID-positive test when compared to a control group without a positive COVID-19 test. The contraction of periodontal disease results in higher levels of transmembrane serine protease 2 (TMPRSS2) within the buccal cavity, which is instrumental in enabling the entry of SARS-CoV-2. Gum inflammation, a symptom of periodontal disease, can lead to alterations in the ACH of teeth within the oral mucosa. Through this innovation, we can calculate ACHs of various teeth and, therefore, determine the correlation between ACH and the risk of contracting SARS-CoV-2 infection. Without the invention, extensive manpower and time would be required to make such calculations and gather data for further research into the effects of SARS-CoV-2 infection, as well as other related biological phenomena within the human body. Furthermore, the novel network framework can be modified and used to calculate dental caries and other periodontal diseases of interest.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/agm3-fd52 |
| Date | January 2024 |
| Creators | Lee, Sang Won |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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