COVID-19 screening with digital holographic microscopy using intra-patient probability functions of spatio-temporal bio-optical attributes.

We present an automated method for COVID-19 screening using the intra-patient population distributions of bio-optical attributes extracted from digital holographic microscopy reconstructed red blood cells. Whereas previous approaches have aimed to identify infection by classifying individual cells, here, we propose an approach to incorporate the attribute distribution information from the population of a given human subjects' cells into our classification scheme and directly classify subjects at the patient level. To capture the intra-patient distribution information in a generalized way, we propose an approach based on the Bag-of-Features (BoF) methodology to transform histograms of bio-optical attribute distributions into feature vectors for classification via a linear support vector machine. We compare our approach with simpler classifiers directly using summary statistics such as mean, standard deviation, skewness, and kurtosis of the distributions. We also compare to a k-nearest neighbor classifier using the Kolmogorov-Smirnov distance as a distance metric between the attribute distributions of each subject. We lastly compare our approach to previously published methods for classification of individual red blood cells. In each case, the methodology proposed in this paper provides the highest patient classification performance, correctly classifying 22 out of 24 individuals and achieving 91.67% classification accuracy with 90.00% sensitivity and 92.86% specificity. The incorporation of distribution information for classification additionally led to the identification of a singular temporal-based bio-optical attribute capable of highly accurate patient classification. To the best of our knowledge, this is the first report of a machine learning approach using the intra-patient probability distribution information of bio-optical attributes obtained from digital holographic microscopy for disease screening.

COVID-19 detection from red blood cells using highly comparative time-series analysis (HCTSA) in digital holographic microscopy.

We present an automated method for COVID-19 screening based on reconstructed phase profiles of red blood cells (RBCs) and a highly comparative time-series analysis (HCTSA). Video digital holographic data -was obtained using a compact, field-portable shearing microscope to capture the temporal fluctuations and spatio-temporal dynamics of live RBCs. After numerical reconstruction of the digital holographic data, the optical volume is calculated at each timeframe of the reconstructed data to produce a time-series signal for each cell in our dataset. Over 6000 features are extracted on the time-varying optical volume sequences using the HCTSA to quantify the spatio-temporal behavior of the RBCs, then a linear support vector machine is used for classification of individual RBCs. Human subjects are then classified for COVID-19 based on the consensus of their cells' classifications. The proposed method is tested on a dataset of 1472 RBCs from 24 human subjects (10 COVID-19 positive, 14 healthy) collected at UConn Health Center. Following a cross-validation procedure, our system achieves 82.13% accuracy, with 92.72% sensitivity, and 73.21% specificity (area under the receiver operating characteristic curve: 0.8357). Furthermore, the proposed system resulted in 21 out of 24 human subjects correctly labeled. To the best of our knowledge this is the first report of a highly comparative time-series analysis using digital holographic microscopy data.

Digital holographic deep learning of red blood cells for field-portable, rapid COVID-19 screening.

Rapid screening of red blood cells for active infection of COVID-19 is presented using a compact and field-portable, 3D-printed shearing digital holographic microscope. Video holograms of thin blood smears are recorded, individual red blood cells are segmented for feature extraction, then a bi-directional long short-term memory network is used to classify between healthy and COVID positive red blood cells based on their spatiotemporal behavior. Individuals are then classified based on the simple majority of their cells' classifications. The proposed system may be beneficial for under-resourced healthcare systems. To the best of our knowledge, this is the first report of digital holographic microscopy for rapid screening of COVID-19.