Biology subjects

Islamzada, E.

Publications and source records attributed to Islamzada, E..

5 recordsLinked to original sources

bioRxiv2024

Biophysical Profiling of Red Blood Cells from Thin-film Blood Smears using Deep Learning

Microscopic inspection of thin-film blood smears is widely used to identify red blood cell (RBC) pathologies, including malaria parasitism and hemoglobinopathies, such as sickle cell disease and thalassemia. Emerging research indicates that non-pathologic changes in RBCs can also be detected in images, such as deformability and morphological changes resulting from the storage lesion. In transfusion medicine, cell deformability is a potential biomarker for the quality of donated RBCs. However, a major impediment to the clinical translation of this biomarker is the difficulty associated with performing this measurement. To address this challenge, we developed an approach for biophysical profiling of RBCs based on cell images in thin-film blood smears. We hypothesize that subtle cellular changes are evident in blood smear images, but this information is currently undetectable by human cognition. To test this hypothesis, we developed a deep learning strategy to analyze Giemsa-stained blood smears to assess the subtle morphologies indicative of RBC deformability and storage-based degradation. Specifically, we prepared thin-film blood smears from 27 RBC samples (9 donors evaluated at 3 storage timepoints) and imaged them using high-resolution microscopy. Using this dataset, we trained a convolutional neural network to evaluate image-based morphological features related to cell deformability. The prediction of donor deformability is strongly correlated to the microfluidic scores and can be used to categorize images into specific deformability groups with high accuracy. We also used this model to evaluates differences in RBC morphology resulting from cold storage. Together, our results demonstrate that deep learning models can exceed the limits of human cognition to detect subtle cellular differences in morphology resulting from deformability and cold storage. This result suggests the potential to assess donor blood quality from thin-film blood smears, which can be acquired ubiquitously in clinical workflows.

bioengineering↗

bioRxiv2021

Deep Learning Image Classification of Red Blood Cell Deformability

Red blood cells (RBCs) must be highly deformable to transit through the microvasculature to deliver oxygen to tissues. The loss of RBC deformability resulting from pathology, natural aging, or storage in blood bags can impede the proper function of these cells. A variety of methods have been developed to measure RBC deformability, but these methods require specialized equipment, long measurement time, and highly skilled personnel. To address this challenge, we investigated whether a machine learning approach could be applied to determine donor RBC deformability using single cell microscope images. We used the microfluidic ratchet device to sort RBCs based on deformability. Sorted cells are then imaged and used to train a deep learning model to classify RBCs based on deformability. This model correctly predicted deformability of individual RBCs with 84 {+/-} 11% accuracy averaged across ten donors. Using this model to score the deformability of RBC samples were accurate to within 4.4 {+/-} 2.5% of the value obtained using the microfluidic ratchet device. While machine learning methods are frequently developed to automate human image analysis, our study is remarkable in showing that deep learning of single cell microscopy images could be used to measure RBC deformability, a property not normally measurable by imaging. Measuring RBC deformability by imaging is also desirable because it can be performed rapidly using a standard microscopy system, potentially enabling RBC deformability studies to be performed as part of routine clinical assessments.

bioengineering↗

bioRxiv2021

Degradation of Red Blood Cell Deformability during Cold Storage in Blood Bags

Red blood cells (RBCs) stored in blood bags develop a storage lesion that include structural, metabolic, and morphologic transformations resulting in a progressive loss of RBC deformability. The speed of RBC deformability loss is donor-dependent, which if properly characterized, could be used as a biomarker to select high-quality RBC units for sensitive recipients or to provide customized storage timelines depending on the donor. We used the microfluidic ratchet device to measure the deformability of red blood cells stored in blood bags every 14 days over a span of 56 days. We observed that storage in blood bags generally prevented RBC deformability loss over the current standard 42-day storage window. However, between 42 and 56 days, the deformability loss profile varied dramatically between donors. In particular, we observed accelerated RBC deformability loss for a majority of male donors, but for none of the female donors. Together, our results suggest that RBC deformability loss could be used to screen for donors who can provide stable RBCs for sensitive transfusion recipients or to identify donors capable of providing RBCs that could be stored for longer than the current 42-day expiration window.

bioengineering↗

bioRxiv2021

Blood Unit Segments Accurately Represent the Biophysical Properties of Red Blood Cells in Blood Bags but Not Hemolysis

BACKGROUNDThe biophysical properties of red blood cells (RBCs) provide potential biomarkers for the quality of donated blood. Blood unit segments provide a simple and nondestructive way to sample RBCs in clinical studies of transfusion efficacy, but it is not known whether RBCs sampled from segments accurately represent the biophysical properties of RBCs in blood bags. STUDY DESIGN AND METHODSRBCs were sampled from blood bags and segments every two weeks during 8 weeks of storage at 4 {degrees}C. RBC deformability was measured by deformabilitybased sorting using the microfluidic ratchet device in order to derive a rigidity score. Standard hematological parameters, including mean corpuscular volume (MCV), red cell distribution width (RDW), mean cell hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and hemolysis were measured at the same time points. RESULTSDeformability of RBCs stored in blood bags was retained over 4 weeks storage but a progressive loss of deformability was observed at weeks 6 and 8. This trend was mirrored in blood unit segments with a strong correlation to the blood bag data. Strong correlations were also observed between blood bag and segment for MCV, MCHC and MCH, but not for hemolysis. CONCLUSIONRBCs sampled from blood unit segments accurately represents the biophysical properties of RBCs in blood bags, but not hemolysis. Blood unit segments provide a simple and non-destructive sample for measuring RBC biophysical properties in clinical studies.

bioengineering↗

bioRxiv2019

Deformability based sorting of stored red blood cells reveals donor-dependent aging curves

A fundamental challenge in the transfusion of red blood cells (RBCs) is that a subset of donated RBC units may not provide optimal benefit to transfusion recipients. This variability stems from the inherent ability of donor RBCs to withstand the physical and chemical insults of cold storage, which ultimately dictate their survival in circulation. The loss of RBC deformability during cold storage is well-established and has been identified as a potential biomarker for the quality of donated RBCs. While RBC deformability has traditionally been indirectly inferred from rheological characteristics of the bulk suspension, there has been considerable interest in directly measuring the deformation of RBCs. Microfluidic technologies have enabled single cell measurement of RBC deformation but have not been able to consistently distinguish differences between RBCs between healthy donors. Using the microfluidic ratchet mechanism, we developed a method to sensitively and consistently analyze RBC deformability. We found that the aging curve of RBC deformability varies significantly across donors, but is consistent for each donor over multiple donations. Specifically, certain donors seem capable of providing RBCs that maintain their deformability during two weeks of cold storage in standard test tubes. The ability to distinguish between RBC units with different storage potential could provide a valuable opportunity to identify donors capable of providing RBCs that maintain their integrity, in order to reserve these units for sensitive transfusion recipients.

bioengineering↗