Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

Abstract

Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.

Measurements of morphological and biophysical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson's disease

“…Based on the principle of holography, QPI techniques exploits the refractive index (RI) distribution of optical contrasts to provide quantitative and label-free images of live cells and tissues. QPI techniques have been applied to study the pathophysiology of various biological samples, including hematology (10), malaria infection (11,12), sickle cell diseases (13)(14)(15)(16), and microbiology (17,18). In particular, 2D QPI techniques or digital holographic microscopy techniques had been utilized for the study of biophysics of neuron cells (19,20) and for imaging alterations in brain tissue slices caused by Alzheimer's disease (21).…”

Measurements of morphological and biochemical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson’s disease

“…Based on the principle of holography, QPI techniques provides quantitative and label-free images of live cells and tissues, exploiting the refractive index (RI) distribution of optical contrasts. QPI techniques have been applied to study the pathophysiology of various biological samples, including haematology 10 , malaria infection 11, 12 , sickle cell diseases 13 – 16 , and microbiology 17, 18 . In particular, 2-D QPI techniques or digital holographic microscopy techniques had been utilized for the study of biophysics of neuron cells 19, 20 and for imaging alterations in brain tissue slices caused by Alzheimer’s disease 21 .…”

Tomographic phase microscopy: principles and applications in bioimaging [Invited]

“…The properties of Hb are sensitive to subtle alterations of pathological states of RBCs resulting from infectious diseases and genetic disorders, e.g., malaria and sickle cell diseases [118,119]. To quantify Hb, mean corpuscular Hb concentration (MCHC) and mean corpuscular Hb content (MCH) are being used for medical diagnosis on a daily basis in medical laboratories [120].…”