Exploiting Fast-Field-Cycling NMR Relaxometry to Differentiate Sickle Cell Hemoglobin from Hemoglobin A

Abstract Hemoglobin S (HbS) is the primary protein within the red blood cells of patients suffering from sickle cell anemia (SCA). SCA is a serious blood disorder that can lead to widespread organ damage and even death. Current diagnostic tests have their limits, whether it is due to cost, reliability, time constraints, staffing, or ability to distinguish between different cell types. In the search for better alternatives, many new techniques are being explored. This study investigates fast-field-cycling NMR (FFC NMR) relaxometry as a low magnetic field alternative for distinguishing HbS from healthy hemoglobin A (HbA). Five blood samples from healthy individuals and two samples from patients with sickle cell disease (SCD) were processed by classical methods. Each HbA and HbS sample was subjected to repeated measurements of the frequency-dependent relaxation rate $${R}_{1}\left(f\right)$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mi>R</mml:mi> <mml:mn>1</mml:mn> </mml:msub> <mml:mfenced> <mml:mi>f</mml:mi> </mml:mfenced> </mml:mrow> </mml:math> . Each NMR dispersion (NMRD) profile was analyzed using the 3-Tau Model (3TM) providing seven physically meaningful fit parameters per sample. The 3TM analysis of NMRD profiles allows HbA and HbS to be clearly distinguished. The surface water dynamic time constant $${\tau }_{l}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mi>τ</mml:mi> <mml:mi>l</mml:mi> </mml:msub> </mml:math> and desorption time constant $${\tau }_{d}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mi>τ</mml:mi> <mml:mi>d</mml:mi> </mml:msub> </mml:math> for HbS were found to be approximately half those for HbA. The bulk water dynamic correlation time $${\tau }_{b}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mi>τ</mml:mi> <mml:mi>b</mml:mi> </mml:msub> </mml:math> was found to be linked to HbS polymerization and directly related to viscosity. The Fe(III) content was important for defining the shape and form of the NMRD profiles. Protein dynamics do not contribute significantly to NMRD profiles. The FFC NMR approach with 3TM analysis shows promise as a diagnostic technique for SCD.