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Relaxometric studies of erythrocyte suspensions infected by Plasmodium falciparum: a tool for staging infection and testing anti-malarial drugs
- Publication Year :
- 2020
-
Abstract
- Purpose Malaria is a global health problem with the most malignant form caused by Plasmodium falciparum (P. falciparum). Parasite maturation in red blood cells (RBCs) is accompanied by changes including the formation of paramagnetic hemozoin (HZ) nanocrystals, and increased metabolism and variation in membrane lipid composition. Herein, MR relaxometry (MRR) was applied to investigate water exchange across RBCs' membrane and HZ formation in parasitized RBCs. Methods Transverse water protons relaxation rate constants (R2 = 1/T2 ) were measured for assessing HZ formation in P. falciparum-parasitized human RBCs. Moreover, water exchange lifetimes across the RBC membrane (τi ) were assessed by measuring longitudinal relaxation rate constants (R1 = 1/T1 ) at 21.5 MHz in the presence of a gadolinium complex dissolved in the suspension medium. Results τi increased after invasion of parasites (ring stage, mean τi / τ i 0 = 1.234 ± 0.022) and decreased during maturation to late trophozoite (mean τi / τ i 0 = 0.960 ± 0.075) and schizont stages (mean τi / τ i 0 = 1.019 ± 0.065). The HZ accumulation in advanced stages was revealed by T2 -shortening. The curves reporting R2 (1/T2 ) vs. magnetic field showed different slopes for non-parasitized RBCs (npRBCs) and parasitized RBCs (pRBCs), namely 0.003 ± 0.001 for npRBCs, 0.009 ± 0.002, 0.028 ± 0.004 and 0.055 ± 0.002 for pRBCs at ring-, early trophozoite-, and late trophozoite stage, respectively. Antimalarial molecules dihydroartemisinin and chloroquine elicited measurable changes in parasitized RBCs, namely dihydroartemisinin modified τi , whereas the interference of chloroquine with HZ formation was detectable by a significant T2 increase. Conclusions MRR can be considered a useful tool for reporting on P. falciparum blood stages and for screening potential antimalarial molecules.
- Subjects :
- Anti malarial
Erythrocytes
medicine.medical_treatment
Plasmodium falciparum
Dihydroartemisinin
Water exchange
Red blood cells
water permeability
030218 nuclear medicine & medical imaging
Gd-complex
Magnetic Resonance Relaxometry
Malaria
chloroquine
dihydroartemisinin
hemozoin
water exchange rate
03 medical and health sciences
Antimalarials
0302 clinical medicine
Suspensions
Chloroquine
parasitic diseases
medicine
Humans
Radiology, Nuclear Medicine and imaging
Malaria, Falciparum
biology
Chemistry
Hemozoin
Advanced stage
Metabolism
biology.organism_classification
Molecular biology
3. Good health
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1b0a1bf536930ac15998880bc8402339