Di Gregorio Enza, Ferrauto Giuseppe, Schwarzer Evelin, Gianolio Eliana, Valente Elena, Ulliers Daniela, Aime Silvio, Skorokhod Oleksii
Molecular Imaging Center, Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
Department of Oncology, University of Torino, Torino, Italy.
Magn Reson Med. 2020 Dec;84(6):3366-3378. doi: 10.1002/mrm.28387. Epub 2020 Jun 30.
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.
Transverse water protons relaxation rate constants (R = 1/T ) were measured for assessing HZ formation in P. falciparum-parasitized human RBCs. Moreover, water exchange lifetimes across the RBC membrane (τ ) were assessed by measuring longitudinal relaxation rate constants (R = 1/T ) at 21.5 MHz in the presence of a gadolinium complex dissolved in the suspension medium.
τ increased after invasion of parasites (ring stage, mean τ / = 1.234 ± 0.022) and decreased during maturation to late trophozoite (mean τ / = 0.960 ± 0.075) and schizont stages (mean τ / = 1.019 ± 0.065). The HZ accumulation in advanced stages was revealed by T -shortening. The curves reporting R (1/T ) 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 τ , whereas the interference of chloroquine with HZ formation was detectable by a significant T increase.
MRR can be considered a useful tool for reporting on P. falciparum blood stages and for screening potential antimalarial molecules.
疟疾是一个全球性的健康问题，其中最恶性的形式由恶性疟原虫（P. falciparum）引起。疟原虫在红细胞（RBC）内成熟的过程伴随着一系列变化，包括顺磁性疟色素（HZ）纳米晶体的形成、代谢增加以及膜脂质成分的改变。在此，采用磁共振弛豫测量法（MRR）来研究寄生红细胞膜上的水交换以及HZ的形成。
通过测量横向水质子弛豫速率常数（R = 1/T ）来评估恶性疟原虫寄生的人类红细胞中HZ的形成。此外，在悬浮介质中溶解钆配合物的情况下，通过在21.5 MHz下测量纵向弛豫速率常数（R = 1/T ）来评估跨红细胞膜的水交换寿命（τ ）。
寄生虫入侵后（环状体阶段，平均τ /= 1.234 ± 0.022）τ 增加，在成熟至晚期滋养体（平均τ /= 0.960 ± 0.075）和裂殖体阶段（平均τ /= 1.019 ± 0.065）时τ 降低。T 缩短揭示了晚期阶段HZ的积累。报告R（1/T ）与磁场关系的曲线显示，未寄生红细胞（npRBCs）和寄生红细胞（pRBCs）的斜率不同，即npRBCs为0.003 ± 0.001，pRBCs在环状体、早期滋养体和晚期滋养体阶段分别为0.009 ± 0.002、0.028 ± 0.004和0.055 ± 0.002。抗疟分子双氢青蒿素和氯喹在寄生红细胞中引起了可测量的变化，即双氢青蒿素改变了τ ，而氯喹对HZ形成的干扰可通过显著的T 增加来检测。
MRR可被视为一种用于报告恶性疟原虫血液阶段和筛选潜在抗疟分子的有用工具。
