Quantitative MRI Protocol Optimisation Using Mathematical Concentration-Response Modelling of Fe?O? Nanoparticles at 1.5 Tesla: An OFAT Framework

Haydar Abdulkadeer Taheer Al-Shimmari
Department of Radiological Techniques, College of Health and Medical Techniques/Baghdad, Middle Technical University, 10047 Bab Al Muadham, Baghdad, Iraq

Ab Hamid Suzana
Department of Radiology and Imaging, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Subapriya Suppiah
Department of Radiology and Imaging, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Duha A. Kadhim
Department of Physics, College of Science, Al-Mustansiriyah University, Baghdad- Iraq

Muslim A. Abid
Department of Physics, College of Science, Al-Mustansiriyah University, Baghdad- Iraq

Muhammed Mizher Radhi
Department of Radiological Techniques, College of Health and Medical Techniques/Baghdad, Middle Technical University, 10047 Bab Al Muadham, Baghdad, Iraq

Mohanad Raad Hameed
Al-Bahja trading Company/ Philips healthcare exclusive representative

Abstract

Background: Gadolinium-based contrast agents present safety concerns including tissue deposition and nephrogenic systemic fibrosis. Iron oxide nanoparticles (IONPs) represent a promising alternative, but no systematically derived, statistically validated MRI acquisition protocol exists for IONP contrast agents at clinical field strengths. This study addresses that gap by constructing a stepwise quantitative MRI optimisation framework through a controlled in vivo one-factor-at-a-time (OFAT) protocol at 1.5 Tesla.

Methods: Green-synthesised Fe?O? SPIONs (core diameter 10.2±3.8 nm; Ms=32 emu/g; Mr/Ms=0.019) were administered intravenously to New Zealand White rabbits (n=60; IACUC MTU/074) across three studies. Study 1 (n=40; four groups) characterised T1 and T2 signal behaviour at 0.00716, 0.01432, and 0.02148 M versus saline control. Two mathematical models were fitted: a quadratic model for T1 [?SI%(T1)=??·[C]+??·[C]²] and a power model for T2 [?SI%(T2)=??·[C]?]. Study 2 applied OFAT optimisation of sequence (TSE vs FFE), repetition time (TR), echo time (TE), and flip angle (FA). Study 3 benchmarked the optimised protocol against gadolinium (Magnevist®). Statistics: ANOVA, post-hoc LSD, ?², Pearson r, t-test (SPSS v25.0).

Results: T1 quadratic model: R²=0.9952 [?SI%(T1)=178.6·[C]+63,447·[C]²]. T2 power model: R²=0.9951 [?SI%(T2)=?163,807·[C]^{2.368}]. T1/T2 dominance ratio peaked at 0.01432 M (D=2.55). ANOVA: ?²=0.661 (T1); p<0.001. OFAT: TSE>FFE (p<0.05); TR 500 ms (p<0.05); TE boundary at 5 ms (?²=0.968); FA 90° (?²=0.723; p<0.001). IONP ?SI%=+30.28% vs gadolinium +40.47% (p<0.001; ?²=0.267).

Conclusions: Two empirical models characterise T1 and T2 concentration-response. The OFAT-derived optimisation strategy defines a five-level acquisition protocol (TSE; TR 500 ms; TE 5 ms; FA 90°; min. effective dose 0.01432 M) applicable to green-synthesised Fe?O? contrast agents at 1.5 Tesla.

Keywords: Iron Oxide Nanoparticles ,Optimisation ,Ofat; Concentration-Response ,Quadratic Model ,Power Model ,T1/T2 Dominance Ratio ,1.5 Tesla ,Gadolinium ,Pearson Correlation