A phantom system for assessing the effects of membrane lipids on water proton relaxation

Quantitative MRI (qMRI) is a method for the non-invasive study of brain-structure-associated changes expressed with measurable units. The qMRI-derived parameters have been shown to reflect brain tissue composition such as myelin content. Nevertheless, it remains a major challenge to identify and quantify the contributions of specific molecular components to the MRI signal. Here, we describe a phantom system that can be used to evaluate the contribution of membrane lipids to qMRI-derived parameters. We used a hydration-dehydration dry film technique to formulate liposomes that can be used as a model of the bilayer lipid membrane. The liposomes were comprised of the most abundant types of lipid found in the human brain. We then applied clinically available qMRI techniques with adjusted bias corrections in order to test the ability of the phantom system to estimate multiple qMRI parameters such as proton density (PD), T₁ , T₂ , T₂ * and magnetization transfer. In addition, we accurately measured the phantom sample water fraction (normalized PD). A similar protocol was also applied to the human brain in vivo. The phantom system allows for a reliable estimation of qMRI parameters for phantoms composed of various lipid types using a clinical MRI scanner. We also found a comparable reproducibility between the phantom and in vivo human brain qMRI estimations. To conclude, we have successfully created a biologically relevant liposome phantom system whose lipid composition can be fully controlled. Our lipid system and analysis can be used to measure the contributions to qMRI parameters of membrane lipids found in the human brain under scanning conditions that are relevant to in vivo human brain scans. Such a model system can be used to test the contributions of lipidomic changes in normal and pathological brain states.