Magnetization transfer (MT) imaging has been widely used for estimating myelin content in the brain. Recently, two other approaches, namely simultaneous tissue relaxometry of R1 and R2 relaxation rates and proton density (SyMRI) and the ratio of T1-weighted to T2-weighted images (T1w/T2w ratio), were also proposed as methods for measuring myelin. SyMRI and MT imaging have been reported to correlate well with actual myelin by histology. However, for T1w/T2w ratio, such evidence is limited. In 20 healthy adults, we examined the correlation between these three methods, using MT saturation index (MTsat) for MT imaging. After calibration, white matter (WM) to gray matter (GM) contrast was the highest for SyMRI among these three metrics. Even though SyMRI and MTsat showed strong correlation in the WM (r = 0.72), only weak correlation was found between T1w/T2w and SyMRI (r = 0.45) or MTsat (r = 0.38) (correlation coefficients significantly different from each other, with p values < 0.001). In subcortical and cortical GM, these measurements showed moderate to strong correlations to each other (r = 0.54 to 0.78). In conclusion, the high correlation between SyMRI and MTsat indicates that both methods are similarly suited to measure myelin in the WM, whereas T1w/T2w ratio may be less optimal.

Conventional magnetic resonance images are usually evaluated using the image signal contrast between tissues and not based on their absolute signal intensities. Quantification of tissue parameters, such as relaxation rates and proton density, would provide an absolute scale; however, these methods have mainly been performed in a research setting. The development of rapid quantification, with scan times in the order of 6 minutes for full head coverage, has provided the prerequisites for clinical use. The aim of this review article was to introduce a specific quantification method and synthesis of contrast-weighted images based on the acquired absolute values, and to present automatic segmentation of brain tissues and measurement of myelin based on the quantitative values, along with application of these techniques to various brain diseases. The entire technique is referred to as “SyMRI” in this review. SyMRI has shown promising results in previous studies when used for multiple sclerosis, brain metastases, Sturge-Weber syndrome, idiopathic normal pressure hydrocephalus, meningitis, and postmortem imaging.

Background and Objectives:The glymphatic system is a whole-brain perivascular network, which promotes CSF/interstitial fluid exchange. Alterations to this system may play a pivotal role in amyloid β (Aβ) accumulation. However, its involvement in Alzheimer’s disease (AD) pathogenesis is not fully understood. Here, we investigated the changes in noninvasive MRI measurements related to the perivascular network in patients with mild cognitive impairment (MCI) and AD. Additionally, we explored the associations of MRI measures with neuropsychological score, PET standardized uptake value ratio (SUVR), and Aβ deposition.Methods:MRI measures, including perivascular space (PVS) volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM), and index of diffusivity along the perivascular space (ALPS index) of patients with MCI, those with AD, and healthy controls from the Alzheimer’s Disease Neuroimaging Initiative database were compared. MRI measures were also correlated with the levels of CSF biomarkers, PET SUVR, and cognitive score in the combined subcohort of patients with MCI and AD. Statistical analyses were performed with age, sex, years of education, and APOE status as confounding factors.Results:In total, 36 patients with AD, 44 patients with MCI, and 31 healthy controls were analyzed. Patients with AD had significantly higher total, WM, and basal ganglia PVSVF (Cohen’s d = 1.15-1.48; p < 0.001), and FW-WM (Cohen’s d = 0.73; p < 0.05) and a lower ALPS index (Cohen’s d = 0.63; p < 0.05) than healthy controls. Meanwhile, the MCI group only showed significantly higher total (Cohen’s d = 0.99; p < 0.05) and WM (Cohen’s d = 0.91; p < 0.05) PVSVF. Low ALPS index was associated with lower CSF Aβ42 (rs = 0.41, pfdr = 0.026), FDG-PET uptake (rs = 0.54, pfdr < 0.001), and worse multiple cognitive domain deficits. High FW-WM was also associated with lower CSF Aβ42 (rs = −0.47, pfdr = 0.021) and worse cognitive performances.Conclusion:Our study indicates that changes in PVS-related MRI parameters occur in MCI and AD, possibly due to impairment of the glymphatic system. We also report the associations between MRI parameters and Aβ deposition, neuronal change, and cognitive impairment in AD.