Investigating Parkinson’s disease using rotating frame MRI

Introduction In our previous study performed at 4T on individuals with Parkinson’s Disease (PD) and age-matched controls we have demonstrated that rotating frame relaxation methods employing so-called adiabatic HS1 pulses are capable to separate PD from control subjects based on the values of adiabatic relaxation times in the substantia nigra (SN) [1]. With the goal of investigating the physiological origin of these findings, another previous study from our group demonstrated that adiabatic T1ρ can ascertain cellular loss in in the substantia nigra of an animal model missing dopaminergic neurons [2]. On the other hand, the physiological basis for considering T2ρ as a possible biomarker of PD relies on the facts that T2ρ is likely sensitive to iron content, and that ferritin concentration (iron storage) is hypothesized to correlate with disease progression. Based on these observations, a methodology that could combine T1ρ and T2ρ relaxation mechanisms is anticipated to offer improved sensitivity for characterizing PD. Recently, our group has developed a novel rotating frame relaxation method which operates in sub-adiabatic regime, entitled RAFF (relaxation along a fictitious field) [3]. RAFF utilizes frequency swept pulses with sine and cosine modulation functions. When sweeping frequency sub-adiabatically, the vector sum of dα/dt (here α is the angle between ωeff and the Z’ axis of the rotating frame of reference) and ωeff leads to the so-called fictitious filed, E. The angle ε between E and ωeff is chosen to satisfy ωeff =dα/dt, and thus RAFF measurements include both T1ρ and T2ρ relaxations. In the present work we employed RAFF to studying PD subjects, and compared these relaxation measurements with adiabatic T1ρ and T2ρ acquired with different modulation functions (HS1 vs HS4, which are supposed to generate MR contrast [4,5]) and conventional spin-lock (SL) T1ρ methods. The general goal is not only to explore the sensitivity of a variety of rotating frame relaxation measurements to characterize the SN of PD, but also to provide a set of measurements which can be used to extract intrinsic parameters of the tissue based on modeling of the relaxation mechanisms [4,5]. As an initial step for addressing the contribution of relevant relaxation pathways in the SN, we finally acquired adiabatic T1,2ρ from two samples with different concentration of ferritin.