T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease

Abstract

In the current study, we have evaluated the performance of magnetic resonance (MR) T1rho (T1ρ) imaging and CSF biomarkers (T-tau, P-tau and Aβ-42) in characterization of Alzheimer's disease (AD) patients from mild cognitive impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n = 17) and control (n = 17) subjects underwent a standardized clinical assessment and brain MRI on a 1.5-T clinical-scanner. T1ρ images were obtained at four different spin-lock pulse duration (10, 20, 30 and 40 ms). T1ρ maps were generated by pixel-wise fitting of signal intensity as a function of the spin-lock pulse duration. T1ρ values from gray matter (GM) and white matter (WM) of medial temporal lobe were calculated. The binary logistic regression using T1ρ and CSF biomarkers as variables was performed to classify each group. T1ρ was able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8% controls and 46.7% MCI. T1ρ and CSF biomarkers in combination predicted 86.4% controls and 66.7% MCI. When comparing controls with AD, T1ρ predicted 68.2% controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3% for AD. Combination of T1ρ and CSF biomarkers improved the prediction rate to 81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1ρ predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and 83.0% AD. Collectively CSF biomarkers and T1ρ were able to predict 59.3% MCI and 84.6% AD. On receiver operating characteristic analysis T1ρ showed higher sensitivity while CSF biomarkers showed greater specificity in delineating MCI and AD from controls. No significant correlation between T1ρ and CSF biomarkers, between T1ρ and age, and between CSF biomarkers and age was observed. The combined use of T1ρ and CSF biomarkers have promise to improve the early and specific diagnosis of AD. Furthermore, disease progression form MCI to AD might be easily tracked using these two parameters in combination.

Keywords: AD, Alzheimer's disease; Alzheimer's disease; Aβ1-42, amyloid beta 42; CSF biomarkers; CSF, cerebrospinal fluid; FOV, field of view; GM, gray matter; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; MPRAGE, magnetization prepared rapid acquisition gradient-echo; MRI, magnetic resonance imaging; MTL, medial temporal lobe; Medial temporal lobe; Mild cognitive impairment; PET, positron emission tomography; ROC, receiver operating characteristic.; T-tau, total tau; T1rho; T1ρ, T1rho; TE, echo time; TI, inversion time; TR, repetition time; TSL, total spin lock; WM, white matter.

Fig. 1

T1rho (T_1ρ) contrast from medial temporal lobe overlaid on anatomic fluid attenuated T_1ρ weighted images of control (A), medial cognitive impairment (MCI, B), and Alzheimer's disease (AD, C) patients. A progressive increase in T_1ρ contrast in medial temporal lobe (MTL) region was observed from control to MCI to AD. No T_1ρ contrast from CSF was depicted.

Fig. 2

The error bars show the mean GM and WM T_1ρ values from medial temporal lobe (MTL) in control, MCI and AD. (**) indicates the significance difference (p < 0.05) for the mean T_1ρ values between two groups.

Fig. 3

The scattered maps between age and T_1ρ values for controls, MCI subjects and AD patients show no significant correlations.

Fig. 4

The scattered maps between age and CSF biomarkers show no significant change in the CSF biomarkers with age.

Fig. 5

The scattered maps between T_1ρ values and CSF biomarkers depict no significant correlation in any group.