Methods

This prospective study was approved by Institutional Ethics Committee of Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) and informed consent was obtained from all participants. Patients diagnosed to be having MCI (10), and AD (10) at the decade old well-established Dementia Clinic at SCTIMST were included in the study. Ten cognitively normal elderly control volunteers were recruited from the local population through advertisements. All participants underwent detailed clinical, neurological and neuropsychological evaluation and had no contraindications to MRI scanning. MRI scans were acquired in each subject using a 3T whole-body scanner (GE, 750W Discovery) with a 32 channel phased array head coil. MRI gradient echo images for QSM reconstruction and calculation of OEF were acquired with the same spoiled 3D multi-echo gradient-echo sequence with five equally spaced echoes (TR/TE1/FA = 62.1 ms/20 ms/15, matrix = 512 x 512, slice thickness = 2 mm, slices = 70, acquisition time = 6:29 minutes). A T1-weighted BRAVO sequence (TR/TE/FA = 7.9 ms/3 ms/12°, acquisition time = 4:26 minutes) with 1 mm isotropic spatial resolution was used for evaluating grey matter volume changes. QSM images were reconstructed retrospectively from the SWAN data by implementing the Morphology Enabled Dipole Inversion (MEDI) method. Initially, the brightness and contrast of the images were adjusted and zoomed by factor of two to avoid partial volume effects. The region interest measures of iron changes in QSM data were extracted bilaterally from caudate, putamen, globus pallidus, thalamus, hippocampus, precuneus, and posterior cingulate (Figure 1). The susceptibility measurements of four candidate veins namely posterior superior sagittal sinus, posterior cortical vein, internal cerebral veins and straight sinus were performed using QSM map (Figure 2). Also, a mean and standard deviation of susceptibility from a reference region, was also measured from the Cerebrospinal fluid of the third ventricle. Oxygen extraction fraction (OEF) was obtained using the relation where Δχdo is the magnetic susceptibility difference between fully deoxygenated (we used 4.π.0.18 ppm) and fully oxygenated blood and Hct (we used 0.45) is the blood haematocrit. Then the oxygen extraction (OEF) can be obtained by the relation OEF= 1- Yv under usual conditions at which Ya ≈100%. Statistical analysis of entire data was performed using SPSS software with significance set at P<0.05.

Results and Discussion

Both MCI and AD had elevated susceptibility values within the anterior cingulate, precuneus, posterior cingulate and hippocampus (Table 2). The OEF was decreased in the internal cerebral vein, posterior cortical vein and vein of Galen in AD compared to controls. While the OEF in the posterior sagittal sinus, straight sinus and transverse sagittal sinus was increased in both patient groups in comparison to controls (Table 1). However, the OEF values failed to reveal any correlation with susceptibility values. The increased OEF findings are consistent with the capillary dysfunction hypothesis of AD; increased capillary dysfunction leads to increased oxygen extraction in order to compensate the metabolic requirements of the brain tissues. Although none of these parameters were statistically significant, they showed a trend towards differentiation of MCI and AD from controls in this pilot study. Future studies are required to validate the usefulness of this technique as potential biomarker.

Acknowledgements

This study was supported by funds from Science and Engineering Research Board (SERB) to S.R in the form of National postdoctoral fellowship (N-PDF).