The Neurochemical and Microstructural Changes in the Brain of Systemic Lupus Erythematosus Patients: A Multimodal MRI Study

Abstract

The diagnosis and pathology of neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging. Herein, we used multimodal imaging to assess anatomical and functional changes in brains of SLE patients instead of a single MRI approach generally used in previous studies. Twenty-two NPSLE patients, 21 non-NPSLE patients and 20 healthy controls (HCs) underwent 3.0 T MRI with multivoxel magnetic resonance spectroscopy, T1-weighted volumetric images for voxel based morphometry (VBM) and diffusional kurtosis imaging (DKI) scans. While there were findings in other basal ganglia regions, the most consistent findings were observed in the posterior cingulate gyrus (PCG). The reduction of multiple metabolite concentration was observed in the PCG in the two patient groups, and the NPSLE patients were more prominent. The two patient groups displayed lower diffusional kurtosis (MK) values in the bilateral PCG compared with HCs (p < 0.01) as assessed by DKI. Grey matter reduction in the PCG was observed in the NPSLE group using VBM. Positive correlations among cognitive function scores and imaging metrics in bilateral PCG were detected. Multimodal imaging is useful for evaluating SLE subjects and potentially determining disease pathology. Impairments of cognitive function in SLE patients may be interpreted by metabolic and microstructural changes in the PCG.

Figure 1

(A) Axial view of basal ganglia slice showing the volumes of interest for multivoxel MRS. (B–D) Examples of attained spectra of the RPCG by LCModel evaluation of metabolite values: (B) HC, (C) non-NPSLE patient and (D) NPSLE patient. We found NAA decreased significantly in NPSLE patients (p < 0.01), followed by non-NPSLE patients (p > 0.05), while tCr levels decreased in NPSLE (p < 0.01) and non-NPSLE patients (p < 0.01) compared with HC. Abbreviations: MRS = magnetic resonance spectroscopy; NPSLE = neuropsychiatric systemic lupus erythematosus; HC = healthy control; RPCG = right posterior cingulate gyrus; NAA = N-acetylaspartate; Cho = choline; tCr = total creatine; MI = myoinositol; Glx = glutamine + glutamate.

Figure 2. MK values in 8 brain regions in 3 groups.

We found that NPSLE and non-NPSLE groups had significantly lower MK values in bilateral PCG (p < 0.01) and LDT (p < 0.05) compared with the HC group, while the two patient groups did not show differences. ^*Statistically significant. Abbreviations: MK = diffusional kurtosis; NPSLE = neuropsychiatric systemic lupus erythematosus; HC = healthy control; PCG = posterior cingulate gyrus; DT = dorsal thalamus; LN = lentiform nucleus; PWM = posterior paratrigonal white matter.

Figure 3. Decreased GM volume in NPSLE patients compared with non-NPSLE patients and HCs.

Red and yellow designate differences in GM volume that were statistically significant at p < 0.05 after correction for multiple comparisons. (A) Coronal, sagittal and axial views of regions with decreased GM in NPSLE patients compared with HCs. (B) Coronal, sagittal and axial views of regions with decreased GM in NPSLE patients compared with non-NPSLE patients. (C) Axial sections showing details of regions with GM decreases in NPSLE patients. Differences between the HCs and NPSLE patients are shown in red; differences between the non-NPSLE and NPSLE patients are shown in yellow. The figure shows that NPSLE patients had decreased GM volume in the limbic cortex, bilateral frontal lobe, temporal lobe, occipital lobe and right thalamus compared with non-NPSLE patients and HCs. Abbreviations: NPSLE = neuropsychiatric systemic lupus erythematosus; HC = healthy control; PCG = posterior cingulate gyrus; GM = grey matter.

Figure 4. Correlations between imaging metrics and cognitive function scores.

The positive correlations between MoCA scores and MK values in RPCG (A) and LPCG (B). The positive correlations between MMSE scores and MK values in RPCG (C). Abbreviations: PCG = posterior cingulate gyrus; MMSE = Mini-mental State examination; MoCA = Montreal Cognitive Assessment; NAA = N-acetylaspartate; MK = diffusional kurtosis.

Figure 5. Images of volumes of interest of the bilateral PCG, DT, LN and PWM are depicted in pictures (A,B) for DKI.

Abbreviations: DKI = diffusional kurtosis imaging; PCG = posterior cingulate gyrus; DT = dorsal thalamus; LN = lentiform nucleus; PWM = posterior paratrigonal white matter.