Quanquan Gu

Automatic Classification of Early Parkinson's Disease with Multi-Modal MR Imaging

Background In recent years, neuroimaging has been increasingly used as an objective method for the diagnosis of Parkinsons disease (PD). Most previous studies were based on invasive imaging modalities or on a single modality which was not an ideal diagnostic tool. In this study, we developed a non-invasive technology intended for use in the diagnosis of early PD by integrating the advantages of various modals. Materials and Methods Nineteen early PD patients and twenty-seven normal volunteers participated in this study. For each subject, we collected resting-state functional magnetic resonance imaging (rsfMRI) and structural images. For the rsfMRI images, we extracted the characteristics at three different levels: ALFF (amplitude of low-frequency fluctuations), ReHo (regional homogeneity) and RFCS (regional functional connectivity strength). For the structural images, we extracted the volume characteristics from the gray matter (GM), the white matter (WM) and the cerebrospinal fluid (CSF). A two-sample t-test was used for the feature selection, and then the remaining features were fused for classification. Finally a classifier for early PD patients and normal control subjects was identified from support vector machine training. The performance of the classifier was evaluated using the leave-one-out cross-validation method. Results Using the proposed methods to classify the data set, good results (accuracy  = 86.96%, sensitivity  = 78.95%, specificity  = 92.59%) were obtained. Conclusions This method demonstrates a promising diagnosis performance by the integration of information from a variety of imaging modalities, and it shows potential for improving the clinical diagnosis and treatment of PD.

Regionally progressive accumulation of iron in Parkinson's disease as measured by quantitative susceptibility mapping.

The progression of Parkinsons disease (PD) seems to vary according to the disease stage, which greatly influences the management of PD patients. However, the underlying mechanism of progression in PD remains unclear. This study was designed to explore the progressive pattern of iron accumulation at different stages in PD patients. Sixty right‐handed PD patients and 40 normal controls were recruited. According to the disease stage, 45 patients with Hoehn–Yahr stage ≤ 2.5 and 15 patients with Hoehn–Yahr stage ≥ 3 were grouped into early‐stage PD (EPD) and late‐stage PD (LPD) groups, respectively. The iron content in the cardinal subcortical nuclei covering the cerebrum, cerebellum and midbrain was measured using quantitative susceptibility mapping (QSM). The substantia nigra pars compacta (SNc) showed significantly increased QSM values in the EPD patients compared with the controls. In the LPD patients, while the SNc continued to show increased QSM values compared with the controls and EPD patients, the regions showing increased QSM values spread to include the substantia nigra pars reticulata (SNr), red nucleus (RN) and globus pallidus (GP). Our data also indicated that iron deposition was more significant in the GP internal segment (GPi) than in the GP external segment. No other regions showed significant changes in QSM values among the groups. Therefore, we were able to confirm a regionally progressive pattern of iron accumulation in the different stages of PD, indicating that iron deposition in the SNc is affected exclusively in the early stages of the disease, while the SNr, RN and GP, and particularly the GPi segment, become involved in advanced stages of the disease. This is a preliminary study providing objective evidence of the iron‐related progression in PD. Copyright

Abnormal amygdala function in Parkinson's disease patients and its relationship to depression.

Depression is a common occurrence in patients with Parkinsons disease (PD). Thus, there may be a common neural mechanism underlying the two diseases. Lewy body accumulation in specific brain areas of PD patients may damage emotion-related functions, leading to depression. Among these areas, the amygdala may present with the earliest to be damaged in PD. However, it is still unclear whether amygdala structural and functional changes are related to depression in PD. We enrolled 19 depressed PD patients, 19 non-depressed PD patients, and 28 normal control subjects. Clinical assessment, including the Unified Parkinsons Disease Rating Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination, was carried out on all the patients. Structural and resting-state functional brain images were also acquired to assess volumetric and functional changes of the amygdala in the patients. Results showed that although there is no significant volume change, left amygdala activity increased in the PD group compared with the normal control group, and it correlated with Hamilton Rating Scale for Depression scores. Furthermore, functional connectivity between the right amygdala and fronto-parietal areas was found to be decreased in the depressed PD patients compared with non-depressed PD patients. These results suggest that abnormal amygdala function may underlie the occurrence of depression in PD.

Disrupted white matter integrity in depressed versus non-depressed Parkinson's disease patients: A tract-based spatial statistics study

Depression is a common occurrence in patients with Parkinsons disease (PD), however, its pathophysiology still remains unclear. With increasing evidence suggesting that depression is a disconnection syndrome, we hypothesized that depression in PD is caused by degenerated fiber connections in the brain. We examined whole brain white matter integrity in 15 depressed PD patients and 15 non-depressed PD patients. All the patients were assessed with the Unified Parkinsons Disease Rating Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination. White matter difference between the two groups and its correlation with disease severity was calculated. In depressed PD patients, decreased fractional anisotropy was found in the left uncinate fasciculus, superior longitudinal fasciculus, anterior thalamic radiation, forceps minor, and the inferior longitudinal fasciculus. Fractional anisotropy in the left deep temporal cortex was negatively correlated with severity of depression (r = -0.671, p = 0.034). Our results suggest that disrupted fiber connections in the anterior part of the left hemisphere may contribute to depression in PD patients.

Influence of regional iron on the motor impairments of Parkinson's disease: A quantitative susceptibility mapping study

Because the roles of striatal‐thalamo‐cortical and cerebello‐thalamo‐cortical circuits in the heterogeneous motor impairments of Parkinsons disease (PD) are becoming recognized, this study was designed to investigate the relationships between regional iron in the cardinal subcortical nuclei in these circuits and the different motor impairments.

Greater Loss of White Matter Integrity in Postural Instability and Gait Difficulty Subtype of Parkinson's Disease

BACKGROUND Patients with the postural instability and gait difficulty (PIGD) subtype of Parkinson disease (PD) are at a higher risk of dysfunction and are less responsive to dopamine replacement therapy. The PIGD subtype was found to largely associate with white matter lesions, but details of the diffusion changes within these lesions have not been fully investigated. Voxel-based analysis for diffusion tensor imaging data is one of the preferred measures to compare diffusion changes in each voxel in any part of the brain. METHODS PD patients with the PIGD (n=12) and non-PIGD subtypes (n=12) were recruited to compare diffusion differences in fractional anisotropy, axial diffusivity, and radial diffusivity with voxel-based analysis. RESULTS Significantly reduced fractional anisotropy in bilateral superior longitudinal fasciculus, bilateral anterior corona radiata, and the left genu of the corpus callosum were shown in the PIGD subtype compared with the non-PIGD subtype. Increased radial diffusivity in the left superior longitudinal fasciculus was found in the PIGD subtype with no statistical differences in axial diffusivity found. CONCLUSIONS Our study confirms previous findings that white matter abnormalities were greater in the PIGD subtype than in the non-PIGD subtype. Additionally, our findings suggested: (1) compared with the non-PIGD subtype, loss of white matter integrity was greater in the PIGD subtype; (2) bilateral superior longitudinal fasciculus may play a critical role in microstructural white matter abnormalities in the PIGD subtype; and (3) reduced white matter integrity in the PIGD subtype could be mainly attributed to demyelination rather than axonal loss.

Cortical abnormalities in Parkinson’s disease patients and relationship to depression: A surface-based morphometry study

Depression is a common occurrence in patients with Parkinsons disease (PD). Brain deficits may be the underlying cause of depression in PD. In the present study, we investigated whether morphometric alterations contribute to depression in PD. Seventeen depressed PD patients, 17 non-depressed PD patients and 45 normal controls were enrolled in the study. All subjects went through neurological and psychiatric clinical assessments. T1 weighted magnetic resonance imaging and surface-based morphometric analyses were performed to examine morphometric abnormalities in PD patients and their relationship to depression. We found that compared with normal controls, PD patients exhibited significantly decreased cortical thickness in the left precentral gyrus and the right postcentral gyrus extending to the middle frontal gyrus. Compared with non-depressed PD patients, depressed patients showed significantly increased cortical areas in the orbitofrontal regions and insula, which may imply white matter atrophy in these areas. The results of orbitofrontal and insula white matter atrophy are consistent with our previous finding that white matter integrity and functional connectivity are damaged in these regions in depressed PD patients, confirming their contribution to depression in PD.

Abnormal baseline brain activity in Parkinson's disease with and without REM sleep behavior disorder: A resting-state functional MRI study.

To investigate the differences in spontaneous brain activity between Parkinsons disease (PD) patients with rapid eye movement sleep behavior disorder (RBD), PD patients without RBD, and normal controls, which may shed new light on the neural mechanism of RBD.

Decreased Inter-Hemispheric Functional Connectivity in Cognitively Intact Elderly APOE ɛ4 Carriers: A Preliminary Study

The apolipoprotein E (APOE) ɛ4 allele is the best-known genetic risk factor for developing sporadic Alzheimers disease (AD). According to neuroimaging studies, the APOE ɛ4 allele is associated with localized altered brain function. However, in long-range circuitry, APOE ɛ4 allele-related alterations in functional communication between hemispheres have rarely been directly investigated. We examined the alteration of resting-state functional connectivity (RSFC) between inter-hemispheric homotopic regions in cognitively intact, elderly APOE ɛ4 carriers. The voxel-mirrored homotopic connectivity method was used to assess the inter-hemispheric RSFC. The current study included 13 cognitively intact, elderly APOE ɛ4 carriers (with at least one copy of APOE ɛ4 allele) and 22 well-matched ɛ3 homozygotes. Comparisons between the two groups were conducted, and subsequently, the correlation between the differential inter-hemispheric RSFC and cognitive ability was analyzed. Compared with ɛ3 homozygotes, APOE ɛ4 carriers showed decreased inter-hemispheric RSFC in the bilateral medial temporal lobe (MTL) and orbital frontal cortex (OFC). Moreover, in APOE ɛ4 carriers, the inter-hemispheric RSFC of the MTL correlated with the Wechsler Memory Scale-Logical Memory (WMS-LM) (immediate and delayed performance, r = 0.64, p <  0.05; r = 0.65, p <  0.05, respectively), and the inter-hemispheric RSFC of the OFC correlated with the WMS-LM delayed performance (r = 0.71, p <  0.05). In our study, the presence of the APOE ɛ4 allele was linked with decreased inter-hemispheric RSFC, which was attributed to memory performance in carriers.

Longitudinal Alterations of Local Spontaneous Brain Activity in Parkinson’s Disease

Abstract We used resting-state fMRI to evaluate longitudinal alterations in local spontaneous brain activity in Parkinson’s disease (PD) over a 2-year period. Data were acquired from 23 PD patients at baseline and follow-up, and 27 age- and sex-matched normal controls. Regional homogeneity (ReHo) and voxel-based-morphometry (VBM) were used to identify differences in local spontaneous brain activity and grey matter volume. With disease progression, we observed a progressive decrease in ReHo in the sensorimotor cortex, default-mode network, and left cerebellum, but increased ReHo in the supplementary motor area, bilateral temporal gyrus, and hippocampus. Moreover, there was a significant positive correlation between the rates of ReHo change in the left cerebellum and the rates of change in the Unified Parkinson’s Disease Rating Scale-III scores. VBM revealed no significant differences in the grey matter volume among the three sets of acquisitions. We conclude that ReHo may be a suitable non-invasive marker of progression in PD.