Po-Shan Wang

Fractal dimension analysis for quantifying cerebellar morphological change of multiple system atrophy of the cerebellar type (MSA-C).

Multiple system atrophy of the cerebellar type (MSA-C) is a degenerative neurological disease of the central nervous system. This study aims to demonstrate that the morphological changes of cerebellar structure, specifically, the cerebellum white matter (CBWM) and cerebellum gray matter (CBGM) from T1-weighted magnetic resonance (MR) images, can be quantified by three-dimensional (3D) fractal dimension (FD) analysis, which is a measure of complexity. Twenty-three MSA-C patients and twenty-one normal subjects participated in this study. The results of this study show that MSA-C patients presented significantly lower FD values compared to the control group, and that morphological change in the CBWM dominates the cerebellar degeneration. In addition, the FD analysis method is superior to conventional volumetric methods in quantifying the structural changes of WM and GM because it exhibits smaller variances and less gender effect. Since a decrease of cerebellar FD value indicates degeneration of the cerebellar structure, this study further suggests that the morphological changes of cerebellar structures (CBGM and CBWM) can be characterized by FD analysis.

Use of diffusion tensor imaging to identify similarities and differences between cerebellar and Parkinsonism forms of multiple system atrophy.

IntroductionWe performed diffusion tensor imaging to determine if multiple system atrophy (MSA)-cerebellar (C) and MSA-Parkinsonism (P) show similar changes, as shown in pathological studies.MethodsNineteen patients with MSA-C, 12 patients with MSA-P, 20 patients with Parkinson disease, and 20 healthy controls were evaluated with the use of voxel-based morphometry analysis of diffusion tensor imaging.ResultsThere was an increase in apparent diffusion coefficient values in the middle cerebellar peduncles and cerebellum and a decrease in fractional anisotropy in the pyramidal tract, middle cerebellar peduncles, and white matter of the cerebellum in patients with MSA-C and MSA-P compared to the controls (P < 0.001). In addition, isotropic diffusion-weighted image values were reduced in the cerebellar cortex and deep cerebellar nuclei in patients with MSA-C and increased in the basal ganglia in patients with MSA-P.ConclusionThese results indicate that despite their disparate clinical manifestations, patients with MSA-C and MSA-P share similar diffusion tensor imaging features in the infratentorial region. Further, the combination of FA, ADC and iDWI images can be used to distinguish between MSA (either form) and Parkinson disease, which has potential therapeutic implications.

Differences between spinocerebellar ataxias and multiple system atrophy-cerebellar type on proton magnetic resonance spectroscopy.

Purpose A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS) may help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy- cerebellar type (MSA-C). Material and Methods This prospective study recruited 156 patients with ataxia, including spinocerebellar ataxia (SCA) types 1, 2, 3, 6 and 17 (N = 94) and MSA-C (N = 62), and 44 healthy controls. Single voxel proton MRS in the cerebellar hemispheres and vermis were measured. The differences were evaluated using nonparametric statistic tests. Results When compared with healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all patients(p<0.002). The Cho/Cr was lower in SCA2 and MSA-C (p<0.0005). The NAA/Cr and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS features of SCA1 were in between (p<0.018). The cerebellar NAA/Cho was lower in SCA2 than SCA1, SCA3 or SCA6 (p<0.04). The cerebellar NAA/Cho in MSA-C was lower than SCA3 (p<0.0005). In the early stages of diseases (SARA score<10), significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed comparing with healthy controls (p<0.017). The Cho/Cr was lower in MSA-C or SCA2 (p<0.0005). Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or SCA6 (p<0.016). Conclusion By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C). Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study.

Morphological regionalization using fetal magnetic resonance images of normal developing brains

Regional differences in human brain development during infancy have been studied for many years, but little is known about how regionalization of the brain proceeds during intrauterine life. We investigated the regionalization of cerebral volume and cortical convolutions based on the volumetric magnetic resonance images (MRIs) of 43 fetuses, ranging from 21 to 37 weeks of gestation. Two plausible parcellations of MRI are proposed, and curvature index together with gyrification index are used to quantify the regional cortical convolutions. Our results elucidate that the cortical foldings among different brain regions develop at comparable rates, suggesting a similar uniformity of changes in size of the cortical sheet in these regions over time. On the contrary, the growth of the cerebral volume presents regional difference, with the frontal and parieto‐temporal regions growing significantly faster than other regions due to the contribution from expansion of basal ganglia. This quantitative regional information suggests that cerebral volume is not a relevant parameter to measure in relation to gyrification, and that the size of the cortical sheet is more likely to be directly related to cortical folding. The availability of quantitative regional information on normal fetal brains in utero will allow clinical application of this information when probing neurodevelopmental disorders in the future.

Early detection of periodic sharp wave complexes on EEG by independent component analysis in patients with Creutzfeldt-Jakob disease.

Summary: Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common human prion disease. EEG is the method of choice to support the diagnosis of a human prion disease. Periodic sharp wave complexes (PSWCs) on the EEG usually indicate a progressive stage of CJD. However, PSWCs only become obvious at around 8 to 12 weeks after the onset of clinical symptoms, and in a few cases, even later. Independent component analysis (ICA) is a new technique to separate statistically independent components from a mixture of data. This study recruited seven patients who fit the criteria of CJD between 2002 and 2005 and 10 patients with Alzheimer’s disease (AD) as control subjects. Using an ICA algorithm, we were able to split typical PSWCs into several independent temporal components in conjunction with spatial maps. The PSWCs were not observed in the initial EEG studies of patients with either AD or CJD. However, the ICA algorithm was able to extract periodic discharges and epileptiform discharges from raw EEG of patients with CJD at as early as 3 to 5 weeks after disease onset. Such discharges otherwise could hardly be discerned by visual inspection. In conclusion, ICA may increase the sensitivity of EEG and facilitate the early diagnosis of CJD.

Disrupted cerebellar connectivity reduces whole-brain network efficiency in multiple system atrophy

Multiple system atrophy of the cerebellar type is a sporadic neurodegenerative disorder of the central nervous system. We hypothesized that the white matter degeneration of the cerebellum and pons in this disease may cause a breakdown of cerebellar structural networks and further reduce the network efficiency of cerebellar‐connected cerebral regions. Diffusion tensor tractography was used to construct the structural networks of 19 cerebellar‐type multiple system atrophy patients, who were compared with 19 age‐ and sex‐matched controls. Graph theory was used to assess the small‐world properties and topological organization of structure networks in both the control and patient groups. Our results showed that the cerebellar‐type multiple system atrophy patients exhibited altered small‐world architecture with significantly increased characteristic shortest path lengths and decreased clustering coefficients. We also found that white matter degeneration in the cerebellum was characterized by reductions in network strength (number and integrity of fiber connections) of the cerebellar regions, which further induced extensively decreased network efficiency for numerous cerebral regions. Finally, we found that the reductions in nodal efficiency of the cerebellar lobules and bilateral sensorimotor, prefrontal, and basal ganglia regions negatively correlated with the severity of ataxia for the cerebellar‐type multiple system atrophy patients. This study demonstrates for the first time that the brains of cerebellar‐type multiple system atrophy patients exhibit disrupted topological organization of white matter structural networks. Thus, this study provides structural evidence of the relationship between abnormalities of white matter integrity and network efficiency that occurs in cerebellar‐type multiple system atrophy.

Altered Resting-State Functional Connectivity of Striatal-Thalamic Circuit in Bipolar Disorder

Bipolar disorder is characterized by internally affective fluctuations. The abnormality of inherently mental state can be assessed using resting-state fMRI data without producing task-induced biases. In this study, we hypothesized that the resting-state connectivity related to the frontal, striatal, and thalamic regions, which were associated with mood regulations and cognitive functions, can be altered for bipolar disorder. We used the Pearsons correlation coefficients to estimate functional connectivity followed by the hierarchical modular analysis to categorize the resting-state functional regions of interest (ROIs). The selected functional connectivities associated with the striatal-thalamic circuit and default mode network (DMN) were compared between bipolar patients and healthy controls. Significantly decreased connectivity in the striatal-thalamic circuit and between the striatal regions and the middle and posterior cingulate cortex was observed in the bipolar patients. We also observed that the bipolar patients exhibited significantly increased connectivity between the thalamic regions and the parahippocampus. No significant changes of connectivity related to the frontal regions in the DMN were observed. The changed resting-state connectivity related to the striatal-thalamic circuit might be an inherent basis for the altered emotional and cognitive processing in the bipolar patients.

Association between Proton Magnetic Resonance Spectroscopy Measurements and CAG Repeat Number in Patients with Spinocerebellar Ataxias 2, 3, or 6

The aim of this study was to correlate magnetic resonance spectroscopy (MRS) measurements, including that for the N-acetyl aspartate (NAA)/creatine (Cr) ratio in the vermis (denoted V-NAA), right cerebellar hemisphere (R-NAA), and left (L-NAA) cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA) score for patients with spinocerebellar ataxia (SCA) types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score) in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

Blind Source Separation of Concurrent Disease-Related Patterns from EEG in Creutzfeldt–Jakob Disease for Assisting Early Diagnosis

Creutzfeldt–Jakob disease (CJD) is a rare, transmissible and fatal prion disorder of brain. Typical electroencephalography (EEG) patterns, such as the periodic sharp wave complexes (PSWCs), do not clearly emerge until the middle stage of CJD. To reduce transmission risks and avoid unnecessary treatments, the recognition of the hidden PSWCs forerunners from the contaminated EEG signals in the early stage is imperative. In this study, independent component analysis (ICA) was employed on the raw EEG signals recorded at the first admissions of five patients to segregate the co-occurrence of multiple disease-related features, which were difficult to be detected from the smeared EEG. Clear CJD-related waveforms, i.e., frontal intermittent rhythmical delta activity (FIRDA), fore PSWCs (triphasic waves) and periodic lateralized epileptiform discharges (PLEDs), have been successfully and simultaneously resolved from all patients. The ICA results elucidate the concurrent appearance of FIRDA and PLEDs or triphasic waves within the same EEG epoch, which has not been reported in the previous literature. Results show that ICA is an objective and effective means to extract the disease-related patterns for facilitating the early diagnosis of CJD.

Classification of bipolar disorder using basal-ganglia-related functional connectivity in the resting state

The emotional and cognitive symptoms of bipolar disorder (BD) are suggested to involve in a distributed neural network. The resting-state functional magnetic resonance imaging (fMRI) offers an important tool to investigate the alterations in brain network level of BD. The aim of this study was to discriminate BD patients from healthy controls using whole-brain resting-state functional connectivity patterns. The majority of most discriminating functional connectivities were between the basal ganglia and three core neurocognitive networks, including the default mode, executive control and salience networks. Using these resting-state functional connectivities between the basal ganglia and three core neurocognitive networks as the features, the clustering accuracy achieved 90%.