Huiwei Zhang

Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder

Rapid eye movement sleep behaviour disorder has been evaluated using Parkinsons disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. 18F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0±5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5±7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6±5.0 years) and 16 moderate parkinsonian patients (age 56.9±12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P<0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinsons disease-related network activity was also elevated (P<0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism.

Metabolic brain network in the Chinese patients with Parkinson's disease based on 18F-FDG PET imaging

The objective of this study was to validate Parkinsons disease-related pattern (PDRP) as a measure of network biomarker of Parkinsons disease (PD) in Chinese population by using 18F-fluorodeoxyglucose (FDG) and Positron Emission Tomography (PET). Resting-state brain FDG PET imaging was performed in a cohort of 33 PD patients and 33 age/gender-matched healthy controls to identify a PDRP. PDRP expression was then computed in a new cohort of 30 PD patients and 30 healthy controls using a voxel-based network quantification algorithm. Differences in PDRP expression were compared across groups and correlations with severities of PD were investigated. As a result, we identified a PDRP characterized by relative increases in pallidothalamic, pontine, and cerebellar metabolism, associated with concurrent metabolic decreases in the premotor and posterior parietal areas. PDRP expression in each of the two PD groups was significantly elevated relative to that of the healthy controls (P < 0.001). Receiver operating characteristic (ROC) analysis revealed that the PDRP-based discrimination for PD patients and controls had high sensitivity and specificity (both = 93.9%) in the derivation cohort, which declined slightly in the validation cohort (both = 90.0%) at the same diagnostic threshold. Moreover, PDRP scores correlated positively with Hoehn and Yahr scores (r ≥ 0.590, P ≤ 0.001) and Unified Parkinsons Disease Rating Scale motor scores (r ≥ 0.646, P < 0.001) in both patient groups. In conclusion, PDRP is highly reproducible in Chinese cohorts based on FDG PET imaging. Network activity of PDRP can differentiate PD patients from healthy controls and correlates with the severities of the disease.

Metabolic Imaging of Bilateral Anterior Capsulotomy in Refractory Obsessive Compulsive Disorder: an FDG PET Study

The therapeutic benefits of bilateral capsulotomy for the treatment of refractory obsessive compulsive disorder (OCD) are probably attributed to interruption of the cortico-striato-thalamo-cortical circuitry. We evaluated resting brain metabolism and treatment response in OCD patients using positron emission tomography (PET) imaging. [18F]-fluoro-deoxy-glucose PET was performed in eight OCD patients precapsulotomy and postcapsulotomy. We determined metabolic differences between preoperative images in patients and those in eight age-matched healthy volunteers, and postoperative changes and clinical correlations in the patients. The OCD patients showed widespread metabolic increases in normalized glucose metabolism in the bilateral orbitofrontal cortex and inferior frontal gyrus, cingulate gyrus, and bilateral pons/cerebellum, and metabolic decreases bilaterally in the precentral and lingual gyri. Bilateral capsulotomy resulted in significant metabolic decreases bilaterally in the prefrontal cortical regions, especially in the dorsal anterior cingulate cortex (ACC) and in the medial dorsal thalamus and caudate nucleus. In contrast, metabolism increased bilaterally in the precentral and lingual gyri. Clinical improvement in patients correlated with metabolic changes in the bilateral dorsal ACC and in the right middle occipital gyrus after capsulotomy. This study underscores the importance of the internal capsule in modulating ventral prefrontal and dorsal anterior cingulate neuronal activity in the neurosurgical management of OCD patients.

Metabolic imaging of deep brain stimulation in anorexia nervosa: a 18F-FDG PET/CT study.

Objectives Anorexia nervosa (AN), a disorder of unknown etiology, has the highest mortality rate of any psychiatric disorder. Drawing the brain metabolic pattern of AN may help to target the core biological and psychological features of the disorder and to perfect the diagnosis and recovery criteria. In this study, we used 18F-FDG PET to show brain metabolic network for AN. Methods Glucose metabolism in 6 AN patients and 12 age-matched healthy controls was studied using 18F-FDG PET. SPM2 was used to compare brain metabolism in AN patients with that in healthy controls. Four of 6 AN patients took deep brain stimulation (DBS) targeted in nucleus accumbens (NAcc). About 3 to 6 months after the surgery, the 4 AN patients took another 18F-FDG PET scan to assess the change in brain glucose metabolism. Results The SPM (statistical parametric mapping ) analysis showed hypermetabolism in the frontal lobe (bilateral, BA10, BA11, BA47), the limbic lobe (bilateral, hippocampus, and amygdala), lentiform nucleus (bilateral), left insula (BA13), and left subcallosal gyrus (BA25). It also showed hypometabolism in the parietal lobe (bilateral, BA7, BA40). The hypermetabolism in frontal lobe, hippocampus, and lentiform nucleus decreased after NAcc-DBS. Conclusions The changes in brain glucose metabolism illustrated the brain metabolic pattern in AN patients. Furthermore, the pattern can be modulated by NAcc-DBS, which confirmed specificity of the pattern. The regions with altered metabolism could interconnect to form a network and integrate information related to appetite. Our study may provide information for targeting the potential candidate brain regions for understanding the pathophysiology of AN and assessing the effects of existing and future treatment approaches.

Data-driven identification of intensity normalization region based on longitudinal coherency of (18)F-FDG metabolism in the healthy brain.

Objectives In brain 18F‐FDG PET data intensity normalization is usually applied to control for unwanted factors confounding brain metabolism. However, it can be difficult to determine a proper intensity normalization region as a reference for the identification of abnormal metabolism in diseased brains. In neurodegenerative disorders, differentiating disease‐related changes in brain metabolism from age‐associated natural changes remains challenging. This study proposes a new data‐driven method to identify proper intensity normalization regions in order to improve separation of age‐associated natural changes from disease related changes in brain metabolism. Methods 127 female and 128 male healthy subjects (age: 20 to 79) with brain18F‐FDG PET/CT in the course of a whole body cancer screening were included. Brain PET images were processed using SPM8 and were parcellated into 116 anatomical regions according to the AAL template. It is assumed that normal brain 18F‐FDG metabolism has longitudinal coherency and this coherency leads to better model fitting. The coefficient of determination R2 was proposed as the coherence coefficient, and the total coherence coefficient (overall fitting quality) was employed as an index to assess proper intensity normalization strategies on single subjects and age‐cohort averaged data. Age‐associated longitudinal changes of normal subjects were derived using the identified intensity normalization method correspondingly. In addition, 15 subjects with clinically diagnosed Parkinsons disease were assessed to evaluate the clinical potential of the proposed new method. Results Intensity normalizations by paracentral lobule and cerebellar tonsil, both regions derived from the new data‐driven coherency method, showed significantly better coherence coefficients than other intensity normalization regions, and especially better than the most widely used global mean normalization. Intensity normalization by paracentral lobule was the most consistent method within both analysis strategies (subject‐based and age‐cohort averaging). In addition, the proposed new intensity normalization method using the paracentral lobule generates significantly higher differentiation from the age‐associated changes than other intensity normalization methods. Conclusion Proper intensity normalization can enhance the longitudinal coherency of normal brain glucose metabolism. The paracentral lobule followed by the cerebellar tonsil are shown to be the two most stable intensity normalization regions concerning age‐dependent brain metabolism. This may provide the potential to better differentiate disease‐related changes from age‐related changes in brain metabolism, which is of relevance in the diagnosis of neurodegenerative disorders. HighlightsA method to differentiate disease‐related metabolic changes from age‐associated natural changes.A concept of longitudinal coherency to identify proper age‐associated metabolic changes.A data‐driven method to find out optimal intensity normalization enhancing longitudinal coherency.Normalization using paracentral lobule can best describe age‐dependent brain metabolism.Development on normal subjects and preliminary verification on PD patients.

Dopamine transporter changes after unilateral deep brain stimulation in progressive Parkinson's disease: a case report.

Deep brain stimulation (DBS) at the subthalamic nucleus has been approved as an effective treatment for refractory symptoms of Parkinson’s disease (PD). Studies have shown that bilateral DBS surgery in PD patients results in clinical improvement without reducing dopamine transporter function. Here, we report our longitudinal findings in one PD patient, ie, decreases in striatal dopamine transporter binding during one year of follow-up after unilateral DBS at the subthalamic nucleus. Based on this case, we hypothesize that clinical benefit after unilateral DBS may be not directly associated with changes in function at the subthalamic nucleus.

Reproducible network and regional topographies of abnormal glucose metabolism associated with progressive supranuclear palsy: Multivariate and univariate analyses in American and Chinese patient cohorts

Progressive supranuclear palsy (PSP) is a rare movement disorder and often difficult to distinguish clinically from Parkinsons disease (PD) and multiple system atrophy (MSA) in early phases. In this study, we report reproducible disease‐related topographies of brain network and regional glucose metabolism associated with PSP in clinically‐confirmed independent cohorts of PSP, MSA, and PD patients and healthy controls in the USA and China. Using 18F‐FDG PET images from PSP and healthy subjects, we applied spatial covariance analysis with bootstrapping to identify a PSP‐related pattern (PSPRP) and estimate its reliability, and evaluated the ability of network scores for differential diagnosis. We also detected regional metabolic differences using statistical parametric mapping analysis. We produced a highly reliable PSPRP characterized by relative metabolic decreases in the middle prefrontal cortex/cingulate, ventrolateral prefrontal cortex, striatum, thalamus and midbrain, covarying with relative metabolic increases in the hippocampus, insula and parieto‐temporal regions. PSPRP network scores correlated positively with PSP duration and accurately discriminated between healthy, PSP, MSA and PD groups in two separate cohorts of parkinsonian patients at both early and advanced stages. Moreover, PSP patients shared many overlapping areas with abnormal metabolism in the same cortical and subcortical regions as in the PSPRP. With rigorous cross‐validation, this study demonstrated highly comparable and reproducible PSP‐related metabolic topographies at network and regional levels across different patient populations and PET scanners. Metabolic brain network activity may serve as a reliable and objective marker of PSP, although cross‐validation applying recent diagnostic criteria and classification is warranted.

Modified Fluorodeoxyglucose Metabolism in Motor Circuitry by Subthalamic Deep Brain Stimulation

Background: Adjustment of the motor circuitry has been described in the treatment of Parkinson disease (PD). Objectives: To evaluate the modulation of the motor circuitry of PD patients by subthalamic deep brain stimulation (STN DBS) using 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). Methods: Resting-state brain 18F-FDG PET imaging was performed for 8 PD patients before surgery and also 1 year after STN DBS treatment; changes in regional glucose metabolism were identified. The PD-related pattern (PDRP) of metabolic covariation was also evaluated. In addition, the correlations between glucose metabolism and clinical alleviation were determined. Results: Pronounced elevations in parietal and occipital glucose metabolism due to STN DBS modification were found; an obvious reduction in caudate, putamen, cerebellum, and frontal cortex glucose metabolism was detected after STN DBS interventions. The alleviation of rigidity correlated with an increment in glucose metabolism in the parietal lobe. STN DBS inhibited the PDRP; the decrease in the PDRP correlated with the inhibition of the glucose metabolism of the caudate and the augmented glucose metabolism of the occipital lobe. Conclusion: STN DBS modulates cortical function through the cortical-striatothalamocortial motor circuitry and cerebellothalamocortical motor circuitry.

Validation of abnormal glucose metabolism associated with Parkinson’s disease in Chinese participants based on 18F-fluorodeoxyglucose positron emission tomography imaging

Purpose We previously identified disease-related cerebral metabolic characteristics associated with Parkinson’s disease (PD) in the Chinese population using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging. The present study aims to assess data reproducibility and robustness of the metabolic activity characteristics across independent cohorts. Patients and methods Forty-eight patients with PD and 48 healthy controls from Chongqing district, in addition to 33 patients with PD and 33 healthy controls from Shanghai district were recruited. Each subject underwent brain 18F-FDG PET/CT imaging in a resting state. Based on the brain images, differences between the groups and PD-related cerebral metabolic activities were graphically and quantitatively evaluated. Results Both PD patient cohorts exhibited analogous cerebral patterns characterized by metabolic increase in the putamen, globus pallidus, thalamus, pons, sensorimotor cortex and cerebellum, along with metabolic decrease in parieto-occipital areas. Additionally, the metabolic pattern was highly indicative of the disease, with a significant elevation in PD patients compared with healthy controls (p<0.001) in both the derivation (Shanghai) and validation (Chongqing) cohorts. Conclusion This dual-center study demonstrated the high comparability and reproducibility of PD-related cerebral metabolic activity patterns across independent Chinese cohorts and may serve as an objective diagnostic marker for the disease.

Glucose Metabolic Brain Network Differences between Chinese Patients with Lewy Body Dementia and Healthy Control

Dementia with Lewy bodies (DLB) is the second most common degenerative dementia of the central nervous system. The technique 18F-fluorodeoxyglucose positron emission tomography (18F FDG PET) was used to investigate brain metabolism patterns in DLB patients. Conventional statistical methods did not consider intern metabolism transforming connections between various brain regions; therefore, most physicians do not understand the underlying neuropathology of DLB patients. In this study, 18F FDG-PET images and graph-theoretical methods were used to investigate alterations in whole-brain intrinsic functional connectivity in a Chinese DLB group and healthy control (HC) group. This experimental study was performed on 22 DLB patients and 22 HC subjects in Huashan Hospital, Shanghai, China. Experimental results indicate that compared with the HC group, the DLB group has severely impaired small-world network. Compared to those of the HC group, the clustering coefficients of the DLB group were higher and characteristic path lengths were longer, and in terms of global efficiencies, those of the DLB group was also lower. Moreover, four significantly altered regions were observed in the DLB group: Inferior frontal gyrus, opercular part (IFG.R), olfactory cortex (OLF.R), hippocampus (HIP.R), and fusiform gyrus (FFG.L). Amongst them, in the DLB group, betweenness centrality became strong in OLF.R, HIP.R, and FFG.L, whereas betweenness centrality became weaker in IFG.R. Finally, IFGoperc.R was selected as a seed and a voxel-wise correlation analysis was performed. Compared to the HC group, the DLB group showed several regions of strengthened connection with IFGoperc.R; these regions were located in the prefrontal cortex and regions of weakened connection were located in the occipital cortex. The results of this paper may help physicians to better understand and characterize DLB patients.