Metabolic network as an objective biomarker in monitoring deep brain stimulation for Parkinson's disease: a longitudinal study.

BACKGROUND: With the advance of subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD), it is desired to identify objective criteria for the monitoring of the therapy outcome. This paper explores the feasibility of metabolic network derived from positron emission tomography (PET) with 18F-fluorodeoxyglucose in monitoring the STN DBS treatment for PD. METHODS: Age-matched 33 PD patients, 33 healthy controls (HCs), 9 PD patients with bilateral DBS surgery and 9 controls underwent 18F-FDG PET scans. The DBS patients were followed longitudinally to investigate the alternations of the PD-related metabolic covariance pattern (PDRP) expressions. RESULTS: The PDRP expression was abnormally elevated in PD patients compared with HCs (P < 0.001). For DBS patients, a significant decrease in the Unified Parkinson's Disease Rating Scale (UPDRS, P = 0.001) and PDRP expression (P = 0.004) was observed 3 months after STN DBS treatment, while a rollback was observed in both UPDRS and PDRP expressions (both P < 0.01) 12 months after treatment. The changes in PDRP expression mediated by STN DBS were generally in line with UPDRS improvement. The graphical network analysis shows increased connections at 3 months and a return at 12 months confirmed by small-worldness coefficient. CONCLUSIONS: The preliminary results demonstrate the potential of metabolic network expression as complimentary objective biomarker for the assessment and monitoring of STN DBS treatment in PD patients. Clinical Trial Registration ChiCTR-DOC-16008645.  http://www.chictr.org.cn/showproj.aspx?proj=13865 .

Correlations between dopaminergic dysfunction and abnormal metabolic network activity in REM sleep behavior disorder.

Striatal dopamine transporter (DAT) deficiency and abnormal expression of Parkinson's disease (PD)-related pattern (PDRP) have been observed in patients with idiopathic REM sleep behavior disorder (IRBD). This study aimed to investigate the correlations between these two measures with comparison to PD using a dual tracer imaging design. Age-matched 37 IRBD patients, 86 PD patients, and 15 control subjects underwent concurrent PET scans with 11C-CFT to quantify dopaminergic dysfunction and 18F-FDG to quantify PDRP expression. IRBD patients were divided into two subgroups: those with relatively normal (IRBD-RN) or abnormal (IRBD-AB) striatal DAT binding. Significantly decreased DAT binding and increased PDRP scores were present in all patient groups, except for IRBD-RN, relative to the controls. There was a significant effect of hemisphere and hemisphere × group interaction for DAT binding but not for PDRP expression. Significant correlations were observed between DAT binding and PDRP expression in the IRBD-AB and PD groups but not in the IRBD-RN group. IRBD patients present with an intermediate state in striatal DAT distribution and PDRP activity between PD and normal controls. The modest correlations between the two measures in both IRBD and PD suggest that differences in network activity cannot be fully explained by nigrostriatal dopaminergic denervation.

Study of the Influence of Age in 18F-FDG PET Images Using a Data-Driven Approach and Its Evaluation in Alzheimer's Disease.

Objectives: 18F-FDG PET scan is one of the most frequently used neural imaging scans. However, the influence of age has proven to be the greatest interfering factor for many clinical dementia diagnoses when analyzing 18F-FDG PET images, since radiologists encounter difficulties when deciding whether the abnormalities in specific regions correlate with normal aging, disease, or both. In the present paper, the authors aimed to define specific brain regions and determine an age-correction mathematical model. Methods: A data-driven approach was used based on 255 healthy subjects. Results: The inferior frontal gyrus, the left medial part and the left medial orbital part of superior frontal gyrus, the right insula, the left anterior cingulate, the left median cingulate, and paracingulate gyri, and bilateral superior temporal gyri were found to have a strong negative correlation with age. For evaluation, an age-correction model was applied to 262 healthy subjects and 50 AD subjects selected from the ADNI database, and partial correlations between SUVR mean and three clinical results were carried out before and after age correction. Conclusion: All correlation coefficients were significantly improved after the age correction. The proposed model was effective in the age correction of both healthy and AD subjects.

Differences in Aß brain networks in Alzheimer's disease and healthy controls.

The prevailing ß-amyloid (Aß)-cascade hypothesis is the most classical Alzheimer's disease (AD) pathogenesis. In this hypothesis, excessive Aß plaque deposition in human brain is considered to be the cause of AD. Carbon 11-labeled Pittsburgh compound B Positron emission tomography (11C-PiB PET) is the latest technology to detect Aß plaques in vivo. Thus, it is possible to investigate the difference of Aß brain networks between AD patients and Health Controls (HC) by analyzing 11C-PiB PET images. In this study, a graph-theoretical method was employed to investigate the topological properties of Aß networks in 18 Chinese AD patients and 16 HC subjects from Huashan Hospital, Shanghai. The results showed that both groups demonstrated small-world property, and this property was more obvious in AD group. Additionally, the clustering coefficients and path lengths were significantly lower in AD group. The global efficiency was larger in AD than in HC. A direct comparison between with and without regression found that sex, age and weight had no significant effect on the Aß network. Moreover, three altered regions in AD group were identified, including left cuneus (CUN.L), right caudate nucleus (CAU.R) and left superior frontal gyrus (SFGdor. L). A voxel-wise correlation analysis showed that in AD patients, the regions of strengthened connection with CUN.L were mainly located in frontal cortex and parietal cortex, the regions of strengthen connection with CAU.R were mainly located in temporal cortex. Finally, a machine learning based analysis demonstrated that the three regions could be better biomarkers than the whole brain for AD classification.

A novel individual-level morphological brain networks constructing method and its evaluation in PET and MR images.

Mapping the human brain is one of the great scientific challenges of the 21st century. Brain network analysis is an effective technique based on graph theory that is widely used to investigate network patterns in the human brain. Currently, mapping an individual brain network using a single image has been a hotspot in the field of brain science; techniques, such as the Kullback-Leibler (KL) method, have applications in structural Magnetic Resonance (MR) imaging. However, maintaining an image's intensity, shape, texture and gradient information during feature extraction is very challenging. In this study, we propose a novel method for individual-level network construction based on the high-resolution Brainnetome Atlas, which shows 246 brain regions. Principal components (PCs) were obtained for each brain region using principal component analysis (PCA) for feature extraction. Individual brain networks were followed and used to construct the PC similarity measurement based on the mutual information (MI) method. To evaluate the robustness of the proposed method, three independent experiments were carried out. In the first, 34 healthy subjects underwent two Carbon 11-labeled Pittsburgh compound B Positron emission tomography (11C-PiB PET) scans; in the second, 32 healthy subjects underwent two structural MRI scans; and in the last, 10 Alzheimer's disease (AD) subjects and 10Healthy Control (HC) subjects underwent 11C-PiB PET scans. For each subject, network metrics including clustering coefficient, path length, small-world coefficient, efficiency and node betweenness centrality were calculated. The results suggested that both the individual PET and structural MRI networks exhibited a good small-word property, and the variances within subjects was also quite small in all metrics, The average value of Coefficient of variation (CV) map was 0.33 and 0.32 for PiB PET and MR images respectively, and intra-class correlation coefficients (ICC) range from approximately 0.4 to 0.7, indicating that the new method was well adapted to the subjects. The results of intra-class correlation coefficients from the test-retest experiment were consistent with previous research employing KL divergence, but with low computational complexity. Further, differences between AD subjects and HC subjects can be observed in network metrics. The method proposed herein provides a new perspective for investigating individual brain connectivity; it would enable neuroscientists to further understand the functions of the human brain.

18F-FDG imaging of a rare cutaneous infection by Mycobacterium avium complex.

A 17-year-old male patient was admitted into our hospital with granulomatous eruption (primarily on the lower extremities), diarrhea, fever, and weight loss for 6 months. F-FDG PET/CT scan was performed to rule out the possibility of malignant metastasis or paraneoplastic syndromes. F-FDG PET/CT scan showed multiple bone and skin lesions with significantly intense FDG uptakes and lymph nodes with moderate FDG uptake. A biopsy of the skin lesions was performed, and the tissue was sent for a broad-range polymerase chain reaction amplification, which showed that the pathogenic organism was Mycobacterium avium complex.

A method of semi-quantifying ß-AP in brain PET-CT 11C-PiB images.

Alzheimer's disease (AD) is a common health problem for elderly populations. Positron emission tomography-computed tomography (PET-CT)11C-PiB for beta-P (amyloid-ß peptide, ß-AP) imaging is an advanced method to diagnose AD in early stage. However, in practice radiologists lack a standardized value to semi-quantify ß-AP. This paper proposes such a standardized value: SVß-AP. This standardized value measures the mean ratio between the dimension of ß-AP areas in PET and CT images. A computer aided diagnosis approach is also proposed to achieve SVß-AP. A simulation experiment was carried out to pre-test the technical feasibility of the CAD approach and SVß-AP. The experiment results showed that it is technically feasible.

Differences in the metabolic status of healthy adults with and without active brown adipose tissue.

BACKGROUND: Previous studies have proven the existence of active brown adipose tissue (BAT) in adults; however, its effect on systematic metabolism remains unclear. AIM: The current study was designed to investigate the differences in the metabolic profiles of healthy adults with and without active BAT using positron emission tomography-computed tomography (PET-CT) scans in the un-stimulated state. METHODS: A cross-sectional analysis was performed to assess the health of adults using PET-CT whole-body scans at Huashan Hospital Medical Centre between November 2009 and May 2010. A total of 62 healthy adults with active BAT were enrolled in the BAT-positive group. For each positive subject, a same-gender individual who underwent PET-CT the same day and who had no detectable BAT was chosen as the negative control. Body composition was measured, and blood samples were collected for assays of metabolic profiles and other biomarkers. RESULTS: In both the male and female groups, BAT-positive individuals were younger and had lower body mass indexes, fasting insulin, insulin resistance, and leptin, but a greater level of high-density lipoprotein cholesterol compared with the negative controls. In the male group, body fat content and levels of tumor necrosis factor-α were significantly lower in the BAT-positive than in the negative control group. CONCLUSIONS: The healthy adults with active BAT in an un-stimulated state had favorable metabolic profiles suggesting that active BAT may be a potential target for preventing and treating obesity and other metabolic disorders.

[Influence of visual and auditory masking on the brain glucose metabolism in an idiopathic tinnitus patient].

OBJECTIVE: To study the influence of the audio-visual block (AB) on the brain glucose metabolism of idiopathic tinnitus patients. METHODS: The brain positron emission tomography (PET) test was performed on one chronic idiopathic tinnitus patient under audio-visual block and non-block (NB) conditions respectively. The visual analysis and statistical parameter mapping (SPM) analysis were both used to detect the brain glucose metabolism difference under AB and NB conditions. RESULTS: Under NB conditions, significant hyperactivity was detected at auditory and visual cortex on both sides of the brain. However, this phenomenon was not shown under AB conditions. Instead, a hyperactivity of brain was presented in the left Wernicke's area. CONCLUSIONS: The generation of chronic idiopathic tinnitus probably has no relationship with the auditory cortex abnormity. Wernicke's area might be involved in the central perception of tinnitus.

Efficacy of conventional whole-body ¹8F-FDG PET/CT in the incidental findings of parotid masses.

OBJECTIVE: The objective of this study was to evaluate the incidence of incidental parotid masses with conventional whole-body ¹8F-deoxyglucose (FDG) PET/CT and assess the ability of PET/CT to characterize these unexpected parotid lesions. METHODS: Fifty eight incidental findings of parotid masses with routine FDG PET/CT whole-body scan were reviewed in this retrospective analysis, which were selected from the patients without any known or suspected parotid disease in our PET center, from June 2005 to May 2009. 51 cases were operated or underwent a biopsy after a short-term PET/CT study; the remaining 7 cases had a follow-up. Parotid mass that showed both noncontrast CT (irregular shape and blurry border) and PET malignant features (high FDG uptake, SUV(max) > 3.0) was considered as positive for malignancy. Correlation of FDG PET/CT with histology or follow-up outcome was performed. RESULTS: Fifty eight unexpected findings of parotid masses accounted for 0.3% of the total cases in 4 years, including 11 (19.0%) malignant tumors and 47 (81.0%) benign lesions. 13 lesions manifested single nodule with malignant CT features and intense FDG activity, of which 6 were proved to be malignant; thus, sensitivity and positive predictive values were 54.5% (6 of 11) and 46.2% (6 of 13), respectively. 45 lesions showed either single nodule with benign CT features, or a low FDG uptake (SUV(max) ≤ 3.0), of which 40 were true negatives; therefore, specificity and negative predictive values were 85.1% (40 of 47) and 88.9% (40 of 45), respectively. All parotid masses except 9 benign and 1 malignant showed a high FDG uptake. Compared with SUV only, combined interpretation of PET and CT results displayed a lower sensitivity (90.9-54.5%), but a higher specificity (19.1-85.1%) and a higher overall accuracy. CONCLUSIONS: Whole-body FDG-PET/CT at the time of surveying the entire body condition is helpful for detecting the asymptomatic parotid masses. Combined noncontrast CT is an essential evidence for improving the diagnostic accuracy of FDG-PET/CT for parotid masses.

Modulation of metabolic brain function by bilateral subthalamic nucleus stimulation in the treatment of Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) was proposed as an effective way to improve the symptoms of Parkinson's disease (PD). We studied metabolic modulation in the brain by bilateral STN stimulation using FDG PET. Five PD patients (age 61.6 +/- 3.9 years) at advanced stage were scanned under OFF and ON conditions of stimulation. Network analysis was used to evaluate the effect of stimulation on the expression of an abnormal Parkinson's disease-related spatial covariance pattern (PDRP). In addition, statistical parametric mapping was used to assess the effect of this intervention on regional glucose metabolism. We found that bilateral STN DBS led to a significant reduction (P < 0.02) in the PDRP network activity on an individual subject basis between OFF and ON conditions, parallel to significant improvement (P < 0.002) of clinical symptoms in these patients. The treatment also decreased glucose metabolism in the right lentiform nucleus and cerebellum, and in the bilateral ventral thalamus and precuneus, but increased metabolism in the left midbrain and pons. This was consistent with the notion that clinical benefit in a PD patient was associated with the suppression of hyperactive motor circuitry following STN stimulation. These findings suggest that DBS is more likely to function by regulating the entire neural network rather than merely exciting or inhibiting certain nuclei.

Granulomatous slack skin: assessment of disease progression and treatment response using positron emission tomography/computed tomography.

Granulomatous slack skin (GSS) is an extremely rare subtype of cutaneous T-cell lymphoma. A 14-year-old boy had suffered from progressive infiltrative erythema and plaques that gradually evolved into lax masses and pendulous skin on his axilla, anterior wall of the abdomen, bilateral inguinal region, and thighs. Histopathologic examination of the skin lesion and inguinal lymph node demonstrated granulomatous infiltration with multinucleated giant cells. Positron emission tomography (PET)/computed tomography (CT) scan was performed after acute exacerbation and exhibited slightly high fluorodeoxyglucose (FDG) distribution of skin lesions, without any evidence of abnormality in the metabolism of FDG in lymph nodes or other extralymphatic organs. Concurrent use of corticosteroid and recombinant interferon-alpha successfully controlled the disease, and posttreatment PET/CT scan confirmed the response to the therapy with decreased levels of FDG uptake. PET/CT is suggested to be helpful in the assessment of disease progression and treatment response in the management of patients with GSS.

Non-Hodgkin's lymphoma of supraclavicular lymph nodes can mimic metastasis of breast cancer during chemotherapy on FDG PET/CT.

A 43-year-old woman who had a history of right mastectomy for breast cancer presented with fever and swelling in the right supraclavicular region during her second course of chemotherapy. An FDG PET/CT was performed to evaluate this patient, which revealed mildly increased FDG activity in the lymph node in the supraclavicular region. A metastatic lesion from the known breast cancer was considered. However, biopsy results demonstrated that the abnormal activity in the right supraclavicular region is due to T-cell lymphoma.

Misdiagnoses of 11C-choline combined with 18F-FDG PET imaging in brain tumours.

BACKGROUND AND OBJECTIVE: The widely applied F-FDG is known for its disadvantage in brain tumour PET imaging because of its high background uptake. C-choline can achieve high contrast of brain tumour imaging and was expected to have higher sensitivity and specificity. We analysed the misdiagnoses in C-choline PET imaging in brain tumours with the aim of improving the accuracy of diagnosis with C-choline PET imaging. PATIENTS AND METHODS: We selected 10 patients proven to have been misdiagnosed on the basis of histopathological correlation and clinical follow-up among 94 patients (110 studies) who underwent C-choline PET/CT for diagnosed or suspected brain tumour between 23 March 2005 and 8 February 2007. C-choline PET imaging were performed on a Biograph Sensation 16 PET/CT scanner (Siemens Medical Systems), F-FDG imaging was also performed as reference. RESULTS: Of all 10 misdiagnosed patients, five were false positive (one abscess, one tuberculosis, one benign gliocyte proliferation, one inflammatory granuloma and one demyelination), four were false negative (two metastases from lung cancer, one lymphoma, one grade II glioma) and one was misdiagnosed by wrong interpretation due to lack of experience. The rate of false positives was (5/110) 4.55%; the rate of false negatives was (4/110) 3.64%; the accuracy of C-choline alone was (93/110) 84.5%; by comparison, the accuracy of F-FDG alone was (78/110) 70.9%. CONCLUSIONS: C-choline imaging has a certain rate of false positivity and false negativity. With proper application, C-choline might have greater potential than F-FDG for brain tumour PET imaging.