Coupling Between Human Brain Cortical Thickness and Glucose Metabolism from Regional to Connective Level: A Positron Emission Tomography/Magnetic Resonance Imaging Study.

Background: Balance between brain structure and function is implicated in aging and many brain disorders. This study aimed to investigate the coupling between brain structure and function using 18F-fludeoxyglucose positron emission tomography (PET)/magnetic resonance imaging (MRI). Methods: One hundred thirty-eight subjects who underwent brain 18F-FDG PET/MRI were recruited. The structural and functional coupling at the regional level was explored by calculating within-subject Spearman's correlation between glucose metabolism (GluM) and cortical thickness (CTh) across the cortex for each subject, which was then correlated with age to explore its physiological effects. Then, subjects were divided into groups of middle-aged and young adults and older adults (OAs); structural connectivity (SC) based on CTh and functional connectivity (FC) based on GluM were constructed for the two groups, respectively, followed by exploring the connective-level structural and functional coupling on SC and FC matrices. The global and local efficiency values of the brain SC and FC were also evaluated. Results: Of the subjects, 97.83% exhibited a significant negative correlation between regional CTh and GluM (r = -0.24 to -0.71, p < 0.05, FDR correction), and this CTh-GluM correlation was negatively correlated with age (R = -0.35, p < 0.001). For connectivity matrices, many regions showed positive correlation between SC and FC, especially in the OA group. Besides, FC exhibited denser connections than SC, resulting in both higher global and local efficiency, but lower global efficiency when the network size was corrected. Conclusions: This study found couplings between CTh and GluM at both regional and connective levels, which reflected the aging progress, and might provide new insight into brain disorders. Impact statement The intricate interplay between brain structures and functions plays a pivotal role in unraveling the complexities inherent in the aging process and the pathogenesis of neurological disorders. This study revealed that 97.83% subjects showed negative correlation between the brain's regional cortical thickness and glucose metabolism, while at the connective level, many regions showed positive correlations between structural and functional connectivity. The observed coupling at the regional and connective levels reflected physiological progress, such as aging, and provides insights into the brain mechanisms and potential implications for the diagnosis and treatment of brain disorders.

The associations between synaptic density and "A/T/N" biomarkers in Alzheimer's disease: An 18F-SynVesT-1 PET/MR study.

A newly developed SV2A radiotracer, 18F-SynVesT-1, was used in this study to investigate synaptic density and its association with Alzheimer's disease (AD) "A/T/N" biomarkers. The study included a cohort of 97 subjects, consisting of 64 patients with cognitive impairment (CI) and 33 individuals with normal cognition (CU). All subjects underwent 18F-SynVesT-1 PET/MR and 18F-florbetapir PET/CT scans. Additionally, a subgroup of individuals also underwent 18F-MK-6240, 18F-FDG PET/CT, plasma Aß42/Aß40 and p-tau181 tests. The differences in synaptic density between the groups and the correlations between synaptic density and AD "A/T/N" biomarkers were analyzed. The results showed that compared to the CU group, the CI with Aß+ (CI+) group exhibited the most pronounced synapse loss in the hippocampus, with some loss also observed in the neocortex. Furthermore, synaptic density in the hippocampus and parahippocampal gyrus showed associations with AD biomarkers detected by both imaging and plasma tests in the CI group. The associations between synaptic density and FDG uptake and hippocampal volume were also observed in the CI+ group. In conclusion, the study demonstrated significant synaptic density loss, as measured by the promising tracer 18F-SynVesT-1, and its close correlation with "A/T/N" biomarkers in patients with both Alzheimer's clinical syndrome and pathological changes.

Positive rate and quantification of amyloid pathology with [18F]florbetapir in the urban Chinese population.

OBJECTIVES: Amyloid deposition is considered the initial pathology in Alzheimer's disease (AD). Personalized management requires investigation of amyloid pathology and the risk factors for both amyloid pathology and cognitive decline in the Chinese population. We aimed to investigate amyloid positivity and deposition in AD patients, as well as factors related to amyloid pathology in Chinese cities. METHODS: This cross-sectional multicenter study was conducted in Shanghai and Zhengzhou, China. All participants were recruited from urban communities and memory clinics. Amyloid positivity and deposition were analyzed based on amyloid positron emission tomography (PET). We used partial least squares (PLS) models to investigate how related factors contributed to amyloid deposition and cognitive decline. RESULTS: In total, 1026 participants were included: 768 participants from the community-based cohort (COMC) and 258 participants from the clinic-based cohort (CLIC). The overall amyloid-positive rates in individuals with clinically diagnosed AD, mild cognitive impairment (MCI), and normal cognition (NC) were 85.8%, 44.5%, and 26.9%, respectively. The global amyloid deposition standardized uptake value ratios (SUVr) (reference: cerebellar crus) were 1.44 ± 0.24, 1.30 ± 0.22, and 1.24 ± 0.14, respectively. CLIC status, apolipoprotein E (ApoE) ε4, and older age were strongly associated with amyloid pathology by PLS modeling. CONCLUSION: The overall amyloid-positive rates accompanying AD, MCI, and NC in the Chinese population were similar to those in published cohorts of other populations. ApoE ε4 and CLIC status were risk factors for amyloid pathology across the AD continuum. Education was a risk factor for amyloid pathology in MCI. Female sex and age were risk factors for amyloid pathology in NC. CLINICAL RELEVANCE STATEMENT: This study provides new details about amyloid pathology in the Chinese population. Factors related to amyloid deposition and cognitive decline can help to assess patients' AD risk. KEY POINTS: • We studied amyloid pathology and related risk factors in the Chinese population. •·The overall amyloid-positive rates in individuals with clinically diagnosed AD, MCI, and NC were 85.8%, 44.5%, and 26.9%, respectively. • These overall amyloid-positive rates were in close agreement with the corresponding prevalence for other populations.

The Effect of Gender and APOE ɛ4 Status on Brain Amyloid-ß Deposition in Different Age Groups of Mild Cognitively Impaired Individuals: A PET-CT Study.

BACKGROUND: Gender, APOE ɛ4 status and age have different effects on brain amyloid deposition in patients with mild cognitively impaired (MCI). OBJECTIVE: To investigate the effect of gender×APOE ɛ4 status interaction on Aß deposition in the brains of individuals with MCI in different age groups by PET scanning. METHODS: 204 individuals with MCI were classified into younger or older groups based on whether they were under or over 65 years of age. APOE genotyping, structural MRI, amyloid PET scans, and neuropsychological tests were performed. The effect of gender×APOE ɛ4 status interaction on Aß deposition was assessed in different age groups. RESULTS: APOE ɛ4 carriers had higher amyloid deposition than noncarriers in the whole group. Females with MCI had more amyloid deposition in the medial temporal lobe than males in the whole cohort and younger group. Older individuals with MCI had higher amyloid deposition than younger individuals. In stratified analysis by age, female APOE ɛ4 carriers had significantly increased amyloid deposition compared to their male counterparts only in the medial temporal lobe in the younger group. Amyloid deposition was increased in female APOE ɛ4 carriers compared to noncarriers in the younger group, whereas higher amyloid deposition was observed in male APOE ɛ4 carriers in the older group. CONCLUSION: Women in the younger group with MCI who were APOE ɛ4 carriers had more amyloid deposition in the brain, while men in the older group with MCI who were APOE ɛ4 carriers had higher amyloid deposition.

Brain glucose metabolism and dopamine transporter changes in rats with morphine-induced conditioned place preference.

Addiction to morphine is a chronic brain disease leading to compulsive abuse. Drug addiction animal models with and without conditioned place preference (CPP) training have been used to investigate cue-elicited drug craving. We used 18 F-fluorodeoxyglucose (18 F-FDG) and 11 C-2-ß-carbomethoxy-3-ß-(4-fluorophenyl)tropane (11 C-CFT) micro-PET/CT scans to examine the regional changes in brain glucose metabolism and dopamine transporter (DAT) availability to study their relationship underlying drug memory in morphine-treated rat models with and without CPP. Standardized uptake value ratio (SUVr) of 18 F-FDG significantly decreased in the medial prefrontal cortex (mPFC) and cingulate with short-term morphine administration compared with the baseline condition. Voxelwise analysis indicated glucose metabolism alterations in the somatosensory cortex, hippocampus and cingulate in morphine-treated rats and in the striatum, thalamus, medial prefrontal cortex, primary motor cortex and many regions in the cortex in the CPP group compared with the baseline condition. Alterative glucose metabolism was also observed in the striatum, primary somatosensory cortex and some cortical regions in the CPP group compared with morphine alone group. DAT expression alterations were only observed in the long-term morphine compared with the short-term morphine group. This study shows that cerebral glucose metabolism significantly altered during morphine administration and CPP process mainly in the mPFC, striatum and hippocampus, which indicates that the function of these brain regions is involved in cue-induced craving and memory retrieval.

Brain Functional Alterations and Association with Cognition in People with Preclinical Subjective Cognitive Decline and Objective Subtle Cognitive Difficulties.

Subjective cognitive decline (SCD) and objective subtle cognitive difficulties (Obj-SCD) are considered the initial stages of aberrant cognition prior to mild cognitive impairment (MCI) due to Alzheimer's disease (AD). We aimed to determine the difference of brain function of SCD and Obj-SCD, furthermore, to figure out which one could be the marker of early AD. One hundred and eighty-five participants were enrolled in this study to determine the amyloid pathology and glucose metabolism changes in SCD and Obj-SCD. The association of amyloid deposition and glucose metabolism with cognitive domains were also investigated. Obj-SCD displayed significantly increased amyloid deposition in frontal and temporal lobes compared to SCD and normal cognitive control (NCC). No difference of amyloid deposition between SCD and NCC, and no difference of glucose metabolism among the three groups were observed. Amyloid deposition was associated with function of memory, language and executive domains, and glucose metabolism was only associated with executive function in Obj-SCD. Amyloid deposition was only associated with executive function in SCD. Obj-SCD could be the early stage of AD, which displayed significant increased amyloid deposition, and the increased amyloid deposition was associated with cognitive function in different domains.

Non-tumoral uptake of 68Ga-FAPI-04 PET: A retrospective study.

Objective: Fibroblast activation protein (FAP)-targeting radiopharmaceutical based on the FAP-specific inhibitor (FAPI) is considered as a potential alternative agent to FDG for tumor-specific imaging. However, FAP is also expressed in normal adult tissues. The aim of this study was to explore the image features of non-tumoral regions with high uptake of 68Ga-FAPI-04 in positron emission tomography (PET) imaging and to reveal the physiological mechanisms of these regions. Material: A total of 137 patients who underwent whole-body 68Ga-FAPI-04 PET/MR (n=46) or PET/CT (n=91) were included in this retrospective study. Three experienced nuclear medicine physicians determined the non-tumoral regions according to other imaging modalities (CT, MRI, 18F-FDG PET, or ultrasound), clinical information, or pathological results. The regions of interest (ROIs) were drawn manually, and the maximum standardized uptake value (SUVmax) was measured. Results: A total of 392 non-tumoral uptake regions were included in this study. The included physiological regions were uterus (n=38), submandibular gland (n=118), nipple (n=37), gingiva (n=65), and esophagus (n=31). The incidence of 68Ga-FAPI-04 uptake in physiological regions was independent of age, the tracer uptakes in the gingiva and esophagus were more common in male patients (p=0.006, 0.009), while that in the nipple was more common in female patients (p < 0.001). The included benign regions were inflammatory lymph node (n =10), pneumonia (n=13), atherosclerosis (n=10), pancreatitis (n=18), osteosclerosis (n=45), and surgical scar (n=7). No significant difference was observed in SUVmax between physiological and benign regions. Conclusions: A number of organs exhibit physiological uptakes of 68Ga-FAPI-04. Our study showed that regions with high 68Ga-FAPI-04 uptake did not necessarily represent malignancy. Being familiar with physiological and typical benign 68Ga-FAPI-04 uptake regions can be helpful for physicians to interpret images and to make an accurate diagnosis.

Graph Analysis of Functional Brain Topology Using Minimum Spanning Tree in Subjective Cognitive Decline.

BACKGROUND: Subjects with subjective cognitive decline (SCD) are proposed as a potential population to screen for Alzheimer's disease (AD). OBJECTIVE: Investigating brain topologies would help to mine the neuromechanisms of SCD and provide new insights into the pathogenesis of AD. METHODS: Objectively cognitively unimpaired subjects from communities who underwent resting-state BOLD-fMRI and clinical assessments were included. The subjects were categorized into SCD and normal control (NC) groups according to whether they exhibited self-perceived cognitive decline and were worried about it. The minimum spanning tree (MST) of the functional brain network was calculated for each subject, based on which the efficiency and centrality of the brain network organization were explored. Hippocampal/parahippocampal volumes were also detected to reveal whether the early neurodegeneration of AD could be seen in SCD. RESULTS: A total of 49 subjects in NC and 95 subjects in SCD group were included in this study. We found the efficiency and centrality of brain network organization, as well as the hippocampal/parahippocampal volume were preserved in SCD. Besides, SCD exhibited normal cognitions, including memory, language, and execution, but increased depressive and anxious levels. Interestingly, language and execution, instead of memory, showed a significant positive correlation with the maximum betweenness centrality of the functional brain organization and hippocampal/parahippocampal volume. Neither depressive nor anxious scales exhibited correlations with the brain functional topologies or hippocampal/parahippocampal volume. CONCLUSION: SCD exhibited preserved efficiency and centrality of brain organization. In clinical practice, language and execution as well as depression and anxiety should be paid attention in SCD.

Aging-Related Modular Architectural Reorganization of the Metabolic Brain Network.

Background: Modules in brain network represent groups of brain regions that are collectively involved in one or more cognitive domains. Exploring aging-related reorganization of the brain modular architecture using metabolic brain network could further our understanding about aging-related neuromechanism and neurodegenerations. Materials and Methods: In this study, 432 subjects who performed 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) were enrolled and divided into young and old adult groups, as well as female and male groups. The modular architecture was detected, and the connector and hub nodes were identified to explore the topological role of the brain regions based on the metabolic brain network. Results: This study revealed that human metabolic brain network was modular and could be clustered into three modules. The modular architecture was reorganized from young to old ages with regions related to sensorimotor function clustered into the same module; and the number of connector nodes was reduced and most connector nodes were localized in temporo-occipital areas related to visual and auditory functions in old ages. The major gender difference is that the metabolic brain network was delineated into four modules in old female group with the nodes related to sensorimotor function split into two modules. Discussion: Those findings suggest aging is associated with reorganized brain modular architecture. Clinical Trial Registration number: ChiCTR2000036842. Impact statement Distinguishing the basic biology underlying aging from that underlying disease is critical for the prevention, diagnosis, and treatment of the aging-related brain disorders. In this study, we tried to uncover aging-related brain modular reorganization by using metabolic brain network. We found the modular architecture was slightly reorganized from young to old ages with regions related to sensorimotor function more converged. The number of connector nodes was reduced and most connector nodes were localized into the temporo-occipital regions. The major gender difference was that metabolic brain network was delineated into four modules in the old female group with the sensorimotor functions split into two modules.

Comparison of [68 Ga]Ga-FAPI-04 and [18F]-FDG for the detection of primary and metastatic lesions in patients with gastric cancer: a bicentric retrospective study.

INTRODUCTION: The low sensitivity of [18F]-fluorodeoxyglucose ([18F]-FDG) for the diagnosis of gastric cancer limits its application. In this study, we aimed to investigate the potential advantage of [68 Ga]Ga-FAPI-04 over [18F]-FDG in the evaluation of gastric cancer. METHODS: This was a bicentric retrospective analysis of a prospective parent study (clinical trial: HS-KY-2020-826 (Huashan Hospital) and DF-2020-102 (Shanghai East Hospital)). Thirty-eight patients with gastric cancer (31 with adenocarcinoma and 7 with signet ring cell carcinoma) were included in this study. All of the participants underwent [68 Ga]Ga-FAPI-04 and [18F]-FDG imaging by positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance (MR). The scans were interpreted by two experienced nuclear medicine physicians, and the maximum standardized uptake value (SUVmax) was calculated. Histopathological findings obtained from biopsy or resected surgical specimens were used as a reference for the final diagnosis. RESULTS: For the detection of primary gastric cancer, the sensitivities of [68 Ga]Ga-FAPI-04 PET and [18F]-FDG PET were 100% (38/38) and 82% (31/38), respectively (P = 0.016). Four cases of adenocarcinoma and three cases of signet ring cell carcinoma were missed by [18F]-FDG PET. The mean SUVmax of [68 Ga]Ga-FAPI-04 in tumours greater than 4 cm (11.0 ± 4.5) was higher than that in tumours less than 4 cm (4.5 ± 3.2) (P = 0.0015). The mean SUVmax of [68 Ga]Ga-FAPI-04 was higher in T2-4 tumours (9.7 ± 4.4) than in T1 tumours (3.1 ± 1.5) (P = 0.0002). For the detection of metastatic lesions, the sensitivities of [68 Ga]Ga-FAPI-04 PET and [18F]-FDG PET in 10 patients with regional lymph node metastasis and distant metastasis were 6/10 and 5/10, respectively. CONCLUSION: In this selected cohort, [68 Ga]Ga-FAPI-04 PET had a superior detection rate than [18F]-FDG PET for primary gastric cancer. [68 Ga]Ga-FAPI-04 PET could provide better performance with regard to gastric cancer diagnosis and staging. Prospective clinical trials are warranted.

Altered Default Mode Network Is Associated With Cognitive Impairment in CADASIL as Revealed by Multimodal Neuroimaging.

Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy caused by mutations in the NOTCH3 gene is a hereditary cerebral small vessel disease, manifesting with stroke, cognitive impairment, and mood disturbances. Functional or structural changes in the default mode network (DMN), which plays important role in cognitive and mental maintenance, have been found in several neurological and mental diseases. However, it remains unclear whether DMN is altered in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: Multimodal imaging methods, including MRI and positron emission tomography (PET), were applied to evaluate the functional, structural, and metabolic characteristics of DMN in 25 patients with CADASIL and 42 healthy controls. Results: Compared with controls, patients with CADASIL had decreased nodal efficiency and degree centrality of the dorsal medial pre-frontal cortex and hippocampal formation within DMN. Structural MRI and diffusion tensor imaging (DTI) showed decreased gray matter volume and fiber tracks presented in the bilateral hippocampal formation. Meanwhile, PET imaging showed decreased metabolism within the whole DMN in CADASIL. Furthermore, correlation analyses showed that these nodal characteristics, gray matter volume, and metabolic signals of DMN were related to cognitive scores in CADASIL. Conclusions: Our results suggested that altered network characteristics of DMN might play important roles in cognitive deficits of CADASIL.

Metabolic Brain Network and Surgical Outcome in Temporal Lobe Epilepsy: A Graph Theoretical Study Based on 18F-fluorodeoxyglucose PET.

Drug-resistant temporal lobe epilepsy (TLE) is a potential candidate for surgery; however, nearly one-third subjects had a poor surgical prognosis. We studied the underlying neuromechanism related to the surgical prognosis using graph theory based on metabolic brain network. Sixty-four unilateral TLE subjects with preoperative 18F-fluorodeoxyglucose (FDG) PET scanning were retrospectively enrolled and divided into Ia (Engel class Ia, n = 32) and non-Ia (Engel class Ib-IV, n = 32) groups according to more than 3-year follow-up after unilateral anterior temporal lobectomy (ATL). The metabolic brain network was constructed and the changed metabolic connectivity of Ia and non-Ia was detected compared with 15 matched healthy controls (HCs). Further, the network properties, including small-worldness and global efficiency, were calculated and hub nodes were also identified for the 3 groups respectively. Non-Ia group exhibited increased connectivity between contralateral fusiform gyrus and contralateral lingual gyrus; while Ia showed decreased connectivity mainly among bilateral frontal, temporal and parietal cortex. Graph theoretical analysis revealed that non-Ia group showed increased small-worldness (35%

Alteration of neuroinflammation detected by 18F-GE180 PET imaging in place-conditioned rats with morphine withdrawal.

BACKGROUND: Accumulating evidence indicates that neuroinflammation (NI) significantly contributes to drug addiction, but the conversion of NI after drug withdrawal is not clear. Here, we conducted 18F-flutriciclamide (GE180) positron emission tomography (PET) imaging to investigate the conversion of NI during drug withdrawal and conditioning-induced aversion by measuring the change in microglial activation with 18F-GE180. METHODS: Twelve male adult Sprague-Dawley rats were subjected to morphine withdrawal by the administration of naloxone, and six of them were used to model conditioned place aversion (CPA). 18F-GE180 PET imaging was performed for 11 rats on the last day of the morphine treatment phase and for 10 rats on the response assessment phase of the behavior conditioning procedure. A 18F-GE180 template was established for spatial normalization of each individual image, and the differential 18F-GE180 uptakes between the drug withdrawal (DW) group and the drug addiction (DA) group, the CPA group and the DA group, and the CPA group and the DW group were compared by a voxel-wise two-sample t test using SPM8. RESULTS: Both the DW group and the CPA group spent less time in the conditioning cage during the post-test phase compared with the pretest phase, but only the difference in the CPA group was significant (63.2 ± 34.6 vs. - 159.53 ± 22.02, P < 0.005). Compared with the DA group, the uptake of 18F-GE180 increased mainly in the hippocampus, visual cortex, thalamus and midbrain regions and decreased mainly in the sensory-related cortices after the administration of naloxone in both the DW and CPA groups. Increased 18F-GE180 uptake was only observed in the mesolimbic regions after conditioned aversion compared with the DW group. CONCLUSION: In morphine-dependent rats, Neuroinflammation (NI) became more severe in the addiction-involved brain regions but remitted in the sensory-related brain regions after the administration of naloxone, and this NI induced by withdrawal was further aggravated after conditioned aversion formation thus may help to consolidate the withdrawal memory.

PET Imaging for Dynamically Monitoring Neuroinflammation in APP/PS1 Mouse Model Using [18F]DPA714.

Background: In the pathogenesis of Alzheimer's disease (AD), microglia play an increasingly important role. Molecular imaging of neuroinflammatory targeting microglia activation and the high expression of 18-kDa translocator protein (TSPO) has become a hot topic of research in recent years. Dynamic monitoring neuroinflammation is crucial for discovering the best time point of anti-inflammatory therapy. Motivated by this, Positron emission tomography (PET) imaging in an APP/PS1 mouse model of AD, using 18F-labeled DPA-714 to monitor microglia activation and neuroinflammation, were performed in this paper. Methods: We prepared [18F]DPA714 and tested the biological characteristics of the molecular probe in normal mice. To obtain a higher radiochemical yield, we improved the [18F]-fluorination conditions in the precursor dosage, reaction temperature, and synthesis time. We performed [18F]DPA714 PET scanning on APP/PS1 mice at 6-7, 9-10, 12-13, and 15-16 months of age, respectively. The same experiments were conducted in Wild-type (Wt) mice as a control. Referring to the [18F]DPA714 concentrated situation in the brain, we performed blocking experiments with PK11195 (1 mg/kg) in 12-13-months-old APP/PS1 mice to confirm the specificity of [18F]DPA714 for TSPO in the APP/PS1 mice. Reconstructed brain PET images, fused with the Magnetic Resonance Imaging (MRI) template atlas, and the volumes of interests (VOIs) of the hippocampus and cortex were determined. The distribution of [18F]DPA714 in the brain tissues of 15-16-months-old APP/PS1 and Wt mice were studied by immunofluorescence staining. Results: Through the reaction of 18F, with 2 mg precursor dissolved in 300 ul acetonitrile at 105°C for 10 min, we obtained the optimal radiochemical yield of 42.3 ± 5.1% (non-decay correction). Quantitative analysis of brain PET images showed that the [18F]DPA714 uptake in the cortex and hippocampus of 12-13-months-old APP/PS1 mice was higher than that of the control mice of the same age (cortex/muscle: 2.77 ± 0.13 vs. 1.93 ± 0.32, p = 0.0014; hippocampus/muscle: 3.33 ± 0.10 vs. 2.10 ± 0.35, p = 0.0008). The same significant difference was found between 15- and 16-months-old APP/PS1 mice (cortex/muscle: 2.64 ± 0.14 vs. 1.86 ± 0.52, p=0.0159; hippocampus/muscle: 2.89 ± 0.53 vs. 1.77 ± 0.48, p = 0.0050). Immunofluorescence staining showed that the activation of microglia and the level of TSPO expression in the cortex and hippocampus of APP/PS1 mice were significantly higher than Wt mice. Conclusion: [18F]DPA714, a molecular probe for targeting TSPO, showed great potential in monitoring microglia activation and neuroinflammation, which can be helpful in discovering the best time point for anti-inflammatory therapy in AD.

Decreased striatal vesicular monoamine transporter 2 (VMAT2) expression in a type 1 diabetic rat model: A longitudinal study using micro-PET/CT.

AIMS: Diabetes mellitus is a risk factor for Parkinson's disease. These diseases share similar pathogenic pathways, such as mitochondrial dysfunction, inflammation, and altered metabolism. Despite these similarities, the pathogenic relationship between these two diseases is unclear. [18F]FP-(+)-DTBZ is a promising radiotracer targeting VMAT2, which has been used to measure ß-cell mass and to diagnose Parkinson's disease. The aim of this study was to examine the effect of type 1 diabetes on VMAT2 expression in the striatum using [18F]FP-(+)-DTBZ. MATERIALS AND METHODS: A longitudinal study of type 1 diabetic rats was established by intraperitoneally injecting male Wistar rats with streptozotocin. Rats injected with saline were used as the control group. Glucose level, body weight, and [18F]FP-(+)-DTBZ uptake in the striatum and pancreas were evaluated at 0.5, 1, 4, 6 and 12 months after STZ or saline injection. RESULTS: At one-half month post-STZ injection, the glucose levels in these rats increased and then returned to a normal level at 6 months. Along with increased glucose levels, body weight was also decreased significantly and returned slowly to a normal level. ß-Cell mass and striatal [18F]FP-(+)-DTBZ uptake were impaired significantly at 2 weeks post-STZ injection in type 1 diabetic rats and returned to a normal level at 6 and 4 months post-STZ injection. CONCLUSIONS: Due to increased glucose levels and decreased ß-cell mass, decreased [18F]FP-(+)-DTBZ uptake in the striatum was observed in type 1 diabetic rats. Decreased BCM and increased glucose levels were correlated with VMAT2 expression in the striatum which indicated DM is a risk factor for PD.

Maturation of topological organization of brain networks in male adolescent rats: A longitudinal FDG-PET study.

Recent studies have found developmental alterations of the brain during the adolescent period. However, maturation-related changes of the topological properties in brain networks are unexplored so far. We therefore used fluoro-d-glucose positron emission tomography (FDG PET) to explore the maturation-related topological metabolic changes in brain networks from adolescence to adulthood with a longitudinal study in rats (male, n = 6), followed by a graph theoretical analysis. Our results showed reduced normalization characteristic path length and increased small world index of brain networks. Specifically, we found that relative to adulthood, in the adolescent stage rats had significantly increased nodal centrality in right entorhinal cortex, left frontal association cortex, and cerebellum, areas relating to memory, executive function and higher cognitive control and motor control; and significantly reduced nodal centrality in left superior colliculus and left retrosplenial cortex. These findings suggest that moving from adolescence to adulthood, networks of the brain mature accompanied by reassignment of hub regions to increase network efficiency. These results provide an animal model of brain network maturation from adolescence to adulthood which are relevant for understanding of development of psychiatric disorders during adolescence or transition from adolescence to adulthood.

Expert Consensus on clinical application of FDG PET/CT in infection and inflammation.

To further promote the clinical application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in infection and inflammation and standardize the diagnostic process, the experts in relevant fields in China carried out discussion and formed the Expert Consensus on the clinical application of FDG PET/CT in infection and inflammation. This consensus is intended to provide a reference for imaging physicians to select a reasonable diagnostic plan. However, it should be noted that it couldn't include or solve all the problems in clinical operation. Imaging physicians and technicians should develop a comprehensive and reasonable diagnostic procedure according to their professional knowledge, clinical experience and currently available medical resources when facing specific patients.

Changes in brain glucose metabolism and connectivity in somatoform disorders: an 18F-FDG PET study.

Somatoform disorders (SFD) are defined as a syndrome characterized by somatic symptoms which cannot be explained by organic reasons. Chronic or recurrent forms of somatization lead to heavy emotional and financial burden to the patients and their families. However, the underlying etiology of SFD is largely unknown. The purpose of this study is to investigate the changed brain glucose metabolic pattern in SFD. In this study, 18 SFD patients and 21 matched healthy controls were enrolled and underwent an 18F-FDG PET scan. First, we explored the altered brain glucose metabolism in SFD. Then, we calculated the mean 18F-FDG uptake values for 90 AAL regions, and detected the changed brain metabolic connectivity between the most significantly changed regions and all other regions. In addition, the Pearson coefficients between the neuropsychological scores and regional brain 18F-FDG uptake values were computed for SFD patients. We found that SFD patients showed extensive hypometabolism in bilateral superolateral prefrontal cortex, insula, and regions in bilateral temporal gyrus, right angular gyrus, left gyrus rectus, right fusiform gyrus, right rolandic operculum and bilateral occipital gyrus. The metabolic connectivity between right insula and prefrontal areas, as well as within prefrontal areas was enhanced in SFD. And several brain regions were associated with the somatic symptoms, including insula, putamen, middle temporal gyrus, superior parietal gyrus and orbital part of inferior frontal gyrus. Our study revealed widespread alterations of the brain glucose metabolic pattern in SFD patients. Those findings might elucidate the neuronal mechanisms with glucose metabolism and shed light on the pathology of SFD.

The Diagnostic Value Of Using 18F-Fluorodeoxyglucose Positron Emission Tomography To Differentiate Between Low- And High-Grade Meningioma.

OBJECTIVE: This study aims to evaluate the potential role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in detecting high-grade meningiomas and predicting the prognosis of patients after meningioma surgery. PATIENTS AND METHODS: A total of 124 patients met the final inclusion criterion. Tumor to gray ratio (TGR) was compared with Ki-67 labeling index, and its correlations with pre-operative neurological function and treatment status were also evaluated. Receiver-operating characteristic (ROC) curve was drawn to determine a cut-off value which could discriminate meningioma of different grades. Prognostic factors including TGR were analyzed using Kaplan-Meier survival curve and cox proportional model. RESULTS: The TGR of higher World Health Organization (WHO) grade meningioma was significantly higher than that in lower grade (p < 0.001), and it was correlated with the Ki-67 labeling index (p < 0.001, r = 0.1545). The TGR of 1.30 was the best cutoff value for the detection of high grade (WHO grade II&III) meningioma from low grade (WHO grade I) according to ROC analysis, with a sensitivity of 61.5%, the specificity of 86.7%, and accuracy of 81.5%. The TGR (p < 0.001), treatment status (p = 0.035), tumor grade (p < 0.001) and Ki-67 labeling index (p < 0.001) were significantly associated with progression-free survival (PFS). Cox proportional hazards model demonstrated that TGR (p = 0.013) was an independent prognostic factor for PFS. CONCLUSION: A high uptake of FDG was correlated with a more proliferative biological behavior and is a risk factor for tumor recurrence.

Reduced resting-state brain functional network connectivity and poor regional homogeneity in patients with CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests principally as a suite of cognitive impairments, particularly in the executive domain. Executive functioning requires the dynamic coordination of neural activity over large-scale networks. It remains unclear whether changes in resting-state brain functional network connectivity and regional homogeneities (ReHos) underly the mechanisms of executive dysfunction evident in CADASIL patients. METHODS: In this study, 22 CADASIL patients and 44 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was used to measure functional brain network connectivity, and ReHos were calculated to evaluate local brain activities. We used seed-based functional connectivity (FC) analyses to determine whether dysfunctional areas (as defined by ReHos) exhibited abnormal FC with other brain areas. Relationships among the mean intra-network connectivity z-scores of dysfunctional areas within functional networks, and cognitive scores were evaluated using Pearson correlation analyses. RESULTS: Compared to the controls, CADASIL patients exhibited decreased intra-network connectivity within the bilateral lingual gyrus (LG) and the right cuneus (CU) (thus within the visual network [VIN)], and within the right precuneus (Pcu), inferior frontal gyrus (IFG), and precentral gyrus (thus within the frontal network [FRN]). Compared to the controls, patients also exhibited significantly lower ReHos in the right precuneus and cuneus (Pcu/CU), visual association cortex, calcarine gyri, posterior cingulate, limbic lobe, and weaker FC between the right Pcu/CU and the bilateral parahippocampal gyrus (PHG), and between the right Pcu/CU and the right postcentral gyrus. Notably, the mean connectivity z-scores of the bilateral LG and the right CU within the VIN were positively associated with compromised attention, calculation and delayed recall as revealed by tests of the various cognitive domains explored by the Mini-Mental State Examination. CONCLUSIONS: The decreases in intra-network connectivity within the VIN and FRN and reduced local brain activity in the posterior parietal area suggest that patients with CADASIL may exhibit dysfunctional visuomotor behaviors (a hallmark of executive function), and that all visual information processing, visuomotor planning, and movement execution may be affected.