Aerobic glycolysis imaging of epileptic foci during the inter-ictal period

Zhang, Miao; Qin, Qikai; Zhang, Shuning; Liu, Wei; Meng, Hongping; Xu, Mengyang; Huang, Xin‐Yun; Lin, Xiaozhu; Lin, MingDe; Hermán, Péter; Hyder, Fahmeed; Stevens, Raymond C.; Wang, Zheng; Li, Biao; Thompson, Garth J.

doi:10.1016/j.ebiom.2022.104004

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…However, gas-free calibrated fMRI methods are available and have been applied in murine and human brain. 63–67 We measured the influence of brief (30 s) and moderate (5% CO 2 ) hypercapnic exposure on neuronal and hemodynamic activity, and our results clearly show that widespread neuronal activity is indeed influenced by CO 2 with global neurovascular uncoupling.…”

Section: Discussionmentioning

confidence: 81%

Spatiotemporal features of neurovascular (un)coupling with stimulus-induced activity and hypercapnia challenge in cerebral cortex and olfactory bulb

James

Sanggaard

Akif

et al. 2023

J Cereb Blood Flow Metab

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Carbon dioxide (CO2) is traditionally considered as metabolic waste, yet its regulation is critical for brain function. It is well accepted that hypercapnia initiates vasodilation, but its effect on neuronal activity is less clear. Distinguishing how stimulus- and CO2-induced vasodilatory responses are (dis)associated with neuronal activity has profound clinical and experimental relevance. We used an optical method in mice to simultaneously image fluorescent calcium (Ca2+) transients from neurons and reflectometric hemodynamic signals during brief sensory stimuli (i.e., hindpaw, odor) and CO2 exposure (i.e., 5%). Stimuli-induced neuronal and hemodynamic responses swiftly increased within locally activated regions exhibiting robust neurovascular coupling. However, hypercapnia produced slower global vasodilation which was temporally uncoupled to neuronal deactivation. With trends consistent across cerebral cortex and olfactory bulb as well as data from GCaMP6f/jRGECO1a mice (i.e., green/red Ca2+ fluorescence), these results unequivocally reveal that stimuli and CO2 generate comparable vasodilatory responses but contrasting neuronal responses. In summary, observations of stimuli-induced regional neurovascular coupling and CO2-induced global neurovascular uncoupling call for careful appraisal when using CO2 in gas mixtures to affect vascular tone and/or neuronal excitability, because CO2 is both a potent vasomodulator and a neuromodulator.

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Section: Discussionmentioning

confidence: 81%

Spatiotemporal features of neurovascular (un)coupling with stimulus-induced activity and hypercapnia challenge in cerebral cortex and olfactory bulb

James

Sanggaard

Akif

et al. 2023

J Cereb Blood Flow Metab

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“…Moreover, 18 F-FDG PET has been widely used in the presurgical assessment of patients with DRE by identifying the hypometabolic seizure onset zones, especially when MRI and scalp EEG are unable to do so or are discordant [11]. Previous studies have shown that interhemispheric metabolic asymmetry on interictal PET could indicate the location of the epileptogenic zone, and the oxygen-glucose index based on PET images showed unique value in identifying foci during the interictal period in patients with DRE [27,28]. PET serves an important role in understanding the neuro-behavioural characteristics of TSC patients, including autism, attention deficit hyperactivity disorder and cognitive impairment, and it has become an indispensable, noninvasive clinical approach for preoperative evaluation in TSC patients with intractable epilepsy [29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Predictive model for epileptogenic tubers from all tubers in patients with tuberous sclerosis complex based on 18F-FDG PET: an 8-year single-centre study

Wang,

Li,

et al. 2023

BMC Med

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Background More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. Methods Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. Results PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70–0.83) than the LDA (AUC = 0.7506; 95% CI 0.68–0.82) and ANN models (AUC = 0.7425; 95% CI 0.67–0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71–0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71–0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74–0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75–0.87). Conclusions The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

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“…Although conventional diabetes diagnostic indicators such as fasting plasma glucose and HbA1c are simple and practicable, they do not provide the specificity to distinguish pathways related to pancreatic β-cell mass destruction or dysfunction [ 160 , 161 ]. Noninvasive imaging tools (such as PET and MRI) and novel biomarkers can provide abundant pathological characteristics about β-cells [ 162 , 163 , 164 , 165 , 166 ] or related diagnostic information [ 140 , 167 , 168 , 169 , 170 , 171 , 172 , 173 ], which may help improve monitoring disease progress and severity, support the development of diabetes management strategies, evaluate and even guide drug development [ 174 , 175 ]. Artificial intelligence (AI) is likely to play an increasingly important role in diabetes diagnosis (such as medical image analysis and subtype classification), clinical decision support, management, risk identification, prevention [ 133 , 134 , 135 , 136 ], and prognosis [ 176 ].…”

Section: Conclusion and Perspectivementioning

confidence: 99%

GLP-1R Signaling and Functional Molecules in Incretin Therapy

et al. 2023

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Glucagon-like peptide-1 receptor (GLP-1R) is a critical therapeutic target for type 2 diabetes mellitus (T2DM). The GLP-1R cellular signaling mechanism relevant to insulin secretion and blood glucose regulation has been extensively studied. Numerous drugs targeting GLP-1R have entered clinical treatment. However, novel functional molecules with reduced side effects and enhanced therapeutic efficacy are still in high demand. In this review, we summarize the basis of GLP-1R cellular signaling, and how it is involved in the treatment of T2DM. We review the functional molecules of incretin therapy in various stages of clinical trials. We also outline the current strategies and emerging techniques that are furthering the development of novel therapeutic drugs for T2DM and other metabolic diseases.

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Aerobic glycolysis imaging of epileptic foci during the inter-ictal period

Cited by 9 publications

References 36 publications

Spatiotemporal features of neurovascular (un)coupling with stimulus-induced activity and hypercapnia challenge in cerebral cortex and olfactory bulb

Spatiotemporal features of neurovascular (un)coupling with stimulus-induced activity and hypercapnia challenge in cerebral cortex and olfactory bulb

Predictive model for epileptogenic tubers from all tubers in patients with tuberous sclerosis complex based on 18F-FDG PET: an 8-year single-centre study

GLP-1R Signaling and Functional Molecules in Incretin Therapy

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