Studies Of Cerebral Metabolism Research Articles

Abstract 152: Exploring Age‐related Changes in Brain Metabolism among Individuals with Cardiovascular Risk Factors: An FDG‐PET Analysis

Introduction Patients with cognitive impairment often have a history of cardiovascular disease (CVD) or multiple cardiovascular risk factors (CRFs) such as hypertension, obesity, and hypercholesterolemia. The literature reports that CVD with CRFs may increase the risk of developing vascular dementia and Alzheimer’s Disease. 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) allows for the in vivo study of cerebral glucose metabolism, and can detect metabolic alterations in several neurological diseases. As we age, the brain undergoes both structural and functional changes; the regional distribution of these alterations mirrors cognitive decline. This study aims to assess the effect of aging on regional glucose uptake in subjects with known cardiovascular risk factors. Methods In total, 40 subjects (mean age 55.9 ± 11.89 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET scanning, and 70 whole brain structures were analyzed in each subject. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. All subjects underwent whole‐body FDG‐PET/CT imaging 180 minutes after the administration of 4.0 MBq/kg dose of FDG. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). MIMneuro provides region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P < 0.05. Results Various significant associations between age and FDG uptake across all 70 brain regions of interest were observed. In particular, age was found to have an inverse correlation with regional metabolism in the middle temporal gyrus (r= ‐0.364, p=0.021), superior frontal gyrus (r= ‐0.433, p=0.005), superior parietal lobule (r= ‐0.354, p=0.025), supplementary motor area (r= ‐0.436, p=0.005), and temporal operculum (r= ‐0.370, p=0.019). Conclusion The results demonstrate a significant inverse correlation between age and FDG uptake in five regions among individuals with cardiovascular risk factors. This information may be useful in the determination of whether such scans might be useful in the evaluation of patients with a history of CVD/CRF or with mild cognitive impairment (MCI). Previous literature has reported that increased medial temporal gyrus atrophy is a predictor of dementia in subjects with MCI, and alterations within this lobe mark the beginning of the disease process. Our strongest inverse correlation, the superior frontal gyrus, has been shown to be related to working memory; hypometabolism in this region has previously correlated with severity of cognitive impairments in attention, executive function, and language. Further research is needed to determine the potential for using FDG‐PET imaging as a tool for early detection and intervention for cognitive decline. If patients with CVD or CRFs can be properly diagnosed, if there exists a metabolic signature of regional functional change, intervention may prove highly beneficial for cognitive function, quality of life, and overall well‐being.

A pilot study of cerebral metabolism and serotonin 5-HT2A receptor occupancy in rats treated with the psychedelic tryptamine DMT in conjunction with the MAO inhibitor harmine.

Rationale: The psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are often attributed to agonism at brain serotonin 5-HT2A receptors by N,N-dimethyltryptamine (DMT). To reduce first pass metabolism of oral DMT, ayahuasca preparations additionally contain reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as harmine. However, there is lacking biochemical evidence to substantiate this pharmacokinetic potentiation of DMT in brain via systemic MAO-A inhibition. Objectives: We measured the pharmacokinetic profile of harmine and/or DMT in rat brain, and tested for pharmacodynamic effects on brain glucose metabolism and DMT occupancy at brain serotonin 5-HT2A receptors. Methods: We first measured brain concentrations of harmine and DMT after treatment with harmine and/or DMT at low sub-cutaneous doses (1mg/kg each) or harmine plus DMT at moderate doses (3mg/kg each). In the same groups of rats, we also measured ex vivo the effects of these treatments on the availability of serotonin 5-HT2A receptors in frontal cortex. Finally, we explored effects of DMT and/or harmine (1mg/kg each) on brain glucose metabolism with [18F]FDG-PET. Results: Results confirmed that co-administration of harmine inhibited the formation of the DMT metabolite indole-3-acetic acid (3-IAA) in brain, while correspondingly increasing the cerebral availability of DMT. However, we were unable to detect any significant occupancy by DMT at 5-HT2A receptors measured ex vivo, despite brain DMT concentrations as high as 11.3µM. We did not observe significant effects of low dose DMT and/or harmine on cerebral [18F]FDG-PET uptake. Conclusion: These preliminary results call for further experiments to establish the dose-dependent effects of harmine/DMT on serotonin receptor occupancy and cerebral metabolism.

Imaging secondary neuronal degeneration

ObjectiveDistal nerve degeneration refers to the process of disintegration of a neuron or neuronal circuit as a consequence of distal damage. The end result of multiple etiologies, this finding is becoming common due to the increasing number of imaging tests done. This paper aims to define the different types of distal nerve damage, review the anatomy and function of the most commonly affected tracts, and illustrate distal nerve damage through diagrams and representative cases from routine practice. ConclusionKnowing the distant response that can be expected according to the topography of a neuronal lesion is crucial to avoid diagnostic errors. Axonal degeneration and transsynaptic degeneration can be both antegrade and retrograde. Studies of cerebral metabolism, perfusion sequences, and diffusion sequences are showing increasingly earlier changes related to the same process; radiologists need to be aware of these changes.

Carretera perdida: imagen de la degeneración neuronal secundaria

ObjectiveDistal nerve degeneration refers to the process of disintegration of a neuron or neuronal circuit as a consequence of distal damage. The end result of multiple etiologies, this finding is becoming common due to the increasing number of imaging tests done. This paper aims to define the different types of distal nerve damage, review the anatomy and function of the most commonly affected tracts, and illustrate distal nerve damage through diagrams and representative cases from routine practice. ConclusionKnowing the distant response that can be expected according to the topography of a neuronal lesion is crucial to avoid diagnostic errors. Axonal degeneration and transsynaptic degeneration can be both antegrade and retrograde. Studies of cerebral metabolism, perfusion sequences, and diffusion sequences are showing increasingly earlier changes related to the same process; radiologists need to be aware of these changes.

Is Bariatric Surgery Brain Surgery?

Roux-en-Y gastric bypass (RYGB) reliably produces sustained weight losses, reduces circulating blood glucose, and lowers risk of type 2 diabetes (1). Accompanying these benefits, however, is symptomatic hypoglycemia, reported by up to one-third of post–bariatric surgery patients (2,3). In an estimated <1% of RYGB patients (4), postprandial hyperinsulinemic hypoglycemia causes severe symptoms including neuroglycopenia with significant morbidity. New mechanistic insights and treatment options for these patients are needed. Potential contributors include rapid glucose delivery into the bloodstream, improved β-cell function, and gut adaptations, but the role of the central nervous system (CNS) is an important and underdeveloped area of research (3). In their article in this issue of Diabetes , Almby et al. (5) investigate whether RYGB alters the brain response to hypoglycemia in humans—a topic with further relevance to the CNS contribution to RYGB’s modification of overall glucose homeostasis. Human neuroimaging studies document RYGB-induced changes in brain function and suggest reversibility of obesity-associated findings (6–8). Studies of cerebral metabolism measuring [18F]-fluorodeoxyglucose uptake by positron emission tomography (FDG-PET) show that brain glucose uptake is elevated in participants with obesity and partially reversed post-RYGB (6,7), but controlled studies of the cerebral metabolic response to insulin-induced hypoglycemia are lacking. Cerebral blood flow response to insulin-induced hypoglycemia assessed by arterial spin labeling (ASL) showed increased regional blood flow (vs. euglycemia) in the cortex, thalamus (9), and hypothalamus (10) in healthy adults. Almby et al. provide novel data on the effect of RYGB on brain response to hypoglycemia (5). Almby et al. included 11 participants that underwent, before and …

Cerebral glucose metabolism in bipolar disorder: A voxel-based meta-analysis of positron emission tomography studies.

BackgroundPrevious positron emission tomography studies have reported the changes of cerebral glucose metabolism in bipolar disorder. However, the findings across studies remain controversial, containing differing results.MethodsA systematic literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted. We conducted a voxel‐wide meta‐analysis of cerebral glucose metabolism studies, using the seed‐based mapping approach, in patients with bipolar disorder (BD).ResultsWe identified 7 studies suitable for inclusion, which included a total of 126 individuals with BD and 160 healthy controls. The most consistent and robust findings were an increase in cerebral glucose metabolism in the right precentral gyrus and a decrease in the left superior temporal gyrus, left middle temporal gyrus, and cerebellum. Additionally, the sex distribution and illness duration had significant moderating effects on cerebral glucose metabolism alterations.ConclusionsCerebral glucose metabolism alterations in these brain regions are likely to reflect the disease‐related functional abnormalities such as emotion and cognition. These findings contribute to a better understanding of the neurobiological underpinnings of bipolar disorder.Limitations.This study was done at a study level and cannot be addressed at the patient level. Subgroup analysis of BD I and BD II is not possible due to limited literature data.

Multimodal Measurements of Brain Tissue Metabolism and Perfusion in a Neonatal Model of Hypoxic-Ischaemic Injury.

This is the first multimodal study of cerebral tissue metabolism and perfusion post-hypoxic-ischaemic (HI) brain injury using broadband near-infrared spectroscopy (bNIRS), diffuse correlation spectroscopy (DCS), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). In seven piglet preclinical models of neonatal HI, we measured cerebral tissue saturation (StO2), cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), changes in the mitochondrial oxidation state of cytochrome c oxidase (oxCCO), cerebral glucose metabolism (CMRglc) and tissue biochemistry (Lac+Thr/tNAA). At baseline, the parameters measured in the piglets that experience HI (not controls) were 64±6% StO2, 35±11ml/100g/min CBF and 2.0±0.4μmol/100g/min CMRO2. After HI, the parameters measured were 68±6% StO2, 35±6ml/100g/min CBF, 1.3±0.1μmol/100g/min CMRO2, 0.4±0.2 Lac+Thr/tNAA and 9.5±2.0 CMRglc. This study demonstrates the capacity of a multimodal set-up to interrogate the pathophysiology of HIE using a combination of optical methods, MRS, and PET.

CHANGES OF THE LOCAL FUNCTIONAL BRAIN ACTIVITY ASSOCIATED WITH SPEECH DISORDERS IN CHILDREN WITH EPILEPSY AND DEVELOPMENTAL DELAY (PET STUDY)

PET study of cerebral glucose metabolism was performed in 73 children with epilepsy and mental retardation. Expressive speech disorders were associated with decrease of cerebral metabolism rate of glucose (CMRglu) in the upper frontal gyrus, caudate nucleus and thalamus of the left and right hemispheres. In the group with combined expressive and impressive speech disorders the significant CMRglu reduction in the middle temporal and supramarginal gyrus of the left hemisphere was observed. The obtained results confirm that the brain structures associated with the executive functions and complex association processes have a great significance in the speech development.

Changes in [18F]Fluorodeoxyglucose Activities in a Shockwave-Induced Traumatic Brain Injury Model Using Lithotripsy.

We present a longitudinal study of cerebral metabolism using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a rat model of shockwave-induced traumatic brain injury (SW-TBI). Anesthetized rats received 5 or 10 SW pulses to the right anterior lateral or dorsal frontal regions using SW lithotripsy. Animals were scanned for FDG uptake at baseline, 3 h post-injury, and 3 days post-injury, using a small animal PET/computed tomography (CT) scanner. FDG uptake at all time-points was quantified as the ratio of brain activity relative to peripheral activity in the left ventricle (LV) in the heart (Abrain/ALV) for the entire brain, each hemisphere, and four cortices (motor, cingulate, somatosensory, and retrosplenial). The mixed-designed models analysis of variance (ANOVA) for the hemispheric and global FDG uptake ratio showed a significant effect of the time-of-scan (p = 0.038) and measured region (p = 6.12e-09). We also observed a significant effect of the time-of-scan (p = 0.046) and measured region (p = 2.28e-09) for the FDG uptake ratio in four cortical regions. None of the measurements (global or local) showed a significant effect for the number of SW pulses (5 or 10) or SW location (lateral or dorsal frontal regions). Our data suggest that SW-TBI causes hypermetabolism on the impact side of the rat brain at 3 h post-injury compared with the baseline measurements. However, the increase in FDG uptake by day 3 post-injury was not significant. Further studies on post-TBI metabolic changes are needed to understand better the pathophysiology of the injury.

Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease

Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [14C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [14C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease.

Decreased resting state metabolic activity in frontopolar and parietal brain regions is associated with suicide plans in depressed individuals

Suicide plans are a major risk factor for suicide, which is a devastating outcome of depression. While structural and functional brain changes have been demonstrated in relation to suicidal thoughts and behaviour, brain mechanisms underlying suicide plans have not yet been studied. Here, we studied changes in regional cerebral metabolic activity in association with suicide plans in depressed individuals. Using 18FDG-PET, a comparative study of regional cerebral glucose metabolism (rCMRglu) was carried out in depressed individuals with suicidal thoughts and suicide plans, depressed individuals with only suicidal thoughts, depressed individuals without suicide thoughts and plans, and healthy controls. When compared to the other groups, depressed individuals with suicide plans showed relative hypometabolism in the right middle frontal gyrus and the right inferior parietal lobe (Brodmann areas 10 and 39). Suicide plans in depressed individuals appear to be associated with reduced activity in brain areas that are involved in decision-making and choice, more particularly in exploratory behaviour.

Characterizing Resting-State Brain Function Using Arterial Spin Labeling.

Arterial spin labeling (ASL) is an increasingly established magnetic resonance imaging (MRI) technique that is finding broader applications in studying the healthy and diseased brain. This review addresses the use of ASL to assess brain function in the resting state. Following a brief technical description, we discuss the use of ASL in the following main categories: (1) resting-state functional connectivity (FC) measurement: the use of ASL-based cerebral blood flow (CBF) measurements as an alternative to the blood oxygen level-dependent (BOLD) technique to assess resting-state FC; (2) the link between network CBF and FC measurements: the use of network CBF as a surrogate of the metabolic activity within corresponding networks; and (3) the study of resting-state dynamic CBF-BOLD coupling and cerebral metabolism: the use of dynamic CBF information obtained using ASL to assess dynamic CBF-BOLD coupling and oxidative metabolism in the resting state. In addition, we summarize some future challenges and interesting research directions for ASL, including slice-accelerated (multiband) imaging as well as the effects of motion and other physiological confounds on perfusion-based FC measurement. In summary, this work reviews the state-of-the-art of ASL and establishes it as an increasingly viable MRI technique with high translational value in studying resting-state brain function.

Myths, need, contribution to the diagnosis.

The use of diagnostic imaging in the evaluation of patients with headache is an almost mandatory step. Although there are specific conditions (the so-called red flags) indicating the need of diagnostic imaging, daily experience shows that a study of the brain and, often, of the intracranial vessels, is part of the routine of many of these patients. The most common and appropriate study is the MRI integrated with the angiographic evaluation (MRA). An MRI and MRA, properly performed, are able to exclude most of the organic pathologies potentially causing headache. The list of these conditions is long and not useful in this context. It is important to remember that significant MRI changes are found in about 4% of patients with chronic headache but this percentage can rise up to 14% in the atypical forms. The MRI evaluation also allows to define whether the patients, especially the young ones, have a condition of brain signal alterations (multiple bright spots). Some studies reported that these are more frequent in patients with migraine especially with aura and mostly in females. The clinical significance and role of these changes remains to be proven. Another approach of imaging is related to the possibility of assessing, by means of functional studies, the pathophysiological moments responsible for the symptoms. These studies are based mainly on functional MRI which includes cerebral perfusion, cortical activation (induced or by means of resting state techniques) and metabolic studies with spectroscopy. The last approach is the one that assesses the consequences of long standing symptom analyzing morpho-volumetric brain “in toto” or inside the cerebral cortex. These are techniques like computed voxel based morphometry (VBM) or Free Surfer able to evaluate small volumetric changes between groups of healthy subjects and patients.

The neurochemical profile of the hippocampus in isoflurane-treated and unanesthetized rat pups.

In vivo study of cerebral metabolism in neonatal animals by high-resolution magnetic resonance spectroscopy (MRS) is an important tool for deciphering the developmental origins of adult diseases. Up to date, all in vivo spectrum acquisition procedures have been performed in neonatal rodents under anesthesia. However, it is still unknown if the inhaled anesthetic isoflurane, which is commonly used in magnetic resonance imaging studies, could affect metabolite levels in the brain of neonatal rats. Moreover, the unanesthetized MRS preparation that uses neonatal rodent pups is still lacking.Here, a novel restraint protocol was developed for neonatal rats in accordance with the European Directive 2010/63/EU. This protocol shares the same gradation of severity as the protocol for non-invasive magnetic resonance imaging of animals with appropriate sedation or anesthesia. Such immobilization of neonatal rats without anesthesia can be implemented for MRS studies when an interaction between anesthetic and target drugs is expected. Short-term isoflurane treatment did not affect the levels of key metabolites in the hippocampi of anesthetized pups and, in contrast to juvenile and adult rodents, it is suitable for MRS studies in neonatal rats when the interaction between anesthetic and target drugs is not expected.

Update on SPECT and PET in parkinsonism - part 2: biomarker imaging of cognitive impairment in Lewy-body diseases.

To give an update on recent biomarker imaging studies using single-photon emission computed tomography (SPECT) and positron emission tomography (PET) on cognitive impairment in Lewy-body diseases (LBD). Imaging studies of regional cerebral glucose metabolism with [F]fluorodeoxyglucose(FDG)-PET support the concept that Parkinson's disease (PD) with mild cognitive impairment represents a prodromal stage of PD with dementia (PDD). Furthermore, [F]FDG-PET may be suited for risk stratification for dementia in PD. In line with neuropathological studies, preliminary amyloid-beta (Aβ) PET studies suggest that Aβ acts synergistically with Lewy pathology in LBD, leading to an earlier manifestation of cognitive impairment in dementia with Lewy-bodies compared with PDD and a more rapid cognitive decline in PD patients with concomitant Aβ pathology. Molecular neuroimaging with SPECT and PET provides unique in-vivo insights into neuropathological and pathophysiological changes underlying cognitive impairment in LBD. Future prospective studies are needed to confirm the prognostic value of [F]FDG-PET and to define the value of amyloid PET and upcoming techniques, such as tau imaging, for diagnosis and prognosis in LBD.

A Biochemical Approach to Depressive Illness

We also have a fourth possibility, namely that the changes in metabolism may be taking place only in the brain although the same metabolic process is to be found also in other tissues. If this situation exists it may be impossible to infer changes in cerebral tissue from changes in metabolites in blood and urine. Studies of cerebral metabolism in depressive illness are necessary in each of the above situations. In 1, 2 and 3 above they are necessary to justify the assumptions relating general and cerebral metabolism, whilst in case 4 the information is not obtainable by any other technique.

Structural Imaging in Late-Life Depression: Association with Mood and Cognitive Responses to Antidepressant Treatment

Recent positron emission tomography studies of cerebral glucose metabolism have identified the functional neural circuitry associated with mood and cognitive responses to antidepressant treatment in late life depression (LLD). The structural alterations in these networks are not well understood. The present study used magnetic resonance (MR) imaging and voxel-based morphometry to evaluate the association between gray matter volumes and changes in mood symptoms and cognitive function with treatment with the antidepressant citalopram. Open-label trial with baseline brain MR scan. Mood and cognitive assessments performed at baseline and during citalopram treatment. Outpatient clinics of an academic medical center. 17 previously unmedicated patients age 55 years or older with a major depressive episode and 17 non-depressed comparison subjects. 12-week trial of flexibly dosed citalopram. Gray matter volumes, Hamilton Depression Rating Scale, California Verbal Learning Test, Delis-Kaplan Executive Function System. In LLD, higher gray matter volumes in the cingulate gyrus, superior and middle frontal gyri, middle temporal gyrus, and precuneus was associated with greater mood improvement. Higher gray matter volumes in primarily frontal areas were associated with greater improvement in verbal memory and verbal fluency performance. Associations with antidepressant induced improvements in mood and cognition were observed in several brain regions previously correlated with normalization of glucose metabolism after citalopram treatment in LLD. Future studies will investigate molecular mechanisms underlying these associations (e.g., beta-amyloid, inflammation, glutamate).

Mild cognitive disorders with background psycho-vegetative syndrome. Some of the metabolic aspects

Background: Often the mild cognitive disorders develop in background of psycho-vegetative syndrome (PVS) not infrequently in frames of anxiety or anxiety depressive disorders. Cognitive disorders coexist with anxiety and depressive conditions, and later they can aggravate resulting in professional and social disadaptation. These studies of cerebral metabolism in mild cognitive disorders with background PVS will allow to make patient's complaints objective, and to improve the treatment and prevention of cognitive disorders.

Quantitative Analysis of Neurotransmitter Pathways Under Steady State Conditions – A Perspective

In a contribution to this Research Topic Erkki Somersalo and Daniela Calvetti carried out a mathematical analysis of neurotransmitter pathways in brain, modeling compartmental nitrogen flux among several major participants – ammonia, glutamine, glutamate, GABA, and selected amino acids. This analysis is important because cerebral nitrogen metabolism is perturbed in many diseases, including liver disease and inborn errors of the urea cycle. These diseases result in an elevation of blood ammonia, which is neurotoxic. Here, a brief description is provided of the discovery of cerebral metabolic compartmentation of nitrogen metabolism – a key feature of cerebral glutamate–glutamine and GABA–glutamine cycles. The work of Somersalo and Calvetti is discussed as a model for future studies of normal and pathological cerebral ammonia metabolism.

Size isn't everything, comparatively speaking

Size isn't everything, comparatively speaking