Global Hypometabolism Research Articles

Do Tau Deposition and Glucose Metabolism Dissociate in Alzheimer's Disease Trajectory?

Tau aggregation demonstrates close associations with hypometabolism in Alzheimer's disease (AD), although differing pathophysiological processes may underlie their development. To establish whether tau deposition and glucose metabolism have different trajectories in AD progression and evaluate the utility of global measures of these pathological hallmarks in predicting cognitive deficits. 279 participants with amyloid-β (Aβ) status, and T1-weighted MRI scans, were selected from the Alzheimer's Disease Neuroimaging Initiative (http://adni.loni.usc.edu). We created the standard uptake value ratio images using Statistical Parametric Mapping 12 for [18F]AV1451-PET (tau) and [18F]FDG-PET (glucose metabolism) scans. Voxel-wise group and single-subject level SPM analysis evaluated the relationship between global [18F]FDG-PET and [18F]AV1451-PET depending on the Aβ status. Linear models assessed whether tau deposition or glucose metabolism better predicted clinical progression. There was a dissociation between global cerebral glucose hypometabolism and global tau load in amyloid-positive AD and amyloid-negative mild cognitive impairment (MCI) (p > 0.05). Global hypometabolism was only associated with global cortical tau in amyloid-positive MCI. Voxel-level single subject tau load better predicted neuropsychological performance, Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 13 score, and one-year change compared with regional and global hypometabolism. A dissociation between tau pathology and glucose metabolism at a global level in AD could imply that other pathological processes influence glucose metabolism. Furthermore, as tau is a better predictor of clinical progression, these processes may have independent trajectories and require independent consideration in the context of therapeutic interventions.

Does glucose metabolism dissociate from tau deposition in Alzheimer’s disease?

AbstractBackgroundAlzheimer’s disease progression is characterised by accumulation of tau and reductions in cerebral glucose metabolism. However, the spread of tau could be influenced by the presence of amyloid, while changes in cerebral glucose metabolism could be influenced by microglial activation, atrophy, synaptic dysfunction, along with oxidative stress and inflammation. Hence, the association between these biomarkers at a global cortical level remains unclear. Here we sought the establish the global cortical relationship in a novel single subject design.Method380 subjects were recruited from the Alzheimer’s Disease Neuroimaging Initiative (adni.loni.usc.edu) (Table 1). Amyloid status (Aβ+/Aβ‐ ve) and T1‐weghted MRI scans were obtained for all participants. Dynamic PET scans were processed with SPM12 and standard uptake value ratio (SUVR) images were created. Cerebellum grey matter and pons were selected as reference region for [18F]AV1451 and [18F]FDG respectively. Each cognitively impaired SUVR image was compared against the healthy control group using Statistical Parametric Mapping software. We extracted the total number of voxels with increases of [18F]AV1451 and decreases of [18F]FDG compared to the controls; termed ‘global cortical tau load’ and ‘global hypometabolism’ for subsequent analysis.ResultIn this sample of 240 cognitively impaired subjects, in Aβ+ve AD subjects, there was no correlation between global cortical tau load and global hypometabolism. Interestingly, there was minimal correlation in Aβ+ve MCI subjects between global cortical tau and global hypometabolism (r=0.209, p=0.042). There were no significant correlations between global cortical tau load and global hypometabolism in Aβ‐ve cognitively impaired subjects.ConclusionGlucose hypometabolism and tau deposition dissociate at a global level in AD subjects; while in early stages there may be minimal association between these two processes. The dissociation between glucose metabolism and tau deposition in the later stages of AD trajectory suggests that other pathological features including microglial activation, inflammation, and oxidative stress all influence the metabolic decline in AD, perhaps explaining our apparent lack of association later in disease progression. As such, we argue changes in glucose metabolism and tau deposition have distinct trajectories in the context of Alzheimer’s disease and future clinical trials should consider separate evaluation.

English

BACKGROUND PET-CT is an imaging modality which electronically detects positron-emitting radiopharmaceuticals in the human body and reveals its exact anatomical location.1 PET CT measures the metabolic and functional activity of living tissue noninvasively.1 This technology is utilized in diagnosis, planning treatment and predicting outcomes in various neurological conditions.1 Depending upon various patterns of FDG uptake in different parts of brain, 18FDG PET-CT allows us to differentiate between various types of dementia.2 PET CT allows tracking the course of disease and revealing the severity of the disease.2 In this article, we discuss the imaging findings of normal 18 FDG PET-CT of brain and 8 different neurological conditions with their corresponding brain PET-CT findings. METHODS To study the role of 18FDG-PET/CT in neurological conditions, we identified 8 different patients who underwent 18FDG-PET/CT imaging of brain for clinically suspected different neurological diseases at Department of Radiodiagnosis-Centre of Excellence (CERIS), SRIHER, Chennai, between 2015 and 2019. Siemens Biograph Horizon 16-slice PET/CT scanner with TrueV was used. Syngo.Via Version VB30A software was used. 18F- Fluorodeoxyglucose was the radiotracer used [Dose: 3-7 mCi]. After the scan, different patterns of 18 FDG uptake in the brain were analyzed in each of these patients. RESULTS 18 FDG PET-CT showed reduced uptake in the epileptogenic foci in the brain. Alzheimer’s disease showed decreased FDG uptake in bilateral precuneus, posterior cingulate region, parietal cortex and frontal cortex. Fronto-temporal dementia revealed reduced FDG uptake in anterior cingulate gyrus and anterior temporal lobe. Primary progressive aphasia showed asymmetrical reduced metabolic activity in the bilateral frontal and temporal lobes. Progressive supranuclear palsy revealed reduced metabolic activity in bilateral paramedian frontal region, head of caudate nuclei and midbrain; Multi systemic atrophy showed reduced metabolic activity in midbrain, pons, medulla oblongata and the cerebellum; AIDS related dementia showed global hypometabolism with preserved uptake in basal ganglia. CONCLUSIONS 18FDG-PET/CT has a vital complementary role in the evaluation CNS disorders along with clinical examination, other imaging modalities like CT, MRI, and electroencephalogram (EEG). Radiologists should be aware of these different patterns of FDG uptake to aid the clinical diagnosis and early treatment. KEY WORDS 18 FDG PET-CT, 18FDG Uptake, Hypometabolism, PET-CT Brain

Voxel-wise analysis of 18F-fluorodeoxyglucose metabolism in correlation with variations in the presentation of Alzheimer’s disease: a clinician’s guide

BACKGROUND Diagnostic imaging can be applied in the management of Alzheimer’s disease as it provides structural and functional information to exclude possible secondary causes and offers additional information, especially in atypical cases of Alzheimer’s disease. The utility of positron emission tomography/computed tomography (PET/CT) can help in the noninvasive diagnosis of Alzheimer’s disease by voxel-wise quantification of cerebral 18F-fluorodeoxyglucose (FDG) metabolism. 
 METHODS This prospective study was conducted among 10 subjects with Alzheimer’s disease and 10 healthy control subjects who underwent neuropsychological testing and 18F-FDG PET/CT scans. Images of the brain were postprocessed using voxel-wise analysis and segmented into 20 regions of interest. The standardized uptake value (SUV)max/SUVmean/standard deviation of SUVmean results were analyzed accordingly and correlated with the subjects’ Montreal cognitive assessment (MoCA) results that were adjusted for age and education level. 
 RESULTS Hypometabolism at the right parietal lobe significantly correlated with increasing age and lower MoCA scores. Global hypometabolism was observed in subjects who had advanced Alzheimer’s disease but preserved primary somatosensory cortices (S1) region metabolism. Predominance of frontal lobe hypometabolism was a feature of subjects with Alzheimer’s disease having associated depressive symptoms. 
 CONCLUSIONS 18F-FDG PET/CT voxel-wise analysis can be used for quantitative assessment and can assist clinicians in the diagnosis of Alzheimer’s disease and other variations of the disease spectrum.

Spectrum of autoimmune limbic encephalitis on FDG PET/CT

To evaluate the role of FDG PET CT in the management of patients with suspected autoimmune encephalitis (AE). A retrospective analysis of 27 patients of clinically suspected cases of AE, who underwent FDG PET CT, was done. The patterns of FDG uptake in different antibody subtypes were recorded and comparison with normalized data was attempted. Post treatment follow-up scans were also acquired and analyzed. Focal areas of hypermetabolism involving medial temporal regions, basal ganglia and thalami with relative global hypometabolism, both on visual inspection and on semiquantitative analysis. Serologically, 17 patients had antibodies against Voltage gated potassium channel (VGKC) complex /LGI1 receptors, 2 had antibodies against CRMP-5 (Anti-CV-2) and 1 had had antibodies against PCA-1/Anti-Yo receptor. We could not isolate the antibody in 7 seven patients. Suspicious mitotic lesions were identified in 10 patients on the whole body scan, which later were biopsied and characterized. No scan evidence of mitotic pathology was identified in 17 patients, thus were labeled as non para neoplastic. Focal hypermetabolism was found to be a feature of acute phase, whereas hypometabolic areas were seen in sub acute and chronic phases of the disease. On follow-up, the post-treatment FDG PET CT scans obtained in some of these patients showed reversal to normal metabolism in the corresponding areas. FDG PET CT may have an important role both in the identification of AE itself and in the detection of the unknown malignancy that might have caused it.

Transcriptome analysis of the sea cucumber (Apostichopus japonicus) with variation in individual growth.

The sea cucumber (Apostichopus japonicus) is an economically important aquaculture species in China. However, the serious individual growth variation often caused financial losses to farmers and the genetic mechanisms are poorly understood. In the present study, the extensively analysis at the transcriptome level for individual growth variation in sea cucumber was carried out. A total of 118946 unigenes were assembled from 255861 transcripts, with N50 of 1700. Of all unigenes, about 23% were identified with at least one significant match to known databases. In all four pair of comparison, 1840 genes were found to be expressed differently. Global hypometabolism was found to be occurred in the slow growing population, based on which the hypothesis was raised that growth retardation in individual growth variation of sea cucumber is one type of dormancy which is used to be against to adverse circumstances. Besides, the pathways such as ECM-receptor interaction and focal adhesion were enriched in the maintenance of cell and tissue structure and communication. Further, 76645 SSRs, 765242 SNPs and 146886 ins-dels were detected in the current study providing an extensive set of data for future studies of genetic mapping and selective breeding. In summary, these results will provides deep insight into the molecular basis of individual growth variation in marine invertebrates, and be valuable for understanding the physiological differences of growth process.

Coincidental Observation of Global Hypometabolism in the Brain on PET/CT of an AIDS Patient With High-Grade Pulmonary Non-Hodgkin Lymphoma

AIDS-related dementia complex is the most severe form of cognitive dysfunction in a patient infected with human immunodeficiency virus. The use of FDG PET/CT to diagnose AIDS-related dementia complex has been studied previously and shows various specific metabolic patterns from striatal hypermetabolism in early asymptomatic stage to global hypometabolism in advanced stages. We present a case of a 49-year-old patient with long-standing human immunodeficiency virus infection, where global brain hypometabolism was noted coincidentally on FDG PET/CT done for initial staging of primary pulmonary non-Hodgkin lymphoma.

Brain changes in anorexia nervosa

Anorexia Nervosa (AN) is a serious and frequent psychiatric condition with the highest mortality rate within psychiatric diseases. It often starts during adolescence and affects young patients whose brain maturity is still incomplete but brain changes are often underconsidered although AN appears at a critical point of development.Brain regions involved in the pathophysiology of AN are still in debate. However, the illness is often associated with enlargement of the cortical sulci and ventricles as well as with deficits in grey and white matter volumes. Functional modifications have also been evidenced: mainly global hypometabolism (PET), hypoperfusions (SPECT) and recent fMRI studies have shown that the function of the insular and cingulate cortices, in particular, differ in AN.Neuropsychological studies have also shown neurocognitive impairments concerning executive functions, episodic and working memory as well as attentional deficits.In 1999, Geneva University Hospitals set up a medical-psychiatric unit located in the district general hospital. This structure allows dealing with severe somatic problems as medical and nursing staffs are psychiatric and somatic specialists. AN patients are over 16, often hospitalised for the first time and have very low BMI (< 14). From the clinical observation of these patients who show significant attentional deficits, we explored whether cerebral abnormalities were present with structural MRI and Neuropsychological assessments.We will describe the preliminary results of our clinical experience and consider their implication for the understanding of AN mechanisms. We will also discuss the links between psychopathology and brain impairments that could lead to more efficient treatments.Disclosure of interestThe authors have not supplied their declaration of competing interest.

CORRELATIONS BETWEEN VARIOUS MOCA COGNITIVE DOMAIN ASSESSMENTS AND REGIONAL BRAIN FDG-PET HYPOMETABOLISM

Cognitive deficiencies correlate with regional brain hypometabolism. The Montreal Cognitive Assessment (MoCA) is widely utilized for MCI. Subscores of the MoCA were found to be strong predictors of conversion from MCI to AD over 18 months. We examined correlations between total MoCA, its subtest scores and [18F]FDG-PET, and the predictive value of MoCA subtest scores for global hypometabolism two years later. A total of 160 subjects (CN 54, MCI 128, AD 31) were included from the ADNI dataset. MoCA and FDG-PET scan were obtained in the same individuals not more than 6 months apart at the baseline and two-year follow-up visits. MoCA assessment was classified into 6 subtests, language index score (LIS), memory index score (MIS), attention index score (AIS), visuospatial index score (VIS), executive index score (EIS) and orientation index score (OIS). Voxel-based SUVR maps for [18F]FDG were calculated using pons as reference region. Global SUV was estimated as the median SUVR value obtained using masks encompassing fronto-temporo-parietal regions. Voxel-based and regression analysis were conducted between total MoCA, subtest scores and [18F]FDG. Each correlation was corrected for age, gender and education. Demographics in Table 1. The associations between total MoCA score and [18F]FDG showed scattered correlations on temporal, frontal and parietal cortices (Figure 1). LIS was associated with [18F]FDG on Broca's area, premotor cortex and inferior frontal gyrus; MIS, with hippocampus and posterior cingulate cortex (PCC); EIS, with hippocampus and medial temporal gyrus; OIS and AIS, with all cortical area, except occipital cortex, brain stem and cerebellum; VIS, with a small area on inferior parietal and inferior temporal cortex. Comparing between groups, CN and AD groups showed correlation between total MoCA scores and [18F]FDG in the frontal area, with the AD group showing a higher correlation. In contrast, MCI group showed scattered correlation in frontal, temporal, precuneus and PCC. Total MoCA scores or subtest scores at baseline did not predict global hypometabolism two years later in that dataset.

2697 – Reduced glucose metabolism in left lateral parietal cortex of a posttraumatic stress disorder patient: a case report

Introduction Individuals with posttraumatic stress disorder (PTSD) often have symptoms of re-experiencing traumatic life events, recurring nightmares, hyper arousal and insomnia. Evidence is increasing that stress-related hyperglutamatergic states may contribute to dissociative symptoms and neurodegeneration in temporo-parietal cortical areas. Cognitive performance is also be effected in some of the traumatized patients. We are going to present a PTSD case who demonstrates significant memory impairment. Case 38 years-old, male patient. He had experienced combat related traumatic life events June in 2009 and diagnosed with PTSD according to DSM-IV criteria. Disturbance in short time memory, perception, attention, concentration deficiency was observed in the clinical interview. As a result of cognitive assessment, calculating and remembering subtests were lower than the others so it could be associated with cognitive impairment. To evaluate the organic brain pathology CT was applied and it was within normal limits. After than PET was conducted to reveal the metabolic abnormalities. Left parietal cortical global hypo-metabolic activity, global hypometabolism in temporal cortex and regional hypometabolism in medial parietal cortical regions was demonstrated. He has been treated and fallowed up for two years and provided significant improvement in PTSD symptoms but cognitive impairment was still showed constancy. Discussion It is well known that l eft parietal and temporal cortical region would be associated with impaired memory performance. The areas that we have found at PET are known to be involved in episodic memory consolidation and retrieval. Comorbid PTSD and hypometabolism in lateral cortical region has not been well documented in the literature.

Changes in glucose metabolism and metabolites during the epileptogenic process in the lithium‐pilocarpine model of epilepsy

The metabolic and biochemical changes that occur during epileptogenesis remain to be determined. (18) F-Fluorodeoxyglucose positron emission tomography (FDG-PET) and proton magnetic resonance spectroscopy ((1) H MRS) are noninvasive techniques that provide indirect information on ongoing pathologic changes. We, therefore, utilized these methods to assess changes in glucose metabolism and metabolites in the rat lithium-pilocarpine model of epilepsy as markers of epileptogenesis from baseline to chronic spontaneous recurrent seizures (SRS). PET and MRS were performed at baseline, and during the acute, subacute, silent, and chronic periods after lithium-pilocarpine induced status epilepticus (SE). Sequential changes in glucose metabolism on (18) F-FDG PET using SPM2 and the ratios of percent injected dose per gram (%ID)/g of regions of interest (ROIs) in the bilateral amygdala, hippocampus, basal ganglia with the thalamus, cortex, and hypothalamus normalized to the pons were determined. Voxels of interest (VOIs) on (1) H MRS were obtained at the right hippocampus and the basal ganglia. NAA/Cr levels and Cho/Cr at various time points were compared to baseline values. Of 81 male Sprague-Dawley rats, 30 progressed to SRS. (18) F-FDG PET showed widespread global hypometabolism during the acute period, returning to baseline level during the subacute period. Glucose metabolism, however, declined in part of the hippocampus during the silent period, with the hypometabolic area progressively expanding to the entire limbic area during the chronic period. (1) H MRS showed that the NAA/Cr levels in the hippocampus and basal ganglia were reduced during the acute period and were not restored subsequently from the subacute to the chronic period without any significant change in the Cho/Cr ratio throughout the entire experiment. Serial metabolic and biochemical changes in the lithium-pilocarpine model of epilepsy indirectly represent the process of human epileptogenesis. Following initial irreversible neural damage by SE, global glucose metabolism transiently recovered during the subacute period without neuronal recovery. Progressive glucose hypometabolism in the limbic area during the silent and chronic periods may reflect the important role of the hippocampus in the formation of ongoing epileptic network during epileptogenesis.

11C-PiB PET studies in typical sporadic Creutzfeldt–Jakob disease

Objective:Brain amyloid imaging using positron emission tomography (PET) is of increasing importance in the premortem evaluation of dementias, particularly in relation to Alzheimer disease (AD). The purpose of this study...

Brain hypometabolism of glucose in anorexia nervosa: A PET scan study

Cerebral glucose metabolism was studied in 20 underweight anorectic girls and in 10 age- and sex-matched healthy volunteers using positron emission tomography with (18-F)-fluorodeoxy-glucose. Both groups were scanned during rest, with eye closed and with low ambient noise. Compared to controls, the underweight anorectic group showed a global hypometabolism (p = .002) and an absolute (p < .001) as well as relative (p < .01) hypometabolism of glucose in cortical regions, with the most significant differences found in the frontal and the parietal cortices. Within the underweight anorectic and the control groups, no correlations were found between absolute or relative rCMRGlu and BMI, anxiety scores, or Hamilton scores of depression. Different factors might explain this reduction of glucose metabolism in anorexia nervosa. It might be the consequence of neurophysiological or morphological aspects of anorexia nervosa and/or the result of some associated symptoms such as anxiety or depressed feelings. Supported by cognitive studies, we can also hypothesize a primary corticocerebral dysfunctioning in anorexia nervosa.

The use of positron emission tomographic scanning in epilepsy

Positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (18FDG) has demonstrated the epileptogenic lesion in partial epilepsy to be hypometabolic interictally . This finding is useful for localizing the area of resection when surgical therapy is contemplated. 18FDG scans during partial seizures show increased metabolism in areas of ictal onset and spread and in other regions of decreased metabolism that could reflect postictal effects. In the generalized epilepsies, petit mal absences and generalized convulsions induced by electroconvulsive shock therapy (ECT) are associated with global hypermetabolism, while global hypometabolism is seen in the postictal period following ECT. More information about the factors that influence the interictal hypometabolic zone in partial epilepsy should improve the diagnostic value of this finding for presurgical localization and perhaps also for the evaluation of other therapeutic regimens. New techniques for more dynamic PET studies with improved resolution, combined with computerized electroencephalographic analysis, should allow more accurate interpretation of ictal, as well as interictal, phenomena. Application of PET technology to other paroxysmal disorders may provide a basis for new diagnostic classifications that have therapeutic and prognostic value and may allow clearer differentiation among epileptic phenomena, myoclonus, and movement disorders. More clinical and animal research is needed, however, before we can delineate fundamental mechanisms of human epilepsy from PET data. To this end, it is now possible to use combined multidisciplinary parallel approaches in patients and animals to define specific aspects of epileptic disorders clinically, to intensively investigate them with experimental models in the animal laboratory, and to verify the relevance of these experimental results by returning to clinical studies.

Further contribution to the understanding of the post-infarctual anedematous syndrome.

The authors describe an anomalous post-infarctual evolution, already revealed by Sotgiu in 1959 and defined the’ postinfarctual anedematous syndrome’ (SAPI). The syndrome, present in about 12% of MI, demonstrates a clinical picture characterized by a global hypometabolism, absence of edema and state of continuous sub-collapse; an endocrine picture characterized by a corticomedullary adrenal, thyroid and hypophisis hypoactivity. The results confirm that, in contrast to other myocardial infarction cases, in patients with SAPI low values of cortisol, aldosterone and catecholamines exist, with alteration of the glycocorticoid and adrenergic amine circadian-biorhythm. The pharmacodynamic tests, demonstrating the integrity of the adrenal gland, have revealed an alteration of the hypothalamic-pituitary function. According to the authors, the occurrence of SAPI might be interpreted on the basis of a particular vulnerability of the hypothalamic-pituitary system (often depending upon the senile age of the subjects) which is probably amplified by the stress created by the myocardial necrosis.