Regional Metabolic Activity Research Articles

Assessment of regional and total skeletal metabolism using 18F-NaF PET/CT in patients with chronic kidney disease.

The study aims to assess regional and total bone metabolic activity in patients with chronic kidney disease using Na[18F]F PET and correlation between semi-quantitative indices and blood parameters. Seventy-two subjects (mean age 61.8 ± 13.8years) were included. Of these 24/72 patients had end-stage renal disease (ESRD) (GFR < 15mL/min/1.73 m2), 38/72 had chronic kidney disease (CKD) (GFR between 60 and 15mL/min/1.73 m2), and 10/72 were controls with normal renal function. All subjects underwent Na[18F]F PET-CT with a dose activity of 0.06mCi/Kg. Regional and total skeletal metabolism were assessed with mean SUVs in a skeletal volume of interest (VOI), bone to soft tissue index (B/S), global SUV mean (GSUV mean) of the whole bone, and uptake in the femoral neck. Statistically significant differences were observed in a number of 18F-NaF metrics like femoral neck metabolism in CKD and ERSD groups in comparison to control in right (P = 0.003) and left femur (P = 0.006), bone to soft tissue index in the femur (P = 0.016) and GSUV5 (P = 0.006). There is also a significant difference in SUV mean in lumbar vertebrae (L1-L4) among CKD, ESRD, and controls. There was a moderate correlation between 18F-NaF PET scan uptake and blood parameters such as ALP and PTH. Na[18F]F uptake parameters were significantly different in low versus high bone turnover state. The assessment of total skeleton and regional metabolism and bone turnover in CKD patients is feasible with Na[18F]F PET. Na[18F]F can help to detect early changes in bone metabolism and assess the progression of bone disease in this complex condition. Quantification with Na[18F]F PET might provide better assessment of the bone turnover. The difference in Na[18F]F uptake in CKD compared to controls is likely related to a change in bone turnover which, however, requires further validation.

Seasonality in regional brain glucose metabolism.

Daylength and the rates of changes in daylength have been associated with seasonal fluctuations in psychiatric symptoms and in cognition and mood in healthy adults. However, variations in human brain glucose metabolism in concordance with seasonal changes remain under explored. In this cross-sectional study, we examined seasonal effects on brain glucose metabolism, which we measured using 18F-fluorodeoxyglucose-PET in 97 healthy participants. To maximize the sensitivity of regional effects, we computed relative metabolic measures by normalizing the regional measures to white matter metabolism. Additionally, we explored the role of rest-activity rhythms/sleep-wake activity measured with actigraphy in the seasonal variations of regional brain metabolic activity. We found that seasonal variations of cerebral glucose metabolism differed across brain regions. Glucose metabolism in prefrontal regions increased with longer daylength and with greater day-to-day increases in daylength. The cuneus and olfactory bulb had the maximum and minimum metabolic values around the summer and winter solstice respectively (positively associated with daylength), whereas the temporal lobe, brainstem, and postcentral cortex showed maximum and minimum metabolic values around the spring and autumn equinoxes, respectively (positively associated with faster daylength gain). Longer daylength was associated with greater amplitude and robustness of diurnal activity rhythms suggesting circadian involvement. The current findings advance our knowledge of seasonal patterns in a key indicator of brain function relevant for mood and cognition. These data could inform treatment interventions for psychiatric symptoms that peak at specific times of the year.

Chronic lead exposure disrupts neurometabolic activity in mouse brain: An ex vivo1H-[13C]-NMR study

Lead poisoning has been identified as a problem in adults as well as in children. Chronic exposure to lead has been implicated in neurological disorders such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. In the present study, we evaluated the impact of chronic lead exposure on cerebral glutamatergic and GABAergic metabolic activity in mice. C57BL6 mice were provided lead acetate in drinking water for two months. The regional cerebral metabolic activity was measured using 1H-[13C]-NMR spectroscopy in conjunction with infusion of [1,6-13C2]glucose. The blood Pb2+ increased significantly in lead acetate treated mice. Concomitantly, there was a significant reduction in the forelimb strength. The level of myo-inositol was elevated in the cerebral cortex of mice chronically exposed to lead. The glutamatergic neurometabolic activity was found to be reduced following chronic lead exposure in the cerebral cortex, hippocampus, and striatum. In contrast, the GABAergic fluxes were impaired in the hippocampus and thalamus only. The metabolic fluxes in the cerebellum were unperturbed to Pb2+ toxicity. In conclusion, we report that chronic lead exposure in mice leads to an impairment in forelimb strength, and a perturbation in neurometabolism in brain regions involving cognition and movement.

Evaluation of Brain Functions in Conversion Disorder with PET/MRI

IntroductionSince there is no objective criteria, unique clinical symptom or laboratory test to make the diagnosis of conversion disorder; its diagnosis and treatment is challenging which leads to a poor prognosis.ObjectivesThe aim of this study is to investigate the brain metabolic activity of patients with conversion disorder with PET/MRI.Methods12 conversion disorder patients were included. Somatosensory Amplification Scale, Somatoform Dissociation Scale, Patient Health Questionnaire-15, Toronto Alexithymia Scale were filled in by the participants. Neurological, mental status examinations, Wechsler Adult Intelligence Scale-Revised Form (WAIS-R) and brain F18-FDG-PET/MRI were performed. Structured Clinical Interview for DSM-5, Hamilton Depression and Anxiety Scales were administered.Results83% of the patients were female, the mean age was 33 years and average education period was 10,2 years. WAIS-R total scores were consistent with low avarage intelligence level.Cerebral hypermetabolism was detected in the primary visual cortex. Average regional brain metabolic activity had a tendency to increase in bilateral prefrontal, right sensorimotor (SM),cingulate,right inferior parietal,occipital lateral,right temporal lateral cortices and cerebellum. Each region was metabolically correlated with the homologous contralateral regions. Significant correlations in the same direction was found between frontal and occipital lateral &amp; primary visual cortices; cerebellum and left sensorimotor cortex; anterior cingulate cortex(ACC) and superior parietal cortex &amp; cerebellum. No correlations were found between ACC and left SM cortex.ConclusionsFindings of our study indicate that there are moderate changes in regional brain metabolic activities and inter-regional correlations in patients with conversion disorder. In order to confirm these findings, furter functional neuroimaging studies are needed.DisclosureNo significant relationships.

Chapter 8 - Metabolic imaging and plasticity

Positron emission tomography greatly advanced our understanding on the underlying neural mechanisms of movement disorders. PET with flurodeoxyglucose (FDG) is especially useful as it depicts regional metabolic activity level that can predict patients' symptoms. Multivariate pattern analysis has been used to determine and quantify the co-varying brain networks associated with specific clinical traits of neurodegenerative disease. The result is a biomarker, useful for diagnosis, treatments, and follow up studies. Parkinsonian traits and parkinsonisms are associated with specific spatial pattern of metabolic abnormality useful for differential diagnosis. This approach has also been used for monitoring disease progression and novel treatment responses mostly in Parkinson's disease. In this book chapter, we, illustrate and discuss the significance of the brain networks associated with disease and their modification with neuroplastic changes.

RELATIONSHIPS BETWEEN OSTEOCALCIN LEVEL AND HORMONAL METABOLIC DISORDERS IN TYPE 2 DIABETIC MEN WITH VARIOUS DEGREES OF OBESITY (LITERATURE REVIEW AND OWN RESEARCH)

The bone hormone osteocalcin is formed by osteoblasts and is partially released into the bloodstream during bone resorption, being a biomarker of bone remodeling. Osteocalcin also plays an important role in the endocrine regulation of metabolic and energy processes in the body and in their coordination. Osteocalcin uses a feedback mechanism to regulate insulin secretion, insulin sensitivity of peripheral tissues, and adipokine levels. In general, the secretion of osteocalcin and insulin are important factors in the formation of hormonal-metabolic phenotype, body composition, determination of regional distribution and metabolic activity of both bone and adipose tissue.The aim of this study was to establish the relationship between osteocalcin concentration and hormonal changes in men with type 2 diabetes with and without obesity on the background of involutive changes. Results. 64 men with type 2 diabetes, older than 50 years, were divided into 2 groups by BMI: 1) non-obese, BMI &lt;30 kg / m2 (n = 31); 2) -obese, BMI ≥ 30 kg / m2 (n = 33). Lower levels of insulin secretion (lower serum C-peptide and insulin levels) were observed in non-obese patients in the absence of a compensatory increase in proinsulin levels. It can be assumed that the increase in the concentration of osteocalcin in group 1 is compensatory, although it does not have a significant effect on blood glucose levels. However, it may have a protective effect on the severity of insulin resistance syndrome and related metabolic disorders. Lower levels of osteocalcin in the obese group were associated with a higher degree of insulin resistance and insulin secretion. There was no significant difference between the two groups in serum proinsulin levels, as well as in androgen supply, which was assessed by the levels of total testosterone, testosteronestradiol-binding globulin, and free testosterone index. Conclusion. Lower levels of osteocalcin may be a marker of an increased risk of adverse metabolic changes in obese patients with type 2 diabetes, followed by complications compared to non-overweight patients

A pilot study on lung cancer detection based on regional metabolic activity distribution in digital low-dose 18F-FDG PET.

To investigate the potential of automatic lung cancer detection on submillisievert dose 18F-fludeoxyglucose (18F-FDG) scans using different positron emission tomography (PET) parameters, as a primary step towards a potential new indication for 18F-FDG PET in lung cancer screening. We performed a retrospective cohort analysis with 83 patients referred for 18F-FDG PET/CT, including of 34 patients with histology-proven lung cancer and 49 patients without lung disease. Aside clinical standard PET images (PET100%) two additional low-dose PET reconstructions were generated, using only 15 s and 5 s of the 150 s list mode raw data of the full-dose PET, corresponding to 10% and 3.3% of the original 18F-FDG activity. The lungs were subdivided into three segments on each side, and each segment was classified as normal or containing cancer. The following standardized uptake values (SUVs) were extracted from PET per lung segment: SUVmean, SUVhot5, SUVmedian, SUVstd and SUVtotal. A multivariate linear regression model was used and cross-validated. The accuracy for lung cancer detection was tested with receiver operating characteristics analysis and T-statistics was used to calculate the weight of each parameter. The T-statistics showed that SUVstd was the most important discriminative factor for lung cancer detection. The multivariate model achieved an area under the curve of 0.97 for full-dose PET, 0.85 for PET10% with PET3.3% reconstructions resulting in a still high sensitivity the PET10% reconstruction of 80%. This pilot study indicates that segment-based, quantitative PET parameters of low-dose PET reconstructions could be used to automatically detect lung cancer with high sensitivity. Automated assessment of PET parameters in low-dose PET may aid for an early detection of lung cancer.

Показники кісткового ремоделювання у хворих на цукровий діабет 2-го типу з різним конституційно-метаболічним фенотипом

SummaryIntroduction. According to the latest data, osteocalcin – hormonally active productof bone tissue – plays an active role in the humoral control of homeostatic processes. Inparticular, osteocalcin was shown to regulate sensitivity of peripheral tissues to insulin,carbohydrate metabolism, transport and deposition of lipids.An inverse correlations were found between the level of osteocalcin and the degreeof insulin resistance, levels of glucose, insulin and adipokines, manifestation of themetabolic syndrome, visceral obesity, type 2 diabetes, cardiovascular risk. Osteocalcinmay be a significant factor of regulation of energy processes and formation of certainconstitutional and metabolic phenotypic characteristics of the organism, in particular interms of regional distribution and metabolic activity of adipose tissue.Purpose of the study was to study the relationship between the level of osteocalcinand constitutionally-metabolic phenotypic traits.Materials and methods. 44 patients with type 2 diabetes over 50 years old wereallocated into 3 groups by the serum osteocalcin level. Anthropometric measurements(height, weight, waist circumference), determining of insulin resistance degree (HOMAIR), lipid spectrum were carried out. Visceral adiposity index (VAI) was calculated byempirical formulas for men and women, which includes body mass index, waistcircumference, blood level of triglycerides, and high density lipoprotein. The controlgroup included 23 people of the same age without diabetes.Results. In the groups 1–3 of men osteocalcin levels were: <2.0 ng/ml;(2.75±0.21) ng/ml; (5.3±0.39) ng/ml, respectively. In the groups 1–3 of women:<2.0 ng/ml; (2.91±0,15) ng/ml; (6.01±0,56) ng/ml. In all groups of diabetic patientsmean osteocalcin levels were significantly lower than in control subjects withoutdiabetes (in men (10.78±1.08) ng/ml; in women (8.12±1.03) ng/ml; p<0.05).Reducing of osteocalcin level in subjects with type 2 diabetes was associated with asignificant increase in the degree of insulin resistance. Especially high values ofHOMA-IR were observed in patients of group 1 with low osteocalcin levels (HOMA-IRin men (7.25±1.04); in women (8.25±1.45)), comparing with high osteocalcin group 3(in men (4.23±0.87); in women (2.78±0.34); p<0.05).It was found that the decrease of osteocalcin in groups of men with type 2 diabetes wasaccompanied by a significant increase in VAI (in men groups 1–3: (4.21±1.09); (3.05±0.38);(1.43±0.27); p<0.05; in women groups 1–3: (4.86±1.17); (3.15±0.58); (2.75±0.53)).Increase of VAI characterizes the worsening of morphological and functional characteristicsof adipose tissue. In women, such changes were not significant.Our results show the relationship between slowing of osteosynthesis andconstitutional manifestations and metabolic disorders, which in turn are associated withphenotypic changes in patients with type 2 diabetes.Conclusions. Reduction of serum osteocalcin in patients with type 2 diabetesoccurred in parallel with the strengthening of insulin resistance, visceral obesity, anddyslipidemia. The visceral obesity index, which includes both humoral andanthropometric parameters, was more precise and standardized parameter for revealingof constitutional and metabolic phenotypic changes as compared with the waistcircumference.

Gender differences in brown adipose tissue-related brain functional networks: an 18F-FDG-PET study.

Thermogenesis of brown adipose tissue (BAT) is controlled by central modulating mechanisms, although changes in brain metabolism of BAT-positive subjects with different genders are still unclear. We hypothesized that changes in regional cerebral glucose metabolic activity were associated with BAT activities, and this association differed in different genders. Brain glucose metabolism of 26 BAT-positive and 26 BAT-negative healthy subjects was compared using a brain fluorodeoxyglucose (FDG)-PET scan, and gender differences in BAT-related brain functional networks and effect of sex hormones were assessed by comparing the brain PET images of BAT-positive and BAT-negative subjects of different genders and postmenopausal female subjects. Compared with controls, BAT-positive male subjects had a significant hypermetabolic area in the right extranuclear and significant hypometabolic areas in the right inferior parietal lobule and right inferior frontal gyrus; while at the same threshold, BAT-positive female subjects had richer hypermetabolic regions, including bilateral limbic lobes, bilateral frontal lobes, right cerebellum, left sublobar, and right parietal lobe. However, BAT-positive postmenopause female subjects only showed significant hypometabolic regions in left lingual gyrus. BAT-related brain functional networks are different between male and female subjects. Female networks are more significant and more concentrated while male networks are smaller and more dispersed, and these gender differences may be related to sex hormones.

Imaging Guidance for Therapeutic Delivery: The Dawn of Neuroenergetics.

Modern neurocritical care relies on ancillary diagnostic testing in the form of multimodal monitoring to address acute changes in the neurological homeostasis. Much of our armamentarium rests upon physiological and biochemical surrogates of organ or regional level metabolic activity, of which a great deal is invested at the metabolic-hemodynamic-hydrodynamic interface to rectify the traditional intermediaries of glucose consumption. Despite best efforts to detect cellular neuroenergetics, current modalities cannot appreciate the intricate coupling between astrocytes and neurons. Invasive monitoring is not without surgical complication, and noninvasive strategies do not provide an adequate spatial or temporal resolution. Without knowledge of the brain's versatile behavior in specific metabolic states (glycolytic vs oxidative), clinical practice would lag behind laboratory empiricism. Noninvasive metabolic imaging represents a new hope in delineating cellular, nigh molecular level energy exchange to guide targeted management in a diverse array of neuropathology.

Hypsarrhythmia is associated with widespread, asymmetric cerebral hypermetabolism

PurposeHypsarrhythmia is the interictal EEG pattern most often associated with infantile spasms. We set out to evaluate the metabolic impact of hypsarrhythmia among patients with infantile spasms by contrasting regional cerebral metabolic activity among children with and without hypsarrhythmia. MethodsPatients with video-EEG confirmed infantile spasms who underwent simultaneous interictal EEG and FDG-PET as part of a surgical evaluation were retrospectively identified. Pons-normalized relative cerebral metabolic activity (RCA) was ascertained in 18 cortical and 6 subcortical pre-specified regions of interest (ROIs). ResultsWe identified 63 patients with infantile spasms who underwent simultaneous EEG/PET, including children with hypsarrhythmia (n = 9), high-voltage EEG background (n = 20), and multifocal independent spike discharges (MISD) (n = 34). Among them, a putative epileptogenic zone was identified within the left-hemisphere only (n = 27), right-hemisphere only (n = 20), or assumed to be bilateral (n = 16). After adjustment for age at PET, the presence of hypsarrhythmia was associated with hypermetabolism in 11 of 18 cortical ROI’s. After adjustment for lateralized epileptogenic zones, the association between hypsarrhythmia and hypermetabolism was generally stronger within the left hemisphere. ConclusionHypsarrhythmia is associated with widespread—and curiously left more than right—elevations in pons-normalized RCA, which is not evident on routine clinical review of individual PET studies. This study suggests that hypsarrhythmia may be a quasi-ictal phenomenon based on widespread and usually bilateral cortical hypermetabolism.

Opposite subgenual cingulate cortical functional connectivity and metabolic activity patterns in refractory melancholic major depression.

Although in treatment-resistant depression (TRD) subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) is frequently used to examine deregulated brain networks, neurobiological data from other sources may be required to interpret these FC findings. In 16 melancholic TRD patients with a high level of treatment resistance and 16 closely matched healthy never-depressed individuals we verified whether sgACC FC patterns were related to regional metabolic activity (CMRglc) with 18FDG PET imaging. Notwithstanding that TRD patients displayed stronger sgACC FC with the right lateral frontotemporal cortex, metabolically they exhibited the opposite pattern. Our results indicate that the sgACC seed and its functionally connected regions not automatically follow a similar metabolic pattern in TRD, possibly reflecting the refractory state of the sample. Multimodal brain imaging may help to increase our insight into the pathophysiology of TRD.

Correlation of bone marrow cellularity and metabolic activity in healthy volunteers with simultaneous PET/MR imaging.

To evaluate the correlation between bone marrow cellularity (BMC) and metabolic activity in healthy subjects and to see whether yellow marrow is indeed metabolically quiescent. Because metabolic activity can be assumed to reflect vascularity, we assessed the relationship between regional metabolic activity and geographic frequency of metastases as noted in the literature. Two hundred and twenty locations (ten in each side of the pelvis and proximal femur) were evaluated in 11 consecutive healthy volunteers with simultaneous PET/MR. BMC was calculated through precise water-fat fraction quantification with a 6-echo gradient echo. We analyzed correlations between cellularity and SUVr, age, and R2*. We also looked at the relation between our results and the reported prevalence of metastases. There was moderate but statistically significant correlation between BMC and metabolic activity (r = 0.636, p < 0.0001). Interestingly, the iliac and sacrum had higher metabolic activity relative to cellularity, whereas the femoral neck and lesser trochanter showed lower SUVr than other regions with the similar cellularity. The relatively lower metabolic status of the femoral neck conflicted with its reported high frequency of metastasis. Excluding regions with almost no remaining red marrow, cellularity showed inverse relationship with age (r = 0.476, p < 0.0001) and direct relationship with R2* (r = 0.532, p < 0.0010). Metabolic activity of bone marrow was largely dependent on BMC while yellow marrow seems metabolically quiescent. The discrepancy between the assumed vascularity as determined by metabolic activity and reported sites of metastasis suggested that the process of bone metastasis may not depend entirely on vascularity.

Special Issue on “Medical Imaging &amp; Image Processing II”

Medical Imaging is becoming an essential component in various fields of bio-medical research and clinical practice: Neuroscientists detect regional metabolic brain activity from positron emission tomography (PET), functional magnetic resonance imaging (MRI), and magnetic resonance spectrum imaging (MRSI) scans; biologists study cells and generate 3D confocal microscopy data sets; virologists generate 3D reconstructions of viruses from micrographs; and radiologists identify and quantify tumors from MRI and computed tomography (CT) scans [...]

Special Issue on Biomedical Big Data: Understanding, Learning and Applications

The papers in this special issue focus on biomedical Big Data. Biomedical imaging is an essential component in various fields of biomedical research and clinical practice. The study of biologists requires continuous monitoring of cell behavior under microscope. Neuroscientists detect regional metabolic brain activity from positron emission tomography (PET), functional magnetic resonance imaging (MRI), and magnetic resonance spectrum imaging (MRSI) scans. During these researching process, large amount of biomedical data will be produced for processing. The development of advanced imaging equipment and diverse applications also have driven the generation of biomedical big data. The main challenge and bottleneck for the related research is the conversion of “biomedical big data” into interpretable information and hence discoveries. Computer vision theory has a huge potential in many aspects for automated understanding of biomedical data and has been used successfully to speed up and improve applications such as large-scale cell image analysis (image preconditioning, cell segmentation and detection, cell tracking, and cell behavior identification), image reconstruction and registration, organ segmentation and disease classification. Considering the recent advance in machine learning technique, deep learning has revolutionized multiple fields of computer vision, significantly pushing the state of arts of computer vision systems in a broad array of high-level tasks. Hopefully these technique advance will help to deal problems in biomedical big data.

Brain metabolism in patients with freezing of gait after hypoxic-ischemic brain injury: A pilot study.

Movement disorders are 1 of the long-term neurological complications that can occur after hypoxic-ischemic brain injury (HIBI). However, freezing of gait (FOG) after HIBI is rare. The aim of this study was to examine the brain metabolism of patients with FOG after HIBI using F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET).We consecutively enrolled 11 patients with FOG after HIBI. The patients’ overall brain metabolism was measured by F-18 FDG PET, and we compared their regional brain metabolic activity with that from 15 healthy controls using a voxel-by-voxel-based statistical mapping analysis. Additionally, we correlated each patient's FOG severity with the brain metabolism using a covariance analysis.Patients with FOG had significantly decreased brain glucose metabolism in the midbrain, bilateral thalamus, bilateral cingulate gyri, right supramarginal gyrus, right angular gyrus, right paracentral lobule, and left precentral gyrus (PFDR-corrected < .01, k = 50). No significant increases in brain metabolism were noted in patients with FOG. The covariance analysis identified significant correlations between the FOG severity and the brain metabolism in the right lingual gyrus, left fusiform gyrus, and bilateral cerebellar crus I (Puncorrected < 0.001, k = 50).Our data suggest that brain regions in the gait-related neural network, including the cerebral cortex, subcortical structures, brainstem, and cerebellum, may significantly contribute to the development of FOG in HIBI. Moreover, the FOG severity may be associated with the visual cortex and cerebellar regions.

Enjoyment of Spicy Flavor Enhances Central Salty-Taste Perception and Reduces Salt Intake and Blood Pressure.

High salt intake is a major risk factor for hypertension and is associated with cardiovascular events. Most countries exhibit a traditionally high salt intake; thus, identification of an optimal strategy for salt reduction at the population level may have a major impact on public health. In this multicenter, random-order, double-blind observational and interventional study, subjects with a high spice preference had a lower salt intake and blood pressure than subjects who disliked spicy food. The enjoyment of spicy flavor enhanced salt sensitivity and reduced salt preference. Salt intake and salt preference were related to the regional metabolic activity in the insula and orbitofrontal cortex (OFC) of participants. Administration of capsaicin-the major spicy component of chili pepper-enhanced the insula and OFC metabolic activity in response to high-salt stimuli, which reversed the salt intensity-dependent differences in the metabolism of the insula and OFC. In animal study, OFC activity was closely associated with salt preference, and salty-taste information processed in the OFC was affected in the presence of capsaicin. Thus, interventions related to this region may alter the salt preference in mice through fiber fluorometry and optogenetic techniques. In conclusion, enjoyment of spicy foods may significantly reduce individual salt preference, daily salt intake, and blood pressure by modifying the neural processing of salty taste in the brain. Application of spicy flavor may be a promising behavioral intervention for reducing high salt intake and blood pressure.

Cholinergic activity and levodopa-induced dyskinesia: a multitracer molecular imaging study.

ObjectiveTo investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease.MethodsThis study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[123I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [123I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[18F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed.ResultsDensity of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side.InterpretationOur findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.

Lung Metabolic Activation as an Early Biomarker of Acute Respiratory Distress Syndrome and Local Gene Expression Heterogeneity.

Acute respiratory distress syndrome (ARDS) is an inflammatory condition comprising diffuse lung edema and alveolar damage. ARDS frequently results from regional injury mechanisms. However, it is unknown whether detectable inflammation precedes lung edema and opacification and whether topographically differential gene expression consistent with heterogeneous injury occurs in early ARDS. The authors aimed to determine the temporal relationship between pulmonary metabolic activation and density in a large animal model of early ARDS and to assess gene expression in differentially activated regions. The authors produced ARDS in sheep with intravenous lipopolysaccharide (10 ng ⋅ kg ⋅ h) and mechanical ventilation for 20 h. Using positron emission tomography, the authors assessed regional cellular metabolic activation with 2-deoxy-2-[(18)F]fluoro-D-glucose, perfusion and ventilation with NN-saline, and aeration using transmission scans. Species-specific microarray technology was used to assess regional gene expression. Metabolic activation preceded detectable increases in lung density (as required for clinical diagnosis) and correlated with subsequent histologic injury, suggesting its predictive value for severity of disease progression. Local time courses of metabolic activation varied, with highly perfused and less aerated dependent lung regions activated earlier than nondependent regions. These regions of distinct metabolic trajectories demonstrated differential gene expression for known and potential novel candidates for ARDS pathogenesis. Heterogeneous lung metabolic activation precedes increases in lung density in the development of ARDS due to endotoxemia and mechanical ventilation. Local differential gene expression occurs in these early stages and reveals molecular pathways relevant to ARDS biology and of potential use as treatment targets.

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.