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Selective serotonin reuptake inhibitors (SSRIs) are widely used for treating neuropsychiatric disorders. However, the exact mechanism of action and why effects can take several weeks to manifest is not clear. The hypothesis of neuroplasticity is supported by preclinical studies, but the evidence in humans is limited. Here, we investigate the effects of the SSRI escitalopram on presynaptic density as a proxy for synaptic plasticity. In a double-blind placebo-controlled study (NCT04239339), 32 healthy participants with no history of psychiatric or cognitive disorders were randomized to receive daily oral dosing of either 20 mg escitalopram (n = 17) or a placebo (n = 15). After an intervention period of 3-5 weeks, participants underwent a [11C]UCB-J PET scan (29 with full arterial input function) to quantify synaptic vesicle glycoprotein 2A (SV2A) density in the hippocampus and the neocortex. Whereas we find no statistically significant group difference in SV2A binding after an average of 29 (range: 24-38) days of intervention, our secondary analyses show a time-dependent effect of escitalopram on cerebral SV2A binding with positive associations between [11C]UCB-J binding and duration of escitalopram intervention. Our findings suggest that brain synaptic plasticity evolves over 3-5 weeks in healthy humans following daily intake of escitalopram. This is the first in vivo evidence to support the hypothesis of neuroplasticity as a mechanism of action for SSRIs in humans and it offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. While replication is warranted, these results have important implications for the design of future clinical studies investigating the neurobiological effects of SSRIs.
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Disfunção Cognitiva , Inibidores Seletivos de Recaptação de Serotonina , Humanos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Escitalopram , Encéfalo , Sinapses , Disfunção Cognitiva/tratamento farmacológico , Citalopram/farmacologia , Citalopram/uso terapêuticoRESUMO
BACKGROUND: A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR). Further, we evaluate if CAR changes with antidepressant treatment, including a selective serotonin reuptake inhibitor, and if pretreatment CAR can predict treatment outcome. METHODS: Sixty-six patients (76% women) with a moderate to severe depressive episode underwent positron emission tomography imaging with [11C]SB207145 for quantification of brain 5-HT4R binding using BPND as outcome. Serial home sampling of saliva in the first hour from awakening was performed to assess CAR before and after 8 weeks of antidepressant treatment. Treatment outcome was measured by change in Hamilton Depression Rating Scale 6 items. RESULTS: In the unmedicated depressed state, prefrontal and anterior cingulate cortices 5-HT4R binding was positively associated with CAR. CAR remained unaltered after 8 weeks of antidepressant treatment, and pretreatment CAR did not significantly predict treatment outcome. CONCLUSIONS: Our findings highlight a link between serotonergic disturbances in MDD and cortisol dynamics, which likely is involved in disease and treatment mechanisms. Further, our data support 5-HT4R agonism as a promising precision target in patients with MDD and disturbed stress hormone dynamics.
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Transtorno Depressivo Maior , Humanos , Feminino , Masculino , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Receptores 5-HT4 de Serotonina/metabolismo , Receptores 5-HT4 de Serotonina/uso terapêutico , Hidrocortisona/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismoRESUMO
The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via 18F-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (- 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (- 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (ß: 0.44, 95% CI [0.06-0.81], P = 0.024) after adjusting for study design but not BAT volume (ß: 0.39, 95% CI [- 0.01-0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.
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Tecido Adiposo Marrom , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Humanos , Tecido Adiposo Marrom/metabolismo , Apolipoproteínas M/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/metabolismoRESUMO
We investigated the effect of pharmacologically induced weight loss on markers of glucagon resistance in individuals with overweight during treatment with the glucagon-like peptide-1 receptor agonist liraglutide. We performed an open-label study in 14 men with overweight (age 38 ± 11 years, BMI 32 ± 4 kg/m2) without simultaneously diabetes. Subjects were treated with liraglutide, initiated and titrated with 0.6 mg/day/week to reach the final dose of 3.0 mg/day. Subjects were examined at baseline, during titration (Week 4), after 2 weeks of steady state (Week 6) of final dosing of liraglutide and 3 weeks after discontinuation of liraglutide (follow-up). Study participants lost 3.3 ± 1.9 kg (3%) total body weight during the first 4 weeks of treatment with liraglutide. Simultaneously, liver fat content decreased from 12.4 ± 11.6% to 10.2 ± 11.1%, p = 0.025, whereas fat content in the spleen and subcutaneous tissue was unaltered. Markers of glucagon resistance, including plasma glucagon and the glucagon-alanine-index, also decreased significantly during treatment, but total and individual plasma amino acid concentrations did not. Insulin resistance (HOMA-IR) was unchanged during treatment, whereas insulin clearance increased. Treatment with the GLP-1 receptor analogue liraglutide decreased liver fat content, and simultaneously attenuated glucagon concentrations and the glucagon-alanine index in individuals with overweight without diabetes.
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Diabetes Mellitus Tipo 2 , Liraglutida , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucagon , Sobrepeso/tratamento farmacológico , Sobrepeso/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Fígado/metabolismo , Alanina/uso terapêutico , AminoácidosRESUMO
In the original publication [...].
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Patients with Parkinson's disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also influence non-motor symptoms. The aim of this study is to investigate how the cerebral 5-HT system associates to disturbances in cognition and mood in PD patients with DBS-STN turned on and off. We used psychological tests and questionnaires to evaluate cognitive function and the effects on mood from turning DBS-STN off. We applied a novel PET neuroimaging methodology to evaluate the integrity of the cerebral serotonin system. We measured 5-HT1BR binding in 13 DBS-STN-treated PD patients, at baseline and after turning DBS off. Thirteen age-matched volunteers served as controls. The measures for cognition and mood were correlated to the 5-HT1BR availability in temporal limbic cortex. 5-HT1BR binding was proportional to working memory performance and inverse proportional to affective bias for face recognition. When DBS is turned off, patients feel less vigorous; the higher the limbic and temporal 5-HT1BR binding, the more they are affected by DBS being turned off. Our study suggests that cerebral 5-HTR binding is associated with non-motor symptoms, and that preservation of serotonergic functions may be predictive of DBS-STN effects.
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Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations within a given circuit. In this study, we developed a chemogenetic method for selective activation of dopamine neurons in the substantia nigra, which innervates the dorsal striatum in the rat. We used this model to investigate effects of targeted dopamine activation on CSTC circuit function, especially in fronto-cortical regions. We found that chemogenetic activation of these neurons increased movement (as expected with increased dopamine release), rearings and time spent in center, while also lower self-grooming. Furthermore, this activation increased prepulse inhibition of the startle response in females. Remarkably, we observed reduced [18F]FDG metabolism in the frontal cortex, following dopamine activation in the dorsal striatum, while total glutamate levels- in this region were increased. This result is in accord with clinical studies of increased [18F]FDG metabolism and lower glutamate levels in similar regions of the brain of people with OCD. Taken together, the present chemogenetic model adds a mechanistic basis with behavioral and translational relevance to prior clinical neuroimaging studies showing deficits in fronto-cortical glucose metabolism across a variety of clinical populations (e.g. addiction, risky decision-making, compulsivity or obesity).
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Dopamina , Transtorno Obsessivo-Compulsivo , Animais , Ansiedade/tratamento farmacológico , Comportamento Compulsivo/tratamento farmacológico , Corpo Estriado/metabolismo , Dopamina/metabolismo , Feminino , Ácido Glutâmico/metabolismo , RatosRESUMO
Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-uptake. The 3'-deoxy-3'-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01-1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.
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Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mechanisms of the GABA system, however, no studies have currently combined the techniques to create a high-resolution multimodal view of the GABA system. Here, we present a quantitative high-resolution in vivo atlas of the human brain benzodiazepine receptor sites (BZR) located on postsynaptic ionotropic GABAA receptors (GABAARs), generated on the basis of in vivo [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on ex vivo autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association between BZR protein density and ex vivo mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein. This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain.
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Atlas como Assunto , Benzodiazepinas/metabolismo , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptores de GABA-A/metabolismo , Adulto , Autorradiografia/métodos , Autorradiografia/normas , Sítios de Ligação/fisiologia , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/normas , Ligação Proteica/fisiologia , Adulto JovemRESUMO
Patients with Parkinson's disease (PD) often suffer from non-motor symptoms, which may be caused by serotonergic dysfunction. Apart from alleviating the motor symptoms, Deep Brain Stimulation (DBS) in the subthalamic nucleus (STN) may also influence non-motor symptoms. The aim of this study is to investigate how turning DBS off affects the serotonergic system. We here exploit a novel functional PET neuroimaging methodology to evaluate the preservation of serotonergic neurons and capacity to release serotonin. We measured cerebral 5-HT1BR binding in 13 DBS-STN treated PD patients, at baseline and after turning DBS off. Ten age-matched volunteers served as controls. Clinical measures of motor symptoms were assessed under the two conditions and correlated to the PET measures of the static and dynamic integrity of the serotonergic system. PD patients exhibited a significant loss of frontal and parietal 5-HT1BR, and the loss was significantly correlated to motor symptom severity. We saw a corresponding release of serotonin, but only in brain regions with preserved 5-HT1BR, suggesting the presence of a presynaptic serotonergic deficit. Our study demonstrates that DBS-STN dynamically regulates the serotonin system in PD, and that preservation of serotonergic functions may be predictive of DBS-STN effects.
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Estimulação Encefálica Profunda , Doença de Parkinson/terapia , Tomografia por Emissão de Pósitrons , Núcleo Subtalâmico/fisiopatologia , Idoso , Estudos de Casos e Controles , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Receptor 5-HT1B de Serotonina/metabolismo , Neurônios Serotoninérgicos/metabolismo , Serotonina/metabolismoRESUMO
AIM: To investigate the effect of a glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, on pancreatic volume, oedema, cellularity and DNA synthesis in humans. MATERIALS AND METHODS: We performed an open-label study in 14 obese men (age 38 ± 11 years, body mass index 32 ± 4 kg/m2 ) without diabetes. Subjects were examined at baseline, during titration (week 4) of liraglutide towards 3.0 mg/day, and 2 weeks after steady-state treatment (week 6) of a final dose of liraglutide. The primary endpoint was pancreatic volume determined by magnetic resonance imaging. Secondary endpoints included pancreatic oedema and cellularity, positron emission tomography-based [18 F]fluorothymidine (FLT) uptake (DNA synthesis) and plasma pancreatic enzymes. RESULTS: Plasma amylase (+7 U/L [95% confidence intervals 3-11], P < .01) and lipase (+19 U/L [7-30], P < .01) increased during liraglutide treatment. Pancreatic volume did not change from baseline to steady state of treatment (+0.2 cm3 [-8-8], P = .96) and no change in pancreatic cellular infiltration was found (P = .22). During titration of liraglutide, FLT uptake in pancreatic tissue increased numerically (+0.08 [0.00-0.17], P = .0507). CONCLUSIONS: Six weeks of treatment with liraglutide did not affect pancreatic volume, oedema or cellularity in obese men without diabetes.
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Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Edema/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/tratamento farmacológicoRESUMO
It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis.
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Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Guias de Prática Clínica como Assunto , Consenso , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador/normas , Neuroimagem/normas , Tomografia por Emissão de Pósitrons/normas , Compostos Radiofarmacêuticos , Reprodutibilidade dos TestesRESUMO
Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding in interictal migraine patients without aura compared to controls. Methods Eighteen migraine patients, who had been migraine free for >48 hours, and 16 controls were scanned after injection of the 5-HT1B receptor specific radioligand [11C]AZ10419369 for quantification of cerebral 5-HT1B receptor binding. Patients who reported migraine <48 hours after the PET examination were excluded from the final analysis. We defined seven brain regions involved in pain modulation as regions of interest and applied a latent variable model (LVM) to assess the group effect on binding across these regions. Results Our data support a model wherein group status predicts the latent variable ( p = 0.038), with migraine patients having lower 5-HT1B receptor binding across regions compared to controls. Further, in a whole-brain voxel-based analysis, time since last migraine attack correlated positively with 5-HT1B receptor binding in the dorsal raphe and in the midbrain. Conclusion We report here for the first time that migraine patients have low 5-HT1B receptor binding in pain modulating regions, reflecting decreased receptor density. This is either a primary constitutive trait of the migraine brain or secondary to repeated exposure to migraine attacks. We also provide indirect support for the dorsal raphe 5-HT1B receptors being temporarily downregulated during the migraine attack, presumably in response to higher cerebral serotonin levels in the ictal phase.
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Encéfalo/metabolismo , Transtornos de Enxaqueca/metabolismo , Receptor 5-HT1B de Serotonina/metabolismo , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Transtornos de Enxaqueca/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Ensaio Radioligante , Compostos RadiofarmacêuticosRESUMO
Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively capture temporal and spatial information about acute changes in brain neurotransmitter systems. We here evaluate the 5-HT1B receptor partial agonist PET radioligand, [11C]AZ10419369, for its sensitivity to detect changes in endogenous cerebral serotonin levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain serotonin levels, we compared the [11C]AZ10419369 PET signal in the pig brain to simultaneous measurements of extracellular serotonin levels with microdialysis after various acute interventions (saline, escitalopram, fenfluramine). The interventions increased the cerebral extracellular serotonin levels to two to six times baseline, with fenfluramine being the most potent pharmacological enhancer of serotonin release. The interventions induced a varying degree of decline in [11C]AZ10419369 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular serotonin level in the pig brain and the 5-HT1B receptor occupancy indicates that [11C]AZ10419369 binding is sensitive to changes in endogenous serotonin levels to a degree equivalent to that reported of [11C]raclopride to dopamine, a much used approach to detect in vivo change in cerebral dopamine.
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Encéfalo , Modelos Neurológicos , Tomografia por Emissão de Pósitrons , Receptor 5-HT1B de Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina , Serotonina/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/farmacocinética , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , SuínosRESUMO
Quantitative PET/MRI is dependent on reliable and reproducible MR-based attenuation correction (MR-AC). In this study, we evaluated the quality of current vendor-provided thoracic MR-AC maps and further investigated the reproducibility of their impact on 18F-FDG PET quantification in patients with non-small cell lung cancer. Methods: Eleven patients with inoperable non-small cell lung cancer underwent 2-5 thoracic PET/MRI scan-rescan examinations within 22 d. 18F-FDG PET data were acquired along with 2 Dixon MR-AC maps for each examination. Two PET images (PETA and PETB) were reconstructed using identical PET emission data but with MR-AC from these intrasubject repeated attenuation maps. In total, 90 MR-AC maps were evaluated visually for quality and the occurrence of categorized artifacts by 2 PET/MRI-experienced physicians. Each tumor was outlined by a volume of interest (40% isocontour of maximum) on PETA, which was then projected onto the corresponding PETB SUVmean and SUVmax were assessed from the PET images. Within-examination coefficients of variation and Bland-Altman analyses were conducted for the assessment of SUV variations between PETA and PETBResults: Image artifacts were observed in 86% of the MR-AC maps, and 30% of the MR-AC maps were subjectively expected to affect the tumor SUV. SUVmean and SUVmax resulted in coefficients of variation of 5.6% and 6.6%, respectively, and scan-rescan SUV variations were within ±20% in 95% of the cases. Substantial SUV variations were seen mainly for scan-rescan examinations affected by respiratory motion. Conclusion: Artifacts occur frequently in standard thoracic MR-AC maps, affecting the reproducibility of PET/MRI. These, in combination with other well-known sources of error associated with PET/MRI examinations, lead to inconsistent SUV measurements in serial studies, which may affect the reliability of therapy response assessment. A thorough visual inspection of the thoracic MR-AC map and Dixon images from which it is derived remains crucial for the detection of MR-AC artifacts that may influence the reliability of SUV.
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Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Artefatos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The increasing use of the pig as a research model in neuroimaging requires standardized processing tools. For example, extraction of regional dynamic time series from brain PET images requires parcellation procedures that benefit from being automated. COMPARISON WITH EXISTING METHODS: Manual inter-modality spatial normalization to a MRI atlas is operator-dependent, time-consuming, and can be inaccurate with lack of cortical radiotracer binding or skull uptake. NEW METHOD: A parcellated PET template that allows for automatic spatial normalization to PET images of any radiotracer. RESULTS: MRI and [11C]Cimbi-36 PET scans obtained in sixteen pigs made the basis for the atlas. The high resolution MRI scans allowed for creation of an accurately averaged MRI template. By aligning the within-subject PET scans to their MRI counterparts, an averaged PET template was created in the same space. We developed an automatic procedure for spatial normalization of the averaged PET template to new PET images and hereby facilitated transfer of the atlas regional parcellation. Evaluation of the automatic spatial normalization procedure found the median voxel displacement to be 0.22±0.08mm using the MRI template with individual MRI images and 0.92±0.26mm using the PET template with individual [11C]Cimbi-36 PET images. We tested the automatic procedure by assessing eleven PET radiotracers with different kinetics and spatial distributions by using perfusion-weighted images of early PET time frames. CONCLUSION: We here present an automatic procedure for accurate and reproducible spatial normalization and parcellation of pig PET images of any radiotracer with reasonable blood-brain barrier penetration.
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Mapeamento Encefálico/métodos , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Animais , Atlas como Assunto , Radioisótopos de Carbono , Feminino , Radioisótopos de Flúor , Masculino , Processamento de Sinais Assistido por Computador , SuínosRESUMO
For quantitative tracer distribution in positron emission tomography, attenuation correction is essential. In a hybrid PET/CT system the CT images serve as a basis for generation of the attenuation map, but in PET/MR, the MR images do not have a similarly simple relationship with the attenuation map. Hence attenuation correction in PET/MR systems is more challenging. Typically either of two MR sequences are used: the Dixon or the ultra-short time echo (UTE) techniques. However these sequences have some well-known limitations. In this study, a reconstruction technique based on a modified and optimized non-TOF MLAA is proposed for PET/MR brain imaging. The idea is to tune the parameters of the MLTR applying some information from an attenuation image computed from the UTE sequences and a T1w MR image. In this MLTR algorithm, an [Formula: see text] parameter is introduced and optimized in order to drive the algorithm to a final attenuation map most consistent with the emission data. Because the non-TOF MLAA is used, a technique to reduce the cross-talk effect is proposed. In this study, the proposed algorithm is compared to the common reconstruction methods such as OSEM using a CT attenuation map, considered as the reference, and OSEM using the Dixon and UTE attenuation maps. To show the robustness and the reproducibility of the proposed algorithm, a set of 204 [18F]FDG patients, 35 [11C]PiB patients and 1 [18F]FET patient are used. The results show that by choosing an optimized value of [Formula: see text] in MLTR, the proposed algorithm improves the results compared to the standard MR-based attenuation correction methods (i.e. OSEM using the Dixon or the UTE attenuation maps), and the cross-talk and the scale problem are limited.
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Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Algoritmos , Fluordesoxiglucose F18 , Humanos , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT water phantom. LONG-TERM STABILITY: The mMR calibration stability was evaluated over a 3-year period where 54 cross-calibrations were acquired, showing that the mMR on average underestimated the concentration by 16 %, consistently due to the use of MR-based µ-maps. The mMR produced the narrowest calibration ratio range with the lowest standard deviation, implying it is the most stable of the six systems in the study over a 3-year period. MMR ACCURACY WITH PREDEFINED µ-MAPS: With the latest mMR software version, VB20P, it is possible to utilize predefined phantom µ-maps. We evaluated both the system-integrated, predefined µ-map of the long mMR water phantom and our own user-defined CT-based µ-map of the mCT water phantom, which is used for cross-calibration. For seven scans, which were reconstructed with correctly segmented µ-maps, the mMR produced cross-calibration ratios of 1.00-1.02, well within the acceptance range [0.95-1.05], showing high accuracy. CONCLUSIONS: The mMR is the most stable PET system in this study, and the mean underestimation is no longer an issue with the easily accessible µ-map, which resulted in correct cross-calibration ratios in all seven tests. We will share the user-defined µ-map of the mCT phantom and the protocol with interested mMR users.
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UNLABELLED: A spatial bias in brain PET/MR exists compared with PET/CT, because of MR-based attenuation correction. We performed an evaluation among 4 institutions, 3 PET/MR systems, and 4 PET/CT systems using an anthropomorphic brain phantom, hypothesizing that the spatial bias would be minimized with CT-based attenuation correction (CTAC). METHODS: The evaluation protocol was similar to the quantification of changes in neurologic PET studies. Regional analysis was conducted on 8 anatomic volumes of interest (VOIs) in gray matter on count-normalized, resolution-matched, coregistered data. On PET/MR systems, CTAC was applied as the reference method for attenuation correction. RESULTS: With CTAC, visual and quantitative differences between PET/MR and PET/CT systems were minimized. Intersystem variation between institutions was +3.42% to -3.29% in all VOIs for PET/CT and +2.15% to -4.50% in all VOIs for PET/MR. PET/MR systems differed by +2.34% to -2.21%, +2.04% to -2.08%, and -1.77% to -5.37% when compared with a PET/CT system at each institution, and these differences were not significant (P ≥ 0.05). CONCLUSION: Visual and quantitative differences between PET/MR and PET/CT systems can be minimized by an accurate and standardized method of attenuation correction. If a method similar to CTAC can be implemented for brain PET/MRI, there is no reason why PET/MR should not perform as well as PET/CT.
Assuntos
Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/instrumentação , Imagem Multimodal/instrumentação , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/instrumentação , HumanosRESUMO
BACKGROUND: In the absence of CT or traditional transmission sources in combined clinical positron emission tomography/magnetic resonance (PET/MR) systems, MR images are used for MR-based attenuation correction (MR-AC). The susceptibility effects due to metal implants challenge MR-AC in the neck region of patients with dental implants. The purpose of this study was to assess the frequency and magnitude of subsequent PET image distortions following MR-AC. METHODS: A total of 148 PET/MR patients with clear visual signal voids on the attenuation map in the dental region were included in this study. Patients were injected with [(18)F]-FDG, [(11)C]-PiB, [(18)F]-FET, or [(64)Cu]-DOTATATE. The PET/MR data were acquired over a single-bed position of 25.8 cm covering the head and neck. MR-AC was based on either standard MR-ACDIXON or MR-ACINPAINTED where the susceptibility-induced signal voids were substituted with soft tissue information. Our inpainting algorithm delineates the outer contour of signal voids breaching the anatomical volume using the non-attenuation-corrected PET image and classifies the inner air regions based on an aligned template of likely dental artifact areas. The reconstructed PET images were evaluated visually and quantitatively using regions of interests in reference regions. The volume of the artifacts and the computed relative differences in mean and max standardized uptake value (SUV) between the two PET images are reported. RESULTS: The MR-based volume of the susceptibility-induced signal voids on the MR-AC attenuation maps was between 1.6 and 520.8 mL. The corresponding/resulting bias of the reconstructed tracer distribution was localized mainly in the area of the signal void. The mean and maximum SUVs averaged across all patients increased after inpainting by 52% (± 11%) and 28% (± 11%), respectively, in the corrected region. SUV underestimation decreased with the distance to the signal void and correlated with the volume of the susceptibility artifact on the MR-AC attenuation map. CONCLUSIONS: Metallic dental work may cause severe MR signal voids. The resulting PET/MR artifacts may exceed the actual volume of the dental fillings. The subsequent bias in PET is severe in regions in and near the signal voids and may affect the conspicuity of lesions in the mandibular region.