189 research outputs found
Assessing the impact of different penalty factors of the Bayesian reconstruction algorithm Q.Clear on in vivo low count kinetic analysis of [11C]PHNO brain PET-MR studies
INTRODUCTION: Q.Clear is a Bayesian penalised likelihood (BPL) reconstruction algorithm available on General Electric (GE) Positron Emission Tomography (PET)-Computed Tomography (CT) and PET-Magnetic Resonance (MR) scanners. This algorithm is regulated by a β value which acts as a noise penalisation factor and yields improvements in signal to noise ratio (SNR) in clinical scans, and in contrast recovery and spatial resolution in phantom studies. However, its performance in human brain imaging studies remains to be evaluated in depth. This pilot study aims to investigate the impact of Q.Clear reconstruction methods using different β value versus ordered subset expectation maximization (OSEM) on brain kinetic modelling analysis of low count brain images acquired in the PET-MR. METHODS: Six [(11)C]PHNO PET-MR brain datasets were reconstructed with Q.Clear with β100â1000 (in increments of 100) and OSEM. The binding potential relative to non-displaceable volume (BP(ND)) were obtained for the Substantia Nigra (SN), Striatum (St), Globus Pallidus (GP), Thalamus (Th), Caudate (Cd) and Putamen (Pt), using the MIAKAT⢠software. Intraclass correlation coefficients (ICC), repeatability coefficients (RC), coefficients of variation (CV) and bias from BlandâAltman plots were reported. Statistical analysis was conducted using a 2-way ANOVA model with correction for multiple comparisons. RESULTS: When comparing a standard OSEM reconstruction of 6 iterations/16 subsets and 5 mm filter with Q.Clear with different β values under low counts, the bias and RC were lower for Q.Clear with β100 for the SN (RCâ=â2.17), Th (RCâ=â0.08) and GP (RCâ=â0.22) and with β200 for the St (RCâ=â0.14), Cd (RCâ=â0.18)and Pt (RCâ=â0.10). The p-values in the 2-way ANOVA model corroborate these findings. ICC values obtained for Th, St, GP, Pt and Cd demonstrate good reliability (0.87, 0.99, 0.96, 0.99 and 0.96, respectively). For the SN, ICC values demonstrate poor reliability (0.43). CONCLUSION: BP(ND) results obtained from quantitative low count brain PET studies using [(11)C]PHNO and reconstructed with Q.Clear with βâ<â400, which is the value used for clinical [(18)F]FDG whole-body studies, demonstrate the lowest bias versus the typical iterative reconstruction method OSEM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-022-00883-1
Cannabis Use Linked to Altered Functional Connectivity of the Visual Attentional Connectivity in Patients With Psychosis and Controls
Background: Both chronic cannabis use and psychotic disorders are associated with abnormalities in visual atten-tional processing. Using functional magnetic resonance imaging (fMRI), we sought to determine whether there would be a difference in functional connectivity in patients and controls with and without a history of cannabis use in the visual and dorsal attention networks. Methods: Resting-state fMRI data were acquired in patients with early psy-chosis with (EPC = 29) and without (EPNC = 25); and controls with (HCC = 16) and without (HCNC = 22) cannabis use. Results: There was a patient effect in both Visual-Dorsal Attention Internetwork (F(1,87) = 5.326, P = .023) and the Visual Network (F(1,87) = 4.044, P = .047) and a cannabis effect in the Dorsal Attention Network (F(1,87) = 4.773, P = .032). These effects were specific to the networks examined with no evidence for significant patient or cannabis effects in other canonical networks. Patients with a history of cannabis use showed increased connec-tivity in the Dorsal Attention Network (134%, P = .019) and Visual Dorsal Attention Internetwork (285%, P = .036) compared to non-using controls. In the EPC group con-nectivity of the Visual Network (Ď = 0.379, P = .042) and Visual-Dorsal Attention Internetwork (Ď = 0.421, P = .023) correlated with visual hallucinations which were significantly different from EPNC (P = .011). Dorsal attention network strength correlated with severity of dependence for cannabis (Ď = 0.215, P = .04). Conclusion: We demonstrate specific cannabis and patient effects in networks associated with visual attentional processing. There is a differential association with hallucinatory symptoms in patients with and without a history of cannabis use. This may indicate that dysconnectivity in these networks serves different roles in the context of cannabis use
The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study
Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [11C]-(â+â)-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (D2/3R) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum D2/3R availability was positively associated with prefrontal cortex gray matter volume (pFWE correctedâ=â0.048). This relationship was mainly driven by associative receptor availability (pFWE correctedâ=â0.023). In addition, an interaction effect was observed between sensorimotor striatum D2/3R availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, D2/3R availability was negatively associated with right frontal cortex gray matter volumes, while a positive D2/3R-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE correctedâ=â0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations
Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis.
BACKGROUND
Antipsychotic treatment is associated with metabolic disturbance. However, the degree to which metabolic alterations occur in treatment with different antipsychotics is unclear. Predictors of metabolic dysregulation are poorly understood and the association between metabolic change and change in psychopathology is uncertain. We aimed to compare and rank antipsychotics on the basis of their metabolic side-effects, identify physiological and demographic predictors of antipsychotic-induced metabolic dysregulation, and investigate the relationship between change in psychotic symptoms and change in metabolic parameters with antipsychotic treatment.
METHODS
We searched MEDLINE, EMBASE, and PsycINFO from inception until June 30, 2019. We included blinded, randomised controlled trials comparing 18 antipsychotics and placebo in acute treatment of schizophrenia. We did frequentist random-effects network meta-analyses to investigate treatment-induced changes in body weight, BMI, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, and glucose concentrations. We did meta-regressions to examine relationships between metabolic change and age, sex, ethnicity, baseline weight, and baseline metabolic parameter level. We examined the association between metabolic change and psychopathology change by estimating the correlation between symptom severity change and metabolic parameter change.
FINDINGS
Of 6532 citations, we included 100 randomised controlled trials, including 25â952 patients. Median treatment duration was 6 weeks (IQR 6-8). Mean differences for weight gain compared with placebo ranged from -0¡23 kg (95% CI -0¡83 to 0¡36) for haloperidol to 3¡01 kg (1¡78 to 4¡24) for clozapine; for BMI from -0¡25 kg/m2 (-0¡68 to 0¡17) for haloperidol to 1¡07 kg/m2 (0¡90 to 1¡25) for olanzapine; for total-cholesterol from -0¡09 mmol/L (-0¡24 to 0¡07) for cariprazine to 0¡56 mmol/L (0¡26-0¡86) for clozapine; for LDL cholesterol from -0¡13 mmol/L (-0.21 to -0¡05) for cariprazine to 0¡20 mmol/L (0¡14 to 0¡26) for olanzapine; for HDL cholesterol from 0¡05 mmol/L (0¡00 to 0¡10) for brexpiprazole to -0¡10 mmol/L (-0¡33 to 0¡14) for amisulpride; for triglycerides from -0¡01 mmol/L (-0¡10 to 0¡08) for brexpiprazole to 0¡98 mmol/L (0¡48 to 1¡49) for clozapine; for glucose from -0¡29 mmol/L (-0¡55 to -0¡03) for lurasidone to 1¡05 mmol/L (0¡41 to 1¡70) for clozapine. Greater increases in glucose were predicted by higher baseline weight (p=0¡0015) and male sex (p=0¡0082). Non-white ethnicity was associated with greater increases in total cholesterol (p=0¡040) compared with white ethnicity. Improvements in symptom severity were associated with increases in weight (r=0¡36, p=0¡0021), BMI (r=0¡84, p<0¡0001), total-cholesterol (r=0¡31, p=0¡047), and LDL cholesterol (r=0¡42, p=0¡013), and decreases in HDL cholesterol (r=-0¡35, p=0¡035).
INTERPRETATION
Marked differences exist between antipsychotics in terms of metabolic side-effects, with olanzapine and clozapine exhibiting the worst profiles and aripiprazole, brexpiprazole, cariprazine, lurasidone, and ziprasidone the most benign profiles. Increased baseline weight, male sex, and non-white ethnicity are predictors of susceptibility to antipsychotic-induced metabolic change, and improvements in psychopathology are associated with metabolic disturbance. Treatment guidelines should be updated to reflect our findings. However, the choice of antipsychotic should be made on an individual basis, considering the clinical circumstances and preferences of patients, carers, and clinicians.
FUNDING
UK Medical Research Council, Wellcome Trust, National Institute for Health Research Oxford Health Biomedical Research Centre
Effects of benzodiazepine exposure on real-world clinical outcomes in individuals at clinical high risk for psychosis
Background and Hypothesis
Animal models indicate GABAergic dysfunction in the development of psychosis, and that benzodiazepine (BDZ) exposure can prevent the emergence of psychosis-relevant phenotypes. However, whether BDZ exposure influences real-world clinical outcomes in individuals at clinical high risk for psychosis (CHR-P) is unknown.
Study Design
This observational cohort study used electronic health record data from CHR-P individuals to investigate whether BDZ exposure (including hypnotics, eg, zopiclone) reduces the risk of developing psychosis and adverse clinical outcomes. Cox proportional-hazards models were employed in both the whole-unmatched sample, and a propensity score matched (PSM) subsample.
Study Results
567 CHR-P individuals (306 male, mean[ÂąSD] ageâ
=â
22.3[Âą4.9] years) were included after data cleaning. The BDZ-exposed (nâ
=â
105) and BDZ-unexposed (nâ
=â
462) groups differed on several demographic and clinical characteristics, including psychotic symptom severity. In the whole-unmatched sample, BDZ exposure was associated with increased risk of transition to psychosis (HRâ
=â
1.61; 95% CI: 1.03â2.52; Pâ
=â
.037), psychiatric hospital admission (HRâ
=â
1.93; 95% CI: 1.13â3.29; Pâ
=â
.017), home visit (HRâ
=â
1.64; 95% CI: 1.18â2.28; Pâ
=â
.004), and Accident and Emergency department attendance (HRâ
=â
1.88; 95% CI: 1.31â2.72; Pâ
â
.05). In an analysis restricted to antipsychotic-naĂŻve individuals, BDZ exposure reduced the risk of transition to psychosis numerically, although this was not statistically significant (HRâ
=â
0.59; 95% CI: 0.32â1.08; Pâ
=â
.089).
Conclusions
BDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity
Effects of Benzodiazepine Exposure on Real-World Clinical Outcomes in Individuals at Clinical High-Risk for Psychosis
Background and HypothesisAnimal models indicate GABAergic dysfunction in the development of psychosis, and that benzodiazepine (BDZ) exposure can prevent the emergence of psychosis-relevant phenotypes. However, whether BDZ exposure influences real-world clinical outcomes in individuals at clinical high risk for psychosis (CHR-P) is unknown.Study DesignThis observational cohort study used electronic health record data from CHR-P individuals to investigate whether BDZ exposure (including hypnotics, eg, zopiclone) reduces the risk of developing psychosis and adverse clinical outcomes. Cox proportional-hazards models were employed in both the whole-unmatched sample, and a propensity score matched (PSM) subsample.Study Results567 CHR-P individuals (306 male, mean[ÂąSD] ageâ
=â
22.3[Âą4.9] years) were included after data cleaning. The BDZ-exposed (nâ
=â
105) and BDZ-unexposed (nâ
=â
462) groups differed on several demographic and clinical characteristics, including psychotic symptom severity. In the whole-unmatched sample, BDZ exposure was associated with increased risk of transition to psychosis (HRâ
=â
1.61; 95% CI: 1.03â2.52;Â Pâ
=â
.037), psychiatric hospital admission (HRâ
=â
1.93; 95% CI: 1.13â3.29;Â Pâ
=â
.017), home visit (HRâ
=â
1.64; 95% CI: 1.18â2.28;Â Pâ
=â
.004), and Accident and Emergency department attendance (HRâ
=â
1.88; 95% CI: 1.31â2.72;Â Pâ
<â
.001). However, after controlling for confounding-by-indication through PSM, BDZ exposure did not modulate the risk of any outcomes (all Pâ
>â
.05). In an analysis restricted to antipsychotic-naĂŻve individuals, BDZ exposure reduced the risk of transition to psychosis numerically, although this was not statistically significant (HRâ
=â
0.59; 95% CI: 0.32â1.08;Â Pâ
=â
.089).ConclusionsBDZ exposure in CHR-P individuals was not associated with a reduction in the risk of psychosis transition or adverse clinical outcomes. Results in the whole-unmatched sample suggest BDZ prescription may be more likely in CHR-P individuals with higher symptom severity.</div
Altered glutamatergic response and functional connectivity in treatment resistant schizophrenia:the effect of riluzole and therapeutic implications
An Improved Technique for Measurement of Cold HI in Molecular Cloud Cores
The presence of atomic gas mixed with molecular species in a "molecular"
cloud may significantly affect its chemistry, the excitation of some species,
and can serve as probe of the cloud's evolution. Cold neutral atomic hydrogen
(HI) in molecular clouds is revealed by its self absorption of background
galactic HI 21-cm emission. The properties of this gas can be investigated
quantitatively through observation of HI Narrow Self-Absorption (HINSA). In
this paper, we present a new technique for measuring atomic gas physical
parameters from HINSA observations that utilizes molecular tracers to guide the
HINSA extraction. This technique offers a significant improvement in the
precision with which HI column densities can be determined over previous
methods, and it opens several new avenues of study of relevance to the field of
star formation.Comment: Accepted for Astrophycal Journal 8/200
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