Pulse sequences for measuring exchange rates between proton species: From unlocalised NMR spectroscopy to chemical exchange saturation transfer imaging

Within the field of NMR spectroscopy, the study of chemical exchange processes through saturation transfer techniques has a long history. In the context of MRI, chemical exchange techniques have been adapted to increase the sensitivity of imaging to small fractions of exchangeable protons, including the labile protons of amines, amides and hydroxyls. The MR contrast is generated by frequency-selective irradiation of the labile protons, which results in a reduction of the water signal associated with transfer of the labile protons’ saturated magnetization to the protons of the surrounding free water. The signal intensity depends on the rate of chemical exchange and the concentration of labile protons as well as on the properties of the irradiation field. This methodology is referred to as CEST (chemical exchange saturation transfer) imaging. Applications of CEST include imaging of molecules with short transverse relaxation times and mapping of physiological parameters such as pH, temperature, buffer concentration and chemical composition due to the dependency of this chemical exchange effect on all these parameters. This article aims to describe these effects both theoretically and experimentally. In depth analysis and mathematical modelling are provided for all pulse sequences designed to date to measure the chemical exchange rate. Importantly, it has become clear that the background signal from semi-solid protons and the presence of the Nuclear Overhauser Effect (NOE), either through direct dipole-dipole mechanisms or through exchange-relayed signals, complicates the analysis of CEST effects. Therefore, advanced methods to suppress these confounding factors have been developed, and these are also reviewed. Finally, the experimental work conducted both in vitro and in vivo is discussed and the progress of CEST imaging towards clinical practice is presented

Confirmatory Factor Analysis of the French Version of the Savoring Beliefs Inventory.

The Savoring Beliefs Inventory (SBI) is a measure designed to assess attitudes toward savoring positive experience within three temporal orientations: the past (reminiscence), the present moment (present enjoyment), and the future (anticipation). The aim of this study was to validate the structure of the SBI-French version. The scale was tested with 335 French-speaking participants. Two models were estimated: a one-factor model representing a general construct of savoring and a three-factor model differentiating between anticipation, present enjoyment, and reminiscence. Several indicators of model fit were used: the root mean square error of approximation (RMSEA), the comparison fit index (CFI), the Tucker-Lewis fit index (TLI), and the standardized root mean residual (SRMR). A chi-square difference test was used to compare the two models. The model fit of the three-factor model assessed by the SRMR showed to be excellent, while it could be considered as satisfactory according to the CFI and TLI coefficients. RMSEA, however, was slightly less adequate. The model fit for the one-factor model seemed less adequate than the three-factor solution. Further, the chi-square difference test revealed that the three-factor model had significantly better fit than the one-factor model. Finally, the reliability of the four scores (anticipating pleasure, present moment pleasure, reminiscing pleasure, and total score) was very good. These results show that the French version of the SBI is a valid and valuable scale to measure attitudes regarding the ability to savor positive experience, whether it be in anticipation, reminiscence, or the present moment

The value of arterial spin labelling (ASL) perfusion MRI in the assessment of post-treatment progression in adult glioma: A systematic review and meta-analysis

BACKGROUND: The distinction between viable tumor and therapy-induced changes is crucial for the clinical management of patients with gliomas. This study aims to quantitatively assess the efficacy of arterial spin labeling (ASL) biomarkers, including relative cerebral blood flow (rCBF) and absolute cerebral blood flow (CBF), for the discrimination of progressive disease (PD) and treatment-related effects. METHODS: Eight articles were included in the synthesis after searching the literature systematically. Data have been extracted and a meta-analysis using the random-effect model was subsequently carried out. Diagnostic accuracy assessment was also performed. RESULTS: This study revealed that there is a significant difference in perfusion measurements between groups with PD and therapy-induced changes. The rCBF yielded a standardized mean difference (SMD) of 1.25 [95% CI 0.75, 1.75] (p < .00001). The maximum perfusion indices (rCBFmax and CBFmax) both showed equivalent discriminatory ability, with SMD of 1.35 [95% CI 0.78, 1.91] (p < .00001) and 1.56 [95% CI 0.79, 2.33] (p < .0001), respectively. Similarly, accuracy estimates were comparable among ASL-derived metrices. Pooled sensitivities [95% CI] were 0.85 [0.67, 0.94], 0.88 [0.71, 0.96], and 0.93 [0.73, 0.98], and pooled specificities [95% CI] were 0.83 [0.71, 0.91], 0.83 [0.67, 0.92], 0.84 [0.67, 0.93], for rCBF, rCBFmax and CBFmax, respectively. Corresponding HSROC area under curve (AUC) [95% CI] were 0.90 [0.87, 0.92], 0.92 [0.89, 0.94], and 0.93 [0.90, 0.95]. CONCLUSION: These results suggest that ASL quantitative biomarkers, particularly rCBFmax and CBFmax, have the potential to discriminate between glioma progression and therapy-induced changes

Endogenous chemical exchange saturation transfer (CEST) MR imaging for the diagnosis and therapy response assessment of brain tumors: A systematic review

Purpose: To generate a narrative synthesis of published data on the use of endogenous chemical exchange saturation transfer (CEST) MR imaging in brain tumors. Materials and Methods: A systematic database search (PubMed, Ovid Embase, Cochrane Library) was used to collate eligible studies. Two researchers independently screened publications according to predefined exclusion and inclusion criteria, followed by comprehensive data extraction. All included studies were subjected to a bias risk assessment using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Results: The electronic database search identified 430 studies, of which 36 studies fulfilled the inclusion criteria. The final selection of included studies was categorized into 5 groups as follows: grading gliomas, 19 studies (areas under the curve (AUC) 0.500-1.000); predicting molecular subtypes of gliomas, 5 studies (AUC 0.610-0.920); distinction of different brain tumor types, 7 studies (AUC 0.707-0.905); therapy response assessment, 3 studies (AUC not given) and differentiating recurrence from treatment-related changes, 5 studies (AUC 0.880- 0.980). A high bias risk was observed in a substantial proportion of studies. Conclusion: Endogenous CEST imaging offers valuable, potentially unique information in brain tumors, but its diagnostic accuracy remains incompletely known. Further research is required to assess the method’s role in support of molecular genetic diagnosis, to investigate its use in the post treatment phase, and to compare techniques with a view to standardization

Dynamics between insight and medication adherence in first-episode psychosis: Study of 3-year trajectories.

While specialized early intervention programs represent the gold standard in terms of optimal management of first-episode psychosis (FEP), poor medication adherence remains a predominant unmet need in the treatment of psychosis. In this regard, an interaction between insight and adherence in FEP patients has been hypothesized but has been challenged by multiple pitfalls. Latent profile analysis and trajectory modeling techniques were used to evaluate insight and adherence of 331 FEP patients engaged at the beginning, middle, and end of a 3-year specialized early psychosis program. A Bayesian model comparison approach was used to compare scores of clinical, functional, and socioeconomic outcomes at the end point of the study. Nearly one-third of the patients maintain a high level of insight and adherence during the entire program. At the end of the 3-year follow-up, more than three-quarters of patients are considered adherent to their medication. Patients with low levels of insight and adherence at the beginning of the program improve first in terms of adherence and then of insight. Furthermore, patients with high levels of insight and adherence are most likely to reach functional recovery and to experience an increase in environmental quality of life. Latent FEP subpopulations can be identified based on insight and adherence. Medication adherence was the first variable to improve, but a gain in insight possibly plays a role in the reinforcement of adherence

Effects of a Weight Loss Program on Metabolic Syndrome, Eating Disorders and Psychological Outcomes: Mediation by Endocannabinoids?

To evaluate the effects of weight loss on endocannabinoids, cardiometabolic and psychological parameters, eating disorders (ED) as well as quality of life (QoL) and to elucidate the role of endocannabinoids in metabolic syndrome (MS). In total, 114 patients with obesity were prospectively included in a 12-month weight loss program. Plasma endocannabinoids were measured by mass spectrometry; ED, psychological and QoL-related parameters were evaluated by self-reported questionnaires; physical activity was measured by accelerometer. Nutritional assessment was done by a 3-day food diary. Among completers (n = 87), body weight decreased in 35 patients (-9.1 ± 8.6 kg), remained stable in 39 patients, and increased in 13 patients (+5.8 ± 3.4 kg). 75% of patients with MS at baseline were free of MS at follow-up, and their baseline plasma N-palmitoylethanolamide (PEA) values were significantly lower when compared to patients with persisting MS. At baseline, there was a positive relationship between PEA and waist circumference (p = 0.005, R2 = 0.08), fasting glucose (p &lt; 0.0001, R2 = 0.12), total cholesterol (p = 0.001, R2 = 0.11), triglycerides (p = 0.001, R2 = 0.11), LDL-cholesterol (p = 0.03, R2 = 0.05) as well as depression score (p = 0.002, R2 = 0.29). Plasma PEA might play a role in metabolic improvement after weight loss. Even in subjects without weight loss, a multidisciplinary intervention improves psychological outcomes, ED, and QoL

Moderating role of cannabis use between insight and depression in early psychosis.

A high level of insight in first episode psychosis (FEP) is positively correlated to important prognostic factors such as medication adherence and functional outcome but is associated with increased depression level and suicidal behavior. This is the first study questioning the potential moderating role of cannabis use in the relationship between insight and depression one year after a FEP. In this prospective observational study, we enrolled 214 FEP patients who had provided informed consent and been referred to a specialized early psychosis program and followed for 36 months. A series of multivariate regression models were used. Baseline insight, medication adherence and cannabis use (level of use on a continuum) were entered as independent variables, while the PANSS (positive and negative), the MADRS and the SOFAS scores after one year were alternately selected as the dependent variable. We found a three-way interaction term between cannabis use, insight and medication adherence on depression level one year after the entry into the program. A high level of insight was significantly associated with higher MADRS scores in patients with high cannabis use, while depression decreased in high-insight patients with low cannabis use. Cannabis use continuation during the year following a first episode psychosis may play a significant role in the development or the maintenance of post-psychotic depression in patients who present with high level of insight and adherence to medication, stressing the need for specific therapeutic strategies in this subgroup of patients

Replica Field Theory for Deterministic Models (II): A Non-Random Spin Glass with Glassy Behavior

We introduce and study a model which admits a complex landscape without containing quenched disorder. Continuing our previous investigation we introduce a disordered model which allows us to reconstruct all the main features of the original phase diagram, including a low $T$ spin glass phase and a complex dynamical behavior.Comment: 35 pages with uu figures, Roma 102