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BMC Psychiatry Jun 2024Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum.
METHODS
PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment.
RESULTS
Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (V). Regional SV2A V was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003).
CONCLUSIONS
Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn.
PROSPERO
CRD42022359018.
Topics: Humans; Psychotic Disorders; Neuroimaging; Synapses; Positron-Emission Tomography; Brain; Nerve Tissue Proteins; Membrane Glycoproteins
PubMed: 38898401
DOI: 10.1186/s12888-024-05788-y -
Nihon Hoshasen Gijutsu Gakkai Zasshi 2024
Topics: Positron-Emission Tomography; Image Processing, Computer-Assisted; Humans; Artificial Intelligence
PubMed: 38897932
DOI: 10.6009/jjrt.2024-2365 -
Science Advances Jun 2024Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and...
Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and therapeutic monitoring. Here, we validated the accuracy of CMKLR1 as an imaging biomarker of the lung inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, we demonstrated expression as a transient signature of monocyte-derived macrophages (MDMφ) enriched in patients with idiopathic pulmonary fibrosis (IPF). Consistently, we identified MDMφ as the major driver of the uptake of CMKLR1-targeting peptides in a murine model of bleomycin-induced lung fibrosis. Furthermore, CMKLR1-targeted positron emission tomography in the murine model enabled quantification and spatial mapping of inflamed lung regions infiltrated by CMKLR1-expressing macrophages and emerged as a robust predictor of subsequent lung fibrosis. Last, high expression by bronchoalveolar lavage cells identified an inflammatory endotype of IPF with poor survival. Our investigation supports the potential of CMKLR1 as an imaging biomarker for endotyping and risk stratification of fibrotic lung diseases.
Topics: Animals; Humans; Mice; Idiopathic Pulmonary Fibrosis; Pneumonia; Macrophages; Biomarkers; Disease Models, Animal; Positron-Emission Tomography; Pulmonary Fibrosis; Bleomycin; Lung; Male; Female; Mice, Inbred C57BL
PubMed: 38896611
DOI: 10.1126/sciadv.adm9817 -
BioRxiv : the Preprint Server For... Jun 2024Research on brain functional connectivity often relies on intra-individual moment-to-moment correlations of functional brain activity, typically using techniques like...
Research on brain functional connectivity often relies on intra-individual moment-to-moment correlations of functional brain activity, typically using techniques like functional MRI (fMRI). Inter-individual correlations are also employed on data from fMRI and positron emission tomography (PET). Many past studies have not specified tasks for participants, keeping them in an implicit "resting" condition. This lack of task specificity raises questions about how different tasks impact inter-individual correlation estimates. In our analysis of fMRI data from 100 unrelated participants, scanned during seven task conditions and in a resting state, we calculated Regional Homogeneity (ReHo) for each task as a regional measure of brain functions. We found that changes in ReHo due to different tasks were relatively small compared with the variations across brain regions. Cross-region variations of ReHo were highly correlated between different tasks. Similarly, whole-brain inter-individual correlation patterns were remarkably consistent across the tasks, showing correlations greater than 0.78. Changes in inter-individual correlations between tasks were primarily driven by connectivity in the visual, somatomotor, default mode network, and the interactions between them. The subtle yet statistically significant differences in functional connectivity may be linked to specific brain regions associated with the studied tasks. Future studies should consider task design when exploring inter-individual connectivity in specific brain systems.
PubMed: 38895341
DOI: 10.1101/2024.06.02.597063 -
BioRxiv : the Preprint Server For... Jun 2024Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small...
BACKGROUND
Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.
METHODS
1) African Green monkeys (AGM) received doxorubicin (30-60 mg/m/biweekly IV, cumulative dose: 240 mg/m). Blinded histopathologic analyses of collagen deposition and cell vacuolization in the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study. The primary outcome was change in maximal tissue-to-background ratio (TBRmax) of the thoracic aorta from baseline to their end-of-treatment clinical PET/CT.
RESULTS
In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin cohort 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and increased intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs controls 11.5 ± 4.2 vacuoles/field, p<0.0001) than untreated controls.In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (pre-doxorubicin TBRmax 1.46±0.16 vs post-doxorubicin TBRmax 1.44±0.14, p=0.14). The absence of change in TBRmax was consistent across all univariate analyses.
CONCLUSIONS
In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation.Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.
PubMed: 38895275
DOI: 10.1101/2024.05.30.596741 -
General Psychiatry 2024Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains...
BACKGROUND
Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains limited.
AIMS
This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD.
METHODS
This study enrolled 28 drug-naive adults with OCD aged 18-40 years and 16 healthy controls (HCs). Three-dimensional T1-weighted structural magnetic resonance imaging and F-SynVesT-1 positron emission tomography were conducted. Cognitive function was assessed using the Wisconsin Cart Sorting Test (WCST) in patients with OCD and HCs. Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction.
RESULTS
Compared with HCs, patients with OCD showed reduced synaptic density in regions of the cortico-striato-thalamo-cortical circuit such as the bilateral putamen, left caudate, left parahippocampal gyrus, left insula, left parahippocampal gyrus and left middle occipital lobe (voxel p<0.001, uncorrected, with cluster level above 50 contiguous voxels). The per cent conceptual-level responses of WCST were positively associated with the synaptic density reduction in the left middle occipital gyrus (R=0.1690, p=0.030), left parahippocampal gyrus (R=0.1464, p=0.045) and left putamen (R=0.1967, p=0.018) in patients with OCD.
CONCLUSIONS
Adults with OCD demonstrated lower F-labelled difluoro analogue of F-SynVesT-1 compared with HCs, indicating potentially lower synaptic density. This is the first study to explore the synaptic density in patients with OCD and provides insights into potential biological targets for cognitive dysfunctions in OCD.
PubMed: 38894874
DOI: 10.1136/gpsych-2023-101208 -
CNS Neuroscience & Therapeutics Jun 2024The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering...
AIMS
The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering higher level of consciousness compared to patients with the unresponsive wakefulness syndrome (UWS). However, differentiation of the MCS and UWS poses challenge in clinical practice. This study aimed to explore glucose metabolic pattern (GMP) obtained from F-labeled-fluorodeoxyglucose positron emission tomography (F-FDG-PET) in distinguishing between UWS and MCS.
METHODS
Fifty-seven patients with disorders of consciousness (21 cases of UWS and 36 cases of MCS) who had undergone repeated standardized Coma Recovery Scale-Revised (CRS-R) evaluations were enrolled in this prospective study. F-FDG-PET was carried out in all patients and healthy controls (HCs). Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate GMPs. The expression score of whole-brain GMP was obtained, and its diagnostic accuracy was compared with the standardized uptake value ratio (SUVR). The diagnostic efficiency was validated by one-year later clinical outcomes.
RESULTS
UWS-MCS GMP exhibited hypometabolism in the frontal-parietal cortex, along with hypermetabolism in the unilateral lentiform nucleus, putamen, and anterior cingulate gyrus. The UWS-MCS-GMP expression score was significantly higher in UWS compared to MCS patients (0.90 ± 0.85 vs. 0 ± 0.93, p < 0.001). UWS-MCS-GMP expression score achieved an area under the curve (AUC) of 0.77 to distinguish MCS from UWS, surpassing that of SUVR based on the frontoparietal cortex (AUC = 0.623). UWS-MCS-GMP expression score was significantly correlated with the CRS-R score (r = -0.45, p = 0.004) and accurately predicted the one-year outcome in 73.7% of patients.
CONCLUSION
UWS and MCS exhibit specific glucose metabolism patterns, the UWS-MCS-GMP expression score significantly distinguishes MCS from UWS, making SSM/PCA a potential diagnostic methods in clinical practice for individual patients.
Topics: Humans; Female; Male; Middle Aged; Adult; Glucose; Fluorodeoxyglucose F18; Brain; Positron-Emission Tomography; Persistent Vegetative State; Aged; Prospective Studies; Young Adult
PubMed: 38894559
DOI: 10.1111/cns.14787 -
Diagnostics (Basel, Switzerland) Jun 2024We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline F-FDG-PET/CT could predict developing metastatic disease...
We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline F-FDG-PET/CT could predict developing metastatic disease and overall survival (OS) in gastroesophageal cancer (GEC). Patients referred for primary staging who underwent F-FDG-PET/CT from 2008 to 2019 were evaluated retrospectively. Overall, 243 GEC patients (mean age = 64) were enrolled. Clinical, histopathology, and sarcopenia data were obtained, and primary tumor radiomics features were extracted. For classification (early-stage vs. advanced disease), the association of the studied parameters was evaluated. Various clinical and radiomics models were developed and assessed. Accuracy and area under the curve (AUC) were calculated. For OS prediction, univariable and multivariable Cox analyses were performed. The best model included PET/CT radiomics features, clinical data, and sarcopenia score (accuracy = 80%; AUC = 88%). For OS prediction, various clinical, CT, and PET features entered the multivariable analysis. Three clinical factors (advanced disease, age ≥ 70 and ECOG ≥ 2), along with one CT-derived and one PET-derived radiomics feature, retained their significance. Overall, F-FDG PET/CT radiomics seems to have a potential added value in identifying GEC patients with advanced disease and may enhance the performance of baseline clinical parameters. These features may also have a prognostic value for OS, improving the decision-making for GEC patients.
PubMed: 38893731
DOI: 10.3390/diagnostics14111205 -
Diagnostics (Basel, Switzerland) May 2024Incorrect scatter scaling of positron emission tomography (PET) images can lead to halo artifacts, quantitative bias, or reconstruction failure. Tail-fitted scatter...
Incorrect scatter scaling of positron emission tomography (PET) images can lead to halo artifacts, quantitative bias, or reconstruction failure. Tail-fitted scatter scaling (TFSS) possesses performance limitations in multiple cases. This study aims to investigate a novel method for scatter scaling: maximum-likelihood scatter scaling (MLSS) in scenarios where TFSS tends to induce artifacts or are observed to cause reconstruction abortion. [Ga]Ga-RGD PET scans of nine patients were included in cohort 1 in the scope of investigating the reduction of halo artifacts relative to the scatter estimation method. PET scans of 30 patients administrated with [Ga]Ga-uPAR were included in cohort 2, used for an evaluation of the robustness of MLSS in cases where TFSS-integrated reconstructions are observed to fail. A visual inspection of MLSS-corrected images scored higher than TFSS-corrected reconstructions of cohort 1. The quantitative investigation near the bladder showed a relative difference in tracer uptake of up to 94.7%. A reconstruction of scans included in cohort 2 resulted in failure in 23 cases when TFSS was used. The lesion uptake values of cohort 2 showed no significant difference. MLSS is suggested as an alternative scatter-scaling method relative to TFSS with the aim of reducing halo artifacts and a robust reconstruction process.
PubMed: 38893602
DOI: 10.3390/diagnostics14111075 -
Cancers May 2024We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy...
Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High-Risk Prostate Cancer: Insights from a Phase I/II Study.
We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. : All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. : Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.
PubMed: 38893216
DOI: 10.3390/cancers16112097