White matter fibre density in the brain's inhibitory control network is associated with falling in low activity older adults.

Recent research has indicated that the relationship between age-related cognitive decline and falling may be mediated by the individual's capacity to quickly cancel or inhibit a motor response. This longitudinal investigation demonstrates that higher white matter fibre density in the motor inhibition network paired with low physical activity was associated with falling in elderly participants. We measured the density of white matter fibre tracts connecting key nodes in the inhibitory control network in a large sample (n = 414) of older adults. We modelled their self-reported frequency of falling over a 4-year period with white matter fibre density in pathways corresponding to the direct and hyperdirect cortical-subcortical loops implicated in the inhibitory control network. Only connectivity between right inferior frontal gyrus and right subthalamic nucleus was associated with falling as measured cross-sectionally. The connectivity was not, however, predictive of future falling when measured 2 and 4 years later. Higher white matter fibre density was associated with falling, but only in combination with low levels of physical activity. No such relationship existed for selected control brain regions that are not implicated in the inhibitory control network. Albeit statistically robust, the direction of this effect was counterintuitive (more dense connectivity associated with falling) and warrants further longitudinal investigation into whether white matter fibre density changes over time in a manner correlated with falling, and mediated by physical activity.

Perspective: The Case for Acute Large Vessel Ischemic Stroke in COVID-19 Originating Within Thrombosed Pulmonary Venules.

The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.

Age-related normative changes in cerebral perfusion: Data from The Irish Longitudinal Study on Ageing (TILDA).

OBJECTIVE: To establish normative reference values for total grey matter cerebral blood flow (CBFGM) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older. BACKGROUND: Quantitative assessment of CBFGM may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBFGM from pathological reduction has been hampered by the lack of reference values for cerebral perfusion. METHODS: The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBFGM data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations. RESULTS: The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBFGM for the cohort was 36.5 ± 8.2 ml/100 g/min. CBFGM decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = -0.3, -0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001). CONCLUSIONS: This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBFGM measured at 3T using pCASL-MRI. Significant age- and sex-related differences exist in CBFGM.

Computerised working memory-based cognitive remediation therapy does not affect Reading the Mind in The Eyes test performance or neural activity during a Facial Emotion Recognition test in psychosis.

Working memory-based cognitive remediation therapy (CT) for psychosis has recently been associated with broad improvements in performance on untrained tasks measuring working memory, episodic memory and IQ, and changes in associated brain regions. However, it is unclear whether these improvements transfer to the domain of social cognition and neural activity related to performance on social cognitive tasks. We examined performance on the Reading the Mind in the Eyes test (Eyes test) in a large sample of participants with psychosis who underwent working memory-based CT (N = 43) compared to a control group of participants with psychosis (N = 35). In a subset of this sample, we used functional magnetic resonance imaging (fMRI) to examine changes in neural activity during a facial emotion recognition task in participants who underwent CT (N = 15) compared to a control group (N = 15). No significant effects of CT were observed on Eyes test performance or on neural activity during facial emotion recognition, either at p < 0.05 family-wise error or at a p < 0.001 uncorrected threshold, within a priori social cognitive regions of interest. This study suggests that working memory-based CT does not significantly impact an aspect of social cognition which was measured behaviourally and neurally. It provides further evidence that deficits in the ability to decode mental state from facial expressions are dissociable from working memory deficits, and suggests that future CT programmes should target social cognition in addition to working memory for the purposes of further enhancing social function.

Quantitative effects of acquisition duration and temporal resolution on the measurement accuracy of prostate dynamic contrast-enhanced MRI data: a phantom study.

OBJECTIVES: The aim of this study was to investigate the effect of the temporal resolution (T res) and acquisition duration (AD) on the measurement accuracy of contrast concentration-time curves (CTCs), and derived phenomenological and pharmacokinetic parameter values, in a dynamic contrast-enhanced MRI experiment using a novel phantom test device. MATERIALS AND METHODS: 'Ground truth' CTCs were established using a highly precise optical imaging system. These precisely known CTCs were produced in an anthropomorphic environment, which mimicked the male pelvic region, and presented to the MRI scanner for measurement. The T res was varied in the range [2-24.4 s] and the AD in the range [30-600 s], and the effects on the measurement accuracy were quantified. RESULTS: For wash-in parameter measurements, large underestimation errors (up to 40%) were found using T res values ≥16.3 s; however, the measured wash-out rate did not vary greatly across all T res values tested. Errors in derived K trans and v e values were below 14 and 12% for acquisitions with {T res ≤ 8.1 s, AD ≥ 360 s} and {T res ≤ 16.3 s, AD ≥ 360 s}, respectively, but increased dramatically outside these ranges. CONCLUSIONS: Errors in measured wash-in, wash-out, K trans, and v e parameters were minimised using T res ≤ 8.1 s and AD ≥ 360 s, with large errors recorded outside of this range.

Signal Propagation in the Human Visual Pathways: An Effective Connectivity Analysis.

Although the visual system has been extensively investigated, an integrated account of the spatiotemporal dynamics of long-range signal propagation along the human visual pathways is not completely known or validated. In this work, we used dynamic causal modeling approach to provide insights into the underlying neural circuit dynamics of pattern reversal visual-evoked potentials extracted from concurrent EEG-fMRI data. A recurrent forward-backward connectivity model, consisting of multiple interacting brain regions identified by EEG source localization aided by fMRI spatial priors, best accounted for the data dynamics. Sources were first identified in the thalamic area, primary visual cortex, as well as higher cortical areas along the ventral and dorsal visual processing streams. Consistent with hierarchical early visual processing, the model disclosed and quantified the neural temporal dynamics across the identified activity sources. This signal propagation is dominated by a feedforward process, but we also found weaker effective feedback connectivity. Using effective connectivity analysis, the optimal dynamic causal modeling revealed enhanced connectivity along the dorsal pathway but slightly suppressed connectivity along the ventral pathway. A bias was also found in favor of the right hemisphere consistent with functional attentional asymmetry. This study validates, for the first time, the long-range signal propagation timing in the human visual pathways. A similar modeling approach can potentially be used to understand other cognitive processes and dysfunctions in signal propagation in neurological and neuropsychiatric disorders. Significance statement: An integrated account of long-range visual signal propagation in the human brain is currently incomplete. Using computational neural modeling on our acquired concurrent EEG-fMRI data under a visual evoked task, we found not only a substantial forward propagation toward "higher-order" brain regions but also a weaker backward propagation. Asymmetry in our model's long-range connectivity accounted for the various observed activity biases. Importantly, the model disclosed the timing of signal propagation across these connectivity pathways and validates, for the first time, long-range signal propagation in the human visual system. A similar modeling approach could be used to identify neural pathways for other cognitive processes and their dysfunctions in brain disorders.

Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder.

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N=32) and were paired with age, gender, and education matched healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N=17) or remitted ADHDs (remitters, N=15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P<0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD.

White matter alterations in patients with MRI-negative temporal lobe epilepsy and their asymptomatic siblings.

OBJECTIVE: The identification of "endophenotypes"-measurable variations along the pathways between genes and distal disease state-may help deconstruct focal epilepsies into more sensitive phenomena and improve future efforts to map the genetic underpinnings of the disorder. In this study, we set out to determine if diffusion tensor imaging (DTI)-inferred white matter (WM) alterations represent a suitable structural endophenotype for focal epilepsy. METHODS: We recruited 25 patients with sporadic mesial temporal lobe epilepsy (MTLE) with normal magnetic resonance imaging (MRI) findings, 25 of their gender-matched, asymptomatic siblings, and 60 control subjects. Whole-brain, voxelwise statistics were conducted to identify regions of microstructural degeneration in patients with MTLE and/or their asymptomatic siblings. WM tracts exhibiting evidence of microstructural disruption were then reconstructed using deterministic tractography. Diffusion metrics including fractional anisotropy (FA) and mean diffusivity (MD) were compared across groups using a series of one-way multivariate analyses of covariance (MANCOVAs). RESULTS: Voxelwise statistics revealed significant FA reductions in the corpus callosum (CC), bilateral superior longitudinal fasciculi (SLF), bilateral inferior longitudinal fasciculi (ILF), and left corticospinal tract (CST) in MTLE patients only. MD increases were observed in MTLE patients and their asymptomatic siblings in the left SLF and left CST. Deterministic tractography supported the voxelwise results, revealing significant FA alterations in the left SLF and CST in patients only and significant MD alterations in MTLE patients and their unaffected siblings. The diffusion scalars of MTLE patients and their asymptomatic siblings were highly correlated in the SLF and CST ipsilateral to patients' sides of seizure onset. SIGNIFICANCE: These findings confirm the presence of microstructural WM alterations in patients with MRI-negative MTLE and provide preliminary support for a diffusion-based endophenotype in the disorder. Further studies of narrow-sense heritability in larger cohorts of first-degree relatives of MTLE patients are required to confirm these results.

DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli.

BACKGROUND: The aim of the present study was to investigate the association of fMRI blood oxygen-level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD). METHODS: We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyrosequencing. RESULTS: Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation. LIMITATIONS: It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn. CONCLUSION: Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery.

Whole Body MRI in the Staging of Esophageal Cancer--A Prospective Comparison with Whole Body 18F-FDG PET-CT.

BACKGROUND: Positron emission tomography and computed tomography (PET-CT) is established in the staging of esophageal cancer. In this study, an MRI protocol was designed to emulate the anatomical (T1-weighed (T1W) and T2W imaging) and functional information (diffusion-weighted imaging) provided by PET-CT. METHODS: In all, 49 patients with carcinoma of the esophagus underwent PET-CT and whole-body MRI (WBMRI). WBMRI was carried out using dedicated sequences tailored to detect metastatic disease at each area corresponding to the anatomical coverage of PET-CT. Nodal status was determined from histopathology and endoscopic ultrasound biopsy (EUS). RESULTS: PET-CT and WBMRI identified the primary tumor in 46/49 (94%) and 48/49 (98%) patients, respectively. Nodal analysis in patients undergoing surgery (n = 18) yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 27, 100, 100, 47 and 56% for PET-CT, compared with 30, 100, 100, 53 and 61% for WBMRI. When nodal analysis included both surgical specimens and EUS criteria (n = 39), sensitivity, specificity, PPV, NPV and accuracy were 46, 91, 93, 40 and 59% for PET-CT compared with 59, 92, 94, 50 and 67% for WBMRI. Both imaging modalities identified distant metastases in 2 patients. CONCLUSION: WBMRI has similar accuracy to PET-CT in detecting the primary tumor, nodal deposits and for exclusion of systemic metastatic disease.

Effect of childhood maltreatment on brain structure in adult patients with major depressive disorder and healthy participants.

BACKGROUND: Childhood maltreatment has been found to play a crucial role in the development of psychiatric disorders. However, whether childhood maltreatment is associated with structural brain changes described for major depressive disorder (MDD) is still a matter of debate. The aim of this study was to investigate whether patients with MDD and a history of childhood maltreatment display more structural changes than patients without childhood maltreatment or healthy controls. METHODS: Patients with MDD and healthy controls with and without childhood maltreatment experience were investigated using high-resolution magnetic resonance imaging (MRI), and data were analyzed using voxel-based morphometry. RESULTS: We studied 37 patients with MDD and 46 controls. Grey matter volume was significantly decreased in the hippocampus and significantly increased in the dorsomedial prefrontal cortex (DMPFC) and the orbitofrontal cortex (OFC) in participants who had experienced childhood maltreatment compared with those who had not. Patients displayed smaller left OFC and left DMPFC volumes than controls. No significant difference in hippocampal volume was evident between patients with MDD and healthy controls. In regression analyses, despite effects from depression, age and sex on the DMPFC, OFC and hippocampus, childhood maltreatment was found to independently affect these regions. LIMITATIONS: The retrospective assessment of childhood maltreatment; the natural problem that patients experienced more childhood maltreatment than controls; and the restrictions, owing to sample size, to investigating higher order interactions among factors are discussed as limitations. CONCLUSION: These results suggest that early childhood maltreatment is associated with brain structural changes irrespective of sex, age and a history of depression.Thus, the study highlights the importance of childhood maltreatment when investigating brain structures.

Role of radiomics as a predictor of disease recurrence in ovarian cancer: a systematic review.

Ovarian cancer is associated with high cancer-related mortality rate attributed to late-stage diagnosis, limited treatment options, and frequent disease recurrence. As a result, careful patient selection is important especially in setting of radical surgery. Radiomics is an emerging field in medical imaging, which may help provide vital prognostic evaluation and help patient selection for radical treatment strategies. This systematic review aims to assess the role of radiomics as a predictor of disease recurrence in ovarian cancer. A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Studies meeting inclusion criteria investigating the use of radiomics to predict post-operative recurrence in ovarian cancer were included in our qualitative analysis. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. Six retrospective studies met the inclusion criteria, involving a total of 952 participants. Radiomic-based signatures demonstrated consistent performance in predicting disease recurrence, as evidenced by satisfactory area under the receiver operating characteristic curve values (AUC range 0.77-0.89). Radiomic-based signatures appear to good prognosticators of disease recurrence in ovarian cancer as estimated by AUC. The reviewed studies consistently reported the potential of radiomic features to enhance risk stratification and personalise treatment decisions in this complex cohort of patients. Further research is warranted to address limitations related to feature reliability, workflow heterogeneity, and the need for prospective validation studies.

Current applications and future potential of ChatGPT in radiology: A systematic review.

This study aimed to comprehensively evaluate the current utilization and future potential of ChatGPT, an AI-based chat model, in the field of radiology. The primary focus is on its role in enhancing decision-making processes, optimizing workflow efficiency, and fostering interdisciplinary collaboration and teaching within healthcare. A systematic search was conducted in PubMed, EMBASE and Web of Science databases. Key aspects, such as its impact on complex decision-making, workflow enhancement and collaboration, were assessed. Limitations and challenges associated with ChatGPT implementation were also examined. Overall, six studies met the inclusion criteria and were included in our analysis. All studies were prospective in nature. A total of 551 chatGPT (version 3.0 to 4.0) assessment events were included in our analysis. Considering the generation of academic papers, ChatGPT was found to output data inaccuracies 80% of the time. When ChatGPT was asked questions regarding common interventional radiology procedures, it contained entirely incorrect information 45% of the time. ChatGPT was seen to better answer US board-style questions when lower order thinking was required (P = 0.002). Improvements were seen between chatGPT 3.5 and 4.0 in regard to imaging questions with accuracy rates of 61 versus 85%(P = 0.009). ChatGPT was observed to have an average translational ability score of 4.27/5 on the Likert scale regarding CT and MRI findings. ChatGPT demonstrates substantial potential to augment decision-making and optimizing workflow. While ChatGPT's promise is evident, thorough evaluation and validation are imperative before widespread adoption in the field of radiology.

Slower speed of blood pressure recovery after standing is associated with accelerated brain aging: Evidence from The Irish Longitudinal Study on Ageing (TILDA).

Background: Impaired recovery of blood pressure (BP) in response to standing up is a prevalent condition in older individuals. We evaluated the relationship between the early recovery of hemodynamic responses to standing and brain health in adults over 50. Methods: Participants from The Irish Longitudinal Study on Ageing (TILDA) (n=411; age 67.6 ± 7.3 years; 53.4 % women) performed an active stand challenge while blood pressure and heart rate were continuously monitored. The recovery of these parameters was determined as the slope of the BP and HR response, following the initial drop/rise after standing. We have previously reported a novel and validated measure of brain ageing using MRI data, which measures the difference between biological brain age and chronological age, providing a brain-predicted age difference (brainPAD) score. Results: Slower recovery of systolic and diastolic BP was found to be significantly associated with higher brainPAD scores (i.e., biologically older brains), where a one-year increase in brainPAD was associated with a decrease of 0.02 mmHg/s and 0.01 mmHg/s in systolic and diastolic BP recovery, respectively, after standing. Heart rate (HR) recovery was not significantly associated with brainPAD score. Conclusion: These results demonstrate that slower systolic and diastolic BP recovery in the early phase after standing is associated with accelerated brain aging in older individuals. This suggests that the BP response to standing, measured using beat-to-beat monitoring, has the potential to be used as a marker of accelerated brain aging, relying on a simple procedure and devices that are easily accessible.

Radiomics; Contemporary Applications in the Management of Anal Cancer; A Systematic Review.

INTRODUCTION: The management of anal cancer relies on clinical and histopathological features for treatment decisions. In recent years, the field of radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving management of pelvic cancers. The aim of this study was to evaluate the current application of radiomics in the management of anal cancer. METHODS: A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Inclusion criteria encompassed randomized and non-randomized trials investigating the use of radiomics to predict post-operative recurrence in anal cancer. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. RESULTS: The systematic review identified a total of nine studies, with 589 patients examined. There were three main outcomes assessed in included studies: recurrence (6 studies), progression-free survival (2 studies), and prediction of human papillomavirus (HPV) status (1 study). Radiomics-based risk stratification models were found to provide valuable insights into treatment response and patient outcomes, with all developed signatures demonstrating at least modest accuracy (range: .68-1.0) in predicting their primary outcome. CONCLUSION: Radiomics has emerged as a promising tool in the management of anal cancer. It offers the potential for improved risk stratification, treatment planning, and response assessment, thereby guiding personalized therapeutic approaches.

Computed tomography (CT) derived radiomics to predict post-operative disease recurrence in gastric cancer; a systematic review and meta-analysis.

INTRODUCTION: Radiomics offers the potential to predict oncological outcomes from pre-operative imaging in order to identify 'high risk' patients at increased risk of recurrence. The application of radiomics in predicting disease recurrence provides tailoring of therapeutic strategies. We aim to comprehensively assess the existing literature regarding the current role of radiomics as a predictor of disease recurrence in gastric cancer. METHODS: A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Inclusion criteria encompassed retrospective and prospective studies investigating the use of radiomics to predict post-operative recurrence in ovarian cancer. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. RESULTS: Nine studies met the inclusion criteria, involving a total of 6,662 participants. Radiomic-based nomograms demonstrated consistent performance in predicting disease recurrence, as evidenced by satisfactory area under the receiver operating characteristic curve values (AUC range 0.72 - 1). The pooled AUCs calculated using the inverse-variance method for both the training and validation datasets were 0.819 and 0.789 respectively CONCLUSION: Our review provides good evidence supporting the role of radiomics as a predictor of post-operative disease recurrence in gastric cancer. Included studies noted good performance in predicting their primary outcome. Radiomics may enhance personalised medicine by tailoring treatment decision based on predicted prognosis.

Whole-Body MRI Screening for Carriers of Germline TP53 Mutations-A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review evaluated whole-body MRI (WB-MRI) as a cancer screening tool for individuals carrying germline TP53 mutations, a population known to be at a significantly elevated risk of malignancy. The primary objective is to assess the diagnostic performance of WB-MRI in detecting cancer in this cohort. METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials were searched until 18 August 2023. Eligible studies were selected based on predefined inclusion criteria. The data extracted included information on study characteristics, patient demographics, and the WB-MRI diagnostic performance. RESULTS: This systematic review identified eight eligible studies, comprising 506 TP53 mutation carriers. The mean age was 34.6 ± 16.3 (range 1-74) years. In total, 321/506 (63.4%) of the patients were female and 185/506 (36.6%) were male. In addition, 267/506 (52.8%) had a previous oncological diagnosis. Thirty-six new cancers were diagnosed with WB-MRI (36/506 (7.1%)). The overall pooled proportion of cancer detected on MRI was 7% (95% confidence interval 5-10). In total, 44 new lesions were picked up, as multiple lesions were found in some patients. CONCLUSION: WB-MRI is an effective cancer screening tool for TP53 mutation carriers. While these findings suggest the potential for WB-MRI to contribute to early cancer detection in this high-risk population, further research and the standardisation of protocols internationally are warranted to optimise its clinical utility.

Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment.

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood-brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression.

BACKGROUND: Family history of major depressive disorder (MDD) increases individuals' vulnerability to depression and alters the way depression manifests itself. Emotion processing and attention shifting are functions altered by MDD and family history of the disease; therefore, it is important to recognize the neural correlates of these functions in association with both factors. METHODS: Our study determines neural correlates of emotion processing and attention shifting for healthy individuals and patients with MDD with and without family history of depression. We compared the performance and neural activity in a functional magnetic resonance imaging experiment examining emotion processing and attention shifting in all participants. RESULTS: Our sample included 4 study groups: healthy controls without family history of depression (n = 25), patients with MDD without family history of the disease (n = 20), unaffected healthy first-degree relatives of patients with MDD (n = 21) and patients with MDD with family history of MDD (n = 30). Compared with healthy controls, unaffected first-degree relatives overactivate the somatosensory cortex and the attention controlling areas during both emotion processing and attention shifting. Patients with family history of MDD have stronger neural activation in subcortical areas during shifting attention from negative stimuli. Patients without family history of MDD have less activation in the paralimbic regions and more activation in core limbic areas, especially during emotion processing. LIMITATIONS: The conclusions about the intergroup differences in activation can be drawn only about neural areas engaged in the task. CONCLUSION: Unaffected first-degree relatives of patients with MDD overreact to external emotional cues and compensate for the vulnerability with increased involvement of executive control. Patients with a family history of MDD have less executive control over their attentional shifts in the face of negative stimuli. Patients without a family history of MDD process emotional stimuli in a more visceral way than controls.