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Subjective expectations are known to be associated with clinical outcomes. However, expectations exist about different aspects of recovery, and few studies have focused on expectations about specific treatments. Here, we present results from a prospective observational study of patients receiving lumbar steroid injections against low back pain (N = 252). Patients completed questionnaires directly before (T1), directly after (T2), and 2 weeks after (T3) the injection. In addition to pain intensity, we assessed expectations (and certainty therein) about treatment effects, using both numerical rating scale (NRS) and the Expectation for Treatment Scale (ETS). Regression models were used to explain (within-sample) treatment outcome (pain intensity at T3) based on pain levels, expectations, and certainty at T1 and T2. Using cross-validation, we examined the models' ability to predict (out-of-sample) treatment outcome. Pain intensity significantly decreased (P < 10−15) 2 weeks after injections, with a reduction of the median NRS score from 6 to 3. Numerical Rating Scale measures of pain, expectation, and certainty from T1 jointly explained treatment outcome (P < 10−15, R2 = 0.31). Expectations at T1 explained outcome on its own (P < 10−10,f2=0.19) and enabled out-of-sample predictions about outcome (P < 10−4), with a median error of 1.36 on a 0 to 10 NRS. Including measures from T2 did not significantly improve models. Using the ETS as an alternative measurement of treatment expectations (sensitivity analysis) gave consistent results. Our results demonstrate that treatment expectations play an important role for clinical outcome after lumbar injections and may represent targets for concomitant cognitive interventions. Predicting outcomes based on simple questionnaires might be useful to support treatment selection.

The human brain efficiently extracts the temporal statistics of sensory environments and automatically generates expectations about future events. An influential Hypothesis holds that these expectations can find their implementation in neural oscillations, notably in the delta band (.5-3 Hz). Rhythmic fluctuations of cortical excitement are thought to align and match up in phase to the temporal structure of the sensory environment. This alignment is thought to result in the more excitable phase range of neural oscillations to overlap with the predicted onset of sensory events which in turn results in more efficient processing of sensory input, especially so in audition. An unresolved issue concerns whether such phase-aligned rhythmic brain activity is driven exclusively by the exogenous temporal structure of the input, or whether it also reflects phase re-alignment due to endogenous expectations based on stimulus probability and task relevance. In a seminal study, Stefanics et al. (2010) presented stimuli in a rhythmic stream and observed that delta phase consistency across trials was modulated by endogenous target onset expectations: delta phase consistency was higher prior to more probable (strongly expected) compared to less probable (weakly expected) target onsets. The present study replicates Experiment II of the original study, most importantly the modulation of delta phase consistency by endogenous expectations, and underlines a direct relationship between phase locking and behaviour. Our additional analyses locate the sources of the delta phase-alignment to motor, pre-motor, parietal, and temporal areas, and provide evidence for an ongoing delta oscillation, in line with the interpretation of oscillatory phase alignment rather than a transient evoked response. Importantly, this work shows that the phase of delta oscillations can be modulated by top-down control, and hence qualifies as a potential mechanism for the neural implementation of (rhythmic) temporal predictions.

Background: Microcirculation is essential for skin homeostasis and repair. A variety of growth factors have been identified as important regulators of wound healing. However, direct observation and longitudinal monitoring of skin remodeling in an unperturbed in vivo environment remains challenging. Methods: We report on non-invasive longitudinal imaging of the wound healing process in transgenic mice overexpressing vascular endothelial growth factor A (VEGF-A) in keratinocytes by means of large-scale optoacoustic microscopy (LSOM). This rapid, label-free, high throughput intravital microscopy method averts the use of dorsal skin-fold chambers, allowing for fully non-invasive repeated imaging of intact wounds with capillary resolution over field-of-view spanning several centimeters. Results: We observed VEGF-driven enhancement of dermal vascularization in ears, dorsal skin and healing wounds and quantified the hemoglobin content, fill fraction, vessel diameter and tortuosity. The in vivo findings were further corroborated by detailed side-by-side classical histological whole-mount vascular stainings and pan-endothelial CD31 immunofluorescence. Conclusion: The new approach is suitable for supplementing or replacing the cumbersome histological procedures in a broad range of skin regeneration and tissue engineering applications., Theranostics, 12 (2), ISSN:1838-7640

Four right-handed, healthy subjects participated in a visual stimulation experiment. Subjects were viewing a dartboardshaped flickering checkerboard stimulus, divided into 4 rings and 12 segments, defining 48 sectors in the visual field. Local contrast in each sector was continuously varying across four levels and updated every 3 s. To maintain fixation, subjects had to respond to a stimulus at the center of the visual field. During the entire experiment, in which subjects performed 8 runs, each consisting of 100 trials, brain activity was measured with functional magnetic resonance imaging (MRI). Using a 3-T Siemens Trio MRI scanner, 220 echo-planar images were acquired in each run, with a repetition time of 1.5 s and voxel size of 3 x 3 x 3 mm. The dataset is publicly available from OpenNeuro and additionally includes region of interest maps for visual areasV1 to V4, left and right, obtained from another retinotopic mapping experiment. As such, the dataset allows for accu-rate mapping of receptive fields and their properties across several stages of human visual cortex.(C) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ), Data in Brief, 47, ISSN:2352-3409

Background The goal of this study was to assess the value and acceptance of Standardized or Simulated Patients (SPs) for training clinically inexperienced undergraduate medical students in psychiatric history taking, psychopathological assessment, and communication with psychiatric patients. Methods As part of a newly developed introductory course to psychiatry, pairs of 3rd year medical students conducted psychiatric assessments of SPs, including history and psychopathological state, under the supervision of a clinical lecturer. Prior to the assessment, students attended introductory lectures to communication in psychiatry and psychopathology but were clinically inexperienced. After the interview, the students’ summary of their findings was discussed with other students and the lecturer. Students, lecturers, and actors were invited to a survey after the course. Questions for the students included self-reports about perceived learning success and authenticity of the interviews. Results 41 students, 6 actors and 8 lecturers completed the survey (response rates of 48%, 50%, and 100%, respectively). The survey results indicated that, despite their lack of clinical experience, students learned how to conduct a psychiatric interview, communicate in a non-judgmental and empathetic manner, take a psychiatric history and perform a psychopathological examination. SPs were perceived as authentic. The survey results suggested that this setting allowed for an enjoyable, non-distressful and motivating learning experience within a restricted time frame of just two afternoons. Conclusion The results indicated that the SP approach presented is useful for teaching clinical skills in psychiatry to students with limited previous clinical experience and knowledge of psychiatry. We argue that SPs can be used to teach practical psychiatric skills already during an early phase of the curriculum. Limitations of our study include a limited sample size, a temporal gap between the course and the survey, reliance on self-reports, and lack of comparison to alternative interventions., BMC Medical Education, 23 (1), ISSN:1472-6920

After a first episode of major depressive disorder (MDD), there is substantial risk for a long-term remitting-relapsing course. Prevention and early interventions are thus critically important. Various studies have examined the feasibility of detecting at-risk individuals based on out-of-sample predictions about the future occurrence of depression. However, functional magnetic resonance imaging (fMRI) has received very little attention for this purpose so far. Here, we explored the utility of generative models (i.e. different dynamic causal models, DCMs) as well as functional connectivity (FC) for predicting future episodes of depression in never-depressed adults, using a large dataset (N = 906) of task-free ("resting state") fMRI data from the UK Biobank (UKB). Connectivity analyses were conducted using timeseries from pre-computed spatially independent components of different dimensionalities. Over a three-year period, 50% of selected participants showed indications of at least one depressive episode, while the other 50% did not. Using nested cross-validation for training and a held-out test set (80/20 split), we systematically examined the combination of 8 connectivity feature sets and 17 classifiers. We found that a generative embedding procedure based on combining regression DCM (rDCM) with a support vector machine (SVM) enabled the best predictions, both on the training set (0.63 accuracy, 0.66 area under the curve, AUC) and the test set (0.62 accuracy, 0.64 AUC; p < 0.001). However, on the test set, rDCM was only slightly superior to predictions based on FC (0.59 accuracy, 0.61 AUC). Interpreting model predictions based on SHAP (SHapley Additive exPlanations) values suggested that the most predictive connections were widely distributed and not confined to specific networks. Overall, our analyses suggest (i) ways of improving future fMRI-based generative embedding approaches for the early detection of individuals at-risk for depression and that (ii) achieving accuracies of clinical utility may require combination of fMRI with other data modalities., NeuroImage, 273, ISSN:1053-8119, ISSN:1095-9572

Assessing our confidence in the choices we make is important to making adaptive decisions, and it is thus no surprise that we excel in this ability. However, standard models of decision-making, such as the drift-diffusion model (DDM), treat confidence assessment as a post hoc or parallel process that does not directly influence the choice, which depends only on accumulated evidence. Here, we pursue the alternative hypothesis that what is monitored during a decision is an evolving sense of confidence (that the to-be-selected option is the best) rather than raw evidence. Monitoring confidence has the appealing consequence that the decision threshold corresponds to a desired level of confidence for the choice, and that confidence improvements can be traded off against the resources required to secure them. We show that most previous findings on perceptual and value-based decisions traditionally interpreted from an evidence-accumulation perspective can be explained more parsimoniously from our novel confidence-driven perspective. Furthermore, we show that our novel confidence-driven DDM (cDDM) naturally generalizes to decisions involving any number of alternative options - which is notoriously not the case with traditional DDM or related models. Finally, we discuss future empirical evidence that could be useful in adjudicating between these alternatives., Psychonomic Bulletin & Review, ISSN:1531-5320, ISSN:1069-9384

Research question Pulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial N-methyl-D-aspartate (NMDA)-receptor agonist D-cycloserine has shown promising results in enhancing efficacy of CBT, thus we hypothesised that it would similarly augment the effects of pulmonary rehabilitation in the brain. Positive findings would support further development in phase 3 clinical trials. Methods 72 participants with mild-to-moderate COPD were recruited to a double-blind pre-registered (ClinicalTrials.gov identifier: NCT01985750) experimental medicine study running parallel to a pulmonary rehabilitation course. Participants were randomised to 250 mg D-cycloserine or placebo, administered immediately prior to the first four sessions of pulmonary rehabilitation. Primary outcome measures were differences between D-cycloserine and placebo in brain activity in the anterior insula, posterior insula, anterior cingulate cortices, amygdala and hippocampus following completion of pulmonary rehabilitation. Secondary outcomes included the same measures at an intermediate time point and voxel-wise difference across wider brain regions. An exploratory analysis determined the interaction with breathlessness anxiety. Results No difference between D-cycloserine and placebo groups was observed across the primary or secondary outcome measures. D-cycloserine was shown instead to interact with changes in breathlessness anxiety to dampen reactivity to breathlessness cues. Questionnaire and measures of respiratory function showed no group difference. This is the first study testing brain-active drugs in pulmonary rehabilitation. Rigorous trial methodology and validated surrogate end-points maximised statistical power. Conclusion Although increasing evidence supports therapeutic modulation of NMDA pathways to treat symptoms, we conclude that a phase 3 clinical trial of D-cycloserine would not be worthwhile., ERJ Open Research, 9 (2)

Purpose To introduce a mathematical framework and in-silico validation of turbulent flow spectrum imaging (TFSI) of stenotic flow using phase-contrast MRI, evaluate systematic errors in quantitative turbulence parameter estimation, and propose a novel method for probing the Lagrangian velocity spectra of turbulent flows. Theory and Methods The spectral response of velocity-encoding gradients is derived theoretically and linked to turbulence parameter estimation including the velocity autocorrelation function spectrum. Using a phase-contrast MRI simulation framework, the encoding properties of bipolar gradient waveforms with identical first gradient moments but different duration are investigated on turbulent flow data of defined characteristics as derived from computational fluid dynamics. Based on theoretical insights, an approach using velocity-compensated gradient waveforms is proposed to specifically probe desired ranges of the velocity autocorrelation function spectrum with increased accuracy. Results Practical velocity-encoding gradients exhibit limited encoding power of typical turbulent flow spectra, resulting in up to 50% systematic underestimation of intravoxel SD values. Depending on the turbulence level in fluids, the error due to a single encoding gradient spectral response can vary by 20%. When using tailored velocity-compensated gradients, improved quantification of the Lagrangian velocity spectrum on a voxel-by-voxel basis is achieved and used for quantitative correction of intravoxel SD values estimated with velocity-encoding gradients. Conclusion To address systematic underestimation of turbulence parameters using bipolar velocity-encoding gradients in phase-contrast MRI of stenotic flows with short correlation times, tailored velocity-compensated gradients are proposed to improve quantitative mapping of turbulent blood flow characteristics., Magnetic Resonance in Medicine, 87 (3), ISSN:0740-3194, ISSN:1522-2594

Theoretical frameworks such as predictive coding suggest that the perception of the body and world – interoception and exteroception – involve intertwined processes of inference, learning, and prediction. In this framework, attention is thought to gate the influence of sensory information on perception. In contrast to exteroception, there is limited evidence for purely attentional effects on interoception. Here, we empirically tested if attentional focus modulates cortical processing of single heartbeats, using a newly-developed experimental paradigm to probe purely attentional differences between exteroceptive and interoceptive conditions in the heartbeat evoked potential (HEP) using EEG recordings. We found that the HEP is significantly higher during interoceptive compared to exteroceptive attention, in a time window of 524–620 ms after the R-peak. Furthermore, this effect predicted self-report measures of autonomic system reactivity. Our study thus provides direct evidence that the HEP is modulated by pure attention and suggests that this effect may provide a clinically relevant readout for assessing interoception., NeuroImage, 186, ISSN:1053-8119, ISSN:1095-9572

Chronic, non-healing wounds constitute a major health problem, and the current therapeutic options are limited. Therefore, pharmaceuticals that can be locally applied to complicated wounds are urgently needed. Such treatments should directly target the underlying causes, which include diabetes mellitus, chronic local pressure and/or vascular insufficiency. A common consequence of these disorders is impaired wound angiogenesis. Here, we investigated the effect of topical application of a nitric oxide-releasing phosphodiesterase 5 inhibitor (TOP-N53)-containing liquid hydrogel on wound repair in mice. The drug-loaded hydrogel promoted re-epithelialization and angiogenesis in wounds of healthy and healing-impaired diabetic mice. Using a non-invasive label-free optoacoustic microscopy approach combined with automated vessel analysis, we show that the topical application of TOP-N53 formulation increases the microvascular network density and promotes the functionality of the newly formed blood vessels, resulting in enhanced blood perfusion of the wounds. These results demonstrate a remarkable healing-stimulating activity of topically applied TOP-N53 formulation, supporting its further development as a wound therapeutic., Pharmaceutics, 14 (11)

Optoacoustic (OA, photoacoustic) imaging capitalizes on the low scattering of ultrasound within biological tissues to provide optical absorption-based contrast with high resolution at depths not reachable with optical microscopy. For deep tissue imaging applications, OA image formation commonly relies on acoustic inversion of time-resolved tomographic data. The excitation of OA responses and subsequent propagation of ultrasound waves can be mathematically described as a forward model enabling image reconstruction via algebraic inversion. These model-based reconstruction methods have been shown to outperform alternative inversion approaches and can further render OA images from incomplete datasets, strongly distorted signals or other suboptimally recorded data. Herein, we provide a general perspective on model-based OA reconstruction methods, review recent progress, and discuss the performance of the different algorithms under practical imaging scenarios., Frontiers in Physics, 10, ISSN:2296-424X

Purpose Stroke is one of the most prevalent vascular diseases. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and follow alterations of receptor expression and metabolism in ischemic stroke. The aim of this study was to assess the cannabinoid type 2 receptor (CB2R) levels in transient middle cerebral artery occlusion (tMCAO) mouse models at subacute stage using positron emission tomography (PET) with our novel tracer [18F]RoSMA-18-d6 and structural imaging by magnetic resonance imaging (MRI). Procedures Our recently developed CB2R PET tracer [18F]RoSMA-18-d6 was used for imaging neuroinflammation at 24 h after reperfusion in tMCAO mice. The RNA expression levels of CB2R and other inflammatory markers were analyzed by quantitative real-time polymerase chain reaction using brain tissues from tMCAO (1 h occlusion) and sham-operated mice. [18F]fluorodeoxyglucose (FDG) was included for evaluation of the cerebral metabolic rate of glucose (CMRglc). In addition, diffusion-weighted imaging and T2-weighted imaging were performed for anatomical reference and delineating the lesion in tMCAO mice. Results mRNA expressions of inflammatory markers TNF-α, Iba1, MMP9 and GFAP, CNR2 were increased to 1.3–2.5 fold at 24 h after reperfusion in the ipsilateral compared to contralateral hemisphere of tMCAO mice, while mRNA expression of the neuronal marker MAP-2 was markedly reduced to ca. 50 %. Reduced [18F]FDG uptake was observed in the ischemic striatum of tMCAO mouse brain at 24 h after reperfusion. Although higher activity of [18F]RoSMA-18-d6 in ex vivo biodistribution studies and higher standard uptake value ratio (SUVR) were detected in the ischemic ipsilateral compared to contralateral striatum in tMCAO mice, the in vivo specificity of [18F]RoSMA-18-d6 was confirmed only in the CB2R-rich spleen. Conclusions This study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18F]FDG measure of CMRglc in the ischemic striatum of tMCAO mice at subacute stage. [18F]RoSMA-18-d6 might be a promising PET tracer for detecting CB2R alterations in animal models of neuroinflammation without neuronal loss., Molecular Imaging and Biology, 24 (5), ISSN:1860-2002, ISSN:1536-1632

This review provides a dynamical systems perspective on psychiatric symptoms and disease, and discusses its potential implications for diagnosis, prognosis, and treatment. After a brief introduction into the theory of dynamical systems, we will focus on the idea that cognitive and emotional functions are implemented in terms of dynamical systems phenomena in the brain, a common assumption in theoretical and computational neuroscience. Specific computational models, anchored in biophysics, for generating different types of network dynamics, and with a relation to psychiatric symptoms, will be briefly reviewed, as well as methodological approaches for reconstructing the system dynamics from observed time series (like fMRI or EEG recordings). We then attempt to outline how psychiatric phenomena, associated with schizophrenia, depression, PTSD, ADHD, phantom pain, and others, could be understood in dynamical systems terms. Most importantly, we will try to convey that the dynamical systems level may provide a central, hub-like level of convergence which unifies and links multiple biophysical and behavioral phenomena, in the sense that diverse biophysical changes can give rise to the same dynamical phenomena and, vice versa, similar changes in dynamics may yield different behavioral symptoms depending on the brain area where these changes manifest. If this assessment is correct, it may have profound implications for the diagnosis, prognosis, and treatment of psychiatric conditions, as it puts the focus on dynamics. We therefore argue that consideration of dynamics should play an important role in the choice and target of interventions.

Wide-scale adoption of optoacoustic imaging in biology and medicine critically depends on availability of affordable scanners combining ease of operation with optimal imaging performance. Here we introduce LightSpeed: a low-cost real-time volumetric handheld optoacoustic imager based on a new compact software-defined ultrasound digital acquisition platform and a pulsed laser diode. It supports the simultaneous signal acquisition from up to 192 ultrasound channels and provides a hig-bandwidth direct optical link (2x 100G Ethernet) to the host-PC for ultra-high frame rate image acquisitions. We demonstrate use of the system for ultrafast (500Hz) 3D human angiography with a rapidly moving handheld probe. LightSpeed attained image quality comparable with a conventional optoacoustic imaging systems employing bulky acquisition electronics and a Q-switched pulsed laser. Our results thus pave the way towards a new generation of compact, affordable and high-performance optoacoustic scanners.

The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive coding or, more generally, the “Bayesian brain” notion that the brain continuously updates a hierarchical model to infer the causes of its sensory inputs. Specifically, predictive coding views perceptual inference as an NMDAR-dependent process of minimizing hierarchical precision-weighted prediction errors (PEs). Disturbances of this putative process play a key role in hierarchical Bayesian theories of schizophrenia.Here, we provide empirical evidence for this clinical theory, demonstrating the existence of multiple, hierarchically related PEs in a “roving MMN” paradigm. We applied a computational model, the Hierarchical Gaussian Filter (HGF), to single-trial EEG data from healthy volunteers that received the NMDAR antagonist S-ketamine in a placebo-controlled, double-blind, within-subject fashion. Using an unrestricted analysis of the entire time-sensor space, our computational trial-by-trial analysis indicated that low-level PEs (about stimulus transitions) are expressed early (102-207ms post-stimulus), while high-level PEs (about transition probability) are reflected by later components (152-199ms, 215-277ms) of single-trial responses. Furthermore, we find that ketamine significantly diminished the expression of high-level PE responses, implying that NMDAR antagonism disrupts inference on abstract statistical regularities.Our findings are consistent with long-standing notions that NMDAR dysfunction may cause positive symptoms in schizophrenia by impairing hierarchical Bayesian inference about the world’s statistical structure. Beyond their relevance for schizophrenia, our results illustrate the potential of computational single-trial analyses for assessing potential disease mechanisms.

Wide-field fluorescence imaging is an indispensable tool for studying large-scale biodynamics. Limited space-bandwidth product and strong light diffusion make conventional implementations incapable of high-resolution mapping of fluorescence biodistribution in three dimensions. We introduce a volumetric wide-field fluorescence microscopy based on optical astigmatism combined with fluorescence source localization, covering 5.6×5.6×0.6 mm3 imaging volume. Two alternative configurations are proposed exploiting multifocal illumination or sparse localization of point emitters, which are herein seamlessly integrated in one system. We demonstrate real-time volumetric mapping of the murine cortical microcirculation at capillary resolution without employing cranial windows, thus simultaneously delivering quantitative perfusion information across both brain hemispheres. Morphological and functional changes of cerebral vascular networks are further investigated after an acute ischemic stroke, enabling cortex-wide observation of concurrent collateral recruitment events occurring on a sub-second scale. The reported technique thus offers a wealth of unmatched possibilities for non- or minimally invasive imaging of biodynamics across scales., Nature Communications, 13 (1), ISSN:2041-1723

Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity, or (3) directly attributable to repeated exposure to western diet. To close this gap, we performed a randomized, controlled study (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for 8 weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain., Cell Metabolism, 35 (4), ISSN:1550-4131, ISSN:1932-7420

Abnormal cerebral accumulation of amyloid-beta peptide (Aβ) is a major hallmark of Alzheimer’s disease. Non-invasive monitoring of Aβ deposits enables assessing the disease burden in patients and animal models mimicking aspects of the human disease as well as evaluating the efficacy of Aβ-modulating therapies. Previous in vivo assessments of plaque load have been predominantly based on macroscopic fluorescence reflectance imaging (FRI) and confocal or two-photon microscopy using Aβ-specific imaging agents. However, the former method lacks depth resolution, whereas the latter is restricted by the limited field of view preventing a full coverage of the large brain region. Here, we utilized a fluorescence molecular tomography (FMT)-magnetic resonance imaging (MRI) pipeline with the curcumin derivative fluorescent probe CRANAD-2 to achieve full 3D brain coverage for detecting Aβ accumulation in the arcAβ mouse model of cerebral amyloidosis. A homebuilt FMT system was used for data acquisition, whereas a customized software platform enabled the integration of MRI-derived anatomical information as prior information for FMT image reconstruction. The results obtained from the FMT-MRI study were compared to those from conventional planar FRI recorded under similar physiological conditions, yielding comparable time courses of the fluorescence intensity following intravenous injection of CRANAD-2 in a region-of-interest comprising the brain. In conclusion, we have demonstrated the feasibility of visualizing Aβ deposition in 3D using a multimodal FMT-MRI strategy. This hybrid imaging method provides complementary anatomical, physiological and molecular information, thereby enabling the detailed characterization of the disease status in arcAβ mouse models, which can also facilitate monitoring the efficacy of putative treatments targeting Aβ.

Purpose Abnormal tau accumulation within the brain plays an important role in tauopathies such as Alzheimer’s disease and frontotemporal dementia. High-resolution imaging of tau deposits at the whole-brain scale in animal disease models is highly desired. Methods We approached this challenge by non-invasively imaging the brains of P301L mice of 4-repeat tau with concurrent volumetric multi-spectral optoacoustic tomography (vMSOT) at ~ 115 μm spatial resolution using the tau-targeted pyridinyl-butadienyl-benzothiazole derivative PBB5 (i.v.). In vitro probe characterization, concurrent vMSOT and epi-fluorescence imaging of in vivo PBB5 targeting (i.v.) was performed in P301L and wild-type mice, followed by ex vivo validation using AT-8 antibody for phosphorylated tau. Results PBB5 showed specific binding to recombinant K18 tau fibrils by fluorescence assay, to post-mortem Alzheimer’s disease brain tissue homogenate by competitive binding against [11C]PBB3 and to tau deposits (AT-8 positive) in post-mortem corticobasal degeneration and progressive supranuclear palsy brains. Dose-dependent optoacoustic and fluorescence signal intensities were observed in the mouse brains following i.v. administration of different concentrations of PBB5. In vivo vMSOT brain imaging of P301L mice showed higher retention of PBB5 in the tau-laden cortex and hippocampus compared to wild-type mice, as confirmed by ex vivo vMSOT, epi-fluorescence, multiphoton microscopy, and immunofluorescence staining. Conclusions We demonstrated non-invasive whole-brain imaging of tau in P301L mice with vMSOT system using PBB5 at a previously unachieved ~ 115 μm spatial resolution. This platform provides a new tool to study tau spreading and clearance in a tauopathy mouse model, foreseeable in monitoring tau targeting putative therapeutics., European Journal of Nuclear Medicine and Molecular Imaging, 49 (7), ISSN:1619-7070, ISSN:1619-7089

Background: Recent advances in computational psychiatry have identified latent cognitive and perceptual states that predispose to psychotic symptoms. Behavioral data fit to Bayesian models have demonstrated an overreliance on priors (i.e., prior overweighting) during perception in select samples of individuals with hallucinations, corresponding to increased precision of prior expectations over incoming sensory evidence. However, the clinical utility of this observation depends on the extent to which it reflects static symptom risk or current symptom state. Methods: To determine whether task performance and estimated prior weighting relate to specific elements of symptom expression, a large, heterogeneous, and deeply phenotyped sample of hallucinators (n = 249) and nonhallucinators (n = 209) performed the conditioned hallucination (CH) task. Results: We found that CH rates predicted stable measures of hallucination status (i.e., peak frequency). However, CH rates were more sensitive to hallucination state (i.e., recent frequency), significantly correlating with recent hallucination severity and driven by heightened reliance on past experiences (priors). To further test the sensitivity of CH rate and prior weighting to symptom severity, a subset of participants with hallucinations (n = 40) performed a repeated-measures version of the CH task. Changes in both CH frequency and prior weighting varied with changes in auditory hallucination frequency on follow-up. Conclusions: These results indicate that CH rate and prior overweighting are state markers of hallucination status, potentially useful in tracking disease development and treatment response.

Purpose To compare EPI and GRE readout in high-flow velocity regimes and evaluate their impact on measurement accuracy in silico and in vitro. Theory and methods Phase-contrast sequences for EPI and GRE were simulated using CFD velocity data to assess displacement artifacts as well as effective spatial resolution. In silico findings were validated experimentally using a steady flow phantom. Results For EPI factor 5 and simulated stenotic flow with peak velocity of 2.2 m s - 1 , displacement artifacts resulted in misregistration of 7.3 mm at echo time and the effective resolution was locally reduced by factors 5 and 8 compared to GRE for flow along phase and frequency encoding directions, respectively. In vitro, a maximum velocity difference between EPI factor 5 and GRE of 0.97 m s - 1 was found. Conclusions Four-dimensional flow MRI using EPI readout results not only in considerable velocity misregistration but also in spatially varying degradation of resolution. The proposed work indicates that EPI is inferior to standard GRE for 4D flow MRI.

Background The autistic spectrum is characterized by profound impairments of social interaction. The exact subpersonal processes, however, that underlie the observable lack of social reciprocity are still a matter of substantial controversy. Recently, it has been suggested that the autistic spectrum might be characterized by alterations of the brain’s inference about the causes of socially relevant sensory signals. Methods We used a novel reward-based learning task that required integration of nonsocial and social cues in conjunction with computational modeling. Thirty-six healthy subjects were selected based on their score on the Autism-Spectrum Quotient (AQ), and AQ scores were assessed for correlations with cue-related model parameters and task scores. Results Individual differences in AQ scores were significantly correlated with participants’ total task scores, with high AQ scorers performing more poorly in the task (r = −.39, 95% confidence interval = −0.68 to −0.13). Computational modeling of the behavioral data unmasked a learning deficit in high AQ scorers, namely, the failure to integrate social context to adapt one’s belief precision—the precision afforded to prior beliefs about changing states in the world—particularly in relation to the nonsocial cue. Conclusions More pronounced autistic traits in a group of healthy control subjects were related to lower scores associated with misintegration of the social cue. Computational modeling further demonstrated that these trait-related performance differences are not explained by an inability to process the social stimuli and their causes, but rather by the extent to which participants consider social information to infer the nonsocial cue., Biological Psychiatry, 87 (2), ISSN:0006-3223, ISSN:1873-2402

Talks, Benjamin James, Catherine Campbell, Stephanie J. Larcombe, Lucy Marlow, Sarah L. Finnegan, Christopher T. Lewis, Samuel J.E. Lucas, Olivia K. Harrison, and Kyle T.S. Pattinson. Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude. High Alt Med Biol. 23:69-77, 2022. Background: Interoception refers to an individual's ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesized that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods: Two groups of 18 participants were recruited to complete a respiratory interoceptive task three times at 2-week intervals. The control group remained in Birmingham (140 m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2,624 m, and test 3 at 2,728 m after an 11-day trek at high altitude (up to 4,800 m). Results: By measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea level measures of anxiety, agoraphobia, and neuroticism. Conclusions: This suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike., High Altitude Medicine & Biology, 23 (1), ISSN:1527-0297, ISSN:1557-8682

Optoacoustic (OA) methods have become powerful tools in biomedical research capable of retrieving functional information from biological tissues in vivo. Acquisition of OA signals generally relies on direct physical contact of a transducer or an acoustic coupling medium with the tissue surface, which prevents applicability, e.g., in open surgeries or wounded tissues. Non-contact OA imaging has been achieved with air-coupled piezoelectric transducers, which provide a straightforward approach for remote sensing of ultrasound vibrations. However, sensitivity was hampered by a suboptimal alignment between the illumination and detection fields. Herein, we devised an air-coupled transducer featuring a central aperture for light delivery with coaxially aligned optical and acoustic foci, thus providing optimal sensitivity for OA signal detection. Imaging of phantoms and a mouse ear in vivo is showcased by raster-scanning the transducer with light being delivered through a multimode optical fiber., AIP Advances, 12 (3), ISSN:2158-3226

Optoacoustic mesoscopy combines rich optical absorption contrast with high spatial resolution at tissue depths beyond reach for microscopic techniques employing focused light excitation. The mesoscopic imaging performance is commonly hindered by the use of inaccurate delay-and-sum reconstruction approaches and idealized modeling assumptions. In principle, image reconstruction performance could be enhanced by simulating the optoacoustic signal generation, propagation, and detection path. However, for most realistic experimental scenarios, the underlying total impulse response (TIR) cannot be accurately modelled. Here we propose to capture the TIR by scanning of a sub-resolution sized absorber. Significant improvement of spatial resolution and depth uniformity is demonstrated over 3 mm range, outperforming delay-and-sum and model-based reconstruction implementations. Reconstruction performance is validated by imaging subcutaneous murine vasculature and human skin in vivo. The proposed experimental calibration and reconstruction paradigm facilitates quantitative inversions while averting complex physics-based simulations. It can readily be applied to other imaging modalities employing TIR-based reconstructions., Photoacoustics, 28, ISSN:2213-5979

Deposits of amyloid-β (Aβ) in the brains of rodents can be analysed by invasive intravital microscopy on a submillimetre scale, or via whole-brain images from modalities lacking the resolution or molecular specificity to accurately characterize Aβ pathologies. Here we show that large-field multifocal illumination fluorescence microscopy and panoramic volumetric multispectral optoacoustic tomography can be combined to longitudinally assess Aβ deposits in transgenic mouse models of Alzheimer's disease. We used fluorescent Aβ-targeted probes (the luminescent conjugated oligothiophene HS-169 and the oxazine-derivative AOI987) to transcranially detect Aβ deposits in the cortex of APP/PS1 and arcAβ mice with single-plaque resolution (8 μm) and across the whole brain (including the hippocampus and the thalamus, which are inaccessible by conventional intravital microscopy) at sub-150 μm resolutions. Two-photon microscopy, light-sheet microscopy and immunohistochemistry of brain-tissue sections confirmed the specificity and regional distributions of the deposits. High-resolution multiscale optical and optoacoustic imaging of Aβ deposits across the entire brain in rodents thus facilitates the in vivo study of Aβ accumulation by brain region and by animal age and strain.

Modern optical neuroimaging approaches are expanding the ability to elucidate complex brain function. Diverse imaging contrasts enable direct observation of neural activity with functional sensors along with the induced hemodynamic responses. To date, decoupling the complex interplay of neurovascular coupling and dynamical physiological states has remained challenging when employing single-modality functional neuroimaging readings. A hybrid fluorescence optoacoustic tomography platform combined with a custom data processing pipeline based on statistical parametric mapping is devised, attaining the first noninvasive observation of simultaneous calcium and hemodynamic activation patterns using optical contrasts. Correlated changes in the oxy- and deoxygenated hemoglobin, total hemoglobin, oxygen saturation, and rapid GCaMP6f fluorescence signals are observed in response to peripheral sensory stimulation. While the concurrent epifluorescence serves to corroborate and complement the functional optoacoustic observations, the latter further aids in decoupling the rapid calcium responses from the slowly varying background in the fluorescence recordings mediated by hemodynamic changes. The hybrid imaging platform expands the capabilities of conventional neuroimaging methods to provide more comprehensive functional readings for studying neurovascular and neurometabolic coupling mechanisms and related diseases., Advanced Science, 9 (24), ISSN:2198-3844

We present data collected for the research article “Advances in Spiral fMRI: A High-resolution Study with Single-shot Acquisition” (Kasper et al. 2022). All data was acquired on a 7T ultra-high field MR system (Philips Achieva), equipped with a concurrent magnetic field monitoring setup based on 16 NMR probes. For task-based fMRI, a visual quarterfield stimulation paradigm was employed, alongside physiological monitoring via peripheral recordings. This data collection contains different datasets pertaining to different purposes: (1) Measured magnetic field dynamics (k0, spiral k-space trajectories, 2nd order spherical harmonics, concomitant fields) during ultra-high field fMRI sessions from six subjects, as well as concurrent temperature curves of the gradient coil, to explore MR system and subject-induced variability of field fluctuations and assess the impact of potential correction methods. (2) MR Raw Data, i.e., coil and concurrent encoding magnetic field (trajectory) data, of a single subject, as well as nominal spiral gradient waveforms, precomputed B0 and coil sensitivity maps, to enable testing of alternative image reconstruction approaches for spiral fMRI data. (3) Reconstructed image time series of the same subject alongside behavioral and physiological logfiles, to reproduce the fMRI preprocessing and analysis, as well as figures presented in the research article related to this article, using the published analysis code repository. All data is provided in standardized formats for the respective research area. In particular, ISMRMRD (HDF5) is used to store raw coil data and spiral trajectories, as well as measured field dynamics. Likewise, the NIfTI format is used for all imaging data (anatomical MRI and spiral fMRI, B0 and coil sensitivity maps)., Data in Brief, 42, ISSN:2352-3409

An ultrasound detection scheme based on a transparent polyvinylidene-fluoride indium-tin-oxide (PVDF-ITO) piezoelectric film is developed for ultrawideband sensitive detection of optoacoustic (OA) signals down to a noise equivalent pressure (NEP) of 8.4 Pa over an effective detection bandwidth extending beyond 30 MHz. The high signal-to-noise ratio and low noise performance are facilitated by employing a two-stage amplifier structure. The PVDF-ITO detector is directly mounted on a commercial high numerical aperture objective lens of a scanning optical resolution OA microscopy system to obtain submicron resolution images without signal averaging, as demonstrated both in phantoms and in vivo measurements in mice. The transparent detection scheme further allows for the OA imaging modality to be easily integrated with other imaging techniques for diverse multi-modal biomedical imaging investigations.

There is growing evidence for the vascular contribution to cognitive impairment and dementia in Alzheimer’s disease (AD) and other neurodegenerative diseases. While perfusion deficits have been observed in patients with Alzheimer’s disease and tauopaties, little is known about the role of tau in vascular dysfunction. In the present study, regional cerebral blood (rCBF) was characterized in P301L mice with arterial spin labeling. No differences in rCBF in P301L mice compared to their age-matched non-transgenic littermates at mid (10-12 months of age) and advanced (19-21 months of age) disease stages. This was concomitant with preservation of cortical brain structure as assessed with structural T2-weighted magnetic resonance imaging. These results show that hypoperfusion and neurodegeneration are not a phenotype of P301L mice. More studies are thus needed to understand the relationship of tau, neurodegeneration and vascular dysfunction and its modulators in AD and primary tauopathies., Journal of Cerebral Blood Flow & Metabolism, 42 (4), ISSN:0271-678X, ISSN:1559-7016

Large-scale visualization of nanoparticle kinetics is essential for optimizing drug delivery and characterizing

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor and executive function. Central to BG function are striatal cells expressing D1 (D1R) and D2 (D2R) dopamine receptors. D1R and D2R cells are considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. However, whether they maintain a uniform function across the striatum and what influence they exert outside the BG is unclear. Here, we address these questions by combining optogenetic activation of D1R and D2R cells in the mouse ventrolateral caudoputamen with fMRI. Striatal D1R/D2R stimulation evokes distinct activity within the BG-thalamocortical network and differentially engages cerebellar and prefrontal regions. Computational modeling of effective connectivity confirms that changes in D1R/D2R output drive functional relationships between these regions. Our results suggest a complex functional organization of striatal D1R/D2R cells and hint toward an interconnected fronto-BG-cerebellar network modulated by striatal D1R and D2R cells., Cell Reports, 37 (13), ISSN:2666-3864, ISSN:2211-1247

Supplemental Digital Content is Available in the Text. Testing the boundaries of the “neurologic pain signature” using salient breathlessness stimuli and somatomotor finger opposition, with additional modulation using opioids., Brain biomarkers of pain, including pain-predictive “signatures” based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we used 2 data sets to test the neurologic pain signature (NPS), an established pain neuromarker. In study 1, brain activity was measured using high-field functional magnetic resonance imaging (7T fMRI, N = 40) during 5 to 25 seconds of experimental breathlessness (induced by inspiratory resistive loading), conditioned breathlessness anticipation, and finger opposition. In study 2, we assessed anticipation and breathlessness perception (3T, N = 19) under blinded saline (placebo) and remifentanil administration. The NPS responded to breathlessness, anticipation, and finger opposition, although no direct comparisons with painful events were possible. Local NPS patterns in anterior or midinsula, S2, and dorsal anterior cingulate responded to breathlessness and finger opposition and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness, and somatomotor demand.

Dynamic Causal Modeling (DCM) is a Bayesian framework for inferring on hidden (latent) neuronal states, based on measurements of brain activity. Since its introduction in 2003 for functional magnetic resonance imaging data, DCM has been extended to electrophysiological data, and several variants have been developed. Their biophysically motivated formulations make these models promising candidates for providing a mechanistic understanding of human brain dynamics, both in health and disease. However, due to their complexity and reliance on concepts from several fields, fully understanding the mathematical and conceptual basis behind certain variants of DCM can be challenging. At the same time, a solid theoretical knowledge of the models is crucial to avoid pitfalls in the application of these models and interpretation of their results. In this paper, we focus on one of the most advanced formulations of DCM, i.e. conductance-based DCM for cross-spectral densities, whose components are described across multiple technical papers. The aim of the present article is to provide an accessible exposition of the mathematical background, together with an illustration of the model's behavior. To this end, we include step-by-step derivations of the model equations, point to important aspects in the software implementation of those models, and use simulations to provide an intuitive understanding of the type of responses that can be generated and the role that specific parameters play in the model. Furthermore, all code utilized for our simulations is made publicly available alongside the manuscript to allow readers an easy hands-on experience with conductance-based DCM., NeuroImage, 245, ISSN:1053-8119, ISSN:1095-9572

Background Occipital transcranial direct current stimulation (tDCS) is an effective and safe treatment for migraine attack prevention. Structural brain alterations have been found in migraineurs in regions related to pain modulation and perception, including occipital areas. However, whether these structural alterations can be dynamically modulated through tDCS treatment is understudied. Objective To track longitudinally grey matter volume changes in occipital areas in episodic migraineurs during and up to five months after occipital tDCS treatment in a single-blind, and sham-controlled study. Methods 24 episodic migraineurs were randomized to either receive verum or sham occipital tDCS treatment for 28 days. To investigate dynamic grey matter volume changes patients underwent structural MRI at baseline (prior to treatment), 1.5 months and 5.5 months (after completion of treatment). 31 healthy controls were scanned with the same MRI protocol. Morphometry measures assessed rate of changes over time and between groups by means of tensor-based morphometry. Results Before treatment, migraineurs reported 5.6 monthly migraine days on average. A cross-sectional analysis revealed grey matter volume increases in the left lingual gyrus in migraineurs compared to controls. Four weeks of tDCS application led to a reduction of 1.9 migraine days/month and was paralleled by grey matter volume decreases in the left lingual gyrus in the treatment group; its extent overlapping with that seen at baseline. Conclusion This study shows that migraineurs have increased grey matter volume in the lingual gyrus, which can be modified by tDCS. Tracking structural plasticity in migraineurs provides a potential neuroimaging biomarker for treatment monitoring. Trial registration ClinicalTrials.gov, NCT03237754. Registered 03 August 2017 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03237754., The Journal of Headache and Pain, 22 (1), ISSN:1129-2377, ISSN:1129-2369

Propagation of electromechanical waves in excitable heart muscles follows complex spatiotemporal patterns holding the key to understanding life-threatening arrhythmias and other cardiac conditions. Accurate volumetric mapping of cardiac wave propagation is currently hampered by fast heart motion, particularly in small model organisms. Here we demonstrate that ultrafast four-dimensional imaging of cardiac mechanical wave propagation in entire beating murine heart can be accomplished by sparse optoacoustic sensing with high contrast, ∼115-µm spatial and submillisecond temporal resolution. We extract accurate dispersion and phase velocity maps of the cardiac waves and reveal vortex-like patterns associated with mechanical phase singularities that occur during arrhythmic events induced via burst ventricular electric stimulation. The newly introduced cardiac mapping approach is a bold step toward deciphering the complex mechanisms underlying cardiac arrhythmias and enabling precise therapeutic interventions.

Spherical matrix arrays represent an advantageous tomographic detection geometry for non-invasive deep tissue mapping of vascular networks and oxygenation with volumetric photoacoustic tomography (VPT). Hybridization of VPT with ultrasound (US) imaging remains difficult with this configuration due to the relatively large inter-element pitch of spherical arrays. We suggest a new approach for combining VPT and US contrast-enhanced 3D imaging employing injection of clinically-approved microbubbles. Power Doppler (PD) and US localization imaging were enabled with a sparse US acquisition sequence and model-based inversion based on infimal convolution of total variation (ICTV) regularization. In vitro experiments in tissue-mimicking phantoms and in living mouse brain demonstrate the powerful capabilities of the new dual-mode imaging approach attaining 80 μm spatial resolution and a more than 10 dB signal to noise improvement with respect to a classical delay and sum beamformer. Microbubble localization and tracking allowed for flow velocity mapping up to 40 mm/s.

Animal models of Alzheimer's disease amyloidosis that recapitulate cerebral amyloid-beta pathology have been widely used in preclinical research and have greatly enabled the mechanistic understanding of Alzheimer's disease and the development of therapeutics. Comprehensive deep phenotyping of the pathophysiological and biochemical features in these animal models is essential. Recent advances in positron emission tomography have allowed the non-invasive visualization of the alterations in the brain of animal models and in patients with Alzheimer's disease. These tools have facilitated our understanding of disease mechanisms and provided longitudinal monitoring of treatment effects in animal models of Alzheimer's disease amyloidosis. In this review, we focus on recent positron emission tomography studies of cerebral amyloid-beta accumulation, hypoglucose metabolism, synaptic and neurotransmitter receptor deficits (cholinergic and glutamatergic system), blood-brain barrier impairment, and neuroinflammation (microgliosis and astrocytosis) in animal models of Alzheimer's disease amyloidosis. We further propose the emerging targets and tracers for reflecting the pathophysiological changes and discuss outstanding challenges in disease animal models and future outlook in the on-chip characterization of imaging biomarkers towards clinical translation., Pharmaceuticals, 14 (11), ISSN:1424-8247

The ability to sense, monitor, and control respiration – e.g., respiratory interoception (henceforth, respiroception) is a core homeostatic ability. Beyond the regulation of gas exchange, enhanced awareness of respiratory sensations is directly related to psychiatric symptoms such as panic and anxiety. Indeed, chronic breathlessness (dyspnea) is associated with a fourfold increase in the risk of developing depression and anxiety, and the regulation of the breath is a key aspect of many mindfulness-based approaches to the treatment of mental illness. Physiologically speaking, the ability to accurately monitor respiratory sensations is important for optimizing cardiorespiratory function during athletic exertion, and can be a key indicator of illness. Given the important role of respiroception in mental and physical health, it is unsurprising that there is increased interest in the quantification of respiratory psychophysiology across different perceptual and metacognitive levels of the psychological hierarchy. Compared to other more popular modalities of interoception, such as in the cardiac domain, there are relatively few methods available for measuring aspects of respiroception. Existing inspiratory loading tasks are difficult to administer and frequently require expensive medical equipment, or offer poor granularity in their quantification of respiratory-related perceptual ability. To facilitate the study of respiroception, we here present a new, fully automated and computer-controlled apparatus and psychophysiological method, which can flexibly and easily measure respiratory-related interoceptive sensitivity, bias and metacognition, in as little as 30 min of testing, using easy to make 3D printable parts., Biological Psychology, 170, ISSN:0301-0511, ISSN:1873-6246

Objectives: To investigate the technical feasibility of whole-body intravoxel incoherent motion (IVIM) imaging. Materials and Methods: Whole-body MR images of eight healthy volunteers were acquired at 3T using a spin-echo echo-planar imaging sequence with eight b-values. Coronal parametrical whole-body maps of diffusion (D), pseudodiffusion (D*), and the perfusion fraction (Fp) were calculated. Image quality was rated qualitatively by two independent radiologists, and inter-reader reliability was tested with intra-class correlation coefficients (ICCs). Region of interest (ROI) analysis was performed in the brain, liver, kidney, and erector spinae muscle. Results: Depiction of anatomic structures was rated as good on D maps and good to fair on D* and Fp maps. Exemplary mean D (10−3mm2/s), D* (10−3mm2/s) and Fp (%) values (± standard deviation) of the renal cortex were as follows: 1.7 ± 0.2; 15.6 ± 6.5; 20.9 ± 4.4. Inter-observer agreement was "substantial” to "almost perfect” (ICC = 0.80 - 0.92). The coefficient of variation of D* was significantly lower with the proposed algorithm compared to the conventional algorithm (p

Magma degassing is thought to play a major role in magma fractionation, transport, storage, and volcanic eruption dynamics. However, the conditions that determine when and how magma degassing operates prior to and during an eruption remain poorly constrained. We performed experiments to explore if the initial presence of gas bubbles in magma influences the capability of gas to escape from the magma. Vesiculation of natural H2O-poor (<, Bulletin of Volcanology, 77, ISSN:0258-8900, ISSN:1432-0819