Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study.

Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP). Thirty participants (20 with a major depressive episode resistant to at least one antidepressant and 10 healthy controls-HC, aged 25-50, only females) were exposed to a 1-h single session of EMONO and followed for 1 week. We defined response as a reduction of at least 50% in the MADRS score 1 week after exposure. Cerebral connectivity of the Anterior Cingulate Cortex (ACC), using ROI-based resting state fMRI, and BTP, using ultrasound Tissue Pulsatility Imaging, were compared before and rapidly after exposure (as well as during exposure for BTP) among HC, non-responders and responders. We conducted analyses to compare group × time, group, and time effects. Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the three groups between baseline and gas exposure, but the increase in BTP within the first 10 min was only significant in responders. We found that a single session of EMONO can rapidly modify the functional connectivity in the subgenual ACC-precuneus, nodes within the default mode network, in depressed participants responders to EMONO. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of N2O, as well as potential markers for treatment response with this fast-acting antidepressant.

Brain tissue pulsatility mediates cognitive and electrophysiological changes in normal aging: Evidence from ultrasound tissue pulsatility imaging (TPI).

Aging is characterized by a cognitive decline of fluid abilities and is also associated with electrophysiological changes. The vascular hypothesis proposes that brain is sensitive to vascular dysfunction which may accelerate age-related brain modifications and thus explain age-related neurocognitive decline. To test this hypothesis, cognitive performance was measured in 39 healthy participants from 20 to 80 years, using tests assessing inhibition, fluid intelligence, attention and crystallized abilities. Brain functioning associated with attentional abilities was assessed by measuring the P3b ERP component elicited through an auditory oddball paradigm. To assess vascular health, we used an innovative measure of the pulsatility of deep brain tissue, due to variations in cerebral blood flow over the cardiac cycle. Results showed (1) a classical effect of age on fluid neurocognitive measures (inhibition, fluid intelligence, magnitude and latency of the P3b) but not on crystallized measures, (2) that brain pulsatility decreases with advancing age, (3) that brain pulsatility is positively correlated with fluid neurocognitive measures and (4) that brain pulsatility strongly mediated the age-related variance in cognitive performance and the magnitude of the P3b component. The mediating role of the brain pulsatility in age-related effect on neurocognitive measures supports the vascular hypothesis of cognitive aging.

Ultrasound Tissue Pulsatility Imaging Suggests Impairment in Global Brain Pulsatility and Small Vessels in Elderly Patients with Orthostatic Hypotension.

BACKGROUND: Orthostatic hypotension (OH) is highly prevalent in the elderly, and this population can be exposed to serious complications, including falls and cognitive disorders, as well as overall mortality. However, the pathophysiology of OH is still poorly understood, and innovative methods of cerebral blood flow (CBF) assessment have been required to accurately investigate cerebrovascular reactivity in OH. OBJECTIVES: We want to compare brain tissue pulsatility (BTP) changes during an orthostatic challenge in elderly patients over 80 with and without OH. MATERIALS AND METHODS: Forty-two subjects aged 80 and over were recruited from the geriatric unit of the Hospital of Tours, France, and were divided into two groups according to the result of an orthostatic challenge. The noninclusion criteria were any general unstable medical condition incompatible with orthostatic challenge, having no temporal acoustic window, severe cognitive impairment (Mini Mental Status Examination <15), history of stroke, and legal guardianship. We used the novel and highly sensitive ultrasound technique of tissue pulsatility imaging to measure BTP changes in elderly patients with (n = 22) and without OH (n = 17) during an orthostatic challenge. RESULTS: We found that the mean brain tissue pulsatility related to global intracranial pulsatility, but not maximum brain tissue pulsatility related to large arteries pulsatility, decreased significantly in OH patients, with a delay compared with the immediate drop in peripheral blood pressure. CONCLUSION: Global pulsatile CBF changes and small vessels pulsatility, rather than changes in only large arteries, may be key mechanisms in OH to account for the links between OH and cerebrovascular disorders.

Multi-layered adaptive neoangiogenesis Intra-Operative quantification (MANIOQ).

Quantification of vascularization volume can provide valuable information for diagnosis and prognosis in vascular pathologies. It can be adapted to inform the surgical management of gliomas, aggressive brain tumors characterized by exuberant sprouting of new blood vessels (neoangiogenesis). Filtered ultrafast Doppler data can provide two main parameters: vascularization index (VI) and fractional moving blood volume (FMBV) that clinically reflect tumor micro vascularization. Current protocols lack robust, automatic, and repeatable filtering methods. We present a filtrating method called Multi-layered Adaptive Neoangiogenesis Intra-Operative Quantification (MANIOQ). First, an adaptive clutter filtering is implemented, based on singular value decomposition (SVD) and hierarchical clustering. Second a method for noise equalization is applied, based on the subtraction of a weighted noise profile. Finally, an in vivo analysis of the periphery of the B-mode hyper signal area allows to measure the vascular infiltration extent of the brain tumors. Ninety ultrasound acquisitions were processed from 23 patients. Compared to reference methods in the literature, MANIOQ provides a more robust tissue filtering, and noise equalization allows for the first time to keep axial and lateral gain compensation (TGC and LGC). MANIOQ opens the way to an intra-operative clinical analysis of gliomas micro vascularization.

Tumoral and peritumoral vascularization of brain tumours: a study comparing an intraoperative ultrasensitive Doppler and a preoperative first-pass perfusion MRI.

INTRODUCTION: Surgery for gliomas can be guided by neuronavigation using magnetic resonance imaging (MRI) and intraoperative B-mode ultrasound. An ultrasensitive Doppler (USD) using plane waves is a new method of microvascularization imaging which can be used intraoperatively and could identify tumoral and peritumoral areas with neoangiogenesis but its value requires evaluation. The aim of this pilot study then was to evaluate the correlations between ultrasound measurements of glioma vascularization (tumoral and peritumoral region) obtained by a USD intraoperatively and first-pass perfusion measurements obtained on preoperative MRI. METHODS: 18 patients with proven glial tumors were selected for the analysis. They underwent preoperative MRI and intraoperative USD acquisition. The MRI scans were re-aligned to the reference ultrasound slice plane, and for each patient a segmentation of the tumoral and peritumoral zone was performed. Two perfusion parameters were studied: relative cerebral tumor blood volume (rCCBV) in MRI and fractional moving blood volume (FMBV) in a USD. We studied the correlations between mean rCCBV and mean FMBV measured in the tumoral and peritumoral zones in the reference ultrasound slice plane. RESULTS: The mean rCCBV and mean FMBV measured in the tumoral zone were significantly and strongly correlated (r = 0.80; p < 0.001). The mean rCCBV and mean FMBV measured in the peritumoral zone were not statistically correlated, although a tendency towards a correlation was noted (r = 0.45; p = 0.067). CONCLUSION: There was a good correlation between a tumor FMBV obtained by a USD intraoperatively and rCCBV on a preoperative MRI validating the reliability of USD for intraoperative analyses of tumor microvascularization in gliomas.

Vibration-controlled transient elastography for noninvasive evaluation of liver steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to a large spectrum of liver disorders and is the most common cause of metabolic liver disease. The current gold standard for diagnosing NAFLD is liver biopsy, which can lead to severe complications. PURPOSE: Among the noninvasive diagnostic options, we chose to use a FibroScan and developed an algorithm applying the Voigt rheological model to assess the viscoelastic properties of the liver and evaluate its performance for the diagnosis of steatosis. METHODS: Twenty-two healthy volunteers and 20 patients with steatosis were included. For each subject, we used a modified FibroScan, whose data had been processed by our algorithm to separate the two viscoelastic components, stiffness µ, and viscosity η. The liver elasticity µFibroscan measured by the FibroScan was also recorded. Mann-Whitney tests and receiver operating characteristics (ROCs) curve analyses were performed to compare the parameters between the two groups, and Pearson's correlation coefficients were used to assess the correlations between the parameters. RESULTS: We found a good correlation between η and µFibroscan (r = 0.75), and poor correlations between µ and both η and µFibroscan (r = 0.33 and r = 0.03, respectively). We also showed that η and µFibroscan were higher in patients with steatosis compared to healthy volunteers, with area under the ROCs (AUROC) curve at 0.814 and 0.891, respectively. Conversely, µ was not different between the two groups (AUROC = 0.557). CONCLUSIONS: Our novel method successfully separated the two viscoelastic properties of the liver, of which the parameter η is a sensitive indicator for steatosis.

Decrease in ultrasound Brain Tissue Pulsations as a potential surrogate marker of response to antidepressant.

Previous cross-sectional studies found excessive Brain Tissue Pulsations (BTP) in mid-life depression, which could constitute a mechanism of brain damage in depression. However, it remains unclear whether successful antidepressant therapy restores BTP amplitudes. In this prospective study, we investigated longitudinal changes in BTP in patients with a major depressive episode (MDE), among responders and non-responders to escitalopram. Fifty-two individuals with a MDE, free of antidepressants at baseline, were included in an 8-week open-labeled escitalopram trial. Ultrasound Tissue Pulsatility Imaging (TPI) was applied to measure resting BTP and BTP reactivity in an orthostatic challenge, at baseline and at week 8. TPI data were available for 48 participants divided into responders (n = 28, 58.3%) and non-responders (n = 20, 41.7%) according to change in the MADRS score. MaxBTP significantly decreased between baseline and week 8, only in responders. In addition, changes in MaxBTP during the orthostatic challenge were no longer significant at week 8 but only in responders. Because excessive BTP constitutes a potential mechanism for brain damage, our results suggest that a successful pharmacotherapy could benefit patients to lower the risk of brain damage in individuals with depression, a population exposed to stroke, small arteries disease and brain atrophy. TPI could provide a surrogate biomarker to monitor antidepressant response and brain health in depression in clinical routine.

Ultrasound Brain Tissue Pulsatility is decreased in middle aged and elderly type 2 diabetic patients with depression.

We used Tissue Pulsatility Imaging (TPI) to compare the Brain Tissue Pulsatility (BTP) in depressed (n=11) and non-depressed (n=13) type-2 diabetic non-demented patients aged 50 years and older. Both maximum and mean BTP were significantly decreased in depressed diabetic subjects compared to non-depressed diabetic subjects.

Acousto-elasticity of transversely isotropic incompressible soft tissues: characterization of skeletal striated muscle.

Using shear wave elastography, we measure the changes in the wave speed with the stress produced by a striated muscle during isometric voluntary contraction. To isolate the behaviour of an individual muscle from complementary or antagonistic actions of adjacent muscles, we select theflexor digiti minimimuscle, whose sole function is to extend the little finger. To link the wave speed to the stiffness, we develop an acousto-elastic theory for shear waves in homogeneous, transversely isotropic, incompressible solids subject to an uniaxial stress. We then provide measurements of the apparent shear elastic modulus along, and transversely to, the fibre axis for six healthy human volunteers of different age and sex. The results display a great variety across the six subjects. We find that the slope of the apparent shear elastic modulus along the fibre direction changes inversely to the maximum voluntary contraction (MVC) produced by the volunteer. We propose an interpretation of our results by introducing the S (slow) or F (fast) nature of the fibres, which harden the muscle differently and accordingly, produce different MVCs. A natural follow-up on this study is to apply the method to patients with musculoskeletal disorders or neurodegenerative diseases.

Joint Blind Deconvolution and Robust Principal Component Analysis for Blood Flow Estimation in Medical Ultrasound Imaging.

This article addresses the problem of high-resolution Doppler blood flow estimation from an ultrafast sequence of ultrasound images. Formulating the separation of clutter and blood components as an inverse problem has been shown in the literature to be a good alternative to spatio-temporal singular value decomposition (SVD)-based clutter filtering. In particular, a deconvolution step has recently been embedded in such a problem to mitigate the influence of the point spread function (PSF) of the imaging system. Deconvolution was shown in this context to improve the accuracy of the blood flow reconstruction. However, the PSF needs to be measured experimentally, and measuring it requires nontrivial experimental setups. To overcome this limitation, we propose herein a blind deconvolution method able to estimate both the blood component and the PSF from Doppler data. Numerical experiments conducted on simulated and in vivo data demonstrate qualitatively and quantitatively the effectiveness of the proposed approach in comparison with the previous method based on experimentally measured PSF and two other state-of-the-art approaches.

Left amygdala volume and brain tissue pulsatility are associated with neuroticism: an MRI and ultrasound study.

Brain changes associated with the personality trait of neuroticism have been partly elucidated. While subcortical brain volume changes, especially a larger amygdala, appear consistent in high neuroticism, functional changes, such as cerebral blood flow (CBF) differences, have shown conflicting results, possibly because of the limitations in methods of CBF measurement. In our study, we investigated changes in amygdala volume and CBF-related function associated with neuroticism in healthy and depressed subjects using both conventional magnetic resonance imaging (MRI) measures of brain volume and the innovative technique of ultrasound Tissue Pulsatility Imaging (TPI), which has a high level of detection in measuring brain tissue pulsatility (BTP). Middle-aged females with depression (n = 25) and without depression (n = 25) underwent clinical examination, magnetic resonance imaging (MRI) and ultrasound assessment (TPI). Neuroticism was positively associated with left amygdala volume and mean BTP in individuals without depression, in both simple and multiple regressions that included potential confounding factors such as age and body mass index. No association was found in the depressed group. We confirmed the role of the left amygdala in the brain physiology of neuroticism in nondepressed individuals. Moreover, we identified a novel mechanism associated with high neuroticism, namely BTP, that may reflect greater CBF and account for the increased risk of cerebrovascular disease in individuals with high neuroticism. Because neuroticism is considered a risk factor for depression, our paper provides potential objective biomarkers for the identification of subjects at risk for depression.

A systematic review of ultrasound imaging and therapy in mental disorders.

BACKGROUND: Increasing evidence suggests that ultrasound (US) imaging may provide biomarkers and therapeutic options in mental disorders. We systematically reviewed the literature to provide a global overview of the possibilities of US for psychiatry. METHODS: Original English language articles published between January 2000 and September 2019 were identified through databases searching and analyzed to summarize existing evidence according to PRISMA methodology. RESULTS: A total of 81 articles were included. Various US techniques and markers have been used in mental disorders, including Transcranial Doppler and Intima-Media Thickness. Most of the studies have focused on characterizing the pathophysiology of mental disorders, especially vascular physiology. Studies on therapeutic applications are still scarce. DISCUSSION: US imaging has proved to be useful in characterizing vascular impairment and structural and functional brain changes in mental disorders. Preliminary findings also suggest potential interests for therapeutic applications. Growing evidence suggests that US imaging could provide a non-invasive, portable and low-cost tool for pathophysiological characterization, prognostic assessment and therapeutic applications in mental disorders.

When classical music relaxes the brain: An experimental study using Ultrasound Brain Tissue Pulsatility Imaging.

INTRODUCTION: Recent evidence suggests that biomechanical parameters of the brain, such as Brain Tissue Pulsatility (BTP), could be involved in emotional reactivity. However, no study has investigated the impact of an emotional task on BTP. We used the ultrasound method of Tissue Pulsatility Imaging (TPI) to assess changes in BTP to exciting and relaxing classical music, in a musical perception task, as a validated paradigm to assess emotional reactivity. METHODS: 25 healthy volunteers were exposed via earphones to four 5-minute musical excerpts (two exciting and two relaxing musical excerpts) presented in a randomized order and intersected by 5 silence periods. Measures of BTP, Heart Rate (HR) and Skin Conductance (SC) were collected during the entire task. RESULTS: The BTP significantly decreased with relaxing music compared to silence, and especially with the excerpt 'Entrance of the Shades' by Minkus. The HR and SC, but not Heart Rate Variability, were also decreased with relaxing music. We found no significant effect of exciting music. DISCUSSION: We report, for the first time, that classical relaxing music decreases the amplitude of the brain pulsatile movements related to cerebral blood flow and mechanical properties of the brain parenchyma, which provides further evidence of the involvement of BTP in emotional reactivity. In addition, we validate the use of TPI as a non-invasive, portable and low cost tool for studies in psychophysiology, with the potential to be implemented as a biomarker in musicotherapy trials notably.

Simulation of shear wave propagation in a soft medium using a pseudospectral time domain method.

Elastography applications require the use of efficient models to simulate the propagation of shear waves in soft media such as human tissues. These models are needed to improve understanding of the measured displacement field, to reconstruct the viscoelasticity of heterogeneous tissues, and to test inversion algorithms. This paper reports a numerical model based on a pseudospectral time domain method developed to simulate shear and compression wave propagation in an axisymmetric heterogeneous viscoelastic medium. This model was adapted to the study of soft tissues where the ratio between the compression and the shear wave velocity was about a thousand and validated in the homogeneous situation by comparison with an analytical model based on elastodynamic Green's functions. Displacements obtained experimentally using transient elastography are presented, compared with simulation results, and discussed.

Methodology for developing a high-precision ultrasound flow meter and fluid velocity profile reconstruction.

This article reports the methodology used to develop a high-precision ultrasound transit time flow meter dedicated to liquid hydrocarbons. This kind of flow meter is designed for custody transfer applications requiring accuracy better than 0.15% of reading. We focus here on certain specific points to achieve this accuracy. The transit time method needs to estimate accurately the time delay between signals received by a pair of transducers. In this study, we review different ways of estimating this time delay. We also propose a specific configuration of the flow meter paths. In particular, this configuration compensates for the swirl phenomenon, which has a significant impact on the accuracy of the flow meter. We also propose a theoretical parametric profile to reconstruct the fluid velocity profile in order to perform in situ diagnosis of the flow. The parameters of the model are estimated from the measurements of the flow meter. Simulations and experimental results showed that this method provides characterization of the flow in disturbed and undisturbed flow conditions.

Biomechanical characterization of ex vivo human brain using ultrasound shear wave spectroscopy.

The characterization of brain tissue is crucial to better understand neurological disorders. Mechanical characterization is an emerging tool in that field. The purpose of this work was to validate a transient ultrasound technique aimed at measuring dispersion of mechanical parameters of the brain tissue. The first part of this work was dedicated to the validation of that technique by comparing it with two proven rheology methods: a rotating plate rheometer, and a viscoelastic spectroscopy apparatus. Experiments were done on tissue mimicking gels. Results were compared on storage and loss modulus in the 20-100 Hz band. Our method was validated for the measurement of storage modulus dispersion, with some reserves on the measurement of loss modulus. The second part of this work was the measurement of the mechanical characteristics of ex vivo human white matter. We were able to measure the dispersion of the storage and loss modulus in the 20-100 Hz band, fitting the data with a custom power law model.

Measurement of shear wave speed dispersion in the placenta by transient elastography: A preliminary ex vivo study.

BACKGROUND: Placental elasticity may be modified in women with placental insufficiency. Shear wave elastography (SWE) can measure this, using acoustic radiation force, but the safety of its use in pregnant women has not yet been demonstrated. Transient elastography (TE) is a safer alternative, but has not yet been applied to the placenta. Moreover, the dispersion of shear wave speed (SWS) as a function of frequency has received relatively little study for placental tissue, although it might improve the accuracy of biomechanical assessment. OBJECTIVE: To explore the feasibility and reproducibility of TE for placental analysis, to compare the values of SWS and Young's modulus (YM) from TE and SWE, and to analyze SWS dispersion as a function of frequency ex vivo in normal placentas. MATERIALS AND METHODS: Ten normal placentas were analyzed ex vivo by an Aixplorer ultrasound system as shear waves were generated by a vibrating plate and by using an Aixplorer system. The frequency analysis provided the value of the exponent n from a fractional rheological model applied to the TE method. We calculated intra- and interobserver agreement for SWS and YM with 95% prediction intervals, created Bland-Altman plots with 95% limits of agreement, and estimated the intraclass correlation coefficient (ICC). MAIN RESULTS: The mean SWS was 1.80 m/s +/- 0.28 (standard deviation) with the TE method at 50 Hz and 1.82 m/s +/-0.13 with SWE (P = 0.912). No differences were observed between the central and peripheral regions of placentas with either TE or SWE. With TE, the intraobserver ICC for SWS was 0.68 (0.50-0.82), and the interobserver ICC for SWS 0.65 (0.37-0.85). The mean parameter n obtained from the fractional rheological model was 1.21 +/- 0.12, with variable values of n for any given SWS. CONCLUSIONS: TE is feasible and reproducible on placentas ex vivo. The frequency analysis of SWS provides additional information about placental elasticity and appears to be able to distinguish differences between placental structures.

Ultrasound Measures of Brain Pulsatility Correlate with Subcortical Brain Volumes in Healthy Young Adults.

Increasing evidence suggests that brain pulsatility is involved in the pathophysiology of various neurological and psychiatric disorders. However, it remains unclear whether high brain pulsatility is damaging to or protective of the brain in normal conditions, and this could depend on the age of the individual and the methods used to measure brain pulsatility. The goal of our study was to investigate associations between subcortical volumes and brain pulsatility as assessed with ultrasound in healthy young adults using both a conventional method (transcranial Doppler pulsatility index [TCD-PI]) and the innovative method of tissue pulsatility imaging (TPI), which allows a high level of detection of small brain movements (micrometers). Twenty-five females aged 18-55 with no history of significant medical disorder underwent magnetic resonance imaging and ultrasound assessment. The volumes of six subcortical regions known to be particularly sensitive to change in cerebral blood flow were measured and compared with brain pulsatility as assessed with TCD-PI and TPI. TCD-PI and TPI measures positively correlated with all subcortical regions, with the caudate nucleus having the strongest association. Linear regressions found that TCD-PI and TPI measures of brain pulsatility explained 16% to 67% of the variance of the subcortical volumes. Our results suggest that a greater pulsatility as assessed with ultrasound in healthy young adults may constitute a protective factor for brain structure. Ultrasound measures of brain pulsatility may be appropriate to provide costless, non-invasive, portable and highly sensitive markers of cerebral blood flow pulsatility related to brain structure.