Contractile properties are less affected at long than short muscle length after eccentric exercise.

PURPOSE: The aim of the present study was to investigate whether the electrically evoked muscle responses are differently affected over time by the knee joint angle after an exercise-induced muscle damage (EIMD). We hypothesized that low-frequency-evoked responses would be less affected at long than short muscle length, and that mechanisms located within the muscle and tendinous tissues would be involved. METHODS: Fifteen males performed 45 min loaded downhill walking (DW) exercise. Maximal voluntary contraction torque (MVC), optimal angle for torque production, voluntary activation level (VAL), twitch, doublet at 10 and 100 Hz (Db10 and Db100, respectively), rate of torque development (RTD), post-activation potentiation (PAP), muscle shear elastic modulus (µ) and aponeurosis stiffness were assessed before, after, and 4, 24, 48, 72 and 168 h after the exercise at a knee angle of 40°, 90° and 120° (0°: full extension). RESULTS: MVC, VAL and Db100 were similarly decreased across joint angles after the DW and optimal angle was not affected. Twitch, Db10, Db10/Db100, PAP and RTD were less affected and muscle µ more increased at long than short muscle lengths (p < 0.05), especially during the first 24 h after the DW exercise. CONCLUSION: Low-frequency-evoked responses were more preserved at long than short muscle length the first 24 h after the DW exercise, suggesting that joint angle should be taken into account to assess muscular alterations after EIMD. This length-dependence could be associated to the higher sensitivity to Ca2+ and the higher increase in muscle stiffness at long than short muscle length.

Poor Correlation between Diaphragm Thickening Fraction and Transdiaphragmatic Pressure in Mechanically Ventilated Patients and Healthy Subjects.

BACKGROUND: The relationship between the diaphragm thickening fraction and the transdiaphragmatic pressure, the reference method to evaluate the diaphragm function, has not been clearly established. This study investigated the global and intraindividual relationship between the thickening fraction of the diaphragm and the transdiaphragmatic pressure. The authors hypothesized that the diaphragm thickening fraction would be positively and significantly correlated to the transdiaphragmatic pressure, in both healthy participants and ventilated patients. METHODS: Fourteen healthy individuals and 25 mechanically ventilated patients (enrolled in two previous physiologic investigations) participated in the current study. The zone of apposition of the right hemidiaphragm was imaged simultaneously to transdiaphragmatic pressure recording within different breathing conditions, i.e., external inspiratory threshold loading in healthy individuals and various pressure support settings in patients. A blinded offline breath-by-breath analysis synchronously computed the changes in transdiaphragmatic pressure, the diaphragm pressure-time product, and diaphragm thickening fraction. Global and intraindividual relationships between variables were assessed. RESULTS: In healthy subjects, both changes in transdiaphragmatic pressure and diaphragm pressure-time product were moderately correlated to diaphragm thickening fraction (repeated measures correlation = 0.40, P < 0.0001; and repeated measures correlation = 0.38, P < 0.0001, respectively). In mechanically ventilated patients, changes in transdiaphragmatic pressure and thickening fraction were weakly correlated (repeated measures correlation = 0.11, P = 0.008), while diaphragm pressure-time product and thickening fraction were not (repeated measures correlation = 0.04, P = 0.396). Individually, changes in transdiaphragmatic pressure and thickening fraction were significantly correlated in 8 of 14 healthy subjects (ρ = 0.30 to 0.85, all P < 0.05) and in 2 of 25 mechanically ventilated patients (ρ = 0.47 to 0.64, all P < 0.05). Diaphragm pressure-time product and thickening fraction correlated in 8 of 14 healthy subjects (ρ = 0.41 to 0.82, all P < 0.02) and in 2 of 25 mechanically ventilated patients (ρ = 0.63 to 0.66, all P < 0.01). CONCLUSIONS: Overall, diaphragm function as assessed with transdiaphragmatic pressure was weakly related to diaphragm thickening fraction. The diaphragm thickening fraction should not be used in healthy subjects or ventilated patients when changes in diaphragm function are evaluated.

Mechanical induction of the tumorigenic ß-catenin pathway by tumour growth pressure.

The tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells. Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In the early stage of mouse colon tumour development in the Notch(+)Apc(+/1638N) mouse model, we observed mechanistic pressure stress in the non-tumorous epithelial cells caused by hyper-proliferative adjacent crypts overexpressing active Notch, which is associated with increased Ret and ß-catenin signalling. We thus developed a method that allows the delivery of a defined mechanical pressure in vivo, by subcutaneously inserting a magnet close to the mouse colon. The implanted magnet generated a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts after intravenous injection. The magnetically induced pressure quantitatively mimicked the endogenous early tumour growth stress in the order of 1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain imaging and shear wave elastography. The exertion of pressure mimicking that of tumour growth led to rapid Ret activation and downstream phosphorylation of ß-catenin on Tyr654, imparing its interaction with the E-cadherin in adherens junctions, and which was followed by ß-catenin nuclear translocation after 15 days. As a consequence, increased expression of ß-catenin-target genes was observed at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic ß-catenin pathway suggests unexplored modes of tumour propagation based on mechanical signalling pathways in healthy epithelial cells surrounding the tumour, which may contribute to tumour heterogeneity.

Acoustoelasticity in transversely isotropic soft tissues: Quantification of muscle nonlinear elasticity.

Recent developments in the field of elastography aim at developing the quantification of new mechanical properties of tissues, that are complementary to the shear modulus, which is characteristic of the linear elastic properties of a quasi-incompressible medium. In this context, measurement of the elastic nonlinearity of tissues was recently proposed based on acoustoelasticity. Up to now, most of the experimental applications of acoustoelasticity theory using Landau formalism in human tissues have assumed isotropy. However, this strong hypothesis does not hold in all human tissues, such as muscles that are generally considered as transversely isotropic (TI). In this work, after reviewing the constraints imposed by TI symmetry on the linear and nonlinear elastic properties of TI media, the acoustoelasticity theory in TI incompressible media is developed and implemented experimentally on a TI polyvinyl alcohol phantom and on ex vivo muscular tissues. Based on this theory and on the evolutions of the shear wave speed, with respect to uniaxial static stress, the nonlinear elastic parameter A is experimentally quantified. The estimations of A in ex vivo bovine and porcine muscles are on the order of hundreds of kPa. This work paves the way for more thorough muscle mechanical properties characterization as well as for the development of a potential new biomarker.

Ultrafast ultrasound coupled with cervical magnetic stimulation for non-invasive and non-volitional assessment of diaphragm contractility.

KEY POINTS: Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non-volitional method for assessing diaphragm contractility in humans, yet it requires invasive procedures such as oesophageal and gastric catheter balloons.  Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown.  Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure.  This approach provides a novel fully non-invasive and non-volitional tool for the assessment of diaphragm contractility in humans. ABSTRACT: Measuring twitch transdiaphragmatic pressure (Pdi,tw ) elicited by cervical magnetic stimulation (CMS) is considered as a reference method for the standardized evaluation of diaphragm function. Yet, the measurement of Pdi requires invasive oesophageal and gastric catheter-balloons. Ultrafast ultrasound is a non-invasive imaging technique enabling frame rates high enough to capture transient events such as evoked muscle contractions. This study investigated relationships between indices derived from ultrafast ultrasound and Pdi,tw , and how these indices might be used to estimate Pdi,tw . CMS was performed in 13 healthy volunteers from 30% to 100% of maximal stimulator intensity in units of 10% in a randomized order. Pdi,tw was measured and the right hemidiaphragm was imaged using a custom ultrafast ultrasound sequence with 1 kHz framerate. Maximal diaphragm axial velocity (Vdi ,max ) and diaphragm thickening fraction (TFdi,tw ) were computed. Intra-session reliability was assessed. Repeated-measures correlation (R) and Spearman correlation coefficients (ρ) were used to assess relationships between variables. Intra-session reliability was strong for Pdi,tw and Vdi,max and moderate for TFdi,tw . Vdi,max correlated with Pdi,tw in all subjects (0.64 < ρ < 1.00, R = 0.75; all P < 0.05). TFdi,tw correlated with Pdi,tw in eight subjects only (0.85 < ρ < 0.93, R = 0.69; all P < 0.05). Coupling ultrafast ultrasound and CMS shows promise for the non-invasive and fully non-volitional assessment of diaphragm contractility. This approach opens up the prospect of both diagnosis and follow-up of diaphragm contractility in clinical populations.

Reconstruction of bi-dimensional images in Fourier-transform acousto-optic imaging.

We present a new, to the best of our knowledge, method to perform acousto-optic imaging based on a spatiotemporal structuration of long-duration acoustic plane waves. This approach is particularly relevant when using detectors with long integration times. We show how it is possible to reconstruct an image by measuring its two-dimensional Fourier components. A proof of concept is presented using a photorefractive detection scheme, demonstrating equal performances to direct imaging. The overall acquisition time is compatible with medical monitoring applications.

Ultrasound shear wave elastography for assessing diaphragm function in mechanically ventilated patients: a breath-by-breath analysis.

BACKGROUND: Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings. METHODS: A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson's correlation coefficients (r) were used to investigate within-individual relationships between variables, and repeated measure correlations (R) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation. RESULTS: Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (R = 0.45, 95% CIs [0.35 0.54], p < 0.001). Individual correlation displays a significant correlation in 8 patients out of 25 (r = 0.55-0.86, all p < 0.05, versus r = - 0.43-0.52, all p > 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi-ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi-ΔSMdi relationship (median (Q1-Q3), 25 (18-33) vs. 21 (15-26) breaths.min-1, respectively). CONCLUSIONS: We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients. TRIAL REGISTRATION: NCT03832231 .

Evaluation of capacitive micromachined ultrasonic transducers for passive monitoring of microbubble-assisted ultrasound therapies.

Passive cavitation detection can be performed to monitor microbubble activity during brain therapy. Microbubbles under ultrasound exposure generate a response characterized by multiple nonlinear emissions. Here, the wide bandwidth of capacitive micromachined ultrasonic transducers (CMUTs) was exploited to monitor the microbubble signature through a rat skull and a macaque skull. The intrinsic nonlinearity of the CMUTs was characterized in receive mode. Indeed, undesirable nonlinear components generated by the CMUTs must be minimized as they can mask the microbubble harmonic response. The microbubble signature at harmonic and ultra-harmonic components (0.5-6 MHz) was successfully extracted through a rat skull using moderate bias voltage.

Artifacts and Technical Restrictions in 2D Shear Wave Elastography.

2 D shear wave elastography (2D-SWE) is the latest evolution of elastography techniques and allows real-time quantitative assessment of the medium stiffness. The aim of this review is to identify, describe, explain and illustrate some technical restrictions and artifacts in 2D-SWE. Encountered artifacts and technical restrictions may be categorized according to acquisition technique, medium, or operator: · Acquisition technique: B-mode & SWE entanglement, transducer frequency, posterior elastographic shadowing artifact, mirrored elastogram artifact, "vertical striped" artifact, resolution limits in SWE, non-equivalence of elastographic devices. · Medium: SWE in liquid medium, "black hole phenomenon", pseudo-liquid lesions, musculotendinous anisotropy, intrinsic stiffness variations of tendons and muscles, depth of analysis, movement artifacts. · Operator: Region of interest compression, acquisition and measurement parameters (ROI size, ROI location, elastogram acquisition time). Clear knowledge of the underlying physical basis is necessary in 2D-SWE because radiologists have to deal with technical restrictions and a wide range of artifacts. Proper use of 2D-SWE ensures the reliability and reproducibility of the technique.

Posture-related stiffness mapping of paraspinal muscles.

The paraspinal compartment acts as a bone-muscle composite beam of the spine. The elastic properties of the paraspinal muscles play a critical role in spine stabilization. These properties depend on the subjects' posture, and they may be drastically altered by low back pain. Supersonic shear wave elastography can be used to provide quantitative stiffness maps (elastograms), which characterize the elastic properties of the probed tissue. The aim of this study was to challenge shear wave elastography sensitivity to postural stiffness changes in healthy paraspinal muscles. The stiffness of the main paraspinal muscles (longissimus, iliocostalis, multifidus) was measured by shear wave elastography at the lumbosacral level (L3 and S1) for six static postures performed by volunteers. Passive postures (rest, passive flexion, passive extension) were performed in a first shear wave elastography session, and active postures (upright, bending forward, bending backward) with rest posture for reference were performed in a second session. Measurements were repeated three times for each posture. Sixteen healthy young adults were enrolled in the study. Non-parametric paired tests, multiple analyses of covariance, and intra-class correlations were implemented for analysis. Shear wave elastography showed good to excellent reliability, except in the multifidus at S1, during bending forward, and in the multifidus at L3, during bending backward. Yet, during bending forward, only poor quality was recorded for nine volunteers in the longissimus. Significant intra- and inter-muscular changes were observed with posture. Stiffness significantly increased for the upright position and bending forward with respect to the reference values recorded in passive postures. In conclusion, shear wave elastography allows reliable assessment of the stiffness of the paraspinal muscles except in the multifidus at S1 and longissimus, during bending forward, and in the multifidus at L3, during bending backward. It reveals a different biomechanical behaviour for the multifidus, the longissimus, and the iliocostalis.

Structured ultrasound-modulated optical tomography.

Ultrasound-modulated optical tomography (UOT) is an imaging technique that couples light and ultrasound in order to perform in-depth imaging of highly scattering media. In previous work, we introduced plane wave UOT, an imaging method analogous to x-ray tomography based on the filtered backprojection for image reconstruction. Angle-limited measurements, however, led to drastic loss of lateral spatial resolution. Here, we present a new structured ultrasonic plane wave UOT method that allows partial recovery of the resolution. For image reconstruction, we present a generalization of the Fourier slice theorem along with a generalized filtered backprojection formalism. The method is successfully tested on simulated and experimental data.

Controlled mechanical vibration and impacts on skin biology.

BACKGROUND AND OBJECTIVE: Different biological models have shown how mechanical stimulation may induce physiological responses from solicited cells, tissues, or organs. In models of cultured skin cells, the frequency of the mechanical stress appears to be a paramount parameter, generating a biological response in some cells, particularly from dermal fibroblasts. Our objective was to explore in ex vivo human skin explants the effects of mechanical stimulation. MATERIALS AND METHODS: Mechanical stimulations were provided by a torque test device, with different end effectors, able to generate cyclic strains at different frequencies (from 40 to 120 Hz). Skin explant samples were stimulated twice daily by the device for one minute, over 10 days. RESULTS: At days 0, 5, and 10, samples were processed by immunohistological procedures, allowing some structural dermal proteins to be quantified (fluorescence). As compared to untreated skin explant samples, the stimulation procedure clearly led some proteins of the dermal-epidermal and some dermal proteins to be overexpressed. This stimulation was found to be frequency-dependent, with the greatest overall increases occurring at 60 and 90 Hz. CONCLUSION: For the first time, ultrafast ultrasound imaging in vitro (phantom mimicking skin mechanical properties) was used to analyze mechanical waves transmitted to the skin layers as a function of end effector shape.

Ultrasonic Adaptive Sound Speed Estimation for the Diagnosis and Quantification of Hepatic Steatosis: A Pilot Study.

PURPOSE: To evaluate the ability of a new ultrasound (US) method based on sound speed estimation (SSE) with respect to the detection, quantification, and grading of hepatic steatosis using magnetic resonance (MR) proton density fat fraction (PDFF) as the reference standard and to calculate one US fat index based on the patient's SSE. MATERIALS AND METHODS: This study received local IRB approval. Written informed consent was obtained from patients. We consecutively included N = 50 patients as the training cohort and a further N = 50 as the validation cohort who underwent both SSE and abdominal MR. Hepatic steatosis was classified according to MR-PDFF cutoffs as: S0 ≤ 6.5 %, S1 6.5 to 16.5 %, S2 16.5 to 22 %, S3 ≥ 22 %. Receiver operating curve analysis was performed to evaluate the diagnostic performance of SSE in the diagnosis of steatosis (S1-S3). Based on the optimal data fit derived from our study, we proposed a correspondence between the MR-PDFF and a US fat index. Coefficient of determination R2 was used to evaluate fit quality and was considered robust when R2 > 0.6. RESULTS: The training and validation cohorts presented mean SSE values of 1.570 ±â€Š0.026 and 1.568 ±â€Š0.023 mm/µs for S0 and 1.521 ±â€Š0.031 and 1.514 ±â€Š0.019 mm/µs for S1-S3 (p < 0.01) patients, respectively. An SSE threshold of ≤ 1.537 mm/µs had a sensitivity of 80 % and a specificity of 85.7 % in the diagnosis of steatosis (S1-S3) in the training cohort. Robust correspondence between MR-PDFF and the US fat index was found both for the training (R2 = 0.73) and the validation cohort (R2 = 0.76). CONCLUSION: SSE can be used to detect, quantify and grade liver steatosis and to calculate a US fat index.

EEG and functional ultrasound imaging in mobile rats.

We developed an integrated experimental framework that extends the brain exploration capabilities of functional ultrasound imaging to awake and mobile rats. In addition to acquiring hemodynamic data, this method further allows parallel access to electroencephalography (EEG) recordings of neuronal activity. We illustrate this approach with two proofs of concept: a behavioral study on theta rhythm activation in a maze running task and a disease-related study on spontaneous epileptic seizures.

Two-color interpolation of the absorption response for quantitative acousto-optic imaging.

Diffuse optical tomography (DOT) is a reliable and widespread technique for monitoring qualitative changes in absorption inside highly scattering media. It has been shown, however, that acousto-optic (AO) imaging can provide significantly more qualitative information without the need for inversion algorithms due to the spatial resolution afforded by ultrasound probing. In this Letter, we show how, by using multiple-wavelength AO imaging, it is also possible to perform quantitative measurements of absorber concentration inside scattering media.

Testicular ultrasensitive Doppler preliminary experience: a feasibility study.

Background Ultrasensitive Doppler is a novel non-invasive ultrasound (US) Doppler technique that improves sensitivity and resolution for the detection of slow flow. Purpose To investigate the feasibility of ultrasensitive Doppler (USD) for testicular disease diagnosis, using both qualitative and quantitative results. Material and Methods This prospective study was conducted in 160 successive men referred for scrotal US including B-mode and conventional Color-Doppler. A new USD sequence and algorithm dedicated to academic research were implemented into the US system. The quality criterion for a successful examination was the detection of well delineated intratesticular vessels. Qualitative USD results were described in terms of tumor vascular architecture and flow intensity for different pathologies for 41 patients. The testicular vascularization (TV), defined as a vessel's surface ratio, was quantified using customized MATLAB® software and compared in azoospermic and normal patients. Results USD was acquired successfully in 153/160 patients (95.6%). The tumor vascular architecture differed depending on the nature of the tumors. Leydig cell tumors exhibited mostly circumferential vascularization, while germ cell tumors exhibited straight vessels through the tumors, or anarchic vascular maps. USD improved the diagnostic performance of testicular Doppler US in a case of incomplete spermatic cord torsion and acute epididymitis. The reproducibility of TV measurements established an interclass correlation of 0.801. Non-Klinefelter syndrome non-obstructive azoospermia patients exhibited a lower TV compared to normal patients, to Klinefelter syndrome, and to obstructive azoospermia patients ( P < 0.002, P < 0.005, and P < 0.05, respectively). Conclusion Testicular USD can become a promising technique for improving US diagnosis of tumors, acute scrotum, and for determining infertility status.

3D functional ultrasound imaging of the cerebral visual system in rodents.

3D functional imaging of the whole brain activity during visual task is a challenging task in rodents due to the complex tri-dimensional shape of involved brain regions and the fine spatial and temporal resolutions required to reveal the visual tract. By coupling functional ultrasound (fUS) imaging with a translational motorized stage and an episodic visual stimulation device, we managed to accurately map and to recover the activity of the visual cortices, the Superior Colliculus (SC) and the Lateral Geniculate Nuclei (LGN) in 3D. Cerebral Blood Volume (CBV) responses during visual stimuli were found to be highly correlated with the visual stimulus time profile in visual cortices (r=0.6), SC (r=0.7) and LGN (r=0.7). These responses were found dependent on flickering frequency and contrast, and optimal stimulus parameters for largest CBV increases were obtained. In particular, increasing the flickering frequency higher than 7Hz revealed a decrease of visual cortices response while the SC response was preserved. Finally, cross-correlation between CBV signals exhibited significant delays (d=0.35s +/-0.1s) between blood volume response in SC and visual cortices in response to our visual stimulus. These results emphasize the interest of fUS imaging as a whole brain neuroimaging modality for brain vision studies in rodent models.

Feasibility of Imaging and Treatment Monitoring of Breast Lesions with Three-Dimensional Shear Wave Elastography.

Purpose Firstly to evaluate the feasibility and diagnostic performance of three-dimensional (3 D) shear wave elastography (SWE) volume measurements in patients with breast lesions compared to breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) lesion volumes and 3D-US B-mode volumes. Secondly to assess the treatment monitoring performance of 3D-SWE in patients under neoadjuvant chemotherapy for breast cancer by comparing it to 3D-US lesion volume. Materials and Methods This prospective study was approved by the institutional review board. Informed consent was provided. 33 patients with 33 lesions were included. The feasibility of 3D-SWE was evaluated in 23 patients. In the 10 remaining patients receiving neoadjuvant chemotherapy, 3D-SWE was evaluated before and during treatment. Tumor volume and qualitative and quantitative elasticity analysis measurements were performed and compared to the tumor volume as estimated by 3D-US and DCE-MRI. Statistical analysis was performed using the Pearson correlation coefficient. Results 3D-SWE was feasible in patients with breast lesions. Tumor volume calculated with 3D-US and 3D-SWE showed very good and moderate concordances with DCE-MRI volume, respectively (Pearson correlation coefficients equal to ρ = r = 0.88, p < 0.00 002 and ρ = r = 0.5, p = 0.32, respectively). Modification of tumor elasticity and heterogeneity was correlated with response to treatment. In good responders, elasticity and elasticity heterogeneity diminished. Conclusion Tumor 3D-US volume measurements showed very good concordance with DCE-MRI volume. 3D-SWE can provide valuable information: reduction of tissue stiffness during treatment could be a potential indicator of response. These preliminary results should be confirmed on a larger number of patients.

4D microvascular imaging based on ultrafast Doppler tomography.

4D ultrasound microvascular imaging was demonstrated by applying ultrafast Doppler tomography (UFD-T) to the imaging of brain hemodynamics in rodents. In vivo real-time imaging of the rat brain was performed using ultrasonic plane wave transmissions at very high frame rates (18,000 frames per second). Such ultrafast frame rates allow for highly sensitive and wide-field-of-view 2D Doppler imaging of blood vessels far beyond conventional ultrasonography. Voxel anisotropy (100 µm × 100 µm × 500 µm) was corrected for by using a tomographic approach, which consisted of ultrafast acquisitions repeated for different imaging plane orientations over multiple cardiac cycles. UFT-D allows for 4D dynamic microvascular imaging of deep-seated vasculature (up to 20 mm) with a very high 4D resolution (respectively 100 µm × 100 µm × 100 µm and 10 ms) and high sensitivity to flow in small vessels (>1 mm/s) for a whole-brain imaging technique without requiring any contrast agent. 4D ultrasound microvascular imaging in vivo could become a valuable tool for the study of brain hemodynamics, such as cerebral flow autoregulation or vascular remodeling after ischemic stroke recovery, and, more generally, tumor vasculature response to therapeutic treatment.