Long-term cognitive disability after traumatic brain injury: Contribution of the DEX relative questionnaires.

Executive functions are high-level cognitive processes commonly impaired after severe traumatic brain injury (sTBI), which may be associated with persistent anosognosia. The dysexecutive questionnaire (DEX) was designed to assess different domains of executive functioning in daily life. Two versions of the DEX exist (DEX-S completed by the patient, DEX-O completed by a relative) to compare cognitive complaints and patient's awareness. This work was aimed at studying the relevance of DEX-O for assessing daily-life limitations, the persistence of anosognosia and its association with global disability (GOSE) and magnetic resonance imaging (MRI) markers of brain alterations. Sixty-three patients (and relatives) were included within 63.4 months (±20.7) after sTBI. DEX-S and DEX-O scores were significantly positively correlated. We obtained significant correlations between DEX-S and episodic memory and phasic alert but not with executive assessment, GOSE and diffusion MRI markers. DEX-O was significantly correlated with executive function, episodic memory, attention (phasic alert sustained and divided attention), with the GOSE and the volume of the body of the corpus callosum (MRI marker). Anosognosia score (DEX-O minus DEX-S) correlated with mean diffusivity measure. These results highlight the clinical interest of DEX-O in assessing long-term disability.

Multichannel processing for dispersion curves extraction of ultrasonic axial-transmission signals: Comparisons and case studies.

Some pioneering studies have shown the clinical feasibility of long bones evaluation using ultrasonic guided waves. Such a strategy is typically designed to determine the dispersion information of the guided modes to infer the elastic and structural characteristics of cortical bone. However, there are still some challenges to extract multimode dispersion curves due to many practical limitations, e.g., high spectral density of modes, limited spectral resolution and poor signal-to-noise ratio. Recently, two representative signal processing methods have been proposed to improve the dispersion curves extraction. The first method is based on singular value decomposition (SVD) with advantages of multi-emitter and multi-receiver configuration for enhanced mode extraction; the second one uses linear Radon transform (LRT) with high-resolution imaging of the dispersion curves. To clarify the pros and cons, a face to face comparison was performed between the two methods. The results suggest that the LRT method is suitable to separate the guided modes at low frequency-thickness-product ( fh) range; for multimode signals in broadband fh range, the SVD-based method shows more robust performances for weak mode enhancement and noise filtering. Different methods are valuable to cover the entire fh range for processing ultrasonic axial transmission signals measured in long cortical bones.

MRI volumetry and diffusion tensor imaging for diagnosis and follow-up of late post-traumatic injuries.

BACKGROUND: Traumatic Brain Injury (TBI) is a major cause of acquired disability and can cause devastating and progressive post-traumatic encephalopathy. TBI is a dynamic condition that continues to evolve over time. A better understanding of the pathophysiology of these late lesions is important for the development of new therapeutic strategies. OBJECTIVES: The primary objective was to compare the ability of fluid-attenuated reversion recovery (FLAIR) and diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) markers to identify participants with a Glasgow outcome scale extended (GOS-E) score of 7-8, up to 10 years after their original TBI. The secondary objective was to study the brain regionalization of DTI markers. Finally, we analyzed the evolution of late-developing brain lesions using repeated MRI images, also taken up to 10 years after the TBI. METHODS: In this retrospective study, participants were included from a cohort of people hospitalized following a severe TBI. Following their discharge, they were followed-up and clinically assessed, including a DTI-MRI scan, between 2012 and 2016. We performed a cross-sectional analysis on 97 participants at a median (IQR) of 5 years (3-6) post-TBI, and a further post-TBI longitudinal analysis over 10 years on a subpopulation (n = 17) of the cohort. RESULTS: Although the area under the curve (AUC) of FLAIR, fractional anisotropy (FA), and mean diffusivity (MD) were not significantly different, only the AUC of FA was statistically greater than 0.5. In addition, only the FA was correlated with clinical outcomes as assessed by GOS-E score (P<10-4). On the cross-sectional analysis, DTI markers allowed study post-TBI white matter lesions by region. In the longitudinal subpopulation analysis, the observed number of brain lesions increased for the first 5 years post-TBI, before stabilizing over the next 5 years. CONCLUSIONS: This study has shown for the first time that post-TBI lesions can present in a two-phase evolution. These results must be confirmed in larger studies. French Data Protection Agency (Commission nationale de l'informatique et des libertés; CNIL) study registration no: 1934708v0.

Prognostic value of global deep white matter DTI metrics for 1-year outcome prediction in ICU traumatic brain injury patients: an MRI-COMA and CENTER-TBI combined study.

PURPOSE: A reliable tool for outcome prognostication in severe traumatic brain injury (TBI) would improve intensive care unit (ICU) decision-making process by providing objective information to caregivers and family. This study aimed at designing a new classification score based on magnetic resonance (MR) diffusion metrics measured in the deep white matter between day 7 and day 35 after TBI to predict 1-year clinical outcome. METHODS: Two multicenter cohorts (29 centers) were used. MRI-COMA cohort (NCT00577954) was split into MRI-COMA-Train (50 patients enrolled between 2006 and mid-2014) and MRI-COMA-Test (140 patients followed up in clinical routine from 2014) sub-cohorts. These latter patients were pooled with 56 ICU patients (enrolled from 2014 to 2020) from CENTER-TBI cohort (NCT02210221). Patients were dichotomised depending on their 1-year Glasgow outcome scale extended (GOSE) score: GOSE 1-3, unfavorable outcome (UFO); GOSE 4-8, favorable outcome (FO). A support vector classifier incorporating fractional anisotropy and mean diffusivity measured in deep white matter, and age at the time of injury was developed to predict whether the patients would be either UFO or FO. RESULTS: The model achieved an area under the ROC curve of 0.93 on MRI-COMA-Train training dataset, and 49% sensitivity for 96.8% specificity in predicting UFO and 58.5% sensitivity for 97.1% specificity in predicting FO on the pooled MRI-COMA-Test and CENTER-TBI validation datasets. CONCLUSION: The model successfully identified, with a specificity compatible with a personalized decision-making process in ICU, one in two patients who had an unfavorable outcome at 1 year after the injury, and two-thirds of the patients who experienced a favorable outcome.

In vivopulse-echo measurement of apparent broadband attenuation andQfactor in cortical bone: a preliminary study.

Quantitative ultrasound (QUS) methods have been introduced to assess cortical bone health at the radius and tibia through the assessment of cortical thickness (Ct.Th), cortical porosity and bulk wave velocities. Ultrasonic attenuation is another QUS parameter which is not currently used. We assessed the feasibility ofin vivomeasurement of ultrasonic attenuation in cortical bone with a broadband transducer with 3.5 MHz center frequency. Echoes from the periosteal and endosteal interfaces were fitted with Gaussian pulses using sparse signal processing. Then, the slope of the broadband ultrasonic attenuation (Ct.nBUA) in cortical bone and quality factorQ11-1were calculated with a parametric approach based on the center-frequency shift. Five human subjects were measured at the one-third distal radius with pulse-echo ultrasound, and reference data was obtained with high-resolution x-ray peripheral computed tomography (Ct.Th and cortical volumetric bone mineral density (Ct.vBMD)). Ct.Th was used in the calculation of Ct.nBUA whileQ11-1is obtained solely from ultrasound data. The values of Ct.nBUA (6.7 ± 2.2 dB MHz-1.cm-1) andQ11-1(8.6 ± 3.1%) were consistent with the literature data and were correlated to Ct.vBMD (R2=0.92,p<0.01, RMSE = 0.56 dB.MHz-1.cm-1, andR2=0.93,p<0.01, RMSE = 0.76%). This preliminary study suggests that the attenuation of an ultrasound signal propagating in cortical bone can be measuredin vivoat the one-third distal radius and that it provides an information on bone quality as attenuation values were correlated to Ct.vBMD. It remains to ascertain that Ct.nBUA andQ11-1measured here exactly reflect the true (intrinsic) ultrasonic attenuation in cortical bone. Measurement of attenuation may be considered useful for assessing bone health combined with the measurement of Ct.Th, porosity and bulk wave velocities in multimodal cortical bone QUS methods.

Measuring anisotropy of elastic wave velocity with ultrasound imaging and an autofocus method: application to cortical bone.

This work investigates the feasibility of estimating the parameters of an exact transverse isotropy model in cortical bone. The model describes the anisotropy of the velocity of compressional and shear bulk elastic waves. We propose to achieve this with ultrasound imaging relying on the transmission of unfocused beams and with an autofocus method. The latter is based on the principle that the reconstructed ultrasound image shows optimal quality if the velocity model is correct. The autofocus approach is applied to a composite image of the interface between cortical bone and marrow. It is obtained by incoherent summation of four types of images exploiting four different ray paths in the cortical bone layer, three of them involving mode-converted shear waves. If the parameters of the model are correct, spatial co-localization of the interface appears in the four images. As a result, intensity and sharpness in the composite image are maximal. The five parameters of the model of transverse isotropy are successfully estimated in a tube made of a bone-mimicking material. The estimates are in good agreement with resonant ultrasound spectroscopy (RUS) measurements. The tube thickness is recovered with an error smaller than 0.3%. In vivo results at the forearm of a volunteer are promising, four parameters could be estimated and are in good agreement with ex vivo RUS measurements. Moreover x-ray peripheral computed tomography corroborates the thickness of the cortical bone layer in the ultrasound image. Weak-anisotropy and exact transverse isotropy models provide very close measurements of the thickness of the tube and the radius bone. Thus, we recommend using the model of weak transverse isotropy for real-time anatomical imaging because more computationally efficient. For material characterization however, the model of exact transverse isotropy is preferred because the elastic anisotropy of cortical bone is moderate, rather than weak.

Homogenization of cortical bone reveals that the organization and shape of pores marginally affect elasticity.

With ageing and various diseases, the vascular pore volume fraction (porosity) in cortical bone increases, and the morphology of the pore network is altered. Cortical bone elasticity is known to decrease with increasing porosity, but the effect of the microstructure is largely unknown, while it has been thoroughly studied for trabecular bone. Also, popular micromechanical models have disregarded several micro-architectural features, idealizing pores as cylinders aligned with the axis of the diaphysis. The aim of this paper is to quantify the relative effects on cortical bone anisotropic elasticity of porosity and other descriptors of the pore network micro-architecture associated with pore number, size and shape. The five stiffness constants of bone assumed to be a transversely isotropic material were measured with resonant ultrasound spectroscopy in 55 specimens from the femoral diaphysis of 29 donors. The pore network, imaged with synchrotron radiation X-ray micro-computed tomography, was used to derive the pore descriptors and to build a homogenization model using the fast Fourier transform (FFT) method. The model was calibrated using experimental elasticity. A detailed analysis of the computed effective elasticity revealed in particular that porosity explains most of the variations of the five stiffness constants and that the effects of other micro-architectural features are small compared to usual experimental errors. We also have evidence that modelling the pore network as an ensemble of cylinders yields biased elasticity values compared to predictions based on the real micro-architecture. The FFT homogenization method is shown to be particularly efficient to model cortical bone.

In vivo ultrasound imaging of the bone cortex.

Current clinical ultrasound scanners cannot be used to image the interior morphology of bones because these scanners fail to address the complicated physics involved for exact image reconstruction. Here, we show that if the physics is properly addressed, bone cortex can be imaged using a conventional transducer array and a programmable ultrasound scanner. We provide in vivo proof for this technique by scanning the radius and tibia of two healthy volunteers and comparing the thickness of the radius bone with high-resolution peripheral x-ray computed tomography. Our method assumes a medium that is composed of different homogeneous layers with unique elastic anisotropy and ultrasonic wave-speed values. The applicable values of these layers are found by optimizing image sharpness and intensity over a range of relevant values. In the algorithm of image reconstruction we take wave refraction between the layers into account using a ray-tracing technique. The estimated values of the ultrasonic wave-speed and anisotropy in cortical bone are in agreement with ex vivo studies reported in the literature. These parameters are of interest since they were proposed as biomarkers for cortical bone quality. In this paper we discuss the physics involved with ultrasound imaging of bone and provide an algorithm to successfully image the first segment of cortical bone.

A method for the measurement of dispersion curves of circumferential guided waves radiating from curved shells: experimental validation and application to a femoral neck mimicking phantom.

Our long-term goal is to develop an ultrasonic method to characterize the thickness, stiffness and porosity of the cortical shell of the femoral neck, which could enhance hip fracture risk prediction. To this purpose, we proposed to adapt a technique based on the measurement of guided waves. We previously evidenced the feasibility of measuring circumferential guided waves in a bone-mimicking phantom of a circular cross-section of even thickness. The goal of this study is to investigate the impact of the complex geometry of the femoral neck on the measurement of guided waves. Two phantoms of an elliptical cross-section and one phantom of a realistic cross-section were investigated. A 128-element array was used to record the inter-element response matrix of these waveguides. This experiment was simulated using a custom-made hybrid code. The response matrices were analyzed using a technique based on the physics of wave propagation. This method yields portions of dispersion curves of the waveguides which were compared to reference dispersion curves. For the elliptical phantoms, three portions of dispersion curves were determined with a good agreement between experiment, simulation and theory. The method was thus validated. The characteristic dimensions of the shell were found to influence the identification of the circumferential wave signals. The method was then applied to the signals backscattered by the superior half of constant thickness of the realistic phantom. A cut-off frequency and some portions of modes were measured, with a good agreement with the theoretical curves of a plate waveguide. We also observed that the method cannot be applied directly to the signals backscattered by the lower half of varying thicknesses of the phantom. The proposed approach could then be considered to evaluate the properties of the superior part of the femoral neck, which is known to be a clinically relevant site.

A hybrid FDTD-Rayleigh integral computational method for the simulation of the ultrasound measurement of proximal femur.

The development of novel quantitative ultrasound (QUS) techniques to measure the hip is critically dependent on the possibility to simulate the ultrasound propagation. One specificity of hip QUS is that ultrasounds propagate through a large thickness of soft tissue, which can be modeled by a homogeneous fluid in a first approach. Finite difference time domain (FDTD) algorithms have been widely used to simulate QUS measurements but they are not adapted to simulate ultrasonic propagation over long distances in homogeneous media. In this paper, an hybrid numerical method is presented to simulate hip QUS measurements. A two-dimensional FDTD simulation in the vicinity of the bone is coupled to the semi-analytic calculation of the Rayleigh integral to compute the wave propagation between the probe and the bone. The method is used to simulate a setup dedicated to the measurement of circumferential guided waves in the cortical compartment of the femoral neck. The proposed approach is validated by comparison with a full FDTD simulation and with an experiment on a bone phantom. For a realistic QUS configuration, the computation time is estimated to be sixty times less with the hybrid method than with a full FDTD approach.

Iterative high-resolution wavenumber inversion applied to broadband acoustic data.

This paper presents the results of an iterative high-resolution wavenumber inversion algorithm applied to acoustic waveguides in which wave propagation is described by propagating modes. Following work on the first description of the inversion algorithm, a generalization to broadband signals is performed and experimental data are investigated. The algorithm leads to dispersion curves for propagating modes in the case of an ultrasonic waveguide and an elastic plate. Results are compared with spatial-temporal Fourier transforms.

The role of the coupling term in transient elastography.

The transient radiation of low-frequency elastic waves through isotropic and homogeneous soft media is investigated using the Green's function approach. A careful analysis of the coupling term is performed and yields the introduction of a very near field region in which its amplitude behaves as 1/r. To address the calculation of impulse responses, a simplified Green's function is proposed for semi-infinite media and compared to exact solutions. Impulse response calculations are successfully compared with experimental measurements obtained for circular radiators of different diameters using transient elastography. Results presented in this paper provide a better understanding of the role of the coupling term in elastography and should be used to compensate diffraction and coupling effects observed in transient elastography.