Human Calf Research Articles

Millimeter wave radiation to measure blood flow in healthy human subjects

Objective.Peripheral Artery Disease (PAD) is a progressive cardiovascular condition affecting 8-10 million adults in the United States. PAD elevates the risk of cardiovascular events, but up to 50% of people with PAD are asymptomatic and undiagnosed. In this study, we tested the ability of a device, REFLO (Rapid Electromagnetic FLOw), to identify low blood flow using electromagnetic radiation and dynamic thermography toward a non-invasive PAD diagnostic.Approach.During REFLO radio frequency (RF) irradiation, the rate of temperature increase is a function of the rate of energy absorption and blood flow to the irradiated tissue. For a given rate of RF energy absorption, a slow rate of temperature increase implies a large blood flow rate to the tissue. This is due to the cooling effect of the blood. Post-irradiation, a slow rate of temperature decrease is associated with a low rate of blood flow to the tissue. Here, we performed two cohorts of controlled flow experiments on human calves during baseline, occluded, and post-occluded conditions. Nonlinear regression was used to fit temperature data and obtain the rate constant, which was used as a metric for blood flow.Main results.In the pilot study, (N= 7) REFLO distinguished between baseline and post-occlusion during the irradiation phase, and between baseline and occlusion in the post-irradiation phase. In the reliability study, (N= 5 with 3 visits each), two-way ANOVA revealed that flow and subject significantly affected skin heating and cooling rates, while visit did not.Significance.Results suggest that MMW irradiation can be used to distinguish between blood flow rates in humans. Utilizing the rate of skin cooling rather than heating is more consistent for distinguishing flow. Future modifications and clinical testing will aim to improve REFLO's ability to distinguish between flow rates and evaluate its ability to accurately identify PAD.

Toward structure and metabolism of glycogen C1-C6 in humans at 7T by localized 13C MRS using low-power bilevel broadband 1H decoupling.

This work aims to develop and implement a pulse-acquire sequence for three-dimensional (3D) single-voxel localized 13C MRS in humans at 7T, in conjunction with bilevel broadband 1H decoupling, and to test its feasibility in vitro and in vivo in human calf muscle with emphasis on the detection of glycogen C1-C6. A localization scheme suitable for measuring fast-relaxing 13C signals in humans at 7T was developed and implemented using the outer volume suppression (OVS) and one-dimensional image selected in vivo spectroscopy (ISIS-1D) schemes, similar to that which was previously reported in humans at 4T. The 3D 13C localization scheme was followed by uniform 13C adiabatic excitation, all complemented with an option for bilevel broadband 1H decoupling to improve both 13C sensitivity and spectral resolution at 7T. The performance of the pulse-acquire sequence was investigated in vitro on phantoms and in vivo in the human calf muscle of three healthy volunteers, while measuring glycogen C1-C6. In addition, T1 and T2 of glycogen C1-C6 were measured in vitro at 7T, as well as T1 of glycogen C1 in vivo. The glycerol C2 and C1,3 lipid resonances were efficiently suppressed in vitro at 7T using the OVS and ISIS-1D schemes, allowing distinct detection of glycogen C2-C6. While some glycerol remained in calf muscle in vivo, the intense lipid at 130 ppm was efficiently suppressed. The 13C sensitivity and spectral resolution of glycogen C1-C6 in vitro and glycogen C1 in vivo were improved at 7T using bilevel broadband 1H decoupling. The T1 and T2 of glycogen C1-C6 in vitro at 7T were consistent compared with those at 8.5T, while the T1 of glycogen C1 in vivo at 7T resulted similar to that in vitro. Localized 13C MRS is feasible in human calf muscle in vivo at 7T, and this will allow further extension of this method for 13C MRS measurements such as in the brain.

Velocity-compensated intravoxel incoherent motion of the human calf muscle.

To determine whether intravoxel incoherent motion (IVIM) describes the blood perfusion in muscles better, assuming pseudo diffusion (Bihan Model 1) or ballistic motion (Bihan Model 2). IVIM parameters were measured in 18 healthy subjects with three different diffusion gradient time profiles (bipolar with two diffusion times and one with velocity compensation) and 17 b-values (0-600 s/mm2) at rest and after muscle activation. The diffusion coefficient, perfusion fraction, and pseudo-diffusion coefficient were estimated with a segmented fit in the gastrocnemius medialis (GM) and tibialis anterior (TA) muscles. Velocity-compensated gradients resulted in a decreased perfusion fraction (6.9% ± 1.4% vs. 4.4% ± 1.3% in the GM after activation) and pseudo-diffusion coefficient (0.069 ± 0.046 mm2/s vs. 0.014 ± 0.006 in the GM after activation) compared to the bipolar gradients with the longer diffusion encoding time. Increased diffusion coefficients, perfusion fractions, and pseudo-diffusion coefficients were observed in the GM after activation for all gradient profiles. However, the increase was significantly smaller for the velocity-compensated gradients. A diffusion time dependence was found for the pseudo-diffusion coefficient in the activated muscle. Velocity-compensated diffusion gradients significantly suppress the IVIM effect in the calf muscle, indicating that the ballistic limit is mostly reached, which is supported by the time dependence of the pseudo-diffusion coefficient.

Real-Time Speed-of-Sound Estimation In Vivo via Steered Plane Wave Ultrasound.

Speed-of-sound (SoS) is an intrinsic acoustic property of human tissues and has been regarded as a potential biomarker of tissue health. To foster the clinical use of this emerging biomarker in medical diagnostics, it is important for SoS estimates to be derived and displayed in real time. Here, we demonstrate that concurrent global SoS estimation and B-mode imaging can be achieved live on a portable ultrasound scanner. Our innovation is hinged upon the design of a novel pulse-echo SoS estimation framework that is based on steered plane wave imaging. It has accounted for the effects of refraction and imaging depth when the medium SoS differs from the nominal value of 1540 m/s that is conventionally used in medical imaging. The accuracy of our SoS estimation framework was comparatively analyzed with through-transmit time-of-flight measurements in vitro on 15 custom agar phantoms with different SoS values (1508-1682 m/s) and in vivo on human calf muscles ( N = 9 ; SoS range: 1560-1586 m/s). Our SoS estimation framework has a mean signed difference (MSD) of - 0.6 ± 2.3 m/s in vitro and - 2.2 ± 11.2 m/s in vivo relative to the reference measurements. In addition, our real-time system prototype has yielded simultaneous SoS estimates and B-mode imaging at an average frame rate of 18.1 fps. Overall, by realizing real-time tissue SoS estimation with B-mode imaging, our innovation can foster the use of tissue SoS as a biomarker in medical ultrasound diagnostics.

Design and Implementation of a Cost‐Effective, Portable Impedance Analyzer Device with AD5941

This study proposes a cost‐effective, small‐size, and portable impedance analyzer using the AD5941 Analog Front End (AFE) that makes frequency sweep measurement for various applications. The design utilizes a microcontroller and an AD5941 circuit for impedance measurement. The AD541 is a high precision impedance converter system that consists of a 16‐bit, 1.6 MSPS, analog to digital converter (ADC), an integrated waveform generator, and a digital signal processing (DSP) block. The AD5941 has many advantages over the AD5933 which was used in numerous studies in the past decade. Also, the device implements the four‐wire impedance method which is an impedance measuring technique that reduces the effect of electrodes to achieve higher accuracy. A supporting Graphic User Interface (GUI) software is employed to control the Impedance Analyzer device and to visualize the measurement. This impedance analyzer achieves a frequency resolution of 0.015 Hz and can generate sinusoid up to 200 kHz. In frequency range from 10 kHz to 150 kHz, the device can measure impedance in the range of 10 Ω–100 kΩ with less than 4.3% of error in comparison with benchtop impedance analyzer, Microtest 6632. Moreover, our impedance measurement device has undergone testing involving human calf measurements and electrochemical quantification, particularly for estimating Sodium Chlorite. The experimental outcomes demonstrate that our design not only fulfills the criteria of an impedance analyzer device but also performs effectively across diverse applications. © 2024 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC.

Combining Dipole and Loop Coil Elements for 7 T Magnetic Resonance Studies of the Human Calf Muscle.

Combining proton and phosphorus magnetic resonance spectroscopy offers a unique opportunity to study the oxidative and glycolytic components of metabolism in working muscle. This paper presents a 7 T proton calf coil design that combines dipole and loop elements to achieve the high performance necessary for detecting metabolites with low abundance and restricted visibility, specifically lactate, while including the option of adding a phosphorus array. We investigated the transmit, receive, and parallel imaging performance of three transceiver dipoles with six pair-wise overlap-decoupled standard or twisted pair receive-only coils. With a higher SNR and more efficient transmission decoupling, standard loops outperformed twisted pair coils. The dipoles with standard loops provided a four-fold-higher image SNR than a multinuclear reference coil comprising two proton channels and 32% more than a commercially available 28-channel proton knee coil. The setup enabled up to three-fold acceleration in the right-left direction, with acceptable g-factors and no visible aliasing artefacts. Spectroscopic phantom measurements revealed a higher spectral SNR for lactate with the developed setup than with either reference coil and fewer restrictions in voxel placement due to improved transmit homogeneity. This paper presents a new use case for dipoles and highlights their advantages for the integration in multinuclear calf coils.

Influence of Magnetic Field Strength on Intravoxel Incoherent Motion Parameters in Diffusion MRI of the Calf.

Background: The purpose of this study was to investigate the dependence of Intravoxel Incoherent Motion (IVIM) parameters measured in the human calf on B0. Methods: Diffusion-weighted image data of eight healthy volunteers were acquired using five b-values (0-600 s/mm2) at rest and after muscle activation at 0.55 and 7 T. The musculus gastrocnemius mediale (GM, activated) was assessed. The perfusion fraction f and diffusion coefficient D were determined using segmented fits. The dependence on field strength was assessed using Student's t-test for paired samples and the Wilcoxon signed-rank test. A biophysical model built on the three non-exchanging compartments of muscle, venous blood, and arterial blood was used to interpret the data using literature relaxation times. Results: The measured perfusion fraction of the GM was significantly lower at 7 T, both for the baseline measurement and after muscle activation. For 0.55 and 7 T, the mean f values were 7.59% and 3.63% at rest, and 14.03% and 6.92% after activation, respectively. The biophysical model estimations for the mean proton-density-weighted perfusion fraction were 3.37% and 6.50% for the non-activated and activated states, respectively. Conclusions: B0 may have a significant effect on the measured IVIM parameters. The blood relaxation times suggest that 7 T IVIM may be arterial-weighted whereas 0.55 T IVIM may exhibit an approximately equal weighting of arterial and venous blood.

Simultaneous creatine and phosphocreatine mapping of skeletal muscle by CEST MRI at 3T.

To confirm that CrCEST in muscle exhibits a slow-exchanging process, and to obtain high-resolution amide, creatine (Cr), and phosphocreatine (PCr) maps of skeletal muscle using a POlynomial and Lorentzian Line-shape Fitting (PLOF) CEST at 3T. We used dynamic changes in PCr/CrCEST of mouse hindlimb before and after euthanasia to assign the Cr and PCr CEST peaks in the Z-spectrum at 3T and to obtain the optimum saturation parameters. Segmented 3D EPI was employed to obtain multi-slice amide, PCr, and Cr CEST maps of human skeletal muscle. Subsequently, the PCrCEST maps were calibrated using the PCr concentrations determined by 31 P MRS. A comparison of the Z-spectra in mouse hindlimb before and after euthanasia indicated that CrCEST is a slow-exchanging process in muscle (<150.7 s-1 ). This allowed us to simultaneously extract PCr/CrCEST signals at 3T using the PLOF method. We determined optimal B1 values ranging from 0.3 to 0.6 μT for CrCEST in muscle and 0.3-1.2 μT for PCrCEST. For the study on human calf muscle, we determined an optimum saturation time of 2 s for both PCr/CrCEST (B1 = 0.6 μT). The PCr/CrCEST using 3D EPI were found to be comparable to those obtained using turbo spin echo (TSE). (3D EPI/TSE PCr: (2.6 ± 0.3) %/(2.3 ± 0.1) %; Cr: (1.3 ± 0.1) %/(1.4 ± 0.07) %). Our study showed that in vivo CrCEST is a slow-exchanging process. Hence, amide, Cr, and PCr CEST in the skeletal muscle can be mapped simultaneously at 3T by PLOF CEST.

2D sodium MRI of the human calf using half-sinc excitation pulses and compressed sensing.

Sodium MRI can be used to quantify tissue sodium concentration (TSC) in vivo; however, UTE sequences are required to capture the rapidly decaying signal. 2D MRI enables high in-plane resolution but typically has long TEs. Half-sinc excitation may enable UTE; however, twice as many readouts are necessary. Scan time can be minimized by reducing the number of signal averages (NSAs), but at a cost to SNR. We propose using compressed sensing (CS) to accelerate 2D half-sinc acquisitions while maintaining SNR and TSC. Ex vivo and in vivo TSC were compared between 2D spiral sequences with full-sinc (TE = 0.73 ms, scan time ≈ 5 min) and half-sinc excitation (TE = 0.23 ms, scan time ≈ 10 min), with 150 NSAs. Ex vivo, these were compared to a reference 3D sequence (TE = 0.22 ms, scan time ≈ 24 min). To investigate shortening 2D scan times, half-sinc data was retrospectively reconstructed with fewer NSAs, comparing a nonuniform fast Fourier transform to CS. Resultant TSC and image quality were compared to reference 150 NSAs nonuniform fast Fourier transform images. TSC was significantly higher from half-sinc than from full-sinc acquisitions, ex vivo and in vivo. Ex vivo, half-sinc data more closely matched the reference 3D sequence, indicating improved accuracy. In silico modeling confirmed this was due to shorter TEs minimizing bias caused by relaxation differences between phantoms and tissue. CS was successfully applied to in vivo, half-sinc data, maintaining TSC and image quality (estimated SNR, edge sharpness, and qualitative metrics) with ≥50 NSAs. 2D sodium MRI with half-sinc excitation and CS was validated, enabling TSC quantification with 2.25 × 2.25 mm2 resolution and scan times of ≤5 mins.

Chronic changes in muscle architecture and aponeurosis structure following calf muscle strain injuries.

Muscle strain injuries in the human calf muscles are frequent sports injuries with high recurrence. Potential structural and functional changes in the medial head of the musculus gastrocnemius (GM) and the associated aponeurosis are not well documented. To test whether a GM muscle strain injury affects muscle fascicle length, pennation angle, and the morphology of the deep aponeurosis at rest and during muscle contraction long time after the injury. Additionally, electromyography (EMG) of the GM and the soleus muscle during a unilateral heel rise was measured in the injured and uninjured calf. GM fascicle length, pennation angle, and aponeurosis thickness was analyzed on dynamic ultrasonography (US) recordings in 10 participants with a chronic calf strain. In addition, US images taken across the distal portion and mid-belly of the GM were analyzed at three different ankle positions. EMG recordings were obtained during a unilateral heel rise. The pennation angle of the injured distal GM was significantly larger compared to the uninjured GM in the contracted, but not the relaxed state. Pennation angle increased more in the injured compared to the uninjured GM during contraction. Fascicle length was shorter in the most distal portion of the injured GM. Fascicles at the distal portion of the injured GM showed a pronounced curvilinear shape as the muscle contracted and the aponeurosis was enlarged in the injured compared to the uninjured GM. The ratio between GM and soleus EMG activity showed a significantly higher relative soleus activity in the injured compared to the healthy calf. The greater change in pennation angle and curvilinear fascicle shape during contraction suggest that a long-term consequence after a muscle strain injury is that some muscle fibers at the distal GM are not actively engaged. The significantly enlarged aponeurosis indicates a substantial and long-lasting connective tissue involvement following strain injuries.

A Fast Magnetic Flux Density Measurement Method With Skip-Echo Acquired Turbo Spin Echo (SATE).

The measurements of magnetic flux density ( Bz) needed in magnetic resonance electrical impedance tomography (MREIT) and magnetic resonance current density imaging (MRCDI) techniques often utilize spin echo (SE)-based sequences for data acquisition. The low imaging speed of SE-based methods significantly hampers the clinical applications of MREIT and MRCDI. Here, we propose a new sequence for substantially accelerating the acquisition of Bz measurements. A skip-echo acquired turbo spin echo (SATE) imaging sequence based on the conventional turbo spin echo (TSE) technique was proposed by adding a skip-echo module in front of the TSE acquisition module. The skip-echo module consisted of a series of refocusing pulses without acquisition. In SATE, amplitude-modulated crusher gradients were used to remove the stimulated echo pathways, and the radiofrequency (RF) pulse shape was specially selected to preserve more signals. In efficiency evaluation experiments performed on a spherical gel phantom, we demonstrated that SATE had improved measurement efficiency compared to the conventional TSE sequence via skipping one echo before acquiring signals. The accuracy of the Bz measurements by SATE was validated against those by the multi-echo injection current nonlinear encoding (ME-ICNE) method, while SATE was able to accelerate the data acquisition up to 10-fold. Volumetric coverage of Bz maps obtained in the phantom, pork, and human calf illustrated that SATE can reliably measure volumetric Bz distributions within clinically acceptable time. The proposed SATE sequence provides a fast and effective approach for volumetric coverage of Bz measurements, greatly facilitating the clinical applications of MREIT and MRCDI techniques.

Robust cardiac mapping at 3T using adiabatic spin-lock preparations.

The aim of this study is to develop and optimize an adiabatic ( ) mapping method for robust quantification of spin-lock (SL) relaxation in the myocardium at 3T. Adiabatic SL (aSL) preparations were optimized for resilience against and inhomogeneities using Bloch simulations. Optimized -aSL, Bal-aSL and -aSL modules, each compensating for different inhomogeneities, were first validated in phantom and human calf. Myocardial mapping was performed using a single breath-hold cardiac-triggered bSSFP-based sequence. Then, optimized preparations were compared to each other and to conventional SL-prepared maps (RefSL) in phantoms to assess repeatability, and in 13 healthy subjects to investigate image quality, precision, reproducibility and intersubject variability. Finally, aSL and RefSL sequences were tested on six patients with known or suspected cardiovascular disease and compared with LGE, , and ECV mapping. The highest preparation efficiency was obtained in simulations for modules comprising 2 HS pulses of 30 ms each. In vivo maps yielded significantly higher quality than RefSL maps. Average myocardial values were 183.28 25.53 ms, compared with 38.21 14.37 ms RefSL-prepared . maps showed a significant improvement in precision (avg. 14.47 3.71% aSL, 37.61 19.42% RefSL, p < 0.01) and reproducibility (avg. 4.64 2.18% aSL, 47.39 12.06% RefSL, p < 0.0001), with decreased inter-subject variability (avg. 8.76 3.65% aSL, 51.90 15.27% RefSL, p < 0.0001). Among aSL preparations, -aSL achieved the better inter-subject variability. In patients, -aSL preparations showed the best artifact resilience among the adiabatic preparations. times show focal alteration colocalized with areas of hyper-enhancement in the LGE images. Adiabatic preparations enable robust in vivo quantification of myocardial SL relaxation times at 3T.

Identification of new resonances in downfield 1 H MRS of human calf muscle in vivo: Potentially metabolite precursors for skeletal muscle NAD.

The purpose of this study was to identify and characterize newly discovered resonances appearing in the downfield proton MR spectrum (DF 1 H MRS) of the human calf muscle in vivo at 7T. Downfield 1 H MRS was performed on the calf muscle of five healthy volunteers at 7T. A spectrally selective 90° E-BURP RF pulse with an excitation center frequency at 10.3 ppm and an excitation bandwidth of 2 ppm was used for DF 1 H MRS acquisition. In all participants, we observed new resonances at 9.7, 10.1, 10.3, and 10.9 ppm in the DF 1 H MRS. Phantom experiments at 37°C strongly suggest the new resonance at 9.7 ppm could be from H2-proton of the nicotinamide rings in nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) while the resonance at 10.1 ppm could be attributed to the indole -NH proton of L-tryptophan. We observed that the resonances at 10.1 and 10.9 ppm are significantly suppressed when the water resonance is saturated, indicating that these peaks have either 1 H chemical exchange or cross-relaxation with water. Conversely, the resonances at 9.7 and 10.3 ppm exhibit moderate signal reduction in the presence of water saturation. We have identified new proton resonances in vivo in human calf muscle occurring at chemical shifts of 9.7, 10.1, 10.3, and 10.9 ppm. These preliminary results are promising for investigating the role of NR/NMN and L-tryptophan metabolism in understanding the de novo and salvage pathways of NAD+ synthesis in skeletal muscle.

Quantification of cross-relaxation in downfield 1 H MRS at7T in human calf muscle.

The purpose of this study was to characterize the 1 H downfield MR spectrum from 8.0 to 10.0ppm of human skeletal muscle at 7T and determine the T1 and cross-relaxation rates of observed resonances. We performed downfield MRS in the calf muscle of 7 healthy volunteers. Single-voxel downfield MRS was collected using alternately selective or broadband inversion-recovery sequences and spectrally selective 90° E-BURP RF pulse excitation centered at 9.0ppm with bandwidth = 600 Hz (2.0ppm). MRS was collected using TIs of 50-2500 ms. We modeled recovery of the longitudinal magnetization of three observable resonances using two models: (1) a three-parameter model accounting for the apparent T1 recovery and (2) a Solomon model explicitly including cross-relaxation effects. Three resonances were observed in human calf muscle at 7T at 8.0, 8.2, and 8.5ppm. We found broadband (broad) and selective (sel) inversion recovery T1 = mean ± SD (ms): T1-broad,8.0ppm = 2108.2 ± 664.5, T1-sel,8.0ppm = 753.6 ± 141.0 (p = 0.003); T1-broad,8.2ppm = 2033.5 ± 338.4, T1-sel,8.2ppm = 135.3 ± 35.3 (p < 0.0001); and T1-broad,8.5ppm = 1395.4 ± 75.4, T1-sel,8.5ppm = 107.1 ± 40.0 (p < 0.0001). Using the Solomon model, we found T1 = mean ± SD (ms): T1-8.0ppm = 1595.6 ± 491.1, T1-8.2ppm = 1737.2 ± 963.7, and T1-8.5ppm = 849.8 ± 282.0 (p =0.04). Post hoc tests corrected for multiple comparisons showed no significant difference in T1 between peaks. The cross-relaxation rate σAB = mean ± SD (Hz) of each peak was σAB,8.0ppm = 0.76 ± 0.20, σAB,8.2ppm = 5.31 ± 2.27, and σAB,8.5ppm = 7.90 ± 2.74 (p < 0.0001); post hoc t-tests revealed the cross-relaxation rate of the 8.0ppm peak was significantly slower than the peaks at 8.2 ppm (p =0.0018) and 8.5ppm (p =0.0005). We found significant differences in effective T1 and cross-relaxation rates of 1 H resonances between 8.0 and 8.5ppm in the healthy human calf muscle at 7T.

Apparent diffusion coefficients of 31P metabolites in the human calf muscle at 7 T

PurposeIn this study, we aimed to measure the apparent diffusion coefficients (ADCs) of major phosphorous metabolites in the human calf muscle at 7 T with a diffusion-weighted (DW)-STEAM sequence.MethodsA DW-STEAM sequence with bipolar gradients was implemented at 7 T, and DW MR spectra were acquired in three orthogonal directions in the human calf muscle of six healthy volunteers (TE/TM/TR = 15 ms/750 ms/5 s) at three b-values (0, 800, and 1200 s/mm2). Frequency and phase alignments were applied prior to spectral averaging. Averaged DW MR spectra were analyzed with LCModel, and ADCs of 31P metabolites were estimated.ResultsFour metabolites (phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and glycerol phosphorylcholine (GPC)) were quantified at all b-values with mean CRLBs below 10%. The ADC values of PCr, ATP, Pi, and GPC were (0.24 ± 0.02, 0.15 ± 0.04, 0.43 ± 0.14, 0.40 ± 0.09) × 10–3 mm2/s, respectively.ConclusionThe ADCs of four 31P metabolites were successfully measured in the human calf muscle at 7 T, among which those of ATP, Pi and GPC were reported for the first time in humans. This study paves the way to investigate 31P metabolite diffusion properties in health and disease on the clinical MR scanner.

Ultrasound Matrix Imaging-Part I: The Focused Reflection Matrix, the F-Factor and the Role of Multiple Scattering.

This is the first article in a series of two dealing with a matrix approach for aberration quantification and correction in ultrasound imaging. Advanced synthetic beamforming relies on a double focusing operation at transmission and reception on each point of the medium. Ultrasound matrix imaging (UMI) consists in decoupling the location of these transmitted and received focal spots. The response between those virtual transducers form the so-called focused reflection matrix that actually contains much more information than a confocal ultrasound image. In this paper, a time-frequency analysis of this matrix is performed, which highlights the single and multiple scattering contributions as well as the impact of aberrations in the monochromatic and broadband regimes. Interestingly, this analysis enables the measurement of the incoherent input-output point spread function at any pixel of this image. A fitting process enables the quantification of the single scattering, multiple scattering and noise components in the image. From the single scattering contribution, a focusing criterion is defined, and its evolution used to quantify the amount of aberration throughout the ultrasound image. In contrast to the state-of-the-art coherence factor, this new indicator is robust to multiple scattering and electronic noise, thereby providing a contrasted map of the focusing quality at a much better transverse resolution. After a validation of the proof-of-concept based on time-domain simulations, UMI is applied to the in-vivo study of a human calf. Beyond this specific example, UMI opens a new route for speed-of-sound and scattering quantification in ultrasound imaging.

Fast NURBS-based parametric modeling of human calves with high-accuracy for personalized design of graduated compression stockings

Background and objectivesAccurate human body models are increasingly demanded by high-quality human-centered ergonomic applications, especially the design and manufacturing of compressive functional apparels. However, existing parametric models in related works are not capable to accurately describe detailed local shape features of human. MethodsIn this work, a high-accuracy parametric modeling approach for human limb was proposed. 3D Scans of human calves were studied. Key data points of the scanned human calves were identified according to human anatomy, forming a quasi-triangular mesh of feature points. Then, non-uniform rational B-splines (NURBS) method was implemented. Control points were calculated from the key data points, with which the human calf shapes can be reconstructed by the smooth NURBS surface, giving rise to a new parametric model of human calves. Error between the scanned and reconstructed calf shapes were analyzed to verify the effectiveness of this model. ResultsError analysis showed that, this proposed method delivers a high-efficiency and high-accuracy parametric shape modeling approach with averaged error observed as only 0.37% for all the 260 subjects, much less compared to previous relative works (around 5%). For tentative application, customized medical compression stockings were designed based on this model and proved as valid to exert desired gradient compression on the according calf mannequin. ConclusionsBy introducing the non-uniform rational B-splines method, a parametric model capable of characterizing human limbs with high-accuracy was proposed. Using very small amount of data, this model is expected to highly facilitate remote customized design and provide 3D shape references for design of compressive garments. Moreover, the proposed methods can inspire developments of other mixed modeling methods for high-accuracy applications.

The moisturizing effect of Capparis spinosa fruit extract targeting filaggrin synthesis and degradation.

Small molecular natural products, such as betaine, have unique moisturizing advantages. Capparis spinosa L. fruit is rich in quaternary ammonium alkaloids such as betaine and stachydrine. However, few studies investigated its efficacy and mechanism on human skin. Polysaccharides-free C. spinosa fruit extract (CS) was obtained to study its moisturizing effect and mechanisms focusing on filaggrin (FLG) synthesis and degradation. The clinical moisturizing test was carried out on human arms, calves, and faces after CS treatment for 0.5-6h. The change in the level of FLG, caspase 14, loricrin, and transglutaminase 5 (TGM 5) was measured by immunofluorescence after CS treatment for 4 and 24 h in a reconstructed epidermis model. Also, the content of pyrrolidone carboxylic acid (PCA) in the stratum corneum was tested by high-performance liquid chromatography (HPLC) both in the epidermis model and human calves. Compared with glycerin (positive control), 5% CS showed a strong skin hydration effect on arms and calves when applied for 0.5-6h. Also, the face hydration increased at 0.5 and 4 h. In addition, 3% CS applied to the recombinant epidermis model under low humidity promoted the immunodetected levels of caspase 14 and PCA content but reduced the levels of FLG at 4h, however, the levels of FLG, loricrin, and TGM 5 were promoted at 24 h. Meanwhile, CS treatment for 4h in human calves increased the PCA content in the stratum corneum by 29.9%. Topical application of CS on human skin showed an instant and long-lasting increase in skin hydration by regulating the FLG network. It promoted FLG degradation to form PCA at 4h both in vivo and in vitro, increasing FLG synthesis after 24 h, potentially reforming the FLG monomer reservoir to alleviate the skin's dry condition.

Repeatability assessment of sodium (23Na) MRI at 7.0 T in healthy human calf muscle and preliminary results on tissue sodium concentrations in subjects with Addison’s disease

ObjectivesTo determine the relaxation times of the sodium nucleus, and to investigate the repeatability of quantitative, in vivo TSC measurements using sodium magnetic resonance imaging (23Na-MRI) in human skeletal muscle and explore the discriminatory value of the method by comparing TSCs between healthy subjects and patients with Addison’s disease.Materials and methodsIn this prospective study, ten healthy subjects and five patients with Addison’s disease were involved. 23Na-MRI data sets were acquired using a density-adapted, three-dimensional radial projection reconstruction pulse sequence (DA-3DPR) with a modification for the relaxation times measurements. Differences in TSC between muscle groups and between healthy participants were analysed using a nonparametric Friedman ANOVA test. An interclass correlation coefficient (ICC) was used as the repeatability index. Wilcoxon rank sum test was used for evaluation of differences in TSC between study participants.ResultsThe mean T1 in the gastrocnemius medialis (GM), the tibialis anterior (TA), and the soleus (S) was 25.9 ± 2.0 ms, 27.6 ± 2.0 ms, and 28.2 ± 2.0 ms, respectively. The mean short component of T2*, T2*short were GM: 3.6 ± 2.0 ms; TA: 3.2 ± 0.5 ms; and S: 3.0 ± 1.0 ms, and the mean long component of T2*, T2*long, were GM: 12.9 ± 0.9 ms; TA: 12.8 ± 0.7 ms; and S: 12.9 ± 2.0 ms, respectively. In healthy volunteers, TSC values in the GM were 19.9 ±0.1 mmol/L, 13.8 ±0.2 mmol/L in TA, and 12.6 ± 0.2 mmol/L in S, and were significantly different (p = 0.0005). The ICCs for GM, TA and S were 0.784, 0.818, 0.807, respectively. In patients with Addison’s disease, TSC in GC, TA, and S were 10.2 ± 1.0 mmol/L, 8.4 ± 0.6 mmol/L, and 7.2 ± 0.1 mmol/L, respectively.ConclusionsTSC quantification in a healthy subject’s calf at 7.0 T is reliable; the technique is able to distinguish sodium level differences between muscles and between healthy subjects and Addison’s disease patients.

Magnetic Resonance Elastography Reconstruction for Anisotropic Tissues.

Elastography has become widely used clinically for characterising changes in soft tissue mechanics that are associated with altered tissue structure and composition. However, some soft tissues, such as muscle, are not isotropic as is assumed in clinical elastography implementations. This limits the ability of these methods to capture changes in anisotropic tissues associated with disease. The objective of this study was to develop and validate a novel elastography reconstruction technique suitable for estimating the linear viscoelastic mechanical properties of transversely isotropic soft tissues. We derived a divergence-free formulation of the governing equations for acoustic wave propagation through a linearly transversely isotropic viscoelastic material, and transformed this into a weak form. This was then implemented into a finite element framework, enabling the analysis of wave input data and tissue structural fibre orientations, in this case based on diffusion tensor imaging. To validate the material constants obtained with this method, numerous in silico phantom experiments were run which encompassed a range of variations in wave input directions, material properties, fibre structure and noise. The method was also tested on ex vivo muscle and in vivo human volunteer calf muscles, and compared with a previous curl-based inversion method. The new method robustly extracted the transversely isotropic shear moduli (G⊥', G∥', G″) from the in silico phantom tests with minimal bias, including in the presence of experimentally realistic levels of noise in either fibre orientation or wave data. This new method performed better than the previous method in the presence of noise. Anisotropy estimates from the ex vivo muscle phantom agreed well with rheological tests. In vivo experiments on human calf muscles were able to detect increases in muscle shear moduli with passive muscle stretch. This new reconstruction method can be applied to quantify tissue mechanical properties of anisotropic soft tissues, such as muscle, in health and disease.