[Show abstract][Hide abstract] ABSTRACT: Quantitative Cardiovascular Magnetic Resonance (CMR) techniques have gained high interest in CMR research. Myocardial T2 mapping is thought to be helpful in diagnosis of acute myocardial conditions associated with myocardial edema. In this study we aimed to establish a technique for myocardial T2 mapping based on gradient-spin-echo (GraSE) imaging.
The local ethics committee approved this prospective study. Written informed consent was obtained from all subjects prior to CMR. A modified GraSE sequence allowing for myocardial T2 mapping in a single breath-hold per slice using ECG-triggered acquisition of a black blood multi-echo series was developed at 1.5 Tesla. Myocardial T2 relaxation time (T2-RT) was determined by maximum likelihood estimation from magnitude phased-array multi-echo data. Four GraSE sequence variants with varying number of acquired echoes and resolution were evaluated in-vitro and in 20 healthy volunteers. Inter-study reproducibility was assessed in a subset of five volunteers. The sequence with the best overall performance was further evaluated by assessment of intra- and inter-observer agreement in all volunteers, and then implemented into the clinical CMR protocol of five patients with acute myocardial injury (myocarditis, takotsubo cardiomyopathy and myocardial infarction).
In-vitro studies revealed the need for well defined sequence settings to obtain accurate T2-RT measurements with GraSE. An optimized 6-echo GraSE sequence yielded an excellent agreement with the gold standard Carr-Purcell-Meiboom-Gill sequence. Global myocardial T2 relaxation times in healthy volunteers was 52.2 ± 2.0 ms (mean ± standard deviation). Mean difference between repeated examinations (n = 5) was −0.02 ms with 95% limits of agreement (LoA) of [−4.7; 4.7] ms. Intra-reader and inter-reader agreement was excellent with mean differences of −0.1 ms, 95% LoA = [−1.3; 1.2] ms and 0.1 ms, 95% LoA = [−1.5; 1.6] ms, respectively (n = 20). In patients with acute myocardial injury global myocardial T2-RTs were prolonged (mean: 61.3 ± 6.7 ms).
Using an optimized GraSE sequence CMR allows for robust, reliable, fast myocardial T2 mapping and quantitative tissue characterization. Clinically, the GraSE-based T2-mapping has the potential to complement qualitative CMR in patients with acute myocardial injuries.
Journal of Cardiovascular Magnetic Resonance 02/2015; 17(1). DOI:10.1186/s12968-015-0127-z · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multispectral photoacoustic laser diode systems have multiple wavelengths available simultaneously. In addition to multispectral imaging, this can be exploited to increase the signal to noise ratio (SNR) by combining these wavelengths to form a combined image, but at the loss of spectral information. Here, a novel signal processing concept is introduced, which optimizes the SNR in the reconstructions of single wavelength data from combined acquisitions while simultaneously permitting to obtain a higher SNR fused image from the same data. The concept is derived for an arbitrary number of wavelengths; it is also applicable at low pulse repetition frequencies. The concept is applied in an experiment using two wavelengths, verifying the theoretical results.
[Show abstract][Hide abstract] ABSTRACT: We report an experimental finding of photoacoustic signal enhancement from finite sized DNA–gold nanoparticle networks. We synthesized DNA-functionalized hollow and solid gold nanospheres (AuNS) to form finite sized networks, which were characterized by means of optical extinction spectroscopy, dynamic light scattering, and scanning electron microscopy in transmission mode. It is shown that the signal amplification scales with network size for networks comprising either hollow or solid AuNS as well as networks consisting of both types of nanoparticles. The laser intensities applied in our multispectral setup (λ = 650 nm, 850 nm, 905 nm) were low enough to maintain the structural integrity of the networks. This reflects that the binding and recognition properties of the temperature-sensitive cross-linking DNA-molecules are retained.
[Show abstract][Hide abstract] ABSTRACT: Purpose: To evaluate the use of the recently proposed ultrafast B1(+) mapping approach DREAM (Dual Refocusing Echo Acquisition Mode) for a refinement of patient adaptive radiofrequency (RF) shimming. Materials and Methods: Volumetric DREAM B1(+) calibration scans centered in the upper abdomen were acquired in 20 patients and three volunteers with written informed consent at a clinical dual source 3 Tesla (T) MR system. Based on these data, RF transmit settings were optimized by central-slice based RF-shimming (CS-RF shim) and by a refined, multi-slice adaptive approach (MS-RF shim). Simulations were performed to compare flip angle accuracy and B1(+) homogeneity (cv = stddev/mean) achieved by CS-RF shim versus MS-RF shim for transversal and coronal slices, and for volume shimming on the spine. Results: By MS-RF shim, mean deviation from nominal flip angle was reduced to less than 11% in all slices, all targets, and all subjects. Relative improvements in B1(+) cv (MS-RF shim versus CS-RF) were up to 14%/39%/47% in transversal slices/coronal slices/spine area. Conclusion: Volumetric information about B1(+) can be used to further improve the accuracy and homogeneity of the B1(+) field yielding higher diagnostic confidence, and will also be of value for various quantitative methods which are sensitive to flip angle imperfections.
Journal of Magnetic Resonance Imaging 10/2014; 40(4). DOI:10.1002/jmri.24438 · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In pulse-echo ultrasound imaging (PEUI) of soft tissues, the scattered sound field is governed by spatial fluctuations of the two mechanical parameters compressibility and mass density. Spatial fluctuations in compressibility act as isotropic monopole radiators while spatial fluctuations in mass density act as anisotropic dipole radiators. Conventional strategies for linear image reconstruction in PEUI, e.g., delay-and-sum, minimum variance, and synthetic aperture focusing, exclusively account for monopole scattering. This neglect of the inhomogeneous mass density might be accompanied by a loss of diagnostically relevant information, e.g., the detection of tissue abnormalities. In this study, we formulate a linear inverse scattering problem to recover separate, space-resolved maps of the spatial fluctuations in both mechanical parameters from measurements of the scattered acoustic pressure. The physical model accounts for frequency-dependent absorption and dispersion in accordance with the time causal model. The computational costs are effectively reduced by the usage of the fast multipole algorithm. The concept is evaluated using simulated and experimentally obtained radio frequency data.
The Journal of the Acoustical Society of America 04/2014; 135(4):2179. DOI:10.1121/1.4877088 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: When applying quantitative ultrasound (QUS) measurements to bone for predicting osteoporotic fracture risk, the multipath transmission of sound waves frequently occurs. In the last 10 years, the interest in separating multipath QUS signals for their analysis awoke, and led to the introduction of several approaches. Here, we compare the performances of the two fastest algorithms proposed for QUS measurements of bone: the modified least-squares Prony method (MLSP), and the space alternating generalized expectation maximization algorithm (SAGE) applied in the frequency domain. In both approaches, the parameters of the transfer functions of the sound propagation paths are estimated. To provide an objective measure, we also analytically derive the Cramér-Rao lower bound of variances for any estimator and arbitrary transmit signals. In comparison with results of Monte Carlo simulations, this measure is used to evaluate both approaches regarding their accuracy and precision. Additionally, with simulations using typical QUS measurement settings, we illustrate the limitations of separating two superimposed waves for varying parameters with focus on their temporal separation. It is shown that for good SNRs around 100 dB, MLSP yields better results when two waves are very close. Additionally, the parameters of the smaller wave are more reliably estimated. If the SNR decreases, the parameter estimation with MLSP becomes biased and inefficient. Then, the robustness to noise of the SAGE clearly prevails. Because a clear influence of the interrelation between the wavelength of the ultrasound signals and their temporal separation is observable on the results, these findings can be transferred to QUS measurements at other sites. The choice of the suitable algorithm thus depends on the measurement conditions.
IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control 09/2013; 60(9):1884-1895. DOI:10.1109/TUFFC.2013.2773 · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In diagnostic ultrasound imaging, the image reconstruction quality is crucial for reliable diagnosis. Applying reconstruction algorithms based on the acoustic wave equation, the obtained image quality depends significantly on the physical material parameters accounted for in the equation. In this contribution, we extend a proposed iterative nonlinear one-parameter compressibility reconstruction algorithm by the additional reconstruction of the object's inhomogeneous mass density distribution. The improved iterative algorithm is able to reconstruct inhomogeneous maps of the object's compressibility and mass density simultaneously using only one conventional linear transducer array at a fixed location for wave transmission and detection. The derived approach is based on an acoustic wave equation including spatial compressibility and mass density variations, and utilizes the Kaczmarz method for iterative material parameter reconstruction. We validate our algorithm numerically for an unidirectional pulse-echo breast imaging application, and thus generate simulated measurements acquired from a numerical breast phantom with realistic compressibility and mass density values. Applying these measurements, we demonstrate with two reconstruction experiments the necessity to calculate the mass density in case of tissues with significant mass density inhomogeneities. When reconstructing spatial mass density variations, artefacts in the breast's compressibility image are reduced resulting in improved spatial resolution. Furthermore, the compressibility relative error magnitude within a diagnostically significant region of interest (ROI) decreases from 3.04% to 2.62%. Moreover, a second image showing the breast's inhomogeneous mass density distribution is given to provide additional diagnostic information. In the compressibility image, a spatial resolution moderately higher than the classical half-wavelength limit is observed.
Physics in Medicine and Biology 08/2013; 58(17):6163-6178. DOI:10.1088/0031-9155/58/17/6163 · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonlinear ultrasound diffraction tomography reconstructs material parameters of a medium from transmitted and scattered sound waves taking into account multiple scattering. A few nonlinear approaches propose algorithms to reconstruct the spatially varying speed of sound (SoS) or alternatively the spatially varying compressibility and mass density. These methods consider longitudinal wave propagation, but not the shear wave propagation which is important in elastic media like in muscle tissue or bone. Here, we present an extension of a nonlinear reconstruction algorithm based on the Kaczmarz method to reconstruct bulk and shear moduli in isotropic solids simultaneously. The morphology of the solid inclusion can be imaged using this approach. This is a first step towards the reconstruction of hard tissues like bone and cartilage possibly enabling the assessment of the cortical thickness of bones.
[Show abstract][Hide abstract] ABSTRACT: In this contribution, we propose a method to track single microbubbles. The aim of this method is the reconstruction of microvessels. An experiment with a vessel phantom was set up. The flow rate of a suspension (concentration 20/ml) of cyanoacrylate microbubbles was adjusted by a syringe pump. B-Mode images were acquired with a Vevo 2100 small animal imaging system (Visualsonics) at 255 fps. The positions of single microbubbles were identified from B-Mode images by a median filter based foreground/background separation algorithm. These positions were used by a novel Markov chain monte carlo data association (MCMCDA) algorithm to estimate the microbubbles' velocity. The mean values (8.7, 4.17, and 2.63 mm/s) of estimated single mircobubble speeds were in good agreement with the adjusted flow speed (8.8, 3.5 and 1.8 mm/s).
2013 IEEE International Ultrasonics Symposium (IUS); 07/2013
[Show abstract][Hide abstract] ABSTRACT: While established linear pulse-echo ultrasound imaging concepts like synthetic aperture (SA) focusing and delay-and-sum (DAS) beamforming solely image tissue features under single scattering, nonlinear reconstruction methods have been proposed to compute quantitative maps of the tissue's material parameters (e.g. compressibility, mass density, speed of sound) under multiple scattering. In the present contribution, we apply a previously proposed nonlinear simultaneous compressibility and mass density reconstruction algorithm and investigate numerically the image reconstruction quality in contrast to linear SA under cylindrical wave (cw) excitation and linear DAS under plane wave (pw) excitation. Using raw data acquired from a Shepp-Logan phantom (SLP) with typical soft tissue compressibility and mass density values, nonlinear reconstruction using cylindrical wave excitation provides high-resolution images with a mean magnitude of relative error of about 4.27% and 3.18% within a region of interest (ROI) in the compressibility and mass density image, outperforming the image quality reached under plane wave excitation. Applying identical raw data, SA and DAS with both predefined and adapted apodization weights yield less-detailed image reconstructions solely showing tissue boundaries. Furthermore, calculating full width at half maximum (FWHM) resolutions of all methods, the nonlinear approach mainly yields smaller axial and lateral resolutions in contrast to SA and DAS.
2013 IEEE International Ultrasonics Symposium (IUS); 07/2013
[Show abstract][Hide abstract] ABSTRACT: We investigated the separate recovery of spatial fluctuations in compressibility and mass density by plane wave pulse-echo ultrasound imaging based on sparse recovery (SR). Using simulated radio frequency (RF) data obtained from a sparse and a nonsparse object, we demonstrated that the recovery of space-resolved maps of both material parameters with small relative root mean-squared errors (RMSEs) was feasible. For a signal-to-noise ratio of 40 dB, the relative RMSEs were smaller than 4%. For noiseless RF data, recovery was flawless. Using real RF data acquired from a human common carotid artery (in vivo), the presented concept yielded two space-resolved maps emphasizing different features of the object.
2013 IEEE International Ultrasonics Symposium (IUS); 07/2013
[Show abstract][Hide abstract] ABSTRACT: Solid state laser systems are commonly employed for photoacoustic imaging, but cheap and handy pulsed laser diodes are an attractive alternative. They emit low pulse energies, but fast averaging is possible due to high achievable repetition rates in order to improve the Signal to Noise ratio (SNR). While averaging is limited by the time of flight of the acoustic signal, photoacoustic coded excitation (PACE) can be used to overcome this limitation. Here, we examine the performance of these PACE codes based on pulse position modulation (PPM). PPM codes rely on varying time distances between successive laser pulses. By varying time differences, the autocorrelation sidelobes of the PPM code, which are a measure for the amount of distortion caused by the coding, can be kept low. For short codes or high sampling rates, low maximum autocorrelation side lobe amplitudes equal to the single pulse amplitude are possible. The gain in SNR was calculated theoretically and compared to previously published sequences. The theoretical results were verified in experiments. PPM codes achieve a coding gain that exceeds that of previously reported codes. For long codes the performance drops. Because the reconstruction is not perfect, side lobes induced by the code can degrade image quality.
2013 IEEE International Ultrasonics Symposium (IUS); 07/2013
[Show abstract][Hide abstract] ABSTRACT: We extended our concept for fast image acquisition in pulse-echo ultrasound imaging based on sparse recovery (SR) to compensate for the combined effects of absorption and dispersion. Using measurement data obtained from a multi-tissue phantom (A) and a human thyroid (B, in vivo), we demonstrated that image quality can be significantly improved by this extension. Emitting only two steered plane waves, our extended SR-based concept outperformed synthetic aperture (SA) imaging (128 wave emissions), delay-and-sum beamforming (11 wave emissions), and minimum variance beamforming (11 wave emissions) in terms of contrast for object A. Lateral -6 dB-widths were similar to SA. For object B, SR improved the visibility of anatomical contours in contrast to the algorithms used for comparison.
2013 IEEE International Ultrasonics Symposium (IUS); 07/2013
[Show abstract][Hide abstract] ABSTRACT: The effect of variations in microbubble shell composition on microbubble resonance frequency is revealed through experiment. These variations are achieved by altering the mole fraction and molecular weight of functionalized polyethylene glycol (PEG) in the microbubble phospholipid monolayer shell and measuring the microbubble resonance frequency. The resonance frequency is measured via a chirp pulse and identified as the frequency at which the pressure amplitude loss of the ultrasound wave is the greatest as a result of passing through a population of microbubbles. For the shell compositions used herein, we find that PEG molecular weight has little to no influence on resonance frequency at an overall PEG mole fraction (0.01) corresponding to a mushroom regime and influences the resonance frequency markedly at overall PEG mole fractions (0.050-0.100) corresponding to a brush regime. Specifically, the measured resonance frequency was found to be 8.4, 4.9, 3.3 and 1.4 MHz at PEG molecular weights of 1000, 2000, 3000 and 5000 g/mol, respectively, at an overall PEG mole fraction of 0.075. At an overall PEG mole fraction of just 0.01, on the other hand, resonance frequency exhibited no systematic variation, with values ranging from 5.7 to 4.9 MHz. Experimental results were analyzed using the Sarkar bubble dynamics model. With the dilatational viscosity held constant (10(-8) N·s/m) and the elastic modulus used as a fitting parameter, model fits to the pressure amplitude loss data resulted in elastic modulus values of 2.2, 2.4, 1.6 and 1.8 N/m for PEG molecular weights of 1000, 2000, 3000 and 5000 g/mol, respectively, at an overall PEG mole fraction of 0.010 and 4.2, 1.4, 0.5 and 0.0 N/m, respectively, at an overall PEG mole fraction of 0.075. These results are consistent with theory, which predicts that the elastic modulus is constant in the mushroom regime and decreases with PEG molecular weight to the inverse 3/5 power in the brush regime. Additionally, these results are consistent with inertial cavitation studies, which revealed that increasing PEG molecular weight has little to no effect on inethe rtial cavitation threshold in the mushroom regime, but that increasing PEG molecular weight decreases inertial cavitation markedly in the brush regime. We conclude that the design and synthesis of microbubbles with a prescribed resonance frequency is attainable by tuning PEG composition and molecular weight.
Ultrasound in medicine & biology 05/2013; 39(7). DOI:10.1016/j.ultrasmedbio.2013.02.462 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The detection of microbubble contrast agents with ultrasound imaging techniques is the subject of ongoing research. Commonly, the nonlinear response of the agent is employed for detection. The performance of these techniques is, however, affected by nonlinear sound propagation. As an alternative, the change in echo response resulting from microbubble destruction can be employed to detect the agent. In this work, we propose a novel criterion for microbubble destruction detection that allows the rejection of tissue at a defined significance level even for highly echogenic structures in the presence of nonlinear propagation. Most clinical systems provide the hardware requirements for acquisitions consisting of multiple pulses transmitted at the same position, as used in Doppler imaging. Therefore, we develop a processing strategy that distinguishes contrast agent from other stationary or moving structures using these sequences. The proposed criterion is based on the variance of the phase shift of consecutive echoes in the sequence, which, in addition to tissue rejection, permits the distinction of motion from agent disruption. Phantom experiments are conducted to show the validity of the criterion and demonstrate the performance of the new method for contrast detection. Each detection series consists of 20 identical pulses at 9.5 MHz (4.7 MPa peak negative pressure) transmitted at a pulse repetition frequency of 5 kHz. The sequence is applied to phantoms under varied motion and flow conditions. As a first step toward molecular imaging, the technique is applied to microbubbles targeted to vascular endothelial growth factor receptor 2 (VEGFR2) in vitro. The results show a uniform rejection of the background signal while maintaining a contrast enhancement by more than 40 dB. The area under the receiver operating characteristics (ROC) curve is used as the performance metric for the separation of contrast agent and tissue signals, and values larger than 97% demonstrate that an excellent separation was achieved.
IEEE transactions on ultrasonics, ferroelectrics, and frequency control 05/2013; 60(5):909-23. DOI:10.1109/TUFFC.2013.2648 · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effect of modifying the shell composition of a population of microbubbles on their size demonstrated through experiment. Specifically, these variations include altering both the mole fraction and molecular weight of functionalized polymer, polyethylene glycol (PEG) in the microbubble phospholipid monolayer shell (1-15mol% PEG, and 1000-5000g/mole, respectively). The size distribution is measured with an unbiased image segmentation program written in MATLAB which identifies and sizes bubbles from micrographs. For a population of microbubbles with a shell composition of 5mol% PEG2000, the mean diameter is 1.42μm with a variance of 0.244μm. For the remainder of the shell compositions studied herein, we find that the size distributions do not show a statistically significant correlation to either PEG molecular weight or mole fraction. All the measured distributions are nearly Gaussian in shape and have a monomodal peak.
[Show abstract][Hide abstract] ABSTRACT: This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition - in particular, poly (ethylene glyclol) (PEG) - is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the "brush" regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those - not necessarily involving microubbles - to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly "theranostic" vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery.