Pulse Inversion Research Articles

Suppression of the Tissue Component With the Total Least‐Squares Algorithm to Improve Second Harmonic Imaging of Ultrasound Contrast Agents

ABSTRACTThe second harmonic (SH) of ultrasound contrast agents (UCAs) is widely used in contrast‐enhanced ultrasound imaging; however, is affected by the nonlinearity of surrounding tissue. Suppression of the tissue component based on the total least‐squares (STLS) algorithm is proposed to enhance the SH imaging of UCAs. The image blocks of pulse‐inversion‐based SH images before and after UCA injections are set as the reference and input of the total least‐squares model, respectively. The optimal coefficients of the model are obtained by minimizing the Frobenius norm of perturbations in the input and output signals. After processing all image blocks, the complete SH image of UCAs is obtained by subtracting the optimal output of the model (i.e., the estimated tissue SH image) from the SH image after UCA injection. Simulation and in vivo experiments confirm that the STLS approach offers clearer capillaries. For in vivo experiments, the STLS‐based contrast‐to‐tissue ratios and contrasts increase by 26.90% and 56.27%, as well as 26.99% and 56.43%, respectively, compared with those based on bubble‐echo deconvolution and pulse inversion bubble‐wavelet imaging methods. The STLS approach enhances the SH imaging of UCAs by effectively suppressing more tissue SH components, having the potential to provide more accurate diagnostic information for clinical applications.

Vibrational squeezing via spin inversion pulses

Magnetic resonance force microscopy (MRFM) describes a range of approaches to detect nuclear spins with mechanical sensors. MRFM has the potential to enable magnetic resonance imaging with near-atomic spatial resolution, opening up exciting possibilities in solid state and biological research. In many cases, the spin-mechanics coupling in MRFM is engineered with the help of periodic radio frequency pulses. In this paper, we report that such pulses can result in unwanted parametric amplification of the mechanical vibrations, causing misinterpretation of the measured signal. We show how the parametric effect can be canceled by auxiliary radio frequency pulses or by appropriate post-correction after careful calibration. Future MRFM measurements may even make use of the parametric amplification to reduce the impact of amplifier noise.

A Radiological Clip Design Using Ultrasound Identification to Improve Localization.

We demonstrate the use of ultrasound to receive an acoustic signal transmitted from a radiological clip designed from a custom circuit. This signal encodes an identification number and is localized and identified wirelessly by the ultrasound imaging system. We designed and constructed the test platform with a Teensy 4.0 microcontroller core to detect ultrasonic imaging pulses received by a transducer embedded in a phantom, which acted as the radiological clip. Ultrasound identification (USID) signals were generated and transmitted as a result. The phantom and clip were imaged using an ultrasonic array (Philips L7-4) connected to a Verasonics™ Vantage 128 system operating in pulse inversion (PI) mode. Cross-correlations were performed to localize and identify the code sequences in the PI images. USID signals were detected and visualized on B-mode images of the phantoms with up to sub-millimeter localization accuracy. The average detection rate across 30,400 frames of ultrasound data was 98.1%. The USID clip produced identifiable, distinguishable, and localizable signals when imaged. Radiological clips are used to mark breast cancer being treated by neoadjuvant chemotherapy (NAC) via implant in or near treated lesions. As NAC progresses, available marking clips can lose visibility in ultrasound, the imaging modality of choice for monitoring NAC-treated lesions. By transmitting an active signal, more accurate and reliable ultrasound localization of these clips could be achieved and multiple clips with different ID values could be imaged in the same field of view.

Advancing 7T perfusion imaging by pulsed arterial spin labeling: Using a parallel transmit coil for enhanced labeling robustness and temporal SNR.

Non-invasive perfusion imaging by Arterial spin labeling (ASL) can be advantageous at Ultra-high field (UHF) MRI, since the image SNR and the T1 relaxation time both increase with the static field. However, ASL implementation, especially at 7T, is not trivial. Especially for ASL, UHF MRI comes with many challenges, mainly due to B1+ inhomogeneities. This study aimed to investigate the effects of different transmit coil configurations on perfusion-weighted imaging at 7T using a flow-sensitive alternating inversion recovery (FAIR) technique with time-resolved frequency offset corrected inversion (TR-FOCI) pulses for labeling and background suppression. We conducted a performance comparison between a parallel transmit (pTx) system equipped with 32 receive (Rx) and 8 transmit (Tx) channels and a standard setup with 32Rx and 2Tx channels. Our findings demonstrate that the pTx system, characterized by a more homogeneous B1 transmit field, resulted in a significantly higher contrast-to-noise ratio, temporal signal-to-noise ratio, and lower coefficient of variance (CoV) than the standard 2Tx setup. Additionally, both setups demonstrated comparable capabilities for functional mapping of the hand region in the motor cortex, achieving reliable results within a short acquisition time of approximately 5 minutes.

Respiratory motion-corrected T1 mapping of the abdomen.

The purpose of this study was to investigate an approach for motion-corrected T1 mapping of the abdomen that allows for free breathing data acquisition with 100% scan efficiency. Data were acquired using a continuous golden radial trajectory and multiple inversion pulses. For the correction of respiratory motion, motion estimation based on a surrogate was performed from the same data used for T1 mapping. Image-based self-navigation allowed for binning and reconstruction of respiratory-resolved images, which were used for the estimation of respiratory motion fields. Finally, motion-corrected T1 maps were calculated from the data applying the estimated motion fields. The method was evaluated in five healthy volunteers. For the assessment of the image-based navigator, we compared it to a simultaneously acquired ultrawide band radar signal. Motion-corrected T1 maps were evaluated qualitatively and quantitatively for different scan times. For all volunteers, the motion-corrected T1 maps showed fewer motion artifacts in the liver as well as sharper kidney structures and blood vessels compared to uncorrected T1 maps. Moreover, the relative error to the reference breathhold T1 maps could be reduced from up to 25% for the uncorrected T1 maps to below 10% for the motion-corrected maps for the average value of a region of interest, while the scan time could be reduced to 6-8s. The proposed approach allows for respiratory motion-corrected T1 mapping in the abdomen and ensures accurate T1 maps without the need for any breathholds.

Cerebrospinal Fluid Dynamics Analysis Using Time-Spatial Labeling Inversion Pulse (Time-SLIP) Magnetic Resonance Imaging in Mice.

Background/Objectives: Abnormalities in cerebrospinal fluid (CSF) dynamics cause diverse conditions, such as hydrocephalus, but the underlying mechanism is still unknown. Methods to study CSF dynamics in small animals have not been established due to the lack of an evaluation system. Therefore, the purpose of this research study is to establish the time-spatial labeling inversion pulse (Time-SLIP) MRI technique for the evaluation of CSF dynamics in mice. Methods: We performed the Time-SLIP technique on 10 wild-type mice and 20 Tiptoe-walking Yoshimura (TWY) mice, a mouse model of ossification of the posterior longitudinal ligament (OPLL). We defined the stir distance as the distance of CSF stirring and calculated the mean ± standard deviation. The intraclass correlation coefficient of intraobserver reliability was also calculated. Furthermore, in TWY mice, the correlation coefficient between stir distance and canal stenosis ratio (CSR) was calculated. Results: The stir distance was significantly lower in TWY mice at 12 weeks and 17 weeks of age (1.20 ± 0.16, 1.21 ± 0.06, and 1.21 ± 0.15 mm at 12 weeks and 1.32 ± 0.21, 1.28 ± 0.23, and 1.38 ± 0.31 mm at 17 weeks for examiners A, B, and C). The intrarater reliability of the three examiners was excellent (>0.90) and there was a strongly negative correlation between stir distance and CSR in TWY mice (>-0.80). Conclusions: In this study, we established the Time-SLIP technique in experimental mice. This technique allows for a better understanding of CSF dynamics in small laboratory animals.

Reduced B0/B1 + sensitivity in velocity-selective inversion arterial spin labeling using adiabatic refocusing pulses.

To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.

Visualization of Cerebrospinal Fluid Outflow and Egress along the Nerve Roots of the Lumbar Spine.

Intrinsic cerebrospinal fluid (CSF) dynamics in the brain have been extensively studied, particularly the egress sites of tagged intrinsic CSF in the meninges. Although spinal CSF recirculates within the central nervous system (CNS), we hypothesized that CSF outflows from the lumbar spinal canal. We aimed to visualize and semi-quantify the outflow using non-contrast MRI techniques. We utilized a 3 Tesla clinical MRI with a 16-channel spine coil, employing time-spatial labeling inversion (Time-SLIP) with tag-on and tag-off acquisitions, T2-weighted coronal 2D fluid-attenuated inversion recovery (FLAIR) and T2-weighted coronal 3D centric ky-kz single-shot FSE (cSSFSE). Images were acquired using time-spatial labeling inversion pulse (Time-SLIP) with tag-on and tag-off acquisitions with varying TI periods. Ten healthy volunteers with no known spinal diseases participated. Variations in tagged CSF outflow were observed across different thoracolumbar nerve root segments in all participants. We quantified CSF outflow at all lumbar levels and the psoas region. There was no significant difference among the ROIs for signal intensity. The tagged CSF outflow from the spinal canal is small but demonstrates egress to surrounding tissues. This finding may pave the way for exploring intrathecal drug delivery, understanding of CSF-related pathologies and its potential as a biomarker for peripheral neuropathy and radiculopathy.

Successful detection of multiple communicating holes in multiple spinal extradural arachnoid cysts by using time-spatial labeling inversion pulse magnetic resonance imaging: illustrative case.

Spinal extradural arachnoid cysts (SEACs) communicate with the subarachnoid space through small communicating dural holes. The precise preoperative detection of all communicating holes, followed by minimally invasive dural closure, is the ideal treatment to prevent postoperative spinal deformities, especially in cases of multiple SEACs. However, standard imaging methods often fail to detect communicating hole locations. Although a few cases of successful single-hole detection via cinematic magnetic resonance imaging (MRI) have been reported, this modality's ability to detect multiple holes has not been demonstrated. The authors describe the case of a 14-year-old male with myelopathy due to multiple SEACs at T5-8 and T8-12. Myelography revealed a complete block at the T8 level; no cephalic cyst or communicating holes were identified. Time-spatial labeling inversion pulse (T-SLIP) MRI revealed cerebrospinal fluid flow into the cyst at T10 and T7. A limited laminectomy or hemilaminectomy was performed at T7 and T10, and two dural holes were closed without a total cystectomy. The patient's gait disturbance and rectal disorder disappeared. The cysts were confirmed to have completely disappeared on conventional MRI at 1 year postoperatively. T-SLIP MRI, a cinematic MRI, is useful for detecting multiple communicating holes in SEACs.

Real-time quantification of in vivo cerebrospinal fluid velocity using the functional magnetic resonance imaging inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory-gated approaches, such as 4D flow magnetic resonance imaging (MRI), cannot capture CSF movement in real time because of limited temporal resolution and, in addition, deteriorate in accuracy at low fluid velocities. Other techniques like real-time phase-contrast-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability, even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional MRI (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath-holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Wideband black-blood late gadolinium enhancement imaging for improved myocardial scar assessment in patients with cardiac implantable electronic devices.

Wideband phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) enables myocardial scar imaging in implantable cardioverter defibrillators (ICD) patients, mitigating hyperintensity artifacts. To address subendocardial scar visibility challenges, a 2D breath-hold single-shot electrocardiography-triggered black-blood (BB) LGE sequence was integrated with wideband imaging, enhancing scar-blood contrast. Wideband BB, with increased bandwidth in the inversion pulse (0.8-3.8 kHz) and T2 preparation refocusing pulses (1.6-5.0 kHz), was compared with conventional and wideband PSIR, and conventional BB, in a phantom and sheep with and without ICD, and in six patients with cardiac devices and known myocardial injury. ICD artifact extent was quantified in the phantom and specific absorption rate (SAR) was reported for each sequence. Image contrast ratios were analyzed in both phantom and animal experiments. Expert radiologists assessed image quality, artifact severity, and scar segments in patients and sheep. Additionally, histology was performed on the sheep's heart. In the phantom, wideband BB reduced ICD artifacts by 62% compared to conventional BB while substantially improving scar-blood contrast, but with a SAR more than 24 times that of wideband PSIR. Similarly, the animal study demonstrated a considerable increase in scar-blood contrast with wideband BB, with superior scar detection compared with wideband PSIR, the latter confirmed by histology. In alignment with the animal study, wideband BB successfully eliminated severe ICD hyperintensity artifacts in all patients, surpassing wideband PSIR in image quality and scar detection. Wideband BB may play a crucial role in imaging ICD patients, offering images with reduced ICD artifacts and enhanced scar detection.

Advanced Excitation Symmetry Analysis Method (ESAM) for improved automated ultrasonic testing of polished materials

One of the strategic plans of the international NDT community is to define standards for developing advanced and digitalized non-destructive testing for automated set-up in mass production [1,2]. Excitation Symmetry Analysis Method (ESAM) are new coded signal processing tools exploring symmetry properties [3]. ESAM method aims to extract the nonlinearity from an ultrasound output by studying the property of symmetry of the transfer function. More precisely, the extraction of nonlinearity is done using basis function associated to a group which is associated to an a priori transfer function. As soon as the linear tomography uses the invariant properties of amplitude dependence, nonlinear tomography should exploit the invariance properties (or symmetry properties) of the complex system. Consequently, the invariance of the stationary properties of a complex medium would be supposed to be associated to a signature of the degradation, that will be extracted with advanced signal processing tools. The idea remains the same: studying the symmetry and more precisely the time reversal one and the inversion. A signal processing is used to measure discrepancies in the autocorrelation function (output signal called chirp coda) for two inputs: a signal and its inversion (pulse inversion). The experiments were done on different sample with and without cracks. It has been shown that when the nonlinearities are extracted from the chirp coda amplitude are non- negligible in crack area and nonlinearities are out of phase. Then, mixing symmetries like time reversal and pulse inversion enable the detection of defect that are difficult to detect with conventional ultrasound method. Indeed, for such crack a destructive mechanical analysis called Jomini is done where the material is polished and examined with microscope. The sensitivity improvement of chirp-coded signal processing has been validated in various domains. Coded excitation techniques, used in communication systems such as radar and sonar provide improved SNR without increasing the amplitude of excitation. The typical test equipment consists of a preamplifier Juvitek TRA-02 (0.02 - 5 MHz) connected to a computer, an amplifier ENI model A150 (55 dB at 0.3-35 MHz), a shear wave transducer Technisonic (2.25 MHz), and a longitudinal wave transducer Panametrics V155 (5 MHz). The experimental device was tested with the V3 calibration block, improved, and specially scaled in order to access to a wide range of multivalued parameters: mechanical properties, ultrasonic parameters (celerity and attenuation) and local geometric data.

The significance of cerebrospinal fluid dynamics in adolescent idiopathic scoliosis using time-SLIP MRI

Adolescent idiopathic scoliosis (AIS) affects approximately 3% of the global population. Recent studies have drawn attention to abnormalities in the dynamics of the CSF as potential contributors. This research aims to employ the Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRI to assess and analyze cerebrospinal fluid (CSF) dynamics in AIS patients. 101 AIS patients underwent Time-SLIP MRI. Images were taken at the mid-cervical and craniocervical junction regions. The sum of the maximum movement distances of CSF on the ventral and dorsal sides of the spinal canal within a single timeframe was defined and measured as Travel Distance (TD). Correlations between TD, age, Cobb angle, and Risser grade were analyzed. TD comparisons were made across Lenke classifications. TD for all patients was a weak correlation with the Cobb angle (r = − 0.16). Comparing TD between Lenke type 1 and 5, type 5 patients display significantly shorter TD (p < 0.05). In Risser5 patients with Lenke type 5 showed a significant negative correlation between Cobb angle and TD (r = − 0.44). Lenke type 5 patients had significantly shorter CSF TD compared to type1, correlating with worsening Cobb angles. Further analysis and exploration are required to understand the mechanism of onset and progression.

Modern Magnetic Resonance Imaging Modalities to Advance Neuroimaging in Astronauts.

INTRODUCTION: The rapid development of the space industry requires a deeper understanding of spaceflight's impact on the brain. MRI research reports brain volume changes following spaceflight in astronauts, potentially affecting cognition. Recently, we have demonstrated that this evidence of volumetric changes, as measured by typical T1-weighted sequences (e.g., magnetization-prepared rapid gradient echo sequence; MPRAGE), is error-prone due to the microgravity-related redistribution of cerebrospinal fluid in the brain. More modern neuroimaging methods, particularly dual-echo MPRAGE (DEMPRAGE) and magnetization-prepared rapid gradient echo sequence utilizing two inversion pulses (MP2RAGE), have been suggested to be resilient to this error. Here, we tested if these imaging modalities offered consistent segmentation performance improvements in some commonly employed neuroimaging software packages.METHODS: We conducted manual gray matter tissue segmentation in traditional T1w MRI images to utilize for comparison. Automated tissue segmentation was performed for traditional T1w imaging, as well as on DEMPRAGE and MP2RAGE images from the same subjects. Statistical analysis involved a comparison of total gray matter volumes for each modality, and the extent of tissue segmentation agreement was assessed using a test of similarity (Dice coefficient).RESULTS: Neither DEMPRAGE nor MP2RAGE exhibited consistent segmentation performance across all toolboxes tested.DISCUSSION: This research indicates that customized data collection and processing methods are necessary for reliable and valid structural MRI segmentation in astronauts, as current methods provide erroneous classification and hence inaccurate claims of neuroplastic brain changes in the astronaut population.Berger L, Burles F, Jaswal T, Williams R, Iaria G. Modern magnetic resonance imaging modalities to advance neuroimaging in astronauts. Aerosp Med Hum Perform. 2024; 95(5):245-253.

Implementation of Pulse Inversion Harmonic Imaging on 2d Convex Transducer on Anatomical Information of first-trimester Pregnancy Ultrasound Image

This study aims to compare the imaging results of Pulse Inversion Harmonic Imaging (PIHI) on transabdominal ultrasound with convex 2D transducer with and without PIHI on transvaginal ultrasound in providing anatomical information on first-trimester pregnancies. Involving 30 pregnant women meeting inclusion and exclusion criteria, the research was conducted at Swamedika Clinic Jakarta in August 2023. A quasi-experimental method was employed with evaluation performed by ultrasound experts and assessment by a radiologist unaware of PIHI use. The findings indicate that the use of PIHI on transabdominal ultrasound yields clear images of the boundary walls, fetal objects, and yolk sac boundary with appropriate frequency, gain, and depth settings. However, the comparative analysis between images with PIHI on transabdominal and without PIHI on transvaginal did not show significant differences. This study highlights the potential of PIHI in enhancing the quality of ultrasound images in the first trimester of pregnancy, although the results did not significantly differ from transvaginal technique without PIHI.

Automatic Brain Tissue and Lesion Segmentation and Multi-Parametric Mapping of Contrast-Enhancing Gliomas without the Injection of Contrast Agents: A Preliminary Study.

This study aimed to develop a rapid, 1 mm3 isotropic resolution, whole-brain MRI technique for automatic lesion segmentation and multi-parametric mapping without using contrast by continuously applying balanced steady-state free precession with inversion pulses throughout incomplete inversion recovery in a single 6 min scan. Modified k-means clustering was performed for automatic brain tissue and lesion segmentation using distinct signal evolutions that contained mixed T1/T2/magnetization transfer properties. Multi-compartment modeling was used to derive quantitative multi-parametric maps for tissue characterization. Fourteen patients with contrast-enhancing gliomas were scanned with this sequence prior to the injection of a contrast agent, and their segmented lesions were compared to conventionally defined manual segmentations of T2-hyperintense and contrast-enhancing lesions. Simultaneous T1, T2, and macromolecular proton fraction maps were generated and compared to conventional 2D T1 and T2 mapping and myelination water fraction mapping acquired with MAGiC. The lesion volumes defined with the new method were comparable to the manual segmentations (r = 0.70, p < 0.01; t-test p > 0.05). The T1, T2, and macromolecular proton fraction mapping values of the whole brain were comparable to the reference values and could distinguish different brain tissues and lesion types (p < 0.05), including infiltrating tumor regions within the T2-lesion. Highly efficient, whole-brain, multi-contrast imaging facilitated automatic lesion segmentation and quantitative multi-parametric mapping without contrast, highlighting its potential value in the clinic when gadolinium is contraindicated.

Transmit beam design for tissue harmonic volume imaging of muscular tissues with a row-column array

Row-Column-addressed Arrays (RCAs), which have recently become commercially available, transmit along the rows and receive along columns of a 2D array in order to produce 3D volume images with low channel count. Imaging of the inherently three-dimensional, layered, and fibrous structure of muscular tissues in 3D using an RCA can improve evaluations of muscle function and disease compared to conventional 2D cross-sectional imaging, but volume images obtained using an RCA suffer from low lateral spatial resolution, low contrast, and grating lobe artifacts. Tissue harmonic imaging (THI) employs nonlinear acoustic effects to image at twice the transmit frequency, and can yield increased spatial resolution, increased contrast, and decreased artifacts from grating lobes. Here we investigate transmission considerations for THI in muscular tissues using a commercially available RCA (Vermon RC6gV). The parameter space is explored efficiently with frequency domain simulations of the 3D Westervelt equation. Pulse inversion imaging is applied experimentally using both steered plane wave and focused transmits to evaluate THI with an RCA in tissue phantoms and in muscular tissue. Pulse inversion volume images are compared to conventional images in terms of signal-to-noise, contrast, and ability to identify layers and fibrous structures in muscle in 3D. [Work supported by NIH HEAL Initiative R61AT012282.]

Contrast-free microvessel imaging using null subtraction imaging combined with harmonic imaging

Ultrasound localization microscopy (ULM) has superior spatial resolution; however, it requires contrast agents and long data acquisition and processing time. Null subtraction imaging (NSI) is a nonlinear beamforming technique that improves the spatial resolution and reduces grating lobes with low computational cost. We combined pulse-inversion (PI) nonlinear imaging with NSI to increase resolution. Pulses with center frequency of 10.42 MHz and its inverted version were transmitted to obtain the second harmonic at 20.84 MHz (wavelength of ∼74 μm). The transducer pitch was 35% larger than the wavelength of the receive signal, which would introduce grating lobes in the field of view. A total of 1000, 9-angle (−8 to 8 degree in 2 degrees step) coherently compounded frames were acquired in 1 s. SVD filters were applied in raw RF data to filter out tissue signal. The dc offset was set to 0.1 in NSI imaging. Grating lobes, which were obvious in DAS images, were removed in the NSI images. Higher spatial resolution and contrast were observed from the NSI microvessel images. The spatial resolution of the NSI images using harmonic imaging approached one fourth of a wavelength with computation time increased by only 40% compared to DAS.

Nonlinear Frequency Mixing Ultrasound Imaging of Nanoscale Contrast Agents.

Nanoscale ultrasound contrast agents show promise as alternatives for diagnostics and therapies due to their enhanced stability and ability to traverse blood vessels. Nonetheless, their reduced size limits echogenicity. This study introduces an enhanced nanobubble frequency mixing ultrasound imaging method, by capitalizing on their nonlinear acoustic response to dual-frequency excitation. A single broadband transducer (L12-3v) controlled by a programmable ultrasound system was used to transmit a dual-frequency single-cycle wavefront. The frequency mixing effect enabled simultaneous transducer capture of nanobubble-generated sum and difference frequencies in real time without the need for additional hardware or post-processing, by substituting the single-frequency wavefront in a standard contrast harmonic pulse inversion imaging protocol, with the dual-frequency wavefront. Optimization experiments were conducted in tissue mimicking phantoms. Among the dual-frequency combinations that were tested, the highest contrast was obtained using 4&8 MHz. The nanobubble contrast improved with increased mechanical index, and achieved a maximal contrast improvement of 8.4 ± 0.5 dB compared to 4 MHz pulse inversion imaging. In imaging of a breast cancer tumor mouse model, after a systemic nanobubble injection, the contrast was improved by 3.4 ± 1.7, 4.8 ± 1.8, and 6.3 ± 1.6 dB for mechanical indices of 0.04, 0.08, and 0.1, respectively. Nonlinear frequency mixing significantly improved the nanobubble contrast, which facilitated their imaging in-vivo. This study offers a new avenue to enhance ultrasound imaging utilizing nanobubbles, potentially leading to advancements in other diagnostic applications.

An Adaptive Harmonic Separation Technique for Ultrasound Harmonic Imaging

ObjectiveAn adaptive harmonic separation (HS) technique is proposed to overcome the limitations in conventional filtering techniques for ultrasound (US) tissue harmonic imaging (THI). MethodsBased on expectation-maximization source separation, the proposed HS technique adaptively models the depth-varying fundamental and harmonic components in the frequency domain and separates the two by applying their calculated posterior probabilities. Phantom experiments with a Tx center frequency of 2 MHz are conducted to evaluate the proposed HS-based US THI schemes. ResultsThe phantom images show that the proposed single-pulse THI scheme utilizing the HS technique provides not only an average improvement of 19.2% in axial resolution compared to the conventional bandpass filtering scheme but also similar image quality to that of the conventional pulse-inversion (PI) scheme which requires two Tx/Rx sequences for each scan line. Furthermore, when combined with the PI technique, the HS technique provides a uniform axial resolution over the entire 170 mm imaging depth with an average improvement of 17.1% compared to the conventional PI scheme. ConclusionThese results show that the proposed adaptive HS technique is capable of improving both the frame rate and the image quality of US THI.