Congxian Jia

Multifunctional nanoparticles as coupled contrast agents

Engineering compact imaging probes with highly integrated modalities is a key focus in bionanotechnology and will have profound impact on molecular diagnostics, imaging and therapeutics. However, combining multiple components on a nanometre scale to create new imaging modalities unavailable from individual components has proven to be challenging. In this paper, we demonstrate iron oxide and gold-coupled core-shell nanoparticles (NPs) with well-defined structural characteristics (for example, size, shell thickness and core-shell separation) and physical properties (for example, electronic, magnetic, optical, thermal and acoustic). The resulting multifunctional nanoprobes not only offer contrast for electron microscopy, magnetic resonance imaging and scattering-based imaging but, more importantly, enable a new imaging mode, magnetomotive photoacoustic imaging, with remarkable contrast enhancement compared with photoacoustic images using conventional NP contrast agents.

3-D Correlation-Based Speckle Tracking

Widely-used 1-D/2-D speckle tracking techniques in elasticity imaging often experience significant speckle decorrelation in applications involving large elevational motion (i.e., out of plane motion). The problem is more pronounced for cardiac strain rate imaging (SRI) since it is very difficult to confine cardiac motion to a single image plane. Here, we present a 3-D correlation-based speckle tracking algorithm. Conceptually, 3-D speckle tracking is just an extension of 2-D phase-sensitive correlation-based speckle tracking. However, due to its high computational cost, optimization schemes, such as dynamic programming, decimation and two-path processing, are introduced to reduce the computational burden. To evaluate the proposed approach, a 3-D bar phantom under uniaxial compression was simulated for benchmark tests. A more sophisticated 3-D simulation of the left ventricle of the heart was also made to test the applicability of 3-D speckle tracking in cardiac SRI. Results from both simulations clearly demonstrated the feasibility of 3-D correlation-based speckle tracking. With the ability to follow 3-D speckle in 3-D space, 3-D speckle tracking outperforms lower-dimensional speckle tracking by minimizing decorrelation caused by pure elevational translation. In other words, 3-D tracking can push toward solely deformation-limited, decorrelation-optimized speckle tracking. Hardware implementation of the proposed 3-D speckle tracking algorithm using field programmable gate arrays (FPGA) is also discussed.

Noninvasive Ultrasound Elasticity Imaging (UEI) of Crohn's Disease: Animal Model

Inflammation occurs in episodic flares in Crohns disease, which are part of the waxing and waning course of the disease. Healing between flares allows the intestine to reconstitute its epithelium, but this healing results in the deposition of fibrotic scar tissue as part of the healing process. Repeated cycles of flares and healing often lead to clinically significant fibrosis and stenosis of the intestine. Patients are treated empirically with steroids, with their many side effects, in the hope that they will respond. Many patients would be better treated with surgery if we could identify which patients truly have intestinal fibrosis. Ultrasound elasticity imaging (UEI) offers the potential to radically improve the diagnosis and management of local tissue elastic property, particularly intestinal fibrosis. This method allows complete characterization of local intestine tissue with high spatial resolution. The feasibility of UEI on Crohns disease is demonstrated by directly applying this technique to an animal model of inflammatory bowel disease (IBD). Five female Lewis rats (150-180g) were prepared with phosphate buffered solution (PBS) as a control group and six were prepared with repeated intrarectal administration of trinitrobenzenesulfonic acid (TNBS) as a disease group. Preliminary strain measurements differentiate the diseased colons from the normal colons (p < 0.0002) and compared well with direct mechanical measurements and histology (p < 0.0005). UEI provides a simple and accurate assessment of local severity of fibrosis. The preliminary results on an animal model also suggest the feasibility of translating this imaging technique directly to human subjects for both diagnosis and monitoring.

Cardiac activation mapping using ultrasound current source density imaging (UCSDI)

We describe the first mapping of biological current in a live heart using ultrasound current source density imaging (UCSDI). Ablation procedures that treat severe heart arrhythmias require detailed maps of the cardiac activation wave. The conventional procedure is time-consuming and limited by its poor spatial resolution (5-10 mm). UCSDI can potentially improve on existing mapping procedures. It is based on a pressure-induced change in resistivity known as the acousto-electric (AE) effect, which is spatially confined to the ultrasound focus. Data from 2 experiments are presented. A 540 kHz ultrasonic transducer (f/# = 1, focal length = 90 mm, pulse repetition frequency = 1600 Hz) was scanned over an isolated rabbit heart perfused with an excitation-contraction decoupler to reduce motion significantly while retaining electric function. Tungsten electrodes inserted in the left ventricle recorded simultaneously the AE signal and the low-frequency electrocardiogram (ECG). UCSDI displayed spatial and temporal patterns consistent with the spreading activation wave. The propagation velocity estimated from UCSDI was 0.25 plusmn 0.05 mm/ms, comparable to the values obtained with the ECG signals. The maximum AE signal-to-noise ratio after filtering was 18 dB, with an equivalent detection threshold of 0.1 mA/ cm2. This study demonstrates that UCSDI is a potentially powerful technique for mapping current flow and biopotentialsin the heart.

Two-dimensional strain imaging of controlled rabbit hearts.

Ultrasound strain imaging using 2-D speckle tracking has been proposed to quantitatively assess changes in myocardial contractility caused by ischemia. Its performance must be demonstrated in a controlled model system as a step toward routine clinical application. In this study, a well-controlled 2-D cardiac elasticity imaging technique was developed using two coplanar and orthogonal linear probes simultaneously imaging an isolated retroperfused rabbit heart. Acute ischemia was generated by left anterior descending (LAD) artery ligation. An excitation-contraction decoupler, 2,3-butanedione monoxime, was applied at a 4-mM concentration to reversibly reduce myocardial contractility. Results using a single probe demonstrate that directional changes in the in-plane principal deformation axes can help locate the bulging area as a result of LAD ligation, which matched well with corresponding Evans Blue staining, and strains or strain magnitude, based on principal stretches, can characterize heart muscle contractility. These two findings using asymmetric displacement accuracy (i.e., normal single-probe measurements with good axial but poor lateral estimates) were further validated using symmetric displacement accuracy (i.e., dual-probe measurements using only accurate axial tracking estimates from each). However, the accuracy of 2-D cardiac strain imaging using a single probe depends on the probes orientation because of the large variance in lateral displacement estimates.

LV segmentation through the analysis of radio frequency ultrasonic images

LV segmentation is often an important part of many automated cardiac diagnosis strategies. However, the segmentation of echocardiograms is a difficult task because of poor image quality. In echocardiography, we note that radio-frequency (RF) signal is a rich source of information about the moving LV as well. In this paper, first, we will investigate currently used, important RF derived parameters: integrated backscatter coefficient (IBS), mean central frequency (MCF) and the maximum correlation coefficients (MCC) from speckle tracking. Second, we will develop a new segmentation algorithm for the segmentation of the LV boundary, which can avoid local minima and leaking through uncompleted boundary. Segmentations are carried out on the RF signal acquired from a Sonos7500 ultrasound system. The results are validated by comparing to manual segmentation results.

11B-6 Detection of Electrical Current in a Live Rabbit Heart using Ultrasound

This paper describes the first direct measurement of a cardiac activation wave using ultrasound. Arrhythmia caused by abnormal propagation of the activation wave is sometimes corrected with ablation procedures. The standard techniques to map the wave are slow and have limited spatial resolution (5 mm). The technique described here is based on the acousto-electric (AE) effect. The AE effect is a modulation of electric resistivity by ultrasound. When an ultrasound beam intersects a current field, a high frequency voltage is produced. In this study an isolated rabbit heart in a Langendorff setup was used. An excitation-contraction decoupler was used to eliminate motion while retaining electric function. The heart was paced from the apex, while two tungsten electrodes inserted in the left ventricles recorded both the AE signal, as well as the standard low frequency electrocardiogram (ECG). A 540 kHz transducer with f/#=l and focal length of 90 mm was focused in the heart and pulsed at 1600 Hz. Pulse echo (PE) and AE signals were acquired simultaneously, sampled at 12.5 MHz and averaged over 128 cycles. The AE signal appeared at the same time as the ECG signal and was extinguished with the ultrasound blocked. Its phase shifted by 180deg when the transducer was moved up by half of a wavelength. Scanning the transducer in a line parallel to the long axis of the heart produced a time shift in the AE signal of 0.12 mm/s, a value similar to what has been reported previously. This study suggests that ultrasound current source density imaging (UCSDI) of the heart can potentially be used to map cardiac activation waves.

Magnetomotive photoacoustic imaging: in vitro studies of magnetic trapping with simultaneous photoacoustic detection of rare circulating tumor cells.

Photoacoustic (PA) imaging has been demonstrated to be a promising modality in molecular imaging for detection of nanoparticle-targeted diseased cells or tissues. However, intrinsic absorbers, such as blood, produce strong PA background signals that severely degrade the detection sensitivity and specificity of targeted objects. Magnetomotive photoacoustic (mmPA) imaging, a newly developed molecular imaging modality, introduced dynamic manipulation into traditional PA imaging. Unlike conventional PA imaging, magnetomotive manipulation with simultaneous ultrasound/PA imaging of agents incorporating magnetic nanoparticles enables direct visualization of the signal generating object and can dramatically reduce background signals from strong optical absorbers. This paper briefly reviews recent developments in mmPA imaging, including uses of composite contrast agent, design of magnet system, and data processing for motion filtering. The use of mmPA imaging in detecting rare circulating tumor cells in blood vessels, which remains a big challenge for real-time in vivo examination using current methodologies, was also addressed.

Differential-absorption photoacoustic imaging.

We present differential-absorption photoacoustic imaging, which detects the difference between transient and ground-state absorption, for contrast enhancement based on suppressing undesired objects. Two tubes were imaged. One contains a Pt(II) octaethylporphine (PtOEP) dye solution and serves as an object of interest, while the other contains an IR-783 (from Sigma-Aldrich) dye solution and serves as an object to suppress. Although the IR-783 tube dominates the conventional photoacoustic image, it is suppressed by 43 dB and consequently significantly overwhelmed by the PtOEP tube in the differential-absorption photoacoustic image. Imaging depth in this mode is also discussed.

Phase rotation methods in filtering correlation coefficients for ultrasound speckle tracking

In speckle-tracking-based myocardial strain imaging, large interframe/volume peak-systolic strains cause peak hopping artifacts separating the highest correlation coefficient peak from the true peak. A correlation coefficient filter was previously designed to minimize peak hopping artifacts. For large strains, however, the correlation coefficient filter must follow the strain distribution to remove peak hopping effectively. This processing usually means interpolation and high computational load. To reduce the computational burden, a narrow band approximation using phase rotation is developed in this paper to facilitate correlation coefficient filtering. Correlation coefficients are first phase rotated to increase coherence, then filtered. Rotated phase angles are determined by the local strain and spatial position. This form of correlation coefficient filtering enhances true correlation coefficient peaks in large strain applications if decorrelation due to deformation does not completely destroy the coherence among neighboring correlation coefficients. The assumed strain used in the filter can also deviate from the true strain and still be effective. Further improvement in displacement estimation can be expected by combining correlation coefficient filtering with a new Viterbi-based displacement estimator.