A New Nonlinear Compounding Technique for Ultrasound B-mode Medical Imaging

Compounding techniques have been used in ultra-fast ultrasound imaging to improve image quality by reducing clutter noise, smoothing speckle variance and enhancing its spatial resolution at the cost of reducing frame rate. However, the reduction of clutter noise and side lobes inside the anechoic regions is minimal when combining conventional spatial compounding and delay-and-sum (DAS) beamforming. Despite the availability of advanced beamforming algorithms such as filtered-delay-multiply-and-sum (FDMAS), its prevalence is hindered by relatively high computational cost. In this study, a new nonlinear compounding technique known as filtered multiply and sum (FMAS) was proposed to improve the B-mode image quality without increasing the overall computational complexity. With three compunding angles, the lateral resolution for DAS-FMAS was improved by 36% and 19% compared to DAS and FDMAS. The proposed DAS-FMAS technique also provided improvements of 14.1 dB and 7.29 dB in contrast ratio than DAS and FDMAS

Acoustical structured illumination for super-resolution ultrasound imaging.

Structured illumination microscopy is an optical method to increase the spatial resolution of wide-field fluorescence imaging beyond the diffraction limit by applying a spatially structured illumination light. Here, we extend this concept to facilitate super-resolution ultrasound imaging by manipulating the transmitted sound field to encode the high spatial frequencies into the observed image through aliasing. Post processing is applied to precisely shift the spectral components to their proper positions in k-space and effectively double the spatial resolution of the reconstructed image compared to one-way focusing. The method has broad application, including the detection of small lesions for early cancer diagnosis, improving the detection of the borders of organs and tumors, and enhancing visualization of vascular features. The method can be implemented with conventional ultrasound systems, without the need for additional components. The resulting image enhancement is demonstrated with both test objects and ex vivo rat metacarpals and phalanges

Co-registered photoacoustic and ultrasound tomographic imaging of human colorectal and ovarian cancer: light delivery, system development, and clinical study

Ovarian cancer remains the deadliest of all the gynecological malignancies. Conventional screening tests, including pelvic examination, transvaginal ultrasound (TVUS), and blood testing for cancer antigen 125 (CA-125), lack sufficient specificity for early ovarian cancer diagnosis. Imaging modalities such as computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have been used for surgical guidance. However, all of these modalities have limitations in detecting small lesions. Globally, colorectal cancer is the second most commonly diagnosed malignancy and the fourth most common cause of cancer mortality. Accurate staging and post-treatment surveillance of this prevalent disease are critical because treatment strategies are predicated upon the stage at presentation and the patient’s response to pre-surgical therapy – in some instances, detailed imaging allows certain patients to avoid surgery altogether. While colonoscopy and biopsy are the gold-standard diagnostic tests for colorectal cancers, multiple imaging modalities are also utilized, including optical imaging, endoscopic ultrasound (EUS), pelvic magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). Unfortunately, each of these modalities has critical weakness in evaluating colorectal tumors. In staging colorectal tumors and evaluating their therapeutic response, more precise imaging modalities could transform the standard of care. This dissertation explores co-registered photoacoustic and ultrasound tomographic imaging of two fatal cancers: ovarian cancer and colorectal cancer. It is composed of three main parts: light delivery optimization/fiber optics, system development and optimization, and pilot patient and sample study. To begin, we designed, optimized, and evaluated an hand-held photoacoustic and ultrasound probe suitable for endo-cavity subsurface tumor imaging. Compared to previous designs, the prototype probe, consisting of four 1 mm multi-mode optical fibers attached to 1.5 mm diameter ball-shaped fiber tips sandwiched between a transvaginal ultrasound transducer and a custom-made sheath, demonstrated a higher light output and better beam homogeneity on the tissue subsurface. Second, we developed a novel fiber diffuser tip using microspheres dispersed within an ultraviolet (UV) adhesive to scatter light. This diffuser keeps the skin surface fluence under the maximum permissible exposure (MPE), while enabling higher laser energy injection to enhance the photoacoustic (PA) signal generated from the tissue. Third, we proposed an improved beamformer, named lag-based delay multiply and sum combined with coherence factor (DMAS-LAG-CF). Simulations and phantom experiments demonstrate that compared with conventional delay and sum (DAS), the proposed algorithm can provide 1.39 times better resolution and 10.77 dB higher contrast. For patient data, similar improvements in contrast ratios have been observed. However, since diagnostic accuracy in distinguishing between cancer and benign/normal groups is the significant measure, we have extracted the photoacoustic histogram features of mean, kurtosis, and skewness. When mean and skewness are used as features, DMAS-LAG-CF can improve cancer diagnosis, with an AUC of 0.91 in differentiating malignant from benign ovarian lesions. Fourth, to investigate the ability of co-registered photoacoustic and ultrasound tomographic imaging to assess human colorectal cancer, we conducted a pilot study on 23 ex-vivo human colorectal tissue samples that were collected immediately after surgical resection. Co-registered photoacoustic images of malignancies showed significantly increased PAT signals compared to normal regions of the same sample. We found statistically significant differences between untreated colorectal tumors and normal tissues, based on the quantitative relative total hemoglobin concentration (rHbT) computed from four optical wavelengths, spectral features such as the mean spectral slope and 0.5 MHz intercept extracted from PAT and US spectral data, and image features such as the first and second order statistics along with the standard deviation of the mean radon transform of PAT images. Using either a logistic regression model or a support vector machine, the best set of parameters of rHbT and PAT intercept achieved AUC values of 0.97 and 0.95 for the training and testing data sets, respectively, in predicting histologically confirmed invasive carcinoma. One limitation of the current system is its poor image resolution (~ 250 μm axial resolution) limited by the commercial endo-cavity ultrasound transducer array (6 MHz central frequency, 80% bandwidth). For better image resolution in high frequency PAT/US imaging, we first decoded the pin configuration of a high-frequency transducer array (15 MHz central frequency, 9-18 MHz bandwidth) and adapted it to our home-made 128 channel ultrasound pulsing and receiving system (sampling rate: 40 MHz). To further improve the performance, we are building a 64-channel FPGA-based high frequency photoacoustic imaging system with a sampling rate of 80 MHz and signal-to-noise ratio (SNR) of 40 dB. For in-vivo patient study, this system will be integrated with an endo-rectal probe with a side-firing fiber tip. Fifth, we investigated the laser safety of photoacoustic imaging, in preparation for its use in clinical reproductive medicine. Using preimplantation mouse blastocyst stage embryos, we assessed potential DNA damage from photoacoustic laser exposure. Different embryo groups were exposed to either 5- or 10- minute 15-Hz laser doses (typical clinical doses), or a 1-minute 1-kHz laser dose (a significantly higher dose). We demonstrated that typical lasers and exposure times used for photoacoustic imaging do not induce increased cell death in mouse blastocysts. Sixth, we demonstrated a novel fiber endface photoacoustic generator using IR 144 laser dye dispersed within an ultraviolet (UV) adhesive. The generator provides wide acoustic bandwidth in the transducer frequency range of 2-7 MHz, high thermal conversion efficiency (\u3e 90%), good PA intensity controllability (via the easily controlled IR 144 concentration), and high feasibility (simple procedures). Through a series of experimental validations, we show this fiber-based endface photoacoustic generator can be a useful tool for a broad range of biomedical applications, such as calibrating the local absorption coefficient of biological tissue for quantitative photoacoustic tomography

Advanced signal processing methods for plane-wave color Doppler ultrasound imaging

Conventional medical ultrasound imaging uses focused beams to scan the imaging scene line-by-line, but recently however, plane-wave imaging, in which plane-waves are used to illuminate the entire imaging scene, has been gaining popularity due its ability to achieve high frame rates, thus allowing the capture of fast dynamic events and producing continuous Doppler data. In most implementations, multiple low-resolution images from different plane wave tilt angles are coherently averaged (compounded) to form a single high-resolution image, albeit with the undesirable side effect of reducing the frame rate, and attenuating signals with high Doppler shifts. This thesis introduces a spread-spectrum color Doppler imaging method that produces high-resolution images without the use of frame compounding, thereby eliminating the tradeoff between beam quality, frame rate and the unaliased Doppler frequency limit. The method uses a Doppler ensemble formed of a long random sequence of transmit tilt angles that randomize the phase of out-of-cell (clutter) echoes, thereby spreading the clutter power in the Doppler spectrum without compounding, while keeping the spectrum of in-cell echoes intact. The spread-spectrum method adequately suppresses out-of-cell blood echoes to achieve high spatial resolution, but spread-spectrum suppression is not adequate for wall clutter which may be 60 dB above blood echoes. We thus implemented a clutter filter that re-arranges the ensemble samples such that they follow a linear tilt angle order, thereby compacting the clutter spectrum and spreading that of the blood Doppler signal, and allowing clutter suppression with frequency domain filters. We later improved this filter with a redesign of the random sweep plan such that each tilt angle is repeated multiple times, allowing, after ensemble re-arrangement, the use of comb filters for improved clutter suppression. Experiments performed using a carotid artery phantom with constant flow demonstrate that the spread-spectrum method more accurately measures the parabolic flow profile of the vessel and outperforms conventional plane-wave Doppler in both contrast resolution and estimation of high flow velocities. To improve velocity estimation in pulsatile flow, we developed a method that uses the chirped Fourier transform to reduce stationarity broadening during the high acceleration phase of pulsatile flow waveforms. Experimental results showed lower standard deviations compared to conventional intensity-weighted-moving-average methods. The methods in this thesis are expected to be valuable for Doppler applications that require measurement of high velocities at high frame rates, with high spatial resolution