Effect of Pulse Shaping on Subharmonic Aided Pressure Estimation In Vitro and In Vivo.

OBJECTIVES: Subharmonic imaging (SHI) is a technique that uses the nonlinear oscillations of microbubbles when exposed to ultrasound at high pressures transmitting at the fundamental frequency ie, f METHODS: Eight waveforms with different envelopes were optimized with respect to acoustic power at which the SHAPE study is most sensitive. The study was run with four input transmit cycles, first in vitro and then in vivo in three canines to select the waveform that achieved the best sensitivity for detecting changes in portal pressures using SHAPE. A Logiq 9 scanner with a 4C curvi-linear array was used to acquire 2.5 MHz radio-frequency data. Scanning was performed in dual imaging mode with B-mode imaging at 4 MHz and a SHI contrast mode transmitting at 2.5 MHz and receiving at 1.25 MHz. Sonazoid, which is a lipid stabilized gas filled bubble of perfluorobutane, was used as the contrast agent in this study. RESULTS: A linear decrease in subharmonic amplitude with increased pressure was observed for all waveforms (r from -0.77 to -0.93; P \u3c .001) in vitro. There was a significantly higher correlation of the SHAPE gradient with changing pressures for the broadband pulses as compared to the narrowband pulses in both in vitro and in vivo results. The highest correlation was achieved with a Gaussian windowed binomial filtered square wave with an r-value of -0.95. One of the three canines was eliminated for technical reasons, while the other two produced very similar results to those obtained in vitro (r from -0.72 to -0.98; P CONCLUSIONS: Using this waveform is an improvement to the existing SHAPE technique (where a square wave was used) and should make SHAPE more sensitive for noninvasively determining portal hypertension

A STUDY ON QUALITY OF LIFE IN PATIENTS FOLLOWING MYOCARDIAL INFARCTION

Abstract : Subjective well being has been widely researched in the past few decades and in practical terms it is a term that encompasses the various ways people evaluate their lives including concepts such as life satisfaction, work and health etc. Since, it is well known, that psychological factors including stress, anxiety, poor sleeping habits etc are known to be important causes of life style disorders like myocardial infraction, we started with the hypothesis that subjective well being of post acute MI patients must be poorer compared to normal subjects in the same age group. A comparative study between normal subjects and post acute myocardial infarction patients was undertaken to compare their subjective well being and current mental health status, at Safdarjung Hospital, New Delhi using standardized questionnaires. The results showed significantly higher negative affect like inadequate mental mastery over immediate environment, perceived ill health including disturbed sleep, deficiency in social contacts, and a general ill being about life in the MI group (P<0.05). Regarding the positive emotions, the normal subjects showed a higher general well being positive affect, higher transcedence and higher perception of social support. (P<0.05). The GHQ also yielded significantly better sleeping habits, less anxiety, better perception of health and more satisfaction with life in the normal subjects compared to post acute MI patients. (P<0.05)

Investigating the Influence of the Physiological Environment on Quantitative Contrast-enhanced Ultrasound Imaging

Ultrasound Doppler studies have long been used for quantifying blood flow velocity, and microbubble contrast agents can be used to amplify the Doppler signal. However, the highly nonlinear response of the bubbles to ultrasound can affect measurement accuracy and this has limited their application. Reliable quantitative imaging protocols, however, require the relationship between the response of the microbubble population and the received ultrasound signal to be fully characterized. The complexity of this relationship currently poses a significant barrier to the development of clinically useful techniques. Materials and methods: The experiment was focused at evaluating the attenuation and the backscatter caused by bubbles under varying physiological conditions. Theoretical modeling of the bubble motion was performed for a shelled bubble surrounded by blood cells and then attenuation and the backscatter coefficient (BSC) were calculated theoretically under different conditions. The experiment was divided into the following three parts: variation of temperature, variation of hematocrit, and variation of vessel diameter. In all three parts, attenuation and backscatter caused by lipid bubbles in blood and water were calculated. A 3.5-MHz focused transducer having a focal length of 0.02 m (0.83 in) was used in the experiments. The hydrophone used was a needle hydrophone having a probe of 40 μm. The bubbles used were coated with a lipid shell (Avanti Polar Lipids) and had a concentration of about 107 microbubbles/mL. Results: Attenuation in the sample with blood and bubbles increases from 5 (±0.33) at room temperature to 9.45 (±0.38) at 37°C. For the sample containing blood and bubbles, the BSC increases from 9 × 10−19 m−1/sr (±4.6 × 10−18) at room temperature to 5.3 × 10−18 m−1/sr (±3.6 × 10−17) at 37°C and 5.2 × 10−16 m−1/sr (±3.78 × 10−18) at 40 °C. An increase in attenuation is observed as the hematocrit level is increased; however, the experimental values of the BSC do not change much with change in the hematocrit level. Highest attenuation is seen in the 200-μm vessel of nearly 35 dB/cm (±5) in a sample containing blood and bubbles. The backscatter for the sample containing blood and bubbles increases from 2.5 × 10−19 m−1/sr (±2.8 × 10−20) in the 200-μm vessel to 5.07 × 10−17 m−1/sr (±3.9 × 10−18) in the 4-mm vessel. Conclusion: It has been re-established that as temperature increases from room temperature to body temperature, considerable signal is lost and attenuation and backscatter increase with temperature. Blood cells surrounding the bubbles do alter the attenuation; however, they do not have any effect on the backscatter by the bubbles. This result is different from previous studies, and therefore, more work must be done to validate these results in a more sophisticated experimental setup. Confinement of bubbles inside small vessels affects both attenuation and backscatter. Hence, while designing experiments, care must be taken about choosing the vessels in the body through which the bubble will travel and the parameters must be measured accordingly

Subharmonic Aided Pressure Estimation (SHAPE) of Portal Hypertension

Portal hypertension is difficult to diagnose at its early stage as symptoms rarely manifest until the later stages of liver disease. As pressures in the portal vein cannot be directly measured, portal pressures are estimated using the hepatic venous pressure gradient (HVPG). This is defined as the difference between the wedged and free hepatic venous pressures. Patients with an HVPG greater than 10 mmHg are at increased risk of developing varices, while patients with an HVPG above 12 mmHg are at risk of variceal bleeding (which is associated with mortality rates of 15-20 %). The current clinical technique for measuring HVPG is invasive and requires insertion of a balloon catheter via a transjugular approach into the hepatic vasculature. Noninvasive techniques such as ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) have a very poor sensitivity to portal pressure estimation and are therefore, not accurate enough to be used routinely for diagnosis of portal hypertension. Thus, an alternative accurate, noninvasive ultrasound-based procedure would be a major development in the diagnosis of portal hypertension making the diagnosis safer, quicker and relatively cheaper. Hence, the fundamental hypothesis of this project is that portal vein pressures can be monitored and quantified noninvasively in humans using contrast-enhanced subharmonic-aided pressure estimation (SHAPE). SHAPE is based on the inverse relationship between the subharmonic amplitude of contrast microbubbles (obtained by transmitting at the fundamental frequency fo and receiving at fo/2) and the ambient pressure. The hypothesis of this study is that portal vein pressures can be monitored and quantified noninvasively in humans using SHAPE. Sonazoid was the contrast agent used for this study. In the first part of this study, the effect of pulse shaping on SHAPE was studied. It was concluded that the shape of the input pulse changes the subharmonic signal generated by UCAs and also the gradient observed with changing hydrostatic pressure. There was a significantly higher correlation of the SHAPE gradient with changing pressures for the broadband pulses as compared to the narrowband pulses in both in vitro and in vivo results. The highest correlation was achieved with a Gaussian windowed binomial filtered square wave with an r-value of -0.95. One of the 3 canines was eliminated for technical reasons, while the other 2 produced very similar results to those obtained in vitro (r from -0.72 to -0.98; p12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (0.27± 2.04 vs -4.90 ±3.28 dB; p<0.0001). SHAPE was also used for monitoring disease progression of portal hypertensive patients. These patients had follow-up clinic visits or CT/MRI scans every 6 months and at those times a repeat SHAPE examination was performed collecting data from the portal and hepatic vein in triplicate. Liver function tests (albumin, bilirubin and coagulation panel), MELD scores and presence of ascites and varices were used for treatment response. For all the cases SHAPE findings were consistent with clinical expectations. The change in the SHAPE gradient relative to baseline decreased significantly for the responders (n=9) (i.e., implying improvement) compared to the non-responders (n=2; -4.70 ±3.27 dB vs 1.77±0.55 dB; p<0.001). Results matched the corresponding clinical outcomes of improved MELD scores, improvement in underlying cause of portal hypertension and increased bilirubin and reduced ascites indicating a reduction in portal hypertension amongst responders. SHAPE has proven to be a useful and reliable tool to predict portal pressures and also monitor disease progression in portal hypertensive patients.Ph.D., Biomedical Engineering -- Drexel University, 201

Ultrasonic Implantation and Imaging of Sound-Sensitive Theranostic Agents for the Treatment of Arterial Inflammation

For site-specific diseases such as atherosclerosis, it is desirable to noninvasively and locally deliver therapeutics for extended periods of time. High-intensity focused ultrasound (HIFU) provides targeted drug delivery, yet remains unable to sustain delivery beyond the HIFU treatment time. Furthermore, methods to validate HIFU-enhanced drug delivery remain limited. In this study, we report on HIFU-targeted implantation of degradable drug-loaded sound-sensitive multicavity PLGA microparticles (mcPLGA MPs) as a theranostic agent for the treatment of arterial lesions. Once implanted into the targeted tissue, mcPLGA MPs eluted dexamethasone for several days, thereby reducing inflammatory markers linked to oxidized lipid uptake in a foam cell spheroid model. Furthermore, implanted mcPLGA MPs created hyperechoic regions on diagnostic ultrasound images, and thus noninvasively verified that the target region was treated with the theranostic agents. This novel and innovative multifunctional theranostic platform may serve as a promising candidate for noninvasive imaging and treatment for site-specific diseases such as atherosclerosis

Pulse Shaping for Improved Diagnosis of Portal Hypertension Using Subharmonic Aided Pressure Estimation

Subharmonic aided pressure estimation (SHAPE) is based on the inverse relationship between the subharmonic amplitude of contrast microbubbles (obtained by transmitting at the fundamental frequency fo and receiving at fo/2) and the ambient pressure (see fig.1). A noninvasive ultrasound based pressure estimation procedure would be a major development in the diagnosis of portal hypertension and less invasive than the current catheter-based hepatic venous pressure gradient (HVPG) measurement. The hypothesis of this study was that portal vein pressures can be monitored and quantified noninvasively in humans using SHAPE. First selected waveforms were optimized in vitro and in canines, then SHAPE was correlated with measured HVPG in patients undergoing a transjugular liver biopsy (TJLB).https://jdc.jefferson.edu/radiologyposters/1004/thumbnail.jp