Lori Bridal

A multiplicative model for improving microvascular flow estimation in dynamic contrast-enhanced ultrasound (DCE-US): theory and experimental validation

Perfusion parameter estimation from dynamic contrast-enhanced ultrasound (DCE-US) data relies on fitting parametric models of flow to curves describing linear echo power as a function of time. The least squares criterion is generally used to fit these models to data. This criterion is optimal in the sense of maximum likelihood under the assumption of an additive white Gaussian noise. In the current work, it is demonstrated that this assumption is not held for DCEUS. A better-adapted maximum likelihood criterion based on a multiplicative model is proposed. It is tested on simulated bolus perfusion data and on 11 sequences acquired in vivo during bolus perfusion of contrast agent in the cortex of healthy murine kidney, an area where the perfusion is expected to be approximately homogeneous. Results on simulated data show a significant improvement (p <; 0.05) of the precision and the accuracy for the estimations of perfusion parameters time to peak (TTP), wash-in rate (WiR), and mean transit time (MTT). On the 11 in vivo sequences, the new method leads to a significant reduction (p <; 0.05) in the variation of parametric maps for 9 sequences for TTP and 10 sequences for WiR and MTT. The mean percent decreases of the coefficient of variation are 40%, 25%, and 59% for TTP, WiR, and MTT, respectively. This method should contribute to a more robust and accurate estimation of perfusion parameters and an improved resolution of parametric imaging.

2D-2 Automatic Detection of Ultrasound Contrast Microbubble Shell Rupture

Characterizing occurrence of ultrasound contrast agent (UCA) microbubble destruction is important for development of functional and therapeutic applications. Previously [Ammi, et. al., 2006], it was demonstrated that post-excitation acoustic emissions detected with passive cavitation detection (PCD) result from inertial cavitation (IC) of UCA after shell rupture. That work relied on time-consuming visual inspection of PCD data to identify IC signals and characterized only minimum rarefactional pressure thresholds for rupture of a single Optisontrade microbubble in the sampled population. This work introduces an algorithm for automatic detection of IC signals. The algorithm was applied to the 71424 waveforms in the PCD data set. At each incident frequency (0.9, 2.8 or 4.6 MHz) and pulse duration (3, 5 or 7 cycles) combination, ruptured microbubble occurrence with incident peak rarefactional pressure (PRP) was well described by a logistic regression curve with an inflection point near 50% occurrence and a plateau at 100%. With a 5-cycle pulse duration at 0.9, 2.8 and 4.6 MHz the incident PRPs leading to 5% microbubble rupture were 0.66, 0.83 and 1.1 MPa; and 1.1, 1.6 and 2.5 MPa for 50%. This automatic algorithm combined with the PCD approach provides a practical tool for the characterization of UCA destruction occurrence across a significant range of incident PRPs

Quantitative-ultrasound detection of cancer in human lymph nodes based on support vector machines

Histological assessment of lymph nodes excised from cancer patients suffers from an unsatisfactory rate of false-negative determinations. We are evaluating high-frequency quantitative ultrasound (QUS) to detect metastatic regions in lymph nodes freshly excised from cancer patients. Three-dimensional (3D) RF data were acquired from 289 lymph nodes of 82 colorectal-, 15 gastric-, and 70 breast-cancer patients with a custom scanner using a 26-MHz, single-element transducer. Following data acquisition, individual nodes underwent step-sectioning at 50-µm to assure that no clinically significant cancer foci were missed. RF datasets were analyzed using 3D regions-of-interest that were processed to yield 13 QUS estimates including spectral-based and envelope-statistics-based parameters. QUS estimates are associated with tissue microstructure and are hypothesized to provide contrast between non-cancerous and cancerous regions. Leave-one-out classifications, ROC curves, and areas under the ROC (AUC) were used to co...

Characterization of liquid-filled nanoparticles for detection and drug-delivery in tumors

Liquid-filled nanoparticles provide long half-life circulation favoring accumulation in the interstitial space of tumors through enhanced permeation and retention. However, these relatively incompressible nanoparticles are much less echogenic than those with a gas-core. We have worked to characterize and optimize the acoustic response of PLGA-shelled, perfluorooctyl bromide (PFOB) core nanoparticles (radii 70 to 200 nm ; shell-thickness-to-radius ratio 0.25 to 1). Acoustic response (attenuation coefficient, ultrasonic velocity, and relative backscattered intensity) was explored in vitro for ranges of concentration, shell-thickness, acoustic pressures and pulse durations (20 to 40 MHz). Modification of the surface chemistry of the polymeric shell with fluorescent, pegylated, or/and biotinylated phospholipids was not associated with apparent response modification. Successful incorporation of paclitaxel in the shell has been achieved but currently the thick-shells of these nanoparticles impede ultrasound-tri...

Using passive cavitation detection to observe postexcitation response of ultrasound contrast agents

Passive cavitation detection was used to improve the experimental characterization of single ultrasound contrast agent microbubble responses to short, large amplitude pulses. Two situations were examined: isolated microbubbles in an unconstrained environment, and isolated microbubbles flowing through a tube. The microbubbles were categorized according to a classification scheme based on the presence or absence of postexcitation signals, which are secondary broadband spikes that may follow the principle oscillation of the ultrasound contrast agent in response to an insonifying pulse. Experiments were conducted for different frequencies, peak rarefactional pressures, flow rates, and types of microbubble. Postexcitation activity was found to increase as frequency decreased, acoustic pressure increased, and flow rate increased. Additionally, lipid-shelled microbubbles were found to exhibit greater postexcitation at lower acoustic pressure thresholds than albumin-shelled microbubbles.

Ultrasound contrast imaging of angiogenisis in a murine tumor model

Microvascularization modifications should precede tumor size-changes during anti-angiogenic therapy. We applied contrast functional ultrasound imaging (fUSI) to detect changes in Wilms tumors with anti-angiogenic treatment (Bevacizumab). Human Wilms tumor cells was grafted in left kidney of 32 mice. Once tumors had >5mm diameter, mice received : placebo, N=14; Bevacizumab for 21days, N=11; and Bevacizumab for 10days followed by placebo for 11days, N = 7. On days -1, +1, +9, +14 and +21 with respect to treatment start, fUSI was performed (CPS mode, SonoVue). Linear time intensity curves were obtained from regions in kidney cortex and matched-depth of tumor for first bolus passage and 50s following acoustic destruction of contrast. Excised tumor weight decreased with increased treatment duration: 3.7+/-1.8 g (placebo), 2.3+/1.9 g (Bevacizumab-10days, placebo-11days), 1.4+/-0.7 g (Bevacizumab-21 days) [p<0.05]. Area under the bolus-passage curve (AUC) and the plateau intensity of the destruction-reperfusion were greater from D+9 to D+21 [p<0. 04] in the placebo than Bevacizumab-21day. For the group treated during the first 10 days, fUSI values were comparable to those of the treated group until D+14, then increased to become slightly superior to those of the placebo group by D+21. Noninvasive fUSI demonstrated revascularization after suspension of anti-VEGF therapy.