Ismayil M. Guracar

Quantitative Volumetric Perfusion Mapping of the Microvasculature Using Contrast Ultrasound

Objectives:Contrast-enhanced ultrasound imaging has demonstrated significant potential as a noninvasive technology for monitoring blood flow in the microvasculature. With the application of nondestructive contrast imaging pulse sequences combined with a clearance-refill approach, it is possible to create quantitative time-to-refill maps of tissue correlating to blood perfusion rate. One limitation to standard two-dimensional (2D) perfusion imaging is that the narrow elevational beamwidth of 1- or 1.5-D ultrasound transducers provides information in only a single slice of tissue, and thus it is difficult to image exactly the same plane from study to study. We hypothesize that inhomogeneity in vascularization, such as that common in many types of tumors, makes serial perfusion estimates inconsistent unless the same region can be imaged repeatedly. Our objective was to evaluate error in 2D quantitative perfusion estimation in an in vivo sample volume because of differences in transducer positioning. To mitigate observed errors due to imaging plane misalignment, we propose and demonstrate the application of quantitative 3-dimensional (3D) perfusion imaging. We also evaluate the effect of contrast agent concentration and infusion rate on perfusion estimates. Materials and Methods:Contrast-enhanced destruction-reperfusion imaging was performed using parametric mapping of refill times and custom software for image alignment to compensate for tissue motion. Imaging was performed in rats using a Siemens Sequoia 512 imaging system with a 15L8 transducer. A custom 3D perfusion mapping system was designed by incorporating a computer-controlled positioning system to move the transducer in the elevational direction, and the Sequoia was interfaced to the motion system for timing of the destruction-reperfusion sequence and data acquisition. Perfusion estimates were acquired from rat kidneys as a function of imaging plane and in response to the vasoactive drug dopamine. Results:Our results indicate that perfusion estimates generated by 2D imaging in the rat kidney have mean standard deviations on the order of 10%, and as high as 22%, because of differences in initial transducer position. This difference was larger than changes in kidney perfusion induced by dopamine. With application of 3D perfusion mapping, repeatability in perfusion estimated in the kidney is reduced to a standard deviation of less than 3%, despite random initial transducer positioning. Varying contrast agent administration rate was also observed to bias measured perfusion time, especially at low concentrations; however, we observed that contrast administration rates between 2.7 × 108 and 3.9 × 108 bubbles/min provided results that were consistent within 3% for the contrast agent type evaluated. Conclusions:Three-dimensional perfusion imaging allows a significant reduction in the error caused by transducer positioning, and significantly improves the reliability of quantitative perfusion time estimates in a rat kidney model. When performing perfusion imaging, it is important to use appropriate and consistent contrast agent infusion rates to avoid bias.

Two-dimensional ultrasound display system

A user defines a line of study by two or more icons placed on a two-dimensional motion image. A velocity profile or the estimated spectra at each point along the line of study are displayed as a function of position along the line of study. The velocity and variance parameters displayed are computed in reference to velocity direction angles selected by the user. The information displayed is obtained from scan converted information to facilitate the process. One or more spectral strips may be displayed in addition at one or more range gate positions.

Dual process ultrasound contrast agent imaging

Methods and systems for detecting contrast agents is provided. Differences between different sized vessels throughout a period of contrast agent enhancement are identified without significantly depleting the available contrast agent. Dual detection paths are used for imaging, such as one path for detecting nonlinear response and another path for detecting differences between the responses to two or more pulses. Where echoes from two or more pulses of acoustic energy are combined to detect the nonlinear response, the nonlinear response may also include signals originating from a loss-of-correlation (LOC) or motion between received pulses. These signals generated from LOC or motion can be produced from agent disruption where a second received echo is different from a first received echo due to a change in a bubbles shape (i.e., destruction), or from simple spatial translation between acoustic pulses as seen from the same spatial location, respectively. Together the LOC or motion signals and the nonlinear signals can differentiate contrast agent from tissue. Additional information is gained by detecting signals more responsive to difference or motion information. Each path detects different relative amounts of nonlinear response and responses caused by differences between echo signals of multiple pulses. Various systems and methods for detecting contrast agents where one path preferentially detects difference or motion signals and another path preferentially detects nonlinear energy are provided.

Methods and apparatus for ultrasound imaging with automatic color image positioning

A method and apparatus for quantifying and displaying ultrasound signals in an ultrasonic system are provided. A first signal value for each of at least one spatial location in a region of interest is acquired at a first time, and the signal values are summed to obtain a first surface integral value. A second signal value for each of said at least one spatial location in said region of interest is acquired at a second time, and the second signal values are summed to obtain a second surface integral value. The first surface integral value is summed with the second surface integral value to obtain a time based integral. The time based integral is displayed. Other quantities based on any of various ultrasound parameters, such as Doppler energy, Doppler velocity and B-mode intensity, are calculated and displayed as quantities or as waveforms as a function of time. Furthermore, various comparisons of quantities and waveforms are provided. Image plane data or other ultrasound data are used in the calculations. Finally, a histogram data structure is provided to aid calculation of the various quantities.

Validation of Dynamic Contrast Enhanced Ultrasound in Rodent Kidneys as an Absolute Quantitative Method for Measuring Blood Perfusion

Contrast-enhanced ultrasound (CEUS) has demonstrated utility in the monitoring of blood flow in tissues, organs and tumors. However, current CEUS methods typically provide only relative image-derived measurements, rather than quantitative values of blood flow in milliliters/minute per gram of tissue. In this study, CEUS derived parameters of blood flow are compared with absolute measurements of blood flow in rodent kidneys. Additionally, the effects of contrast agent infusion rate and transducer orientation on image-derived perfusion measurements are assessed. Both wash-in curve and time-to-refill algorithms are examined. Data illustrate that for all conditions, image-derived flow measurements were well-correlated with transit-time flow probe measurements (R > 0.9). However, we report differences in the sensitivity to flow across different transducer orientations as well as the contrast analysis algorithm utilized. Results also indicate that there exists a range of contrast agent flow rates for which image-derived estimates are consistent.

Medical ultrasonic contrast agent imaging method and apparatus

A medical ultrasonic imaging system transmits a set of two or more substantially identical transmit pulses into a tissue containing a contrast agent. The associated received pulses are filtered with a broadband filter that passes both the fundamental and at least one harmonic component of the echoes. The filtered received pulses are then applied to a clutter filter that suppresses harmonic and fundamental responses from slowly moving and stationary tissue, while clearly showing contrast agent response due to the loss of correlation effect. The disclosed system includes other signal paths for generating conventional B-mode images as well as combined images that include both components from the contrast-specific image as well as components from the B-mode image. An improved user interface allows the user to switch among these three images. Preferably the transmitter generates transmitted pulses having two or more spatially distinct focus zones, thereby improving the uniformity of contrast agent imaging over the imaged region.

Motion corrected cadence CPS ultrasound for quantifying response to vasoactive drugs in a rat kidney model

OBJECTIVE To establish the ability of contrast-enhanced motion corrected cadence pulse sequencing (CPS) to detect changes in renal blood flow induced by vasoactive substances in rats. METHODS Ultrasound contrast media was administered as a constant rate infusion into a phantom at a known rate and CPS data acquired. Rats were anesthetized and predrug CPS estimates of replenishment rate were made for the right kidney. Real-time motion correction was applied, and parametric images were generated from the CPS data. Group 1 rats (n = 7) were administered a vasodilator and group 2 rats (n = 3) were administered a vasoconstrictor. The CPS imaging of the kidney was repeated after ample time for drug effects to occur. RESULTS Contrast CPS accurately estimated flow velocity in the phantom model. In addition, CPS defined statistically significant differences between pre- and postdrug blood flow in the renal medulla (vasodilator, P < .01; vasoconstrictor, P < .0001) and cortex (vasoconstrictor, P < .0001). CONCLUSIONS We conclude that motion-corrected CPS ultrasound provides real-time quantification of renal blood flow alterations and may prove useful for the assessment of blood flow in transplanted kidneys.

Contrast imaging beam sequences for medical diagnostic ultrasound

A transmit sequence for contrast agent imaging that improves sensitivity and minimizes image artifacts. The number of pulses and the interleaving of spatially distinct pulses between spatially co-linear pulses are selected such that a substantially similar pulse sequence for substantially each line in a scanned region is generated. A collateral pulse from a different scan line is interleaved between at least two imaging pulses along a scan line of interest. Such pulse sequences provide sensitive contrast agent imaging with minimized spatial variation. In another aspect, responsive signals representing the first and second scan lines are obtained. Intensities associated with the signals are determined. The intensities associated with the first scan line are compared to a value. The signals associated with the first scan line are replaced by the signals associated with the second scan line, signals associated with the first and second scan lines, or neighboring signals in time or space as a function of the comparison. Thus, signals associated with an image artifact may be replaced by signals along other scan lines so good spatial resolution is maintained.

Medical diagnostic ultrasound system and method for improved flow or movement detection with multiple clutter filters

A method and system for flow or movement detection is provided. More than one clutter filter is used. Each clutter filters magnitude versus frequency response is optimized differently. Estimates of the flow or movement are generated from the data output by each of the clutter filters. Using selection or combination of the resulting estimates, the best attributes of each filter are used for imaging.

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

PURPOSE To evaluate the feasibility and reproducibility of ultrasonography (US) performed with dual-selectin-targeted contrast agent microbubbles (MBs) for assessment of inflammation in a porcine acute terminal ileitis model, with histologic findings as a reference standard. MATERIALS AND METHODS The study had institutional Animal Care and Use Committee approval. Acute terminal ileitis was established in 19 pigs; four pigs served as control pigs. The ileum was imaged with clinical-grade dual P- and E-selectin-targeted MBs (MBSelectin) at increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 × 10(8) MB per kilogram of body weight) and with control nontargeted MBs (MBControl). For reproducibility testing, examinations were repeated twice after the MBSelectin and MBControl injections. After imaging, scanned ileal segments were analyzed ex vivo both for inflammation grade (by using hematoxylin-eosin staining) and for expression of selectins (by using quantitative immunofluorescence analysis). Statistical analysis was performed by using the t test, intraclass correlation coefficients (ICCs), and Spearman correlation analysis. RESULTS Imaging signal increased linearly (P < .001) between a dose of 0.5 and a dose of 5.0 × 10(8) MB/kg and plateaued between a dose of 10 and a dose of 20 × 10(8) MB/kg. Imaging signals were reproducible (ICC = 0.70), and administration of MBSelectin in acute ileitis resulted in a significantly higher (P < .001) imaging signal compared with that in control ileum and MBControl. Ex vivo histologic grades of inflammation correlated well with in vivo US signal (ρ = 0.79), and expression levels of both P-selectin (37.4% ± 14.7 [standard deviation] of vessels positive; P < .001) and E-selectin (31.2% ± 25.7) in vessels in the bowel wall of segments with ileitis were higher than in control ileum (5.1% ± 3.7 for P-selectin and 4.8% ± 2.3 for E-selectin). CONCLUSION Quantitative measurements of inflammation obtained by using dual-selectin-targeted US are reproducible and correlate well with the extent of inflammation at histologic examination in a porcine acute ileitis model as a next step toward clinical translation.