Poster - Thurs Eve-12: A needle-positioning robot co-registered with volumetric x-ray micro-computed tomography images for minimally-invasive small-animal interventions.

Preclinical research protocols often require the delivery of biological substances to specific targets in small animal disease models. To target biologically relevant locations in mice accurately, the needle positioning error needs to be < 200 µm. If targeting is inaccurate, experimental results can be inconclusive or misleading. We have developed a robotic manipulator that is capable of positioning a needle with a mean error < 100 µm. An apparatus and method were developed for integrating the needle-positioning robot with volumetric micro-computed tomography image guidance for interventions in small animals. Accurate image-to-robot registration is critical for integration as it enables targets identified in the image to be mapped to physical coordinates inside the animal. Registration is accomplished by injecting barium sulphate into needle tracks as the robot withdraws the needle from target points in a tissue-mimicking phantom. Registration accuracy is therefore affected by the positioning error of the robot and is assessed by measuring the point-to-line fiducial and target registration errors (FRE, TRE). Centroid points along cross-sectional slices of the track are determined using region growing segmentation followed by application of a center-of-mass algorithm. The centerline points are registered to needle trajectories in robot coordinates by applying an iterative closest point algorithm between points and lines. Implementing this procedure with four fiducial needle tracks produced a point-to-line FRE and TRE of 246 ± 58 µm and 194 ± 18 µm, respectively. The proposed registration technique produced a TRE < 200 µm, in the presence of robot positioning error, meeting design specification.

Volume measurement variability in three-dimensional high-frequency ultrasound images of murine liver metastases.

The identification and quantification of tumour volume measurement variability is imperative for proper study design of longitudinal non-invasive imaging of pre-clinical mouse models of cancer. Measurement variability will dictate the minimum detectable volume change, which in turn influences the scheduling of imaging sessions and the interpretation of observed changes in tumour volume. In this paper, variability is quantified for tumour volume measurements from 3D high-frequency ultrasound images of murine liver metastases. Experimental B16F1 liver metastases were analysed in different size ranges including less than 1 mm3, 1-4 mm3, 4-8 mm3 and 8-70 mm3. The intra- and inter-observer repeatability was high over a large range of tumour volumes, but the coefficients of variation (COV) varied over the volume ranges. The minimum and maximum intra-observer COV were 4% and 14% for the 1-4 mm3 and <1 mm3 tumours, respectively. For tumour volumes measured by segmenting parallel planes, the maximum inter-slice distance that maintained acceptable measurement variability increased from 100 to 600 microm as tumour volume increased. Comparison of free breathing versus ventilated animals demonstrated that respiratory motion did not significantly change the measured volume. These results enable design of more efficient imaging studies by using the measured variability to estimate the time required to observe a significant change in tumour volume.

Time-shift estimation and focusing through distributed aberration using multirow arrays.

The effects of element height on time-shift estimation and transmit focus compensation are demonstrated experimentally. Multirow ultrasonic transducer arrays were emulated by combining adjacent elements of a 3.0-MHz, 0.6-mm pitch, two-dimensional array to define larger virtual elements. Pulse-echo data were acquired through tissue-mimicking distributed aberrators, and time-shift maps estimated from those data were used for transmit focus compensation. Compensated beams formed by arrays with fine row pitches were similar, but focus restoration was significantly less effective for "1.75-D" arrays with a coarse row pitch. For example, when focus compensation was derived from strongly aberrated random scattering data [70-ns nominal rms arrival time fluctuation with 7 mm FWHM (full-width at half-maximum) correlation length], the mean -20 dB lateral beamwidths were 5.2 mm for f/2.0 arrays with 0.6- and 1.8-mm row pitches and 9.5 mm for an f/2.0 array with 5.4-mm pitch. Time-shift maps estimated from random scattering data acquired with 5.4-mm pitch arrays included large discontinuities caused by low correlation of signals received on vertically and diagonally adjacent emulated elements. The results indicate that multirow arrays designed for use with aberration correction should have element dimensions much less than 75% of the correlation length of the aberration and perhaps as small as 25 to 30% of the correlation length.

Angular scatter ultrasound imaging of wavelength scale targets.

A bistatic ultrasound imaging system is demonstrated that uses two 32-element linear phased array transducers oriented at an angle of 40 degrees to one another. The system simultaneously acquires and displays in real time one conventional backscatter image and one "angular scatter" image formed using side-scattered echoes from the same B-mode sector region. Experiments are presented that show differences in the magnitudes of backscatter and angular scatter signals acquired from three nylon monofilaments with diameters less than one wavelength and from soft tissue structures in vivo. The relative magnitudes of angular scatter signals from the monofilaments are qualitatively consistent with a theoretical analysis of acoustic scattering from elastic cylinders. Larger tissue features are more clearly defined in angular scatter images. This result is attributed to the orientation of specularly reflecting surfaces and the expected influence of scattering angle on the system's sensitivity to different scatterer spacings.

Design and characterization of a real-time angular scatter ultrasound imaging system.

A novel ultrasound imaging system has been implemented using two 32-element linear phased array transducers oriented at an angle of 40 degrees to one another. The system simultaneously acquires and displays, in real time, a conventional backscatter image and an angular scatter image formed using side-scattered echoes from the same region. The design of the system is shaped by the influence of the scatter angle on the spatial resolution and receive signal processing requirements of the instrument. The subtended scatter angles are restricted to values >90 degrees to ensure that the angular scatter receiver effectively tracks the transmitted pulse and that the spatial resolution in the two images is comparable. The system is sufficiently tolerant of small variations in the average acoustic velocity of the medium to guarantee reliable pulse tracking in biomedical applications. The angular scatter signal magnitude is significantly weighted by the directivity of the receive array. The imaging system will most effectively demonstrate angular variations in scattering at scatter angles between 125 and 145 degrees , where the angular response of the receiver is near its peak.