High-precision motion estimation has become essential in ultrasound-based techniques such as time-domain Doppler and elastography. Normalized cross-correlation (NCC) has been shown as one of the best motion estimators. However, a significant drawback is its associated computational cost, especially when RF signals are used. In this paper, a method based on sum tables developed elsewhere is adapted for fast NCC calculation in ultrasound-based motion estimation, and is tested with respect to the speed enhancement of the specific application of ultrasound-based motion estimation. Both the numerator and denominator in the NCC definition are obtained through pre-calculated sum tables to eliminate redundancy of repeated NCC calculations. Unlike a previously reported method, a search region following the principle of motion estimation is applied in the construction of sum tables. Because an exhaustive search and high window overlap are typically used for highest quality imaging, the computational cost of the proposed method is significantly lower than that of the direct method using the NCC definition, without increasing bias and variance characteristics of the motion estimation or sacrificing the spatial resolution. Therefore, high quality, high spatial resolution, and high calculation speed can be all simultaneously obtained using the proposed methodology. The high efficiency of this method was verified using RF signals from a human abdominal aorta in vivo. For the parameters typically used, a real-time, very high frame rate of 310 frames/s was achieved for the motion estimation. The proposed method was also extended to 2-D NCC motion estimation and motion estimation with other algorithms. The technique could thus prove very useful and flexible for real-time motion estimation as well as in other fields such as optical flow and image registration.

The role played by the thoracolumbar fascia in chronic low back pain (LBP) is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP).

Focused ultrasound (FUS) in combination with microbubbles (MBs) has been successfully used in the delivery of various-size therapeutic agents across the blood–brain barrier (BBB). This study revealed that FUS-induced BBB opening size, defined by the size of the largest molecule that can permeate through the BBB, can be controlled by the acoustic pressure as dictated by cavitational mechanisms. Focused ultrasound was applied onto the mouse hippocampus in the presence of systemically administered MBs for trans-BBB delivery of fluorescently labeled dextrans with molecular weights 3 to 2,000 kDa (hydrodynamic diameter: 2.3 to 54.4 nm). The dextran delivery outcomes were evaluated using ex vivo fluorescence imaging. Cavitation detection was employed to monitor the MB cavitation activity associated with the delivery of these agents. It was found that the BBB opening size was smaller than 3 kDa (2.3 nm) at 0.31 MPa, up to 70 kDa (10.2 nm) at 0.51 MPa, and up to 2,000 kDa (54.4 nm) at 0.84 MPa. Relatively smaller opening size (up to 70 kDa) was achieved with stable cavitation only; however, inertial cavitation was associated with relatively larger BBB opening size (above 500 kDa). These findings indicate that the BBB opening size can be controlled by the acoustic pressure and predicted using cavitation detection.

The therapeutic efficacy of neurological agents is severely limited, because large compounds do not cross the blood-brain barrier (BBB). Focused ultrasound (FUS) sonication in the presence of microbubbles has been shown to temporarily open the BBB, allowing systemically administered agents into the brain. Until now, polydispersed microbubbles (1-10 ¿m in diameter) were used, and, therefore, the bubble sizes better suited for inducing the opening remain unknown. Here, the FUS-induced BBB opening dependence on microbubble size is investigated. Bubbles at 1-2 and 4-5 ¿m in diameter were separately size-isolated using differential centrifugation before being systemically administered in mice ( n = 28). The BBB opening pressure threshold was identified by varying the peak-rarefactional pressure amplitude. BBB opening was determined by fluorescence enhancement due to systemically administered, fluorescent-tagged, 3-kDa dextran. The identified threshold fell between 0.30 and 0.46 MPa in the case of 1-2 ¿m bubbles and between 0.15 and 0.30 MPa in the 4-5 ¿m case. At every pressure studied, the fluorescence was greater with the 4-5 ¿m than with the 1-2 ¿m bubbles. At 0.61 MPa, in the 1-2 ¿m bubble case, the fluorescence amount and area were greater in the thalamus than in the hippocampus. In conclusion, it was determined that the FUS-induced BBB opening was dependent on both the size distribution in the injected microbubble volume and the brain region targeted.

The in vivo cavitation response associated with blood-brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity® microbubbles (mean diameter range: 1.1-3.3 µm, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 µm in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity® microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15-0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected without craniotomy in mice and IC may not be required for BBB opening at relatively low pressures.