Physics in medicine and biology
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Burst-tone focused ultrasound exposure in the presence of microbubbles has been demonstrated to be effective at inducing temporal and local opening of the blood-brain barrier (BBB), which promises significant clinical potential to deliver therapeutic molecules into the central nervous system (CNS). Traditional contrast-enhanced imaging confirmation after focused ultrasound (FUS) exposure serves as a post-operative indicator of the effectiveness of FUS-BBB opening, however, an indicator that can concurrently report the BBB status and BBB-opening effectiveness is required to provide effective feedback to implement this treatment clinically. In this study, we demonstrate the use of subharmonic acoustic emission detection with implementation on a confocal dual-frequency piezoelectric ceramic structure to perform real-time monitoring of FUS-BBB opening. ⋯ Using this ESD change threshold detection as a surrogate to on/off control the FUS exposure in stage-2 experiments, we demonstrated both excellent sensitivity (92%) and specificity (92.3%) in discriminating BBB-opening occurrence can be obtained in animal treatments, while concurrently achieving a high positive predicted value (95.8%). Wideband ESD was also highly correlated with the occurrence and level of erythrocyte extravasations (r (2) = 0.81). The proposed system configuration and corresponding analysis based on subharmonic acoustic emissions has the potential to be implemented as a real-time feedback control structure for reliable indication of intact FUS-BBB opening for CNS brain drug delivery.
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Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. ⋯ This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions.
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We recently developed a dynamic multi-bed PET data acquisition framework to translate the quantitative benefits of Patlak voxel-wise analysis to the domain of routine clinical whole-body (WB) imaging. The standard Patlak (sPatlak) linear graphical analysis assumes irreversible PET tracer uptake, ignoring the effect of FDG dephosphorylation, which has been suggested by a number of PET studies. In this work: (i) a non-linear generalized Patlak (gPatlak) model is utilized, including a net efflux rate constant kloss, and (ii) a hybrid (s/g)Patlak (hPatlak) imaging technique is introduced to enhance contrast to noise ratios (CNRs) of uptake rate Ki images. ⋯ As such, we recommend gPatlak for highly quantitative imaging tasks, while, for tasks emphasizing lesion detectability (e.g. TBR, CNR) over quantification, or for high levels of noise, hPatlak is instead preferred. Finally, gPatlak and hPatlak CNR was systematically higher compared to routine SUV values.
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Ultrafast imaging using plane or diverging waves has recently enabled new ultrasound imaging modes with improved sensitivity and very high frame rates. Some of these new imaging modalities include shear wave elastography, ultrafast Doppler, ultrafast contrast-enhanced imaging and functional ultrasound imaging. Even though ultrafast imaging already encounters clinical success, increasing even more its penetration depth and signal-to-noise ratio for dedicated applications would be valuable. ⋯ Multiplane wave with 4 plane waves emissions yields a 5.8 ± 0.5 dB increase in signal-to-noise ratio and approximately 10 mm in penetration in a calibrated ultrasound phantom (0.7 d MHz(-1) cm(-1)). In shear wave elastography, the same multiplane wave configuration yields a 2.07 ± 0.05 fold reduction of the particle velocity standard deviation and a two-fold reduction of the shear wave velocity maps standard deviation. In functional ultrasound imaging, the mapping of cerebral blood volume results in a 3 to 6 dB increase of the contrast-to-noise ratio in deep structures of the rodent brain.
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A 3D-2D image registration method is presented that exploits knowledge of interventional devices (e.g. K-wires or spine screws-referred to as 'known components') to extend the functionality of intraoperative radiography/fluoroscopy by providing quantitative measurement and quality assurance (QA) of the surgical product. The known-component registration (KC-Reg) algorithm uses robust 3D-2D registration combined with 3D component models of surgical devices known to be present in intraoperative 2D radiographs. ⋯ Using advanced pKC models, screws that did not match the device models specified in the surgical plan were detected with an accuracy of >99%. Visualization of registered devices relative to surgical planning and the pedicle acceptance window provided potentially valuable QA of the surgical product and reliable detection of pedicle screw breach. 3D-2D registration combined with 3D models of known surgical devices offers a novel method for intraoperative QA. The method provides a near-real-time independent check against pedicle breach, facilitating revision within the same procedure if necessary and providing more rigorous verification of the surgical product.