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Histotripsy is an emerging noninvasive, non-thermal, and non-ionizing focused ultrasound (US) therapy that can be used to destroy targeted tissue. Histotripsy has evolved from early laboratory prototypes to clinical systems which have been comprehensively evaluated in the preclinical environment to ensure safe translation to human use. This review summarizes the observations and results from preclinical histotripsy studies in the liver, kidney, and pancreas. Key findings from these studies include the ability to make a clinically relevant treatment zone in each organ with maintained collagenous architecture, potentially allowing treatments in areas not currently amenable to thermal ablation. Treatments across organ capsules have proven safe, including in anticoagulated models which may expand patients eligible for treatment or eliminate the risk associated with taking patients off anti-coagulation. Treatment zones are well-defined with imaging and rapidly resorb, which may allow improved evaluation of treatment zones for residual or recurrent tumor. Understanding the effects of histotripsy in animal models will help inform physicians adopting histotripsy for human clinical use.

Originally described by Davis et al in 2013, 4D-Digital Subtraction Angiography (4D-DSA) has developed into a commercially available application of DSA in the angiography suite. 4D-DSA provides the user with 3D time-resolved images, allowing observation of a contrast bolus at any desired viewing angle through the vasculature and at any time point during the acquisition (any view at any time). 4D-DSA mitigates some limitations that are intrinsic to both 2D- and 3D-DSA images. The clinical applications for 4D-DSA include evaluations of AVMs and AVFs, intracranial aneurysms, and atherosclerotic occlusive disease. Recent advances in blood flow quantification using 4D-DSA indicate that these data provide both the velocity and geometric information necessary for the quantification of blood flow. In this review, we will discuss the development, acquisition, reconstruction, and current neurovascular applications of 4D-DSA volumes., (© 2021 by American Journal of Neuroradiology.)

Background and Purpose: Quantification of blood flow using a 4D-DSA would be useful in the diagnosis and treatment of cerebrovascular diseases. A protocol optimizing identification of density variations in the time-density curves of a 4D-DSA has not been defined. Our purpose was to determine the contrast injection protocol most likely to result in the optimal pulsatility signal strength., Materials and Methods: Two 3D-printed patient-specific models were used and connected to a pulsatile pump and flow system, which delivered 250-260 mL/min to the model. Contrast medium (Isovue, 370 mg I/mL, 75% dilution) was injected through a 6F catheter positioned upstream from the inlet of the model. 4D-DSA acquisitions were performed for the following injection rates: 1.5, 2.0, 2.5, 3.0 and 3.5 mL/s for 8 seconds. To determine pulsatility, we analyzed the time-density curve at the inlets using the oscillation amplitude and a previously described numeric metric, the sideband ratio. Vascular geometry from 4D-DSA reconstructions was compared with ground truth and micro-CT measurements of the model. Dimensionless numbers that characterize hemodynamics, Reynolds and Craya-Curtet, were calculated for each injection rate., Results: The strongest pulsatility signal occurred with the 2.5 mL/s injections. The largest oscillation amplitudes were found with 2.0- and 2.5-mL/s injections. Geometric accuracy was best preserved with injection rates of >1.5 mL/s., Conclusions: An injection rate of 2.5 mL/s provided the strongest pulsatility signal in the 4D-DSA time-density curve. Geometric accuracy was best preserved with injection rates above 1.5 mL/s. These results may be useful in future in vivo studies of blood flow quantification., (© 2019 by American Journal of Neuroradiology.)

Purpose: Particle image velocimetry (PIV), an in vitro experimentation technique that optically measures velocity components to analyze fluid velocity fields, has become increasingly popular to study flow dynamics in various vascular territories. However, it can be difficult and expensive to create patient-specific clear models for PIV due to the importance of refractive index matching of the model and the fluid. We aim to implement and test the use of poly-vinyl alcohol (PVA) in a lost-core casting technique to create low-cost, patient-specific models for PIV., Methods: Anonymized patient vascular anatomies were segmented and processed in Mimics/3Matic to create patient-specific cores from 3D digital subtraction angiographies. The cores were 3D-printed with PVA and post-processed with a 80:20 water:glue mixture to smooth the surface. Two silicones, Sylgard 184 and Solaris, were used to encapsulate the model and the PVA core was dissolved using warm water. Computed tomography scans were used to evaluate geometric accuracy using circumferences and surface differences in the model., Results: Mean geometric differences in circumference along the inlet centerline and the mean surface difference in the aneurysm between the final Silicone Model and the desired STL Print geometry were statistically insignificant (0.6 mm, 95% CI [- 1.4, 2.8] and 0.3 mm 95% CI [- 0.1, 0.7], respectively). Particle illumination within each model was successful. The cost of one 10 cm × 10 cm × 5 cm model was $69., Conclusion: This technique was successful to implement and test the use of PVA in a lost-core casting technique to create low-cost, patient-specific in vitro models for PIV experimentation.

Background and Purpose: 4D-DSA provides time-resolved 3D-DSA volumes with high temporal and spatial resolutions. The purpose of this study is to investigate a shifted least squares method to estimate the blood velocity from the 4D DSA images. Quantitative validation was performed using a flow phantom with an ultrasonic flow probe as ground truth. Quantification of blood velocity in human internal carotid arteries was compared with measurements generated from 3D phase-contrast MR imaging., Materials and Methods: The centerlines of selected vascular segments and the time concentration curves of each voxel along the centerlines were determined from the 4D-DSA dataset. The temporal shift required to achieve a minimum difference between any point and other points along the centerline of a segment was calculated. The temporal shift as a function of centerline point position was fit to a straight line to generate the velocity. The proposed shifted least-squares method was first validated using a flow phantom study. Blood velocities were also estimated in the 14 ICAs of human subjects who had both 4D-DSA and phase-contrast MR imaging studies. Linear regression and correlation analysis were performed on both the phantom study and clinical study, respectively., Results: Mean velocities of the flow phantom calculated from 4D-DSA matched very well with ultrasonic flow probe measurements with 11% relative root mean square error. Mean blood velocities of ICAs calculated from 4D-DSA correlated well with phase-contrast MR imaging measurements with Pearson correlation coefficient r = 0.835., Conclusions: The availability of 4D-DSA provides the opportunity to use the shifted least-squares method to estimate velocity in vessels within a 3D volume., (© 2018 by American Journal of Neuroradiology.)

Background and Purpose: Safe and effective use of newly developed devices for aneurysm treatment requires the ability to make accurate measurements in the angiographic suite. Our purpose was to determine the parameters that optimize the geometric accuracy of three-dimensional (3D) vascular reconstructions., Methods: An in vitro flow model consisting of a peristaltic pump, plastic tubing, and 3D printed patient-specific aneurysm models was used to simulate blood flow in an intracranial aneurysm. Flow rates were adjusted to match values reported in the literature for the internal carotid artery. 3D digital subtraction angiography acquisitions were obtained using a commercially available biplane angiographic system. Reconstructions were done using Edge Enhancement (EE) or Hounsfield Unit (HU) kernels and a Normal or Smooth image characteristic. Reconstructed images were analyzed using the vendor's aneurysm analysis tool. Ground truth measurements were derived from metrological scans of the models with a microCT. Aneurysm volume, surface area, dome height, minimum and maximum ostium diameter were determined for the five models., Results: In all cases, measurements made with the EE kernel most closely matched ground truth values. Differences in values derived from reconstructions displayed with Smooth or Normal image characteristics were small and had only little impact on the geometric parameters considered., Conclusions: Reconstruction parameters impact the accuracy of measurements made using the aneurysm analysis tool of a commercially available angiographic system. Absolute differences between measurements made using reconstruction parameters determined as optimal in this study were, overall, very small. The significance of these differences, if any, will depend on the details of each individual case., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)