Clinical translation of abdominal histotripsy: a review of preclinical studies in large animal models.

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.

In Vitro Assessment of Flow Variability in an Intracranial Aneurysm Model Using 4D Flow MRI and Tomographic PIV.

Aneurysm rupture has been suggested to be related to aneurysm geometry, morphology, and complex flow activity; therefore, understanding aneurysm-specific hemodynamics is crucial. 4D Flow MRI has been shown to be a feasible tool for assessing hemodynamics in intracranial aneurysms with high spatial resolution. However, it requires averaging over multiple heartbeats and cannot account for cycle-to-cycle hemodynamics variations. This study aimed to assess cycle-to-cycle flow dynamics variations in a patient-specific intracranial aneurysm model using tomographic particle image velocimetry (tomo-PIV) at a high image rate under pulsatile flow conditions. Time-resolved and time-averaged velocity flow fields within the aneurysm sac and estimations of wall shear stress (WSS) were compared with those from 4D Flow MRI. A one-way ANOVA showed a significant difference between cardiac cycles (p value < 0.0001); however, differences were not significant after PIV temporal and spatial resolution was matched to that of MRI (p value 0.9727). This comparison showed the spatial resolution to be the main contributor to assess cycle-to-cycle variability. Furthermore, the comparison with 4D Flow MRI between velocity components, streamlines, and estimated WSS showed good qualitative and quantitative agreement. This study showed the feasibility of patient-specific in-vitro experiments using tomo-PIV to assess 4D Flow MRI with high repeatability in the measurements.

Fabrication of Low-Cost Patient-Specific Vascular Models for Particle Image Velocimetry.

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.

Impact of image reconstruction parameters when using 3D DSA reconstructions to measure intracranial aneurysms.

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.