Volumetric ultrasound localization microscopy of the whole brain microvasculature

Technologies to visualize whole organs across scales in vivo are essential for our understanding of biology in health and disease. To date, only post-mortem techniques such as perfused computed tomography scanning or optical microscopy of cleared tissues achieve cellular resolution across entire organs and imaging methods with equal performance in living mammalian organs have yet to be developed. Recently, 2D ultrasound localization microscopy has successfully mapped the fine-scale vasculature of various organs down to a 10 μm precision. However, reprojection issues and out-of-plane motion prevent complex blood flow quantification and fast volumetric imaging of whole organs. Here, we demonstrate for the first time in vivo volumetric ultrasound localization microscopy mapping of the rodent brain vasculature. We developed a complete methodological pipeline that includes specific surgery, a dedicated 3D ultrasound acquisition sequence, localization and tracking algorithms, motion correction and realignment, as well as the post-processing quantification of cerebral blood flow. We illustrate the power of this approach, by mapping the whole rat brain vasculature at a resolution of 12 μm, revealing mesoscopic to macroscopic vascular architectures and cerebral blood flows ranging from 1 to 100 mm/s. Our results pave the way to the investigation of in vivo vascular processes across the mammalian brain in health and disease, in a wide range of contexts and models.

Validation of Automated Ultrasound-based Registration for Navigated Scaphoid Fixation

Fractures of the scaphoid bone may be treated in a minimally-invasive fashion. Conventionally, fluoroscopy is required to guide the placement of an osteosynthesis screw. In this work, an alternative method based on volumetric ultrasound is validated. Methods: The fully automatic and fast image processing pipeline involves two machine learning architectures for segmentation and registration. A pre-operatively acquired 3D bone model is registered to the 3D bone surface segmented from the intra-operative ultrasound. Screw positioning is planned in an automated fashion and evaluated in an in-vitro setting: Volumetric ultrasound images of a 3D-printed phantom of a human wrist are acquired for 22 different probe poses. For 220 test runs with different initial displacements, the resulting screw placement within a defined safe zone is evaluated. If the screw lies within the safe zone, its placement is assumed to be successful. Results: An isolated analysis of the registration results in a surface distance error of the registered meshes of 0.49 ± 0.01mm, with successful screw placement in all of the evaluated 220 test runs. The full pipeline, combining segmentation and registration, achieves a mean surface distance error of 0.79 ± 0.37mm, leading to successful screw placements for 149 out of 220 test runs. Poses not suited for the registration could be determined. Excluding these from the analysis, 139 out of 160 test runs are successful. Conclusion: The method proves to be promising when evaluating the registration alone, even given the challenging setup of sub-optimal probe positions. The experiments also demonstrate that further improvement regarding the segmentation is necessary.

Real-Time Volumetric Ultrasound Research Platform with 1024 Parallel Transmit and Receive Channels

Volumetric ultrasound imaging is of great importance in many medical fields, especially in cardiology, but also in therapy monitoring applications. For development of new imaging technologies and scanning strategies, it is crucial to be able to use a hardware platform that is as free and flexible as possible and does not restrict the user in his research in any way. For this purpose, multi-channel ultrasound systems are particularly suitable, as they are able to control each individual element of a matrix array without the use of a multiplexer. We set out to develop a fully integrated, compact 1024-channel ultrasound system that provides full access to all transmission parameters and all digitized raw data of each transducer element. For this purpose, we synchronize four research scanners of our latest “DiPhAS” ultrasound research system generation, each with 256 parallel channels, all connected to a single PC on whose GPUs the entire signal processing is performed. All components of the system are housed in a compact, movable 19-inch rack. The system is designed as a general-purpose platform for research in volumetric imaging; however, the first-use case will be therapy monitoring by tracking radiation-sensitive ultrasound contrast agents.