Human-scale navigation of magnetic microrobots in hepatic arteries.

Using external actuation sources to navigate untethered drug-eluting microrobots in the bloodstream offers great promise in improving the selectivity of drug delivery, especially in oncology, but the current field forces are difficult to maintain with enough strength inside the human body (>70-centimeter-diameter range) to achieve this operation. Here, we present an algorithm to predict the optimal patient position with respect to gravity during endovascular microrobot navigation. Magnetic resonance navigation, using magnetic field gradients in clinical magnetic resonance imaging (MRI), is combined with the algorithm to improve the targeting efficiency of magnetic microrobots (MMRs). Using a dedicated microparticle injector, a high-precision MRI-compatible balloon inflation system, and a clinical MRI, MMRs were successfully steered into targeted lobes via the hepatic arteries of living pigs. The distribution ratio of the microrobots (roughly 2000 MMRs per pig) in the right liver lobe increased from 47.7 to 86.4% and increased in the left lobe from 52.2 to 84.1%. After passing through multiple vascular bifurcations, the number of MMRs reaching four different target liver lobes had a 1.7- to 2.6-fold increase in the navigation groups compared with the control group. Performing simulations on 19 patients with hepatocellular carcinoma (HCC) demonstrated that the proposed technique can meet the need for hepatic embolization in patients with HCC. Our technology offers selectable direction for actuator-based navigation of microrobots at the human scale.

Design of a Low-Cost, Self-Adaptive and MRI-Compatible Cardiac Gating System.

OBJECTIVE: Cardiac gating, synchronizing medical scans with cardiac activity, is widely used to make quantitative measurements of physiological events and to obtain high-quality scans free of pulsatile artefacts. This can provide important information for disease diagnosis, targeted control of medical microrobots, etc. The current work proposes a low-cost, self-adaptive, MRI-compatible cardiac gating system. METHOD: The system and its processing algorithm, based on the monitoring and analysis of blood pressure waveforms, are proposed. The system is tested in an in vitro experiment and two living pigs using four-dimensional (4D) flow magnetic resonance imaging (MRI) and two-dimensional phase-contrast (2D-PC) sequences. RESULTS: in vitro and in vivo experiments reveal that the proposed system can provide stable cardiac synchronicity, has good MRI compatibility, and can cope with the fringe magnetic field of the MRI scanner, radiofrequency signals during image acquisition, and heart rate changes. High-resolution 4D flow imaging is successfully acquired both in vivo and in vitro. The difference between the 2D and 4D measurements is ≤ 21%. The incidence of false triggers is 0% in all tests, which is unattainable for other known cardiac gating methods. CONCLUSION: The system has good MRI compatibility and can provide a stable and accurate trigger signal based on pressure waveform. It opens the door to applications where the previous gating methods were difficult to implement or not applicable.

Design of a Patient-Specific Respiratory-Motion-Simulating Platform for In Vitro 4D Flow MRI.

Four-dimensional (4D) flow magnetic resonance imaging (MRI) is a leading-edge imaging technique and has numerous medicinal applications. In vitro 4D flow MRI can offer some advantages over in vivo ones, especially in accurately controlling flow rate (gold standard), removing patient and user-specific variations, and minimizing animal testing. Here, a complete testing method and a respiratory-motion-simulating platform are proposed for in vitro validation of 4D flow MRI. A silicon phantom based on the hepatic arteries of a living pig is made. Under the free-breathing, a human volunteer's liver motion (inferior-superior direction) is tracked using a pencil-beam MRI navigator and is extracted and converted into velocity-distance pairs to program the respiratory-motion-simulating platform. With the magnitude displacement of about 1.3 cm, the difference between the motions obtained from the volunteer and our platform is ≤ 1 mm which is within the positioning error of the MRI navigator. The influence of the platform on the MRI signal-to-noise ratio can be eliminated even if the actuator is placed in the MRI room. The 4D flow measurement errors are respectively 0.4% (stationary phantom), 9.4% (gating window = 3 mm), 27.3% (gating window = 4 mm) and 33.1% (gating window = 7 mm). The vessel resolutions decreased with the increase of the gating window. The low-cost simulation system, assembled from commercially available components, is easy to be duplicated.

Assessment of hepatic arterial hemodynamics with 4D flow MRI: in vitro analysis of motion and spatial resolution related error and in vivo feasibility study in 20 volunteers.

OBJECTIVES: To assess the ability of four-dimensional (4D) flow MRI to measure hepatic arterial hemodynamics by determining the effects of spatial resolution and respiratory motion suppression in vitro and its applicability in vivo with comparison to two-dimensional (2D) phase-contrast MRI. METHODS: A dynamic hepatic artery phantom and 20 consecutive volunteers were scanned. The accuracies of Cartesian 4D flow sequences with k-space reordering and navigator gating at four spatial resolutions (0.5- to 1-mm isotropic) and navigator acceptance windows (± 8 to ± 2 mm) and one 2D phase-contrast sequence (0.5-mm in -plane) were assessed in vitro at 3 T. Two sequences centered on gastroduodenal and hepatic artery branches were assessed in vivo for intra - and interobserver agreement and compared to 2D phase-contrast. RESULTS: In vitro, higher spatial resolution led to a greater decrease in error than narrower navigator window (30.5 to -4.67% vs -6.64 to -4.67% for flow). In vivo, hepatic and gastroduodenal arteries were more often visualized with the higher resolution sequence (90 vs 71%). Despite similar interobserver agreement (κ = 0.660 and 0.704), the higher resolution sequence had lower variability for area (CV = 20.04 vs 30.67%), flow (CV = 34.92 vs 51.99%), and average velocity (CV = 26.47 vs 44.76%). 4D flow had lower differences between inflow and outflow at the hepatic artery bifurcation (11.03 ± 5.05% and 15.69 ± 6.14%) than 2D phase-contrast (28.77 ± 21.01%). CONCLUSION: High-resolution 4D flow can assess hepatic artery anatomy and hemodynamics with improved accuracy, greater vessel visibility, better interobserver reliability, and internal consistency. KEY POINTS: • Motion-suppressed Cartesian four-dimensional (4D) flow MRI with higher spatial resolution provides more accurate measurements even when accepted respiratory motion exceeds voxel size. • 4D flow MRI with higher spatial resolution provides substantial interobserver agreement for visualization of hepatic artery branches. • Lower peak and average velocities and a trend toward better internal consistency were observed with 4D flow MRI as compared to 2D phase-contrast.

Quantification and 3D Localization of Magnetically Navigated Superparamagnetic Particles Using MRI in Phantom and Swine Chemoembolization Models.

OBJECTIVE: Superparamagnetic nanoparticles (SPIONs) can be combined with tumor chemoembolization agents to form magnetic drug-eluting beads (MDEBs), which are navigated magnetically in the MRI scanner through the vascular system. We aim to develop a method to accurately quantify and localize these particles and to validate the method in phantoms and swine models. METHODS: MDEBs were made of Fe3O4 SPIONs. After injected known numbers of MDEBs, susceptibility artifacts in three-dimensional (3D) volumetric interpolated breath-hold examination (VIBE) sequences were acquired in glass and Polyvinyl alcohol (PVA) phantoms, and two living swine. Image processing of VIBE images provided the volume relationship between MDEBs and their artifact at different VIBE acquisitions and post-processing parameters. Simulated hepatic-artery embolization was performed in vivo with an MRI-conditional magnetic-injection system, using the volume relationship to locate and quantify MDEB distribution. RESULTS: Individual MDEBs were spatially identified, and their artifacts quantified, showing no correlation with magnetic-field orientation or sequence bandwidth, but exhibiting a relationship with echo time and providing a linear volume relationship. Two MDEB aggregates were magnetically steered into desired liver regions while the other 19 had no steering, and 25 aggregates were injected into another swine without steering. The MDEBs were spatially identified and the volume relationship showed accuracy in assessing the number of the MDEBs, with small errors (≤ 8.8%). CONCLUSION AND SIGNIFICANCE: MDEBs were able to be steered into desired body regions and then localized using 3D VIBE sequences. The resulting volume relationship was linear, robust, and allowed for quantitative analysis of the MDEB distribution.

Navigation of Microrobots by MRI: Impact of Gravitational, Friction and Thrust Forces on Steering Success.

INTRODUCTION: Magnetic resonance navigation (MRN) uses MRI gradients to steer magnetic drug-eluting beads (MDEBs) across vascular bifurcations. We aim to experimentally verify our theoretical forces balance model (gravitational, thrust, friction, buoyant and gradient steering forces) to improve the MRN targeted success rate. METHOD: A single-bifurcation phantom (3 mm inner diameter) made of poly-vinyl alcohol was connected to a cardiac pump at 0.8 mL/s, 60 beats/minutes with a glycerol solution to reproduce the viscosity of blood. MDEB aggregates (25 ± 6 particles, 200 [Formula: see text]) were released into the main branch through a 5F catheter. The phantom was tilted horizontally from - 10° to +25° to evaluate the MRN performance. RESULTS: The gravitational force was equivalent to 71.85 mT/m in a 3T MRI. The gradient duration and amplitude had a power relationship (amplitude=78.717 [Formula: see text]). It was possible, in 15° elevated vascular branches, to steer 87% of injected aggregates if two MRI gradients are simultaneously activated ([Formula: see text] = +26.5 mT/m, [Formula: see text]= +18 mT/m for 57% duty cycle), the flow velocity was minimized to 8 cm/s and a residual pulsatile flow to minimize the force of friction. CONCLUSION: Our experimental model can determine the maximum elevation angle MRN can perform in a single-bifurcation phantom simulating in vivo conditions.

Exercise Intolerance in Patients with Chronic Iliocaval Venous Occlusion: Initial Experience with Noninvasive Exercise Testing before and after Intervention.

Patients with chronic iliocaval occlusions after thrombosis often present with exercise intolerance, which improves after venous reconstruction. Three male patients with chronic iliocaval occlusions underwent a cardiorespiratory fitness test before and 2.5-11 months after venous reconstruction using stents. After the intervention, average absolute oxygen consumption increased by 29.5%, maximal oxygen consumption relative to body weight increased by 38.7%, total work at maximum exercise increased by 74.4%, and exercise time increased by 18.7%. The cardiorespiratory fitness test may be a useful noninvasive tool to objectively evaluate exercise intolerance due to chronic venous occlusions and response to therapy.