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.

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.

Paclitaxel and mortality in patients with claudication and de novo femoropopliteal lesions: a historical cohort study.

OBJECTIVE: To compare the mortality rates of patients with claudication and de novo femoropopliteal lesions treated with and without paclitaxel coated devices (PCD). BACKGROUND: A recent meta-analysis, mostly including patients with claudication and de novo femoropopliteal lesions but also with recurrent stenoses and critical limb ischemia, has shown a significant excess mortality in patients treated with PCD. METHODS: Comparison of two historical cohorts of patients presenting with claudication and de novo femoropopliteal lesions treated with and without PCD between 2008 and 2018. RESULTS: After review of 5219 arteriograms in patients presenting with peripheral artery disease, 700 consecutive patients were included consisting in 72.6% of male (n = 508). Mean age was 68.1 ± 8.5 years. 45.7% of the patients (n = 320) had a treatment including a PCD. Mean femoropopliteal lesion length was 123 ± 91 mm including 44.6% of occlusions. Patients of the control group were censored at crossover to paclitaxel when applicable. Mortality rates at 1, 2 and 5 years were 4.6%, 7.5%, 19.4% and 1.6%, 6.2%, 16.6% in the non-PCD and PCD groups respectively. The relative risks of death when using PCD were 0.35 (p = 0.03), 0.83 (p = NS) and 0.86 (p = NS) at 1, 2 and 5 years respectively. CONCLUSION: There was no excess mortality in patients with claudication and de novo femoropopliteal lesions treated with paclitaxel coated devices at 1, 2 and 5 years of follow-up in this cohort. The current study suggests that additional prospective randomized studies properly powered to study mortality are necessary.

Development of Silica-Immobilized Vaccines for Improving Thermo-Tolerance and Shelf-Life.

INTRODUCTION: It is estimated that 50% of vaccines produced annually are wasted because effectivity is dependent on protein structure and heat exposure disrupts the intermolecular interactions that maintain this structure. Since 90% of vaccines require a temperature-controlled supply chain, it is necessary to create a cold chain system to minimize vaccine waste. We have developed a more sustainable technology via the adsorption of Invasion Plasmid Antigen D (IpaD) onto mesoporous silica gels, improving the thermal stability of protein-based therapeutics. METHODS: The solution depletion method using UV-Vis was utilized to study the adsorption of IpaD onto silica gels. The silica-IpaD complex is heated above the denaturing temperature of the protein and then the IpaD is removed using N,N-Dimethyldodecylamine N-oxide (LDAO) and their secondary structure is tested using circular dichroism (CD). RESULTS: Pore diameter, pore volume and surface area were characterized for seven different silica gels. Silica gels designated as 6389, 6378, and 6375 had an adsorption percentage above 95% at pore volumes of 2.2, 2.8 and 3.8 cm3 mg-1, respectively. CD analyses confirmed that the adsorbed IpaD after the heat treatment displayed a similar "W" shape CD signal as the native IpaD, indicating the conservation of α-helices. In contrast, the unprotected IpaD after being exposed to high temperature shows a flat CD signal, demonstrating the loss of secondary structure. CONCLUSION: We have successfully increased the thermo-tolerance for IpaD using mesoporous silica and continue to further optimize mesoporous silica's physiochemical properties to improve adsorption and desorption yields.

The Value of Regional Cerebral Blood Flow SPECT and FDG PET in Operculoinsular Epilepsy.

PURPOSE: Operculoinsular epilepsy (OIE) can be challenging to diagnose. While the value of SPECT cerebral blood flow and PET F-FDG studies for presurgical evaluation of patients with medial temporal lobe epilepsy (MTLE) is well established, it remains unclear whether they can help identify an operculoinsular epileptic focus. This study assesses the value of interictal/ictal regional cerebral blood flow (rCBF) SPECT and FDG PET for OIE diagnosis. METHODS: Eighteen patients with proven OIE who underwent interictal/ictal rCBF SPECT and/or FDG-PET prior to epilepsy surgery were identified from our clinical database and were compared with a group of 18 patients who underwent MTLE surgery. Regional cerebral blood flow SPECT and FDG PET images were reevaluated visually by an expert reader blind to clinical data. RESULTS: Interictal/ictal rCBF SPECT correctly identified an operculoinsular focus in 11 (65%) of 17 OIE patients and was misleading in 3 cases (18%). Secondary activation in areas connected to the insula was often observed. In the MTLE group, the area of maximal increased perfusion was congruent in 12 (75%) of 16 patients and extended to the ipsilateral insula in 1 patient. FDG PET findings were concordant with the epileptic focus in 8 (47%) of 17 OIE patients and were misleading in 4 (24%), whereas they were concordant in all MTLE patients. CONCLUSIONS: Interictal/ictal rCBF SPECT can identify a concordant operculoinsular focus in a significant proportion of OIE patients and offers a valuable diagnostic tool in nonlesional cases. By contrast, the value of interictal FDG PET in this population is more equivocal.