Motor Skill Training Assistance Using Haptic Attributes

In this paper we describe our efforts to develop a new strategy for providing assistance using haptics in a virtual environment when training for a motor skill. Using a record and play strategy, the proposed assistance method will provide closest possible replication of expert’s skill. We have defined a new paradigm called “Haptic Attributes ” where we relate a unique haptic force profile to every task performed using motor skills. This has been combined with an earlier concept called Sympathetic Haptic to develop a new paradigm in training complex skill based tasks such as writing, surgery or playing musical instruments. As a demonstration, a virtual environment that can be used for training handwriting was designed and implemented. Position based feedback assistance and training with no assistance were tested against our method in a series of human subject tests. Results prove our method to be superior to training methods tested which use position based or no assistance. 1

Improving haptic experience through biomechanical measurements

Haptic interfaces have been used as a surrogate for many real world applications such as rehabilitation, calligraphy, design and surgical training. While development of haptically enabled systems are opening new avenues intraining, very few studies have explored if they provide realistic and matching muscle activations compared to real world activities. In this paper a novel methodology based on muscle activity is proposed for evaluation of haptic systems. To test this methodology experiments were performed on a haptic writing simulator and comparisons were made to corresponding real pen and paper task. The behavior of two muscles, flexor carpi ulnaris and extensor digitorum communis was studied with the help of surface EMG's, during the execution of similar real and haptic based tasks. Human participant studies were carried out and results indicate that in the majority of parameters studied, the haptics based writing simulator used in this study resulted in muscle exertion and excitation similar to that of pen and paper tasks. It was seen that the proposed methodology could be used to tune the haptic system to mimic real life writing more closely. This study showed that the proposed methodology can lead to improved haptic simulators by studying the bio-mechanical reaction in humans

Reversible Electroporation–Mediated Liposomal Doxorubicin Delivery to Tumors Can Be Monitored With 89Zr-Labeled Reporter Nanoparticles

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation–related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep

Reversible Electroporation–Mediated Liposomal Doxorubicin Delivery to Tumors Can Be Monitored With 89

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation–related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep

Cytoskeletal Remodeling and Gap Junction Translocation Mediates Blood–Brain Barrier Disruption by Non-invasive Low-Voltage Pulsed Electric Fields

High-voltage pulsed electric fields (HV-PEF) delivered with invasive needle electrodes for electroporation applications is known to induce off-target blood–brain barrier (BBB) disruption. In this study, we sought to determine the feasibility of minimally invasive PEF application to produce BBB disruption in rat brain and identify the putative mechanisms mediating the effect. We observed dose-dependent presence of Evans Blue (EB) dye in rat brain when PEF were delivered with a skull mounted electrode used for neurostimulation application. Maximum region of dye uptake was observed while using 1500 V, 100 pulses, 100 µs and 10 Hz. Results of computational models suggested that the region of BBB disruption was occurring at thresholds of 63 V/cm or higher; well below intensity levels for electroporation. In vitro experiments recapitulating this effect with human umbilical vein endothelial cells (HUVEC) demonstrated cellular alterations that underlie BBB manifests at low-voltage high-pulse conditions without affecting cell viability or proliferation. Morphological changes in HUVECs due to PEF were accompanied by disruption of actin cytoskeleton, loss of tight junction protein—ZO-1 and VE-Cadherin at cell junctions and partial translocation into the cytoplasm. Uptake of propidium iodide (PI) in PEF treated conditions is less than 1% and 2.5% of total number of cells in high voltage (HV) and low-voltage (LV) groups, respectively, implying that BBB disruption to be independent of electroporation under these conditions. 3-D microfabricated blood vessel permeability was found to increase significantly following PEF treatment and confirmed with correlative cytoskeletal changes and loss of tight junction proteins. Finally, we show that the rat brain model can be scaled to human brains with a similar effect on BBB disruption characterized by electric field strength (EFS) threshold and using a combination of two bilateral HD electrode configurations