Magnetic resonance imaging and navigation of ferromagnetic thermoseeds to deliver thermal ablation therapy

Minimally invasive therapies aim to deliver effective treatment whilst reducing off-target burden, limiting side effects, and shortening patient recovery times. Remote navigation of untethered devices is one method that can be used to deliver targeted treatment to deep and otherwise inaccessible locations within the body. Minimally invasive image-guided ablation (MINIMA) is a novel thermal ablation therapy for the treatment of solid tumours, whereby an untethered ferromagnetic thermoseed is navigated through tissue to a target site within the body, using the magnetic field gradients generated by a magnetic resonance imaging (MRI) system. Once at the tumour, the thermoseed is heated remotely using an alternating magnetic field, to induce cell death in the surrounding cancer tissue. The thermoseed is then navigated through the tumour, heating at pre-defined locations until the entire volume has been ablated. The aim of this PhD project is to develop MINIMA through a series of proof-of-concept studies and to assess the efficacy of the three key project components: imaging, navigation, and heating. First, an MR imaging sequence was implemented to track the thermoseeds during navigation and subsequently assessed for precision and accuracy. Secondly, movement of the thermoseeds through a viscous fluid was characterised, by measuring the effect of different navigation parameters. This was followed by navigation experiments performed in ex vivo tissue. To assess thermoseed heating, a series of in vitro experiments were conducted in air, water, and ex vivo liver tissue, before moving onto in vivo experiments in the rat brain and a murine subcutaneous tumour model. These final experiments allowed the extent of cell death induced by thermoseed heating to be determined, in both healthy and diseased tissue respectively

Microdispositivos:: herramientas para aplicaciones médicas

Abstract: This article reviews the literature on the latest advances in microdevices for medical applications. The objective is to show an overview of the latest devices and their applications, as well as future development vectors in the area. A search of about 170 articles was performed, most of them published between the years 2015 and 2021, of which 53 were chosen as they were the most topical and impactful in the research fields referred to drug delivery, minimally invasive surgery, and cranial and vascular intromissions. It is concluded that, although microdevices are at an advanced stage of research, they still have many challenges to be solved, which has not allowed clinical trials to be completed in many cases. One of the great challenges ahead is to increase the precision in locomotion and to make the devices capable of performing more complex tasks with the help of smaller-scale electronic devices.Resumen: El presente artículo realiza una revisión de la literatura sobre los últimos avances en cuanto a los micro dispositivos para aplicaciones médicas. El objetivo es mostrar un panorama general de los últimos dispositivos y sus aplicaciones, así como los futuros vectores de desarrollo en el área. Se realizó una búsqueda de alrededor de 170 artículos, la mayoría de ellos publicados entre los años 2015 y 2021, de los cuales se eligieron 53 al ser los de mayor actualidad e impacto en los campos de investigación referidos a la administración de fármacos, la cirugía mínimamente invasiva, y las intromisiones craneales y vasculares. Se concluye que, si bien los micro dispositivos están en una etapa avanzada de investigación, aún tienen muchos desafíos por solucionar, lo cual no ha permitido completar en muchos casos las pruebas clínicas. Uno de los grandes desafíos futuros es incrementar la precisión en locomoción y conseguir que los dispositivos puedan realizar tareas más complejas con ayuda de dispositivos electrónicos de menor escala

A novel approach to fabricate bioinspired programmable composite materials: the 3D Printing way

L'abstract è presente nell'allegato / the abstract is in the attachmen

Scalable strategies for tumour targeting of magnetic carriers and seeds

With the evolving landscape of medical oncology, focus has shifted away from nonspecific cytotoxic treatment strategies toward therapeutic paradigms more characteristic of targeted therapies. These therapies rely on delivery vehicles such as nano-carriers or micro robotic devices to boosts the concentration of therapeutics in a specific targeted site inside the body. The use of externally applied magnetic field is suggested to be a predominant approach for remote localisation of magnetically responsive carriers and devices to the target region that could not be otherwise reached. However, the fast decline of the magnetic fields and gradients with increasing distances from the source is posing a major challenge for its clinical application. The aim of this thesis was to investigate potential magnetic delivery strategies which can circumvent some of the typical limitations of this technique. Two different approaches were explored to this end. The first approach was to characterise the ability of a conventional permanent magnet on targeting individual nano-carriers and develop novel magnetic designs which improve the targeting efficiency. The second approach was evaluating the feasibility of a magnetic resonance imaging system to move a millimetre-sized magnetic particle within the body. Phantom and in vivo magnetic targeting experiments illustrated the significant increase in effective targeting depth when our novel magnetic design was used for targeting nano-carriers compared with conventional magnets. In the later part of the thesis, the proof of concept and characterisation experiments showed that a 3 mm magnetic particle can be moved in ex vivo brain tissue using a magnetic resonance imaging system using clinically relevant gradient strengths. The magnetic systems introduced in this thesis provide the potential to target nano-carriers and millimetre-sized thermoseeds to tumours located at deep regions of human body through vasculature and soft tissue respectively

Minimally invasive therapies for the brain using magnetic particles

Delivering a therapy with precision, while reducing off target effects is key to the success of any novel therapeutic intervention. This is of most relevance in the brain, where the preservation of surrounding healthy tissue is crucial in reducing the risk of cognitive impairment and improving patient prognosis. Our scientific understanding of the brain would also benefit from minimally invasive investigations of specific cell types so that they may be observed in their most natural physiological environment. Magnetic particles based techniques have the potential to deliver cellular precision in a minimally invasive manner. When inside the body, Magnetic particles can be actuated remotely using externally applied magnetic fields while their position can be detected non-invasively using MRI. The magnetic forces applied to the particles however, rapidly decline with increasing distance from the magnetic source. It is therefore critical to understand the amount of force needed for a particular application. The properties of the magnetic particle such as the size, shape and magnetic content, as well as the properties of the applied magnetic field, can then be tailored to that application. The aim of this thesis was to develop magnetic particle based techniques for precise manipulation of cells in the brain. Two different approaches were explored, utilising the versatile nature of magnetic actuation for two different applications. The first approach uses magnetic nanoparticles to mechanically stimulate a specific cell type. Magnetic particles conjugated with the antibody ACSA-1 would selectively bind to astrocytes to evoke the controlled release of ATP and induce a calcium flux which are used for communication with neighbouring cells. This approach allows for the investigation into the role of astrocytes in localised brain regions using a naturally occurring actuation process (mechanical force) without effecting their natural environment. The second approach uses a millimetre sized magnetic particle which can be navigated through the brain and ablate localised regions of cells using a magnetic resonance imaging system. The magnetic particle causes a distinct contrast in MRI images, allowing for precise detection of its location so that it may be iteratively guided along a pre-determined path to avoid eloquent brain regions. Once at the desired location, an alternating magnetic field can be applied causing the magnetic particle to heat and deliver controllable, well defined regions of cell death. The forces needed for cell stimulation are orders of magnitude less than the forces needed to guide particles through the brain. Chapters 4 and 5 use external magnets to deliver forces in the piconewton range. While stimulation was demonstrated in small animals, scaling up this technique to human proportions remains a challenge. Chapters 6 and 7 use a preclinical MRI system to generate forces in the millinewton range, allowing the particle to be moved several centimetres through the brain within a typical surgical timescale. When inside the scanner, an alternating magnetic field causes the particle to heat rapidly, enabling the potential for multiple ablations within a single surgery. For clinical translation of this technique, MRI scanners would require a dedicated propulsion gradient set and heating coil

Proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress

Published proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress, hosted by York University, 27-30 May 2018

Magnetic Hammer Actuation for Tissue Penetration using a Millirobot

Untethered magnetic navigation of millirobots within a human body using a magnetic resonance imaging (MRI) scanner is a promising technology for minimally invasive surgery or drug delivery. Because MRI scanners have a large static magnetic field, they cannot generate torque on magnetic millirobots and must instead use gradient-based pulling. However, gradient values are too small to produce forces large enough to penetrate tissue. This letter presents a method to produce large pulsed forces on millirobots. A ferromagnetic sphere is placed inside a hollow robot body and can move back and forth. This movement is created by alternating the magnetic gradient direction. On the posterior side, a spring allows the sphere to change direction smoothly. On the anterior side, a hard rod creates a surface for the sphere to impact. This impact results in a large pulsed force. The purpose of this study was to understand the functioning of magnetic hammer actuation and control, as well as demonstrate the viability of this mechanism for tissue penetration. This letter begins with modeling and simulating this system. Next, different control strategies are presented and tested. The system successfully penetrated lamb brain samples. Finally, preliminary tests inside a clinical MRI scanner demonstrate the potential of this actuation system