Ultra High Field (7T) Magnetic Resonance Imaging of Intracranial Vessel Wall

Intracranial vessel wall imaging may be accomplished with high-field (7T) magnetic resonance (MRI). To determine its feasibility, a 7T MR protocol was defined using Polyvinyl-alcohol cryogel (PVA-C) phantom vessels and healthy subjects. A 2D matrix construct of PVA-C vessel phantoms of different diameters and wall thicknesses was scanned. Three observers measured the phantom images, one of which three times. Physical measurements were performed using a digital caliper. Ten volunteers were scanned using three different MRI sequences (TSE-3D, FLAIR, MPRAGE). Imaging assessment was performed in different circle of Willis (COW) segments. Reliability and accuracy of the measurements was analyzed by inter and intraobserver correlation and by comparison to physical measurements. Phantom measurements showed overall high inter and intraobserver reliability and accuracy (ICC≅0.9). However, precision diminished for smaller vessels (\u3c3mm). TSE was superior on vessel wall definition compared with FLAIR on both, phantoms and volunteers. On healthy subjects, vessel wall was recognized consistently, but precise definition of distal COW segments was not achieved. Vessel wall was significantly overestimated (p\u3c0.05) when comparing to intracranial vessel diameters from prior studies due to partial volume effects. Vessel wall imaging is feasible with 7T MR. However, precision and definition decreases consistently with the vessel caliber. PVA adequately mimics 7T MR vessel wall imaging properties

Tissue mimicking materials for imaging and therapy phantoms: a review

Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development

The development of a soft tissue mimicking hydrogel: Mechanical characterisation and 3D printing

Accurate tissue phantoms are difficult to design due to the complex hyperelastic, viscoelastic and biphasic properties of real soft tissues. The aim of this work is to demonstrate the tissue mimicking ability of a composite hydrogel (CH), constituting of poly(vinyl alcohol) (PVA) and phytagel (PHY), as a soft tissue phantom over a range mechanical properties, for a variety of biomedical and tissue engineering applications. Its compressive stress-strain behaviour, relaxation response, tensile impact stresses and surgical needle-tissue interactions were mapped and characterised with respect to its constituent hydrogel formulation. The mechanical characterisation of biological tissues was also investigated and the results were used as the ground truth for mimicking. The best mimicking hydrogel compositions were determined by combining the most relevant mechanical properties for each desired application. This thesis demonstrates the use of the tissue mimicking composite hydrogel formulations as tissue phantoms for various surgical procedures, including convection enhanced drug delivery, and traumatic brain injury studies. To expand the applications of the CH, a preliminary biological evaluation of the hydrogel was performed using human dermal fibroblasts. Cell seeded on the collagen-coated composite hydrogel showed good attachment and viability. Finally, a novel fabrication method with the aim of creating samples that replicate the anisotropic properties of biological tissues was developed. A cryogenic 3D printing method utilising the liquid to solid phase change of the composite hydrogel ink was achieved by rapidly cooling the ink solution below its freezing point. The setup was able to successfully create complex 3D brain mimicking material. The method was validated by showing that the mechanical and microstructural properties of the 3D printed material was well matched to its cast-moulded equivalent. This greatly widens the applications of the CH as a mechanically accurate tool for in-vitro testing and also demonstrates promise for future mechanobiology and tissue engineering studies.Open Acces

Integrated navigation and visualisation for skull base surgery

Skull base surgery involves the management of tumours located on the underside of the brain and the base of the skull. Skull base tumours are intricately associated with several critical neurovascular structures making surgery challenging and high risk. Vestibular schwannoma (VS) is a benign nerve sheath tumour arising from one of the vestibular nerves and is the commonest pathology encountered in skull base surgery. The goal of modern VS surgery is maximal tumour removal whilst preserving neurological function and maintaining quality of life but despite advanced neurosurgical techniques, facial nerve paralysis remains a potentially devastating complication of this surgery. This thesis describes the development and integration of various advanced navigation and visualisation techniques to increase the precision and accuracy of skull base surgery. A novel Diffusion Magnetic Resonance Imaging (dMRI) acquisition and processing protocol for imaging the facial nerve in patients with VS was developed to improve delineation of facial nerve preoperatively. An automated Artificial Intelligence (AI)-based framework was developed to segment VS from MRI scans. A user-friendly navigation system capable of integrating dMRI and tractography of the facial nerve, 3D tumour segmentation and intraoperative 3D ultrasound was developed and validated using an anatomically-realistic acoustic phantom model of a head including the skull, brain and VS. The optical properties of five types of human brain tumour (meningioma, pituitary adenoma, schwannoma, low- and high-grade glioma) and nine different types of healthy brain tissue were examined across a wavelength spectrum of 400 nm to 800 nm in order to inform the development of an Intraoperative Hypserpectral Imaging (iHSI) system. Finally, functional and technical requirements of an iHSI were established and a prototype system was developed and tested in a first-in-patient study

Streamlining the Design and Use of Array Coils for In Vivo Magnetic Resonance Imaging of Small Animals

Small-animal models such as rodents and non-human primates play an important pre-clinical role in the study of human disease, with particular application to cancer, cardiovascular, and neuroscience models. To study these animal models, magnetic resonance imaging (MRI) is advantageous as a non-invasive technique due to its versatile contrast mechanisms, large and flexible field of view, and straightforward comparison/translation to human applications. However, signal-to-noise ratio (SNR) limits the practicality of achieving the high-resolution necessary to image the smaller features of animals in an amount of time suitable for in vivo animal MRI. In human MRI, it is standard to achieve an increase in SNR through the use of array coils; however, the design, construction, and use of array coils for animal imaging remains challenging due to copper-loss related issues from small array elements and design complexities of incorporating multiple elements and associated array hardware in a limited space. In this work, a streamlined strategy for animal coil array design, construction, and use is presented and the use for multiple animal models is demonstrated. New matching network circuits, materials, assembly techniques, body-restraining systems and integrated mechanical designs are demonstrated for streamlining high-resolution MRI of both anesthetized and awake animals. The increased SNR achieved with the arrays is shown to enable high-resolution in vivo imaging of mice and common marmosets with a reduced time for experimental setup

Ultra-High Field Strength MR Image-Guided Robotic Needle Delivery Device for In-Bore Small Animal Interventions

Current methods of accurate soft tissue injections in small animals are prone to many sources of error. Although efforts have been made to improve the accuracy of needle deliveries, none of the efforts have provided accurate soft tissue references. An MR image-guided robot was designed to function inside the bore of a 9.4T MR scanner to accurately deliver needles to locations within the mouse brain. The robot was designed to have no noticeable negative effects on the image quality and was localized in the MR images through the use of an MR image visible fiducial. The robot was mechanically calibrated and subsequently validated in an image-guided phantom experiment, where the mean needle targeting accuracy and needle trajectory accuracy were calculated to be 178 ± 54µm and 0.27 ± 0.65º, respectively. Finally, the device successfully demonstrated an image-guided needle targeting procedure in situ

Innovative techniques to devise 3D-printed anatomical brain phantoms for morpho-functional medical imaging

Introduction. The Ph.D. thesis addresses the development of innovative techniques to create 3D-printed anatomical brain phantoms, which can be used for quantitative technical assessments on morpho-functional imaging devices, providing simulation accuracy not obtainable with currently available phantoms. 3D printing (3DP) technology is paving the way for advanced anatomical modelling in biomedical applications. Despite the potential already expressed by 3DP in this field, it is still little used for the realization of anthropomorphic phantoms of human organs with complex internal structures. Making an anthropomorphic phantom is very different from making a simple anatomical model and 3DP is still far from being plug-and-print. Hence, the need to develop ad-hoc techniques providing innovative solutions for the realization of anatomical phantoms with unique characteristics, and greater ease-of-use. Aim. The thesis explores the entire workflow (brain MRI images segmentation, 3D modelling and materialization) developed to prototype a new complex anthropomorphic brain phantom, which can simulate three brain compartments simultaneously: grey matter (GM), white matter (WM) and striatum (caudate nucleus and putamen, known to show a high uptake in nuclear medicine studies). The three separate chambers of the phantom will be filled with tissue-appropriate solutions characterized by different concentrations of radioisotope for PET/SPECT, para-/ferro-magnetic metals for MRI, and iodine for CT imaging. Methods. First, to design a 3D model of the brain phantom, it is necessary to segment MRI images and to extract an error-less STL (Standard Tessellation Language) description. Then, it is possible to materialize the prototype and test its functionality. - Image segmentation. Segmentation is one of the most critical steps in modelling. To this end, after demonstrating the proof-of-concept, a multi-parametric segmentation approach based on brain relaxometry was proposed. It includes a pre-processing step to estimate relaxation parameter maps (R1 = longitudinal relaxation rate, R2 = transverse relaxation rate, PD = proton density) from the signal intensities provided by MRI sequences of routine clinical protocols (3D-GrE T1-weighted, FLAIR and fast-T2-weighted sequences with ≤ 3 mm slice thickness). In the past, maps of R1, R2, and PD were obtained from Conventional Spin Echo (CSE) sequences, which are no longer suitable for clinical practice due to long acquisition times. Rehabilitating the multi-parametric segmentation based on relaxometry, the estimation of pseudo-relaxation maps allowed developing an innovative method for the simultaneous automatic segmentation of most of the brain structures (GM, WM, cerebrospinal fluid, thalamus, caudate nucleus, putamen, pallidus, nigra, red nucleus and dentate). This method allows the segmentation of higher resolution brain images for future brain phantom enhancements. - STL extraction. After segmentation, the 3D model of phantom is described in STL format, which represents the shapes through the approximation in manifold mesh (i.e., collection of triangles, which is continuous, without holes and with a positive – not zero – volume). For this purpose, we developed an automatic procedure to extract a single voxelized surface, tracing the anatomical interface between the phantom's compartments directly on the segmented images. Two tubes were designed for each compartment (one for filling and the other to facilitate the escape of air). The procedure automatically checks the continuity of the surface, ensuring that the 3D model could be exported in STL format, without errors, using a common image-to-STL conversion software. Threaded junctions were added to the phantom (for the hermetic closure) using a mesh processing software. The phantom's 3D model resulted correct and ready for 3DP. Prototyping. Finally, the most suitable 3DP technology is identified for the materialization. We investigated the material extrusion technology, named Fused Deposition Modeling (FDM), and the material jetting technology, named PolyJet. FDM resulted the best candidate for our purposes. It allowed materializing the phantom's hollow compartments in a single print, without having to print them in several parts to be reassembled later. FDM soluble internal support structures were completely removable after the materialization, unlike PolyJet supports. A critical aspect, which required a considerable effort to optimize the printing parameters, was the submillimetre thickness of the phantom walls, necessary to avoid distorting the imaging simulation. However, 3D printer manufacturers recommend maintaining a uniform wall thickness of at least 1 mm. The optimization of printing path made it possible to obtain strong, but not completely waterproof walls, approximately 0.5 mm thick. A sophisticated technique, based on the use of a polyvinyl-acetate solution, was developed to waterproof the internal and external phantom walls (necessary requirement for filling). A filling system was also designed to minimize the residual air bubbles, which could result in unwanted hypo-intensity (dark) areas in phantom-based imaging simulation. Discussions and conclusions. The phantom prototype was scanned trough CT and PET/CT to evaluate the realism of the brain simulation. None of the state-of-the-art brain phantoms allow such anatomical rendering of three brain compartments. Some represent only GM and WM, others only the striatum. Moreover, they typically have a poor anatomical yield, showing a reduced depth of the sulci and a not very faithful reproduction of the cerebral convolutions. The ability to simulate the three brain compartments simultaneously with greater accuracy, as well as the possibility of carrying out multimodality studies (PET/CT, PET/MRI), which represent the frontier of diagnostic imaging, give this device cutting-edge prospective characteristics. The effort to further customize 3DP technology for these applications is expected to increase significantly in the coming years

Manufacturing Methods for Magnetic Resonance Microscopy Tools with Application to Neuroscience

Magnetresonanztomographie (MR) ist ein unverzichtbares nicht-invases und hochselektives bildgebendes Verfahren in der Medizin. MR Tomographie wird kommerziell in der klinischen Diagnostik und der Forschung für Gehirnkrankheit, z.B. Epilepsie, Alzheimer und Parkinson, angewandt. In den Neurowissenschaften haben sich Kleintiere als biologische Modelle für die grundlegenden Studien zur diesen Gehirnkrankheiten etabliert. MR Methoden sind ein wertvolles Werkzeug um die Morphologie und den Metabolismus von Kleintieren zu untersuchen. Die Modelle für die Untersuchung von Gehirnkrankheiten schließen Zellen/Zellkulturen und organotypische hippocampale Schnittkulturen (OHSC) mit ein. Obwohl die MR Mikroskopie für die Untersuchung von OHSC schon angewandt wurde fehlt eine effektive Plattform für umfangreiche longitudinale Studien an OHSC wie sie in den Neurowissenschaften üblich sind. Zwei Detektorkonzepte für die MR Mikroskopie inklusive ihrer Auslegung, der Herstellung und der Charakterisierung, werden in dieser Arbeit beschrieben. Beide Konzepte basieren auf Herstellungsmethoden welche hohe Fertigungsgenauigkeiten zulassen und in ihrem Herstellungsvolumen skalierbar sind. Hohle solenoide Mikrospulen welche für hochauflösende Untersuchung von Zell und Zellanhäufungen geeignet sind werden eingeführt. Die Herstellung basiert auf dem automatisierten wickeln von Mikrospulen, eine skalierbare und hochpräzise Fertigungsmethode der Mikrotechnologie. Zudem werde induktiv gekoppelte Ober ächenspulen eingeführt. Diese Oberflächenspulen fokussieren den magnetischen Fluss und werden deshalb Lenz Linsen genannt. Die Lenz Linsen werden mit kabelgebundenen und induktiv gekoppelten Spulen verglichen. Ihre Breitband-Fähigkeit machen sie zu einem idealen Kandidaten für die Nutzung in verschiedensten MR Tomographie Systemen. Die Lenz Linsen wurden für den Einsatz in einer MR kompatiblen Inkubationsplattform ausgelegt, welche in dieser Arbeit entwickelt wurde. Der MR Inkubator erweitert die Funktionalität eines MR Tomographen um neurologische Gewebe (z.B. OHSC) über mehrere Stunden andauernde MR Messungen am Leben zu erhalten. Der MR Inkubator erlaubt longitudinale Studien an OHSC und bietet damit eine Plattform für umfangreiche Studien in den Neurowissenschaften. Die Lenz Linsen wurden zusammen mit dem MR Inkubator für MR Mikroskopie Mes- sung von akuten/ xierten hippocampalen Schnitten und OHSC genutzt. Die Resultate dieser MR Mikoskopie Messungen zeigen dass in OHSC die grobe Zytoarchitektur sicht- bar ist, ohne dass die OHSC während der Messungen sterben. Somit ist das eingeführte System bereit für longitudinale Studien an OHSC, welche bereits für die Aufklärung der Epilepsieprogression begonnen wurden

Registration of pre-operative lung cancer PET/CT scans with post-operative histopathology images

Non-invasive imaging modalities used in the diagnosis of lung cancer, such as Positron Emission Tomography (PET) or Computed Tomography (CT), currently provide insuffcient information about the cellular make-up of the lesion microenvironment, unless they are compared against the gold standard of histopathology.The aim of this retrospective study was to build a robust imaging framework for registering in vivo and post-operative scans from lung cancer patients, in order to have a global, pathology-validated multimodality map of the tumour and its surroundings.;Initial experiments were performed on tissue-mimicking phantoms, to test different shape reconstruction methods. The choice of interpolator and slice thickness were found to affect the algorithm's output, in terms of overall volume and local feature recovery. In the second phase of the study, nine lung cancer patients referred for radical lobectomy were recruited. Resected specimens were inflated with agar, sliced at 5 mm intervals, and each cross-section was photographed. The tumour area was delineated on the block-face pathology images and on the preoperative PET/CT scans.;Airway segments were also added to the reconstructed models, to act as anatomical fiducials. Binary shapes were pre-registered by aligning their minimal bounding box axes, and subsequently transformed using rigid registration. In addition, histopathology slides were matched to the block-face photographs using moving least squares algorithm.;A two-step validation process was used to evaluate the performance of the proposed method against manual registration carried out by experienced consultants. In two out of three cases, experts rated the results generated by the algorithm as the best output, suggesting that the developed framework outperforms the current standard practice.Non-invasive imaging modalities used in the diagnosis of lung cancer, such as Positron Emission Tomography (PET) or Computed Tomography (CT), currently provide insuffcient information about the cellular make-up of the lesion microenvironment, unless they are compared against the gold standard of histopathology.The aim of this retrospective study was to build a robust imaging framework for registering in vivo and post-operative scans from lung cancer patients, in order to have a global, pathology-validated multimodality map of the tumour and its surroundings.;Initial experiments were performed on tissue-mimicking phantoms, to test different shape reconstruction methods. The choice of interpolator and slice thickness were found to affect the algorithm's output, in terms of overall volume and local feature recovery. In the second phase of the study, nine lung cancer patients referred for radical lobectomy were recruited. Resected specimens were inflated with agar, sliced at 5 mm intervals, and each cross-section was photographed. The tumour area was delineated on the block-face pathology images and on the preoperative PET/CT scans.;Airway segments were also added to the reconstructed models, to act as anatomical fiducials. Binary shapes were pre-registered by aligning their minimal bounding box axes, and subsequently transformed using rigid registration. In addition, histopathology slides were matched to the block-face photographs using moving least squares algorithm.;A two-step validation process was used to evaluate the performance of the proposed method against manual registration carried out by experienced consultants. In two out of three cases, experts rated the results generated by the algorithm as the best output, suggesting that the developed framework outperforms the current standard practice

Patient-Specific Polyvinyl Alcohol Phantoms for Applications in Minimally Invasive Surgery

In biomedical engineering, phantoms are physical models of known geometric and material composition that are used to replicate biological tissues. Phantoms are vital tools in the testing and development of novel minimally invasive devices, as they can simulate the conditions in which devices will be used. Clinically, phantoms are also highly useful as training tools for minimally invasive procedures, such as those performed in regional anaesthesia, and for patient-specific surgical planning. Despite their widespread utility, there are many limitations with current phantoms and their fabrication methods. Commercial phantoms are often prohibitively expensive and may not be compatible with certain imaging modalities, such as ultrasound. Much of the phantom literature is complicated or hard to follow, making it difficult for researchers to produce their own models and it is highly challenging to create anatomically realistic phantoms that replicate real patient pathologies. Therefore, the aim of this work is to address some of the challenges with current phantoms. Novel fabrication methods and frameworks are presented to enable the creation of phantoms that are suitable for use in both the development of novel devices and as clinical training tools, for applications in minimally invasive surgery. This includes regional anaesthesia, brain tumour resection, and percutaneous coronary interventions. In such procedures, imaging is of key importance, and the phantoms developed are demonstrated to be compatible across a range of modalities, including ultrasound, computed tomography, MRI, and photoacoustic imaging