Development of Renal Phantoms for the Evaluation of Current and Emerging Ultrasound Technology

The primary aim of this project was to develop novel anatomically realistic renal phantoms for the evaluation of current and emerging ultrasound techniques capable of diagnosing all grades of renal artery stenosis. Renal artery stenosis is considered the most common cause of potentially curable secondary hypertension which if left untreated can lead to renal failure. Its early detection is very important as it offers the possibility of various drug treatments, which are considerably less invasive and poses less risk to the patient. Computer-aided modelling techniques were used to generate a range of anatomically realistic phantoms of the renal artery from medical images of a 64-slice CT scan which was acquired from a healthy volunteer with normal renal vasculature. These phantoms comprised of a normal healthy vessel and vessels with increasing stenosis (30%, 50% 70% and 85%). Using these novel phantoms a comparative study between four of the imaging techniques currently used to detect renal artery stenosis (ultrasound, magnetic resonance imaging, computed tomography and digital subtraction angiography (DSA)) was carried out. A novel kidney perfusion phantom was also developed with the ability to achieve flow velocities comparable with those found in the blood vessels of the renal macrocirculation (renal artery and renal vein) and microcirculation (kidney). By developing an understanding of disease progression in the renal artery and kidney through experimentation, it is possible to improve the outcome of various treatment regimes by early detection of the disease. Recent and ongoing ultrasound technological developments such as ultrasound contrast agents should render accessible the technically more challenging imaging of the renal artery and kidneys and potentially replace invasive intra-arterial DSA technique

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

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

A Mock Circulatory System Incorporating a Compliant 3D-Printed Anatomical Model to Investigate Pulmonary Hemodynamics

A realistic mock circulatory system (MCS) could be a valuable in vitro testbed to study human circulatory hemodynamics. The objective of this study was to design a MCS replicating the pulmonary arterial circulation, incorporating an anatomically representative arterial model suitable for testing clinically relevant scenarios. A second objective of the study was to ensure the system's compatibility with magnetic resonance imaging (MRI) for additional measurements. A latex pulmonary arterial model with two generations of bifurcations was manufactured starting from a 3D-printed mold reconstructed from patient data. The model was incorporated into a MCS for in vitro hydrodynamic measurements. The setup was tested under physiological pulsatile flow conditions and results were evaluated using wave intensity analysis (WIA) to investigate waves traveling in the arterial system. Increased pulmonary vascular resistance (IPVR) was simulated as an example of one pathological scenario. Flow split between right and left pulmonary artery was found to be realistic (54 and 46%, respectively). No substantial difference in pressure waveform was observed throughout the various generations of bifurcations. Based on WIA, three main waves were identified in the main pulmonary artery (MPA), that is, forward compression wave, backward compression wave, and forward expansion wave. For IPVR, a rise in mean pressure was recorded in the MPA, within the clinical range of pulmonary arterial hypertension. The feasibility of using the MCS in the MRI scanner was demonstrated with the MCS running 2 h consecutively while acquiring preliminary MRI data. This study shows the development and verification of a pulmonary MCS, including an anatomically correct, compliant latex phantom. The setup can be useful to explore a wide range of hemodynamic questions, including the development of patient- and pathology-specific models, considering the ease and low cost of producing rapid prototyping molds, and the versatility of the setup for invasive and noninvasive (i.e., MRI) measurements

MODERNIZATION OF THE MOCK CIRCULATORY LOOP: ADVANCED PHYSICAL MODELING, HIGH PERFORMANCE HARDWARE, AND INCORPORATION OF ANATOMICAL MODELS

A systemic mock circulatory loop plays a pivotal role as the in vitro assessment tool for left heart medical devices. The standard design employed by many research groups dates to the early 1970\u27s, and lacks the acuity needed for the advanced device designs currently being explored. The necessity to update the architecture of this in vitro tool has become apparent as the historical design fails to deliver the performance needed to simulate conditions and events that have been clinically identified as challenges for future device designs. In order to appropriately deliver the testing solution needed, a comprehensive evaluation of the functionality demanded must be understood. The resulting system is a fully automated systemic mock circulatory loop, inclusive of anatomical geometries at critical flow sections, and accompanying software tools to execute precise investigations of cardiac device performance. Delivering this complete testing solution will be achieved through three research aims: (1) Utilization of advanced physical modeling tools to develop a high fidelity computational model of the in vitro system. This model will enable control design of the logic that will govern the in vitro actuators, allow experimental settings to be evaluated prior to execution in the mock circulatory loop, and determination of system settings that replicate clinical patient data. (2) Deployment of a fully automated mock circulatory loop that allows for runtime control of all the settings needed to appropriately construct the conditions of interest. It is essential that the system is able to change set point on the fly; simulation of cardiovascular dynamics and event sequences require this functionality. The robustness of an automated system with incorporated closed loop control logic yields a mock circulatory loop with excellent reproducibility, which is essential for effective device evaluation. (3) Incorporating anatomical geometry at the critical device interfaces; ascending aorta and left atrium. These anatomies represent complex shapes; the flows present in these sections are complex and greatly affect device performance. Increasing the fidelity of the local flow fields at these interfaces delivers a more accurate representation of the device performance in vivo

Improving Electrical Impedance Tomography of brain function with a novel servo-controlled electrode helmet

Electrical Impedance Tomography (EIT) is a medical imaging technique which reconstructs the internal conductivity of an object from boundary measurements. EIT has the potential to provide a novel means of imaging in acute stroke, epilepsy or traumatic brain injury. Previous studies, whilst demonstrating the potential of the technique, have not been successful clinically.The work in this thesis aims to address fundamental limitations including measurement drift in electronic hardware, lack of an anatomically realistic tank phantom for rigorous testing, poor electrode-skin contact and mis-location of scalp electrodes. Chapter 1 provides an introduction of the principles of bioimpedance and EIT, as well as a review of previous clinical studies. Chapter 2 details the development of a novel anatomically realistic head phantom, simulating the human adult head with scalp electrodes, using a 3D printer and cylindrical holes to provide simulated conductivity. This replicated the varying spatial conductivity of the skull within 5 % of the true value. Two multifrequency EIT systems with parallel voltage recording were optimised for recording in the adult head with scalp electrodes, in chapter 3. Measurement drift was reduced by better case design and temperature control and data quality was improved with an updated interface to the current source and signal processing. The UCL ScouseTom system, performed best, with lower noise in all resistor and tank measurements, but the differences were masked during scalp recordings. Further, both systems produced similar results in the realistic adult head tank from chapter 2. Recent advances in EIT imaging coupled with the developments in chapters 2 and 3 provided opportunity to reassess the feasibility of monitoring epilepsy with EIT. Biologically representative perturbations was localised to within 8 mm in the head tank, with less than half the image error of previous studies. However, the key limitations of application time and measurement drift with scalp electrodes had yet to be addressed. Therefore the focus of the work in chapter 5 and chapter 6 was the design and testing of a novel self-adjusting electrode helmet. Skin-electrode impedance was continuously optimised by constant pressure, rotation and feedback control, and position sensors returned the co-ordinates of electrode tips. Finally, experiments with this helmet were undertaken to assess the feasibility of future clinical recordings

Potential for Photoacoustic Imaging of Neonatal Brain

Photoacoustic imaging is a hybrid imaging technique that combines many of the merits of both optical and ultrasound imaging. Photoacoustic imaging (PAI) has been hypothesized as a technique for imaging neonatal brain. However, PAI of the brain is more challenging than traditional methods (e.g. near infrared spectroscopy) due to the presence of the skull layer. To evaluate the potential limits the skull places on 3D PAI of the neonatal brain, we constructed a neonatal skull phantom (~1.52-mm thick) with a mixture of epoxy and titanium dioxide powder that provided acoustic insertion loss (1-5MHz) similar to human infant skull bone. The phantom was molded into a realistic infant skull shape by means of a CNC-machined mold that was based upon a 3D CAD model. Then, propagation of photoacoustic (PA) signals through the skull phantom was examined. A photoacoustic point source was raster-scanned within the imaging cavity of a 128-channel PAI system to capture the imaging operator with and without the intervening skull phantom layer. Then, effects of the skull phantom on PA signals and consequently on PA images was evaluated in detail. We captured 3D photoacoustic images of tubes filled with indocyanine green (ICG). The system was capable of reconstructing an image of a tube filled with 50 μM ICG in presence of the skull. Image processing method was developed to correct photoacoustic images from the effects of the skull. The method was tested on an image of an object captured through the skull, which demonstrated that the effects of the skull on PA images are predictable and modifiable

Potential for photoacoustic imaging of the neonatal brain

Photoacoustic imaging (PAI) has been proposed as a non-invasive technique for imaging neonatal brain injury. Since PAI combines many of the merits of both optical and ultrasound imaging, images with high contrast, high resolution, and a greater penetration depth can be obtained when compared to more traditional optical methods. However, due to the strong attenuation and reflection of photoacoustic pressure waves at the skull bone, PAI of the brain is much more challenging than traditional methods (e.g. near infrared spectroscopy) for optical interrogation of the neonatal brain. To evaluate the potential limits the skull places on 3D PAI of the neonatal brain, we constructed a neonatal skull phantom (1.4-mm thick) with a mixture of epoxy and titanium dioxide powder that provided acoustic insertion loss (1-5MHz) similar to human infant skull bone. The phantom was molded into a realistic infant skull shape by means of a CNCmachined mold that was based upon a 3D CAD model. To evaluate the effect of the skull bone on PAI, a photoacoustic point source was raster scanned within the phantom brain cavity to capture the imaging operator of the 3D PAI system (128 ultrasound transducers in a hemispherical arrangement) with and without the intervening skull phantom. The resultant imaging operators were compared to determine the effect of the skull layer on the PA signals in terms of amplitude loss and time delay. © 2013 Copyright SPIE

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