Polyvinyl Alcohol Cryogel Based Vessel Mimicking Material for Modelling the Progression of Atherosclerosis

Purpose The stiffness of Polyvinyl-alcohol cryogel can be adjusted through application of consecutive freeze-thaw cycles. This material has potential applications in the production of tissue mimicking phantoms in diagnostic ultrasound. The aim of this study was to use PVA-c to produce a range of geometrically and acoustically identical vessel phantoms modelling stages of atherosclerosis which could be verified through mechanical testing, thus allowing for more precision in quantitative in-vitro flow analysis of atherosclerosis. Methods A series of anatomically realistic walled renal artery flow phantoms were constructed using PVA-c. In order to ensure precise modelling of atherosclerosis, a modified procedure of ISO27:2017 was used to compare the mechanical properties of PVA-c. Results were compared for the standard “dumbbell” test object and a modified vessel test object. The geometric accuracy and reproducibility of the vessel models were tested before and after implantation in flow phantoms. Results No significant difference was found between the mechanical properties of the dumbbell test samples and the vessels for any number of freeze thaw cycles, with a correlation coefficient of R2 = 0.9767 across the dataset, indicating that a direct comparison between the mechanical properties of the dumbbell test samples and the phantom vessels was established. The geometric reproducibility showed that before and after implantation there was no significant difference between individual vessel geometries (p = 0.337 & p = 0.176 respectively). Conclusions Polyvinyl-alcohol cryogel is a useful material for the production of arterial flow phantoms. Care should be taken when using this material to ensure its mechanical properties have been correctly characterised. The guidelines of ISO37:2017 potentially provide the best procedure to ensure this

Review of Ultrasound Elastography Quality Control and Training Test Phantoms

While the rapid development of ultrasound elastography techniques in recent decades has sparked its prompt implementation in the clinical setting adding new diagnostic information to conventional imaging techniques, questions still remain as to its full potential and efficacy in the hospital environment. A limited number of technical studies have objectively assessed the full capabilities of the different elastography approaches, perhaps due, in part, to the scarcity of suitable tissue-mimicking materials and appropriately designed phantoms available. Few commercially-available elastography phantoms possess the necessary test target characteristics or mechanical properties observed clinically, or indeed reflect the lesion-to-background elasticity ratio encountered during clinical scanning. Thus, while some phantoms may prove useful, they may not fully challenge the capabilities of the different elastography technniques, proving limited when it comes to quality control (QC) and/or training purposes. Although a variety of elastography tissue-mimicking materials, such as agar and gelatine dispersions, co-polymer in oil and poly(vinyl) alcohol cryogel, have been developed for specific research purposes, such work has yet to produce appropriately designed phantoms to adequately challenge the variety of current commercially-available elastography applications. Accordingly, there is a clear need for the further development of elastography TMMs and phantoms to keep pace with the rapid developments in elastography technology, to ensure the performance of these new diagnostic approaches are validated, and for clinical training purposes

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

Criteria for the design of tissue-mimicking phantoms for the standardization of biophotonic instrumentation

A lack of accepted standards and standardized phantoms suitable for the technical validation of biophotonic instrumentation hinders the reliability and reproducibility of its experimental outputs. In this Perspective, we discuss general criteria for the design of tissue-mimicking biophotonic phantoms, and use these criteria and state-of-the-art developments to critically review the literature on phantom materials and on the fabrication of phantoms. By focusing on representative examples of standardization in diffuse optical imaging and spectroscopy, fluorescence-guided surgery and photoacoustic imaging, we identify unmet needs in the development of phantoms and a set of criteria (leveraging characterization, collaboration, communication and commitment) for the standardization of biophotonic instrumentation

The use of Fluid Haemodynamics in the Diagnosis of Cardiovascular Disease

Currently the diagnostic methods used to detect cardiovascular disease largely rely on the inference of the presence of arterial stenosis. There is a clinical interest in the development of a diagnostic screening technique which can indicate the risk of developing cardiovascular disease at an early stage so that non-surgical treatments can be applied. The goal of this work was to develop and validate a diagnostic screening technique for cardiovascular disease using the mechanical biomarker wall shear stress. Improvements in wall shear stress measurements were made by using a 2D Fourier transform to extract additional spectral information from the ultrasound pulse and decrease the spectral variance by integrating across the bandwidth of transmitted frequencies. This technique was validated for a series of anatomically realistic flow phantoms which precisely mimicked the progression of wall stiffening that characterises cardiovascular disease. The newly developed spectral analysis technique demonstrated a higher diagnostic performance than the other techniques tested, both in terms of a greater degree of significance in detecting differences in vessel wall stiffness and in terms of the sensitivity and specificity of the technique. The technique could not be tested in pulsatile flow due to hardware limitations, but preliminary testing indicated that the increased performance of the technique would likely transfer to a physiological flow regime. The results of this work indicated that the algorithm had the potential to rival the diagnostic power of the current gold standard while being applicable at an earlier stage of cardiovascular disease

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

Wall shear stress measurement in carotid artery phantoms with variation in degree of stenosis using plane wave vector doppler

Wall shear stress (WSS) plays an important role in the formation, growth, and rupture of atherosclerotic plaques in arteries. This study measured WSS in diseased carotid artery phantoms with degrees of stenosis varying from 0 to 60% with both steady and pulsatile flow. Experiments were performed using in silico and real flow phantoms. Blood velocities were estimated using plane wave (PW) vector Doppler. Wall shear stress was then estimated from the velocity gradient near the wall multiplied by the viscosity of a blood-mimicking fluid. The estimated WSS using the in silico phantom agreed within 10% of the ground-truth values (root-mean-square error). The phantom experiment showed that the mean WSS and maximum WSS increased with the increasing degree of stenosis. The simulation and experiment results provide the necessary validation data to give confidence in WSS measurements in patients using the PW vector Doppler technique

Ultrasound metrology and phantom materials for validation of photoacoustic thermometry

High intensity focused ultrasound is an emerging non-invasive cancer therapy during which a focused ultrasound beam is used to destroy cancer cells within a confined volume of tissue. In order to increase its successful implementation in practice, an imaging modality capable of accurately mapping the induced temperature rise in tissue is necessary. Photoacoustic thermometry, a rapidly emerging technique for non-invasive temperature monitoring, exploits the temperature dependence of the Grüneisen parameter of tissues, which leads to changes in the recorded photoacoustic signal amplitude with temperature. However, the implementation of photoacoustic thermometry approaches is hindered by a lack of rigorous validation. This includes both the equipment and methodology used. This work investigates the effect of temperature on ultrasound transducers used in photoacoustic thermometry imaging as well as characterisation of potential phantom materials for its validation. The variation in transducer sensitivity with temperature is investigated using two approaches. The first one utilises a reference transducer whose output power is known as a function of temperature to characterise the sensitivity of the hydrophone. As the knowledge of variability of transducer output with temperature is not readily available, two standard metrology techniques using radiation force balances and laser vibrometry are extended beyond room temperature to characterise the effect of temperature on the output of PZT tranducers. For the second approach to transducer sensitivity calibration, a novel method is developed utilising water as a laser-generated ultrasound source and validated using the self-reciprocity calibration method. The calibrated hydrophone is then used to characterise the relevant temperature-dependent properties of several phantom materials in a custom-built setup. The measurement results are used to determine the most suitable phantom for photoacoustic thermometry. Finally, the phantom is heated and imaged in a proof-of-concept photoacoustic thermometry setup using a linear array. These contributions are of vital importance for allowing the translation of photoacoustic thermometry into clinical practice

Measurement of left ventricular deformation using 3D echocardiography

Bakgrunn: 3D speckle tracking ekkokardiografi (STE) er en hjerteultralydmetode som gir mulighet for måling av deformasjonsparametere, som strain, rotasjon, tvist og torsjon. Den største begrensningen for 3D STE er lav tids- og romlig oppløsning. Økes den ene oppløsingen vil den andre bli redusert. I tillegg vil andre faktorer som antall flettede bilder, sektorstørrelse og dybde påvirke begge oppløsningene. Denne avhandlingen har hatt som mål å finne tilstander og opptaksinnstillinger for å optimalisere nøyaktigheten til 3D STE-parametere i et kontrollert miljø. Videre har det vært som mål å finne regional deformasjon fra 3D STE i en klinisk studie på pasienter med aortaklaffestenose (AS) ved bruk av optimaliserte innstillinger. Materiale og metode: Studie 1 og 2 utforsket nøyaktigheten til 3D STE ved bruk av et in vitro-oppsett med et fantom av venstre ventrikkel. Studie 1 sammenlignet 3D STE strain mot sonomikromertri som gullstandard i longitudinell, sirkumferensiell og radiell retning. Ved å bruke et annet fantom i studie 2 ble 3D STE tvist sammenlignet mot sonomikrometri tvist for å finne nøyaktigheten til 3D STE tvistmålinger. Studie 3 inkluderte 85 pasienter med variabel grad av AS i en tverrsnittstudie. 3D ekkokardiografi ble utført og 3D STE-parametere ble sammenlignet mellom grupper av pasienter med mild, moderat og alvorlig AS. Resultater: Studie 1 fant godt samsvar mellom 3D STE og sonomikrometri med optimalt volum rate på 36,6 volumer per sekund (VPS) ved bruk av 6 sammenflettede bilder. I studie 2 hadde 3D STE godt samsvar ved bruk av både 4 og 6 sammenflettede bilder med volum rater på henholdsvis 20,3 og 17,1 VPS. Studie 3 fant lavere global longitudinal strain i pasienter med alvorlig AS sammenlignet med mild AS. Basal og midtre longitudinal strain var også lavere i alvorlig sammenlignet med mild AS. Apikal-basal ratio var høyere for moderat i forhold til mild AS. Maks apikal-basal tvist var høyere hos pasienter med alvorlig sammenlignet med mild og moderat AS. Konklusjon: Måling av venstre ventrikkelfunksjon med 3D STE er mest nøyaktig med volum rater < 40 VPS. Høy romlig oppløsning virker å være mer viktig enn tidsoppløsning. Pasienter med alvorlig AS har lavere global, basal og midtre longitudinal strain enn pasienter med mild AS, ved bruk av 3D STE. De har også høyere tvist enn mild og moderat AS. Områder som involverer apeks, har høyere spredning av data og har antagelig lavere nøyaktighet ved bruk av 3D STE.Background: 3D speckle tracking echocardiography (STE) enables measurement of multiple parameters of deformation, such as strain, rotation, twist and torsion. The main limitation of 3D STE is low temporal and spatial resolution. Increasing resolution in time will decrease resolution in space, and vice versa. In addition, other factors such as number of stitched images, sector size and depth, influence the resolution. This thesis aimed to find conditions and acquisition settings to optimize accuracy for 3D STE parameters in a controlled in vitro environment. Secondly, it aimed to evaluate regional deformation by 3D STE in a clinical study on patients with aortic valve stenosis (AS) using optimized settings. Materials and methods: Study 1 and 2 explored the accuracy of 3D STE using an in vitro setup with a left ventricle (LV) phantom. Study 1 compared 3D STE strain to strain by sonomicrometry as the gold standard. Measurements were compared in both longitudinal, circumferential and radial direction. Using a different twisting phantom in study 2, 3D STE twist was compared to twist by sonomicrometry to evaluate the accuracy of 3D STE twist. Study 3 was a cross-sectional analysis of 85 patients with variable degree of AS in a cross-sectional study. 3D echocardiography was done, and 3D STE parameters were compared between groups of patients with mild, moderate and severe AS. Results: Study 1 found 3D STE strain to have good agreement with sonomicrometry. Optimal acquisition settings were found to be volume rate 36.6 volumes per second (VPS) obtained by 6 stitched images. Study 2 found 3D STE twist to have good agreement with sonomicrometry when using both 4 and 6 stitched images with volume rates 20.3 and 17.1 VPS, respectively. Study 3 found global longitudinal strain to be lower in patients with severe AS compared to those with mild AS. Basal and mid longitudinal strains were also lower in severe AS than in mild AS. Apical basal ratio was higher for moderate than mild AS. Peak apical-basal twist was higher in patients with severe AS than in those with mild and moderate AS. Conclusion: Assessment of LV function by 3D STE is most accurate at volume rates < 40 VPS. High spatial resolution seems to be more important than temporal resolution. Patients with severe AS have lower global, as well as lower regional basal and mid longitudinal strain compared to patients with mild AS, assessed with 3D STE. They also have higher twist than mild and moderate AS. Segments involving the apex have high dispersion and probably lower accuracy in 3D STE.Doktorgradsavhandlin