Development and Evaluation of an Actuator System based on Centrifugal Force for Magnetic Resonance Elastography

Magnetic resonance elastography (MRE) serves as an important diagnostic tool. It represents one of numerous approaches to monitor tissue stiffness. The most fundamental challenges that MRE face are posed by two linking factors: Constructing a mechanical device that induces tissue motion to the depth of interest and meaningfully resolving said movement in the complex magnetic resonance imaging (MRI) signal. This work aims to address these challenges by improving the quantification of tissue stiffness through the development of a new actuation system for MRE. Firstly, a 3D printed pneumatic turbine vibrator was developed to induce sinusoidal mechanical waves. It used an eccentrically rotating mass generating a centrifugal force in the turbine. Contrary to conventionally used acoustic pressure drivers, the pneumatic turbine was capable of producing wave amplitudes in the range of appropriate shear waves in human tissue - especially at higher frequencies due to the centrifugal force increasing quadratically in relation to the rotational frequency. A technical assessment showed that the turbine generated vibrations in the range of 30 Hz to 150 Hz. The extent of artifacts caused by the materials brought into the field of view was restricted to the proximity of the actuator. It did not affect image quality in the region of interest. The turbine was MR-safe and an in-house certification according to §3 MPG was conducted, which enabled in-house clinical in vivo studies. The actuation system was additionally extended to a dual turbine actuator in order to investigate if the attenuation of shear waves could be further compensated by using two wave sources. Secondly, a motion encoding sequence was developed to meaningfully encode the tissue motion in the MRI signal. It was a spin-echo echo-planar-imaging sequence (SE-EPI) and contained a motion encoding gradient (MEG) adjustable for actuation frequencies ranging from 40 Hz to 120 Hz. To accurately reconstruct the wave velocities, i.e tissue elasticity, a trigger was implemented that synchronized the motion encoding sequence to the mechanical waves. Thirdly, the actuator system was evaluated regarding its performance for MRE image acquisition in a clinical MRI scanner. Silicone-based tissue elasticity mimicking phantoms were developed as test objects with known elasticity. Their shear moduli were in the range of 1.47 kPa to 7.29 kPa, which corresponds to the range of human soft tissue elasticities. A prostate phantom and an anthropomorphic abdominal phantom were manufactured. MR images were acquired with the SE-EPI sequence and were sufficient in terms of signal to noise ration (liver: SNR = 71.5) and contrast to noise ratio (liver: CNR = 16.5). The phantoms may also be used for multi-modal imaging; besides MRI, computed tomography (liver: 106+/-6 HU) and ultrasound imaging by adding scatter particles is feasible. The actuator did not interfere with the imaging procedure and could be integrated into existing clinic equipment. Three actuation set-ups were evaluated: a single, a large surface and a dual source actuation. For each, the strength of the MEG was varied from 5 mT/m to 20 mT/m for actuation frequencies ranging from 50 Hz to 80 Hz. The dual source actuation demonstrated a more uniform penetration of a larger volume of interest, especially in the peripheral region of the abdominal phantom. The obtained elasticity maps showed elasticity values (liver: 1.12+/-0.16 kPa, filling material: 4.37+/-0.52 kPa) in accordance to the results obtained by rheometric testing of the silicone samples. Additionally, an in vivo MRE examination was conducted, which served as a proof-of-principle for the successful implementation of the first developed MRE actuator system in our clinic. For both liver and prostate MRE, the actuator was well tolerated by the volunteer. Since the developed actuation technique is non-invasive, its incorporation into routine MRI protocols will facilitate patient acceptance, while its short additional set-up time will also increase clinical acceptance. MRE is a unique technique for the identification of various pathologies and the quantification of the shear modulus has the potential to become a further independent parameter for MRI diagnostics in a variety of clinical applications

On the Recognition of Emotion from Physiological Data

This work encompasses several objectives, but is primarily concerned with an experiment where 33 participants were shown 32 slides in order to create ‗weakly induced emotions‘. Recordings of the participants‘ physiological state were taken as well as a self report of their emotional state. We then used an assortment of classifiers to predict emotional state from the recorded physiological signals, a process known as Physiological Pattern Recognition (PPR). We investigated techniques for recording, processing and extracting features from six different physiological signals: Electrocardiogram (ECG), Blood Volume Pulse (BVP), Galvanic Skin Response (GSR), Electromyography (EMG), for the corrugator muscle, skin temperature for the finger and respiratory rate. Improvements to the state of PPR emotion detection were made by allowing for 9 different weakly induced emotional states to be detected at nearly 65% accuracy. This is an improvement in the number of states readily detectable. The work presents many investigations into numerical feature extraction from physiological signals and has a chapter dedicated to collating and trialing facial electromyography techniques. There is also a hardware device we created to collect participant self reported emotional states which showed several improvements to experimental procedure

A Corpus-driven Approach toward Teaching Vocabulary and Reading to English Language Learners in U.S.-based K-12 Context through a Mobile App

In order to decrease teachers’ decisions of which vocabulary the focus of the instruction should be upon, a recent line of research argues that pedagogically-prepared word lists may offer the most efficient order of learning vocabulary with an optimized context for instruction in each of four K-12 content areas (math, science, social studies, and language arts) through providing English Language Learners (ELLs) with the most frequent words in each area. Educators and school experts have acknowledged the need for developing new materials, including computerized enhanced texts and effective strategies aimed at improving ELLs’ mastery of academic and STEM-related lexicon. Not all words in a language are equal in their role in comprehending the language and expressing ideas or thoughts. For this study, I used a corpus-driven approach which is operationalized by applying a text analysis method. For the purpose of this research study, I made two corpora, Teacher’s U.S. Corpus (TUSC) and Science and Math Academic Corpus for Kids (SMACK) with a focus on word lemma rather than inflectional and derivational variants of word families. To create the corpora, I collected and analyzed a total of 122 textbooks used commonly in the states of Florida and California. Recruiting, scanning and converting of textbooks had been carried out over a period of more than two years from October 2014 to March 2017. In total, this school corpus contains 10,519,639 running words and 16,344 lemmas saved in 16,315 word document pages. From the corpora, I developed six word lists, namely three frequency-based word lists (high-, mid-, and low-frequency), academic and STEM-related word lists, and essential word list (EWL). I then applied the word lists as the database and developed a mobile app, Vocabulary in Reading Study – VIRS, (available on App Store, Android and Google Play) alongside a website (www.myvirs.com). Also, I developed a new K-12 dictionary which targets the vocabulary needs of ELLs in K-12 context. This is a frequency-based dictionary which categorizes words into three groups of high, medium and low frequency words as well as two separate sections for academic and STEM words. The dictionary has 16,500 lemmas with derivational and inflectional forms

Smart knives: controlled cutting schemes to enable advanced endoscopic surgery

With the backdrop of the rapidly developing research in Natural Orifice Transluminal Endoscopic Surgery (NOTES), analysis of the literature supported the view that inventing new, controlled tissue dissection methods for flexible endoscopic surgery may be necessary. The literature also confirmed that white space exists for research into and the development of new cutting tools. The strategy of “deconstructing dissection” proposed in this thesis may provide dissection control benefits, which may help address the unique manoeuvring challenges for tissue dissection at flexible endoscopy. This assertion was supported by investigating six embodiments of the strategy which provided varying degrees of enhanced tissue dissection control. Seven additional concepts employing the strategy which were not prototyped also were offered as potential solutions that eventually might contribute evidence in defence of the strategy. One concept for selective ablation — dye-mediated laser ablation — was explored in-depth by theoretical analysis, experimentation and computation. The ablation process was found to behave relatively similar to unmediated laser ablation, but also to depend on cyclic carbonisation for sustained ablation once the dye had disappeared. An Arrhenius model of carbonisation based on the pyrolysis and combustion of wood cellulose was used in a tissue ablation model, which produced reasonable results. Qualitative results from four methods for dye application and speculation on three methods for dye removal complete the framework by which dye-mediated laser ablation might deliver on the promise offered by “deconstructing dissection”. Overall, this work provided the “deconstructing dissection” strategic framework for controlled cutting schemes and offered plausible evidence that the strategy could work by investigating embodiments of the scheme. In particular, dye-mediated laser ablation can provide selective ablation of tissue, and a theoretical model for the method of operation was offered. However, some practical hurdles need to be overcome before it can be useful in a clinical setting

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)