There have been reports on the use of Ultrasound (US) for monitoring fracture repair and for measuring muscle volume. Change in muscle mass is a useful bio-marker for monitoring the use and disuse of muscle, and the affects of age, disease and injury. The main modality for imaging bone is X-ray and for muscle volume Magnetic Resonance (MR). Previous studies have shown US to have advantages over X-ray and MR. US can image all stages of the fracture repair process and can detect signs of healing 4-6 weeks before X-ray allowing earlier detection of possible complications. Compared to MR, US is less resource intensive, easier to access and also has fewer exclusion criteria for patients. Despite these advantages, the limited field of view that US can provide results in high operator dependency for scan interpretation and also for length and volume measurements. Three-dimensional Ultrasound (3D US) has been developed to overcome these limitations and has been used to provide extended field of view images of the foetus and the heart and to obtain accurate volume measurements for organs. In this thesis it is hypothesized that 3D US can provide a more comprehensive method of imaging fracture repair than X-ray and is also a viable alternative to MR for determining muscle volumes in vivo. Initially, an electromagnetically (EM) tracked 3D US system was evaluated for clinical use using phantom-based experiments. It was found that the presence of metal objects in or near the EM field caused distortion and resulted in errors in the volume measurements of phantoms of up to ±20%. An optically tracked system was also evaluated and it was found that length measurements of a phantom could be made to within ±1.3%. Fracture repair was monitored in five patients with lower limb fractures. Signs of healing were visible earlier on 3D US with a notable, although variable, lag between callus development on X-ray compared to 3D US. 3D US provided a clearer view of callus formation and the changes in density of the callus as it matured. Additional information gained by applying image processing methods to the 3D US data was used to develop a measure of callus density and to identify the frequency dependent appearance of the callus. Volume measurements of the rectus femoris quadricep muscle were obtained using 3DUS from eleven healthy volunteers and were validated against volume measurements derived using MR. The mean difference between muscle volume measurements obtained using 3D US and MR was 0.53 cm3 with a standard deviation of 1.09 cm3 and 95% confidence intervals of 0.20 - 1.27 cm3 In conclusion, 3D US demonstrates great potential as a tool for imaging components of the musculoskeletal system and as means of measuring callus density.

In the past decade, the application of adaptive beamforming methods to medical ultrasound imaging has become a field of increased interest, due to their ability to achieve superior ultrasound image quality. Such enhancements, however, come at a high computational cost. This thesis attempts to address the following simple question: Can we maintain a superior image quality while reducing the computational cost of adaptive beamforming? Our goal is to effectively combine low-complexity nonadaptive beamforming, such as the Delay-and-Sum (DAS) technique, with high-complexity adaptive beamforming, such as the Minimum variance Distortionless Response (MVDR) technique, implemented using the Generalized Sidelobe Canceller (GSC), to obtain high-quality images at low computational cost. We propose a simple two-pass beamforming scheme for that purpose. During the first pass, our scheme processes buffered input vectors using the inexpensive DAS method and computes the corresponding envelope. Based on that envelope information, selected outputs may be recomputed during the second pass (to improve beamforming performance) using the expensive GSC beamforming method. The purpose of the first pass is to identify which nonadaptively beamformed outputs can be spared from a heavy computational load of adaptive beamforming taking place in the second pass. We have evaluated our scheme using simulated ultrasound images of a 12-point phantom and a point-scatterer-cyst phantom, achieving substantial threshold-dependent computational savings without significant degradation in image resolution and contrast, compared to pure GSC beamforming. / Graduate / rehoumahichem@gmail.com

Given the great promise of High Intensity Focused Ultrasound (HIFU) as a therapeutic modality, the aim of the present study is to develop and optimise a technique that uses externally applied focused ultrasound energy and remote, ultrasound-based treatment monitoring to destroy subcutaneous fat safely, effectively and non-invasively. Based on initial cavitation and temperature measurements performed ex vivo in excised porcine fat at four different frequencies (0.5, 1.1, 1.6 & 3.4MHz) over a range of pressure amplitudes and exposure durations, it was concluded that 0.5MHz is the optimal frequency for this application since it is capable of instigating inertial cavitation at relatively modest pressures while enhancing focal heat deposition. Histological assessment of tissue treated above the cavitation threshold at 0.5MHz both ex vivo and in vivo demonstrated damage to adipocytes and connective tissue. Furthermore, a good correlation was identified between the energy of broadband emissions detected by the passive cavitation detector (PCD) and the focal temperature rise at 0.5MHz during ex vivo experimentation, which could be exploited as a tool for non-invasive monitoring of successful treatment delivery. In addition, localisation of cavitation activity by means of passive cavitation detection was achieved and shown to provide a strong indicator of the location of induced histological damage. Based on the specific requirements identified during initial experimentation, an application-specific HIFU transducer, cavitation detector and real-time treatment monitoring software was developed and tested ex vivo. This treatment system was found capable of producing extensive damage to adipocytes and collagen confined to the subcutaneous fat layer at the desired treatment depth, which coincided with the location of cavitation activity as displayed by the real-time treatment monitoring software.

Targeted therapy is a significant area of research in pharmaceutical and biomedical science. Its overall aim is to achieve maximum impact on malignant cells with minimum side effects to healthy tissue. In this thesis the capabilities of magnetic microbubbles as targeted therapeutic delivery vehicles are explored. New characterisation techniques were developed in order to understand and improve the current magnetic microbubble formulation. Electron microscopy was used to analyse the nanoscale structure of microbubble shells and observe nanoparticles attached to the shell surface. A new flow phantom was developed and the targeting of magnetic microbubbles against flow conditions corresponding to those in the human body was found to be feasible in numerous vessel sizes and flow conditions. Magnetic targeting of microbubbles was also observed in a perfused porcine liver model. Magnetic targeting was then attempted against flowing blood and a decrease in targeting efficiency observed. This was also seen for biochemical targeting and collisions with red blood cells identified as the most likely cause. Importantly, the number of magnetically targeted microbubbles significantly exceeded those targeted via biochemical interactions in both blood and water. In the second part of the thesis new types of magnetic microbubble were developed. The first exploits the fusion of nano-scale magnetic droplets with phospholipid microbubbles. In the second magnetic nanoparticles were incorporated directly into the lipid shell. The new magnetic microbubble formulation could be magnetically targeted, observed via contrast ultrasound and was successfully used to deliver siRNA to neuroblastoma cells.

Sonoporation, enhanced by ultrasound contrast agents has been explored as a promising non-viral technique to achieve gene transfection and targeting drug delivery in recent years. However, the short lifespan of traditional ultrasound contrast agents like Optison® microbubbles under moderate intensity ultrasound exposure limits their application. Liposomes, as drug carriers consisting of curved spherical closed phospholipid bilayer shells, have the following characteristics: 1) The ability to encapsulate and carry hydrophilic or hydrophobic molecules. 2) The biocompatibility with cell membranes. 3) The nanometer size and the relative ease of adding special ligands to their surface to target a specific disease site. 4) The stability in the blood stream. 5) Targeted ultrasound irradiation can induce rupture of liposomes letting the drug encapsulated in them leak out to achieve controlled release of the therapeutic agents at a certain concentration and a delivery rate. In this thesis, several liposome synthesis methods are presented. Liposomes synthesized in our laboratory were characterized acoustically and optically. Anti rabbit IgG conjugated with Alexafluor 647 was delivered into Jurkat cells in a suspension containing liposomes by 10 % duty cycle ultrasound tonebursts of 2.2 MHz (the in situ spatially averged and temporally averaged intensity, ISATA = 80W/cm2) with an efficiency of 13 %. It has been experimentally shown that liposomes may be an alternative stable agent to Optison® to cause sonoporation. Furthermore, a type of nanometer-sized liposome (<300nm) was synthesized to explore the feasibility of ultrasound-triggered release from drug encapsulated lipsomes. It has been demonstrated encapsulated fluorescence materials (FITC) can be released from liposomes with an average diameter of 210 nm when exposed to high intensity focused ultrasound (HIFU) at 1.142MHz (ISPTA= 900 W/cm2). Rupture of relatively large liposomes (>100nm) and porelike defects in the membrane of small liposomes due to the excitation of HIFU were the main causes of the content release. The great enhancement of HIFU-mediated release in the nanometer-sized liposomes may prove useful for clinical applications. The presence of fine particles in Martian and lunar soil poses a significant threat to NASA’s viable long-term exploration and habitation of either the moon or Mars. It has been experimentally shown that the acoustic levitating radiation force produced by a 13.8 kHz 128 dB sound-level standing wave between a 3 cm-aperture acoustic tweeter and a reflector separated by 9 cm is strong enough to overcome the van der Waals adhesive force between the dust-particles and the reflector-surface. The majority of fine particles (> 2μm diameter) on a reflector surface can be dislodged and removed by a technique combining acoustic levitation and airflow methods. This dust removal technique may be used in space-stations or other enclosures for habitation.

Therapeutic ultrasound (TUS) is a treatment modality that is used to accelerate tissue healing. TUS is thought to affect cellular processes of tissue healing, especially those that occur in the inflammatory and early proliferative phases. TUS can be applied using various parameter selections including intensity, wavelength, duty cycle and treatment duration and no clear consensus exists on optimal parameters for healing enhancement. Macrophages are important mediators of inflammation and their actions are critical to normal progression into the proliferative phase of healing. They complete many functions during these periods of tissue healing, among those being release of cytokines and growth factors. These paracrine factors affect other inflammatory cells, resident cells of the healing tissue, including fibroblasts and endothelial cells that are necessary for restoration of damaged tissue. The hypothesis of this investigation is that TUS enhances early healing, in part, through stimulation of macrophage release of paracrine factors involved in coordination of the cellular aspects of tissue healing and that specific levels of TUS are most stimulatory for macrophages. This study examined macrophage release of interleukin-1beta (IL-1Beta), vascular endothelial growth factor (VEGF), transforming growth factor-Beta 1 (TGF-B1) and fibroblast mitogens, in response to varied levels of TUS. Fibroblasts incubated up to 48-hours in media conditioned by TUS-stimulated macrophages were not induced to proliferate regardless of the parameters sets of TUS applied. TUS (1 MHz, 400mW/cm2 SATA, 20% duty cycle, 10-minute exposure) induced macrophage release of VEGF and IL-1Beta within 10-minutes post-TUS, without any additional release being stimulated at 1-hour post-insonation. No other combination of TUS parameters studied induced release of IL-1Beta and VEGF. TUS did not induce release of TGF-Beta 1 at either time point post-TUS. VEGF and IL-1Beta release occurred in conjunction with lactate dehydrogenase (LDH) release from treated macrophages, indicating non-specific cell membrane permeabilization was involved in the cellular response. For IL-1Beta, TUS-stimulated release was inhibited at lower exposure temperatures. Inhibition of TUS-induced release at lower temperatures indicates that a cellular metabolic process, most likely exocytosis, was also stimulated by TUS. Based on these results, it appears that TUS exposure at 1 MHz, 400mW/cm2 SATA, 20% duty cycle induces non-specific and cell-mediated release of secretory proteins. Thus, enhanced release of cytokines and growth factors from macrophages is a possible mechanism by which TUS enhances tissue healing.

Thesis advisor: Cyril P. Opeil / The physiology of the vasculature in the central nervous system (CNS) which includes the blood-brain-barrier (BBB) and other factors, prevents the transport of most anticancer agents to the brain and restricts delivery to infiltrating brain tumors. The heterogeneous vascular permeability in tumor vessels (blood-tumor barrier; BTB), along with several other factors, creates additional hurdles for drug treatment of brain tumors. Different methods have been used to bypass the BBB/BTB, but they have their own limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Magnetic Resonance Imaging guided Focused Ultrasound (MRIgFUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and BTB. The purpose of this thesis was to use this alternative approach to deliver chemotherapeutic agents through the BBB/BTB for brain tumor treatment in a rodent model to overcome the hinderances encountered in prior approaches tested for drug delivery in the CNS. The results presented in thesis demonstrate that MRIgFUS can be used to achieve consistent and reproducible BBB/BTB disruption in rats. It enabled us to achieve clinically-relevant concentrations of doxorubicin (~ 4.8±0.5 µg/g) delivered to the brain with the sonication parameters (0.69 MHz; 0.55 MPa; 10 ms bursts; 1 Hz PRF; 60 s duration), microbubble concentration (Definity, 10 µl/kg), and liposomoal doxorubicin (Lipo-DOX) dose (5.67 mg/kg) used. The resulting doxorubicin concentration was reduced by 32% when the agent was injected 10 minute after the last sonication. Three weekly sessions of FUS and Lipo-DOX appeared to be safe in the rat brain, despite some minor tissue damage. Importantly, the severe neurotoxicity seen in earlier works using other approaches does not appear to occur with delivery via FUS-BBB disruption. The resuls from three weekly treatments of FUS and Lipo-DOX in a rat glioma model are highly promising since they demonstrated that the method significantly inhibits tumor growth and improves survival. Animals that received three weekly sessions of FUS + Lipo-DOX (N = 8) had a median survival time that was increased significantly (P<0.001) compared to animals who received Lipo-DOX only (N = 6), FUS only (N = 8), or no treatment (N = 7). Median survival for animals that received FUS + Lipo-DOX was increased by 100% relative to untreated controls, whereas animals who received Lipo-DOX alone had only a 16% improvement. Animals who received only FUS showed no improvement. No tumor cells were found in histology in 4/8 animals in the FUS + Lipo-DOX group, and only a few tumor cells were detected in two animals. Tumor doxorubicin concentrations increased monotonically (823±600, 1817±732 and 2432±448 ng/g) in the control tumors at 9, 14 and 17 days respectively after administration of Lipo-DOX. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P<0.05, P<0.01, and P<0.0001 at days 9, 14, and 17, respectively) and were greater than the control tumors by a factor of two or more (2222±784, 3687±796 and 5658±821 ng/g) regardless of the stage of tumor growth. The transfer coefficient Ktrans was significantly (p<0.05) enhanced compared to control tumors only at day 9 but not at day 14 or 17. These results suggest that FUS-induced enhancements in tumor drug delivery for Lipo-DOX are relatively consistent over time, at least in this tumor model. These results are encouraging for the use of large drug carriers, as they suggest that even large/late-stage tumors can benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da). Overall, this thesis research provides pre-clinical data toward the development of MRIgFUS as a noninvasive method for the delivery of agents such as Lipo-DOX across the BBB/BTB to treat patients with diseases of the central nervous system. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

No description available.

The world is getting connected in both small and bigger systems. Internet of Things (IoT) has flourished the past years and we no longer just connect our computers and phones but also our cars, wallets, keys and even the furniture and lighting in homes are talking. It is time to take things one step further, give your food and supplies a voice. This master thesis has the purpose to construct a smart inventory using the IoT. Its outcome is a prototype that consists of three main parts: 1) a number of sensor nodes to measure what products are left, 2) a hub to collect the inventory from the sensor nodes through acoustic communication and store it, and 3) an app on a mobile device to receive the inventory from a hub via Bluetooth and display it in a list for the user. The acoustic communication between the sensor node and the hub are thoroughly investigated taking into account the distance and angle as well as reliability. The Bluetooth communication between the hub and the mobile device with the app can be established automatically when the app is opened or when the user requests an update. The finished prototype has been tested and its performance evaluated. The results show that it functions with great satisfaction, being capable of measuring inventory, storing it and display it on the app. The sensor node and hub have highly reliable communicate within the distance of 1.9 m, a horizontal angle of 25 degrees and a vertical angle of 30 degrees. When the system is exposed to a lot of disturbance it has a reliability of 66% and the Bluetooth connection between the hub and the app can automatically connect about 70% of the times. This smart inventory system can be used in homes, storage rooms, offices, workshops and stores without Internet connection so that no one outside of Bluetooth coverage can get the information, or be expand with Internet connection so that the inventory can be updated anywhere and anytime around the world.

A traqueostomia percutânea é um procedimento realizado rotineiramente na Unidade de Terapia Intensiva (UTI), guiada por broncoscopia. Recentemente, a ultrassonografia tem surgido como uma ferramenta potencialmente útil para assistir à traqueostomia percutânea e reduzir as complicações relacionadas ao procedimento. Um ensaio clínico randomizado, aberto, paralelo, de não inferioridade, foi conduzido comparando a traqueostomia percutânea guiada por ultrassonografia com a traqueostomia percutânea guiada por broncoscopia, em pacientes sob ventilação mecânica na UTI. O desfecho primário, a falência do procedimento, foi definido como um desfecho composto, incluindo (1) a conversão para traqueostomia cirúrgica, (2) o uso associado e não planejado da broncoscopia ou da ultrassonografia, ou (3) a ocorrência de uma complicação maior. Um total de 4.965 pacientes foram avaliados quanto a elegibilidade. Desses, 171 pacientes foram elegíveis e 118 foram submetidos ao procedimento, com 60 pacientes randomizados para o grupo ultrassonografia e 58 pacientes randomizados para o grupo broncoscopia. A falência do procedimento ocorreu em um (1,7%) paciente no grupo ultrassonografia e um (1,7%) paciente no grupo broncoscopia, sem diferença no risco absoluto entre os grupos (intervalo de confiança de 90%, -5,57 a 5,85), na análise \"conforme tratados\", não incluindo a margem de não inferioridade pré-especificada de 6%. Nenhum outro paciente apresentou uma complicação maior em ambos os grupos. As complicações menores relacionadas ao procedimento ocorreram em 20 (33,3%) pacientes no grupo ultrassonografia e em 12 (20,7%) pacientes no grupo broncoscopia, (P = 0,122). A duração do procedimento foi de 11 [7-19] vs. 13 [8-20] minutos (P = 0,468), respectivamente, e os desfechos clínicos também não foram diferentes entre os grupos. Em conclusão, a traqueostomia percutânea guiada por ultrassonografia é eficiente, segura e associada com taxas de complicações semelhantes à traqueostomia percutânea guiada por broncoscopia, em pacientes sob ventilação mecânica na UTI / Percutaneous Dilational Tracheostomy (PDT) is routinely performed in the intensive care unit (ICU) with bronchoscopy guidance. Recently, ultrasound has emerged as a potentially useful tool in order to assist PDT and reduce procedure-related complications. An open-label, parallel, non-inferiority, randomized controlled trial was conducted comparing the ultrasound-guided PDT with the bronchoscopy-guided PDT in mechanically ventilated critically ill patients. The primary outcome was procedure failure, defined as a composite end-point of conversion to a surgical tracheostomy; unplanned associated use of bronchoscopy or ultrasound during PDT; or the occurrence of a major complication. A total of 4,965 patients were assessed for eligibility. Of these, 171 patients were eligible and 118 underwent the procedure, with 60 patients randomly assigned to the ultrasound group and 58 patients to the bronchoscopy group. Procedure failure occurred in one (1.7%) patient in the ultrasound group and one (1.7%) patient in the bronchoscopy group, with no absolute risk difference between the groups (90% confidence interval, -5.57 to 5.85), in the \'as treated\' analysis, not including the pre-specified margin of 6% for noninferiority. No other patient had any major complication in both of the groups. Procedure-related minor complications occurred in 20 (33.3%) patients in the ultrasound group and in 12 (20.7%) patients in the bronchoscopy group, (P=0.122). The median procedure length was 11 [7-19] vs. 13 [8-20] minutes (P=0.468), respectively, and the clinical outcomes were also not different between the groups. In conclusion, ultrasound-guided PDT is effective, safe and associated with similar complication rates and clinical outcomes compared with bronchoscopy-guided tracheostomy in mechanically ventilated critically ill patients