Development of a novel magnetic resonance imaging contrast agent for pressure measurements using lipid-coated microbubbles

The aim of this study was to prepare gas-filled lipid-coated microbubbles as potential MRI contrast agents for imaging of fluid pressure. Air-filled microbubbles were produced with phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) in the presence or absence of cholesterol and/or polyethylene-glycol distearate (PEG-distearate). Microbubbles were also prepared containing a fluorinated phospholipid, perfluoroalkylated glycerol-phosphatidylcholine, F-GPC shells encompassing perfluorohexane-saturated nitrogen gas. These microbubbles were evaluated in terms of physico-chemical characteristics such as size and stability. In parallel to these studies, DSPC microbubbles were also formulated containing nitrogen (N2) gas and compared to air-filled microbubbles. By preventing advection, signal drifts were used to assess their stability. DSPC microbubbles were found to have a drift of 20% signal change per bar of applied pressure in contrast to the F-GPC microbubbles which are considerably more stable with a lower drift of 5% signal change per bar of applied pressure. By increasing the pressure of the system and monitoring the MR signal intensity, the point at which the majority of the microbubbles have been damaged was determined. For the DSPC microbubbles this occurs at 1.3 bar whilst the F-GPC microbubbles withstand pressures up to 2.6 bar. For the comparison between air-filled and N2-filled microbubbles, the MRI sensitivity is assessed by cycling the pressure of the system and monitoring the MR signal intensity. It was found that the sensitivity exhibited by the N2-filled microbubbles remained constant, whilst the air-filled microbubbles demonstrated a continuous drop in sensitivity due to continuous bubble damage.

Evaluation of the sonically induced narrowing of nuclear magnetic resonance spectra of solids

The Nuclear Magnetic Resonance (NMR) spectra of liquids contain a wealth of quantitative information that may be derived, for instance, from chemical shifts and spin-spin couplings. The available information depends on the incoherent rapid molecular motion that causes complicating effects present in the solid state to average to zero. Whereas liquid state NMR spectra show narrow lines, the corresponding NMR spectra from the solid state are normally composed of exceedingly broad resonance lines due to highly restricted molecular motion. It is, therefore, difficult to obtain directly as detailed information from the spectra of solids as from those derived from the liquid state. Studies on a new technique (SINNMR, the sonically induced narrowing of the NMR spectra of solids) to remove line broadening effects in the NMR spectra of the solid state are reported within this thesis. SINNMR involves narrowing the NMR absorptions from solid particles by irradiating them with ultrasound when they are suspended in a support liquid. It is proposed that ultrasound induces incoherent motion of the suspended particles, producing motional characteristics of the particles similar to those of rather large molecules. The first report of apparently successful experiments involving SINNMR[1] emphasised both the irreproducibility of the technique and the uncertainty regarding its true origin. If SINNMR can be made reproducible and the effect definitively attributed to the sonically induced incoherent motional averaging of particles, the technique could offer a simple alternative to the now classical magic-angle spinning (MAS) NMR[2] and the recently reported dynamic angle spinning (DAS)[3] and double rotation (DOR)[4] techniques. Evidence is presented in this thesis to support the proposal that ultrasound may be used to narrow the NMR spectral resonances from solids by inducing incoherent motion of particles suspended in support liquids and, additionally, for some solids, by inducing rotational motion of molecular constituents in the lattices of solids. Successful SINNMR line narrowing using 20 kHz ultrasound is reported for a variety of samples: including trisodium orthophosphate, polytetrafluoroethylene and aluminium alloys. Investigations of SINNMR line narrowing in trisodium phosphate have revealed the relationship between ultrasonic power, particle size and support liquid density for the production of optimum SINNMR conditions. It is also proposed that the incoherent motion of particles induced by 20 kHz ultrasound can originate from interactions between acoustically induced cavitation microjets and particles.

Changes in urethral sphincter size following rehabilitation in older women with stress urinary incontinence

Introduction and hypothesis The purpose of this study was to evaluate the effects of a pelvic floor muscle (PFM) rehabilitation program on the striated urethral sphincter in women over 60 years with stress urinary incontinence (SUI). We hypothesized that the PFM rehabilitation program would also exercise the striated urethral sphincter and that this would be demonstrated by hypertrophy of the sphincter on magnetic resonance imaging (MRI). Methods Women with at least weekly episodes of SUI were recruited. Participants were evaluated before and after a 12-week group PFM rehabilitation intervention with T2-weighted fast-spin-echo MRI sequences recorded in the axial plane at rest to assess urethral sphincter size. Data on SUI symptoms and their bother were also collected. No control group was included. Results Seventeen women participated in the study. The striated urethral sphincter increased significantly in thickness (21 %, p < 0.001), cross-sectional area (20 %, p = 0.003), and volume (12 %, p = 0.003) following the intervention. The reported number of incontinence episodes and their bother also decreased significantly. Conclusions This study appears to demonstrate that PFM training for SUI also trains the striated urethral sphincter and that improvement in incontinence signs and symptoms is associated with sphincter hypertrophy in older women with SUI. These findings support previous ultrasound (US) data showing an increase in urethral cross-sectional area following PFM training and extend the previous findings by more specifically assessing the area of hypertrophy and by demonstrating that older women present the same changes as younger women when assessed using MRI data.

Impact of the timing of metoprolol administration during STEMI on infarct size and ventricular function

Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI). This study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval. We performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short- and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (−25 min) or short (−5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed in the acute and chronic phases in both clinical and experimental settings. For 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9 g vs. 28.1 g; p = 0.06) and higher left ventricular ejection fraction (LVEF) (48.3% vs. 43.9%; p = 0.019) on day 5 CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214 min vs. 160 min; p < 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR). In anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study.

Changes in urethral sphincter size following rehabilitation in older women with stress urinary incontinence

Introduction and hypothesis The purpose of this study was to evaluate the effects of a pelvic floor muscle (PFM) rehabilitation program on the striated urethral sphincter in women over 60 years with stress urinary incontinence (SUI). We hypothesized that the PFM rehabilitation program would also exercise the striated urethral sphincter and that this would be demonstrated by hypertrophy of the sphincter on magnetic resonance imaging (MRI). Methods Women with at least weekly episodes of SUI were recruited. Participants were evaluated before and after a 12-week group PFM rehabilitation intervention with T2-weighted fast-spin-echo MRI sequences recorded in the axial plane at rest to assess urethral sphincter size. Data on SUI symptoms and their bother were also collected. No control group was included. Results Seventeen women participated in the study. The striated urethral sphincter increased significantly in thickness (21 %, p < 0.001), cross-sectional area (20 %, p = 0.003), and volume (12 %, p = 0.003) following the intervention. The reported number of incontinence episodes and their bother also decreased significantly. Conclusions This study appears to demonstrate that PFM training for SUI also trains the striated urethral sphincter and that improvement in incontinence signs and symptoms is associated with sphincter hypertrophy in older women with SUI. These findings support previous ultrasound (US) data showing an increase in urethral cross-sectional area following PFM training and extend the previous findings by more specifically assessing the area of hypertrophy and by demonstrating that older women present the same changes as younger women when assessed using MRI data.

Tracking people in 3D using position, size and shape

This paper presents a prototype tracking system for tracking people in enclosed indoor environments where there is a high rate of occlusions. The system uses a stereo camera for acquisition, and is capable of disambiguating occlusions using a combination of depth map analysis, a two step ellipse fitting people detection process, the use of motion models and Kalman filters and a novel fit metric, based on computationally simple object statistics. Testing shows that our fit metric outperforms commonly used position based metrics and histogram based metrics, resulting in more accurate tracking of people.

ERP success: Does organisation size matter?

Organisations invest enormous sums of money in acquiring Enterprise Resource Planning (ERP) systems, presumably expecting positive impacts to the organisation and its functions. Despite the optimistic motives some ERP projects have reported nil or detrimental impacts. This paper studies the proposition that the size of an organisation (e.g. small, large) may have contributed to the differences in receiving benefits reported in prior studies in this domain. The alleged differences in organisational performance are empirically measured using a prior validated model, using five constructs and fortytwo sub-constructs. Information is gathered from three hundred and ten respondents representing twenty-seven public sector organisations. Results suggests that (1) larger organisations have received more benefits compared to small organisations, (2) small organisations demonstrated higher reliance on their ERP systems, (3) employment cohorts demonstrate significant differences in perceived benefits in small and large organisations.