Measurement of outflow facility using iPerfusion

Elevated intraocular pressure (IOP) is the predominant risk factor for glaucoma, and reducing IOP is the only successful strategy to prevent further glaucomatous vision loss. IOP is determined by the balance between the rates of aqueous humour secretion and outflow, and a pathological reduction in the hydraulic conductance of outflow, known as outflow facility, is responsible for IOP elevation in glaucoma. Mouse models are often used to investigate the mechanisms controlling outflow facility, but the diminutive size of the mouse eye makes measurement of outflow technically challenging. In this study, we present a new approach to measure and analyse outflow facility using iPerfusion™, which incorporates an actuated pressure reservoir, thermal flow sensor, differential pressure measurement and an automated computerised interface. In enucleated eyes from C57BL/6J mice, the flow-pressure relationship is highly non-linear and is well represented by an empirical power law model that describes the pressure dependence of outflow facility. At zero pressure, the measured flow is indistinguishable from zero, confirming the absence of any significant pressure independent flow in enucleated eyes. Comparison with the commonly used 2-parameter linear outflow model reveals that inappropriate application of a linear fit to a non-linear flow-pressure relationship introduces considerable errors in the estimation of outflow facility and leads to the false impression of pressure-independent outflow. Data from a population of enucleated eyes from C57BL/6J mice show that outflow facility is best described by a lognormal distribution, with 6-fold variability between individuals, but with relatively tight correlation of facility between fellow eyes. iPerfusion represents a platform technology to accurately and robustly characterise the flow-pressure relationship in enucleated mouse eyes for the purpose of glaucoma research and with minor modifications, may be applied in vivo to mice, as well as to eyes from other species or different biofluidic systems

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

Spectral and Temporal Interrogation of Cerebral Hemodynamics Via High Speed Laser Speckle Contrast Imaging

Laser Speckle Contrast Imaging (LSCI) is a non-scanning wide field-of-view optical imaging technique specifically developed for cerebral blood flow (CBF) monitoring. In this project, a versatile Laser speckle contrast imaging system has been designed and developed to monitor CBF changes and examine the physical properties of cerebral vasculature during functional brain activation experiments. The hardware of the system consists of a high speed CMOS camera, a coherent light source, a trinocular microscope, and a PC that does camera controlling and data storage. The simplicity of the system’s hardware makes it suitable for biological experiments. In controlled flow experiments using a custom made microfluidic channel, the linearity of the CBF estimates was evaluated under high speed imaging settings. Under the camera exposure time setting in the range of tens of micro-seconds, results show a linear relationship between the CBF estimates and the flow rates within the microchannel. This validation permitted LSCI to be used in high frame rate imaging and the method is only limited by the camera speed. In an in vivo experiment, the amount of oxygen intake via breathing by a rat was reduced to 12% to induce the dilation of the vessels. Results demonstrated a positive correlation between the system’s CBF estimates and the pulse wave velocity derived from aortic blood pressure. To exemplify the instantaneous pulsatility flow study acquired at high sampling rate, a pulsatile cerebral blood flow analysis was conducted on two vessels, an arteriole and a venule. The pulsatile waveform results, captured under sampling rate close to 2000 Hz. The pulse of the arteriole rises 13ms faster than the pulse of the venule, and it takes 6ms longer for the pulse of the arteriole to fall below the lower fall-time boundary. By using the second order derivative (accelerated) CBF estimates, the vascular stiffness was evaluated. Results show the arteriole and the venule have increased-vascular-stiffness indices of 0.95 and 0.74. On the other side, the arteriole and the venule have decreased-vascular-stiffness indices of 0.125 and 0.35. Both vascular stiffness indices suggested that the wall of arteriole is more rigid than the venule. The proposed LSCI system can monitor the mean flow over function activation experiment, and the interrogation of blood flow in terms of physiological oscillations. The proposed vascular stiffness metrics for estimating the stroke preliminary symptom, may eventually lead to insights of stroke and its causes

Digital Image Processing And Metabolic Parameter Linearity To Noninvasively Detect Analyte Concentration

Spectroscopy is the scientific technique of quantifying and measuring electromagnetic, or light, reflectance or absorption. Atoms emit and/or absorb light when light passes through. The excitations provide specific energy signatures that relate to the element that is emitting or absorbing the light. Non-invasive biosensors monitor physical health properties such as heart rate, oxygen saturation, and tissue blood flow as a result of spectroscopy. Several attempts have been made to non-invasively detect metabolic chemical, or analyte, concentration with various spectroscopic techniques. The primary limitation is due to signal-to-noise ratio. This research focuses on a unique method that combines emission spectroscopy and machine learning to non-invasively detect glucose and other metabolic analyte concentrations. Artificial neural network is applied to train a predictive model that enables the remote sensing capability. The data acquisition requires capturing digital images of the spectral reflectance. Image processing and segmentation determines discrete variables that correlate with the metabolic analytes. The clinical trial protocol includes n=90 subjects, and a venipuncture comprehensive metabolic panel blood test within two minutes prior to a non-invasive spectral reading. Results indicate a strong correlation between the spectral system and the clinical gold standard, relative to metabolic analyte concentration

The consequences of a new software package for the quantification of gated-SPECT myocardial perfusion studies

Semiquantitative analysis of myocardial perfusion scintigraphy (MPS) has reduced inter- and intraobserver variability, and enables researchers to compare parameters in the same patient over time, or between groups of patients. There are several software packages available that are designed to process MPS data and quantify parameters. In this study the performances of two systems, quantitative gated SPECT (QGS) and 4D-MSPECT, in the processing of clinical patient data and phantom data were compared. The clinical MPS data of 148 consecutive patients were analysed using QGS and 4D-MSPECT to determine the end-diastolic volume, end-systolic volume and left ventricular ejection fraction. Patients were divided into groups based on gender, body mass index, heart size, stressor type and defect type. The AGATE dynamic heart phantom was used to provide reference values for the left ventricular ejection fraction. Although the correlations were excellent (correlation coefficients 0.886 to 0.980) for all parameters, significant differences (p < 0.001) were found between the systems. Bland-Altman plots indicated that 4D-MSPECT provided overall higher values of all parameters than QGS. These differences between the systems were not significant in patients with a small heart (end-diastolic volume < 70 ml). Other clinical factors had no direct influence on the relationship. Additionally, the phantom data indicated good linear responses of both systems. The discrepancies between these software packages were clinically relevant, and influenced by heart size. The possibility of such discrepancies should be taken into account when a new quantitative software system is introduced, or when multiple software systems are used in the same institution.Vascular Biology and Interventio

Quantification of Myocardial Perfusion in Human Subjects Using 82Rb and Wavelet-Based Noise Reduction

Quantification of myocardial perfusion with 82Rb has been difficult to achieve because of the low signal-to-noise ratio of the dynamic data curves. This study evaluated the accuracy of flow estimates after the application of a novel multidimensional wavelet-based noise-reduction protocol. Methods: Myocardial perfusion was estimated using 82Rb and a two-compartment model from dynamic PET scans on 11 healthy volunteers at rest and after hyperemic stress with dipyridamole. Midventricular planes were divided into eight regions of interest, and a wavelet transform protocol was applied to images and time–activity curves. Flow estimates without and with the wavelet approach were compared with those obtained using H215O. Results: Over a wide flow range (0.45–2.75 mL/g/min), flow achieved with the wavelet approach correlated extremely closely with values obtained with H215O (y = 1.03 x -0.12; n = 23 studies, r = 0.94, P < 0.001). If the wavelet noise-reduction technique was not used, the correlation was less strong (y = 1.11 x + 0.24; n = 23 studies, r = 0.79, P < 0.001). In addition, the wavelet approach reduced the regional variation from 75% to 12% and from 62% to 11% (P < 0.001 for each comparison) for resting and stress studies, respectively. Conclusion: The use of a wavelet protocol allows near-optimal noise reduction, markedly enhances the physiologic flow signal within the PET images, and enables accurate measurement of myocardial perfusion with 82Rb in human subjects over a wide range of flows

Development of Portable Diffuse Optical Spectroscopic Systems For Treatment Monitoring

The goal of this dissertation is to demonstrate the utility of portable, small-scale diffuse optical spectroscopic (DOS) systems for the diagnosis and treatment monitoring of various diseases. These systems employ near-infrared light (wavelength range of 650nm to 950nm) to probe human tissue and are sensitive to changes in scattering and absorption properties of tissues. The absorption is mainly influenced by the components of blood, namely oxy- and deoxy-hemoglobin (HbO2 and Hb) and parameters that can be derived from them (e.g. total hemoglobin concentration [THb] and oxygen saturation, StO2). Therefore, I focused on diseases in which these parameters change, which includes vascular diseases such as Peripheral Atrial Disease (PAD) and Infantile Hemangiomas (IH) as well as musculoskeletal autoimmune diseases such as Rheumatoid Arthritis (RA). In each of these specific diseases, current monitoring techniques are limited by their sensitivity to disease progression or simply do not exist as a quantitative metric. As part of this project, I first designed and built a wireless handheld DOS device (WHDD) that can perform DOS measurements at various tissue depths. This device was used in a 15-patient pilot study for infantile hemangiomas (IH) to differentiate diseased skin from normal skin and monitor the vascular changes during intervention. In another study, I compare the ultra-small form- factor WHDD’s ability to monitor synovitis and disease progression during a patient’s treatment of RA against the capabilities of a proven frequency domain optical tomographic (FDOT) system that has shown to differentiate patients with and without RA. Learning from clinical utility of the WHDD from these two studies, I adapted the WHDD technology to develop a compact multi- channel DOS measurement system to monitor perfusion changes in the lower extremities before and after surgical intervention for patients with peripheral artery disease (PAD). Using this multi- channel system, which we called the vascular optical spectroscopic measurement (VOSM) system, our group conducted a 20-subject pilot study to quantify its ability to monitor blood perfusion before and after revascularization of stenotic arteries in the lower extremities. This proof-of- concept study demonstrated how DOS may help vascular surgeons perform revascularization procedures in the operating room and assists in post-operative treatment monitoring of vascular diseases