Mechanical strain promotes osteoblast ECM formation and improves its osteoinductive potential

Background

Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT.

Methods

Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated.

Results

EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques.

Conclusion

EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.     

Magnetic resonance imaging for in vivo assessment of three-dimensional patellar tracking

We have developed a non-invasive measurement technique which can ultimately be used to quantify three-dimensional patellar kinematics of human subjects for a range of static positions of loaded flexion and assessed its accuracy. Knee models obtained by segmenting and reconstructing one high-resolution scan of the knee were registered to bone outlines obtained by segmenting fast, low-resolution scans of the knee in static loaded flexion. We compared patellar tracking measurements made using the new method to measurements made using Roentgen stereophotogrammetric analysis in three cadaver knee specimens loaded through a range of flexion in a test rig. The error in patellar spin and tilt measurements was less than 1.02 degrees and the error in lateral patellar shift was 0.88 mm. Sagittal plane scans provided more accurate final measurements of patellar spin and tilt, whereas axial plane scans provided more accurate measurements of lateral translation and patellar flexion. Halving the number of slices did not increase measurement error significantly, which suggests that scan times can be reduced without reducing accuracy significantly. The method is particularly useful for multiple measurements on the same subject because the high-resolution bone-models need only be created once; thus, the potential variability in coordinate axes assignment and model segmentation during subsequent measurements is removed.     

Ventilation distribution in rats: Part 2 -- A comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

ABSTRACT: BACKGROUND: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. METHODS: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. RESULTS: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. CONCLUSION: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.     

Basic principles of electrohaemodynamics

Electrohaemodynamics (EHD) is a method of measuring cardiac output continuously, also cardiac index, stroke volume, blood flow through limbs, vascular resistance, useful work output from the heart, elastic properties of arterial walls, and contractile and rate of energy generation properties of heart muscle. The method is based on simultaneous measurements of the time variations of arterial blood pressure and electrical conductance in a portion of human body. The measurements, in the form of analogue signals, are processed by means of a microprocessor or a mini-computer. The processing is based on equations which combine haemodynamics with measurements of electrical conductance and arterial pressure variation. Direct comparison of simultaneous cardiac output measurements using EHD and thermal dilution, as well as indirect comparisons with the Fick and dye dilution methods, show that EHD is at least as accurate as these methods. The reproducibility of EHD is within one percent when the subjects are in the steady state, which appears to be better than any other known technique.     

An analysis of estimation of pulmonary blood flow by the single-breath method

The single-breath method of determining pulmonary blood flow is a simple technique involving no inert gas or special maneuvers such as rebreathing or breath holding. The use of this elegant technique has been limited, however, largely because of questions regarding its accuracy. Previous analyses of the method have indicated that large errors in the estimated blood flow could result if data reduction is not handled carefully. In addition, an uncertain amount of error is introduced, if the CO2 retained by the lung tissue while measurements are being made is not taken into account in the calculations. This paper presents a rigorous approach for estimating the pulmonary blood flow by the single-breath method, which would minimize considerably the effects of measurement errors and would also allow for possible CO2 absorption by the lung tissue. It is based on the exact solution of the underlying equations that describe the dynamics of gas exchange in the lung. The analytic solution provides insight into the difficulties involved in extracting the desired information from the experimental data.     

A new nasal acoustic reflection technique to estimate pharyngeal cross-sectional area during sleep.

The conventional acoustic reflection technique in which acoustic waves are launched through the mouth cannot be applied during sleep, nor can it be applied to the nasopharynx, which is the major site of occlusion in patients with obstructive sleep apnea syndrome. We propose a new technique of nasal acoustic reflection to measure pharyngeal cross-sectional areas including the nasopharynx. The acoustic waves are introduced simultaneously to both nostrils during spontaneous nasal breathing. A new algorithm takes into account the nasal septum with asymmetric nasal cavities on both sides and assumes prior knowledge of the cross-sectional area of the nasal cavities and the position of the nasal septum. This method was tested on an airway model with a septum and on healthy human subjects. The conventional technique gave inaccurate measurements for pharyngeal cross-sectional areas for an airway model with asymmetric branching, whereas the new technique measured them almost perfectly. The oro- and hypopharyngeal cross-sectional area measurements acquired by the new method were not different from those obtained by the conventional method in normal subjects. This new method can be used as a monitor of upper airway dimensions in nocturnal polysomnography.     

Determination of the electron density in the tokamak edge plasma from the time evolution of a laser-induced fluorescence signal from atomic helium

The time evolution of a laser-induced fluorescence signal from neutral helium He I in the edge and divertor plasmas in modern magnetic confinement devices is considered. Computations are performed on the basis of a nonstationary collisional-radiative model involving ten singlet and nine triplet states of helium that affect the time evolution of the fluorescence signal. A new method is proposed for determining the electron density from measurements of the time derivative of the profile of the fluorescence spectral line.     

Dynamic measurements of CO diffusing capacity using discrete samples of alveolar gas

It has been shown that measurements of the diffusing capacity of the lung for CO made during a slow exhalation [DLCO(exhaled)] yield information about the distribution of the diffusing capacity in the lung that is not available from the commonly measured single-breath diffusing capacity [DLCO(SB)]. Current techniques of measuring DLCO(exhaled) require the use of a rapid-responding (less than 240 ms, 10-90%) CO meter to measure the CO concentration in the exhaled gas continuously during exhalation. DLCO(exhaled) is then calculated using two sample points in the CO signal. Because DLCO(exhaled) calculations are highly affected by small amounts of noise in the CO signal, filtering techniques have been used to reduce noise. However, these techniques reduce the response time of the system and may introduce other errors into the signal. We have developed an alternate technique in which DLCO(exhaled) can be calculated using the concentration of CO in large discrete samples of the exhaled gas, thus eliminating the requirement of a rapid response time in the CO analyzer. We show theoretically that this method is as accurate as other DLCO(exhaled) methods but is less affected by noise. These findings are verified in comparisons of the discrete-sample method of calculating DLCO(exhaled) to point-sample methods in normal subjects, patients with emphysema, and patients with asthma.     

Comparison of two hydrodensitometric methods for estimating percent body fat.

This study compared the two following hydrodensitometric methods for estimating percent body fat (%BF): 1) estimation of residual volume (RV) by helium dilution before and after measurement of immersed mass at RV, and 2) determination of immersed mass at a comfortable level of expiration (approximately functional residual capacity) with measurement of the associated gas volume by oxygen dilution. Twelve men [27.9 +/- 7.5 (SD) yr; 79.32 +/- 12.79 kg; 180.5 +/- 9.9 cm] were tested for %BF via both methods on each of two separate visits within 3 days by using a counterbalanced design. The two helium dilution measurements yielded a technical error of measurement of 0.2% BF and an intraclass correlation coefficient of 0.999. Corresponding values for the oxygen dilution method were 0.4% BF and 0.999, respectively. There was no difference (P = 0.80) between the helium dilution (16.9 +/- 9.3% BF) and oxygen dilution (16.9 +/- 9.4% BF) methods, and the individual differences ranged from -0.7 to 0.6% BF. The interclass correlation coefficient between the two methods was 0.999 with a SE of estimate of 0.4% BF. Whereas both methods were precise and reliable and yielded similar results, the oxygen dilution technique was more expedient and was preferred by the subjects because they were not required to exhale to RV.     

Comparison of dermal vs internal light administration in human lungs using the TDLAS‐GASMAS technique—Phantom studies

Oxygen and water vapor content, in the lungs of a 3D‐printed phantom model based on CT‐images of a preterm infant, is evaluated using Tunable Diode Laser Absorption Spectroscopy (TDLAS) in Gas in Scattering Media Absorption Spectroscopy (GASMAS), that is, the TDLAS‐GASMAS technique. Oxygen gas is detected through an absorption line near 764 nm and water vapor through an absorption line near 820 nm. A model with a lung containing interior structure is compared to a model with a hollow lung. Compared to the model with the hollow lung, both the mean absorption path length and the transmitted intensity are found to be lower for the model with the structured lung. A new approach, where laser light is delivered internally into the model through an optical fiber, is compared to dermal light administration, that is, illumination onto the skin, for the model with structure inside the lung. The internal light administration generally resulted in larger gas absorption, and higher signal‐to‐noise ratios, compared to the dermal light administration. The results from the phantom measurements show great promise for the internal illumination approach and a natural next step would be to investigate it further in clinical studies.     

Cardiac output by rebreathing in patients with cardiopulmonary diseases

Noninvasive estimates of cardiac output by rebreathing soluble gases (Qc) can be unreliable in patients with cardiopulmonary diseases because of uneven distribution of ventilation to lung gas volume and pulmonary blood flow. To evaluate this source of error, we compared rebreathing Qc with invasive measurements of cardiac output performed by indicator-dilution methods (COID) in 39 patients with cardiac or pulmonary diseases. In 16 patients with normal lung volumes and 1-s forced expiratory volumes (FEV1), Qc measured with acetylene [Qc(C2H2)] overestimated COID insignificantly by 2 +/- 9% (SD). In subjects with mild to moderate obstructive lung disease, Qc(C2H2) slightly overestimated COID by 6 +/- 15% (P = 0.11). In patients with restrictive disease or combined obstructive and restrictive disease, Qc(C2H2) underestimated COID significantly by 9 +/- 14% (P less than 0.04). The magnitude of the discrepancy between Qc and COID correlated with size of the volume rebreathed and an index of uneven ventilation calculated from helium mixing during rebreathing that determined a dead space to inspired volume ratio (VRD/VI). Rebreathing volumes less than 40% of the predicted FEV or VRD/VI of 0.4 or greater identified all subjects with a discrepancy between Qc(C2H2) and COID of 20% or greater.     

Contingent kernel density estimation

Kernel density estimation is a widely used method for estimating a distribution based on a sample of points drawn from that distribution. Generally, in practice some form of error contaminates the sample of observed points. Such error can be the result of imprecise measurements or observation bias. Often this error is negligible and may be disregarded in analysis. In cases where the error is non-negligible, estimation methods should be adjusted to reduce resulting bias. Several modifications of kernel density estimation have been developed to address specific forms of errors. One form of error that has not yet been addressed is the case where observations are nominally placed at the centers of areas from which the points are assumed to have been drawn, where these areas are of varying sizes. In this scenario, the bias arises because the size of the error can vary among points and some subset of points can be known to have smaller error than another subset or the form of the error may change among points. This paper proposes a "contingent kernel density estimation" technique to address this form of error. This new technique adjusts the standard kernel on a point-by-point basis in an adaptive response to changing structure and magnitude of error. In this paper, equations for our contingent kernel technique are derived, the technique is validated using numerical simulations, and an example using the geographic locations of social networking users is worked to demonstrate the utility of the method.     

A Measurement Model of Disease Damage in Paired Organs

Diagnostic test can be used to classify subjects as “diseased” or “undiseased”. If measurements are obtained on a quantitative scale they may serve additionally to quantify the damage caused by the disease. If a whole bundle of measurements is available but no gold standard exists, the evaluation of these measurements may be improved by using latent variables. The subject of this investigation is an application of latent variable techniques in the evaluation of diagnostic measurements concerning paired organs. A method is presented which allows to quantify the association between the true disease damage of affected organs. Furthermore, the corresponding association of the error components of several measurements can be quantified. The method is based upon a one factor model of the diagnostic measurements. The method supports the investigation of the pathogenetic process of the underlying disease and the improvement of diagnostic measurements. It is applied to data from the Erlangen Glaucoma Registry.     

In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography.

Lung morphology and function in human subjects can be monitored with computed tomography (CT). Because many human respiratory diseases are routinely modeled in rodents, a means of monitoring the changes in the structure and function of the rodent lung is desired. High-resolution images of the rodent lung can be attained with specialized micro-CT equipment, which provides a means of monitoring rodent models of lung disease noninvasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution are sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator and not on the respiratory mechanics of the individual animals. In addition, intubation and ventilation can have unnatural effects on the respiratory dynamics of the animal, because the airway pressure, tidal volume, and respiratory rate are selected by the operator. In these experiments, important information about the symptoms of the respiratory disease being studied may be missed because the respiration is forced to conform to the ventilator settings. In this study, we implement a method of respiratory-gated micro-CT for use with anesthetized free-breathing rodents. From the micro-CT images, quantitative analysis of the structure of the lungs of healthy unconscious mice was performed to obtain airway diameters, lung and airway volumes, and CT densities at end expiration and during inspiration. Because the animals were free breathing, we were able to calculate tidal volume (0.09 +/- 0.03 ml) and functional residual capacity (0.16 +/- 0.03 ml).     

The measurement of body segment inertial parameters using dual energy X-ray absorptiometry

Accurate body segment parameter (BSP) information is required for dynamic analyses of motion and the current methods available for obtaining these BSPs have been criticized. The purpose of this study was to determine whether dual energy X-ray absorptiometry (DXA) could accurately measure the BSPs of scanned objects and thus be used as a tool for measuring the BSPs of human subjects. Whole body mass (WBM) of 11 males was measured from a DXA scan and the values were compared to criterion scale-measured values by calculating the mean percent error. Two objects (plastic cylinder, human cadaver leg) were also scanned and DXA measurements of mass, length, centre of mass location (CM) and moment of inertia about the centre of mass (I_CM) were made using custom software. Criterion BSP measurements were then made and compared to DXA BSP values by calculating the percent error. Criterion I_CM measurements of the two objects were made using a pendulum technique and a second criterion I_CM calculation was made for the cylinder using a geometric formula. A mean percent error of −1.05% ±1.32% was found for WBM measurements of the human subjects. Errors for the cylinder and cadaver leg were under 3.2% for all BSPs except for I_CM when DXA was compared to the pendulum method (14.3% and 8.2% for cylinder and leg, respectively). The errors between DXA and the pendulum method were attributed to uncertainty in the pendulum technique (J. Biomech. 2002, in Review). I_CM error of the cylinder when DXA was compared to the geometric calculation was 2.63%. This error, combined with the low errors for all other BSPs, indicated that DXA can be used as a simple and accurate means of obtaining direct BSP information on living humans.     

Advances in magnetic resonance imaging of lung physiology.

This review presents an overview of some recent magnetic resonance imaging (MRI) techniques for measuring aspects of local physiology in the lung. MRI is noninvasive, relatively high resolution, and does not expose subjects to ionizing radiation. Conventional MRI of the lung suffers from low signal intensity caused by the low proton density and the large degree of microscopic field inhomogeneity that degrades the magnetic resonance signal and interferes with image acquisition. However, in recent years, there have been rapid advances in both hardware and software design, allowing these difficulties to be minimized. This review focuses on some newer techniques that measure regional perfusion, ventilation, gas diffusion, ventilation-to-perfusion ratio, partial pressure of oxygen, and lung water. These techniques include contrast-enhanced and arterial spin-labeling techniques for measuring perfusion, hyperpolarized gas techniques for measuring regional ventilation, and apparent diffusion coefficient and multiecho and gradient echo techniques for measuring proton density and lung water. Some of the major advantages and disadvantages of each technique are discussed. In addition, some of the physiological issues associated with making measurements are discussed, along with strategies for understanding large and complex data sets.     

Clearance of technetium-99m-DTPA and HRCT findings in the evaluation of patients with Idiopathic Pulmonary Fibrosis

Background

Different lung function equipment and different respiratory manoeuvres may produce different Peak Expiratory Flow (PEF) results. Although the PEF is the most common lung function test, there have been few studies of these effects and no previous study has evaluated both factors in a single group of patients.

Methods

We studied 36 subjects (PEF range 80–570 l/min). All patients recorded PEF measurements using a short rapid expiration following maximal inspiration (PEF technique) or a forced maximal expiration to residual volume (FVC technique). Measurements were made using a Wright's peak flow meter, a turbine spirometer and a Fleisch pneumotachograph spirometer.

Results

The mean PEF was 8.7% higher when the PEF technique was used (compared with FVC technique, p < 0.0001). The mean PEF recorded with the turbine spirometer was 5.5% lower than the Wright meter reading. The Fleisch spirometer result was 19.5% lower than the Wright reading. However, adjustment of the Wrights measurements from the traditional Wright's scale to the new EU Peak Flow scale produced results that were only 7.2% higher than the Fleisch pneumotachograph measurements.

Conclusion

Peak flow measurements are affected by the instruction given and by the device and Peak Flow scale used. Patient management decisions should not be based on PEF measurement made on different instruments.     

A method improving the accuracy of fluorescence recovery after photobleaching analysis

Fluorescence recovery after photobleaching has been an established technique of quantifying the mobility of molecular species in cells and cell membranes for more than 30 years. However, under nonideal experimental conditions, the current methods of analysis still suffer from occasional problems; for example, when the signal/noise ratio is low, when there are temporal fluctuations in the illumination, or when there is bleaching during the recovery process. We here present a method of analysis that overcomes these problems, yielding accurate results even under nonideal experimental conditions. The method is based on circular averaging of each image, followed by spatial frequency analysis of the averaged radial data, and requires no prior knowledge of the shape of the bleached area. The method was validated using both simulated and experimental fluorescence recovery after photobleaching data, illustrating that the diffusion coefficient of a single diffusing component can be determined to within ∼1%, even for small signal levels (100 photon counts), and that at typical signal levels (5000 photon counts) a system with two diffusion coefficients can be analyzed with <10% error.     

Fetal ECG extraction during labor using an adaptive maternal beat subtraction technique.

Fetal ECG (FECG) monitoring using abdominal maternal signals is a non-invasive technique that allows early detection of changes in fetal wellbeing. Several other signal components have stronger energy than the FECG, the most important being maternal ECG (MECG) and, especially during labor, uterine EMG. This study proposes a new method to subtract MECG after detecting and removing abdominal signal segments with high-amplitude variations due to uterine contractions. The method removes MECG from abdominal signals using an approximation of the current MECG segment based on a linear combination of previous MECG segments aligned on the R-peak. The coefficients of the linear model are computed so that the squared error of the approximation over the whole current segment is minimized. Abdominal signal segments strongly affected by uterine contractions are detected by applying median filtering. The methods proposed are tested on real abdominal data recorded during labor, with FECG recorded using scalp electrodes synchronously recorded for comparison.