K-edge subtraction synchrotron X-ray imaging in bio-medical research.

High contrast in X-ray medical imaging, while maintaining acceptable radiation dose levels to the patient, has long been a goal. One of the most promising methods is that of K-edge subtraction imaging. This technique, first advanced as long ago as 1953 by B. Jacobson, uses the large difference in the absorption coefficient of elements at energies above and below the K-edge. Two images, one taken above the edge and one below the edge, are subtracted leaving, ideally, only the image of the distribution of the target element. This paper reviews the development of the KES techniques and technology as applied to bio-medical imaging from the early low-power tube sources of X-rays to the latest high-power synchrotron sources. Applications to coronary angiography, functional lung imaging and bone growth are highlighted. A vision of possible imaging with new compact sources is presented.

Quantitative Imaging of Regional Aerosol Deposition, Lung Ventilation and Morphology by Synchrotron Radiation CT.

To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R2 = 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.

Association of breathing sound spectra with glottal dimensions in exercise-induced vocal cord dysfunction.

The objective of this study was to evaluate associations between the breathing sound spectra and glottal dimensions in exercise-induced vocal cord dysfunction (EIVCD) during a bicycle ergometry test. Nineteen subjects (mean age 21.8 years and range 13-39 years) with suspected EIVCD were studied. Vocal folds were continuously imaged with videolaryngoscopy and breathing sounds were recorded during the bicycle exercise test. Twelve subjects showed paradoxical movement of the vocal folds during inspiration by the end of the exercise. In seven subjects, no abnormal reactions in vocal folds were found; they served as control subjects. The glottal quotient (interarytenoid distance divided by the anteroposterior glottal distance) was calculated. From the same time period, the tracheal-vocal tract resonance peaks of the breathing sound spectra were analyzed, and stridor sounds were detected and measured. Subjects with EIVCD showed significantly higher resonance peaks during the inspiratory phase compared to the expiratory phase (p < 0.014). The glottal quotient decreased significantly in the EIVCD group (p < 0.001), but not in the control group. 8 out of 12 EIVCD patients (67%) showed stridor sounds, while none of the controls did. There was a significant inverse correlation between the frequencies of the breathing sound resonance peaks and the glottal quotient. The findings indicate that the typical EIVCD reaction of a paradoxical approximation of the vocal folds during inspiration, measured here as a decrease in the glottal quotient, is significantly associated with an increase in inspiratory resonance peaks. The findings are applicable in the documentation of EIVCD findings using videolaryngoscopy, in addition to giving clinicians tools for EIVCD recognition. However, the study is limited by the small number of subjects.

Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities.

BACKGROUND: It is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. METHODS: In a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV̇). Heterogeneity of ventilation was calculated as the coefficient of variation in sV̇ (CVsV̇ ). The coefficient of variation in lung densities (CVD ) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FI O2 0.21; ZEEP and FI O2 1.0; PEEP 12 cmH2 O and FI O2 1.0 (Open Lung-PEEP = OLP). RESULTS: The mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV̇ and poor aeration at ZEEP-0.21 than at OLP: 12.9 ± 9.0 vs. 0.6 ± 0.4% in the non-dependent level, and 17.5 ± 8.2 vs. 0.4 ± 0.1% in the dependent one (P = 0.041). The CVsV̇ of the total imaged lung at PEEP 12 cmH2 O was significantly lower than on ZEEP, regardless of FI O2 , indicating more heterogeneity of ventilation during ZEEP (0.23 ± 0.03 vs. 0.54 ± 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. CONCLUSION: ZEEP together with low FI O2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.

Radiation dose and image quality in K-edge subtraction computed tomography of lung in vivo.

K-edge subtraction computed tomography (KES-CT) allows simultaneous imaging of both structural features and regional distribution of contrast elements inside an organ. Using this technique, regional lung ventilation and blood volume distributions can be measured experimentally in vivo. In order for this imaging technology to be applicable in humans, it is crucial to minimize exposure to ionizing radiation with little compromise in image quality. The goal of this study was to assess the changes in signal-to-noise ratio (SNR) of KES-CT lung images as a function of radiation dose. The experiments were performed in anesthetized and ventilated rabbits using inhaled xenon gas in O2 at two concentrations: 20% and 70%. Radiation dose, defined as air kerma (Ka), was measured free-in-air and in a 16 cm polymethyl methacrylate phantom with a cylindrical ionization chamber. The dose free-in-air was varied from 2.7 mGy to 8.0 Gy. SNR in the images of xenon in air spaces was above the Rose criterion (SNR > 5) when Ka was over 400 mGy with 20% xenon, and over 40 mGy with 70% xenon. Although in human thorax attenuation is higher, based on these findings it is estimated that, by optimizing the imaging sequence and reconstruction algorithms, the radiation dose could be further reduced to clinically acceptable levels.

Quantitative functional imaging and kinetic studies with high-Z contrast agents using synchrotron radiation computed tomography.

1. There is an increasing demand in diagnostic radiology for extracting additional morphological and functional quantitative parameters from three-dimensional computed tomography (CT) images. Synchrotron radiation computed tomography (SRCT) is the state-of-the-art method in preclinical X-ray CT, because its performance is close to the theoretical limits in terms of accuracy and precision. 2. The SRCT method with monochromatic X-ray beams yields absolute high-Z element contrast agent concentrations, without errors arising from beam hardening or scatter artefacts, by using digital subtraction techniques of the sinograms. Each pixel of the reconstructed difference images provides a quantitative concentration versus time curve of inhaled or injected high-Z contrast agents (xenon or iodine) with a high sensitivity. This is the key point of two functional imaging techniques that were developed at the European Synchrotron Radiation Facility: brain perfusion and lung function (ventilation and perfusion). 3. These two imaging techniques provide parametric images expressed in absolute perfusion parameters (blood volume, blood flow, mean transit time and capillary permeability) or ventilation parameters (lung volume, regional lung ventilation, bronchial lumen size, regional airway and lung compliance) with a high accuracy and precision. 4. The aim of the present brief review is to give a snapshot of the status and perspectives of these two imaging techniques, with emphasis on the performances and interests for functional imaging. Two separate sections will then describe the results obtained so far using SRCT as an in vivo functional imaging tool for measuring changes in haemodynamics and ventilation, in the investigation of experimental pathophysiology and in the effects of therapeutic intervention.

Simultaneous in vivo synchrotron radiation computed tomography of regional ventilation and blood volume in rabbit lung using combined K-edge and temporal subtraction.

In K-edge subtraction (KES) imaging with synchrotron radiation computed tomography (SRCT), two images are taken simultaneously using energies above and below the K-absorption edge of a contrast agent. A logarithmic difference image reveals the contrast agent concentration with good accuracy. Similarly, in temporal subtraction imaging (TSI) the reference image is taken before the introduction of the contrast agent. Quantitative comparisons of in vivo images of rabbit lung indicated that similar results for concentrations of iodine in blood vessels and xenon in airways are obtained by KES and TSI, but the level of noise and artifacts was higher in the latter. A linear fit showed that in the lung parenchyma rho(TSI) = (0.97 +/- 0.03)rho(KES) + (0.00 +/- 0.05) for xenon and rho(TSI) = (1.21 +/- 0.15)rho(KES) + (0.0 +/- 0.1) for iodine. For xenon the calculation of time constant of ventilation gave compatible values for both of the methods. The two methods are combined for the simultaneous determination of the xenon concentration (by KES) and the iodine concentration (by TSI) in lung imaging, which will allow simultaneous in vivo determination of ventilation and perfusion.

Effect of tidal volume on distribution of ventilation assessed by synchrotron radiation CT in rabbit.

A respiration-gated synchrotron radiation computed tomography (SRCT) technique, which allows visualization and direct quantification of inhaled stable xenon gas, was used to study the effect of tidal volume (Vt) on regional lung ventilation. High-resolution maps (pixel size 0.35 x 0.35 mm) of local washin time constants (tau) and regional specific ventilation were obtained in five anesthetized, paralyzed, and mechanically ventilated rabbits in upright body position at the fourth, sixth, and eighth dorsal vertebral levels with a Vt from 4.9 +/- 0.3 to 7.9 +/- 0.4 ml/kg (means +/- SE). Increasing Vt without an increase in minute ventilation resulted in a proportional increase of mean specific ventilation up to 65% in all studied lung levels and reduced the scattering of washin tau values. The tau values had log-normal distributions. The results indicate that an increase in Vt decreases nonuniformity of intraregional ventilatory gas exchange. The findings suggest that (SRCT) provides a new quantitative tool with high spatial discrimination ability for assessment of changes in peripheral pulmonary gas distribution during mechanical ventilation.

Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent.

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.