Deokiee Chon

Characterization of the interstitial lung diseases via density-based and texture-based analysis of computed tomography images of lung structure and function1 ☆

RATIONALE AND OBJECTIVES Efforts to establish a quantitative approach to the computed tomography (CT)-based character ization of the lung parenchyma in interstitial lung disease (including emphysema) has been sought. The accuracy of these tools must be site independent. Multi-detector row CT has remained the gold standard for imaging the lung, and it provides the ability to image both lung structure as well as lung function. MATERIAL AND METHODS Imaging is via multi-detector row CT and protocols include careful control of lung volume during scanning. Characterization includes not only anatomic-based measures but also functional measures including regional parameters derived from measures of pulmonary blood flow and ventilation. Image processing includes the automated detection of the lungs, lobes, and airways. The airways provide the road map to the lung parenchyma. Software automatically detects the airways, the airway centerlines, and the branch points, and then automatically labels the airway tree segments with a standardized set of labels, allowing for intersubject as well intrasubject comparisons across time. By warping all lungs to a common atlas, the atlas provides the range of normality for the various parameters provided by CT imaging. RESULTS Imaged density and textural changes mark underlying structural changes at the most peripheral regions of the lung. Additionally, texture-based alterations in the parameters of blood flow may provide early evidence of pathologic processes. Imaging of stable xenon gas provides a regional measure of ventilation which, when coupled with measures of flow, provide for a textural analysis regional of ventilation-perfusion matching. CONCLUSION With the improved resolution and speed of CT imaging, the patchy nature of regional parenchymal pathology can be imaged as texture of structure and function. With careful control of imaging protocols and the use of objective image analysis methods it is possible to provide site-independent tools for the assessment of interstitial lung disease. There remains a need to validate these methods, which requires interdisciplinary and cross-institutional efforts to gather appropriate data bases of images along with a consensus on appropriate ground truths associated with the images. Furthermore, there is the growing need for scanner manufacturers to focus on not just visually pleasing images, but on quantitatifiably accurate images.

CT-measured regional specific volume change reflects regional ventilation in supine sheep

Computer tomography (CT) imaging techniques permit the noninvasive measurement of regional lung function. Regional specific volume change (sVol), determined from the change in lung density over a tidal breath, should correlate with regional ventilation and regional lung expansion measured with other techniques. sVol was validated against xenon (Xe)-CT-specific ventilation (sV) in four anesthetized, intubated, mechanically ventilated sheep. Xe-CT used expiratory gated axial scanning during the washin and washout of 55% Xe. sVol was measured from the tidal changes in tissue density (H, houndsfield units) of lung regions using the relationship sVol = [1,000(Hi - He)]/[He(1,000 + Hi)], where He and Hi are expiratory and inspiratory regional density. Distinct anatomical markings were used to define corresponding lung regions of interest between inspiratory, expiratory, and Xe-CT images, with an average region of interest size of 1.6 +/- 0.7 ml. In addition, sVol was compared with regional volume changes measured directly from the positions of implanted metal markers in an additional animal. A linear relationship between sVol and sV was demonstrated over a wide range of regional sV found in the normal supine lung, with an overall correlation coefficient (R(2)) of 0.66. There was a tight correlation (R(2) = 0.97) between marker-measured volume changes and sVol. Regional sVol, which involves significantly reduced exposure to radiation and Xe gas compared with the Xe-CT method, represents a safe and efficient surrogate for measuring regional ventilation in experimental studies and patients.

Differences in regional wash-in and wash-out time constants for xenon-CT ventilation studies.

UNLABELLED Xenon-enhanced computed tomography (Xe-CT) has been used to measure regional ventilation by determining the wash-in (WI) and wash-out (WO) rates of stable Xe. We tested the common assumption that WI and WO rates are equal by measuring WO-WI in different anatomic lung regions of six anesthetized, supine sheep scanned using multi-detector-row computed tomography (MDCT). We further investigated the effect of tidal volume, image gating (end-expiratory EE versus end-inspiratory EI), local perfusion, and inspired Xe concentration on this phenomenon. RESULTS WO time constant was greater than WI in all lung regions, with the greatest differences observed in dependent base regions. WO-WI time constant difference was greater during EE imaging, smaller tidal volumes, and with higher Xe concentrations. Regional perfusion did not correlate with WI-WO. We conclude that Xe-WI rate can be significantly different from the WO rate, and the data suggest that this effect may be due to a combination of anatomic and fluid mechanical factors such as Rayleigh-Taylor instabilities set up at interfaces between two gases of different densities.

Xenon gas flow patterns evaluated by high-speed multi-row detector CT

Regional lung ventilation can be measured via Xenon-enhanced computed tomography (Xe-CT) by determining washin (WI) and washout (WO) rates of stable Xe. It has been assumed that WI = WO, ignoring Xe solubility in blood and tissue and then other geometric isssues. We test this by measuring WO-WI in lung by Xe-CT. Also, we investigate the effect of tidal volume (TV) and end inspiratory (EI) vs end expiratory (EE) scan gating on WO and WI measurements. 3 anesthetized, supine sheep were scanned using multidetector-row computed tomography (MDCT). Imaging was gated to both EE and EI during a WI (33 breaths) and WO (20 breaths) maneuver using 55% Xe for WI and room air for WO. Time constants (TCs) of Xe WI and WO were obtained by exponential fitting. WO and WI TCs were compared: 1) apex and base 2) dependent, middle, and nondependent 3) EE and EI 4) three TVs. The vertical gradient of WO-WI showed WO > WI in dependent vs non-dependent regions. WO-WI in both dependent and nondependent region at the lung base and apex was larger when measured at EE compared to EI. As TV increases, the global WO-WI difference decreased. TV showed greater influence on WO than WI. Xe WO was longer than WI possibly reflecting Xe solubility in blood and tissue. Higher TVs and gating to EE provided greater effects on WO than WI TCs which may relate to the number of partial volumed conducting airways contributing to the regional voxel-based measures. We conclude that WO mode is more susceptible to errors caused by either xenon solubility or tidal volume than WI mode and EE scanning may more accurately reflect alveolar ventilation.

In vivo micro-CT imaging of the murine lung via a computer controlled intermittent iso-pressure breath hold (IIBH) technique

Micro-CT, a technique for imaging small objects at high resolution using micro focused x-rays, is becoming widely available for small animal imaging. With the growing number of mouse models of pulmonary pathology, there is great interest in following disease progression and evaluating the alteration in longitudinal studies. Along with the high resolution associated with micro CT comes increased scanning times, and hence minimization of motion artifacts is required. We propose a new technique for imaging mouse lungs in vivo by inducing an intermittent iso-pressure breath hold (IIBH) with a fixed level of positive airway pressure during image acquisition, to decrease motion artifacts and increase image resolution and quality. Mechanical ventilation of the respiratory system for such a setup consists of three phases, 1) tidal breathing (hyperventilated), 2) a breath hold during a fixed level of applied positive airway pressure, 3) periodic deep sighs. Image acquisition is triggered over the stable segment of the IIBH period. Comparison of images acquired from the same mouse lung using three imaging techniques (normal breathing / no gating, normal breathing with gating at End Inspiration (EI) and finally the IIBH technique) demonstrated substantial improvements in resolution and quality when using the IIBH gating. Using IIBH triggering the total image acquisition time increased from 15 minutes to 35 minutes, although total x-ray exposure time and hence animal dosage remains the same. This technique is an important step in providing high quality lung imaging of the mouse in vivo, and will provide a good foundation for future longitudinal studies.