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1 Department of Radiology, Columbus Children's Hospital, Ohio State University, Columbus, Ohio
Correspondence and requests for reprints should be addressed to Frederick R. Long, M.D., Columbus Children's Hospital, A-1010, Department of Radiology, 700 Children's Drive, Columbus, OH 43205–2696. E-mail: flong{at}chi.osu.edu
ABSTRACT
A standard technique that controls for respiratory motion and lung volumes during imaging is necessary if high-resolution computed tomography is to be used as an outcome measure in children with cystic fibrosis. End-inspiratory and expiratory imaging allows for the detection and differentiation of early lung disease. In children ages 0–5 years, a noninvasive controlled ventilation technique is ideal, and can be used in combination with raised-volume infant pulmonary function tests. In older children, a spirometric-assisted or spirometric-triggered technique should be used. With optimal technique, radiation dose settings (kVp and mA) can be lowered to achieve a diagnostic screening high-resolution computed tomography of the lungs at a dose equivalent to that of the chest radiograph.
Key Words: computed tomography, infants and children • computed tomography, radiation dose • lung, high-resolution computed tomography • positive-pressure ventilation, methods
If the promise of high-resolution computed tomography (HRCT) is to be realized to detect early cystic fibrosis (CF) disease, monitor response to treatment, and serve as a sensitive outcome measure in drug trials, images that are of high quality need to be obtained in a standardized, reproducible manner. In addition to optimizing well-known technical factors important in obtaining a high-resolution image, such as thin-slice thickness, small field of view, and the use of a high-frequency reconstruction algorithm (1), HRCT imaging should also be performed without respiratory motion and at full lung inflation. The major challenge in performing pediatric HRCT is the fact that most children between 0 and 5 years of age cannot cooperate with end-inspiratory breath-hold maneuvers, and children ages 6–13 years may have some difficulty with these maneuvers.
The deleterious effects of performing HRCT imaging without respiratory and volume control to diagnose bronchiectasis and air trapping (AT) in children with CF have been documented. In a study of four anatomic locations in the lungs of 16 sedated young children with CF (2), bronchiectasis was identified on 30% of the HRCT images obtained at end inspiration compared with 6% of images obtained during quiet breathing (p = 0.044). AT was seen in 45% of the images obtained at end expiration without respiratory motion compared with 19% of the images obtained during quiet breathing (p = 0.012). No significant effect was shown for the diagnosis of bronchial wall thickening, which is believed to have been due to high interobserver variability.
The results of this study (2) highlight the importance of end-inspiratory imaging in the evaluation of bronchiectasis, which is an important imaging end point in CF lung disease. Bronchiectasis is not uncommon in young children with CF, and was found in 10–20% of airways measured in a cross-sectional study of children with CF ages 0–5 years (3). In some instances, the involved bronchi are dilated due to abnormal compliance resulting from lost structural integrity, which is believed to be secondary to digestion of elastin in the airway wall in the setting of chronic inflammation. These abnormally compliant bronchi are revealed at full lung inflation and disappear on images obtained at low lung volumes, such as during quiet breathing. Lung volumes more than double between end inspiration at or near total lung capacity compared with tidal lung volumes during quiet breathing, which are near FRC. Thus, this early bronchiectasis, which appears to be progressive (3), differs from the commonly understood definition of bronchiectasis seen in adults, in which the bronchi are fixed and irreversibly dilated. In addition, because early bronchiectatic airways in children may collapse at lower lung volumes, these airways may be misinterpreted as having wall thickening or mucus plugging on images obtained during quiet breathing (Figure 1).
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Technique is also important in identifying AT, which is another important sign of airways disease that can be identified with great sensitivity by HRCT (6). AT is associated with thickening and narrowing of the airways, resulting in diminished airflow. AT may be the earliest indicator of disease in infants when caused by disease in the peripheral airways that are below the resolution power of CT (7). On HRCT, AT is usually recognized on the basis of finding areas of abnormally low lung attenuation relative to adjacent normal lung on expiratory images. In some instances, AT can be seen on inspiratory images, but it is not as clearly seen. The pattern of AT detected by HRCT in any given patient will differ depending on the rate of change of lung volumes and the depth of expiration at the time of imaging (8, 9). In addition, respiratory motion can obscure the identification of AT on CT (2). Imaging as soon as the lungs reach resting end exhalation (near FRC) appears to be adequate and sensitive to detecting AT (2).
AT may be assessed visually or quantified from HRCT images using lung density analysis (9). It is unclear which method is more accurate or sensitive, but quantitative methods have inherent potential advantages. In children, lung density analysis is complicated by the fact that the measurements are hard to standardize and the values change with lung growth and development. Little is known about how density changes with growth, but some normative data exist (10). To try to circumvent this problem, Goris and colleagues (11) developed a computer-assisted histogram analysis method of measuring AT from expiratory images using inspiratory lung density as an internal control.
There are a number of options available for achieving respiratory and volume control in children for HRCT scanning. General anesthesia with endotracheal intubation has been the traditional method, and is effective but not without significant risk and expense, making it impractical to use for routine HRCT follow-up of CF lung disease. A noninvasive method has been developed, called controlled ventilation (CV)-CT, which does not require endotracheal intubation for accomplishing motionless imaging at end-inspiratory and end-expiratory lung volumes (12–14). This technique involves hyperventilation to induce a physiologic respiratory pause. Transient apnea is produced by driving down the CO2 concentration in the blood by giving a short series of augmented breaths using positive pressure applied via a facemask. At our institution, facemask ventilation is performed by trained respiratory therapists. During the apneic period, the lungs can be imaged at full inflation by maintaining positive facemask pressure at 25–30 cm water pressure, or the lungs can be imaged at resting end exhalation by applying no mask pressure. The technique does require deep conscious sedation, and thus must be done by personnel experienced in both pediatric sedation and ventilation. This does not necessarily mandate, however, that an anesthesiologist is required.
The necessary sedation for CV-CT can be achieved a number of ways using agents employed at children's hospitals for the purpose of performing CT and magnetic resonance imaging studies without motion artifacts. At our institution, we have used oral chloral hydrate or intravenous pentobarbital given by sedation nurses under physician supervision, according to our institutional conscious sedation protocols, which follow the American Academy of Pediatrics guidelines (15). Both chloral hydrate and pentobarbital used for this purpose have good safety profiles (16). At our institution, hundreds of CV-HRCT exams have been performed in children with CF without complication, which reflects, in part, the overall good baseline health status of these patients.
An advantage of CV-HRCT is that it can be combined with raised-volume infant pulmonary function tests (PFTs) that use a similar technique (17). Raised-volume infant PFTs are already routinely performed at a number of Cystic Fibrosis Foundation Therapeutic Development Network (CFF TDN) sites where the necessary equipment has been installed and personnel trained. Although both the CT and PFT exams require sedation, both studies can be completed consecutively under a single sedation in over 90% of cases (13). The resulting structural and functional information is complementary and of the highest quality.
Another option to consider, particularly if only an HRCT is needed, is anesthesia support using a short-acting anesthesic without endotracheal intubation. Such short-acting drugs include sevoflurane (18), in which sedation is maintained only during the time necessary to complete the CT study. While the child is sedated, the examination can be performed in a similar manner to CV by ventilating with positive pressure via a facemask.
In children who are at least 6 years old and who can breath hold, there is value in performing the CT with spirometric control to ensure that lung volumes can be reproducibly obtained (19). As a general rule, a study in which the child is just sent to the radiology department for the inspiratory and expiratory HRCT is often unsatisfactory because the degree of variability in actual volumes obtained when the child is told to "take in a big breath and hold it" or "blow your breath all the way out and hold it." Because children with CF are accustomed to using a spirometer, they are ideal candidates for spirometric control. This control is accomplished by training the child to use the spirometer to attain true full inflation and end exhalation prior to scanning, and then using the spirometer during the study to trigger the scan acquisition (19) or document the actual volumes imaged during the scan.
As any CT protocol developed will involve frequent CT scans, in the population of patients with CF, the issue of limiting the overall cumulative dose is significant (20, 21). The lowest doses reasonably achievable for identification of airways disease on HRCT, adjusted for size of the patient, are still to be worked out; however, preliminary work has provided general guidelines on how dose can be minimized to acceptable levels by taking advantage of the inherent high contrast of lung structures and the small body mass of children (22).
The factors that determine the dose received by the patient from a CT study are the kilovolt potential (kVp), tube current expressed in milliamps, and the length of time the patient is exposed to the X-ray beam. The length of time is affected by the rotation speed of the gantry, and the pitch (23). Another factor is the brand of the CT scanner, as different manufacturers filter the X-ray beam differently; of these factors, the kVp exerts the greatest effect. Not long ago, the typical setting for lung imaging in children was 120 kVp, which provided good penetration of the chest wall to image lungs with a uniform exposure. However, studies indicate that the kVp can be lowered in children, who have thinner chest walls (22). In fact, a kVp as low as 80 is feasible to diagnose airways disease in children. At 80 kVp, there may be some streak artifact at the edges or periphery of the lungs, especially in the upper lobes due to the shoulders (24). This streak artifact does not appear to impact significantly on the diagnostic quality of the study unless the arms are not kept over the head during scanning, in which case there will be major streak artifacts obscuring the apices of the lungs. At 80 kVp in infants, an effective amperage of at least 15 mA is needed using a 0.4 s rotation speed (Figure 2). One can adjust for increasing size of the child by raising the amperage (Figure 3). Note that, at these low-dose settings, differentiation of the soft tissues in the mediastinum is poor. The effective dose to an infant whose chest is scanned helically, using a 64-slice MDCT scanner (GE Volume CT; General Electric Medical Systems, Milwaukee, WI) at 80 kVp, 40 mA, gantry rotation of 0.5 seconds, and a pitch of 1.35 (effective mAs = 15), is estimated to be 0.22 milli-Sieverts (mSv) using the IMPACT dose calculator (London, U.K., www.impactscan.org). This compares favorably to natural background radiation for a year, which is estimated to be 3 mSv.
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From such a dataset, novel quantitative measures to assess airways disease may be developed or discovered, allowing much easier matching of airways on follow-up examinations—a task that is almost impossible when incremental scanning is performed. Such a dataset is also easier to score by a reader who is then able to follow the course of each individual bronchus. Although quantitative analysis of the lungs is not currently performed routinely on a clinical basis, it has special potential in the detection of early disease (e.g., bronchial wall thickening). The development of quantitative methods should augment the value of CT in CF. Visual scoring, no matter what system is used, is time consuming, and is limited by the number of expert observers available.
It is unclear whether there will be a conflict between doses needed for visual versus quantitative interpretation, as these questions are still to be investigated. For example, to what extent is lung segmentation dose dependent? It is clear that dose will affect lung density measurements that could alter the results of using an automated, computer-assisted AT analysis program.
A few other technical factors should be mentioned. If using a multidetector CT scanner, it is important to reconstruct, on the day of imaging, all of the data at the thinnest possible slice thickness in both bone and soft tissue algorithm to avoid a subsequent loss of data. Some imaging data are lost when archived. It is important to reconstruct the data in both a high-frequency algorithm for lung detail and in the standard algorithm for potential three-dimensional reconstructions. There may be more than one type of high-frequency reconstruction algorithm provided by the CT vendor. Some reconstruction algorithms may be higher frequency than desired, degrading image quality. Greater resolution on CT can be gained by retrospectively retargeting to a smaller field of view. In general, this is not necessary for visual scoring, but could be important when performing quantitative measures. Finally, the window width and level used needs to be optimized for greatest accuracy of quantitative measurements. Typically, a window width of –1,500 and level of –450 Hounsfield units is optimal for lung structure measurements (23, 26).
In conclusion, this article highlights the importance of control of respiratory motion and lung volumes for HRCT imaging of CF lung disease, and discusses methods for achieving that control. A low-dose protocol using 80 kVp for pediatric HRCT lung imaging is described, as well as technical considerations for performing quantitative CT analysis.
FOOTNOTES
Conflict of Interest Statement: F.R.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
(Received in original form November 22, 2006; accepted in final form March 27, 2007)
REFERENCES
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  P. A. de Jong, H. A. Tiddens, M. H. Lequin, T. E. Robinson, A. S. Brody, J. Donadieu, R. Chiron, and C. Maccia Substantial differences in percentage of predicted FEV. Chest, May 1, 2008; 133(5): 1289 - 1289. [Full Text] [PDF]
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