Using Electron Bean Computed Tomography (EBCT) to Assess Pulmonary Function in Patients with Cystic Fibrosis

Terry Robinson, M.D.

Spring 1997

High Resolution Computed Tomography (HRCT) and ultrafast Electron Beam Computed Tomography (EBCT) imaging of the chest show considerable promise for delineating early changes (damage) in the CF airway and the ability to assess the spectrum of CF pulmonary disease. HRCT scoring systems for CF lung disease, a relatively new assessment method, are able to detect reversible and irreversible components of CF lung disease.1-5 These scoring systems have demonstrated significant correlation with routine pulmonary function measurements,2-6 and have demonstrated greater sensitivity in disease progression than clinical scores or regular chest X-ray scores in 30 CF patients who were followed for an average of 30 months. 4,6 However, HRCT has critical limitations: the need for cooperation or sedation in younger patients to minimize motion artifacts, the level of radiation exposure, inability to standardize images according to respiratory cycle (lung volume), and relatively high cost. Consequently, HRCT has not become a widely used assessment measure. But with the advent of new therapies aimed at the young CF patient, there is an obvious need for noninvasive, reproducible, and objective outcome measures in CF that is more acute than ever.

EBCT, a new, ultrafast imaging system, was initiated at Lucile Salter Packard Children's Hospital at Stanford, California, in May 1996. Much interest in the EBCT has focused on its novel capabilities as a noninvasive method to assess coronary artery disease. However, EBCT also allows easier viewing of the chest in children than conventional CT scanners. While the images are at least as accurate, the EBCT is ten-fold faster, alleviating the need for sedation, and reducing the X-ray dose per image. Additionally, by utilizing a system that triggers the EBCT scanner at specific breath levels7, reproducible CT images of the chest can be assured for serial evaluations. By developing a CF CT scoring system, which will incorporate CT images taken at known points in the breathing cycle and lung function "markers," we hope to detect initial signs of disease progression, to identify regional changes and distribution of airway disease, and to differentiate transient from irreversible airway and lung tissue changes. In fact, initial pilot studies using inspiratory/expiratory imaging on the EBCT scanner on our CF patients with mild pulmonary disease have demonstrated increased detection of airway abnormalities which could not be detected by standard chest X-ray and pulmonary function measures routinely used to assess CF patients.

In preparation for our EBCT pulmonary function assessment study, we have completed a pilot study in patients with severe CF pulmonary disease to establish and validate a new CF chest CT scoring system which evaluates both reversible and irreversible components of CF lung disease. We will use this scoring system to follow CF patients during short- term interventions for pulmonary exacerbations, comparing EBCT scores with conventional clinical pulmonary function measurement techniques (including lung function tests), as well as measuring changes in scores before and after treatments. This knowledge will allow, we hope, use of EBCT as an objective noninvasive outcome measure for interventions in children and adults with CF.

While EBCT scanning will likely improve diagnostic sensitivity in patients with cystic fibrosis, there are still limitations that need to be addressed before EBCT scanning can provide a more comprehensive evaluation of the course of CF pulmonary disease in children and adults. Ensuring reproducible CT imaging is essential for evaluating the course of CF lung disease over time. The amount of air in the lungs (lung volume) directly affects characteristics of CT lung imaging. It is necessary, therefore, to establish consistent lung volumes when EBCT scans are obtained. To assure that CT images are reproducible, a system which triggers CT scanning at specific lung volumes is essential.7 In this project such a system will be incorporated, which will allow us to obtain reproducible imaging at designated lung volumes.

This project encompasses three phases of development. In the first phase we will recruit 20 CF patients, older children, adolescents, and young adults, who have mild to severe pulmonary disease and are having a pulmonary exacerbation, to validate our EBCT CF radiological scoring system. Each patient will have two EBCT scans 14 days apart.

In the second phase of this project we hope to incorporate the EBCT scoring system in children with CF less than six years of age, with development of respiratory- gated EBCT scans in infants with CF, incorporating present infant pulmonary function technology. In phase 3, we hope to apply our EBCT scoring system as a primary outcome measure for therapeutic trials (for example, gene therapy).

There are currently 36 ultrafast EBCT scanners manufactured by Imatron, Inc., in the United States with four new sites in development. In addition, most current conventional CT scanners have the capability of high resolution CT imaging. We anticipate that respiratory CT imaging incorporating our CF CT scanning system will be applicable for both EBCT and HRCT scoring techniques. This study, funded by CFRI, should take approximately six months before useful results are obtained and made available. Once available, this assessment technique should prove invaluable for any CF patient or physician whose treatment center has access to either ultrafast or HRCT imaging.

References:

  1. Nathanson, I., et al.Pediatric Pulmonology., 1991;11:81-86.
  2. Bhalla, M., et al. Radiology, 1991;179:783-788.
  3. Sexaeur. W., et al.American Journal of Respiratory and Critical Care Medicine, 1995;151:A739.
  4. Logan, P.M., et al. IJMS 1996;165(1):27-31.
  5. Maffessanti, M., et al. Journal of Thorasic Imaging, 1996;11(1):27-38.
  6. Sexaeur, W.P., Shah, R., New Insight into Cystic Fibrosis, 1996;4(4):7-11.
  7. Kalender, W.A., et al. Radiology, 1990;175:265-268.

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