The Role of Medical Imaging in Alpha-1 Antitrypsin Deficiency

It is difficult for modern physicians to imagine medicine without the convenience of medical imaging. When I worked as a junior doctor in Borneo, the older doctors were clearly much better at bedside diagnoses than us younger ones. What could be the reason for this? One possible explanation was the relative scarcity of imaging modalities in the hospital decades earlier; now, with medical imaging codified in the diagnostic protocols of many diseases, imaging isn’t just a luxury—it is oftentimes a legal necessity. 

Today, researchers and radiologists alike are hungrier for better and better imaging technologies, something that can be abundantly observed at medical radiology conferences. With newer technologies allowing us to view the human body like never before, the time may soon come when traditional imaging modalities like X-rays are viewed as antiquated and inadequate. 

However, before we get too far ahead of ourselves, it is important to recognize that even the existing medical imaging techniques that we have are not fully utilized in the diagnosis and the monitoring of all diseases. Researchers from the Duke University School of Medicine in Durham, North Carolina compiled a list of common imaging features in alpha-1 antitrypsin deficiency (AATD) that they believe can provide a vital window into the disease. It is their study, as published in Therapeutic Advances in Chronic Disease, that we will discuss in this article. 

Computed Tomography Lung Imaging  

In AATD, computed tomography (CT) imaging is recommended for newly diagnosed patients with clinical features of chronic obstructive pulmonary disorder (COPD) and/or impaired lung function. This aims to establish the baseline presentation of the disease. High-resolution CT (HRCT) is recommended for this purpose so that the distribution of emphysema and bullae can be clearly visualized. This is important because emphysema morphology often guides clinical decision-making on whether to initiate pharmacological treatment and whether surgical intervention is appropriate.

Through the use of HRCT, panlobular emphysema is visualized as the expansion of air spaces uniformly from the bronchioles to the alveoli. In advanced emphysema, the lumens around the alveoli are only slightly enlarged when compared to normal alveoli. This is difficult to discern on normal CT scans. 

Read more about AATD etiology

HRCT has been recognized as being particularly useful in AATD because it is excellent for tracking disease progression. The authors of the study wrote, “Specifically, the degree of HRCT scan abnormality has been shown to be significantly correlated with forced expiratory volume in 1s (FEV₁), specific airway conductance, residual volume/total lung capacity, and transfer factor of the lung for carbon monoxide.” They added that it is also correlated with “patient health status as assessed by the St. George’s Respiratory Questionnaire and the Short-Form health survey.”

To reduce the impact of reader inaccuracy in determining disease severity, quantitative CT methods have been proposed. This relies on software that can automatically recognize and characterize lung contours and produce histograms of lung attenuation values. This allows physicians to more accurately differentiate the nuanced presentation of emphysematous lung tissue from nonemphysematous tissue, thus improving their ability to determine the severity and distribution of emphysema in patients with AATD.

Magnetic Resonance Imaging in the Lungs 

Another imaging modality that is readily available in most hospitals is magnetic resonance imaging (MRI). However, it is rarely used for lung imaging due to the high proportion of air, and therefore low levels of hydrogen, in the lungs. However, inhaled hyperpolarized contrast agents, such as helium and xenon, have been suggested as a solution to this problem, allowing regional lung function to be revealed without any background signal. 

MRI lung imaging has gained interest over the years due to the abilities of helium and xenon to report on important parameters of lung function. For example, they can reveal ventilation and apparent diffusion coefficients (ADC), which is an established marker for alveolar structure and thus allows physicians to track emphysema progression. Additionally, we must not forget that MRI does not utilize ionizing radiation, which is an important benefit in itself. 

Research examining the use of MRI in tracking emphysema progression is still in its infancy, but existing studies provide reasons to be encouraged. A Danish study using ³He MRI to track emphysema progression reported a significant correlation between time trends in diffusing capacity of the lungs for carbon monoxide (DLco) and MRI ADC. Another Canadian study showed that ³He MRI parameters revealed significant differences between AATD and non-AATD COPD patients in terms of ventilation and ADC, indicating greater parenchymal destruction in the basal regions of the lungs in AATD patients with COPD. Other parameters such as CT lung area and DLco failed to do so.

Read more about AATD epidemiology

Other studies looked into the usefulness of ¹²⁹Xe MRI in displaying early signs of lung disease in patients who had the PI*MZ AATD genotype. The initial results were promising: ¹²⁹Xe MRI displayed regional abnormalities that were not detectable by CT in 4 PI*MZ individuals with normal pulmonary function tests. Clinical trials are now being conducted to evaluate the efficacy of ¹²⁹Xe MRI to similarly reveal lung disease in asthma, cystic fibrosis, and COPD. 

Potential of CT and MRI in Lung Diseases

This study showcased the huge potential of CT and MRI in diagnosing and tracking the progression of lung diseases like AATD. Although not curative in themselves, they can provide physicians with formidable tools in shaping sound clinical decision-making. Will lung imaging technologies continue to advance in a way that reveals greater lung information while keeping costs low? Only time will tell. 

References

Huang YCT, Wencker M, Driehuys B. Imaging in alpha-1 antitrypsin deficiency: a window into the disease. Ther Adv Chronic Dis. 2021;12_suppl:20406223211024523. doi:10.1177/20406223211024523

Friedman PJ. Imaging studies in emphysema. Proc Am Thorac Soc. 2008;5(4):494-500. doi:10.1513/pats.200708-128ET