Ventilation Perfusion imaging assessing lung physiology is one of the earliest clinical applications in Nuclear Medicine, only predated by thyroid scanning as a procedure in the specialty. The earliest documented measurements of regional pulmonary perfusion using radioactive tracers were conducted by Dr. John West and his colleagues in the UK in 1961. They utilized radioactive tracers to assess gravitational differences in pulmonary blood flow, marking a significant advancement in understanding lung physiology. Building upon these foundational studies, Dr. George Taplin’s group at UCLA made a pivotal contribution in 1963 by introducing the use of iodine-131-labeled macroaggregated albumin (¹³¹I-MAA) for perfusion lung scanning. This innovation significantly enhanced the diagnosis of pulmonary embolism and facilitated more detailed studies of regional lung function. See Figure 1
21ST CENTURY LUNG SCANS: WHAT’S OLD IS NEW AGAIN!
Dr. Andrew Ross,Past President,The Canadian Association of Nuclear Medicine Professor at Dalhousie University
Ventilation Perfusion imaging assessing lung physiology is one of the earliest clinical applications in Nuclear Medicine, only predated by thyroid scanning as a procedure in the specialty. The earliest documented measurements of regional pulmonary perfusion using radioactive tracers were conducted by Dr. John West and his colleagues in the UK in 1961. They utilized radioactive tracers to assess gravitational differences in pulmonary blood flow, marking a significant advancement in understanding lung physiology. Building upon these foundational studies, Dr. George Taplin’s group at UCLA made a pivotal contribution in 1963 by introducing the use of iodine-131-labeled macroaggregated albumin (¹³¹I-MAA) for perfusion lung scanning. This innovation significantly enhanced the diagnosis of pulmonary embolism and facilitated more detailed studies of regional lung function. See Figure 1
Assessment of ventilation closely followed with Taplin introducing xenon-133 (¹³³Xe). They first presented their research in Canada. “Colloidal Radioalbumin Aggregates for Organ Scanning” (Authors: G.V. Taplin, E.K. Dore, D.E. Johnson, H. Kaplan) was presented at the 10th Annual Meeting of the Society of Nuclear Medicine in Montreal in 1963.
Combination imaging of ventilation and perfusion followed and with the development of the new efficient anger camera technology, expanded use of VQ scanning with it becoming the standard of practice for evaluation of pulmonary embolism. At this time, the only other imaging method for embolism detection was direct visualization with angiography which was expensive and invasive.
The development of the Molybdenum generator for Nuclear Medicine departments led to the incorporation of Technetium-99M based tracers. In the late 1960s, â¹â¹áµTc MAA was developed and quickly replaced the iodine-based product which had worse imaging characteristics as well as higher radiation dose to the patient. The development of Technetium-99M aerosols occurred in the late 1970’s and saw increased use thereafter although Xenon remained as an agent even until today.
Despite all these advances, the major limitation of VQ scanning was it’s indirect assessment of the lung parenchyma and resultant issues with specificity. As well, it’s nonstandard reporting led to concerns regarding reproducibility. Efforts to address these issues continued and culminated in the publication of the PIOPED criteria in 1990. Although addressing standardization, there were issues with this study, most significantly a high rate of inconclusive studies (up to 40%). As well, the utilization of probability based reporting, although scientifically sound, was an area of clinical frustration with the test. Concurrently, the fast evolution of helical CT scanning and its incorporation into evaluation of pulmonary imaging was occurring. The issues of a difficult to understand and somewhat nebulous system of reporting based on probability versus the CT direct visualization of clot and binary reporting of either embolism positive or negative led to the decline of VQ scanning in this clinical scenario.
However, even with these issues, there was still clinical use in situations such as patients with CT availability, contrast allergy or renal impairment which negated the ability to use CT scanning. Further, increasing concern about radiation exposure with the wide proliferation of CT technology led to further development of lung scanning. VQ scanning was shown to have significantly lower doses particularly to the female breast and thyroid.
Through the 1990s, further advances were occurring for ventilation perfusion imaging. Most significantly was the adoption of SPECT aquisition. This method provided 3D visualization which demonstrated a significant improvement in terms of diagnostic accuracy of lung scanning. Overall, clinical validity was demonstrated to equal CTPE. This was cemented in guidelines adopted by the EANM in 2007 with SPECT as the standard for this procedure. Furthermore, these guidelines provided a binary system of reporting with either “pulmonary embolism present” or “pulmonary embolism absent” doing away with the probabilistic system. This dramatically reduced the number of indeterminant scans to a level on par with CT.
As well during this period, advances occurred in ventilation imaging agents. While xenon 133 was effective it had drawbacks including high radiation dose and contamination. Another radioactive gas, Krypton 81, with better imaging characteristics and dose, developed in the UK had seen some use over the decades although was limited because of availability and cost. Although these gases possess theoretical advantages of ideal physiologic behaviour, they are dynamic with changing distribution over time within the lungs which negates the ability to perform SPECT. Utilization of nebulizers with technetium agents partially addressed these problems; however, administration of such was time consuming and led to potential contamination and other technical issues. Moreover, in patients with breathing difficulties, the agent provided less than ideal images and in many such patients, SPECT imaging was technically suboptimal.
These limitations were overcome by the development and marketing of another technetium based ventilation agent called Technegas in Australia in the 90’s. This involves superheating (1500°C) a droplet of technetium in a small carbon cup in pure argon environment. The result is a technetium based “pseudo gas” which can be administered to patients in 3–5 breaths and provides very high quality stable imaging. The agent allowed for SPECT imaging in virtually all patients. The EANM guidelines adopted it as the ventilation agent of choice (if Krypton was unavailable) and was further endorsed by the Canadian Association of Nuclear Medicine guidelines in 2018 as the imaging agent of choice.
These 21st century technological adoptions cemented ventilation perfusion imaging as an imaging technique comparable to CT for pulmonary embolism evaluation but more significantly providing robust physiologic assessment of the lungs. The imaging technical advancement of full ring digital gamma imaging systems provides even more opportunity in terms of faster image exams and integration of new analysis software with the incorporation of artificial intelligence.
These factors have led to a resurgence of investigation and articles assessing ventilation perfusions imaging. Our center has been investigating ventilation perfusion imaging utilizing Technegas in patients who have undergone lung and stem cell transplants. This group is prone to significant pulmonary complications including Bronchiolitis Obliterans Syndrome. The current clinical evaluation assessing for this are pulmonary function tests which are insensitive until the later stages of the process which delays the institution of therapy. Utilizing data from the VQ SPECT/CT with Technegas and software which provided measures of ventilation distribution and changes over time, patients developing the complication demonstrate deterioration with increasing degrees of heterogeneity of ventilation which was more sensitive than PFTs. (Figure 2)
Others have investigated similar protocols in common pathologies such as COPD and asthma. These patterns of changes of ventilation as well have shown the ability to better predict lung status than current evaluation methods such as pulmonary function tests. With this data, follow up VQ studies show potential to provide more sensitive and clinically important information about response to treatment.
So, as the specialty of Nuclear Medicine has seen a 21st century renaissance along with it has come one of its oldest studies. Fueled by technical innovation including SPECT, digital detectors, software and newer ventilation agents, it is being utililized in old and new indications.
