How Artificial Intelligence is shaping the future of low-dose CT.

- Obtaining high-precision, high-quality images while minimizing exposure dose -
When performing CT examinations, it has always been a challenge to maximize diagnostic accuracy by obtaining high-precision images while minimizing the effects of radiation exposure. With this in mind, Professor Kazuo Awai of Hiroshima University and Mr. Toshio Takiguchi of Canon Medical Systems spent some time discussing the risks of radiation exposure, as well as the effectiveness of lung cancer screening using low-dose CT and the future of low-dose CT systems.

Reducing exposure dose for all patients by including AIDR 3D in every CT system

Mr. Takiguchi : It is said that more CT examinations are performed per capita in Japan than in any other country. According to a government survey on social healthcare services, the number of CT examinations conducted has increased over the past 20 years, and is estimated to reach 30 million examinations per year.1) What are your thoughts on this?
Prof. Awai : The fact that CT examinations are widely available reflects the high level of healthcare services in Japan, and it is certainly not a bad thing that a large number of patients can access CT examinations. However, it is important to focus on whether these examinations are performed appropriately. For example, an examination request that specifies a scan range from the neck to the pelvis would be considered inappropriate for a patient when only a lung exam is necessary. A committee for the appropriate use of imaging systems within the Japanese Radiological Society has started discussions on the appropriate use of CT examinations and guidelines will be issued in the near future. In addition, from April 2020, as a result of the partial revision of the Ordinance for Enforcement of the Healthcare Act, it is now mandatory to provide patients a clear explanation regarding the need for CT examinations as well as to manage and record the exposure dose . These new guidelines should lead to the optimized and validated use of CT examinations.2)
Mr. Takiguchi : Approximately 14,000 CT systems are currently in operation in Japan, with about half of them manufactured by Canon Medical. In most of these systems, CT image reconstruction technology incorporating the iterative reconstruction method, AIDR 3D, is installed. By advocating the widespread use of this technology, we feel that we can help to reduce the exposure dose in CT examinations.

Lung cancer screening with low-dose CT

Mr. Takiguchi : I have heard that the use of low-dose CT in lung cancer screening is gradually expanding in Japan.
Prof. Awai : In 2011, the National Lung Screening Trial was conducted in the United States, involving approximately 53,000 participants found to be at high risk of developing lung cancer. The study participants were divided into two groups: a group examined by low-dose CT scanning and a group examined by chest radiography. The participants in both groups were screened annually over a period of 3 years. The study showed a 20% reduction in lung cancer mortality in the group who were screened with low-dose CT scanners, as compared to the group screened by chest radiography.3) Following the publication of this report, using low-dose CT scanning for lung cancer screening started to be adopted worldwide.

Mr. Takiguchi : Professor Awai, you were involved in a study in which the citizens of Miyoshi City, Hiroshima participated. That study also demonstrated the usefulness of low-dose CT scanning for lung cancer screening.4)
Prof. Awai : In January 2015, Miyoshi City began to offer lung cancer screening using low-dose CT scanning at Miyoshi Central Hospital. We have been involved in this project from the initial stages, providing technical and medical support. The project focused on screening heavy smokers between 50 and 75 years old living in Miyoshi City. Approximately 1200 lung cancer screening tests, using CT, are performed each year, and 27 cases of lung cancer have been found over a 5-year period. The CT system employed in the first year of this project was a 320-slice area-detector CT system incorporating AIDR 3D from Canon Medical Systems Corporation. In participants who gave their informed consent, we performed an ultra-low-dose CT scan (0.15 mSv) in addition to a standard low-dose screening CT scan (1.5 mSv) in order to allow the diagnostic capabilities of these two scanning methods to be directly compared.5) Standard low-dose CT scans were reconstructed with the traditional back projection (FBP) method, while ultra-low-dose CT scans were reconstructed with forward projected model-based Iterative Reconstruction Solutions, abbreviated to FIRST on Canon CT scanners. The results of the study have clearly demonstrated the usefulness of ultra-low-dose CT scanning for lung cancer screening. I expect that by 2025, the lung cancer mortality rate in Miyoshi City will fall due to the early detection and early treatment made possible by lung cancer screening using CT.

Mr. Takiguchi : In conventional helical multi-slice CT the time to perform the lung scan is 20 seconds. With a 320-slice area-detector CT, which was introduced in 2007, the width of the detector is expanded to 16 cm, allowing the scan time to be significantly reduced. The development of the 320-slice area-detector CT focused on reducing both the scan time and radiation dose.
Prof. Awai : It is thanks to Canon Medical Systems' image reconstruction technology that Miyoshi City has been able to gain the acceptance of its citizens, allowing the city to offer lung cancer screening using low-dose CT. Also, in Europe, the NELSON Trial, a large-scale randomized controlled trial of lung cancer screening using CT, has shown a 24% reduction in lung cancer mortality in the male population.6) The amount of scientific evidence demonstrating the usefulness of CT screening for the early detection of lung cancer is steadily increasing. However, the possibility that annual CT screening may actually induce lung cancer must also be considered. It is therefore essential to minimize the exposure dose while maintaining a high level of diagnostic performance.

Epidemiological and biological research on the risks of radiation exposure

Mr. Takiguchi : Do adult patients and pediatric patients differ with regard to radiation exposure risks in CT examinations?
Prof. Awai : It is very difficult to perform epidemiological studies on radiation exposure. For example, to investigate the effects of a 50-mGy dose, it would be necessary to conduct a long-term follow-up study with a population of approximately 80,000 people. And for a 25-mGy dose, a population study of approximately 320,000 people would be needed.7) For this reason, it is almost impossible to find any report on this topic. However, in 2012, the world was stunned when the results of a study involving a 23-year follow-up of approximately 180,000 pediatric and young adult cases were presented.8) The study showed that the risk of developing leukemia or brain tumors was slightly increased in pediatric patients who underwent CT scanning. The study was critically analyzed and carefully reviewed from various standpoints, including the validity of subject selection in the study as well as the interpretation of the data. The repeat analysis of the data still supported the findings of that study.9) Although the validity of the study has been analyzed in many subsequent studies, with some supporting the findings and others not supporting the findings, a large number of recent analyses appear to validate the study findings. To my knowledge, there have not been such epidemiological studies involving adults since.

Mr. Takiguchi : Lately, DNA damage associated with radiation exposure has been the focus of such studies.
Prof. Awai : In cooperation with Professor Satoshi Tashiro at the Research Institute for Radiation Biology and Medicine of Hiroshima University, we are currently conducting a study to investigate damage to lymphocytes by obtaining data before and after CT scanning. Radiation exposure has a variety of effects on DNA. The most severe effect is a double-stranded DNA break. When a double-stranded DNA break occurs, a histone protein called γH2AX is released, so we employed γH2AX as a biomarker for assessing DNA damage. The results of an in-vitro study showed that some DNA damage induced by CT scanning is repaired within a few days.10) However, during the repair process, errors such as gene translocations or the formation of dicentric chromosomes may occur. The accumulation of such errors due to multiple damage-inducing events may lead to the development of cancer.

Mr. Takiguchi : Does the degree of damage correspond to the intensity of radiation?
Prof. Awai : The findings of the in-vitro study showed a direct relationship between the exposure dose in CT scanning and the amount of γH2AX released.10) Therefore, our research team decided to investigate the differences in the rates of double-stranded DNA breaks and chromosomal abnormalities between low-dose scanning and standard-dose scanning. This study included patients who were referred to the department of thoracic surgery at our hospital and gave informed consent to participate. The patients were divided into two groups, and CT scanning was performed. The results for low-dose CT did not show any effects on the DNA, but the results for standard-dose CT showed that the rates of double-stranded DNA breaks and chromosomal abnormalities were increased.11) The median exposure dose for low-dose CT was 1.5 mSv, while that for standard-dose CT was 5.0 mSv. This suggests that the effects of radiation on DNA and chromosomes would be minimized if the exposure dose for standard-dose CT could be reduced to 1.5 mSv. Therefore, in the future, we look forward to CT systems being developed that can provide high-precision images at an exposure dose as low as 1.5 mSv.
Mr. Takiguchi : We still have a long way to go before we can perform all CT examinations at an exposure dose of 1.5 mSv, but this information provides us with a clear development goal.

Application of groundbreaking deep learning reconstruction - AiCE

Prof. Awai : There has been remarkable technological progress in CT in recent years, but in CT scanning it is inevitable that employing a lower exposure dose will result in higher noise levels and some degradation of image quality. To address this issue, Canon Medical Systems has developed AIDR 3D, which is based on the iterative reconstruction method. This has led to dramatic improvements in image quality at low doses.
Mr. Takiguchi : In parallel with the technological improvements in the hardware, such as the detector material and the data acquisition system (DAS), the software technologies used for reconstructing the acquired images have also been remarkably improved. Our company initially aimed to achieve the goal of halving the exposure dose. That resulted in our decision to install AIDR 3D in all our CT systems as part of the standard configuration, rather than as an extra-cost option. We have installed AIDR 3D in every single CT system currently in operation at all customer sites throughout Japan.
Prof. Awai : In 2015, the practical application of the model-based iterative reconstruction method known as FIRST was started. FIRST is an advanced image reconstruction method that provides high resolution, while dramatically reducing noise. As a result, image accuracy is further improved compared to AIDR 3D. In 2018, Canon Medical Systems developed Advanced intelligent Clear-IQ Engine (AiCE), which is a reconstruction method based on deep learning. (see figure).
AiCE has the advantage of providing high-quality images at lower doses. Another important advantage of AiCE is that the time required for data processing is significantly reduced. In the 1980s, it took about 30 minutes to process data of 40 images. Back in those days, physicians would sit back and wait for the whole morning for the study results to finally come out. Today, the images are available only 3 minutes after the examination is completed. Canon Medical Systems always considers operational workflow when designing their products.
Thanks to its many advanced features, AiCE is a truly outstanding image reconstruction method that is unmatched by other technologies currently available. I look forward to the development of an even more sophisticated version of AiCE.

Mr. Takiguchi : We are striving to achieve even higher image quality at lower exposure doses by further improving AiCE. Also, in cooperation with Professor Awai, we are currently undertaking the development of a new CT technology known as spectral CT, which is another area of great interest.
Prof. Awai : Deep learning certainly should address the fundamental limitations of dual energy, and provide clear benefits for some clinical applications, particularly in classifying tissue. However, the next technological leap that promises real clinical progress, is the photon-counting CT that can read out multiple energy levels, while providing higher spatial resolution, and further reducing dose.
My professional relationship with Canon Medical Systems is extremely rewarding, and I always enjoy the frank and open discussions I have with your company.
Mr. Takiguchi : This is very exciting. Canon Medical Systems Corporation will continue to focus on the development of CT systems that offer high-precision images while reducing the burden on the patient by minimizing the exposure dose. To achieve these goals, we need to continuously refine our latest technologies based on the guidance we receive from leading physicians. Thank you very much, Professor Awai, for sharing your valuable experience and insights with us today.

Find out more about low dose CT solutions

1) Radiology and Clinical Examination Subcommittee, Clinical Medicine Committee, Science Council of Japan: Recommendations on reduction of medically necessary radiation exposure in CT examinations, August 3, 2017
http://www.scj.go.jp/ja/info/kohyo/pdf/kohyo-23-t248-1.pdf
2) Japan Radiological Society: Guidelines on safety management systems related to medical radiation (November 2019 edition)
3) National Lung Screening Trial Research Team. N Engl J Med 2011; 365: 395-409
4) Awaya Y et al. J Hiroshima Med Ass 2016; 69: 729-735
5) Fujita M et al. Jpn J Radiol 2017; 35: 179-189
6) de Koning HJ et al. N Engl J Med 2020; 382: 503-513
7) Brenner DJ et al. Proc Natl Acad Sci USA 2003; 100: 13761-13766
8) Pearce MS et al. Lancet 2012; 380: 499-505
9) Berrington de Gonzalez A et al. Br J Cancer 2016; 114: 388-394
10) Fukumoto W et al. Eur Radiol 2017; 27: 1660-1666
11) Sakane H et al. Radiology 2020; 190389