Magnetic resonance imaging for lung cancer detection: Experience in a population of more than 10,000 healthy individuals
- Nai-Yuan Wu1, 2, 3,
- Hui-Cheng Cheng1, 4,
- James S Ko1, 4,
- Yu-Chen Cheng1, 4,
- Po-Wei Lin1, 4,
- Wei-Chan Lin1, 4,
- Cheng-Yen Chang†4Email author and
- Der-Ming Liou†2Email author
© Wu et al; licensee BioMed Central Ltd. 2011
Received: 15 April 2010
Accepted: 13 June 2011
Published: 13 June 2011
Recent refinements of lung MRI techniques have reduced the examination time and improved diagnostic sensitivity and specificity. We conducted a study to assess the feasibility of MRI for the detection of primary lung cancer in asymptomatic individuals.
A retrospective chart review was performed on images of lung parenchyma, which were extracted from whole-body MRI examinations between October 2000 and December 2007. 11,766 consecutive healthy individuals (mean age, 50.4 years; 56.8% male) were scanned using one of two 1.5-T scanners (Sonata and Sonata Maestro, Siemens Medical Solutions, Erlangen, Germany). The standard protocol included a quick whole-lung survey with T2-weighted 2-dimensional half Fourier acquisition single shot turbo spin echo (HASTE) and 3-dimensional volumetric interpolated breath-hold examination (VIBE). Total examination time was less than 10 minutes, and scanning time was only 5 minutes. Prompt referrals and follow-ups were arranged in cases of suspicious lung nodules.
A total of 559 individuals (4.8%) had suspicious lung nodules. A total of 49 primary lung cancers were diagnosed in 46 individuals: 41 prevalence cancers and 8 incidence cancers. The overall detection rate of primary lung cancers was 0.4%. For smokers aged 51 to 70 years, the detection rate was 1.4%. TNM stage I disease accounted for 37 (75.5%). The mean size of detected lung cancers was 1.98 cm (median, 1.5 cm; range, 0.5-8.2 cm). The most histological types were adenocarcinoma in 38 (77.6%).
Rapid zero-dose MRI can be used for lung cancer detection in a healthy population.
Lung cancer is the leading cause of cancer death worldwide [1–3]. The overall 5-year survival rate is approximately 15% in the United States and less than 10% in Europe [4–6]. Because most lung cancers generate no symptoms at early stages, they are usually diagnosed at an advanced stage and have a poor prognosis. However, many lung cancer deaths could be avoided if tumors were detected at an early stage when they were still resectable. For stage Ia non-small cell lung cancer, the 5-year survival rate is higher than 80%. Prognosis and treatment outcomes have been found to be related to the disease stage at the time of diagnosis [7–9]. Various modalities have been investigated for detecting early lung cancer and consequently reducing lung cancer mortality. In the 1970s, several randomized controlled trials of chest radiography, alone or combined with sputum cytology, were performed. However, because of the poor sensitivity of these methods, the reported data indicated no evidence of benefit in terms of reduction in lung cancer mortality [10–12]. In the 1990s, many observational clinical trials were begun of low-dose spiral computed tomography (LDCT). Those studies showed that although LDCT can detect more early lung cancers than chest radiography, it does not result in a decrease in lung cancer deaths [13–19].
Until recently, magnetic resonance imaging (MRI) was regarded as an inappropriate tool for lung cancer screening because of its insufficient anatomic detail, along with being time-consuming and expensive. The advanced MRI techniques for lungs have reduced the examination time to less than 10 minute (< 8 breath-holds) and improved diagnostic sensitivity and specificity. We conducted a study to assess the feasibility of performing rapid MRI for lung cancer detection. We report our techniques and findings herein.
In October 2000, Taipei Veterans General Hospital in Taiwan launched whole-body MRI examinations in routine clinical practice . All examinations were paid for by the examinees, who were referred from clinician or self-registered. So far, more than 20,000 examinations have been carried out for 17,000 people. We performed a retrospective chart review for all whole-body MRI examinations between October 2000 and December 2007. Institutional Review Board of Taipei Veterans General Hospital in Taiwan approved this retrospective chart review and waived the requirement for informed consent because all images and follow-up data were obtained as part of routine clinical care (VGHIRB No: 201006010IC).
For this study, analysis was focused on images of lung parenchyma. We did not take into account imaging findings of the mediastinum, chest wall, diaphragm, or metastatic lung lesions diagnosed simultaneously with primary cancer. Examinees with a prior history of cancer were excluded from the study. Examinees with normal lung imaging but diagnosed with other cancers by whole-body MRI were also excluded. Demographic details of examinees as well as smoking habits and prior medical history were analyzed.
All examinees could choose their own MRI examinations, either noncontrasted whole-body MRI or with additional contrasted MRI examinations, such as contrast magnetic resonance angiography (MRA) or breast MRI. For examinees who had additional contrasted MRI, HASTE was applied before contrast agent injection, and VIBE was applied after contrast agent injection using 0.5 mmol/kg of gadodiamide (Omniscan) at an injection rate of 3 mL/sec.
All images were viewed by 1 of 5 radiologists (HCC, JSK, YCC, PWL, WCL), who had 4 to 19 years of experience (average, 9.6 years) after board certification. We classified and defined all lesions as (1) normal or extrapulmonary abnormality: negative result in lungs or lesions in the extrapulmonary area, for instance, in the neck or abdomen, (2) lung abnormality of little clinical significance: pulmonary lesions rather than nodules, for instance, pleural thickening or fibrosis, (3) probable benignancy: lung nodules measuring ≤ 0.5 cm with well-defined border and visible only by VIBE and not by HASTE, (4) indeterminate nodules: lung nodules measuring ≤ 0.5 cm with mild irregular border and visible only by VIBE and not by HASTE, (5) possible malignancy: lung nodules measuring > 0.5 cm and <1 cm and visible only by VIBE and not by HASTE, (6) probable malignancy: lung nodules visible by both VIBE and HASTE; or lung nodules measuring ≥ 1 cm; or newly developed lung nodules at the second or more MRI examinations. The latter three were considered to be suspicious lung nodules [16, 20].
For examinees with possible malignancies or indeterminate small lung nodules, serial follow-ups were arranged either by MRI or by standard-dose computed tomography (CT) every 3 to 6 months for a minimum of 24 months. Nodules remaining the same size or regressing during follow-up for at least 2 years were considered to be benign [21, 22]. When growth was found, referrals to thoracic surgeons were arranged. For examinees with probable malignancies, immediate standard-dose CT and referrals to thoracic surgeons were arranged. The decision as to how to perform investigative procedures was left to the referred surgeon. All cytological and histological findings from biopsies and surgical specimens were documented. When a cancer was diagnosed, the examinee received standard care, including tumor staging and appropriate treatment. Outcomes of referrals were followed, and cancer-related details were logged.
Statistical analysis was performed using Microsoft Excel 2003 (Microsoft Corporation, Redmond, WA, USA). The results are presented as mean, median, and range. The Yates-corrected chi-Square test was used for categorical variables to evaluate difference. Results were considered statistically significant at p < 0.05.
Characteristics of individuals undergoing lung magnetic resonance imaging examination
Interindividual comparison of noncontrasted and contrasted lung magnetic resonance imaginga
Normal or extrapulmonary abnormality
Lung abnormality of little clinical significance
Indeterminate small nodule measuring ≤0.5 cm
Subtotal of suspicious lung nodulesb
Distribution of detected primary lung cancers by magnetic resonance imaging
Of the 49 lung cancers, the mean age of the individual at diagnosis was 60.8 years (range, 36-87 years), and 25 (51.0%) were in males. Eleven cases were in people who had smoked, and the median number of pack-years of smoking was 35 (range, 10-80). Characteristics of individuals with detected primary lung cancers are shown in Table 3. Suspected lung cancers were subjected to various procedures for proper histopathological documentation. Thoracotomy (including video-assisted thoracoscopic surgery) was performed for 40 cancers, lobectomy for 33 cancers, wedge resection for 6, and segmentectomy for 1. Three cancers were histologically proved by bronchoscopic biopsy, 1 by CT-guided lung biopsy, 1 by sputum cytology, 1 by biopsy at supraclavicular lymph node, and 1 by endoscopic biopsy at metastatic duodenal lesion. Two individuals refused any procedures or therapies and later developed rib metastases or progressive pulmonary nodules. Forty cancers had pathological staging, and 9 had clinical staging. Twenty-five cancers were TNM stage Ia disease (51.0%), 12 stage Ib disease (24.5%), 4 stage IIIa (8.2%), 2 stage IIIb (4.1%), and 6 stage IV disease (12.2%). The mean size of detected lung cancers was 1.98 cm (median, 1.5 cm; range, 0.5-8.2 cm). Thirty-six cancers (73.5%) had a primary tumor measuring ≤3 cm, and 29 (59.2%) ≤2 cm. Histological types were as follows: 38 adenocarcinoma (77.6%), 5 bronchioloalveolar carcinoma (10.2%), 2 large cell carcinoma (4.1%), 1 squamous cell carcinoma (2.0%), and 1 carcinoid tumorlet (2.0%). There were 3 female individuals with synchronous double primary lung cancers. One biopsy proved to be non-small cell lung carcinoma with no primary tumor origin in the lungs when retrospectively and prospectively assessed. Two cases did not have tissue proof because the individuals refused any procedures.
Comparison between prevalence lung cancers and incidence lung cancers by magnetic resonance imaging examination
Mean size (cm)
Cancer detection rate (%)
Follow-up (duration, 2-9 years) for the 49 cancers showed 8 deaths due to lung cancer, 2 stage IIIa cancers, 2 stage IIIb cancers, and 4 stage IV cancers. One stage Ib individual developed recurrent tumors 2 years later and underwent pulmonary resection again. Thirty-three individuals (67.3%) were alive and free of disease at the time of this writing.
Eight false-positive individuals whose standard-dose CT also suggested malignancies underwent invasive procedures: 2 CT-guided biopsies and 6 thoracotomies (including video-assisted thoracoscopic surgery). Infectious diseases were histologically confirmed in these 8 people, with cryptococcal infections in 6.
To date, several studies have investigated the feasibility of LDCT for screening for primary lung cancers. By enrolling heavy smokers and older people, these studies targeted groups at high risk for lung cancer, resulting in cancer detection rates ranging from 0.4% to 2.7% and lung nodule prevalence rates ranging from 5.1% to 43% [13–19]. In our study, there were no limitations on smoking history and age because all examinations were self-paid and all examinees were self-enrolled. Consequently, our group included a higher proportion of never-smokers and a wider age range (11-94 years). If we calculate the results for smokers between 51 and 70 years old, as did the LDCT studies, the detection rate is 1.4% (6 of 434), and the prevalence of suspicious lung nodules is 9.0% (39 of 434). The proportion of lung cancers among suspicious nodules detected by MRI was 15.4% (6 of 39), higher than in reports for LDCT, which range from 2.2% to 11.6%. While using standard-dose CT as a standard-of reference for nodule detection, previous studies have showed that MRI can achieve high sensitivity for nodules larger than 1 cm, which are clinical approachable [23, 24]. Undoubtedly LDCT is more sensitive than MRI in detecting lung nodules and includes more and smaller nodules. However, for any diagnostic tool, higher sensitivity is usually accompanied by lower specificity. Most of the additional lung nodules detected by LDCT are smaller than 0.5 cm. According to guidelines for managing small lung nodules, nodules smaller than 1 cm are associated with more follow-up visits but not more lung cancers [21, 22]. We believe that it is why our results showed that MRI had a lower prevalence of suspicious nodules than did LDCT but had a cancer detection rate similar to that of LDCT.
Contrasted MRI can detect more morphological details than noncontrasted MRI, and is especially better at depicting peripheral one-third parenchymal vascular markings (around 0.2 cm in diameter). The expected detection limit for contrasted MRI is about 0.3 cm (2 × 2 pixels), better than noncontrasted MRI about 0.5 cm (3 × 4 pixels). Nevertheless, our results showed that no significant difference in cancer detection rates was found between contrasted and noncontrasted MRI (0.5% vs 0.4%, p = 0.24). It was assumed that the proportion of lost to follow-up and false-negative rate of contrasted MRI were similar to that of noncontrasted MRI because all examinations and follow-ups were performed in the same institution. Therefore, the possible explanation might be the same as previous comparison between MRI and LDCT. More subtle lung nodules do not necessarily bring out more lung cancers.
The radiation exposure should be justified when recommending the use of LDCT as a screening tool. Several authors have addressed the radiation hazards of multiple LDCT examinations [25–27]. When lung cancer screening involves the general population and is not targeted just at the high-risk population, the use of MRI can avoid the ethical problems of unnecessary ionizing radiation, which in the long term may contribute to lung cancer risk [28, 29]. In addition, when contrast study is necessary, gadodiamide is noniodinated and has a better safety record with less nephrotoxicity .
In our results, there was no significance of cancer detection rate between smokers and never-smokers. However, most studies of lung cancer screening are aimed at smokers only. Many studies have demonstrated that lung cancer in never-smokers is an important public health issue, especially in females who tend to have more non-smoking associated cancers than males [31, 32]. Clearly, to perform lung cancer screening in general population deserves more consideration and further researches.
Although the results of this study provide helpful insight into the use of MRI, the study has several limitations. A certain number of examinees were lost to follow-up. Moreover, follow-up periods and follow-up tools were not identical in all individuals. Standard-dose CT and plain chest radiography were performed only for those with suspected lung lesions; therefore, comparison of MRI with standard-dose CT and chest radiography for all nodules was not possible. Without a reference study, the percentage of false-negative cases could not be evaluated. In addition, like other one-arm observational nonrandomized trials, our study does not provide information on potential stage shift and reduction of lung cancer mortality by screening. Today, several randomized controlled trials of LDCT are under way worldwide [33–35]. We hope that our results will prompt subsequent randomized controlled trials of MRI that are not affected by lead time and length time bias and overdiagnosis.
Based on the results of more than 10,000 MRI examinations, the 1.5T MRI with advanced pulse sequences approach described here, which takes less than 10 minutes to perform, is useful in lung cancer detection for asymptomatic individuals and avoids unnecessary ionizing radiation.
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