呼吸器外科専門医が考えるMR検査の近未来展望: The future is at hand: MRI examinations of lung and thoracic disease
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The future is at hand:

MRI examinations of lung and thoracic disease

Thoracic Surgeon, Katsuo Usuda, M.D., Ph.D.

 

Introduction

I have been a thoracic surgery specialist for many years.  Over the years I have developed a passion for limiting radiation exposure to my patients.  In doing so I have published many clinical studies concerning MRI (magnetic resonance imaging) examinations highlighting not only their effectiveness and their low cost but also the fact that there is no radioactive exposure to patients.

I have published in many medical journals, which I have included links to on this site, and much of my research shows the advantages of MRI versus other means of staging and diagnosing lung cancers.  Even though my research shows clear advantages, MRI has not become standard practice, with many doctors still relying heavily on PET-CT.  I would like to use this blog to help disseminate my research to reach a larger audience and to slowly change ideas on the standard practices of the staging and diagnosing of lung cancers.

1.Comparison between current PET-CT and MRI

PET-CT (FDG-PET/CT: 18-fluoro-2-deoxy-glucose positron emission tomography / computed tomography) has been the primary method for the diagnosing and staging of metastatic lesions according to the cancer screening protocols of Japan.  When getting a PET-CT, FDG (18-fluoro-2-deoxy-glucose) is able to show the glucose metabolism of the target lesion.  The fact that PET-CT is not only more expensive than DWI and you will also need a contrast medium of FDG (a radioisotope) but the patient will also be exposed to harmful radiation in the process.  Naturally FDG shows glucose metabolism of the lesion.  PET-CT is not a perfect examination because of false negatives with small size tumors or tumors with little glucose metabolism, and it will also show a false positive for inflammatory lesions. PET-CT needs the injection of the radioisotope, the cost of the examination is approximately 30,000 yen with a 30% deductible.  Whereas an MRI is economical at approximately 6,000 yen, 1/5 the cost of PET-CT with a 30% deductible (Figure  1).

2.   Medical costs of examinations in Japan (Figure 2)

Recently the medical costs of healthcare has been increasing dramatically.  Medical costs for each medical examination is 10,000 yen (1,000 points of practice scores) for CT, 13,300 yen (1,330 points) for MRI of 1.5T, and 16,000 yen (1,600 points) for MRI of 3T.  An additional cost of 5,000 yen (500 points) is needed for the contrast medium in CT or MRI.  The other medical costs include 22,000 yen (2,200 points) for bone scintigraphy and 18,000 yen (1,800 points) for gallium scintigraphy. Furthermore, the cost of a positron emission tomography-computed tomography (PET-CT) using 18F-FDG (18-fluoro-2-deoxy-glucose) is 86,250 yen (8,625 points), which is considerably expensive.  The cost of an MRI is cheaper, only 15- 20% of that of PET-CT.  MRIs can reduce the costs for hospitals and patients by 84% compared to PET-CT while still providing the same or better results.

Usuda K, et al. Economic Benefits and Diagnostic Quality of Diffusion-weighted Magnetic Resonance Imaging for Primary Lung cancer.  Ann Thoracic Cardiovasc Surgery 2017; 23 (6), 275-280.

Here is a diagnostic performance of MRI when compared to that of PET-CT where the results are the same or better.  We believe this blog will have a positive effect globally in terms of the acceptance of using MRI in the diagnosing and the staging of lung cancer.

3.Usefulness of MRI  (evidence of the MRI)  (Figure 3)

The MR diffusion weighted image (diffusion-weighted magnetic resonance imaging: DWI) is used to depict the suppressed region of the diffusion phenomenon (Brownian movement of the water molecule), and the following efficacy has been proved.

Generally, cell density of malignant tumors is higher and there is a decrease in movement of water molecules of the malignant tumors compared to benign lesions.

Apparent diffusion coefficient (ADC) means a standard value of diffusion which is useful for discriminating malignancy from benignity in humans.  Usually, a malignant tumor shows a low value of 0.8 to 1.4 x 10-3mm2/sec. On the other hand, it is known that ADC of benign lesions are more than 2.0 x 10-3mm2/sec.  In this blog, a lot of ADC values are presented as diagnostic values.

The MR diffusion-weighted image (DWI) was applied first in the cranial nerve region and has been primarily used to discover acute ischemic strokes. In common MRIs, only a cerebral infarction that had passed is depicted as white, but a new cerebral infarction is not depicted. However, with DWIs, a new cerebral infarction is depicted 1 hour after its onset. Within 4.5 hours after the onset of a new cerebral infarction, thrombus dissolving drugs are administered to the patient according to the supporting stroke treatment guidelines 2015.  DWI became an established examination for prostate cancer in the treatment guidelines of prostate cancer 2015.  Small early prostate cancers in the inner gland are able to be identified using DWI. The characteristic of DWI is highly sensitive, and it came to be able to detect cancers of the transitional regions that may be overlooked by a biopsy.  DWI has a much lower risk factor than a biopsy and is able to detect a cancerous lesion with incredible sensitivity.

The usefulness of MRI for lung cancer is presented in Figure 4.

After a report by Webb et al. of Radiologic Diagnostic Oncology Group of 1991, Japanese guidelines for the use of MRI for lung cancer was restrictive for many years only being used in mediastinum invasion, chest wall invasion or vessel invasion.  Due to the fact that the diagnostic ability of MRI is the same as that of CT for the diagnosis of the T factor and N factor of lung cancer many doctors who were already familiar with CT were reluctant to adopt the use of MRI.  With cost and radiation use becoming more of an issue over the years the Japanese guidelines for the use of MRI for lung cancer have changed drastically.

The Japanese Lung Cancer Guidelines for 2018 for MRI are shown in Figure 4.  An additional MRI examination is recommended when pulmonary nodules cannot be judged as malignant by high resolution CT (recommended intensity 2), and when the N factor diagnosis is not determined by CT (recommended intensity 2).

4.   Usefulness of MRI for diagnosis of pulmonary nodules and masses (PNMs) (Figure 5, 6)

Next two meta-analysis of MRI (DWI) reported that MRI (DWI) is useful for a differential diagnosis of benign and malignant PNMs.

Li B, et al. A systematic review and meta-analysis of the accuracy of diffusion-weighted MRI in the detection of malignant pulmonary nodules and masses. Acad Radiol 2014; 21: 21-9.

Shen G, et al. Apparent diffusion coefficient values of diffusion-weighted imaging for distinguish­ing focal pulmonary lesions and characterizing the subtype of lung cancer: a meta-analysis. Eur Radiol 2016; 26: 556-66.

The next two papers mentioned that the diagnosability of MRI (DWI) is same or better than that of PET-CT.  Our results are presented in Figure 5 and 6.

Mori T, et al. Diffusion-weighted magnetic resonance imaging for diagnosing malignant pulmonary nodules/masses: comparison with posi­tron emission tomography. J Thorac Oncol 2008; 3: 358-64.

Usuda K, et al. Diagnostic performance of diffusion weighted imaging of malignant and benign pulmonary nodules and masses: comparison with positron emission tomography.  Asian pac J cancer Prev. 15 (11):4629-4635, 2014.

 

5.   Usefulness of MRI (DWI) for lung cancer clinical staging (Figures 7-11)

Here are some radiological images of three cases of lung cancers in Figure 7-10.  In case 1, an adenocarcinoma shows a nodular mass in CT, an FDG accumulation in PET-CT and a decreased diffusion in MRI (DWI). The adenocarcinoma had a metastasis of the #12u lymph node pathologically. In case 2, an adenocarcinoma did not have FDG accumulation of #12L lymph node, but diffusion decrease of the #12u lymph node.  Pathological positive lymph node metastasis revealed that MRI (DWI) showed the correct diagnosis.  In case 3, a large cell carcinoma had FDG accumulation of #4L lymph node, but no diffusion decrease of the #4L lymph node.  Pathological positive lymph node metastasis revealed MRI (DWI) showed the correct diagnosis.

The size of metastatic lymph nodes detected by MRI (DWI) or PET-CT are shown in Figure 11.  MRI (DWI) can detect smaller metastatic lymph nodes. The average value of the maximum diameter of carcinomas in metastatic lymph node stations was not detected by either DWI or PET-CT (A), was detected by DWI (B), and was detected by PET-CT (C).  The maximum diameter of carcinomas in metastatic lymph node stations were 3.0 ±0.9 mm in A, 7.2 ±4.1 mm in B, and 11.9 ±4.1 mm in C. There were significant differences among the groups.

A comparison between MRI (DWI) and PET-CT for lymph node metastases of lung cancer (Figure 12).  The sensitivity and the accuracy of metastatic lymph nodes:  MRI (DWI) > PET-CT.   Peerlings et al. reported that the sensitivity of MRI (DWI) for metastatic lymph nodes of lung cancer was 0.87 and the specificity of MRI (DWI) for no metastatic lymph nodes of lung cancer was 0.88.

Peerlings J, et al. The di­agnostic value of MR imaging in determining the lymph node status of patients with non-small cell lung cancer: a meta-analysis. Radiology 2016; 281: 86-98.

Shen et al. concluded that an assessment of MRI (DWI) was useful for N factor of lung cancer.

Shen G, et al. Performance of DWI in the nodal characterization and assessment of lung cancer: a meta-analysis. AJR Am J Roentgenol 2016; 206: 283-90.

Our article which dealt with 160 lung cancers showed that the accuracy of MRI(DWI)was 96.2%, which was significantly better than that (94.3%) of PET-CT.  The sensitivity and the accuracy of MRI (DWI) are significantly higher than those of PET-CT (Figure 11).

Usuda K, et al. Advantages of diffusion-weighted imaging over positron emission tomography-computed tomography in assessment of hilar and mediastinal lymph node in lung cancer.  Ann Surg Oncol 20; 1676-1683: 2013.

Usuda K, et al. Diffusion-weighted imaging is superior to PET in the detection and nodal assessment of lung cancers. Ann. Thorac. Surg. 91(6): 1689-1695, 2011.

Usuda K, et al. Diagnostic Performance of Diffusion Weighted Imaging for Multiple Hilar and Mediastinal Lymph Nodes with FDG Accumulation.  Asian Pac. J. Cancer Prev. 16, 6401-6406, 2015.

Concerning advantages of MRI (DWI), sensitivity and accuracy of MRI (DWI) are significantly higher than those of PET-CT (Figure 13).

6.   Usefulness of MRI for the invasion into blood vessels, heart, chest wall, diaphragm and the mediastinum by lung cancer

This fact has been well known for more than 30 years. The evaluation, by MRI, for the invasion into blood vessel, heart, chest wall, diaphragm and the mediastinum by lung cancer is the gold standard.  CT or PET-CT is not reliable enough.

7.   MRI (DWI) is valuable for the evaluation of lung cancer with multiple FDG accumulation in PET-CT (Figure 14,15). 

MRI (DWI) is valuable for an evaluation of lymph nodes affected by pneumoconiocis or silicosis.  MRI (DWI) can judge the FDG accumulation of pneumoconioisis as negative.

Usuda K, et al. Diagnostic Performance of Diffusion Weighted Imaging for Multiple Hilar and Mediastinal Lymph Nodes with FDG Accumulation.  Asian Pac. J. Cancer Prev. 16, 6401-6406, 2015.

8.   Usefulness of the MRI (DWI) for detecting metastatic or recurrent lesions of lung cancer

The detection of metastatic or recurrent lesions is easy based on the diffusion decrease by the MRI (DWI) and a qualitative diagnosis can be possible by measuring ADC.

Usuda K, et al. Recurrence and metastasis of lung cancer demonstrate decreased diffusion on diffusion-weighted magnetic resonance imaging. Asian Pac J Cancer Prev. 15; 6843-6848, 2014.

9.   Diffusion-weighted whole-body imaging with background suppression (DWIBS) (Whole-body DWI)

The research group of Dr. Taro Takahara and Professor Dr. Yutaka Imai of Tokai University have developed an epoch-making method, diffusion-weighted whole-body imaging with background suppression (DWIBS) which searched a whole body with one MRI (DWI) exploration in 2004.  The diagnostic ability of PET-CT and that of DWIBS are similar. Some diagnostic abilities are better in DWIBS than in PET-CT, others are better in PET-CT than DWIBS. However, patients cannot receive a PET-CT more than once a year on health insurance because it is expensive, approximately 30,000 yen with a 30% deductible. On the other hand, DWIBS is an MR imaging so we do not need a contrast medium. Therefore, a patient can get an MRI once every one to three months on health insurance.

We presented the good points of DWIBS compared to PET-CT (Figure 16).  Also, we showed a comparison between DWIBS and PET-CT (Figure 17).

One of the most famous journals in American radiology is “Radiology”.  Mark L. Schiebler,M.D. as EDITORIAL of Radiology in 2016 cited our paper of whole-body DW MRI (DWIBS) for lung cancer. He mentioned that if the diagnostic ability of whole-body DW MRI (DWIBS) is proved to be equivalent to PET-CT for clinical staging of lung cancer while also reducing medical cots it will ultimately  replace PET-CT in the future.  Furthermore he predicted that only whole-body DW MRI (DWIBS) will be utilized for the diagnosis and staging of lung cancer.

Mark L. Schiebler,M.D.   Can solitary pulmonary nodules be accurately characterized with diffusion-weighted MRI?  Radiology 2019; 290:535–536 https://doi.org/10.1148/radiol.2018182442
(Quoted sentence) There is a single report by Usuda et al. that shows that DW MRI can be used to adequately stage NSCLC. In their study of 67 patients with NSCLC, PET/CT plus brain MRI showed a pathologic staging accuracy of 0.69, while in the same group, whole-body DW MRI had a pathologic staging accuracy of 0 .75. This data (8) clearly points to a need for an adequately powered prospective randomized trial to help definitively answer this question. Specifically, if whole-body DW MRI can be shown to have equipoise with 18F-FDG PET for the clinical staging of NSCLC, this would reduce the costs of patient work-up because 18F-FDG PET would no longer be needed. Perhaps in the near future, only whole-body DW MRI will be needed for clinical staging in patients with a new diagnosis of NSCLC.

(Quoted paper) Usuda K, et al. Diagnostic Performance of Whole-Body Diffusion-Weighted Imaging Compared to PET-CT Plus Brain MRI in Staging Clinically Resectable Lung Cancer. Asian Pac J Cancer Prev. 2016; 17: 2775-2780.

Usuda K, et al. Diffusion-weighted whole-body imaging with background suppression (DWIBS) is effective and economical for detection of metastasis or recurrence of lung cancer. Thoracic cancer 2021:12 (5):676 – 684. 

10.   Usefulness of the MRI (DWI) for the diagnosis of the mediastinal tumor ( Figure 18-20)

MRI (DWI) can judged these lesions as malignant or benign.

Usuda K, et al, Diffusion Weighted Imaging Can Distinguish Benign from Malignant Mediastinal Tumors and Mass Lesions. Comparison with Positron Emission Tomography. Asian Pac. J. Cancer Prev. 16, 6469-6475, 2015.

Gumustas S, et al. Malignant versus benign mediastinal lesions. Quantitative assessment with diffusion weighted MR imaging. Eur Radiol. 2011: 21, 2255-60.

11.   Usefulness of the MRI for the differential diagnosis of the pleural lesion including malignant pleural mesothelioma (Figure 21-25)

MRI (DWI) can assess pleural lesions including malignant pleural mesothelioma as malignant or benign.

Usuda K, et al.Diffusion-Weighted Imaging Can Differentiate between Malignant and Benign Pleural Diseases Cancers (Basel). 2019 Jun 12;11(6). pii: E811. doi: 10.3390/cancers11060811.

Pessôa, FM, et al. Applications of magnetic resonance imaging of the thorax in pleural diseases: A state-of-the-art review. Lung 2016, 194, 501–509.

12.   Usefulness of the MRI for the differential diagnosis of suture recurrence and suture granuloma after pulmonary resection for lung cancer (Figure 26-27)

MRI (DWI) can assess new suture lesions after pulmonary resection of lung cancer.

Usuda K, et al. Differentiation between suture recurrence and suture granuloma after pulmonary resection for lung cancer by diffusion-weighted magnetic resonance imaging or FDG-PET /CT. Transl Oncol. 2021;14(2): 100992.doi: 10.1016/j.tranon.2020.100992.

13.   Usefulness of the MRI for the response evaluation of chemotherapy /radiotherapy of lung cancer. (Figure 28-29)

Although CT are used for the response evaluation of chemotherapy /radiotherapy of lung cancer, the response evaluation is based on the lesion size. In the situation sometimes the real lesion may be unknown. Even in the situation, the qualitative diagnosis of the lesion is possible using ADC in MRI (DWI).

Usuda K, et al. Diffusion-weighted magnetic resonance imaging is useful for the response evaluation of chemotherapy and/or radiotherapy to recurrent lesions of lung cancer Transl Oncol. 2019;12(5):699-704.

Ciliberto M, et al. Comparison between whole-body MRI and Fluorine-18 fluorodeoxyglucose PET or PET/CT in oncology: a systematic review. Radiol Oncol 47, 206–218.

Conclusion

MRI (DWI) is useful for differential diagnosis of benign and malignant lesions in whole body. MRI (DWI) can be available for the assessment of pulmonary masses, N factor, M factor and stage of lung cancer. MRI (DWI) is useful for mediastinal tumors, pleura lesions including malignant pleural mesothelioma, suture lesions after resection, and response evaluation of chemotherapy/radiotherapy of lung cancer. MRI (DWI) can reduce medical cost of examination. DWIBS can make examinations of lung cancer be simplified for lung cancer staging and post-therapeutic follow-up.

ABOUT ME
薄田 勝男
呼吸器外科専門医として長年肺癌診療に携わってまいりました。 このサイトでは肺がん診断におけるMRIの有効性をご紹介しております。

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