Differentiation of malignant tumor from benign tumor is essential for radiological examination in routine clinical practice. Currently, CT and MR imaging have been applied for morphological evaluation, although FDG-PET and PET/CT are currently applicable molecular imaging technique in various clinical and academic interest. In contrast to FDG-PET or PET/CT, chemical exchange saturation transfer (CEST) imaging is also suggested as a new technique for MR-based molecular imaging techniques in vivo and in vitro studies (1-5). However, no major reports have been reported the direct comparison of capabilities for differentiating malignant and benign pulmonary lesions between CEST imaging and PET/CT.

We hypothesized that newly developed CEST imaging, demonstrating the exchange between protons of free tissue water and amide groups (-NH) of endogenous proteins and peptides (i.e. amide proton transfer imaging: APT imaging), may have a similar potential for differentiating malignant from benign pulmonary nodules and masses, when compared with FDG-PET/CT. The purpose of this study was to directly and prospectively compare the capability of CEST imaging targeted to amide groups (-NH) for differentiation of malignant from benign pulmonary lesions with FDG-PET/CT.

Thirty-six consecutive patients (26 men, 10 women; mean age 67 years) with pulmonary nodules or masses prospectively underwent CEST imaging at 3T MR system (Vantage Titan 3T, Toshiba Medical Systems Corporation, Otawara, Tochigi, Japan), FDG-PET/CT, pathological examinations from specimens obtained by transbronchial or CT-guided biopsies or surgical resection, and/ or follow-up examinations. According to pathological examination results, all lesions were divided as follows: benign (n=10) vs. malignant (n=26) groups. In addition, malignant groups were consisted with 16 invasive adenocarcinomas, 6 squamous cell carcinomas and 4 adenocarcinoma in situes.

To obtain CEST data in each subject, respiratory-synchronized fast advanced spin-echo images were conducted following a series of magnetization transfer (MT) pulses. Then, magnetization transfer ratio asymmetry (MTR_asym) was calculated from z-spectra in each pixel, and MTR_asym map was computationally generated. Then, ROIs were placed over each lesion, and determine MTR_asym and SUV_max.

To determine the relationship between MTR_asym at 3.5 ppm and SUV_max, Pearson’s correlation was evaluated. To determine the MTR_asym difference at 3.5 ppm and SUV_max between malignant and benign nodules or masses, Student’s t-test was performed. To compare the capability of MTR_asym at 3.5 ppm and SUV_max for differentiating malignant from benign groups, ROC analysis was performed. Finally, sensitivity, specificity and accuracy were compared each other by means of McNemar’s test. A p value less than 0.05 was considered as significant in this study.

Representative cases are shown in Figure 1 and 2. There was no correlation between MTR_asym and SUV_max (r=0.28, p=0.10). There were significant differences of both indexes between malignant (MTR_asym: 0.1±5.6 %, SUV_max: 3.0±0.8) and benign (MTR_asym: -4.2±4.6 %, p<0.05; SUV_max: 2.5±4.4, p<0.05) groups. Area under the curve (Az) of MTR_asym at 3.5ppm (Az=0.75) had no significant difference with that of SUV_max (Az=0.70, p=0.67). Compared results of diagnostic performance between two methods are shown in Figure 3. There were no significant difference of sensitivity, specificity and accuracy between MTR_asym and SUV_max (p>0.05). On 3T MR system, CEST imaging has a potential for differentiating malignant from benign lesions as well as FDG-PET/CT, and is considered at least as valuable as PET/CT in this setting. Although MTR_asym at 3.5ppm and SUV_max shows significant differences between malignant and benign pulmonary lesions, there was no significant correlation between MTR_asym at 3.5ppm and FDG uptake. Therefore, CEST imaging can provide additional information for management of pulmonary lesions, when applied with PET/CT.