Head and neck (HN) cancer is the 6^th most common cancer and the 9^th most common cause of cancer-related death (1, 2). Surgery is the most effective treatment for managing primary HN cancer. Yet, many patients present with advanced-stage tumors at the time of diagnosis and thus require more invasive treatment, including radiochemotherapy, immunotherapy, and targeted therapy (3). Also, diagnosis remains challenging considering its specific location (masses originating from the larynx, the nasopharynx, oropharynx, oral cavity hypopharynx, salivary glands, etc.). In addition, HN cancer might cause various symptoms that commonly accompany benign conditions (1). Thus, the differentiation of benign from cancerous masses is very important.

Tissue biopsy and pathologic examination remain the gold standard for evaluating the nature of HN lesions; nevertheless, only a part of the tissue can be obtained using this method. In addition, this approach is invasive and not always well accepted by the patient (4).

Endoscopy, head MRI, computed tomography (CT of the sinuses and head, dental cone beam CT), panoramic dental x-ray, and positron emission tomography (PET)/CT or chest imaging are the most common imaging methods used to assess the HN region. MRI is frequently used to detect, differentiate, grade, or draw the extent of HN tumors (1, 5). Among different MRI models, diffusion-weighted imaging (DWI) can quantitatively evaluate the Brownian motion diffusion of water molecules in tissues at a cellular level expressed as an apparent diffusion coefficient (ADC). DWI with a single-shot echo-planar sequence (SS-EP-DWI), which is commonly applied to investigate HN regions (6), is sensitive to chemical shifts, signal loss and geometric distortion, metallic dental implant-related magnetic susceptibility artifacts, and motion artifacts (7). Moreover, stimulus and fast spin echo DWI with periodically rotated overlapping parallel lines with enhanced reconstruction (FSE-PROPELLER DWI) is useful to distinguish parotid pleomorphic adenoma from Warthin tumor with less distortion of tumors than SS-EP-DWI (7). However, the value of FSE-PROPELLER DWI in distinguishing malignant from benign HN tumors has not been fully explored.

The major limitations of DWI include low signal-to-noise ratios and prolonged acquisition time. Over the years, a new synthetic MRI sequence based on a quantitative approach has been developed. This tool can estimate absolute physical properties, proton density (PD), and longitudinal and transverse relaxation times (T1, T2), which are independent of the MRI scanners or scanning parameters at a given field strength (8). Also, quantitative values (PD, T1, and T2) can be simultaneously acquired on the synthetic MRI, which enables a significant reduction in examination time with good accuracy and reproducibility for use in clinical practice (individual patient follow-up and comparison analysis (9–11). This approach has been used in the study of multiple systemic diseases of the brain (12), knee (13), spine (14), prostate (15), breast (16), bladder (17), and nasopharynx (18).

In this study, we further assessed the value of synthetic MRI in differentiating malignant from benign HN tumors compared with FSE-PROPELLER DWI and a combination of these two methods. To the best of our knowledge, this is the first study that focused on synthetic MRI and FSE-PROPELLER DWI to characterize HN tumors.

We examined the tissue magnetic property parameters acquired on the synthetic MRI with MAGIC and ADC acquired on the FSE-PROPELLER DWI in discriminating malignant from benign HN lesions. The purpose of evaluating parameter correlation is to identify preferred parameters and facilitate the translation of scientific research into clinical practice. Except for PD values, T1, T2, and ADC values were lower in malignant than in benign HN tumors. ADC, T1, and T2 values are widely used parameters for differentiating malignant from benign HN tumors. The diagnostic performance of the T2 value is comparable to the ADC value. However, the diagnostic performance of the T1 and PD values was not as good as that of the ADC value. We also found that T2+ADC showed optimal diagnostic performance.

In this study, the malignant tumor had a lower T1 value related to hyper-cellularity, smaller extracellular space, and lower free water content (18). Meng et al. found that the T1 value for nasopharyngeal carcinoma was significantly lower than that for benign hyperplasia in the nasopharynx, regardless of the ROI used (18). Contrary Gao and his team found no difference in the T1 values between malignant and benign breast lesions (21). The different types of tumors in these studies may contribute to the discrepancy.

T2 value can be affected by various factors, including the main magnetic field strength and the intrinsic properties of the tissue and the environment. Tissue water content is the most important influencing factor (22). A previous study reported a linear relationship between the T2 value and water content (23); thus, increased T2 values indicate increased tissue water content (24). In our study, 75% of benign HN tumors were pleomorphic adenomas followed by basal cell adenomas, and 64% of malignant HN tumors were squamous cell carcinomas followed by lymphomas. We speculate that the higher T2 values of benign HN tumors could be ascribed to their tissue composition, lower cell density, and higher free water content (5). Nevertheless, the lower T2 values in malignant tumors are due to the increased solid components, smaller extracellular spaces, and lower free water content (5, 18, 25). Several studies have reported higher T2 values in benign breast lesions vs. in malignant lesions (21). This difference could be attributed to increased tissue water content or interaction between water and alkaline metal cations in the pathological tissue (22).

PD value, which primarily reflects the water content in tissue, is frequently used in brain imaging (26). This study found that the difference in PD value in the malignant compared with benign HN tumors was not statistically significant. Yet, Gao et al. demonstrated that the PD value was significantly lower in malignant than that benign breast lesions (21). The different types of tumors enrolled in these studies may contribute to the contradiction.

Here we found that the ADC values of malignant tumors were significantly lower than those of benign tumors. Higher ADC values correlate with lower cellularity (27). Malignant tumors demonstrate lower ADC values than benign tumors due to their relatively higher cellularity (4). Srinivasan et al. also found that malignant lesions showed lower ADC values than benign lesions (28).

In this study, the overall diagnostic performance of synthetic MRI-derived parameters in discriminating malignant from the benign HN lesions was inferior to the ADC value. However, the diagnostic performance showed no significant differences between ADC and T2 values. Also, T2+ADC showed optimal diagnostic efficacy in distinguishing malignant from benign tumors; T2+ADC showed a significantly higher differential performance vs. T1, T2, or PD value alone, but it did not improve the diagnostic performance of the ADC value. Despite this, the PD, T1, and T2 are intrinsic magnetic properties and independent from the MRI scanners or scanning parameters at a given field strength (15), predicting the potential advantage of using synthetic MRI-derived parameters compared to the ADC value alone (17). In addition, synthetic MRI can generate multiple contrast-weighted images and quantification maps in a single scan, greatly improving work efficiency (10). Thus, synthetic MRI plus FSE-PROPELLER DWI might be a promising tool for differentiating benign from malignant HN lesions.

The present study has a few limitations. First, this is a single-center retrospective study with small sample size, next, we will expand the sample size for further study. Second, ROIs were manually drawn at the slice with the largest tumor diameter, leading to potential operator errors. In the future, the whole tumor should be selected to determine whether the tumor volume is more meaningful and accurate for tumor characterizing. Finally, test-retest repeatability was not assessed.

The quantitative T1, T2, and PD values obtained by synthetic MRI and ADC value obtained by FSE-PROPELLER DWI helped discriminate malignant from benign HN tumors. The overall diagnostic performance of synthetic MRI was inferior to FSE-PROPELLER DWI. However, the T2 value was comparable to the ADC value, and the combination of synthetic MRI and FSE-PROPELLER DWI could provide improved diagnostic efficacy.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

BW: Conceptualization, Methodology, Software, Data curation, Writing - original draft, Visualization, Investigation, Writing - review & editing. ZZ: Data curation, Writing - original draft, Visualization, Investigation, Writing - review & editing. JZ: data analysis, statistical analysis. LL: Data curation. ZL: Data curation, Writing - original draft. XM: Visualization, Investigation. KW: Conceptualization, Methodology, Software, Writing - review & editing. LX: Conceptualization, Methodology, Software, Validation, Writing - review & editing. YZ: Supervision. JC: Supervision. All authors contributed to the article and approved the submitted version.