Introduction

Colorectal cancer is a common malignancy of the digestive tract [1]. Many factors are associated with therapeutic schedule and prognosis of rectal cancer, including tumor grade, T stage, N stage, and related imaging indicators based on MRI, such as circumferential resection margin (CRM), and extramural vascular invasion (EMVI) statuses [2,3]. Magnetic resonance imaging (MRI) is the first choice for preoperative diagnosis and staging of rectal cancer. Functional MRI methods have become increasingly used for clinical applications in recent years. Among them, IVIM provides diffusion and perfusion information within tissue through the biexponential modelling of images acquired by multiple b values [4]. Amide proton transfer (APT) weighted imaging is a noninvasive molecular imaging technique based on the effect of chemical exchange saturation transfer (CEST). It indirectly measures the endogenous moving proteins and peptides by detecting the reduction in bulk water intensity, which reflects changes of the internal metabolism [5,6]. In this study, we analyze the value of APT weighted and IVIM imaging in evaluation of prognostic factors for rectal adenocarcinoma, thereby to evaluate their reference values for assessing the malignant degree and predicting tumor aggressiveness, compared with diffusion weighted imaging (DWI)

Methods

Preoperative pelvic MRI data of 93 patients with surgical pathologically confirmed diagnosis of rectal adenocarcinoma were retrospectively evaluated. MRI were performed on a 3T scanner (Ingenia CX, Philips Healthcare, Best, the Netherlands) with a 32-channel phase array coil. All patients underwent high-resolution T2-weighted imaging (T2WI), APT, IVIM, and DWI. The APT parameters were: TR/TE = 6540/8.3 ms; FOV = 230×181 mm2; scan matrix = 116×90; voxel size = 2×2×5mm3; 9 slices; TSE factor = 174; acquisition time = 6 min 0 sec. The IVIM parameters were: TR/TE = 4888/90ms; FOV = 240×240 mm2; scan matrix = 72×67; voxel size = 3.3×3.58×5mm3; 24 slices; b=0,10,20,50,100,200,400,800,1200; acquisition time = 4 min 53 sec. Parameters including APT signal intensity (APT SI), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC) were measured in different histopathologic grades, stages, and structure invasion statuses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy, and the corresponding area under the curves (AUCs) were calculated. DeLong test was used to compare the differences of ROC curves. The forward model of binary logistic regression was applied for parameter fusion. Differences with a P<0.05 were considered statistically significant.

Results

The APT SI and D values showed significant differences between low- and high-grade rectal adenocarcinomas ([2.226±0.347%] vs. [2.668±0.638%], and [0.842±0.148×10-3 mm2/s] vs. [0.777±0.178×10-3 mm2/s], respectively, both P<0.05). Figures 1-2 show image examples from low and high-grade patients. A significant difference of the D value was observed between positive and negative extramural vascular invasion (EMVI) tumors ([0.771±0.175×10-3 mm2/s] vs. [0.858±0.151×10-3 mm2/s], P<0.05). No significant difference of APT SI, D, D*, f or ADC was observed in different T stages, N stages, perineural and lymphovascular invasions (all P>0.05) (Table 1). The AUCs of APT SI and D values in distinguishing low- from high-grade adenocarcinomas were 0.737 and 0.663, respectively. The AUC was increased to 0.806 thought the combination of APT SI and D values (Fig. 3). The AUC of the D value for evaluating EMVI involvement was 0.646 (Fig. 4).

Discussion

In our study, we performed a comprehensive investigation of correlations of APT and IVIM parameters with rectal cancer prognostic factors, in comparison with results by DWI. We demonstrated that the APT SIs of low-grade adenocarcinomas were significantly lower compared to those of high-grade adenocarcinomas. Therefore, APT weighted imaging may be helpful to identify the pathological grade of rectal cancer. The higher APT SIs in high-grade tumors can be due to the abundant proteins production, rapid cell proliferation and angiogenesis. In present study, lower D values were observed in high-grade than those of low-grade rectal adenocarcinomas. The D value, that represents the pure diffusion of free water molecules, was decreased with the increasing cellularity, tight cellular structure in high-grade tumors. Parameters derived from APT and IVIM showed no significant differences between pT1-2 and pT3-4 stages, or between pN1-2 and pN0 stages, further study is needed to evaluate the significance. In addition, the D value was observed to be lower in the positive EMVI group than in the negative group in this study. The high-resolution T2WI images should be combined to improve the diagnosis accuracy of EMVI, which was considered positive if vessel wall irregularity, abnormal extension, suspected the empty signal was replaced by tumor tissue. Additionally, no significant difference of APT and IVIM parameters were found in groups with and without different types of structure invasion in our study, which may be because the tumor microenvironment reflected by APT or IVIM parameters is insufficient to cause significant changes in perineural and lymphovascular invasion.

Conclusion

APT SI and D values were helpful to differentiate the low- and high-grade of rectal adenocarcinoma, and their combination could improve the diagnostic performance. The D value can help determine EMVI status. However, it is still debatable whether APT or IVIM can help distinguish stage, perineural invasion, and lymphovascular invasion. In conclusion, APT and IVIM were helpful to assess tumor grade and EMVI status of the rectal adenocarcinoma.

Acknowledgements

We sincerely thank the participants in this study.

References

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