Introduction

Conventional MRI has been highly regarded for its ability to detect tumours in the follow-up process and to differentiate malignant from benign bladder lesions.¹ However, each of these methods has its own limitations, and generally accepted thresholds for identifying tumour types have not been established.^{2, 3}
Amide proton transfer (APT) imaging, a novel MRI technique based on chemical exchange saturation transfer (CEST), provides more information on subcellular protein levels than current standard MR protocols.⁴
We aimed to investigate the potential of APT imaging in the diagnosis of malignant and benign UB lesions and compare its diagnostic efficacy with that of DWI.

Methods

Eighty patients with UB lesions were enrolled prospectively from a single centre. The MRI scans were conducted on a 3.0T Ingenia system (Philips Healthcare, Best, the Netherlands).
APT signal intensity in UB lesions was quantified by the asymmetric magnetization transfer ratio (MTR_asym). MTR_asym and apparent diffusion coefficient (ADC) values were measured and compared between malignant and benign UB lesions, and their diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis.

Results

In this study, 32 patients had pathologically confirmed benign UB lesions, including 2 bladder leiomyomas, 1 submucosal amyloidosis, 1 inflammatory myofibroblastic tumour and 28 inflammatory lesions, and 48 patients had pathologically confirmed urothelial carcinoma.
Urothelial carcinomas showed significantly higher MTR_asym values (1.53% [0.74%] vs. 0.85% [0.23%]) and lower ADC values (1.24 ± 0.34×10^-3 mm²/s vs. 1.43 ± 0.22×10^-3 mm²/s) than benign UB lesions. The MTR_asym value (AUC = 0.928) was significantly better in differentiating urothelial carcinoma from benign UB lesions than the ADC value (AUC = 0.722) according to the area under the ROC curve.

Discussion

The present results revealed that urothelial carcinoma showed higher MTR_asym values than benign UB lesions. This result may contribute to the higher concentrations of endogenous cellular proteins in malignant UB lesions than in benign UB lesions because malignant UB lesions are characterized by a high proliferation rate and increased cellular density.
In addition, we also found that urothelial carcinoma showed lower ADC values than benign UB lesions. The higher density of tissue cells in malignant UB lesions greatly restricts water molecule diffusion, which accounts for the lower ADC value.
We also compared the diagnostic ability of APT imaging and DWI in differentiating urothelial carcinoma from benign UB lesions. We noticed that the AUC of the MTR_asym value was significantly higher than that of the ADC value. This result showed that the diagnostic performance of APT imaging in differentiating urothelial carcinoma from benign UB lesions is better than that of DWI.
Malignant UB lesions exhibit aggressive biological behaviours and are more likely present with a large tumour size, high nuclear grade, increased cellular density, and high proliferation rate. Perfusion disorders, hypoxia and acidification are intrinsic properties of altered tumour cell metabolism. Cancer cells usually have higher intracellular pH than normal cells when investigated under similar environmental conditions. The sources of the APT signal and contrast, to a large extent, could be attributed to the concentration of endogenous cellular proteins in tissue and the peptides responsible for exchanging amide protons with water protons (pH dependent). Nuclear atypia of malignant tumours can induce the interaction of macromolecules with hydrophobic cell membranes and promote the release of proteins and peptides, and urothelial carcinoma might show a higher pH value, both of which might be responsible for the increase in the MTR_asym value.
The ADC value, a diffusion coefficient reflecting the degree of diffusion of water molecules in tissues, is highly sensitive to cellularity changes. However, the main disadvantage of conventional DWI is that it is nonspecific in terms of microstructure components, and the observed values of the ADC can be affected by, for example, effects of flow apart from the effects of diffusion, the timing of the gradient pulse and the b value. Furthermore, the measured ADC value is acquired by averaging the images collected in a gradient order oriented along three perpendicular directions. The resulting value is only an approximation, which may lead to a large overestimation of the true ADC value in tissues experiencing anisotropic diffusion.

Conclusion

APT imaging has the potential to discriminate malignant from benign UB lesions with a performance superior to that of DWI.

Acknowledgements

No acknowledgement found.

References

1. Lenis AT, Lec PM, Chamie K, et al. Bladder Cancer: A Review. JAMA 2020; 324: 1980.

2. Avcu S, Koseoglu MN, Ceylan K, et al. The value of diffusion-weighted MRI in the diagnosis of malignant and benign urinary bladder lesions. Br J Radiol 2011; 84: 875–882.

3. Wang H, Pui MH, Guo Y, et al. Diffusion-weighted MRI in bladder carcinoma: the differentiation between tumor recurrence and benign changes after resection. Abdom Imaging 2014; 39: 135–141.

4. Kamimura K, Nakajo M, Yoneyama T, et al. Amide proton transfer imaging of tumors: theory, clinical applications, pitfalls, and future directions. Jpn J Radiol 2019; 37: 109–116.