Introduction: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. Methods: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. Results: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). Conclusion: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.

Amide proton transfer (APT) MRI, a novel molecular MRI technique, could indirectly measure the peptide or protein concentration within tissues based on frequent exchange between amide proton and the surrounding water protons. This new technology has been used in tumor diagnosis. Given pathological conditions linked to tissue fibrogenesis are similar to carcinogenesis, we proposed the hypothesis that APT MRI can be applied to assess collagen deposition in RF. To test this, we constructed animal models for RF and enrolled CKD patients, respectively. The results suggested APT values were more sensitive to the early stage of fibrosis than ADC values, and the cortical APT was highly positively correlated with the degree of fibrosis. We further identified that the combination of two MRI protocols, cortical apparent diffusion coefficient and cortical APT, was an excellent indicator for the diagnosis of fibrosis, with much higher accuracy than a single method. To the best of our knowledge, this is the first study to explore the value of APT imaging for assessing renal interstitial fibrosis. Our findings identify APT as a novel and precise imaging diagnostic tool for future noninvasive assessment of RF. It complements with the existing imaging biomarkers and adds value to conventional MRI.

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