Amide proton transfer-weighted magnetic resonance imaging for the diagnosis of triple-negative breast cancer: a comparative study with diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging.

Background: Amide proton transfer-weighted (APTw) imaging is an emerging molecular magnetic resonance imaging (MRI) technique that enables the noninvasive quantification of endogenous mobile proteins and peptides. This study aimed to preliminarily evaluate the diagnostic performance of multipool chemical exchange saturation transfer (CEST)-derived parameters for differentiating benign from malignant breast lesions and identifying triple-negative breast cancer (TNBC) and to compare this modality with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI). Methods: This prospective single-center study included 148 patients with breast lesions who underwent 3 T APTw, DWI, and DCE-MRI examinations. Pathological results were used to classify lesions as benign or malignant and to determine molecular subtypes based on immunohistochemistry. Twelve CEST-derived metabolic parameters, the apparent diffusion coefficient (ADC), and DCE-MRI parameters [volume transfer constant (Ktrans), rate constant (Kep), and extracellular extravascular volume fraction (Ve)] were compared between benign and malignant lesions, as well as between TNBC and non-TNBC subtypes. Diagnostic performance was assessed via the receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculations. Results: A total of 148 breast lesions were included in the analysis, among which 43 were benign and 105 malignant [luminal A: n=26; luminal B: n=31; human epidermal growth factor receptor 2 (HER2)-enriched: n=16; TNBC: n=32]. Among the 12 metabolic parameters from APTw imaging, only amide values of the malignant group were significantly higher than those of the benign group (P=0.002). Malignant lesions also exhibited lower ADC values and higher Ktrans and Kep values (P<0.05). The combination of amide, ADC, Ktrans, and Kep yielded an AUC of 0.932 [95% confidence interval (CI): 0.891-0.968]. For differentiating TNBC from non-TNBC, the CEST-derived parameter downfield nuclear Overhauser effect-suppressed apparent exchange-dependent relaxation (DNS-AREX) showed significant differences, achieving an AUC of 0.762 (95% CI: 0.665-0.842), with a sensitivity of 91.7% and a specificity of 68.5%. No significant differences were observed for DWI or DCE-MRI parameters between TNBC and non-TNBC. Conclusions: Multipool CEST provides complementary value to conventional MRI for breast lesion characterization. The CEST-derived parameter DNS-AREX demonstrated a modest but statistically significant ability to identify TNBC, while conventional DWI and DCE-MRI parameters did not exhibit significant predictive ability. APTw imaging may serve as a noninvasive imaging biomarker for molecular subtyping in breast cancer.