ObjectivesThis study aims to explore the role of quantitative intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in characterizing changes in osteosarcoma (OS) patients receiving neoadjuvant chemotherapy (NACT). Material and methodsTwenty-seven patients with histologically proven OS were examined prospectively and divided into good-response group (n = 14) and poor-response group (n = 13). IVIM and DCE-MRI sequences were performed at baseline (pre-NACT) and after three cycles of NACT (post-NACT). Apparent diffusion coefficient (ADC) and IVIM bi-exponential model parameters, including diffusion coefficient (D-Bi), perfusion coefficient (D*-Bi), and perfusion fraction (f-Bi), were evaluated. DCE-MRI parameters, including quantitative parameters (volume transfer constant [Ktrans], elimination rate constant [Kep], and extravascular extracellular space volume ratio [Ve]) and semi-quantitative parameters (initial area under the gadolinium curve [IAUGC] and contrast enhancement rate [CER]), were also measured. ResultsD-Bi, D*-Bi, and f-Bi post-NACT and ΔD-Bi were statistically different between the good- and poor-response groups (Z1 = − 3.348, Z2 = − 2.572, Z3 = − 2.378, t = 2.235, P < 0.05). ADC, f-Bi, Ktrans, IAUGC, Kep, and CER post-NACT were statistically different from those at pre-NACT (P < 0.05). The receiver operating characteristic curve showed that f-Bi post-NACT had the best performance among all parameters, with area under the curve of 0.769, sensitivity of 1, and specificity of 0.538. The correlation analysis showed that the efficacy of NACT was negatively correlated with D-Bi, D*-Bi post-NACT, and ΔD-Bi (r1 = − 0.530, r2 = − 0.411, r3 = − 0.434, P1 = 0.008, P2 = 0.046, P3 = 0.034) and significantly positively correlated with f-Bi post-NACT (r = 0.482, P = 0.017). ConclusionsThe IVIM quantitative parameters D-Bi, D*-Bi, and f-Bi post-NACT and ΔD-Bi could be used as noninvasive imaging biomarkers for early response assessment of NACT in OS.