Radiologists' Rating for Comparative Qualitative Assessment of Intravoxel Incoherent Motion Using Novel Analysis Methods.

OBJECTIVE: The objective was to assess qualitative interpretability and quantitative precision and reproducibility of intravoxel incoherent motion ( IVIM) parametric images evaluated using novel IVIM analysis methods for diagnostic accuracy. METHODS: Intravoxel incoherent motion datasets of 55 patients (male/female = 41:14; age = 17.8 ± 5.5 years) with histopathology-proven osteosarcoma were analyzed. Intravoxel incoherent motion parameters-diffusion coefficient ( D ), perfusion fraction ( f ), and perfusion coefficient ( D* )-were estimated using 5 IVIM analysis methods-(i) biexponential (BE) model, (ii) BE-segmented fitting 2-parameter (BESeg-2), (iii) BE-segmented fitting 1-parameter (BESeg-1), (iv) BE model with total variation penalty function (BE + TV), and (v) BE model with Huber penalty function (BE + HPF). Qualitative scoring in a 5-point Likert scale (uninterpretable: 1; poor: 2; fair: 3; good: 4; excellent: 5) was performed by 2 radiologists for 4 criteria: (a) tumor shape and margin, (b) morphologic correlation, (c) noise suppression, and (d) overall interpretability. Interobserver agreement was evaluated using Spearman rank-order correlation ( rs ). Precision and reproducibility were evaluated using within-subject coefficient of variation (wCV) and between-subject coefficient of variation (bCV). RESULTS: BE + TV and BE + HPF produced significantly ( P < 10 -3 ) higher qualitative scores for D (fair-good [3.3-3.8]) than BE (poor [2.3]) and for D* (poor-fair [2.2-2.7]) and f (fair-good [3.2-3.8]) than BE, BESeg-2, and BESeg-1 ( D* : uninterpretable-poor [1.3-1.9] and f : poor-fair [1.5-3]). Interobserver agreement for qualitative scoring was rs = 0.48-0.59, P < 0.009. BE + TV and BE + HPF showed significantly ( P < 0.05) improved reproducibility in estimating D (wCV: 24%-31%, bCV: 21%-31% improvement) than the BE method and D* (wCV: 4%-19%, bCV: 5%-19% improvement) and f (wCV: 25%-49%, bCV: 25%-47% improvement) than BE, BESeg-2, and BESeg-1 methods. CONCLUSIONS: BE + TV and BE + HPF demonstrated qualitatively and quantitatively improved IVIM parameter estimation and may be considered for clinical use further.

Intravoxel incoherent motion (IVIM) for response assessment in patients with osteosarcoma undergoing neoadjuvant chemotherapy.

PURPOSE: To explore the role of quantitative Intravoxel incoherent motion (IVIM) parameters and their histogram analysis in characterizing changes in Osteosarcoma receiving neoadjuvant chemotherapy (NACT) and evaluating therapeutic response. METHODS: Forty patients (N = 40; Male:Female = 30:10; Age = 17.7 ± 5.9years; Metastatic:localized = 17:23) with histologically confirmed Osteosarcoma treated with 3-cycles of NACT were analyzed prospectively. All patients underwent Diffusion weighted imaging (DWI) with 11 b-values (0-800 s/mm2) using 1.5 T MRI scanner at pre-treatment (t0), after 1-cycle (t1) and after 3-cycles (t2) of NACT. Non-invasive response evaluation of NACT was performed using RECIST1.1 criteria. Apparent-diffusion-coefficient (ADC) and IVIM parameters - Diffusion-coefficient (D), Perfusion-coefficient (D*) & Perfusion-fraction (f) and their relative percentage changes from time-point t0-t1 (Δ2) and t0-t2 (Δ2) were evaluated and histogram analysis was performed at three time-points and compared with respect to RECIST1.1 scores. RESULTS: Using RECIST1.1 criteria, 11 (27.5%), 21 (52.5%) and 8 (20%) patients were in Partial-responder (PR), Stable-disease (SD) and Progressive-disease (PD) groups respectively. Pre-NACT (t0), average ADC, D,D*&f in tumor volume were 1.36 ± 0.33 × 10-3 mm2/s, 1.3 ± 0.3 × 10-3 mm2/s, 28.44 ± 10.34 × 10-3 mm2/s & 13.95 ± 2.83% respectively. Using ANOVA test, during NACT (t1, t2), D*-variance (p = 0.038, 0.003) and f-skewness (p = 0.03, 0.03) and at t2, D*-entropy (p = 0.001) and f-entropy (p = 0.002) and their Δ2 changes (p = 0.001, 0.003) were statistically significant among response groups. At t1, D*-variance and f-skewness jointly showed AUC = 0.77 & 0.74 in classifying PR (Sensitivity = 73%; Specificity = 70%) and SD (Sensitivity = 74; Specificity = 75%) groups respectively in patient cohort. Δ1 & Δ2 changes of D*-mean, D*-variance, D*-entropy and f-entropy correlated well (0.5-0.6) with tumor-diameter and tumor-volume changes. CONCLUSIONS: Quantitative IVIM parameters, especially D* &f and their histogram analysis were informative and can be used as noninvasive surrogate markers for early response assessment during the course of NACT in Osteosarcoma.