Esha Baidya Kayal1, Devasenathipathy Kandasamy2, Kedar Khare3, Sameer Bakhshi4, Raju Sharma2, Amit Mehndiratta5. 1. Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India. 2. Department of Radiology, All India Institute of Medical Sciences, New Delhi, India. 3. Department of Physics, Indian Institute of Technology Delhi, New Delhi, India. 4. Department of Medical Oncology, Dr. B.R. Ambedkar Institute-Rotary Cancer Hospital (IRCH), All India Institute of Medical Sciences, New Delhi, India. 5. Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India; Department of Biomedical Engineering, All India Institute of Medical Sciences, New Delhi, India. Electronic address: amit.mehndiratta@keble.oxon.org.
Abstract
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.
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.