Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.
Department of Radiology, All India Institute of Medical Sciences, New Delhi, India.
Eur J Radiol. 2019 Oct;119:108635. doi: 10.1016/j.ejrad.2019.08.004. Epub 2019 Aug 10.
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.
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/mm) 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.
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 mm/s, 1.3 ± 0.3 × 10 mm/s, 28.44 ± 10.34 × 10 mm/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.
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.
探讨定量体素内不相干运动（IVIM）参数及其直方图分析在评估骨肉瘤接受新辅助化疗（NACT）后变化及评估治疗反应中的作用。
前瞻性分析 40 例经组织学证实的骨肉瘤患者（N=40；男：女=30：10；年龄=17.7±5.9 岁；转移：局部=17：23），这些患者接受了 3 个周期的 NACT。所有患者均在治疗前（t0）、1 个周期后（t1）和 3 个周期后（t2）使用 1.5T MRI 扫描仪进行 11 个 b 值（0-800 s/mm）的弥散加权成像（DWI）。使用 RECIST1.1 标准进行 NACT 的无创反应评估。评估治疗前（t0）、治疗后 1 个周期（t1）和治疗后 2 个周期（t2）时的表观扩散系数（ADC）和 IVIM 参数-扩散系数（D）、灌注系数（D*）和灌注分数（f）及其相对于 t0-t1（Δ2）和 t0-t2（Δ2）的相对百分比变化，并在三个时间点进行直方图分析，并与 RECIST1.1 评分进行比较。
根据 RECIST1.1 标准，11 例（27.5%）、21 例（52.5%）和 8 例（20%）患者分别为部分缓解（PR）、稳定疾病（SD）和进展性疾病（PD）组。治疗前（t0），肿瘤体积的平均 ADC、D、D和 f 值分别为 1.36±0.33×10 mm/s、1.3±0.3×10 mm/s、28.44±10.34×10 mm/s 和 13.95±2.83%。使用方差分析检验，在 NACT 期间（t1、t2），D-方差（p=0.038，0.003）和 f-偏度（p=0.03，0.03），以及在 t2 时，D*-熵（p=0.001）和 f-熵（p=0.002）及其 Δ2 变化（p=0.001，0.003）在不同反应组之间具有统计学意义。在 t1 时，D*-方差和 f-偏度联合对 PR（灵敏度=73%；特异性=70%）和 SD（灵敏度=74%；特异性=75%）组进行分类，AUC 分别为 0.77 和 0.74。在患者队列中。D*-均值、D*-方差、D*-熵和 f-熵的 Δ1 和 Δ2 变化与肿瘤直径和肿瘤体积的变化相关性良好（0.5-0.6）。
定量 IVIM 参数，特别是 D*和 f 及其直方图分析是有用的，可以作为骨肉瘤 NACT 过程中早期反应评估的无创替代标志物。
