Korean J Radiol.  2019 May;20(5):801-811. 10.3348/kjr.2018.0453.

Monitoring Response to Neoadjuvant Chemotherapy of Primary Osteosarcoma Using Diffusion Kurtosis Magnetic Resonance Imaging: Initial Findings

• Liu C
• Xi Y
• Li M
• Jiao Q
• Zhang H
• Yang Q
• Yao W

• KMID: 2442714
• DOI: http://doi.org/10.3348/kjr.2018.0453

Abstract

OBJECTIVE
To determine whether diffusion kurtosis imaging (DKI) is effective in monitoring tumor response to neoadjuvant chemotherapy in patients with osteosarcoma.
MATERIALS AND METHODS
Twenty-nine osteosarcoma patients (20 men and 9 women; mean age, 17.6 ± 7.8 years) who had undergone magnetic resonance imaging (MRI) and DKI before and after neoadjuvant chemotherapy were included. Tumor volume, apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), and change ratio (ΔX) between pre- and post-treatment were calculated. Based on histologic response, the patients were divided into those with good response (≥ 90% necrosis, n = 12) and those with poor response (< 90% necrosis, n = 17). Several MRI parameters between the groups were compared using Student's t test. The correlation between image indexes and tumor necrosis was determined using Pearson's correlation, and diagnostic performance was compared using receiver operating characteristic curves.
RESULTS
In good responders, MDpost, ADCpost, and MKpost values were significantly higher than in poor responders (p < 0.001, p < 0.001, and p = 0.042, respectively). The ΔMD and ΔADC were also significantly higher in good responders than in poor responders (p < 0.001 and p = 0.01, respectively). However, no significant difference was observed in ΔMK (p = 0.092). MDpost and ΔMD showed high correlations with tumor necrosis rate (r = 0.669 and r = 0.622, respectively), and MDpost had higher diagnostic performance than ADCpost (p = 0.037) and MKpost (p = 0.011). Similarly, ΔMD also showed higher diagnostic performance than ΔADC (p = 0.033) and ΔMK (p = 0.037).
CONCLUSION
MD is a promising biomarker for monitoring tumor response to preoperative chemotherapy in patients with osteosarcoma.

Keyword

Bone neoplasm; Functional MRI; Diffusion; Treatment

MeSH Terms

Bone Neoplasms
Diffusion*
Drug Therapy*
Female
Humans
Magnetic Resonance Imaging*
Male
Necrosis
Osteosarcoma*
ROC Curve
Tumor Burden

Figure

• 

  Fig. 1 Screenshot of placement of ROI, and DKI parameter maps using Body Diffusion Toolbox (Mathworks).DKI = diffusion kurtosis imaging, ROI = region of interest

• 

  Fig. 2 Nine-year-old female with osteosarcoma in left femur and histopathology of poor responder.Images before (A–F) and after (G–L) chemotherapy are shown. A. Coronal T1WI shows tumor located in metaphysis of left distal femur and extended to diaphysis. B. Axial T2WI with FS shows tumor heterogeneity. C. ADC map shows hyperintense tumor (ADC = 0.97 × 10−3 mm2/s). D. MK map shows mixed high and low signal intensity tumor (MK = 0.85). E. MD map shows mixed high and low signal intensity tumor (MD = 1.37 × 10−3 mm2/s). F. Photomicrography (HE, × 200) confirms osteosarcoma. G. Coronal T2WI shows no significant change in intramedullary extension. H. Axial T2WI with FS magnetic resonance image shows changes in tumor structure compared to that of pre-chemotherapy. I. ADC value increased after chemotherapy (ADC = 1.43 × 10−3 mm2/s). J. MK value decreased after chemotherapy (MK = 0.61). K. MD value also increased after chemotherapy (MD = 1.87 × 10−3 mm2/s). L. Photomicrography (HE, × 200) shows viable cellular areas. Necrosis was found in 60% of tumor. ADC = apparent diffusion coefficient, Dapp = diffusivity map, FS = fat saturation, HE = hematoxylin and eosin stain, Kapp = kurtosis map, MD = mean diffusivity, MK = mean kurtosis, T1WI = T1-weighted imaging, T2WI = T2-weighted imaging

• 

  Fig. 3 Nineteen=year-old male with osteosarcoma and histopathology of good responses to neoadjuvant chemotherapy.Images before (A–F) and after (G–L) chemotherapy are shown. Compared to pre-chemotherapy, tumor size decreased on axial fat-saturated T2WI (B–H) whereas intramedullary extension changed little on coronal T1WI (A, G). ADC value significantly increased from 0.89 × 10−3 mm2/s to 1.72 × 10−3 mm2/s (C, I), whereas MK values significantly decreased from 0.93 to 0.53 (D, J). MD value also significantly increased from 1.26 × 10−3 mm2/s to 2.33 × 10−3 mm2/s (E, K). F. Photomicrography (HE, × 200) showed osteosarcoma with CT-guided biopsy before chemotherapy. L. Photomicrography (HE, × 200) depicts tumor necrosis rate of approximately 95% after chemotherapy.

• 

  Fig. 4 Box plots show ΔMD10th, ΔADC10th, ΔMK10th, and Δtumor volume10th in good responders and poor responders.A. Compared to poor responders, there was statistically significant difference in ΔMD of good responders (p < 0.001). B. ΔADC was significantly higher in good responders than in poor responders (p = 0.010). C. No significant difference in ΔMK was observed between good responders and poor responders (p = 0.092). D. There was also no significant difference in Δtumor volume (p = 0.068). ΔX = change ratio

• 

  Fig. 5 Scatterplot showing relationship between tumor necrosis rate and MDpost and ΔMD.A. MDpost was positively correlated with necrosis rate (r = 0.669, p < 0.001). B. ΔMD also showed positive correlation with necrosis rate (r = 0.622, p < 0.001).

• 

  Fig. 6 A. ROC curves showing diagnostic performance of MDpost, ADCpost, and MKpost in assessing good response to neoadjuvant chemotherapy. MDpost resulted in highest AUC of 0.91 (95% CI: 0.753, 0.986. p < 0.001), and MDpost had higher diagnostic performance than ADCpost (p = 0.037) and MKpost (p = 0.011). B. ROC curves showing diagnostic performance of ΔMD, ΔADC, and ΔMK. ΔMD presented highest AUC (0.92, 95% CI: 0.759, 0.988, p < 0.001), with optimal cutoff value at 13.5% (sensitivity, 100%; specificity, 70.6%), and ΔMD showed higher diagnostic performance than ΔADC (p = 0.033) and ΔMK (p = 0.037). AUC = area under curve, CI = confidence interval, ROC = receiver operating characteristic

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