Skip to main content
Log in

SLIC-supervoxels-based response evaluation of osteosarcoma treated with neoadjuvant chemotherapy using multi-parametric MR imaging

  • Oncology
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objective

Histopathological examination (HPE) is the current gold standard for assessing chemotherapy response to tumor, but it is possible only after surgery. The purpose of the study was to develop a noninvasive, imaging-based robust method to delineate, visualize, and quantify the proportions of necrosis and viable tissue present within the tumor along with peritumoral edema before and after neoadjuvant chemotherapy (NACT) and to evaluate treatment response with correlation to HPE necrosis after surgery.

Methods

The MRI dataset of 30 patients (N = 30; male:female = 24:6; age = 17.6 ± 2.7 years) with osteosarcoma was acquired using 1.5 T Philips Achieva MRI scanner before (baseline) and after 3 cycles of NACT (follow-up). After NACT, all patients underwent surgical resection followed by HPE. Simple linear iterative clustering supervoxels and Otsu multithresholding were combined to develop the proposed method—SLICs+MTh—to subsegment and quantify viable and nonviable regions within tumor using multiparametric MRI. Manually drawn ground-truth ROIs and SLICs+MTh-based segmentation of tumor, edema, and necrosis were compared using Jacquard index (JI), Dice coefficient (DC), precision (P), and recall (R). Postcontrast T1W images (PC-T1W) were used to validate the SLICs+MTh-based necrosis. SLICs+MTh-based necrosis volume at follow-up was compared with HPE necrosis using paired t test (p ≤ 0.05).

Results

Active tumor, necrosis, and edema were segmented with moderate to satisfactory accuracy (JI = 62–78%; DC = 72–87%; P = 67–87%; R = 63–88%). Qualitatively and quantitatively (DC = 74 ± 9%), the SLICs+MTh-based necrosis area correlated well with the hypointense necrosis areas in PC-T1W. No significant difference (paired t test, p = 0.26; Bland–Altman plot, bias = 2.47) between SLICs+MTh-based necrosis at follow-up and HPE necrosis was observed.

Conclusion

The proposed multiparametric MRI-based SLICs+MTh method performs noninvasive assessment of NACT response in osteosarcoma that may improve cancer treatment monitoring, planning, and overall prognosis.

Key Points

• The simple linear iterative clustering supervoxels and Otsu multithresholding-based technique (SLICs+MTh) successfully estimates the proportion of necrosis, viable tumor, and edema in osteosarcoma in the course of chemotherapy.

• The proposed technique is noninvasive and uses multiparametric MRI to measure necrosis as an indication of anticancer treatment response.

• SLICs+MTh-based necrosis was in satisfactory agreement with histological necrosis after surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

DC:

Dice coefficient

DWI800 :

Diffusion weighting factor of 800 s/mm2

HPE:

Histopathological examination

JI:

Jacquard index

NACT:

Neoadjuvant chemotherapy

NR:

Non responder

P:

Precision

PR:

Partial responder

R:

Recall

SLICs+MTh:

Simple linear iterative clustering supervoxels and Otsu multithresholding

T2W-fatsat:

T2-weighted with fat saturation

References

  1. Landis SH, Murray T, Bolden S, Wingo PA (1999) Cancer statistics, 1999. CA Cancer J Clin 49:8–31. https://doi.org/10.3322/canjclin.49.1.8

    Article  CAS  PubMed  Google Scholar 

  2. Bacci G, Picci P, Ferrari S et al (1993) Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin. Cancer 72:3227–3238. https://doi.org/10.1002/1097-0142(19931201)72:11<3227::AID-CNCR2820721116>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  3. Bacci G, Briccoli A, Ferrari S et al (2001) Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli’s 4th protocol. Eur J Cancer 37:2030–2039. https://doi.org/10.1016/S0959-8049(01)00229-5

    Article  CAS  PubMed  Google Scholar 

  4. Wittig JC, Bickels J, Priebat D et al (2002) Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. Am Fam Physician 65:1123–1132. https://doi.org/10.1111/j.1529-8019.2010.01352.x

    Article  PubMed  Google Scholar 

  5. Wang C, Du L, Si M et al (2013) Noninvasive assessment of response to neoadjuvant chemotherapy in osteosarcoma of long bones with diffusion-weighted imaging: an initial in vivo study. PLoS One 8:e72679. https://doi.org/10.1371/journal.pone.0072679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tatum JL, Gillies R, Arbeit JM et al (2006) Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. Int J Radiat Biol 82:699–757. https://doi.org/10.1080/09553000601002324

    Article  CAS  PubMed  Google Scholar 

  7. Rejniak KA, Lloyd MC, Reed DR, Bui MM (2015) Diagnostic assessment of osteosarcoma chemoresistance based on virtual clinical trials. Med Hypotheses 85:348–354. https://doi.org/10.1016/j.mehy.2015.06.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Arunachalam HB, Mishra R, Armaselu B et al (2017) Computer aided image segmentation and classification for viable and non-viable tumor identification in osteosarcoma. Pac Symp Biocomput 22:195–206. https://doi.org/10.1142/9789813207813_0020

    Article  PubMed  Google Scholar 

  9. Mishra R, Daescu O, Leavey P, et al (2017) Histopathological diagnosis for viable and non-viable tumor prediction for osteosarcoma using convolutional neural network. In: Cai Z, Daescu O, Li M (eds) Bioinformatics research and applications. ISBRA 2017. Lecture notes in computer science. Springer, Cham

    Chapter  Google Scholar 

  10. Ayala A, Zomosa J (1983) Primary bone tumors: percutaneous needle biopsy. Radiologic-pathologic study of 222 biopsies. Radiology 149:675–679. https://doi.org/10.1148/radiology.149.3.6580673

    Article  CAS  PubMed  Google Scholar 

  11. Brisse H, Ollivier L, Edeline V et al (2004) Imaging of malignant tumours of the long bones in children: monitoring response to neoadjuvant chemotherapy and preoperative assessment. Pediatr Radiol 34:595–605. https://doi.org/10.1007/s00247-004-1192-x

    Article  PubMed  Google Scholar 

  12. Leung JC, Dalinka MK (2000) Magnetic resonance imaging in primary bone tumors. Semin Roentgenol 35:297–305. https://doi.org/10.1053/sroe.2000.7340

    Article  CAS  PubMed  Google Scholar 

  13. Fletcher BD (1991) Response of osteosarcoma and Ewing sarcoma to chemotherapy: imaging evaluation. AJR Am J Roentgenol 157:825–833. https://doi.org/10.2214/ajr.157.4.1892044

    Article  CAS  PubMed  Google Scholar 

  14. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  15. Hylton N (2007) Dynamic contrast-enhanced magnetic resonance imaging as an imaging biomarker. J Clin Oncol 24:3293–3298. https://doi.org/10.1200/JCO.2006.06.8080

    Article  CAS  Google Scholar 

  16. Iima M, Le Bihan D (2016) Clinical intravoxel incoherent motion and diffusion MR imaging: past, present, and future. Radiology 278:13–32. https://doi.org/10.1148/radiol.2015150244

    Article  PubMed  Google Scholar 

  17. Harry VN, Semple SI, Parkin DE, Gilbert FJ (2010) Use of new imaging techniques to predict tumour response to therapy. Lancet Oncol 11:92–102. https://doi.org/10.1016/S1470-2045(09)70190-1

    Article  PubMed  Google Scholar 

  18. Deng J, Wang Y (2017) Quantitative magnetic resonance imaging biomarkers in oncological clinical trials: current techniques and standardization challenges. Chronic Dis Transl Med 3:8–20. https://doi.org/10.1016/j.cdtm.2017.02.002

    Article  PubMed  PubMed Central  Google Scholar 

  19. Monsky W, Jin B, Molloy C et al (2012) Semi-automated volumetric quantification of tumor necrosis in soft tissue sarcoma using contrast enhanced MRI. Anticancer Res 32:4951–4961

    PubMed  PubMed Central  Google Scholar 

  20. Monsky WL, Garza AS, Kim I et al (2011) Treatment planning and volumetric response assessment for yttrium-90 radioembolization: semiautomated determination of liver volume and volume of tumor necrosis in patients with hepatic malignancy. Cardiovasc Intervent Radiol 34:306–318. https://doi.org/10.1007/s00270-010-9938-3

    Article  PubMed  Google Scholar 

  21. Ranga A, Agarwal Y, Garg KJ (2017) Gadolinium based contrast agents in current practice: risks of accumulation and toxicity in patients with normal renal function. Indian J Radiol Imaging 27:141–147. https://doi.org/10.4103/0971-3026.209212

    Article  PubMed  PubMed Central  Google Scholar 

  22. Grobner T (2006) Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108. https://doi.org/10.1093/ndt/gfk062

    Article  CAS  PubMed  Google Scholar 

  23. Koh DM, Collins DJ (2007) Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol 188:1622–1635. https://doi.org/10.2214/AJR.06.1403

    Article  Google Scholar 

  24. Achanta R, Shaji A, Smith K, Lucchi A, Fua P, Süsstrunk S (2012) SLIC superpixels compared to state-of-the-art superpixel methods. IEEE Trans Pattern Anal Mach Intell 34:2274–2281. https://doi.org/10.1109/TPAMI.2012.120

    Article  Google Scholar 

  25. Otsu N (1979) A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 9:62–66. https://doi.org/10.1109/TSMC.1979.4310076

    Article  Google Scholar 

  26. ESMO/European Sarcoma Network Working Group (2012) Bone sarcomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23:vii100–vii109. https://doi.org/10.1093/annonc/mds254

    Article  Google Scholar 

  27. Salzer-Kuntschik M, Brand G, Delling G (1983) Determination of the Degree of Morphological Regression Following Chemotherapy in Malignant Bone Tumors. Pathologie 4:135–141

    CAS  Google Scholar 

  28. Verma K, Kumar Singh B, Thokec AS (2015) An enhancement in adaptive median filter for edge preservation. Procedia Comput Sci 48:29–36. https://doi.org/10.1016/j.procs.2015.04.106

    Article  Google Scholar 

  29. Sredhar K, Panlal B (2012) Enhancement of images using morphological transformations. Int J Comput Sci Inf Technol 4:33–50. https://doi.org/10.5121/ijcsit.2012.4103

    Article  Google Scholar 

  30. Soltaninejad M, Yang G, Lambrou T et al (2017) Automated brain tumour detection and segmentation using superpixel-based extremely randomized trees in FLAIR MRI. Int J CARS 12:183–203. https://doi.org/10.1007/s11548-016-1483-3

    Article  Google Scholar 

  31. Adjei PE, Nunoo-mensah H, Agbesi RJA, Ndjanzoue JRY (2018) Brain tumor segmentation using SLIC superpixels and optimized thresholding algorithm. Int J Comput Appl 181:1–5. https://doi.org/10.5120/ijca2018917915

    Article  Google Scholar 

  32. Liao X, Zhao J, Jiao C, Lei L, Qiang Y, Cui Q (2016) A segmentation method for lung parenchyma image sequences based on superpixels and a self-generating neural forest. PLoS One 11:e0160556. https://doi.org/10.1371/journal.pone.0160556

    Article  Google Scholar 

  33. Tian Z, Liu L, Zhang Z, Fei B (2017) Superpixel-based segmentation for 3D prostate MR images. IEEE Trans Med Imaging 35:791–801. https://doi.org/10.1109/TMI.2015.2496296

    Article  Google Scholar 

  34. Nishio M, Kono AK, Kubo K, Koyama H, Nishii T, Sugimura K (2015) Tumor segmentation on 18F FDG-PET images using graph cut and local spatial information. Open J Med Imaging 5:174–181. https://doi.org/10.4236/ojmi.2015.53022

    Article  Google Scholar 

  35. Conze P, Noblet V, Rousseau F, Heitz F, Memeo R, Pessaux P (2016) Random forests on hierarchical multi-scale supervoxels for liver tumor segmentation in dynamic contrast-enhanced CT scans. International symposium on biomedical imaging (ISBI). pp 416–419

  36. Just N (2014) Improving tumour heterogeneity MRI assessment with histograms. Br J Cancer 111:2205–2213. https://doi.org/10.1038/bjc.2014.512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Costelloe CM, Raymond AK, Fitzgerald NE et al (2010) Tumor necrosis in osteosarcoma: inclusion of the point of greatest metabolic activity from F-18 FDG PET / CT in the histopathologic analysis. Skeletal Radiol 39:131–140. https://doi.org/10.1007/s00256-009-0785-8

    Article  PubMed  Google Scholar 

  38. Young H, Baum R, Cremerius U et al (1999) Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. Eur J Cancer 35:1773–1782

    Article  CAS  Google Scholar 

  39. Raymond A, Chawla S, Carrasco C et al (1987) Osteosarcoma chemotherapy effect: a prognostic factor. Semin Diagn Pathol 4:212–236

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank and acknowledge the valuable input of the intern, Sneha Patil, in data processing and various stages of implementation of the proposed algorithm. The authors would also like to acknowledge the support from Dr. Thilaka Muthiah for copyediting the manuscript for grammar, language, and clarity and the cooperation from MRI technicians Mr. Lalit Gupta and Mr. Udit Kumar during MRI data acquisition.

Funding

This study has not received any funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amit Mehndiratta.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Dr. Amit Mehndiratta, Assistant Professor, Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, India, and Department of Biomedical Engineering, All India Institute of Medical Sciences, Delhi, India.

Conflict of interest

The authors declare that they have no conflict of interest.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained with reference number: IEC-103/05.02.2016, RP-26/2016. Approving body: Institute Ethics Committee, Room No.-102, First-Floor, Old O.T.Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110,029, India.

Methodology

• Prospective

• Diagnostic or prognostic study

• Performed at one institution

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 14236 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baidya Kayal, E., Kandasamy, D., Sharma, R. et al. SLIC-supervoxels-based response evaluation of osteosarcoma treated with neoadjuvant chemotherapy using multi-parametric MR imaging. Eur Radiol 30, 3125–3136 (2020). https://doi.org/10.1007/s00330-019-06647-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-019-06647-1

Keywords

Navigation