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Raman spectroscopic grading of astrocytoma tissues: using soft reference information

  • Claudia Beleites
  • Kathrin Geiger
  • Matthias Kirsch
  • Stephan B. Sobottka
  • Gabriele Schackert
  • Reiner Salzer
Original Paper

Abstract

Gliomas are the most frequent primary brain tumours. During neurosurgical treatment, locating the exact tumour border is often difficult. This study assesses grading of astrocytomas based on Raman spectroscopy for a future application in intra-surgical guidance. Our predictive classification models distinguish the surgically relevant classes “normal tissue” and “low” and “high grade astrocytoma” in Raman maps of moist bulk samples (80 patients) acquired with a fibre-optic probe. We introduce partial class memberships as a strategy to utilize borderline cases for classification. Borderline cases supply the most valuable training and test data for our application. They are (a) examples of the sought boundary and (b) the cases for which new diagnostics are needed. Besides, the number of suitable training samples increases considerably: soft logistic regression (LR) utilizes 85% more spectra and 50% more patients than linear discriminant analysis (LDA). The predictive soft LR models achieve ca. 85, 67 and 84% (normal, low and high grade) sensitivity and specificity. We discuss the different heuristics of LR and LDA in the light of borderline samples. While we focus on prediction, the spectroscopic interpretation of the predictive models agrees with previous descriptive studies. Unsaturated lipids are used to differentiate between normal and tumour tissues, while the total lipid content prominently contributes to the determination of the tumour grade. The high-wavenumber region above 2,800 cm−1 alone did not allow successful grading. We give a proof of concept for Raman spectroscopic grading of moist astrocytoma tissues and propose to include borderline samples into classifier training and testing.

Keywords

Gliomas Astrocytomas Grading Classification Tumour Raman spectroscopy Linear discriminant analysis Logistic regression Soft classification 

Notes

Acknowledgements

C. Beleites acknowledges financial support by a scholarship of Deutsche Telekom Stiftung, the IRCCS Burlo Garofolo and the Associazione per i Bambini Chirurgici del Burlo.

Supplementary material

216_2011_4985_MOESM1_ESM.pdf (486 kb)
ESM 1 Fig. S1. More detailed version of the diagram in Fig. 8: the stability of the predictions of the different models (columns) for each predicted class separately (rows). The boxes mark median and quartiles, the whiskers extend to the last value inside 1.5 IQR from the box, all further values are marked by points [47]. Fig. S2. Both MAE and RMSE have the same pattern across the models, and are very similar for all but the LR–highwn models. Low-grade tissues are the most difficult class as they lie in between the normal and high-grade tumour tissue: normal tissue is confused with low-grade tumours, but not with high-grade tissue, and vice versa. The soft LR models have slightly increased MAE for the predicted memberships of crisply labelled spectra, which is counterweighted by a decreased MAE of the soft spectra. Their RMSE does not show this increase in these cases, but rather an improvement. Also the improvement for soft samples is more pronounced. Together, these findings allow the conclusion that the LR–soft models have more small deviations from the reference, while the LR–crisp and LDA models have larger deviations for fewer spectra. This is in accordance with the LR–soft modelling smoother class transitions. The boxes mark median and quartiles, the whiskers extend to the last value inside 1.5 IQR from the box, all further values are marked by points [47]. Fig. S3. Upper part: detailed Versions of the contributions to the rotated LDA model: median and quartiles, lower part: spectra before (bottom; black: mean normal grey matter spectrum subtracted for “centering”) and after “centering” (second lowest row). Fig. S4. Performance of the LDA (continuous) and crisp LR (dashed) models (top row), and crisp and soft LR (lower row), respectively: median, 5th and 95th percentiles observed over the 125 iterations of the cross-validation, thresholds 0.01–0.99. Both LDA and crisp LR models have virtually the same performance for the low-grade tumours, and LDA reaches slightly higher sensitivities for normal tissue. The advantage of the LDA models is most pronounced for the high-grade tumours. Soft LR outperforms crisp LR for all classes, the improvement is most pronounced for normal tissue, but most important for A °II (PDF 485 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Claudia Beleites
    • 1
    • 2
  • Kathrin Geiger
    • 3
  • Matthias Kirsch
    • 3
  • Stephan B. Sobottka
    • 3
  • Gabriele Schackert
    • 3
  • Reiner Salzer
    • 2
  1. 1.CENMAT and DI3University of TriesteTriesteItaly
  2. 2.Analytical ChemistryDresden University of TechnologyDresdenGermany
  3. 3.University Hospital Carl-Gustav CarusDresden University of TechnologyDresdenGermany

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