Raman spectroscopy and convolutional neural networks for monitoring biochemical radiation response in breast tumour xenografts.

Tumour cells exhibit altered metabolic pathways that lead to radiation resistance and disease progression. Raman spectroscopy (RS) is a label-free optical modality that can monitor post-irradiation biomolecular signatures in tumour cells and tissues. Convolutional Neural Networks (CNN) perform automated feature extraction directly from data, with classification accuracy exceeding that of traditional machine learning, in cases where data is abundant and feature extraction is challenging. We are interested in developing a CNN-based predictive model to characterize clinical tumour response to radiation therapy based on their degree of radiosensitivity or radioresistance. In this work, a CNN architecture is built for identifying post-irradiation spectral changes in Raman spectra of tumour tissue. The model was trained to classify irradiated versus non-irradiated tissue using Raman spectra of breast tumour xenografts. The CNN effectively classified the tissue spectra, with accuracies exceeding 92.1% for data collected 3 days post-irradiation, and 85.0% at day 1 post-irradiation. Furthermore, the CNN was evaluated using a leave-one-out- (mouse, section or Raman map) validation approach to investigate its generalization to new test subjects. The CNN retained good predictive accuracy (average accuracies 83.7%, 91.4%, and 92.7%, respectively) when little to no information for a specific subject was given during training. Finally, the classification performance of the CNN was compared to that of a previously developed model based on group and basis restricted non-negative matrix factorization and random forest (GBR-NMF-RF) classification. We found that CNN yielded higher classification accuracy, sensitivity, and specificity in mice assessed 3 days post-irradiation, as compared with the GBR-NMF-RF approach. Overall, the CNN can detect biochemical spectral changes in tumour tissue at an early time point following irradiation, without the need for previous manual feature extraction. This study lays the foundation for developing a predictive framework for patient radiation response monitoring.

Raman microspectroscopy and machine learning for use in identifying radiation-induced lung toxicity.

OBJECTIVE: In this work, we explore and develop a method that uses Raman spectroscopy to measure and differentiate radiation induced toxicity in murine lungs with the goal of setting the foundation for a predictive disease model. METHODS: Analysis of Raman tissue data is achieved through a combination of techniques. We first distinguish between tissue measurements and air pockets in the lung by using group and basis restricted non-negative matrix factorization. We then analyze the tissue spectra using sparse multinomial logistic regression to discriminate between fibrotic gradings. Model validation is achieved by splitting the data into a training set containing 70% of the data and a test set with the remaining 30%; classification accuracy is used as the performance metric. We also explore several other potential classification tasks wherein the response considered is the grade of pneumonitis and fibrosis sickness. RESULTS: A classification accuracy of 91.6% is achieved on the test set of fibrotic gradings, illustrating the ability of Raman measurements to detect differing levels of fibrotic disease among the murine lungs. It is also shown via further modeling that coarser consideration of fibrotic grading via binning (ie. 'Low', 'Medium', 'High') does not degrade performance. Finally, we consider preliminary models for pneumonitis discrimination using the same methodologies.