Detection of Microstructural Medial Prefrontal Cortex Changes Using Magnetic Resonance Imaging Texture Analysis in a Post-Traumatic Stress Disorder Rat Model

Background: Radiomics is characterized by high-throughput extraction of texture features from medical images and the mining of information that can potentially be used to define neuroimaging markers in many neurological or psychiatric diseases. However, there have been few studies concerning MRI radiomics in post-traumatic stress disorder (PTSD). The study's aims were to appraise changes in microstructure of the medial prefrontal cortex (mPFC) in a PTSD animal model, specifically single-prolonged stress (SPS) rats, by using MRI texture analysis. The feasibility of using a radiomics approach to classify PTSD rats was examined.

Methods: Morris water maze and elevated plus maze were used to assess behavioral changes in the rats. Two hundred and sixty two texture features were extracted from each region of interest in T2-weighted images. Stepwise discriminant analysis (SDA) and LASSO regression were used to perform feature selection and radiomics signature building to identify mPFC radiomics signatures consisting of optimal features, respectively. Receiver operating characteristic curve plots were used to evaluate the classification performance. Immunofluorescence techniques were used to examine the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) in the mPFC. Nuclear pycnosis was detected using 4',6-diamidino-2-phenylindole (DAPI) staining.

Results: Behavioral results indicated decreased learning and spatial memory performance and increased anxiety-like behavior after SPS stimulation. SDA analysis showed that the general non-cross-validated and cross-validated discrimination accuracies were 86.5% and 80.4%. After LASSO dimensionality reduction, 10 classification models were established. For classifying PTSD rats between the control and each SPS group, these models achieved AUCs of 0.944, 0.950, 0.959, and 0.936. Among four SPS groups, the AUCs were 0.927, 0.943, 0.967, 0.916, 0.932, and 0.893, respectively. The number of GFAP-positive cells and intensity of GFAP-IR within the mPFC increased 1 day after SPS treatment, and then decreased. The intensity of NeuN-IR and number of NeuN-positive cells significantly decreased from 1 to 14 days after SPS stimulation. The brightness levels of DAPI-stained nuclei increased in SPS groups.

Conclusion: Non-invasive MRI radiomics features present an efficient and sensitive way to detect microstructural changes in the mPFC after SPS stimulation, and they could potentially serve as a novel neuroimaging marker in PTSD diagnosis.