Abstract
Hypertrophic scars remain a major clinical problem in the rehabilitation of burn survivors and lead to physical, aesthetic, functional, psychological, and social stresses. Prediction of healing outcome and scar formation is critical for deciding on the best treatment plan. Both subjective and objective scales have been devised to assess scar severity. Whereas scales of the first type preclude cross-comparison between observers, those of the second type are based on imaging modalities that either lack the ability to image individual layers of the scar or only provide very limited fields of view. To overcome these deficiencies, this work aimed at developing a predictive model of scar formation based on polarization sensitive optical frequency domain imaging (PS-OFDI), which offers comprehensive subsurface imaging. We report on a linear regression model that predicts the size of a scar 6 months after third-degree burn injuries in rats based on early post-injury PS-OFDI and measurements of scar area. When predicting the scar area at month 6 based on the homogeneity and the degree of polarization (DOP), which are signatures derived from the PS-OFDI signal, together with the scar area measured at months 2 and 3, we achieved predictions with a Pearson coefficient of 0.57 (p < 10−4) and a Spearman coefficient of 0.66 (p < 10−5), which were significant in comparison to prediction models trained on randomly shuffled data. As the model in this study was developed on the rat burn model, the methodology can be used in larger studies that are more relevant to humans; however, the actual model inferred herein is not translatable. Nevertheless, our analysis and modeling methodology can be extended to perform larger wound healing studies in different contexts. This study opens new possibilities for quantitative and objective assessment of scar severity that could help to determine the optimal course of therapy.
Highlights
Burns is a global public health problem, accounting for an estimated 265,000 deaths annually (WHO, 2016)
We used the homogeneity of the birefringence (Hom) and the slope of the degree of polarization (DOP) (DOPSlope) as signatures derived from the polarization sensitive optical frequency domain imaging (PS-Optical Frequency Domain Imaging (OFDI)) measurements
Where xi is the measured value for the scar size, xi is the value predicted by a given model, and n is the number of samples
Summary
Burns is a global public health problem, accounting for an estimated 265,000 deaths annually (WHO, 2016). In search of more objective diagnostic burn criteria, a wide spectrum of methods has been explored: biopsy and histology (Sheridan, 2012), fluorescent imaging (Sheridan et al, 2015), near-infrared light spectroscopy (Cross et al, 2007), confocal, and multiphoton microscopy (Chen et al, 2011), laser Doppler techniques (Jaskille et al, 2010), and non-contact high-frequency ultrasonography (Lin et al, 2011), as well as thermography (Liddington and Shakespeare, 1996) To date, these strategies fall into one of two categories: (1) they lack the ability to image individual layers of the wound and provide an accumulated bulk signal, making the diagnosis of burn depth unreliable, and (2) providing high spatial resolution and depth-sectioning, the limited field of view and long acquisition times make them impractical in a clinical setting. Optical Frequency Domain Imaging (OFDI) and related implementations of optical coherence tomography (OCT) provide depth-resolved images of the tissue architecture and functional vasculature with an interesting trade off of the field of view, spatial resolution, and imaging speed, that can help to overcome the barriers encountered by alternative modalities (Park et al, 2001; Kim et al, 2012; Villiger et al, 2013a,b)
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