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Hypertrophic scars (HTS) are a pathologic reaction of the skin and soft tissue to burn or other traumatic injury. Scar tissue can cause patients serious functional and cosmetic issues. Scar management strategies, specifically scar assessment techniques, are vital to improve clinical outcome. To date, no entirely objective method for scar assessment...
Citations
... Our research group has previously utilized the Dc pig model, instead of the Yk pig model, to generate HTS in multiple research areas. [12][13][14][15][16][17][18][19][20][21][22][23] However, our data suggests that it is not accurate to purport that Yk pigs do not generate hypertrophic scars. Instead, they generate a different phenotype more representative of how patients with Fitzpatrick skin types I-III heal and scar. ...
... The open wound area on day 0 was calculated using Image J software as previously described (NIH, Bethesda, MD). 24 For each wound, the open wound area was likewise calculated at days 7,14,21,18,35,42,56,70,84, and 90 and normalized to the day 0 area to obtain a percentage of open wound area. All images had their scales set prior to calculating area to standardize for camera distance. ...
Background
Wound healing can result in various outcomes, including hypertrophic scar (HTS). Pigs serve as models to study wound healing as their skin shares physiologic similarity with humans. Yorkshire (Yk) and Duroc (Dc) pigs have been used to mimic normal and abnormal wound healing, respectively. The reason behind this differential healing phenotype was explored here.
Methods
Excisional wounds were made on Dc and Yk pigs and were sampled and imaged for 98 days. PCR arrays were used to determine differential gene expression. Vancouver Scar Scale (VSS) scores were given. Re-epithelialization was analyzed. H&E, Mason's trichrome, and immunostains were used to determine cellularity, collagen content, and blood vessel density, respectively.
Results
Yk wounds heal to a “port wine” HTS, resembling scarring in Fitzpatrick skin types (FST) I-III. Dc wounds heal to a dyspigmented, non-pliable HTS, resembling scarring in FST IV–VI. Gene expression during wound healing was differentially regulated versus uninjured skin in 40/80 genes, 15 of which differed between breeds. Yk scars had a higher VSS score at all time points. Yk and Dc wounds had equivalent re-epithelialization, collagen disorganization, and blood vessel density.
Conclusions
Our findings demonstrate that Dc and Yk pigs can produce HTS. Wound creation and healing were consistent among breeds, and differences in gene expression were not sufficient to explain differences in resulting scar phenotype. Both pig breeds should be used in animal models to investigate novel therapeutics to provide insight into a treatment's effectiveness on various skin types.
... Polarization imaging techniques are widely used in biomedical studies and have been regarded as potential label-free tools for diagnosis, because of their sensitivity to microstructural changes in tissues [1][2][3][4][5][6][7][8][9][10][11]. As a method that can completely characterize the polarization properties of samples, Mueller matrix polarimetry is especially fit to detect the density and distribution behavior of anisotropic fibrous components of turbid samples [12][13][14][15][16][17][18], and has been applied to clinical practices to assist the diagnosis of several different types of diseases, such as Alzheimer's disease, breast cancer and colon cancer [19][20][21]. ...
Polarization imaging techniques are emerging tools to provide quantitative information of anisotropic structures, such as the density and orientation distribution of fibers in tissue samples. Recently, it is found that when using Mueller matrix polarimetry to obtain the structural features of tissue samples, some information can be revealed by relatively low-resolution polarization parameter images. Thus, to analyze what kinds of anisotropic optical and structural information contained in high-resolution polarization images are preserved in low-resolution ones, here we carry out a comparative study of the influence of imaging resolution on the Mueller matrix derived linear retardance parameters. We measure the microscopic Mueller matrix of human healthy breast duct tissues and ductal carcinoma in situ (DCIS) tissues, which have distinct typical fibrous structures, using objectives with different numerical aperture. Then we quantitatively compare a group of image texture feature parameters of the linear retardance parameters images under high and low imaging resolutions. The results demonstrate that the fibers density information contained in the texture features of linear retardance δ parameter image are preserved well with the decline of imaging resolution. While for the azimuthal orientation parameter θ which closely related to the spatial location, we still need high imaging resolution to obtain quantitative structural information. The study provides an important criterion to decide which information of fibrous structures can be extracted accurately using transmission Mueller matrix microscope with low numerical aperture objectives.
... On the other hand, it is known that polarization can carry additional information since it is a more general physical feature of light than intensity and orthogonal to wavelength [9.]. The combination of multispectral imaging with the polarization states of light at different angles will represent a step forward the analysis of skin lesions [10,11]. Therefore, in this work we propose the non-invasive assessment of skin lesions through a polarized multispectral (PMS) imaging system that includes an analyzer with 0º, 45º and 90º polarization configurations. ...
The effective and non-invasive diagnosis of skin cancer is a hot topic in biophotonics since the current gold standard, a biopsy, is slow and costly. Non-invasive optical techniques such as polarization and multispectral imaging have arisen as powerful tools to overcome these constraints. The combination of these techniques provides a comprehensive characterization of skin chromophores including polarization, color and spectral features. Hence, in this work we propose a polarized multispectral imaging device that works from 414 nm to 995 nm and at 0º, 45º and 90º polarization configurations. Preliminary results performed over 20 nevi and 20 melanoma found statistically significant descriptors (p<0.05) that discriminated between these two lesion etiologies. A further analysis of more lesions is expected to contribute in reducing the false positives during the diagnosis process and, as a consequence, the number of necessary biopsies.
... In order to provide an objective and stable skin assessment, researchers have attempted the use of optical imaging techniques [9,10]. Among them, multispectral imaging has been increasingly considered as one of the most feasible and appealing strategies [11,12]. ...
We propose a snapshot hyperspectral imaging system and methods for skin morphological feature analysis and real-time monitoring of skin activities. The analysis method includes a strategy using weighted subtractions between sub-channel images to extract absorption information due to specific chromophores within skin tissue, for example hemoglobin and melanin. Based on morphological analysis results, we carry out real-time monitoring of the skin features to verify the ability of this method to provide temporal responses of the skin tissue activities, which is experimentally shown to be useful in the measurement of heartrate, monitoring of the tissue recovery after a body exercise, and studying of the tissue response due to a vascular occlusion. Compared to conventional multispectral imaging system, the proposed system improves the device simplicity and is immune to motion artifacts. Coupled with the extraction algorithms, the hyperspectral imaging promises a robust skin assessment tool with abilities for qualitative visualization and potentially quantitative analysis of skin features, useful in the applications of cosmetics and clinical dermatology.
... SFDI has been applied to characterize burn severity. [5][6][7][8][9][10] Additionally, in preclinical burn wound models, SFDI has been applied to the evaluation of infection 11 and hypertrophic scarring, 12 and diffuse reflectance spectroscopy has been applied to the monitoring of tissue constructs. 13 Porcine skin optical properties measured in this work broadly agree with those previously reported. ...
There is a need for noninvasive, quantitative methods to characterize wound healing in the context of longitudinal investigations related to regenerative medicine. Such tools have the potential to inform the assessment of wound status and healing progression and aid the development of new treatments. We employed spatial frequency domain imaging (SFDI) to characterize the changes in optical properties of tissue during wound healing progression in a porcine model of split-thickness skin grafts and also in a model of burn wound healing with no graft intervention. Changes in the reduced scattering coefficient measured using SFDI correlated with structural changes reported by histology of biopsies taken concurrently. SFDI was able to measure spatial inhomogeneity in the wounds and predicted heterogeneous healing. In addition, we were able to visualize differences in healing rate, depending on whether a wound was debrided and grafted, versus not debrided and left to heal without intervention apart from topical burn wound care. Changes in the concentration of oxy- and deoxyhemoglobin were also quantified, giving insight into hemodynamic changes during healing.
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... The second one analyzes the polarization at several angles from an SFDI measurement. 21,22 The polarization dependence of scattering will indicate the dominant fibers orientation as demonstrated onto collagen-rich samples such as tendons. Figure 7 provides examples taken from the literature: subsurface imaging of optical properties [ Fig. 7(a)], depth-sensitive imaging in a phantom [ Fig. 7(b)], ex vivo orientation imaging [ Fig. 7(c)], endogenous tomographic imaging in a phantom [ Fig. 7(d)], 3-D corrected imaging of a human hand [ Fig. 7(e)], and oxygen saturation imaging of a pig bowel during blood supply occlusion and release [ Fig. 7(f)]. ...
Spatial frequency domain imaging (SFDI) has witnessed very rapid growth over the last decade, owing to its unique capabilities for imaging optical properties and chromophores over a large field-of-view and in a rapid manner. We provide a comprehensive review of the principles of this imaging method as of 2019, review the modeling of light propagation in this domain, describe acquisition methods, provide an understanding of the various implementations and their practical limitations, and finally review applications that have been published in the literature. Importantly, we also introduce a group effort by several key actors in the field for the dissemination of SFDI, including publications, advice in hardware and implementations, and processing code, all freely available online.
... 39 Demarcation of margins of skin cancers, not visible to the naked eye, has been conducted by several researchers, starting with setups focusing on linear depolarization to other systems, [40][41][42][43] utilizing full Stokes vector polarimetry and out-of-plane approaches. [44][45][46] The skin stratum corneum has been shown to be highly scattering hence producing strong depolarization. 47,48 Changes in retardation have been associated with the presence of collagen in the dermis. ...
... For this reason, scars have a strong response to polarized light as collagen in wounds recombines in the direction of local forces. 46 ...
Calibration, quantification, and standardization of the polarimetric instrumentation, as well as interpretation and understanding of the obtained data, require the development and use of well-calibrated phantoms and standards. We reviewed the status of tissue phantoms for a variety of applications in polarimetry; more than 500 papers are considered. We divided the phantoms into five groups according to their origin (biological/nonbiological) and fundamental polarimetric properties of retardation, depolarization, and diattenuation. We found that, while biological media are generally depolarizing, retarding, and diattenuating, only one of all the phantoms reviewed incorporated all these properties, and few considered at least combined retardation and depolarization. Samples derived from biological tissue, such as tendon and muscle, remain extremely popular to quickly ascertain a polarimetric system, but do not provide quantifiable results aside from relative direction of their principal optical axis. Microspheres suspensions are the most utilized phantoms for depolarization, and combined with theoretical models can offer true quantification of depolarization or degree of polarization. There is a real paucity of birefringent phantoms despite the retardance being one of the most interesting parameters measurable with polarization techniques. Therefore, future work should be directed at generating truly reliable and repeatable phantoms for this metric determination. Diattenuating phantoms are rare and application-specific. Given that diattenuation is considered to be low in most biological tissues, the lack of such phantoms is seen as less problematic. The heterogeneity of the phantoms reviewed points to a critical need for standardization in this field. Ultimately, all research groups involved in polarimetric studies and instruments development would benefit from sharing a limited set of standardized polarimetric phantoms, as is done earlier in the round robin investigations in ellipsometry.
... The simplicity of structured illumination imaging lends itself to multimodal measurements with other clinical techniques. Ghassemi et al. 82 combined out-of-plane Stokes polarimetry with multispectral SFDI to study hypertrophic scars for surface roughness and pathophysiology with a single system. Though each modality has a unique illumination pathway, the shared collection pathway produces inherently coregistered measurements for direct correlation. ...
... However, a recent study successfully correlated the invasive histopathology of a porcine burn model with the noninvasive combined sensitivity of SFDI and LSI to corroborate their potential for clinical use. 90 Similarly, other combinations for multimodal systems, e.g., polarimetry with spectral SFDI 82 and laser Doppler imaging with SFDI, 111 have been used to investigate burn wound infections and scar formation with noncontact endogenous imaging. ...
Diffuse optical imaging probes deep living tissue enabling structural, functional, metabolic, and molecular imaging. Recently, due to the availability of spatial light modulators, wide-field quantitative diffuse optical techniques have been implemented, which benefit greatly from structured light methodologies. Such implementations facilitate the quantification and characterization of depth-resolved optical and physiological properties of thick and deep tissue at fast acquisition speeds. We summarize the current state of work and applications in the three main techniques leveraging structured light: spatial frequency-domain imaging, optical tomography, and single-pixel imaging. The theory, measurement, and analysis of spatial frequency-domain imaging are described. Then, advanced theories, processing, and imaging systems are summarized. Preclinical and clinical applications on physiological measurements for guidance and diagnosis are summarized. General theory and method development of tomographic approaches as well as applications including fluorescence molecular tomography are introduced. Lastly, recent developments of single-pixel imaging methodologies and applications are reviewed.
... This is, further, evidenced in another study in pediatric scald burns showing initial perfusion related to duration of healing out to 14 days [19]. Similarly, after the peak of angiogenesis in wound healing, collagen deposition in the proliferative phase can affect scar formation, which may also be assessed with imaging techniques [20]. While these imaging technologies hold great promise for assessment of wounds across time, their full potential remains unknown. ...
... Unfortunately, effective fluid resuscitation is a critical component of burn wound care that can often intensify the occurrence of edema [38]. Spectroscopic techniques have been able to quantify increases in water concentration in scar formation [20] and through the formation of edema with drugs [39]. Acute studies in rat burn models have also shown an increase in relative water fraction over the first 3 hours of burn wounds [29]. ...
Background and ojectives:
The current standard for diagnosis of burn severity and subsequent wound healing is through clinical examination, which is highly subjective. Several new technologies are shifting focus to burn care in an attempt to help quantify not only burn depth but also the progress of healing. While accurate early assessment of partial thickness burns is critical for dictating the course of treatment, the ability to quantitatively monitor wound status over time is critical for understanding treatment efficacy. SFDI and LSI are both non-invasive imaging modalities that have been shown to have great diagnostic value for burn severity, but have yet to be tested over the course of wound healing.
Methods:
In this study, a hairless rat model (n = 6, 300-450 g) was used with a four pronged comb to create four identical partial thickness burns (superficial n = 3 and deep n = 3) that were used to monitor wound healing over a 28 days period. Weekly biopsies were taken for histological analysis to verify wound progression. Both SFDI and LSI were performed weekly to track the evolution of hemodynamic (blood flow and oxygen saturation) and structural (reduced scattering coefficient) properties for the burns.
Results:
LSI showed significant changes in blood flow from baseline to 220% in superficial and 165% in deep burns by day 7. In superficial burns, blood flow returned to baseline levels by day 28, but not for deep burns where blood flow remained elevated. Smaller increases in blood flow were also observed in the surrounding tissue over the same time period. Oxygen saturation values measured with SFDI showed a progressive increase from baseline values of 66-74% in superficial burns and 72% in deep burns by day 28. Additionally, SFDI showed significant decreases in the reduced scattering coefficient shortly after the burns were created. The scattering coefficient progressively decreased in the wound area, but returned towards baseline conditions at the end of the 28 days period. Scattering changes in the surrounding tissue remained constant despite the presence of hemodynamic changes.
Conclusions:
Here, we show that LSI and SFDI are capable of monitoring changes in hemodynamic and scattering properties in burn wounds over a 28 days period. These results highlight the potential insights that can be gained by using non-invasive imaging technologies to study wound healing. Further development of these technologies could be revolutionary for wound monitoring and studying the efficacy of different treatments. Lasers Surg. Med. 49:293-304, 2017. © 2017 Wiley Periodicals, Inc.
... Multispectral imaging (MSI) refers to imaging systems that penetrate certain features of physical object within the field of view by using a number of spectral bands [1][2][3]. It has been used in various applications such as but not limited to airborne mapping, astronomical imaging, dentistry, dermatology, histopathology and ophthalmology [4]. ...
In this paper, we introduce a novel feature-point-matching based framework for achieving an optimized joint-alignment of sequential images from multispectral imaging (MSI). It solves a low-rank and semidefinite matrix that stores all pairwise-image feature-mappings by minimizing the total amount of point-to-point matching cost via a convex optimization of a semidefinite programming formulation. This unique strategy takes a complete consideration of the information aggregated by all point-matching costs and enables the entire set of pairwise-image feature-mappings to be solved simultaneously and near-optimally. Our framework is capable of running in an automatic or interactive fashion, offering an effective tool for eliminating spatial misalignments introduced into sequential MSI images during the imaging process. Our experimental results obtained from a database of 28 sequences of MSI images of human eye demonstrate the superior performances of our approach to the state-of-the-art techniques. Our framework is potentially invaluable in a large variety of practical applications of MSI images.
