Pejhman Ghassemi

Noninvasive imaging technologies for cutaneous wound assessment: A review.

The ability to phenotype wounds for the purposes of assessing severity, healing potential and treatment is an important function of evidence‐based medicine. A variety of optical technologies are currently in development for noninvasive wound assessment. To varying extents, these optical technologies have the potential to supplement traditional clinical wound evaluation and research, by providing detailed information regarding skin components imperceptible to visual inspection. These assessments are achieved through quantitative optical analysis of tissue characteristics including blood flow, collagen remodeling, hemoglobin content, inflammation, temperature, vascular structure, and water content. Technologies that have, to this date, been applied to wound assessment include: near infrared imaging, thermal imaging, optical coherence tomography, orthogonal polarization spectral imaging, fluorescence imaging, laser Doppler imaging, microscopy, spatial frequency domain imaging, photoacoustic detection, and spectral/hyperspectral imaging. We present a review of the technologies in use or development for these purposes with three aims: (1) providing basic explanations of imaging technology concepts, (2) reviewing the wound imaging literature, and (3) providing insight into areas for further application and exploration. Noninvasive imaging is a promising advancement in wound assessment and all technologies require further validation.

A polarized multispectral imaging system for quantitative assessment of hypertrophic scars.

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 has been embraced by the medical community. In this study, we introduce for the first time, a novel polarized multispectral imaging system combining out-of-plane Stokes polarimetry and Spatial Frequency Domain Imaging (SFDI). This imaging system enables us to assess the pathophysiology (hemoglobin, blood oxygenation, water, and melanin) and structural features (cellularity and roughness) of HTS. To apply the proposed technique in an in vivo experiment, dermal wounds were created in a porcine model and allowed to form into scars. The developed scars were then measured at various time points using the imaging system. Results showed a good agreement with clinical Vancouver Scar Scale assessment and histological examinations.

Out-of-plane Stokes imaging polarimeter for early skin cancer diagnosis

Optimal treatment of skin cancer before it metastasizes critically depends on early diagnosis and treatment. Imaging spectroscopy and polarized remittance have been utilized in the past for diagnostic purposes, but valuable information can be also obtained from the analysis of skin roughness. For this purpose, we have developed an out-of-plane hemispherical Stokes imaging polarimeter designed to monitor potential skin neoplasia based on a roughness assessment of the epidermis. The system was utilized to study the rough surface scattering for wax samples and human skin. The scattering by rough skin-simulating phantoms showed behavior that is reasonably described by a facet scattering model. Clinical tests were conducted on patients grouped as follows: benign nevi, melanocytic nevus, melanoma, and normal skin. Images were captured and analyzed, and polarization properties are presented in terms of the principal angle of the polarization ellipse and the degree of polarization. In the former case, there is separation between different groups of patients for some incidence azimuth angles. In the latter, separation between different skin samples for various incidence azimuth angles is observed.

A new approach for optical assessment of directional anisotropy in turbid media

A study of polarized light transport in scattering media exhibiting directional anisotropy or linear birefringence is presented in this paper. Novel theoretical and experimental methodologies for the quantification of birefringent alignment based on out-of-plane polarized light transport are presented here. A polarized Monte Carlo model and a polarimetric imaging system were devised to predict and measure the impact of birefringence on an impinging linearly polarized light beam. Ex-vivo experiments conducted on bovine tendon, a biological sample consisting of highly packed type I collagen fibers with birefringent property, showed good agreement with the analytical results.

A portable automatic pressure delivery system for scar compression therapy in large animals

Compression therapy has long been a standard treatment for hypertrophic scar prevention. However, due to the lack of objective, quantitative assessments, and measurements of scar severity, as well as the lack of a self-operated, controllable, and precise pressure delivery technique, limited concrete evidence exists, demonstrating compression therapys efficacy. We have designed and built an automatic pressure delivery system to apply and maintain constant pressure on scar tissue in an animal model. A force sensor positioned on a compression plate reads the imposed force in real-time and sends the information to a feedback system controlling two position actuators. The actuators move accordingly to maintain a preset value of pressure onto the skin. The system was used in an in vivo model of compression therapy on hypertrophic scars. It was shown that the system was capable of delivering a constant pressure of 30 mmHg on scar wounds for a period of two weeks, and that phenotypic changes were seen in the wounds.

Biphasic presence of fibrocytes in a porcine hypertrophic scar model.

The duroc pig has been described as a promising animal model for use in the study of human wound healing and scar formation. However, little is known about the presence and chronology of the fibrocyte cell population in the healing process of these animals. Wounds known to form scar were created on red duroc swine (3” x 3”) with a dermatome to a total depth of either 0.06 inches or 0.09 inches. These wounds were allowed to heal completely and biopsies were done at scheduled time points during the healing process. Biopsies were formalin fixed and paraffin embedded for immunohistochemical analysis. Porcine reactive antibodies to CD-45 and procollagen-1 and a human reactive antibody to LSP-1 were used to detect the presence of fibrocytes in immunohistochemistry, an immunocytochemistry. Initial immunohistochemical studies showed evidence of a biphasic presence of fibrocytes. Pigs with 0.06 inches deep wounds showed positive staining for CD-45 and LSP-1 within highly cellular areas at days 2 and 4 after wounding. Additional animals with 0.09 inches deep wounds showed positive staining within similar areas at days 56, 70, and 113 after wounding. There was no immunohistochemical evidence of fibrocytes in skin biopsies taken at days 14, 28, or 42. Procollagen-1 staining was diffused in all samples. Cultured cells were stained for CD-45, LSP-1, and procollagen-1 by immunocytochemistry. These data confirm that fibrocytes are indeed present in this porcine model. We conclude that these cells are present after initial wounding and later during scar formation and remodeling. We believe that this is an evidence of a biphasic presence of fibrocytes, first as an acute response to skin wounding followed by later involvement in the remodeling process, prompted by continued inflammation in a deep partial thickness wound.

A multimodal assessment of melanin and melanocyte activity in abnormally pigmented hypertrophic scar.

Using a validated swine model of human scar formation, hyperpigmented and hypopigmented scar samples were examined for their histological and optical properties to help elucidate the mechanisms and characteristics of dyspigmentation. Full-thickness wounds were created on the flanks of red Duroc pigs and allowed to heal. Biopsies from areas of hyperpigmentation, hypopigmentation, and uninjured tissue were fixed and embedded for histological examination using Azure B and primary antibodies to S100B, HMB45, and &agr;-melanocyte-stimulating hormone (&agr;-MSH). Spatial frequency domain imaging (SFDI) was then used to examine the optical properties of scars. Hyperpigmentation was first noticeable in healing wounds around weeks 2 to 3, gradually becoming darker. There was no significant difference in S100B staining for the presence of melanocytes between hyperpigmented and hypopigmented scar samples. Azure B staining of melanin was significantly greater in histological sections from hyperpigmented areas than in sections from both uninjured skin and hypopigmented scar (P < .0001). There was significantly greater staining for &agr;-MSH in hyperpigmented samples compared with hypopigmented samples (P = .0121), and HMB45 staining was positive for melanocytes in hyperpigmented scar. SFDI at a wavelength of 632 nm resulted in an absorption coefficient map correlating with visibly hyperpigmented areas of scars. In a red Duroc model of hypertrophic scar formation, melanocyte number is similar in hyperpigmented and hypopigmented tissues. Hyperpigmented tissues, however, show a greater amount of melanin and &agr;-MSH, along with immunohistochemical evidence of stimulated melanocytes. These observations encourage further investigation of melanocyte stimulation and the inflammatory environment within a wound that may influence melanocyte activity. Additionally, SFDI can be used to identify areas of melanin content in mature, pigmented scars, which may lead to its usefulness in wounds at earlier time points before markedly apparent pigmentation abnormalities.

Monitoring the impact of pressure on the assessment of skin perfusion and oxygenation using a novel pressure device

Skin perfusion and oxygenation is easily disrupted by imposed pressure. Fiber optics probes, particularly those spectroscopy or Doppler based, may relay misleading information about tissue microcirculation dynamics depending on external forces on the sensor. Such forces could be caused by something as simple as tape used to secure the fiber probe to the test subject, or as in our studies by the full weight of a patient with spinal cord injury (SCI) sitting on the probe. We are conducting a study on patients with SCI conducting pressure relief maneuvers in their wheelchairs. This study aims to provide experimental evidence of the optimal timing between pressure relief maneuvers. We have devised a wireless pressure-controlling device; a pressure sensor positioned on a compression aluminum plate reads the imposed pressure in real time and sends the information to a feedback system controlling two position actuators. The actuators move accordingly to maintain a preset value of pressure onto the sample. This apparatus was used to monitor the effect of increasing values of pressure on spectroscopic fiber probes built to monitor tissue oxygenation and Doppler probes used to assess tissue perfusion.

Monitoring the influence of compression therapy on pathophysiology and structure of a swine scar model using multispectral imaging system

Scar contractures can lead to significant reduction in function and inhibit patients from returning to work, participating in leisure activities and even render them unable to provide care for themselves. Compression therapy has long been a standard treatment for scar prevention but due to the lack of quantifiable metrics of scar formation scant evidence exists of its efficacy. We have recently introduced a multispectral imaging system to quantify pathophysiology (hemoglobin, blood oxygenation, melanin, etc) and structural features (roughness and collagen matrix) of scar. In this study, hypertrophic scars are monitored in-vivo in a porcine model using the imaging system to investigate influence of compression therapy on its quality.

A novel spectral imaging system for quantitative analysis of hypertrophic scar

Scarring can lead to significant cosmetic, psychosocial, and functional consequences in patients with hypertrophic scars from burn and trauma injuries. Therefore, quantitative assessment of scar is needed in clinical diagnosis and treatment. The Vancouver Scar Scale (VSS), the accepted clinical scar assessment tool, was introduced in the nineties and relies only on the physician subjective evaluation of skin pliability, height, vascularity, and pigmentation. To date, no entirely objective method has been available for scar assessment. So, there is a continued need for better techniques to monitor patients with scars. We introduce a new spectral imaging system combining out-of-plane Stokes polarimetry, Spatial Frequency Domain Imaging (SFDI), and three-dimensional (3D) reconstruction. The main idea behind this system is to estimate hemoglobin and melanin contents of scar using SFDI technique, roughness and directional anisotropy features with Stokes polarimetry, and height and general shape with 3D reconstruction. Our proposed tool has several advantages compared to current methodologies. First and foremost, it is non-contact and non-invasive and thus can be used at any stage in wound healing without causing harm to the patient. Secondarily, the height, pigmentation, and hemoglobin assessments are co-registered and are based on imaging and not point measurement, allowing for more meaningful interpretation of the data. Finally, the algorithms used in the data analysis are physics based which will be very beneficial in the standardization of the technique. A swine model has also been developed for hypertrophic scarring and an ongoing pre-clinical evaluation of the technique is being conducted.