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Technological Advances in Wound Bed Measurements

Introduction Chronic wounds represent a major challenge for the caregiver. Over the last few years, an increasing number of new technologies have been shown to be beneficial in wound management. These new opportunities to accelerate the tissue repair process together with a better knowledge of the pathogenetic mechanisms of chronic wounds have led to a more targeted therapeutic control of the different wound healing phases. In order to obtain biochemical and mechanical information about the wound bed and the surrounding skin, different options of noninvasive and invasive measurements have been developed and tested. The use of instruments to measure cutaneous parameters in wound care is in an embryonic state, and doctors and nurses still rely on the use of clinical observations. Skin lesions and, especially, the way lesions evolve over time are monitored simply according to the common sense of the caregivers, who may not use updated or efficient equipment for collecting objective measurements. Monitoring of acute and chronic wounds can be performed by measuring in an objective, precise, and reproducible way and by simply adapting the existing and proven technologies to this specific matter. Today, by using a three-dimensional scanner and a digital camera, it is possible to obtain a geometric and chromatic characterization of the wound and, therefore, via a data processing software package, obtain the numerical values of a series of parameters essential to characterizing the lesion. Reproducible, objective measurements can also be taken in remote locations without the presence of wound care experts. By using telemedicine, the data can be transmitted remotely to the main reference centers where experts may assign therapies as well as monitor the lesions continuously and reliably. Wound measurement techniques have received consistent attention in clinical practice and research through the three main areas of interest in wound care: vascular ulcers, diabetic foot ulcers, and pressure ulcers.1 Today, each discipline focuses on measuring the physical parameters that may contribute substantially to the development of new pathogenetic mechanisms or to the acquisition and definition of new therapeutic technologies. Chronic ulcers. Chronic ulcers may be classified into the following main categories: vascular ulcers (venous, arterial, mixed), diabetic foot ulcers, pressure ulcers, and ulcers of various etiology. Vascular ulcers represent 75 percent of all chronic ulcers in general and are divided into venous (65%) and arterial and mixed arterial-venous ulcers (10%). Venous ulcers. Venous ulcers may be of various sizes, mainly affect the medial surface of the limb, and may have a medium-large extension. The borders of these ulcers are irregular in shape and are sometimes difficult to record. The perilesional skin is often affected by a process called lipodermatosclerosis featuring hyperpigmentation and hardening of the skin, which becomes fragile and easily ulcerative. Arterial ulcers. Arterial ulcers are a consequence of an ischemic state that may affect both small and large vessels. These lesions have small dimensions with regular borders, while the perilesional skin is pale and often lacking in skin adnexa. The wound bed of these lesions, both venous and arterial, may take on various colors according to the tissue: black if the tissue is necrotic, yellow when the tissue is mostly sloughy, and various tones of red if there is a good granulation tissue. The color of the wound bed represents one of the main indicators on the state of health of the ulcer and provides clinical indications about the microbiological balance. Diabetic foot ulcers. Diabetic foot ulcers are extremely aggressive and may lead to serious complications, such as amputation of the limb. They may have various dimensions, mainly in a distal position around the toes with subsequent propagation of the phlogistic process to deeper structures of the foot. Foot ulcers are at greater risk of infection and subsequent critical functioning of the limb. Pressure ulcers affect patients suffering from immobilization due to different diseases, mainly oncological. Today, a four-stage classification is the most accepted, but several limitations are present due to the difficulty in assessing of the amount of devitalized tissue. Wound Bed Assessment When speaking of cutaneous wounds, one refers to defects of the skin surface. It is generally believed that a full and correct characterization of the level of tissue damage must be carried out by analyzing two distinct groups of parameters: dimensional parameters and chromatic parameters. Recently, the concept of wound bed preparation2 has been introduced and classified according to the clinical parameters of chronic wounds. This new aspect of wound care has to be considered as a more comprehensive approach, involving several individual components, which allows the opportunity to investigate clinical, microbiological, and cellular wound aspects from one individual viewpoint. In order to monitor the different aspects of wound bed preparation, various instrumental techniques are now under investigation in order to obtain a better and more objective characterization of the tissue repair process. The main physical wound parameters that have received the most attention over the past few years in terms of measurement techniques are listed in Table 1. The advantage of this new scientific discipline is the ability to study living skin in real time. There are also other aspects to be taken in account while measuring, such as the standardizations of measurement, which include frequent calibration of the instrument, a controlled environment where temperature and relative humidity are monitored, the knowledge of technical aspects of the device by the user involved, and also the basic knowledge of the biological aspect to be evaluated. Wound Color Wound color is of great importance in the assessment of granulation tissue, in looking for signs of clinical infection, and for the evaluation of progress of the therapeutic regimen in acute and chronic lesions. Wound color assessment is easily and routinely done by recording photographs. Color coding, which takes into account the black, yellow, and red areas as the main variables in a wound, is often used in clinical trials to characterize the healing phases of the wound bed.3 The accuracy of color measurement taken from a photograph is compromised by several aspects, such as the camera used, the lighting in the room, the distance from the wound, and the flash used. A correct standardization of these parameters is essential in order to obtain a uniform record of the same patient during treatment. In this respect, the advent of digital equipment is becoming more and more useful because of the possibility to interface the camera with computer software that is able to record wound color and planimetry. After the photograph is taken in the clinic, the color of the picture may be analyzed via the computer software by digital image techniques. Color photographs are digitized by a high-quality color video camera and transferred to the computer memory, where after correction of the geometric and photometric distortion, the wound area is classified into red, dark-yellow, light-yellow, and black.4 Objective assessment of wound color can also be made with a tri-stimulus colorimeter (Chroma Meter CR 200, Minolta). With this technique the L* a* b* system, as recommended by CIE (Commission Internationale de l’Eclairage), is used for skin color assessment (Figure 1). The L* value gives the relative brightness of the color ranging from total black (L* = 0) to total white (L* = 100). The a* value represents the color hue ranging from red (positive results) and green (negative results). The b* value represents the color hue ranging from blue (negative results) and yellow (positive results). Measurements are usually also taken on normal skin for comparison, and values are expressed as DL*, Da*, Db* (D=Delta). Four consecutive measurements are made for each point and mean ± SD is calculated. In a recent study, we investigated whether the tri-stimulus colorimetric assessment of chronic wounds could distinguish between viable and nonviable wound tissue.5 Our results indicated that colorimetric evaluation is more accurate than clinical scoring in diagnosing granulation tissue. The measurement technique has shown high reproducibility and can help overcome bias derived from clinical scoring. This may lead to more accurate wound bed analysis and preparation and to the benefit of earlier skin grafting for these patients. Wound Odor Acute and, especially, chronic wounds have a significant range of odors. This is principally due to the different levels of bacterial colonization of the lesions rather than the treatment used.6 Electronic noses, which are used industrially to monitor environmental characteristics and to check manufactured products, have been applied in preliminary studies evaluating topical dressings in patients with chronic wounds. When exposed to odors, the electronic nose is able to measure the changes in electrical resistance using polymer sensors.7 The signals generated are digitized and stored in data acquisition software in order to create a neural network system, which will allow pattern recognition of aromas. Preliminary studies in patients with venous leg ulcers have shown that the electronic nose was able to identify groups of streptococci and staphylococci from the dressings used for treatment. The relevance and potential areas of application in experimental and clinical wound management are many, since this technology may be able to distinguish different levels of microbiological wound balance. Wound Temperature In more recent times, the measurement of the surface temperature of the human body has not been routinely undertaken in many clinical environments, not because the measurement lacks clinical significance, but because it has been difficult to acquire. Attempts to measure skin temperature per se have not, however, been so successful. Conventional mercury thermometers have generally been ineffective for surface temperature measurements because they are difficult to attach to the body surface properly, they require a significant amount of time for the sensor portion of the device to equilibrate to the body surface temperature, and they are prone to low readings due to an inadequate surface thermal connection. Numerous techniques and devices are employed in the measurement of temperature. Many of these techniques, such as the use of glass mercury thermometers or electronic display devices using thermocouples or thermistors, are generally understood and, as a result, are well accepted in clinical medical practice. The infrared method is fundamentally different from the other methods in that there is no temperature device to heat. Infrared thermography has long been recognized as a reliable, highly technical diagnostic tool and refers to the process of recording and interpreting variations in temperature on the surface of the skin in color or shades of gray (Figure 2). A reproducible technique is essential for temperature measurements, and infrared noncontact thermometry has been found to be a fast and stable method that is relatively insensitive to user technique (Figure 3). Increased skin temperature has long been associated with infection, thus providing a useful and objective method to monitor the healing process in complicated chronic wounds, such as pressure ulcers and diabetic foot ulcers. A low tissue temperature of the wound bed has been shown to slow healing, mainly by causing a decrease in oxygen release.8 Wound bed temperature in chronic leg ulcers ranges between 24 and 26°C when the ulcer is left uncovered. Using an occlusive hydrocolloid dressing causes the temperature values to increase slightly, promoting the healing process.9 Recently, a noncontact thermal wound therapy has been shown to prevent the inhibitory effect of chronic wound fluid on the growth of dermal fibroblasts.10 In this study, chronic wound fluid was heated starting from a temperature of 25°C and reaching 35°C after one hour of heating. This temperature level was maintained constant for up to 72 hours. Wound Bed pH The pH of intact skin ranges from about 4.8 to 6.0, while the interstitial fluid exhibits a pH near neutral. The low pH on the skin is attributed mainly to the presence of the so-called “acid mantle,” a natural skin barrier to the external environment.11 The pH measurement is defined as the negative logarithm of the activity of hydrogen ions in an aqueous solution used to express the acidity and alkalinity on a scale of 0 to 14. The most common pH instrument is the flat glass electrode (Figure 4), which is used on the skin after careful moistening of the tip of the electrode with distilled water. Measurement of surface pH is a noninvasive technique that has been used in the past to evaluate the barrier properties of the stratum corneum and to study the relationship between change in skin surface microflora and the development of skin irritation. The role of wound bed pH has proven to be of fundamental importance during the healing of chronic wounds, and prolonged chemical acidification of the wound bed has been shown to increase the healing rate in chronic venous leg ulcers.12 The principal explanation for the mechanism of interaction between the acidic wound bed and the wound healing process is related to the potential to increase tissue oxygen availability through oxygen dissociation and to reduce the histotoxicity of bacterial end products, thus stimulating the wound’s healing process. Wound pH measurement was used to predict the skin graft survival in an experimental and clinical study by Sayegh, et al.13 In this trial, the technique was found to be easy and reproducible in assessing the graft take of patients with burns and chronic ulcers and provided numerical parameters that enabled the percentage of success or failure of the surgical treatment to be determined. The wound bed pH of chronic venous leg ulcers and pressure ulcers was found to be alkaline or neutral14 when compared to intact surrounding skin; it was also found to change its value according to the staging of the ulcers, moving to an acidic state during epithelialization.15 Moist wound healing under synthetic dressings provides the optimum environment for normal repair and regeneration, and the acidic wound fluid collected during this local treatment has been shown to inhibit the bacterial growth and to promote fibroblast proliferation.16 Moreover, the use of occlusive dressings, such as hydrocellular foam on venous leg ulcers, was able to turn the pH of granulating wound bed from alkaline to acidic and to maintain this acidic environment up to dressing removal at 72 hours.17 We believe that the capacity of these dressings to absorb wound fluid and to reduce the frequency of dressing change are two fundamental aspects that contribute to maintaining a constant wound microenvironment. Measurement of wound bed pH is a simple and noninvasive technique that could provide more information than what we have obtained up to now, particularly during wound bed preparation where the microbiological burden is a crucial aspect in obtaining complete healing. Wound Bed Perfusion Adequate blood supply is an essential aspect to be considered during chronic wound management. A well-vascularized wound bed provides nutrients and oxygen in order to sustain the newly formed granulation tissue and to maintain an active immunological response against the microbiological burden present on the wound bed. Direct measurement of tissue oxygen tension in chronic wounds is technically difficult and is noninvasively and continuously recorded by a transcutaneous sensor placed on the surrounding skin and usually kept at the unphysiological temperature of 40°C in order to obtain reliable values.18 The laser Doppler perfusion imaging system (LDI) is a noninvasive instrument developed in the late 1980s to investigate the skin microvasculature.19 The advantage of this method is principally due to the creation of a two-dimensional flow map of a specific tissue and to the visualization of the spatial variation of its perfusion. Another important aspect is the fact that the instrument is positioned at 50cm distance from the area under investigation, allowing an easy and reproducible assessment inside the wound bed. The LDI includes an optical scanner that guides a low power helium-neon laser beam. The light is backscattered from moving erythrocytes according to the Doppler principle and detected by a photodetector. A color-coded image representing tissue perfusion is generated and visualized on the computer screen. The instrument has been used to examine the effects of postural changes on blood flow,20 as well as postural vasoregulation and mediators of reperfusion injury in venous ulceration.21 It has also been used to monitor changes in experimental skin wounds and island flaps22 and to assess burn wound depth.23 Recently, Newton, et al., have shown that this technique is reliable in diabetic foot ulcer assessment where the oxygen supply to skin is often impaired by several factors.24 Wound Bed Area and Volume Today, recording wound area and volume is a routine step during patient assessment and provides information on the progress of healing. Wound measurement is usually recorded at baseline and at weekly intervals by an expert caregiver trained for this purpose who is able to use simple and noninvasive tools. There are many wound measuring tools available in wound care from the simple acetate tracing to the most sophisticated computerized equipment, but they cannot be used everywhere and by everyone. A specific project on wound area and volume assessment is in progress at the Department of Dermatology, University of Pisa.25 The project aims at setting up a prototypic system that is capable of acquiring the forms and colors of wounds, processing the obtained data, and providing an objective determination of the values related to specific parameters considered to be significant by the dermatological staff involved in the project. The acquisition of data starts from the definition of a three-dimensional model and from a two-dimensional picture of the lesion. This model could be defined using a three-dimensional scanner—a technology that, although tested recently, has been proven useful for professional applications. The coherent light LASER models seem particularly useful for acquiring forms and colors of wounds because they carry out the three-dimensional scanning using a light LASER beam without physical contact with the wound. By using various perspectives and specific software, it is possible to obtain a three-dimensional model of the wound. At the same time, a digital camera takes a classical two-dimensional photograph of the lesion already in numerical format, which represents the real lesion in a two-dimensional environment. A specific chromatic elaboration of the picture allows us to change the real colored image to one in which the colors are those used in medical practice: red, yellow, and black. Many manufacturers offer drivers and elaboration software together with the digital camera. The most important phase in the process consists of mapping the two-dimensional image onto the polygonal mesh of the three-dimensional object (Figure 5). It is important to underline that, apart from the methodology and instruments that have just been described, the acquiring of a three-dimensional color image could be made even simpler. Some three-dimensional scanners may conduct the acquisition phases of two- and three-dimensional images and the respective two-dimensional mapping on the three-dimensional model and produce a complete three-dimensional model of the object (Figure 6). Whatever equipment is used, a multidimensional model can be achieved, which, therefore, contains not only quantitative geometrical information but also qualitative information regarding the colors of the injury. Recently, a novel noninvasive instrument to assess the physical dimensions of wounds has been described by Plasmann, et al.26 The measurement process starts from the image acquisition and processing and after the surface reconstruction arrives at the definition of wound dimensions. The technology uses structured light, a method that is able to identify the area via a set of parallel stripes of alternating colors between red and blue, which are projected onto the wound area and recorded by a CCD camera. The wound volume is calculated using a computer that elaborates the three-dimensional map obtained from the known position of the focal points of projector and camera and from the observed intersection points of the stripes of light with the wound surface. The authors reported an accuracy of about two percent for area and three percent for volume and more reproducible results with a minimum of interobserver error compared to established techniques. Conclusions The advent of computerized technologies is currently providing a variety of diagnostic and therapeutic devices that will be used in research and in clinical practice and that will provide fruitful information about the multitude of wound management dilemmas. The skin has the advantage of being easily accessible and simply measurable, but the information that we could obtain from this tissue is as yet quite unknown for most of the physical parameters already explored. In the near future, a greater interaction with the engineering fields is desirable in order to share complementary applications of measuring devices already available on the market but unknown by one side of the team. The objective assessment of chronic wounds during tissue repair will become a specific aspect within wound management, which will not replace the clinical assessment of expert caregivers but may bring numerous advantages in terms of understanding and awareness of the problem. Major innovations will be in terms of 1) easy and accurate data collection, storage, and recall; 2) the chance to have a pictorial and graphical record of a patient’s wound with data that can be directly inserted into documents; 3) an easily accessible database for later comparisons of treatment techniques; and 4) a standard database of patient information. Optimization of noninvasive instrumental techniques should benefit from controlled standardization of measurements. The environmental conditions may significantly alter specific physical parameters of wound bed, thus a basic knowledge of the wound aspect to be evaluated is of paramount importance. By using different combinations of the above mentioned noninvasive techniques, valuable information can be gained regarding pathophysiological phenomena of wound healing and the effect of therapeutic procedures in several types of chronic wounds. Acknowledgment The authors wish to thank Mrs. Graziana Battaglia and Mr. Ivor Rowan for technical assistance in preparing the manuscript.

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