Hemodynamic 3D Infrared Thermal Stereoscopic Imaging (TSI) Investigation in Chronic Vascular Leg Ulcers: A Feasibility Study

  Abstract: Hemodynamic 3D infrared thermal stereoscopic imaging (TSI) was tested as a new non-invasive diagnostic method for studying chronic vascular leg ulcers. The aim was to test this new diagnostic approach in investigating mixed arterio-venous wounds. Duplex ultrasonography is the most useful test for investigating hemodynamic alterations in patients with vascular cutaneous ulcers; however, it fails to provide any information about microvascular dysfunctions, which could play a significant role in the development of skin wounds. The study of thermal patterns at the wound site represents a method of investigating cutaneous microcirculation—temperature gradients indicating abnormal blood flow in the margins and bed of wounds with vascular disorders are well correlated with clinical findings. Methods. In order to evaluate the predominance of the arterial or venous component in vascular mixed ulcers of the leg and to understand the underlying pathology of the ulcers, 3D thermography was tested in three different hemodynamic positions. A total of 20 physiological and 20 pathological patients were assessed standing, supine, or in a discharging position (legs raised above heart level). Results. A relatively constant temperature trend was observed in healthy subjects, while a different reaction was recorded in those with ulcerated legs. Moreover, a different temperature trend was noted among the varying hemodynamic positions and a trend difference was also observed between arterial and venous ulcers in clinical investigation tests. Conclusion. TSI appears to be a safe, user-friendly, rapid, and promising procedure for distinguishing both arterial and venous involvement in mixed arterio-venous leg ulcers.   In the Western world, leg ulcers are mainly caused by venous insufficiency, arterial insufficiency, neuropathy, diabetes, or a combination of these factors. Venous ulcers are the most common type of leg ulcers and account for approximately 70% of cases.¹ Arterial disease accounts for 5% and mixed venous and arterial wounds accounts for 20% of total cases of leg ulcers.¹ Venous ulcers have a considerable socioeconomic impact in Western countries due to their high prevalence, cost of investigations and treatment, and loss of working days. .² Venous ulcers occur in » 0.3% of the adult population in Western countries.³ The prevalence of combined active and healed ulcers is » 1%.⁴ The overall prognosis of venous leg ulcers is poor: only 50% heal at 4 months,⁵ 20% remain open at 2 years, and 8% remain open at 5 years.⁶ The annual recurrence rate varies from 6% to 15%.⁷ The annual cost of venous ulcers has been estimated to be £400 to £600 million for the United Kingdom⁸ and more than $1 billion for the United States.⁹ The total cost of chronic venous insufficiency to society, both direct and indirect, is estimated to be $1 billion (US) in each of three European countries (Germany, France, and the United Kingdom).   Duplex ultrasonography is the most useful test for investigating hemodynamic alterations in patients with suspected venous or arterial cutaneous ulcers. Duplex ultrasonography can detect, localize, and grade venous obstruction, valvular incompetence, and arterial stenosis.¹ However, it fails to provide any information about possible microvascular dysfunctions, which could play a significant role in tissue breakdown and the development of skin wounds.¹⁰   The study of thermal patterns at the wound site represents a method of investigating cutaneous microcirculation. Temperature is an important and useful parameter for diagnosing various diseases.¹¹ The correlation of body temperature and diseases has been known for centuries, but more recently due to the advent of new technologies, skin temperature has been used as a convenient and effective diagnostic tool.¹² In 1956, the first documented application of thermography for early pre-clinical diagnosis of breast cancer was reported.¹³ Infrared thermal imaging has been used to study blood flow, detect breast cancer and muscular performance,¹⁴ and quantify sensitive changes in skin temperature in relation to disease.¹⁵   Thermography can estimate circulation and vascular patency by visualizing temperature distribution¹⁶; in fact, temperature gradients are largely dependent on peripheral blood flow vessels, for example, a decrease in temperature is probably due to slow-moving blood circulation (venous drainage deficiency) or an increase in temperature profile, probably caused by the inflammation.¹⁷   So far, thermometry has been used to assess the diabetic foot and is considered an effective way to assess ulceration risks.¹⁶ Thermal measurement techniques specific to the diabetic foot include electrical contact thermometry, cutaneous thermal discrimination thresholds, infrared thermography, and liquid crystal thermography.¹⁸   The present study reports a new method (3D infrared stereoscopic thermography), which associates skin temperature information with real time reconstruction of all elements of ulcer morphology, such as bed, edges, margins, etc. This ensures rapid and precise surface determination of the areas of interest and is also important for monitoring the ulcer over time in order to provide an accurate assessment irrespective of the viewing angle and distance that may vary between follow-up visits. Furthermore, infrared thermography can provide information regarding skin blood flow in different hemodynamic conditions (ie, standing, supine, and in a discharging position [legs raised above the heart]). This hemodynamic approach could help to understand the different underlying pathophysiology of cutaneous wounds.   Infrared thermography, other than the advantage of being non-invasive,¹⁹ is also fast, reliable, non-contact, capable of producing multiple recordings at short time intervals, and safe for patients and doctors alike.   The aim of the present study was to assess whether 3D stereoscopic thermography applied as a hemodynamic approach could be useful in investigating mixed arterio-venous leg ulcers. Duplex ultrasonography, which remains the primary diagnostic method for this kind of ulcer, is often not able to decipher which component (venous or arterial) is predominant and plays a pathogenetic role in ulcer development.   

Methods

  Thermal device. The 3D thermal stereoscopic vision device (Menci Software srl, Arezzo, Italy) consists of multiple physical components: a pair of Canon EOS 400D digital reflex cameras (10 megapixel) correctly calibrated and positioned on a Manfrotto Mini Salon 190 camera stand in order to create a 3D reconstruction of a body area up to 200 mm x 200 mm, resolution 1 mm, and 500 m in accuracy. The system acquires high-fidelity 3D models of skin and wound colors. The data acquisition process does not require static positioning of the subject. The 70-cm acquisition distance allows for easy management of the device around the patient’s bedside. No marks or references are required. Visible and infrared data are overlapped on the 3D model in real time. A ThermoVision™ A320 infrared camera system (FLIR Systems AB, Danderyd, Sweden) was used to acquire infrared images. The A320 is designed to deliver accurate thermographic images and repeatable temperature measurements in a wide range of automatic applications. Each thermal image is built from 76,800 individual elements sampled using the camera’s on-board electronics and software for measuring temperature. Data can be transferred quickly using the MPEG-4 compressed image format.   Hemodynamic procedure. In order to distinguish the extent of the hemodynamic arterial and venous contribution in mixed arterio-venous leg ulcers we carried out 3D thermal imaging at the site of wounds on patients standing, supine, with their legs raised above the heart (discharging position). The procedure is quick and easy and only requires taking three photos.   Study population. The control group (CNTL) consisted of 20 healthy subjects, 10 male and 10 female. The age range was 55 years ± 7 for all subjects. The male weight range was 72 kg ± 8 kg and the female weight range was 56 kg ± 9 kg. In the tested groups, 20 patients with mixed arterio-venous ulcers in the third distal area were assessed. In order to increase the significance of the test and to standardize controls (healthy patients or CNTL), only female patients with an age range of 62 years ± 9 and weight 58 kg ± 7 kg were selected. All patients with infected ulcers or diabetes were excluded.   

Statistical Analysis

  Statistical analyses were carried out with InStat software (GraphPad Inc., La Jolla, CA). Unless otherwise indicated, all analyses were conducted with the Mann Whitney non-parametric test, used for studies with small numbers of replicates. The Dunnett’s multiple comparison test of all ulcers versus control group (CNTL, healthy female legs) was carried out. Additionally, a t test with the Welch correction was also performed.   

Results

  In healthy subjects the temperature trend of the third distal region of the leg, assessed in different hemodynamic positions, appears to have a constant trend despite slight and not statistically significant differences among the standing, supine, and discharging positions (Figure 1). Conversely, the comparison between male and female subjects showed a statistical difference both when standing (P = 0.0224) via the unpaired t test with Welch correction, and when supine (P = 0.0245), whereas there were no significant differences in the discharging position.   Table 1 shows the mean temperatures (˚C) acquired in three different hemodynamic positions for both ulcer patients and healthy patients (only females were considered).   The delta ([D] Discharging – Standing) values were assessed to get an idea of the difference between the discharging and standing positions. Since healthy patients had a variation less than ± 10%, a variation greater than 10% was considered relevant and predictive of a different hemodynamic condition (Table 1).   The samples that were not considered significant had a flat temperature trend while significant samples had a rising or decreasing trend (Table 2). Figure 2 contains a diagram of the temperature trend of all ulcers detected, and at least three easily distinguished different hemodynamic reactions can be classified in rising, decreasing, or flat temperature trends. Figure 2 shows the following: 55% rise in temperature, 30% drop in temperature, and 15% stable condition. Figures 3–5 show the temperatures (˚C) for increasing, decreasing, and flat trends, respectively. As each hemodynamic evaluation was carried out in three different positions, two different trends were otained (Figure 6). Patient 3 was stable between standing and supine positions with a rise in temperature when the leg was raised above heart level. Conversely, in patient 10 temperature recovery was noted when supine and the patient also remained stable in a discharging position.   

Discussion

  The data analyses revealed that mixed arterio-venous leg ulcers represent a borderline hemodynamic condition in which arterial and venous components seem to play different roles in the pathogenesis of each individual case. The problem is that the therapeutic approach is diametrically opposed in the presence of either an arterial disorder or venous impairment.   In contrast, conventional diagnostic imaging systems provide relatively modest quantitative hemodynamic information about microcirculatory function, which is a crucial aspect in determining ulcer pathogenesis.²⁰ In fact, the exchange of nutrients and metabolites between blood and tissue occurs at the capillary level, which means capillary circulation integrity impacts overall skin health.¹⁰   Despite what is known regarding the importance of microcirculatory conditions in the development of skin wounds, in clinical practice, a detailed microcirculatory analysis is still missing, probably due to a lack of practical means to observe it.²¹ However, technological advances have enhanced microcirculation imaging quality. Several techniques can be used in an in vivo study to investigate skin blood flow, including transcutaneous oxygen tension, tissue pH measurement, photoplethysmography, capillaroscopy, laser Doppler flowmetry, laser Doppler imaging, orthogonal polarization spectral imaging technique, optical coherence tomography, reflectance-mode confocal laser-scanning microscopy, and intravital microscopy.^10,22,23 Each method has its own advantages and limitations (eg, laser Doppler could be very useful in detecting these pathologies; however, until now it has been too complicated, slow, and expensive, and has therefore been used almost exclusively for research). Tissue oximeter technology could also be an interesting diagnostic tool; however, point data acquisition is a clear limitation to the dissemination of technology in this field. Moreover, as with the laser Doppler, the tissue oximeter is slow.¹⁰   The authors selected infrared thermography technology for the present study because it is user-friendly, fast, and costs less than other technologies.¹⁸ Unfortunately, thermography, like bi-dimensional photos, offers limited repeatability. Three-dimensional imaging is an excellent solution because the operator is free to change picture orientation when monitoring patients without influencing the power of the acquired data. Furthermore, stereoscopic solutions in 3D reconstruction processing allow for taking pictures in a very short time, thus avoiding patient discomfort and unfocused or blurred photos. Three-dimensional thermal infrared stereoscopic imaging seems to be an intelligent technique for assessing and monitoring vascular leg ulcers.   One issue of concern is how this technology would translate to use in clinical practice. Initially, valid information was not available to compare with other technologies, with the patient normally supine on the bed. However, some interesting clinical cases using the hemodynamic approach helped the authors re-evaluate the potential of this technique.   

Case Summaries

  Case 3 presents a 67-year-old woman affected by mixed arterio-venous leg ulcer onset 8 months earlier (Figure 7). Figure 8 testifies very well as in supine position ulcer margin temperature was lower than in discharging position. As venous blood is colder than arterial blood, the rise in temperature most likely occurs in the discharging position due to venous blood reflux; therefore, the authors considered that 3D infrared thermal stereoscopic imaging (TSI) could have a role in hemodynamic venous leg ulcer research. Laser Doppler supported the TSI hypothesis of venous predominance of the ulcer since it showed an increase of cutaneous flow following compression, which rose from 25 PU (perfusion units) to 80 PU post compression. Therefore, in the authors’ opinion, 3D TSI has the potential be a valid tool in hemodynamic assessment of arterio-venous leg ulcers.   It is evident from the data analysis that patients can be split into three categories: rising, decreasing, and stable temperature trends between the discharging and standing positions (Figures 9A–C). Basically, patients who experience a rise in temperature in the discharging position could be considered to have a high prevalence of venous impairment (55%), and patients with a decrease in temperature in the discharging position as suffering from arterial impairment (30%), while patients with a stable trend between the discharging and standing positions are affected by comparable venous and arterial impairment (15%). A temperature variation of more than 10% was considered significant. Interestingly, a more accurate examination of the data sheds light on two different trends within the same category. In fact the same discharging temperature could be due to two different situations. Figure 6 illustrates how case 3 and case 10 have a similar discharging temperature (discharging temperature - standing temperature [˚C]); however, in case 10 the temperature recovery occurs in the supine position, while in case 3, in order to achieve a temperature recovery, it was necessary to raise the leg above the heart level. Another example that reinforces the potential of this diagnostic procedure can be observed in the comparison between case 2 versus case 17. Both are considered to be primarily due to arterial impairment, but in case 17 there were no significant differences between the standing and supine positions. In case 2 there was a dramatic temperature drop when passing from a standing to a supine position. Moreover, case 18 belongs to the same arterial group and the marked temperature recovery between the standing and supine positions could be indicative of significant venous blood congestion coexisting with advanced arterial impairment.   Other interesting clinical cases reinforce the potential of this diagnostic procedure.   A year and a half before being examined in our center, a young woman was involved in a motorcycle accident with almost complete destruction of the skin on her foot. She underwent extensive plastic surgery, but as a result of dehiscence of the stitches, an ulcer had formed and was becoming larger. The ulcer was treated with compression bandages. The hemodynamic 3D thermal procedure revealed cold areas in the ulcer in all positions. The thermal trend varied greatly with temperature peaks and dips irrespective of leg position (standing, supine, or discharging). The authors hypothesized that the cause was altered vasomotion, most likely due to damaged innervations post trauma.²⁴ Sympathetic innervations significantly affect how and where blood flow is distributed in response to metabolic demand. The ulcer was treated with laser therapy to improve microcirculation before employing a tissue regeneration procedure. The temperatures have positive absolute values, approximately 31˚C at the first two follow-up visits, with an increase of 2˚C at the third follow-up after microcirculation stimulation therapy.   Finally, a patient with two venous leg ulcers who was suffering from essential thrombocythemia presented to the authors’ department. This patient had different thermal patterns at the two wound sites: from the supine to the discharging position the right ulcer showed a rise in wound temperature, while the left did not show any significant temperature change. The rise in temperature in the right ulcer most likely occurred in the discharging position due to the venous blood reflux, while in the left ulcer it is possible that the thrombosis in the microcirculation prevented cutaneous flow recovery. Moreover, the left ulcer was more painful than the right. Based on this hypothesis, compression therapy was reduced in the left leg and the ulcer subsequently improved. This is another example in which hemodynamic thermography made it possible to investigate cutaneous microcirculation, understand the underlying ulcer pathology, and determine the best treatment.   Unfortunately, the interpretation of thermal patterns can be difficult because skin temperature is influenced by both internal structures and external conditions, such as basal metabolism rate, gender, obesity, skin infection or inflammation, room temperature, etc.¹⁶ The authors have noted, for example, that physiological temperature data were higher in males than in females in all hemodynamic positions, which was expected considering the different basal metabolism rates, and at the same time, tissue inflammation may also raise temperatures in all hemodynamic positions. Therefore, these elements must always be taken into account in the interpretative process of thermal patterns.   

Conclusion

  This preliminary experience has demonstrated how hemodynamic 3D TSI could represent an interesting tool for assessing and monitoring mixed arterio-venous leg ulcers. Three-dimensional thermography has the added advantage of real time reconstruction of all ulcer morphology elements, such as bed, edges, margins, etc. This ensures rapid and precise surface determination of the areas of interest and is also important for monitoring the ulcer over time in order to provide an accurate assessment irrespective of the viewing angle and distance that may vary between follow-up visits.   While the hemodynamic approach dramatically increases the potential of the diagnostic procedure, the present feasibility study suggests the need to introduce an interpretative algorithm in order to guide the physician in the correct diagnostic direction. Furthermore, studies comparing thermography with other techniques to investigate microcirculation in order to confirm the reliability of the authors’ method would be of interest.   

Acknowledgements

  The authors wish to thank Prof. Leonardo Masotti of the University of Florence, Electronic Engineering Dept. and President of DEKA M.E.L.A., srl for his advice, and Mr. Luca Menci, Engineer and Founder of Menci Software, srl, for his advice and technological assistance. This work was supported by Regione Toscana, Project “Trophos” line 1.5 (B), 2008.   

References

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