Digital Image Analysis: A Reliable Tool in the Quantitative Evaluation of Cutaneous Lesions and Beyond CORRESPONDENCE RESEARCH LETTERS Digital Image Analysis: A Reliable Tool in the Quantitative Evaluation of Cutaneous Lesions and Beyond Q uantitative evaluation of cutaneous lesions inclinical trials can be problematic for diseasessuch as lower extremity ulcers, vitiligo, and alopecia. Because of the irregular shapes of these lesions, calculation of their circumference, diam- eter, and area can be cumbersome using traditional manual tracings. As a result, most trials using manual tracings will measure the longest diameter or approxi- mate circumference of a target lesion. To compound the problem, in some diseases, access to the lesions is diffi- cult. These lesions include erosions of the oral or geni- tal mucosa. New software is now readily available that incorporates digital technologies and allows for digital image analysis (DIA) to circumvent these traditional problems. Digital image analysis provides a means to calculate desired target diameter and area with ease. Our objective was to compare the interrater reliabil- ity and application feasibility of Image Pro Express (Me- dia Cybernetics, Silver Spring, Maryland) DIA software with traditional manual tracings to determine the area of lower extremity ulcers. Methods. Our study was imbedded in a larger random- ized, double-blind, placebo-controlled trial, and inclu- sion and exclusion criteria was previously described by Sumpio et al.1 After approval from the respective insti- tutional review boards, participants were recruited from vascular surgery and podiatry clinics from a total of 16 sites in the United States. Each site provided both digital images and transparen- cies with manual tracings of the target ulcers (Figure 1). Of the 3 possible readers, 2 readers outlined the target ul- cers from both the digital images and the transparencies. At all sites, digital images were obtained using a Nikon (Mel- ville, New York) Coolpix 8800 camera. Furthermore, all images were obtained using standardized procedures; no- tably, the target ulcers were positioned 6 inches away from the camera and facing the light, to avoid any shadows. A metric ruler was placed on both the digital images and trans- parencies to allow for measurement calibration. Once the digital images were obtained, they were uploaded into an IBM (Chicago, Illinois) desktop computer, and the perim- eter of each ulcer was outlined electronically by the 2 read- ers using a wireless mouse (Figure 2). Concurrently, the respective transparencies with manual tracings outlined by the 2 readers were scanned into the computer using a stan- dard IBM flatbed scanner. We then used the Image Pro Ex- press DIA software to determine the diameter and subse- quent area of the target ulcers for both the digital images and the manual tracings. Continuous variables were calculated as means ± SDs and were compared by t test or analysis of variance where appropriate. Categorical variables were com- pared by �2 analysis. Finally, agreement between raters was determined by intraclass correlation coefficient. Reliability of DIA was determined by comparing the area obtained from DIA to the area obtained from manual tracings. P � .05 was considered statistically significant. Results. A total of 99 patients with lower extremity ul- cers were recruited into the study. The mean ± SD pa- tient age was 66 ± 13 years; 65% were men (n = 65), and 64% were white (n = 64). In addition, 77% of the lower extremity ulcers were from participants who were diag- nosed as having diabetes mellitus (n = 76). Of the 99 patients in the study, 91 patients had manual tracings and 91 had digital images; 87 had both. The mean ± SD lower extremity ulcer area measured by reader 1 was 3.27 ± 3.53 cm2 in the manual tracings and 3.08 ± 3.15 cm2 in the digital images. Similarly, the lower extremity ulcer mean ± SD area measured by reader 2 was 3.28 ± 3.50 cm2 in the manual tracings and 3.11 ± 3.18 cm2 in the digital images. The intraclass correlation coeffi- cient between the 2 readers for manual tracing and digi- tal images was 0.9994 and 0.9978, respectively. There was no statistically significant differences in areas between manual tracings and digital images (paired t test P = .12; 95% confidence interval, −0.51 to 0.06 cm2). Comment. In our study, we demonstrated that area can be reliably measured across raters using DIA in targeted lower extremity ulcers. Also, we have shown that the results from the DIA approach are not significantly dif- ferent from those of traditional manual tracings. While traditional manual tracings have been the gold standard method by which to evaluate lower extremity ulcer circumference, diameter, and area, manual trac- ings can be cumbersome given the irregular shapes of these lesions. However, DIA can provide quantitative evalua- tion of target lower extremity ulcers with greater ease and efficiency. Therefore, we propose that if DIA is as reli- able as traditional manual tracings, DIA may be used to estimate the size of lower extremity ulcers when the in- vestigator sees fit. The use of DIA is not limited to lower extremity ulcers but also potentially extends to other difficult-to- measure lesions. Specifically, DIA may serve a vital role in the quantitative evaluation of other diseases involving irregular-border cutaneous lesions, such as vitiligo and alopecia, as well as difficult to access lesions, such as erosions of the oral or genital mucosa. In fact, DIA may prove to be not only useful and reli- able but also more precise than traditional manual tracings. (REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 10), OCT 2007 WWW.ARCHDERMATOL.COM 1331 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by a Carnegie Mellon University User on 04/05/2021 The greatest limitation of the DIA technology is for use on lesions that cannot be accurately represented in 2 dimensions, such as large ulcers that wrap around the curvature of the limb. In this circumstance, several standardized images of the ulcer and complex recon- struction may be necessary. However, In general, patient positioning, body curvature, or tapering of the limbs, as well as compromised accessibility can be mm mm mm Figure 1. Three digital images with electronic manual tracings (left) and corresponding traditional manual tracings (right). All scales are given in millimeters. (REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 10), OCT 2007 WWW.ARCHDERMATOL.COM 1332 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by a Carnegie Mellon University User on 04/05/2021 sources of measurement error for manual tracings, and in general, DIA provides a technology that can at least partially overcome these problems. Finally, it is important to note that DIA provides information beyond the quantitative evaluation of traditional manual tracings. Because DIA involves digital photog- raphy, it provides an image and thus a basis for objec- tive evaluation of other end points such as infection, lesion thickness, granulation status, surrounding edema, and lesion progression over time, if used at sequential time points. Overall, additional studies are needed to further assess the uses of DIA in quantita- tive evaluation of other cutaneous lesions and beyond. Correspondence: Dr Chen, Department of Dermatol- ogy, Emory University School of Medicine, 101 Woo- druff Cir, Atlanta, GA 30322 (schen2@emory.edu). Financial Disclosure: None reported. Funding/Support: This project was supported in part by an unrestricted educational grant from Otsuka Pharma- ceuticals; National Institutes of Health (NIH) grant NHLBI R01-47345 and the Veterans Administration Merit Re- view Board (Dr Sumpio); and Mentored Patient Ori- ented Career Development Award K23AR02185-01A1 from the National Institute on Arthritis and Musculo- skeletal and Skin Disease, NIH, and the American Skin Association David Martin Carter Research Scholar Award (Dr Chen). 1. Sumpio BE, Chen SC, Moran E, et al. Adjuvant pharmacological therapy in the management of ischemic foot ulcers: results of the HEALing of Ischemic Foot Ulcers With Cilostazol Trial (HEAL-IT). Int J Angiol. 2006;15(2):76-82. Wound Assessment by 3-Dimensional Laser Scanning R ecent advances in our understanding of the biol-ogy of cutaneous tissue repair have influencedcurrent therapeutic strategies for chronic wound management and will continue to influence chronic wound management strategies into the future.1 An effective and accurate monitoring of skin lesions should be performed by measuring in an objective, pre- cise, and reproducible way the complete status and evo- lution of the wound.2 The main goal of current research projects is to design an easy-to-use technological sys- tem that can monitor the qualitative and quantitative evo- lution of a skin lesion. This level of monitoring can be achieved by using 3-di- mensional scanners: in particular, systems based on ac- tive optical approaches.3 There are 2 different areas of potential applications of such types of devices: in medi- cal treatment (to improve the efficacy of therapeutic regi- mens)4 and pharmacologic scientific research (to assess the quality and effectiveness of new chemicals or clini- cal procedures).5 Methods. We prospectively examined 15 patients with venous leg ulcers. The patients who underwent sequen- tial imaging of chronic wounds for this study all at- tended the leg ulcer clinic of the Wound Healing Re- search Unit at the University of Pisa, Pisa, Italy. Our sequential imaging system is equipped with a Vivid 900 laser scanner (Minolta, Osaka, Japan), which is used for digitizing or scanning the wound shape. With regard to the calculation of the “external” surface and volume of a wound, it is necessary to assess its original shape to de- termine the missing volume virtually. At the time of pa- tient presentation, information on the shape of the skin be- fore the wound occurred is missing, and the technique for virtual reconstruction of the original wound surface must be as easy and user-friendly as possible. The system, rely- ing on an analysis of the shape of the surface immediately outside the wound perimeter, creates an interpolating vir- tual surface that is continuously connected to the existing surface outside the wound and to that covering it. The parameters we studied were the mean wound area (measured in square centimeters) and mean volume (cu- bic centimeters). To assess interrater reproducibility, scans were evaluated by 2 independent investigators. For as- sessment of intrarater reproducibility, a single investi- gator performed 2 consecutive measurements 5 min- utes apart. Immediately after the first wound assessment of the first observer, a second observer, blinded to the findings of the first analysis, measured the same wound. The means and standard deviations of duplicate de- terminations for each wound were used for analysis. The reproducibility of measurements was evaluated by means of an intraclass correlation coefficient (ICC) and its 95% confidence interval (CI). Results. The measured total areas and volumes for inde- pendent raters and for subsequent measures of 1 rater are Figure 2. Procedure for using the Image Pro Express (Media Cybernetics, Silver Spring, Maryland) digital image analysis (DIA) software: (1) position target lesion toward camera at a set distance and toward a light source for standardization; (2) place ruler for calibration (present scale is in millimeters); (3) take digital photograph; (4) download image into computer running DIA software; (5) trace target, as demonstrated in this image; and (6) query DIA software to perform diameter and area calculations. Zakiya M. Pressley, MD Jovonne K. Foster, MS Paul Kolm, PhD Liping Zhao, MS Felicia Warren, BA William Weintraub, MD Bauer E. Sumpio, MD, PhD Suephy C. Chen, MD, MS (REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 10), OCT 2007 WWW.ARCHDERMATOL.COM 1333 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by a Carnegie Mellon University User on 04/05/2021