Pixel Statistical Analysis of Diabetic vs. Non-diabetic Foot-Sole Spectral Terahertz Reflection Images
In this article, we present a series of hydration mapping images of the foot soles of diabetic and non-diabetic subjects measured by terahertz reflectance. In addition to the hydration images, we present a series of RYG-color-coded (red yellow green) images where pixels are assigned one of the three colors in order to easily identify areas in risk of ulceration. We also present the statistics of the number of pixels with each color as a potential quantitative indicator for diabetic foot-syndrome deterioration.
KeywordsTerahertz imaging Diabetic foot Tissue hydration Biomedical applications
Diabetes mellitus is nowadays considered a global pandemic owing to its high prevalence worldwide, affecting ∼8.5% of the world population . It generates extraordinary costs for patients and public health systems across the world. Diabetes occurs when the pancreas does not produce enough insulin or the insulin it produces is not used effectively by the body . Insulin is a hormone that regulates blood sugar levels. Over time, high sugar levels cause severe damage to various organs and systems, especially the nerves and blood vessels . The combination of microvascular and neurological deterioration causes diabetic foot syndrome. A patient with diabetic foot presents dehydration and loss of sensation in his/her lower limbs  which, in many cases, leads to the formation of ulcers that can become infected and if not properly and timely treated, result in the amputation of the affected limb . Due to the complexity and prevalence of this condition, an early diagnostic test to avoid these consequences is highly desirable.
Terahertz radiation has certain characteristics that allow multiple applications in various areas. Particularly, in medicine [6, 7, 8] and biology [9, 10, 11], given that the hydration level of biological tissues can be determined non-destructively by terahertz radiation since it is strongly absorbed by water, furthermore, THz photon energy is too low to cause ionization, and therefore, tissue damage. Terahertz has been proposed as a potential tool for the diagnosis of skin burns [12, 13] as well as skin , breast , colon [16, 17], and other forms of cancer , as well as other health conditions such as corneal deterioration .
We recently proposed terahertz imaging as a potential diagnostic tool for the diabetic foot . In that publication, the hydration was monitored on the sole of the foot of a control group and a group of diabetic patients. Although significant differences were observed regarding the water content of both groups, it is still necessary to define indicators to perform a better diagnosis of the syndrome, follow up the treatments given to the patients, and help in the prevention of injuries. In order to overcome these limitations, we propose a new form of image display that shows the clearly distinguished areas of the foot sole in three different colors depending on the degree of hydration: red for low hydration (W% < 47%), yellow for medium hydration (47% < W% < 58%), and green for good hydration (W% > 58%) which, in turn, indicate the degree of deterioration as high-, medium-, and low-risk, respectively.
2.1 Subject Selection
The right foot of a group of 38 diagnosed diabetic patients from the Hospital Regional Leon of the Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado was imaged with one exception, which was a patient that already had undergone right-foot amputation, in that case, the left foot was imaged instead. Of the images taken, 26 were discarded because they were unsuitable for analysis, mainly because the patient moved during the data acquisition. In addition, 33 volunteers were recruited among students and employees of the Centro de Investigaciones en Optica A.C.; none of them was a diagnosed diabetic, however, no control test was applied to this group. Of those images, 12 were discarded following the same criteria as for the diabetic patients. This is the same set of measurement presented in our previous article .
2.2 Imaging Setup
A platform was designed to maintain the patient in a sitting position, while his/her feet rested on a high-density polyethylene window. Underneath the window, a raster scanning XY platform moved a ± 12.5° emitter-lens-lens-detector confocal ensemble whose focus lies on the polyethylene window. A point-by-point terahertz time-domain signal was acquired using a Menlo systems Tera-K-15 spectrometer properly interfaced with the XY platforms. Further details on the setup can be found in .
2.3 Signal Processing
2.4 RYG-Image Construction
From the amount of water in different regions of the sole of the foot, quantitative indicators of the degree of deterioration of the skin can be determined and with it, the risk of developing an ulcer. The RYG images allow a better visualization of regions of interest, that is, areas on the sole of the foot with larger risk level. In addition, they help the diagnostician to determine the severity and extent of the diabetic foot problem. The statistics of the number of red, yellow, and green pixels in conjunction to the absolute hydration values serve as quantitative measures of the problem and can therefore be used in the evaluation of the patients’ evolution and the assessment of new treatments. While very encouraging, it is worth mentioning that these results present a few limitations. Firstly, the lack of a golden standard for early diabetic foot deterioration is not incorporated. Secondly, the control group was not screened for diabetes, so there is a possibility that there are a few diabetics within our control group. Thirdly, there is an age difference between the control group, which contains a number of young graduate students, and the diabetic group, which is mostly in the 50- to 65-year band; this could result in a bias of our results. Yet, we consider that our results suggest great potential of the technique and we are working in gaining access to larger control and diabetic groups in order to conduct a more rigorous clinical trial.
The authors would like to acknowledge the financial support of CONACyT through grants 280392, 255114 and 252939 and scholarships 291236 and 290915. We also want to thank H. L. Lopez-Lemus who helped with the logistics of the measurements at ISSSTE-Leon, and the ethics committee paperwork.
Compliance with Ethical Standards
The protocol for measurements on human subjects was approved by the Ethics Committee of the Hospital Regional Leon of the Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado on the 18/SEP/2014. All patients signed an informed consent form.
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