David Diaz

Diffuse photon density wave measurements and Monte Carlo simulations.

Abstract. Diffuse photon density wave (DPDW) methodology is widely used in a number of biomedical applications. Here, we present results of Monte Carlo simulations that employ an effective numerical procedure based upon a description of radiative transfer in terms of the Bethe–Salpeter equation. A multifrequency noncontact DPDW system was used to measure aqueous solutions of intralipid at a wide range of source–detector separation distances, at which the diffusion approximation of the radiative transfer equation is generally considered to be invalid. We find that the signal–noise ratio is larger for the considered algorithm in comparison with the conventional Monte Carlo approach. Experimental data are compared to the Monte Carlo simulations using several values of scattering anisotropy and to the diffusion approximation. Both the Monte Carlo simulations and diffusion approximation were in very good agreement with the experimental data for a wide range of source–detector separations. In addition, measurements with different wavelengths were performed to estimate the size and scattering anisotropy of scatterers.

Diffuse near-infrared spectroscopy prediction of healing in diabetic foot ulcers: A human study and cost analysis

Wound size reduction has been the standard benchmark for determination of efficacy for diabetic ulcer treatments but due to interclinician error and difficulty measuring irregular wound shapes, this method is unreliable with a positive predictive value of less than 60%. Diffuse near‐infrared spectroscopy (DNIRS) uses 70‐MHz modulated light in the diagnostic window (650–900 nm) noninvasively to quantify levels of oxy‐ and deoxy‐hemoglobin in the wound bed, which when measured over time, can show a trend toward or away from healing based on the changes in oxy‐hemoglobin concentration from week to week. In this study, DNIRS was used to monitor 24 human diabetic foot ulcers longitudinally over the course of 20 weekly or biweekly measurement sessions. In just 4 weeks, the DNIRS system has an 82% positive predictive value (sensitivity of 0.9 and specificity of 0.86; p < 0.002). These data indicate that it could be possible to predict healing in 4 weeks using DNIRS, which can provide objective guidance toward the continuation of costly treatments. Discontinuing ineffective treatments after 4 weeks could have potentially saved over

Development of a multi-frequency diffuse photon density wave device for the characterization of tissue damage at multiple depths

12,600 per patient, based on the treatment regimen of patients in this study.

Pressure injury prediction using diffusely scattered light

The ability to determine the depth and degree of cutaneous and subcutaneous tissue damage is critical for medical applications such as burns and pressure ulcers. The Diffuse Photon Density Wave (DPDW) methodology at near infrared wavelengths can be used to non-invasively measure the optical absorption and reduced scattering coefficients of tissue at depths of several millimeters. A multi-frequency DPDW system with one light source and one detector was constructed so that light is focused onto the tissue surface using an optical fiber and lens mounted to a digitally-controlled actuator which changes the distance between light source and detector. A variable RF generator enables the modulation frequency to be selected between 50 to 400MHz. The ability to digitally control both source-detector separation distance and modulation frequency allows for virtually unlimited number of data points, enabling precise selection of the volume and depth of tissue that will be characterized. Suspensions of Intralipid and india ink with known absorption and reduced scattering coefficients were used as optical phantoms to assess device accuracy. Solid silicon phantoms were formulated for stability testing. Standard deviations for amplitude and phase shift readings were found to be 0.9% and 0.2 degrees respectively, over a one hour period. The ability of the system to quantify tissue damage in vivo at multiple depths was tested in a porcine burn model.

Blood flow analysis for prediction of pressure ulcer development using diffuse correlation spectroscopy

Abstract. Pressure injuries (PIs) originate beneath the surface of the skin at the interface between bone and soft tissue. We used diffuse correlation spectroscopy (DCS) and diffuse near-infrared spectroscopy (DNIRS) to predict the development of PIs by measuring dermal and subcutaneous red cell motion and optical absorption and scattering properties in 11 spinal cord injury subjects with only nonbleachable redness in the sacrococcygeal area in a rehabilitation hospital and 20 healthy volunteers. A custom optical probe was developed to obtain continuous DCS and DNIRS data from sacrococcygeal tissue while the subjects were placed in supine and lateral positions to apply pressure from body weight and to release pressure, respectively. Rehabilitation patients were measured up to four times over a two-week period. Three rehabilitation patients developed open PIs (POs) within four weeks and eight patients did not (PNOs). Temporal correlation functions in the area of redness were significantly different (p<0.01) during both baseline and applied pressure stages for POs and PNOs. The results show that our optical method may be used for the early prediction of ulcer progression.

Assessment of sacrococcygeal pressure ulcers using diffuse correlation spectroscopy

Microcirculation is essential for supply of oxygen and nutrients to organ tissues as well as the removal of waste products of metabolism. Consequently, microcirculatory blood flow is of substantial interest to clinicians for assessing tissue health, particularly in regards to pressure injuries and suspected deep tissue injury. We used optical methods of noninvasive diffuse correlation spectroscopy (DCS) and diffuse near infrared spectroscopy (DNIRS) to predict the development of pressure injuries by measuring dermal and subcutaneous red cell motion. We recruited 14 rehabilitation patients with non blanchable redness in the sacrococcygeal area and 20 healthy volunteers from Magee Rehabilitation Hospital in Philadelphia, PA. Among the rehabilitation patients, 3 developed open pressure injuries (PO) within four weeks of enrolling while 11 patients did not (PNO). Our measurement protocol consisted of three stages in order to collect blood flow changes during baseline, applied body weight pressure, and released pressure stages. The characteristic time of DCS temporal correlation function scattered light intensity, \( \tau_{\exp } \), characterized the tissue blood flow and were compared for both patient groups. Results from baseline measurements showed \( \tau_{\exp } \) values approximately five times larger (p=0.0002) for POs compared with PNOs, suggesting POs have faster blood flow than PNOs in their respective areas of redness. Similar differences were obtain for two next monitoring stages. Preliminary results suggest the used method is able to accurately predict the progression of early stage pressure injuries in the sacrococcygeal area.

Ultrasound for healing chronic wounds

Microcirculation is essential for proper supply of oxygen and nutritive substances to the biological tissue and the removal of waste products of metabolism. The determination of microcirculatory blood flow (mBF) is therefore of substantial interest to clinicians for assessing tissue health; particularly in pressure ulceration and suspected deep tissue injury. The goal of this pilot clinical study was to assess deep-tissue pressure ulceration by non-invasively measuring mBF using Diffuse Correlation Spectroscopy (DCS). DCS provides information about the flow of red blood cells in the capillary network by measuring the temporal autocorrelation function of scattering light intensity. A novel optical probe was developed in order to obtain measurements under the load of the subject’s body as pressure is applied (ischemia) and then released (reperfusion) on sacrococcygeal tissue in a hospital bed. Prior to loading measurements, baseline readings of the sacral region were obtained by measuring the subjects in a side-lying position. DCS measurements from the sacral region of twenty healthy volunteers have been compared to those of two patients who initially had similar non-blanchable redness. The temporal autocorrelation function of scattering light intensity of the patient whose redness later disappeared was similar to that of the average healthy subject. The second patient, whose redness developed into an advanced pressure ulcer two weeks later, had a substantial decrease in blood flow while under the loading position compared to healthy subjects. Preliminary results suggest the developed system may potentially predict whether non-blanchable redness will manifest itself as advanced ulceration or dissipate over time.

20 kHz ultrasound assisted treatment of chronic wounds with concurrent optic monitoring

Over 500,000 patients are treated for venous ulcers annually, accounting for approximately 1% of total healthcare costs in the western world.1, 2 Direct wound care costs often exceed

Diffuse photon density wave measurements in comparison with the Monte Carlo simulations

2,400 per month,1, 2 but despite this, the pain and resulting limitations on mobility and productivity mean venous ulcers force many patients to give up work. Not only does this create an economic drain, but it can potentially lead to further costs associated with anxiety and depression.3 Hence, even modest reductions in healing time could reduce healthcare costs significantly. The ideal solution could be used at home by patients, reducing hospital visits for patients with limited mobility and providing moreconvenient treatment for chronic wounds. We recruited 16 patients between the ages of 18 and 80 years and with chronic venous ulcers from Drexel University Wound Healing Center for a trial of ultrasound treatment of their wounds with concurrent optical monitoring. Eligibility included having had a documented venous ulcer for at least 8 weeks with a surface area 1cm2 using a standard calculation of length width.4 Furthermore, patients with moderate to severe vascular insufficiency (ankle brachial index <0.75 or toe brachial index <0.5) were excluded, as tissue oxygen perfusion and subsequent wound healing are known to be diminished in these individuals.5 Patients with invasive bacterial infection or on antibiotics were also excluded. Following enrolment, the subjects were randomly assigned to one of two experimental groups: active ultrasound treatment or treatment with a sham applicator. Treatment sessions lasted 15 minutes and were conducted once a week for a period of 12 treatments, or until closure. Throughout the study, all subjects received standard wound care that included weekly or Figure 1. The ultrasound applicator used during the clinical study.

Diffuse Correlation Spectroscopy to Assess Capillary Flow Relative to Vascular Disease and Cigarette Smoking

This paper describes a novel, wearable, battery powered ultrasound applicator that was evaluated as a therapeutic tool for healing of chronic wounds, such as venous ulcers. The low frequency and low intensity (~100mW/cm2) applicator works by generating ultrasound waves with peak-to-peak pressure amplitudes of 55 kPa at 20 kHz. The device was used in a pilot human study (n=25) concurrently with remote optical (diffuse correlation spectroscopy - DCS) monitoring to assess the healing outcome. More specifically, the ulcers’ healing status was determined by measuring tissue oxygenation and blood flow in the capillary network. This procedure facilitated an early prognosis of the treatment outcome and – once verified - may eventually enable customization of wound management. The outcome of the study shows that the healing patients of the ultrasound treated group had a statistically improved (p<0.05) average rate of wound healing (20.6%/week) compared to the control group (5.3%/week). In addition, the calculated blood flow index (BFI) decreased more rapidly in wounds that decreased in size, indicating a correlation between BFI and wound healing prediction. Overall, the results presented support the notion that active low frequency ultrasound treatment of chronic venous ulcers accelerates healing when combined with the current standard clinical care. The ultrasound applicator described here provides a user-friendly, fully wearable system that has the potential for becoming the first device suitable for treatment of chronic wounds in patients homes, which - in turn - would increase patients’ compliance and improve quality of life.