SBIR-STTR Award

Chronic wounds are non-healing wounds such as diabetic ulcers and pressure ulcers. Each year, 6.5 million cases occur in the U.S., costing the economy billions of dollars. Cost-effective and efficient management of chronic wounds depends on quick assessment and diagnosis of the underlying reasons for compromised healing. Ischemia is one of the main complications associated with chronic wounds. Thus, a quantitative method to assess and monitor tissue oxygenation and perfusion status of cronic wounds can be an indispensable tool for prevention and cost-effective management of chronic wounds. In this STTR phase I proposal, we test the ability of a newly developed near-infrared imaging method called modulated imaging as a non-contact wound perfusion and oxygenation imager. Two main features of the modulated imaging device are (a) its capability to provide 2D topographic maps of hemoglobin concentrations and oxygen saturation, and (b) its depth-sectioning capability to provide 3D tomographic images. In this study, these features are tested on an animal wound model that simulates chronic wounds undergoing ischemia. Specific aims are to (1) implement ischemic skin flaps in rats to simulate chronic wounds with compromised tissue oxygenation and perfusion; (2) Acquire full range of multi-spectral, multi- spatial-frequency images of skin flaps before and after surgery; (3) process and optimize images for 2D/3D mapping of hemoglobin concentrations, oxygen saturation, and water content in superficial wound. The results of this work will provide essential design for building a dedicated prototype imaging oximeter system for evaluating clinical wounds in Phase II.

Thesaurus Terms:
biomedical equipment development, biosensor device, chronic disease /disorder, ischemia, oxygen transport, skin ulcer, three dimensional imaging /topography, wound healing blood circulation, body water, diagnosis design /evaluation, hemoglobin bioengineering /biomedical engineering, bioimaging /biomedical imaging, infrared spectrometry, laboratory rat, optical tomography, surgery

The use of tissue transfer flaps is a method of moving tissue from a donor location to recipient location and re-attaching the arteries &veins to the blood vessels at the recipient site. These procedures enable reconstructive surgery after trauma, as well as after surgical resection of cancer. Flap transfer surgery is subject to failure via a number of modes including vascular insufficiency caused by mechanical obstruction of the artery or vein, injury caused to the transferred tissues due to the lack of blood flow during the flap transfer, or due to ischemia-reperfusion injury. The first postoperative days after free tissue transfer are characterized by the risk of microvascular complications and loss of transferred tissue by necrosis. Loss of a free flap is a devastating experience to both the surgeon and the patient. Tissue oxygenation and maintenance of microvascular blood flow in grafted tissues are crucial for flap viability. Several studies have demonstrated that frequent monitoring and early detection of compromise results in earlier intervention which reduces the number of devastating complications that lead to tissue loss. Early in the era of microsurgery, flap monitoring was performed with only clinical observation of skin color, capillary refill, and dermal bleeding. However, issues related to staffing and subjective variations in clinical assessment of a flap's perfusion have led to the search for objective methods of flap monitoring. One promising technology for measuring local tissue oxygenation in-vivo is diffuse optical spectroscopy (DOS). DOS is a quantitative near-infrared (NIR) spectroscopy technique that can determine absolute concentrations of chromophores such as oxy &deoxy hemoglobin, fat and water. Modulated Imaging (MI) is a NIR imaging method invented at BLI that is based on the principles of DOS and employs patterned illumination to interrogate biological tissues. This non-contact approach enables rapid quantitative determination of the optical properties and in-vivo concentrations of chromophores over a wide field-of-view. The central aim of the proposed research is to further the development of Modulated Imaging and to assess the viability of this as a means to determine status of tissue reconstruction flaps. In Phase I, we carried out an in-vivo MI study using a dorsal pedicle flap rodent model. The dorsal pedicle flap is easily implemented to establish controlled ischemia and re-perfusion of the wounds. This allowed us to employ MI to deduce spatially resolved maps of tissue hemoglobin, oxygenation and hydration over the course of several days. In Phase II we propose to develop and validate an MI instrument for clinical use. Investigations will first evaluate the performance of MI in a controlled model of partial vascular congestion using adult Yorkshire pigs. This will be followed by a study in which MI and a potentially competing FDA cleared device will be employed in a clinical situation in order to assess local flap status. In parallel with the Phase II research outlined herein, we will aggressively pursue commercialization of a medical device based on MI.

Public Health Relevance:
The use of tissue transfer flaps is a method of moving tissue from a donor location to recipient location and re-attaching the arteries &veins to the blood vessels at the recipient site. The medical utility of this process is to allow for reconstructive surgery after trauma, as well as after surgical resection of cancer. This type of reconstructive surgery is subject to failure caused by to mechanical obstruction of the artery or vein;injury caused to the transferred tissues due to the lack of blood flow when a free tissue flap is performed, (the tissue is disconnected prior to re-attaching the blood vessels);or due to a type of injury call ischemia- reperfusion injury, which is a type of injury that results after blood flow has been returned to the transferred tissue. Tissue oxygenation and maintenance of microvascular blood flow in grafted tissues are crucial for flap to survive. The first postoperative days after free tissue transfer are characterized by the risk of microvascular complications and loss of transferred tissue by necrosis. Loss of a free flap is a devastating experience to both the surgeon and the patient. In this proposal we will develop and validate an instrument that has the potential to identify flap failure earlier than is currently achievable. A successful effort has the potential to enable development of a new medical device that will have the capability to guide reconstructive surgery and post-surgical recovery, both reducing post-surgery complication rate and reducing uncertainty in flap healing. This may shorten the duration of hospital stay and associated heath care costs in addition to improving surgical outcomes.

Thesaurus Terms:
21+ Years Old;Abscission;Adult;Adult Human;Algorithms;Arterial Obstruction;Arterial Occlusion;Arteries;Artery Obstruction;Asses;Au Element;Biological;Bleeding;Blood Vessels;Blood Capillaries;Blood Flow;Body Tissues;Calibration;Cancers;Capillaries;Caring;Clinic;Clinical;Clinical Assessments;Complication;Computer Software;Consultations;Data;Data Analyses;Data Analysis;Dermal;Development;Devices;Diabetic Angiopathies;Diabetic Vascular Complications;Diabetic Vascular Diseases;Diabetic Vascular Disorder;Diffuse;Donkey;Dorsal;Early Diagnosis;Early Treatment;Electronics;Enrollment;Equus Asinus;Esthetic Surgery;Evaluation;Excision;Extirpation;Fda Approved;Flr;Failure (Biologic Function);Family Suidae;Fats;Fatty Acid Glycerol Esters;Feedback;Fiber;Flaps;Gold;Healed;Height;Hemoglobin;Hemorrhage;Hydration;Hydration Status;Hydrogen Oxide;Illumination;Image;Imagery;Imaging Device;Imaging Tool;Injury;Institutes;Investigation;Ischemia;Ischemia-Reperfusion Injury;Island Flaps;Loinc Axis 2 Property;Loinc Axis 4 System;Lead;Length Of Stay;Lighting;Location;Maintenance;Malignant Neoplasms;Malignant Tumor;Maps;Marketing;Measurement;Measures;Mechanics;Medical;Medical Device;Medical Center;Methods;Microsurgery;Modeling;Monitor;Motion;Nir Spectroscopy;Near-Infrared Spectrometry;Near-Infrared Spectroscopy;Necrosis;Necrotic;Number Of Days In Hospital;Operative Procedures;Operative Surgical Procedures;Optics;Outcome;Oximetry;Oxygen Saturation Measurement;Patients;Pattern;Pb Element;Performance;Perfusion;Phase;Pigs;Pilot Projects;Plastic Surgical Procedures;Post-Operative;Postoperative;Postoperative Period;Procedures;Process;Property;Protocol;Protocols Documentation;Reconstructive Surgical Procedures;Recovery;Recruitment Activity;Removal;Reperfusion Damage;Reperfusion Injury;Research;Risk;Rodent Model;Services;Simulate;Site;Skin;Software;Spectroscopy;Spectrum Analyses;Spectrum Analysis;Suidae;Surgeon;Surgical;Surgical Flaps;Surgical Interventions;Surgical Procedure;Surgical Removal;Swine;System;Techniques;Technology;Testing;Time;Tissue Grafts;Tissues;Trauma;Uncertainty;Variant;Variation;Veins;Venous;Visualization;Water;Adult Human (21+);Adulthood;Animal Facility;Artery Occlusion;Base;Blood Loss;Capillary;Chromophore;Commercialization;Computer Program/Software;Cost;Developmental;Digital;Doubt;Early Detection;Early Intervention;Early Therapy;Enroll;Experience;Failure;Healing;Heavy Metal Pb;Heavy Metal Lead;Hospital Days;Hospital Length Of Stay;Hospital Stay;Human Subject;Image Registration;Imaging;Imaging Method;Imaging Modality;Improved;In Vivo;Insight;Instrument;Malignancy;Mechanical;Microvascular Complications;Microvascular Complications Of Diabetes;Microvascular Disease;Neoplasm/Cancer;Optical;Pilot Study;Plastic Surgery;Porcine;Reconstruction;Reconstructive Surgery;Recruit;Resection;Sensor;Skin Color;Suid;Surgery;Tissue Grafting;Tissue Oxygen Saturation;Tissue Oxygenation;Tissue Reconstruction;Vascular