Early prediction of pressure injury development using diffuse correlation spectroscopy

Pressure injuries (PIs) are a serious secondary complication for patients with prolonged immobility that are often caused by prolonged ischemia and reperfusion injury. The cost to manage a single full-thickness pressure injury is estimated to be as high as $120,000 and hospitals are not reimbursed for treatment of PIs that are not documented as "present on admission." Detection of early pressure injuries is currently performed through visual inspection. However, these methods are inadequate because they only evaluate the surface of the skin and provide no information to the underlying health of deep tissue, where PIs often manifest. For this reason, deep tissue pressure injury (DTPI) is often not evident until the injury has evolved to an advanced PI and tissue breakdown. Therefore, there is a well-defined need to develop a method to noninvasively examine tissue below the surface of the skin to identify deep tissue pressure injury earlier than it can be detected by current methods. The goals of this research were to enable early detection of PI in high risk patients and to develop a procedure capable of differentiating between patients who develop advanced pressure injuries and those who do not. Diffuse correlation spectroscopy (DCS), a noninvasive optical method, was used to measure microcirculatory blood flow in skin and subcutaneous tissue. Data was collected from the DCS device and analyzed in the form of τ_exp, which is a value calculated directly from the measured temporal correlation function (TCF) of scattered light intensity. In addition a multi-distance DCS algorithm was developed in order to calculate the optical properties from multiple TCFs, thereby providing more information on the health of underlying tissue. This method was validated in vitro through the use of optical phantoms and later applied to human data. The DCS device was first tested in a clinical study that included 16 spinal cord injury patients with erythema in the sacrum from a rehabilitation hospital. Patients were measured in a three-step protocol to monitor blood flow during baseline, applied pressure, and released pressure stages. Four of the 16 patients developed an open ulcer (Advanced PIs) while the other 12 patients did not develop an open ulcer (No PIs). The baseline results showed that Advanced PIs had τ_exp values 7-8 times lower than No PIs, suggesting Advanced PIs had significantly faster blood flow than that of No PIs. Patients from an acute care setting were also measured, including individuals in the surgical intensive care unit (SICU), individuals in the trauma and surgical step-down units, and surgical patients in the post-anesthesia care unit (PACU). During these studies, several modifications were made to the device in order to increase the efficiency of the protocol and usability for a layperson. The results from these studies showed the same trends found from the rehab study. The patient who developed a PI from the SICU had an average τ_exp value about two times lower than that of other SICU patients who did not develop a PI, suggesting faster blood flow. Also the patient who developed a PI from the surgical study had a τ_exp value ~2.5 times lower post-op compared to pre-op, the highest ratio among all patients. Furthermore, when applying the multi-distance DCS algorithm to the data collected from surgical patients and showed a difference of 6.5 times between post-op and pre-op blood flow for the patient who developed an Advanced PI. The successful implementation of DCS technology as a pressure injury assessment method would result in improved and personalized patient care. It would permit clinicians to immediately assess the severity and extent of a subcutaneous injury and change the preventive treatment, if needed. It would also decrease morbidity and minimize the hospital's liability to patients who develop PIs in their care.Ph.D., Biomedical Engineering -- Drexel University, 201

Comparison of optical measurements of critical closing pressure acquired before and during induced ventricular arrhythmia in adults

Significance: The critical closing pressure (CrCP) of cerebral circulation, as measured by diffuse correlation spectroscopy (DCS), is a promising biomarker of intracranial hypertension. However, CrCP techniques using DCS have not been assessed in gold standard experiments. Aim: CrCP is typically calculated by examining the variation of cerebral blood flow (CBF) during the cardiac cycle (with normal sinus rhythm). We compare this typical CrCP measurement with a gold standard obtained during the drops in arterial blood pressure (ABP) caused by rapid ventricular pacing (RVP) in patients undergoing invasive electrophysiologic procedures. Approach: Adults receiving electrophysiology procedures with planned ablation were enrolled for DCS CBF monitoring. CrCP was calculated from CBF and ABP data by three methods: (1) linear extrapolation of data during RVP ( CrCP RVP ; the gold standard); (2) linear extrapolation of data during regular heartbeats ( CrCP Linear ); and (3) fundamental harmonic Fourier filtering of data during regular heartbeats ( CrCP Fourier ). Results: CBF monitoring was performed prior to and during 55 episodes of RVP in five adults. CrCP RVP and CrCP Fourier demonstrated agreement ( R = 0.66 , slope = 1.05 (95%CI, 0.72 to 1.38). Agreement between CrCP RVP and CrCP Linear was worse; CrCP Linear was 8.2 ± 5.9    mmHg higher than CrCP RVP (mean ± SD; p < 0.001 ). Conclusions: Our results suggest that DCS-measured CrCP can be accurately acquired during normal sinus rhythm

Alterations in cerebral and cardiac mitochondrial function in a porcine model of acute carbon monoxide poisoning

Objectives: The purpose of this study is the development of a porcine model of carbon monoxide (CO) poisoning to investigate alterations in brain and heart mitochondrial function. Design: Two group large animal model of CO poisoning. Setting: Laboratory. Subjects: Ten swine were divided into two groups: Control (n = 4) and CO (n = 6). Interventions: Administration of a low dose of CO at 200 ppm to the CO group over 90 min followed by 30 min of re-oxygenation at room air. The Control group received room air for 120 min. Measurements: Non-invasive optical monitoring was used to measure cerebral blood flow and oxygenation. Cerebral microdialysis was performed to obtain semi real time measurements of cerebral metabolic status. At the end of the exposure, both fresh brain (cortical and hippocampal tissue) and heart (apical tissue) were immediately harvested to measure mitochondrial respiration and reactive oxygen species (ROS) generation and blood was collected to assess plasma cytokine concentrations. Main results: Animals in the CO group showed significantly decreased Complex IV-linked mitochondrial respiration in hippocampal and apical heart tissue but not cortical tissue. There also was a significant increase in mitochondrial ROS generation across all measured tissue types. The CO group showed a significantly higher cerebral lactate-to-pyruvate ratio. Both IL-8 and TNFα were significantly increased in the CO group compared with the Control group obtained from plasma. While not significant there was a trend to an increase in optically measured cerebral blood flow and hemoglobin concentration in the CO group. Conclusions: Low-dose CO poisoning is associated with early mitochondrial disruption prior to an observable phenotype highlighting the important role of mitochondrial function in the pathology of CO poisoning. This may represent an important intervenable pathway for therapy and intervention

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate–pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0–8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8–24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB