Jenny E. Freeman

Early changes in the skin microcirculation and muscle metabolism of the diabetic foot.

BACKGROUND Changes in the large vessels and microcirculation of the diabetic foot are important in the development of foot ulceration and subsequent failure to heal existing ulcers. We investigated whether oxygen delivery and muscle metabolism of the lower extremity were factors in diabetic foot disease. METHODS We studied 108 patients (21 control individuals who did not have diabetes, 36 patients with diabetes who did not have neuropathy, and 51 patients with both diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to investigate the haemoglobin saturation (S(HSI)O2; % of oxyhaemoglobin in total haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and foot; we also used 31P-MRI scans to study the cellular metabolism of the foot muscles by measuring the concentrations of inorganic phosphate and phosphocreatine and calculating the ratio of inorganic phosphate to phosphocreatine (Pi/PCr). FINDINGS The forearm S(HSI)O2 during resting was different in all three groups, with the highest value in controls (mean 42 [SD 17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups (p<0.0001). In the foot at resting, S(HSI)O2 was higher in the control (38 [22]) and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12]; p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p<0.0001). INTERPRETATION Our results indicate that tissue S(HSI)O2 is reduced in the skin of patients with diabetes, and that this impairment is accentuated in the presence of neuropathy in the diabetic foot. Additionally, energy reserves of the foot muscles are reduced in the presence of diabetes, suggesting that microcirculation could be a major reason for this difference.

Medical hyperspectral imaging to facilitate residual tumor identification during surgery

Introduction: Adequate evaluation of breast tumor resection at surgery continues to be an important issue in surgical care, as over 30% of postoperative tumors recur locally unless radiation is used to destroy remaining tumor cells in the field. Medical Hyperspectral Imaging (MHSI) delivers near-real time images of biomarkers in tissue, providing an assessment of pathophysiology and the potential to distinguish different tissues based on spectral characteristics. Method: We have used an experimental DMBA-induced rat breast tumor model to examine the intraoperative utility of MHSI, in distinguishing tumor from normal breast and other tissues. Rats bearing tumors underwent surgical exposure and MHSI imaging, followed by partial resection of the tumors, then MHSI imaging of the resection bed, and finally total resection of tumors and of grossly normal-appearing glands. Resected tissue underwent gross examination, MHSI imaging, and histopathological evaluation. Results: An algorithm based on spectral characteristics of tissue types was developed to distinguish between tumor and normal tissues. Tissues including tumor, blood vessels, muscle, and connective tissue were clearly identified and differentiated by MHSI. Fragments of residual tumor 0.5 - 1 mm in size intentionally left in the operative bed were readily identified. MHSI demonstrated a sensitivity of 89% and a specificity of 94% for detection of residual tumor, comparable to that of histopathological examination of the tumor bed (85% and 92%, respectively). Conclusion: We conclude that MHSI may be useful in identifying small residual tumor in a tumor resection bed and for indicating areas requiring more extensive resection and more effective biopsy locations to the surgeon. 3

Evaluation of a Novel Noninvasive Respiration Monitor Providing Continuous Measurement of Minute Ventilation in Ambulatory Subjects in a Variety of Clinical Scenarios

BACKGROUND:Currently there is no technology that noninvasively measures the adequacy of ventilation in nonintubated patients. A novel, noninvasive Respiratory Volume Monitor (RVM) has been developed to continuously measure and display minute ventilation (MV), tidal volume (TV), and respiratory rate (RR) in a variety of clinical settings. We demonstrate the RVM’s accuracy and precision as compared with a standard spirometer under a variety of clinically relevant breathing patterns in nonintubated subjects. METHODS:Thirty-one voluntary subjects completed the primary study. MV, TV, and RR measurements were collected from the RVM and spirometer simultaneously for each participant on day 1 and day 2 and analyzed to determine accuracy, precision, and bias for normal, fast, slow, irregular, and closed-glottis breathing. RESULTS:Data demonstrated that RVM and spirometer measurements of MV and TV are equivalent in a wide range of ambulatory subjects with an average error <10% (95% confidence interval for accuracy <16%, precision <12%, and bias <11%). Repeated measures analysis of variance found no significant difference between spirometry and RVM individual measurements of MV, TV, and RR (P > 0.7), whereas a paired-difference equivalent test demonstrated, with 99% power, that both MV and TV measurements from the 2 devices are equivalent within ±15%. CONCLUSIONS:This study demonstrates RVM’s clinically relevant accuracy and precision in measuring MV, TV, and RR over a 24-hour period and during various breathing patterns.

Emerging Technology: Hyperspectral Imaging:

Clinical decision-making in managing the patient with peripheral vascular disease is dependent upon patient history, physical examination, and noninvasive and invasive testing. Noninvasive testing currently includes the ankle-brachial index, pulse volume recordings, and transcutaneous oximetry. Each test yields information regarding perfusion and tissue oxygenation, but has limitations. The ankle-brachial index compares lower extremity blood pressure with the upper extremity, but it must be interpreted with caution in a patient with calcified atherosclerotic vessels, as is seen with diabetic patients, which can lead to an overestimation of actual pressure. Pulse volume recordings are mainly a qualitative estimation of distal perfusion and are highly dependent on the operator, which introduces both intraobserver and interobserver variability. Duplex ultrasound evaluation looses sensitivity in the small vessels of the limb and can be limited by instrument and operator. Transcutaneous oximetry is a quantitative measure of skin (end organ) oxygenation, but is limited by only evaluating one small area of the foot at a given time. Hyperspectral imaging was developed to possibly provide quantitative information regarding the spatial tissue oxygen saturation in patients with peripheral vascular disease.

Systemic Effects of Shock and Resuscitation Monitored by Visible Hyperspectral Imaging

Hyperspectral imaging (HSI) has been useful in monitoring several medical conditions, which to date have generally involved local changes in skin oxygenation of isolated regions of interest such as skin flaps or small burns. Here, by contrast, we present a study in which HSI was used to assess the local cutaneous manifestations of significant systemic events. HSI of the ventral surface of the lower jaw was used to monitor changes in skin oxygenation during hypovolemic shock induced by hemorrhage with additional pulmonary contusion injury in a porcine model, and to monitor the subsequent recovery of oxygenation with resuscitation. Quantitative and qualitative changes were observed in the level of skin oxygenation during shock and recovery. Quantitative values were obtained by fitting reference spectra of oxyhemoglobin and deoxyhemoglobin to sample spectra. Qualitative changes included changes in the observed spatial distribution or pattern of skin oxygenation. A mottled pattern of oxygen saturation was observed during hemorrhagic shock, but not observed during hypovolemic shock or following resuscitation. Historically, the assessment of skin color and mottling has been an important, albeit inexact, component of resuscitation algorithms. Now, it is possible to analyze these variables during shock and resuscitation in an objective manner. The clinical utility of these advances needs to be determined.

Continuous noninvasive respiratory volume monitoring for the identification of patients at risk for opioid-induced respiratory depression and obstructive breathing patterns.

BACKGROUND Opioid-induced respiratory depression (OIRD) and postoperative apnea (POA) can lead to complications after surgery or traumatic injury. Previously, real-time monitoring of respiratory insufficiency and identification of apneic events have been difficult. A noninvasive respiratory volume monitor (RVM) that reports minute ventilation (MV), tidal volume, and respiratory rate is now available. The RVM was used to report the effect of opioids on respiratory status as well as demonstrate apneic breathing patterns in a hospital postanesthesia care unit. METHODS RVM traces were collected from 132 patients. Predicted MV (MVPRED) for each patient was used to calculate and the “percent predicted” MV (MVMEASURED / MVPRED × 100%) before opioid administration. Patients were stratified patients into two categories: “at risk,” MV of less than 80% MVPRED, and “not at risk,” MV of 80% MVPRED or greater. After opioid dosing, patients with MV of less than 40% MVPRED were categorized as “unsafe.” POA was defined as more than five apneic or hypopneic events per hour. RESULTS Of the 132 patients, 50 received opioids. Baseline MV was 7.2 ± 0.5 L/min. The MV-based protocol classified 18 of 50 patients as at risk before opioid administration. After the first opioid dose administration, at-risk patients experienced an average MV decrease (36.7% ± 8.5% MVPRED) and 13 of 18 decreased into unsafe; the 32 not at-risk patients experienced a lesser average MV decrease (76.9% ± 6.3% MVPRED). Only 1 of 32 not at-risk patients had a decrease in MV to unsafe. The proposed protocol had a sensitivity of 93% and a specificity of 86%. Of the 132 patients, 26 displayed POA. Of the 26 patients, 12 experienced POA without receiving opioids. Of the 26 patients with POA, 14 also received opioids, and of those, 6 were classified as unsafe. CONCLUSION This investigation indicates that at risk and unsafe respiratory patterns occur frequently after procedure. RVM provides continuous noninvasive objective measurements of OIRD and POA. The RVM may prove a useful tool in opioid dosing and in recognition and management of POA and strong potential value in the rapid detection of OIRD and apnea in the contemporary combat casualty environment. LEVEL OF EVIDENCE Care management study, level V.

Visible hyperspectral imaging: monitoring the systemic effects of shock and resuscitation

Hyperspectral (HS) imaging has been useful in the monitoring of several medical conditions, which to date have generally involved changes in skin oxygenation in isolated regions of interest such as skin flaps or small burns. Here, by contrast, we present a study in which HSI was used to assess the cutaneous manifestations of significant systemic events. HS imaging of the ventral surface of the lower jaw was used to monitor changes in skin oxygenation during hypovolemic shock induced by pulmonary contusion and hemorrhage in a porcine model, and to monitor the subsequent recovery of oxygenation following resuscitation. Changes are seen both quantitatively, in the level of skin oxygenation as determined by the fitting of reference hemoglobin and deoxyhemoglobin spectra to sample spectra, and qualitatively, in the observed spatial distribution or pattern of oxygenation-related changes in the skin. Linear regression was used to correlate these changes with invasively obtained parameters to include mixed venous oxygen saturation and systemic arterial blood pressure. Historically, the assessment of skin color and mottling has been an important, albeit inexact, component of resuscitation algorithms. Now, it is possible to analyze these variables during shock and resuscitation in an objective manner. The clinical utility of these advances needs to be determined.

Non-invasive respiratory volume monitoring in patients with traumatic thoracic injuries:

Background Respiratory decompensation is common after traumatic thoracic injuries such as multiple rib fractures and pulmonary contusions. A continuous, non-invasive, impedance-based respiratory volume monitor generates right and left tidal volume measurements, reflecting air exchange in the lungs and derives an instantaneous respiratory rate. The feasibility of using unilateral respiratory volume monitor–based tidal impedance measurements to monitor respiratory status in trauma patients is evaluated. Methods Three intensive care unit patients with three or more rib fractures following blunt trauma had continuous respiratory volume monitor measurements with a novel non-invasive impedance-based device (ExSpiron, Respiratory Motion Inc., Waltham, MA) and corresponding clinical data to permit analysis. Tidal impedance measurements were collected from both the injured and non-injured sides and converted into bilateral respiratory volume monitor measurements using advanced algorithms. Results In Patient 1, following evacuation of a pneumothorax, the respiratory volume monitor showed a significant increase in tidal measurements coupled with a compensatory decrease in tidal measurements on the uninjured side and a decrease in respiratory rate. In Patient 2, tidal measurements were only slightly decreased on both the injured side and uninjured side; respiratory rate remained unchanged. This patient remained stable and required no intervention. Patient 3 demonstrated a sustained decrease in tidal measurements on the injured side that corresponded with radiograph findings and clinical deterioration leading to the need for endotracheal intubation. Conclusions The results from these cases demonstrate that respiratory volume monitor can generate unilateral respiratory tidal measurements and respiratory rate in patients with traumatic thoracic injuries. Continuous respiratory volume monitor in patients with thoracic trauma has strong potential for application in the military, aeromedical, and other austere environments where respiratory monitoring is problematic. Future studies to investigate the utility of this technology are warranted.

Operational realities in the postanesthesia care unit: staffing and monitoring for safe postoperative care.

• Volume 119 • Number 6 www.anesthesia-analgesia.org 1249 Copyright

Use of hyperspectral imaging to profile cutaneous responses to bioweapons: a concept paper

Bioterrorism is no longer a hypothetical construct but a reality. Nevertheless, disease detection and intervention currently remain largely reliant on clinical assessment. Technology providing early detection of disease could impact the care of individual patients and the evolution of epidemic spread. Hyperspectral Imaging (HSI) is a remote sensing technology developed originally by the Department of Defense that combines high-resolution imaging with chemical spectroscopy. In other medical applications HSI is emerging as a new means of early or more sensitive detection of changes in tissue that can be used to define pathology, predict clinical outcomes and adapt therapy. As a small, robust, camera based, non-invasive device, HSI may be well suited to aid in defense against biological warfare or epidemic disease by providing early detection or confirmation of disease and by monitoring the efficacy of vaccination or therapy. Crossover applications exist in the evaluation and treatment of emerging diseases. HSI is well suited to be a screening tool to provide earlier or more accurate detection of disease in an at risk population to better treat and contain disease.