Intraoperative assessment of microperfusion with visible light spectroscopy for prediction of anastomotic leakage in colorectal anastomoses.

PURPOSE: Anastomotic leakage is associated with increased morbidity and mortality. However, there is no accurate tool to predict its occurrence. We evaluated the predictive value of visible light spectroscopy (VLS), a novel method to measure tissue oxygenation [saturated O(2) (StO(2) )], for anastomotic leakage of the colon and the rectum. METHOD: Oxygen saturation in the bowel was measured in 77 colorectal resections. The anastomosis was between 2 and 30 cm (mean 13 cm) from the anal verge. The oxygen saturation was measured in the colon and rectum before and after anastomosis construction. This was compared with a reference measurement in the caecum. Data on postoperative complications were prospectively collected. RESULTS: Anastomotic leakage occurred in 14 (18%) patients. When compared with a leaking anastomosis, normal anastomoses showed rising O(2) values during the operation (mean StO(2) 72.1 ± 9.0-76.7 ± 8.0 vs 73.9 ± 7.9-73.1 ± 7.4) (P ≤ 0.05). There were also higher StO(2) values in the caecum compared with those which ultimately leaked (73.6 ± 5.7 normal anastomoses, 69.6 ± 5.6 anastomotic leaks) (P ≤ 0.05). Both StO(2) values were predictive of anastomotic leakage. CONCLUSION: Tissue oxygenation O(2) appears to be a potentially useful means of predicting anastomotic leakage after colorectal anastomosis.

Intraoperative assessment of microperfusion with visible light spectroscopy in esophageal and colorectal anastomoses.

BACKGROUND: We evaluated the technical feasibility and stability of measurements using visible light spectroscopy to measure microvascular oxygen saturation (StO(2)) in gastrointestinal anastomoses. METHODS: In consecutive esophageal (n = 14) or colorectal (n = 30) resections, during which an uncomplicated anastomosis was performed, measurements of serosal StO(2) were performed during the procedure. RESULTS: In esophageal resections, median (+/- standard error) StO(2) was stable before and after anastomosis in the proximal esophagus (before: 66.0 +/- 4.6, after: 68.3 +/- 6.0%) and the gastric conduit (before: 70.6 +/- 8.6, after: 69.8 +/- 8.0%). Mean colorectal StO(2) before and after anastomosis increased in the proximal part (71.3 +/- 8.4 to 76.6 +/- 8.2%; p < 0.005). Mean StO(2) in the distal part remained stable (72.4 +/- 6.6 to 74.8 +/- 6.7%). CONCLUSIONS: Visible light spectroscopy is a feasible and fast method for intraoperative assessment of microperfusion of the serosa in esophageal and colorectal anastomosis. Future clinical studies will define its role in the prediction of anastomotic leakage.

Preoperative irradiation with 5 x 5 Gy in a murine isolated colon loop model does not cause anastomotic weakening after colon resection.

INTRODUCTION: There are conflicting studies on the influence of fractionated preoperative 5 days of 5 Gy irradiation on tissue oxygenation and subsequent colonic anastomotic strength. To elucidate the effect of preoperative irradiation on anastomotic strength, an isolated colon loop model was developed. METHODS: Male Wistar rats (n = 164) were randomly divided into three groups. One group remained untreated (control). In the other two groups, a loop of descending colon was exteriorized to create a hernia of the abdominal wall. After 4 weeks' recovery, this loop was locally irradiated with 5 x 5 Gy of gamma-rays or sham irradiated. One week after (sham-) irradiation, an anastomosis was performed in all groups. Tissue oxygenation (StO2) was determined with visible light spectroscopy. The animals were sacrificed 3 or 7 days after the operation and the anastomosis was tested for bursting pressure and breaking strength. RESULTS: Irradiated rats showed significantly more weight loss (90% SD 4.3 of initial body weight vs. 96% SD 2.8, p < or = 0.05) and enteritis (18% vs. 5%, p = 0.013) compared to sham and control animals. StO2 was not influenced by irradiation and was not predictive for anastomotic strength. The control group showed significantly lower bursting pressure and breaking strength compared to (sham-) irradiated animals. CONCLUSION: We developed a new isolated loop model for intermittent irradiation of the colon. Preoperative irradiation of the distal part of a colon anastomosis was successfully administered with acceptable side effects and did not cause reduced tissue oxygenation nor clinical signs of anastomotic weakening, nor objective reduction in bursting pressure and breaking strength.

Bedside functional imaging of the premature infant brain during passive motor activation.

BACKGROUND: Changes in regional brain blood flow and hemoglobin oxygen saturation occur in the human cortex in response to neural activation. Traditional functional radiologic methods cannot provide continuous, portable measurements. Imaging methods, which use near-infrared light allow for non-invasive measurements by taking advantage of the fact that hemoglobin is a strong absorber at these wavelengths. AIMS: To test the feasibility of a new optical functional imaging system in premature infants, and to obtain preliminary brain imaging of passive motor activation in this population. METHODS: A new optical imaging system, the Diffuse Optical Tomography System (DOTS), was used to provide real-time, bedside assessments. Custom-made soft flexible fiberoptic probes were placed on two extremely ill, mechanically ventilated 24 week premature infants, and three healthier 32 week premature infants. Passive motor stimulation protocols were used during imaging. RESULTS: Specific movement of the arm resulted in reproducible focal, contralateral changes in cerebral absorption. The data suggest an overall increase in blood volume to the imaged area, as well as an increase in deoxyhemoglobin concentration. These findings in premature infants differ from those expected in adults. CONCLUSIONS: In the intensive care setting, continuous non-invasive optical functional imaging could be critically important and, with further study, may provide a bedside monitoring tool for prospectively identifying patients at high risk for brain injury.

Noninvasive functional imaging of human brain using light.

Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatio-temporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring.

Bedside imaging of intracranial hemorrhage in the neonate using light: comparison with ultrasound, computed tomography, and magnetic resonance imaging.

Medical optical imaging (MOI) uses light emitted into opaque tissues to determine the interior structure. Previous reports detailed a portable time-of-flight and absorbance system emitting pulses of near infrared light into tissues and measuring the emerging light. Using this system, optical images of phantoms, whole rats, and pathologic neonatal brain specimens have been tomographically reconstructed. We have now modified the existing instrumentation into a clinically relevant headband-based system to be used for optical imaging of structure in the neonatal brain at the bedside. Eight medical optical imaging studies in the neonatal intensive care unit were performed in a blinded clinical comparison of optical images with ultrasound, computed tomography, and magnetic resonance imaging. Optical images were interpreted as correct in six of eight cases, with one error attributed to the age of the clot, and one small clot not seen. In addition, one disagreement with ultrasound, not reported as an error, was found to be the result of a mislabeled ultrasound report rather than because of an inaccurate optical scan. Optical scan correlated well with computed tomography and magnetic resonance imaging findings in one patient. We conclude that light-based imaging using a portable time-of-flight system is feasible and represents an important new noninvasive diagnostic technique, with potential for continuous monitoring of critically ill neonates at risk for intraventricular hemorrhage or stroke. Further studies are now underway to further investigate the functional imaging capabilities of this new diagnostic tool.

Imaging transgenic animals.

Transgenic and eugenic animals as small as 30 g can be studied non-invasively by radionuclides with resolutions of 1-2 mm, by MRI with resolution of 100 microns and by light fluorescence and bioluminescence with high sensitivities. The technologies of radionuclide emission, magnetic resonance imaging, magnetic resonance spectroscopy, optical tomography, optical fluorescence and optical bioluminescence are currently being applied to small-animal studies. These technologies and examples of their applications are reviewed in this chapter.

Stationary headband for clinical time-of-flight optical imaging at the bedside.

Conventional brain-imaging modalities may be limited by high cost, difficulty of bedside use, noncontinuous operation, invasiveness or an inability to obtain measurements of tissue function, such as oxygenation during stroke. Our goal was to develop a bedside clinical device able to generate continuous, noninvasive, tomographic images of the brain using low-power nonionizing optical radiation. We modified an existing stage-based time-of-flight optical tomography system to allow imaging of patients under clinical conditions. First, a stationary head-band consisting of thin, flexible optical fibers was constructed. The headband was then calibrated and tested, including an assessment of fiber lengths, the existing system software was modified to collect headband data and to perform simultaneous collection of data and image reconstruction, and the existing hardware was modified to scan optically using this headband. The headband was tested on resin models and allowed for the generation of tomographic images in vitro; the headband was tested on critically ill infants and allowed for optical tomographic images of the neonatal brain to be obtained in vivo.

Ice-Front Propagation Monitoring in Tissue by the use of Visible-Light Spectroscopy.

For demonstrating that visible-light spectroscopy can be used for ice-front detection within freezing tissue, proton magnetic resonance images were correlated to time-evolving transmittance spectra as an ice front progressed across a tissue sample. The experimental apparatus was designed to be compatible with magnetic resonance imaging, to produce one-dimensional freezing, and to allow both reflectance and transillumination emitter-detector configurations about a normally progressing planar ice front in chicken muscle. This demonstration has potentially important medical applications in cryopreservation (freezing of biological materials for preservation) and cryosurgery (destruction of tissue by freezing).

Visualizing gene expression in living mammals using a bioluminescent reporter.

Control of gene expression often involves an interwoven set of regulatory processes. As information regarding regulatory pathways may be lost in ex vivo analyses, we used bioluminescence to monitor gene expression in living mammals. Viral promoters fused to firefly luciferase as transgenes in mice allowed external monitoring of gene expression both superficially and in deep tissues. In vivo bioluminescence was detectable using either intensified or cooled charge-coupled device cameras, and could be detected following both topical and systemic delivery of substrate. In vivo control of the promoter from the human immunodeficiency virus was demonstrated. As a model for DNA-based therapies and vaccines, in vivo transfection of a luciferase expression vector (SV-40 promoter and enhancer controlling expression) was detected. We conclude that gene regulation, DNA delivery and expression can now be noninvasively monitored in living mammals using a luciferase reporter. Thus, real-time, noninvasive study of gene expression in living animal models for human development and disease is possible.

Imaging brain structure and function, infection and gene expression in the body using light.

Light can be used to probe the function and structure of human tissues. We have been exploring two distinct methods: (i) externally emitting light into tissue and measuring the transmitted light to characterize a region through which the light has passed, and (ii) internally generating light within tissue and using the radiated light as a quantitative homing beacon. The emitted-light approach falls within the domain of spectroscopy, and has allowed for imaging of intracranial haemorrhage in newborns and of brain functions in adults. The generated-light approach is conceptually parallel to positron emission tomography (PET) or nuclear medicine scanning, and has allowed for real-time, non-invasive monitoring and imaging of infection and gene expression in vivo using low-light cameras and ordinary lenses. In this paper, we discuss recent results and speculate on the applications of such techniques.

The value of neurophysiologic approaches in the anticipation and evaluation of neonatal hypoglycemia.

The association of low blood glucose with central nervous system (CNS) injury was first described in 1937 by Hartmann and Jaudon. In the early 60 years since publication of these observations the effects of hypoglycemia upon the brain remain poorly understood. Technology capable of accurately determining plasma glucose concentrations has been developed. Investigators have sought to establish critical values below which glucose levels should not be allowed to fall. Despite these efforts the definitive level of glucose capable of producing brain injury in any particular patient remains unknown. Glucose homeostasis within the neonatal CNS represents a dynamic process consisting of many interrelated variables including gestational and chronologic age, genotype, relative health, blood flow, metabolic rate and availability of other suitable substrates. New technique for assessing the glucose delivery: consumption ratio and directly monitoring the cellular consequences of glucose deprivation within discrete regions of the brain will help to answer the question 'How long is too low and how long is too long?'

Neonatal hypoglycemia, Part I: Background and definition.

Hypoglycemia in the neonate remains a common problem. The association of low blood glucose concentrations and abnormal development has prompted extensive research into the anticipation, evaluation, and treatment of neonatal hypoglycemia. Glucose homeostasis in the fetus and neonate is a developmentally regulated dynamic process involving a number of intricate physiologic mechanisms. In addition, the determination of glucose concentrations is dependent upon both the type of tissue analyzed and the limitations of the specific method employed. The complexity of glucose metabolism makes it difficult to precisely define "normal" and "abnormal" glucose levels in preterm and term neonates.

Imaging brain injury using time-resolved near infrared light scanning.

Conventional brain imaging modalities are limited in that they image only secondary physical manifestations of brain injury, which may occur well after the actual insult to the brain and represent irreversible structural changes. A real-time continuous bedside monitor that images functional changes in cerebral blood flow or oxygenation might allow for recognition of brain tissue ischemia or hypoxia before the development of irreversible injury. Visible and near infrared light pass through human bone and tissue in small amounts, and the emerging light can be used to form images of the interior structure of the tissue and measure tissue blood flow and oxygen utilization based on light absorbance and scattering. We developed a portable time-of-flight and absorbance system which emits pulses of near infrared light into tissue and measures the transit time of photons through the tissue. Images can then be reconstructed mathematically using either absorbance or scattering information. Pathologic brain specimens from adult sheep and human newborns were studied with this device using rotational optical tomography. Images generated from these optical scans show that neonatal brain injuries such as subependymal and intraventricular hemorrhages can be successfully identified and localized. Resolution of this system appears to be better than 1 cm at a tissue depth of 5 cm, which should be sufficient for imaging some brain lesions as well as for detection of regional changes in cerebral blood flow and oxygenation. We conclude that light-based imaging of cerebral structure and function is feasible and may permit identification of patients with impending brain injury as well as monitoring of the efficacy of intervention. Construction of real-time images of brain structure and function is now underway using a fiber optic headband and nonmechanical rotational scanner allowing comfortable, unintrusive monitoring over extended periods of time.

Guest editorial: special section on near infrared spectroscopy and imaging of tissues.

This Special Section Guest Editorial provides an overview of the topical area and an introduction to the articles featured in the special section.

Photonic detection of bacterial pathogens in living hosts.

The study of pathogenic processes is often limited to ex vivo assays and cell-culture correlates. A greater understanding of infectious diseases would be facilitated by in vivo analyses. Therefore, we have developed a method for detecting bacterial pathogens in a living host and used this method to evaluate disease processes for strains of Salmonella typhimurlum that differ in their virulence for mice. Three strains of Salmonella were marked with bioluminescence through transformation with a plasmid conferring constitutive expression of bacterial luciferase. Detection of photons transmitted through tissues of animals infected with bioluminescent Salmonella allowed localization of the bacteria to specific tissues. In this manner progressive infections were distinguished from those that were persistent or abortive. We observed patterns of bioluminescence that suggested the caecum may play a pivotal role in Salmonella pathogenesis. In vivo efficacy of an antibiotic was monitored using this optical method. This study demonstrates that real time non-invasive analyses of pathogenic events and pharmacological monitoring can be performed in vivo.

Transcranial optical path length in infants by near-infrared phase-shift spectroscopy.

BACKGROUND: Near-infrared spectroscopy (NIRS) is an emerging technique for noninvasive, bedside monitoring of cerebral oxygenation and blood flow. Traditionally, it has relied on the Beer's Law relationship in which the concentration of light-absorbing oxygen-carrying pigments is proportional to their light absorbance, and inversely proportional to an optical path length (a measure of the distance traveled by photons passing through the tissue). In practice, NIRS has been based upon assumptions that mean transcranial optical path length, the average optical path length for a given patient, is constant among patients and independent of the wavelength of light used. OBJECTIVE: The objective of our study was to measure mean optical transcranial path length in infants as a step in allowing quantitation of cerebral oxygenation. METHODS: We measured mean transcranial optical path length in 34 infants, aged 1 day to 3 years, using amplitude-modulated phase-shift spectroscopy at 754 nm and 816 nm. Optical transcranial path lengths (mean +/- SEM) were 8.6 +/- 0.9 cm, 11.1 +/- 0.9 cm, and 11.3 +/- 0.9 cm at 754 nm, and 8.8 +/- 0.9 cm, 11.2 +/- 0.8 cm, and 11.1 +/- 0.9 cm at 816 nm, using emitter-detector separations of 1.8, 2.5, and 3.0 cm, respectively. Optical path length increased as emitter-detector separation, head circumference, or age increased. Variance in the ratio of mean optical path lengths at the two different wavelengths exceeded that accounted for by variation in repeated measures alone (p < 0.001), suggesting that optical path length is also not independent of wavelength. CONCLUSIONS: NIRS instrument emitter-detector geometry, subject age, head size, and wavelength used each influence optical path length. Quantitative NIRS measurements in clinical use may require concurrent measurement of both absorbance and optical path length at each wavelength, or use of newer measures that are not based upon Beer's Law assumptions.

Maximizing the stability of oxygen delivered via nasal cannula.

BACKGROUND: The effective fractional inspired oxygen concentration (FiO2) of supplemental oxygen provided to infants via nasal cannula may be adjusted by changing cannula flow rate or oxygen concentration, factors within our control. However, FiO2 also varies with changes in the patient's breathing, factors beyond our control. While a stable oxygen delivery is desirable, combinations of flow and concentration that maximize stability over time need to be studied. OBJECTIVE: To assess the impact of different weaning strategies on the stability of inspired oxygen concentrations delivered to infants via nasal cannulas and to identify optimum strategies maximizing that stability. DESIGN: Theoretical analysis and comparison with previously published measurements. METHODS: We derived equations predicting the FiO2 delivered to infants via nasal cannula, incorporating traditional adjustments of cannula flow rate and oxygen concentration, as well as considering the impact of the infant's inspiratory time, tidal volume, and fraction of nasal breathing. We compared predicted results with previously published measures and evaluated strategies to maximize oxygen delivery stability over time. RESULTS: Predicted values correlated well with published hypopharyngeal measurements (r = .97) and were unbiased, accurate predictors of FiO2. Effective FiO2 was least likely to be affected by changes in patient-controlled controlled factors when the nasal cannula flow rate was as low as possible. CONCLUSIONS: To minimize variability in oxygen delivery via nasal cannula to infants, cannula flow should be reduced to the lowest possible flow by using undiluted (100%) oxygen. Supplemental oxygen may then be weaned by making small reductions in cannula flow. Cannula oxygen concentration should be reduced below 100% only after the minimum calibrated flow rate is reached. Such a strategy may maximize the stability of delivered oxygen over time as well as minimize the size of changes in delivered oxygen at each step of the weaning process.