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Guidelines and protocols for orthoses in burn scar contracture rehabilitation are limited. The current study aims to determine the optimal frequency of casting, potentially facilitating the development of a serial casting protocol. Previous literature supporting casting has low generalizability due to methodology limitations. Seven patients with burn scar contracted joints, who did not respond to traditional therapy, were recruited in this study. Patients were serially casted once, three times, or five times a week. Joint range of motion was maximized with stretching and exercise techniques before every new cast application. Across all patients, active range of motion increased from 65.8 ± 27.8 degrees to 108.1 ± 23.3 degrees with casting; or from 57.8 ± 16.2% to 96.7 ± 2.9% of normal. Similarly, scars improved from 9.5 ± 1.5 to 4.9 ± 1.4 on the Modified Vancouver Scar Scale score. This therapeutic effect was achieved within an average of 8.5 ± 3.7 days and 4.0 ± 2.2 new cast applications. Given the study findings, the procedures outlined could be used to develop a standardized serial casting protocol for burn scar contracture rehabilitation.

Purpose: To determine the effects of non-ictal electroencephalogram (EEG) changes on cerebrovascular autoregulation (AR) using the cerebral oximetry index (COx). Materials and Methods: Mean arterial blood pressure (MAP), cerebral tissue oxygenation (CrSO2), and EEG were acquired for 96 h. From all of the EEG recordings, 30 min recording segments were extracted using the endotracheal suction events as the guide. EEG recordings were classified as EEG normal and EEG abnormal groups. Each 30 min segment was further divided into six 5 min epochs. Continuous recordings of MAP and CrSO2 by near-infrared spectroscopy (NIRS) were extracted. The COx value was defined as the concordance (R) value of the Pearson correlation between MAP and CrSO2 in a 5 min epoch. Then, an Independent-Samples Mann-Whitney U test was used to analyze the number of epochs within the 30 min segments above various R cutoff values (0.2, 0.3, and 0.4) in normal and abnormal EEG groups. A p-value < 0.05 was considered significant, and all analyses were two-tailed. Results: Among 16 sedated, mechanically ventilated children, 382 EEG recordings of 30 min segments were analyzed. The proportions of epochs in each 30 min segment above the R cutoff values were similar between the EEG normal and EEG abnormal groups (p > 0.05). The median concordance values for CSrO2 and MAP in EEG normal and EEG abnormal groups were similar (0.26 (0.17–0.35) and 0.18 (0.12–0.31); p = 0.09). Conclusions: Abnormal EEG patterns without ictal changes do not affect cerebrovascular autoregulation in sedated and mechanically ventilated children.

The objective of this paper is to demonstrate flex-embedded and surface-assembled photonic devices, inductive telemetry, and passive integration to form next-generation miniaturized biophotonic sensors. A hybrid combination of embedding and surface-assembled devices on flex is pursued to reduce the lateral and thickness dimensions of biophotonic systems. Embedding of premanufactured discrete passive devices is demonstrated by inserting in cavities, followed by printed fan-out connections to form the bridge connects between devices and other system components. Initial prototypes showed functional response to color shifts and reliability under bending loads on tissue phantoms. Measurements also confirmed responses to muscle activity as seen through changes in the backscattered light intensity during fist-closure with human subject hands. Initial bending test and reliability after water immersion indicate the stability of the chosen material systems towards flexible and wearable applications. This system concept can eventually be integrated with other system components such as RF transceivers for data telemetry, leading to completely autonomous wireless photosensors for wearable and implantable systems.

Miniaturized 3D package integration with piezo-magnetostrictive telemetry is analyzed towards advanced wireless medical systems. The paper is composed of three aspects. The first is to analyze telemetry using a multiferroic or piezo-magnetostrictive power interface. Parametric analysis was performed to estimate the impact of material, geometry and input magnetic fields. The second aspect is the process integration of devices and telemetry interfaces in 3D embedded packages for smallest form-factors. The telemetric interface and sensor devices are packaged in a flexible substrate with 3D interconnections, leading to miniaturized solutions. The sensor-communication and the power source flex layers are separately fabricated and connected with via-fill layers that are flex-compatible. Flex integration allows the devices to be functional on curved surfaces. In the final part, coupled magnetostrictive and piezoelectric films were considered to power devices in neural recording, neurostimulation and biophotonic systems. Power analysis requirements and piezo-magnetostrictive solutions for these specific scenarios is shown to illustrate the geometric compatibility towards emerging needs.

To evaluate the effects of closed endotracheal tube suctioning on systemic oxygen saturation, cerebral regional oxygen saturation, and somatic regional (renal) oxygen saturation and hemodynamic variables in children.Prospective observational.A tertiary care PICU.Children aged 0-18 years, requiring invasive mechanical ventilation and with an arterial line.Closed endotracheal suction.The study included 19 sedated and intubated children, 0-18 years old. They were enrolled in an ongoing prospective observational study. We used near-infrared spectroscopy for cerebral regional oxygen saturation and somatic regional (renal) oxygen saturation. The timing of each closed endotracheal tube suctioning event was accurately identified from video recordings. We extracted systemic oxygen saturation, cerebral regional oxygen saturation, somatic regional (renal) oxygen saturation, heart rate, and systolic blood pressure and diastolic blood pressure for 5 minutes before and 5 minutes after each event and used these data for analysis. One-minute average values of these variables were used for repeated-measures analysis. We analyzed 287 endotracheal tube suctioning episodes in 19 children. Saline was instilled into the endotracheal tube during 61 episodes. The mean heart rate (107.0 ± 18.7 vs 110.2 ± 10.4; p0.05), mean arterial blood pressure (81.5 ± 16.1 vs 83.0 ± 15.6 mm Hg; p0.05), and the mean cerebral regional oxygen saturation (64.8 ± 8.3 vs 65.8 ± 8.3; p0.05) were increased after suctioning. The mean systemic oxygen saturation (96.9 ± 2.7 vs 96.7 ± 2.7; p = 0.013) was decreased, whereas the mean somatic regional (renal) oxygen saturation was not significantly different after endotracheal tube suctioning. Repeated-measures analysis revealed transient increases in heart rate, respiratory rate, systolic blood pressure, and diastolic blood pressure; a sustained increase in cerebral regional oxygen saturation; and transient decreases in systemic oxygen saturation and somatic regional (renal) oxygen saturation. Saline instillation did not affect oxygenation or hemodynamic variables.Closed endotracheal tube suctioning in sedated children is associated with transient but clinically insignificant changes in heart rate, blood pressure, cerebral regional oxygen saturation, systemic oxygen saturation, and somatic regional (renal) oxygen saturation. Saline instillation during endotracheal tube suctioning had no adverse effects on systemic or cerebral oxygenation.

Heart rate variability (HRV) has been used as prognostic tool in various disorders in pediatric and adult patients. In our study we aimed to evaluate heart rate variability indices and their association with neurological outcome in three children with anoxic brain injury following drowning. Three children included in the study were admitted following drowning and required mechanical ventilation and targeted temperature management. All physiologic data, including electrocardiography (ECG) and EEG were collected for a period of 3–5 days after enrollment. ECG signals were analyzed in both time and frequency domains. The spectral power of the low-frequency (LF) band (0.04–0.15 Hz) and that of the high-frequency (HF) band (0.15–0.4 Hz), the standard deviation of the average R to R ECG intervals (SDANN) were calculated. Mean low-frequency/high-frequency power ratios (LF/HF) were compared using a two-tailed t -test and ANOVA with Tukey–Kramer multiple comparisons. The power in the LF band, the LF/HF power ratio, and the SDANN, were lower in children who had a poor outcome, and during periods of isoelectric or burst suppression EEG patterns.

Background Immunofluorescent staining coupled with axial optical sectioning allows for assessment of native three-dimensional structure of brain tissue. Typical challenges of analyzing network structure include limitations driven by magnification/field of view, spatial resolution, tissue thickness, staining quality of dense cell types, data quantifiability and the quantity of simultaneous staining targets. New Method This manuscript demonstrates many methodological advancements. Software-aided alignment of the cortical slice and stereotaxic atlas maximizes ROI-identification accuracy. Tissue compression during antigen retrieval enhances epitope availability without damaging tissue. A thorough factorial experiment focusing on Smi-311 staining highlights the enhancements in image quality from our extended staining protocol. Mosaic scanning techniques and subsequent four-channel alignment ensures high data quality. Results Cortical column datasets [800μm x 3000μm x 70μm] utilizing sequential optical sectioning were successfully generated from three rats. Each rat provided three coronal sections in each of two regions, M1 and S1BF, from which data cubes were generated per hemisphere, totaling 36 high-magnification four-color datasets. Comparison with Existing Method(s) Typical confocal assessments of brain tissue do not utilize such thick tissue slices nor collect entire cortical columns from the cortical surface to the grey/white interface at a resolution that can map fine filamentous processes. The simultaneous collection of our four specific structural markers - neuronal, astrocytic, vascular and nuclear – is novel and the quantitative optimization of staining protocols through a factorial design rare. Conclusions Building upon this preliminary success in protocol development, future work will encompass volumetric modeling and quantitative analysis of regional network architecture.

Complete removal of epileptogenic cortex while preserving eloquent areas is crucial in patients undergoing epilepsy surgery. In this manuscript, the feasibility was explored of developing a new methodology based on dynamic intrinsic optical signal imaging (DIOSI) to intraoperatively detect and differentiate epileptogenic from eloquent cortices in pediatric patients with focal epilepsy. From 11 pediatric patients undergoing epilepsy surgery, negatively-correlated hemodynamic low-frequency oscillations (LFOs, ~ 0.02–0.1 Hz) were observed from the exposed epileptogenic and eloquent cortical areas, as defined by electrocorticography (ECoG), using a DIOSI system. These LFOs were classified into multiple groups in accordance with their unique temporal profiles. Causal relationships within these groups were investigated using the Granger causality method, and 83% of the ECoG-defined epileptogenic cortical areas were found to have a directed influence on one or more cortical areas showing LFOs within the field of view of the imaging system. To understand the physiological origins of LFOs, blood vessel density was compared between epileptogenic and normal cortical areas and a statistically-significant difference (p, Highlights • Low-frequency hemodynamic oscillations (~ 0.02–0.1 Hz) in epileptogenic cortex • High sensitivity (93%) and adequate specificity (70%) in differentiating epileptogenic cortex from eloquent one • Significant changes in vessel density (p

Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas where from interictal epileptiform discharges (IEDs) emerge. These areas, named irritative zones, have been useful to define candidate seizures-onset zones during pre-surgical workup. Since human histological data are mostly available from final resected zones, systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones—independent of them being epileptogenic—are challenging. Combining BSI and histological analysis from all types of irritative zones is only possible through the use of preclinical animal models. Here, we recorded 32-channel spontaneous electroencephalographic data from rats that have focal cortical dysplasia (FCD) and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections containing irritative zones were stained to quantify anatomical, functional, and inflammatory biomarkers specific for epileptogenesis, and the results were compared with those obtained using the contralateral healthy brain tissue. We found abnormal anatomical structures in all irritative zones (i.e., larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (i.e., NR2B) and inflammation (i.e., ILβ1, TNFα and HMGB1). We conclude that irritative zones in this rat preclinical model of FCD comprise abnormal tissues disregarding whether they are actually involved in icto-genesis or not. We hypothesize that seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and preventive treatment of potential epileptic foci. Further verifications in humans are yet needed.

A non-contact, combined laser Doppler and total diffuse reflectance spectroscopy system was developed to simultaneously and continuously measure hemoglobin oxygenation, hemoglobin concentration, and regional flow from in vivo tissues.

Background Optical spectroscopy can be used to assess the pathophysiological characteristics of diseased and injured biological tissue in vivo in a non-destructive way. It is often used in conjunction with a contact optical probe for the purposes of operating and sensing in a sterile field. Since the probe is often held by the hand of an investigator during data acquisition, any hand instability can affect the quality of acquired data and, hence, degrade the accuracy of diagnosis. This study was designed to quantitatively characterize these artifacts, and then propose an effective engineering solution to remove them. Methods Time-dependent diffuse reflectance spectra ( Rd ( λ , t )) were acquired from the normal cortex region of pediatric patients undergoing epilepsy surgery. They were acquired at a rate of 33Hz, and their range was 400 and 900nm. Two distinct ways of collecting data were tested: one with the fiber optical probe held by the surgeon's hand during data acquisition, and the other with the probe held by a specially designed probe holder. The probe holder was designed and constructed to minimize the variations in probe contact pressure and contact point for the full duration of any given investigation. Spectral data acquired using versus not using the probe holder were characterized and compared in the time, wavelength, and frequency domains, using both descriptive and inferential statistics. Results Hand motion manifested as strong random variations in Rd ( λ , t ) which impacted temporal and frequency characteristics of Rd ( λ , t ). The percentage standard deviation %STD of Rd ( λ , t ) acquired without probe holder could be as high as 60%, and they are significantly higher than those with probe holder at all wavelengths. This difference is especially prominent between 400 and 600nm. Rd ( λ , t ) acquired without the probe holder also processed a higher spectral power energy in the frequency domain than those with the probe holder. The correlation analysis revealed that the hand motions induced synchronistic variations in Rd ( λ , t ) between 600 and 800nm, but this synchronicity is not obvious between 400 and 600nm. Conclusion The results of this investigation demonstrate the nature and the magnitude of hand motion induced artifacts in in vivo diffuse reflectance spectra and propose one potential solution ( i.e. , a probe holder) to remove them. These findings allow us to improve the quality of time-dependent, diffuse reflectance signals acquired to study the dynamic characteristics of biological tissues, like brain, in vivo .

Extracellular Adenosine-5′-triphosphate (ATP) is an important multi-functional molecule which can mediate numerous physiological activities by activating purinergic P2 receptors. The objective of this study was to develop a novel optical ATP sensor for in-situ extracellular ATP measurement in biological tissues. The optical ATP sensor was made by applying two layers of sol-gel coating to the end of an optical fiber probe end. The first layer contained ruthenium complex for sensing changes in oxygen concentration which resulted from oxidation of ATP by glycerol kinase and glycerol 3-phosphate oxidase entrapped in the second layer. It was demonstrated that the optical ATP sensor was capable of detecting ATP concentration at a broad range of 10−3 mM to 1.5 mM. A compensation method was established to enable the optical sensor to determine ATP concentration at different oxygen levels. This study also demonstrated the capability of ATP sensor to measure extracellular ATP content in biological tissues (i.e., porcine intervertebral disc). In addition, it was shown that the optical ATP sensor was not affected by pH and derivatives of extracellular ATP. Therefore, the newly developed optical ATP sensor is a good option for in-situ extracellular ATP measurement.

Summary Purpose: Medically refractory epilepsy caused by cortical tubers resulting from tuberous sclerosis complex (TSC) often requires surgical intervention. The locations of cortical tubers generally are determined by preoperative magnetic resonance imaging (MRI). In this pilot study, we explored the feasibility of using the optical characteristics of cortical tubers as a potential means to guide their resection intraoperatively. Methods: Optical characteristics of normal cortex and cortical tubers were measured intraoperatively using diffuse reflectance spectroscopy in three children undergoing epilepsy surgery for drug-resistant seizures. Unique diffuse reflectance spectroscopic features of cortical tubers were identified and their physiologic associations determined. Key Findings: Diffuse reflectance spectra revealed several features that distinguish cortical tubers from normal cortex. In tubers, diffuse reflectance intensities at oxy- and deoxyhemoglobin isobestic points, like 500, 530, and 570 nm, were consistently higher than those in normal cortex. According to the profile of diffuse reflectance spectra from 520–580 nm, hemoglobin oxygenation in tubers often was lower than in normal cortex. Significance: Albeit preliminary, our findings suggest that the optical characteristics of cortical tubers differ from intervening normal cortex, likely reflecting the lower cerebral blood volumes and reduced hemoglobin oxygenation of cortical tubers. The results of this study can be used to design biomedical instruments that aid tuberectomies.

This paper reports the development of a probability-based spectroscopic diagnostic algorithm capable of simultaneously discriminating tumor core and tumor margins from normal human brain tissues. The algorithm uses a nonlinear method for feature extraction based on maximum representation and discrimination feature (MRDF) and a Bayesian method for classification based on sparse multinomial logistic regression (SMLR). Both the autofluorescence and the diffuse-reflectance spectra acquired in vivo from patients undergoing craniotomy or temporal lobectomy at the Vanderbilt University Medical Center were used to train and validate the algorithm. The classification accuracy was observed to be approximately 96%, 80%, and 97% for the tumor, tumor margin, and normal brain tissues, respectively, for the training data set and approximately 96%, 94%, and 100%, respectively, for the corresponding tissue types in an independent validation data set. The inherently multi-class nature of the algorithm facilitates a rapid and simultaneous classification of tissue spectra into various tissue categories without the need for a hierarchical multi-step binary classification scheme. Further, the probabilistic nature of the algorithm makes it possible to quantitatively assess the certainty of the classification and recheck the samples that are classified with higher relative uncertainty.

The applicability of optical spectroscopy for intraoperative detection of brain tumors/tumor margins was investigated in a pilot clinical trial consisting of 26 brain tumor patients. The results of this clinical trial suggest that brain tumors and infiltrating tumor margins (ITM) can be effectively separated from normal brain tissues in vivo using combined autofluorescence and diffuse-reflectance spectroscopy. A two-step empirical discrimination algorithm based on autofluorescence and diffuse reflectance at 460 and 625 nm was developed. This algorithm yields a sensitivity and specificity of 100 and 76%, respectively, in differentiating ITM from normal brain tissues. Blood contamination was found to be a major obstacle that attenuates the accuracy of brain tumor demarcation using optical spectroscopy. Overall, this study indicates that optical spectroscopy has the potential to guide brain tumor resection intraoperatively with high sensitivity.

Neural tissue engineering is one of the most promising approaches for healing nerve damage, which bypasses the limits of contemporary conventional treatments. In a previous study, we developed a fibrous scaffold via electrospinning poly (glycerol dodecanedioate) (PGD) and gelatin that mimics the structure of a native extracellular matrix (ECM) for soft tissue engineering application. In this study, fumaric acid (FA) was incorporated into the PGD synthesis process, which produced a PGD derivative referred to as poly (glycerol dodecanedioate co-fumarate) (PGDF). This introduced a new functional group, a double bond, into the polymer thus providing new modification possibilities. Arg-Gly-Asp-Cys (RGDC) and laminin peptides were chosen as biomolecules to modify the fiber and facilitate cell attachment and differentiation efficiency. The release of FA into the medium was quantified to investigate the bioreactivity of the derived scaffolds. In combination with UV crosslinking, the developed PGDF fiber mats were able to withstand degradation processes for up to 2 months, which ensures that neural tissue engineering applications are viable. Cell viability and motor neuron differentiation efficiency were demonstrated to be significantly improved with the addition of FA, RGDC and laminin peptides.

Goal: We aim to evaluate the mechanisms underlying the neurovascular/metabolic coupling in the epileptogenic cortices of rats with chronic focal epilepsy. Methods: We performed and analyzed intracranial recordings obtained from the seizure-onset zones during ictal periods on epileptic rats, and then, used these data to fit a metabolically coupled balloon model. Normal rats undergoing forepaw stimulation were used as control. Results: We found a significant higher contribution from high local field potential frequency bands to the cerebral blood flow (CBF) responses in the epileptogenic cortices during ictal neuronal activities. The hemodynamic responses associated with ictal activities were distance-dependent with regard to the seizure focus, though varied in profiles from those obtained from acute seizure models. Parameters linking the CBF and relative concentration of deoxyhemoglobin to neuronal activity in the biophysical model were significantly different between epileptic and normal rats. Conclusion: We found that the coefficient associated with the strength of the functional hyperemic response was significantly larger in the epileptogenic cortices, and changes in hemoglobin concentration associated with ictal activity reflected the existence of a significantly higher baseline for oxygen metabolism in the epileptogenic cortices. Significance: Introducing methods to estimate these physiological parameters would enhance our understanding of the neurovascular/metabolic coupling in epileptic brains and improve the localization accuracy on irritative zones and seizure-onset zones through neuroimaging techniques.

Alterations in the connectivity patterns of the fMRI-based resting-state networks (RSNs) have been reported in several types of epilepsies. Evidence pointed out these alterations might be associated with the genesis and propagation of interictal epileptiform discharges (IEDs). IEDs also evoke blood-oxygen-level dependent (BOLD) responses, which have been used to delineate irritative zones during preoperative work-up. Therefore, one may expect a relationship between the topology of the IED-evoked BOLD response network and the altered spatial patterns of the RSNs. In this study, we used EEG recordings and fMRI data obtained simultaneously from a chronic model of focal epilepsy in Wistar rats to verify our hypothesis. We found that IED-evoked BOLD response networks comprise both cortical and subcortical structures with a rat-dependent topology. In all rats, IEDs evoke both activation and deactivation types of BOLD responses. Using a Granger causality method, we found that in many cases areas with BOLD deactivation have directed influences on areas with activation (p

Advances in optics and molecular imaging have occurred rapidly in the past decade. One technique poised to take advantage of these developments is optical spectroscopy (OS). All optical spectroscopic techniques have in common tissue interrogation with light sources ranging from the ultraviolet (UV) to the infrared (IR) ranges of the spectrum, and collection of information on light reflected (reflectance spectroscopy) or light interactions with tissue and emergence at different wavelengths (fluorescence and Raman spectroscopy). OS can provide information regarding intrinsic tissue optical properties such as tissue structure, nuclear density, and the presence or absence of endogenous or exogenous fluorophores. Among other applications, this information has been used to distinguish tumor from normal brain tissues, to detect tumor margins in intrinsic, infiltrating gliomas, to identify radiation damage to tissues, and to assess tissue viability and predict the onset of apoptosis in vitro and in vivo. Potential applications of OS include detection of specific central nervous system (CNS) structures, such as brain nuclei, identification of cell types by the presence of specific neurotransmitters, and the detection of optically labeled cells or drugs during therapeutic interventions. All have potential utility in neuro-oncology, have been investigated in our laboratories, and will be the subject of this review.

Purpose: Promising results of optical signals have been reported in the literature for the diagnosis of Barrett’s esophagus, oral cavity lesions, brain tumor margins, cervical intraepithelial neoplasia, skin cancer and bladder cancer. The potential usefulness of these techniques in renal tissues and neoplasms has not been described to date. This initial study examined the feasibility of using fluorescence and diffuse reflectance spectroscopy to differentiate between malignant and benign renal tissues. Materials and Methods: An ex vivo study was conducted to identify optical characteristics of various renal tissue types. Pathologically confirmed benign and malignant renal samples were obtained from nephrectomy specimens from patients undergoing radical nephrectomy. Fluorescence and diffuse reflectance spectra were measured from benign and malignant renal tissues. Results: All renal tissues, malignant or benign, contain 2 primary emission peaks—a strong one at approximately 285 nm excitation, approximately 340 nm emission (Peak A), and a weak one at approximately 340 nm excitation, approximately 460 nm emission (Peak B). Peak A of normal renal tissue typically locates at the shorter excitation wavelength region than that of malignant tissue. The intensity of Peak B from benign tissues tends to be greater than that from malignant renal tissues. Diffuse reflectance intensities from malignant renal tissues between 600 and 800 nm are markedly greater than those from normal renal tissue. Empirical discrimination algorithms developed based on selected fluorescence and diffuse reflectance spectral characteristics yields accurate differentiation between benign and malignant renal tissues. Conclusions: Highly accurate differentiation between normal human renal tissues and renal cell cancers is feasible using combined fluorescence and diffuse reflectance spectroscopy in an ex vivo setting. If successful in future clinical studies, optical spectroscopy could aid in margin detection and tissue discrimination while performing nephron sparing surgery.

OBJECTIVE: Adult gliomas have indistinct borders. As the ratio of neoplastic cells to normal cells becomes lower, the ability to detect these cells diminishes. We describe a device designed to augment intraoperative identification of both solid tumor and infiltrating tumor margins. METHODS: A novel, intraoperative, optical spectroscopic tool, using both white light reflectance and 337-nm excitation fluorescence spectroscopy, is described. Discrimination algorithms have been developed to segregate neoplastic tissues from normal glial and neuronal elements. The spectroscopy device was used to measure 5 to 10 locations during glioma resection. Beneath the tool, a biopsy sample was obtained and the pathological results were reviewed in a blinded fashion. Samples were classified as solid tumor, infiltrating tumor, or normal gray or white matter. Comparisons were made between the optical spectra and the histopathological results of sampled areas in evaluating the sensitivity and specificity of the tool for tissue discrimination. RESULTS: Spectral data were obtained from 24 patients with glioma and from 11 patients with temporal lobe epilepsy. A sensitivity of 80% and a specificity of 89% in discriminating solid tumor from normal tissues were obtained. In addition, infiltrating tumor margins were distinguished from normal tissues with a sensitivity of 94% and a specificity of 93%. CONCLUSION: We have developed a handheld, optical spectroscopic device that may be used rapidly and in near real time with high sensitivity and reproducibility as an optical tissue discrimination tool in glioma surgery.

OBJECTIVE: Magnetic resonance imaging abnormalities in malignant brain tumors after irradiation may represent either recurrent tumor or radiation injury. Optical spectroscopy may represent a novel technique to identify radiation damage in brain tissues and to differentiate contrast-enhancing lesions from recurrent tumor. METHODS: Fluorescence and diffuse reflectance spectra were acquired from 90 patients: 15 undergoing surgical resection for presumed recurrent tumor after radiation therapy, 15 with epilepsy and hippocampal sclerosis, and 60 with tumors who had not received irradiation. Optical spectra were acquired from 6 to 10 sites and were compared with a biopsy obtained from beneath the optical spectroscopy probe; the data then were classified by a neuropathologist blinded to the spectroscopy data. A probe for the intraoperative collection of diffuse reflectance and fluorescence spectra was used. RESULTS: Thirteen of 15 patients (29 of 129 spectra) with previous irradiation showed a unique spectral feature characterized by a fluorescence peak centered at 500 nm (F500). All biopsy specimens showing histopathological signs of radiation injury had the F500 on their corresponding spectra (18 of 18). The F500 was identified in another 10% (11 of 111 spectra) of samples with previous irradiation but no histologically identifiable signs of radiation damage. The F500 was never seen in the normal temporal lobe of epilepsy patients with hippocampal sclerosis (0 of 105) and was seen in only 1.5% of tumor patients who did not undergo previous irradiation (6 of 433). CONCLUSION: Optical spectroscopy detects radiation damage in brain tissues. The F500 spectral peak may allow accurate selection of tissues for biopsy in evaluating patients with new, contrast-enhancing lesions in the setting of previous irradiation.

Background A current limitation of hepatic radiofrequency ablation (RFA) is an inability to detect ablation margins in real time. Thermal injury from RFA alters the biochemical properties governing tissue fluorescence. We hypothesized that the changes in hepatic fluorescence measured during hepatic RFA could be used to detect irreversible hepatocyte damage accurately and to determine ablation margins in real time. Methods RFA was performed on healthy pig livers and monitored in vivo simultaneously for fluorescence and temperature by a fiberoptic micro-interrogation probe connected to a spectroscopy system. Ablations were stopped based on previously established real-time fluorescence spectral data, not based on temperature or time. To determine where in the ablated tissue cell death occurred, biopsies for transmission electron microscopy were taken from 4 areas of 3 specimens: (1) nonablated liver, (2) hemorrhagic zone/normal liver interface, (3) hemorrhagic zone/coagulated zone interface, and (4) coagulated zone. In vitro fluorescence emission intensity was determined at each biopsy site. Results Peak hepatic fluorescence intensity occurred at 470 nm and decreased as RFA progressed. Transmission electron microscopy evidence of irreversible hepatocyte damage occurred at the interface of the coagulation zone and the hemorrhagic zone and correlated with a 87.5% ± 9% decrease in fluorescence emission intensity. Tissue fluorescent changes from thermal injury were unaffected by tissue cooling. Conclusion Fluorescence spectroscopy accurately detected hepatocellular thermal injury from RFA in real time and can detect irreversible cell damage during tissue thermal therapy.

Radiofrequency ablation (RFA) is an evolving technology used to treat unresectable liver tumors. Currently, there is no accurate method to determine RFA margins in real-time during the procedure. We hypothesized that a fiber-optic based spectroscopic monitoring system could detect thermal damage from RFA in real-time. Fluorescence (F) and diffuse reflectance (Rd) spectra were continuously acquired from within the expected ablation zone during canine hepatic RFA using a fiber-optic microinterrogation probe (MIP). The F and Rd spectral feedback were continuously monitored and ablations were stopped based on changes in spectra alone. After each ablation, the MIP tract was marked with India ink and the ablation zone was excised. The relationship of the MIP to the zone of ablation was examined grossly and microscopically. F and Rd spectral changes occurred in three characteristic phases as the ablation zone progresses past the MIP. Phase 1 indicates minimal deviation from normal lives. Phase 2 occurs as the MIP lies within the hemorrhagic zone of the ablated tissue. Phase 3 correlates with complete tissue coagulation. The absolute magnitude of spectral change correlates with the gross and histologic degree of thermal damage. Optical spectroscopy is a technology that allows real-time detection of thermal tissue damage. In this study, both F and Rd spectroscopy accurately defined the advancing hemorrhagic edge of the zone of ablation and the central coagulation zone. These results suggest that F and Rd spectroscopy can be used to create a real-time feedback system to accurately define RFA margins.

Thermal energy generated by radio-frequency current or other means may be employed in treating liver tumors by means of thermal coagulation when conventional resection is impossible. Currently, these thermal energy-based therapeutic procedures suffer from the lack of an adequate feedback control system, making it difficult to determine the optimal therapeutic endpoint. In this study, the potential of optical spectroscopy to provide such an objective endpoint for these procedures is presented. Freshly harvested canine liver samples were exposed to 50/spl deg/C, 60/spl deg/C, and 70/spl deg/C water baths for times ranging from 0 to 60 min. Transmission and reflectance were measured from each sample using an integrating sphere and the optical properties of each sample were accordingly derived. Excitation-emission matrices were recorded from the samples using a spectrofluorometer to identify the intrinsic fluorescence characteristics of native and thermally coagulated liver tissues. In addition, fluorescence and diffuse reflectance spectra were separately obtained from the samples prepared using a portable spectroscopic system. Results of this study show that fluorescence and optical properties of liver tissues exhibit clear and consistent changes through the thermal coagulation process. Specifically, the primary peak in the fluorescence spectra from liver tissues shifts from 480 nm in the native state to 510 nm in the fully coagulated state. In addition, a three- to fourfold increase in the absolute intensity of the diffuse reflectance spectra is observed upon complete coagulation of liver tissues. These dynamic spectral features indicate that fluorescence and diffuse reflectance spectroscopy may provide a direct measure of the biochemical and structural changes associated with tissue thermal damage in the liver.

Here we present a new methodology that investigates the intrinsic structural and hemodynamic characteristics of in vivo brain tissue, in a non-contact fashion, and can be easily incorporated in an intra-operative environment. Within this methodology, relative total diffuse reflectance spectra (RTD(λ)) were acquired from targets using a hybrid spectroscopy imaging system. A spectral interpretation algorithm was subsequently applied to RTD(λ) to retrieve optical properties related to the compositional and structural characteristics of each target. Estimation errors of the proposed methodology were computationally evaluated using a Monte Carlo simulation model for photon migration under various conditions. It was discovered that this new methodology could handle moderate noise and achieve very high accuracy, but only if the refractive index of the target is known. The accuracy of the technique was also validated using a series of tissue phantom studies, and consistent and accurate estimates of μs’(λ)/μa(λ) were obtained from all the phantoms tested. Finally, a small-scale animal study was conducted to demonstrate the clinical utility of the reported method, wherein a forepaw stimulation model was utilized to induce transient hemodynamic responses in somatosensory cortices. With this approach, significant stimulation-related changes (p < 0.001) in cortical hemodynamic and structural characteristics were successfully measured.

A simple but effective method of spectral processing was developed to minimize or remove the effects of the presence of superficial blood on tissue optical spectra and, hence, enhance the performance of optical-spectroscopic-based in vivo tissue diagnosis and surgical guidance. This spectral-processing algorithm was developed using the principles of absorption-induced light attenuation wherein the ratio of fluorescence intensity (F) and the hth power of diffuse reflectance intensity (Rd) at a given emission wavelength /spl lambda//sub m/ is immune to spectral distortions induced by the presence of blood on the tissue surface. Here, the exponent h is determined by the absorption coefficients of whole blood at the excitation and emission wavelengths. The theoretical basis of this spectral processing was verified using simulations and was experimentally validated. Furthermore, the optical spectra of brain tissues collected in vivo was processed using this algorithm to evaluate its impact on brain tissue differentiation using combined fluorescence and diffuse reflectance spectroscopy. Based on the simulation, as well as experimental results, it was observed that using F/Rd/sup h/ h can effectively reduce or remove spectral distortions induced by superficial blood contamination on tissue optical spectra. Thus, optical spectroscopy can also be used intraoperatively for applications such as surgical guidance of tumor resection.

A non-contact optical spectroscopy system was developed, using a wide-field illumination, to study the human brain in vivo. The optical signal recorded from a point on the exposed brain surface using this new system was a fraction of the total reflectance RTm(?). The system was designed to be used in conjunction with a reflectance standard with known optical properties in order to convert RTm(?) to the absolute total reflectance RTA(?). Furthermore, a new Monte-Carlo -based spectral interpretation algorithm was developed to retrieve hemodynamic and structural properties from RTA(?). Specifically, the algorithm was able to produce the ratio of the absorption and reduced scattering spectra (i.e., ?a(?)/?s'(?)), the level of hemoglobin oxygenation, and the scattering power. . A reflectance standard that can be used in conjunction with the non-contact spectroscopy system for in vivo measurements of RTA(?) was also developed. The system is currently used in the in vivo studies of pediatric brain tumors and epileptic lesions.

Regenerative medicine is the process of replacing or regenerating animal cells, tissues, or organs to restore or establish normal function. This field has the potential to solve the problem of the shortage of organs available for donation and of organ transplant rejection. Recently, application of Complementary and Alternative Medicine (CAM) as a means to accelerate the process of regeneration is a new approach. The CAM therapies offer a natural and cost-effective intervention to change the course of chronic disease and may regenerate failing organ systems. The paper by Dr. Y.–J. Chen et al. explores how the Hepatitis B virus-encoded X regulates the expression of epidermal growth factor receptor, an important gene for growth of hepatocytes. Dr. H.–Y. Liu et al. demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy. Dr. S. –H. Hsu et al. prepared peripheral nerve conduits containing the negatively charged Tremella fuciformis polysaccharide (TF) and successfully used the TF-immobilized conduits to repair a large (15 mm) critical gap defect in rats. Y. Lee et al. found that L-glutamate-induced neurotoxicity could be suppressed by the treatment with constituents of Rhodiola rosea, indicating that the Rhodiola rosea may have therapeutic potential for the treatment of inflammation and neurodegenerative disease. Dr. B.–Y. Yang et al. tried to apply percutaneous electrical stimulation to improve bone remodeling and bone healing in rats. X-ray and micro-CT showed that the electrical treatment could increase the amount of newly formed cranial bone. W. Liu et al. examined the contribution of side population (SP) cells from kidney and bone marrow to the reconstitution of kidney SP pools after ischemia-reperfusion injury (IRI). They found that following renal IRI, kidney SP cells were acutely depleted and then progressively restorated to baseline levels by both self-proliferation and extrarenal source, that is, bone marrow-derived cell homing. Dr. F. Yahya et al. showed that methanol extract of Bauhinia purpurea leaves could exert potential hepatoprotective activity in rats via its antioxidant activity and high phenolic content. T. Jayakumar et al. reviewed the effects of andrographolide, a major bioactive chemical constituent in Andrographis paniculata (Burm.f.) Nees, against cardiovascular disease, platelet activation, infertility, and NF-kB activation. Dr. H.–M. Chiang et al. showed the antioxidant activity of a Neonauclea reticulata water extract against ultraviolet B (UVB) irradiation in human skin fibroblast cell cultures (Hs68) by inhibiting MMP-1, -3, and -9 expressions and increasing levels of collagen activity. Dr. W.–Y. Su et al. developed a biphasic calcium phosphate cement, consisting of α-tricalcium phosphate (α-TCP) and hydroxyapatite (HAP), which is a potential biomaterial for bone repair. C. Y. Ho et al. showed that acupuncture and electroacupuncture could have positive effects on regeneration of median nerve in rats. J. Xiao et al. demonstrated that administration of garlic-derived antioxidant S-allylmercaptocysteine (SAMC) could ameliorate hepatic injury in a nonalcoholic fatty liver disease rat model. Dr. S.–C. Lee et al. investigated the effect of ferulic acid (FA) against peripheral nerve injury. They found that FA appears to promote peripheral nerve regeneration across a 15 mm critical defect gap in the rat sciatic nerve injury model. Suppression of macrophages by FA at the site of peripheral nerve injury may contribute to its nerve growth-promoting capability. By compiling these articles, we hope to stimulate our readers and researchers to provide continuing efforts to fully understand the effects of CAM therapies on regenerating tissues or organs. Yueh-Sheng Chen Wei-Chiang Lin Cheryl Miller

Background Dravet syndrome (DS) is a rare form of intractable epilepsy. Children with DS often start having seizures in infancy, and gradually develop other seizure types. Several studies have demonstrated that certain gene mutations and submicroscopic copy number variations (CNV) in DS patients are strongly associated with intractable epilepsy. In this study, directed DNA sequencing and microarray technology were used to investigate genomic variations in DS patients. Methods A total of nine DS patients were enrolled in this genetic study. A detailed medical history was obtained from each participant, and appropriate neurological examinations performed. Seizure types and epilepsy syndromes were classified according to ILAE criteria. The complete coding regions of SCN1A, SCN1B, SCN2A, GABRG2, and GABRD, including the intron/exon boundaries, were sequenced using DNA samples drawn from participants. In addition, whole genome CNV analysis was conducted via SNP microarray analysis. Results DNA sequencing revealed a mutation in the SCN1A gene in five (55.6%) of the DS patients, within which three missense mutations, c.719T > C (p.Leu240Pro), c.2807A > T (p.Asp936Val), c.4349A > C (p.Gln1450Pro), and two frameshift mutations, c.2277insAACA (p.His759fsX772) and c.3972insT (p.Leu1324fsX1331) were observed. Upon CNV analysis, a novel duplication region, 4q13.1–q13.2, was detected in one DS patient; this variant region contained a gene, EPHA5, related to cerebral neuron development. Conclusion This study extended the spectrum of SCN1A mutations in Taiwanese DS patients and confirms the high sensitivity of SCN1A for the DS phenotype. In addition, a novel duplication region identified within EPHA5 should be considered in future screening procedures for DS.

In this pilot study, we explored the potential of using a diffuse reflectance imaging system to extract interictal pathophysiological characteristics of epileptic cortex in an intraoperative setting. The imaging system was able to simultaneously measure diffuse reflectance signals at two distinct wavelengths (500 and 700 nm) from the entire exposed cortical surface. It was used to study ten pediatric patients during their epilepsy surgery. Diffuse reflectance images, Rd(x,y,λ,t) at 500 nm and 700 nm, were acquired at a 5 Hz rate for at least 200 seconds. Post imaging analysis identified a unique local frequency oscillation (LFO), below respiration rate, existed in Rd(x,y,500 nm,t) and Rd(x,y,700 nm,t). Mapping the spectral densities of LFOs over the cortical surface identified the spatial distribution of the LFOs. In almost all ten patients studied, the location demonstrating strong LFOs coincided with the epileptic cortex determined using ECoG. However, some LFOs were found in close proximity to functional areas according to fMRI. We further used the correlation coefficient map to identify those pixels with similar waveforms for better demarcation. These preliminary results support the feasibility of using wavelength-dependent diffuse reflectance imaging to intra-operatively detect epileptic cortex.

Low-frequency oscillations in cortical hemodynamics were observed from the cortex of pediatric patients undergoing epilepsy surgery; they may be used to identify the functional and/or the epileptic cortex intraoperatively.

Both in medical research and clinical settings, regional hemoglobin concentrations ([Hb]) in the microcirculation of biological tissues are highly sought. Diffuse reflectance spectroscopy has been proven to be a favorable method by which to detect regional [Hb]. This paper introduces a new algorithm to retrieve [Hb] information from diffuse reflectance spectra. The proposed algorithm utilizes the natural logarithmic operation and the differential wavelet transform to effectively quench the scattering effects, and then employs the concept of isosbestic wavelength in the transformed spectra to reduce the effects of hemoglobin oxygenation. As a result, the intensity at the defined isosbestic wavelength of the transformed spectra is a good indicator of [Hb] estimation. The algorithm was derived and validated using theoretical spectra produced by Monte Carlo simulation of photon migration. Its accuracy was further evaluated using liquid tissue phantoms, and its clinical utility with an in vivo clinical study of brain tumors. The results demonstrate the applicability of the algorithm for real-time [Hb] estimations from diffuse reflectance spectra, acquired by means of a fiber-optic spectroscopy system.

We explore the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to characterize a myocardial infarct at different developing stages. An animal study is conducted using rats with surgically induced myocaridal infarction (MI). In vivo fluorescence spectra at 337-nm excitation and diffuse reflectance between 400 and 900 nm are measured from the heart. Spectral acquisition is performed: 1. for normal heart tissue; 2. for the area immediately surrounding the infarct; and 3. for the infarcted tissue itself, one, two, three, and four weeks into MI development. Histological and statistical analyses are used to identify unique pathohistological features and spectral alterations associated with the investigated regions. The main alterations (p

This paper presents an electronic tongue system with blind source separation (BSS) and wireless sensor network (WSN) for remote multi-ion sensing applications. Electrochemical sensors, such as ion-sensitive field-effect transistor (ISFET) and extended-gate field-effect transistor (EGFET), only provide the combined concentrations of all ions in aqueous solutions. Mixed hydrogen and sodium ions in chemical solutions are observed by means of H + ISFET and H + EGFET sensor array. The BSS extracts the concentration of individual ions using independent component analysis (ICA). The parameters of ISFET and EGFET sensors serve as a priori knowledge that helps solve the BSS problem. Using wireless transceivers, the ISFET/EGFET modules are realized as wireless sensor nodes. The integration of WSN technology into our electronic tongue system with BSS capability makes distant multi-ion measurement viable for environment and water quality monitoring. Keywords: Electronic tongue, ion-sensitive field-effect transistor (ISFET), extended-gate field-effect transistor (EGFET), wireless sensor network (WSN), blind source separation (BSS), independent component analysis (ICA)

An animal study was carried out to validate the feasibility of developing an optical tissue characterization system, based on combined diffuse reflectance and fluorescence spectroscopy, to delineate and grade a myocardial infarct in vivo.

Variations in blood oxygen saturation (SatO2) and blood volume fraction (BVF) in tissue have been associated with various pathophysiological conditions such as cancer development. These variations can be assessed directly through the absorption properties of hemoglobin in the visible wavelength region, which is detectable using optical techniques such as diffuse reflectance spectroscopy. In this pilot study, we derived a new methodology that quantitatively extracted the spectral profile characteristics of hemoglobin absorption from a diffuse reflectance spectrum using wavelet transformation. The variations in the extracted profile characteristics were then related to the alterations in SatO2 and BVF levels. The applicability of the methodology was evaluated using a set of diffuse reflectance spectra produced theoretically using a Monte Carlo simulation for photon migration.

According to the Epilepsy Foundation, about 45,000 children under the age of 15 develop epilepsy each year. One of the long-standing challenges in the field of pediatric epilepsy research is to differentiate between normal and epileptic brain areas. This problem is especially important for children with intractable epilepsy, because surgical intervention must be used to alleviate their epileptic symptoms. Optical spectroscopy may be used to assess the pathophysiological characteristics of the epileptic brain tissue intraoperatively in a non-destructive manner, which, in turn, allows surgeons to plan an epilepsy surgery. Herein, the study is focused on demonstrating the feasibility of using time-dependent, diffuse reflectance spectroscopy specifically to detect pathophysiological characteristics associated with epileptic brain tissue. In a pediatric patient undergoing epilepsy surgery, time-dependent, diffuse reflectance spectra were measured from the epileptic cortex and the surrounding tissue using a fiber-optic spectroscopy system. The system was designed to acquire diffuse reflectance spectra from 300 - 1100 nm at a maximum acquisition rate of 33 Hz. Spectral and temporal variations in the acquired spectral sequences were compared to the corresponding electrocorticographic results, and thosevariations unique to the epileptic cortex were identified using statistical methods. Furthermore, these spectral variations were related to the physiological and morphological characteristics of the brain tissue. The preliminary results obtained from this in vivo study demonstrate the feasibility of differentiating epileptic cortex tissue from normal tissue using time-dependent, diffuse reflectance data.

This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative correlation time indices from all investigated sites were sub-grouped according to the corresponding histological classifications. The difference between the mean indices of two subgroups was evaluated by standard t-test. These comparison and calculation procedures were carried out for all possible wavelength combinations between 400 nm and 800 nm with 2 nm increments. The positive group consisted of seven pathologically abnormal test sites, and the negative group consisted of 13 normal test sites from non-epileptic tumor patients. A standard t-test showed significant difference between negative correlation time indices from the two groups at the wavelength combinations of 700-760 nm versus 550-580 nm. An empirical discrimination algorithm based on the negative correlation time indices in this range produced 100% sensitivity and 85% specificity. Based on these results time-dependent diffuse reflectance spectroscopy with optimized data analysis methods differentiates epileptic brain tissue from normal brain tissue adequately, therefore can be utilized for surgical guidance, and may enhance the surgical outcome of pediatric epilepsy surgery.

The short- and long-term effects of probe contact pressure on in vivo diffuse reflectance and fluorescence spectroscopy were investigated using an animal model. Elevation in probe contact pressure induced major profile alterations in the diffuse reflectance spectra between 400 and 650 nm, and led to significant intensity increases in the fluorescence spectra. The pressure threshold that was required to induce statistically significant spectral alterations was dependent upon the type of tissue. The observed spectral alterations may be attributed to decreases in local blood volume, blood oxygenation, and tissue metabolism, resulting from high probe contact pressure.

Optical spectroscopy for in vivo tissue diagnosis is performed traditionally in a static manner; a snap shot of the tissue biochemical and morphological characteristics is captured through the interaction between light and the tissue. This approach does not capture the dynamic nature of a living organ, which is critical to the studies of brain disorders such as epilepsy. Therefore, a time-dependent diffuse reflectance spectroscopy system with a fiber-optic probe was designed and developed. The system was designed to acquire broadband diffuse reflectance spectra (240 ~ 932 nm) at an acquisition rate of 33 Hz. The broadband spectral acquisition feature allows simultaneous monitoring of various physiological characteristics of tissues. The utility of such a system in guiding pediatric epilepsy surgery was tested in a pilot clinical study including 13 epilepsy patients and seven brain tumor patients. The control patients were children undergoing suregery for brain tumors in which measurements were taken from normal brain exposed during the surgery. Diffuse reflectance spectra were acquired for 12 seconds from various parts of the brain of the patients during surgery. Recorded spectra were processed and analyzed in both spectral and time domains to gain insights into the dynamic changes in, for example, hemodynamics of the investigated brain tissue. One finding from this pilot study is that unsynchronized alterations in local blood oxygenation and local blood volume were observed in epileptogenic cortex. These study results suggest the advantage of using a time-dependent diffuse reflectance spectroscopy system to study epileptogenic brain in vivo.

The effects of myocardial infarction on in vivo diffuse reflectance and fluorescence characteristics of myocardial tissue were investigated. Spectral alterations induced by infarct development in myocardial tissue are reported.

The effects of probe contact pressure on in vivo diffuse reflectance and fluorescence spectroscopy was investigated. Spectral alterations induced by contact probe pressure and the minimal pressure required to induce such effects are reported here.

It is estimated that approximately 17,000 malignant brain tumors are diagnosed in adults and 1,500 in children every year in the United States. Although primary brain tumors account for only 1.4% of all cancers, the 5-year survival rate of these patients (35%) is low. The most common initial therapy received by brain tumor patients is surgical resection. Many studies have shown that the degree of resection significantly influences the time to recurrence and the overall survival of brain tumor patients. Currently, surgical navigation systems and ultrasonography are used intraoperatively to help neurosurgeons locate brain tumor and maximize resection. Despite the applications of these technologies, significant residual tumor mass is often found to be left behind in patients following brain tumor resection. Hence, there is a need for an objective, intraoperative real-time system that is capable of accurately differentiating brain tumors from normal brain tissue, and detecting tumor margins with sub-millimeter spatial resolution.

Recently, optical spectroscopy has shown considerable promise to be used as a potential clinical tool for human brain tumor detection and therapeutic guidance. Our group showed for the first time the possibility of using combined autofluorescence and diffuse reflectance spectroscopy and established its applicability for human brain tumor demarcation in previous in vitro and in vivo studies. We report in this paper the results of a clinical study designed to further evaluate the efficacy of the approach for demarcation of brain tumors and tumor margins from normal brain tissues in intra-operative clinical setting. Using a portable system, optical spectra were collected from the brain of 110 patients undergoing craniotomy at the Vanderbilt University Medical Center. Spectral measurements were taken from multiple sites of tumor core, tumor margin and normal areas of brain tissues and the resulting spectra were correlated with the corresponding histopathologic diagnosis. Using histology as the gold standard, a probabilistic multi-class diagnostic algorithm was developed to simultaneously distinguish tumor core and tumor margin from normal brain tissue sites using independent training and validation sets of data. An unbiased estimate of the accuracy of the model indicates that combined autofluorescence and diffuse reflectance spectroscopy was able to distinguish tumor core and tumor margin from normal brain tissues with an average predictive accuracy of ~88%.