MEG correlates of speech planning in simple vs. interactive picture naming in children and adults.

The picture naming task is common both as a clinical task and as a method to study the neural bases of speech production in the healthy brain. However, this task is not reflective of most naturally occurring productions, which tend to happen within a context, typically in dialogue in response to someone else's production. How the brain basis of the classic "confrontation picture naming" task compares to the planning of utterances in dialogue is not known. Here we used magnetoencephalography (MEG) to measure neural activity associated with language production using the classic picture naming task as well as a minimal variant of the task, intended as more interactive or dialogue-like. We assessed how neural activity is affected by the interactive context in children, teenagers, and adults. The general pattern was that in adults, the interactive task elicited a robust sustained increase of activity in frontal and temporal cortices bilaterally, as compared to simple picture naming. This increase was present only in the left hemisphere in teenagers and was absent in children, who, in fact, showed the reverse effect. Thus our findings suggest a robustly bilateral neural basis for the coordination of interaction and a very slow developmental timeline for this network.

Imaging Photoplethysmography for Noninvasive Anastomotic Perfusion Assessment in Intestinal Surgery.

INTRODUCTION: Anastomotic leakage after gastrointestinal surgery has a high impact on patient's quality of life and its origin is associated with inadequate perfusion. Imaging photoplethysmography (iPPG) is a noninvasive imaging technique that measures blood-volume changes in the microvascular tissue bed and detects changes in tissue perfusion. MATERIALS AND METHODS: Intraoperative iPPG imaging was performed in 29 patients undergoing an open segment resection of the small intestine or colon. During each surgery, imaging was performed on fully perfused (true positives) and ischemic intestines (true negatives) and the anastomosis (unknowns). Imaging consisted of a 30-s video from which perfusion maps were extracted, providing detailed information about blood flow within the intestine microvasculature. To detect the predictive capabilities of iPPG, true positive and true negative perfusion conditions were used to develop two different perfusion classification methods. RESULTS: iPPG-derived perfusion parameters were highly correlated with perfusion-perfused or ischemic-in intestinal tissues. A perfusion confidence map distinguished perfused and ischemic intestinal tissues with 96% sensitivity and 86% specificity. Anastomosis images were scored as adequately perfused in 86% of cases and 14% inconclusive. The cubic-Support Vector Machine achieved 90.9% accuracy and an area under the curve of 96%. No anastomosis-related postoperative complications were encountered in this study. CONCLUSIONS: This study shows that noninvasive intraoperative iPPG is suitable for the objective assessment of small intestine and colon anastomotic perfusion. In addition, two perfusion classification methods were developed, providing the first step in an intestinal perfusion prediction model.

Development of a CT-Compatible, Anthropomorphic Skull and Brain Phantom for Neurosurgical Planning, Training, and Simulation.

BACKGROUND: Neurosurgical procedures are complex and require years of training and experience. Traditional training on human cadavers is expensive, requires facilities and planning, and raises ethical concerns. Therefore, the use of anthropomorphic phantoms could be an excellent substitute. The aim of the study was to design and develop a patient-specific 3D-skull and brain model with realistic CT-attenuation suitable for conventional and augmented reality (AR)-navigated neurosurgical simulations. METHODS: The radiodensity of materials considered for the skull and brain phantoms were investigated using cone beam CT (CBCT) and compared to the radiodensities of the human skull and brain. The mechanical properties of the materials considered were tested in the laboratory and subsequently evaluated by clinically active neurosurgeons. Optimization of the phantom for the intended purposes was performed in a feedback cycle of tests and improvements. RESULTS: The skull, including a complete representation of the nasal cavity and skull base, was 3D printed using polylactic acid with calcium carbonate. The brain was cast using a mixture of water and coolant, with 4 wt% polyvinyl alcohol and 0.1 wt% barium sulfate, in a mold obtained from segmentation of CBCT and T1 weighted MR images from a cadaver. The experiments revealed that the radiodensities of the skull and brain phantoms were 547 and 38 Hounsfield units (HU), as compared to real skull bone and brain tissues with values of around 1300 and 30 HU, respectively. As for the mechanical properties testing, the brain phantom exhibited a similar elasticity to real brain tissue. The phantom was subsequently evaluated by neurosurgeons in simulations of endonasal skull-base surgery, brain biopsies, and external ventricular drain (EVD) placement and found to fulfill the requirements of a surgical phantom. CONCLUSIONS: A realistic and CT-compatible anthropomorphic head phantom was designed and successfully used for simulated augmented reality-led neurosurgical procedures. The anatomic details of the skull base and brain were realistically reproduced. This phantom can easily be manufactured and used for surgical training at a low cost.

Tissue-mimicking phantom materials with tunable optical properties suitable for assessment of diffuse reflectance spectroscopy during electrosurgery.

Emerging intraoperative tumor margin assessment techniques require the development of more complex and reliable organ phantoms to assess the performance of the technique before its translation into the clinic. In this work, electrically conductive tissue-mimicking materials (TMMs) based on fat, water and agar/gelatin were produced with tunable optical properties. The composition of the phantoms allowed for the assessment of tumor margins using diffuse reflectance spectroscopy, as the fat/water ratio served as a discriminating factor between the healthy and malignant tissue. Moreover, the possibility of using polyvinyl alcohol (PVA) or transglutaminase in combination with fat, water and gelatin for developing TMMs was studied. The diffuse spectral response of the developed phantom materials had a good match with the spectral response of porcine muscle and adipose tissue, as well as in vitro human breast tissue. Using the developed recipe, anatomically relevant heterogeneous breast phantoms representing the optical properties of different layers of the human breast were fabricated using 3D-printed molds. These TMMs can be used for further development of phantoms applicable for simulating the realistic breast conserving surgery workflow in order to evaluate the intraoperative optical-based tumor margin assessment techniques during electrosurgery.

Imaging PPG for In Vivo Human Tissue Perfusion Assessment during Surgery.

Surgical excision is the golden standard for treatment of intestinal tumors. In this surgical procedure, inadequate perfusion of the anastomosis can lead to postoperative complications, such as anastomotic leakages. Imaging photoplethysmography (iPPG) can potentially provide objective and real-time feedback of the perfusion status of tissues. This feasibility study aims to evaluate an iPPG acquisition system during intestinal surgeries to detect the perfusion levels of the microvasculature tissue bed in different perfusion conditions. This feasibility study assesses three patients that underwent resection of a portion of the small intestine. Data was acquired from fully perfused, non-perfused and anastomosis parts of the intestine during different phases of the surgical procedure. Strategies for limiting motion and noise during acquisition were implemented. iPPG perfusion maps were successfully extracted from the intestine microvasculature, demonstrating that iPPG can be successfully used for detecting perturbations and perfusion changes in intestinal tissues during surgery. This study provides proof of concept for iPPG to detect changes in organ perfusion levels.

Hyperspectral Imaging for Tissue Classification after Advanced Stage Ovarian Cancer Surgery-A Pilot Study.

The most important prognostic factor for the survival of advanced-stage epithelial ovarian cancer (EOC) is the completeness of cytoreductive surgery (CRS). Therefore, an intraoperative technique to detect microscopic tumors would be of great value. The aim of this pilot study is to assess the feasibility of near-infrared hyperspectral imaging (HSI) for EOC detection in ex vivo tissue samples. Images were collected during CRS in 11 patients in the wavelength range of 665−975 nm, and processed by calibration, normalization, and noise filtering. A linear support vector machine (SVM) was employed to classify healthy and tumorous tissue (defined as >50% tumor cells). Classifier performance was evaluated using leave-one-out cross-validation. Images of 26 tissue samples from 10 patients were included, containing 26,446 data points that were matched to histopathology. Tumorous tissue could be classified with an area under the curve of 0.83, a sensitivity of 0.81, a specificity of 0.70, and Matthew's correlation coefficient of 0.41. This study paves the way to in vivo and intraoperative use of HSI during CRS. Hyperspectral imaging can scan a whole tissue surface in a fast and non-contact way. Our pilot study demonstrates that HSI and SVM learning can be used to discriminate EOC from surrounding tissue.

Diffuse reflectance spectroscopy sensor to differentiate between glial tumor and healthy brain tissue: a proof-of-concept study.

Glial tumors grow diffusely in the brain. Survival is correlated to the extent of tumor removal, but tumor borders are often invisible. Resection beyond the borders as defined by conventional methods may further improve prognosis. In this proof-of-concept study, we evaluate diffuse reflectance spectroscopy (DRS) for discrimination between glial tumors and normal brain ex vivo. DRS spectra and histology were acquired from 22 tumor samples and nine brain tissue samples retrieved from 30 patients. The content of biological chromophores and scattering features were estimated by fitting a model derived from diffusion theory to the DRS spectra. DRS parameters differed significantly between tumor and normal brain tissue. Classification using random forest yielded a sensitivity and specificity for the detection of low-grade gliomas of 82.0% and 82.7%, respectively, and the area under curve (AUC) was 0.91. Applied in a hand-held probe or biopsy needle, DRS has the potential to provide intra-operative tissue analysis.

Augmented reality navigation for cranial biopsy and external ventricular drain insertion.

OBJECTIVE: The aim of this study was to evaluate the accuracy (deviation from the target or intended path) and efficacy (insertion time) of an augmented reality surgical navigation (ARSN) system for insertion of biopsy needles and external ventricular drains (EVDs), two common neurosurgical procedures that require high precision. METHODS: The hybrid operating room-based ARSN system, comprising a robotic C-arm with intraoperative cone-beam CT (CBCT) and integrated video tracking of the patient and instruments using nonobtrusive adhesive optical markers, was used. A 3D-printed skull phantom with a realistic gelatinous brain model containing air-filled ventricles and 2-mm spherical biopsy targets was obtained. After initial CBCT acquisition for target registration and planning, ARSN was used for 30 cranial biopsies and 10 EVD insertions. Needle positions were verified by CBCT. RESULTS: The mean accuracy of the biopsy needle insertions (n = 30) was 0.8 mm ± 0.43 mm. The median path length was 39 mm (range 16-104 mm) and did not correlate to accuracy (p = 0.15). The median device insertion time was 149 seconds (range 87-233 seconds). The mean accuracy for the EVD insertions (n = 10) was 2.9 mm ± 0.8 mm at the tip with a 0.7° ± 0.5° angular deviation compared with the planned path, and the median insertion time was 188 seconds (range 135-400 seconds). CONCLUSIONS: This study demonstrated that ARSN can be used for navigation of percutaneous cranial biopsies and EVDs with high accuracy and efficacy.

Influence of sampling accuracy on augmented reality for laparoscopic image-guided surgery.

PURPOSE: This study aims to evaluate the accuracy of point-based registration (PBR) when used for augmented reality (AR) in laparoscopic liver resection surgery. MATERIAL AND METHODS: The study was conducted in three different scenarios in which the accuracy of sampling targets for PBR decreases: using an assessment phantom with machined divot holes, a patient-specific liver phantom with markers visible in computed tomography (CT) scans and in vivo, relying on the surgeon's anatomical understanding to perform annotations. Target registration error (TRE) and fiducial registration error (FRE) were computed using five randomly selected positions for image-to-patient registration. RESULTS: AR with intra-operative CT scanning showed a mean TRE of 6.9 mm for the machined phantom, 7.9 mm for the patient-specific phantom and 13.4 mm in the in vivo study. CONCLUSIONS: AR showed an increase in both TRE and FRE throughout the experimental studies, proving that AR is not robust to the sampling accuracy of the targets used to compute image-to-patient registration. Moreover, an influence of the size of the volume to be register was observed. Hence, it is advisable to reduce both errors due to annotations and the size of registration volumes, which can cause large errors in AR systems.

Correction: Fusion of augmented reality imaging with the endoscopic view for endonasal skull base surgery; a novel application for surgical navigation based on intraoperative cone beam computed tomography and optical tracking.

[This corrects the article DOI: 10.1371/journal.pone.0227312.].

Fusion of augmented reality imaging with the endoscopic view for endonasal skull base surgery; a novel application for surgical navigation based on intraoperative cone beam computed tomography and optical tracking.

OBJECTIVE: Surgical navigation is a well-established tool in endoscopic skull base surgery. However, navigational and endoscopic views are usually displayed on separate monitors, forcing the surgeon to focus on one or the other. Aiming to provide real-time integration of endoscopic and diagnostic imaging information, we present a new navigation technique based on augmented reality with fusion of intraoperative cone beam computed tomography (CBCT) on the endoscopic view. The aim of this study was to evaluate the accuracy of the method. MATERIAL AND METHODS: An augmented reality surgical navigation system (ARSN) with 3D CBCT capability was used. The navigation system incorporates an optical tracking system (OTS) with four video cameras embedded in the flat detector of the motorized C-arm. Intra-operative CBCT images were fused with the view of the surgical field obtained by the endoscope's camera. Accuracy of CBCT image co-registration was tested using a custom-made grid with incorporated 3D spheres. RESULTS: Co-registration of the CBCT image on the endoscopic view was performed. Accuracy of the overlay, measured as mean target registration error (TRE), was 0.55 mm with a standard deviation of 0.24 mm and with a median value of 0.51mm and interquartile range of 0.39--0.68 mm. CONCLUSION: We present a novel augmented reality surgical navigation system, with fusion of intraoperative CBCT on the endoscopic view. The system shows sub-millimeter accuracy.

Haemoglobin levels in autoimmune haemolytic anaemias at diagnosis: relationship with immunoproteins on red blood cells.

Previous investigations of the relationship between characteristics of immunoproteins on red blood cells (RBCs) and the occurrence of autoimmune haemolysis yielded divergent results. Here, we studied these characteristics in autoimmune haemolytic anaemias (AIHAs) to determine their relationship with the degree of anaemia at diagnosis. We studied at diagnosis 52 cases of warm AIHA with positive direct antiglobulin test. Immunohaematological testing and determination of immunoglobulin class, complement, and immunoglobulin G (IgG) were performed using gel technology (GCT). Median haemoglobin (Hb) levels significantly differed between cases with IgG1 only or negative for IgG subclasses (7.4 g/dl), those with IgG3 or IgG1 + IgG3 (6.5 g/dl), and those with multiple immunoglobulins (5 g/dl). Logistic regression indicated that IgG3 detection was the only variable significantly related to the occurrence of RBC transfusion in AIHA (odds ratio 4.05, 95 % CI 1.1-14.7). In our study, the type of immunoprotein(s) on the RBC surface was associated with different Hb levels at AIHA diagnosis. IgG3 and multiple immunoglobulins were associated with lower Hb levels; IgG3 was also associated with a higher percentage of patient transfusions in the first week after diagnosis. Thus, qualitative differences in these immunoproteins may lead to deeper and more prolonged anaemia levels, influencing the need for RBC transfusion.

Autoimmune hemolytic anemia with gel-based immunohematology tests: neural network analysis.

In a previous report, we investigated the capability of commercially available immunohematology tests based on gel technology to add useful information for the diagnosis of autoimmune hemolytic anemia (AIHA). In this report, we analyzed the same casuistic to find useful information on the importance of different immunohematology tests for the AIHA diagnosis, but using the artificial neural network (ANN) analysis. We studied 588 samples with a positive direct antiglobulin test (DAT), of which 52 samples came from patients with AIHA. The samples were analyzed with the ANN using the multilayer perceptron with the backpropagation algorithm. Using the ANN in the observed data set, the predictive value for the presence of AIHAs was 94.7%. The rate of DAT-positive cases that were not AIHA and that were correctly classified was 99.4%. The receiver operating curve area for the model was 0.99. The independent variable importance analysis found that the gel centrifugation test anti-IgG titer was an important contributor to the network performance, but other variables such as the IgG subclasses can also be considered important. The use of the ANN permitted us to identify immunohematology tests that were "hidden" with the common statistical models used previously. This was the case for the IgG subclasses. However, it is very likely that the information given to the network from those tests is quantitative rather than qualitative.

Autoimmune hemolytic anemia with gel-based immunohematology tests.

We used gel centrifugation tests (GCTs) to analyze the relationship between the diagnosis and immunohematology tests used for autoimmune hemolytic anemia (AIHA). The study included 588 samples positive for the direct antiglobulin test (DAT). Of these, 52 were from patients diagnosed with AIHA. Immunoglobulin (Ig) class, IgG1, IgG3, and complement were measured. DAT strength had the strongest correlation with AIHA diagnosis (odds ratio [OR], 23), followed by anti-IgG titer 300 (OR, 8.4), anti-IgG titer 1,000 (OR, 10.5), and C3d agglutination strength (OR, 1.7). Decision tree analysis revealed that DAT strength and anti-IgG titer higher than 100 were the best predictors of AIHA. Multidimensional scanning analysis found a high grade of similarity among DAT strength, anti-IgG titer, and IgG strength in the AIHA samples. This observation was not detected in DAT-positive samples from patients without AIHA. DAT strength remained the best diagnostic indicator for AIHA and had the strongest association with AIHA compared with other commercially available immunohematology tests. The other tests, despite good correlation with AIHA diagnosis, did not add useful information.

On the effects of the lateral strains on the fiber Bragg grating response.

In this paper, a combined experimental-numerical based work was undertaken to investigate the Bragg wavelength shift response of an embedded FBG sensor when subjected to different conditions of multi-axial loading (deformation). The following cases are examined: (a) when an isotropic host material with no constrains on planes normal to the embedded sensor's axis is biaxially loaded, (b) when the same isotropic host material is subjected to hydrostatic pressure and (c) when the hydrostatically loaded host material is an anisotropic one, as in the case of a composite material, where the optical fiber is embedded along the reinforcing fibers. The comparison of the experimental results and the finite element simulations shows that, when the axial strain on the FBG sensor is the dominant component, the standard wavelength-shift strain relation can be used even if large lateral strains apply on the sensor. However when this is not the case, large errors may be introduced in the conversion of the wavelength to axial strains on the fiber. This situation arises when the FBG is placed parallel to high modulus reinforcing fibers of a polymer composite.

Distributed strain measurements using fiber Bragg gratings in small-diameter optical fiber and low-coherence reflectometry.

Optical low coherence reflectometry and fiber Bragg gratings written in small diameter (50 micrometer) optical fibers were used for measurements of non-homogenous internal strain fields inside an epoxy specimen with sub-grating length resolution. The results were compared with measurements using Fiber Bragg gratings in standard size (125 micrometer) single mode fibers and show that smaller fibers are less intrusive at stress heterogeneities.

ABO hemolytic disease of the fetus and newborn: an iatrogenic complication of heterologous assisted reproductive technology-induced pregnancy.

BACKGROUND: ABO hemolytic disease of the fetus and newborn (ABO HDFN) may manifest itself in cases of mothers belonging to blood group O and newborns of groups A or B and more frequently in group A and less so in group B. CASE STUDY: The case subjects are twin-birth newborns with ABO HDFN, of group AB born to a mother of group O. These cases of ABO HDFN prove inconsistent with Mendel's law of segregation. RESULTS AND CONCLUSION: This case study finds its explanation in new methods of assisted reproduction, particularly heterologous in vitro fertilization with ovodonation.

Characterization of anti-D monoclonal antibody reagents based on their reactivity with the weak D phenotype.

BACKGROUND: Anti-D monoclonal antibody (MoAb) reagents have improved D typing in routine tests. However, they exhibit a wide range of reactivity with the weak D phenotype depending on the characteristics of the different MoAbs used. We analyzed the reactivity of immunoglobulin (IgM) anti-D by cluster analysis to characterize MoAb that have similar reactivities with the weak D phenotype. STUDY DESIGN AND METHODS: We used 36 consecutive samples with weak D phenotype in routine testing and determined their reactivity with different IgM and IgG anti-D MoAbs. The samples were characterized as belonging to a weak D type or category using commercial molecular biology kits. RESULTS: The various anti-D MoAbs showed a wide grade of reactivity with the weak D samples. Similarities and dissimilarities in the behavior of the anti-D MoAbs with the weak D phenotype samples were detected with cluster analysis and the multidimensional scaling analysis. These analyses indicated different families of MoAbs characterized as having a high degree of homogeneity in their reactivity with the weak D phenotype. Between these MoAb families, the most effective at reacting with the weak D phenotype were RUM-1 and 175-2. CONCLUSIONS: The results show that it is possible to classify the anti-D MoAbs on the basis of their reactivity with the weak D phenotype. This provides information about different MoAbs' properties on the basis of their belonging to a given of anti-D family.

Non-invasive detection of fetal rhesus D status: a comparison between polymerase chain reaction and flow cytometry.

OBJECTIVE: A non-invasive prenatal determination of the fetal RhD status might be useful for the management of pregnancies in RhD-negative women whose partners are RhD positive. METHODS: Maternal peripheral blood of 32 RhD-negative women (17-24 weeks of gestation) was collected, and circulating fetal cells were enriched by CD71 mini-magnetic activated cell sorting. The RhD status of the fetuses was assessed using multiparametric flow cytometry, and results were compared to those of reverse transcriptase (RT)-polymerase chain reaction (PCR), or PCR, which acted as control. Flow-cytometric study of fetal cells employed monoclonal antibodies directed against CD71, glycophorin A (GPA) and RhD antigens. RESULTS: The median percentage of CD71- and RhD-positive cells was 0.83% (range 0.14-6.44%), and that of CD71 and GPA-positive cells was 10.07% (range 0.52-45.84%). Flow-cytometric analysis correlated with RT-PCR results of RNA obtained from whole maternal blood. In 1 case, an incorrect result was due to the failure of the amplification of the specific RhD band on RNA extracted from the CD71-positive fraction. In two instances, we observed false-positive results for RhD in PCR of DNA obtained from maternal plasma. CONCLUSION: Based on our results, flow-cytometric analysis might be proposed as a clinical tool for the non-invasive prenatal determination of the fetal RhD status independently of fetal gender.

Lower hemoglobin levels in human immunodeficiency virus-infected patients with a positive direct antiglobulin test (DAT): relationship with DAT strength and clinical stages.

BACKGROUND: There are conflicting opinions regarding the effect of positive direct antiglobulin test (DAT) on hemoglobin (Hb) levels in human immunodeficiency virus-infected (HIV+) patients. STUDY DESIGN AND METHODS: A total of 166 samples from HIV+ outpatients were studied. The DAT was performed with the tube test and column agglutination technology (CAT). RESULTS: The DAT was positive in 18.67 percent with the tube method and 33.73 percent with the CAT. Patients with DAT-positive results showed lower Hb levels than DAT-negative patients, 12.3 g per dL versus 14.3 g per dL (p = 0.0002). The univariate logistic regression enabled us to study the phenomenon better and fit the probability of having a DAT-positive result on the basis of the Hb levels. The relationship between the CAT and the tube test when washing the red blood cells (RBC) at 4 degrees C was stronger than when washing these at room temperature (phi = 0.8156; p = 0.000). The Hb levels were significantly lower in the positive DATs of Stage C (acquired immune deficiency syndrome [AIDS]) and Stage B (symptomatic non-AIDS patients), which showed decreasing Hb values for increasing agglutination strengths (p = 0.000). Anemia was related with the DAT results (odds ratio [OR], 8.005; p = 0.000) but not to the AIDS condition (OR, 1.741; p = 0.221). DISCUSSION: Our study indicates that the DAT-positive results may be specifically related to lower Hb levels in HIV+ patients. The immunologic RBC clearance could be part of the anemic multifactorial condition in HIV+ patients.