Detection Of Hypoxia Research Articles

Fetal Heart Rate Analysis for Automatic Detection of Perinatal Hypoxia Using Normalized Compression Distance and Machine Learning.

Accurate identification of Perinatal Hypoxia from visual inspection of Fetal Heart Rate (FHR) has been shown to have limitations. An automated signal processing method for this purpose needs to deal with time series of different lengths, recording interruptions, and poor quality signal conditions. We propose a new method, robust to those issues, for automated detection of perinatal hypoxia by analyzing the FHR during labor. Our system consists of several stages: (a) time series segmentation; (b) feature extraction from FHR signals, including raw time series, moments, and usual heart rate variability indices; (c) similarity calculation with Normalized Compression Distance, which is the key element for dealing with FHR time series; and (d) a simple classification algorithm for providing the hypoxia detection. We analyzed the proposed system using a database with 32 fetal records (15 controls). Time and frequency domain and moment features had similar performance identifying fetuses with hypoxia. The final system, using the third central moment of the FHR, yielded 92% sensitivity and 85% specificity at 3 h before delivery. Best predictions were obtained in time intervals more distant from delivery, i.e., 4–3 h and 3–2 h.

Renal Hypoxia in CKD; Pathophysiology and Detecting Methods.

Chronic kidney disease (CKD) is a major public health problem. Accumulating evidence suggests that CKD aggravates renal hypoxia, and in turn, renal hypoxia accelerates CKD progression. To eliminate this vicious cycle, hypoxia-related therapies, such as hypoxia-inducible factor (HIF) activation (prolyl hydroxylase domain inhibition) or NF-E2-related factor 2 activation, are currently under investigation. Clinical studies have revealed heterogeneity in renal oxygenation; therefore, the detection of patients with more hypoxic kidneys can be used to identify likely responders to hypoxia-oriented therapies. In this review, we provide a detailed description of current hypoxia detection methods. HIF degradation correlates with the intracellular oxygen concentration; thus, methods that can detect intracellular oxygen tension changes are desirable. The use of a microelectrode is a classical technique that is superior in quantitative performance; however, its high invasiveness and the fact that it reflects the extracellular oxygen tension are disadvantages. Pimonidazole protein adduct immunohistochemistry and HIF activation detection reflect intracellular oxygen tension, but these techniques yield qualitative data. Blood oxygen level-dependent magnetic resonance imaging has the advantage of low invasiveness, high quantitative performance, and application in clinical use, but its biggest disadvantage is that it measures only deoxyhemoglobin concentrations. Phosphorescence lifetime measurement is a relatively novel in vivo oxygen sensing technique that has the advantage of being quantitative; however, it has several disadvantages, such as toxicity of the phosphorescent dye and the inability to assess deeper tissues. Understanding the advantages and disadvantages of these hypoxia detection methods will help researchers precisely assess renal hypoxia and develop new therapeutics against renal hypoxia-associated CKD.

Automatic detection of hypoxia in renal tissue stained with HIF-1alpha

ObjectiveThe objective of this study was the identification of the stain HIF-alpha using the Image Cytometry, and to help to count the positive cells (with HIF-alpha) and the negative cells (without HIF-alpha) from the same sample. Method17 images of renal tissues from male rats of Winstar lineage; overall, there were 12.587 objects (cells) in the images for analysis.The acquired images were then analyzed through the free softwares CellProfiler (version 2.1.1) and CellProfiler Analyst (version 2.0).In the software CellProfiler Anlyst, there was a separation with the classes of the object, using a classifier, and the classes were: 1) class with HIF-alpha and 2) class without HIF-alpha. ResultsWith the data obtained through Score All, it was possible to calculate the percentage of cells that had HIF-alpha; out of 12.587 objects of the sample, 6.773 (54%) had HIF-alpha and 5.814 (46%) did not have HIF-alpha.Data of sensibility 0.90, specificity 0.84 and standard deviation 0.10 and 0.12. ConclusionThe research shows that the free software CellProfiler, through the light microscope, was able to identify the stains, perform the machine's learning, and subsequently count and separate cells from distinct classes (with and without the stain of HIF-alpha).

Assessment of hypoxia and TNF-alpharesponse by a vector with HRE and NF-kappaB response elements.

Hypoxia and inflammatory cytokine activation (H&I) are common processes in many acute and chronic diseases. Thus, a single vector that responds to both hypoxia and inflammatory cytokines, such as TNF-alpha, is useful for assesing the severity of such diseases. Adaptation to hypoxia is regulated primarily by hypoxia inducible transcription factor (HIF alpha) nuclear proteins that engage genes containing a hypoxia response element (HRE). Inflammation activates a multitude of cytokines, including TNF-alpha, that invariably modulate activation of the nuclear factor kappa B (NF-kB) transcription factor. We constructed a vector that encompassed both a hypoxia response element (HRE), and a NF-kappaB responsive element. We show that this vector was functionally responsive to both hypoxia and TNF-alpha, in vitro and in vivo. Thus, this vector might be suitable for the detection and assessment of hypoxia or TNF-alpha.

A NIR turn-on fluorescent probe applied in cytochrome P450 reductase detection and hypoxia imaging in tumor cells

In vivo monitoring of the hypoxic area is urgently required. Near infrared (NIR) fluorescence-active fluorophores with excellent photo stability are preferable for in vivo imaging. A novel rational designed turn-on fluorescent probe with high selectivity and long-wavelength was synthesized which was applied in bioreductase (cytochrome P450 reductase which overexpressed in tumor cells) and hypoxia detection. The NIR probe (AZO-DCM) is based on a photo stability fluorophore dicyanomethylene-4H-pyran dye (DCM) with an azo bond as probe quencher and hypoxic trigger. After reacted with cytochrome P450 reductase, azo bond was cleaved and DCM released with fluorescent on. The designed probe showed high anti-interference ability which cannot disturb by many interfering substances, such as biothiols, inorganic salts (included sulfite salt) and amino acid. AZO-DCM performed good selectivity and sensitivity to cytochrome P450 reductase and hypoxia. The fluorescent intensity was increased more than 150-fold after response to cytochrome P450 reductase and NADH system in 4 min. The reaction mechanism also proved by HPLC experiment. Probe AZO-DCM displayed excellent properties in identifying different hypoxic status of tumor cells in vivo.

Fetal State Assessment from Cardiotocogram Data Using Artificial Neural Networks

Cardiotocography is the most widely used method in obstetrics practice for monitoring fetal health status. The main goal of monitoring is early detection of fetal hypoxia. A cardiotocogram is a recording of fetal heart rate and uterine activity signals. The accurate analysis of cardiotocograms is critical for further treatment. Therefore, fetal state assessment using machine learning methods from cardiotocogram data has received significant attention in the literature. In this paper, a comparative study of fetal state assessment is presented by using three artificial neural network models, namely the multilayer perceptron neural network, probabilistic neural network, and generalized regression neural network. The performances of the models are evaluated using publicly available cardiotocogram data by running a tenfold cross-validation procedure. The models’ performances are compared in terms of overall classification accuracy. For further analysis, receiver operation characteristic analysis and the cobweb representation technique are used.

Oxygen Sensing Difluoroboron β-Diketonate Polylactide Materials with Tunable Dynamic Ranges for Wound Imaging.

Difluoroboron β-diketonate poly(lactic acid) materials exhibit both fluorescence (F) and oxygen sensitive room-temperature phosphorescence (RTP). Introduction of halide heavy atoms (Br and I) is an effective strategy to control the oxygen sensitivity in these materials. A series of naphthyl-phenyl (nbm) dye derivatives with hydrogen, bromide and iodide substituents were prepared for comparison. As nanoparticles, the hydrogen derivative was hypersensitive to oxygen (0-0.3%), while the bromide analogue was suited for hypoxia detection (0-3% O2). The iodo derivative, BF2nbm(I)PLA, showed excellent F to RTP peak separation and an 0-100% oxygen sensitivity range unprecedented for metal-free RTP emitting materials. Due to the dual emission and unconventionally long RTP lifetimes of these O2 sensing materials, a portable, cost-effective camera was used to quantify oxygen levels via lifetime and red/green/blue (RGB) ratiometry. The hypersensitive H dye was well matched to lifetime detection, simultaneous lifetime and ratiometric imaging was possible for the bromide analogue, whereas the iodide material, with intense RTP emission and a shorter lifetime, was suited for RGB ratiometry. To demonstrate the prospects of this camera/material design combination for bioimaging, iodide boron dye-PLA nanoparticles were applied to a murine wound model to detect oxygen levels. Surprisingly, wound oxygen imaging was achieved without covering (i.e. without isolating from ambient conditions, air). Additionally, would healing was monitored via wound size reduction and associated oxygen recovery, from hypoxic to normoxic. These single-component materials provide a simple tunable platform for biological oxygen sensing that can be deployed to spatially resolve oxygen in a variety of environments.

Photoacoustic Imaging for the Detection of Hypoxia in the Rat Femoral Artery and Skeletal Muscle Microcirculation.

Photoacoustic (PA) imaging is an emerging technology that combines structural and functional imaging of tissues using laser and ultrasound energy. We evaluated the ability of PA imaging system to measure real-time systemic and microvascular mean oxygen saturation (mSAO2) in a rat model of hypoxic shock. Male Sprague Dawley rats (n = 6) underwent femoral artery catherization and were subjected to acute hypoxia by lowering the fraction of inspired oxygen (FiO2) from 1.0 to 0.21, and then to 0.08. PA measurements of mSaO2 were taken in the femoral artery near the catheter tip using the Vevo 2100 LAZR at each FiO2 and compared to co-oximetry on blood removed from the femoral catheter. Both co-oximetry and PA imaging measured a similar stepwise decline in femoral artery mSaO2 as FiO2 was lowered. We also measured mSaO2 in the feed arteriole of the rat spinotrapezius muscle and adjacent microvessels (n = 6) using PA imaging. A significant decrease in mSaO2 in both the feed arteriole and adjacent microvessels was recorded as FiO2 was decreased from 1.0 to 0.08. Moreover, we detected a rapid return toward baseline mSaO2 in the feed arteriole and microvessels when FiO2 was increased from 0.08 to 1.0. Thus, PA imaging is noninvasive imaging modality that can accurately measure real-time oxygen saturation in the macro and microcirculation during acute hypoxia. This proof-of-concept study is a first step in establishing PA imaging as an investigational tool in critical illness.

In vitro Detection of Hypoxia using a Ratiometric Quantum Dot-based Oxygen Sensor.

A quantum-dot based ratiometric fluorescent oxygen probe for the detection of hypoxia in live cells is reported. The system is comprised of a water-soluble near-infrared emissive quantum dot conjugated to perylene dye. The response to the oxygen concentration is investigated using enzymatic oxygen scavenging in water, while in vitro studies were performed with HeLa cells incubated under varying O2 levels. In both cases a significant enhancement in dye/QD emission intensity ratio was observed in the deoxygenated environment, demonstrating the possible use of this probe for cancer research.

The early detection of hypoxia‐ and pro‐angiogenesis gene expression is a novel diagnostic tool for cerebral palsy

The early detection of hypoxia‐ and pro‐angiogenesis gene expression is a novel diagnostic tool for cerebral palsy

The Relationship Between Oxygen Reserve Index and Arterial Partial Pressure of Oxygen During Surgery.

The use of intraoperative pulse oximetry (SpO2) enhances hypoxia detection and is associated with fewer perioperative hypoxic events. However, SpO2 may be reported as 98% when arterial partial pressure of oxygen (PaO2) is as low as 70 mm Hg. Therefore, SpO2 may not provide advance warning of falling arterial oxygenation until PaO2 approaches this level. Multiwave pulse co-oximetry can provide a calculated oxygen reserve index (ORI) that may add to information from pulse oximetry when SpO2 is >98%. This study evaluates the ORI to PaO2 relationship during surgery. We studied patients undergoing scheduled surgery in which arterial catheterization and intraoperative arterial blood gas analysis were planned. Data from multiple pulse co-oximetry sensors on each patient were continuously collected and stored on a research computer. Regression analysis was used to compare ORI with PaO2 obtained from each arterial blood gas measurement and changes in ORI with changes in PaO2 from sequential measurements. Linear mixed-effects regression models for repeated measures were then used to account for within-subject correlation across the repeatedly measured PaO2 and ORI and for the unequal time intervals of PaO2 determination over elapsed surgical time. Regression plots were inspected for ORI values corresponding to PaO2 of 100 and 150 mm Hg. ORI and PaO2 were compared using mixed-effects models with a subject-specific random intercept. ORI values and PaO2 measurements were obtained from intraoperative data collected from 106 patients. Regression analysis showed that the ORI to PaO2 relationship was stronger for PaO2 to 240 mm Hg (r = 0.536) than for PaO2 over 240 mm Hg (r = 0.0016). Measured PaO2 was ≥100 mm Hg for all ORI over 0.24. Measured PaO2 was ≥150 mm Hg in 96.6% of samples when ORI was over 0.55. A random intercept variance component linear mixed-effects model for repeated measures indicated that PaO2 was significantly related to ORI (β[95% confidence interval] = 0.002 [0.0019-0.0022]; P < 0.0001). A similar analysis indicated a significant relationship between change in PaO2 and change in ORI (β [95% confidence interval] = 0.0044 [0.0040-0.0048]; P < 0.0001). These findings suggest that ORI >0.24 can distinguish PaO2 ≥100 mm Hg when SpO2 is over 98%. Similarly, ORI > 0.55 appears to be a threshold to distinguish PaO2 ≥150 mm Hg. The usefulness of these values should be evaluated prospectively. Decreases in ORI to near 0.24 may provide advance indication of falling PaO2 approaching 100 mm Hg when SpO2 is >98%. The clinical utility of interventions based on continuous ORI monitoring should be studied prospectively.

Abstract 4228: Imaging and targeting of hypoxic microenvironments in prostate cancer

Abstract Cancer cells display an adaptive response to hypoxia through the activation of several genes mediated by the binding of hypoxia inducible factors (HIFs) to hypoxia response elements (HRE) in the promoter region of target gene that results in their increased transcription [1]. HIFs promote key steps in tumorigenesis, including angiogenesis, metabolism, proliferation, metastasis, and differentiation [1]. Bacterial or yeast cytosine deaminase (yCD) converts the nontoxic prodrug 5-fluorocytosine (5-FC) to the anti-cancer drug 5-fluorouracil (5-FU) that is widely used in cancer treatment [2]. Using a lentivirus approach, we established controlled expression of yCD by HRE in prostate cancer cells (PC-3). These cells also report on HIF-1α expression with regulated luciferase (Luc) expression, allowing detection of hypoxia, and the generation of 5-FU from 5-FC by yCD in the presence of hypoxia. Transduction efficiency and reporter activity in response to hypoxia was evaluated by performing luciferase assays, and bioluminescence imaging (BLI) of cells in vitro or in vivo using a Xenogen IVIS Spectrum system. Cell viability in vitro in response to hypoxia in the presence of 5-FC was assessed by MTS assay. In vivo studies were performed by inoculating 2×10⁁6 PC-3-HRE-Luc cells and PC-3-HRE-yCD+Luc cells on either flank of 5-week-old male severely combined immune deficient (SCID) mice. BLI was performed once tumors reached ∼200mm3 followed by 5-FC injection through the tail vein (200mg/kg) and intraperitoneally (250mg/kg). BLI was performed 3 days after the first 5-FC injection and continued through the treatment protocol. At the end of the treatment protocol, tumors were excised, and a part of the tumor was processed for immunohistochemistry. Bioluminescence was detected in both PC3-HRE-Luc and PC-3-HRE-yCD+Luc cells only in response to the hypoxia mimetic cobalt chloride or hypoxia (1% O2) confirming the regulation of luciferase by hypoxia and activation of CD. Expression of yCD and its ability to convert the prodrug 5-FC to 5-FU, with increased cell kill was evident under hypoxia. In vivo, engineered PC-3-HRE-yCD+Luc cells reported hypoxia, and showed significant reduction of hypoxic regions and tumor volume. Morphologically, PC-3-HRE-yCD+Luc tumors exhibited extensive necrosis. We are currently evaluating the effects of eliminating hypoxic cancer cells on distant metastasis as well as on aggressive subpopulations such as cancer stem cells in the primary tumor.

Abstract 2408: Melatonin action in xenograft model of breast cancer, comparing radiopharmaceuticals in the detection of intratumor heterogeneity by PET/CT confirmed by immunohistochemical markers

Abstract Breast cancer is the most common cancer among women and has a high mortality rate. The rapid tumor growth makes difficult the perfusion of O2 mainly in the tumor center, and this hypoxia in tumor microenvironment can exerts selective pressure on the tumor cells, selecting subpopulations with advantage for survival in adverse conditions, characterizing the intratumor heterogeneity. In this context, melatonin, a hormone naturally produced by the pineal gland, has shown antitumor activity, as immunomodulatory, antioxidant, pro-apoptotic, anti-proliferative, antimetastatic, antiangiogenic and with potencial effects in intratumor heterogeneity. The aims of this study was to evaluate the effectiveness of melatonin in a xenograft model of breast cancer, focusing on intratumor heterogeneity verified by PET/CT and by immunohistochemical markers of hypoxia. The tumors were developed by the implantation of 5 million triple-negative breast cancer cells (MDA-MB-231) into the flank of female Balb/c nude mice (n = 14). Treatment with melatonin (n = 7) or vehicle (n = 7) was initiated 10 days after tumor implantation and continued for 14 days. At the end, micro-PET/CT scanning was performed with 18F-FDG, which is an analogue of glucose, and with 18F-FAZA, a specific radiopharmaceutical for hypoxia detection. The radiopharmaceuticals were injected by retro-orbital via and the images were acquired using Albira PET/SPECT/CT Carestream Molecular Imaging. Then, markers of hypoxia were evaluated by immunohistochemistry in mammary tumors. The results showed that tumor growth in animals treated with melatonin was lower than those treated with vehicle (p&amp;lt;0.05). There was tumor regression in one animal treated with melatonin, showing 18.72 mm3 at start of treatment and no longer being detected after seven days of treatment. 18F-FDG can be used as hypoxia marker, however, studies show that can occurs overlapping areas of aerobic and anaerobic glycolysis in the tumor, difficulting the identification of hypoxic areas. 18F-FAZA has a hypoxia-specific uptake mechanism and a better spread by the tumor. Results of PET/CT showed that 18F-FDG had homogeneous uptake in breast tumors. In some tumors with high volume, there was no uptake in the tumor center, corresponding to areas of necrosis. In addition, there was an intratumor 18F-FAZA uptake heterogeneity, indicating possible hypoxic areas. Also, PET/CT results showed that there was less hypoxic areas in animals treated with melatonin, which was confirmed by immunohistochemical markers. Taken together, our results showed an important action of melatonin, in control of mammary tumor growth, decreasing hypoxia areas and controlling cancer progression. Financial support: Fundação de Amparo à Pesquisa do Estado de São Paulo Citation Format: André L. Mota, Bruna V. Jardim-Perassi, Thaiz F. Borin, Nathália M. Sonehara, Lorena Pozzo, Emerson S. Bernardes, Bruno Cogliati, Debora APC Zuccari. Melatonin action in xenograft model of breast cancer, comparing radiopharmaceuticals in the detection of intratumor heterogeneity by PET/CT confirmed by immunohistochemical markers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2408.

Can postmortem computed tomography detect antemortem hypoxic-ischemic encephalopathy?

The purpose of this study was to evaluate the usefulness of brain postmortem computed tomography (PMCT) findings for the detection of global hypoxia or hypoperfusion leading to hypoxic-ischemic encephalopathy (HIE) prior to death. Cadavers of individuals who died from non-traumatic causes were subjected to PMCT and pathological autopsy. Cases with an episode of cardiopulmonary arrest, hypoxia, or hypoperfusion that required intensive respiratory management at least 24h before death and exhibited findings of HIE in conventional autopsy (HIE group, n=6) were compared with those without such episodes prior to death (control group; overall, n=37; age-matched, n=8) with regard to four parameters: (1) width of the central sulcus (CS), (2) attenuation difference at the basal ganglia (BG) level, (3) attenuation difference between cerebral gray matter (GM) and cerebral white matter (WM), and (4) attenuation difference between cerebellar GM and cerebral GM. The results revealed significant differences in the width of the CS (P<0.001), attenuation difference at the BG level (P<0.001), and attenuation difference between cerebral GM and cerebral WM (P=0.009) between the HIE group and the overall control group. When the age-matched control group and the HIE group were compared, there was a significant difference in the width of the CS (P=0.026) and attenuation difference at the BG level (P<0.001). Our results suggest that effacement of the sulcus of the cerebral hemisphere and the loss of contrast at the BG level on brain PMCT indicate the existence of HIE prior to death.

Micro PET imaging of 18F-Fluoromisonidazole in an MDA-MB-231 triple negative human breast cancer xenograft model

Background: While 18 F-Fluoromisonidazole ( 18 F-FMISO) is the most frequently used positron emission tomography (PET) tracer for detecting hypoxia, it has not been studied in a metastatic triple-negative [lack expression of estrogen receptor (ER), progesterone receptor (PR) and human EGF receptor 2 (HER2)] human breast cancer cell xenografts model to our best knowledge. This study focuses on whether 18 F-FMISO can detect the hypoxic status of triple-negative human breast cancer (TNBC). Methods: The TNBC cells MDA-MB-231 were successfully inoculated in right forelimb of nude mice. Nude mice models with TNBC xenografts were assessed by micro-PET imaging with 18 F-FMISO, and hypoxic status of the TNBC xenografts was determined by immunohistochemistry. We also compared 18 F-FDG uptake, the most commonly used PET tracer in clinical practice, with 18 F-FMISO uptake to find out its correlation in MDA-MB-231 xenografts. Results: For 18 F-FMISO, intestines and liver as well as bladder could be seen in micro-PET images. 18 F-FDG showed physiologically high uptake in brain, heart, bladder and intestinal tracts. The quantitative radioactivity of 18 F-FMISO and 18 F-FDG in tumor were 2.18±0.15 and 3.84±0.54 %ID/g, respectively. The quantitative radioactivity of 18 F-FMISO and 18 F-FDG in muscle were 1.23±0.08 and 0.59±0.09 %ID/g, respectively. The tumor-to-muscle ratios were 1.79±0.015 and 7.11±2.84 for 18 F-FMISO and 18 F-FDG, respectively. Immunofluorescent images from MDA-MB-231 cryosections showed significant hypoxia. Conclusions: 18 F-FMISO PET may be used for detection of hypoxia in tumor microenvironment of triple negative human breast cancer.

Imaging Agents in Targeting Tumor Hypoxia.

Tissue hypoxia may occur in many diseases, specifically during the occurrence and growth of malignant solid-tumors. Targeting hypoxia is one of the most significant characteristics of tumors in diagnosis, monitoring, and treatment. This review summarizes the current oxygen-sensitive imaging agents used to target tumor hypoxia, including positron-emission computed tomography/single photon-emission computed tomography radionuclide labeled tracers, magnetic resonance imaging contrast agents for hypoxia detection, and hypoxia-sensitive optical imaging probes. Researchers have utilized nanotechnology as a useful toolkit to improve the effects of oxygen-sensitive imaging agents. We emphasize the progress and influence of nanotechnology in these materials and technologies. This review demonstrates that hypoxia imaging agents have promising prospects, and may provide helpful information for tumor diagnosis and prognosis.

Near-Infrared Spectra in Buccal Tissue as a Marker for Detection of Hypoxia.

Hypoxia caused by high altitude exposure can impair cerebral and mental functions. Blood flow and oxygenation of the buccal tissue can be reliable markers to detect hypoxia. In this study, near infrared spectroscopy was used in combination with a novel optical probe to evaluate the applicability of the novel probe in measuring hypoxia markers in buccal tissue under a hypoxic condition. Six healthy participants were tested at altitudes from 2000 to 16,000 ft inside a hypobaric chamber. The buccal reference measurements of blood flow and oxygen saturation were synchronized with the spectral measurements of the novel near infrared probe and the relationship between the reference measurements and spectral data were evaluated by multivariate partial least square method. In addition, finger oxygen saturation was measured during the experiment and the recordings were compared with buccal oxygen saturation. The spectral analysis illustrated that the spectral data from the near infrared probe correlated strongly with the absorption features of both buccal flow and oxygenation measured by the reflectance sensors (average R(2) = 0.89). The results showed probably overestimated values for buccal oxygen saturation recorded by the reference pulse oximeter in comparison with finger oxygen saturation, with the mean difference increasing from 1.8% at 2000 ft to 11.4% at 16,000 ft. The novel near infrared probe showed promising results for simultaneous measurement of blood flow and oxygen saturation in the buccal tissue. The suggested method can be used as a new technique for early indication of hypoxia in future clinical applications.

Imaging latent tuberculosis infection with radiolabeled nitroimidazoles.

Imaging latent tuberculosis infection with radiolabeled nitroimidazoles.

Fetal heart rate monitoring of short term variation (STV): a methodological observational study.

BackgroundCardiotocography (CTG) has high sensitivity, but less specificity in detection of fetal hypoxia. There is need for adjunctive methods easy to apply during labor. Low fetal heart rate short term variation (STV) is predictive for hypoxia during the antenatal period. The objectives of our study were to methodologically evaluate monitoring of STV during labor and to compare two different monitors (Sonicaid™ and EDAN™) for antenatal use.MethodsA prospective observational study at the obstetric department, Karolinska University hospital, Stockholm (between September 2011 and April 2015). In 100 women of ≥ 36 weeks gestation, STV values were calculated during active labor. In a subset of 20 women we compared STV values between internal and external signal acquisition. Additionally we compared antenatal monitoring with two different monitors in another 20 women.ResultsMedian STV in 100 fetuses monitored with scalp electrode during labor (EDAN™) was 7.1 msec (range 1.3–25.9) with no difference between early (3–6 cm) and late (7–10 cm) labor (7.1 vs 6.8 msec; p = 0.80). STV calculated from scalp electrode signals were positively correlated with delta-STV (STV internal –external) (R = 0.70; p < 0.01). No significant differences were found between Sonicaid™ and EDAN™ in antenatal external monitoring of STV (median difference 0.9 msec, Spearman Rank Correlation Sonicaid vs delta-STV; R = 0.35; p = 0.14).ConclusionsMedian intrapartum STV was 7.1 msec. Significant differences were found between internal and external signal acquisition, a finding that suggests further intrapartum studies to be analysed separately depending upon type of signal acquisition. Antenatal external monitoring with Sonicaid™ and EDAN™ indicates that the devices perform equally well in the identification of acidemic fetuses. Further studies are needed to assess the clinical value of intrapartum STV.

Silane modified upconversion nanoparticles with multifunctions: imaging, therapy and hypoxia detection.

Herein, we report a facile route to synthesize silane coated upconversion nanoparticles (UCNPs@silane) with an ultrathin layer (the thickness: 1–2 nm), which not only provides good biocompatibility, but also affords hydrophobic interspace to load organic molecules to realize multifunctions. Besides the function of upconversion imaging of UCNPs, cancer therapy and oxygen level detection can also be realized by the addition of chemotherapy drug, PTX, and oxygen sensitive molecules, Platinum (II) octaethylporphine (PtOEP). In bio-experiments, besides the MTT assays, therapy efficacy of UCNPs@PTX@silane can also be detected with the confocal laser scanning microscopy (CLSM) by staining methods. UCNPs@PtOEP@silane can afford minimally invasive analysis of dissolved oxygen and then respond sensitively to the variance of intracellular oxygen concentration affected by therapeutic UCNPs@PTX@silane.