Biomedical subjects

Qingming Luo

Publications and source records attributed to Qingming Luo.

At least 37 records · Page 2Linked to original sources

PubMed2005

Knowledge guided analysis of microarray data.

To microarray expression data analysis, it is well accepted that biological knowledge-guided clustering techniques show more advantages than pure mathematical techniques. In this paper, Gene Ontology is introduced to guide the clustering process, and thus a new algorithm capturing both expression pattern similarities and biological function similarities is developed. Our algorithm was validated on two well-known public data sets and the results were compared with some previous works. It is shown that our method has advantages in both the quality of clusters and the precision of biological annotations. Furthermore, the clustering results can be adjusted according to different stringency requirements. It is expected that our algorithm can be extended to other biological knowledge, for example, metabolic networks.

Algorithms↗

PubMed2005

Microfluidic chip toward cellular ATP and ATP-conjugated metabolic analysis with bioluminescence detection.

In this article, a microfluidic platform integrating capillary electrophoresis and bioluminescence (BL) detection that was fabricated in poly(dimethylsiloxane) (PDMS) with lab-on-a-chip technology was demonstrated for cellular metabolic analyses. A microchannels network, "cross combining with Y", was designed to perform on-chip sample preparation, separation, and BL detection of ATP and ATP-conjugated metabolites, using firefly luciferin-luciferase BL system. A dynamic modification of the channel wall of PDMS proved to be crucial to reverse the direction of electroosmotic flow (EOF), which was uniquely achieved by a prewash cycle with a cationic surfactant didodecyldimethylammonium bromide. The influences of surfactant on the EOF and BL reaction were also investigated. Quantitative analyses revealed a dynamic linear range over 2 orders of magnitude for ATP, with a detection limit down to submicromolar (midattomole). The method was validated by measuring cellular ATP of E. coli. with direct on-chip cell lysis. Further work was emphasized on ATP-conjugated metabolite analysis, using galactose as an example. Assays of galactose in human urine samples confirmed the reliability of the protocol, which revealed good prospect of this platform for ATP-conjugated submetabolomic profiling.

Adenosine Triphosphate↗

PubMed2005

Transabdominal fetal pulse oximetry with near-infrared spectroscopy.

OBJECTIVE: The purpose of this study was to determine the feasibility of noninvasive fetal pulse oximetry in the human fetus with transabdominal continuous-wave near-infrared spectroscopy. STUDY DESIGN: The instrument has 3 wavelength light-emitting diodes (735, 805, and 850 nm) as light sources and a photomultiplier tube as a detector. This instrument was used in 6 pregnant women (>36 weeks of gestation). First, a fetal heart rate was obtained with a fetal heart rate monitor. Then, the depth of fetal tissue (head) from the maternal abdomen was determined by ultrasound examination; the distance between the optodes (light source and the detector) was set to be approximately twice the depth of the fetus (7-11 cm). The data analysis was based on the modified Beer-Lambert law and the use of optical densities at 735 and 850 nm to obtain the concentration changes of the oxyhemoglobin and deoxyhemoglobin. The saturation was expressed as the percent of oxygen saturation equal to 100 x oxyhemoglobin/(oxyhemoglobin + deoxyhemoglobin). We recorded the spectroscopy data and the fetal heart rate for approximately 3 to 10 minutes in each patient. RESULTS: The mean oxygen saturation values of each of the 6 individual fetuses ranged from 50% to 74% (overall mean saturation, 61% +/- 14.8% [SD]). CONCLUSION: This preliminary data indicate that transabdominal fetal pulse oximetry is feasible for human patient application. The measured values were similar to those that are obtained with transvaginal pulse oximetry. Future studies should correlate transabdominally obtained measurements with those measurements that are obtained by transvaginal fetal pulse oximetry.

Abdomen↗

PubMed2005

In vivo optical imaging of human adenoid cystic carcinoma cell metastasis.

A noninvasive, whole-body, real-time fluorescence optical imaging of stable high-level green fluorescent protein (GFP)-expressing human adenoid cystic carcinoma (ACC-M-GFP) was demonstrated for in vivo visualization of metastatic behavior in nude mice. Five-week-old female nude mice were injected with ACC-M-GFP in the primary organ: submandibular gland. Metastases were only visualized by GFP expression in the lung. However, metastatic lesions of ACC-M-GFP in the lung, muscle, bladder and bony were found by imaging of GFP expression in intact mice through tail vein injection of ACC-M-GFP cells. The construction of highly fluorescent and stable GFP transfectants of ACC-M has revealed the multi-organ metastatic capability of ACC-M cells through this optical imaging.

Animals↗

PubMed2005

BDNF acutely modulates synaptic transmission and calcium signalling in developing cortical neurons.

Brain-derived neurotrophic factor (BDNF), like other neurotrophins, has long-term effects on neuronal survival and differentiation; furthermore, BDNF has been reported to exert an acute potentiation of synaptic activity and are critically involved in long-term potentiation(LTP). We found that BDNF rapidly induced potentiation of synaptic activity and an increase in the intracellular Ca2+ concentration in cultured cortical neurons. Within minutes of BDNF application to cultured cortical neurons, spontaneous firing rate was dramatically increased as was the frequency and amplitude of excitatory spontaneous postsynaptic currents (EPSCs). Fura-2 recordings showed that BDNF acutely elicited an increase in intracellular calcium concentration ([Ca2+]i). This effect was partially dependent on extracellular Ca2+. In calcium-free perfusion medium a substantial calcium signal remained which disappeared after loading of cortical neurons with 5 microM U-73122. BDNF-induce Ca2+ transients were completely blocked by K252a and partially blocked by Cd2+. The results demonstrate that BDNF can enhance synaptic transmission and induce directly a rise in [Ca2+]i that require two routes: the release of Ca2+ from intracellular calcium stores and influx of extracellular Ca2+ mainly through voltage-dependent Ca2+ channels in cultured cortical neurons.

Animals↗

PubMed2004

Hyperosmotic chemical agent's effect on in vivo cerebral blood flow revealed by laser speckle.

We investigated the influence of a hyperosmotic agent (glycerol) on the normal physiological function of tissue by applying the glycerol in vitro and in vivo to rabbit dura mater to assess the changes in the tissue's optical properties. We used a laser speckle imaging technique to study the effect of epidurally applied glycerol on resting cerebral blood flow (CBF). Our results showed that resting CBF decreased as the transparency of the dura mater increased. The challenges for the design of an optical clearing technique were not only the clearing effects and the duration of the action of the chemical agents but also the influence of the glycerol on the tissue's normal physiological function.

Algorithms↗

PubMed2004

Metabolic imaging of tumors using intrinsic and extrinsic fluorescent markers.

One of the biochemical "hallmarks" of malignancy is enhanced tumor glycolysis, which is primary due to the overexpression of glucose transporters (GLUTs) and the increased activity of mitochondria-bound hexokinase in tumors. Easy methods for assessing glucose utilization in vitro and in vivo should find widespread application in biological and biomedical studies, as illustrated by the adoption of FDG PET imaging in medicine. We have recently synthesized a new NIR fluorescent pyropheophorbide conjugate of 2-deoxyglucose (2DG), Pyro-2DG, as a GLUT-targeted photosensitizer. In this study, we have evaluated the in vivo uptake of Pyro-2DG and found that Pyro-2DG selectively accumulated in two tumor models, 9L glioma in the rat and c-MYC-induced mammary tumor in the mouse, compared to surrounding normal muscle tissues at a ratio of about 10:1. By simultaneously performing redox ratio and fluorescence imaging, a high degree of correlation between the PN/(Fp+PN) redox ratio, where PN denotes reduced pyridine nucleotides (NADH) and Fp denotes oxidized flavoproteins, and the Pyro-2DG uptake was found in both murine tumor models, indicating that Pyro-2DG could serve as an extrinsic NIR fluorescent metabolic index for the tumors. The fact that only a low level of correlation was observed between the redox ratio and the uptake of Pyro-acid (the free fluorophore without the 2-deoxyglucose moiety) supports the hypothesis that Pyro-2DG is an index of the mitochondrial status (extent of PN reduction) of a tumor.

Animals↗

PubMed2004

Laser speckle imaging of blood flow in microcirculation.

Monitoring the spatio-temporal characteristics of microcirculation is crucial for studying the functional activities of biotissue and the mechanism of disease. However, conventional methods used to measure blood flow suffer from limited spatial resolution or the injection of exogenous substances or the need of scanning to obtain the dynamic of regional blood flow. Laser speckle imaging (LSI) technique makes up these disadvantages by obtaining the regional blood flow distribution with high spatio-temporal resolution without the need to scan. In this paper, LSI was introduced to investigate the dynamic responses of the rat mesenteric microcirculation to an incremental dose of phentolamine. The results showed that when the dose of phentolamine was less than 4 microg ml(-1), local application of phentolamine on the mesentery would increase the blood perfusion as the concentration increased. When the dose increased further, the improvement decreased. At a dose of 200 microg ml(-1), a microcirculation impediment was caused. At the same time, different responses between veinules and arterioles were manifested. These suggested that LSI is promising to be a useful contribution to drug development and testing.

Animals↗

PubMed2004

Monte Carlo modeling of optical coherence tomography imaging through turbid media.

We combine a Monte Carlo technique with Mie theory to develop a method for simulating optical coherence tomography (OCT) imaging through homogeneous turbid media. In our model the propagating light is represented by a plane wavelet; its line propagation direction and path length in the turbid medium are determined by the Monte Carlo technique, and the process of scattering by small particles is computed according to Mie theory. Incorporated into the model is the numerical phase function obtained with Mie theory. The effect of phase function on simulation is also illustrated. Based on this improved Monte Carlo technique, OCT imaging is directly simulated and phase information is recorded. Speckles, resolution, and coherence gating are discussed. The simulation results show that axial and transversal resolutions decrease as probing depth increases. Adapting a light source with a low coherence improves the resolution. The selection of an appropriate coherence length involves a trade-off between intensity and resolution.

Computer Simulation↗

PubMed2003

Efficient characterization of regional mesenteric blood flow by use of laser speckle imaging.

We present a noninvasive full-field method--laser speckle imaging (LSI)--for measuring the regional mesenteric blood flow without scanning. A system of LSI was designed and validated in a model experiment. Dynamics of regional blood flow in the rat mesentery under the influence of noradrenaline were monitored by this method. Spatial and temporal characteristics of the mesenteric blood-flow response were achieved with high resolution. These suggested that LSI might provide a new approach to microcirculation studies.

Animals↗

PubMed2003

Effects of dehydration on the optical properties of in vitro porcine liver.

BACKGROUND AND OBJECTIVES: It is of crucial importance to determine the effects of dehydration on the optical properties of tissue so that optimization of therapy and device for laser applications in medicine can be made. STUDY DESIGN/MATERIALS AND METHODS: After being incubated directly or indirectly in an oven of 37 degrees C for different periods of time, the porcine liver samples were weighed with an electronic scale and their optical properties were measured by a double integrating sphere system. RESULTS: When samples were incubated directly for 20 hours, the average weight loss was 68.5% +/- 1.2%, and the absorption coefficient and scattering coefficient increased 146.1% +/- 26.9% and 10.8% +/- 1.1%, respectively. In comparison, there was only 21.5% +/- 1.0% of water loss for the control samples, and the absorption coefficient increased 30.7% +/- 7.6%, while the reduced scattering coefficient increased 386.5% +/- 29.7%. The effective attenuation coefficients increased 111% and 103% for dehydration group and control group, respectively. CONCLUSIONS: The absorption coefficient and effective attenuation coefficient increase with dehydration level of tissue. However, there is no direct correlation between dehydration and reduced scattering coefficient.

Animals↗

PubMed2003

Modified laser speckle imaging method with improved spatial resolution.

A two-dimensional map of blood flow is crucial for physiological studies. We present a modified laser speckle imaging method (LSI) that is based on the temporal statistics of a time-integrated speckle. A model experiment was performed for the validation of this technique. The spatial and temporal resolutions of this method were studied in theory and compared with current laser speckle contrast analysis (LASCA); the comparison indicates that the spatial resolution of the modified LSI is five times higher than that of current LASCA. Cerebral blood flow under different temperatures was investigated by our modified LSI. Compared with the results obtained by LASCA, the blood flow map obtained by the modified LSI possessed higher spatial resolution and provided additional information about changes in blood perfusion in small blood vessels. These results suggest that this is a suitable method for imaging the full field of blood flow without scanning and provides much higher spatial resolution than that of current LASCA and other laser Doppler perfusion imaging methods.

Algorithms↗

PubMed2003

Spatiotemporal characteristics of cerebral blood volume changes in rat somatosensory cortex evoked by sciatic nerve stimulation and obtained by optical imaging.

The spatiotemporal characteristics of changes in cerebral blood volume associated with neuronal activity were investigated in the hindlimb somatosensory cortex of alpha-chloralose-urethane anesthetized rats (n=10) with optical imaging at 570 nm through a thinned skull. Activation of the cortex was carried out by electrical stimulation of the contralateral sciatic nerve with 5-Hz, 0.3-V pulses (0.5 ms) for 2 s. The stimulation evoked a monophasic decrease in optical reflectance at the cortical parenchyma and arterial sites soon after the onset of stimulation, whereas no similar response was observed at vein compartments. The optical signal changes reached 10% of the peak response 0.70 +/- 0.32 s after the start of stimulation, and no significant time lag in this 10% start latency time was observed between the response at the cortical parenchyma and artery compartments. The decrease in optical reflectance reached a peak (0.25 +/- 0.047%) 2.66 +/- 0.61 s after stimulus onset at parenchymal sites, which is 0.40 +/- 0.20 s earlier (P<0.05) than that at arterial sites (0.50 +/- 0.068% 3.06 +/- 0.70 s). Varying the locations within the cortical parenchyma and arterial compartments did not significantly affect the temporal characteristics of the evoked signal. These results suggest that stimulation of the sciatic nerve evokes an increase in local blood volume in both capillaries (cortical parenchyma) and arterioles soon after the onset of a stimulus, but the blood volume increase evoked in capillaries could not be entirely accounted for by the dilation of arterioles.

Animals↗

PubMed2002

Highly Nd3+-doped Y3Al5O12 crystal fiber tip for laser thermotherapy.

Based on phonon relaxation, a 12-at. % neodymium-doped YAG (Y3AlrO12) crystal fiber tip has been developed for photothermal conversion. The near-cylindrical tip, with an average diameter of 0.68 mm and a length of 1.8 mm, is fabricated on a 0.65-mm-thick 220-mm-long pure YAG single-crystal fiber by laser-heated growth. Pumped by an 810-nm wavelength diode laser with a pump power of less than 2 W, the temperatures of the tip reach 725 degrees C in air, 78 degrees C in egg white, and 79 degrees C in porcine liver, with acceptable reproducibilities and thermal response times. The photothermal conversion efficiency of the doped tip is approximately 89%, and the high stability of the tip is also proved. Experimental results show that the doped fiber tip is promising for laser thermotherapy applications.

Aluminum Oxide↗

PubMed2002

A laser pumped Nd(3+)-doped YAG fiber-optic thermal tip for laser thermotherapy.

BACKGROUND AND OBJECTIVE: Photo-thermal converters have been successfully used in laser surgery; however, most of the currently used converters are likely to be damaged in the operations due to various problems, preventing them from being efficiently and repeatedly used in laser thermotherapy. Aiming to solve these problems, we report a new type of fiber-optic photo-thermal converter with higher stability. STUDY DESIGN/MATERIALS AND METHODS: A laser-pumped highly Nd(3+)-doped Y(3)Al(5)O(12) (YAG) crystal fiber tip had been fabricated for photo-thermal conversion by means of phonon relaxation. The 15at.% neodymium-doped near cylindrical YAG crystal fiber tip, with maximum diameter of 1.1 mm and length of 2.7 mm, was fabricated on a 1 mm-thick 42 mm-long pure YAG single crystal fiber by laser heated pedestal growth (LHPG) method. RESULTS AND CONCLUSION: Pumping by a Ti:Sapphire laser with central wavelength of 805 nm, the tip generated a temperature rise of 15 degrees C in egg white with pumping power of 710 mW, the tip temperature increased approximately linearly with the increased pumping power. The distribution of the temperature in two media had also been measured. Experimental results indicated that the tip was promising for laser thermotherapy applications.

Equipment Design↗

PubMed2002

Kinetic thermal response and damage in laser coagulation of tissue.

BACKGROUND AND OBJECTIVES: Laser induced interstitial coagulation has become a method of treating different types of tumors. Theoretical modeling and analysis may be used to better understand the complex process involved in the laser coagulation and optimized the dosimetry of laser thermotherapy. STUDY DESIGN/MATERIALS AND METHODS: A full dynamic theoretical model was developed to simulate the dynamic evolution of coagulation in tissue, which accounted for the dynamics of the temperature and damage dependence of optical properties, thermal properties, and blood-perfusion rate. The simulation of the temperature distribution, coagulation depth and its hysteresis during laser thermotherapy for full-dynamic model are compared with the calculations from other models. RESULTS: Increased scattering in the near surface of applicator prevents light penetration into deeper region. Moreover, rise in temperature increases both blood flow at the periphery of coagulation region and thermal properties, which reduces the damage depth and its hysteresis. It results in a considerable overestimation of the temperature distribution and damage depth ignoring the dynamic of optical properties. The coagulation would be limited in a smaller region and there is no hysteresis if blood perfusion is regarded as a constant. In contrast, the hysteresis is overestimated if blood perfusion is ignored. Ignoring the dynamics of thermal parameters, there is also overestimation of the rise in temperature and damage depth. CONCLUSIONS: Mathematical modeling techniques that simulate laser coagulation may not provide reliable information unless they take into account these dynamic parameters.

Animals↗

PubMedDate not supplied

Redox ratio of mitochondria as an indicator for the response of photodynamic therapy.

The effect of photodynamic therapy (PDT) treatment on the metabolic state of tumor mitochondria is investigated by imaging of tumor redox status. PDT is performed using the photosensitizer pyropheophorbide-2-deoxyglucosamide (Pyro-2DG), which utilizes the glucose import pathway. It is found that Pyro-2DG-induced PDT resulting in a highly oxidized state of tumor mitochondria. This is determined from the redox ratio changes derived from the intrinsic oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) [i.e., reduced nicotinamide adenine dinucleotide (NADH)] fluorescence signals observed using a cryoimager. Thus, the redox ratio is a sensitive indicator for providing reliable and informative measurements of PDT-induced tissue damage. In the PDT treated region of the tumor, highly oxidized flavoprotein and diminishing NADH fluorescence is detected, suggesting that flavoprotein and NADH are oxidized by singlet oxygen produced in the photosensitization process.

Animals↗

PubMedDate not supplied

Temporal clustering analysis of cerebral blood flow activation maps measured by laser speckle contrast imaging.

Temporal and spatial orchestration of neurovascular coupling in brain neuronal activity is crucial for comprehending the mechanism of functional cerebral metabolism and pathophysiology. Laser speckle contrast imaging (LSCI) through a thinned skull over the somatosensory cortex is utilized to map the spatiotemporal characteristics of local cerebral blood flow (CBF) in anesthetized rats during sciatic nerve stimulation. The time course of signals from all spatial loci among the massive dataset is hard to analyze, especially for the thousands of images, each of which composes millions of pixels. We introduce a temporal clustering analysis (TCA) method, which is proven as an efficient method to analyze functional magnetic resonance imaging (fMRI) data in the temporal domain. The timing and location of CBF activation shows that contralateral hindlimb sensory cortical microflow is activated to increase promptly in less than 1 s after the onset of 2-s electrical stimulation and is evolved in different discrete regions. This pattern is similar but slightly elaborated from the results obtained from laser Doppler flowmetry (LDF) and fMRI. We present this combination to investigate interacting brain regions, which might lead to a better understanding of the nature of brain parcellation and effective connectivity.

Animals↗