Vivo Measurements (vivo + measurement)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Inductively coupled helmholtz coil on a dedicated imaging platform for the in vivo1H-MRS measurement of intramyocellular lipids in the hind leg of rats

MAGNETIC RESONANCE IN MEDICINE, Issue 4 2009
Michael Neumaier PhD
Abstract Skeletal muscle triglycerides are markers for insulin resistance in type 2 diabetes. Recently, MR spectroscopy was adapted for in vivo measurement of triglycerides in animal models and for the characterization of new therapeutic approaches. Because of small MR spectroscopy voxel sizes used in skeletal muscles, surface coils are used for signal reception. Furthermore, to obtain well-resolved and undistorted lipid spectra, muscle fibers must be aligned parallel to the magnetic field. Consequently, to achieve a high signal-to-noise ratio and spectral quality, a coil setup must combine high sensitivity with a reliable and reproducible positioning of muscle and voxel. These demands are difficult to match using surface coils. Here, a coil platform is described, which uses inductively coupled Helmholtz coil setup combined with a leg retainer system for rats. The new system allows for measurement of intramyocellular lipids with high signal-to-noise ratio and for significantly improved animal handling, positioning, and throughput. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source]


Use of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an EPR oximetry probe: Potential for in vivo measurement of tissue oxygenation in mouse brain

MAGNETIC RESONANCE IN MEDICINE, Issue 6 2006
Jiangang Shen
Abstract Measurement of oxygen concentration and distribution in the brain is essential for understanding the pathophysiology of stroke. Low-frequency electron paramagnetic resonance (EPR) spectroscopy with a paramagnetic probe is an attractive imaging modality that potentially can be used to map O2 concentration in the brain. We examined two nitroxides, 3-methoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [2] and 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [3], as pro-imaging agents to deliver 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [1] across the blood,brain barrier (BBB). In primary cultured neurons, nitroxide [3] but not [2] was hydrolyzed by intracellular esterases to [1], which, being anionic at physiologic pH, was well retained intracellularly. In contrast, [2] was not well retained by neurons. In vivo pharmacokinetic and pharmacodynamic studies in mice suggested that esterase-labile nitroxide [3] crossed the BBB, and was converted to [1] and retained. Retention occurred in brain tissue and not in the extensive vasculature, as evidenced by the fact that removal of blood by whole-body saline perfusion did not eliminate the nitroxide EPR signal from the brain. The EPR linewidths of [1] and [3] were more O2 -sensitive than that of the commonly-used oximetry probe 4-oxo-2,2,6,6-tetramethylpiperidine-d16 -1- 15N-oxyl [4]. Moreover, we used [3] in vivo to estimate O2 concentration in mouse brains. These results indicate that nitroxide [3] could be useful for mapping O2 distribution in the brain following stroke. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source]


In vivo measurement of brain metabolites using two-dimensional double-quantum MR spectroscopy,exploration of GABA levels in a ketogenic diet

MAGNETIC RESONANCE IN MEDICINE, Issue 4 2003
Zhiyue J. Wang
Abstract A localized proton 2D double-quantum (DQ) spin-echo spectroscopy technique was implemented on 1.5 T clinical MRI scanners for the detection of ,-aminobutyrate (GABA) in the brain. The 2D approach facilitates separation of peaks overlapping with GABA in 1D DQ-filtered (DQF) spectra. This technique was applied to four normal adult volunteers and four children with intractable epilepsy. The coefficient of variation of the level of GABA and overlapping macromolecules at F2 = 3.0 ppm and F1 = 4.8 ppm was 0.08 in normal subjects. Three patients received 2D MRS scans before and after initiation of the ketogenic diet (KD): one patient showed a trend of decreasing GABA throughout the study, and two patients showed low initial GABA levels that increased over time. In addition to major metabolites and GABA, low-level metabolites (valine, leucine, and glutathione) were also identified in the 2D spectra. Magn Reson Med 49:615,619, 2003. © 2003 Wiley-Liss, Inc. [source]


Checkpoints and pitfalls in the experimental neuropathology of circulatory disturbance

NEUROPATHOLOGY, Issue 1 2003
Toshihiko Kuroiwa
In neural tissue injury many pathological processes are common to different neurological disorders, including cerebral ischemia. Because ischemia has a fundamentally simple impact on neural tissue, good laboratory modeling can help improve the general understanding of the neuropathological processes involved. Summarized here are some basic principles that should be followed to ensure that cerebral ischemia studies are reproducible and informative: (i) selection of an appropriate model of cerebral ischemia in an appropriate species (although rodents are widely used for genomic studies, the use of larger animals, with brain structures macroscopically similar to those of humans, is appropriate for many studies, e.g. of white matter lesions or the pathophysiology of cerebral edema); (ii) correct maintenance of physiological parameters, including body temperature, systemic blood pressure, and blood gas tensions, under appropriate general anesthesia; (iii) selection of an appropriate method of cerebral blood flow (CBF) monitoring (decisions include whether or not the experiment requires real-time monitoring, in vivo measurement, and CBF mapping); (iv) appropriate timing of drug application in therapeutic studies (many drugs that are effective when given immediately after a short period of ischemi are ineffective in clinical trials, probably because of longer periods of ischemia and delayed drug delivery in clinical settings); and (v) multiparametric evaluation of therapeutic effect (with the recent increase in diagnosis of cases of mild stroke, measurement of mortality and infarct size have proven to be insufficient for the evaluation of therapeutic effect). Use of mild ischemia models and batteries of neurological tests for individual neurological functions, such as motor, somatosensory, and visual function, are becoming important in experimental ischemia research. In histological evaluation, assessment of the extent of both selective neuronal loss and the infarct will become mandatory. Regional analysis of each brain structure and coordination of the results with the apparent neurological dysfunction is a promising approach. [source]


Evaluation of the atrophogenic potential of different glucocorticoids using optical coherence tomography, 20-MHz ultrasound and profilometry; a double-blind, placebo-controlled trial

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2006
M. Coßmann
Summary Background, Skin atrophy is one of the main side-effects of topical corticosteroid therapy. Although the use of high-frequency ultrasound is an established method that has been studied previously, it allows measurements of the slow-reacting dermal thickness only. Objectives, To investigate the decreasing epidermal thickness, which occurs earlier, we used optical coherence tomography (OCT), a high-resolution noninvasive imaging technique, and compared it with 20-MHz ultrasound and profilometry. Patients/methods, In this double-blind placebo-controlled trial 20 healthy volunteers applied four different corticosteroids and the cream base formulation as placebo to the volar part of both arms once a day over a 4-week period. The epidermal thickness, the dermal thickness and the skin surface roughness were assessed using OCT, high-frequency ultrasound and profilometry. Results, Each of the three methods allowed the detection and monitoring of significant corticosteroid-induced skin atrophy and its reversibility. The changes correlated with the potency of the steroids. The epidermal thickness decreased significantly in all test areas, even in the placebo and the untreated fields. As expected, the reduction in epidermal thickness was more pronounced and could be detected earlier by OCT than the reduction of dermal thickness using ultrasound. The epidermal surface roughness investigated using profilometry showed a slight smoothing. Conclusions, OCT allows a simple, fast and noninvasive in vivo measurement of the epidermal thickness. To evaluate the atrophogenic potential of corticosteroids it is more suitable than high-frequency ultrasound as epidermal thickness decreases earlier. In addition, epidermal thickness is a more sensitive indicator of steroid atrophy as the degree of thinning is much higher compared with the dermal atrophy. Profilometry might give further information; however, it would not be suitable for clinical use as the results were generally less pronounced. In the future, OCT might be useful to detect corticosteroid-induced side-effects at the beginning for monitoring the therapy. [source]


Peripheral CD4 loss of regulatory T cells is associated with persistent viraemia in chronic HIV infection

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007
C. A. R. Baker
Summary Chronic HIV infection is associated with T cell abnormalities and altered effector function. Regulatory T cells (Treg) are CD4+ T cells that play a critical role in regulating the immune system. The impact of regulatory T cells on HIV infection and disease progression may be highly significant. We hypothesize that chronic antigenic stimulation from a persistent, high viraemic state may promote a population of Treg that contributes to HIV-associated immune dysfunction. We evaluated the pattern of Treg in chronically infected, HIV-positive individuals over a course of 6 months. Treg are depleted at a distinct rate from that of absolute CD4 cells and loss of Treg is slower in the presence of viral suppression. In vitro depletion of CD25+ CD4+ cells resulted in increased Gag-specific CD4 and CD8 responses. A significant correlation between ex vivo measurement of Treg and Gag-specific CD4 T cell responses was observed (r = ,0·41, P = 0·018) with a trend observed with Gag-specific CD8 T cell responses (P = 0·07). The impact of HIV infection on the Treg population directly complicates the measured effect of Treg on the immune dysfunction although our data support the important role of Treg on modulating the effector T cell response in chronic infection. [source]


Classification of Compression Bandages: Practical Aspects

DERMATOLOGIC SURGERY, Issue 5 2008
HUGO PARTSCH MD
BACKGROUND Compression bandages appear to be simple medical devices. However, there is a lack of agreement over their classification and confusion over the use of important terms such as elastic, inelastic, and stiffness. OBJECTIVES The objectives were to propose terms to describe both simple and complex compression bandage systems and to offer classification based on in vivo measurements of subbandage pressure and stiffness. METHODS A consensus meeting of experts including members from medical professions and from companies producing compression products discussed a proposal that was sent out beforehand and agreed on by the authors after correction. RESULTS Pressure, layers, components, and elastic properties (P-LA-C-E) are the important characteristics of compression bandages. Based on simple in vivo measurements, pressure ranges and elastic properties of different bandage systems can be described. Descriptions of composite bandages should also report the number of layers of bandage material applied to the leg and the components that have been used to create the final bandage system. CONCLUSION Future descriptions of compression bandages should include the subbandage pressure range measured in the medial gaiter area, the number of layers, and a specification of the bandage components and of the elastic property (stiffness) of the final bandage. [source]


Understanding immune cell trafficking patterns via in vivo bioluminescence imaging

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002
Stefanie Mandl
Abstract Cell migration is a key aspect of the development of the immune system and mediating an immune response. There is extensive and continual redistribution of cells to different anatomic sites throughout the body. These trafficking patterns control immune function, tissue regeneration, and host responses to insult. The ability to monitor the fate and function of cells, therefore, is imperative to both understanding the role of specific cells in disease processes and to devising rational therapeutic strategies. Determining the fate of immune cells and understanding the functional changes associated with migration and proliferation require effective means of obtaining in vivo measurements in the context of intact organ systems. A variety of imaging methods are available to provide structural information, such as X-ray CT and MRI, but only recently new tools have been developed that reveal cellular and molecular changes as they occur within living animals. We have pioneered one of these techniques that is based on the observations that light passes through mammalian tissues, and that luciferases can serve as internal biological sources of light in the living body. This method, called in vivo bioluminescence imaging, is a rapid and noninvasive functional imaging method that employs light-emitting reporters and external photon detection to follow biological processes in living animals in real time. This imaging strategy enables the studies of trafficking patterns for a variety of cell types in live animal models of human biology and disease. Using this approach we have elucidated the spatiotemporal trafficking patterns of lymphocytes within the body. In models of autoimmune disease we have used the migration of "pathogenic" immune cells to diseased tissues as a means to locally deliver and express therapeutic proteins. Similarly, we have determined the tempo of NK-T cell migration to neoplastic lesions and measured their life span in vivo. Using bioluminescence imaging individual groups of animals can be followed over time significantly reducing the number of animals per experiment, and improving the statistical significance of a study since changes in a given population can be studied over time. Such rapid assays that reveal cell fates in vivo will increase our basic understanding of the molecular signals that control these migratory pathways and will substantially speed up the development and evaluation of therapies. J. Cell. Biochem. Suppl. 39: 239,248, 2002. © 2002 Wiley-Liss, Inc. [source]


In vivo measurements of T1 relaxation times in mouse brain associated with different modes of systemic administration of manganese chloride

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2005
Yu-Ting Kuo MD
Abstract Purpose To measure regional T1 and T2 values for normal C57Bl/6 mouse brain and changes in T1 after systemic administration of manganese chloride (MnCl2) at 9.4 T. Materials and Methods C57Bl/6 mice were anesthetized and baseline T1 and T2 measurements obtained prior to measurement of T1 after administration of MnCl2 at 9.4 T. MnCl2 was administered systemically either by the intravenous (IV), intraperitoneal (IP), or subcutaneous (SC) routes. T1 and T2 maps for each MRI transverse slice were generated using commercial software, and T1 and T2 values of white matter (WM), gray matter (GM), pituitary gland, and lateral ventricle were obtained. Results When compared with baseline values at low-field, significant lengthening of the T1 values was shown at 9.4 T, while no significant change was seen for T2 values. Significant T1 shortening of the normal mouse brain was observed following IV, IP, and SC administration of MnCl2, with IV and IP showing similar acute effects. Significant decreases in T1 values were seen for the pituitary gland and the ventricles 15 minutes after either IV or IP injection. GM showed greater uptake of the contrast agent than WM at 15 and 45 minutes after either IV or IP injections. Although both structures are within the blood-brain barrier (BBB), GM and WM revealed a steady decrease in T1 values at 24 and 72 hours after MnCl2 injection regardless of the route of administration. Conclusion Systemic administration of MnCl2 by IV and IP routes induced similar time-course of T1 changes in different regions of the mouse brain. Acute effects of MnCl2 administration were mainly influenced by either the presence or absence of BBB. SC injection also provided significant T1 change at subacute stage after MnCl2 administration. J. Magn. Reson. Imaging 2005;21:334,339. © 2005 Wiley-Liss, Inc. [source]


Potential of ,flat' fibre evanescent wave spectroscopy to discriminate between normal and malignant cells in vitro

JOURNAL OF MICROSCOPY, Issue 2 2007
Z. HAMMODY
Summary The present study focuses on evaluating the potential of flattened AgClBr fibre-optic evanescent wave spectroscopy (FTIR-FEWS) technique for detection and identification of cancer cells in vitro using cell culture as a model system. The FTIR-FEWS results are compared to those from FTIR-microspectroscopy (FTIR-MSP) method extensively used to identify spectral properties of intact cells. Ten different samples of control and malignant cells were measured in parallel by the above two methods. Our results show a significant similarity between the results obtained by the two methodologies. The absorbance level of Amide I/Amide II, phosphates and carbohydrates were significantly altered in malignant compared to the normal cells using both systems. Thus, common biomarkers such as Amide I/Amide II, phosphate and carbohydrate levels can be derived to discern between normal and cancer cells. However, marked differences are also noted between the two methodologies in the protein bands due to CH3 bending vibration (1480,1350 cm,1). The spectral differences may be attributed to the variation in the penetration depth of the two methodologies. The use of flattened fibre rather than the standard cylindrical fibre has several practical advantages and is considered as an important step towards in vivo measurements in real time, such as that of skin nevi and melanoma using special designs of fibre-optic,based sensors. [source]


Liver fat and lipid oxidation in humans

LIVER INTERNATIONAL, Issue 9 2009
Anna Kotronen
Abstract Background: Studies in animals show that changes in hepatic fatty acid oxidation alter liver fat content. Human data regarding whole-body and hepatic lipid oxidation are controversial and based on studies of only a few subjects. Aims: We examined whether whole-body and hepatic lipid oxidation are altered in subjects with non-alcoholic fatty liver disease (NAFLD) compared with controls. Methods: In vivo measurements of rates of substrate oxidation and insulin sensitivity (using the euglycaemic hyperinsulinaemic clamp technique in combination with indirect calorimetry and infusion of [3- 3H]glucose) were performed in subjects with NAFLD [mean liver fat 14.0% (interquartile range 7.5,20.5%), n=29] and in control subjects [1.6% (1.0,3.0%), n=29]. Liver fat was measured using proton magnetic resonance spectroscopy. Plasma concentrations of 3-hydroxybutyrate (3-OHB) were measured as markers of hepatic lipid oxidation. Results: In the basal state, substrate oxidation rates and serum 3-OHB concentrations were comparable in subjects with and without NAFLD. Plasma 3-OHB concentrations were similarly suppressed by insulin in both the groups. During the insulin infusion, whole-body lipid oxidation was inversely correlated with insulin-stimulated glucose disposal (r=,0.48, P<0.0001), which was lower in subjects with NAFLD [3.7±0.2 mg/(kg fat-free mass min)] than in the control subjects [5.0±0.3 mg/(kg fat-free mass min), P=0.0008]. Conclusions: Hepatic lipid oxidation is unchanged in NAFLD. Whole-body lipid oxidation is increased because of peripheral insulin resistance. These data imply that alterations in hepatic fatty acid oxidation do not contribute to liver fat content in humans. [source]


Computational Network Model Prediction of Hemodynamic Alterations Due to Arteriolar Remodeling in Interval Sprint Trained Skeletal Muscle

MICROCIRCULATION, Issue 3 2007
Kyle W. Binder
ABSTRACT Objectives: Exercise training is known to enhance skeletal muscle blood flow capacity, with high-intensity interval sprint training (IST) primarily affecting muscles with a high proportion of fast twitch glycolytic fibers. The objective of this study was to determine the relative contributions of new arteriole formation and lumenal arteriolar remodeling to enhanced flow capacity and the impact of these adaptations on local microvascular hemodynamics deep within the muscle. Methods: The authors studied arteriolar adaptation in the white/mixed-fiber portion of gastrocnemius muscles of IST (6 bouts of running/day; 2.5 min/bout; 60 m/min speed; 15% grade; 4.5 min rest between bouts; 5 training days/wk; 10 wks total) and sedentary (SED) control rats using whole-muscle Microfil casts. Dimensional and topological data were then used to construct a series of computational hemodynamic network models that incorporated physiological red blood cell distributions and hematocrit and diameter dependent apparent viscosities. Results: In comparison to SED controls, IST elicited a significant increase in arterioles/order in the 3A through 6A generations. Predicted IST and SED flows through the 2A generation agreed closely with in vivo measurements made in a previous study, illustrating the accuracy of the model. IST shifted the bulk of the pressure drop across the network from the 3As to the 4As and 5As, and flow capacity increased from 0.7 mL/min in SED to 1.5 mL/min in IST when a driving pressure of 80 mmHg was applied. Conclusions: The primary adaptation to IST is an increase in arterioles in the 3A through 6A generations, which, in turn, creates an approximate doubling of flow capacity and a deeper penetration of high pressure into the arteriolar network. [source]


Towards metabolic mapping of the human retina

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2007
D. Schweitzer
Abstract Functional alterations are first signs of a starting pathological process. A device that measures parameter for the characterization of the metabolism at the human eye-ground would be a helpful tool for early diagnostics in stages when alterations are yet reversible. Measurements of blood flow and of oxygen saturation are necessary but not sufficient. The new technique of auto-fluorescence lifetime measurement (FLIM) opens in combination with selected excitation and emission ranges the possibility for metabolic mapping. FLIM not only adds an additional discrimination parameter to distinguish different fluorophores but also resolves different quenching states of the same fluorophore. Because of its high sensitivity and high temporal resolution, its capability to resolve multi-exponential decay functions, and its easy combination with laser scanner ophthalmoscopy, multi-dimensional time-correlated single photon counting was used for fundus imaging. An optimized set up for in vivo lifetime measurements at the human eye-ground will be explained. In this, the fundus fluorescence is excited at 446 or 468 nm and the time-resolved autofluorescence is detected in two spectral ranges between 510 and 560 nm as well as between 560 and 700 nm simultaneously. Exciting the fundus at 446 nm, several fluorescence maxima of lifetime t1 were detected between 100 and 220 ps in lifetime histograms of 40° fundus images. In contrast, excitation at 468 nm results in a single maximum of lifetime t1 = 190 ± 16 ps. Several fundus layers contribute to the fluorescence intensity in the short-wave emission range 510,560 nm. In contrast, the fluorescence intensity in the long-wave emission range between 560 and 700 nm is dominated by the fluorescence of lipofuscin in the retinal pigment epithelium. Comparing the lateral distribution of parameters of a tri-exponential model function in lifetime images of the fundus with the layered anatomical fundus structure, the shortest component (t1 = 190 ps) originates from the retinal pigment epithelium and the second lifetime (t2 = 1,000 ps) from the neural retina. The lifetime t3 , 5.5 ns might be influenced by the long decay of the fluorescence in the crystalline lens. In vitro analysis of the spectral properties of expected fluorophores under the condition of the living eye lightens the interpretation of in vivo measurements. Taking into account the transmission of the ocular media, the excitation of NADH is unlikely at the fundus. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source]


Anatomical information is needed in ultrasound imaging of muscle to avoid potentially substantial errors in measurement of muscle geometry

MUSCLE AND NERVE, Issue 5 2009
Menno R. Bénard MSc
Abstract This study validates two-dimensional (2D) ultrasound measurements of muscle geometry of the human medial gastrocnemius (GM) and investigates effects of probe orientation on errors in these measurements. Ultrasound scans of GM muscle belly were made both on human cadavers (n = 4) and on subjects in vivo (n = 5). For half of the cadavers, ultrasound scans obtained according to commonly applied criteria of probe orientation deviated 15° from the true fascicle plane. This resulted in errors of fascicle length and fascicle angle up to 14% and 23%, respectively. Fascicle-like structures were detectable over a wide range of probe tilt and rotation angles, but they did not always represent true fascicles. Errors of measurement were either linear or quadratic functions of tilt angle. Similar results were found in vivo. Therefore, we conclude that similar errors are likely to occur for in vivo measurements. For all cadavers, at the distal end of GM, the true fascicle plane was shown to be perpendicular to the distal aponeurosis. Using transverse images of GM to detect the curvature of the deep aponeurosis at the distal end of the muscle belly is a simple strategy to help identify the fascicle plane. For subsequent longitudinal imaging, probe alignment within this plane will help minimize measurement errors of fascicle length, fascicle angle, and muscle thickness. Muscle Nerve, 2009 [source]


Comparative velocity investigations in cerebral arteries and aneurysms: 3D phase-contrast MR angiography, laser Doppler velocimetry and computational fluid dynamics

NMR IN BIOMEDICINE, Issue 8 2009
Dorothea I. Hollnagel
Abstract In western populations, cerebral aneurysms develop in approximately 4% of humans and they involve the risk of rupture. Blood flow patterns are of interest for understanding the pathogenesis of the lesions and may eventually contribute to deciding on the most efficient treatment procedure for a specific patient. Velocity mapping with phase-contrast magnetic resonance angiography (PC-MRA) is a non-invasive method for performing in vivo measurements on blood velocity. Several hemodynamic properties can either be derived directly from these measurements or a flow field with all its parameters can be simulated on the basis of the measurements. For both approaches, the accuracy of the PC-MRA data and subsequent modeling must be validated. Therefore, a realistic transient flow field in a well-defined patient-specific silicone phantom was investigated. Velocity investigations with PC-MRA in a 3,Tesla MR scanner, laser Doppler velocimetry (LDV) and computational fluid dynamics (CFD) were performed in the same model under equal flow conditions and compared to each other. The results showed that PC-MRA was qualitatively similar to LDV and CFD, but showed notable quantitative differences, while LDV and CFD agreed well. The accuracy of velocity quantification by PC-MRA was best in straight artery regions with the measurement plane being perpendicular to the primary flow direction. The accuracy decreased in regions with disturbed flow and in cases where the measurement plane was not perpendicular to the primary flow. Due to these findings, it is appropriate to use PC-MRA as the inlet and outlet conditions for numerical simulations to calculate velocities and shear stresses in disturbed regions like aneurysms, rather than derive these values directly from the full PC-MRA measured velocity field. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Diffusion tensor imaging in fixed brain tissue at 7.0 T

NMR IN BIOMEDICINE, Issue 2 2003
David N. Guilfoyle
Abstract The purpose of this work is to assess the feasibility of performing quantitative in vitro brain tissue diffusion tensor imaging (DTI) measurements and to examine their comparability to in vivo measurements. DTI of fixed tissue at high field strength is potentially a very valuable investigative tool as very high spatial resolution can be achieved. DTI was applied to human and mouse brain fixed tissue samples as well as in vivo measurements of the mouse brain. T1 and T2 relaxography of the fixed tissue samples was also performed to provide further characterization of the tissue. All experiments were performed at 7,T. The fractional anisotropy (FA) of the human fixed brain tissue samples is found to be higher in the corpus callosum than in the occipital white matter region, consistent with in vivo measurements reported in the literature. Our FA measurements of the corpus callosum of a mouse brain are also found to be the same both in vitro and in vivo. This preliminary work supports the use of DTI in both fixed human and fixed animal brain tissue as a valid investigative tool. With the increased availability of brain banks in different brain disorders, DTI in fixed tissue may prove to be a very useful method for the study of white matter abnormalities. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Lactate efflux and the neuroenergetic basis of brain function

NMR IN BIOMEDICINE, Issue 7-8 2001
Robert G. Shulman
Abstract In the unstimulated brain energy is primarily supplied by the oxidation of glucose. However the oxygen-to-glucose index (OGI), which is the ratio of metabolic rates of oxygen to glucose, CMRO2/CMRglc, diverges from the theoretical value of 6 as activity is increased. In vivo measurements of brain lactate show its concentration to increase with stimulation. The decreasing OGI with stimulation had led to the suggestion that activation, unlike resting activity, is supported by anaerobic glycolysis. To date a unifying concept that accommodates glucose oxidation at rest with lactate generation and OGI decrease during stimulation of brain is lacking. Furthermore, energetics that change with increasing activity are not consistent with a neuroenergetic model that has been proposed from 1- 13C-glucose MRS experiments. That model, based upon in vivo MRS measurements and cellular studies by Pellerin and Magistretti, showed that glutamate neurotransmitter cycling was coupled to glucose oxidation over a wide range of brain activities from rest down to deep anesthesia. Here we reconcile these paradoxical observations by suggesting that anaerobic glucose consumption (which can provide energy rapidly) increases with activation to meet the power requirements of millisecond neuronal firing. It is proposed, in accord with our neuroenergetic model, that the extra glucose mobilized rapidly for glial clearance of glutamate, is not needed for the oxidative processes that are responsible for neuronal firing and glutamate release, and consequently it is effluxed as lactate. A stoichiometric relation between OGI and lactate concentration is derived from the neuroenergetic model, showing that the enhanced glucose uptake during activation is consistent with neuronal activity being energetically supported by glucose oxidation. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Blue-Violet Excited Autofluorescence Spectroscopy and Imaging of Normal and Cancerous Human Bronchial Tissue after Formalin Fixation

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2007
Tanja Gabrecht
Autofluorescence (AF) imaging is a powerful tool for the detection of (pre-)neoplastic lesions in the bronchi. Several endoscopic imaging systems exploit the spectral and intensity contrast of AF between healthy and (pre-)neoplastic bronchial tissues, yet, the mechanisms underlying these contrasts are poorly understood. In this report, the effect of formalin fixation on the human bronchi AF, hence on the contrast, was studied by spectrofluorometric point measurements and DAFE (Diagnostic AutoFluorescence Endoscopy) broad field imaging. Generally, formalin-fixed samples have higher AF intensity than in vivo, whereas the emission spectral shape is similar. Additionally, the spectrofluorometric data showed a moderate decrease of the AF intensity on (pre-)neoplastic lesions relative to the healthy bronchial samples. However, this decrease was lower than that reported from in vivo measurements. Neither spectral measurements nor imaging revealed spectral contrast between healthy bronchial tissue and (pre-)neoplastic lesions in formalin. These results indicate that epithelial thickening and blood supply in the adjacent lamina propria are likely to play a key role in the generation of the AF contrast in bronchial tissues. Our results show that the AF contrast in bronchial tissues was significantly affected by standard, 10% buffered, formalin fixation. Therefore, these samples are not suited to AF contrast studies. [source]


Is a short, sharp shock equivalent to long-term punishment?

PLANT CELL & ENVIRONMENT, Issue 4 2009
Contrasting the spatial pattern of acute, chronic ozone damage to soybean leaves via chlorophyll fluorescence imaging
ABSTRACT Experimental investigations of ozone (O3) effects on plants have commonly used short, acute [O3] exposure (>100 ppb, on the order of hours), while in field crops damage is more likely caused by chronic exposure (<100 ppb, on the order of weeks). How different are the O3 effects induced by these two fumigation regimes? The leaf-level photosynthetic response of soybean to acute [O3] (400 ppb, 6 h) and chronic [O3] (90 ppb, 8 h d,1, 28 d) was contrasted via simultaneous in vivo measurements of chlorophyll a fluorescence imaging (CFI) and gas exchange. Both exposure regimes lowered leaf photosynthetic CO2 uptake about 40% and photosystem II (PSII) efficiency (Fq,/Fm,) by 20% compared with controls, but this decrease was far more spatially heterogeneous in the acute treatment. Decline in Fq,/Fm, in the acute treatment resulted equally from decreases in the maximum efficiency of PSII (Fv,/Fm,) and the proportion of open PSII centres (Fq,/Fv,), but in the chronic treatment decline in Fq,/Fm, resulted only from decrease in Fq,/Fv,. Findings suggest that acute and chronic [O3] exposures do not induce identical mechanisms of O3 damage within the leaf, and using one fumigation method alone is not sufficient for understanding the full range of mechanisms of O3 damage to photosynthetic production in the field. [source]


Magnetic resonance cerebral metabolic rate of oxygen utilization in hyperacute stroke patients

ANNALS OF NEUROLOGY, Issue 2 2003
Jin-Moo Lee MD
The purpose of this study was to explore the feasibility of obtaining magnetic resonance,measured cerebral metabolic rate of oxygen utilization (MR-CMRO2) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 ± 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom onset. Diffusion-weighted, perfusion-weighted, and multiecho gradient-echo/spin-echo images were acquired; cerebral blood flow and oxygen extraction fraction maps were obtained from which CMRO2 was calculated as the product of cerebral blood flow and oxygen extraction fraction. The final infarct lesions obtained from tp3 T2-weighted images and the "penumbra" obtained from the tp1 perfusion-weighted image,defined lesion were coregistered onto tp1 CMRO2 maps. CMRO2 values in the region of brain that eventually infarcted were reduced to 0.40 ± 0.24 of the respective region on the contralateral hemisphere. The "salvaged penumbra" defined by the area of mismatch between the final infarct and the tp1 perfusion-weighted lesion demonstrated an average CMRO2 value of 0.55 ± 0.11 of the contralateral hemisphere. Although our results are preliminary and require further evaluation, the ability to obtain in vivo measurements of MR-CMRO2 noninvasively potentially can provide information for determining brain tissue viability in acute ischemic stroke patients. [source]


Angiogenesis and blood vessel stability in inflammatory arthritis

ARTHRITIS & RHEUMATISM, Issue 3 2010
Aisling Kennedy
Objective To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo. Methods Macroscopic vascularity and ST oxygen levels were determined in vivo in patients with inflammatory arthritis who were undergoing arthroscopy. Vessel maturity/stability was quantified in matched ST samples by dual immunofluorescence staining for factor VIII (FVIII)/,-smooth muscle actin (,-SMA). NCAM and 8-oxo-7,8-dihydro-2,-deoxyguanosine (8-oxodG) were examined by immunohistochemistry. Angiogenesis was assessed in vitro, using human dermal endothelial cells (HDECs) in a Matrigel tube formation assay. Results A significant number of immature vessels (showing no pericyte recruitment) was observed in tissue from patients with inflammatory arthritis (P < 0.001), in contrast to osteoarthritic and normal tissue, which showed complete recruitment of pericytes. Low in vivo PO2 levels in the inflamed joint (median [range] 22.8 [3.2,54.1] mm Hg) were inversely related to increased macroscopic vascularity (P < 0.04) and increased microscopic expression of FVIII and ,-SMA (P < 0.04 and P < 0.03, respectively). A significant proportion of vessels showed focal expression of NCAM and strong nuclear 8-oxodG expression, implicating a loss of EC,pericyte contact and increased DNA damage, levels of which were inversely associated with low in vivo PO2 (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O2 (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05). Conclusion Our findings indicate the presence of unstable vessels in inflamed joints associated with hypoxia, incomplete EC,pericyte interactions, and increased DNA damage. These changes may further contribute to persistent hypoxia in the inflamed joint to further drive this unstable microenvironment. [source]


AER lecture: Some reflections on corneal thickness

ACTA OPHTHALMOLOGICA, Issue 2007
N EHLERS
The corneal thickness as an object for studies was recognized in the renaissance. A value of 1 mm, representing the maximally swollen human cornea, was reported. Optical in vivo measurements were done by Blix in 1880 reporting a thickness of about 0.5 mm, the value that we today know is correct. Blix lived in "the golden age of physiologic optics". His interest was the contribution of the cornea to the optical refraction of the eye, and was thus the distance between the anterior and the posterior surface rather than the thickness of the cornea as such. A biomechanical interest in corneal thickness was initiated by the studies of tonometry, in particular Hans Goldmann's development of applanation tonometry. He predicted correctly that corneal thickness would influence the estimated pressure reading. Another physiological aspect of the cornea is its transparency. Earlier explanations by equal refractive index was revolutionized by the interference theory by David Maurice. Optical transparency required a regular fiber pattern, and thus a stabilized thickness and stromal hydration. This led to extensive interest in the permeability of the limiting layers, in particular the transport of fluid across the endothelium. The physiological concepts required a regulated or stabilized thickness. The thickness as such became interesting. The human cornea is thinner in the center than more peripherally and the central, presumably regulated central thickness (CCT) became a biometric and clinical study object. The exact individual value became of interest. Several optical and later ultrasonic principles were presented. Questions addressed were: Is CCT a life-long, age independent characteristics. Is CCT diagnostic for certain disease conditions (e.g. Macular dystrophy of Groenouw). Is CCT a useful clinical parameter to follow disease processes (e.g. progression in keratoconus or acute changes in graft rejections). Today refractive surgery has revived the interest in biomechanical and optical properties of the cornea. Modern computer technology allows for a description of the "thickness profile" of the entire cornea. This gives us access to an overwhelming amount of data, and reopen many issues of the past. We must realize, however, that what we see is the pendulum swinging back to the problems of the last century. The machinery is smarter but many of the basic questions remain to be solved. [source]


UVA1 and UVB irradiated skin investigated by optical coherence tomography in vivo: a preliminary study

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2005
T. Gambichler
Summary In histological studies, it has frequently been demonstrated that ultraviolet (UV) exposure, in particular UVB, can induce significant thickening of the viable epidermis and/or stratum corneum. Since skin biopsy alters the original skin morphology and always requires an iatrogenic trauma, we aimed to introduce optical coherence tomography (OCT) in vivo for the investigation of changes of epidermal thickness (ET) following UVA1 and UVB irradiation. Twelve healthy subjects received daily 60 J/cm2 of UVA1 and 1.5 minimal erythema doses UVB on their upper back over 3 consecutive days. Twenty-four hours after the last irradiation, OCT assessments were performed on UV exposed and adjacent nonirradiated control sites. Data of ET as expressed by comparison of the averaged A-scans differed significantly between nonirradiated (94.2 ± 15.7 µm), UVA1 (105.4 ± 12.8 µm) and UVB (125.7 ± 22.1 µm) exposed sites. In comparison to the nonirradiated sites, UVA1 exposed skin showed significant (P = 0.022) increase of ET of 11% and UVB exposed sites a significant (P < 0.001) increase of 25%. ET of UVA1 and UVB exposed skin sites differed significantly (P =0.005). Our results obtained from OCT in vivo measurements confirm data of previous histological studies indicating that not only erythemogenic doses of UVB, but also suberythemogenic doses of UVA1 may have a significant impact on ET. OCT appears to be a promising bioengineering technique for photobiological studies. However, further studies are needed to establish its measurement precision and validity, and to investigate in vivo spectral dependence on UV induced skin changes such as skin thickening. [source]