PubMed Health⌕ Search

Biomedical subjects

Jeff F Dunn

Publications and source records attributed to Jeff F Dunn.

18 recordsLinked to original sources
PubMed2006

Blood-oxygen-level-dependent magnetic resonance signal and cerebral oxygenation responses to brain activation are enhanced by concurrent transient hypertension in rats.

Neuronal activation results in increases in blood-oxygen-level-dependent (BOLD) signal increases in magnetic resonance images, increases in cerebral blood flow (CBF), and changes in tissue oxygenation. We hypothesized that transient hypertension concurrent with neuronal activation would interfere with the normal physiological responses to neuronal activation potentially leading to additive responses. Anesthetized rats were prepared for functional magnetic resonance imaging studies in which increases in BOLD signal were measured in response to: (1) electrical forepaw stimulation, (2) different graded levels of transient hypertension produced with norepinephrine, and both 1 and 2. In other experiments with a similar protocol, changes in CBF and cortical oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) were measured using Laser Doppler Flowmetry and near-infrared (IR) spectroscopy. BOLD signal within the sensory-motor cortex increased during forepaw stimulation. These matched increases in CBF and oxyHb and decreases in deoxyHb. During moderate or severe transient hypertension, there was a blood pressure-dependent increase in BOLD signal, CBF, and oxyHb; and a decrease in deoxyHb. When transient hypertension and forepaw stimulation were combined, the responses of oxyHb, deoxyHb, or BOLD signal were generally a summation of each response. In contrast, the CBF response to forepaw stimulation was relatively unaffected by transient hypertension. We conclude that during stimulation with concurrent hypertension, the normal changes in tissue oxygenation that accompany neuronal activation are enhanced by the increases produced by hypertension despite an excellent autoregulation of CBF. The latter could reflect highly transient decreases in oxygen consumption or likely a redistribution of flow through more nonexchange vessels.

Animals↗
PubMed2005

Delayed arteriogenesis in hypercholesterolemic mice.

BACKGROUND: Hypercholesterolemia has been reported to inhibit ischemia-induced angiogenesis. To address its effects on arteriogenesis, we investigated arterial growth in hypercholesterolemic low-density lipoprotein receptor(-/-)/ApoB-48(-/-) (HCE) mice. METHODS AND RESULTS: The extent and the time course of arteriogenesis after femoral artery ligation was evaluated in HCE and strain-matched control mice. Distal limb perfusion was measured by laser Doppler imaging, whereas MRI was used to visualize arterial flow and micro-computed tomography to assess vascular growth. After femoral artery ligation, serial laser Doppler imaging demonstrated significantly delayed restoration of perfusion in untreated HCE compared with control mice (day 3, 0.09 versus 0.19, P<0.05). Treatment with Ad-PR39 in control mice led to a significant restoration of arterial blood flow and tissue perfusion at day 3, whereas in HCE mice, hindlimb perfusion began increasing only by day 7. Micro-CT analysis confirmed increased growth of smaller arterioles (16 to 63 microm in diameter) in the Ad-PR39-treated control compared with HCE mice. The delay in arteriogenesis in HCE mice correlated with delayed tissue appearance of F4/80+ cells. Analysis of gene expression after Ad-PR39 treatment demonstrated that HCE mice had significantly reduced expression of FGF receptor 1, hypoxia-inducible factor-1alpha, vascular cell adhesion molecule-1, macrophage scavenger receptor-1, and cyclophilin A compared with controls 3 days after arterial ligation that equalized by day 7, mimicking relative changes in arteriogenesis and tissue perfusion. CONCLUSIONS: Hypercholesterolemia results in delayed native arteriogenesis because of reduced early monocyte/macrophage influx and delayed and impaired arterial growth response to growth factor therapy.

Animals↗
PubMed2005

Magnetic-resonance-imaging-coupled broadband near-infrared tomography system for small animal brain studies.

A novel magnetic-resonance-coupled broadband near-infrared (NIR) tomography system for small animal brain studies is described. Several features of the image formation approach are new in NIR tomography and represent major advances in the path to recovering high-resolution hemoglobin and oxygen saturation images of tissue. The NIR data were broadband and continuous wave and were used along with a second-derivative-based estimation of the path length from water absorption. The path length estimation from water was then used along with the attenuation spectrum to recover absorption and reduced scattering coefficient images at multiple wavelengths and then to recover images of total hemoglobin and oxygen saturation. Going beyond these basics of NIR tomography, software has been developed to allow inclusion of structures derived from MR imaging (MRI) for the external and internal tissue boundaries, thereby improving the accuracy and spatial resolution of the properties in each tissue type. The system has been validated in both tissue-simulating phantoms, with 10% accuracy observed, and in a rat cranium imaging experiment. The latter experiment used variation in inspired oxygen (FiO2) to vary the observed hemoglobin and oxygen saturation images. Quantitative agreement was observed between the changes in deoxyhemoglobin values derived from NIR and the changes predicted with blood-oxygen-level-dependent (BOLD) MRI. This system represents the initial stage in what will likely be a larger role for NIR tomography, coupled to MRI, and illustrates that the technological challenges of using continuous-wave broadband data and inclusion of a priori structural information can be met with careful phantom studies.

Algorithms↗
PubMed2005

Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study.

PURPOSE: To determine quantitatively the changes in oxygenation of intracranial tumors induced by efaproxiral, an allosteric hemoglobin modifier. Efaproxiral reduces hemoglobin-oxygen binding affinity, which facilitates oxygen release from hemoglobin into surrounding tissues and potentially increases the pO(2) of the tumors. METHODS AND MATERIALS: The study was performed on 10 male Fisher 344 rats with 9L intracranial tumors. Electron paramagnetic resonance (EPR) oximetry was used to measure quantitatively the changes in the pO(2) in the tumors. Lithium phthalocyanine (LiPc) crystals were implanted in the tumors and in the normal brain tissue in the opposite hemispheres. We monitored the cerebral pO(2) starting 7 to 10 days after the tumor cells were implanted. NMR imaging determined the position and size of tumor in the brain. After an initial baseline EPR measurement, efaproxiral (150 mg/kg) was injected intravenously over 15 minutes, and measurements of tumor and normal brain oxygen tension were made alternately at 10-minute intervals for the next 60 minutes; the procedure was repeated for 6 consecutive days. RESULTS: Efaproxiral significantly increased the pO(2) of both the intracranial tumors and the normal brain tissue on all days. The maximum increase was reached at 52.9 to 59.7 minutes and 54.1 to 63.2 minutes after injection, respectively. The pO(2) returned to baseline values at 106 to 126.5 minutes after treatment. The maximum tumor and normal tissue pO(2) values achieved after efaproxiral treatment from Day 1 through Day 6 ranged from 139.7 to 197.7 mm Hg and 103.0 to 135.9 mm Hg, respectively. The maximum increase in tumor tissue pO(2) values from Day 2 to Day 5 was greater than the maximum increase in normal tissue pO(2). CONCLUSION: We obtained quantitative data on the timing and extent of efaproxiral-induced changes in the pO(2) of intracerebral 9L tumors. These results illustrate a unique and useful capability of in vivo EPR oximetry to obtain repeated noninvasive measurements of tumor oxygenation over a number of days. The information on the dynamics of tumor pO(2) after efaproxiral administration illustrates the ability of efaproxiral to increase intracranial tumor oxygenation.

Aniline Compounds↗
PubMed2005

Modeling of the response of ptO2 in rat brain to changes in physiological parameters.

It is known that oxygen tension in tissue (ptO2) will change in response to an alteration of physiological parameters including: pCO2 in arterial blood, blood flow, capillary density, oxygen carrying capacity, and p50 of hemoglobin. We have used modeling to compute the change of PtO2 in response to changes of each physiological parameter and related these changes to experimental data. The oxygen distribution in a Krogh cylinder was computed assuming a linear decrease of hemoglobin saturation from the arterial to the venous end of the capillary. Parameters of the model were used to compute the baseline cerebral PtO2 expressed as the mean value of the PtO2 over the whole cylinder. These parameters were adjusted to derive PtO2 values close to those measured at the relevant experimental conditions. Then each desired parameter was varied to calculate the change in PtO2 related to this parameter. Effects of different factors on cerebral PtO2 were modeled and compared with experimental values obtained with various experimental interventions including: changing CBF, modifying p50 with the allosteric modifier RSR13, modification of capillary density, and hemoglobin content. An acceptable agreement of the computed and the experimental changes of the cerebral PtO2 was obtained for these experimental conditions.

Acclimatization↗
PubMed2005

Cerebral PtO2, acute hypoxia, and volatile anesthetics in the rat brain.

We describe our results on the effect in rats of two commonly used, volatile anesthetics on cerebral tissue PO2 (PtO2) and other physiological parameters at FiO2 levels ranging from 0.35 to 0.1. The study was performed in 12 rats that had lithium phthalocyanine (LiPc) crystals implanted in the left cerebral cortex. FiO2 was maintained at 0.35 during surgical manipulation and baseline EPR measurements, after which time, each animal was exposed to varying levels of FiO2 (0.26, 0.21, 0.15, and 0.10) for 30 minutes at each level. No significant difference in PtO2 was observed between the isoflurane and halothane groups at any FiO2 level, and the cerebral arterial PO2 (PaO2) also was similar for both groups. However, the cerebral PtO2 under both isoflurane and halothane anesthesia was lower during hypoxia (FiO2 < or = 0.15) than under normoxia (FiO2 = 0.21) and there was a significant difference in mean arterial blood pressure (MABP) between isoflurane and halothane groups under both mild and severe hypoxia. The pH and cerebral arterial PCO2 (PaCO2) were similar for the halothane and isoflurane groups during normoxia (FiO2 = 0.21) and mild hypoxia (FiO2 = 0,15), but following severe hypoxia (FiO2 = 0.10), both parameters were lower in the halothane anesthetized animals. These results confirm that cerebral PO2 cannot be inferred directly from measurements of other parameters, indicating that methodology incorporating continuous direct measurement of brain oxygen will lead to a better understanding of cerebral oxygenation under anesthesia and hypoxia.

Anesthetics, Inhalation↗
PubMed2004

Effect of RSR13, an allosteric hemoglobin modifier, on oxygenation in murine tumors: an in vivo electron paramagnetic resonance oximetry and bold MRI study.

PURPOSE: RSR13, an allosteric modifier of hemoglobin, reduces hemoglobin-oxygen binding affinity facilitating oxygen release from hemoglobin, resulting in increases in tissue pO(2). The purpose of this study was noninvasively to monitor the time course and effect of RSR13 on tumor oxygenation, directly using in vivo electron paramagnetic resonance (EPR oximetry), and indirectly using blood oxygen level dependent magnetic resonance imaging (BOLD MRI). METHODS AND MATERIALS: The study was performed in transplanted radiation-induced fibrosarcoma tumors (RIF-1) in 18 female C3H/HEJ mice, which had two lithium phthalocyanine (LiPc) deposits implanted in the tumor when the tumors reached about 200-600 mm(3). Baseline EPR measurements were made daily for 3 days. Then, for 6 consecutive days and after an initial baseline EPR measurement, RSR13 (150 mg/kg) or vehicle (same volume) was injected intraperitoneally, and measurements of intratumoral oxygen were made at 10-min intervals for the next 60 min. In each mouse, every third day, instead of EPR oximetry, BOLD MRI measurements were made for 60 min after administration of the RSR13. RESULTS: Based on EPR measurements, RSR13 produced statistically significant temporal increases in tumor pO(2) over the 60-min time course, which reached a maximum at 35-43 min postdose. The average time required to return to the baseline pO(2) was 70-85 min. The maximum increase in tumor tissue pO(2) values after RSR13 treatment from Day 1 to Day 5 (8.3-12.4 mm Hg) was greater than the maximum tumor tissue pO(2) value for Day 6 (4.7 mm Hg, p < 0.01). The maximum increase in pO(2) occurred on Day 2 (12.4 mm Hg) after RSR13 treatment. There was little change in R(2)*, indicating that the RSR13 had minimal detectable effects on total deoxyhemoglobin and hemoglobin-oxygen saturation. CONCLUSION: The extent of the increase in tumor pO(2) achieved by RSR13 would be expected to lead to a significant increase in the effectiveness of tumor radiotherapy. The lack of a change in the BOLD MRI signal suggests that the tumor physiology was largely unchanged by RSR13. These results illustrate a unique and useful capability of in vivo EPR oximetry and BOLD MRI to obtain repeated measurements of tumor oxygenation and physiology. The dynamics of tumor pO(2) after RSR13 administration may be useful for the design of clinical protocols using allosteric hemoglobin effectors.

Aniline Compounds↗
PubMed2004

Monitoring angiogenesis in brain using steady-state quantification of DeltaR2 with MION infusion.

An MRI method for quantification of cerebral blood volume (CBV) in time-course studies of angiogenesis is described. Angiogenesis was stimulated by acclimation to hypoxia. The change in relaxation rate, R2, which is relatively sensitive to the microvasculature, was quantified before and after infusion of a superparamagnetic vascular contrast agent (MION). The DeltaR2 was measured in serum and brain parenchyma with a multiecho sequence. In vitro and in vivo calibration curves of MION concentration vs. R2 were approximated by a linear function. CBV was 3.14 +/- 0.32% (mean +/- SE, n=13) and 6.42 +/- 0.54% (n=4) before and after acclimation. A second acclimated group was hemodiluted to control for polycythemia. CBV was not significantly different between hemodiluted and nonhemodiluted groups. In animals where NMR measurements were taken before and after acclimation, there was a 120% increase in CBV. The NMR technique was validated using quantitative morphometrics, which showed an increase of 147% in CBV with acclimation. We found a linear correlation between MRI and the morphometric results for CBV, as well as demonstrating a quantitative equivalence for relative changes in CBV. This article describes a simple, repeatable method of imaging brain microvascular volume using a plasma-based contrast agent that can be applied to longitudinal studies of angiogenesis.

Animals↗
PubMed2004

Comparison of EPR oximetry and Eppendorf polarographic electrode assessments of rat brain PtO2.

EPR oximetry is a promising, relatively non-invasive method for monitoring the partial pressure of oxygen in tissue (PtO2) that has proved useful in following changes under various physiologic and pathophysiologic conditions. Optimal utilization of the method will be facilitated by systematic comparisons with other available methods. Here we report on the absolute values of rat brain PtO2 using EPR and the more widely used Eppendorf polarographic microelectrode system in the same brain. EPR used an L-band (1.2 GHz) spectrometer and implanted lithium phthalocyanine (LiPc) as the oxygen-sensitive paramagnetic material. Eppendorf measurements were made by a needle probe moved vertically through the cortex at 0.5 mm intervals in three tracks including one adjacent to the location of the LiPc. Several conclusions were drawn, including, (1) the average PtO2 measured by the two methods was similar but EPR reported a significantly higher average PtO2, (2) there was poor correlation between the values in the same animal on the same side of the brain, (3) the Eppendorf reported a larger range of values and (4) the heterogeneity of oxygen levels in the brain and the areas sampled by the two methods provide an adequate explanation for the observed differences.

Animals↗
PubMed2004

Macroscopic structure of articular cartilage of the tibial plateau: influence of a characteristic matrix architecture on MRI appearance.

OBJECTIVE: The purpose of our study was to describe the structural organization of the extracellular matrix of articular cartilage of the tibial plateau and its influence on MRI appearance. MATERIALS AND METHODS: Spin-echo images of 11 resected tibial plateaus acquired at 7 T were compared with the structure of the extracellular matrix as shown by fracture sectioning the samples in the plane of imaging. Four samples were scanned at two different orientations relative to the main magnetic field (B(0)). T2 maps were acquired in two orientations on three of these four samples. RESULTS: On the basis of the presence of reproducible regional variations in the shape of the matrix, a characteristic matrix architecture was described. The location of peak signal intensity and T2 on MRI correlated with the level at which the matrix was estimated to be aligned at approximately 55 degrees to B(0) (r = 0.91). This correlation of matrix orientation relative to B(0) with T2 and signal intensity on MRI was not altered by regional variations in the shape of the matrix or by imaging samples at two different orientations. CONCLUSION: The structure of the extracellular matrix, through its orientation-dependent influence on T2 decay, exerts a strong influence on the MRI appearance of cartilage. At the tibial plateau, a characteristic matrix architecture is associated with an equally characteristic MRI appearance.

Adult↗
PubMed2003

Measurements of oxygen in tissues: overview and perspectives on methods.

The goal of this manuscript is to provide a summary of the major techniques that currently are being applied to measure oxygenation of tissues in vivo. Oxygen is one of the key components of metabolism. Oxygen is also a major variable in many diseases, both with respect to the pathophysiological processes and influencing the efficacy of treatment. Unfortunately, however, the measurement of tissue oxygenation is non-trivial. Consequently many different methods have been developed to try to make this measurement. This paper presents a summary, largely in tabular form, of most of the current methods for assessing tissue oxygenation. The table attempts to cover the most pertinent aspects of the techniques and their applications, including their potential niche, limitations, and advantages. Citations are given for each method to point the reader in the direction of relevant literature.

Humans↗
PubMed2003

Brain tissue and sagittal sinus pO2 measurements using the lifetimes of oxygen-quenched luminescence of a ruthenium compound.

The study was done to assess the performance of a system that measures the partial pressures of oxygen (pO2) from the lifetimes of oxygen-quenched luminescence of ruthenium compounds immobilized at the tip of fiber-optic optodes (Oxylite system). The system was used to measure the pO2 in brain tissue (thalamus and hypothalamus) and in the sagittal sinus of isoflurane-anesthetized rats at different FiO2's. The pO2 recorded in the hypothalamus (HPtO2) was consistently higher than the pO2 in the thalamus (TPtO2) at all FiO2. HPtO2 was closely related to PvO2 during normoxia but not during hypoxia. The equilibrium time of Oxylite system was found to be rapid compared to in vivo tissue response to changes in FiO2.

Animals↗
PubMed2003

The effects of anesthesia on cerebral tissue oxygen tension: use of EPR oximetry to make repeated measurements.

While very useful data can be obtained from measurements of pO2 within various compartments of the vascular system, such measurements do not necessarily provide accurate information on the pO2 in the brain. Anesthetics can significantly affect the tissue pO2 in the brain by several mechanisms involving both delivery and utilization. Electron Paramagnetic Resonance (EPR or ESR) oximetry has the potential for non-invasively carrying out repeated direct measurements of pO2 in tissues during the course of anesthesia. In this paper we describe the use of EPR oximetry for studying the influence of anesthesia on tissue pO2, and present illustrative results from experiments with five different anesthetics in rats. The results indicate that the tissue O2 can be measured directly using EPR oximetry, and data can be obtained non-invasively during the course of anesthesia.

Anesthetics↗
PubMed2003

In vivo electron paramagnetic resonance oximetry with particulate materials.

Electron paramagnetic resonance (EPR) methods can be used to study tissue pO(2) (PtO(2)) in anesthetized or awake animals (EPR oximetry). The method takes advantage of the fact that some paramagnetic materials have an EPR linewidth that is sensitive to the pO(2) in which the material is located. This article provides an overview of the method of EPR oximetry using implanted particulate materials as the sensors of pO(2). Characteristics of these materials are described to help the reader understand the factors involved in choosing the optimum particulate material. Examples of biological studies are included that show how EPR oximetry may be used on both awake and anesthetized animals.

Animals↗
PubMed2003

Near-infrared imaging in the small animal brain: optimization of fiber positions.

We investigate fiber placement issues associated with a hybrid magnetic resonance imaging (MRI) near-infrared (NIR) imaging technique for small animal brain studies. Location of the optical fibers on the cranium is examined, with an emphasis on maximizing the recovered resolution and contrast in the region of interest, which in this case is the murine brain. In a series of simulation studies, singular value decomposition of the Jacobian is used in order to determine the measurement sites that provide the most information about the region of interest. The modeling results indicate that data collected using fibers arranged on one side of the head near the brain contain as much information about optical changes within the brain as those positioned equally spaced around the entire periphery of the head. Practical space limitation considerations favor the one-sided fiber array geometry in the case where the NIR acquisition is expected to occur simultaneously with MRI.

Animals↗
PubMed2002

Changes in oxygenation of intracranial tumors with carbogen: a BOLD MRI and EPR oximetry study.

PURPOSE: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. MATERIALS AND METHODS: The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R(2)*. On a different group of 9L tumors, tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. RESULTS: The average decline in R(2)* with carbogen breathing was 13 +/- 1 s(-1) in the CNS-1 tumors and 29 +/- 4 s(-1) in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO(2) in the two 9L tumors measured was 8.6 +/- 0.5 and 3.6 +/- 0.6 mmHg during air breathing, and rose to 20 +/- 7 and 16 +/- 4 mmHg (mean +/- SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO(2) and R(2)* continued in some subjects over the entire 40 minutes. CONCLUSION: EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors.

Animals↗
PubMed2002

Ventral medulla pHi measured in vivo by 31P NMR is not regulated during hypercapnia in anesthetized rat.

Chemoreceptors in the ventral medulla contribute to the respiratory response to hypercapnia. Do they 'sense' intracellular pH (pHi)? We measured pHi in the ventral medulla or cortex (control) using 31P-NMR obtained via a novel 3 x 5 mm2 surface coil in anesthetized rats breathing air or 7% CO2. During air breathing over 240 min, pHi decreased slightly from 7.13 +/- 0.02 to 7.05 +/- 0.02 (SEM; n = 5; 2 cortex, 3 ventral medulla). During 180 min of hypercapnia, cortical pHi (n = 4) decreased from 7.17 +/- 0.02 to 6.87 +/- 0.01 by 90 min and recovered by 150 min. Ventral medulla pHi showed no such regulation. It decreased from 7.11 +/- 0.02 to 6.88 +/- 0.02 at 90 min and recovered only after cessation of hypercapnia (n = 5), results consistent with pHi being the chemoreceptor stimulus. However, non-chemoreceptor neurons that contribute to our medullary NMR signal also do not appear to regulate pHi in vitro. Regional differences in pHi regulation between cortex and ventral medulla may be due to both chemosensitive and non-chemosensitive neurons.

Adenosine Triphosphatases↗