Imaging Epicardial Oxygen

Measurements of oxygen concentration and metabolic status in the heart are important to understanding the mechanisms that control cardiac respiration and its response to changing workload and substrate delivery. This paper presents images, recorded from a perfused rat heart, that reveal regional changes in concentrations of epicardial oxygen and of mitochondrial NADH in response to local ischemia, heterogeneous perfusion, and barbiturate inhibition. A fluorescence/phosphorescence imaging system was developed to acquire digital images of oxygen concentration and NADH fluorescence from the epicardium of perfused hearts. The oxygen imaging technique is based upon quenching of Pd(II) meso-tetra(p-sulfonatophenyl)porphin phosphorescence by dissolved oxygen. Images of oxygen and NADH fluorescence provided complimentary information about oxygen supply and demand in the heart. The utility of two-dimensional measurements of the mitochondrial bioenergetic status is illustrated by the comparison of gradients for NADH and oxygen across the boundary separating locally ischemic tissue from normoxic epicardium. Images of oxygen concentration provide a powerful means for studying the dynamics of regional oxygen supply/demand relationships in cardiac muscle. © 1998 Biomedical Engineering Society. PAC98: 8764Ni, 8780+s, 0760Yi, 8280Ch     

Optical oxygen sensor based on phosphorescence lifetime quenching and employing a polymer immobilised metalloporphyrin probe

A gaseous oxygen sensor is described based on the measurement of phosphorescence lifetime of the dye palladium coproporphyrin, immobilised in a range of membrane materials including polyvinyl chloride, polymethylmethacrylate, polystyrene and silicone rubber. The lifetime of the dye in these materials is described, measured using a simple system consisting of a pulsed xenon flash lamp light source and a PC-based data acquisition system. The linearity of the sensing membranes over the 0–100 per cent oxygen range is presented together with data on temperature sensitivity, the effects of CO₂, N₂O, H₂O and halothane, and the effects of ageing over a 90 day period. The sensors based upon polystyrene immobilised dye appear to provide the optimum characteristics for a gaseous oxygen sensor.     

Mathematical models of the spatial distribution of retinal oxygen tension and consumption,including changes upon illumination

To better understand oxygen utilization by the retina, a mathematical model of oxygen diffusion and consumption in the cat outer, avascular retina was developed by analyzing previously recorded profiles of oxygen tension (PO₂) as a function of retinal depth. Simple diffusion modelling of the oxygen distribution through the outer retina is possible because the PO₂ depends only on diffusion from the choroidal and retinal circulations and on consumption within the tissue. Several different models were evaluated in order to determine the best one from the standpoints of their ability to represent the data and to agree with physiological reality. For the steady state one-dimensional diffusion model adopted (the special three-layer diffusion model), oxygen consumption was constant through the middle layer and zero in the layers near the choroid and near the inner retina. On the average, the oxygen consuming layer, as found by nonlinear regression for each profile, extended from about 75% to 85% of the retinal depth from the vitreous. This is a narrow band through the mid-region of the photoreceptors. Oxygen consumption of the entire avascular retina, determined from fitting eight PO₂ profiles measured in light-adapted retinas, averaged 2.7 ml O₂(STP)/(100 g tissue · min), while the value determined from fitting thirty-two PO₂ profiles measured in dark-adapted retinas averaged 4.4 ml O₂(STP)/(100 g tissue · min). Consumption in the light was thus only 60% of that in the dark. This suggests that the outer retina is at greater risk of hypoxic injury in the dark than in the light, a fuinding of considerable clinical significance.     

Muscle microvascular oxygenation in chronic heart failure: role of nitric oxide availability

Aim: To test the hypothesis that diminished vascular nitric oxide availability might explain the inability of individuals with chronic heart failure (CHF) to maintain the microvascular PO₂’s (PO_2mv ∝ O₂ delivery‐to‐uptake ratio) seen in healthy animals. Methods: We superfused sodium nitroprusside (SNP; 300 μm ), Krebs–Henseleit (control, CON) and l ‐nitro arginine methyl ester (l ‐NAME; 1.5 mm ) onto the spinotrapezius muscle and measured PO_2mv by phosphorescence quenching in female Sprague–Dawley rats (n = 26) at rest and during twitch contractions (1 Hz). Seven rats served as controls (Sham) while CHF was induced by myocardial infarction. CHF rats were grouped as moderate (MOD; n = 15) and severe CHF (SEV; n = 4) according to morphological data and baseline PO_2mv. Results: In contrast to Sham and MOD,l ‐NAME did not affect the PO_2mv response (dynamics and steady‐state) of SEV when compared with CON. SNP restored the PO_2mv profile of SEV to that seen in Sham animals during CON. Specifically, the effect of l ‐NAME expressed as Δ(l ‐NAME – CON) were: Baseline PO_2mv [in mmHg, ΔSham = ?7.0 ± 1.6 (P < 0.05); ΔSEV =?1.2 ± 2.1], end‐contractions PO_2mv [in mmHg, ΔSham = ?5.0 ± 1.0 (P < 0.05); ΔSEV = ?2.5 ± 0.5] and time constant of PO_2mv decrease [in s, ΔSham = ?6.5 ± 3.0 (P < 0.05); ΔSEV = ?3.2 ± 1.8]. Conclusion: These data provide the first direct evidence that the pathological profiles of PO_2mv associated with severe CHF can be explained, in part, by a diminished vascular NO availability.     

Decreased feeding associated with acute hypoxia in rats

Rats obtained less food than normal on a cyclic-ratio schedule during brief, 1-hr exposure to either moderate hypobaric hypoxia (BP=435 Torr, PO₂≈91 Torr) or to hypoxic hypoxia (BP=750 Torr, PO₂≈90 Torr), but not during hypobaric exposure with 36.5% oxygen (BP=435 Torr, PO₂≈159 Torr). The depressed rate of feeding associated with hypoxia was nevertheless well regulated. Interpreted in terms of a regulatory model, these results suggest that hypoxia suppresses eating because it degrades the taste of food, not because it impairs feeding regulation or general activity.     

Transmural Oxygen Tension Gradients in Rat Cerebral Cortex Arterioles

Modified needle oxygen microelectrodes and vital microscopy were used to measure transmural oxygen tension gradients (PO₂) in pial arterioles with lumen diameters of 20–90  μm. A relationship between the magnitude of the transmural PO₂ gradient and arteriole wall tone was found: in control conditions, PO₂ gradients were 1.17 ± 0.06 mmHg/μm (n  = 40), while in conditions of arteriolar wall dilation the transmural PO₂ gradient decreased to 0.68 ± 0.04 mmHg/μm (p  <  0.001, n  = 38). These data provide the first measurements of transmural PO₂ gradients in pial arterioles of different calibers at different levels of vascular tone and have fundamental importance for assessing the role of arterial microvessels in tissue oxygen supply processes. The results obtained here provide evidence that oxygen consumption by the vessel wall is within the range characteristic of enveloping tissues and that oxygen consumption by the endothelial cell layer probably has no significant effect on the magnitude of the transmural PO₂ gradient. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 4, pp. 394–405, April, 2008.     

An Analysis of Hypoxia in Sheep Brain using a Mathematical Model

Cerebral blood flow (CBF) increases as arterial oxygen content falls with hypoxic (low PO₂), anemic (low hemoglobin) and carbon monoxide (CO) (high carboxyhemoglobin) hypoxia. Despite a higher arterial PO₂, CO hypoxia provokes a greater increase in CBF than hypoxic hypoxia. We analyzed published data using a compartmental mathematical model to test the hypothesis that differences in PO₂ in tissue, or a closely related vascular compartment, account for the greater response to CO hypoxia. Calculations showed that tissue, but not arteriolar, PO₂ was lower in CO hypoxia because of the increased oxyhemoglobin affinity with CO hypoxia. Analysis of studies in which oxyhemoglobin affinity was changed independently of CO supports the conclusion that changes in tissue PO₂ (or closely related capillary or venular PO₂) are predictive of alterations in CBF. We then sought to determine the role of tissue PO₂ in anemic hypoxia, with no change in arterial and little, if any, change in venous PO₂. Calculations predict a small fall in tissue PO₂ as hematocrit decreases from 55% to 20%. However, calculations show that changes in blood viscosity can account for the increase in CBF in anemic hypoxia over this range of hematocrits. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 8722-q, 8745Ft     

Spatial frequency domain imaging of intrinsic optical property contrast in a mouse model of Alzheimer's disease

Extensive changes in neural tissue structure and function accompanying Alzheimer’s disease (AD) suggest that intrinsic signal optical imaging can provide new contrast mechanisms and insight for assessing AD appearance and progression. In this work, we report the development of a wide-field spatial frequency domain imaging (SFDI) method for non-contact, quantitative in vivo optical imaging of brain tissue composition and function in a triple transgenic mouse AD model (3xTg). SFDI was used to generate optical absorption and scattering maps at up to 17 wavelengths from 650 to 970 nm in 20-month-old 3xTg mice (n = 4) and age-matched controls (n = 6). Wavelength-dependent optical properties were used to form images of tissue hemoglobin (oxy-, deoxy-, and total), oxygen saturation, and water. Significant baseline contrast was observed with 13–26% higher average scattering values and elevated water content (52 ± 2% vs. 31 ± 1%); reduced total tissue hemoglobin content (127 ± 9 μM vs. 174 ± 6 μM); and lower tissue oxygen saturation (57 ± 2% vs. 69 ± 3%) in AD vs. control mice. Oxygen inhalation challenges (100% oxygen) resulted in increased levels of tissue oxy-hemoglobin (ctO₂Hb) and commensurate reductions in deoxy-hemoglobin (ctHHb), with ~60–70% slower response times and ~7 μM vs. ~14 μM overall changes for 3xTg vs. controls, respectively. Our results show that SFDI is capable of revealing quantitative functional contrast in an AD model and may be a useful method for studying dynamic alterations in AD neural tissue composition and physiology.     

Histopathological features of murine systemic vasculitis caused by <Emphasis Type="Italic">Candida albicans</Emphasis> extract – an animal model of Kawasaki Disease

Objective and Design: We examined the histopathological features of systemic vasculitis caused in mice by injection of a Candida albicans (C. albicans) extract and investigated the principal genetic roles in the development of vasculitis.Materials and Methods: C. albicans extract was injected intraperitoneally for five consecutive days in the 1st and 5th weeks to CD-1, C57BL/6N, C3H/HeN, BALB/cAnN, DBA/2N and CBA/JN mice. At week 8, mice were killed, and histological examination was performed by light microscopy.Results: Arteritis had developed in 66% of CD-1 mice. The extramural coronary arteries and aortic root close to the orifice of coronary arteries were most frequently involved. Histologically, the characteristic feature of the arteritis was proliferative and granulomatous inflammation accompanied by numerous macrophages, lymphocytes, plasma cells and neutrophils. Fibrocellular intimal thickening with destruction of the internal elastic lamina and media was also observed. Five mouse strains after injection of C. albicans extract were clearly classified into a resistant group (CBA/JN, DBA/2N and BALB/cAnN mice) and a sensitive group (C3H/HeN and C57BL/6N mice). The inbred mouse strains which showed the same histocompatibility-2 (H-2) haplotype exhibited a different susceptibility to development of vasculitis.Conclusion: This arteritis murine model shows unique histological features that have not been observed in other animal vasculitis models and it most closely resembles Kawasaki disease in humans. The genetic control of susceptibility to induction of vasculitis by the C. albicans extract is dependent to the mouse strains, but is not linked to the H-2 loci.Received 5 July 2003; returned for revision 8 September 2003; accepted by M. Katori 3 October 2003     

Exercise breathing pattern during chronic altitude exposure

Summary Breathing pattern in response to maximal exercise was examined in four subjects during a 7-day acclimatisation to a simulated altitude of 4247 m (barometric pressure,PB = 59.5 kPa). Graded exercise tests to exhaustion were performed during normoxia (day 0), and on days 2 and 7 of hypoxia, respectively. Ventilation was significantly augmented in the hypoxic environment, as were both the mean inspiratory flow (V _T/T _I) and inspiratory duty cycle (T _I/T _TOT) components of it.V _I/T _I was increased due to a significant increase in tidal volume (VT) and a corresponding decrease in inspiratory time duration (TI). Throughout a range of exercise ventilation,T _I/T _TOT was increased due to an apparently greater decrease in expiratory time duration (T _E) with respect to TI. In all cases, the relation betweenV _T andT _I displayed a typical range 2 behaviour, with evidence of a range 3 occurring at very high ventilatory rates. There was essentially no difference observed in theV _T-T _I relation during exercise between the normoxic and hypoxic conditions. No significant changes were observed in the breathing pattern in response to exercise within the exposure period (from day 2 to day 7), although there was a discernible tendency to a higher stage 3 plateau by day 7 of altitude exposure.     

Assessment of iron nanoparticle distribution in mouse models using ultrashort-echo-time MRI

Microscopic magnetic field inhomogeneities caused by iron deposition or tissue-air interfaces may result in rapid decay of transverse magnetization in MRI. The aim of this study is to detect and quantify the distribution of iron-based nanoparticles in mouse models by applying ultrashort-echo-time (UTE) sequences in tissues exhibiting extremely fast transverse relaxation. In 24 C57BL/6 mice (two controls), suspensions containing either non-oxidic Fe or AuFeO_x nanoparticles were injected into the tail vein at two doses (200 μg and 600 μg per mouse). Mice underwent MRI using a UTE sequence at 4.7 T field strength with five different echo times between 100 μs and 5000 μs. Transverse relaxation times T₂* were computed for the lung, liver, and spleen by mono-exponential fitting. In UTE imaging, the MRI signal could reliably be detected even in liver parenchyma exhibiting the highest deposition of nanoparticles. In animals treated with Fe nanoparticles (600 μg per mouse), the relaxation time substantially decreased in the liver (3418 ± 1534 μs (control) versus 228 ± 67 μs), the spleen (2170 ± 728 μs versus 299 ± 97 μs), and the lungs (663 ± 101 μs versus 413 ± 99 μs). The change in transverse relaxation was dependent on the number and composition of the nanoparticles. By pixel-wise curve fitting, T₂* maps were calculated showing nanoparticle distribution. In conclusion, UTE sequences may be used to assess and quantify nanoparticle distribution in tissues exhibiting ultrafast signal decay in MRI.     

In vivo diffusion tensor MRI of the mouse retina: a noninvasive visualization of tissue organization

Diffusion tensor MRI (DTI) is a method for the noninvasive assessment of cellular organization and integrity in vivo. In this study, in vivo DTI was performed to demonstrate its ability to reflect photoreceptor cell alignment in adult C57BL/6 wild‐type mice. Age‐matched retinal degeneration 1 (rd1) mice were employed as a negative control, i.e. loss of the photoreceptor cell layer. In wild‐type mice, DTI‐estimated cell alignment suggests that the MR‐detected outer retinal layer comprises cells aligning perpendicular to the retinal surface, consistent with the known organization of photoreceptor cells. The MR‐detected outer retinal layer exhibits a lower apparent diffusion coefficient and higher fractional anisotropy than the other two MR‐detected retinal layers (p < 0.05 for all comparisons). In rd1 mice, the remaining MR‐detected retinal layer exhibits different cell alignment, apparent diffusion coefficient and fractional anisotropy from that of the MR‐detected outer retinal layer in wild‐type mice (p < 0.05 for all comparisons), reflecting the degeneration of photoreceptor cells in rd1 mouse retina. Overall, our findings suggest that in vivo DTI assessment of mouse retina with normal physiology or degenerative pathology is feasible. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of anesthesia on renal R2* measured by blood oxygen level‐dependent MRI

Blood oxygen level‐dependent (BOLD) MRI is increasingly being used to assess renal tissue oxygenation during disease based on the transverse relaxation rate (R₂*). In preclinical small animal models, the requisite use of anesthesia during imaging may lead to functional changes which influence R₂* and confound results. The purpose of this study was to evaluate the effects of four common anesthetic compounds on renal R₂* in healthy mice. Five female ICR mice were imaged with BOLD MRI approximately 25 min after induction with isoflurane (Iso; 1% or 1.5%, delivered in 100% O₂), ketamine/xylazine (KX), sodium pentobarbital (PB) or 2,2,2‐tribromoethanol (TBE). A significant effect of anesthetic agent on R₂* was observed in all tissue layers of the kidney, including the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla (IM). Pairwise significant differences in R₂* between specific agents were found in the cortex, OSOM and ISOM, with the largest difference observed in the ISOM between 1.5% Iso (26.6 ± 1.7 s^–1) and KX (66.0 ± 7.1 s^–1). The difference between 1% Iso and KX in the ISOM was not abolished when KX was administered with supplemental 100% O₂ or when 1% Iso was delivered in 21% O₂, indicating that the fraction of inspired oxygen did not account for the observed differences. Our results indicate that the choice of anesthesia has a large influence on the observed R₂* in mouse kidney, and anesthetic effects must be considered in the design and interpretation of renal BOLD MRI studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Overoxidation of peroxiredoxins in vivo in cultured human umbilical vein endothelial cells and in damaging light-exposed mouse retinal tissues

Reduced and overoxidized forms of peroxiredoxins (Prxs) in vivo were assessed in cultured human umbilical vein endothelial cells (HUVEC) and in damaging light-exposed mouse retinal tissues by two-dimensional (2D) gel electrophoresis and Western blot analysis. Acidic isoelectric point (pI) shift of protein spots of Prx2, 3, 4, and 6, which indicate formation of overoxidized Prx was clearly observed after treatment with H₂O₂ but was not observed after treatment with the radical initiators 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) and 2,2′-azobis [2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH); this finding indicated selective oxidation of Prx molecules by H₂O₂. Following the exposure of the eyes of mice to visible light (5000 lx) for up to 4 h, no acidic spot shift was observed in Prx1, 2, and 6 in both retinal and retinal pigment epithelial samples; this finding indicated the possible involvement of the photosensitization reaction rather than free radicals derived from H₂O₂ in this pathology. Detection of overoxidized Prxs may be applicable for assessing the mechanisms of cell/tissue damage caused by oxidative stress in vivo.     

Intracellular amyloid beta alters the tight junction of retinal pigment epithelium in 5XFAD mice

Extracellular deposit of amyloid beta (Aβ) is a common pathologic feature in both age-related macular degeneration (AMD) and Alzheimer's disease, but the role of intracellular Aβ on the tight junction of the retinal pigment epithelium (RPE) is unknown. In this study, we investigated the intracellular Aβ expression and its role on the outer blood retinal barrier in the retina of 5XFAD mice, a mouse model of Alzheimer's disease. The retina of 5XFAD mice showed the pathologic features of AMD with intracellular Aβ in the RPE. As intracellular Aβ accumulated, zonular occludens-1 and occludin were markedly attenuated and lost their integrity as tight junctions in the RPE of 5XFAD mice. Also, Aβ₄₂ uptake by ARPE-19 cells induced the tight junction breakdown of zonular occludens-1 and occludin without cell death. These results implicate that intracellular Aβ₄₂ could play a role in the breakdown of the outer blood retinal barrier in 5XFAD mice. Thus, we suggested that 5XFAD mice could be a mouse model of dry AMD with regard to the Aβ₄₂ related pathology.     

Task failure from inspiratory resistive loaded breathing: a role for inspiratory muscle fatigue?

The use of non-invasive resistive breathing to task failure to assess inspiratory muscle performance remains a matter of debate. CO₂ retention rather than diaphragmatic fatigue was suggested to limit endurance during inspiratory resistive breathing. Cervical magnetic stimulation (CMS) allows discrimination between diaphragmatic and rib cage muscle fatigue. We tested a new protocol with respect to the extent and the partitioning of inspiratory muscle fatigue at task failure. Nine healthy subjects performed two runs of inspiratory resistive breathing at 67 (12)% of their maximal inspiratory mouth pressure, respiratory rate ( f_R), paced at 18 min^–1, with a 15-min pause between runs. Diaphragm and rib cage muscle contractility were assessed from CMS-induced esophageal (P_es,tw), gastric (P_ga,tw), and transdiaphragmatic (P_di,tw) twitch pressures. Average endurance times of the first and second runs were similar [9.1 (6.7) and 8.4 (3.5) min]. P_di,tw significantly decreased from 33.1 to 25.9 cmH₂O in the first run, partially recovered (27.6 cmH₂O), and decreased further in the second run (23.4 cmH₂O). P_es,tw also decreased significantly (–5.1 and –2.4 cmH₂O), while P_ga,tw did not change significantly (–2.0 and –1.9 cmH₂O), indicating more pronounced rib cage rather than diaphragmatic fatigue. End-tidal partial pressure of CO₂ (P_ETCO₂) rose from 37.2 to 44.0 and 45.3 mmHg, and arterial oxygen saturation (S_aO₂) decreased in both runs from 98% to 94%. Thus, task failure in mouth-pressure-targeted, inspiratory resistive breathing is associated with both diaphragmatic and rib cage muscle fatigue. Similar endurance times despite different degrees of muscle fatigue at the start of the runs indicate that other factors, e.g. increases in P_ETCO₂, and/or decreases in S_aO₂, probably contributed to task-failure.     

Effects of obesity on breathing pattern, ventilatory neural drive and mechanics

The purpose of this study was to assess whether obesity induces changes in breathing pattern and ventilatory neural drive and mechanics. Measurements performed in 34 male obese subjects (BMI, 39 ± 6 kg/m²) and 18 controls (BMI, 23 ± 3 kg/m²) included anthropometric parameters, spirometry, breathing patterns, mouth occlusion pressure, maximal inspiratory pressure and work of breathing. The results show that spirometric flow (FEV₁% pred, FVC% pred) and maximal inspiratory pressure (P_Imax) were significantly lowers (p < 0.001) in obese subjects compared to controls. The (fR/VT) ratio was higher in obese subjects than in controls (p < 0.001). The increase in (fR/VT) was associated with an increase in the ratio of mean inspiratory pressure to maximal inspiratory pressure (P_I/P_Imax) and the duty cycle (T_I/T_TOT) (p < 0.001). The energy cost of breathing (W_rest/W_crit), which reflects the oxygen consumed by the respiratory muscle was greater in obese subject than in controls (p < 0.001) inducing an increase in the effective inspiratory impedance on the respiratory muscles. It is concluded that obese subjects show impairment in breathing pattern and respiratory mechanics as assessed by rapid shallow breathing leading to ventilatory failure.     

Genetics of primary and timing effects in the mnd mouse

The mnd mouse shows a spontaneous adultonset hereditary neurological disease, with motor abnormality by 6 months of age, progressing to severe spastic paralysis and premature death. The disease is autosomal recessive, with heterozygote effects seen under stress. It maps to mouse chromosome (chr) 8. Histopathology with Nissl stains documents substantial abnormalities of upper and lower motor neurons, and there is retinal degeneration beginning in the first month, even without light exposure. Increasing levels of autofluorescent lipopigment are found in both neuronal and non-neuronal tissues as the mnd mice age. Recently, NCL-like inclusions and accumulating subunit c have also been described. When mnd is outcrossed to the AKR/J genetic background, ca. 40% of the mnd/mnd F2 progeny show early onset (onset by 4.5-5 months and death by 7 months.) This accelerated timing effect seems to be strainspecific, and unlinked to the mnd gene itself. Our current working hypothesis is that the timing effect is due to 2 or 3 unlinked dominant genes with incomplete penetrance at any single locus. In a combined RFLP/PCR fragment genetic analysis, the strongest deviation from the expected ratio of AKR vs B6 alleles occurs with markers on proximal half of chr 1. Additional loci on chrs 5 and 10 may also be involved. The mechanism of interaction of these modifying genes with the primary mnd gene may offer new therapeutic avenues. © 1995 Wiley-Liss, Inc.     

A compartmental model for oxygen transport in brain microcirculation

A compartmental model is formulated for oxygen transport in the cerebrovascular bed of the brain. The model considers the arteriolar, capillary and venular vessels. The vascular bed is represented as a series of compartments on the basis of blood vessel diameter. The formulation takes into account such parameters as hematocrit, vascular diameter, blood viscosity, blood flow, metabolic rate, the nonlinear oxygen dissociation curve, arterial PO₂, P₅₀ (oxygen tension at 50% hemoglobin saturation with O₂) and carbon monoxide concentration. The countercurrent diffusional exchange between paired arterioles and venules is incorporated into the model. The model predicts significant longitudinal PO₂ gradients in the precapillary vessels. However, gradients of hemoglobin saturation with oxygen remain fairly small. The longitudinal PO₂ gradients in the postcapillary vessels are found to be very small. The effect of the following variables on tissue PO₂ is studied: blood flow, PO₂ in the arterial blood, hematocrit, P₅₀, concentration of carbon monoxide, metabolic rate, arterial diameter, and the number of perfused capillaries. The qualitative features of PO₂ distrbution in the vascular network are not altered with moderate variation of these parameters. Finally, the various types of hypoxia, namely hypoxic, anemic and carbon monoxide hypoxia, are discussed in light of the above sensitivity analysis.     

Quantitative BOLD response of the renal medulla to hyperoxic challenge at 1.5 T and 3.0 T

The aim of this study was to gage the magnitude of changes of the apparent renal medullary transverse relaxation time (ΔT₂*) induced by inhalation of pure oxygen (O₂) or carbogen (95% O₂, 5% CO₂) versus baseline breathing of room air. Eight healthy volunteers underwent 2D multi‐gradient echo MR imaging at 1.5 T and 3.0 T. Parametrical T₂* relaxation time maps were computed and average T₂* was measured in regions of interest placed in the renal medulla and cortex. The largest T₂* changes were measured in the renal medulla, with a relative ?T₂* of 33.8 ± 22.0% (right medulla) and 34.7 ± 17.6% (left medulla) as compared to room air for oxygen breathing (p > 0.01), and 53.8 ± 23.9% and 53.5 ± 33.9% (p < 0.01) for carbogen breathing, respectively at 3 T. At 1.5 T, the corresponding values were 13.7 ± 18.5% and 24.1 ± 17.1% (p < 0.01) for oxygen breathing and 23.9 ± 17.2% and 38.9 ± 37.6% (p < 0.01) for carbogen breathing. As a result, we showed that renal medullary T₂* times responded strongly to inhalation of hyperoxic gases, which may be attributed to the hypoxic condition of the medulla and subsequent reduction in deoxyhemoglobin. Copyright © 2012 John Wiley & Sons, Ltd.