pO2 Maps Research Articles

Assessment of blood-brain barrier leakage and brain oxygenation in Connexin-32 knockout mice with systemic neuroinflammation using pulse electron paramagnetic resonance imaging techniques.

The determination of blood-brain barrier (BBB) integrity and partial pressure of oxygen (pO2) in the brain is of substantial interest in several neurological applications. This study aimed to assess the feasibility of using trityl OX071-based pulse electron paramagnetic resonance imaging (pEPRI) to provide a quantitative estimate of BBB integrity and pO2 maps in mouse brains as a function of neuroinflammatory disease progression. Five Connexin-32 (Cx32)-knockout (KO) mice were injected with lipopolysaccharide to induce neuroinflammation for imaging. Three wild-type mice were also used to optimize the imaging procedure and as control animals. An additional seven Cx32-KO mice were used to establish the BBB leakage of trityl using the colorimetric assay. All pEPRI experiments were performed using a preclinical instrument, JIVA-25 (25 mT/720 MHz), at times t = 0, 4, and 6 h following lipopolysaccharide injection. Two pEPRI imaging techniques were used: (a) single-point imaging for obtaining spatial maps to outline the brain and calculate BBB leakage using the signal amplitude, and (b) inversion-recovery electron spin echo for obtaining pO2 maps. A statistically significant change in BBB leakage was found using pEPRI with the progression of inflammation in Cx32 KO animals. However, the change in pO2 values with the progression of inflammation for these animals was not statistically significant. For the first time, we show the ability of pEPRI to provide pO2 maps in mouse brains noninvasively, along with a quantitative assessment of BBB leakage. We expect this study to open new queries from the field to explore the pathology of many neurological diseases and provide a path to new treatments.

Toward a Nanoencapsulated EPR Imaging Agent for Clinical Use.

Progress toward developing a novel radiocontrast agent for determining pO2 in tumors in a clinical setting is described. The imaging agent is designed for use with electron paramagnetic resonance imaging (EPRI), in which the collision of a paramagnetic probe molecule with molecular oxygen causes a spectroscopic change which can be calibrated to give the real oxygen concentration in the tumor tissue. The imaging agent is based on a nanoscaffold of aluminum hydroxide (boehmite) with sizes from 100 to 200 nm, paramagnetic probe molecule, and encapsulation with a gas permeable, thin (10-20 nm) polymer layer to separate the imaging agent and body environment while still allowing O2 to interact with the paramagnetic probe. A specially designed deuterated Finland trityl (dFT) is covalently attached on the surface of the nanoparticle through 1,3-dipolar addition of the alkyne on the dFT with an azide on the surface of the nanoscaffold. This click-chemistry reaction affords 100% efficiency of the trityl attachment as followed by the complete disappearance of the azide peak in the infrared spectrum. The fully encapsulated, dFT-functionalized nanoparticle is referred to as RADI-Sense. Side-by-side in vivo imaging comparisons made in a mouse model made between RADI-Sense and free paramagnetic probe (OX-071) showed oxygen sensitivity is retained and RADI-Sense can create 3D pO2 maps of solid tumors CONCLUSIONS: A novel encapsulated nanoparticle EPR imaging agent has been described which could be used in the future to bring EPR imaging for guidance of radiotherapy into clinical reality.

Evolution of the hypoxic compartment on sequential oxygen partial pressure maps during radiochemotherapy in advanced head and neck cancer.

Longitudinal Positron Emission Tomography (PET) with hypoxia-specific radiotracers allows monitoring the time evolution of regions of increased radioresistance and may become fundamental in determining the radiochemotherapy outcome in Head-and-Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the evolution of the hypoxic target volume on oxygen partial pressure maps (pO2-HTV) derived from 18FMISO-PET images acquired before and during radiochemotherapy and to uncover correlations between extent and severity of hypoxia and treatment outcome. 18FMISO-PET/CT images were acquired at three time points (before treatment start, in weeks two and five) for twenty-eight HNSCC patients treated with radiochemotherapy. The images were converted into pO2 maps and corresponding pO2-HTVs (pO2-HTV1, pO2-HTV2, pO2-HTV3) were contoured at 10mmHg. Different parameters describing the pO2-HTV time evolution were considered, such as the percent and absolute difference between the pO2-HTVs (%HTVi,j and HTVi-HTVj with i,j=1, 2, 3, respectively) and the slope of the linear regression curve fitting the pO2-HTVs in time. Correlations were sought between the pO2-HTV evolution parameters and loco-regional recurrence (LRR) using the Receiver Operating Characteristic method. The Area Under the Curve values for %HTV1,2, HTV1-HTV2, HTV1-HTV3 and the slope of the pO2-HTV linear regression curve were 0.75 (p=0.04), 0.73 (p=0.02), 0.73 (p=0.02) and 0.75 (p=0.007), respectively. Other parameter combinations were not statistically significant. The pO2-HTV evolution during radiochemotherapy showed predictive value for LRR. The changes in the tumour hypoxia during the first two treatment weeks may be used for adaptive personalized treatment approaches.

Spatially resolved estimation of metabolic oxygen consumption from optical measurements in cortex.

.Significance: The cerebral metabolic rate of oxygen () is an important indicator of brain function and pathology. Knowledge about its magnitude is also required for proper interpretation of the blood oxygenation level-dependent (BOLD) signal measured with functional MRI. Despite the need for estimating , no gold standard exists. Traditionally, the estimation of has been pursued with somewhat indirect approaches combining several different types of measurements with mathematical modeling of the underlying physiological processes. The recent ability to measure the level of oxygen () in cortex with two-photon resolution in in vivo conditions has provided a more direct way for estimating , but has so far only been used to estimate the average close to cortical penetrating arterioles in rats.Aim: The aim of this study was to propose a method to provide spatial maps of based on two-photon measurements.Approach: The method has two key steps. First, the maps are spatially smoothed to reduce the effects of noise in the measurements. Next, the Laplace operator (a double spatial derivative) in two spatial dimensions is applied on the smoothed maps to obtain spatially resolved estimates.Result: The smoothing introduces a bias, and a balance must be found where the effects of the noise are sufficiently reduced without introducing too much bias. In this model-based study, we explored this balance using synthetic model-based data, that is, data where the spatial maps of were preset and thus known. The corresponding maps were found by solving the Poisson equation, which relates and . MATLAB code for using the method is provided.Conclusion: Through this model-based study, we propose a method for estimating with high spatial resolution based on measurements of in cerebral cortex.

Mapping transient hypoxia from in situ activation of 15O by photon beams: A simulation study

BackgroundQuantifying acute hypoxia is desirable yet challenging in radiation therapy. Here, we report a simulation study on the feasibility of mapping acute hypoxia, generated in a 2D simulation vasculature of a pancreas model, using in situ15O washout images. The influence of varying tissue types and photon beam energies (i.e., 20, 25, 30 and 50 MeV) was investigated. Method and materialsAn ex vivo autoradiography 64Cu-ATSM image of a rat tumor was used as a surrogate for the microvessel density map. It was then input to a reaction diffusion model to simulate a steady state partial oxygen pressure (pO2) map. The resulting in situ15O-PET image was generated using a high-energy photon beam and included both mobile and immobile 15O. An image of 15O washout was produced by subtracting the immobile decay portion from the overall decay curve in the in situ PET image, (i.e., fitting the sum of the two exponentials for mobile and immobile oxygen) using different decay constants. Finally, the pO2 map and in situ15O washout images were thresholded and compared. ResultsThe reaction diffusion model showed a heterogeneous distribution of pO2 with mean values of 27.4 and 16.8 mmHg, depending on microvessel permeability, tumor vasculature structure, and architecture. A 62% threshold of the mean intensity in the in situ15O washout image was found to agree reasonably well with the original hypoxia map using 5 mmHg as a cutoff value. These parameters yielded two sets of images with hypoxia fractions of 0.146 and 0.152, respectively. ConclusionsThis simulation study demonstrates the feasibility of mapping acute hypoxia using tissue in situ activation with high-energy photons. With recent advances in in-room or in-beam PET and more work being performed on thresholding the in situ15O washout, mapping acute hypoxia in real time may become a reality.

Imaging of Tumor-Specific Hypoxia Dynamics and Its Significance in Radiation Biology

Hypoxia has been known to be a feature associated with tumor radioresistance. So far, clinical strategies to overcome chronic hypoxia due to the limitation of the oxygen diffusion have been designed. However, intermittent or acute/cycling hypoxia, whose frequency can range between a few cycles per minutes to hours, is receiving increased attention, because this type of hypoxia has been reported to have an influence on tumor malignancy as well as treatment resistance via increased expression of pro-survival pathways. Therefore, a priori information on fluctuating hypoxia can be important in clinical treatment planning, but complicated dynamics makes it difficult to elucidate biological significance of intermittent hypoxia.Here, we illustrate the use of pulsed electron spin resonance imaging (ESRI) as a novel imaging method to directly monitor fluctuating oxygenation i.e. cycling hypoxia in transplanted tumors. A common resonator platform for both ESRI and magnetic resonance imaging (MRI) provided pO2 maps with anatomical guidance without positional movement. Oxygen images every 3 min in pO2 could visualize the rapid oxygen fluctuation and distinguish the cycling hypoxia and chronic hypoxia. Furthermore, we have examined the vascular renormalization process by longitudinally pO2 mapping during treatments with a multi-tyrosine kinase inhibitor sunitinib. Transient improvement in tumor oxygenation and the decrease of cycling tumor hypoxia were visualized by ESRI 2 to 4 days following antiangiogenic treatments. Radiation treatment during this time period of improved oxygenation by antiangiogenic therapy resulted in a synergistic delay in tumor growth.In conclusion, this ESRI technique combined with MRI, may offer a powerful clinical tool to noninvasively detect variable hypoxic status in tumors and to identify a window of vascular renormalization to maximize the effects of combination therapy with antiangiogenic drugs.

Another step forward for methods for studying renal oxygenation

All available methods for assessing renal oxygenation are limited either in terms of their temporal or spatial resolution, their ability to quantify tissue oxygen tension (PO2), or in the settings in which they can be applied. Kodama and colleagues have developed a new method that utilizes dynamic nuclear polarization magnetic resonance imaging and an oxygen-sensitive paramagnetic agent (OX63). This new method generates quantitative maps of renal tissue PO2 in millimeters of mercury.

Lipid nanocapsules as in vivo oxygen sensors using magnetic resonance imaging

Hypoxia is common occurrence of the tumour microenvironment, wherein heterogeneous gradients of O2 give rise to tumoural cells which are highly malignant, metastatic, and resistant to therapeutic efforts. Thus, the assessment and imaging of hypoxia is essential for tumour diagnosis and treatment. Magnetic resonance imaging and, more specifically, the quantitative assessment of longitudinal relaxation time enhancement, was shown to enable the mapping of oxygen in tumours with increased sensitivity for lipids as compared to water signal. Unfortunately, this can only be applied to tumours with high lipid content. To overcome this issue, we propose the use of lipid nanocapsules (LNCs). LNCs have been demonstrated as excellent core-shell nanocarriers, wherein the lipidic-core is used for lipophilic drug encapsulation, enabling treatment of highly malignant tumours. Herein, however, we exploited the lipidic-core of the LNCs to develop a simple but effective technique to increase the lipidic content within tissues to enable the assessment and mapping of pO2. LNCs were prepared using the phase-inversion technique to produce 60 nm sized nanoparticles, and in vitro studies demonstrated the permeability and responsiveness of LNCs to O2. To evaluate the ability of LNCs to respond to changes in pO2in vivo, after a hyperoxic challenge, three animal models, namely a normal tissue model (gastrocnemius muscle tissue) and two tumour tissue models (subcutaneous fibrosarcoma and intracerebral glioblastoma) were explored. LNCs were found to be responsive to variation of O2in vivo. Moreover, the use of MRI enabled the mapping of oxygen gradients and heterogeneity within tumours.

EPR-based oximetric imaging: a combination of single point-based spatial encoding and T1 weighting.

Spin-lattice relaxation rate (R1 )-based time-domain EPR oximetry is reported for in vivo applications using a paramagnetic probe, a trityl-based Oxo71. The R1 dependence of the trityl probe Oxo71 on partial oxygen pressure (pO2 ) was assessed using single-point imaging mode of spatial encoding combined with rapid repetition, similar to T1 -weighted MRI, for which R1 was determined from 22 repetition times ranging from 2.1 to 40.0 μs at 300 MHz. The pO2 maps of a phantom with 3 tubes containing 2 mM Oxo71 solutions equilibrated at 0%, 2%, and 5% oxygen were determined by R1 and apparent spin-spin relaxation rate ( R2*) simultaneously. The pO2 maps derived from R1 and R2* agreed with the known pO2 levels in the tubes of Oxo71. However, the histograms of pO2 revealed that R1 offers better pO2 resolution than R2* in low pO2 regions. The SDs of pixels at 2% pO2 (15.2 mmHg) were about 5 times lower in R1 -based estimation than R2*-based estimation (mean ± SD: 13.9 ± 1.77 mmHg and 18.3 ± 8.70 mmHg, respectively). The in vivo pO2 map obtained from R1 -based assessment displayed a homogeneous profile in low pO2 regions in tumor xenografts, consistent with previous reports on R2*-based oximetric imaging. The scan time to obtain the R1 map can be significantly reduced using 3 repetition times ranging from 4.0 to 12.0 μs. Using the single-point imaging modality, R1 -based oximetry imaging with useful spatial and oxygen resolutions for small animals was demonstrated.

147 - Quantitative pO2 Mapping Using Electron Paramagnetic Resonance Imaging in Orthotopic Murine Glioma

Glioblastoma is the most frequent primary malignant brain tumor and its malignant nature is closely associated with hypoxia. Thus, it would be useful for treatment of glioblastomas to evaluate intratumoral distribution of hypoxia for determining the therapeutic planning as well as assessment of its effectiveness during the therapy. Electron paramagnetic resonance imaging (EPRI), is an imaging technique which can generate quantitative maps of oxygen in vivo using the exogenous paramagnetic compound, triarylmethyl. In this study, we examined the feasibility of EPRI for assessment of oxygen distribution in the orthotopic glioblastoma models of U251 and U87. Heterogeneous distribution of pO2 between 0 and 50 mmHg was observed throughout the tumors except for the normal brain tissue. U251 glioblastoma was more likely to be exposed to hypoxia than U87 (median pO2; 29.7 mmHg and 18.2 mmHg, P = 0.028, in U87 and U251, respectively). The ratio of hypoxic fraction where pO2 was less than 10 mmHg showed a good correlation with pimonidazole-positive region. In subcutaneous xenograft model, irradiation was relatively less effective for U251 compared to U87, suggesting the high population of hypoxic cells. In conclusion, EPRI is a feasible method to evaluate oxygen distribution in the brain tumor.

Noninvasive Absolute Electron Paramagnetic Resonance Oxygen Imaging for the Assessment of Tissue Graft Oxygenation

Oxygen is the single most important molecule for sustaining life and, therefore, an important variable in tissue engineering and regenerative medicine. It has been shown that the change in oxygen concentration in an artificial or tissue-engineered graft affects cell survival, differentiation, and tissue growth in profound ways. However, at present, there are no reliable methods to map partial oxygen pressure (pO2) in growing artificial tissues. Here, we adapt and test the suitability of electron paramagnetic resonance oxygen imaging (EPROI) in assessing tissue graft oxygenation in vitro. EPROI is an established method to assess absolute pO2 and has been widely applied to study tumor hypoxia in small animals. In this study, we demonstrate the feasibility of EPROI in evaluating oxygen dynamics in tissue grafts. We measured oxygen concentration in mesenchymal stem cell (MSC)-seeded polylactic-co-glycolic acid (PLGA) scaffolds with variable porosity. The pO2 maps of these scaffolds showed that the mean pO2 inside the scaffolds was smaller than the ambient air pO2 (21% oxygen, 160 torr) and was gradually increased with increasing pore size. We assessed the local oxygen dynamics of the MSC-seeded osteogenic scaffold made from collagen-chitosan hydrogels in a partially sealed Eppendorf tube. The change in pO2 values as a function of time inside the graft showed that the cells had used available oxygen within first 2 h of the experiment and then went to a dormant low oxygen consumption state until the oxygen supply was reestablished. Collectively, these data suggest that EPROI could be successfully used for mapping pO2 in tissue-engineered grafts. The knowledge of tissue graft oxygenation may be used to improve scaffold design and to assess the tissue viability and growth.

Retinal oxygen: from animals to humans.

This article discusses retinal oxygenation and retinal metabolism by focusing on measurements made with two of the principal methods used to study O2 in the retina: measurements of PO2 with oxygen-sensitive microelectrodes invivo in animals with a retinal circulation similar to that of humans, and oximetry, which can be used non-invasively in both animals and humans to measure O2 concentration in retinal vessels. Microelectrodes uniquely have high spatial resolution, allowing the mapping of PO2 in detail, and when combined with mathematical models of diffusion and consumption, they provide information about retinal metabolism. Mathematical models, grounded in experiments, can also be used to simulate situations that are not amenable to experimental study. New methods of oximetry, particularly photoacoustic ophthalmoscopy and visible light optical coherence tomography, provide depth-resolved methods that can separate signals from blood vessels and surrounding tissues, and can be combined with blood flow measures to determine metabolic rate. We discuss the effects on retinal oxygenation of illumination, hypoxia and hyperoxia, and describe retinal oxygenation in diabetes, retinal detachment, arterial occlusion, and macular degeneration. We explain how the metabolic measurements obtained from microelectrodes and imaging are different, and how they need to be brought together in the future. Finally, we argue for revisiting the clinical use of hyperoxia in ophthalmology, particularly in retinal arterial occlusions and retinal detachment, based on animal research and diffusion theory.

Fast dynamic electron paramagnetic resonance (EPR) oxygen imaging using low-rank tensors

Hypoxic tumors are resistant to radiotherapy, motivating the development of tools to image local oxygen concentrations. It is generally believed that stable or chronic hypoxia is the source of resistance, but more recent work suggests a role for transient hypoxia. Conventional EPR imaging (EPRI) is capable of imaging tissue pO2in vivo, with high pO2 resolution and 1mm spatial resolution but low imaging speed (10min temporal resolution for T1-based pO2 mapping), which makes it difficult to investigate the oxygen changes, e.g., transient hypoxia. Here we describe a new imaging method which accelerates dynamic EPR oxygen imaging, allowing 3D imaging at 2 frames per minute, fast enough to image transient hypoxia at the “speed limit” of observed pO2 change. The method centers on a low-rank tensor model that decouples the tradeoff between imaging speed, spatial coverage/resolution, and number of inversion times (pO2 accuracy). We present a specialized sparse sampling strategy and image reconstruction algorithm for use with this model. The quality and utility of the method is demonstrated in simulations and in vivo experiments in tumor bearing mice.

Mapping oxygen concentration in the awake mouse brain.

Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism.

Oxygen Mapping within Healthy and Acutely Infarcted Brain Tissue in Humans Using the NMR Relaxation of Lipids: A Proof-Of-Concept Translational Study.

The clinical applicability of brain oxygenation mapping using the MOBILE (Mapping of Oxygen By Imaging Lipids relaxation Enhancement) magnetic resonance (MR) technique was assessed in the clinical setting of normal brain and of acute cerebral ischemia as a founding proof-of-concept translational study. Changes in the oxygenation level within healthy brain tissue can be detected by analyzing the spin-lattice proton relaxation (‘Global T 1 ’ combining water and lipid protons) because of the paramagnetic properties of molecular oxygen. It was hypothesized that selective measurement of the relaxation of the lipid protons (‘Lipids T 1 ’) would result in enhanced sensitivity of pO2 mapping because of higher solubility of oxygen in lipids than in water, and this was demonstrated in pre-clinical models using the MOBILE technique. In the present study, 12 healthy volunteers and eight patients with acute (48–72 hours) brain infarction were examined with the same clinical 3T MR system. Both Lipids R1 (R1 = 1/T1) and Global R1 were significantly different in the infarcted area and the contralateral unaffected brain tissue, with a higher statistical significance for Lipids R1 (median difference: 0.408 s-1; p<0.0001) than for Global R1 (median difference: 0.154 s-1; p = 0.027). Both Lipids R1 and Global R1 values in the unaffected contralateral brain tissue of stroke patients were not significantly different from the R1 values calculated in the brain tissue of healthy volunteers. The main limitations of the present prototypic version of the MOBILE sequence are the long acquisition time (4 min), hampering robustness of data in uncooperative patients, and a 2 mm slice thickness precluding accurate measurements in small infarcts because of partial volume averaging effects.

Hypoxia Imaging of Tumor and Spatiotemporal Analysis during Oxygen Inhalation

SUMMARYTumor hypoxia is considered a potential therapeutic problem because it reduces the effects of radiation therapy. Clinical experience has shown that long‐term tumor oxygenation cannot be achieved with oxygen inhalation, but the mechanisms behind this phenomenon remain unknown. In this study, we designed an optical system for evaluating spatiotemporal changes in tissue oxygen tension (pO2) by phosphorescence quenching. The system can measure continuous changes in pO2 at a fixed point and can also perform two‐dimensional mapping of pO2 in any part of the tumor tissue. We implanted tumor tissue in a dorsal skinfold chamber (DSC) of C57BL/6 mice and observed tumor growth. The mice received oxygen inhalation and pO2 was measured. Tumor pO2 increased after inhalation but the oxygen level was not maintained despite continuous inhalation of pure oxygen; the tumor returned to a hypoxic state. These results mimic the clinical experience of oxygen inhalation treatment in radiation therapy. Our system reproduces the repeat hypoxic phenomenon in a murine tumor model and can be used to determine the mechanisms of oxygen metabolism in tumors.

High-Resolution Topography-Following Chemical Mapping of Ocean Hypoxia by Use of an Autonomous Underwater Vehicle: The Santa Monica Basin Example

AbstractThis paper reports on the execution of a combined chemical sensing/high-resolution terrain-following autonomous underwater vehicle (AUV) survey to explore the fine structure and functional boundaries of the Santa Monica Basin suboxic zone and its relationship to topography. An AUV mapping vehicle is used in a novel configuration—combining the mapping vehicle tail section, with precision inertial navigation and acoustic communications systems, with CTD/O2, NO3 sensing, and Gulper water sampling systems. The challenge was to perform a long-distance near-bottom physical/chemical survey in deep water without any intermediate surfacing to disrupt the survey or require the vehicle to surface in areas of heavy ship traffic. Some 210 km of AUV cruise track at ≈10 m above bottom were accomplished during a 3-day survey. The dissolved oxygen concentration [O2] data are combined with temperature T, salinity S, and hydrostatic pressure P to produce maps of oxygen partial pressure pO2 that help define the limits at which the oceanic supply of O2 can match the O2 demands required to sustain various forms of marine life. The chemical NO3 sensing was included to define the critical pO2 boundary at which NO3 reduction occurs. The combination of a high-resolution terrain-following AUV with chemical sensors is important for a diverse array of investigations, including the study of vent sites, and for locating the source of chemical signals originating from the seafloor. The hypoxic basin example here permits better discrimination between general climate/circulation controls on hypoxia and more specific point-source-driven processes.

3He pO2 mapping is limited by delayed‐ventilation and diffusion in chronic obstructive pulmonary disease

Lung pO2 mapping with (3)He MRI assumes that the sources of signal decay with time during a breath-hold are radiofrequency depolarization and oxygen-dependent T1 relaxation, but the method is sensitive to other sources of spatio-temporal signal change such as diffusion. The purpose of this work was to assess the use of (3)He pO2 mapping in patients with chronic obstructive pulmonary disease. Ten patients with moderate to severe chronic obstructive pulmonary disease were scanned with a 3D single breath-hold pO2 mapping sequence. Images showed signal increasing over time in some lung regions due to delayed ventilation during breath-hold. Regions of physically unrealistic negative pO2 values were seen in all patients, and regional mean pO2 values of -0.3 bar were measured in the two patients most affected by delayed ventilation (where mean time to signal onset was 3-4 s). Movement of gas within the lungs during breath-hold causes regional changes in signal over time that are not related to oxygen concentration, leading to erroneous pO2 measurements using the linear oxygen-dependent signal decay model. These spatio-temporal sources of signal change cannot be reliably separated at present, making pO2 mapping using this methodology unreliable in chronic obstructive pulmonary disease patients with significant bullous emphysema or delayed ventilation.

Human Vitreous: MR Imaging of Oxygen Partial Pressure

To develop a magnetic resonance (MR) imaging approach to noninvasively image quantitative Po(2) in the human vitreous. Human studies were approved by the institutional review board with informed consent obtained from all subjects and were HIPAA compliant. Animal studies were performed with animal care committee approval. An MR imaging method to measure the longitudinal relaxation rate, or R1, of water was implemented with a 3.0-T MR imager. R1 was calibrated in water phantoms at multiple Po(2) and temperature conditions (n = 10) and in ex vivo animal vitreous (n = 2). Vitreous Po(2) was imaged in three human volunteers (age range, 26-28 years) in multiple sessions on separate days to evaluate reproducibility. The effects of temperature and ambient air were evaluated by acquiring data with the eye open and closed. Statistical analysis consisted of t tests, with P less than .05 indicating significant difference. Calibrations of phantoms and ex vivo vitreous yielded an R1 association with oxygen of 0.209 sec(-1) + Po(2) ⋅ 2.07 × 10(-4) sec(-1)/mm Hg at 37°C, and an association with temperature (Δ[1/R1]/ΔTemperature) of 0.106 sec/°C ± 0.009 (standard deviation). A difference in R1 was found between the phantoms and vitreous. If uncorrected, vitreal Po(2) would be significantly overestimated (P < .001). In vivo human vitreous Po(2) maps were spatially heterogeneous, with a whole vitreous Po(2) of 16.7 mm Hg ± 6.5 (eye closed). Measurements between open and closed eyes showed spatially dependent R1 differences, which translated to temperature differences of 0.34°-0.83°C across the eye. This study established an MR imaging protocol to image quantitative vitreous Po(2) noninvasively and evaluated effects from vitreal macromolecules, temperature gradients, and ambient air on vitreal Po(2) values. Measurement of vitreous Po(2) with MR imaging has the potential to be used to study eye diseases noninvasively.

Chronic and Cyclic Hypoxia in Fractionated Radiation Therapy

Chronic and Cyclic Hypoxia in Fractionated Radiation Therapy