Oxygen-enhanced Magnetic Resonance Research Articles

Comparison of 2D and 3D oxygen-enhanced MRI of the placenta.

Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) of the human placenta is potentially a sensitive marker of in vivo oxygenation. This methodological study shows that full coverage of the placenta is possible using 3D mapping of the change in longitudinal relaxation rate (ΔR1), in a group of healthy pregnant subjects breathing elevated levels of oxygen. Twelve pregnant subjects underwent a comparison of 2D and 3D OE-MRI. ΔR1 was mapped for a single 2D slice (ss-2D), a single matched-slice from the 3D volume (ss-3D) and the full 3D volume (vol-3D). The group-average median ΔR1 values for ss-3D (0.023 s-1) and vol-3D (0.022 s-1) do not differ significantly from ss-2D (0.020 s-1), when compared using a two-tailed paired t-test (ss-3D (p = 0.58) and vol-3D (p = 0.70)). However, median baseline T1 (T1b) for ss-2D was higher (1603 ms) than T1b for ss-3D (1540 ms, p = 0.07) and significantly higher than vol-3D (1515 ms, p = 0.02), when compared using a two-tailed paired t-test. In contrast with previous studies, no correlation of median ΔR1 with gestation age at scan for the normal group (N = 10) was observed for ss-2D, likely due to the smaller gestational range. Full volume OE-MRI maps reveal sensitivity to changes in ΔR1, with some participants showing an enhanced gradient in the intermediate space between the fetal and maternal sides of the placenta in the 3D data. This study shows that it is feasible to acquire whole placental volume OE-MRI data in women with healthy pregnancy.

Oxygen-enhanced MRI assessment of tumour hypoxia in head and neck cancer is feasible and well tolerated in the clinical setting

BackgroundTumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Current positron emission tomography-based hypoxia imaging techniques are not routinely available in many centres. We investigated if an alternative technique called oxygen-enhanced magnetic resonance imaging (OE-MRI) could be performed in HNSCC.MethodsA volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was implemented on 1.5-T clinical scanners. Participants were scanned breathing room air and during high-flow oxygen administration. Oxygen-induced changes in T1 times (ΔT1) and R2* rates (ΔR2*) were measured in malignant tissue and healthy organs. Unequal variance t-test was used. Patients were surveyed on their experience of the OE-MRI protocol.ResultsFifteen patients with HNSCC (median age 59 years, range 38 to 76) and 10 non-HNSCC subjects (median age 46.5 years, range 32 to 62) were scanned; the OE-MRI acquisition took less than 10 min and was well tolerated. Fifteen histologically confirmed primary tumours and 41 malignant nodal masses were identified. Median (range) of ΔT1 times and hypoxic fraction estimates for primary tumours were -3.5% (-7.0 to -0.3%) and 30.7% (6.5 to 78.6%) respectively. Radiotherapy-responsive and radiotherapy-resistant primary tumours had mean estimated hypoxic fractions of 36.8% (95% confidence interval [CI] 17.4 to 56.2%) and 59.0% (95% CI 44.6 to 73.3%), respectively (p = 0.111).ConclusionsWe present a well-tolerated implementation of dynamic, volumetric OE-MRI of the head and neck region allowing discernment of differing oxygen responses within biopsy-confirmed HNSCC.Trial registrationClinicalTrials.gov, NCT04724096. Registered on 26 January 2021.Relevance statementMRI of tumour hypoxia in head and neck cancer using routine clinical equipment is feasible and well tolerated and allows estimates of tumour hypoxic fractions in less than ten minutes.Key points• Oxygen-enhanced MRI (OE-MRI) can estimate tumour hypoxic fractions in ten-minute scanning.• OE-MRI may be incorporable into routine clinical tumour imaging.• OE-MRI has the potential to predict outcomes after radiotherapy treatment.Graphical

Impact of Vasodilation on Oxygen-Enhanced Functional Lung MRI at 0.55 T.

Oxygen-enhanced magnetic resonance imaging (OE-MRI) can be used to assess regional lung function without ionizing radiation. Inhaled oxygen acts as a T1-shortening contrast agent to increase signal in T1-weighted (T1w) images. However, increase in proton density from pulmonary hyperoxic vasodilation may also contribute to the measured signal enhancement. Our aim was to quantify the relative contributions of the T1-shortening and vasodilatory effects of oxygen to signal enhancement in OE-MRI in both swine and healthy volunteers. We imaged 14 anesthetized female swine (47 ± 8 kg) using a prototype 0.55 T high-performance MRI system while experimentally manipulating oxygenation and blood volume independently through oxygen titration, partial occlusion of the vena cava for volume reduction, and infusion of colloid fluid (6% hydroxyethyl starch) for volume increase. Ten healthy volunteers were imaged before, during, and after hyperoxia. Two proton density-weighted (PDw) and 2 T1w ultrashort echo time images were acquired per experimental state. The median PDw and T1w percent signal enhancement (PSE), compared with baseline room air, was calculated after image registration and correction for lung volume changes. Differences in median PSE were compared using Wilcoxon signed rank test. The PSE in PDw images after 100% oxygen was similar in swine (1.66% ± 1.41%, P = 0.01) and in healthy volunteers (1.99% ± 1.79%, P = 0.02), indicating that oxygen-induced pulmonary vasodilation causes ~2% lung proton density increase. The PSE in T1w images after 100% oxygen was also similar (swine, 9.20% ± 1.68%, P < 0.001; healthy volunteers, 10.10% ± 3.05%, P < 0.001). The PSE in T1w enhancement was oxygen dose-dependent in anesthetized swine, and we measured a dose-dependent PDw image signal increase from infused fluids. The contribution of oxygen-induced vasodilation to T1w OE-MRI signal was measurable using PDw imaging and was found to be ~2% in both anesthetized swine and in healthy volunteers. This finding may have implications for patients with regional or global hypoxia or vascular dysfunction undergoing OE-MRI and suggest that PDw imaging may be useful to account for oxygen-induced vasodilation in OE-MRI.

Simultaneous multiple breath washout and oxygen-enhanced magnetic resonance imaging in healthy adults

Lung function testing and lung imaging are commonly used techniques to monitor respiratory diseases, such as cystic fibrosis (CF). The nitrogen (N2) multiple-breath washout technique (MBW) has been shown to detect ventilation inhomogeneity in CF, but the underlying pathophysiological processes that are altered are often unclear. Dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) could potentially be performed simultaneously with MBW because both techniques require breathing of 100% oxygen (O2) and may allow for visualisation of alterations underlying impaired MBW outcomes. However, simultaneous MBW and OE-MRI has never been assessed, potentially as it requires a magnetic resonance (MR) compatible MBW equipment. In this pilot study, we assessed whether MBW and OE-MRI can be performed simultaneously using a commercial MBW device that has been modified to be MR-compatible.We performed simultaneous measurements in five healthy volunteers aged 25–35 years. We obtained O2 and N2 concentrations from both techniques, and generated O2 wash-in time constant and N2 washout maps from OE-MRI data.We obtained good quality simultaneous measurements in two healthy volunteers due to technical challenges related to the MBW equipment and poor tolerance. Oxygen and N2 concentrations from both techniques, as well as O2 wash-in time constant maps and N2 washout maps could be obtained, suggesting that simultaneous measurements may have the potential to allow for comparison and visualization of regional differences in ventilation underlying impaired MBW outcomes.Simultaneous MBW and OE-MRI measurements can be performed with a modified MBW device and may help to understand MBW outcomes, but the measurements are challenging and have poor feasibility.

141 Oxygen-enhanced magnetic resonance imaging and multiple-breath washout with or without short extension as novel functional assessments of cystic fibrosis lung health

141 Oxygen-enhanced magnetic resonance imaging and multiple-breath washout with or without short extension as novel functional assessments of cystic fibrosis lung health

A General Model to Calculate the Spin-Lattice Relaxation Rate (R1) of Blood, Accounting for Hematocrit, Oxygen Saturation, Oxygen Partial Pressure, and Magnetic Field Strength Under Hyperoxic Conditions.

Under normal physiological conditions, the spin-lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen-enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects. To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO2 , PO2 , and B0 under both normal physiological and hyperoxic conditions. Mathematical modeling. One hundred and twenty-six published values of R1 from phantoms and animal models. 5-8.45 T. We propose a two-compartment nonlinear model to calculate R1 as a function of hematocrit, PO2 , and B0. The Akaike Information Criterion (AIC) was used to select the best-performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO2 , and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO2 > 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R2 ), and Bland-Altman analysis. The effect of volume fraction constants and was assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO2 , and PO2 of the literature data points. Bland-Altman, AIC, MSE, coefficient of determination (R2 ), SD. The model estimates agreed well with the literature values of R1 of blood (R2 =0.93, MSE=0.0013 s-2 ), and its performance was consistent across the range of parameters: B0=1.5-8.45 T, SO2 =0.40-1, PO2 =30-700 mmHg. Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen-enhanced MRI and oxygen-delivery experiments. 3 TECHNICAL EFFICACY: Stage 1.

Hypoxia Imaging As a Guide for Hypoxia-Modulated and Hypoxia-Activated Therapy.

Significance: Oxygen imaging techniques, which can probe the spatiotemporal heterogeneity of tumor oxygenation, could be of significant clinical utility in radiation treatment planning and in evaluating the effectiveness of hypoxia-activated prodrugs. To fulfill these goals, oxygen imaging techniques should be noninvasive, quantitative, and capable of serial imaging, as well as having sufficient temporal resolution to detect the dynamics of tumor oxygenation to distinguish regions of chronic and acute hypoxia. Recent Advances: No current technique meets all these requirements, although all have strengths in certain areas. The current status of positron emission tomography (PET)-based hypoxia imaging, oxygen-enhanced magnetic resonance imaging (MRI), 19F MRI, and electron paramagnetic resonance (EPR) oximetry are reviewed along with their strengths and weaknesses for planning hypoxia-guided, intensity-modulated radiation therapy and detecting treatment response for hypoxia-targeted prodrugs. Critical Issues: Spatial and temporal resolution emerges as a major concern for these areas along with specificity and quantitative response. Although multiple oxygen imaging techniques have reached the investigative stage, clinical trials to test the therapeutic effectiveness of hypoxia imaging have been limited. Future Directions: Imaging elements of the redox environment besides oxygen by EPR and hyperpolarized MRI may have a significant impact on our understanding of the basic biology of the reactive oxygen species response and may extend treatment possibilities.

Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients.

To demonstrate, in patients with cystic fibrosis (CF), the correlation between three-dimensional dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements and computed tomography Brody score (CF-CT) and lung function testing (LFT). Twenty-one patients (median age, 25 years; female, n = 8) with a range of CF lung disease and five healthy volunteers (median age, 31 years; female, n = 2) underwent OE-MRI performed on a 1.5-T MRI scanner. Coronal volumes were acquired while patients alternately breathed room air and 100% oxygen. Pre-oxygen T1 was measured. Dynamic series of T1-weighted volumes were then obtained while breathing oxygen. T1-parameter maps were generated and the following OE-MRI parameters were measured: oxygen uptake (ΔPO2max), wash-in time and wash-out time. High-resolution CT and LFT were performed. The relationship between CF-CT, LFT and OE-MRI parameters were evaluated using Pearson correlation for the whole lung and regionally. Mean CF-CT was 24.1±17.1. Mean ΔPO2max and mean wash-in as well as skewness of wash-out showed significant correlation with CF-CT (ΔPO2max: r = -0.741, p < 0.001; mean wash-in: r = 0.501, p = 0.017; skewness of wash-out: r = 0.597, p = 0.001). There was significant correlation for the whole lung and regionally between LFT parameters and OE-MR (ΔPO2max: r = 0.718, p < 0.001; wash-in: r = -0.576, p = 0.003; wash-out skewness: r = -0.552, p = 0.004). Functional lung imaging using OE-MRI has the capability to assess the severity of CF lung disease and shows a significant correlation with LFT and CF-CT. • Oxygen-enhanced MRI might play a future role in evaluation and follow-up of cystic fibrosis. • Heterogeneity of parameter maps reflects localised functional impairment in cystic fibrosis. • Avoidance of cumulative radiation burden in CF is feasible using OE-MRI.

Investigation of hypoxia conditions using oxygen-enhanced magnetic resonance imaging measurements in glioma models.

The objective of this study was to determine whether using oxygen-enhanced magnetic resonance imaging (OE-MRI) to assess hypoxia is feasible and whether historical measurements, pO2 changes, and percentage of signal intensity changes (PSIC) are correlated in an animal model of glioma. A total of 25 Sprague-Dawley rats were used to establish C6 brain or subcutaneous glioma model. Nine rats with brain gliomas underwent OE-MRI followed by histopathologic analysis to assess microvessel density and hypoxia. Another 11 rats were underwent OE-MRI and were followed for a survival analysis. Time–T1-weighted MR signal intensity (SI) curves and PSIC maps were derived from the OE-MRI data. High–regions of interests (ROI-h; PSIC > 10%) and low-ROIs (ROI-l; PSIC < 10%) were defined on the PSIC maps. To validate the PSIC map for identifying tumor hypoxia, we subjected an additional 5 rats with subcutaneous glioma to OE-MRI and pO2 measurements. All tumors showed regional heterogeneity on the PSIC maps. For the brain tumors, the time-SI curves for the ROIs-h showed a greater increase in SI than those for the ROIs-l did. The percentage of tumor area with a low PSIC was significantly correlated with the percentage of hypoxia staining and necrosis (r =0.71; P<0.05). ROIs with a higher PSIC typically had more vessels (r=0.88; P<0.05). A significant difference in survival was shown (log-rank P = 0.035). The time-pO2 curves of the subcutaneous tumors were similar to the time-SI curves. PSIC was significantly correlated with pO2 changes (r =0.82; P<0.05). These findings suggest that OE-MRI measurements can be used to assess hypoxia in C6 glioma models. In these models, the PSIC value was correlated with survival, indicating that PSIC could serve as a prognostic marker for glioma.

Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung During Tidal Breathing.

To quantify the relationship between regional lung ventilation and coarse aerosol deposition in the supine healthy human lung, we used oxygen-enhanced magnetic resonance imaging and planar gamma scintigraphy in seven subjects. Regional ventilation was measured in the supine posture in a 15 mm sagittal slice of the right lung. Deposition was measured by using planar gamma scintigraphy (coronal scans, 40 cm FOV) immediately postdeposition, 1 hour 30 minutes and 22 hours after deposition of 99mTc-labeled particles (4.9 μm MMAD, GSD 2.5), inhaled in the supine posture (flow 0.5 L/s, 15 breaths/min). The distribution of retained particles at different times was used to infer deposition in different airway regions, with 22 hours representing alveolar deposition. The fraction of total slice ventilation per quartile of lung height from the lung apex to the dome of the diaphragm at functional residual capacity was computed, and co-registered with deposition data-apices aligned-using a transmission scan as reference. The ratio of fractional alveolar deposition to fractional ventilation of each quartile (r) was used to evaluate ventilation and deposition matching (r > 1, regional aerosol deposition fraction larger than regional ventilation fraction). r was not significantly different from 1 for all regions (1.04 ± 0.25, 1.08 ± 0.22, 1.03 ± 0.17, 0.92 ± 0.13, apex to diaphragm, p > 0.40) at the alveolar level (r22h). For retention times r0h and r1h30, only the diaphragmatic region at r1h30 differed significantly from 1. These results support the hypothesis that alveolar deposition is directly proportional to ventilation for ∼5 μm particles that are inhaled in the supine posture and are consistent with previous simulation predictions that show that convective flow is the main determinant of aerosol transport to the lung periphery.

Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response

Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) techniques were evaluated as potential non-invasive predictive biomarkers of radiation response. Semi quantitative blood-oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) contrast, and quantitative responses of relaxation rates (ΔR1 and ΔR2*) to an oxygen breathing challenge during hypofractionated radiotherapy were applied. OE-MRI was performed on subcutaneous Dunning R3327-AT1 rat prostate tumors (n = 25) at 4.7 T prior to each irradiation (2F × 15 Gy) to the gross tumor volume. Response to radiation, while inhaling air or oxygen, was assessed by tumor growth delay measured up to four times the initial irradiated tumor volume (VQT). Radiation-induced hypoxia changes were confirmed using a double hypoxia marker assay.Inhaling oxygen during hypofractionated radiotherapy significantly improved radiation response. A correlation was observed between the difference in the 2nd and 1st ΔR1 (ΔΔR1) and VQT for air breathing rats. The TOLD response before the 2nd fraction showed a moderate correlation with VQT for oxygen breathing rats. The correlations indicate useful prognostic factors to predict tumor response to hypofractionation and could readily be applied for patient stratification and personalized radiotherapy treatment planning.

Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema.

PurposeA magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function.MethodNine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts.Principal FindingsPPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups.ConclusionsThe proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting heterogeneous lung disorders was found. This indicated that the technique has potential for early detection of lung dysfunction–before global changes occur.

Photoacoustic monitoring of tumor and normal tissue response to radiation.

Hypoxia is a recognized characteristic of tumors that influences efficacy of radiotherapy (RT). Photoacoustic imaging (PAI) is a relatively new imaging technique that exploits the optical characteristics of hemoglobin to provide information on tissue oxygenation. In the present study, PAI based measures of tumor oxygen saturation (%sO2) were compared to oxygen-enhanced magnetic resonance imaging (MRI) measurements of longitudinal relaxation rate (R1 = 1/T1) and ex-vivo histology in patient derived xenograft (PDX) models of head and neck cancer. PAI was utilized to assess early changes (24 h) in %sO2 following RT and chemoRT (CRT) and to assess changes in salivary gland hemodynamics following radiation. A significant increase in tumor %sO2 and R1 was observed following oxygen inhalation. Good spatial correlation was observed between PAI, MRI and histology. An early increase in %sO2 after RT and CRT detected by PAI was associated with significant tumor growth inhibition. Twenty four hours after RT, PAI also detected loss of hemodynamic response to gustatory stimulation in murine salivary gland tissue suggestive of radiation-induced vascular damage. Our observations illustrate the utility of PAI in detecting tumor and normal tissue hemodynamic response to radiation in head and neck cancers.

TH-CD-204-05: Developing a Non-Invasive MRI Prognostic Biomarker to Predict Response to Hypofractionated Radiotherapy

Purpose: To investigate the usefulness of Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI), the so-called semi-quantitative blood oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) responses, as well as quantitative apparent transverse relaxation rate (R2*) and longitudinal relaxation rate (R1) responses, as a prognostic biomarker of radiation response. Methods: Twenty-two (22) subcutaneous Dunning R3327-AT1 syngeneic rat prostate tumors were evaluated. When tumors reached (0.7–2 cm3), OE-MRI was performed at 4.7 T. The following day tumors were irradiated with 1 fraction of 15 Gy to the gross tumor volume (GTV) while inhaling air or oxygen. MRI and irradiation were repeated 1 week later. Radiation response was assessed by tumor growth delay measurements as time for tumor to reach 4 times the initial irradiated volume (VQT). Survival estimates from VQT were assessed using Kaplan-Meier. Results: Inhaling oxygen during hypofractionation significantly improved response to treatment based on survival probability estimates (P < 0.0001, log-rank test). Significant correlations were determined between VQT and pretherapy or between fraction OE-MRI baseline values and parameter changes before the first and second fraction of dose. Immunohistochemistry confirmed tumor reoxygenation between dose fractions consistent with OE-MRI. Conclusion: Inhaling oxygen during irradiation enhanced response in this tumor type, which was reported to exhibit substantial hypoxia. OE-MRI response to inhaling oxygen was related to response of individual tumors, suggesting utility as prognostic biomarkers. Investigations will be required in other tumor types to validate these observations, but they show that OE-MRI parameters are related to tumor response to hypofractionation, suggesting the potential for patient stratification for personalized radiotherapy treatment planning. This study was supported in part by funds from the National Cancer Institute 5R01CA139043, NCI Cancer Center Support Grant 1P30 CA142543. MRI experiments were performed in the Advanced Imaging Research Center, supported by NIH National Institute of Biomedical Imaging and Bioengineering Resource grant EB015908.

Chronic Lung Allograft Dysfunction: Oxygen-enhanced T1-Mapping MR Imaging of the Lung.

To evaluate oxygen-enhanced T1-mapping magnetic resonance (MR) imaging of the lungs for detection of chronic lung allograft dysfunction (CLAD) in patients who have undergone double lung transplantation. The local ethics committee approved this study. Seventy-six recipients of double lung allografts who underwent MR imaging of the lungs during an outpatient visit between 2011 and 2013 were included in this study after they provided written informed consent. Patients were classified as having CLAD on the basis of spirometric results and were divided into three groups: no CLAD (bronchiolitis obliterans syndrome level 0 [BOS 0]), early CLAD (BOS 0p), and late-stage CLAD (BOS 1-3). Coronal T1 maps of the lungs were acquired with the patient breathing room air and 100% oxygen by using an inversion-recovery snapshot fast low-angle shot sequence at 1.5 T. The median and interquartile range of T1 values at room air and at 100% oxygen and the oxygen transfer function were calculated. Statistical analysis was performed with analysis of variance and the Tukey honestly significant difference test or the Kruskal-Wallis test and the Mann-Whitney U test (α = 0.05). Bonferroni correction was applied for multiple comparisons. The oxygen transfer function was significantly lower in patients in the BOS 0p (P = .025) and BOS 1-3 groups (P = .003) than it was in the patients with BOS 0. Absolute T1 values (room air, P = .66; 100% oxygen, P = .67) did not differ significantly among the groups. The heterogeneity of T1 values, measured by using the interquartile range, showed a strong trend toward higher values in patients with BOS (room air, P = .06; 100% oxygen, P = .08). Oxygen transfer function may serve as an early marker for detection of CLAD.

Dynamic oxygen-enhanced magnetic resonance imaging of the lung in asthma—Initial experience

ObjectivesTo prospectively estimate the feasibility and reproducibility of dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) in the assessment of regional oxygen delivery, uptake and washout in asthmatic lungs. Materials and methodsThe study was approved by the National Research Ethics Committee and written informed consent was obtained. Dynamic OE-MRI was performed twice at one month apart on four mild asthmatic patients (23±5 years old, FEV1=96±3% of predicted value) and six severe asthmatic patients (41±12 years old, FEV1=60±14% of predicted value) on a 1.5T MR scanner using a two-dimensional T1-weighted inversion-recovery turbo spin echo sequence. The enhancing fraction (EF), the maximal change in the partial pressure of oxygen in lung tissue (ΔPO2max_l) and arterial blood of the aorta (ΔPO2max_a), and the oxygen wash-in (τup_l, τup_a) and wash-out (τdown_l, τdown_a) time constants were extracted and compared between groups using the independent-samples t-test (two-tailed). Correlations between imaging readouts and clinical measurements were assessed by Pearson's correlation analysis. Bland–Altman analysis was used to estimate the levels of agreement between the repeat scans and the intra-observer agreement in the MR imaging readouts. ResultsThe severe asthmatic group had significantly smaller EF (70±16%) and median ΔPO2max_l (156±52mmHg) and significantly larger interquartile range of τup_l (0.84±0.26min) than the mild asthmatic group (95±3%, P=0.014; 281±40mmHg, P=0.004; 0.20±0.07min, P=0.001, respectively). EF, median ΔPO2max_l and τdown_l and the interquartile range of τup_l and τdown_l were significantly correlated with age and pulmonary function test parameters (r=−0.734 to −0.927, 0.676–0.905; P=0.001–0.045). Median ΔPO2max_l was significantly correlated with ΔPO2max_a (r=0.745, P=0.013). Imaging readouts showed good one-month reproducibility and good intra-observer agreement (mean bias between repeated scans and between two observations did not significantly deviate from zero). ConclusionsDynamic OE-MRI is feasible in asthma and sensitive to the severity of disease. The technique provides indices related to regional oxygen delivery, uptake and washout that show good one month reproducibility and intra-observer agreement.

Feasibility assessment of using oxygen-enhanced magnetic resonance imaging for evaluating the effect of pharmacological treatment in COPD

ObjectivesOxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and methodsCOPD patients (n=40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler® 320/9μg or formoterol Turbuhaler®. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. ResultsOE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p<0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p<0.05) and increased oxygen extraction from the lung by 58% (p<0.01). Single-dose formoterol increased both lung wash-out time (+47%, p<0.05) and lung oxygenation time (+47%, p<0.05). FEV1 was improved by single-dose formoterol (+12%, p<0.001) and 8 weeks of budesonide/formoterol (+ 18%, p<0.001), consistent with published studies. ConclusionsIn COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.

Non-invasive pre-clinical MR imaging of prostate tumor hypoxia for radiation therapy prognosis

Purpose: To investigate the usefulness of Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) changes in signal intensity related to oxygen challenge for predicting tumor response to radiation therapy. Methods : Dynamic MR signal changes were acquired using Varian 4.7T small animal MR scanner prior to image-guided radiation therapy (IGRT) of small ( n = 6) and large subcutaneous ( n = 5) prostate tumors in adult male rats. An interleaved blood-oxygen level dependent (BOLD) and tissue-oxygen level dependent (TOLD) data acquisition or (IBT) was performed using a baseline of medical air as positive control and using medical oxygen as a breathing challenge. BOLD used a 2-D multi-slice spoiled gradient-echo with multi-echo sequence. TOLD used a 2-D multi-slice spoiled gradient-echo sequence. Voxel changes in signal intensity were determined by a correlation coefficient mapping technique. Irradiation technique planned consisted of 1F × 15 Gy AP/PA or 2F × 7.5 Gy AP/PA to the gross tumor volume (GTV). Tumor growth measurements were recorded over time to assess the response to IGRT. Results: BOLD and TOLD signals variously illustrated positive or negative impulse responses in the tumor ROI due to inhaling medical oxygen. Correlation coefficient mapping demonstrated heterogeneity in tumors after inhaling medical oxygen. BOLD and TOLD signals exhibited increased changes in signal intensities after the first fraction of dose. Multi-fractionation had minimum effect until the second fraction of dose was applied. Tumor growth delays were observed when inhaling medical oxygen during IGRT. Conclusion : OE-MRI is a non-invasive imaging modality that can provide insight to the oxygen status of tumors. Observed increase percent changes in BOLD and TOLD signal intensities after the first fraction of dose suggest tumors experienced reoxygenation. OE-MRI could be used for predicting tumor response to IGRT when using medical oxygen for increasing GTV radiosensitivity, suggesting patient stratification for clinical implementation. ------------------------------ Cite this article as: White DA, Mason RP. Non-invasive pre-clinical MR imaging of prostate tumor hypoxia for radiation therapy prognosis. Int J Cancer Ther Oncol 2014; 2(2):020243. DOI: 10.14319/ijcto.0202.43

Clinical use of oxygen‐enhanced T1 mapping MRI of the lung: Reproducibility and impact of closed versus loose fit oxygen delivery system

To evaluate the reproducibility of oxygen-enhanced magnetic resonance imaging (MRI), and the influence of different gas delivery methods, in a clinical environment. Twelve healthy volunteers were examined on two visits with an inversion recovery snapshot fast low angle shot sequence on a 1.5 T system. Coronal slices were obtained breathing room air as well as 100% oxygen with a flow rate of 15 L/min. For oxygen delivery a standard nontight face mask and a full closed air-cushion face mask were used. T1 relaxation times and the oxygen transfer function (OTF) were calculated. The mean T1 values did not change significantly between the two visits (P > 0.05). The T1 values breathing 100% oxygen obtained using the full closed mask were significantly lower (1093 ± 38 msec; P < 0.05) compared to the standard mask (1157 ± 52 msec). Accordingly, the OTF was significantly higher for the full closed mask (P < 0.05). The OTF changed significantly on the second visit using the standard mask (P < 0.05). The full closed mask showed lower interindividual variation for both the T1 values (3.5% vs. 4.5%) as well as the OTF (12.4% vs. 22.0%) and no difference of the OTF on the second visit (P > 0.05). Oxygen-enhanced T1 mapping MRI produces reproducible data when using a full closed face mask.

Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma.

There is a clinical need for noninvasive, nonionizing imaging biomarkers of tumor hypoxia and oxygenation. We evaluated the relationship of T1 -weighted oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements to histopathology measurements of tumor hypoxia in a murine glioma xenograft and demonstrated technique translation in human glioblastoma multiforme. Preclinical evaluation was performed in a subcutaneous murine human glioma xenograft (U87MG). Animals underwent OE-MRI followed by dynamic contrast-enhanced MRI (DCE-MRI) and histological measurement including reduced pimonidazole adducts and CD31 staining. Area under the curve (AUC) was measured for the R1 curve for OE-MRI and the gadolinium concentration curve for DCE-MRI. Clinical evaluation in five patients used analogous imaging protocols and analyses. Changes in AUC of OE-MRI (AUCOE ) signal were regionally heterogeneous across all U87MG tumors. Tumor regions with negative AUCOE typically had low DCE-MRI perfusion, had positive correlation with hypoxic area (P = 0.029), and had negative correlation with vessel density (P = 0.004). DCE-MRI measurements did not relate to either hypoxia or vessel density in U87MG tumors. Clinical data confirmed comparable signal changes in patients with glioblastoma. These data support further investigation of T1 -weighted OE-MRI to identify regional tumor hypoxia. The quantification of AUCOE has translational potential as a clinical biomarker of hypoxia.