Feasibility of dynamic T2 *-based oxygen-enhanced lung MRI at 3T.

PURPOSE: To demonstrate proof-of-concept of a T2 *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers. METHODS: We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R2 * and wash-in time normalized for breathing rate (τ-nBR). Inter-scanner reproducibility and intra-scanner repeatability were evaluated using intra-class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland-Altman analysis. RESULTS: Simulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R2 * at TE > 0.2 ms. Density correction improved signal fluctuations. Density-corrected mean PSE values, aligned with simulations, display TE-dependence, and an anterior-to-posterior PSE reduction trend at TE1 . ∆R2 * maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior-to-posterior R2 * increase. Mean T2 * values across 32 scans were 0.68 and 0.62 ms for pre- and post-O2 inhalation, respectively. Excellent or good agreement emerged from all intra-, inter-scanner and inter-rater variability tests for PSE and ∆R2 *. However, ICC values for τ-nBR demonstrated limited agreement between repeated measures. CONCLUSION: Our results demonstrate the feasibility of a T2 *-weighted method utilizing a dual-echo RF-spoiled gradient echo approach, simultaneously capturing PSE, ∆R2 * changes, and oxygen wash-in during free-breathing. The excellent or good repeatability and reproducibility on intra- and inter-scanner PSE and ∆R2 * suggest potential utility in multi-center clinical applications.

Independent component analysis (ICA) applied to dynamic oxygen-enhanced MRI (OE-MRI) for robust functional lung imaging at 3 T.

PURPOSE: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI. METHODS: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery. ICA was applied to each echo within a thoracic mask. The ICA component relating to the oxygen-enhancement signal was automatically identified using correlation analysis. The oxygen-enhancement component was reconstructed, and the percentage signal enhancement (PSE) was calculated. The lung PSE of current smokers was compared with nonsmokers; scan-rescan repeatability, ICA pipeline repeatability, and reproducibility between two vendors were assessed. RESULTS: ICA successfully extracted a consistent oxygen-enhancement component for all participants. Lung tissue and oxygenated blood displayed the opposite oxygen-induced signal enhancements. A significant difference in PSE was observed between the lungs of current smokers and nonsmokers. The scan-rescan repeatability and the ICA pipeline repeatability were good. CONCLUSION: The developed pipeline demonstrated sensitivity to the signal enhancements of the lung tissue and oxygenated blood at 3 T. The difference in lung PSE between current smokers and nonsmokers indicates a likely sensitivity to lung function alterations that may be seen in mild pathology, supporting future use of our methods in patient studies.

Modeling the Effect of Hyperoxia on the Spin-Lattice Relaxation Rate R1 of Tissues.

PURPOSE: Inducing hyperoxia in tissues is common practice in several areas of research, including oxygen-enhanced MRI (OE-MRI), which attempts to use the resulting signal changes to detect regions of tumor hypoxia or pulmonary disease. The linear relationship between PO2 and R1 has been reproduced in phantom solutions and body fluids such as vitreous fluid; however, in tissue and blood experiments, factors such as changes in deoxyhemoglobin levels can also affect the ΔR1. THEORY AND METHODS: This manuscript proposes a three-compartment model for estimating the hyperoxia-induced changes in R1 of tissues depending on B0, SO2 , blood volume, hematocrit, oxygen extraction fraction, and changes in blood and tissue PO2 . The model contains two blood compartments (arterial and venous) and a tissue compartment. This model has been designed to be easy for researchers to tailor to their tissue of interest by substituting their preferred model for tissue oxygen diffusion and consumption. A specific application of the model is demonstrated by calculating the resulting ΔR1 expected in healthy, hypoxic and necrotic tumor tissues. In addition, the effect of sex-based hematocrit differences on ΔR1 is assessed. RESULTS: The ΔR1 values predicted by the model are consistent with reported literature OE-MRI results: with larger positive changes in the vascular periphery than hypoxic and necrotic regions. The observed sex-based differences in ΔR1 agree with findings by Kindvall et al. suggesting that differences in hematocrit levels may sometimes be a confounding factor in ΔR1. CONCLUSION: This model can be used to estimate the expected tissue ΔR1 in oxygen-enhanced MRI experiments.

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.

BACKGROUND: 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. PURPOSE: 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. STUDY TYPE: Mathematical modeling. POPULATION: One hundred and twenty-six published values of R1 from phantoms and animal models. FIELD STRENGTH/SEQUENCE: 5-8.45 T. ASSESSMENT: 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 WRBC and Wplasma 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. STATISTICAL TESTS: Bland-Altman, AIC, MSE, coefficient of determination (R2 ), SD. RESULTS: 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. DATA CONCLUSION: 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. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Oxygen-enhanced functional lung imaging using a contemporary 0.55 T MRI system.

The purpose of this study was to evaluate oxygen-enhanced pulmonary imaging at 0.55 T with 3D stack-of-spirals ultrashort-TE (UTE) acquisition. Oxygen-enhanced pulmonary MRI offers the measurement of regional lung ventilation and perfusion using inhaled oxygen as a contrast agent. Low-field MRI systems equipped with contemporary hardware can provide high-quality structural lung imaging by virtue of the prolonged T2 *. Fortuitously, the T1 relaxivity of oxygen increases at lower field strengths, which is expected to improve the sensitivity of oxygen-enhanced lung MRI. We implemented a breath-held T1 -weighted 3D stack-of-spirals UTE acquisition with a 7 ms spiral-out readout. Measurement repeatability was assessed using five repetitions of oxygen-enhanced lung imaging in healthy volunteers (n = 7). The signal intensity at both normoxia and hyperoxia was strongly dependent on lung tissue density modulated by breath-hold volume during the five repetitions. A voxel-wise correction for lung tissue density improved the repeatability of percent signal enhancement maps (coefficient of variation = 34 ± 16%). Percent signal enhancement maps were compared in 15 healthy volunteers and 10 patients with lymphangioleiomyomatosis (LAM), a rare cystic disease known to reduce pulmonary function. We measured a mean percent signal enhancement of 9.0 ± 3.5% at 0.55 T in healthy volunteers, and reduced signal enhancement in patients with LAM (5.4 ± 4.8%, p = 0.02). The heterogeneity, estimated by the percent of lung volume exhibiting low enhancement, was significantly increased in patients with LAM compared with healthy volunteers (11.1 ± 6.0% versus 30.5 ± 13.1%, p = 0.01), illustrating the capability to measure regional functional deficits.

Novel Thoracic MRI Approaches for the Assessment of Pulmonary Physiology and Inflammation.

Excessive pulmonary inflammation can lead to damage of lung tissue, airway remodelling and established structural lung disease. Novel therapeutics that specifically target inflammatory pathways are becoming increasingly common in clinical practice, but there is yet to be a similar stepwise change in pulmonary diagnostic tools. A variety of thoracic magnetic resonance imaging (MRI) tools are currently in development, which may soon fulfil this emerging clinical need for highly sensitive assessments of lung structure and function. Given conventional MRI techniques are poorly suited to lung imaging, alternate strategies have been developed, including the use of inhaled contrast agents, intravenous contrast and specialized lung MR sequences. In this chapter, we discuss technical challenges of performing MRI of the lungs and how they may be overcome. Key thoracic MRI modalities are reviewed, namely, hyperpolarized noble gas MRI, oxygen-enhanced MRI (OE-MRI), ultrashort echo time (UTE) MRI and dynamic contrast-enhanced (DCE) MRI. Finally, we consider potential clinical applications of these techniques including phenotyping of lung disease, evaluation of novel pulmonary therapeutic efficacy and longitudinal assessment of specific patient groups.

Fast and sensitive dynamic oxygen-enhanced MRI with a cycling gas challenge and independent component analysis.

PURPOSE: There is a critical need for non-invasive imaging biomarkers of tumor oxygenation to assist in patient stratification and development of hypoxia targeting therapies. Using a cycling gas challenge and independent component analysis (ICA), we sought to improve the sensitivity and speed of existing oxygen enhanced MRI (OE-MRI) techniques to detect changes in oxygenation with dynamically acquired T1 W signal intensity images (dOE-MRI). METHODS: Mice were implanted with SCCVII, HCT-116, BT-474, or SKOV3 tumors in the dorsal subcutaneous region and imaged at 7T. T1 W images were acquired during a respiratory challenge with alternating 2-minute periods of air and 100% oxygen for three cycles. Data were analyzed with ICA and oxygenation maps were generated and compared to corresponding histology sections stained for hypoxia (pimonidazole) and blood vessels (CD31). RESULTS: Cycling air-oxygen-air gas challenges were well tolerated and ICA permitted extraction of the oxygen-enhancing component in all imaged tumors from four different models. Comparison with synthetic response functions showed that dOE-MRI does not require any a-priori knowledge of the physiological response. The fraction of O2 -negative dOE-MRI voxels that correlate inversely with the ICA gas-cycling component correspond well with the histological hypoxic fraction in SCCVII tumors (r = 0.91, p = 0.0016) but did not correlate in HCT-116 tumors (r = 0.13, p = 0.81). CONCLUSIONS: Using ICA and adding a cycling gas challenge extends the sensitivity of OE-MRI and allows the oxygenation status of tumors to be assessed in as little as six minutes. These findings support further development of OE-MRI as a biomarker of tumor oxygenation.

Pulmonary ventilation imaging in asthma and cystic fibrosis using oxygen-enhanced 3D radial ultrashort echo time MRI.

BACKGROUND: A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research. PURPOSE: To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage. STUDY TYPE: Volunteer and patient repeatability. POPULATION: Eighteen human subjects (five asthma, six CF, and seven normal subjects). FIELD STRENGTH/SEQUENCE: Respiratory-gated free-breathing 3D radial UTE (80 µs) sequence at 1.5T. ASSESSMENT: Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map. STATISTICAL TESTS: The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test-retest repeatability was evaluated using Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test-retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons). DATA CONCLUSION: 3D radial UTE OE-MRI supports quantitative differentiation of diseased vs. healthy lungs using either whole lung VDP or MPSE with excellent test-retest repeatability. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1287-1297.

Functional imaging of the lungs with gas agents.

This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)-hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas--and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children.

Clinical use of oxygen-enhanced T1 mapping MRI of the lung: reproducibility and impact of closed versus loose fit oxygen delivery system.

PURPOSE: To evaluate the reproducibility of oxygen-enhanced magnetic resonance imaging (MRI), and the influence of different gas delivery methods, in a clinical environment. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Implementation of Oxygen Enhanced Magnetic Resonance Imaging (OE-MRI) and a Pilot Genomic Study of Hypoxia in Bladder Cancer Xenografts.

BACKGROUND/AIM: Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery. MATERIALS AND METHODS: The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm3) or large (700 mm3) tumours were imaged, breathing air then 100% O2, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N2, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays. RESULTS: Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour. CONCLUSION: OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.

Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma.

Background and purpose: This study aimed to assess the role of T1 mapping and oxygen-enhanced MRI in patients undergoing radical dose radiotherapy for HPV positive oropharyngeal cancer, which has not yet been examined in an OE-MRI study. Materials and methods: Variable Flip Angle T1 maps were acquired on a 3T MRI scanner while patients (n = 12) breathed air and/or 100 % oxygen, before and after fraction 10 of the planned 30 fractions of chemoradiotherapy ('visit 1' and 'visit 2', respectively). The analysis aimed to assess to what extent (1) native R1 relates to patient outcome; (2) OE-MRI response relates to patient outcome; (3) changes in mean R1 before and after radiotherapy related to clinical outcome in patients with oropharyngeal squamous cell carcinoma. Results: Due to the radiotherapy being largely successful, the sample sizes of non-responder groups were small, and therefore it was not possible to properly assess the predictive nature of OE-MRI. The tumour R1 increased in some patients while decreasing in others, in a pattern that was overall consistent with the underlying OE-MRI theory and previously reported tumour OE-MRI responses. In addition, we discuss some practical challenges faced when integrating this technique into a clinical trial, with the aim that sharing this is helpful to researchers planning to use OE-MRI in future clinical studies. Conclusion: Altogether, these results suggest that further clinical OE-MRI studies to assess hypoxia and radiotherapy response are worth pursuing, and that there is important work to be done to improve the robustness of the OE-MRI technique in human applications in order for it to be useful as a widespread clinical technique.

Imaging biomarkers of lung ventilation in interstitial lung disease from 129Xe and oxygen enhanced 1H MRI.

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.

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.

Review of oxygen-enhanced lung mri: Pulse sequences for image acquisition and T1 measurement.

Oxygen-enhanced MR imaging (OE-MRI) is a special proton imaging technique that can be performed without modifying the scanner hardware. Many fundamental studies have been conducted following the initial reporting of this technique in 1996, illustrating the high potential for its clinical application. This review aims to summarise and analyse current pulse sequences and T1 measurement methods for OE-MRI, including fundamental theories, existing pulse sequences applied to OE-MRI acquisition and T1 mapping. Wash-in and wash-out time identify lung function and are sensitive to ventilation; thus, dynamic OE-MRI is also discussed in this review. We compare OE-MRI with the primary competitive technique, hyperpolarised gas MRI. Finally, an overview of lower-field applications of OE-MRI is highlighted, as relatively recent publications demonstrated positive results. Lower-field OE-MRI, which is lower than 1.5 T, could be an alternative modality for detecting lung diseases. This educational review is aimed at researchers who want a quick summary of the steps needed to perform pulmonary OE-MRI with a particular focus on sequence design, settings, and quantification methods.

Using Variable Flip Angle (VFA) and Modified Look-Locker Inversion Recovery (MOLLI) T1 mapping in clinical OE-MRI.

BACKGROUND AND PURPOSE: The imaging technique known as Oxygen-Enhanced MRI is under development as a noninvasive technique for imaging hypoxia in tumours and pulmonary diseases. While promising results have been shown in preclinical experiments, clinical studies have mentioned experiencing difficulties with patient motion, image registration, and the limitations of single-slice images compared to 3D volumes. As clinical studies begin to assess feasibility of using OE-MRI in patients, it is important for researchers to communicate about the practical challenges experienced when using OE-MRI on patients to help the technique advance. MATERIALS AND METHODS: We report on our experience with using two types of T1 mapping (MOLLI and VFA) for a recently completed OE-MRI clinical study on oropharyngeal squamous cell carcinoma. RESULTS: We report: (1) the artefacts and practical difficulties encountered in this study; (2) the difference in estimated T1 from each method used - the VFA T1 estimation was higher than the MOLLI estimation by 27% on average; (3) the standard deviation within the tumour ROIs - there was no significant difference in the standard deviation seen within the tumour ROIs from the VFA versus MOLLI; and (4) the OE-MRI response collected from either method. Lastly, we collated the MRI acquisition details from over 45 relevant manuscripts as a convenient reference for researchers planning future studies. CONCLUSION: We have reported our practical experience from an OE-MRI clinical study, with the aim that sharing this is helpful to researchers planning future studies. In this study, VFA was a more useful technique for using OE-MRI in tumours than MOLLI T1 mapping.

Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Oxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma. MATERIALS AND METHODS: T2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8-10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy. A mean T1 was extracted from manually segmented tumour regions of interest and a paired two-tailed t-test was used to compare changes across the patient population. Regions of subcutaneous fat and muscle tissue were examined as control ROIs. RESULTS: There was a significant increase in T1 of the tumour ROIs across patients following the 8-10 fractions of chemoradiotherapy (paired t-test, p < 0.001, n = 7). At baseline, prior to receiving chemoradiotherapy, there were no significant changes in T1 across patients from breathing oxygen (n = 9). In the post-chemoRT scans (8-10 fractions), there was a significant decrease in T1 of the tumour ROIs across patients when breathing 100% oxygen (paired t-test, p < 0.001, n = 8). Out of the 12 patients from which we successfully acquired a visit 1 T1-map, only 1 patient did not respond to treatment, therefore, we cannot correlate these results with clinical outcome. CONCLUSIONS: These clinical data demonstrate feasibility and potential for T1-mapping and oxygen enhanced T1-mapping to indicate perfusion or treatment response in tumours of this nature. These data show promise for future work with a larger cohort containing more non-responders, which would allow us to relate these measurements to clinical outcome.

Validating the distribution of specific ventilation in healthy humans measured using proton MR imaging.

Specific ventilation imaging (SVI) uses proton MRI to quantitatively map the distribution of specific ventilation (SV) in the human lung, using inhaled oxygen as a contrast agent. To validate this recent technique, we compared the quantitative measures of heterogeneity of the SV distribution in a 15-mm sagittal slice of lung obtained in 10 healthy supine subjects, (age 37 ± 10 yr, forced expiratory volume in 1 s 97 ± 7% predicted) using SVI to those obtained in the whole lung from multiple-breath nitrogen washout (MBW). Using the analysis of Lewis et al. (Lewis SM, Evans JW, Jalowayski AA. J App Physiol 44: 416-423, 1978), the most likely distribution of SV from the MBW data was computed and compared with the distribution of SV obtained from SVI, after normalizing for the difference in tidal volume. The average SV was 0.30 ± 0.10 MBW, compared with 0.36 ± 0.10 SVI (P = 0.01). The width of the distribution, a measure of the heterogeneity, obtained using both methods was comparable: 0.51 ± 0.06 and 0.47 ± 0.08 in MBW and SVI, respectively (P = 0.15). The MBW estimated width of the SV distribution was 0.05 (10.7%) higher than that estimated using SVI, and smaller than the intertest variability of the MBW estimation [inter-MBW (SD) for the width of the SV distribution was 0.08 (15.8)%]. To assess reliability, SVI was performed twice on 13 subjects showing small differences between measurements of SV heterogeneity (typical error 0.05, 12%). In conclusion, quantitative estimations of SV heterogeneity from SVI are reliable and similar to those obtained using MBW, with SVI providing spatial information that is absent in MBW.