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.

Proton MRI of the Lung: How to Tame Scarce Protons and Fast Signal Decay.

Pulmonary proton MRI techniques offer the unique possibility of assessing lung function and structure without the requirement for hyperpolarization or dedicated hardware, which is mandatory for multinuclear acquisition. Five popular approaches are presented and discussed in this review: 1) oxygen enhanced (OE)-MRI; 2) arterial spin labeling (ASL); 3) Fourier decomposition (FD) MRI and other related methods including self-gated noncontrast-enhanced functional lung (SENCEFUL) MR and phase-resolved functional lung (PREFUL) imaging; 4) dynamic contrast-enhanced (DCE) MRI; and 5) ultrashort TE (UTE) MRI. While DCE MRI is the most established and well-studied perfusion measurement, FD MRI offers a free-breathing test without any contrast agent and is predestined for application in patients with renal failure or with low compliance. Additionally, FD MRI and related methods like PREFUL and SENCEFUL can act as an ionizing radiation-free V/Q scan, since ventilation and perfusion information is acquired simultaneously during one scan. For OE-MRI, different concentrations of oxygen are applied via a facemask to assess the regional change in T1 , which is caused by the paramagnetic property of oxygen. Since this change is governed by a combination of ventilation, diffusion, and perfusion, a compound functional measurement can be achieved with OE-MRI. The known problem of fast T2 * decay of the lung parenchyma leading to a low signal-to-noise ratio is bypassed by the UTE acquisition strategy. Computed tomography (CT)-like images allow the assessment of lung structure with high spatial resolution without ionizing radiation. Despite these different branches of proton MRI, common trends are evident among pulmonary proton MRI: 1) free-breathing acquisition with self-gating; 2) application of UTE to preserve a stronger parenchymal signal; and 3) transition from 2D to 3D acquisition. On that note, there is a visible convergence of the different methods and it is not difficult to imagine that future methods will combine different aspects of the presented methods.

Data-driven mapping of hypoxia-related tumor heterogeneity using DCE-MRI and OE-MRI.

PURPOSE: Previous work has shown that combining dynamic contrast-enhanced (DCE)-MRI and oxygen-enhanced (OE)-MRI binary enhancement maps can identify tumor hypoxia. The current work proposes a novel, data-driven method for mapping tissue oxygenation and perfusion heterogeneity, based on clustering DCE/OE-MRI data. METHODS: DCE-MRI and OE-MRI were performed on nine U87 (glioblastoma) and seven Calu6 (non-small cell lung cancer) murine xenograft tumors. Area under the curve and principal component analysis features were calculated and clustered separately using Gaussian mixture modelling. Evaluation metrics were calculated to determine the optimum feature set and cluster number. Outputs were quantitatively compared with a previous non data-driven approach. RESULTS: The optimum method located six robustly identifiable clusters in the data, yielding tumor region maps with spatially contiguous regions in a rim-core structure, suggesting a biological basis. Mean within-cluster enhancement curves showed physiologically distinct, intuitive kinetics of enhancement. Regions of DCE/OE-MRI enhancement mismatch were located, and voxel categorization agreed well with the previous non data-driven approach (Cohen's kappa = 0.61, proportional agreement = 0.75). CONCLUSION: The proposed method locates similar regions to the previous published method of binarization of DCE/OE-MRI enhancement, but renders a finer segmentation of intra-tumoral oxygenation and perfusion. This could aid in understanding the tumor microenvironment and its heterogeneity. Magn Reson Med 79:2236-2245, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Advances in PET and MRI imaging of tumor hypoxia.

Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.

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.

Pulmonary Functional Imaging for Lung Adenocarcinoma: Combined MRI Assessment Based on IVIM-DWI and OE-UTE-MRI.

PURPOSE: The goal of current study was to introduce noninvasive and reproducible MRI methods for in vivo functional assessment of lung adenocarcinoma (LUAD). METHODS: Forty-four patients with pathologically confirmed LUAD were included in this study. All the lesions were classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA). The IA lesions were further divided into five subtype patterns, including acinar, lepidic, papillary, micropapillary and solid. Tumors were grouped depending on predominant subtype: low grade (AIS, MIA or lepidic predominant), intermediate grade (papillary or acinar predominant) and high grade (micropapillary, or solid predominant). Spirometry was performed according to American Thoracic Society guidelines. For each patient, Intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) analysis and oxygen-enhanced MRI (OE-MRI) analysis were performed. Spearman's test was used to assess the relationship between a) whole lung mean percent signal enhancement (PSE) and pulmonary function tests (PFTs) parameters; b) IVIM-derived parameters and PFTs parameters; c) tumor mean PSE and IVIM-derived parameters. Kruskal -Wallis tests were applied to test the difference of tumor mean PSE and IVIM-derived parameters between different histological tumor grades. Receiver operating characteristics (ROC) analysis was used to evaluate the diagnostic performance. RESULTS: Whole lung mean PSE was significantly positively correlated with PFTs parameters (r = 0.40 ~ 0.44, P < 0.05). f value derived from IVIM-DWI was significantly negatively correlated with PFTs parameters (r = -0.38 ~ -0.47, P < 0.05). Both tumor mean PSE (P = 0.030 < 0.05) and f (P = 0.022 < 0.05) could differentiate different histological grades. f was negatively correlated with tumor mean PSE (r = -0.61, P < 0.001). For the diagnostic performance, the combination of tumor mean PSE and f outperformed than using tumor mean PSE or f alone in both sensitivity and area under the ROC curve. CONCLUSIONS: The combined measurement of OE-MRI and IVIM-DWI may serve as a promising method for the noninvasive and non-radiation evaluation of pulmonary function. Quantitative analyses achieved by OE-MRI and IVIM-DWI offer an approach of the classification of LUAD subtypes.

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.