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Purpose: To simultaneously assess reproducibility of three MRI transverse relaxation parameters ( R2', R2*, and R2 ) for brain tissue oxygenation mapping and to assess changes in these parameters with inhalation of gases that increase and decrease oxygenation, to identify the most sensitive parameter for imaging brain oxygenation.Materials and Methods: Forty-eight healthy subjects (25 male, ages 35 ± 8 years) were scanned at 3.0 Tesla, each with one of four gases (mildly and strongly hypercapnic and hypoxic) administered in a challenge paradigm, using a gas delivery setup designed for patient use. Cerebral blood flow mapping with arterial spin labeling, and simultaneous R2', R2*, and R2 mapping with gradient-echo sampling of free induction decay and echo (GESFIDE) were performed. Reproducibility in air and gas-induced changes were evaluated using nonparametric analysis with correction for multiple comparisons.Results: Our gas delivery setup achieved stable gas challenges as shown by physiological monitoring. Test-retest variability of R2', R2*, and R2 were found to be 0.24 s-1 (8.6% of mean), 0.24 s-1 (1.3% of mean), and 0.15 s-1 (1.0% of mean), respectively. Strong hypoxia produced the most conclusive oxygenation-driven relaxation change, inducing increases in R2' (25 ± 13%, P = 0.03), R2* (5 ± 2%, P = 0.02), and R2 (2 ± 2%, NS).Conclusion: We benchmarked the intra-scan test-retest variability in GESFIDE-based transverse relaxation rate mapping. Using a reliable framework for gas challenge paradigms, we recommend strong hypoxia for validating oxygenation mapping methods, and the use of tissue R2' change, instead of R2* or R2 , as a metric for studying brain tissue oxygenation using transverse relaxation methods.Level Of Evidence: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:704-714. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the ability of multiparametric MRI to identify the early effects of individual treatment, during combined chemo-radiotherapy on brain tumours. Eighty male rats bearing 9L gliosarcomas were randomized into four groups: untreated, anti-angiogenic therapy (SORA group), microbeam radiation therapy (MRT group) and both treatments (MRT+SORA group). Multiparametric MRI (tumour volume, diffusion-weighted MR imaging (ADC), blood volume fraction (BVf), microvessel index (VSI), vessel wall integrity (AUCP846) and tissue oxygen saturation (StO2)) was performed 1 day before and 2, 5 and 8 days after treatment initiation. Unpaired t-tests and one-way ANOVA were used for statistical analyses. Each MR parameter measured in our protocol was revealed to be sensitive to tumour changes induced by any of the therapies used (individually or combined). When compared with untreated tumours, SORA induced a decrease in BVf, VSI, StO2 and AUCP846, MRT generated an increase in ADC and AUCP846 and combined therapies yielded mixed effects: an increase in ADC and AUCP846 and a decrease in BVf, StO2 and AUCP846. MRT and MRT+SORA significantly slowed tumour growth. Despite these two groups presenting with similar tumour sizes, the information yielded from MR multiparameter assessment indicated that, when used concomitantly, each therapy induced distinguishable and appreciable physiological changes in the tumour. Our results suggest that multiparametric MRI can monitor the effects of individual treatments, used concomitantly, on brain tumours. Such monitoring would be useful for the detection of tumour resistance to drug/radiotherapy in patients undergoing concomitant therapies. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose R2′, the reversible component of transverse relaxation, is an important susceptibility measurement for studies of brain physiology and pathologies. In existing literature, different R2′ measurement methods are used with assumption of equivalency. This study explores the choice of measurement method in healthy, young subjects at 3T. Methods In this study, a modified gradient-echo sampling of free induction decay and echo (GESFIDE) sequence was used to compare four standard R2′ measurement methods: asymmetric spin echo (ASE), standard GESFIDE, gradient echo sampling of the spin echo (GESSE), and separate R2 and R2* mapping. Results GESSE returned lower R2′ measurements than other methods ( P < 0.05). Intersubject mean R2′ in gray matter was found to be 2.7 s−1 using standard GESFIDE and GESSE, versus 3.4-3.8 s−1 using other methods. In white matter, mean R2′ from GESSE was 2.3 s−1 while other methods produced 3.7-4.3 s−1. R2 correction was applied to partially reduce the discrepancies between the methods, but significant differences remained, likely due to violation of the fundamental assumption of a single-compartmental tissue model, and hence monoexponential decay. Conclusion R2′ measurements are influenced significantly by the choice of method. Awareness of this issue is important when designing and interpreting studies that involve R2′ measurements. Magn Reson Med 73:1228-1236, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) signal can be used to create maps similar to time-to-maximum of the residue function (Tmax) in Moyamoya patients and to determine whether sfBOLD delays affect the results of brain connectivity mapping. Materials and Methods Ten patients were scanned at 3 Tesla using a gradient-echo echo planar imaging sequence for sfBOLD imaging. Cross correlation analysis was performed between each brain voxel signal and a reference signal comprised of either the superior sagittal sinus (SSS) or whole brain (WB) average time course. sfBOLD delay maps were created based on the time shift necessary to maximize the correlation coefficient, and compared with dynamic susceptibility contrast Tmax maps. Standard and time-shifted resting-state BOLD connectivity analyses of the default mode network were compared. Results Good linear correlations were found between sfBOLD delays and Tmax using the SSS as reference (r2 = 0.8, slope = 1.4, intercept = −4.6) or WB (r2 = 0.7, slope = 0.8, intercept = −3.2). New nodes of connectivity were found in delayed regions when accounting for delays in the analysis. Conclusion Resting-state sfBOLD imaging can create delay maps similar to Tmax maps without the use of contrast agents in Moyamoya patients. Accounting for these delays may affect the results of functional connectivity maps. J. Magn. Reson. Imaging 2015;41:424-430.© 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose MRI is used to obtain quantitative oxygenation and blood volume information from the susceptibility-related MR signal dephasing induced by blood vessels. However, analytical models that fit the MR signal are usually not accurate over the range of small blood vessels. Moreover, recent studies have demonstrated limitations in the simultaneous assessment of oxygenation and blood volume. In this study, a multiparametric MRI framework that aims to measure vessel radii in addition to magnetic susceptibility and volume fraction was introduced. Methods The protocol consisted of gradient-echo sampling of the spin-echo, diffusion, T2, and B0 acquisitions. After correction steps, the data were postprocessed with a versatile numerical model of the MR signal. An important analytical model was implemented for comparison. The approach was validated in phantoms with coiling strings as proxy for blood vessels. Results The feasibility of the vessel radius measurement is demonstrated. The numerical model shows an improved accuracy compared with the analytical approach. However, both methods overestimate the radius. The simultaneous measurement of the magnetic susceptibility and the volume fraction remains challenging. Conclusion The results suggest that this approach could be interesting in vivo to better characterize the microvasculature without contrast agent. Magn Reson Med 72:646-658, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Cerebral blood volume maps are usually acquired using dynamic susceptibility contrast imaging which inherently limits the spatial resolution and signal to noise ratio of the images. In this study, we used ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA), an FDA-approved compound, to obtain high-resolution cerebral blood volume maps with a steady-state approach in seven healthy volunteers. [ABSTRACT FROM AUTHOR]

Quantitative blood oxygenation level dependent approaches have been designed to obtain quantitative oxygenation information using MRI. A mathematical model is usually fitted to the time signal decay of a gradient-echo and spin-echo measurements to derive hemodynamic parameters such as the blood oxygen saturation or the cerebral blood volume. Although the results in rats and human brain have been encouraging, recent studies have pointed out the need for independent estimation of one or more variables to increase the accuracy of the method. In this study, a multiparametric quantitative blood oxygenation level dependent approach is proposed. A combination of arterial spin labeling and dynamic susceptibility contrast methods were used to obtain quantitative estimates of cerebral blood volume and cerebral blood flow. These results were combined with T [ABSTRACT FROM AUTHOR]

Several MR methods have been proposed over the last decade to obtain quantitative estimates of the tissue blood oxygen saturation (StO2) using a quantification of the blood oxygen level dependent effect. These approaches are all based on mathematical models describing the time evolution of the MR signal in biological tissues in the presence of magnetic field inhomogeneities. Although the experimental results are very encouraging, possible biases induced by the model assumptions have not been extensively studied. In this study, a numerical approach was used to examine the influence on T2*, blood volume fraction, and StO2 estimates of possible confounding factors such as water diffusion, intravascular signal, and presence of arterial blood in the voxel. To evaluate the impact of the vessel geometry, straight cylinders and realistic data from two-photon microscopy for microvascular geometry were compared. Our results indicate that the models are sufficiently realistic, based on a good correlation between ground truth and MR estimates of StO2. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Vessel size index (VSI), a parameter related to the distribution of vessel diameters, may be estimated using two MRI approaches: (i) dynamic susceptibility contrast (DSC) MRI following the injection of a bolus of Gd-chelate. This technique is routinely applied in the clinic to assess intracranial tissue perfusion in patients; (ii) steady-state susceptibility contrast with USPIO contrast agents, which is considered here as the standard method. Such agents are not available for human yet and the steady-state approach is currently limited to animal studies. The aim is to compare VSI estimates obtained with these two approaches on rats bearing C6 glioma (n = 7). In a first session, VSI was estimated from two consecutive injections of Gd-Chelate (Gd1 and Gd2). In a second session (4 hours later), VSI was estimated using USPIO. Our findings indicate that both approaches yield comparable VSI estimates both in contralateral (VSI{USPIO} = 7.5 ± 2.0 µm, VSI{Gd1} = 6.5 ± 0.7 µm) and in brain tumour tissues (VSI{USPIO} = 19.4 ± 7.1 µm, VSI{Gd1} = 16.6 ± 4.5 µm). We also observed that, in the presence of BBB leakage (as it occurs typically in brain tumours), applying a preload of Gd-chelate improves the VSI estimate with the DSC approach both in contralateral (VSI{Gd2} = 7.1 ± 0.4 µm) and in brain tumour tissues (VSI{Gd2} = 18.5 ± 4.3 µm) but is not mandatory. VSI estimates do not appear to be sensitive to T1 changes related to Gd extravasation. These results suggest that robust VSI estimates may be obtained in patients at 3 T or higher magnetic fields with the DSC approach. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Early imaging or blood biomarkers of tumor response is needed to customize anti-tumor therapy on an individual basis. This study evaluates the sensitivity and relevance of five potential MRI biomarkers. Sixty nude rats were implanted with human glioma cells (U-87 MG) and randomized into three groups: one group received an anti-angiogenic treatment (Sorafenib), a second a cytotoxic drug [1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU (Carmustine)] and a third no treatment. The tumor volume, apparent diffusion coefficient (ADC) of water, blood volume fraction (BVf), microvessel diameter (vessel size index, VSI) and vessel wall integrity (contrast enhancement, CE) were monitored before and during treatment. Sorafenib reduced tumor CE as early as 1 day after treatment onset. By 4 days after treatment onset, tumor BVf was reduced and tumor VSI was increased. By 14 days after treatment onset, ADC was increased and the tumor growth rate was reduced. With BCNU, ADC was increased and the tumor growth rate was reduced 14 days after treatment onset. Thus, the estimated MRI parameters were sensitive to treatment at different times after treatment onset and in a treatment-dependent manner. This study suggests that multiparametric MR monitoring could allow the assessment of new anti-tumor drugs and the optimization of combined therapies. Copyright © 2010 John Wiley & Sons, Ltd. Multiparametric MRI reveals that both tumor microvasculature and cellularity are altered by anti-angiogenic and cytotoxic therapy. Multiparametric MRI thus has strong potential for the evaluation of the effect of new drugs on brain tumors. In addition, multiparametric MRI could contribute towards an understanding of the mechanisms of action of anti-angiogenic therapies and the optimization of therapeutic combinations. [ABSTRACT FROM AUTHOR]