Honors & Awards

  • Merit based fellowship award, French government (2006)
  • First place Poster award, (GRAMM) Groupe de Recherche sur les Applications du Magnetisme en Medecine (2008)
  • Outstanding Presentation award in general neuroradiology (co-author), American Society of Neuroradiology (ASNR) (2012)
  • Magna Cum Laude awards, ISMRM (2012-2013-2014)
  • Summa Cum Laude awards, ISMRM (2012-2013-2014)
  • Junior Fellow of the Society, ISMRM (2014)
  • Young Investigator W.S. Moore Award Winner, International Society for Magnetic Resonance in Medicine (ISMRM) (2014)

Education & Certifications

  • MS, University Joseph Fourier, France, Physics (2006)
  • Engineering, PHELMA, Grenoble Institute of Technology, France, Biotechnologies. Medical imaging (2006)


  • MR vascular fingerprinting

    Developed numerical simulations of MR signal decay in presence of realistic tissue microstructures. Developed tools for the study of multi-dimensional MR acquisitions (3D spatial, temporal repetitions, multiple contrasts). Combined in silico and in vivo results to artificially increase MRI spatial resolution.



  • Resting-state functional MRI in patients with cerebrovascular diseases

    Developed a new approach for non-contrast imaging of arterial delays (similar to MTT or Tmax) based on MRI BOLD signal fluctuations. Studied brain connectivity deficits in patients with Moyamoya and stroke diseases.



  • MRI imaging with iron oxyde particles in humans

    Developed new methods for high resolution mapping of microvascular properties (blood volume, vessel diameter, vessel density). Studied enhancement of functional MRI (fMRI) and resting-state fMRI sensitivity in presence of a blood pool agent. Studied brain perfusion and vessel architecture using Dynamic Susceptibility Contrast (DSC) and multiple echoes MR sequences. Studied MR phase signal evolution using quantitative magnetic susceptibility mapping (QSM).



  • Non-invasive Brain perfusion measurements in humans using gaseous challenges

    Studied the effect of apnea, O2 and CO2 breathing on brain MRI signal dynamics. Compared MRI results to Near Infrared Spectroscopy (NIRS) estimates.



  • Non-invasive MRI oxymetry in rodents

    Proposed a new approach to quantify the BOLD effect in vivo. Developed a multiple spin and gradient echo MR sequence (Bruker Paravision environment). Developed mathematical models and numerical simulations of MR signal dephasing. Compared in vivo MRI results to blood gas analysis and histology in various physiological conditions (gaseous challenges, hematocrit challenges). Studied variations of brain blood oxygenation in pathologies: stroke model, Traumatic Brain Injury (TBI) model and several tumor models under anti-angiogenic therapy, radiation therapy and chemotherapy. Designed a Matlab user interface.



  • 19F MRI tissue oximetry in rodents

    Designed and implemented 19F MRI surface coil arrays. Calibrated perfluorocarbon compounds (PO2/T1 relationship) with gaseous challenges and designed dedicated hardware. Compared MRI results with optical PO2 probes in rat brain tumors.




All Publications

  • Noncontrast mapping of arterial delay and functional connectivity using resting-state functional MRI: A study in Moyamoya patients. Journal of magnetic resonance imaging Christen, T., Jahanian, H., Ni, W. W., Qiu, D., Moseley, M. E., Zaharchuk, G. 2015; 41 (2): 424-430


    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.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.Good linear correlations were found between sfBOLD delays and Tmax using the SSS as reference (r(2)  = 0.8, slope = 1.4, intercept = -4.6) or WB (r(2)  = 0.7, slope = 0.8, intercept = -3.2). New nodes of connectivity were found in delayed regions when accounting for delays in the analysis.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 2014. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmri.24558

    View details for PubMedID 24419985

  • MR vascular fingerprinting: A new approach to compute cerebral blood volume, mean vessel radius, and oxygenation maps in the human brain. NeuroImage Christen, T., Pannetier, N. A., Ni, W. W., Qiu, D., Moseley, M. E., Schuff, N., Zaharchuk, G. 2014; 89: 262-270


    In the present study, we describe a fingerprinting approach to analyze the time evolution of the MR signal and retrieve quantitative information about the microvascular network. We used a Gradient Echo Sampling of the Free Induction Decay and Spin Echo (GESFIDE) sequence and defined a fingerprint as the ratio of signals acquired pre- and post-injection of an iron-based contrast agent. We then simulated the same experiment with an advanced numerical tool that takes a virtual voxel containing blood vessels as input, then computes microscopic magnetic fields and water diffusion effects, and eventually derives the expected MR signal evolution. The parameter inputs of the simulations (cerebral blood volume [CBV], mean vessel radius [R], and blood oxygen saturation [SO2]) were varied to obtain a dictionary of all possible signal evolutions. The best fit between the observed fingerprint and the dictionary was then determined by using least square minimization. This approach was evaluated in 5 normal subjects and the results were compared to those obtained by using more conventional MR methods, steady-state contrast imaging for CBV and R and a global measure of oxygenation obtained from the superior sagittal sinus for SO2. The fingerprinting method enabled the creation of high-resolution parametric maps of the microvascular network showing expected contrast and fine details. Numerical values in gray matter (CBV=3.1±0.7%, R=12.6±2.4μm, SO2=59.5±4.7%) are consistent with literature reports and correlated with conventional MR approaches. SO2 values in white matter (53.0±4.0%) were slightly lower than expected. Numerous improvements can easily be made and the method should be useful to study brain pathologies.

    View details for DOI 10.1016/j.neuroimage.2013.11.052

    View details for PubMedID 24321559

  • High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol MAGNETIC RESONANCE IN MEDICINE Christen, T., Ni, W., Qiu, D., Schmiedeskamp, H., Bammer, R., Moseley, M., Zaharchuk, G. 2013; 70 (3): 705-710

    View details for DOI 10.1002/mrm.24500

    View details for Web of Science ID 000323543600012

  • Is T2*Enough to Assess Oxygenation? Quantitative Blood Oxygen Level-Dependent Analysis in Brain Tumor RADIOLOGY Christen, T., Lemasson, B., Pannetier, N., Farion, R., Remy, C., Zaharchuk, G., Barbier, E. L. 2012; 262 (2): 495-502


    To analyze the contribution of the transverse relaxation parameter (T2), macroscopic field inhomogeneities (B0), and blood volume fraction (BVf) to blood oxygen level-dependent (BOLD)-based magnetic resonance (MR) measurements of blood oxygen saturation (SO2) obtained in a brain tumor model.This study was approved by the local committee for animal care and use. Experiments were performed in accordance with permit 380 820 from the French Ministry of Agriculture. The 9L gliosarcoma cells were implanted in the brain of eight rats. Fifteen days later, 4.7-T MR examinations were performed to estimate T2*, T2, BVf, and T2*ΔB0corrected in the tumor and contralateral regions. MR estimates of SO2 were derived by combining T2, BVf, and T2*ΔB0corrected according to a recently described quantitative BOLD approach. Scatterplots and linear regression analysis were used to identify correlation between parameters. Paired Student t tests were used to compare the tumor region with the contralateral region.No significant correlations were found between T2* and any parameter in either tumor tissue or healthy tissue. T2* in the tumor and T2* in the uninvolved contralateral brain were the same (36 msec±4 [standard deviation] vs 36 msec±5, respectively), which might suggest similar oxygenation. Adding T2 information (98 msec±7 vs 68 msec±2, respectively) alone yields results that suggest apparent hypo-oxygenation of the tumor, while incorporating BVf (5.3%±0.6 vs 2.6%±0.3, respectively) alone yields results that suggest apparent hyperoxygenation. MR estimates of SO2 obtained with a complete quantitative BOLD analysis, although not correlated with T2* values, suggest normal oxygenation (68%±3 vs 65%±4, respectively). MR estimates of SO2 obtained in the contralateral tissue agree with previously reported values.Additional measurements, such as BVf, T2, and B0, are needed to obtain reliable information on oxygenation with BOLD MR imaging. The proposed quantitative BOLD approach, which includes these measurements, appears to be a promising tool with which to map tumor oxygenation.

    View details for DOI 10.1148/radiol.11110518

    View details for Web of Science ID 000300300200015

    View details for PubMedID 22156990

  • Evaluation of a quantitative blood oxygenation level-dependent (qBOLD) approach to map local blood oxygen saturation NMR IN BIOMEDICINE Christen, T., Lemasson, B., Pannetier, N., Farion, R., Segebarth, C., Remy, C., Barbier, E. L. 2011; 24 (4): 393-403


    Blood oxygen saturation (SO(2)) is a promising parameter for the assessment of brain tissue viability in numerous pathologies. Quantitative blood oxygenation level-dependent (qBOLD)-like approaches allow the estimation of SO(2) by modelling the contribution of deoxyhaemoglobin to the MR signal decay. These methods require a high signal-to-noise ratio to obtain accurate maps through fitting procedures. In this article, we present a version of the qBOLD method at long TE taking into account separate estimates of T(2), total blood volume fraction (BV(f)) and magnetic field inhomogeneities. Our approach was applied to the brains of 13 healthy rats under normoxia, hyperoxia and hypoxia. MR estimates of local SO(2) (MR_LSO(2)) were compared with measurements obtained from blood gas analysis. A very good correlation (R(2) = 0.89) was found between brain MR_LSO(2) and sagittal sinus SO(2).

    View details for DOI 10.1002/nbm.1603

    View details for Web of Science ID 000290081400008

    View details for PubMedID 20960585

  • Resting-State BOLD MRI for Perfusion and Ischemia. Topics in magnetic resonance imaging Kroll, H., Zaharchuk, G., Christen, T., Heit, J. J., Iv, M. 2017; 26 (2): 91-96


    Advanced imaging techniques including computed tomography (CT) angiography, CT perfusion, magnetic resonance (MR) angiography, MR with diffusion- and perfusion-weighted imaging, and, more recently, resting-state BOLD (Blood Oxygen Level Dependent) functional MRI (rs-fMRI) are increasingly used to evaluate patients with acute ischemic stroke. Advanced imaging allows for identification of patients with ischemic stroke and determination of the size of infarcted and potentially salvageable tissue, all of which yield crucial information for proper stroke management. The addition of rs-fMRI for ischemia adds information at the microvascular level, thereby improving the understanding of pathophysiologic mechanisms of impaired cerebral perfusion and tissue oxygenation beyond the known concepts at the macrovascular level. As such, it may further delineate functional and dysfunctional neuronal networks, guide stroke interventions, and improve prognosis and monitoring of patient outcomes.

    View details for DOI 10.1097/RMR.0000000000000119

    View details for PubMedID 28277456

  • Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Ni, W. W., Christen, T., Rosenberg, J., Zun, Z., Moseley, M. E., Zaharchuk, G. 2017; 37 (4): 1213-1222
  • Benchmarking transverse spin relaxation based oxygenation measurements in the brain during hypercapnia and hypoxia. Journal of magnetic resonance imaging : JMRI Ni, W. W., Christen, T., Zaharchuk, G. 2017


    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.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.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).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.1 J. Magn. Reson. Imaging 2017.

    View details for DOI 10.1002/jmri.25582

    View details for PubMedID 28306210

  • MR Vascular Fingerprinting in Stroke and Brain Tumors Models SCIENTIFIC REPORTS LeMasson, B., Pannetier, N., Coquery, N., Boisserand, L. S., Collomb, N., Schuff, N., Moseley, M., Zaharchuk, G., Barbier, E. L., Christen, T. 2016; 6


    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

    View details for DOI 10.1038/srep37071

    View details for Web of Science ID 000388795600001

    View details for PubMedID 27883015

    View details for PubMedCentralID PMC5121626

  • Measuring vascular reactivity with resting-state blood oxygenation level-dependent (BOLD) signal fluctuations: A potential alternative to the breath-holding challenge? Journal of cerebral blood flow and metabolism Jahanian, H., Christen, T., Moseley, M. E., Pajewski, N. M., Wright, C. B., Tamura, M. K., Zaharchuk, G. 2016


    Measurement of the ability of blood vessels to dilate and constrict, known as vascular reactivity, is often performed with breath-holding tasks that transiently raise arterial blood carbon dioxide (PaCO2) levels. However, following the proper commands for a breath-holding experiment may be difficult or impossible for many patients. In this study, we evaluated two approaches for obtaining vascular reactivity information using blood oxygenation level-dependent signal fluctuations obtained from resting-state functional magnetic resonance imaging data: physiological fluctuation regression and coefficient of variation of the resting-state functional magnetic resonance imaging signal. We studied a cohort of 28 older adults (69 ± 7 years) and found that six of them (21%) could not perform the breath-holding protocol, based on an objective comparison with an idealized respiratory waveform. In the subjects that could comply, we found a strong linear correlation between data extracted from spontaneous resting-state functional magnetic resonance imaging signal fluctuations and the blood oxygenation level-dependent percentage signal change during breath-holding challenge ( R(2 )= 0.57 and 0.61 for resting-state physiological fluctuation regression and resting-state coefficient of variation methods, respectively). This technique may eliminate the need for subject cooperation, thus allowing the evaluation of vascular reactivity in a wider range of clinical and research conditions in which it may otherwise be impractical.

    View details for PubMedID 27683452

  • Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease. Journal of cerebral blood flow and metabolism Ni, W. W., Christen, T., Rosenberg, J., Zun, Z., Moseley, M. E., Zaharchuk, G. 2016


    This study aimed to determine whether measurements of cerebrovascular reserve and oxygenation, assessed with spin relaxation rate R2', yield similar information about pathology in pre-operative Moyamoya disease patients, and to assess whether R2' is a better measure of oxygenation than other proposed markers, such as R2* and R2. Twenty-five pre-operative Moyamoya disease patients were scanned at 3.0T with acetazolamide challenge. Cerebral blood flow mapping with multi-delay arterial spin labeling, and R2*, R2, and R2' mapping with Gradient-Echo Sampling of Free Induction Decay and Echo were performed. No baseline cerebral blood flow difference was found between angiographically abnormal and normal regions (49 ± 12 vs. 48 ± 11 mL/100 g/min, p = 0.44). However, baseline R2' differed between these regions (3.2 ± 0.7 vs. 2.9 ± 0.6 s(-1), p < 0.001), indicating reduced oxygenation in abnormal regions. Cerebrovascular reserve was lower in angiographically abnormal regions (21 ± 38 vs. 41 ± 26%, p = 0.001). All regions showed trend toward significantly improved oxygenation post-acetazolamide. Regions with poorer cerebrovascular reserve had lower baseline oxygenation (Kendall's τ = -0.24, p = 0.003). A number of angiographically abnormal regions demonstrated preserved cerebrovascular reserve, likely due to the presence of collaterals. Finally, of the concurrently measured relaxation rates, R2' was superior for oxygenation assessment.

    View details for PubMedID 27207169

  • Comparison of R2' measurement methods in the normal brain at 3 tesla. Magnetic resonance in medicine Ni, W., Christen, T., Zun, Z., Zaharchuk, G. 2015; 73 (3): 1228-1236


    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.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.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.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.

    View details for DOI 10.1002/mrm.25232

    View details for PubMedID 24753286

  • Numerical Modeling of Susceptibility-Related MR Signal Dephasing with Vessel Size Measurement: Phantom Validation at 3T MAGNETIC RESONANCE IN MEDICINE Pannetier, N. A., Sohlin, M., Christen, T., Schad, L., Schuff, N. 2014; 72 (3): 646-658


    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.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.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.The results suggest that this approach could be interesting in vivo to better characterize the microvasculature without contrast agent. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.24968

    View details for Web of Science ID 000340552700006

    View details for PubMedID 24167116

  • Spontaneous BOLD signal fluctuations in young healthy subjects and elderly patients with chronic kidney disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)


    Spontaneous fluctuations in blood oxygenation level-dependent (BOLD) images are the basis of resting-state fMRI and frequently used for functional connectivity studies. However, there may be intrinsic information in the amplitudes of these fluctuations. We investigated the possibility of using the amplitude of spontaneous BOLD signal fluctuations as a biomarker for cerebral vasomotor reactivity. We compared the coefficient of variation (CV) of the time series (defined as the temporal standard deviation of the time series divided by the mean signal intensity) in two populations: 1) Ten young healthy adults and 2) Ten hypertensive elderly subjects with chronic kidney disease (CKD). We found a statistically significant increase (P<0.01) in the CV values for the CKD patients compared with the young healthy adults in both gray matter (GM) and white matter (WM). The difference was independent of the exact segmentation method, became more significant after correcting for physiological signals using RETROICOR, and mainly arose from very low frequency components of the BOLD signal fluctuation (f<0.025 Hz). Furthermore, there was a strong relationship between WM and GM signal fluctuation CV's (R2 = 0.87) in individuals, with a ratio of about 1∶3. These results suggest that amplitude of the spontaneous BOLD signal fluctuations may be used to assess the cerebrovascular reactivity mechanisms and provide valuable information about variations with age and different disease states.

    View details for DOI 10.1371/journal.pone.0092539

    View details for PubMedID 24651703

  • Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease. PloS one Jahanian, H., Ni, W. W., Christen, T., Moseley, M. E., Kurella Tamura, M., Zaharchuk, G. 2014; 9 (3)

    View details for DOI 10.1371/journal.pone.0092539

    View details for PubMedID 24651703

  • Imaging brain oxygenation with MRI using blood oxygenation approaches: methods, validation, and clinical applications. AJNR. American journal of neuroradiology Christen, T., Bolar, D. S., Zaharchuk, G. 2013; 34 (6): 1113-1123


    In many pathophysiologic situations, including brain neoplasms, neurodegenerative disease, and chronic and acute ischemia, an imbalance exists between oxygen tissue consumption and delivery. Furthermore, oxygenation changes following a stress challenge, such as with carbogen gas or acetazolamide, can yield information about cerebrovascular reactivity. The unique sensitivity of the BOLD effect to the presence of deoxyhemoglobin has led to its widespread use in the field of cognitive neurosciences. However, the high spatial and temporal resolution afforded by BOLD imaging does not need to be limited to the study of healthy brains. While the complex relationship between the MR imaging signal and tissue oxygenation hinders a direct approach, many different methods have been developed during the past decade to obtain specific oxygenation measurements. These include qBOLD, phase- and susceptibility-based imaging, and intravascular T2-based approaches. The aim of this review is to give an overview of the theoretic basis of these methods as well as their application to measure oxygenation in both healthy subjects and those with disease.

    View details for DOI 10.3174/ajnr.A3070

    View details for PubMedID 22859287

  • Simultaneous perfusion and permeability measurements using combined spin- and gradient-echo MRI. Journal of cerebral blood flow and metabolism Schmiedeskamp, H., Andre, J. B., Straka, M., Christen, T., Nagpal, S., Recht, L., Thomas, R. P., Zaharchuk, G., Bammer, R. 2013; 33 (5): 732-743


    The purpose of this study was to estimate magnetic resonance imaging-based brain perfusion parameters from combined multiecho spin-echo and gradient-echo acquisitions, to correct them for T1-, T2-, and -related contrast agent (CA) extravasation effects, and to simultaneously determine vascular permeability. Perfusion data were acquired using a combined multiecho spin- and gradient-echo (SAGE) echo-planar imaging sequence, which was corrected for CA extravasation effects using pharmacokinetic modeling. The presented method was validated in simulations and brain tumor patients, and compared with uncorrected single-echo and multiecho data. In the presence of CA extravasation, uncorrected single-echo data resulted in underestimated CA concentrations, leading to underestimated single-echo cerebral blood volume (CBV) and mean transit time (MTT). In contrast, uncorrected multiecho data resulted in overestimations of CA concentrations, CBV, and MTT. The correction of CA extravasation effects resulted in CBV and MTT estimates that were more consistent with the underlying tissue characteristics. Spin-echo perfusion data showed reduced large-vessel blooming effects, facilitating better distinction between increased CBV due to active tumor progression and elevated CBV due to the presence of cortical vessels in tumor proximity. Furthermore, extracted permeability parameters were in good agreement with elevated T1-weighted postcontrast signal values.

    View details for DOI 10.1038/jcbfm.2013.10

    View details for PubMedID 23462570

    View details for PubMedCentralID PMC3652702

  • A Simulation Tool for Dynamic Contrast Enhanced MRI PLOS ONE Pannetier, N. A., Debacker, C. S., Mauconduit, F., Christen, T., Barbier, E. L. 2013; 8 (3)


    The quantification of bolus-tracking MRI techniques remains challenging. The acquisition usually relies on one contrast and the analysis on a simplified model of the various phenomena that arise within a voxel, leading to inaccurate perfusion estimates. To evaluate how simplifications in the interstitial model impact perfusion estimates, we propose a numerical tool to simulate the MR signal provided by a dynamic contrast enhanced (DCE) MRI experiment. Our model encompasses the intrinsic R1 and R2 relaxations, the magnetic field perturbations induced by susceptibility interfaces (vessels and cells), the diffusion of the water protons, the blood flow, the permeability of the vessel wall to the the contrast agent (CA) and the constrained diffusion of the CA within the voxel. The blood compartment is modeled as a uniform compartment. The different blocks of the simulation are validated and compared to classical models. The impact of the CA diffusivity on the permeability and blood volume estimates is evaluated. Simulations demonstrate that the CA diffusivity slightly impacts the permeability estimates (< 5% for classical blood flow and CA diffusion). The effect of long echo times is investigated. Simulations show that DCE-MRI performed with an echo time TE = 5 ms may already lead to significant underestimation of the blood volume (up to 30% lower for brain tumor permeability values). The potential and the versatility of the proposed implementation are evaluated by running the simulation with realistic vascular geometry obtained from two photons microscopy and with impermeable cells in the extravascular environment. In conclusion, the proposed simulation tool describes DCE-MRI experiments and may be used to evaluate and optimize acquisition and processing strategies.

    View details for DOI 10.1371/journal.pone.0057636

    View details for Web of Science ID 000316407400012

    View details for PubMedID 23516414

  • Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 2013


    PURPOSE: Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model. METHODS: Tissue responses to MRT (two orthogonal arrays (2×400Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR_SO2) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia. RESULTS: In tumors, MR_SO2 decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (×5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR_SO2, although vessel inter-distances increased slightly. CONCLUSION: We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia.

    View details for DOI 10.1016/j.radonc.2013.05.013

    View details for PubMedID 23731617

  • Evaluation of the Relationship between MR Estimates of Blood Oxygen Saturation and Hypoxia: Effect of an Antiangiogenic Treatment on a Gliosarcoma Model RADIOLOGY Lemasson, B., Christen, T., Serduc, R., Maisin, C., Bouchet, A., Le Duc, G., Remy, C., Barbier, E. L. 2012; 265 (3): 743-752


    To assess the reproducibility of the magnetic resonance (MR) estimate of blood oxygen saturation (sO(2)) in the rat brain, to evaluate the relationship between low MR estimate of sO(2) values and tissue hypoxia in a hypoxic and necrotic glioscarcoma model (9L gliosarcoma cells), and to evaluate the capability of the MR estimate of sO(2) parameter to help identify modifications induced by an antiangiogenic treatment (sorafenib) in 9L gliosarcoma tumors.Experiments were performed with permits from the French Ministry of Agriculture. Forty-eight male rats bearing a 9L gliosarcoma were randomized in untreated and treated (sorafenib) groups. MR blood volume fraction and MR estimate of sO(2) parameters were estimated 1 day before and 1, 3, 5, and 8 days after the start of the treatment. The in vivo MR estimate of sO(2) measurement was correlated with the ex vivo hypoxia assessment by using pimonidazole staining. Paired and unpaired t tests, as well as parametric Pearson tests, were used for the statistical analyses.In healthy tissues, MR estimate of sO(2) measurements were comparable to literature values and were reproducible (mean across all animals, 68.0% ± 6.5 [standard deviation]). In untreated tumors, MR estimate of sO(2) and immunohistochemical analysis yielded correlated fractional hypoxic-necrotic areas (R(2) = 0.81). In tumors treated with antiangiogenic therapy, tumor MR estimate of sO(2) was decreased with respect to the healthy tissue (P< .001).Results of this study suggest that the MR estimate of sO(2) is a reproducible estimate that could be used as an in vivo probe of hypoxia in brain tumors and as a sensitive reporter of the hypoxic effects of antiangiogenic therapies.

    View details for DOI 10.1148/radiol.12112621

    View details for Web of Science ID 000311420300011

    View details for PubMedID 22996750

  • Contrast-enhanced functional blood volume imaging (CE-fBVI): Enhanced sensitivity for brain activation in humans using the ultrasmall superparamagnetic iron oxide agent ferumoxytol NEUROIMAGE Qiu, D., Zaharchuk, G., Christen, T., Ni, W. W., Moseley, M. E. 2012; 62 (3): 1726-1731


    Functional MRI (fMRI) brain studies performed in the presence of a steady-state or "blood pool" contrast agent yields activation maps that are weighted for cerebral blood volume (CBV). Previous animal experiments suggest significant contrast-to-noise ratio (CNR) improvements, but these studies have not yet been performed in humans due to the lack of availability of a suitable agent. Here we report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA) for functional brain activation in humans, termed contrast enhanced functional blood volume imaging (CE-fBVI). Four subjects were scanned during a unilateral finger tapping task with standard blood-oxygen level dependent (BOLD) imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI response showed both a fast (5.8±1.3 s) and a slow (75.3±27.5 s) component of CBV response to stimuli. A significant CNR gain of approximately 2-3 was found for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related signal dropouts were observed in the inferior frontal and temporal lobes with CE-fBVI. The combination of higher CNR and better spatial specificity, enabled by CE-fBVI using blood pool USPIO contrast agent opens the door to higher resolution brain mapping.

    View details for DOI 10.1016/j.neuroimage.2012.05.010

    View details for Web of Science ID 000307369000040

    View details for PubMedID 22584230

  • Measuring brain oxygenation in humans using a multiparametric quantitative blood oxygenation level dependent MRI approach MAGNETIC RESONANCE IN MEDICINE Christen, T., Schmiedeskamp, H., Straka, M., Bammer, R., Zaharchuk, G. 2012; 68 (3): 905-911


    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 2 and T(2) measurements to derive maps of blood oxygen saturation or cerebral metabolic rate of oxygen. In 12 normal subjects, a mean cerebral blood volume of 4.33 ± 0.7%, cerebral blood flow of 43.8 ± 5.7 mL/min/100 g, blood oxygen saturation of 60 ± 6% and cerebral metabolic rate of oxygen 157 ± 23 μmol/100 g/min were found, which are in agreement with literature values. The results obtained in this study suggest that this methodology could be applied to study brain hypoxia in the setting of pathology.

    View details for DOI 10.1002/mrm.23283

    View details for Web of Science ID 000308098100029

    View details for PubMedID 22162074

  • Quantitative MR estimates of blood oxygenation based on T2*: A numerical study of the impact of model assumptions MAGNETIC RESONANCE IN MEDICINE Christen, T., Zaharchuk, G., Pannetier, N., Serduc, R., Joudiou, N., Vial, J., Remy, C., Barbier, E. L. 2012; 67 (5): 1458-1468


    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 T(2)*, 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.

    View details for DOI 10.1002/mrm.23094

    View details for Web of Science ID 000302619400027

    View details for PubMedID 22183768

  • Vessel size index measurements in a rat model of glioma: comparison of the dynamic (Gd) and steady-state (iron-oxide) susceptibility contrast MRI approaches NMR IN BIOMEDICINE Pannetier, N., Lemasson, B., Christen, T., Tachrount, M., Tropres, I., Farion, R., Segebarth, C., Remy, C., Barbier, E. L. 2012; 25 (2): 218-226


    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 (Gd(1) and Gd(2)). 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{Gd(1)} = 6.5 ± 0.7 µm) and in brain tumour tissues (VSI{USPIO} = 19.4 ± 7.1 µm, VSI{Gd(1)} = 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{Gd(2)} = 7.1 ± 0.4 µm) and in brain tumour tissues (VSI{Gd(2)} = 18.5 ± 4.3 µm) but is not mandatory. VSI estimates do not appear to be sensitive to T(1) 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.

    View details for DOI 10.1002/nbm.1734

    View details for Web of Science ID 000301597300004

    View details for PubMedID 21751270

  • Assessment of multiparametric MRI in a human glioma model to monitor cytotoxic and anti-angiogenic drug effects NMR IN BIOMEDICINE Lemasson, B., Christen, T., Tizon, X., Farion, R., Fondraz, N., Provent, P., Segebarth, C., Barbier, E. L., Genne, P., Duchamp, O., Remy, C. 2011; 24 (5): 473-482


    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.

    View details for DOI 10.1002/nbm.1611

    View details for Web of Science ID 000291597200005

    View details for PubMedID 21674650

  • PO2 Matters in Stem Cell Culture CELL STEM CELL Wion, D., Christen, T., Barbier, E. L., Coles, J. A. 2009; 5 (3): 242-243

    View details for DOI 10.1016/j.stem.2009.08.009

    View details for Web of Science ID 000272545700007

    View details for PubMedID 19733532

  • Brain tumor vessel response to synchrotron microbeam radiation therapy: a short-term in vivo study PHYSICS IN MEDICINE AND BIOLOGY Serduc, R., Christen, T., Laissue, J., Farion, R., Bouchet, A., Van der Sanden, B., Segebarth, C., Braeuer-Krisch, E., Le Duc, G., Bravin, A., Remy, C., Barbier, E. L. 2008; 53 (13): 3609-3622


    The aim of this work focuses on the description of the short-term response of a 9L brain tumor model and its vasculature to microbeam radiation therapy (MRT) using magnetic resonance imaging (MRI). Rat 9L gliosarcomas implanted in nude mice brains were irradiated by MRT 13 days after tumor inoculation using two orthogonal arrays of equally spaced 28 planar microbeams (25 microm width, 211 microm spacing and dose 500 Gy). At 1, 7 and 14 days after MRT, apparent diffusion coefficient, blood volume and vessel size index were mapped by MRI. Mean survival time after tumor inoculation increased significantly between MRT-treated and untreated groups (23 and 28 days respectively, log-rank test, p < 0.0001). A significant increase of apparent diffusion coefficient was observed 24 h after MRT in irradiated tumors versus non-irradiated ones. In the untreated group, both tumor size and vessel size index increased significantly (from 7.6 +/- 2.2 to 19.2 +/- 4.0 mm(2) and +23%, respectively) between the 14th and the 21st day after tumor cell inoculation. During the same period, in the MRT-treated group, no difference in tumor size was observed. The vessel size index measured in the MRT-treated group increased significantly (+26%) between 14 and 28 days of tumor growth. We did not observe the significant difference in blood volume between the MRT-treated and untreated groups. MRT slows 9L tumor growth in a mouse brain but MRI results suggest that the increase in survival time after our MRT approach may be rather due to a cytoreduction than to early direct effects of ionizing radiation on tumor vessels. These results suggest that MRT parameters need to be optimized to further damage tumor vessels.

    View details for DOI 10.1088/0031-9155/53/13/015

    View details for Web of Science ID 000257200800016

    View details for PubMedID 18560052