Michael Moseley - Academia.edu (original) (raw)

Papers by Michael Moseley

Research paper thumbnail of Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI)

Magnetic Resonance in Medicine, May 30, 2018

Purpose-Amplified Magnetic Resonance Imaging (aMRI) was recently introduced as a new brain motion... more Purpose-Amplified Magnetic Resonance Imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a videoprocessing algorithm, Eulerian Video Magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here we strive to improve aMRI by incorporating a phasebased motion amplification algorithm. Methods-Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output. Results-Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI, and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient. Conclusion-Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion, and may reveal subtle physiological variations of the brain due to pathology using processing of the fundamental harmonic, or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

Research paper thumbnail of MR vascular fingerprinting: A new approach to compute cerebral blood volume, mean vessel radius, and oxygenation maps in the human brain

NeuroImage, Apr 1, 2014

In the present study, we describe a fingerprinting approach to analyze the time evolution of the ... more 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 parameters 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 using least square minimization. This approach was evaluated in 5 normal subjects and the results were compared to those obtained 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.

Research paper thumbnail of Professionals From the American Heart Association/American Stroke Association An Updated Definition of Stroke for the 21st Century : A Statement for Healthcare

contributed equally to this document. †The findings and conclusions in this report are those of t... more contributed equally to this document. †The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. ‡The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health or any part of the US federal government. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

Research paper thumbnail of Brain Diffusion Abnormalities in Children with Tension-Type and Migraine-Type Headaches

American Journal of Neuroradiology, Mar 15, 2018

BACKGROUND AND PURPOSE: Tension-type and migraine-type headaches are the most common chronic paro... more BACKGROUND AND PURPOSE: Tension-type and migraine-type headaches are the most common chronic paroxysmal disorders of childhood. The goal of this study was to compare regional cerebral volumes and diffusion in tension-type and migraine-type headaches against published controls. MATERIALS AND METHODS: Patients evaluated for tension-type or migraine-type headache without aura from May 2014 to July 2016 in a single center were retrospectively reviewed. Thirty-two patients with tension-type headache and 23 with migraine-type headache at an average of 4 months after diagnosis were enrolled. All patients underwent DWI at 3T before the start of pharmacotherapy. Using atlas-based DWI analysis, we determined regional volumetric and diffusion properties in the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. Multivariate analysis of covariance was used to test for differences between controls and patients with tension-type and migraine-type headaches. RESULTS: There were no significant differences in regional brain volumes between the groups. Patients with tension-type and migrainetype headaches showed significantly increased ADC in the hippocampus and brain stem compared with controls. Additionally, only patients with migraine-type headache showed significantly increased ADC in the thalamus and a trend toward increased ADC in the amygdala compared with controls. CONCLUSIONS: This study identifies early cerebral diffusion changes in patients with tension-type and migraine-type headaches compared with controls. The hypothesized mechanisms of nociception in migraine-type and tension-type headaches may explain the findings as a precursor to structural changes seen in adult patients with chronic headache. ABBREVIATIONS: ICHD-3 ϭ International Classification of Headache Disorders, Version 3.0; MTH ϭ migraine-type headache; TTH ϭ tension-type headache M igraine-type headache (MTH) is a common and chronic condition with multifactorial neurovascular etiologies characterized by recurrent paroxysmal attacks of throbbing headache with or without autonomic nervous system dysfunction. 1 Along with tension-type headache (TTH), these are the most common paroxysmal disorders of childhood. Neuroimaging in

Research paper thumbnail of Fast susceptibility-weighted imaging with three-dimensional short-axis propeller (SAP)-echo-planar imaging

Journal of Magnetic Resonance Imaging, Jun 23, 2014

Purpose-Susceptibility-Weighted Imaging (SWI) in neuroimaging can be challenging due to long scan... more Purpose-Susceptibility-Weighted Imaging (SWI) in neuroimaging can be challenging due to long scan times of 3D Gradient Recalled Echo (GRE), while faster techniques such as 3D interleaved EPI (iEPI) are prone to motion artifacts. Here we outline and implement a 3D Short-Axis Propeller Echo-Planar Imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI. Methods-Experiments were conducted on a 3T MRI system. 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically. Results-3D GRE images had a better target resolution (0.47 × 0.94 × 2mm, scan time = 5min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2mm) were acquired in a faster scan time (1:52min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data. Conclusion-While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients.

Research paper thumbnail of High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations

Journal of neurosurgery, Sep 1, 2018

B rain arteriovenous malformations (AVMs) are congenital vascular lesions that are composed of a ... more B rain arteriovenous malformations (AVMs) are congenital vascular lesions that are composed of a tangled network of dilated arteries and veins that do not have a normal intervening capillary bed and demonstrate early arteriovenous shunting. These lesions occur in 0.01% to 0.52% of individuals in the general population and carry a lifelong bleeding risk of 1.5% to 4% per year. 13,14,39 In the pediatric population, AVMs account for 35% to 55% of intracranial hemorrhage, with the rate of hemorrhage often dependent on multiple risk factors, such ABBREVIATIONS ASL = arterial spin labeling; AVM = arteriovenous malformation; CE-MRA = contrast-enhanced MRA; CTA = CT angiography; DAP = dose area product; DC = diagnostic confidence; DLP = dose length product; DSA = digital subtraction angiography; fe-SPGR = ferumoxytol-enhanced spoiled gradient recalled acquisition echo; fMRI = functional MRI; LC = lesion conspicuity; MRA = MR angiography; TOF = time of flight.

Research paper thumbnail of Improving dynamic susceptibility contrast MRI measurement of quantitative cerebral blood flow using corrections for partial volume and nonlinear contrast relaxivity: A xenon computed tomographic comparative study

Journal of Magnetic Resonance Imaging, Oct 1, 2009

Purpose-To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved w... more Purpose-To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT). Materials and Methods-18 patients with cerebrovascular disease underwent xeCT and MRI within 36 hrs. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed. Results-Mean xeCT CBF was 43.3±13.7 ml/100g/min (mean±SD). BB correction decreased CBF by a factor of 4.7±0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8±17.2 ml/100 g/min, coefficient of variation [COV]=32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3±10.8 ml/100 g/min, COV=27%). Between patients correlation was moderate even with both corrections (R=0.53). Conclusion-Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

Research paper thumbnail of Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study

Radiology, 2019

To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adul... more To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods: In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 4003 magnification highpower fields with iron-containing macrophages. Results: Ten adults (four male participants [mean age, 65 years 6 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years 6 12 years; age range, 32-65 years]; mean age of all participants, 58 years 6 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P , .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion: MRI measurements of susceptibility, R2*, and R2' (R2*-R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas.

Research paper thumbnail of Arterial Spin-Label Imaging in Patients with Normal Bolus Perfusion-weighted MR Imaging Findings: Pilot Identification of the Borderzone Sign

Radiology, Sep 1, 2009

To determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images ... more To determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images obtained in patients with normal bolus perfusion-weighted (PW) magnetic resonance (MR) imaging findings.

Research paper thumbnail of Noncontrast mapping of arterial delay and functional connectivity using resting-state functional MRI: A study in Moyamoya patients

Journal of Magnetic Resonance Imaging, Jan 13, 2014

Purpose-To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) s... more 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. Methods-Ten patients were scanned at 3T using a gradient-echo EPI 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 to 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 (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. Conclusions-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.

Research paper thumbnail of Identifying systematic errors in quantitative dynamic-susceptibility contrast perfusion imaging by high-resolution multi-echo parallel EPI

NMR in Biomedicine, 2007

Several obstacles usually confound a straightforward perfusion analysis using dynamicsusceptibili... more Several obstacles usually confound a straightforward perfusion analysis using dynamicsusceptibility contrast-based magnetic resonance imaging (DSC-MRI). In this work, it became possible to eliminate some of these sources of error by combining a multiple gradient-echo technique with parallel imaging (PI): first, the large dynamic range of tracer concentrations could be covered satisfactorily with multiple echo times (TE) which would otherwise result in overestimation of image magnitude in the presence of noise. Second, any bias from T 1 relaxation could be avoided by fitting to the signal magnitude of multiple TEs. Finally, with PI, a good tradeoff can be achieved between number of echoes, brain coverage, temporal resolution and spatial resolution. The latter reduces partial voluming, which could distort calculation of the arterial input function. Having ruled out these sources of error, a 4-fold overestimation of cerebral blood volume and flow remained, which was most likely due to the completely different relaxation mechanisms that are effective in arterial voxels compared with tissue. Hence, the uniform tissueindependent linear dependency of relaxation rate upon tracer concentration, which is usually assumed, must be questioned. Therefore, DSC-MRI requires knowledge of the exact dependency of transverse relaxation rate upon tracer concentration in order to calculate truly quantitative perfusion maps.

Research paper thumbnail of Combined arterial spin label and dynamic susceptibility contrast measurement of cerebral blood flow

Magnetic Resonance in Medicine, Jun 1, 2010

Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure c... more Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial-volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patientspecific correction factor, the ratio of ASL-and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 ± 30% (33%) for combined ASL and DSC CBF, 43 ± 21% (47%) for DSC, and 91 ± 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.

Research paper thumbnail of Relationship Between Apparent Diffusion Coefficient and Subsequent Hemorrhagic Transformation Following Acute Ischemic Stroke

Stroke, Oct 1, 2000

Background and Purpose-A method for identifying patients at increased risk for developing seconda... more Background and Purpose-A method for identifying patients at increased risk for developing secondary hemorrhagic transformation (HT) after acute ischemic stroke could be of significant value, particularly in patients being considered for thrombolytic therapy. We hypothesized that diffusion-weighted MRI might aid in the identification of such patients. Methods-We retrospectively analyzed 17 patients with ischemic stroke who received diffusion-weighted MRI within 8 hours of symptom onset and who also received follow-up neuroimaging within 1 week of initial scan. The apparent diffusion coefficient (ADC) for each pixel in the whole ischemic area was calculated, generating a histogram of values. Areas subsequently experiencing HT were then compared with areas not experiencing HT to determine the relationship between ADC and subsequent HT. Results-A significantly greater percentage of pixels possessed lower ADCs (Յ550ϫ10 Ϫ6 mm 2 /s) in HT lesions compared with non-HT lesions (47% versus 19%; PϽ0.001). Moreover, Ͼ40% of the pixels possessed values Յ550ϫ10 Ϫ6 mm 2 /s in all lesions experiencing secondary HT, compared with Ͻ31% of the pixels in the non-HT-destined lesions. Conclusions-HT-destined stroke regions possess a significantly great percentage of low ADC values than non-HTdestined regions. Early measurement of ADC values may be a useful tool for assessing secondary HT risk. (Stroke. 2000;31:2378-2384.

Research paper thumbnail of Erroneous Resting-State fMRI Connectivity Maps Due to Prolonged Arterial Arrival Time and How to Fix Them

Brain connectivity, Aug 1, 2018

In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the tempora... more In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the temporal correlation between spontaneous blood oxygen level-dependent signal fluctuations of spatially remote brain regions. Recently, several groups have shown that temporal shifts are present in rs-fMRI maps in patients with cerebrovascular disease due to spatial differences in arterial arrival times, and that this can be exploited to map arrival times in the brain. This suggests that rs-fMRI connectivity mapping may be similarly sensitive to such temporal shifts, and that standard rs-fMRI analysis methods may fail to identify functional connectivity networks. To investigate this, we studied the default mode network (DMN) in Moyamoya disease patients and compared it with normal healthy volunteers. Our results show that using standard independent component analysis (ICA) and seed-based approaches, arterial arrival delays lead to inaccurate incomplete characterization of functional connectivity within the DMN in Moyamoya disease patients. Furthermore, we propose two techniques to correct these errors, for seed-based and ICA methods, respectively. Using these methods, we demonstrate that it is possible to mitigate the deleterious effects of arterial arrival time on the assessment of functional connectivity of the DMN. As these corrections have not been applied to the vast majority of >200 prior rs-fMRI studies in patients with cerebrovascular disease, we suggest that they be interpreted with great caution. Correction methods should be applied in any rs-fMRI connectivity study of subjects expected to have abnormally delayed arterial arrival times.

Research paper thumbnail of Positron Emission Tomography Imaging of Poststroke Angiogenesis

Stroke, 2009

Background and Purpose-Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play... more Background and Purpose-Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play important roles during neurovascular repair after stroke. In this study, we imaged VEGFR expression with positron emission tomography (PET) to noninvasively analyze poststroke angiogenesis. Methods-Female Sprague-Dawley rats after distal middle cerebral artery occlusion surgery were subjected to weekly MRI, 18 F-FDG PET, and 64 Cu-DOTA-VEGF 121 PET scans. Several control experiments were performed to confirm the VEGFR specificity of 64 Cu-DOTA-VEGF 121 uptake in the stroke border zone. VEGFR, BrdU, lectin staining, and 125 I-VEGF 165 autoradiography on stroke brain tissue slices were performed to validate the in vivo findings. Results-T2-weighed MRI correlated with the "cold spot" on 18 F-FDG PET for rats undergoing distal middle cerebral artery occlusion surgery. The 64 Cu-DOTA-VEGF 121 uptake in the stroke border zone peaked at Ϸ10 days after surgery, indicating neovascularization as confirmed by histology (VEGFR-2, BrdU, and lectin staining). VEGFR specificity of 64 Cu-DOTA-VEGF 121 uptake was confirmed by significantly lower uptake of 64 Cu-DOTA-VEGF mutant in vivo and intense 125 I-VEGF 165 uptake ex vivo in the stroke border zone. No appreciable uptake of 64 Cu-DOTA-VEGF 121 was observed in the brain of sham-operated rats. Conclusions-For the first time to our knowledge, we successfully evaluated the VEGFR expression kinetics noninvasively in a rat stroke model. In vivo imaging of VEGFR expression could become a significant clinical tool to plan and monitor therapies aimed at improving poststroke angiogenesis. (Stroke. 2009;40:270-277.

Research paper thumbnail of <sup>99m</sup> Tc Annexin V Imaging of Neonatal Hypoxic Brain Injury

Stroke, Nov 1, 2000

Background and Purpose:-Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII... more Background and Purpose:-Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII. Methods-Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce HII. Experimental animals (nϭ17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with 99m Tc annexin V. Radionuclide images were recorded 2 hours later. Results-Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier. Conclusions-Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.

Research paper thumbnail of MR imaging and spectroscopy in clinical and experimental cerebral ischemia: a review

American Journal of Roentgenology, Mar 1, 1987

Beach, CA 92663. Address reprint requests to M.

Research paper thumbnail of Serial MRI After Transient Focal Cerebral Ischemia in Rats

Stroke, Aug 1, 2000

Background and Purpose-With the advent of thrombolytic therapy for acute stroke, reperfusion-asso... more Background and Purpose-With the advent of thrombolytic therapy for acute stroke, reperfusion-associated mechanisms of tissue injury have assumed greater importance. In this experimental study, we used several MRI techniques to monitor the dynamics of secondary ischemic damage, blood-brain barrier (BBB) disturbances, and the development of vasogenic edema during the reperfusion phase after focal cerebral ischemia in rats. Methods-Nineteen Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion of 30 minutes, 60 minutes, or 2.5 hours with the suture occlusion model. MRI, including diffusion-weighted imaging (DWI), T2-weighted imaging, perfusion-weighted imaging, and T1-weighted imaging, was performed 5 to 15 minutes before reperfusion, as well as 0.5, 1.5, and 2.5 hours and 1, 2, and 7 days after withdrawal of the suture. Final infarct size was determined histologically at 7 days. Results-In the 30-minute ischemia group (and partially also after 60 minutes), DWI abnormalities reversed transiently during the early reperfusion period but recurred after 1 day, probably due to secondary ischemic damage. After 2.5 hours of ischemia, DWI abnormalities no longer reversed, and signal intensity on both DWI and T2-weighted images increased rapidly in the previously ischemic region due to BBB damage (enhancement on postcontrast T1-weighted images) and edema formation. Early BBB damage during reperfusion was found to be predictive of relatively pronounced edema at subacute time points and was probably related to the increased mortality rates in this experimental group (3 of 7). Conclusions-Reperfusion after short periods of ischemia (30 to 60 minutes) appears to be mainly complicated by secondary ischemic damage as shown by the delayed recurrence of the DWI lesions, whereas BBB damage associated with vasogenic edema becomes a dominant factor with longer occlusion times (2.5 hours).

Research paper thumbnail of An Updated Definition of Stroke for the 21st Century

Stroke, Jul 1, 2013

contributed equally to this document. †The findings and conclusions in this report are those of t... more contributed equally to this document. †The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. ‡The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health or any part of the US federal government. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

Research paper thumbnail of MR Vascular Fingerprinting in Stroke and Brain Tumors Models

Scientific Reports, Nov 24, 2016

In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolu... more 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.

Research paper thumbnail of Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI)

Magnetic Resonance in Medicine, May 30, 2018

Purpose-Amplified Magnetic Resonance Imaging (aMRI) was recently introduced as a new brain motion... more Purpose-Amplified Magnetic Resonance Imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a videoprocessing algorithm, Eulerian Video Magnification (EVM), to amplify cardio-ballistic motion in retrospectively cardiac-gated MRI data. Here we strive to improve aMRI by incorporating a phasebased motion amplification algorithm. Methods-Phase-based aMRI was developed and tested for correct implementation and ability to amplify sub-voxel motions using digital phantom simulations. The image quality of phase-based aMRI was compared with EVM-based aMRI in healthy volunteers at 3T, and its amplified motion characteristics were compared with phase-contrast MRI. Data were also acquired on a patient with Chiari I malformation, and qualitative displacement maps were produced using free form deformation (FFD) of the aMRI output. Results-Phantom simulations showed that phase-based aMRI has a linear dependence of amplified displacement on true displacement. Amplification was independent of temporal frequency, varying phantom intensity, Rician noise, and partial volume effect. Phase-based aMRI supported larger amplification factors than EVM-based aMRI, and was less sensitive to noise and artifacts. Abnormal biomechanics were seen on FFD maps of the Chiari I malformation patient. Conclusion-Phase-based aMRI might be used in the future for quantitative analysis of minute changes in brain motion, and may reveal subtle physiological variations of the brain due to pathology using processing of the fundamental harmonic, or by selectively varying temporal harmonics. Preliminary data shows the potential of phase-based aMRI to qualitatively assess abnormal biomechanics in Chiari I malformation.

Research paper thumbnail of MR vascular fingerprinting: A new approach to compute cerebral blood volume, mean vessel radius, and oxygenation maps in the human brain

NeuroImage, Apr 1, 2014

In the present study, we describe a fingerprinting approach to analyze the time evolution of the ... more 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 parameters 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 using least square minimization. This approach was evaluated in 5 normal subjects and the results were compared to those obtained 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.

Research paper thumbnail of Professionals From the American Heart Association/American Stroke Association An Updated Definition of Stroke for the 21st Century : A Statement for Healthcare

contributed equally to this document. †The findings and conclusions in this report are those of t... more contributed equally to this document. †The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. ‡The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health or any part of the US federal government. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

Research paper thumbnail of Brain Diffusion Abnormalities in Children with Tension-Type and Migraine-Type Headaches

American Journal of Neuroradiology, Mar 15, 2018

BACKGROUND AND PURPOSE: Tension-type and migraine-type headaches are the most common chronic paro... more BACKGROUND AND PURPOSE: Tension-type and migraine-type headaches are the most common chronic paroxysmal disorders of childhood. The goal of this study was to compare regional cerebral volumes and diffusion in tension-type and migraine-type headaches against published controls. MATERIALS AND METHODS: Patients evaluated for tension-type or migraine-type headache without aura from May 2014 to July 2016 in a single center were retrospectively reviewed. Thirty-two patients with tension-type headache and 23 with migraine-type headache at an average of 4 months after diagnosis were enrolled. All patients underwent DWI at 3T before the start of pharmacotherapy. Using atlas-based DWI analysis, we determined regional volumetric and diffusion properties in the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. Multivariate analysis of covariance was used to test for differences between controls and patients with tension-type and migraine-type headaches. RESULTS: There were no significant differences in regional brain volumes between the groups. Patients with tension-type and migrainetype headaches showed significantly increased ADC in the hippocampus and brain stem compared with controls. Additionally, only patients with migraine-type headache showed significantly increased ADC in the thalamus and a trend toward increased ADC in the amygdala compared with controls. CONCLUSIONS: This study identifies early cerebral diffusion changes in patients with tension-type and migraine-type headaches compared with controls. The hypothesized mechanisms of nociception in migraine-type and tension-type headaches may explain the findings as a precursor to structural changes seen in adult patients with chronic headache. ABBREVIATIONS: ICHD-3 ϭ International Classification of Headache Disorders, Version 3.0; MTH ϭ migraine-type headache; TTH ϭ tension-type headache M igraine-type headache (MTH) is a common and chronic condition with multifactorial neurovascular etiologies characterized by recurrent paroxysmal attacks of throbbing headache with or without autonomic nervous system dysfunction. 1 Along with tension-type headache (TTH), these are the most common paroxysmal disorders of childhood. Neuroimaging in

Research paper thumbnail of Fast susceptibility-weighted imaging with three-dimensional short-axis propeller (SAP)-echo-planar imaging

Journal of Magnetic Resonance Imaging, Jun 23, 2014

Purpose-Susceptibility-Weighted Imaging (SWI) in neuroimaging can be challenging due to long scan... more Purpose-Susceptibility-Weighted Imaging (SWI) in neuroimaging can be challenging due to long scan times of 3D Gradient Recalled Echo (GRE), while faster techniques such as 3D interleaved EPI (iEPI) are prone to motion artifacts. Here we outline and implement a 3D Short-Axis Propeller Echo-Planar Imaging (SAP-EPI) trajectory as a faster, motion-correctable approach for SWI. Methods-Experiments were conducted on a 3T MRI system. 3D SAP-EPI, 3D iEPI, and 3D GRE SWI scans were acquired on two volunteers. Controlled motion experiments were conducted to test the motion-correction capability of 3D SAP-EPI. 3D SAP-EPI SWI data were acquired on two pediatric patients as a potential alternative to 2D GRE used clinically. Results-3D GRE images had a better target resolution (0.47 × 0.94 × 2mm, scan time = 5min), iEPI and SAP-EPI images (resolution = 0.94 × 0.94 × 2mm) were acquired in a faster scan time (1:52min) with twice the brain coverage. SAP-EPI showed motion-correction capability and some immunity to undersampling from rejected data. Conclusion-While 3D SAP-EPI suffers from some geometric distortion, its short scan time and motion-correction capability suggest that SAP-EPI may be a useful alternative to GRE and iEPI for use in SWI, particularly in uncooperative patients.

Research paper thumbnail of High-resolution 3D volumetric contrast-enhanced MR angiography with a blood pool agent (ferumoxytol) for diagnostic evaluation of pediatric brain arteriovenous malformations

Journal of neurosurgery, Sep 1, 2018

B rain arteriovenous malformations (AVMs) are congenital vascular lesions that are composed of a ... more B rain arteriovenous malformations (AVMs) are congenital vascular lesions that are composed of a tangled network of dilated arteries and veins that do not have a normal intervening capillary bed and demonstrate early arteriovenous shunting. These lesions occur in 0.01% to 0.52% of individuals in the general population and carry a lifelong bleeding risk of 1.5% to 4% per year. 13,14,39 In the pediatric population, AVMs account for 35% to 55% of intracranial hemorrhage, with the rate of hemorrhage often dependent on multiple risk factors, such ABBREVIATIONS ASL = arterial spin labeling; AVM = arteriovenous malformation; CE-MRA = contrast-enhanced MRA; CTA = CT angiography; DAP = dose area product; DC = diagnostic confidence; DLP = dose length product; DSA = digital subtraction angiography; fe-SPGR = ferumoxytol-enhanced spoiled gradient recalled acquisition echo; fMRI = functional MRI; LC = lesion conspicuity; MRA = MR angiography; TOF = time of flight.

Research paper thumbnail of Improving dynamic susceptibility contrast MRI measurement of quantitative cerebral blood flow using corrections for partial volume and nonlinear contrast relaxivity: A xenon computed tomographic comparative study

Journal of Magnetic Resonance Imaging, Oct 1, 2009

Purpose-To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved w... more Purpose-To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT). Materials and Methods-18 patients with cerebrovascular disease underwent xeCT and MRI within 36 hrs. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed. Results-Mean xeCT CBF was 43.3±13.7 ml/100g/min (mean±SD). BB correction decreased CBF by a factor of 4.7±0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8±17.2 ml/100 g/min, coefficient of variation [COV]=32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3±10.8 ml/100 g/min, COV=27%). Between patients correlation was moderate even with both corrections (R=0.53). Conclusion-Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

Research paper thumbnail of Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study

Radiology, 2019

To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adul... more To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods: In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 4003 magnification highpower fields with iron-containing macrophages. Results: Ten adults (four male participants [mean age, 65 years 6 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years 6 12 years; age range, 32-65 years]; mean age of all participants, 58 years 6 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P , .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion: MRI measurements of susceptibility, R2*, and R2' (R2*-R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas.

Research paper thumbnail of Arterial Spin-Label Imaging in Patients with Normal Bolus Perfusion-weighted MR Imaging Findings: Pilot Identification of the Borderzone Sign

Radiology, Sep 1, 2009

To determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images ... more To determine whether perfusion abnormalities are depicted on arterial spin-labeling (ASL) images obtained in patients with normal bolus perfusion-weighted (PW) magnetic resonance (MR) imaging findings.

Research paper thumbnail of Noncontrast mapping of arterial delay and functional connectivity using resting-state functional MRI: A study in Moyamoya patients

Journal of Magnetic Resonance Imaging, Jan 13, 2014

Purpose-To investigate if delays in resting-state spontaneous fluctuations of the BOLD (sfBOLD) s... more 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. Methods-Ten patients were scanned at 3T using a gradient-echo EPI 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 to 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 (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. Conclusions-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.

Research paper thumbnail of Identifying systematic errors in quantitative dynamic-susceptibility contrast perfusion imaging by high-resolution multi-echo parallel EPI

NMR in Biomedicine, 2007

Several obstacles usually confound a straightforward perfusion analysis using dynamicsusceptibili... more Several obstacles usually confound a straightforward perfusion analysis using dynamicsusceptibility contrast-based magnetic resonance imaging (DSC-MRI). In this work, it became possible to eliminate some of these sources of error by combining a multiple gradient-echo technique with parallel imaging (PI): first, the large dynamic range of tracer concentrations could be covered satisfactorily with multiple echo times (TE) which would otherwise result in overestimation of image magnitude in the presence of noise. Second, any bias from T 1 relaxation could be avoided by fitting to the signal magnitude of multiple TEs. Finally, with PI, a good tradeoff can be achieved between number of echoes, brain coverage, temporal resolution and spatial resolution. The latter reduces partial voluming, which could distort calculation of the arterial input function. Having ruled out these sources of error, a 4-fold overestimation of cerebral blood volume and flow remained, which was most likely due to the completely different relaxation mechanisms that are effective in arterial voxels compared with tissue. Hence, the uniform tissueindependent linear dependency of relaxation rate upon tracer concentration, which is usually assumed, must be questioned. Therefore, DSC-MRI requires knowledge of the exact dependency of transverse relaxation rate upon tracer concentration in order to calculate truly quantitative perfusion maps.

Research paper thumbnail of Combined arterial spin label and dynamic susceptibility contrast measurement of cerebral blood flow

Magnetic Resonance in Medicine, Jun 1, 2010

Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure c... more Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial-volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patientspecific correction factor, the ratio of ASL-and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 ± 30% (33%) for combined ASL and DSC CBF, 43 ± 21% (47%) for DSC, and 91 ± 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.

Research paper thumbnail of Relationship Between Apparent Diffusion Coefficient and Subsequent Hemorrhagic Transformation Following Acute Ischemic Stroke

Stroke, Oct 1, 2000

Background and Purpose-A method for identifying patients at increased risk for developing seconda... more Background and Purpose-A method for identifying patients at increased risk for developing secondary hemorrhagic transformation (HT) after acute ischemic stroke could be of significant value, particularly in patients being considered for thrombolytic therapy. We hypothesized that diffusion-weighted MRI might aid in the identification of such patients. Methods-We retrospectively analyzed 17 patients with ischemic stroke who received diffusion-weighted MRI within 8 hours of symptom onset and who also received follow-up neuroimaging within 1 week of initial scan. The apparent diffusion coefficient (ADC) for each pixel in the whole ischemic area was calculated, generating a histogram of values. Areas subsequently experiencing HT were then compared with areas not experiencing HT to determine the relationship between ADC and subsequent HT. Results-A significantly greater percentage of pixels possessed lower ADCs (Յ550ϫ10 Ϫ6 mm 2 /s) in HT lesions compared with non-HT lesions (47% versus 19%; PϽ0.001). Moreover, Ͼ40% of the pixels possessed values Յ550ϫ10 Ϫ6 mm 2 /s in all lesions experiencing secondary HT, compared with Ͻ31% of the pixels in the non-HT-destined lesions. Conclusions-HT-destined stroke regions possess a significantly great percentage of low ADC values than non-HTdestined regions. Early measurement of ADC values may be a useful tool for assessing secondary HT risk. (Stroke. 2000;31:2378-2384.

Research paper thumbnail of Erroneous Resting-State fMRI Connectivity Maps Due to Prolonged Arterial Arrival Time and How to Fix Them

Brain connectivity, Aug 1, 2018

In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the tempora... more In resting-state functional MRI (rs-fMRI), functional networks are assessed utilizing the temporal correlation between spontaneous blood oxygen level-dependent signal fluctuations of spatially remote brain regions. Recently, several groups have shown that temporal shifts are present in rs-fMRI maps in patients with cerebrovascular disease due to spatial differences in arterial arrival times, and that this can be exploited to map arrival times in the brain. This suggests that rs-fMRI connectivity mapping may be similarly sensitive to such temporal shifts, and that standard rs-fMRI analysis methods may fail to identify functional connectivity networks. To investigate this, we studied the default mode network (DMN) in Moyamoya disease patients and compared it with normal healthy volunteers. Our results show that using standard independent component analysis (ICA) and seed-based approaches, arterial arrival delays lead to inaccurate incomplete characterization of functional connectivity within the DMN in Moyamoya disease patients. Furthermore, we propose two techniques to correct these errors, for seed-based and ICA methods, respectively. Using these methods, we demonstrate that it is possible to mitigate the deleterious effects of arterial arrival time on the assessment of functional connectivity of the DMN. As these corrections have not been applied to the vast majority of >200 prior rs-fMRI studies in patients with cerebrovascular disease, we suggest that they be interpreted with great caution. Correction methods should be applied in any rs-fMRI connectivity study of subjects expected to have abnormally delayed arterial arrival times.

Research paper thumbnail of Positron Emission Tomography Imaging of Poststroke Angiogenesis

Stroke, 2009

Background and Purpose-Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play... more Background and Purpose-Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play important roles during neurovascular repair after stroke. In this study, we imaged VEGFR expression with positron emission tomography (PET) to noninvasively analyze poststroke angiogenesis. Methods-Female Sprague-Dawley rats after distal middle cerebral artery occlusion surgery were subjected to weekly MRI, 18 F-FDG PET, and 64 Cu-DOTA-VEGF 121 PET scans. Several control experiments were performed to confirm the VEGFR specificity of 64 Cu-DOTA-VEGF 121 uptake in the stroke border zone. VEGFR, BrdU, lectin staining, and 125 I-VEGF 165 autoradiography on stroke brain tissue slices were performed to validate the in vivo findings. Results-T2-weighed MRI correlated with the "cold spot" on 18 F-FDG PET for rats undergoing distal middle cerebral artery occlusion surgery. The 64 Cu-DOTA-VEGF 121 uptake in the stroke border zone peaked at Ϸ10 days after surgery, indicating neovascularization as confirmed by histology (VEGFR-2, BrdU, and lectin staining). VEGFR specificity of 64 Cu-DOTA-VEGF 121 uptake was confirmed by significantly lower uptake of 64 Cu-DOTA-VEGF mutant in vivo and intense 125 I-VEGF 165 uptake ex vivo in the stroke border zone. No appreciable uptake of 64 Cu-DOTA-VEGF 121 was observed in the brain of sham-operated rats. Conclusions-For the first time to our knowledge, we successfully evaluated the VEGFR expression kinetics noninvasively in a rat stroke model. In vivo imaging of VEGFR expression could become a significant clinical tool to plan and monitor therapies aimed at improving poststroke angiogenesis. (Stroke. 2009;40:270-277.

Research paper thumbnail of <sup>99m</sup> Tc Annexin V Imaging of Neonatal Hypoxic Brain Injury

Stroke, Nov 1, 2000

Background and Purpose:-Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII... more Background and Purpose:-Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII. Methods-Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce HII. Experimental animals (nϭ17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with 99m Tc annexin V. Radionuclide images were recorded 2 hours later. Results-Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier. Conclusions-Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.

Research paper thumbnail of MR imaging and spectroscopy in clinical and experimental cerebral ischemia: a review

American Journal of Roentgenology, Mar 1, 1987

Beach, CA 92663. Address reprint requests to M.

Research paper thumbnail of Serial MRI After Transient Focal Cerebral Ischemia in Rats

Stroke, Aug 1, 2000

Background and Purpose-With the advent of thrombolytic therapy for acute stroke, reperfusion-asso... more Background and Purpose-With the advent of thrombolytic therapy for acute stroke, reperfusion-associated mechanisms of tissue injury have assumed greater importance. In this experimental study, we used several MRI techniques to monitor the dynamics of secondary ischemic damage, blood-brain barrier (BBB) disturbances, and the development of vasogenic edema during the reperfusion phase after focal cerebral ischemia in rats. Methods-Nineteen Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion of 30 minutes, 60 minutes, or 2.5 hours with the suture occlusion model. MRI, including diffusion-weighted imaging (DWI), T2-weighted imaging, perfusion-weighted imaging, and T1-weighted imaging, was performed 5 to 15 minutes before reperfusion, as well as 0.5, 1.5, and 2.5 hours and 1, 2, and 7 days after withdrawal of the suture. Final infarct size was determined histologically at 7 days. Results-In the 30-minute ischemia group (and partially also after 60 minutes), DWI abnormalities reversed transiently during the early reperfusion period but recurred after 1 day, probably due to secondary ischemic damage. After 2.5 hours of ischemia, DWI abnormalities no longer reversed, and signal intensity on both DWI and T2-weighted images increased rapidly in the previously ischemic region due to BBB damage (enhancement on postcontrast T1-weighted images) and edema formation. Early BBB damage during reperfusion was found to be predictive of relatively pronounced edema at subacute time points and was probably related to the increased mortality rates in this experimental group (3 of 7). Conclusions-Reperfusion after short periods of ischemia (30 to 60 minutes) appears to be mainly complicated by secondary ischemic damage as shown by the delayed recurrence of the DWI lesions, whereas BBB damage associated with vasogenic edema becomes a dominant factor with longer occlusion times (2.5 hours).

Research paper thumbnail of An Updated Definition of Stroke for the 21st Century

Stroke, Jul 1, 2013

contributed equally to this document. †The findings and conclusions in this report are those of t... more contributed equally to this document. †The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. ‡The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health or any part of the US federal government. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

Research paper thumbnail of MR Vascular Fingerprinting in Stroke and Brain Tumors Models

Scientific Reports, Nov 24, 2016

In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolu... more 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.