Wendy W. Ni

High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol

Cerebral blood volume maps are usually acquired using dynamic susceptibility contrast imaging which inherently limits the spatial resolution and signal to noise ratio of the images. In this study, we used ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA), an FDA‐approved compound, to obtain high‐resolution cerebral blood volume maps with a steady‐state approach in seven healthy volunteers. R2* maps (0.8 × 0.8 × 1 mm3) were acquired before and after injection of ferumoxytol and an intraindividual normalization protocol was used to obtain quantitative values. The results show excellent contrast between white and gray matter as well as fine highly detailed vascular structures. An average blood volume of 4% was found in the brain of all volunteers, consistent with prior literature values. A linear relationship was found between ferumoxytol dose (mg/kg) and ΔR2* (1/s) in gray (R2 = 0.98) and white matter (R2 = 0.98). A quadratic relationship was found in the sagittal sinus (R2 = 0.98). The cerebral blood volume maps compare well with lower resolution dynamic susceptibility contrast‐MRI and their use should improve the evaluation of small and heterogeneous lesions and facilitate intrapatient and interpatient comparisons. Magn Reson Med 70:705–710, 2013.

Noncontrast mapping of arterial delay and functional connectivity using resting-state functional MRI: a study in Moyamoya patients.

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.

MR Vascular Fingerprinting: A New Approach to Compute Cerebral Blood Volume, Mean Vessel Radius, and Oxygenation Maps in the Human Brain

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.

Comparison of R2′ measurement methods in the normal brain at 3 tesla

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.

Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease

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 CVs (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.

Imaging of cerebrovascular reserve and oxygenation in Moyamoya disease

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 (Kendalls 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.

Amplified magnetic resonance imaging (aMRI).

This work describes a new method called amplified MRI (aMRI), which uses Eulerian video magnification to amplify the subtle spatial variations in cardiac‐gated brain MRI scans and enables better visualization of brain motion.

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

Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video‐processing 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 phase‐based motion amplification algorithm.

Benchmarking transverse spin relaxation based oxygenation measurements in the brain during hypercapnia and hypoxia

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.