Audrey P. Fan

Fast quantitative susceptibility mapping with L1-regularization and automatic parameter selection.

To enable fast reconstruction of quantitative susceptibility maps with total variation penalty and automatic regularization parameter selection.

Phase-based Regional Oxygen Metabolism (PROM) using MRI

Venous oxygen saturation (Yv) in cerebral veins and the cerebral metabolic rate of oxygen (CMRO2) are important indicators for brain function and disease. Although MRI has been used for global measurements of these parameters, currently there is no recognized technique to quantify regional Yv and CMRO2 using noninvasive imaging. This article proposes a technique to quantify CMRO2 from independent MRI estimates of Yv and cerebral blood flow. The approach uses standard gradient‐echo and arterial spin labeling acquisitions to make these measurements. Using MR susceptometry on gradient‐echo phase images, Yv was quantified for candidate vein segments in gray matter that approximate a long cylinder parallel to the main magnetic field. Local cerebral blood flow for the identified vessel was determined from a corresponding region in the arterial spin labeling perfusion map. Ficks principle of arteriovenous difference was then used to quantify CMRO2 locally around each vessel. Application of this method in young, healthy subjects provided gray matter averages of 59.6% ± 2.3% for Yv, 51.7 ± 6.4 mL/100 g/min for cerebral blood flow, and 158 ± 18 μmol/100 g/min for CMRO2 (mean ± SD, n = 12), which is consistent with values previously reported by positron emission tomography and MRI. Magn Reson Med, 2012.

Quantitative oxygenation venography from MRI phase

To demonstrate acquisition and processing methods for quantitative oxygenation venograms that map in vivo oxygen saturation (SvO2) along cerebral venous vasculature.

Fast quantitative susceptibility mapping using 3D EPI and total generalized variation

Quantitative susceptibility mapping (QSM) allows new insights into tissue composition and organization by assessing its magnetic property. Previous QSM studies have already demonstrated that magnetic susceptibility is highly sensitive to myelin density and fiber orientation as well as to para- and diamagnetic trace elements. Image resolution in QSM with current approaches is limited by the long acquisition time of 3D scans and the need for high signal to noise ratio (SNR) to solve the dipole inversion problem. We here propose a new total-generalized-variation (TGV) based method for QSM reconstruction, which incorporates individual steps of phase unwrapping, background field removal and dipole inversion in a single iteration, thus yielding a robust solution to the reconstruction problem. This approach has beneficial characteristics for low SNR data, allowing for phase data to be rapidly acquired with a 3D echo planar imaging (EPI) sequence. The proposed method was evaluated with a numerical phantom and in vivo at 3 and 7 T. Compared to total variation (TV), TGV-QSM enforced higher order smoothness which yielded solutions closer to the ground truth and prevented stair-casing artifacts. The acquisition time for images with 1mm isotropic resolution and whole brain coverage was 10s on a clinical 3 Tesla scanner. In conclusion, 3D EPI acquisition combined with single-step TGV reconstruction yields reliable QSM images of the entire brain with 1mm isotropic resolution in seconds. The short acquisition time combined with the robust reconstruction may enable new QSM applications in less compliant populations, clinical susceptibility tensor imaging, and functional resting state examinations.

Wave‐CAIPI for highly accelerated 3D imaging

To introduce the wave‐CAIPI (controlled aliasing in parallel imaging) acquisition and reconstruction technique for highly accelerated 3D imaging with negligible g‐factor and artifact penalties.

MicroRNA Processing Pathway Regulates Olfactory Neuron Morphogenesis

The microRNA (miRNA) processing pathway produces miRNAs as posttranscriptional regulators of gene expression. The nuclear RNase III Drosha catalyzes the first processing step together with the dsRNA binding protein DGCR8/Pasha generating pre-miRNAs [1, 2]. The next cleavage employs the cytoplasmic RNase III Dicer producing miRNA duplexes [3, 4]. Finally, Argonautes are recruited with miRNAs into an RNA-induced silencing complex for mRNA recognition (Figure 1A). Here, we identify two members of the miRNA pathway, Pasha and Dicer-1, in a forward genetic screen for mutations that disrupt wiring specificity of Drosophila olfactory projection neurons (PNs). The olfactory system is built as discrete map of highly stereotyped neuronal connections [5, 6]. Each PN targets dendrites to a specific glomerulus in the antennal lobe and projects axons stereotypically into higher brain centers [7-9]. In selected PN classes, pasha and Dicer-1 mutants cause specific PN dendrite mistargeting in the antennal lobe and altered axonal terminations in higher brain centers. Furthermore, Pasha and Dicer-1 act cell autonomously in postmitotic neurons to regulate dendrite and axon targeting during development. However, Argonaute-1 and Argonaute-2 are dispensable for PN morphogenesis. Our findings suggest a role for the miRNA processing pathway in establishing wiring specificity in the nervous system.

Fast image reconstruction with L2‐regularization

We introduce L2‐regularized reconstruction algorithms with closed‐form solutions that achieve dramatic computational speed‐up relative to state of the art L1‐ and L2‐based iterative algorithms while maintaining similar image quality for various applications in MRI reconstruction.

Comparison of cerebral blood flow measurement with [15O]-water positron emission tomography and arterial spin labeling magnetic resonance imaging: A systematic review

Noninvasive imaging of cerebral blood flow provides critical information to understand normal brain physiology as well as to identify and manage patients with neurological disorders. To date, the reference standard for cerebral blood flow measurements is considered to be positron emission tomography using injection of the [15O]-water radiotracer. Although [15O]-water has been used to study brain perfusion under normal and pathological conditions, it is not widely used in clinical settings due to the need for an on-site cyclotron, the invasive nature of arterial blood sampling, and experimental complexity. As an alternative, arterial spin labeling is a promising magnetic resonance imaging technique that magnetically labels arterial blood as it flows into the brain to map cerebral blood flow. As arterial spin labeling becomes more widely adopted in research and clinical settings, efforts have sought to standardize the method and validate its cerebral blood flow values against positron emission tomography-based cerebral blood flow measurements. The purpose of this work is to critically review studies that performed both [15O]-water positron emission tomography and arterial spin labeling to measure brain perfusion, with the aim of better understanding the accuracy and reproducibility of arterial spin labeling relative to the positron emission tomography reference standard.

Regional quantification of cerebral venous oxygenation from MRI susceptibility during hypercapnia

There is an unmet medical need for noninvasive imaging of regional brain oxygenation to manage stroke, tumor, and neurodegenerative diseases. Oxygenation imaging from magnetic susceptibility in MRI is a promising new technique to measure local venous oxygen extraction fraction (OEF) along the cerebral venous vasculature. However, this approach has not been tested in vivo at different levels of oxygenation. The primary goal of this study was to test whether susceptibility imaging of oxygenation can detect OEF changes induced by hypercapnia, via CO2 inhalation, within selected a priori brain regions. Ten healthy subjects were scanned at 3T with a 32-channel head coil. The end-tidal CO2 (ETCO2) was monitored continuously and inspired gases were adjusted to achieve steady-state conditions of eucapnia (41±3mmHg) and hypercapnia (50±4mmHg). Gradient echo phase images and pseudo-continuous arterial spin labeling (pcASL) images were acquired to measure regional OEF and CBF respectively during eucapnia and hypercapnia. By assuming constant cerebral oxygen consumption throughout both gas states, regional CBF values were computed to predict the local change in OEF in each brain region. Hypercapnia induced a relative decrease in OEF of -42.3% in the straight sinus, -39.9% in the internal cerebral veins, and approximately -50% in pial vessels draining each of the occipital, parietal, and frontal cortical areas. Across volunteers, regional changes in OEF correlated with changes in ETCO2. The reductions in regional OEF (via phase images) were significantly correlated (P<0.05) with predicted reductions in OEF derived from CBF data (via pcASL images). These findings suggest that susceptibility imaging is a promising technique for OEF measurements, and may serve as a clinical biomarker for brain conditions with aberrant regional oxygenation.

Reproducibility of T2* mapping in the human cerebral cortex in vivo at 7 tesla MRI

To assess the test–retest reproducibility of cortical mapping of T2* relaxation rates at 7 Tesla (T) MRI. T2* maps have been used for studying cortical myelo‐architecture patterns in vivo and for characterizing conditions associated with changes in iron and/or myelin concentration.