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In JoVE (1)
Other Publications (17)
- Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Medical Image Analysis
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Journal of Magnetic Resonance (San Diego, Calif. : 1997)
- Proceedings of the National Academy of Sciences of the United States of America
- Anesthesia and Analgesia
- Human Brain Mapping
- Radiology
- The British Journal of Psychiatry : the Journal of Mental Science
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Diabetes
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- NeuroImage
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- NeuroImage
Articles by Maolin Qiu in JoVE
JoVE Clinical and Translational Medicine
Real-time fMRI Biofeedback Targeting the Orbitofrontal Cortex for Contamination Anxiety
1Department of Diagnostic Radiology, Yale University School of Medicine, 2Department of Psychiatry, Yale University School of Medicine, 3Yale Child Study Center, Yale University School of Medicine, 4Interdepartmental Neuroscience Program, Yale University School of Medicine
Here we present a method for training people to control a brain area involved in contamination anxiety and for probing the relationship between contamination anxiety and brain connectivity patterns.
Other articles by Maolin Qiu on PubMed
Brain Tissue Segmentation Based on Corrected Gray-scale Analysis
Image signal-to-noise ratio (SNR) and signal intensity (SI) inhomogeneities are factors that strongly affect the accuracy and precision of brain tissue segmentations in magnetic resonance image (MRI). In this work, SNR and contrast of brain images are optimized by TR and inversion recovery time TI in multi-spectrum MRI data sets. SI inhomogeneities are measured in vivo using a recently developed method allowing improved correction. The three-Gaussain distribution model is used to fit histograms of the images to find the initialization parameters for an Expectation-Maximization (EM) segmentation algorithm. Compared with other methods, the field map method provides better correction of SI inhomogeneities and excellent segmentation results.
Measurement and Correction of Transmitter and Receiver Induced Nonuniformities in Vivo
Signal intensity nonuniformities in high field MR imaging limit the ability of MRI to provide quantitative information and can negatively impact diagnostic scan quality. In this paper, a simple method is described for correcting these effects based on in vivo measurement of the transmission field B1+ and reception sensitivity maps. These maps can be obtained in vivo with either gradient echo (GE) or spin echo (SE) imaging sequences, but the SE approach exhibits an advantage over the GE approach for correcting images over a range of flip angles. In a uniform phantom, this approach reduced the ratio of the signal SD to its mean from around 30% before correction to approximately 6% for the SE approach and 9% for the GE approach after correction. The application of the SE approach for correcting intensity nonuniformities is demonstrated in vivo with human brain images obtained using a conventional spin echo sequence at 3.0 T. Furthermore, it is also shown that this in vivo B1+ and reception sensitivity mapping can be performed using segmented echo planar imaging sequences providing acquisition times of less than 2 min. Although the correction presented here is demonstrated with a simultaneous transmit and receive volume coil, it can be extended to the case of separate transmission and reception coils, including surface and phase array coils.
In Vivo Method for Correcting Transmit/receive Nonuniformities with Phased Array Coils
Phased array coils are finding widespread applications in both the research and the clinical setting. However, intensity nonuniformities with such coils can reduce the potential benefits of these coils, particularly for applications such as tissue segmentation. In this work, a method is described for correcting the nonuniform signal response based on in vivo measures of both the transmission field of body coil and the reception sensitivity of phased array coils, separately. For a uniform phantom, the reception sensitivity can be calculated using both Bloch equations and transmission field maps. For a heterogeneous object such as a brain, a minimal contrast acquisition must be obtained to map the receiver nonuniformities. This transmit field/receiver sensitivity (TFRS) approach is compared with the standard methods of using the body coil to obtain a reference scan and low-pass filtering. The quantitative comparison results shows that the TFRS approach provides superior results in correcting intensity nonuniformities for a uniform phantom. This approach reduces the ratio between signal intensity SD of an image and its mean intensity from approximately 21% before correction to 13% after correction. Results are also shown demonstrating the utility of this approach in vivo with human brain images. The method is general and can be applied with most pulse sequences, any coil combination for transmission and reception, and in any anatomic region.
White Matter Tractography by Anisotropic Wavefront Evolution and Diffusion Tensor Imaging
Determination of axonal pathways provides an invaluable means to study the connectivity of the human brain and its functional network. Diffusion tensor imaging (DTI) is unique in its ability to capture the restricted diffusion of water molecules which can be used to infer the directionality of tissue components. In this paper, we introduce a white matter tractography method based on anisotropic wavefront propagation in diffusion tensor images. A front propagates in the white matter with a speed profile governed by the isocontour of the diffusion tensor ellipsoid. By using the ellipsoid, we avoid possible misclassification of the principal eigenvector in oblate regions. The wavefront evolution is described by an anisotropic version of the static Hamilton-Jacobi equation, which is solved by a sweeping method in order to obtain correct arrival times. Pathways of connection are determined by tracing minimum-cost trajectories using the characteristic vector field of the resulting partial differential equation. A validity index is described to rate the goodness of the resulting pathways with respect to the directionality of the tensor field. Connectivity results using normal human DTI brain images are illustrated and discussed. We also compared our method with a similar level set-based tractography technique, and found that the anisotropic evolution increased the validity index of the obtained pathways by 18%.
Factors Influencing Flip Angle Mapping in MRI: RF Pulse Shape, Slice-select Gradients, Off-resonance Excitation, and B0 Inhomogeneities
To understand the various effects that influence actual flip angles, and correct for these effects, it is important to precisely quantify the MRI parameters (such as T1, T2, and perfusion). In this paper actual flip angle maps are calculated using a conventional gradient-echo (GRE) sequence with different radiofrequency (RF) pulse shapes (Gaussian, sinc, and truncated-sinc), slice-selection gradients, off-resonance excitations, and B0 field inhomogeneities. The experimental results demonstrate that RF pulse shapes significantly affect the flip angle distribution and calibration factors. Off-resonance RF excitations, B0 nonuniformities, and slice-selection gradients can lead to degradations in the signal intensities of the images used to map the flip angle, and potentially introduce a bias and increased variance in the measured flip angles.
T1 Measurements Incorporating Flip Angle Calibration and Correction in Vivo
In this work, we propose a variable FA method that combines in vivo flip angle (FA) calibration and correction with a short TR variable FA approach for a fast and accurate T(1) mapping. The precision T(1)s measured across a uniform milk phantom is estimated to be 2.65% using the conventional (slow) inversion recovery (IR) method and 28.5% for the variable FA method without FA correction, and 2.2% when FA correction is included. These results demonstrate that the sensitivity of the variable FA method to RF nonuniformities can be dramatically reduced when these nonuniformities are directly measured and corrected. The acquisition time for this approach decreases to 10 min from 85 min for the conventional IR method. In addition, we report that the averaged T(1)s measured from five normal subjects are 900 +/- 3 ms, 1337 +/- 8 ms and 2180 +/- 25 ms in white matter (WM), gray matter (GM) and cerebral spinal fluid (CSF) using the variable flip angle method with FA correction at 3 T, respectively. These results are consistent with previously reported values obtained with much longer acquisition times. The method reduces the total scan time for whole brain T(1) mapping, including FA measurement and calibration, to approximately 6 min. The novelty of this method lies in the in vivo calibration and the correction of the FAs, thereby allowing a rapid and accurate T(1) mapping at high field for many applications.
Neural Correlates of Epigenesis
The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.
Sevoflurane 0.25 MAC Preferentially Affects Higher Order Association Areas: a Functional Magnetic Resonance Imaging Study in Volunteers
Functional magnetic resonance imaging (fMRI) can objectively measure the subjective effects of anesthesia. Memory-related regions (association areas) are affected by subanesthetic doses of volatile anesthetics. In this study we measured the regional neuronal effects of 0.25 MAC sevoflurane in healthy volunteers and differentiated the effect between primary cortical regions and association areas.
Spatial Nonuniformity of the Resting CBF and BOLD Responses to Sevoflurane: in Vivo Study of Normal Human Subjects with Magnetic Resonance Imaging
Pulsed arterial spin labeling magnetic resonance imaging (MRI) was performed to investigate the local coupling between resting regional cerebral blood flow (rCBF) and BOLD (blood oxygen level dependent) signal changes in 22 normal human subjects during the administration of 0.25 MAC (minimum alveolar concentration) sevoflurane. Two states were compared with subjects at rest: anesthesia and no-anesthesia. Regions of both significantly increased and decreased resting-state rCBF were observed. Increases were limited primarily to subcortical structures and insula, whereas, decreases were observed primarily in neocortical regions. No significant change was found in global CBF (gCBF). By simultaneously measuring rCBF and BOLD, region-specific anesthetic effects on the coupling between rCBF and BOLD were identified. Multiple comparisons of the agent-induced rCBF and BOLD changes demonstrated significant (P < 0.05) spatial variability in rCBF-BOLD coupling. The slope of the linear regression line for AC, where rCBF was increased by sevoflurane, was markedly smaller than the slope for those ROIs where rCBF was decreased by sevoflurane, indicating a bigger change in BOLD per unit change in rCBF in regions where rCBF was increased by sevoflurane. These results suggest that it would be inaccurate to use a global quantitative model to describe coupling across all brain regions and in all anesthesia conditions. The observed spatial nonuniformity of rCBF and BOLD signal changes suggests that any interpretation of BOLD fMRI data in the presence of an anesthetic requires consideration of these insights.
Induced Hepatic Fibrosis in Rats: Hepatic Steatosis, Macromolecule Content, Perfusion Parameters, and Their Correlations--preliminary MR Imaging in Rats
To prospectively evaluate magnetic resonance (MR) imaging for the characterization of liver fibrosis by estimating fat and extracellular matrix content and hepatic perfusion parameters in CCl(4)-treated rats.
Abnormal Anterior Cingulum Integrity in Bipolar Disorder Determined Through Diffusion Tensor Imaging
Convergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder.
Anesthetic Effects on Regional CBF, BOLD, and the Coupling Between Task-induced Changes in CBF and BOLD: an FMRI Study in Normal Human Subjects
Functional MR imaging was performed in sixteen healthy human subjects measuring both regional cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) signal when visual and auditory stimuli were presented to subjects in the presence or absence of anesthesia. During anesthesia, 0.25 mean alveolar concentration (MAC) sevoflurane was administrated. We found that low-dose sevoflurane decreased the task-induced changes in both BOLD and CBF. Within the visual and auditory regions of interest inspected, both baseline CBF and the task-induced changes in CBF decreased significantly during anesthesia. Low-dose sevoflurane significantly altered the task-induced CBF-BOLD coupling; for a unit change of CBF, a larger change in BOLD was observed in the anesthesia condition than in the anesthesia-free condition. Low-dose sevoflurane was also found to have significant impact on the spatial nonuniformity of the task-induced coupling. The alteration of task-induced CBF-BOLD coupling by low-dose sevoflurane introduces ambiguity to the direct interpretation of functional MRI (fMRI) data based on only one of the indirect measures-CBF or BOLD. Our observations also indicate that the manipulation of the brain with an anesthetic agent complicates the model-based quantitative interpretation of fMRI data, in which the relative task-induced changes in oxidative metabolism are calculated by means of a calibrated model given the relative changes in the indirect vascular measures, usually CBF and BOLD.
Small Decrements in Systemic Glucose Provoke Increases in Hypothalamic Blood Flow Prior to the Release of Counterregulatory Hormones
The hypothalamus is the central brain region responsible for sensing and integrating responses to changes in circulating glucose. The aim of this study was to determine the time sequence relationship between hypothalamic activation and the initiation of the counterregulatory hormonal response to small decrements in systemic glucose.
Evaluation of Hepatic Fibrosis with Portal Pressure Gradient in Rats
MRI has the potential of providing a noninvasive assessment of liver pathology. This work introduces a portal pressure gradient (PPG) model derived from fluid mechanics, where the PPG is proportional to the average velocity and inversely proportional to the vessel area in the upper part of portal vein. Using a phase-contrast spoiled gradient echo sequence, the PPG model was verified in a phantom study and was tested in an animal study using 35 rats with various degrees of hepatic fibrosis induced by carbon tetrachloride (CCl(4)). Histological examination was conducted to determine the severity of hepatic fibrosis. The fibrosis score monotonically increased with the duration of CCl(4) treatment. The PPG was highly correlated with nonzero fibrosis scores (r(2) = 0.90, P < 0.05). There was a significant difference between control and cirrhosis groups (P < 0.0006, alpha < 0.0018). The difference between control and fibrosis (noncirrhosis) groups (P < 0.002, alpha < 0.006) was also significant. Without the administration of any contrast agent, the MRI-PPG approach shows promise as a noninvasive means of evaluating liver fibrosis.
Functional Connectivity and Alterations in Baseline Brain State in Humans
This work examines the influence of changes in baseline activity on the intrinsic functional connectivity fMRI (fc-fMRI) in humans. Baseline brain activity was altered by inducing anesthesia (sevoflurane end-tidal concentration 1%) in human volunteers and fc-fMRI maps between the pre-anesthetized and anesthetized conditions were compared across different brain networks. We particularly focused on low-level sensory areas (primary somatosensory, visual, and auditory cortices), the thalamus, and pain (insula), memory (hippocampus) circuits, and the default mode network (DMN), the latter three to examine higher-order brain regions. The results indicate that, while fc-fMRI patterns did not significantly differ (p<0.005; 20-voxel cluster threshold) in sensory cortex and in the DMN between the pre- and anesthetized conditions, fc-fMRI in high-order cognitive regions (i.e. memory and pain circuits) was significantly altered by anesthesia. These findings provide further evidence that fc-fMRI reflects intrinsic brain properties, while also demonstrating that 0.5 MAC sevoflurane anesthesia preferentially modulates higher-order connections.
Arterial Transit Time Effects in Pulsed Arterial Spin Labeling CBF Mapping: Insight from a PET and MR Study in Normal Human Subjects
Arterial transit time (ATT), a key parameter required to calculate absolute cerebral blood flow in arterial spin labeling (ASL), is subject to much uncertainty. In this study, ASL ATTs were estimated on a per-voxel basis using data measured by both ASL and positron emission tomography in the same subjects. The mean ATT increased by 260 +/- 20 (standard error of the mean) ms when the imaging slab shifted downwards by 54 mm, and increased from 630 +/- 30 to 1220 +/- 30 ms for the first slice, with an increase of 610 +/- 20 ms over a four-slice slab when the gap between the imaging and labeling slab increased from 20 to 74 mm. When the per-slice ATTs were employed in ASL cerebral blood flow quantification and the in-slice ATT variations ignored, regional cerebral blood flow could be significantly different from the positron emission tomography measures. ATT also decreased with focal activation by the same amount for both visual and motor tasks (approximately 80 ms). These results provide a quantitative relationship between ATT and the ASL imaging geometry and yield an assessment of the assumptions commonly used in ASL imaging. These findings should be considered in the interpretation of, and comparisons between, different ASL-based cerebral blood flow studies. The results also provide spatially specific ATT data that may aid in optimizing the ASL imaging parameters.
A Whole-brain Voxel Based Measure of Intrinsic Connectivity Contrast Reveals Local Changes in Tissue Connectivity with Anesthetic Without a Priori Assumptions on Thresholds or Regions of Interest
The analysis of spontaneous fluctuations of functional magnetic resonance imaging (fMRI) signals has recently gained attention as a powerful tool for investigating brain circuits in a non-invasive manner. Correlation-based connectivity analysis investigates the correlations of spontaneous fluctuations of the fMRI signal either between a single seed region of interest (ROI) and the rest of the brain or between multiple ROIs. To do this, a priori knowledge is required for defining the ROI(s) and without such knowledge functional connectivity fMRI cannot be used as an exploratory tool for investigating the functional organization of the brain and its modulation under different conditions. In this work we examine two indices that provide voxel based maps reflecting the intrinsic connectivity contrast (ICC) of individual tissue elements without the need for defining ROIs and hence require no a priori information or assumptions. These voxel based ICC measures can also be used to delineate regions of interest for further functional or network analyses. The indices were applied to the study of sevoflurane anesthesia-induced alterations in intrinsic connectivity. In concordance with previous studies, the results show that sevoflurane affects different brain circuits in a heterogeneous manner. In addition ICC analyses revealed changes in regions not previously identified using conventional ROI connectivity analyses, probably because of an inappropriate choice of the ROI in the earlier studies. This work highlights the importance of such voxel based connectivity methodology.
