Maolin Qiu

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.

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. Magn Reson Med 53:408–417, 2005.

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. Magn Reson Med 53:666–674, 2005.

Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging

BACKGROUND 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. AIMS To test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum. METHOD Fractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging. RESULTS Fractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups. CONCLUSIONS Our findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum.

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%.

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.

Small Decrements in Systemic Glucose Provoke Increases in Hypothalamic Blood Flow Prior to the Release of Counterregulatory Hormones

OBJECTIVE—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. RESEARCH DESIGN AND METHODS—Nine nondiabetic volunteers underwent two hyperinsulinemic clamp sessions in which pulsed arterial spin labeling was used to measure regional cerebral blood flow (CBF) at euglycemia (∼95 mg/dl) on one occasion and as glucose levels were declining to a nadir of ∼50 mg/dl on another occasion. Plasma glucose and counterregulatory hormones were measured during both study sessions. RESULTS—CBF to the hypothalamus significantly increased when glucose levels decreased to 77.2 ± 2 mg/dl compared with the euglycemic control session when glucose levels were 95.7 ± 3 mg/dl (P = 0.0009). Hypothalamic perfusion was significantly increased before there was a significant elevation in counterregulatory hormones. CONCLUSIONS—Our data suggest that the hypothalamus is exquisitely sensitive to small decrements in systemic glucose levels in healthy, nondiabetic subjects and that hypothalamic blood flow, and presumably neuronal activity, precedes the rise in counterregulatory hormones seen during hypoglycemia.

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 (∼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. Magn Reson Med, 2010.

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. Magn Reson Med, 2006.

Induced Hepatic Fibrosis in Rats: Hepatic Steatosis, Macromolecule Content, Perfusion Parameters, and Their Correlations—Preliminary MR Imaging in Rats

PURPOSE 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. MATERIALS AND METHODS The animal research protocol was approved by the Institutional Animal Care and Use Committee. Fifty-two rats (38 treated, 14 control) were included. A CCl(4) mixture was injected three times per week for 2-16 weeks. Fat-to-water ratios (FWRs) were calculated. Images were obtained with 12 saturation offset frequencies; magnetization transfer ratios (MTRs) were calculated. Distribution volume (DV), mean transit time (MTT), and portal fraction (PF) of blood inflow were calculated. For pairwise group comparisons, an unequal two-tailed Student t test was used. For pairwise correlations between variables, Pearson correlation coefficients were calculated. For multiple pairwise comparisons, Bonferroni correction was performed by adjusting the significance level (alpha). RESULTS FWR and DV were correlated with CCl(4) treatment duration from 0 through 8 weeks (r = 0.658, P < .001 and r = -0.664, P < .001, respectively; alpha = .010). PF and MTT were correlated with CCl(4) treatment duration from 0 through 16 weeks (r = -0.483, P = .002 and r = 0.414, P = .008, respectively; alpha = .010). DV was inversely correlated with FWR over the same period (r = -0.581, P < .001; alpha = .007). Fibrotic rats without cirrhosis had a higher FWR and lower DV and PF (P < .001, P < .001, and P = .004, respectively; alpha = .017) than control rats, and lower MTR, DV, and MTT (P = .014, .001, and .010, respectively; alpha = .017) than cirrhotic rats. Cirrhotic rats had a higher FWR and a lower PF (P < .001, alpha = .017) than control rats. CONCLUSION Magnetization transfer contrast is not a specific indicator of increased fibrosis in diseased liver; steatosis may influence some perfusion parameters.