Fractional amplitude of low-frequency fluctuation changes in functional dyspepsia: A resting-state fMRI study

Recently, there is an increasing interest in the study of the role of brain dysfunction in the pathogenesis of symptoms of functional dyspepsia (FD). More specifically, abnormal brain activities in patients with FD during the resting state have been proven by several positron emission tomography (PET) studies. Resting-state functional magnetic resonance imaging (fMRI) is also a valuable tool in investigating spontaneous brain activity abnormalities in pathological conditions. In the present study, we examined the amplitude of low-frequency fluctuations (ALFF) and fractional (f)ALFF changes in patients with FD by using fMRI. Twenty-nine patients with FD and sixteen healthy controls participated in this study. Between-group differences in ALFF/fALFF were examined using a permutation-based nonparametric test after accounting for the gender and age effects. The results revealed a significant between-group difference in fALFF but not in ALFF in multiple brain regions including the right insula, brainstem and cerebellum. Seed-based resting-state functional connectivity analysis revealed that FD patients have increased correlations between the right cerebellum and multiple brain regions including the bilateral brainstem, bilateral cerebellum, bilateral thalamus, left para-/hippocampus, left pallidum and left putamen. Furthermore, fLAFF values in the right insula were positively correlated with the severity of the disease. These findings have provided further evidence of spontaneous brain activity abnormalities in FD patients which might contribute to our understanding of the pathophysiology of the disease.     

Longitudinal magnetic resonance imaging of spinal cord injury in mouse: changes in signal patterns associated with the inflammatory response

Contusion-type spinal cord injury (SCI) in mice was followed longitudinally using in vivo magnetic resonance (MR) imaging along with neurobehavioral tests performed on postinjury Days 1, 7, 14 and 28. Magnetic resonance images were acquired from seven injured wild-type mice using a 9.4-T scanner and presented in sagittal and axial views to reflect the current state of the injured cord neuropathology on each day. The data were analyzed individually to gain more insights on the neuroinflammatory response unique to the mouse, to characterize the spatiotemporal evolution of the lesion and to quantify the changes in lesion volume and length with time. The MR intensity patterns on Day 1 showed acute injuries as focal in one group of three mice and as diffuse in the remaining group of four mice. The focal injuries appeared as a region of hypointensity with well-defined boundaries. These injuries first enlarged on Day 7, but then shrunk slightly by Days 14 and 28. In contrast, the diffuse injuries were initially obscure on Day 1, mainly because of loss of contrast between gray and white matters. On Day 7, lesions expanded asymptotically in both rostral and caudal directions with respect to the epicenter, and maintained its size on Days 14 and 28. Previous studies based on postmortem histological analysis have reported lesions behaving more like in the focal group. However, this new injury with diffuse characteristics may have important implications for SCI research carried out with mice. Unique experiments on genetically engineered mice with altered neuroinflammatory response should help clarify the origin of these differences in the lesion formation.     

Influence of attention focus on neural activity in the human spinal cord during thermal sensory stimulation

Perceptions of sensation and pain in healthy people are believed to be the net result of sensory input and descending modulation from brainstem and cortical regions depending on emotional and cognitive factors. Here, the influence of attention on neural activity in the spinal cord during thermal sensory stimulation of the hand was investigated with functional magnetic resonance imaging by systematically varying the participants' attention focus across and within repeated studies. Attention states included (1) attention to the stimulus by rating the sensation and (2) attention away from the stimulus by performing various mental tasks of watching a movie and identifying characters, detecting the direction of coherently moving dots within a randomly moving visual field and answering mentally-challenging questions. Functional MRI results spanning the cervical spinal cord and brainstem consistently demonstrated that the attention state had a significant influence on the activity detected in the cervical spinal cord, as well as in brainstem regions involved with the descending analgesia system. These findings have important implications for the detection and study of pain, and improved characterization of the effects of injury or disease.     

Independent component model of the default-mode brain function: combining individual-level and population-level analyses in resting-state fMRI

Resting-state functional magnetic resonance imaging (RS-fMRI) is a technique used to investigate the spontaneous correlations of blood-oxygen-level-dependent signals across different regions of the brain. Using functional connectivity tools, it is possible to investigate a specific RS-fMRI network, referred to as "default-mode" (DM) network, that involves cortical regions deactivated in fMRI experiments with cognitive tasks. Previous works have reported a significant effect of aging on DM regions activity. Independent component analysis (ICA) is often used for generating spatially distributed DM functional connectivity patterns from RS-fMRI data without the need for a reference region. This aspect and the relatively easy setup of an RS-fMRI experiment even in clinical trials have boosted the combined use of RS-fMRI and ICA-based DM analysis for noninvasive research of brain disorders. In this work, we considered different strategies for combining ICA results from individual-level and population-level analyses and used them to evaluate and predict the effect of aging on the DM component. Using RS-fMRI data from 20 normal subjects and a previously developed group-level ICA methodology, we generated group DM maps and showed that the overall ICA-DM connectivity is negatively correlated with age. A negative correlation of the ICA voxel weights with age existed in all DM regions at a variable degree. As an alternative approach, we generated a distributed DM spatial template and evaluated the correlation of each individual DM component fit to this template with age. Using a "leave-one-out" procedure, we discuss the importance of removing the bias from the DM template-generation process.     

An investigation of motion correction algorithms for pediatric spinal cord DTI in healthy subjects and patients with spinal cord injury

Patient and physiological motion can cause artifacts in DTI of the spinal cord which can impact image quality and diffusion indices. The purpose of this investigation was to determine a reliable motion correction method for pediatric spinal cord DTI and show effects of motion correction on DTI parameters in healthy subjects and patients with spinal cord injury. Ten healthy subjects and ten subjects with spinal cord injury were scanned using a 3 T scanner. Images were acquired with an inner field-of-view DTI sequence covering cervical spine levels C1 to C7. Images were corrected for motion using two types of transformation (rigid and affine) and three cost functions. Corrected images and transformations were examined qualitatively and quantitatively using in-house developed code. Fractional anisotropy (FA) and mean diffusivity (MD) indices were calculated and tested for statistical significance pre- and post- motion correction. Images corrected using rigid methods showed improvements in image quality, while affine methods frequently showed residual distortions in corrected images. Blinded evaluation of pre and post correction images showed significant improvement in cord homogeneity and edge conspicuity in corrected images (p < 0.0001). The average FA changes were statistically significant (p < 0.0001) in the spinal cord injury group, while healthy subjects showed less FA change and were not significant. In both healthy subjects and subjects with spinal cord injury, quantitative and qualitative analysis showed the rigid scaled-least-squares registration technique to be the most reliable and effective in improving image quality.     

CORSICA: correction of structured noise in fMRI by automatic identification of ICA components

When applied to functional magnetic resonance imaging (fMRI) data, spatial independent component analysis (sICA), a data-driven technique that addresses the blind source separation problem, seems able to extract components specifically related to physiological noise and brain movements. These components should be removed from the data to achieve structured noise reduction and improve any subsequent detection and analysis of signal fluctuations related to neural activity. We propose a new automatic method called CORSICA (CORrection of Structured noise using spatial Independent Component Analysis) to identify the components related to physiological noise, using prior information on the spatial localization of the main physiological fluctuations in fMRI data. As opposed to existing spectral priors, which may be subject to aliasing effects for long-TR data sets (typically acquired with TR >1 s), such spatial priors can be applied to fMRI data, regardless of the TR of the acquisitions. By comparing the proposed automatic selection to a manual selection performed visually by a human operator, we first show that CORSICA is able to identify the noise-related components for long-TR data with a high sensitivity and a specificity of 1. On short-TR data sets, we validate that the proposed method of noise reduction allows a substantial improvement of the signal-to-noise ratio evaluated at the cardiac and respiratory frequencies, even in the gray matter, while preserving the main fluctuations related to neural activity.     

High-resolution in vivo diffusion tensor imaging of the injured cat spinal cord using self-navigated,interleaved, variable-density spiral acquisition (SNAILS-DTI)

Diffusion tensor magnetic resonance imaging (DTI) is useful for studying the microstructural changes in the spinal cord following traumatic injury; however, image quality is generally poor due to the small size of the spinal cord, physiological motion and susceptibility artifacts. Self-navigated, interleaved, variable-density spiral diffusion tensor imaging (SNAILS-DTI) is a distinctive pulse sequence that bypasses many of the challenges associated with DTI of the spinal cord, particularly if imaging gradient hardware is of conventional quality. In the current study, we have demonstrated the feasibility of implementing SNAILS-DTI on a clinical 3.0-T MR scanner and examined the effect of navigator filter parameters on image quality and reconstruction time. Results demonstrate high-quality, high-resolution (546 μm×546 μm) in vivo DTI images of the cat spinal cord after traumatic spinal cord injury.     

A serial functional connectivity MRI study in healthy individuals assessing the variability of connectivity measures: reduced interhemispheric connectivity in the motor network during continuous performance

To date, little data is available on the reproducibility of functional connectivity MRI (fcMRI) studies. Here, we tested the variability and reproducibility of both the functional connectivity itself and different statistical methods to analyze this phenomenon. In the main part of our study, we repeatedly examined two healthy subjects in 10 sessions over 6 months with fcMRI. Cortical areas involved in motor function were examined under two different cognitive states: during continuous performance (CP) of a flexion/extension task of the fingers of the right hand and while subjects were at rest. Connectivity to left primary motor cortex (lSM1) was calculated by correlation analysis. The resulting correlation coefficients were transformed to z-scores of the standard normal distribution. For each subject, multisession statistical analyses were carried out with the z-score maps of the resting state (RS) and the CP experiments. First, voxel based t tests between the two groups of fcMRI experiments were performed. Second, ROI analyses were carried out for contralateral right SM1 and for supplementary motor area (SMA). For both ROI, mean and maximum z-score were calculated for each experiment. Also, the fraction of significantly (P<.05) correlated voxels (FCV) in each ROI was calculated. To evaluate the differences between the RS and the CP condition, paired t tests were performed for the mean and maximum z-scores, and Wilcoxon signed ranks tests for matched pairs were carried out for the FCV. All statistical methods and connectivity measures under investigation yielded a distinct loss in left–right SM1 connectivity under the CP condition. For SMA, interindividual differences were apparent. We therefore repeated the fcMRI experiments and the ROI analyses in a group of seven healthy subjects (including the two subjects of the main study). In this substudy, we were able to verify the reduction of left–right SM1 connectivity during unilateral performance. Still, the direction of SMA to lSM1 connectivity change during the CP condition remained undefined as four subjects showed a connectivity increase and three showed a decrease. In summary, we were able to demonstrate a distinct reduction in left–right SM1 synchrony in the CP condition compared to the RS both in the longitudinal and in the multisubject study. This effect was reproducible with all statistical methods and all measures of connectivity under investigation. We conclude that despite intra- and interindividual variability, serial and cross-sectional assessment of functional connectivity reveals stable and reliable results.     

Cervical spondylosis: Evaluation of microstructural changes in spinal cord white matter and gray matter by diffusional kurtosis imaging

Introduction

We investigated microstructural changes in the spinal cord, separately for white matter and gray matter, in patients with cervical spondylosis by using diffusional kurtosis imaging (DKI).

Methods

We studied 13 consecutive patients with cervical myelopathy (15 affected sides and 11 unaffected sides). After conventional magnetic resonance (MR) imaging, DKI data were acquired by using a 3 T MR imaging scanner. Values for fractional anisotropy (FA), apparent diffusion coefficient (ADC), and mean diffusional kurtosis (MK) were calculated and compared between unaffected and affected spinal cords, separately for white matter and gray matter.

Results

Tract-specific analysis of white matter in the lateral funiculus showed no statistical differences between the affected and unaffected sides. In gray matter, only MK was significantly lower in the affected spinal cords than in unaffected spinal cords (0.60 ± 0.18 vs. 0.73 ± 0.13, P = 0.0005, Wilcoxon’s signed rank test).

Conclusions

MK values in the spinal cord may reflect microstructural changes and gray matter damage and can potentially provide more information beyond that obtained with conventional diffusion metrics.     

Mapping of neural activity produced by thermal pain in the healthy human spinal cord and brain stem: a functional magnetic resonance imaging study

Functional magnetic resonance imaging (fMRI) has greatly advanced our current understanding of pain, although most studies to date have focused on imaging of cortical structures. In the present study, we have used fMRI at 3 T to investigate the neural activity evoked by thermal sensation and pain (42°C and 46°C) throughout the entire lower neuroaxis from the first synapse in the spinal cord rostral to the thalamus in healthy subjects. The results demonstrate that noxious thermal stimulation (46°C) produces consistent activity within various structures known to be involved in the pain matrix including the dorsal spinal cord, reticular formation, periaqueductal gray and rostral ventral medulla. However, additional areas of activity were evident that are not considered to be part of the pain matrix, including the olivary nucleus. Thermal stimulation (42°C) reported as either not painful or mildly painful produced quantitative, but not qualitative, differences in neuronal activity depending on the order of experiments. Activity was greater in the spinal cord and brain stem in earlier experiments, compared with repeated experiments after the more noxious (46°C) stimulus had been applied. This study provides significant insight into how the lower neuroaxis integrates and responds to pain in humans.     

Transfer characteristics of arterial pulsatile force in regional intracranial tissue using dynamic diffusion MRI: A phantom study

Introduction

To clarify the mechanism underlying apparent diffusion coefficient (ADC) changes in regional intracranial tissue during the cardiac cycle, we investigated relationships among ADC changes, volume loading, and intracranial pressure using a hemodialyzer phantom in magnetic resonance imaging (MRI).

Materials and Methods

The hemodialyzer phantom consisted of hollow fibers (HF), the external space of HFs (ES), and a gateway of dialysis solution, filled with syrup solution and air. The high-volume and low-volume loadings were periodically applied to HFs by a to-and-fro flow pump, and syrup solution was permitted to enter or leave HFs during the volume loading cycles. ADC maps at each volume loading phase were obtained using ECG-triggered single-shot diffusion echo-planar imaging. Dynamic phase contrast MRI was also used to measure volume loading to the phantom. We compared the ADC changes, volume loading, and intracranial pressure in the phantom during the cardiac cycle.

Results

ADC changes synchronized significantly with absolute volumetric flow rate change. The maximum ADC change was higher in high-volume loading cycles than in low-volume loading cycles. Results showed that the water molecules in ES fluctuated according to the force transferred from HF to ES. ADC changes were dependent upon the volumetric flow rate during the cardiac cycle.

Conclusions

Our original phantom allowed us to clarify the mechanism underlying water fluctuations in intracranial tissues. Measurement of maximum changes in ADC is an effective method to define the transfer characteristics of the arterial pulsatile force in regional intracranial tissue.     

Diffusion-weighted MR imaging for assessing synovitis of wrist and hand in patients with rheumatoid arthritis: A feasibility study

The purpose of this study was to investigate the feasibility of diffusion-weighted imaging (DWI) in detecting synovitis of wrist and hand in patients with rheumatoid arthritis (RA) and evaluate its sensitivity, specificity and accuracy as compared to T₂-weighted imaging (T2WI) with short tau inversion recovery (STIR) with the reference standard contrast-enhanced magnetic resonance imaging (CE-MRI). Twenty-five patients with RA underwent MR examinations including DWI, T2WI with STIR and CE-MRI. MR images were reviewed for the presence and location of synovitis of wrist and hand. The sensitivity, specificity and accuracy of DWI and T2WI with STIR were calculated respectively and then compared. All patients included in this study completed MR examinations and yielded diagnostic image quality of DWI. For individual joint, there was good to excellent inter-observer agreement (k = 0.62–0.83) using DWI images, T2WI with STIR images and CE-MR images, respectively. There was a significance between DWI and T2WI with STIR in analyzing proximal interphalangeal joints II–V, respectively (P < 0.05). The k-values for the detection of synovitis indicated excellent overall inter-observer agreements using DWI images (k = 0.86), T2WI with STIR images (k = 0.85) and CE-MR images (k = 0.91), respectively. Overall, DWI demonstrated a sensitivity, specificity and accuracy of 75.6%, 89.3% and 84.6%, respectively, for detection of synovitis, while 43.0%, 95.7% and 77.6% for T2WI with STIR, respectively. DWI showed positive lesions much better and more than T2WI with STIR. Our results indicate that DWI presents a novel non-invasive approach to contrast-free imaging of synovitis. It may play a role as an addition to standard protocols.     

Quantitative assessment of iron deposition in the midbrain using 3D-enhanced T2 star weighted angiography (ESWAN): A preliminary cross-sectional study of 20 Parkinson’s disease patients

Conventional magnetic resonance imaging (MRI) assesses neurodegenerative structural changes in the cerebral anatomy of Parkinson's disease (PD) patients but cannot detect non-structural abnormalities; however, enhanced T2 star weighted angiography (ESWAN) can precisely indicate PD-related substantia nigra (SN) iron deposition. The differences in ESWAN-based parameters between different PD stages were assessed using midbrain iron deposits of 20 PD patients aged 64.3 ± 12.7 (41–85) years grouped by Hoehn and Yahr staging into minimal (stages ≤ 2.5) or moderate to severe (stages ≥ 3.0) motor impairment groups and 14 healthy control subjects. Conventional MRI and ESWAN measurements of mean phase value (MPV) and midbrain dimensions (width and diameter) revealed similar anatomical characteristics; however, ESWAN revealed the presence of smaller MPVs and SN pars compacta (SNc) (P < 0.01) and a negative correlation between reduction extent and motor impairment (P < 0.01). SNc width to midbrain diameter was reduced in moderate to severe impairment patients versus control and minimal impairment patients (both P < 0.01). A positive correlation was found between MPV and width or SNc width to midbrain diameter ratio (P < 0.01 and P < 0.05, respectively). Minimal impairment group mean MPV and substantia nigra pars reticulata (SNr) width evidenced no significant reduction, unlike significant reductions in the moderate to severe impairment group (P < 0.01). No significant changes were observed in MPV or width in the RN region (P > 0.05). ESWAN allows for early and accurate iron deposition determination in PD patients, particularly useful as a supplement to conventional MRI in early-stage PD patients.