Issues about the fMRI of the human spinal cord

Noninvasive functional studies on human spinal cord by means of magnetic resonance imaging (MRI) are gaining attention because of the promising applications in the study of healthy and injured central nervous system. The findings obtained are generally consistent with the anatomic knowledge based on invasive methods, but the origin and specificity of functional contrast is still debated. In this paper, a review of current knowledge and major issues about functional MRI (fMRI) in the human spinal cord is presented, with emphasis on the main methodological and technical problems and on forthcoming applications as clinical tool.     

Functional exploration of the human spinal cord during voluntary movement and somatosensory stimulation

Demonstrations of the possibility of obtaining functional information from the spinal cord in humans using functional magnetic resonance imaging (fMRI) have been growing in number and sophistication, but the technique and the results that it provides are still perceived by the scientific community with a greater degree of scepticism than fMRI investigations of brain function. Here we review the literature on spinal fMRI in humans during voluntary movements and somatosensory stimulation. Particular attention is given to study design, acquisition and statistical analysis of the images, and to the agreement between the obtained results and existing knowledge regarding spinal cord anatomy and physiology.     

Characterization of cardiac-related noise in fMRI of the cervical spinal cord

Magnetic resonance imaging (MRI) has recently been applied to study spinal cord function in humans. However, spinal functional MRI (fMRI) encounters major technical challenges with cardiac noise being considered a major source of noise. The present study relied on echo-planar imaging of the cervical cord at short TR (TR=250 ms; TE=40 ms; flip=45 degrees), combined with plethysmographic recordings to characterize the spatiotemporal properties of cardiac-induced signal changes in spinal fMRI. Frequency-based analyses examining signal change at the cardiac frequency confirmed mean fluctuations of about 10% (relative to the mean signal) in the spinal cord and surrounding cerebrospinal fluid (CSF), with maximal responses reaching up to 66% in some voxels. A spatial independent component analysis (sICA) confirmed that cardiac noise is an important source of variance in spinal fMRI with several components showing a response coherent with the cardiac frequency spectrum. The time course of the main cardiac components approximated a sinusoidal function tightly coupled to the cardiac systole with at least one component showing a comparable temporal profile across runs and subjects. Spatially, both the frequency-domain analysis and the sICA demonstrated cardiac noise distributed irregularly along the full rostrocaudal extent of the segments scanned with peaks concentrated in the ventral part of the lateral slices in all scans and subjects, consistent with the major channels of CSF flow. These results confirm that cardiac-induced changes are a significant source of noise likely to affect the detection of spinal Blood Oxygen Level Dependent (BOLD) responses. Most importantly, the complex spatiotemporal structure of cardiac noise is unlikely to be accounted for adequately by ad hoc linear methods, especially in data acquired using long TR (i.e. aliasing the cardiac frequency). However, the reliable spatiotemporal distribution of cardiac noise across scanning runs and within subjects may provide a valid means to identify and extract cardiac noise based on sICA methods.     

Spatial normalization, bulk motion correction and coregistration for functional magnetic resonance imaging of the human cervical spinal cord and brainstem

Functional magnetic resonance imaging (fMRI) of the cortex is a powerful tool for neuroscience research, and its use has been extended into the brainstem and spinal cord as well. However, there are significant technical challenges with extrapolating the developments that have been achieved in the cortex to their use in the brainstem and spinal cord. Here, we develop a normalized coordinate system for the cervical spinal cord and brainstem, demonstrating a semiautomated method for spatially normalizing and coregistering fMRI data from these regions. fMRI data from 24 experiments in eight volunteers are normalized and combined to create the first anatomical reference volume, and based on this volume, we define a standardized region-of-interest (ROI) mask, as well as a map of 52 anatomical regions, which can be applied automatically to fMRI results. The normalization is demonstrated to have an accuracy of less than 2 mm in 93% of anatomical test points. The reverse of the normalization procedure is also demonstrated for automatic alignment of the standardized ROI mask and region-label map with fMRI data in its original (unnormalized) format. A reliable method for spatially normalizing fMRI data is essential for analyses of group data and for assessing the effects of spinal cord injury or disease on an individual basis by comparing with results from healthy subjects.     

Applying functional MRI to the spinal cord and brainstem

Functional magnetic resonance imaging of the spinal cord (spinal fMRI) has facilitated the noninvasive visualization of neural activity in the spinal cord (SC) and brainstem of both animals and humans. This technique has yet to gain the widespread usage of brain fMRI, due in part to the intrinsic technical challenges spinal fMRI presents and to the narrower scope of applications it fulfills. Nonetheless, methodological progress has been considerable and rapid. To date, spinal fMRI studies have investigated SC function during sensory or motor task paradigms in spinal cord injury (SCI), multiple sclerosis (MS) and neuropathic pain (NP) patient populations, all of which have yielded consistent and sensitive results. The most recent study in our laboratory has successfully used spinal fMRI to examine cervical SC activity in a SCI patient with a metallic fixation device spanning the C₄ to C₆ vertebrae, a critical step in realizing the clinical utility of the technique. The literature reviewed in this article suggests that spinal fMRI is poised for usage in a wide range of patient populations, as multiple groups have observed intriguing, yet consistent, results using standard, readily available MR systems and hardware. The next step is the implementation of this technique in the clinic to supplement standard qualitative behavioral assessments of SCI. Spinal fMRI may offer insight into the subtleties of function in the injured and diseased SC, and support the development of new methods for treatment and monitoring.     

Assessment of data acquisition parameters,and analysis techniques for noise reduction in spinal cord fMRI data

Purpose

The purpose of this work is to characterize the noise in spinal cord functional MRI, assess current methods aimed at reducing noise, and optimize imaging parameters.

Methods

Functional MRI data were acquired at multiple echo times and the contrast-to-noise ratio (CNR) was calculated. Independently, the repetition time was systematically varied with and without parallel imaging, to maximize BOLD sensitivity and minimize type I errors. Noise in the images was characterized by examining the frequency spectrum, and investigating whether autocorrelations exist. The efficacy of several physiological noise reduction methods in both null (no stimuli) and task (thermal pain paradigm) data was also assessed. Finally, our previous normalization methods were extended.

Results

The echo time with the highest functional CNR at 3 Tesla is at roughly 75 msec. Parallel imaging reduced the variance and the presence of autocorrelations, however the BOLD response in task data was more robust in data acquired without parallel imaging. Model-free based approaches further increased the detection of active voxels in the task data. Finally, inter-subject registration was improved.

Conclusions

Results from this study provide a rigorous characterization of the properties of the noise and assessment of data acquisition and analysis methods for spinal cord and brainstem fMRI.     

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.     

In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change

Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast — attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility — has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed “signal enhancement by extravascular water protons” (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air–tissue and/or bone–tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory.     

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.     

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.     

Functional MRI of the cervical spinal cord during noxious and innocuous thermal stimulation in the alpha-chloralose- and halothane-anesthetized rat

Patterns of neuronal activity in the spinal cord using functional magnetic resonance imaging during noxious (48 degrees C) and innocuous (40 degrees C) thermal stimulation of the rat forepaw were examined. The patterns of functional activity elicited by thermal stimuli were compared in alpha-chloralose- and halothane-anesthetized rats. Although the locations of active pixels were similar during both types of stimulation, the mean percentage signal change was higher during noxious stimulation in both anesthetic groups. Ipsilateral dorsal horn activity was evident during both noxious and innocuous stimulation in all animals. The greatest consistency of ipsilateral dorsal horn activity occurred at the C3 to C5 spinal cord segments in all groups. Consistent contralateral dorsal horn activity appeared in segments C6 to C8 in all groups. C-fos immunohistochemical staining confirmed the presence of neural activity in the spinal cords of all animals.     

Fractional amplitude of low-frequency fluctuation changes in monkeys with spinal cord injury: A resting-state fMRI study

Purpose

Although functional magnetic resonance imaging (fMRI) has revealed that spinal cord injury (SCI) causes anomalous changes in task-induced brain activation, its effect during the resting state remains unclear. The aim of this study is to explore the changes of the brain resting-state function in non-human primates with unilateral SCI.

Materials and methods

Eleven adult female rhesus monkeys were subjected to resting-state fMRI: five with unilateral thoracic SCI and six healthy monkeys, to obtain the fractional amplitude of low-frequency fluctuations (fALFF) of the blood oxygenation level-dependent (BOLD) contrast signal to determine the influence of SCI on the cerebral resting-state function.

Results

The SCI-induced fALFF vary significantly in several encephalic regions, including the left cerebellum, the left thalamus, the right lateral geniculate nucleus, the right superior parietal lobule, and the posterior cingulate gyrus.

Conclusion

Analysis of the resting-state fMRI provides evidence of abnormal spontaneous brain activations in primates with SCI, which may help us understand the pathophysiologic mechanisms underlying the changes in neural plasticity in the central nervous system after SCI.     

COmplex-Model-Based Estimation of thermal noise for fMRI data in the presence of artifacts

Due to the presence of artifacts induced by fast-imaging acquisition in functional magnetic resonance imaging (fMRI) studies, it is very difficult to estimate the variance of thermal noise by traditional methods in magnitude images. Moreover, the existence of incidental phase fluctuations impairs the validity of currently available solutions based on complex datasets. In this article, a time-domain model is proposed to generalize the analysis of complex datasets for nonbrain regions by incorporating artifacts and phase fluctuations. Based on this model, a novel estimation schema has been developed to find an appropriate set of voxels in nonbrain regions according to their levels of artifact and phase fluctuation. In addition, noise intensity from these voxels is estimated. The whole schema is named COmplex-Model-Based Estimation (COMBE). Theoretical and experimental results demonstrate that the proposed COMBE method provides a better estimation of thermal noise in fMRI studies compared with previously proposed methods and suggest that the new method can adapt to a broader range of applications, such as functional connectivity studies, evaluation of sequence designs and reconstruction schemas.     

通过响应矩阵计算横向振荡的振幅函数和相位

 响应矩阵反映了束流位置监测器（BPM）位置处观察到的束流在校正铁磁场空间中的运行规律。根据电子储存环理论模型,采用迭代方法从实测响应矩阵计算束流横向振荡的振幅函数和相位。计算结果的精度主要受响应矩阵测量误差、BPM测量误差和校正铁电源刻度误差影响。计算响应矩阵的误差代表了迭代所采用的工作点的正确度,实际的工作点对应于计算响应矩阵的最小均方差,以此可推导实际的工作点。     

The impulse response function of apertured and misaligned ABCD optical system in phase-space

By expanding the aperture into complex Gaussian functions, the approximate analytical impulse response function of apertured and misaligned ABCD optical system in phase-space is determined, which allows us to formulate the input-output relation completely in terms of Wigner distribution functions. Its shown that the hard-aperture placed before the optical system will change the shape of output signal Wigner distribution and the misalignment of optical system will introduce the output Wigner distribution function a coordinate shift in phase-space. For examining the analytical results some numerical simulation are done and the graphical results as well as the absolute errors between analytical results and numerical integral ones are presented.     

模拟封闭声场脉冲响应的圆锥束跟踪法

本文简要介绍了声场脉冲响应计算机模拟技术的基本状况,给出了一种将虚源法和声线法相结合的模拟方法－圆锥束跟踪法的原理和算法,并将其对一个实例的计算结果与虚源法进行了比较,最后对其实现过程中需要注意的问题进行了讨论。     

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.     

通过响应矩阵计算横向振荡的振幅函数和相位

响应矩阵反映了束流位置监测器（BPM）位置处观察到的束流在校正铁磁场空间中的运行规律。根据电子储存环理论模型,采用迭代方法从实测响应矩阵计算束流横向振荡的振幅函数和相位。计算结果的精度主要受响应矩阵测量误差、BPM测量误差和校正铁电源刻度误差影响。计算响应矩阵的误差代表了迭代所采用的工作点的正确度,实际的工作点对应于计算响应矩阵的最小均方差,以此可推导实际的工作点。     

Process optimization and characterization of arachidonic acid oil degumming using ultrasound-assisted enzymatic method

Ultrasound assisted enzymatic method was applied to the degumming of arachidonic acid (ARA) oil produced by Mortierella alpina. The conditions of degumming process were optimized by response surface methodology with Box- Behnken design. A dephosphorization rate of 98.82% was achieved under optimum conditions of a 500 U/kg of Phospholipase A₁ (PLA₁) dosage, 2.8 mL/100 g of water volume, 120 min of ultrasonic time, and 135 W of ultrasonic power. The phosphorus content of ultrasonic assisted enzymatic degumming oil (UAEDO) was 4.79 mg/kg, which was significantly lower than that of enzymatic degumming oil (EDO, 17.98 mg/kg). Crude Oil (CO), EDO and UAEDO revealed the similar fatty acid compositions, and ARA was dominated (50.97 ~ 52.40%). The oxidation stability of UAEDO was equivalent to EDO and weaker than CO, while UAEDO presented the strongest thermal stability, followed by EDO and CO. Furthermore, aldehydes, acids and alcohols were identified the main volatile flavor components for the three oils. The proportions of major contributing components such as hexanal, nonanal, (E)-2-nonanal, (E, E)-2,4-decadienal, (E)-2-nonenal and aldehydes in UAEDO and EDO were all lower than CO. Overall, Ultrasound assisted enzymatic degumming proved to be an efficient and superior method for degumming of ARA oil.