Group data analysis in brainstem neuroimaging is predicated on accurate co-registration of anatomy. As the brainstem is comprised of many functionally heterogeneous nuclei densely situated adjacent to one another, relatively small errors in co-registration can manifest in increased variance or decreased sensitivity (or significance) in detecting activations. We have devised a 2-stage automated, reference mask guided registration technique (Automated Brainstem Co-registration, or ABC) for improved brainstem co-registration. Our approach utilized a brainstem mask dataset to weight an automated co-registration cost function. Our method was validated through measurement of RMS error at 12 manually defined landmarks. These landmarks were also used as guides for a secondary manual co-registration option, intended for outlier individuals that may not adequately co-register with our automated method. Our methodology was tested on 10 healthy human subjects and compared to traditional co-registration techniques (Talairach transform and automated affine transform to the MNI-152 template). We found that ABC had a significantly lower mean RMS error (1.22 +/- 0.39 mm) than Talairach transform (2.88 +/- 1.22 mm, mu +/- sigma) and the global affine (3.26 +/- 0.81 mm) method. Improved accuracy was also found for our manual-landmark-guided option (1.51 +/- 0.43 mm). Visualizing individual brainstem borders demonstrated more consistent and uniform overlap for ABC compared to traditional global co-registration techniques. Improved robustness (lower susceptibility to outliers) was demonstrated with ABC through lower inter-subject RMS error variance compared with traditional co-registration methods. The use of easily available and validated tools (AFNI and FSL) for this method should ease adoption by other investigators interested in brainstem data group analysis.
The ability to resolve complex fiber populations in muscular tissues is important for relating tissue structure with mechanical function. To address this issue in the case of tongue, we employed diffusion spectrum imaging (DSI), an MRI method for determining three-dimensional myoarchitecture where myofiber populations are variably aligned. By specifically varying gradient field strength, molecular displacement in a tissue can be determined by Fourier-transforming the echo intensity against gradient strength at fixed gradient pulse spacing. The displacement profiles are visualized by graphing three-dimensional isocontour icons for each voxel, with the isocontour shape and size representing the magnitude and direction of the constituting fiber populations. To validate this method, we simulated a DSI experiment within the constraints of arbitrary crossing fibers, and determined that DSI accurately depicts the angular relationships between these fibers. Considering the fiber relationships in the whole bovine tongue, we compared the images obtained by DSI with those obtained by diffusion tensor imaging in an anterior slice of the lingual core, a region known to possess extensive fiber crossing. In contrast to diffusion tensor imaging, which depicts the anterior core solely as a region with low anisotropy due to the presence of mixed-orientation fiber populations, DSI shows two distinct fiber populations, with an explicit orthogonal relationship to each other. In imaging the whole lingual tissue, we discerned arrays of crossing and noncrossing fibers involving the intrinsic and extrinsic muscles, which merged at regions of interface. We conclude that DSI has the capacity to determine three-dimensional fiber orientation in structurally complex muscular tissues.
The "Neurobiological Correlates of Acupuncture" Conference was convened November 17-18, 2005 in Bethesda, Maryland. The conference was sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS). Its goals were to encourage exchange of ideas regarding the direction of neuroimaging in acupuncture research as well as to discuss some of the challenges in this field. The use of neuroimaging, a relatively recent advance in the study of acupuncture, holds the promise of localizing and characterizing brain activity associated with acupuncture interventions in real time and in a minimally invasive way. Among the main challenges to research into the biological mechanisms of acupuncture are the multiple treatment variables and the difficulties of selecting appropriate experimental controls. Despite these challenges, numerous findings from acupuncture neuroimaging experiments were presented and discussed at the conference on topics related to possible signaling networks, sham acupuncture controls, acupoint specificity, acupuncture analgesia, acupuncture-associated brain response, and the potential for using neuroimaging in conjunction with translational and clinical acupuncture research. Future directions in acupuncture neuroimaging research, as recommended by conference participants, should focus on (1) continuing exploration of acupuncture signaling networks; (2) establishing standards and recommendations for performing and reporting acupuncture neuroimaging results; (3) enabling data sharing in the acupuncture neuroimaging community; (4) gaining a better understanding of placebo and control groups in acupuncture neuroimaging experiments; and (5) developing biomarkers that relate to physiologically and/or clinically relevant acupuncture responses to neuroimaging results.
Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve characterized by paresthesias and pain in the first, second, and third digits. We hypothesize that aberrant afferent input in CTS will lead to cortical plasticity. Functional MRI (fMRI) and neurophysiological testing were performed on CTS patients and healthy adults. Median nerve innervated digit 2 (D2), and digit 3 (D3) and ulnar nerve innervated digit 5 (D5) were stimulated during fMRI. Surface-based and ROI-based analyses consistently demonstrated more extensive and stronger contralateral sensorimotor cortical representations of D2 and D3 for CTS patients as compared to healthy adults (P < 0.05). Differences were less profound for D5. Moreover, D3 fMRI activation in both the contralateral SI and motor cortex correlated positively with the D3 sensory conduction latency. Analysis of somatotopy suggested that contralateral SI representations for D2 and D3 were less separated for CTS patients (3.8 +/- 1.0 mm) than for healthy adults (7.5 +/- 1.2 mm). Furthermore, the D3/D2 separation distance correlated negatively with D2 sensory conduction latency-the greater the latency, the closer the D2/D3 cortical representations (r = -0.79, P < 0.05). Coupled with a greater extent of SI representation for these CTS affected digits, the closer cortical representations can be interpreted as a blurred somatotopic arrangement for CTS affected digits. These findings provide further evidence that CTS is not manifest in the periphery alone. Our results are consistent with Hebbian plasticity mechanisms, as our cohort of CTS patients had predominant paresthesias, which produce more temporally coherent afferent signaling from affected digits.
The anatomy of the mammalian tongue consists of an intricate array of variably aligned and extensively interwoven muscle fibers. As a result, it is particularly difficult to resolve the relationship between the tongue's microscopic anatomy and tissue-scale mechanical function. In order to address this question, we employed a method, diffusion spectrum imaging (DSI) with tractography, for displaying the macroscopic orientational properties of the tissue's constituting myofibers. DSI measures spatially variant proton displacement for a given 3D imaging segment (voxel), reflecting the principal orientation(s) of its myofibers. Tractography uses the angular similarity displayed by the principal fiber populations of multiple adjacent voxels to generate tract-like structures. DSI with tractography thus defines a unique set of tracts based on the net orientational behavior of the myofiber populations at different positions in the tissue. By this approach, we demonstrate a novel myoarchitectural pattern for the bovine tongue, consisting of short and orthogonally aligned crossing fiber tracts in the intrinsic core region, and longer, parallel-aligned fiber tracts on the tissue margins and in the regions of extrinsic fiber insertion. The identification of locally aligned myofiber populations by DSI with tractography allows us to reconsider lingual anatomy, not in conventional microscopic terms, but as a set of heterogeneously aligned and macroscopically resolved myofiber tracts. We postulate that the properties associated with these myofiber tracts predict the mechanical behavior of the tissue and thus constitute a method to relate structure and function for anatomically complex muscular tissues.
Past neuroimaging studies of acupuncture have demonstrated variable results for important brainstem nuclei. We have employed cardiac-gated fMRI with T1-variability correction to study the processing of acupuncture by the human brain. Furthermore, our imaging experiments collected simultaneous ECG data in order to correlate heart rate variability (HRV) with fMRI signal intensity. Subjects experienced one of three stimulations over a 31.5 minute fMRI run: (1) electro-acupuncture at 2Hz/15Hz over the acupoint ST-36 (2) electro-acupuncture at a sham non-acupoint, or (3) sensory control tapping over ST-36. The ECG was analyzed with power spectral methods for low frequency and high frequency components, which reflect the balance in the autonomic nervous system. The HRV data was then correlated with the time-varying fMRI signal intensity. Our data suggests that fMRI activity in the hypothalamus, the dorsal raphe nucleus, the periaqueductal gray, and the rostroventral medulla showed significant correlation with LF/HF ratio calculated from simultaneous HRV data. The correlation of time-varying fMRI response with physiological parameters may provide insight into connections between acupuncture modulation of the autonomic nervous system and neuroprocessing.
The goal of this functional magnetic resonance imaging (fMRI) study was to compare the central effects of electroacupuncture at different frequencies with traditional Chinese manual acupuncture. Although not as time-tested as manual acupuncture, electroacupuncture does have the advantage of setting stimulation frequency and intensity objectively and quantifiably. Manual acupuncture, electroacupuncture at 2 Hz and 100 Hz, and tactile control stimulation were carried out at acupoint ST-36. Overall, electroacupuncture (particularly at low frequency) produced more widespread fMRI signal increase than manual acupuncture did, and all acupuncture stimulations produced more widespread responses than did our placebo-like tactile control stimulation. Acupuncture produced hemodynamic signal increase in the anterior insula, and decrease in limbic and paralimbic structures including the amygdala, anterior hippocampus, and the cortices of the subgenual and retrosplenial cingulate, ventromedial prefrontal cortex, frontal, and temporal poles, results not seen for tactile control stimulation. Only electroacupuncture produced significant signal increase in the anterior middle cingulate cortex, whereas 2-Hz electroacupuncture produced signal increase in the pontine raphe area. All forms of stimulation (acupuncture and control) produced signal increase in SII. These findings support a hypothesis that the limbic system is central to acupuncture effect regardless of specific acupuncture modality, although some differences do exist in the underlying neurobiologic mechanisms for these modalities, and may aid in optimizing their future usage in clinical applications.
Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response.
The myoarchitecture of the tongue is believed to consist of a complex network of interwoven fibers, which function together to produce a near limitless array of functional deformations. These deformations contribute mechanically to speech production and to oral cavity food handling during swallowing. We have previously imaged the 3D myoarchitecture of the mammalian tongue in excised tissue with diffusion tensor MRI, a technique which derives the 3D orientation of intramural fibers as a function of the extent to which a direction-specific MR signal attenuates under diffusion-encoding magnetic gradients. The resulting 3D diffusion tensor defines the relative orientations of the myofiber populations within a region of tissue. In this study, we have extended the use of this method to assess lingual myoarchitecture in normal human subjects in vivo. Subjects were imaged using a diffusion-sensitive stimulated-echo pulse sequence with single-shot echo-planar spatial encoding in the midsagittal plane. Differences in lingual fiber orientation were manifested by graduated changes in fiber direction throughout the tissue, without clear anatomical demarcations between regions of the tissue. The anterior tissue was composed generally of orthogonally oriented fibers surrounded by an axially oriented ring of tissue, whereas the posterior portion of the tissue was composed mostly of fibers projecting in the superior and posterior directions. The bulk of the tissue displayed a highly homogeneous, vertically oriented set of fibers, including the anteroinferior region of the tissue and extending nearly to the superior surface. Further analysis of the tissue in terms of diffusion anisotropy demonstrated that the tissue could be represented by varying degrees of anisotropy, with a tendency toward high anisotropy in the dorsal and anteroventral periphery and low anisotropy in the central region of the tissue. These findings demonstrate that the muscular anatomy of the tongue can be displayed as a continuous array of structural units, or tensors, representing fibers of varying orientations throughout the tissue.
OBJECTIVES: This study quantifies and compares patient characteristics in outpatient acupuncture.
SETTING/DESIGN: Prospective primary source evidence was gathered at two prominent outpatient acupuncture clinics in Beijing, China (n = 563, n = 233).
RESULTS: The most common condition was Bell's palsy, which represented 20.6% and 25.3% of total cases at the two clinics, respectively. The second most common condition was cerebrovascular accident (CVA) rehabilitation. These treatments represented 11.9% and 12.0% of treatments at the two clinics, respectively. Other trends at the clinics included the following: (1) neurologic complaints predominated; (2) doctors see a large number of patients per day; (3) the majority of patients overall were female; while (4) the majority of patients treated for CVAs rehabilitation were male. As cultural and socioeconomic differences in perceptions of acupuncture exist between peoples of different countries, this study also compared patient main complaints in China to available data on acupuncture patients seen in other parts of China, Germany, the United Kingdom, Australia, and the United States. Except for the German clinic data, Western clinic acupuncturists saw more musculoskeletal complaints compared to China, where neurologic complaints predominated. Another significant difference between Asian and Western clinics was the number of patients seen per hour. While acupuncturists were reported to see 1.2 patients per hour in U. S. clinics, acupuncturists at the two Beijing, China, clinics saw 7.0 and 10.4 patients per hour, respectively.
CONCLUSION: The main complaints seen in acupuncture outpatient clinics throughout the world likely result from a combination of inherent disease prevalence as well as patients' attitudes toward what acupuncture can treat successfully.
Acupuncture textbooks mention a wide assortment of indications for each acupuncture point and, conversely, each disease or indication can be treated by a wide assortment of acupoints. However, little systematic information exists on how acupuncture is actually used in practice: i.e. which points are actually selected and for which conditions. This study prospectively gathered data on acupuncture point usage in two primarily acupuncture hospital clinics in Beijing, China. Of the more than 150 unique acupoints, the 30 most commonly used points represented 68% of the total number of acupoints needled at the first clinic, and 63% of points needled at the second clinic. While acupuncturists use a similar set of most prevalent points, such as LI-4 (used in >65% of treatments at both clinic sites), this core of points only partially overlaps. These results support the hypothesis that while the most commonly used points are similar from one acupuncturist to another, each practitioner tends to have certain acupoints, which are favorites as core points or to round out the point prescription. In addition, the results of this study are consistent with the recent development of "manualized" protocols in randomized controlled trials of acupuncture where a fixed set of acupoints are augmented depending on individualized signs and symptoms (TCM patterns).
The human tongue is a structurally complex and extremely flexible organ. In order to better understand the mechanical basis for lingual deformations, we modeled a primitive movement of the tongue, sagittal tongue bending. We hypothesized that sagittal bending is a synergistic deformation derived from co-contraction of the longitudinalis and transversus muscles. Our model of tongue bending was based on classical bimetal strip theory, in which curvature is produced when one muscle layer contracts more so than another. Contraction was modulated via mismatched thermal expansion coefficients and temperature change (to simulate muscular contraction). Our results demonstrated that synergistic contraction produced curvature and strain results which were in better correspondence to empirical results derived from tagging MRI than were the results of contraction of the longitudinalis muscle alone. This fundamental reliance of tongue bending on the synergistic contraction of its intrinsic fibers supports the muscular hydrostat theory of tongue function.
While MR imaging with tagged magnetization has shown great utility in the study of muscle mechanics, the evaluation of pulmonary mechanics has long been hindered by the technical difficulties in MR imaging of lung parenchyma. In this study, a fast MR grid-tagging technique is described for dynamic assessment of regional pulmonary deformation. The method is based on a fast FLASH sequence with short TR and short TE. Tagging was achieved by using double DANTE pulse train or inversion pulses. Our results show that this technique is able to detect changes of the tagging grid caused by physiological deformation of the lung. Quantitative analysis of the data shows that this method is capable of assessing local pulmonary mechanics. The application of this technique could improve our understanding of ventilatory control, and thus provide a unique metric for assessing pulmonary disorders. Magn Reson Med 45:24-28, 2001.
The myoarchitecture of the tongue is comprised of a complex array of muscle fiber bundles, which form the structural basis for lingual deformations during speech and swallowing. We used magnetic resonance imaging of the water diffusion tensor to display the primary and secondary fiber architectural attributes of the excised bovine tongue. Fiber orientation mapping provides a subdivision of the tongue into its principal intrinsic and extrinsic muscular components. The anterior tongue consists of a central region of orthogonally oriented intrinsic fibers surrounded by an axially oriented muscular sheath. The posterior tongue consists principally of a central region of extrinsic fibers, originating at the inferior surface and projecting in a fan-like manner in the superior, lateral, and posterior directions, and lateral populations of extrinsic fibers directed posterior-inferior and posterior-superior. Analysis of cross-fiber anisotropy indicates a basic contrast of design between the extrinsic and the intrinsic fibers. Whereas the extrinsic muscles exhibit a uniaxial architecture typical of skeletal muscle, the intrinsic core muscles, comprised of the verticalis and the transversus muscles, show strong cross-fiber anisotropy. This pattern is consistent with the theory that the tongue's core functions as a muscular hydrostat in that conjoint contraction of the transverse and vertical fibers enable the tissue to expand at right angles to these fibers. These findings suggest that three-dimensional analysis of diffusion tensor magnetic resonance imaging provides a structural basis for understanding the micromechanics of the mammalian tongue.
In clinical practice, the assessment of lung mechanics is limited to a global physiological evaluation, which measures, in the aggregate, the contributions of the pulmonary parenchyma, pleura, and chest wall. In this study, we used an MR imaging methodology which applies two-dimensional bands of inverted magnetization directly onto the pulmonary parenchyma, thus allowing for the quantification of local pulmonary tissue deformation, or strain, throughout inhalation. Our results showed that the magnitude of strain was maximal at the base and apex of the lung, but was curtailed at the hilum, the anatomical site of the poorly mobile bronchial and vascular insertions. In-plane shear strain mapping showed mostly positive shear strain, predominant at the apex throughout inhalation, and increasing with expanding lung volume. Anisotropy mapping showed that superior-inferior axial strain was greater than medial-lateral axial strain at the apex and base, while the opposite was true for the middle lung field. This study demonstrates that localized pulmonary deformation can be measured in vivo with tagging MRI, and quantified by applying finite strain definitions from continuum mechanics.
The determination of principal fiber directions in structurally heterogeneous biological tissue substantially contributes to an understanding of its mechanical function in vivo. In this study we have depicted structural heterogeneity through the model of the mammalian tongue, a tissue comprised of a network of highly interwoven fibers responsible for producing numerous variations of shape and position. In order to characterize the three-dimensional-resolved microscopic myoarchitecture of the intrinsic musculature of the tongue, we viewed its fiber orientation at microscopic and macroscopic length scales using NMR (diffusion tensor MRI) and optical (two-photon microscopy) imaging methods. Diffusion tensor imaging (DTI) of the excised core region of the porcine tongue resulted in an array of 3D diffusion tensors, in which the leading eigenvector corresponded to the principal fiber orientation at each location in the tissue. Excised axially oriented lingual core tissues (fresh or paraffin-embedded) were also imaged with a mode-locked Ti-Sapphire laser, (76 MHz repetition rate, 150 femtosecond pulse width), allowing for the visualization of individual myofibers at in situ orientation. Fiber orientation was assessed by computing the 3D autocorrelation of discrete image volumes, and deriving the minimal eigenvector of the center voxel Hessian matrix. DTI of the fibers, comprising the intrinsic core of the tongue, demonstrated directional heterogeneity, with two distinct populations of fibers oriented orthogonal to each other and in-plane to the axial perspective. Microscopic analysis defined this structural heterogeneity as discrete regions of in-plane parallel fibers, with an angular separation of ~80 degrees, thereby recapitulating the macroscopic angular relationship. This analysis, conceived at two different length scales, demonstrates that the lingual core is a spatially complex tissue, composed of repeating orthogonally oriented and in-plane fiber patches, which are capable of jointly producing hydrostatic elongation and displacement.
Our goal was to quantify intramural mechanics in the tongue through an assessment of local strain during the physiological phases of swallowing. Subjects were imaged with an ultrafast gradient echo magnetic resonance imaging (MRI) pulse sequence after the application of supersaturated magnetized bands in the x and y directions. Local strain was defined through deformation of discrete triangular elements defined by these bands and was depicted graphically either as color-coded two-dimensional strain maps or as three-dimensional octahedra whose axes correspond to the principal strains for each element. During early accommodation, the anterior tongue showed positive strain (expansive) in the anterior-posterior direction (x), whereas the middle tongue showed negative strain (contractile) in the superior-inferior direction (y). During late accommodation, the anterior tongue displayed increased positive x-direction and y-direction strain, whereas the posterior tongue displayed increased negative y-direction strain. These findings were consistent with contraction of the anterior-located intrinsic muscles and the posterior-located genioglossus and hyoglossus muscles. During propulsion, posterior displacement of the tongue was principally associated with positive strain directed in the x and y directions. These findings were consistent with posterior passive stretch in the midline due to contraction of the laterally inserted styloglossus muscle, as well as contraction of the posterior located transversus muscle. We conclude that MRI of lingual deformation during swallowing resolves the synergistic contractions of the intrinsic and extrinsic muscle groups.
Contraction of the tongue musculature during speech and swallowing is associated with characteristic patterns of tissue deformation. In order to quantify local deformation (strain) in the human tongue, we used a non-invasive NMR tagging technique that represents tissue as discrete deforming elements. Subjects were studied with a fast gradient echo pulse sequence (TR,TE 2.3/0.8 ms, slice thickness 10 mm, and effective spatial resolution 1.3x1.3 mm). Individual elements were defined by selectively supersaturating bands of magnetic spills in resting tongue tissue along the antero-posterior and superior inferior directions of the mid-sagittal plane, resulting in a rectilinear square grid. Axial and shear strains relative to the rest condition were determined for each clement and represented by two-dimensional surface strain maps. During forward protrusion, the anterior tongue underwent positive antero posterior strain (elongation) (maximum 200%) and symmetrical negative medial lateral and superior inferior strain (contraction). During sagittal curl directed to the hard palate, the tongue exhibited positive asymmetrical antero posterior strain (maximum 160%) that increased radially as a function of distance from the center of curvature (r = 0.9216, p<0.0005), and commensurate negative strain in the medial lateral direction. Similarly, the magnitude of anterior posterior strain during left-directed tongue curl was proportional to the distance from the curved inner surface (r = O.8978, p<0.0005). We conclude that the regulation of tongue position for the motions studied was related to regional activation of the intrinsic lingual musculature.
In order to estimate within-subjects variability in 24-hour energy expenditure at a fixed physical activity programme with a physical activity index of 1.30, this quantity was measured in four apparently healthy subjects once a month over 10 months. The coefficient of variation of the measurements was found to be between 2.7 and 4 per cent and in agreement with previously published data.