In vivo neuronal and astrocytic activation in somatosensory cortex by acupuncture stimuli.

Acupuncture is a medical treatment that has been widely practiced in China for over 3000 years, yet the neural mechanisms of acupuncture are not fully understood. We hypothesized that neurons and astrocytes act independently and synergistically under acupuncture stimulation. To investigate this, we used two-photon in vivo calcium recording to observe the effects of acupuncture stimulation at ST36 (Zusanli) in mice. Acupuncture stimulation in peripheral acupoints potentiated calcium signals of pyramidal neurons and astrocytes in the somatosensory cortex and resulted in late-onset calcium transients in astrocytes. Chemogenetic inhibition of neurons augmented the astrocytic activity. These findings suggest that acupuncture activates neuronal and astrocytic activity in the somatosensory cortex and provide evidence for the involvement of both neurons and astrocytes in acupuncture treatment.

Ancient Chinese medicine and mechanistic evidence of acupuncture physiology.

Acupuncture has been widely used in China for three millennia as an art of healing. Yet, its physiology is not yet understood. The current interest in acupuncture started in 1971. Soon afterward, extensive research led to the concept of neural signaling with possible involvement of opioid peptides, glutamate, adenosine and identifying responsive parts in the central nervous system. In the last decade scientists began investigating the subject with anatomical and molecular imaging. It was found that mechanical movements of the needle, ignored in the past, appear to be central to the method and intracellular calcium ions may play a pivotal role. In this review, we trace the technique of clinical treatment from the first written record about 2,200 years ago to the modern time. The ancient texts have been used to introduce the concepts of yin, yang, qi, de qi, and meridians, the traditional foundation of acupuncture. We explore the sequence of the physiological process, from the turning of the needle, the mechanical wave activation of calcium ion channel to beta-endorphin secretion. By using modern terminology to re-interpret the ancient texts, we have found that the 2nd century B.C.: physiologists were meticulous investigators and their explanation fits well with the mechanistic model derived from magnetic resonance imaging (MRI) and confocal microscopy. In conclusion, the ancient model appears to have withstood the test of time surprisingly well confirming the popular axiom that the old wine is better than the new.

Physiology and cell biology of acupuncture observed in calcium signaling activated by acoustic shear wave.

This article presents a novel model of acupuncture physiology based on cellular calcium activation by an acoustic shear wave (ASW) generated by the mechanical movement of the needle. An acupuncture needle was driven by a piezoelectric transducer at 100 Hz or below, and the ASW in human calf was imaged by magnetic resonance elastography. At the cell level, the ASW activated intracellular Ca(2+) transients and oscillations in fibroblasts and endothelial, ventricular myocytes and neuronal PC-12 cells along with frequency-amplitude tuning and memory capabilities. Monitoring in vivo mammalian experiments with ASW, enhancement of endorphin in blood plasma and blocking by Gd(3+) were observed; and increased Ca(2+) fluorescence in mouse hind leg muscle was imaged by two-photon microscopy. In contrast with traditional acupuncture models, the signal source is derived from the total acoustic energy. ASW signaling makes use of the anisotropy of elasticity of tissues as its waveguides for transmission and that cell activation is not based on the nervous system.

An fMRI study of acupuncture-induced brain activation of aphasia stroke patients.

This investigation aims to test the effect of acupuncture on word generation activation (WGA) in post-stroke aphasia patients. Seven vascular aphasia patients and 14 control subjects were studied using functional magnetic resonance imaging (fMRI). Each performed: (1) a word generation (WG) task alone, followed by (2) repeating WG after insertion of acupuncture needles (WGN) into SJ 8 (a language-implicated acupoint), followed by (3) repeating WGN reinforced by electrical stimulation (WGA) of SJ 8, and finally (4) electrical stimulation (ES) of SJ 8 alone. Significant activation was found in the opercular, triangular, or insula during the ES stimulation in patients when comparing each patient to 14 normal controls. For the WG task, significant activation was found in the inferior frontal gyrus when comparing each patient to 14 normal controls. The signal induced by acupuncture was larger than that of the WG task in the left middle frontal gyrus with the comparison of WGA vs. WGN in seven patients. Further, main significant effects in the right insula in patients were observed when comparing seven patients to 14 normal controls. The activation induced by ES stimulation was only found on the left side in controls. This activation was observed on the lesion side of superior and middle frontal gyrus (SMFG) in patients. This study demonstrates for the first time that language-deficit-implicated acupoint stimulation can selectively activate the brain on the lesion side in post-stroke aphasia patients. These results suggest that acupuncture may have therapeutic benefits in post-stroke aphasia patients.

Coenzyme Q10 reduces beta-amyloid plaque in an APP/PS1 transgenic mouse model of Alzheimer's disease.

We previously reported that coenzyme Q10 (CoQ10) could reduce intracellular deposition in an aged transgenic mouse model. Here, we further tested the effect of CoQ10 on amyloid plaque in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer's disease (AD). By using immunohistochemistry and magnetic resonance imaging to determine the burden of amyloid plaque, we found that oral administration of CoQ10 can efficiently reduce the burden of the plaques in this mouse model. These data demonstrate that in addition to reducing intracellular deposition of Abeta, CoQ10 can also reduce plaque pathology. Our study further supports the use of CoQ10 as a therapeutic candidate for AD.

Hyperphosphorylation and accumulation of neurofilament proteins in transgenic mice with Alzheimer presenilin 1 mutation.

Neurofilaments (NFs) are hyperphosphorylated and accumulate in Alzheimer's disease (AD) brains. In this study, employing the transgenic mouse model, we explored the effect of presenilin 1 (PS-1) mutation on the phosphorylation and distribution of NFs. Western blot analysis showed that there was a significant increase in the phosphorylation of NF-H and NF-M subunits with a concomitant increase in phosphorylated c-Jun N-terminal protein kinase 1/2 (JNK1/2) mitogen-activated protein kinase (MAPK) in hippocampus of PS-1 transgenic mice compared to that of wild-type littermates. Immunohistochemical analysis revealed that phosphorylated NFs accumulated throughout the hippocampal neurons of the transgenic mice. These findings suggest that PS-1 mutation may induce hyperphosphorylation and accumulation of NFs via a JNK1/2-involved mechanism.

Diet supplement CoQ10 delays brain atrophy in aged transgenic mice with mutations in the amyloid precursor protein: an in vivo volume MRI study.

We tested the hypotheses that supplemental intake of the diet supplement Coenzyme Q10 (CoQ10) could delay brain atrophy in double transgenic amyloid precursor protein (APP) / presenilin 1 (PS1), single transgenic APP and PS1 as well as wild type mice by volume MR image in vivo. One hundred and twelve mice (28 APP/PS1, 28 APP, 28 PS1 and 28 wild types) were studied. Half of each genotype group (n = 14 per group) was treated with CoQ10 2400 mg/kg/day, and the other half with placebo for 60 days. Magnetic resonance (MR) images were used to obtain the volumes of the hemispheres and hippocampi. APP / PS1, APP, PS1 and wild type mice treated with CoQ10 exhibited significantly less atrophy in hemisphere and hippocampus than those receiving placebo. The neuro-protective effect of the CoQ10 on hemispheric volume, and hippocampal volume was related to genotype; greater in APP/PS1 than APP and PS1 mice and less in wild type mice. Our result indicated that CoQ10 may have therapeutic potential in the prevention and treatment of MCI and AD.

Simultaneous ultrasound and MRI system for breast biopsy: compatibility assessment and demonstration in a dual modality phantom.

Simultaneous capturing of ultrasound (US) and magnetic resonance (MR) images allows fusion of information obtained from both modalities. We propose an MR-compatible US system where MR images are acquired in a known orientation with respect to the US imaging plane and concurrent real-time imaging can be achieved. Compatibility of the two imaging devices is a major issue in the physical setup. Tests were performed to quantify the radio frequency (RF) noise introduced in MR and US images, with the US system used in conjunction with MRI scanner of different field strengths (0.5 T and 3 T). Furthermore, simultaneous imaging was performed on a dual modality breast phantom in the 0.5 T open bore and 3 T close bore MRI systems to aid needle-guided breast biopsy. Fiducial based passive tracking and electromagnetic based active tracking were used in 3 T and 0.5 T, respectively, to establish the location and orientation of the US probe inside the magnet bore. Our results indicate that simultaneous US and MR imaging are feasible with properly-designed shielding, resulting in negligible broadband noise and minimal periodic RF noise in both modalities. US can be used for real time display of the needle trajectory, while MRI can be used to confirm needle placement.

Coenzyme Q10 attenuates beta-amyloid pathology in the aged transgenic mice with Alzheimer presenilin 1 mutation.

One of the neuropathological features of Alzheimer's disease (AD) is the deposition of senile plaques containing beta-amyloid (A beta). There is limited evidence for the treatment to arrest A beta pathology of AD. In our present study, we tested the effect of coenzyme Q10 (CoQ10), an endogenous antioxidant and a powerful free radical scavenger, on A beta in the aged transgenic mice overexpressing Alzheimer presenilin 1-L235P (leucine-to-proline mutation at codon 235, 16-17 months old). The treatment by feeding the transgenic mice with CoQ10 for 60 days (1,200 mg kg(-1) day(-1)) partially attenuated A beta overproduction and intracellular A beta deposit in the cortex of the transgenic mice compared with the age-matched untreated transgenic mice. Meanwhile, an increased oxidative stress reaction was detected as evidenced by elevated level of malondialdehyde (MDA) and decreased activity of superoxide dismutase (SOD) in the transgenic mice relative to the wild-type mice, and supplementation of CoQ10 partially decreased MDA level and upregulated the activity of SOD. The results indicate that oxidative stress is enhanced in the brain of the transgenic mice, that this enhancement may further promote A beta 42 overproduction in a vicious formation, and that CoQ10 would be beneficial for the therapy of AD.

First-pass myocardial perfusion image registration by maximization of normalized mutual information.

PURPOSE: To evaluate a left ventricular image registration algorithm for first-pass MR myocardial perfusion. MATERIALS AND METHODS: A normalized mutual information based motion correction algorithm was proposed and tested on 27 adenosine stressed myocardial perfusion cases consisting of pretreatment and posttreatment of 15 patients undergone autologous bone marrow mononuclear cell transplant therapy. An image mask approximately covering the left and right ventricles was manually defined to include a region of interest for registration. A two-dimensional multiresolution registration approach was used to register consecutively acquired multislice images with in-plane translations. The method was validated by manual registration and singular value deconvolution based perfusion analysis. RESULTS: The proposed image registration algorithm was found to be robust in minimizing the in-plane motion of the left ventricle in first-pass myocardial perfusion. The image mask including the left and right ventricle was found to be more robust than including the left ventricle alone. A smooth estimate of normalized mutual information coefficients were achieved for images with large contrast changes. CONCLUSION: The proposed semiautomatic multiresolution registration algorithm was able to register first-pass MR myocardial perfusion images and may be useful in quantitative perfusion analysis.

Multi-modal imaging: simultaneous MRI and ultrasound imaging for carotid arteries visualization.

The purpose of this study is to examine the feasibility of simultaneous Magnetic Resonance Imaging (MRI) and Ultrasound (US) imaging in visualizing anatomical structures and functions in human carotid arteries. US has high frame rate in visualizing dynamic changes while high resolution MRI is capable of capturing volumetric structures with the best tissue contrast. Concurrent multi-modal image acquisition allows fusion of US Doppler flow measurement with volumetric MRI. We present a method for acquiring MR images in a known orientation with respect to US image by passive fiducial tracking and demonstrate concurrent real-time imaging in the right Common Carotid Artery (CCA) in both modalities. Preliminary results suggest that US and MRI can operate concurrently with proper shielding. Dispensability measurements are feasible on both modalities at the co-incident plane.

Study of myocardial fiber pathway using magnetic resonance diffusion tensor imaging.

The purpose of this study was to investigate myocardial fiber pathway distribution in order to provide supplemental information on myocardial fiber architecture and cardiac mechanics. Diffusion tensor imaging (DTI) with medium diffusion resolution (15 directions) was performed on normal canine heart samples (N=6) fixed in formalin. With the use of diffusion tensor fiber tracking, left ventricle (LV) myocardial fiber pathways and helix angles were computed pixel by pixel at short-axis slices from base to apex. Distribution of DTI-tracked fiber pathway length and number was analyzed quantitatively as a function of fiber helix angle in step of 9 degrees . The long fiber pathways were found to have small helix angles. They are mostly distributed in the middle myocardium and run circumferentially. Fiber pathways tracked at the middle and upper LV are generally longer than those near the apex. Majority of fiber pathways have small helix angles between -20 degrees and 20 degrees , dominating the fiber architecture in myocardium. Likely, such myocardial fiber pathway measurement by DTI may reflect the spatial connectiveness or connectivity of elastic myofiber bundles along their preferential pathway of electromechanical activation. The dominance of the long and circumferentially running fiber pathways found in the study may explain the circumferential predominance in left ventricular contraction.

Neuroprotective effect of Coenzyme Q10 on ischemic hemisphere in aged mice with mutations in the amyloid precursor protein.

This study was designed to test whether Coenzyme Q10 (CoQ10) supplementation has neuroprotective effect in aged, double-transgenic amyloid precursor protein (APP)/presenilin 1 (PS1), single transgenic APP and PS1 mice exposed to ischemic injury of the brain. Forty-eight mice (12 each of APP/PS1, APP, PS1 and wild-type) were studied. Half of each genotype groups (n=6 per group) was treated with CoQ10 (1200 mg/kg/day) after ischemic injury and the other half with placebo. Magnetic resonance (MR) images were used to measure the volume of induced infarction (IFV), as well as the volume of the hemispheres and hippocampi. Significantly greater volumes of infarction and lesser volumes of hemisphere/hippocampus on the ischemic side were observed in APP/PS1 and APP mice than in PS1 and wild-type mice. This is consistent with amplification of the effect of ischemia in APP carriers. After 28 days of CoQ10 treatment, APP/PS1 or APP mutations have smaller infarct volumes, while the volumes of hemisphere and hippocampus on the infarcted side were larger than those treated with placebo. No differences between CoQ10- and placebo-treated groups in volumes of infarct, hemisphere and hippocampus were observed in PS1 and wild-type mice. We conclude that CoQ10 has a protective effect on the brain from infarction and atrophy induced by ischemic injury in aged and susceptible transgenic mice.

An fMRI study of somatosensory-implicated acupuncture points in stable somatosensory stroke patients.

PURPOSE: To assess differences in brain responses between stroke patients and controls to tactile and electrical acupuncture stimulation using functional MRI (fMRI). MATERIALS AND METHODS: A total of 12 male, clinically stable stroke patients with left side somatosensory deficits, and 12 age-matched male control subjects were studied. fMRI was performed with two different paradigms; namely, tactile stimuli and electrical stimulation at acupuncture points LI4 and LI11 on the affected side of the body. fMRI data were analyzed using SPM99. RESULTS: Tactile stimulation in both patients and controls produced significant activation in primary and secondary sensory and motor cortical areas and cerebellum. Greater activation was present in patients than controls in the somatosensory cortex with both the tactile task and the acupuncture point (acupoint) stimulation. Activation was greater during the tactile task than the acupuncture stimulation in patients and normal controls. CONCLUSION: Differences observed between patients and controls on both tasks may indicate compensatory over recruitment of neocortical areas involved in somatosensory perception in the stroke patients. The observed differences between patients and controls on the acupoint stimulation task may also indicate that stimulation of acupoints used therapeutically to enhance recovery from stroke, selectively activates areas thought to be involved in mediating recovery from stroke via functional plasticity. fMRI of acupoint stimulation may illustrate the functional substrate of the therapeutically beneficial effect of acupuncture in stroke rehabilitation.

Proton-density-weighted spinal fMRI with sensorimotor stimulation at 0.2 T.

Proton-density-weighted fMRI at low field (0.2 T) was carried out in the cervical spinal cord of healthy volunteers in this study to examine the feasibility of detecting proton density alteration accompanying activation in the spinal cord. Subjects were asked to grip both hands simultaneously, providing sensorimotor simulation for spinal fMRI. Over 70% subjects recruited had activation localized at C6-C7 spinal levels with discrete activation detected in both the anterior and posterior horns of the cervical spinal cord, and the average fractional signal change was 4.06%. The 0.2 T low magnetic field and the 24 ms short TE used in this study diminished the BOLD effect to a negligible level, thus the observed signal change was believed to be mainly attributable to proton density increase during neuronal stimulation. Our results suggested the existence of task-driven proton density change in the cervical spinal cord.

Cognitive processing in Chinese literate and illiterate subjects: an fMRI study.

Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) were used to map brain activation during language tasks. While previous studies have compared performance between alphabetic literate and illiterate subjects, there have been no such data in Chinese-speaking individuals. In this study, we used fMRI to examine the effects of education on neural activation associated with silent word recognition and silent picture-naming tasks in 24 healthy right-handed Chinese subjects (12 illiterates and 12 literates). There were 30 single Chinese characters in the silent word recognition task and 30 meaningful road-signs in the silent picture-naming task. When we compared literate and illiterate subjects, we observed education-related differences in activation patterns in the left inferior/middle frontal gyrus and both sides of the superior temporal gyrus for the silent word recognition task and in the bilateral inferior/middle frontal gyrus and left limbic cingulated gyrus for the silent picture-naming task. These results indicate that the patterns of neural activation associated with language tasks are strongly influenced by education. Education appears to have enhanced cognitive processing efficiency in language tasks.

Spinal effects of acupuncture stimulation assessed by proton density-weighted functional magnetic resonance imaging at 0.2 T.

Signal changes can be detected by proton density-weighted functional imaging in both the brain and the spinal cord. These are attributed to changes in extravascular water proton (signal enhancement by extravascular protons) density during neuronal activation. In this study, we used this technique to detect correlations between acupoint stimulation and neural activity in the spinal cord. Stimulation of acupoints associated with treatment of sensorimotor deficits (LI4 and LI11) was performed on 11 volunteers. During stimulation, 8 of the 11 subjects had consistent functional activations in C6/C7. A bilateral activation pattern was common. Our findings show that acupoint stimulation modulates activity in the spinal cord.

Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid toxicity and oxygen-glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore.

Coenzyme Q10 (CoQ10) is an essential biological cofactor which increases brain mitochondrial concentration and exerts neuroprotective effects. In the present study, we exposed SHSY5Y neuroblastoma cells to neurotoxic beta amyloid peptides (Abeta) and oxygen glucose deprivation (OGD) to investigate the neuroprotective effect of 10 microM CoQ10 by measuring (i) cell viability by the MTT assay, (ii) opening of the mitochondrial permeability transition pore via the fluorescence intensity of calcein-AM, and (iii) superoxide anion concentration by hydroethidine. Cell viability (mean +/- S.E.M.) was 55.5 +/- 0.8% in the group exposed to Abeta + OGD, a value lower than that in the Abeta or OGD group alone (P < 0.01). CoQ10 had no neuroprotective effect on cell death induced by either Abeta or OGD, but increased cell survival in the Abeta + OGD group to 57.3 +/- 1.7%, which was higher than in the group treated with vehicle (P < 0.05). The neuroprotective effect of CoQ10 was blocked by administration of 20 microM atractyloside. Pore opening and superoxide anion concentration were increased in the Abeta + OGD group relative to sham control (P < 0.01), and were attenuated to the sham level (P > 0.05) when CoQ10 was administered. Our results demonstrate that CoQ10 protects neuronal cells against Abeta neurotoxicity together with OGD by inhibiting the opening of the pore and reducing the concentration of superoxide anion.

Performance of large-size superconducting coil in 0.21T MRI system.

A high-temperature superconductor (HTS) was used on magnetic resonance imaging (MRI) receiver coils to improve image quality because of its intrinsic low electrical resistivity. Typical HTS coils are surface coils made of HTS thin-film wafers. Their applications are severely limited by the field of view (FOV) of the surface coil configuration, and the improvement in image quality by HTS coil is also reduced as the ratio of sample noise to coil noise increases. Therefore, previous HTS coils are usually used to image small in vitro samples, small animals, or peripheral human anatomies. We used large-size HTS coils (2.5-, 3.5-, and 5.5-in mean diameter) to enhance the FOV and we evaluated their performance through phantom and human MR images. Comparisons were made among HTS surface coils, copper surface coils, and cool copper surface coils in terms of the signal-to-noise ratio (SNR) and sensitivity profile of the images. A theoretical model prediction was also used to compare against the experimental result. We then selected several human body parts, including the wrist, feet, and head, to illustrate the advantage of HTS coil over copper coil when used in human imaging. The results show an SNR gain of 200% for 5.5-in HTS coil versus same size copper coils, while for 2.5- and 3.5-in coils it is 250%. We also address the various factors that affect the performance of large size HTS coils, including the coil-to-sample spacing due to cryogenic probe and the coil-loading effect.

In vivo study of microbubbles as an MR susceptibility contrast agent.

The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison, was studied with rat liver imaging at 7 T. Optison suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (deltaR2*) of 29.1 +/- 1.6 s(-1) (N = 2) and 61.5 +/- 12.9 s(-1) (N = 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro deltaR2* measurements of Optison suspension at different concentrations are also reported.