This study proposes an automated diagnostic method to classify patients with Alzheimer's disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers. Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM. Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (±13.8), 86.9% (±10.5), 96.3% (±4.6), and 70.5% (±11.5), respectively. This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.

Background: To observe brain activation induced by functional electrical stimulation, voluntary contraction, and the combination of both using functional magnetic resonance imaging (fMRI). Methods: Nineteen healthy young men were enrolled in the study. We employed a typical block design that consisted of three sessions: voluntary contraction only, functional electrical stimulation (FES)-induced wrist extension, and finally simultaneous voluntary and FES-induced movement. MRI acquisition was performed on a 3.0 T MR system. To investigate activation in each session, one-sample t-tests were performed after correcting for false discovery rate (FDR; p < 0.05). To compare FES-induced movement and combined contraction, a two-sample t-test was performed using a contrast map (p < 0.01). Results: In the voluntary contraction alone condition, brain activation was observed in the contralateral primary motor cortex (MI), thalamus, bilateral supplementary motor area (SMA), primary sensory cortex (SI), secondary somatosensory motor cortex (SII), caudate, and cerebellum (mainly ipsilateral). During FES-induced wrist movement, brain activation was observed in the contralateral MI, SI, SMA, thalamus, ipsilateral SII, and cerebellum. During FES-induced movement combined with voluntary contraction, brain activation was found in the contralateral MI, anterior cingulate cortex (ACC), SMA, ipsilateral cerebellum, bilateral SII, and SI. The activated brain regions (number of voxels) of the MI, SI, cerebellum, and SMA were largest during voluntary contraction alone and smallest during FES alone. SII-activated brain regions were largest during voluntary contraction combined with FES and smallest during FES contraction alone. The brain activation extent (maximum t score) of the MI, SI, and SII was largest during voluntary contraction alone and smallest during FES alone. The brain activation extent of the cerebellum and SMA during voluntary contraction alone was similar during FES combined with voluntary contraction; however, cerebellum and SMA activation during FES movement alone was smaller than that of voluntary contraction alone or voluntary contraction combined with FES. Between FES movement alone and combined contraction, activated regions and extent due to combined contraction was significantly higher than that of FES movement alone in the ipsilateral cerebellum and the contralateral MI and SI. Conclusions: Voluntary contraction combined with FES may be more effective for brain activation than FES-only movements for rehabilitation therapy. In addition, voluntary effort is the most important factor in the therapeutic process.

To assess the efficacy of pregabalin by showing differences in the neuronal activities of fibromyalgia (FM) patients before and after longitudinal treatment using functional magnetic resonance imaging (fMRI). In total, 21 female patients with FM and 11 age- and gender-matched healthy controls participated. FM patients underwent fMRI at baseline and following pharmacological therapy with pregabalin to diminish their pain. Pressure-pain stimuli were delivered on the subject’s thumbnail bed during fMRI scans. Brain activation regions in fMRI were evaluated for longitudinal changes using a paired t-test. Changes in clinical features were also assessed with the Fibromyalgia Impact Questionnaire (FIQ), Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), Widespread Pain Index (WPI), Symptom Severity Scale Score (SSS), and State-Trait Anxiety Inventory (STAI). Clinical scores were reduced significantly following therapy with five of the six clinical tests (FIQ, BFI, BDI, WPI, SSS; p < 0.05). Brain activation post-treatment was significantly lower than that pre-treatment in 13 regions of the brain (p < 0.001). Our findings confirm that pregabalin influences aspects of the whole pain matrix, using fMRI, inducing longitudinal changes in neuronal activity during the pain state, and that it reduces pain and other core symptoms of FM. This method could be applied to other longitudinal clinical trials of pharmacological treatments for FM.

The purpose of this study was to evaluate the metabolomic changes in 3D-cultured human mesenchymal stem cells (hMSCs) in alginate beads, so as to identify biomarkers during chondrogenesis using ¹H nuclear magnetic resonance (NMR) spectroscopy. hMSCs (2×10⁶ cells/mL) were seeded into alginate beads, and chondrogenesis was allowed to progress for 15 days. NMR spectra of the chondrogenic hMSCs were obtained at 4, 7, 11, and 15 days using a 14.1-T (600-MHz) NMR with the water suppression sequence, zgpr. Real-Time polymerase chain reaction (PCR) was performed to confirm that that the hMSCs differentiated into chondrocytes and to analyze the metabolomic changes indicated by the NMR spectra. During chondrogenesis, changes were detected in several metabolomes as hMSC chondrogenesis biomarkers, e.g., fatty acids, alanine, glutamate, and phosphocholine. The metabolomic changes were compared with the Real-Time PCR results, and significant differences were determined using statistical analysis. We found that changes in metabolomes were closely related to biological reactions that occurred during the chondrogenesis of hMSCs. In this study, we confirm that metabolomic changes detected by ¹H-NMR spectroscopy during chondrogenic differentiation of 3D-cultured hMSCs in alginate beads can be considered as biomarkers of stem cell differentiation.

A reference reagent, 3-(trimethylsilyl) propionic-2, 2, 3, 3-d4 acid sodium (TSP), has been used frequently in nuclear magnetic resonance (NMR) and magnetic resonance spectroscopy (MRS) as an internal reference to identify cell and tissue metabolites, and determine chemical and protein structures. This reference material has been exploited for the quantitative and dynamic analyses of metabolite spectra acquired from cells. The aim of this study was to evaluate the cytotoxicity of TSP on three-dimensionally, agarose gel, cultured cells. A human osteosarcoma cell line (MG-63) was selected, and cells were three dimensionally cultured for two weeks in an agarose gel. The culture system contained a mixture of conventional culture medium and various concentrations (0, 1, 3, 5, 7, 10, 20 30 mM) of TSP. A DNA quantification assay was conducted to assess cell proliferation using Quant-iT PicoGreen dsDNA reagent and kit, and cell viability was determined using a LIVE/DEAD Viability/Cytotoxicity kit. Both examinations were performed simultaneously at 1, 3, 7 and 14 days from cell seeding. In this study, the cytotoxicity of TSP in the 3D culture of MG-63 cells was evaluated by quantifying DNA (cell proliferation) and cell viability. High concentrations of TSP (from 10 to 30 mM) reduced both cell proliferation and viability (to 30% of the control after one week of exposure), but no such effects were found using low concentrations of TSP (0–10mM). This study shows that low concentrations of TSP in 3D cell culture medium can be used for quantitative NMR or MRS examinations for up to two weeks post exposure.

Purpose: To evaluate the temporal and spatial resolution of magnetic resonance (MR) temperature imaging when using the proton resonance frequency (PRF) method combined with the keyhole technique. Materials and Methods: Tissue-mimicking phantom and swine muscle tissue were microwave-heated by a coaxial slot antenna. For the sake of MR hardware safety, MR images were sequentially acquired after heating the subjects using a spoiled gradient (SPGR) pulse sequence. Reference raw (k-space) data were collected before heating the subjects. Keyhole temperature images were reconstructed from full k-space data synthesized by combining the peripheral phase-encoding part of the reference raw data and the center phase-encoding keyhole part of the time sequential raw data. Each keyhole image was analyzed with thermal error, and the signal-to-noise ratio (SNR) was compared with the self-reference (nonkeyhole) images according to the number of keyhole phase-encoding (keyhole-data size) portions. Results: In applied keyhole temperature images, smaller keyhole-data sizes led to more temperature error increases, but the SNR did not decreased comparably. Additionally, keyhole images with a keyhole-data size of <16 had significantly different temperatures compared with fully phase-encoded self-reference images (P < 0.05). Conclusion: The keyhole technique combined with the PRF method improves temporal resolution and SNR in the measurement of the temperature in the deeper parts of body in real time. J. Magn. Reson. Imaging 2011;.