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Steding-Ehrenborg K.,Copenhagen Muscle Research Center | Steding-Ehrenborg K.,Danish Research Center for Magnetic Resonance | Jablonowski R.,Lund University | Arvidsson P.M.,Lund University | And 3 more authors.
Journal of Cardiovascular Magnetic Resonance | Year: 2013

Background: The effects on left and right ventricular (LV, RV) volumes during physical exercise remains controversial. Furthermore, no previous study has investigated the effects of exercise on longitudinal contribution to stroke volume (SV) and the outer volume variation of the heart. The aim of this study was to determine if LV, RV and total heart volumes (THV) as well as cardiac pumping mechanisms change during physical exercise compared to rest using cardiovascular magnetic resonance (CMR). Methods. 26 healthy volunteers (6 women) underwent CMR at rest and exercise. Exercise was performed using a custom built ergometer for one-legged exercise in the supine position during breath hold imaging. Cardiac volumes and atrio-ventricular plane displacement were determined. Heart rate (HR) was obtained from ECG. Results: HR increased during exercise from 60±2 to 94±2 bpm, (p<0.001). LVEDV remained unchanged (p=0.81) and LVESV decreased with -9±18% (p<0.05) causing LVSV to increase with 8±3% (p<0.05). RVEDV and RVESV decreased by -7±10% and -24±14% respectively, (p<0.001) and RVSV increased 5±17% during exercise although not statistically significant (p=0.18). Longitudinal contribution to RVSV decreased during exercise by -6±15% (p<0.05) but was unchanged for LVSV (p=0.74). THV decreased during exercise by -4±1%, (p<0.01) and total heart volume variation (THVV) increased during exercise from 5.9±0.5% to 9.7±0.6% (p<0.001). Conclusions: Cardiac volumes and function are significantly altered during supine physical exercise. THV becomes significantly smaller due to decreases in RVEDV whilst LVEDV remains unchanged. THVV and consequently radial pumping increases during exercise which may improve diastolic suction during the rapid filling phase. © 2013 Steding-Ehrenborg et al.; licensee BioMed Central Ltd.

Marner L.,Neurobiology Research Unit | Marner L.,Center for Integrated Molecular Brain Imaging | Frokjaer V.G.,Neurobiology Research Unit | Frokjaer V.G.,Center for Integrated Molecular Brain Imaging | And 12 more authors.
Neurobiology of Aging | Year: 2012

In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT 2A) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT 2A receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [ 18F]altanserin and [ 11C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([ 11C]DASB). Overall [ 18F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in [ 11C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [ 11C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT 2A receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections. © 2012 Elsevier Inc..

Karabanov A.,U.S. National Institutes of Health | Karabanov A.,Danish Research Center for Magnetic Resonance | Jin S.-H.,U.S. National Institutes of Health | Jin S.-H.,Seoul National University | And 6 more authors.
Journal of Neurophysiology | Year: 2012

Interplay between posterior parietal cortex (PPC) and ipsilateral primary motor cortex (M1) is crucial during execution of movements. The purpose of the study was to determine whether functional PPC-M1 connectivity in humans can be modulated by sensorimotor training. Seventeen participants performed a sensorimotor training task that involved tapping the index finger in synchrony to a rhythmic sequence. To explore differences in training modality, one group (n = 8) learned by visual and the other (n = 9) by auditory stimuli. Transcranial magnetic stimulation (TMS) was used to assess PPC-M1 connectivity before and after training, whereas electroencephalography (EEG) was used to assess PPC-M1 connectivity during training. Facilitation from PPC to M1 was quantified using paired-pulse TMS at conditioning-test intervals of 2, 4, 6, and 8 ms by measuring motor-evoked potentials (MEPs). TMS was applied at baseline and at four time points (0, 30, 60, and 180 min) after training. For EEG, task-related power and coherence were calculated for early and late training phases. The conditioned MEP was facilitated at a 2-ms conditioning-test interval before training. However, facilitation was abolished immediately following training, but returned to baseline at subsequent time points. Regional EEG activity and interregional connectivity between PPC and M1 showed an initial increase during early training followed by a significant decrease in the late phases. The findings indicate that parietal-motor interactions are activated during early sensorimotor training when sensory information has to be integrated into a coherent movement plan. Once the sequence is encoded and movements become automatized, PPC-M1 connectivity returns to baseline. © 2012 the American Physiological Society.

Greve D.N.,Massachusetts General Hospital | Greve D.N.,Harvard University | Svarer C.,Center for Integrated Molecular Brain Imaging | Fisher P.M.,Center for Integrated Molecular Brain Imaging | And 11 more authors.
NeuroImage | Year: 2014

Exploratory (i.e., voxelwise) spatial methods are commonly used in neuroimaging to identify areas that show an effect when a region-of-interest (ROI) analysis cannot be performed because no strong a priori anatomical hypothesis exists. However, noise at a single voxel is much higher than noise in a ROI making noise management critical to successful exploratory analysis. This work explores how preprocessing choices affect the bias and variability of voxelwise kinetic modeling analysis of brain positron emission tomography (PET) data. These choices include the use of volume- or cortical surface-based smoothing, level of smoothing, use of voxelwise partial volume correction (PVC), and PVC masking threshold. PVC was implemented using the Muller-Gartner method with the masking out of voxels with low gray matter (GM) partial volume fraction. Dynamic PET scans of an antagonist serotonin-4 receptor radioligand ([11C]SB207145) were collected on sixteen healthy subjects using a Siemens HRRT PET scanner. Kinetic modeling was used to compute maps of non-displaceable binding potential (BPND) after preprocessing. The results showed a complicated interaction between smoothing, PVC, and masking on BPND estimates. Volume-based smoothing resulted in large bias and intersubject variance because it smears signal across tissue types. In some cases, PVC with volume smoothing paradoxically caused the estimated BPND to be less than when no PVC was used at all. When applied in the absence of PVC, cortical surface-based smoothing resulted in dramatically less bias and the least variance of the methods tested for smoothing levels 5mm and higher. When used in combination with PVC, surface-based smoothing minimized the bias without significantly increasing the variance. Surface-based smoothing resulted in 2-4 times less intersubject variance than when volume smoothing was used. This translates into more than 4 times fewer subjects needed in a group analysis to achieve similarly powered statistical tests. Surface-based smoothing has less bias and variance because it respects cortical geometry by smoothing the PET data only along the cortical ribbon and so does not contaminate the GM signal with that of white matter and cerebrospinal fluid. The use of surface-based analysis in PET should result in substantial improvements in the reliability and detectability of effects in exploratory PET analysis, with or without PVC. © 2013 Elsevier Inc.

Kato Y.,Johns Hopkins University | Holm D.A.,Technical University of Denmark | Holm D.A.,Danish Research Center for Magnetic Resonance | Okollie B.,Johns Hopkins University | Artemov D.,Johns Hopkins University
Neuro-Oncology | Year: 2010

Poor drug delivery to brain tumors caused by aberrant tumor vasculature and a partly intact blood-brain barrier (BBB) and blood-brain tumor barrier (BTB) can significantly impair the efficacy of chemotherapy. Determining drug delivery to brain tumors is a challenging problem, and the noninvasive detection of drug directly in the tumor can be critically important for accessing, predicting, and eventually improving effectiveness of therapy. In this study, in vivo magnetic resonance spectroscopy (MRS) was used to detect an anticancer agent, temozolomide (TMZ), in vivo in murine xenotransplants of U87MG human brain cancer. Dynamic magnetic resonance imaging (MRI) with the low-molecular-weight contrast agent, gadolinium diethylenetriaminepentaacetic acid (GdDTPA), was used to evaluate tumor vascular parameters. Carbon-13-labeled TMZ ([ 13C]TMZ, 99%) was intraperitoneally administered at a dose of ∼140 mg/kg (450 mg/m2, well within the maximal clinical dose of 1000 mg/m2 used in humans) during the course of in vivo MRS experiments. Heteronuclear multiplequantum coherence (HMQC) MRS of brain tumors was performed before and after i.p. administration of [13C]TMZ. Dynamic MRI experiments demonstrated slower recovery of MRI signal following an intravenous bolus injection of GdDTPA, higher vascular flow and volume obtained by T*2 -weighted MRI, as well as enhanced uptake of the contrast agent in the brain tumor compared with normal brain detected by T 1-weighted MRI. These data demonstrate partial breakdown of the BBB/BTB and good vascularization in U87MG xenografts. A [13C]TMZ peak was detected at 3.9 ppm by HMQC from a selected volume of about 0.15 cm 3 within the brain tumor with HMQC pulse sequences. This study clearly demonstrates the noninvasive detection of [13C]TMZ in xenografted U87MG brain tumors with MRS. Noninvasive tracking of antineoplastic agents using MRS can have a significant impact on brain tumor chemotherapy. © The Author(s) 2009.

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