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Biomedical subjects

K D Merboldt

Publications and source records attributed to K D Merboldt.

At least 37 records · Page 2Linked to original sources

Brain or vein--oxygenation or flow? On signal physiology in functional MRI of human brain activation.

Stimulus-related signal changes in functional MRI of human brain activation not only reflect associated adjustments of cerebral blood flow and oxygen consumption, but strongly depend on the MRI technique chosen and the actual experimental setting. A list of relevant parameters includes static field homogeneity of the magnet, MR pulse sequence and signal type, TE, TR, flip angle, gradient strengths, gradient waveforms, receiver bandwidth and voxel size. In principle, a local signal increase during functional activation may reflect a regional change in cerebral blood flow or deoxyhemoglobin concentration or both. This ambiguity was demonstrated using long TE FLASH MRI at high spatial resolution. Subsequently, experimental strategies were evaluated that either discriminate MRI effects in large vessels from those in the cortical microvasculature or separate changes in blood flow velocity from those in blood oxygenation. Examples comprise studies of the human visual and motor cortex.

Brain↗

Correlational imaging of thalamocortical coupling in the primary visual pathway of the human brain.

While the anatomy of the human brain is well defined, the functional connectivity of its structures is far less understood. Modern neuroimaging techniques offer the unique opportunity of visualizing physiologic activation in central nervous structures and of identifying the elements underlying distributed networks for information processing. Following improved spatial resolution of deoxyhemoglobin-sensitive magnetic resonance imaging, we were able to detect simultaneous signal changes in the lateral geniculate nucleus and primary visual cortex during periodic photic stimulation. Visualization of coupled activation by cross-correlation analysis resulted in the first demonstration of thalamocortical interaction in the primary visual pathway of the intact human brain.

Adult↗

The effect of acetazolamide on regional cerebral blood oxygenation at rest and under stimulation as assessed by MRI.

The sensitivity of gradient echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation (CBO) has been introduced for mapping functional brain activation. Here, we report that this approach allows monitoring autoregulation in the human brain under vasodilatory stress. Following the administration of acetazolamide, signal intensities of deoxyhemoglobin-sensitive images increased in cortical and subcortical gray matter and to a lesser extent in white matter. This result reflects a venous hyperoxygenation stemming from an increase in cerebral perfusion with oxygen consumption remaining constant. In addition, pharmacologic induction of vasodilation attenuated activity-related MRI signal changes in the visual cortex under photic stimulation. Although intersubject variability was high, this finding indicates individually persisting autoregulatory responsiveness to functional challenge despite an "exhausted" reserve capacity. It is suggested that recording CBO by MRI will foster our understanding of modulation of vasomotor tone and cerebral perfusion. Furthermore, this technique may prove valuable for assessing the cerebrovascular reserve capacity in patients with carotid artery occlusive disease.

Acetazolamide↗

Functional cooperativity of human cortical motor areas during self-paced simple finger movements. A high-resolution MRI study.

Magnetic resonance imaging of changes in cerebral blood oxygenation (CBO) delineated areas of neural activation during self-paced unilateral middle finger tapping in five normal volunteers. Four contiguous imaging sections parallel to the bicommissural plane covered the hand area of the primary sensori-motor cortex bilaterally. All measurements were performed at 2.0 T using rapid gradient-echo sequences (TR/TE = 63/30 ms) with high spatial resolution (0.8 x 1.6 x 4 mm) and both strong (40 degrees flip angle) and weak (10 degrees) radiofrequency excitation pulses. This allows differentiation of flow and CBO contributions to the observed signal alterations. Functional cooperativity was analysed by a pixel-by-pixel correlation of signal intensity time courses with the stimulus protocol. Areas of activation included the contralateral primary motor cortex, the homologue part of the primary sensory cortex, the supplementary motor area (SMA) and the lateral premotor areas in all volunteers. Task-related activation of ipsilateral primary motor cortex above a threshold correlation coefficient of 0.5 was seen in two out of five volunteers (at 40 degrees) and one out of five (at 10 degrees) when performing the right-hand task. The present MRI findings readily demonstrate in single subjects that the SMA is involved in self-paced finger tapping. Only sparse activation in the ipsilateral primary motor cortex is consistent with the motor paradigm used.

Adult↗

Molecular self-diffusion of intracellular metabolites in rat brain in vivo investigated by localized proton NMR diffusion spectroscopy.

Molecular self-diffusion coefficients of water (0.75 +/- 0.05), N-acetylaspartate (0.27 +/- 0.04), creatines (0.27 +/- 0.04), and cholines (0.28 +/- 0.08) x 10(-5) cm2 s-1 were obtained from localized proton NMR spectra of rat brain in vivo using diffusion-weighted stimulated-echo (STEAM) sequences with a diffusion time of (delta--delta/3) = 17 ms.

Animals↗

Functional MRI of human brain activation at high spatial resolution.

Functional activation maps of the human visual cortex were obtained at a spatial resolution almost two orders of magnitude better than achievable by positron emission tomography and within measuring times of a few seconds. Transient alterations in the concentration of paramagnetic deoxyhemoglobin were conveniently detected at 2.0-T with use of RF-spoiled FLASH MRI sequences employing gradient echo times of 6 to 60 ms and voxel sizes of 2.5 to 39 microliters.

Adult↗

Dynamic high-resolution MR imaging of brain deoxygenation during transient anoxia in the anesthetized rat.

Transient alterations in brain oxygenation during 60-s periods of anoxia were visualized at high spatial resolution (voxel size < or = 0.15 microliter) with the use of serial long echo time FLASH (fast low-angle shot) magnetic resonance images (measuring time > or = 6 s) of halothane-anesthetized rats in vivo. Difference images from normoxia and anoxia exploit the signal decrease associated with increased levels of paramagnetic deoxyhemoglobin in the arterial and venous blood pool. Insights into the spatial heterogeneity of oxygen deprivation are complemented by physiologic information from the time course of pertinent signal changes in different regions of the brain.

Animals↗

Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra.

In vivo concentrations of cerebral metabolites were obtained by means of 52 single-voxel, localized proton magnetic resonance (MR) spectroscopic examinations of different regions of the brain performed in 26 healthy adults aged 21-32 years. The study was performed at 2.0 T with use of a circularly polarized head coil to ensure homogeneous radio-frequency excitation and signal reception. Proton MR spectra were obtained in the stimulated-echo acquisition mode under fully relaxed conditions (repetition time > or = 6,000 msec) and at short echo times (20 msec) to minimize corrections due to T1 and T2 attenuation and depict the spectra of metabolites with strongly coupled resonances. Absolute concentrations were obtained by means of calibration of resonance signal areas with those of pertinent metabolite solutions from separate studies and correction for coil loading and partial volume effects (eg, with perfused capillary networks and cerebrospinal fluid). The results provide a quantitative basis for studies of both normal human neurochemistry in vivo and metabolic alterations in diseases of the brain.

Adult↗

Multiple sclerosis in children: cerebral metabolic alterations monitored by localized proton magnetic resonance spectroscopy in vivo.

In vivo proton magnetic resonance spectroscopy of 8 children (7-16 years) with established multiple sclerosis revealed distinct alterations in regional cerebral metabolism associated with different aspects of the disease: (1) Localized proton spectra (2 to 4-ml volumes of interest) from multiple sclerosis plaques were generally characterized by a decrease in N-acetylaspartate and creatine, and an increase in cholines and myo-inositol relative to age-matched control subjects, (2) neither chronic nor enhancing plaques (by gadolinium-diethylenetriamine pentaacetic acid) during an acute exacerbation showed elevated levels of lactate or lipids, (3) spectra from adjacent white matter that did not appear suspicious in magnetic resonance images were similar to those of normal control subjects, and (4) cortical gray matter related to neighboring multiple sclerosis lesions showed a notable reduction of N-acetylaspartate. The present results show that functional impairment in multiple sclerosis is linked to gross metabolic disturbances of neuronal cell chemistry. We suggest that focal demyelination is accompanied by increased membrane precursors of proliferative turnover and is associated with secondary neuronal shrinkage or loss, perhaps extending into related cortical gray matter.

Adolescent↗

Diffusion imaging of the human brain in vivo using high-speed STEAM MRI.

This paper describes a new method for diffusion imaging of the human brain in vivo that is based on a combination of diffusion-encoding gradients with high-speed STEAM MR imaging. The single-shot sequence 90 degrees-TE/2-90 degrees-TM-(alpha-TE/2-STE)n generates n = 32-64 differently phase-encoded stimulated echoes STE yielding image acquisition times of 576 ms for a 48 x 128 data matrix. Diffusion encoding is performed during the first TE/2-interval as well as during each readout period. Phantom studies reveal a quantitative agreement of calculated diffusion coefficients with literature values. EKG triggering completely eliminates motion artifacts from diffusion-weighted single-shot STEAM images of human brain in vivo. While signal attenuation of the cerebrospinal fluid (CSF) is predominantly due to flow, that observed for gray and white matter results from diffusion. Evaluated diffusion coefficients yield (1.0 +/- 0.1) x 10(-5) cm2 s-1 for gray matter, (0.5 +/- 0.1) x 10(-5) cm2 s-1 for white matter with the diffusion encoding parallel to the main orientation of the myelin sheath of the neurofibrils, and (0.3 +/- 0.1) x 10(-5) cm2 s-1 for white matter and a perpendicular orientation. All studies were performed at 2.0 T using a conventional 10 mT m-1 gradient system.

Brain↗

Decrease of glucose in the human visual cortex during photic stimulation.

Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions.

Adult↗

Localized proton NMR spectroscopy using stimulated echoes: applications to human skeletal muscle in vivo.

Localized proton NMR spectroscopy using stimulated echoes (STEAM) has been used to study metabolites in different proximal skeletal muscles of normal volunteers at rest. Single scan water-suppressed proton NMR spectra obtained at 1.5 and 2.0 T (Siemens Magnetom) from a 64-ml volume-of-interest (VOI) yield resonances due to triglycerides, phosphocreatine plus a minor contribution from creatine, and betaines comprising carnitine and choline-containing compounds. The observation of the pH-dependent resonances of carnosine required multiple acquisitions and echo times as short as 20 ms. T1 and T2 relaxation times of muscle metabolites were obtained by varying the repetition time and echo time of the STEAM sequence, respectively. Although rather long T2 values such as 180 ms for (phospho-) creatine correspond to natural resonance linewidths of only 2 Hz, the observed linewidths of typically 10-12 Hz are entirely determined by the short T2 relaxation times (25-30 ms) of the water protons used for shimming. The spectroscopic results from 24 muscle studies on 17 young male volunteers show remarkable intra- and interindividual differences in the absolute signal intensities of mobile lipids. Further metabolic variations were observed for the relative concentrations of betaines (by a factor of 2) and carnosine (by a factor of 3) when total creatine is assumed to be constant.

Carnitine↗

Diffusion imaging using stimulated echoes.

The application of stimulated echo acquisition mode (STEAM) sequences for NMR imaging of diffusion is especially suited for spins with T1 much greater than T2 as, e.g., encountered in proton NMR studies of biological systems. Molecular self-diffusion coefficients may be calculated from a set of diffusion-weighted images acquired with different gradient strengths. A variation of the diffusion time allows the determination of restricted and/or anisotropic diffusion in cellular systems ranging from plants to humans. Problems associated with the presence of unavoidable macroscopic motions in vivo are demonstrated in diffusion studies of human brain. Motion ghosting in diffusion-weighted images may be overcome by means of a high-speed STEAM sequence yielding single-shot images within subsecond acquisition times.

Diffusion↗

Cerebral glucose is detectable by localized proton NMR spectroscopy in normal rat brain in vivo.

This contribution reports the first direct and noninvasive observation of cerebral glucose in normal anesthetized rats (n = 16) using short-echo-time localized proton NMR spectroscopy (2.35 T, STEAM, TR = 6000 ms, TE = 20 ms, 125 microliters). In addition to resonances from N-acetyl aspartate (NAA), glutamate, total creatine, cholines, taurine, and myoinositol, all spectra exhibit strongly coupled resonances from glucose (3.43, 3.80 ppm) that are readily identifiable using model solutions. The observed level of cerebral glucose in fasted rats covered a range of 15-40% of that of NAA giving absolute concentrations of 1.1-2.8 mM when NAA is taken to be 7 mM. The arterial blood glucose concentration was 7.7 +/- 0.8 mM in the same group of animals.

Animals↗

High-speed STEAM MRI of the human heart.

High-speed STEAM MR images of the normal human heart were obtained from single cardiac cycles using a 2.0-T whole-body system equipped with conventional 10 mT m-1 gradients. The single-shot 90 degrees-TE/2-90 degrees-TM-(alpha-TE/2-Acq)n pulse sequence acquires n differently phase-encoded stimulated echoes. Measuring times of 127-254 ms were achieved using a "repetition time" of 3.96 ms in conjunction with data matrices of 32-64 x 128 pixels covering a field-of-view of 250-350 mm. The sequence provides easy access to anatomical short-axis and long-axis views of the heart by single and double oblique rotation of the image orientation. STEAM images resemble the features of spin-echo images with respect to chemical shifts, susceptibilities, and flow. Thus, no additional techniques are required for the suppression of blood signals. EKG-triggered acquisitions demonstrate that slice-selective STEAM sequences using short TM intervals allow an unambiguous delineation of those parts of the myocardium that remain stationary within the selected plane throughout the entire imaging process. Neither spins leaving nor entering the slice defined by the initial 90 degrees RF pulses give rise to a stimulated echo and therefore do not contribute to the resulting image.

Heart↗