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Biomedical subjects

H Bruhn

Publications and source records attributed to H Bruhn.

At least 19 recordsLinked to original sources

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

Acute demyelinating disease. Classification and non-invasive diagnosis.

Five young patients are described with biopsy-proven acute demyelinating disease. Two cases are classified as Schilder's disease, a particular childhood form of multiple sclerosis (MS) with atypical clinical manifestation, normal or atypical CSF-findings and large bilateral lesions in magnetic resonance imaging (MRI). Two further cases presented with a fulminant bout of MS with typical clinical picture and CSF-findings; they are classified as Marburg's disease. The last case was an acute second bout of classical MS. The biopsy seemed to be justified in 4 cases, but unnecessary in the last case. Localized proton magnetic resonance spectroscopy (MRS) performed in one case allowed us to examine the focal cerebral abnormalities directly and non-invasively. The spectra revealed a pattern typical of acute demyelination suggesting potential for a replacement of biopsy in the future.

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

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

On the identification of cerebral metabolites in localized 1H NMR spectra of human brain in vivo.

Localized 1H NMR spectra of human brain in vivo are affected by signal overlap, strong spin-spin coupling, and complex J modulation, and therefore differ considerably from those obtained at higher magnetic fields. This paper deals with the assignment of 1H NMR resonances of cerebral metabolites under the experimental conditions used for human investigations. Conventional 7.0-T FID spectra and 2.0 T localized, short echo time STEAM spectra (TE = 20 ms) of aqueous metabolite solutions are compared to in vivo brain spectra of human volunteers and patients. In addition to singlet resonances from N-acetyl aspartate (NAA), creatines, and cholines, short echo time STEAM spectra exhibit multiplets due to the NAA aspartyl group, glutamate, taurine, and myo-inositol. Enhanced levels of cerebral glutamine are detected in patients with liver cirrhosis. For the first time elevated levels of brain glucose are observed in patients with diabetes mellitus.

Animals

Non-invasive 1H NMR spectroscopy of the rat brain in vivo using a short echo time STEAM localization sequence.

Fully localized proton NMR spectra were obtained from the brains of normal anaesthetized rats in vivo using stimulated echo (STEAM) spectroscopy sequences. Investigations were carried out at 2.35 T using a 40 cm bore magnet equipped with an actively shielded gradient system. Localized shimming resulted in water proton linewidths of 6.5-7.8 Hz permitting excellent water suppression. Thus, high-quality proton NMR spectra (TE = 20 ms) were acquired within measuring times of 1.5-6.4 min from 64 to 125 microL volumes-of-interest. The spectra show metabolite resonances due to N-acetyl aspartate, glutamate, creatine and phosphocreatine, cholines, taurine and inositols. The assignments of strongly spin-coupled resonances were confirmed by comparison with spectra from model solutions obtained under identical experimental conditions to those used in vivo. T1 relaxation times as well as relative metabolite concentrations were evaluated from spectra obtained for repetition times ranging from 900 to 6000 ms. Sequential acquisitions of 1.5 min spectra before, during and after killing the animals exhibited a rapid accumulation of lactate, but did not reveal significant changes in other metabolite levels for several hours post mortem.

Animals

High-resolution fast low-angle shot magnetic resonance imaging of the normal hand.

Cross-sectional magnetic resonance (MR) images of the normal hand, wrist, and fingers with an inplane resolution of 0.2-0.4 mm and a slice thickness of 1-2 mm were obtained using a 40-cm bore, 2.35-T MRI system equipped with actively shielded 50 mT m-1 gradient coils. A detailed description of the normal anatomy is given. The T1-weighted, multi-slice, fast low-angle shot (FLASH) MR images presented show a substantial improvement in resolution as compared with earlier reports. Typical investigational times of about 15 min offer a fast scan protocol that is suitable for routine clinical applications. The study further demonstrates the potential of dedicated magnets to facilitate and refine diagnostic MR imaging of hand injuries and hand-related diseases.

Adult

Multiple sclerosis in childhood: report of 15 cases.

We report the preliminary results of an ongoing study of multiple sclerosis (MS) in childhood. The investigations include an analysis of the clinical picture and course. Multiple sclerosis in early childhood may present atypically, with a symptomatology suggesting diffuse encephalomyelitis, meningeal reaction, brain oedema, seizures, impaired consciousness and in some cases take a lethal course. Imaging studies including MRI and MR-spectroscopy, CSF-analysis, electrophysiology (VEP, BAEP, SER), and virological and immunological investigations are performed. So far 15 children have been studied. Their age at the onset of the disease ranged from 3 to 15 years. Abnormal CSF-findings with pleocytosis and oligoclonal IgG bands were present in 11 and 10 out of 15 patients respectively. MRI revealed numerous white matter lesions in the brain stem and cerebral hemispheres. VEP, BAEP and SER's were abnormal in most children. Proton magnetic resonance spectra from plaques exhibited a 50-80% decrease in N-acetyl aspartate, which is a potential marker of vital neuronal tissue, a decrease of the creatine pool and an increase of choline-containing compounds. Lactate was not increased. Our observations of MS in early childhood cast doubt on some of the previous notions concerning a latency period of several years between the exposure to a still unknown agent and the manifestation of MS. In view of atypical features in the initial phase, it would seem desirable to record cases of encephalomyelitis of undetermined origin as potential cases of MS and to register the further course for verification or exclusion.

Adolescent

An approach to the functional analysis of lecithin-cholesterol acyltransferase. Activation by recombinant normal and mutagenized apolipoprotein AI.

Apolipoprotein AI (apo AI) of human serum high-density lipoprotein functions as an activator of lecithin-cholesterol acyltransferase (LCAT) and therefore plays an important role in reversed cholesterol transport. The mechanism of the acyltransfer, the activating polypeptide domains of apo AI and the active site of LCAT in this transesterification are not yet known. Synthetic peptides of the apo AI sequence have been designed to determine the activating structure, but did not yet lead to conclusive results. This also applies to spontaneous apo AI mutants. We therefore used the method of site-directed mutagenesis of apo AI cDNAs using the overlap extension approach by the polymerase chain reaction. These constructs were cloned into the procaryotic vector pET8c and expressed under the inducible T7 promoter. The engineered apo AI polypeptides were isolated and purified by affinity chromatography and assayed for their activator activity. The essentials of this approach to the structure and function of activators in general have successfully been exemplified for the LCAT activation by engineering apo AI mutant polypeptides a) by the deletion of two adjacent amphipathic helices (amino acid residues 146-186) and b) by introducing a point mutation (Glu111----Gln).

Amino Acid Sequence

[Localized proton MR spectroscopy. A non-invasive insight into brain metabolism].

Recent progress in image-controlled, localized proton MR spectroscopy offers a non-invasive means of gaining unique insights into brain metabolism in man. Combined studies with MR imaging can be performed within about 1 h. Results obtained in healthy subjects provide the basis for reliable identification and quantification of metabolite concentrations in the CNS and allow determination of their regional variability and age dependence. Clinical applications include infarcts, tumors, and neurodegenerative diseases, and also metabolic disturbances resulting from diseases of the internal organs, such as diabetes mellitus or liver cirrhosis.

Adolescent

0.3-second FLASH MRI of the human heart.

Flow-suppressed FLASH MR images of the human heart have been recorded within a measuring time of 0.3 s using a 2.0-T whole-body research system (Siemens Magnetom) equipped with a conventional 10 mT m-1 gradient system. Subsecond imaging times have been achieved by reducing the repetition time to TR = 4.8 ms and by lowering the spatial resolution to 64 X 128 measured data points. The flip angle of the slice-selective radiofrequency (rf) pulses was adjusted to 10 degrees. Cardiac chambers, ventricular walls, and valves are well delineated in images from a single cardiac cycle using a field of 250 mm and a slice thickness of 8 mm. No motion artifacts were observed as a consequence of the short echo time of TE = 2.8 ms. Distinction between flowing blood and solid structures has been achieved by spatial presaturation of adjacent slices using two slice-selective 90 degrees rf pulses preceding the entire imaging sequence.

Heart

Advances in cardiac applications of subsecond flash MRI.

Flow-suppressed, subsecond FLASH MR images of the normal human heart have been obtained from single cardiac cycles using a 2.0-T whole-body MRI/MRS system (Siemens Magnetom) equipped with conventional 10 mT m-1 gradients. The present results demonstrate further technical improvements as compared to a previous report on the same subject (Magn. Reson. Med. 13:150-157; 1990). Measuring times of 139 msec and 209 msec were achieved by reducing the repetition time to TR = 4.36 msec (TE = 2.8 msec) and the spatial resolution to 32 x 128 or 48 x 128 measured data points, respectively. The flip angle was optimized to 12 degrees. Spatial pre-saturation of 60 mm thick sections adjacent to the imaging plane resulted in a suppression of the blood signal and a clear delineation of the myocardium. Oblique rotation of the imaging slice provides convenient access to the anatomical long axis and short axis views of the heart. EKG-triggered images from separate heartbeats but at different cardiac phases demonstrate that the effective time resolution is considerably less than the actual imaging time.

Electrocardiography