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H E Möller

Publications and source records attributed to H E Möller.

34 records · Page 2Linked to original sources

MR microscopy of lung airways with hyperpolarized 3He.

A technique using hyperpolarized (HP) 3He to image the small airways of the lung by using moderate flip angles and a short scanning period during early inspiration is demonstrated. Flip angles (alpha) ranging from 10-90 degrees were used in guinea pig experiments with scanning during the entire inspiration period. A second series acquired data throughout a short window of the ventilatory cycle with alpha = 45 degrees. The success of the animal studies has motivated implementation of similar imaging techniques in the clinical arena. Human studies involved imaging over the total inspiration period with alpha approximately 10 degrees. The first series of guinea pig experiments demonstrated that larger flip angles (50-90 degrees) destroy the magnetization before it reaches the smaller airways. At moderate flip angles (20-40 degrees), airway branching down to the fourth generation was apparent. Fifth-order branchings were seen in the images of the second series. The trachea down to fourth generation pulmonary airway branching, along with some distal air spaces, was seen in the human lung images.

Animals↗

Localized proton NMR spectroscopy in the striatum of patients with idiopathic spasmodic torticollis.

Single voxel proton spectroscopy was used to study brain metabolism in idiopathic spasmodic torticollis. Peak metabolite ratios in long echo time (135 ms) spectra were evaluated in the basal ganglia of 16 patients (29-65 years). Eight of them were untreated; the other eight were examined 4-6 weeks after administration of botulinum toxin type A. As compared with 60 control spectra, patients showed a significant, therapy-resistant decrease in N-acetyl-L-aspartate (NAA)/choline (Cho). NAA/creatine (Cr) and Cho/Cr were close to normal in the post-treatment group but significantly reduced in untreated patients. This result is consistent with the hypothesis that striatal Cr is reversibly elevated in chronic muscle stimulation. The right and left striatum were affected to the same extent.

Aspartic Acid↗

Hyperpolarized 3He NMR lineshape measurements in the live guinea pig lung.

Spatially localized lineshapes of hyperpolarized (HP) 3He in guinea pig lungs have been measured in vivo. Three different axial slice locations, each containing different compositions of airway sizes and orientations, were studied. Gas peaks from major bronchi (2 ppm) and alveoli (-2 ppm) were distinguished. The gas phase spectra show structural features that are a result of frequency shifts caused by bulk magnetic susceptibility. For a given slice, the spectral lineshapes reflect the airway composition within the slice location, according to theory. The peak assignments given here also agree with previous studies done by Wagshul et al. with HP 129Xe. At each of the slice locations, data were acquired during two phases of the breathing cycle, resulting in a relative frequency shift of approximately 0.3 ppm in the superior slices. Spectra obtained over a number of breaths show the dynamics of the gas buildup in the lung and provide further evidence supporting the peak assignments.

Animals↗

Signal dynamics in magnetic resonance imaging of the lung with hyperpolarized noble gases.

The nonequilibrium bulk magnetic moment of hyperpolarized (HP) noble gases generated by optical pumping has unique characteristics. Based on the Bloch equations, a model was developed describing the signal dynamics of HP gases used in magnetic resonance imaging (MRI) of the lung with special consideration to the breathing cycle. Experimental verification included extensive investigations with HP 3He and 129Xe during both inspiration and held breath in live guinea pigs. Radial acquisition was used to investigate the view variations with a temporal resolution of 5 ms. Agreement between theoretical predictions and in vivo results was excellent. Additionally, information about effects from noble gas diffusion and spin-lattice relaxation was obtained. In vivo results for T1 were 28.8 +/- 1.8 s for 3He and 31.3 +/- 1.8 s for 129Xe. Comparison with in vitro data indicated that relaxation in the pulmonary gas space is dominated by dipolar coupling with molecular oxygen. The results provide a quantitative basis for optimizing pulse sequence design in HP gas MRI of the lung.

Animals↗

Blood-brain barrier phenylalanine transport and individual vulnerability in phenylketonuria.

In vivo nuclear magnetic resonance spectroscopy can be used to measure intracerebral phenylalanine (Phe) concentrations in patients with phenylketonuria (PKU). Stationary levels, obtained under free nutrition, as well as time courses after an oral Phe load (100 mg/kg) were investigated in 11 PKU patients and were correlated with the individual clinical outcome. At blood levels around 1.2 mmol/L, brain Phe was 0.41 to 0.73 mmol/L in clinically "typical" patients, but less than 0.15 mmol/L in three untreated, normally intelligent, adult women. Kinetic investigations revealed higher transport Michaelis constants and lower ratios of the brain influx and consumption rates in these women than in the "typical" control patients (Kt,app = 0.45 to 1.10 mmol/L versus 0.10 mmol/L; T(max)/v(met) = 2.55 to 3.19 versus 7.8 to 14.0). Such variations seem to be major causative factors for the individual vulnerability to PKU.

Adolescent↗

Kinetics of phenylalanine transport at the human blood-brain barrier investigated in vivo.

In vivo proton magnetic resonance spectroscopy was used to investigate intracerebral phenylalanine (Phe) concentrations in nine patients with classical phenylketonuria (PKU). The study included serial examinations (n = 31; plasma Phe levels: 0.47-2.24 mmol/l) of patients either receiving a Phe-restricted diet (200 mg Phe per day; four patients) or a diet rich in Phe (1000 mg Phe per day; three patients). No spectrum showed metabolic abnormalities besides elevated Phe. Difference spectroscopy yielded intracerebral Phe concentrations between 0.20 and 0.76 mmol/l. Regional variations between parieto-occipital periventricular brain, frontal brain, and cerebellum were not statistically significant. Data could be fitted assuming saturable Phe transport into the brain, based on a symmetric Michaelis-Menten model (characterized by an apparent Michaelis transport constant, K(t,app), and a maximum transport velocity, Tmax) and constant Phe consumption in the brain cells (described by a velocity Vmax). Non-linear least-squares fitting of the combined data from all patients yielded K(t,app) = 0.16 +/- 0.11 mmol/l and (Tmax / Vmax) = 9.0 +/- 4.1. Carrier saturation and competitive inhibition of the influx of other large neutral amino acids can be expected at plasma Phe levels usually found in PKU patients.

Adolescent↗

In vivo 31P NMR spectroscopy of human musculoskeletal tumors as a measure of response to chemotherapy.

The value of in vivo 31P NMR spectroscopy to provide indicators of response to cytostatic chemotherapy was studied in patients with malignant musculoskeletal tumors. Characteristics of untreated cancers were strong signals of PME and PDE, moderately increased Pi and low PCr. The intracellular pH was slightly alkaline. The intracellular concentration of free magnesium was 70% of that in muscle. Spectroscopic findings at different times of therapy were compared with the percentage of tumor necrosis after surgical resection in 28 patients. In follow-up studies, energy-rich phosphates declined in nonresponders, while PME, Pi and frequently PDE increased. Treatment response appeared to involve the reversal of these trends. In five responders, a biphasic pattern was observed, i.e. initially the spectrum changed into that of severely ischemic cell injury followed by a successive phase of apparent 'tumor activation'. Pretreatment levels of (PCr+Pi)/total phosphate > or = 0.35 and PCr/ alpha-NTP > or = 1.5, an accelerated increase in total low-energy phosphates/total high-energy phosphates (> or = 3.0%/day) after the initial drug application, and a long-term decrease (< or = -0.4%/day) during later therapy were highly indicative of tumor response to chemotherapy. Such spectroscopic predictors for treatment response proved to be superior to currently used indices such as tumor size.

Adolescent↗

Localized proton NMR spectroscopy in the striatum of patients with idiopathic Parkinson's disease: a multicenter pilot study.

Single voxel proton MRS was used to study brain metabolism in the striatum of patients diagnosed with idiopathic Parkinson's disease (PD). Peak metabolite ratios in long echo time spectra were evaluated in 151 patient spectra and 97 age-matched control spectra collected at four participating institutions using identical hardware and clinical protocols. Combining data from all ages (27-83 years old) showed no significant difference between patient and control ratios. However, in an elderly subset of patients (51-70 years old), a significant decrease in striatal N-acetylaspartate (NAA)/choline (Cho) was observed. Also, a significant decrease in the mean NAA/Cho ratio was observed in patients versus controls for patients not being treated with Sinemet (Du Pont Pharm, Wilmington, DE) (hereafter referred to as levodopa/carbidopa). This result is consistent with the hypothesis that NAA may provide a reversible spectroscopic marker for neuronal dysfunction, although a prospective follow-up study will be needed to confirm this. Quantitation of MRS would be useful to exclude the possibility that a change in Cho levels affected the NAA/Cho ratios.

Adult↗

In vivo study of brain metabolism in galactosemia by 1H and 31P magnetic resonance spectroscopy.

In order to further evaluate different hypotheses concerning brain metabolism in galactosemia, six adult patients aged 18-29 years with classical galactosemia under dietary treatment underwent localized 1H and 31P magnetic resonance spectroscopy (MRS) in addition to conventional T1- and T2-weighted MRI. Galactose-1-phosphate levels in erythrocytes were 1.1-3.7 mg/dl, plasma concentrations of galactitol ranged from 8.4-14.2 mumol/l. Imaging revealed abnormal peripheral myelination in five and enlargement of lateral ventricles in two patients. Brain galactitol in parieto-occipital white matter was below detectability of 1H MRS leading to the assumption that brain concentrations of the free metabolite was well below 1 mmol/kg. Signal intensities of free myo-inositol, which was postulated to be indicative of changes in the second messenger pathway, were within the normal range. MRS data revealed a normal energy status of the brain. In summary 1H and 31P MRS indicated normal metabolite concentrations as compared to healthy controls.

Adolescent↗

In-vivo NMR spectroscopy in patients with phenylketonuria: changes of cerebral phenylalanine levels under dietary treatment.

Localized proton magnetic resonance spectroscopy at short echo times was used to measure phenylalanine (Phe) in parieto-occipital periventricular brain. Six treated adult patients with phenylketonuria were investigated repeatedly following reinstitution of a Phe-restricted diet. Difference spectroscopy clearly enabled the identification of elevated cerebral Phe levels by subtracting spectra obtained from healthy volunteers. Estimates of absolute brain concentrations always yielded values well below the serum levels with ratios [Phe]brain/[Phe]serum ranging from 0.27 to 0.63. A plot of [Phe]brain versus [Phe]serum could be fitted to a straight line (R = 0.90) if [Phe]serum was below 1.3 mM. Measurements at higher serum levels could only be performed in one patient and yielded brain Phe concentrations of 0.63 +/- 0.10 mM suggesting a saturation of the carrier systems. The feasibility to quantify Phe transport across the blood-brain barrier in humans non-invasively employing in-vivo proton spectroscopy can effectively improve the prognostic significance of serum data.

Adolescent↗

MR flow quantification using RACE: clinical application to the carotid arteries.

Real time MR flow quantification was performed with real time acquisition and evaluation of motion (RACE) in a rigid phantom under steady flow conditions and in the common carotid arteries of 43 subjects aged 24-78 years. Hemodynamic information included the intraluminal velocity distribution during the complete cardiac cycle, the distensibility of the arterial wall, and age-dependent changes of the flow curves. Systolic peak velocities of 51 +/- 33 cm/s and time-averaged volume flow rates of 4.3 +/- 2.0 ml/s were measured in healthy subjects. Flow rates below 3.0 ml/s and the observation of abnormal flow patterns indicated stenoses greater than 70% in the region of the bifurcation (sensitivity: 83.3%; specificity: 93.7%; accuracy: 71.4%). Improvements may be achieved from a combination with MR angiography, providing both functional and morphologic vascular information noninvasively within one observer-independent examination. MR imaging, therefore, has a strong potential for the diagnosis of critical stenoses in symptomatic patients.

Adult↗

Kinetics of metabolism in human kidney transplants measured by dynamic 31P NMR spectroscopy.

The technique of ex vivo 31P NMR spectroscopy has been used for the investigation of metabolic turnover in 15 cadaveric human kidneys obtained from brain-dead donors for transplantation. Measurements were carried out at 1.5 T time-dependently during regular hypothermic storage in histidine-tryptophan-alpha-ketoglutarate solution. The minimum delay between explanation and spectroscopy was 2 h 41 min. In one case of a discarded organ the measurements could be extended over a period of 161 h 35 min. A detailed kinetic model describing monoexponential ischemic phosphate turnover, which accounts for various interrelations of the NMR visible metabolites, has been derived. Averaged velocity constants of the decays of nucleotides and phosphomono- and -diesters ranged from 0.0047 to 0.294h-1 at approximately 4 degrees C. Intracellular pH decreased monoexponentially with an averaged velocity constant of 0.31 h-1.

Brain Death↗