PubMed Health⌕ Search

Biomedical subjects

S Blüml

Publications and source records attributed to S Blüml.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization.

PURPOSE: Our aims were to evaluate the metabolic profiles of pediatric brain tumors with short echo time (TE) MR spectroscopy and absolute quantitation of metabolite concentrations (in mmol/kg of tissue) and to describe metabolic features that distinguish individual tumor types and that may help to improve preoperative diagnosis of specific tumors. METHODS: MR imaging examinations of 60 patients with untreated brain tumors (14 medulloblastomas, 5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was performed and absolute metabolite concentrations were determined by using fully automated quantitation. RESULTS: Taurine (Tau) was significantly elevated in medulloblastomas (P < .00001) compared with all other tumors pooled (All Other). Tau was also observed consistently, at lower concentration, in pineal germinomas. Creatine (Cr) was significantly reduced in pilocytic astrocytomas, distinguishing them from All Other (P < .000001). The MR spectra of choroid plexus papillomas exhibited low Cr (P < .01) concentrations; however, myoinositol was elevated (P < .01) and total choline (tCho) (P < .0001) was reduced relative to All Other. Choroid plexus carcinomas had low Cr (P < .01 versus All Other) and the lowest Cr/tCho ratio (P < .0001 versus All Other) among all tumors studied. Guanidinoacetate was reduced in low-grade astrocytomas and anaplastic astrocytomas (P < .00001) versus All Other, whereas ependymoma and anaplastic ependymomas exhibited particularly low N-acetylaspartate (P < .00001 versus All Other). CONCLUSION: Quantitative proton MR spectroscopy reveals features of pediatric brain tumors that are likely to improve preoperative diagnoses.

Adolescent↗
PubMed2005

Oligotide, a defibrotide derivative, protects human microvascular endothelial cells against fludarabine-induced activation, damage and allogenicity.

Fludarabine is a nonmyeloablative immunosuppressant increasingly used as a component of alternative reduced-intensity conditioning regimens prior to allogeneic stem cell transplantation (SCT). However, we have previously shown that 2-fluoroadenine 9-beta-D-arabinofuranoside (F-Ara) as the active metabolized form of fludarabine induces damage, activation and allogenicity in human microvascular endothelial cells (HMEC). We had also identified the pharmaceutic compound Defibrotide (DF), originally used in the treatment of veno-occlusive disease and thrombotic microangiopathy, as being protective against F-Ara-induced dysfunction of HMEC, importantly, without affecting the antileukemic effect of F-Ara. In the present report, we show that a recently developed derivative of DF, Oligotide, similarly downregulates F-Ara-induced activation and damage of HMEC as well as their antigenicity for allogeneic CD8+ T cells. In addition, Oligotide could also block F-Ara-mediated transendothelial migration of peripheral blood cells across the HMEC barrier. Taken together, these observations argue for a potential clinical use of both DF and Oligotide in pre transplant conditioning.

Antineoplastic Agents↗
PubMed2003

Membrane phospholipids and high-energy metabolites in childhood ataxia with CNS hypomyelination.

BACKGROUND: Childhood ataxia with CNS hypomyelination (CACH) is a leukodystrophy with extreme rarefaction of white matter caused by mutations in one of the five subunits of the translation initiation factor 2B (eIF2B). METHODS: Seven children with this disease and nine age-matched control subjects were studied with proton-decoupled phosphorus magnetic resonance (MR) spectroscopy. RESULTS: In patients with CACH, cerebral concentrations of high-energy phosphate metabolites were abnormal. Of the metabolites involved in biosynthesis and catabolism of membrane phospholipids, glycerophosphorylethanolamine was reduced (0.24 +/- 0.18 mmol/kg brain vs 0.44 +/- 0.14; p < 0.02), and phosphorylethanolamine was increased (2.32 +/- 0.53 vs 1.53 +/- 0.22; p < 0.01), whereas the choline-containing phosphorylated metabolites were unchanged. Nucleoside triphosphate (NTP) was reduced (2.44 +/- 0.34 mmol/kg brain tissue vs 3.09 +/- 0.58; p < 0.01), phosphocreatine was elevated (4.11 +/- 0.63 vs 3.27 +/- 0.33; p < 0.01), and inorganic phosphate was reduced (0.77 +/- 0.32 vs 1.06 +/- 0.26; p < 0.05). Intracellular pH was elevated in patients (7.03 +/- 0.04 vs 6.99 +/- 0.02; p < 0.02). CONCLUSIONS: The authors found an altered energy state of the residual cell population investigated. Together with previously identified replacement of white matter by CSF, the present findings raise the possibility that the genetic defect in eIF2B may result in impairment of myelin membrane synthesis or myelin membrane transport in the in vivo CACH brain. Ethanolamine metabolites constitute the plasmalogens, and the present findings may include a defect in plasmalogen metabolism.

Adolescent↗
PubMed2002

Tricarboxylic acid cycle of glia in the in vivo human brain.

In the brain, acetate is exclusively oxidized by glia. To determine the contribution of glial metabolism to the tricarboxylic acid cycle (TCA), 1-(13)C-acetate was infused in six studies in three normal adult subjects and -one epileptic receiving valproic acid for seizure control. Ten grams of 99% 1-(13)C labeled acetate were infused intravenously as a 3.3% w/v solution over 60 min, during which in vivo 13C MR spectra of the brain were acquired. As expected, 13C label rapidly enriched cerebral bicarbonate, glutamate and glutamine C5. The mean rate of acetate oxidation calculated from steady-state 13C enrichment of bicarbonate in fasted normal subjects was 0.13 +/- 0.03 micromol/g/min (n=4), approximately 20% of the total cerebral TCA cycle rate.

Acetates↗
PubMed2001

[1-13C]glucose MRS in chronic hepatic encephalopathy in man.

[1-13C]-labeled glucose was infused intravenously in a single dose of 0.2 g/kg body weight over 15 min in six patients with chronic hepatic encephalopathy, and three controls. Serial 13C MR spectra of the brain were acquired. Patients exhibited the following characteristics relative to normal controls: 1) Cerebral glutamine concentration was increased (12.6 +/- 3.8 vs. 6.5 +/- 1.9 mmol/kg, P < 0.006) and glutamate was reduced (8.2 +/- 1.0 vs. 9.9 +/- 0.6 mmol/kg, P < 0.02). 2) 13C incorporation into glutamate C4 and C2 positions was reduced in patients (80 min after start of infusion C4: 0.43 +/- 0.09 vs. 0.84 +/- 0.15 mmol/kg, P < 0.001; C2: 0.20 +/- 0.03 vs. 0.45 +/- 0.07 mmol/kg, P < 0.0001). 3) 13C incorporation into bicarbonate was delayed (90 +/- 21 vs. 40 +/- 10 min, P < 0.003), and the time interval between detection of glutamate C4 and C2 labeling was longer in patients (22 +/- 8 vs. 12 +/- 3 min, P < 0.03). 4) Glutamate C2 turnover time was reduced in chronic hepatic encephalopathy (17.1 +/- 6.8 vs. 49.6 +/- 8.7 min, P < 0.0002). 5) 13C accumulation into glutamine C2 relative to its substrate glutamate C2 increased progressively with the severity of clinical symptoms (r = 0.96, P < 0.01). These data indicate disturbed neurotransmitter glutamate/glutamine cycling and reduced glucose oxidation in chronic hepatic encephalopathy. [1-13C] glucose MRS provides novel insights into disease progression and the pathophysiology of chronic hepatic encephalopathy.

Aged↗
PubMed2001

Alternative 1-(13)C glucose infusion protocols for clinical (13)C MRS examinations of the brain.

Clinical utility of (13)C MRS is limited by cost and long examination times. Three 1-(13)C glucose infusion protocols-a high-dose i.v., low-dose i.v., and oral administration of 1-(13)C glucose-were compared on a GE 1.5T MR scanner. Resolution and sensitivity were sufficient to identify (13)C glucose (1alpha and 1beta), glutamate (C1-C4), glutamine (C1-C4), aspartate (C2 and C3), lactate, alanine, and bicarbonate in brain spectra. The three protocols were efficacious, as measured by cerebral enrichment of 1-(13)C glucose (62%, 42%, and 38%) and its principal metabolite, 4-(13)C glutamate (13%, 11%, and 16%), respectively. Intravenous infusion of 1-(13)C glucose 0.23 g/kg body weight (low dose) provides equivalent information at one third the cost of previous regimes. Magn Reson Med 46:39-48, 2001.

Administration, Oral↗
PubMed2001

1-(13)C glucose magnetic resonance spectroscopy of pediatric and adult brain disorders.

With protocols designed for use in a clinical environment we investigated the feasibility and diagnostic potential of (13)C MRS after 1-(13)C labeled glucose infusion. (13)C MRS brain examinations were performed in 27 subjects (17 children and pediatric patients, six adult patients, and four adult controls), using a standard 1.5 T clinical MR scanner. 1-(13)C glucose, 99% enriched (20% w/v) was administered intravenously (690 or 210 mg/kg body weight) or orally (730 mg/kg). Cerebral (13)C-enrichment patterns and time courses were compared. 1-(13)C glucose appeared in brain spectra within 2.5-15 min, with ensuing enrichment of its metabolites. No complications were encountered. When data obtained in patients were compared with controls, striking abnormalities in hepatic encephalopathy and in premature brain were observed, consistent with reduced cerebral glucose metabolism. Abnormalities in the (13)C enrichment pattern were also observed in pediatric patients with leukodystrophies and mitochondrial disorders. In this preliminary survey, we conclude that (13)C MRS in combination with glucose infusion is safe and efficient and provides new insights into the pathophysiology of brain disorders.

Adolescent↗
PubMed2001

Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by (13)C MRS and [1-(13)C]glucose infusion.

A non-invasive (13)C magnetic resonance spectroscopy (MRS) technique is described for the determination of the N-acetyl-L-aspartate (NAA) synthesis rate, V(NAA), in the human brain in vivo. In controls, the mean V(NAA) was 9.2 +/- 3.9 nmol/min/g. In Canavan disease, where [NAA] is increased (p < 0.001) and [aspartate] is deceased (p < 0.001), V(NAA) was significantly reduced to 3.6 +/- 0.1 nmol/min/g (p < 0.001). These rates are in close agreement with the activity of the biosynthetic enzyme measured in vitro in animals, and with the rate of urinary excretion of NAA in human subjects with Canavan disease. The present result is consistent with the regulation of NAA synthesis by the activity of a single enzyme, L-aspartate-N-acetyltransferase, in vivo, and with its control in Canavan disease by limited substrate supply and/or product inhibition. The (13)C MRS technique provides the means for further determination of abnormal rates of neuronal NAA synthesis among neurological disorders in which low cerebral [NAA] has been identified.

Adult↗
PubMed2000

Novel peak assignments of in vivo (13)C MRS in human brain at 1.5 T.

(13)C MRS studies at natural abundance and after intravenous 1-(13)C glucose infusion were performed on a 1.5-T clinical scanner in four subjects. Localization to the occipital cortex was achieved by a surface coil. In natural abundance spectra glucose C(3beta,5beta), myo-inositol, glutamate C(1,2,5), glutamine C(1,2,5), N-acetyl-aspartate C(1-4,C=O), creatine CH(2), CH(3), and C(C=N), taurine C(2,3), bicarbonate HCO(-)(3) were identified. After glucose infusion (13)C enrichment of glucose C(1alpha,1beta), glutamate C(1-4), glutamine C(1-4), aspartate C(2,3), N-acetyl-aspartate C(2,3), lactate C(3), alanine C(3), and HCO(-)(3) were observed. The observation of (13)C enrichment of resonances resonating at >150 ppm is an extension of previously published studies and will provide a more precise determination of metabolic rates and substrate decarboxylation in human brain.

Adult↗
PubMed1999

In vivo magnetic resonance spectroscopy of human fetal neural transplants.

To better define the survival and cellular composition of human fetal neurotransplants in vivo, we performed quantitative 1H MRS to determine the concentration of the neuronal amino acid [N-acetylaspartate] within MRI-visible grafts. In all, 71 grafts in 38 patients [24 Parkinson's disease (PD), 14 Huntington's disease (HD)] were examined, as well as 24 untreated PD and HD patients and 13 age-matched normal controls. MRI appearances of edema were present in three out of 71 grafts, the remainder being consistent with histologically identified viable neural transplant tissue. N-acetylaspartate (NAA), creatine, choline, myoinositol and glutamine plus glutamate (Glx) were identified in all post-transplant putamens, with abnormal metabolites, lactate and/or lipid detectable in only three patients. Of 71 grafts, 19 occupied more than 60% of the MRS-examined volume (VOI) (mean 84.2 +/- 3%; range 61-100%). In those, [NAA] was 8.50 +/- 0.99 mM in eight PD spectra and 6.59 +/- 0.81 mM in 11 HD spectra, and was not significantly different from controls. In contrast, transplanted fetal neurones contain less than 0.4 mM of the neuronal amino acid NAA. This suggests that established fetal neurotransplants in the human putamen of both PD and HD patients are populated by adult neurones, axons and dendrites.

Adult↗
PubMed1999

Developmental changes in choline- and ethanolamine-containing compounds measured with proton-decoupled (31)P MRS in in vivo human brain.

Cerebral phosphorylated metabolites, possibly involved in membrane and myelin sheath metabolism, were measured and quantified using proton-decoupled (31)P ({(1)H}-(31)P) MRS in 32 children and 28 adults. Age-dependent changes were determined for phosphorylethanolamine (PE), phosphorylcholine (PC), glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), and phosphocreatine (PCr) concentrations. In the neonate, PE dominates the spectrum and decreases with age along with PC, whereas GPE, GPC, and PCr increase in concentration with postnatal age. PE (1.23 +/- 0.13 mM) and GPE (0.57 +/- 0.08 mM) co-resonate with choline in (1)H MRS. Together with PC (0.57 +/- 0.12 mM) and GPC (0. 94 +/- 0.13 mM) these four metabolites accounted for all of the visible (1)H MRS choline in normal adult brain. Children with diseases that affect myelination were found to have abnormal ¿(1)H¿-(31)P MRS. The new quantitative assay may provide novel insights in determining and monitoring normal and abnormal brain maturation noninvasively. Magn Reson Med 42:643-654, 1999.

Adolescent↗
PubMed1999

Activation of neurotransplants in humans.

Clinical studies report symptomatic benefit in most fetal neurotransplantation treated Parkinson's disease patients. The underlying mechanism is incompletely explained. We investigated whether neural connections between host and transplanted tissue are established. Two Parkinson's disease patients with clinically excellent outcome after transplantation were studied with functional magnetic resonance imaging. A repetitive motor task that provided robust stimulation in the contralateral putamen in volunteers activated graft bearing regions of putamen in patients. In response to contralateral motor tasks, activation was recorded consistently in left putamen in patient 1 and in right putamen in patient 2. Functional magnetic resonance imaging suggests that neuronal rewiring contributes to the functioning of neurotransplants in vivo in humans.

Adult↗
PubMed1999

In vivo quantitation of cerebral metabolite concentrations using natural abundance 13C MRS at 1.5 T.

A method for the quantitation of cerebral metabolites on a clinical MR scanner by natural abundance 13C MRS in vivo is described. Proton-decoupled spectra were acquired with a power deposition within FDA guidelines using a novel coil design. myo-Inositol, quantified by a separate proton MRS, and readily detectable in 13C MRS, was used as an internal reference. Normal concentrations, measured in four control subjects, age 7 months to 12 years, were glutamate 9.9 +/- 0.7, glutamine 5.6 +/- 1.0, and NAA 8.8 +/- 2.8 mmol/kg. In a patient diagnosed with Canavan disease, examined four times, glutamate was reduced to 46% of normal, 4.6 +/- 0.5 mmol/kg. NAA was increased by 50% to 13.2 +/- 1.6 mmol/kg in 13C MRS, consistent with the 41% increase to 12.3 +/- 1.1 from control 8.7 +/- 1.1 mmol/kg assayed by 1H MRS. Limited concentration of glutamate may impact on glutamatergic neurons and excitatory neurotransmission in Canavan disease. Quantitation of cerebral glutamate in human brain may have clinical value in human neuropathologies in which glutamate is believed to play a central role.

Aspartic Acid↗
PubMed1997

Quantitative magnetic resonance imaging and neuropsychological functions in dementia of the Alzheimer type.

BACKGROUND: The aim of the present study was to investigate neuropsychological functions in dementia of the Alzheimer type (DAT) with respect to morphological changes that were revealed by quantitative magnetic resonance imaging (MRI). METHODS: Twenty patients with DAT (NINCDS-ADRDA criteria) and 10 healthy age and sex matched controls were included. The neuropsychological function was evaluated on a test battery covering the severity of dementia, verbal and visual memory, concentration and attention, language skills and general intelligence as well as activities of daily living. 3D MRI sequences were acquired using a 1.5 T Siemens MAGNETOM. Whole brain volume, total intracranial volume (TIV), volume of the frontal and temporal lobes and volumes of the amygdalahippocampus complex (AHC) were assessed using the newly developed software NMR Win. RESULTS: Apart from TIV all morphometric parameters differed significantly between the diagnostic groups. AHC volumes discriminated best between the groups, with only a small overlap. AHC atrophy exceeded generalized atrophy. These findings were confirmed when the data were reanalysed after dividing the DAT patients into a mildly and moderately affected group. The severity of dementia was significantly correlated with the volumes of the AHC and the volumes of the temporal lobes bilaterally, but not with the whole brain volume and the volumes of the frontal lobes. CONCLUSIONS: These results underline the important role of the temporal substructures for aetiology and progression of DAT. They indicate that the volume of the AHC can be monitored by MRI and may be used to follow up the disease process.

Aged↗
PubMed1996

A comparison of magnetization prepared 3D gradient-echo (MP-RAGE) sequences for imaging of intracranial lesions.

In a pilot study including 64 patients with different types of brain tumors we investigated four types of MP-RAGE sequences. The sequences differ in the length of the recovery period and the data acquisition mode (sequential vs. centric phase-encoding). The sequence with sequential encoding and a short recovery period provided images that reached the quality and reliability of spin-echo images. The other MP-RAGE sequences failed in providing equivalent information. In particular, a considerable number of small lesions identified in spin-echo images were not detected in MP-RAGE images. The impact of the evolving magnetization on the point spread function was analyzed by performing simulation calculations. It was found that lesions with short T1 times are rendered with low spatial resolution when sequence parameters are not set appropriately. The low overall quality of images obtained by sequences applying centric encoding may be explained by eddy current effects as reported in other recently published studies.

Brain Neoplasms↗
PubMed1996

Proton magnetic resonance spectroscopy: the new gold standard for diagnosis of clinical and subclinical hepatic encephalopathy?

Human hepatic encephalopathy (HE) is identified by a new noninvasive test, proton magnetic resonance spectroscopy (1H MRS) applied to the brain in a few minutes. Chemical changes identified by 1H MRS are elevated glutamine, decreased choline and decreased myoinositol. The specific association with HE is proven by clinical studies in patients with cirrhosis, overt and subclinical HE, by the appearance of the same changes after transjugular intrahepatic portasystemic shunt, and by their complete reversal by liver transplantation. The importance of the new marker, myoinositol, may lie in its role as an osmolyte regulating cell volume in the astrocytes. Other roles are also postulated. Progress in the management of both HE and subclinical hepatic encephalopathy may depend upon finding means, short of liver transplantation, which will restore cerebral choline and myoinositol. The finding of identical changes in experimental animals simplifies the search.

Animals↗
PubMed1996

[Quantitative magnetic resonance tomography and the severity of deficits in dementia of the Alzheimer type].

The aim of the present study was to investigate the severity of dementia of the Alzheimer type (DAT) with respect to morphological changes revealed by quantitative magnetic resonance imaging (MRI). Seventeen patients with DAT (NINCDS-ADRDA guidelines) and 10 healthy elderly controls were included. The severity of dementia was evaluated on the Mini Mental State Examination (MMSE), the Global Deterioration Scale (GDS) and the Brief Cognitive Rating Scale (BCRS). Three-dimensional MRI sequences were acquired using a 1.5-T Siemens Magnetom. Whole-brain volume and the volume of the amygdala-hippocampus complex (AHC) were assessed using the newly developed software NMRWin. This software provides a semi-automated measure of the whole brain volume, while measurement of substructures requires manual guidance. In addition, the ventricle-brain ratio (VBR) was assessed. All morphometric parameters differed significantly between the two groups. AHC volumes discriminated best between them with only a small overlap. These findings were confirmed when only the data of the mildly demented patients were included in the analysis. The degree of AHC atrophy exceeded that of generalized cerebral atrophy. The severity of dementia as indicated by the MMSE, GDS and BCRS scores was correlated significantly with the volumes of the AHC bilaterally, but not with whole-brain volume or with VBR. These results underline the importance of the mesial temporal substructures in the etiology and progression of DAT and indicate that the volume of the AHC can be monitored by MRI and may be used to follow up the disease process.

Aged↗