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Biomedical subjects

T Ernst

Publications and source records attributed to T Ernst.

At least 55 records · Page 3Linked to original sources

Cerebral (1)H MRS alterations in recreational 3, 4-methylenedioxymethamphetamine (MDMA, "ecstasy") users.

3,4-methylenedioxymethamphetamine (MDMA) is an illicit drug that has been associated with serotonergic axonal degeneration in animals. This study evaluates neurochemical abnormalities in recreational MDMA users. Twenty-two MDMA users and 37 normal subjects were evaluated with magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS) in the mid-frontal, mid-occipital, and parietal brain regions. (1)H MRS showed normal N-acetyl (NA) compounds in all brain regions. The myo-inositol (MI) concentration (+16.3%, P = 0.04) and the MI to creatine (CR) ratio (+14.1%, P = 0. 01) were increased in the parietal white matter of MDMA users. The cumulative lifetime MDMA dose showed significant effects on [MI] in the parietal white matter and the occipital cortex. The normal NA concentration suggests a lack of significant neuronal injury in recreational MDMA users. However, the usage-related increase in MI suggests that exposure to MDMA, even at recreational doses, may cause increased glial content. J. Magn. Reson. Imaging 1999;10:521-526.

Adult↗

Comparison of static and dynamic MRI techniques for the measurement of regional cerebral blood volume.

Two different acquisition and processing strategies to determine the regional cerebral blood volume (rCBV) with magnetic resonance imaging (MRI) are compared. The first method is based on the acquisition of the signal time course during a bolus administration of a contrast agent (dynamic method). The second method evaluates signal changes before and after the contrast agent injection (static method), assuming the contrast agent remains primarily intravascular in the brain after the first pass. Both methods were applied to the same data sets, acquired with either echoplanar imaging (EPI, n = 18) or fast low-angle shot (FLASH, n = 28) techniques. A voxel-by-voxel correlation between the static and dynamic method yielded a correlation coefficient of 0.76 +/- 0.06 for the EPI and 0.71 +/- 0.10 for the FLASH measurements. The static method was less sensitive and showed higher standard deviations for rCBV than the dynamic method. With the development of truly intravascular contrast agents, the static perfusion MRI method, which can be performed with higher signal-to-noise ratio and higher spatial resolution, may become an alternative to ultra-fast MRI for measuring rCBV.

Brain↗

Simultaneous correction for interscan patient motion and geometric distortions in echoplanar imaging.

A method is presented for simultaneous correction of linear geometric distortions and interscan patient motion in echoplanar imaging (EPI). The technique does not require the acquisition of specialized scans other than high-resolution magnetic resonance images. The method is based on a generalized surface-based coregistration algorithm, which accounts for a complete 3-dimensional affine transformation, i.e., rotations, translations, scaling, and shearing, between two volumetric image data sets. Any minimally distorted high-resolution scan may serve as a reference data set, to which the EPI data set is matched. The algorithmic accuracy was assessed using simulated data sets with known affine distortions. The deviation of the parameters determined by the coregistration program from the true values typically was 1% or less. Precise alignment of functional and anatomic information will be important for many future clinical applications.

Algorithms↗

Correlation of regional cerebral blood flow from perfusion MRI and spect in normal subjects.

The objective of this study was to determine the relationship in regional cerebral blood flow (rCBF) as measured with perfusion magnetic resonance imaging (pMRI) and single photon emission computer tomography (SPECT). rCBF was determined in 26 healthy subjects with pMRI and SPECT. After co-registration of pMRI with SPECT, rCBF was determined in 10 brain regions relative to the whole slice value. pMRI was evaluated with and without elimination of large vessels. rCBF from pMRI correlates significantly with rCBF from SPECT (r = 0.69 with and r = 0.59 without elimination of large vessels; p < 0.0001 for both). Elimination of large vessels reduced the interindividual variance of the pMRI measurements in most regions. rCBF from pMRI shows good correlation with rCBF from SPECT. Because pMRI is sensitive to flow in large vessels while SPECT is not, elimination of large vessels in pMRI reduces the interindividual variability of pMRI and improves the-correlation between the two methods. pMRI is a reliable noninvasive method for rCBF measurements.

Adult↗

Progressive multifocal leukoencephalopathy and human immunodeficiency virus-associated white matter lesions in AIDS: magnetization transfer MR imaging.

PURPOSE: To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)-associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. RESULTS: Compared with normal-appearing white matter (magnetization transfer ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesion as small as 0.5 cm2. CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.

AIDS Dementia Complex↗

Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users.

OBJECTIVE: Previous studies found functional changes in the frontal brain region and regions with projections to the frontal lobe in cocaine users. The aim of this study was to investigate persistent neurochemical changes in the frontal lobes of subjects with a history of crack cocaine dependence and to determine whether these changes are different in male and female users. METHOD: The frontal gray and white matter of 64 young asymptomatic and abstinent (> 5 months) cocaine users (34 male and 30 female) and 58 healthy comparison subjects without a history of drug abuse was evaluated with localized proton magnetic resonance spectroscopy (1H-MRS). RESULTS: Two-way analysis of variance showed significant cocaine effects on the concentration of frontal gray matter N-acetyl compounds, on the ratio of frontal white matter N-acetyl compounds to creatine levels, on frontal gray and white matter myoinositol levels, and on the ratio of myoinositol to creatine. Significant gender effects were observed for frontal gray matter choline-containing compounds, the ratio of choline-containing compounds to creatine, and the percentage of CSF in both gray and white matter. Interaction effects of cocaine and gender were observed for creatine, N-acetyl/creatine ratio, and myoinositol/creatine ratio in frontal white matter. CONCLUSIONS: Cocaine use is associated with neuronal injury (with decreased N-acetyl compounds) in the frontal cortex and glial activation (with increased myoinositol) in both frontal gray and white matter. In the frontal lobe, cocaine affects male users differently than female users. Future studies on the effects of cocaine abuse should control for the effects of gender-specific neurotoxicity.

Adult↗

Proton spectroscopy in myotonic dystrophy: correlations with CTG repeats.

OBJECTIVES: To seek cerebral metabolite abnormalities in patients with myotonic dystrophy and to determine whether the degree of cerebral abnormalities (measured by proton magnetic resonance spectroscopy) correlates with severity of the genetic defect (measured by trinucleotide repeats). DESIGN: Fourteen patients with myotonic dystrophy were compared with 24 healthy control subjects. SETTING: A university-affiliated medical center. RESULTS: Compared with healthy subjects, patients with myotonic dystrophy had elevated levels of myoinositol (+19% in the occipital region and +12.9% in the temporoparietal region), total creatine (+7.6% and +6.8%), and choline-containing compounds (+21% and +7.7%). Furthermore, the creatine and myoinositol peak areas correlated with the number of trinucleotide cytosine-thymine-guanine(n) (CTG)n repeats from leukocytes, especially in the temporoparietal brain region (r=0.76; P=.004). CONCLUSIONS: Neurochemical alterations observed with proton magnetic resonance spectroscopy are proportional to the cytosine-thymine-guanine repeat size. Increases in myoinositol and creatine concentrations may be caused by increased glial content, while elevated levels of choline-containing compounds are most likely caused by increased glial content and cell membrane abnormalities. Proton magnetic resonance spectroscopy is a powerful noninvasive tool to study brain biochemistry, which may reflect the extent of neuropathological involvement in patients with myotonic dystrophy.

Adult↗

Physiologic MRI of a tumefactive multiple sclerosis lesion.

Structural and physiologic MRI were performed after subacute onset of left hemiparesis in a patient with MS. MRI showed a large ring-enhancing lesion with surrounding edema and mass effect; differential diagnosis included a neoplasm or a large MS plaque. Physiologic MRI showed reduced blood flow and magnetization transfer, as well as increased diffusion, in the large lesion. Because these findings suggested a tumefactive MS plaque rather than a neoplasm, the patient received steroid treatment for acute MS exacerbation. Three months later the patient improved clinically and on MRI.

Adult↗

Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study.

Cocaine can cause a variety of neuropsychiatric and neurobehavioral complications; however, it is uncertain whether cocaine causes persistent cerebral structural and neurochemical abnormalities in asymptomatic users. We studied 52 African-American men (26 human immunodeficiency virus-negative asymptomatic heavy cocaine users and 26 normal subjects). Ventricle-to-brain ratio (VBR) and white matter lesions (WML) were quantified on magnetic resonance imaging. N-acetyl-containing compounds (NA), total creatine, choline-containing compounds, myo-inositol, and glutamate + glutamine were measured with in vivo proton magnetic resonance spectroscopy, VBR and WML were not significantly different in the cocaine users compared to the normal controls. Elevated creatine (+7%; p = .05) and myo-inositol (+18%; p = .01) in the white matter were associated with cocaine use. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal. Normal NA suggest no neuronal loss or damage in the brain regions examined in these cocaine users. Therefore, we conclude that neurochemical abnormalities observed might result from alterations in nonneuronal brain tissue.

Adolescent↗

BCR/ABL induces multiple abnormalities of cytoskeletal function.

The BCR/ABL oncogene causes human chronic myelogenous leukemia (CML), a myeloproliferative disease characterized by massive expansion of hematopoietic progenitor cells and cells of the granulocyte lineage. When transfected into murine hematopoietic cell lines, BCR/ABL causes cytokine-independence and enhances viability. There is also growing evidence that p210(BCR/ABL) affects cytoskeletal structure. p210(BCR/ABL) binds to actin, and several cytoskeletal proteins are tyrosine phosphorylated by this oncoprotein. Also, at least one aspect of cytoskeletal function is abnormal, in that the affinity of beta1 integrins for fibronectin is altered in CML cells. However, isolated changes in beta1 integrin function would be unlikely to explain the clinical phenotype of CML. We used time-lapse video microscopy to study cell motility and cell morphology on extracellular cell matrix protein-coated surfaces of a series of cell lines before and after transformation by BCR/ABL. BCR/ABL was associated with a striking increase in spontaneous motility, membrane ruffling, formation of long actin extensions (filopodia) and accelerated the rate of protrusion and retraction of pseudopodia on fibronectin-coated surfaces. Also, while untransformed cells were sessile for long periods, BCR/ABL-transformed cells exhibited persistent motility, except for brief periods during cell division. Using cell lines transformed by a temperature-sensitive mutant of BCR/ABL, these kinetic abnormalities of cytoskeletal function were shown to require BCR/ABL tyrosine kinase activity. Similar abnormalities of cytoskeletal function on fibronectin-coated surfaces were observed when hematopoietic progenitor cells purified by CD34 selection from patients with CML were compared with CD34 positive cells from normal individuals. Interestingly, alpha-interferon treatment was found to slowly revert the abnormal motility phenotype of BCR/ABL-transformed cells towards normal. The increase in spontaneous motility and other defects of cytoskeletal function described here will be useful biological markers of the functional effects of BCR/ABL in hematopoietic cells.

3T3 Cells↗

Screening for complement deficiency in bacterial meningitis.

Seventy-seven children with bacterial meningitis were screened for complement deficiency. Both the classical and the alternate pathways were normal in 75 patients. Transiently reduced total haemolytic activity of the classical pathway was documented in a boy with meningococcal meningitis. Total haemolytic activity of both the classical and the alternate pathways were reduced in another patient with pneumococcal meningitis: individual complement components determination indicated predominant activation of the alternate pathway.

Adolescent↗

Frontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopy.

PURPOSE: To evaluate cerebral biochemical abnormalities in patients with frontotemporal dementia and Alzheimer disease and to determine whether proton (hydrogen-1) magnetic resonance (MR) spectroscopy can help differentiate among these two patient groups and healthy (control) subjects. MATERIALS AND METHODS: MR imaging and H-1 MR spectroscopy were performed in 14 patients with frontotemporal dementia, 12 with probable Alzheimer disease (Alzheimer), and 11 healthy (control) elderly subjects. Spectra were acquired from midfrontal and temporoparietal gray matter with a double spin-echo sequence (repetition time, 3,000 msec; echo time, 30 msec). Results were expressed in metabolite concentrations corrected for the presence of cerebrospinal fluid. RESULTS: In frontotemporal dementia patients, the frontal lobe showed reduced N-acetyl compounds (-28%) and glutamate plus glutamine (-16%), suggestive of neuron loss, and increased myo-inositol (MI) (+19%), suggestive of increased glial content. In three frontotemporal dementia patients, a lactate peak was present in the frontal lobe. In Alzheimer patients, no statistically significant abnormalities were observed in the frontal region, but MI was elevated (+8%) in the temporoparietal region. With use of linear discriminant analysis of MR spectroscopy data alone, 92% of the frontotemporal dementia patients were correctly differentiated from the Alzheimer patients and control subjects. The overall accuracy for discrimination among all three groups was 84%. CONCLUSION: H-1 MR spectroscopy demonstrated biochemical abnormalities in patients with frontotemporal dementia and aided differentiation between patients with frontotemporal dementia and Alzheimer disease.

Aged↗

Metabolite abnormalities in progressive multifocal leukoencephalopathy by proton magnetic resonance spectroscopy.

OBJECTIVE: To evaluate progressive multifocal leukoencephalopathy (PML) lesions using proton magnetic resonance spectroscopy (1H MRS). DESIGN: CSF polymerase chain reaction (PCR) detection for JC viral (JCV) DNA; MRI and localized 1H MRS in the PML lesions, normal-appearing contralateral brain regions (CONTRA), and in matched brain regions of normal subjects. SETTING: University-affiliated medical center. PATIENTS OR PARTICIPANTS: 20 AIDS patients with clinical diagnosis of PML, 16 had tissue and/or CSF evidence of JCV infection; 20 age-matched normal subjects. MAIN OUTCOME MEASURES: Metabolites from 1H MRS: N-acetyl aspartate (NA), creatine (CR), choline-containing compounds (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids. RESULTS: CSF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic demyelinating lesions; commonest locations were frontal lobe and cerebellum. 1H MRS in the lesions showed decreased NA (-35%; p < 0.0001) and CR (-18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional increased MI, and excess lactate (15/20 lesions) and lipids (18/20). In the CONTRA, MRS showed trends for increased CR (+15%), CHO (+15%), MI (+13%), and lower GLX (-9%; p = 0.02). Six patients, studied longitudinally (4-18 months), showed progressive spectroscopic changes; two patients with longest survival showed the highest MI. CONCLUSIONS: These MRS findings are consistent with neuropathologic observations of neuronal loss, cell membrane and myelin breakdown, and increased glial activity in PML lesions. The CONTRA abnormalities may be due to remote effects of PML or direct HIV-1 infection. 1H MRS may be useful for characterization and follow-up evaluation of PML lesions.

Adult↗

MR spectroscopy and diffusion-weighted MR imaging in focal brain lesions in AIDS.

Focal brain lesions in AIDS may be difficult to diagnose with conventional imaging techniques. Recent advances in magnetic resonance (MR), including MR spectroscopy (MRS) and diffusion-weighted imaging (DWI), may provide additional information in the evaluation of these diseases. MRS of various AIDS brain lesions show distinct chemical profiles; however, several factors such as location of the voxel, echo time of the study, and disease stage, all have to be taken into consideration when interpreting the results of MRS. DWI demonstrates molecular motion within the tissue and may provide information regarding tissue integrity associated with various disease processes.

AIDS Dementia Complex↗

Hypoxic encephalopathy after near-drowning studied by quantitative 1H-magnetic resonance spectroscopy.

Early prediction of outcome after global hypoxia of the brain requires accurate determination of the nature and extent of neurological injury and is cardinal for patient management. Cerebral metabolites of gray and white matter were determined sequentially after near-drowning using quantitative 1H nuclear magnetic resonance spectroscopy (MRS) in 16 children. Significant metabolite abnormalities were demonstrated in all patients compared with their age-matched normal controls. Severity of brain damage was quantified from metabolite concentrations and ratios. Loss of N-acetylaspartate, a putative neuronal marker, from gray matter preceded that observed in white matter and was more severe. Total creatine decreased, while lactate and glutamine/glutamate concentrations increased. Changes progressed with time after injury. A spectroscopic prognosis index distinguished between good outcome (n = 5) and poor outcome (n = 11) with one false negative (bad outcome after borderline MRS result) and no false positive results (100% specificity). The distinction was made with 90% sensitivity early (after 48 h) and became 100% later (by days 3 and 4). This compared with 50-75% specificity and 70-100% sensitivity based upon single clinical criteria. MRS performed sequentially in occipital gray matter provides useful objective information which can significantly enhance the ability to establish prognosis after near-drowning.

Brain↗

Elimination of artifacts in short echo time H MR spectroscopy of the frontal lobe.

Localized 1H spectra from the frontal part of the human brain are often distorted by "ghost" artifacts, especially with short echo time PRESS sequences. These artifacts are caused by insufficient dephasing of unwanted coherences involving magnetization in the sinuses and the mouth. Because the various unwanted coherences of a PRESS sequence are dephased differently, the order of the slice gradients has a pronounced effect on the spectral quality. For frontal voxels, the last slice gradient has to be applied in the axial direction. With this slice order, the major metabolites can be quantified with an interindividual variability of about 10%.

Artifacts↗

In vivo 1H MRS choline: correlation with in vitro chemistry/histology.

We correlated the in vivo 1H Magnetic Resonance Spectroscopy (MRS) concentration of the choline peak (CHO) with in vitro chemical measures of choline-containing compounds and a histological grade of cellularity in 18 patients with neoplastic and infectious brain lesions. Gas-chromatography-mass-spectrometry (GCMS) was used to measure the concentrations of free choline (Cho), glycerophosphocholine (GPCho), phosphocholine (PCho) and phosphatidylcholine (PtdCho) from biopsies in the same area where MRS was performed. Cellular density, free Cho, PCho and GPCho were the strongest determinants of 1H MRS CHO while PtdCho was not. Just as the 1H MRS 2.0 peak reflects both the concentration of n-acetyl-l-aspartate and neuronal density, the 1H MRS 3.2 peak reflects the concentration of water-soluble choline-containing compounds and cellular density.

Brain↗