Localized proton magnetic resonance spectroscopy of cerebral metabolites.
Explore the source record for details and available documents.
Brain↗
Biomedical subjects
J Frahm
Publications and source records attributed to J Frahm.
Localized proton magnetic resonance spectroscopy of cerebral metabolic disturbances in children with neuronal ceroid lipofuscinosis.
Cerebral metabolic abnormalities in five children with infantile (1), late infantile (1), and juvenile (3) neuronal ceroid lipofuscinosis (NCL) were noninvasively assessed by localized proton magnetic resonance spectroscopy (MRS). Infantile NCL was characterized by a complete loss of N-acetylaspartate (NAA, neuronal marker), a marked reduction of creatines (Cr) and choline-containing compounds (Cho), and an elevation of myo-inositol (Ins, glial marker) and lactate (Lac) in both gray and white matter. Reduced NAA and elevated Lac were also detected in gray and white matter of late infantile NCL, but in this case not only Ins but also Cr and Cho were increased in white matter. In contrast to the infantile forms, juvenile NCL exhibited normal metabolic profiles. In one patient disease progression was indicated by reduced NAA and Cr in gray matter in a follow-up study after four years. The present findings in NCL are consistent with irreversible and generalized neuroaxonal loss as well as alterations of white matter glia similar to those found in leukodystrophies. The severity of metabolic disturbances correlates with clinical symptoms and decreasing age of onset.
Aspartic Acid↗
Somatotopic motor representation in the human anterior cerebellum. A high-resolution functional MRI study.
Though somatotopic encoding of function is a prominent feature in brain structures involved in sensori-motor processing, it has not been well established for the human cerebellum. We delineated the representation of hand, foot and tongue movements in the anterior cerebellar lobe of eight healthy subjects using dynamic high-resolution MRI sensitized to changes in cerebral blood oxygenation (CBO). Activation was determined by pixel-by-pixel correlation of signal intensity time courses with the performance protocol. All subjects showed task-related signal increases in an ipsilateral region during distal limb movements. For the hand task, the centre of activation was located in the intermediate hemispheric portion of Larsell lobules H IV-V. Foot movements activated areas within the central lobule, Larsell lobules II-III, medial and anterior to the corresponding hand areas in all subjects. Responses for tongue movements were less consistent across subjects but found in areas posterior to the respective individual hand representation.
Adult↗
Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy.
Changes in cerebral blood oxygenation due to functional activation of the primary sensorimotor cortex during a unilateral finger opposition task were simultaneously mapped by deoxyhemoglobin-sensitive magnetic resonance imaging (MRI) and monitored by near-infrared spectroscopy (NIRS). Activation foci along the contralateral central sulcus displayed task-associated increases in MRI signal intensity, indicating a concomitant decrease of the focal concentration of deoxyhemoglobin. This interpretation was confirmed by simultaneous reductions in deoxyhemoglobin measured optically. Since observation of the latter effect required exact spatial matching of the MRI-detected activation foci and position of the fiber optic bundles ("optodes") used for transmitting and receiving light, it may be concluded that optical recordings of changes in deoxyhemoglobin during functional challenge probe only a restricted brain tissue region. While deoxyhemoglobin responses seen by NIRS were smaller for ipsi- than for contralateral finger movements, task-related increases in oxyhemoglobin were rather similar between both conditions and, thus, seem to be less specific. Furthermore, no consistent changes were obtained for total hemoglobin during task performance, possibly due to the short timing of the repetitive protocol. In general, results underline, in humans, the hitherto assumed signal physiology for functional brain mapping by oxygenation-sensitive MRI and allow assessment of both constraints and practicability of functional studies by NIRS.
Adult↗
Functional MRI of human brain activation combining high spatial and temporal resolution by a CINE FLASH technique.
Functional mapping of human brain activation has been accomplished at high spatial and temporal resolution (voxel size 4.9 microliter, temporal increment 100 ms). The approach was based on oxygenation-sensitive long-echo time FLASH MRI sequences synchronized to multiply repeated cycles of visual stimulation in a CINE acquisition mode. This high temporal resolution revealed that stimulus-related signal intensity changes in human visual cortex display an initial latency followed by increases extending over several seconds. Furthermore, the temporal characteristics of the complete CINE MRI signal time course depended on the absolute and relative durations of activation and control periods and, for example, caused an apparent absence of a poststimulation "under-shoot" phenomenon. Complementing hyperoxygenation due to rapid hemodynamic adjustments, these results suggest signal intensity modulation by enhanced oxygen consumption and concomitant deoxygenation during prolonged and/or repetitive stimulation.
Artifacts↗
On the 3.35 ppm singlet resonance in proton NMR spectra of brain tissue: scyllo-inositol or methanol contamination?
Explore the source record for details and available documents.
Animals↗
Dynamic monitoring of cerebral metabolites during and after transient global ischemia in rats by quantitative proton NMR spectroscopy in vivo.
Localized proton NMR spectroscopy was used to dynamically monitor alterations of cerebral metabolites before, during, and after a 10 min period of global forebrain ischemia in anesthetized rats. Metabolic assessment was based on user-independent determination of absolute brain concentrations at a nominal temporal resolution of 1.6 min. While the concentrations of N-acetyl aspartate (neuronal marker), creatines, cholines, and myo-inositol (glial marker) remained constant, ischemia induced a rapid decline of brain glucose. One hour after reperfusion, glucose recovered to 4.1 +/- 2.2 mmol/kg wet weight significantly above the basal value of 2.3 +/- 1.3 mmol/kg wet weight. Mirroring glucose depletion, lactate increased from 1.0 +/- 0.6 to 13.5 +/- 1.5 mmol/kg wet weight 10-15 min after the onset of ischemia. During reperfusion lactate clearance was characterized by a first-order rate constant of 0.03/min. The time courses of glucose and lactate reflect the rapid onset of anaerobic glycolysis during states of critically diminished blood flow. Assuming complete ischemia the production of lactate from glucose and cerebral glycogen stores yields a brain glycogen concentration of 4.7 +/- 0.9 mmol glycosyl unit/kg wet weight. Elevation of brain glucose during early reperfusion suggests a transient mismatch of glucose uptake and consumption during the first 1-2 hours post ischemia.
Animals↗
Cerebral proton magnetic resonance spectroscopy in Rett syndrome.
Combined MRI/MRS studies were performed in 9 girls with Rett syndrome of different ages. NAA, as marker of neuronal tissue, was found to decrease with increasing age. There was no evidence for a defective energy metabolism. The data point towards a probably secondary degenerative process in the pathogenesis of Rett syndrome.
Adolescent↗
Hemimegalencephaly: localized proton magnetic resonance spectroscopy in vivo.
Two children with hemimegalencephaly were examined by magnetic resonance imaging (MRI) and localized proton MR spectroscopy (MRS). In both cases, structural changes in the enlarged hemisphere included pachy- or polymicrogyria and gliosis of white matter. Associated metabolic disturbances included a dramatic reduction of glutamate and N-acetylaspartate (NAA) in white matter. Less severe or no alterations were noted in cortical gray matter, basal ganglia, and cerebellum. The older child (13 years) showed increased myoinositol in both gray and white matter as well as markedly increased choline-containing compounds in gray matter. Both children also had mildly decreased NAA levels in the white matter of the contralateral hemisphere. The spectroscopic findings indicate loss of vital neuroaxonal tissue and glial cell proliferation. Metabolic disturbances were more pronounced in the older child. The normal-appearing hemisphere was mildly affected in both cases.
Brain↗
Localized proton magnetic resonance spectroscopy of cerebral abnormalities in children with carbohydrate-deficient glycoprotein syndrome.
Morphologic and metabolic abnormalities in six children aged 2-9 years with carbohydrate-deficient glycoprotein (CDG) syndrome were assessed by magnetic resonance imaging (MRI) and localized proton magnetic resonance spectroscopy (MRS). In all patients, MRI revealed pronounced cerebellar atrophy. Follow-up examinations in two patients suggested early onset and rapid progression in the first years of life. Further pathologies comprised Dandy-Walker malformation, atrophy of the pons, brain stem and olives, supratentorial frontotemporal cortical atrophy, slightly dilated ventricles and a small corpus callosum. Two patients presented with small cysts in the white matter. The prominent metabolic abnormality detected by proton MRS in five patients was a reduction in N-acetylaspartate in white matter by more than 20%, indicating loss of vital neuroaxonal tissue. Further findings in white matter were glutamine and gamma-aminobutyrate increases by a factor of 2. One patient with type III CDG syndrome showed the most severe alterations of metabolite concentrations.
Atrophy↗
Magnetic resonance imaging of regional cerebral blood oxygenation changes under acetazolamide in carotid occlusive disease.
BACKGROUND: Gradient-echo magnetic resonance imaging can demonstrate changes in cerebral blood oxygenation with high spatiotemporal resolution. We have previously shown that this technique allows monitoring of autoregulatory responses under vasodilatory stress in the healthy human brain. Here the approach has been extended to assess impairment of the autoregulatory reserve capacity in patients with carotid occlusive disease. SUMMARY OF REPORT: We studied four patients with unilateral occlusion of the internal carotid artery on a 2.0-T clinical high-field magnetic resonance system. Oxygenation-sensitive imaging was based on long-echo-time, gradient-echo sequences (repetition time, 62.5 milliseconds; echo time, 30 milliseconds) with low flip angles (10 degrees) to emphasize changes in blood oxygenation rather than flow velocity. Dynamic recording monitored signal intensities before and after injecting 1 g of acetazolamide. In sections covering the hand area of the primary sensorimotor cortex, acetazolamide-induced magnetic resonance signal increases were attenuated in the vascular territories of occluded arteries. Lateralization of responses in the left and right hemispheric parts of the section corresponded to decreased hemodynamic reserve capacity as measured globally by transcranial Doppler ultrasonography. CONCLUSIONS: The present findings indicate that magnetic resonance imaging can demonstrate exhaustion of the autoregulatory reserve capacity when monitoring cerebral blood oxygenation changes during vasodilatory stress. We suggest that this method can help to evaluate regional cerebral hemodynamics in patients with carotid occlusive disease.
Acetazolamide↗
Alteration of intracellular metabolite diffusion in rat brain in vivo during ischemia and reperfusion.
BACKGROUND AND PURPOSE: Diffusion-weighted MRI can demonstrate decreases of the apparent diffusion coefficient (ADC) of brain tissue water shortly after the onset of ischemia. To further elucidate underlying mechanisms, this study extended diffusion assessment to intracellular metabolites in rat brain in vivo before, during, and after ischemia. METHODS: Changes in molecular mobility were studied in a rat model of global forebrain ischemia (n = 8, 20-minute occlusion, 120-minute reperfusion) with the use of diffusion-weighted localized proton MR spectroscopy. During ischemia and early reperfusion the time course of ADC changes was monitored by strongly diffusion-weighted spectra. ADC values of N-acetylaspartate, creatines, cholines, and myo-inositol were evaluated from series of differently diffusion-weighted spectra before ischemia, 90 minutes after reperfusion, and 60 minutes postmortem. RESULTS: Parallel to a rise in diffusion-weighted water signal (133 +/- 20%), pertinent intensities of all brain metabolites increased during ischemia. Changes were most pronounced for myo-inositol (46 +/- 9%) and smallest for N-acetylaspartate (12 +/- 4%). During reperfusion water ADC values returned to basal values, whereas metabolite ADC values were decreased by 22% (after 40 minutes). Postmortem ADC values (after 60 minutes) were reduced by 46% for water and 38% for metabolites. CONCLUSIONS: The present findings indicate that water ADC changes during ischemic stroke are accompanied by significant alterations in intracellular mobility in both neuronal and glial cell populations as reflected by N-acetylaspartate and myo-inositol, respectively. Altered metabolite ADC values during reperfusion are consistent with irreversible tissue damage in this model and offer new means to assess circulatory and metabolic compromise.
Animals↗
[Strategies for data analysis of brain activation studies with functional MR tomography].
The sensitivity of gradient-echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation has been introduced for mapping functional brain activation. To benefit from the high spatial and temporal resolution of the respective dynamic MRI data sets, their analysis requires algorithms that are capable of both precisely delineating task-related activation patterns and demonstrating functional connectivity of interacting areas. Here, we present various strategies for data evaluation by means of correlational analyses that surpass the quality of subtraction-based activation maps by improving both sensitivity and robustness. On a pixel-by-pixel basis the approach correlates signal time courses with a reference function, reflecting the temporal sequence of activated and control states. Extended versions employ the calculation of auto- or cross-correlation functions that increase sensitivity, but require periodic stimulations. Following individual correction for non-specific but correlated signal fluctuations, mapping of task-related coherent activation can be improved using neighborhood principles. Such refined strategies are expected to enhance the usefulness of oxygenation-sensitive MRI for studying the functional anatomy of the human brain under both physiological and pathological conditions.
Algorithms↗
Localized proton MR spectroscopy of the human kidney in vivo by means of short echo time STEAM sequences.
In order to obtain proton magnetic resonance spectra from the normal human kidney in vivo, we employed a STEAM sequence with delay times TE = 10 ms and TM = 30 ms. Signals are attenuated during STEAM sequences by J-coupling effects and by macroscopic movement of the sample. The combination of short echo times and respiratory triggering ensured that the kidney was stationary during the pulse sequence, and allowed us to detect strongly coupled resonances between 3 and 4.2 ppm. Analysis of spectra of extracts of bovine kidneys suggested that the renal MR-visible metabolites could include the osmolytes betaine, myo-inositol, and glycerophosphocholine. Four volunteers were subjected to overnight dehydration followed by rehydration, and we found that these signals increased significantly after dehydration, and decreased significantly 4 h after rehydration, thus supporting the assignment of the resonances as osmotically active metabolites.
Adult↗
Cerebral blood oxygenation in rat brain during hypoxic hypoxia. Quantitative MRI of effective transverse relaxation rates.
Oxygenation-sensitive MRI of respiratory challenges in the brain of experimental animals will considerably benefit from a quantitative relationship between cerebral blood oxygenation and MRI parameters. Here, a multi-echo gradient-echo MRI technique was used to determine effective transverse relaxation rates R2* = 1/T2* of rat brain in vivo during short periods of hypoxia and interleaved normoxic phases. The differential contribution delta R2* observed during hypoxia was found to increase linearly with arterial blood deoxygenation for mild to moderate conditions. Severe deoxygenation resulted in a plateau most likely due to enhanced cerebral blood flow.
Animals↗
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↗
Dysfunctional activation of subcortical nuclei in palatal myoclonus detected by high-resolution MRI.
Magnetic resonance images that were sensitized to changes in cerebral blood oxygenation state demonstrated dysfunctional activation of the dentate nuclei, the left inferior olivary nucleus and the left red nucleus in a 56-year-old patient with palatal myoclonus. These findings represent the first demonstration of movement-related activation of cerebellar, brainstem and midbrain nuclei in a single subject and at a spatial resolution comparable to that of anatomic MR images.
Brain Stem↗
The influence of the slice-selection gradient on functional MRI of human brain activation.
Explore the source record for details and available documents.
Brain↗