Assessment of cerebral S100B levels by proton magnetic resonance spectroscopy after lateral fluid-percussion injury in the rat

2005 ◽  
Vol 102 (6) ◽  
pp. 1115-1121 ◽  
Author(s):  
Andrea Kleindienst ◽  
Christos M. Tolias ◽  
Frank D. Corwin ◽  
Christian Müller ◽  
Anthony Marmarou ◽  
...  

Object. After traumatic brain injury (TBI), S100B protein is released by astrocytes. Furthermore, cerebrospinal fluid (CSF) and serum S100B levels have been correlated to outcome. Given that no data exist about the temporal profile of cerebral S100B levels following TBI and their correlation to serum levels, the authors examined whether proton magnetic resonance (MR) spectroscopy is capable of measuring S100B. Methods. Results of in vitro proton MR spectroscopy experiments (2.35-tesla magnet, 25 G/cm, point-resolved spatially localized spectroscopy) revealed an S100B-specific peak at 4.5 ppm and confirmed a positive correlation between different S100B concentrations (10 nM–1 µM) and the area under the curve (AUC) for the S100B peak (r = 0.991, p < 0.001). Thereafter, proton MR spectroscopy was performed in male Sprague—Dawley rats (7 × 5 × 5—mm voxel in each hemisphere, TR 3000 msec, TE 30 msec, 256 acquisitions). Exogenously increased CSF S100B levels (∼ 200 ng/ml) through the intraventricular infusion of S100B increased the AUC of the S100B peak from 0.06 ± 0.02 to 0.44 ± 0.06 (p < 0.05), whereas serum S100B levels remained normal. Two hours after lateral fluid-percussion injury, serum S100B levels increased to 0.61 ± 0.09 ng/ml (p < 0.01) and rapidly returned to normal levels, whereas the AUC of the S100B peak increased to 0.19 ± 0.04 at 2 hours postinjury and 0.41 ± 0.07 (p < 0.05) on Day 5 postinjury. Conclusions. Proton MR spectroscopy proves a strong correlation between the AUC of the S100B peak and S100B concentrations. Following experimental TBI, serum S100B levels increased for only a very short period, whereas cerebral S100B levels were increased up to Day 5 postinjury. Given that experimental data indicate that S100B is actively released following TBI, proton MR spectroscopy may represent a new tool to identify increased cerebral S100B levels in patients after injury, thus allowing its biological function to be better understood.

1999 ◽  
Vol 91 (6) ◽  
pp. 928-934 ◽  
Author(s):  
Akihiko Shiino ◽  
Satoshi Nakasu ◽  
Masayuki Matsuda ◽  
Jyoji Handa ◽  
Shigehiro Morikawa ◽  
...  

Object. Controversy exists about correlations between histological tumor grade and magnetic resonance (MR) spectroscopy data. The authors studied single-voxel proton MR spectroscopy as a noninvasive way to evaluate grade of malignancy in intracranial meningiomas.Methods. The authors compared the results of MR spectroscopy with those derived by the MIB-1 staining index (SI) in 29 meningiomas. Proton MR spectroscopy was performed using stimulated echo acquisition and volume-localized solvent-attenuated proton nuclear MR sequences before surgery or other therapy.Twenty-four tumors were histologically benign (13 meningothelial, three fibrous, four transitional, three angiomatous, and one chordoid); four were atypical (Grade II), and one was papillary (Grade III). The mean MIB-1 SI in the benign group was significantly lower than those in the other groups (p = 0.0041). The mean choline-containing compound (Cho)/creatine and phosphocreatine (Cr) ratios in the benign and nonbenign groups were 2.56 ± 1.26 and 7.85 ± 3.23, respectively (p = 0.0002). A significant linear correlation was observed between the Cho/Cr ratio and the MIB-1 SI (r0.05 = 0.74, p < 0.001). Necrosis was present histologically in four of the five meningiomas classified either as atypical or papillary. Magnetic resonance spectroscopy revealed a methylene signal in these meningiomas that was not detected in benign meningiomas. Of the five meningiomas in which only a lactate signal was observed, two were benign and the MIB-1 SI in these two benign meningiomas was higher than the mean value for the benign group. Alanine, detected in 12 of 30 meningiomas, did not correlate with either tumor grade or Cho/Cr ratio.Conclusions. Proton MR spectroscopy is a useful diagnostic method for determining the proliferative or malignant potential of meningiomas according to the Cho/Cr ratio. A lactate and/or methylene signal suggests a high-grade tumor.


2003 ◽  
Vol 98 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Damien Galanaud ◽  
Olivier Chinot ◽  
François Nicoli ◽  
Sylviane Confort-Gouny ◽  
Yann Le Fur ◽  
...  

Object. Gliomatosis cerebri (GC), a rare entity characterized by a widespread infiltration of brain by tumor, lacks objective and quantitative diagnostic criteria. Single-voxel spectroscopy and chemical shift imaging (two-dimensional proton magnetic resonance [MR] spectroscopy) were performed using both short (20- or 22-msec) and long (135-msec) echo times in nine patients suffering from GC, nine patients with low-grade gliomas (LGGs), and 25 healthy volunteers to establish the precise metabolic pattern of this uncommon brain neoplasm. Methods. The gliomatosis infiltration was characterized by markedly elevated levels of creatine—phosphocreatine (Cr) and myo-inositol (Ins), a reduced level of N-acetyl aspartate (NAA), and a moderately elevated level of choline-containing compounds (Cho). This pattern differs strikingly from LGGs, which are characterized by elevated levels of Cho and Ins, markedly reduced levels of NAA, and low-to-normal Cr concentrations. Although the distinction between GC and LGG, based on histological and MR imaging criteria, is a matter of debate, MR spectroscopy produces valuable information for the differentiation between these two entities and, hence, the choice of therapeutic strategy. It also provides new insight into the pathophysiology of GC because elevated Cr and Ins levels may be related to proliferation of glial elements or, more probably, activation of normal glia. Elevated levels of Cho reflect cellular proliferation and reduced NAA corresponds to reversible neuronal injury and/or focal invasion by the tumor process. Conclusions. Owing to the unfavorable clinical outcome associated with GC compared with that associated with LGG, the findings of this study illustrate the diagnostic and prognostic value of proton MR spectroscopy in the characterization of infiltrating gliomas.


1991 ◽  
Vol 74 (2) ◽  
pp. 270-277 ◽  
Author(s):  
Katsuji Shima ◽  
Anthony Marmarou

✓ The degree of brain-stem dysfunction associated with high-level fluid-percussion injury (3.0 to 3.8 atm) was investigated in anesthetized cats. Measurements were made of the animals' intracranial pressure (ICP), pressure-volume index (PVI), far-field brain-stem auditory evoked responses (BAER's), and cerebral blood flow (CBF). The animals were classified into two groups based on the severity of neuropathological damage to the brain stem after trauma: Group 1 had mild intraparenchymal and subarachnoid hemorrhages and Group 2 had severe intraparenchymal and subarachnoid hemorrhages. The ICP values in Group 1 were insignificantly lower than those in Group 2, while the PVI values in Group 2 were clearly lower (p < 0.05). Immediately after the injury, peaks II, III, and IV of the BAER's demonstrated a transitory and marked suppression. One Group 1 and two Group 2 animals showed the disappearance of peak V. In Group 1, the latencies of peak II, III, and IV gradually increased until 60 to 150 minutes postinjury, then returned to 95% of baseline value at 8 hours; however, the animals in Group 2 showed poor recovery of latencies. Two hours after brain injury, the CBF decreased to 40% of the preinjury measurement in both groups (p < 0.001). In contrast to Group 2, the CBF in Group 1 returned to 86.8% of the preinjury measurement by 8 hours following the injury. Changes in PVI, BAER, and CBF correlated well with the degree of brain-stem injury following severe head injury'- These data indicate that high-level fluid-percussion injury (> 3.0 atm) is predominantly a model of brain-stem injury.


1990 ◽  
Vol 72 (5) ◽  
pp. 763-766 ◽  
Author(s):  
Kiyohiro Houkin ◽  
Ingrid L. Kwee ◽  
Tsutomu Nakada

✓ Serial proton (1H) and phosphorus-31 (31P) magnetic resonance (MR) spectroscopy of cerebral infarction was performed in rats to assess the sensitivity of these techniques for use in clinical cerebral infarction. In this experimental chronic infarction model, 31P spectroscopy tended to return to a “normal” pattern within 24 hours after induction of infarction in spite of pathologically proven completed infarction and, therefore, appeared not to be sensitive enough for clinical application. On the other hand, proton spectroscopy invariably showed persistent high lactate levels and was capable of distinguishing completed infarction from reperfused recovered brain. Persistent high lactate levels appear to be a good MR spectroscopic indicator of completed infarction.


1994 ◽  
Vol 81 (3) ◽  
pp. 443-448 ◽  
Author(s):  
Leslie N. Sutton ◽  
Suzanne L. Wehrli ◽  
Laura Gennarelli ◽  
Zhiyue Wang ◽  
Robert Zimmerman ◽  
...  

✓ High-resolution proton magnetic resonance (MR) spectroscopy was performed on perchlorate extracts of tumors (24 cases) or peritumoral vermis (five cases) obtained at surgery. Fifteen tumors were typical cerebellar astrocytomas and nine were posterior fossa primitive neuroectodermal tumors/medulloblastomas. Spectra obtained from the five samples of peritumoral vermis revealed a pattern of metabolites similar to that reported for cerebellar tissue, but concentrations of most metabolites were low, perhaps due to dilution from peritumoral edema. The astrocytomas were characterized by high levels of valine, alanine, and choline, an increase in the choline:N-acetylaspartate (NAA) ratio, and a shift from glutamate to glutamine. Elevations in lactate, pyruvate, and glucose were the result of ischemia during sampling. The primitive neuroectodermal tumors/medulloblastomas were distinguished from astrocytomas by a greater increase in the choline:NAA ratio, a smaller decrease in the glutamate:glutamine ratio, and a relative increase in glycine, taurine, and inositol levels. These metabolic patterns may be of value diagnostically as in vivo MR spectroscopy achieves higher resolution.


1997 ◽  
Vol 87 (4) ◽  
pp. 525-534 ◽  
Author(s):  
Lawrence L. Wald ◽  
Sarah J. Nelson ◽  
Mark R. Day ◽  
Susan E. Noworolski ◽  
Roland G. Henry ◽  
...  

✓ The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormal metabolite levels in nonenhancing regions of solid tumor.


2004 ◽  
Vol 101 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Antoinette A. Chan ◽  
Aubrey Lau ◽  
Andrea Pirzkall ◽  
Susan M. Chang ◽  
Lynn J. Verhey ◽  
...  

Object. The purpose of this study was to assess the differences in spatial extent and metabolic activity in a comparison of a radiosurgical target defined by conventional strategies that utilize the enhancing lesion and a metabolic lesion defined by proton magnetic resonance spectroscopy (MRS) imaging. The authors evaluated whether these differences manifest themselves in the clinical outcome of patients and assessed the value of incorporating 1H-MRS imaging—derived spatial information into the treatment planning process for gamma knife surgery (GKS). Methods. Twenty-six patients harboring Grade IV gliomas who had previously been treated with external-beam radiation therapy were evaluated by comparing the radiosurgically treated lesion volume with the volume of metabolically active tumor defined on 1H-MRS imaging. The cohort was evenly divided into two groups based on the percentage of overlap between the radiosurgical target and the metabolic lesion volumes. Patients with a percentage of overlap greater than 50% with respect to the metabolic lesion volume were classified as low risk and those with an overlap less than 50% were classified as high risk. Kaplan—Meier estimators were calculated using time to progression and survival as dependent variables. The metabolite levels within the metabolic lesion were significantly greater than those within the radiosurgical target (p ≤ 0.001). The median survival was 15.7 months for patients in the low-risk group and 10.4 months for those in the highrisk group. This difference was statistically significant (p < 0.01). Conclusions. Analysis of the results of this study indicates that patients undergoing GKS may benefit from the inclusion of 1H-MRS imaging in the treatment planning process.


1999 ◽  
Vol 91 (4) ◽  
pp. 660-668 ◽  
Author(s):  
Kees P. J. Braun ◽  
Pieter van Eijsden ◽  
W. Peter Vandertop ◽  
Robin A. de Graaf ◽  
Rob H. J. M. Gooskens ◽  
...  

Object. Brain damage in patients with hydrocephalus is caused by mechanical forces and cerebral ischemia. The severity and localization of impaired cerebral blood flow and metabolism are still largely unknown. Magnetic resonance (MR) spectroscopy offers the opportunity to investigate cerebral energy metabolism and neuronal damage noninvasively and longitudinally. Previous 1H MR spectroscopy studies have shown an increased lactate resonance that is suggestive of anaerobic glycolysis. The aim of this study was to assess cerebral damage and energy metabolism in kaolin-induced hydrocephalus in adult rats by using in vivo 1H and 31P MR spectroscopy. The presence of lactate was correlated with high-energy phosphate metabolism and intracellular pH. The measurement of relative concentrations of N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr) served to assess neuronal damage.Methods. Hydrocephalus was induced in adult rats by surgical injection of kaolin into the cisterna magna. Magnetic resonance studies, using a 4.7-tesla magnet, were performed longitudinally in hydrocephalic animals at 1 (10 rats), 8 (six rats), and 16 weeks (six rats) thereafter, as well as in eight control animals. To evaluate ventricular size and white matter edema T2-weighted MR imaging was performed. The 1H MR spectra were acquired from a 240-µl voxel, positioned centrally in the brain, followed by localized 31P MR spectroscopy on a two-dimensional column that contained the entire brain but virtually no extracranial muscles. The 1H and 31P MR spectroscopy peak ratios were calculated after fitting the spectra in the time domain, intracellular pH was estimated from the inorganic phosphate (Pi) chemical shift, and T2 relaxation times of 1H metabolites were determined from the signal decay at increasing echo times.Conclusions. In hydrocephalic rats, ventricular expansion stabilized after 8 weeks. White matter edema was most pronounced during acute hydrocephalus. Lactate peaks were increased at all time points, without a decrease in phosphocreatine (PCr)/Pi and PCr/adenosine triphosphate (ATP) peak ratios, or pH. Possibly lactate production is restricted to periventricular brain tissue, followed by its accumulation in cerebrospinal fluid, which is supported by the long lactate T2 relaxation time. Alternatively, lactate production may precede impairment of ATP homeostasis. The NAA/Cho and tCr/Cho ratios significantly decreased during the acute and chronic stages of hydrocephalus. These changes were not caused by alterations in metabolite T2 relaxation time. The decreases in the NAA/Cho and tCr/Cho ratios implicate neuronal loss/dysfunction or changes in membrane phospholipid metabolism, as in myelin damage or gliosis. It is suggested that 1H MR spectroscopy can be of additional value in the assessment of energy metabolism and cerebral damage in clinical hydrocephalus.


2004 ◽  
Vol 101 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Andreas Stadlbauer ◽  
Ewald Moser ◽  
Stephan Gruber ◽  
Christopher Nimsky ◽  
Rudolf Fahlbusch ◽  
...  

Object. It is often difficult to delineate the extent of invasion of high- and low-grade gliomas into normal brain tissue by using conventional T1- and T2-weighted magnetic resonance (MR) imaging. Knowledge of the relationship between the tumor infiltration zone and normal brain, however, is one of the prerequisites for performing as radical a tumor resection as possible. Proton MR spectroscopy allows noninvasive measurements of the concentrations and spatial distributions of brain metabolites and, therefore, may provide biochemical information in vivo, that is useful in distinguishing pathological from normal areas of the brain. The authors have developed a method to use the properties of MR spectroscopy to investigate intraoperatively pathological changes in the spatial distribution of choline (Cho)-containing compounds, total creatine, and N-acetylaspartate (NAA) in brain tumors with the aid of frameless stereotaxy. Methods. Maps of the Cho/NAA ratio were calculated and automatic segmentation of the tumors was performed. Spectroscopic images of the segmented tumor were matched to an anatomical three-dimensional (3D) MR imaging set by applying a fully automated mutual-information algorithm. The resulting 3D MR image can be used subsequently for neurosurgical planning, transfer to a frameless stereotactic system, and display in the navigation microscope during surgery leading to 1H-MR spectroscopy-guided navigation. Conclusions. This method may allow better intraoperative identification of tumor border zones based on metabolic changes due to tumor infiltration.


1999 ◽  
Vol 91 (4) ◽  
pp. 653-659 ◽  
Author(s):  
Helen M. Bramlett ◽  
Edward J. Green ◽  
W. Dalton Dietrich

Object. Patients with head injuries often experience respiratory distress that results in a secondary hypoxic insult. The present experiment was designed to assess the histopathological consequences of a secondary hypoxic insult by using an established rodent model of traumatic brain injury (TBI).Methods. Intubated anesthetized rats were subjected to moderate (1.94–2.18 atm) parasagittal fluid-percussion injury (FPI) to the brain. Following the TBI, the animals were maintained for 30 minutes by using either hypoxic (TBI-HY group, nine animals) or normoxic (TBI-NO, 10 animals) gas levels. Sham-operated animals also underwent all manipulations except for the FPI (sham-HY group, seven animals; and sham-NO group, seven animals). Three days after TBI the rats were killed, and quantitative histopathological evaluation was undertaken. Cortical contusion volumes were dramatically increased in the TBI-HY group compared with the TBI-NO group (p < 0.03). Qualitative assessment of cortical and subcortical structures demonstrated significant damage within the hippocampal areas, CA1 and CA2, of TBI-HY animals compared with the TBI-NO animals (both p < 0.03). There was also a significant increase in the frequency of damaged neuronal profiles within the middle and medial sectors of the CA1 hippocampus (p < 0.03) due to the hypoxic insult.Conclusions. The results of this study demonstrate that a secondary hypoxic insult following parasagittal FPI exacerbates contusion and neuronal pathological conditions. These findings emphasize the need to control for secondary hypoxic insults after experimental and human head injury.


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