Factors affecting the extension of peritumoural brain oedema. A CT-study

Summary In human brain tumours the extension of peritumoural brain oedema may vary considerably. 37 brain tumours of various pathology and 2 abscesses were examined to identify the factors and mechanisms responsible for the oedema spreading. Peritumoural oedema profiles were determined towards the white matter and ventricle by measuring the CT-numbers of consecutive tissue blocks of 3.0–3.6 mm from the tumour to the normal white matter or the ventricle. It was found that neither the size of the tumour nor the histology has a close relationship to the amount of peritumoural oedema. The distance of oedema spreading rather is determined by the amount of fluid accumulation in the white matter immediately bordering the tumour. This relationship corresponds to a semilogarithmic function and represents the relation between the tumour-adjacent accumulation of extracellular fluid volume and the distance of extracellular fluid movement. The analysis of this relation leads to the suggestion that pressure gradients and bulk flow are involved in the development of human peritumoural oedema.     

Extracellular space and electrolyte distribution in cortex and white matter of dog brain in cold induced oedema

Summary 24 hours after a circumscribed cold injury of the cortex dog brains were perfused from the lateral ventricle and the frontal subarachnoidal space to the cisterna magna with an artificial CSF containing trace amounts of³⁵S-labelled thiosulphate. Simultaneously the extracellular tracer was administered intravenously. Extracellular fluid volume was estimated and found to be increased from 10 to 15% in the oedematous cortex and from 10 to 27% in the oedematous white matter. The actual size of ECS in oedematous white matter, however, must be larger as indicated by the relative alterations of thiosulphate distribution, tissue water, sodium and chloride. Apparently a small part of the fluid accumulation affects the cellular compartment in oedematous white matter. It may be concluded from the close spatial correspondence of the spreading of I¹³¹ albumin and Evans blue, the increase in water and sodium content, and the enlargement of the TSS that the dilated extracellular channels are filled with a plasma like oedema fluid, derived from blood.This investigation was supported by a grant from the Deutsche Forschungsgemeinschaft.     

Formation and propagation of brain oedema fluid around human brain metastases. A CT study

Summary Computerized tomography (CT) was used to examine the timecourse of the propagation of extravasated contrast medium from small brain metastases into the peritumoural oedematous white matter, following infusion of 200 ml of meglumine amidtrizoate for 3 hours. Four patients with a metastatic brain tumour were examined. CT scans at identical levels were taken 1.5, 3, 6, 9, and 12 hours after start of contrast infusion. Following 4–7 days of dexamethasone treatment (8–12mg/day i.v.) the examination was repeated. A contrast-enhanced area was observed surrounding the clearly delineated tumours, expanding gradually in a circular fashion into the peritumoural white matter oedema. The expanding circular enhancement was measured planimetrically on the various scans. From these values, the increase in radius/hr respectively in volume/hr was calculated, assuming a spherical geometry. This enabled a determination of the rate of oedema fluid formation and of the speed of oedema fluid propagation. The formation rate of oedema fluid amounted to 0.5–3.2ml/hour and the speed of oedema fluid spreading to 1.9 mm/hour. Following treatment with dexamethasone the formation rate of oedema fluid is reduced by 30–50%. The important clinical implications of these new findings are discussed.     

A study on peritumoural brain oedema around meningiomas by CT and MRI scanning

Summary There is a great variability in the amount of peritumoural brain oedema accompanying meningiomas. In a previous study it was found that the degree of brain oedema in the white matter around meningiomas correlated with disruption of the layers (especially the cerebral cortex), which separate the tumour from the white matter, as well as with the size and histological subtype of the tumour.In the present study comprising 9 meningiomas, the volume of oedema was calculated by integration of the cross-sectional oedematous areas on serial MRI slices. The volume of oedema was zero in 3 cases and ranged from 11 to 176.4 ml in the other 6 cases. The MRI-scans also showed disruption of the cortex in all cases, ranging from slight to severe. T₁ and T₂ measurements were made at the level of maximum extension, using a mixed sequence at a field strength of 1.5 T. From the T₂ values tissue water content in % was calculated using the equations: WC=39.36/(R₂ + 37.2) for cortex, and WC=29.63/(R₂ + 27.8) for white matter. These had been obtained by correlating water content with relaxation rates, measured in vitro on human brain autopsy specimens which were subjected to hydration with distilled water or dehydration by hyperosmolar solutions. Mean water content amounted to 82.53% for normal cortex, 74.72% for normal white matter, and 84.59% for oedematous white matter around the tumour.On the assumption that the spread of contrast agent marks the advancement of the front of oedema produced by the tumour, CT-studies were made before, and at 1 1/2, 3 and 6h after contrast infusion. The increase in diameter of the contrast-stained area on the CT-scan allows calculation of the excess of oedema production per unit tumour volume. Of 6 tumours with oedema (mean peritumoural water content of 91% and mean volume of oedema of 69.2 ml) the production excess at the steady-state was 0.18–1.08 ml/h/cm³ tumour volume, whereas 3 tumours without associated oedema had a production excess of 0.03–0.12 ml/h/cm³. Moreover, penetration of the cortex seems to constitute a separate factor determinig the spread of oedema.     

Examination of the metabolism of oedematous brain tissue

Glucose and gas metabolism as well as water, sodium, and potassium content of normal and oedematous white matter slices of rabbit brain have been determined. A cutting technique for the preparation of the slices is described. Although the increase of the relative water content in oedematous white matter is much more pronounced than in oedema of the grey matter, we observed only one significant change: the pyruvate production in vitro is about 20% higher in slices prepared from oedematous brain.     

Measurement of changes in brain water in man by magnetic resonance imaging

John Hunter was undoubtedly aware of the water content of normal brain tissue, and described cerebral oedema. The advent of nuclear magnetic resonance (NMR) shed new light on brain water, and the derivation of spatial information and hence images from NMR signals, has permitted studies of regional brain water in man in vivo. The initial study described here tested whether NMR longitudinal relaxation time (T1) correlates with brain water content in the cerebral cortex and white matter in man, and significant relationships have been demonstrated in cortex (r = 0.65, P less than 0.002) and white matter (r = 0.94, P less than 0.0001), the latter having narrow 95% confidence limits. The residual variance allows the prediction of water content from the T1 of white matter, measured from the image of a single patient, with an accuracy of +/- 4% of total tissue water with 95% confidence. In the further study described, the effects of dexamethasone and an infusion of 20% mannitol on brain water content has been assessed in patients with intrinsic cerebral tumours. Dexamethasone had no significant effect on the T1 of normal brain, oedematous peritumoural white matter, or tumour tissue. It must be concluded that the water content of these tissues is not changed by dexamethasone and that the clinical improvement seen in patients with cerebral tumours immediately after dexamethasone has to be explained by some mechanism other than a reduction in cerebral oedema. Mannitol did reduce the T1 of oedematous peritumoural white matter, and the T1 of tumour tissue, but did not change the T1 of normal brain significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlations between the apparent diffusion coefficient, water content, and ultrastructure after induction of vasogenic brain edema in cats

OBJECT: The authors examined the correlation between changes in the apparent diffusion coefficient, regional water content, and tissue ultrastructure after vasogenic brain edema. METHODS: Vasogenic edema was induced in the white matter of six cats by cortical cold lesioning. The trace of diffusion tensor (Trace[D]) obtained from magnetic resonance imaging to measure the orientationally averaged water diffusibility was compared with the corresponding tissue water content determined by gravimetric studies and with ultrastructural water localization. Edema fluid had spread to the subcortical and deep white matter by 4.5 hours postlesioning. The increase in Trace(D) showed a significant linear correlation with the increase in tissue water content, both in the subcortical and deep white matter as follows: y = 45.5x - 2367 (r = 0.94) and y = 37.0x - 1769 (r = 0.93), respectively, where x is the water content (gram water/gram tissue) and y the Trace(D) (x 10(-6) mm2/second). On histological examination, nerve fibers were found to be dissociated in the white matter and the extracellular space was markedly enlarged with protein-rich fluid. No noticeable hydropic swelling of the cellular components was observed. CONCLUSIONS: A linear correlation was observed between increases in Trace(D) and increases in extracellular water volume in in vivo vasogenic brain edema. A similar correlation between the subcortical and deep white matter showing different arrangements of nerve fibers (parallel compared with intermingled, respectively) indicated that measurement of Trace(D) is a suitable parameter for the evaluation of vasogenic brain edema.     

A study of electrical impedance of oedematous cerebral tissue during operations

Summary In 11 patients, most of whom had cerebral tumours, electrical impedance was recorded during the introduction of an impedance electrode during operation. After removal of the lesion impedance was measured in the tissue adjacent to the walls of the wound cavity. The readings were correlated with water and electrolyte content and with histological findings in the specimens taken from the same places. Electrical impedance appeared to be lowered in regions invaded by tumour and also in the surrounding oedematous areas of white matter. Unless primarily affected, cerebral cortex usually did not show oedema.The increase of water in the oedematous area was accompanied by a proportional increase of tissue Na⁺ and a decrease of tissue K⁺. The method of impedance measurement does not allow the delineation of a tumour from the surrounding oedema.     

intraoperative neuronavigation using diffusion tensor MR tractography for the resection of a deep tumor adjacent to the corticospinal tract

OBJECTIVE AND IMPORTANCE: Delineation of cerebral white matter tracts using MR tractography adds essential information for planning intracranial surgery. Integrating tractography with intraoperative neuronavigation may reduce the likelihood of new neurological deficits after surgery done to remove tumors adjacent to the projection fibers of eloquent cortex. We report the utility of such integration for the resection of deep (paraventricular) tumors. CLINICAL PRESENTATION: A 67-year-old male with malignant melanoma underwent stereotactic radiosurgery for a single metastasis within the paraventricular white matter of the right frontal lobe near the corticospinal tract. The lesion doubled in size within 12 months of radiotherapy. Surgical extirpation was performed aided by intraoperative neuronavigation. TECHNIQUE: MR images of the brain including MR tractography and post-contrast T1-weighted sequences were acquired and imported into a neuronavigational workstation. Asymmetric fusion of contrast-enhanced images and tractography was employed to assist in preservation of the integrity of critical white matter tracts during the surgical procedure. CONCLUSION: Inclusion of tractography in standard imaging protocols for neuronavigational systems may increase the safety of neurosurgical intervention near white matter tracts, including deep areas adjacent to the ventricles.     

Peritumoral oedema and lipid content

Summary The authors analyzed the water and lipid contents of oedematous tissues of white matter obtained during the operation, comparing with the absorption value in the CT scan. As the absorption value lowered its level, the water content increased, while the lipid decreased. However, after subtracting these two components, the content of protein also showed a significant decrement parallel to the absorption value despite the existence of extravasated protein. The decrement of lipid content was considered to be due to a dilution effect by an expanded volume of extravasated oedema fluid, as well as the decrease in protein, rather than the actual loss of tissue component; that is demyelination. It is the relative decrease in protein content which contributes to the low absorption value of oedematous tissue.     

Effects of dexamethasone on tumor-induced brain edema and its distribution in the brain of monkeys.

A human choriocarcinoma was successfully adapted to grow in the brain of monkeys (Macaca mulatta), thus providing a model of tumor-induced brain edema. Four animals were given dexamethasone (3 mg/kg/day) during 3 to 5 days after the onset of clinical signs, and the other five received no treatment for the same period. Tissue water and electrolyte content of treated and untreated animals were compared in cortex and white matter at various distances from the edge of the tumor. In untreated animals, 67.9% and 23.6% swelling was detected in adjacent and remote white matter, respectively, but only 11.8% swelling was noted in adjacent cortex. In animals treated with dexamethasone these percentages of swelling were improved to 32.4% and 11.9% in the corresponding white matter, and to 4.9% in adjacent cortex. The electrolyte changes shown in edematous brain of control animals also demonstrated significant improvement in the dexamethasone-treated group. Tissue radioactivity of 3H-dexamethasone at 60 minutes after intravenous injection was high in the periphery of tumor, adjacent cortex, and white matter, but low in the center of tumor, remote cortex, and white matter. The sites with high concentrations of dexamethasone also showed significant improvement of brain edema after dexamethasone treatment, suggesting that dexamethasone may act directly at these loci.     

Experimental transplantation gliomas in the adult cat brain

Summary In adult cats experimental brain tumours were produced by stereotactical xenotransplantation of the rat glioma clone F 98 into the internal capsule of the left hemisphere. Two to four weeks after transplantation tumours and peritumoural oedema were investigated by magnetic resonance imaging (MRI), electrophysiological recording and analysis of tissue content of water, electrolytes and extravasated serum proteins.Spherical tumours with a diameter of about 10 mm developed at the injection site and were surrounded by massive white matter oedema. Water content in peritumoural white matter increased from 2.63 ± 0.17 to 3.65 ± 0.19 ml/g d.w. (means ± SD), sodium from 187±11 to 351±55 eq/g d.w. and calcium from 7.4±1.1 to 13.3 ± 1.3 ± 1.3 eq/g d.w. Potassium and magnesium did not change. Oedema development was associated with the extravasation of 18.0 ± 16.8mg/g d.w. albumin and 15.8 ± 12.2 mg/g d.w. immunoglobulin. The calculated electrolyte content of oedema fluid approximated that of plasma but the serum protein content was about 40% lower. The ratio of low (albumin) to high (immunoglobulin) molecular weight proteins was the same in blood and oedema fluid. It is, therefore, concluded that peritumoural oedema consist of two components,a whole plasma extravasate and a protein-free ultra-filtrate.Peritumoural oedema could be clearly detected by MRI but differentiation between tumour and oedema was only possible after contrast enhancement with gadolinium-DTPA. The ratios of the intensities of the MR signal correlated linearly with the water content within white matter. MRI, in consequence, allows quantification of oedema provided a reference area with normal water content is present.     

The early prognosis of craniocerebral gunshot wounds in civilian practice as an aid to the choice of treatment

Summary The authors report a series of 56 cases of craniocerebral lesions secondary to missile injuries studied by means of CT scan. CT scans demonstrate the track of the missile, destruction of deep cerebral parenchyma, dissection of the white matter (intracerebral air) and reactive oedema. The prognostic incidence of CT is discussed. The CT scan helps to choose the best therapeutic management with respect to each particular case.     

Influence of the rate of ventricular enlargement on the white matter water content in progressive feline hydrocephalus

The effectiveness of transependymal absorption of cerebrospinal fluid in hydrocephalus was studied by correlating the measured water content of feline hydrocephalic white matter with the rate of enlargement of the ventricles. Two groups of cats were subjected to opening of either the calvaria or the calvaria and dura before the intracisternal injection of kaolin to obtain two profiles of ventricular enlargement. The water content 1, 2, and 3 mm from the lateral ventricles was measured in each group using the dry/wet weight and microgravimetric techniques after sacrificing the animals in each group at 2, 3, or 6 weeks after inducing hydrocephalus. In the animals with both calvarial and dural opening, the ventricles enlarged rapidly in the first 2 to 3 weeks and then continued to increase but at a slower rate. Concomitant with this early increase of ventricular size was a progressive increase in white matter water content both adjacent to and remote from the ventricles, which continued through 6 weeks. When only the calvaria was opened, ventricular size increased gradually, but continued to increase at a constant rate throughout the 6 weeks. Water content adjacent to the ventricle did not increase until the 3rd week, with little spread to adjacent areas by the 6th week. The central canals of the spinal cord were enlarged in both groups at all sampling levels. Neither increased periventricular water nor dilatation of the central canal was associated with stabilization of ventricular size in these studies. The authors conclude that these pathways are not sufficient to arrest the hydrocephalic process in these models.     

The contribution of arachidonic acid to the aetiology and pathophysiology of focal brain oedema; studies using an infusion oedema model

Summary Arachidonic acid solution (2 to 15 mg/ml) was infused into the right forebrain white matter of anaesthetised cats over three hours to evaluate its contribution to the genesis and pathophysiology of vasogenic brain oedema.The 0.6 ml infusion increased local white matter water content by a mean of 11.3 ml/100 g tissue but did not increase cortical water content. Histological studies revealed local expansion and trabeculation of the white matter with aggregations of granulocytic neutrophils in the venules and perivenular brain. The adjacent cortical cytoarchitecture was normal. The white matter around the infusion site was stained lightly and over a variable area (15–20 mm²) by intravenously administered Evans Blue dye 2%.Regional cerebral blood flow (rCBF) adjacent to the frontal infusion did not change significantly during the period of infusion and remained similar to rCBF in the contralateral hemisphere. Following the arachidonic acid infusion regional CBF CO₂ reactivity was normal and three was no asymmetry of either cortical somatosensory evoked potential (SEP) or motor evoked potential (MEP) waveforms.The increase in brain water content and changes in the ICP and ICP related biodynamics (pressure-volume index, lumped craniospinal compliance and CSF outflow resistance) were similar to those seen following infusion of 0.6 ml saline. These studies suggest that free intraparenchymal arachidonic acid, at concentrations exceeding those occurring in most neuropathological conditions, can increase the normal brain parenchymal capillary permeability but does not disrupt focal cerebrovascular and electrophysiological function. The clinical implications of these findings are discussed.Presented in part at Brain Oedema VIII, Bern, Switzerland, June, 1990.     

系统性红斑狼疮性脑病的影像学表现及临床分析

目的探讨系统性红斑狼疮脑病（NPSLE）患者的CT、MRI表现及其与临床的关系。方法收集符合NPSLE诊断标准患者26例,对其临床表现、实验室检查及CT、MR影像学表现进行回顾性分析。结果临床表现：头痛、癫痫、脑血管意外、精神异常、颅内压增高等不同程度的神经精神症状。全部患者脑脊液检查存在异常。抗心脂抗体（ACL）阳性率为53.84%,抗核糖体蛋白（r-RNP）抗体阳性率为61.53%。影像表现：CT扫描阳性率为84.61%（22/26）,MR扫描阳性率为92.30%（24/26）。CT主要表现为脑内灰白质弥漫性及局灶性低密度灶;MRI主要表现为大脑、小脑、脑干及深部白质的异常信号,T1WI呈低或等信号,T2WI呈高信号。脑萎缩12例,脑出血4例,基底节钙化7例。结论MR、CT的影像学表现可以对系统性红斑狼疮脑病的早期发现、鉴别诊断及疗效评价提供参考,但对系统性红斑狼疮脑病的诊断必须密切结合其他临床资料。     

Technical Note: A new Model for Quantitative Analysis of Brain Oedema Resolution Into the Ventricles and the Subarachnoid Space

Summary  Objective. The aim of the current study was to develop an experimental animal model for quantitative analysis of oedema resolution via the subarachnoid space and the ventricular system using fluorescent oedema markers.  Methods. Artificial cerebrospinal fluid (CSF) containing TRITC-albumin (MW 67.000D) and Na⁺-fluorescein (MW 376D) was continuously infused into the white matter of the left frontal lobe of New Zealand white rabbits (n=6) at a rate of 100 μl/h for 3 hrs. A closed cranial window for superfusion of the brain surface with artificial CSF fluid (3 ml/h) was implanted above the left parietal cortex for measurement of the fluorescence markers in the subarachnoid space. Uptake of the fluorescence indicators into the ventricles was quantified by ventriculo-cisternal perfusion (3 ml/h). The effluates were collected at 30 min intervals for 3 hrs after the start of infusion. Clearance of the oedema fluid into the perfusates was measured by fluorescence spectrophotometry.  Results. At an intracranial pressure of 15.0±1.7 mm Hg (mean±SEM) both indicators started to accumulate in the subarachnoid and ventricular perfusates at 90 min following onset of oedema fluid infusion. The concentrations of the indicators in the ventricular system increased to 7.7±5.1% of Na⁺-fluorescein and 16.1±13.0% of TRITC-albumin of the total amount infused were recovered in the ventricular system at 3 hours after start of the oedema infusion, while 3.4±3.2% of Na⁺-fluorescein and 3.7%± 3.2 of TRITC-albumin, respectively, were found in the effluates of the subarachnoid space.  Conclusion. The present study demonstrates that resolution of vasogenic brain oedema into the cerebral ventricular system and the subarachnoid space following its entry into cerbral white matter can be quantitatively analysed using fluorescence markers, which serve as oedema fluid indicators. The results indicate that the oedema fluid is cleared not only into the ventricular system but also via the subarachnoid space.     

Sodium nitroprusside (NPS) stimulates the lactate formation and causes intracellular electrolyte shifts in brain slices

Summary Nitroprusside sodium (NPS) was added to slices from grey and white rabbit brain matter. The respiration, consumption of glucose, formation of lactate and pyruvate, water content, size of the extracellular space, and total and intracellular sodium and potassium concentrations were determined and calculated.0.5 and 1 mM NPS stimulated the glycolytic glucose breakdown, and inhibited the respiration of grey and white slices. The respiration of white matter slices was stimulated by 0.05 and 0.01 mM NPS.The total and intracellular potassium concentrations in slices from grey and white matter were lowered markedly by 1 mM NPS. The total and the intracellular sodium concentrations in grey brain matter slices became higher in the presence of 1 mM NPS. A warning is given against uncritical clinical use of higher concentrations of NPS.Part of the Dissertation, Med. Fakultät Homburg/Saar, 1979.     

Corticosteroid therapy of experimental tumour oedema

Summary Experimental brain tumours were produced in cats by stereotactic implantation of 4 million suspended cells of a rat glioma clone into the internal capsule. Three weeks after implantation a spherical tumour developed with a diameter of up to 10 mm which was surrounded by vasogenic white matter oedema. In untreated animals water content in the peritumoural white matter increased from 69.1 ± 0.9 to 80.0 ± 0.8 ml/100 g w. w., and regional blood flow reciprocally decreased from 32.2. ± 5.6 to 18.9 ± 0.05 ml/100 g/min. A single injection of a crystalline suspension of 10 mg/kg dexamethasone given intramuscularly one week before the animals were killed, led to a significant amelioration of brain oedema. Peritumoural white matter water content decreased to 73.0 ± 0.5 ml/100 g w. w. and blood flow rose to 35.7 ± 2.8 ml/100 g/min. These changes were accompanied by parallel shifts of electrolyte content but they did not correlate with EEG activity, as assessed by Fourier frequency analysis. Corticosteroids did not prevent extravasation of peroxidase or Evans blue across the tumour vessels. The beneficial effect, therefore, is attributed to either an acceleration of resorption or an inhibition of the spread of oedema from the tumour into the peritumoural brain tissue.     

Histopathology of cystic cavities in the cerebral white matter of HTX rats with inherited hydrocephalus.

To investigate the mechanism of cystic cavity formation in the cerebral white matter of the HTX rat, a strain with inherited hydrocephalus, the authors carried out a histopathological study of the brain in pups from birth to postnatal day (P) 26. Cystic cavities were formed in the cerebral white matter on the lateral side of the basal ganglia of all HTX rats with moderate to severe ventricular dilatation and, additionally, in the white matter beneath the paramedian cortex in advanced cases at P10-26. In the initial stage of cyst formation, disarrangement of the ependymal cell layer and spongy alteration of the white matter took place in pups between P1 and P7. The ependymal disarrangement involved disruption and flattening of the ependymal cells, which were often devoid of microvilli, cilia and intercellular junctional complexes. The spongy state was due to expansion of the extracellular space and multiple microcyst formation with fluid accumulation in the early stage, and large cystic cavities in the advanced stage. The cerebrospinal fluid (CSF) in the ventricle communicated with the fluid in the cystic cavities via the disarranged ependymal cell layer. The ependymal damage was more prominent at the lateral wall of the posterior horn than at the anterior horn of the lateral ventricles. These cavities were demarcated by reactive glial cells in the advanced stage. However, the cavities enlarged in accordance with progressive dilatation of the lateral ventricles during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)