Strahlenspätveränderungen nach kleinvolumiger radiochirurgischer Bestrahlung des Rattenhirns Messung des lokalen zerebralen Blutflusses und histopathologische Untersuchungen

BACKGROUND: The goal of this study was to investigate late effects following stereotactic single fraction and small volume irradiation on cerebral blood flow and histologic alterations in the rat brain parenchyma. MATERIAL AND METHODS: 66 Copenhagen rats, separated into eleven groups of six animals each received single doses of 20, 30, 40, 50 and 100 Gy using a 15 MV linear accelerator. Six rats served as controls. Two cylindrical collimators of 2 mm and 3 mm aperture were used. The diameters of the spherical 80% isodose were 3.7 and 4.7 mm, respectively (Table 1). Irradiation was applied to a predefined area in the right frontal lobe. 19 months after irradiation local cerebral blood flow (LCBF) was measured by the autoradiographic method in one animal of each dose group between 20 and 50 Gy. 9 and 19 months after irradiation, half of the animals of each group were sacrificed for brain histology. All animals irradiated with 100 Gy were sacrificed 7 months after irradiation. RESULTS: An increase of local cerebral blood flow was measured in brain structures within the 80% isodose in animals irradiated with 50 Gy (Figure 3) compared to the contralateral hemisphere. Measurements close to necrotic areas showed a strong decrease of local cerebral blood flow (Figure 1). A volume increase of the irradiated hemisphere was seen after 19 months (Figure 2). The histologic examination after 19 months showed necrotic areas in the 30-50 Gy groups (Figure 4b) but not in the 20 Gy groups (Figure 4c). The animals who received 100 Gy demonstrated brain necrosis within 9 months after irradiation (Figure 4a). At both points in time the groups irradiated with the 3-mm collimator showed more pronounced histomorphologic and functional changes compared to the groups irradiated with the 2-mm collimator. CONCLUSION: Alterations of the local cerebral blood flow were measured as a late effect after single dose irradiation. The alterations of the local cerebral blood flow could be explained by the histomorphologic changes of the blood vessels. Using a semi-quantitative classification a dose, time and volume dependence for the endpoint radionecrosis was seen.     

帕金森病动物模型的99Tcm-TRODAT-1显像研究

目的　研究帕金森病 (PD)模型猴99Tcm 2 β [N ,N’ 双 (2 巯乙基 )乙撑二胺基 ]甲基 ,3β (4 氯苯基 )托烷 (TRODAT 1)显像与局部脑血流量 (rCBF)及结构改变间的关系 ,探讨99Tcm TRODAT 1显像早期诊断PD的价值。方法　对 5只猴在制成单侧PD模型前后分别进行99Tcm TRODAT 1和rCBF显像 ,并对 2只PD模型猴进行MRI。结果　99Tcm TRODAT 1显像示 ,正常猴 3h纹状体 小脑的放射性比值为 1.48,PD模型猴健侧纹状体 小脑放射性比值为 1 42 ,损毁侧为 0 .96。PD模型猴双侧纹状体血流灌注与正常猴比较无差别 ,MRI未发现形态及结构改变。结论　99Tcm TRODAT 1能特异性地与多巴胺转运体 (DAT)结合 ,可望用于PD的早期诊断     

Effect of postradiation bleeding on proliferative activity of cells in small intestine crypts of rats.

The effect of postradiation bleeding on the dynamics of duodenal crypts' cells proliferation in rats was studied. The animals, females, three months old, weighing 170 or 180 g, were exposed to radiation of 800 R (115 R/min) and immediately after irradiation were bled by cardiac puncture to 50% of total blood volume. Proliferative activity of duodenal epithelium cells was monitored for a period of five days after irradiation. For control purposes normal, irradiated and only bled animals were used. The results demonstrated that although there are no significant differences in proliferative activity of duodenal epithelium cells in irradiated and bled animals and only irradiated animals, the postradiation reparative processes in irradiated and bled animals is considerably more stable. It is considered that bleeding itself by its hypoxic activity reduced the sensitivity of epithelium to the dose of radiation used. On the other hand, bleeding removed the damaging agents which appear after total body irradiation.     

Changes in regional cerebral blood flow in irradiated regions and normal brain after stereotactic radiosurgery

OBJECTIVE: To elucidate the radiation effect on the normal brain after stereotactic radiosurgery (SRS), we evaluated the change in regional cerebral blood flow (CBF) in targeted and extra-targeted areas according to the radiation dose given. METHODS: Thirteen patients who underwent SRS for brain tumors or arteriovenous malformations were included in this study. Maximum radiation doses to the lesion ranged from 24 to 37 Gy. Mean and regional CBF were measured by 99mTc-HMPAO scintigraphy with graphic analysis, performed at before, 2 weeks and 3 months (5 patients) after SRS. Under the co-registration with the CT with superimposed isodose distribution, ROIs were set on target (37-20 Gy), peri-target (20-5 Gy) and out-of-field (5-2 Gy and less than 2 Gy) areas on the quantitative SPECT images. RESULTS: Significant reductions in mean CBF (by 7%) and regional CBF in the peri-target areas (by 5-7%) and out-of-field areas (by 6-22%) were recognized at 2 weeks and 3 months after SRS. Regional CBF in the target and peri-target areas did not significantly change, presumably because there was little or no normal tissue in these areas. CONCLUSION: These results suggest that subclinical regional CBF reduction occurs after SRS in the normal brain in out-of-field of radiation.     

Frequency of micronuclei in lymphocytes from in vitro gamma-irradiated human peripheral blood

The micronucleus assay technique of H?gstedt was used in studies of time-response and dose-response to single acute 137Cs gamma-ray exposure of human blood in vitro. Time-response following a 2 Gy dose was examined at postradiation times 48, 72, 77, 96, and 120 hours; micronucleated lymphocyte frequencies peaked at 77 hours, dropping insignificantly at 96 hours. Unirradiated control blood showed relatively low values peaking at 77 hours. The dose-response data obtained at 77 hours with single irradiations at dose levels 0.5, 1, 2, or 4 Gy were a good fit to a linear-quadratic relationship: Y = 0.5 + 1.17D + 0.338D2 (Y, micronucleated lymphocyte percentage; D, radiation dose in Gy). The evidence obtained and the rapidity and case of assay performance give us ground to assume that the method is applicable as a initial screening test to estimate the cytogenetic effect of human exposure in vivo.     

Changes in cerebral blood flow induced by balloon test occlusion of the internal carotid artery under hypotension

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study has proved to be a sensitive test for prediction of the outcome of permanent vessel occlusion. In this study, we evaluated the acute changes in regional CBF during BTO under hypotension in order to examine the possible risk of cerebral ischaemia after surgical treatment. Eleven patients in whom surgical carotid sacrifice was planned underwent BTO combined with CBF studies using technetium-99m hexamethyl-propylene amine oxime single-photon emission tomography under hypotension by decreasing the systemic blood pressure by about 50 mm Hg using a ganglion blocking agent. All patients showed a mild to severe decrease in CBF in the ipsilateral ICA territory relative to the contralateral side. A decrease in CBF of greater than 20% was observed in nine patients (82%), and two of them showed a decrease exceeding 40%. However, no ischaemic symptoms were demonstrated during scanning with hypotensive BTO. Our results suggest that in many patients with negative normotensive BTO, a considerable reduction in CBF would occur during hypotension. This procedure may predict a possible risk of hypotensive accident during and/or after surgery.     

Validation studies for brain blood flow assessment by radioxenon tomography

A tomographic technique has been used recently for cerebral blood flow measurements with inhaled radioxenon. Based on experiments in a specially developed dynamic phantom and on studies in primates in vivo, we have analyzed the validity of this method for measurements of both regional and total blood flow in the brain. We have also examined the errors introduced into flow computations as a function of changes in such parameters as: rate of xenon input, size of region of interest, magnitude of regional flow rates, and inter-regional flow differences. Our findings indicate a reasonable degree of accuracy for flow measurements in gray matter regions that are 3 cm in diameter or larger, while white matter blood flow is generally overestimated. The accuracy for regional flow assessments degrades as a function of: diminishing region size, increasing inter-regional flow differences, and flow rates in excess of 100 ml/100 g/min. Measurements for brain regions 2 cm or smaller in diameter can be in error by 25-50% as a result of partial volume averaging. Although the technique is not ideal for accurate flow measurements in small regions of the brain, it nevertheless provides a convenient means of assessing perfusion in major vascular territories of the brain in routine clinical applications.     

Statistical parametric mapping in brain single photon computed emission tomography after carbon monoxide intoxication

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml x 100 g(-1) x min(-1) with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.     

方格星虫多糖对小鼠抗辐射能力的影响

目的 探讨方格星虫(sipunculus nudus)多糖对辐射损伤小鼠的保护作用.方法 C57小鼠给予方格星虫多糖15 d后,用60Co γ射线进行8 Gy一次性全身照射,辐照后继续给药,观察照后30 d生存情况和照后3 d外周血细胞计数、血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量.结果 方格星虫多糖能提高受照小鼠30 d存活率,延长其平均生存时间,提高机体的抗氧化能力.结论 方格星虫多糖对辐射损伤小鼠具有明显的保护作用,能提高小鼠的抗辐射能力.

Abstract：

Objective To investigate the protective effect of polysaccharides from sipunculus nudus on radiation injury in mice.Methods C57 mice were lavaged with polysaccharides from sipunculus nudus for 15 days and then had whole-body radiation exposure to 60Co γ (8 Gy). After that, the mice continued to be lavaged with polysaccharides once a day. Observations were made to see the survival of the treated animals 30 days after exposure, and WBC, SOD and MDA levels in the serum were monitored 3 days after radiation.Results Polysaccharides from sipunculus nudus could increase the 30-day survival rate and prolong the average survival time of the radiated mice. Polysaccharides from sipunculus nudus could also improve anti-oxygenation of the radiated mice.Conclusions Polysaccharides from sipunculus nudus had obvious protective effect on radiated mice and improved the anti-radiation capacity of mice     

Histamine prevents functional and morphological alterations of submandibular glands induced by ionising radiation

Purpose:?Xerostomia is a common, disturbing side-effect among patients treated with radiotherapy for head-and-neck cancer. The aim of the present work was to investigate whether histamine could prevent salivary gland dysfunction and histological alterations exerted by ionising radiation.

Materials and methods:?Forty-eight rats were divided into four groups. Histamine and histamine-5 Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24?h before irradiation. Histamine-5 Gy and untreated-5 Gy groups were irradiated with a single dose of whole-body Cesium-137 irradiation. Control and untreated-5 Gy groups were given daily saline injections. Three days post irradiation metacholine-induced salivary secretion was measured or animals were sacrificed and submandibular gland (SMG) removed, stained and histological characteristics were evaluated. Proliferation and apoptosis markers were studied by immunohistochemistry.

Results:?Radiation decreased salivary secretion by 40% in comparison to untreated rats, which was associated with loss of SMG mass, alteration of epithelial architecture, partial loss of secretor granular material, diminished proliferation and a remarkable apoptotic response. In contrast, histamine completely reversed the reduced salivation induced by radiation, conserved glandular mass with normal appearance and preserved the structural organisation of secretor granules. Radiation-induced toxicity is prevented by histamine essentially by suppressing apoptosis of ductal and acinar cells, reducing the number of apoptotic cells per field (19.0?±?3.8 vs. 106.0?±?12.0 in untreated animals, P?<?0.001), and also by preventing the radiation-induced decrease in cell proliferation.

Conclusions:?Histamine prevents morphological and functional radiation-induced damage on SMG, representing a potential radioprotector for treatment of patients undergoing radiotherapy for head and neck malignancies.     

Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI

Purpose:

To determine whether quantitative arterial spin labeling (ASL) can be used to evaluate regional cerebral blood flow in Parkinson's disease with dementia (PDD) and without dementia (PD).

Materials and Methods:

Thirty‐five PD patients, 11 PDD patients, and 35 normal controls were scanned by using a quantitative ASL method with a 3 Tesla MRI unit. Regional cerebral blood flow was compared in the posterior cortex using region‐of‐interest analysis.

Results:

PD and PDD patients showed lower regional cerebral blood flow in the posterior cortex than normal controls (P = 0.002 and P = 0.001, respectively, analysis of variance with a Bonferroni post hoc test).

Conclusion:

This is the first study to detect hypoperfusion in the posterior cortex in PD and PDD patients using ASL perfusion MRI. Because ASL perfusion MRI is completely noninvasive and can, therefore, safely be used for repeated assessments, this method can be used to monitor treatment effects or disease progression in PD. J. Magn. Reson. Imaging 2011;33:803–807. © 2011 Wiley‐Liss, Inc.     

Voltammetric measurement of blood nitric oxide in irradiated rats

PURPOSE. To investigate the effect of blood nitric oxide (NO) as a mediator of the neurovascular syndrome in rats following gamma-irradiation. MATERIAL AND METHODS: Using a voltametric method together with a carbon fibre based sensor, NO measurements were carried out in sham-irradiated and irradiated animals either in blood from the abdominal aorta or in blood samples from the heart. RESULTS: In in vitro conditions, properties of the probe were not altered by the ionizing radiation. Significant increases of +17% and +25.6% were observed in the voltametric signal height at 90 min and 24 h respectively after a 15 Gy gamma-ray exposure. These effects were followed on days 3 and 4 by a progressive decrease in the signal height of 7% and 18% respectively. Dose-effect relationships were observed at 90 min and 24 h after exposure to gamma-rays in the range of 3-15 Gy. Finally, the NO dependence on the measured voltametric signal was controlled by using inhibitors of the NO synthase (NOS) and by performing nitrate assays. CONCLUSIONS: Specific blood NO voltametric measurements are possible. Functional changes associated with NO after gamma-ray exposure are discussed.     

A study of the acute effect of smoking on cerebral blood flow using 99mTc-ECD SPET

Cigarette smoking is known to be associated with atherosclerosis, is an important risk factor for stroke and has other serious effects. The aim of this study was to evaluate the acute effect of cigarette smoking on cerebral blood flow using statistical parametric mapping (SPM). Ten healthy volunteers with a smoking habit were studied using technetium-99m-labelled ethylcysteinate dimer single-photon emission tomography (SPET). We evaluated the regional cerebral blood flow under the smoking and resting states. The regional cerebral blood flow on smoking-activated SPET was significantly decreased in the whole brain as compared with that on resting SPET. Our findings therefore suggest that one of the acute effects of cigarette smoking is to induce a diffuse decrease in cerebral blood flow.     

The preparation of 11C-labelled fluoromethane for the study of regional cerebral blood flow using positron emission tomography

Fluoromethane, previously labelled with 18F and used as a tracer in the measurement of regional cerebral blood flow, was 11C-labelled by the reaction of 11C-methyl iodide with tetraethylammonium fluoride. Sufficient quantities of radiotracer were prepared with a minimum amount of handling from 15 min target irradiations in the 14N(p, alpha)11C reaction. Total synthesis time was 25 min from end-of-bombardment, allowing serial blood flow measurements 30 min apart. The use of 11C-fluoromethane as a cerebral blood flow tracer in positron emission tomography is discussed.     

Temporal and dose characteristics of nucleic acids reduction in the leucocytes of irradiated mice

The kinetics of the changes of the nucleic acids level in the leucocytes of mice, as well as the leucocyte count were traced over a 30 day period, after a 2 Gy gamma irradiation. The changes of these parameters, which are dose-bound, were examined at the 24th and 72nd hour after irradiation with doses, belonging to the 0,1 to 6,0 Gy dose range. During the progress of the radiation damage the changes in the nucleic acids show a phase character that reaches its minimum on day 3 postradiation, with a recovery about day 30. The relation nucleic acids level/radiation dose is described with a logarithmic function. With both time intervals the nucleic acids level decreases with the logarithm of the dose, the reduction in the nucleic acids concentration being more clearly marked on day 3 postradiation. The rate of the nucleic acids level change is not adequate to that of the leucocyte count.     

Regulation of cerebral blood flow during exercise

Constant cerebral blood flow (CBF) is vital to human survival. Originally thought to receive steady blood flow, the brain has shown to experience increases in blood flow during exercise. Although increases have not consistently been documented, the overwhelming evidence supporting an increase may be a result of an increase in brain metabolism. While an increase in metabolism may be the underlying causative factor for the increase in CBF during exercise, there are many modulating variables. Arterial blood gas tensions, most specifically the partial pressure of carbon dioxide, strongly regulate CBF by affecting cerebral vessel diameter through changes in pH, while carbon dioxide reactivity increases from rest to exercise. Muscle mechanoreceptors may contribute to the initial increase in CBF at the onset of exercise, after which exercise-induced hyperventilation tends to decrease flow by pial vessel vasoconstriction. Although elite athletes may benefit from hyperoxia during intense exercise, cerebral tissue is well protected during exercise, and cerebral oxygenation does not appear to pose a limiting factor to exercise performance. The role of arterial blood pressure is important to the increase in CBF during exercise; however, during times of acute hypotension such as during diastole at high-intensity exercise or post-exercise hypotension, cerebral autoregulation may be impaired. The impairment of an increase in cardiac output during exercise with a large muscle mass similarly impairs the increase in CBF velocity, suggesting that cardiac output may play a key role in the CBF response to exercise. Glucose uptake and CBF do not appear to be related; however, there is growing evidence to suggest that lactate is used as a substrate when glucose levels are low. Traditionally thought to have no influence, neural innervation appears to be a protective mechanism to large increases in cardiac output. Changes in middle cerebral arterial velocity are independent of changes in muscle sympathetic nerve activity, suggesting that sympathetic activity does not alter medium-sized arteries (middle cerebral artery).CBF does not remain steady, as seen by apparent increases during exercise, which is accomplished by a multi-factorial system, operating in a way that does not pose any clear danger to cerebral tissue during exercise under normal circumstances.     

Cerebral blood flow evaluation of arteriovenous malformations with stable xenon CT

Twenty patients with supratentorial arteriovenous malformations (AVMs) were evaluated with angiography, conventional CT, and stable xenon CT to determine cerebral blood flow. Contralateral and ipsilateral regions of interest relative to the AVM were evaluated from cerebral blood flow maps and correlated with angiography. A significant decrease in cerebral blood flow was observed in the ipsilateral cortical gray matter adjacent to the AVM relative to the corresponding contralateral cortex (mean difference = 9.52 ml/100 g/min, p less than .01). The larger AVMs (greater than 8 cm3) were associated with a more marked decrease with a mean difference of 12.22 ml/100 g/min (p less than .02). Regions of interest were also chosen on the basis of angiographic findings, which suggested areas of decreased flow. Comparison of these areas with analogous contralateral areas also showed a significant decline in cerebral blood flow (mean difference = 8.86 ml/100 g/min); this decline was greater with larger AVMs (volume greater than 8 cm3), which had a mean difference of 11.38 ml/100 g/min (p less than .01). Our correlative study enabled us to pinpoint the regions most likely to have reduced flow from an AVM.     

Changes in baseline cerebral blood flow in humans do not influence regional cerebral blood flow response to photic stimulation

The effect of changes in baseline regional cerebral blood flow (rCBF) values on the cerebral blood flow response during neuronal activation was studied with functional magnetic resonance imaging (fMRI). Using a breath-holding challenge as a hypercapnic stimulus, rCBF alterations during photic stimulation under normo- and hypercapnia were determined in nine volunteers. With breath-holding, baseline rCBF in areas corresponding to the visual cortex significantly increased from 54 +/- 5 ml/100 g/min to 85 +/- 9 ml/100 g/min (P < 0.001). Despite this significant change in baseline flow values, the rCBF increase during visual stimulation was very similar under normo- and hypercapnic conditions (28 +/- 8 ml/100 g/min versus 26 +/- 8 ml/100 g/min, respectively). This study supports the notion that within wide physiologic variations, task-induced cerebral blood flow changes are independent of baseline rCBF values.     

Level of Flt3-ligand in plasma: a possible new bio-indicator for radiation-induced aplasia

Purpose : To follow plasma Flt3-ligand (FL) concentrations in irradiated animals in order to evaluate it as an indicator of bone marrow damage for the management of accidental radiation-induced aplasia. Materials and methods : Non-human primates were irradiated at doses ranging from 2 to 8 Gy, using whole- or partial-body irradiation. Plasma FL concentrations and blood cell counts were determined daily. Results : FL concentrations increased as early as day 2 after irradiation, whatever the irradiation dose. Increase in plasma FL concentration on day 5 post-irradiation was correlated with radiation dose and with the severity of radiation-induced aplasia. During the course of aplasia, FL concentrations in plasma were inversely correlated with neutrophil counts. A peak in FL concentration appeared before the neutrophil nadir, and the subsequent decrease in FL concentration was correlated with the recovery of blood-cell populations. Conclusions : Monitoring plasma FL concentration can be used as an indicator of radiation-induced marrow aplasia, and this may be of use in accidental irradiation situations.     

Xenon/CT blood flow mapping of the kidney and liver

A noninvasive technique for measuring blood flow by xenon-enhanced X-ray transmission CT has been developed and reported quite extensively in recent years. In this method nonradioactive xenon gas is inhaled, and the temporal changes in radiographic enhancement produced by the inhalation are measured by sequential CT. Time-dependent xenon concentration within various tissue segments is used to derive local blood flow maps. The method has been amply discussed in relation to assessment of local cerebral blood flow. Its application to other body organs is explored in this paper, in which results from six preliminary blood flow studies in the liver and kidneys of nonhuman primates are reported. Blood flow in renal cortex ranged from 150 to 280 ml/100 cc/min and hepatic tissue perfusion from 80 to 120 ml/100 cc/min. The advantages and limitations of the method in such applications are discussed.