Blood-brain barrier disruption by low-frequency ultrasound.
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Blood-Brain Barrier↗
Biomedical subjects
Tibo Gerriets
Publications and source records attributed to Tibo Gerriets.
Brain edema and intracerebral necrosis caused by transcranial low-frequency 20-kHz ultrasound: a safety study in rats.
BACKGROUND AND PURPOSE: Ultrasound-accelerated thrombolysis is a promising approach toward acute stroke treatment. In previous in vitro studies, we demonstrated enhanced thrombus destruction induced by 20-kHz ultrasound. However, little is known about biological interactions of low-frequency ultrasound with brain tissue. The aim of this in vivo MRI study was to assess safety aspects of transcranial low-frequency ultrasound in rats. METHODS: The cranium of 33 male Wistar rats was sonificated for 20 minutes (20-kHz continuous wave). Power output was varied between 0 and 2.6 W/cm2. Tympanal and rectal temperature was monitored. Diffusion-weighted imaging and T2-weighted imaging was performed before and 4 hours, 24 hours, and 5 days after sonification. Apparent diffusion coefficients (ADCs) and T2 relaxation time (T2-RT) were measured in regions of interest in the cortex and the basal ganglia. The animals were euthanized for histological evaluation thereafter. RESULTS: Tympanal temperature increased significantly during insonation with 1.1 and 2.6 W/cm2. ADCs decreased significantly at 0.5 and 1.1 W/cm2, indicating cytotoxic edema. T2-RT increased significantly in the 0.5 and 1.1 W/cm2 group, consistent with vasogenic edema. No changes were detectable in the low-power output group (0.2 W/cm2). After sonification with 2.6 W/cm2, a significant loss of neurons could be detected on histopathology. Furthermore, 3 animals developed circumscript cortical lesions that could be identified as parenchymal necrosis. CONCLUSIONS: Low-frequency ultrasound caused vasogenic and cytotoxic brain edema and intracerebral necrosis in a dose-dependent fashion. This study indicates therapeutic low-frequency ultrasound as being potentially harmful and underlines the necessity of careful evaluation in further animal models.
Animals↗
EmboDop: insufficient automatic microemboli identification.
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Automation↗
MRI for short-term follow-up of acute pulmonary embolism. Assessment of thrombus appearance and pulmonary perfusion: a feasibility study.
Tha aim of this study was to demonstrate the feasibility of MRI for short-term follow-up examinations in patients with acute pulmonary embolism (PE), and to assess temporal changes of pulmonary perfusion and thrombus characteristics that may be helpful in determining thrombus age. Thirty-three patients (15 female, 18 male, mean age 59.4 years) with acute PE were examined initially and 1 week later using both 16-row computed tomography (CT) and MRI with magnetic resonance angiography (MRA), real-time MRI and magnetic resonance (MR) pulmonary perfusion imaging. MRA and MR pulmonary perfusion used contrast-enhanced 3D flash sequences, and real-time MRI used true fast imaging with steady-state precession sequences (repetition time/echo time 3.1/1.5, bandwidth 975 Hz, 256 matrix size, acquisition time 0.4 s per image) in three orthogonal planes. Follow-up examinations were feasible for all patients. Diagnosis of PE was concordant between MRI and CT in all patients. The signal intensity of embolic material increased after 1 week for real-time MRI [132+/-5 vs. 232+/-22 (standard error of the mean), p<0.001], but not significantly for MRA. MR pulmonary perfusion of areas affected by PE increased (area under the curve initially 9.6+/-7.4, at follow-up 40.7+/-7.6, p<0.001). A decreasing time-to-peak in normal lung areas (15.7+/-0.96 and 13.2+/-0.55, respectively, p<0.05) indicated systemic circulatory effects of PE, and subsiding pulmonary artery obstruction improved arterial inflow for the entire lung. Follow-up examinations of patients with acute PE are feasible with MRI, and a relation between thrombus appearance and thrombus age can be implied.
Adult↗
Is heparin treatment the optimal management for cerebral venous thrombosis? Effect of abciximab, recombinant tissue plasminogen activator, and enoxaparin in experimentally induced superior sagittal sinus thrombosis.
BACKGROUND: Based on a newly developed model of reversible superior sagittal sinus (SSS) thrombosis in the rat, we investigated the effect of thrombolytic and anticoagulant treatment on recanalization, brain parenchymal changes, and motor deficits. METHODS: Thrombosis of the SSS was induced by topical application of ferric chloride. Occlusion was confirmed by magnetic resonance angiography (MRA). Six hours after operation, single treatment with 10 mg recombinant tissue plasminogen activator (rtPA)/kg and 6 mg abciximab/kg or subcutaneous injection of 450 IU/kg enoxaparin twice daily was started, each group containing 10 rats. Follow-up MRI with T2- and diffusion-weighted images was performed on the first, second, and seventh postoperative day. RESULTS: Control and enoxaparin-treated animals developed diffuse brain edema without infarction or intracerebral bleeding. This was indicated by an increase of T2 relaxation time and a decrease of the apparent diffusion coefficient in the parasagittal and lateral cortex. In these groups, the degree of recanalization after 7 days was comparable (48% versus 52%). Enoxaparin-treated animals showed significant amelioration of functional deficits. Clinical outcome was best in the abciximab-treated group, with a residual sinus occlusion of 36% after 1 week. Highest recanalization was achieved by lysis with rtPA (85%). CONCLUSIONS: Enoxaparin treatment in rats with cerebral venous thrombosis significantly influences clinical outcome. However, it has no effect on recanalization. GPIIb/IIIa antagonists and rtPA accelerate thrombolysis. They may represent an alternative in treatment of cerebral venous thrombosis.
Abciximab↗
Cerebral venous thrombosis: an all or nothing disease? Prognostic factors and long-term outcome.
BACKGROUND: There is insufficient data on short- and especially long-term prognosis of cerebral venous thrombosis (CVT). METHODS: In 79 consecutive patients, we analyzed factors for acute death and functional outcome at hospital discharge and after 6 months as well as long-term prognosis >/=12 months. Neurological deficits were graded on the National Institute of Health Stroke Scale (NIHSS), functional outcome on the modified Rankin Scale (mRS). Primary outcome was defined as mRS >/= 3 at 6 months, secondary outcomes were death during hospital treatment and number as well as type of complications during follow-up >/=12 months after hospital discharge. Forty-two patients were recruited prospectively, 37 were identified by chart review. Information on outcome was based on neurological examinations at our outpatient clinic. RESULTS: Factors significantly related to acute death were age, the NIHSS on admission, more than two seizures despite antiepileptic treatment, venous infarct, and hemorrhagic transformation of the venous infarct. Primary outcome after 6 months in 74 patients was excellent with 73% of patients reaching a mRS 0-1, 4% a mRS of 2, and 23% a mRS 3-6, including 12 deaths in the acute stage of illness. Factors significantly related to a mRS >/= 3 at 6 months in a logistic regression analysis were age and items 1a-c of the NIHSS on admission related to consciousness. Fifty-eight surviving patients had a follow-up >/= 12 months (median: 31; mean: 52 +/- 61 months). Most frequent complication on long-term follow-up was epilepsy in nine patients and recurrent venous thrombosis in seven patients. CONCLUSIONS: When the acute stage of illness has been survived, CVT has a good prognosis unlike arterial ischemic stroke.
Acute Disease↗
A new model of reversible sinus sagittalis superior thrombosis in the rat: magnetic resonance imaging changes.
OBJECTIVE: The causes of cerebral sinus and vein occlusion and the accompanying parenchymal changes remain largely unexplained. The clinical variability and low incidence of the disease complicate systematic clinical investigations. Animal studies are indispensable; however, existing animal models of sinus thrombosis do not allow for long-term follow-up studies and are not suitable for pharmacological recanalization because sinus thrombosis is induced by ligation and injection of thrombogenic substances and does not resemble sinus thrombosis in humans. METHODS: We induced thrombosis of the superior sagittal sinus (SSS) by careful topical application of ferric chloride onto the SSS of rats, leading to highly reproducible occlusions. Magnetic resonance imaging was performed immediately after initiation of thrombosis and on postoperative Days 1, 2, and 7. Diffusion- and T2-weighted images allowed for calculation of the apparent diffusion coefficient and T2 relaxation time. Vascular status was assessed by venous magnetic resonance angiography. Neurological deficits were assessed with the rotarod test. RESULTS: Seven days after induction of thrombosis, partial recanalization (50.7% of the SSS remaining occluded) was accompanied by a resolution of early generalized changes of the apparent diffusion coefficient and of T2 relaxation time, indicating edema of the entire brain parenchyma. Compared with sham-treated animals, clinical skills in the experimental group improved over time, which was statistically independent from the degree of recanalization. Histopathological analysis revealed no signs of cerebral infarction. CONCLUSION: This is the first animal model of SSS thrombosis that offers the possibility to investigate pathophysiological aspects of the disease as well as the influence of therapy on the nature of disease progression.
Animals↗
Reversible MR imaging abnormalities following cerebral venous thrombosis.
BACKGROUND AND PURPOSE: Although rare, cerebral venous thrombosis (CVT) is being diagnosed more frequently owing to improved imaging techniques. The venous infarcts caused by CVT in 50% of patients are largely reversible and differ from arterial stroke. Our purpose was to study the time-dependent changes of venous infarcts on MR images and to define the variables that influence lesion volume in humans. METHODS: MR images and venous angiograms were evaluated in 15 consecutive patients with venous infarcts due to CVT of sinus, cortical, or internal veins. All patients were treated with intravenous dose-adjusted heparin followed by oral anticoagulation for 12 months. Reduction of signal intensity changes on T1- and T2-weighted images was correlated to the degree of recanalization, age, initial absolute lesion size, and hemorrhage. RESULTS: Within the first 30 days, we found a significant correlation between the volume of the lesion on T1-weighted images and recanalization. However, early recanalization did not influence the final lesion volume after 12 months. Eleven patients showed complete resolution of changes on T1- and T2-weighted images. Age of the patients influenced initial absolute volume of brain damage. CONCLUSION: In venous stroke, even large parenchymal changes can resolve completely independent from recanalization of the thrombosed veins and sinuses. A plausible hypothesis is that venous infarcts largely consist of a persistent edema and that the lesion volume is influenced by the development of collateral veins. However, further investigations are necessary to understand the underlying abnormal mechanisms.
Administration, Oral↗
Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography.
BACKGROUND AND PURPOSE: Investigating focal cerebral ischemia requires animal models that are relevant to human stroke. Complications and side effects are common among these models. The present study describes potential pitfalls in 3 techniques for middle cerebral artery occlusion (MCAO) in rats using magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). METHODS: Rats were subjected to temporary MCAO for 90 minutes using the suture technique (group I; n=10) or to permanent MCAO using the suture technique (group II; n=10) or the macrosphere technique (group III; n=10). Clinical evaluation was performed after 3 hours and 24 hours. After 24 hours, animals underwent MRI and MRA to determine lesion size and the intracranial vascular status. RESULTS: Hemispheric lesion volume was significantly smaller in group I (14.6%) compared with groups II (35.2%; P<0.01) and III (21.3%; P<0.05). Two animals (1 each in group II and III) did not demonstrate neurological deficits and had no lesion on MRI and a patent MCA main stem on MRA. Subarachnoid hemorrhage was detected in 2 animals (1 each in group I and II). MRA indicated a patent MCA main stem in 2 animals (group II), although both rats displayed neurological deficits. Hypothalamic infarction with subsequent pathological hyperthermia was detected in all animals in group II and in 1 rat in group III. CONCLUSIONS: Model failures occurred frequently in all groups. MRI and MRA helps to identify animals that need to be excluded from experimental stroke studies.
Animals↗
Comments on 'computed tomographic parameters predicting fatal outcome in large middle cerebral artery infarction'.
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Humans↗
Diffusion-weighted magnetic resonance imaging and neurobiochemical markers after aortic valve replacement: implications for future neuroprotective trials?
BACKGROUND AND PURPOSE: Cardiac surgery carries a high risk of neurological complications; therefore, these patients would be an appropriate target population for neuroprotective strategies. In this study, we evaluated postoperative diffusion-weighted imaging (DWI) as a potential surrogate marker for brain embolism and its relationship to neurobiochemical markers of brain injury. METHODS: Of a total of 45 consecutive patients undergoing aortic valve replacement, 37 completed preoperative and postoperative MRI. At the time of the MRI studies, serum S100beta and neuron-specific enolase concentrations were determined. Preexisting T2 and postoperative DWI lesion volumes were quantified. All patients had a blinded neurological examination before and after operation. RESULTS: New perioperative DWI lesions were present in 14 patients (38%), of whom only 3 developed focal neurological deficits. Eighteen small lesions were found in the white matter or vascular border zones in all but 2 patients with territorial stroke. The appearance of new DWI lesions correlated with age, pre-existing T2 lesion volume, and postoperative S100beta concentrations on days 2 to 4 after surgery. In a forward stepwise canonical discrimination model, only T2 lesion volume was selected as a relevant variable. CONCLUSIONS: The incidence of postoperative DWI lesions in aortic valve replacement is high, and a suitable marker for neuroprotective trials would be a reduction in the number of such lesions. The volume of preexisting T2 lesions is related to the development of perioperative DWI lesions.
Aged↗
Influence of recanalization on outcome in dural sinus thrombosis: a prospective study.
BACKGROUND AND PURPOSE: Recanalization in dural sinus thrombosis (DST) has been observed previously; however, systematic prospective data are lacking. The influence of recanalization on DST outcome has not yet been thoroughly evaluated. METHODS: Thirty-seven consecutive patients with DST were prospectively examined. Neurological deficits were graded with the National Institutes of Health Stroke Scale (NIHSS) on hospital admission and discharge. Functional outcome was assessed with the modified Rankin Scale (mRS) on hospital discharge and after 12 months. All patients were treated with intravenous heparin in the acute stage of illness, followed by oral anticoagulation for 12 months. Imaging follow-up with MR angiography and, in a few cases, with CT or conventional angiography was performed on hospital discharge and after 6 and 12 months. RESULTS: Twelve-month functional outcome was excellent in 89% of patients with an mRS of 0 or 1. A recanalization rate of 60% was already observed on hospital discharge (22+/-6 days); thereafter, recanalization rates increased insignificantly. Early recanalization was not related to NIHSS score on hospital discharge or an mRS of 0 on discharge or after 12 months. CONCLUSIONS: We found a high frequency of early recanalization but without influence on clinical outcome parameters. Frequent imaging follow-ups in DST are not useful because they provide no information on patient outcome.
Adult↗
Strategies for the reduction of cerebral microembolism during transmyocardial laser revascularization.
BACKGROUND AND OBJECTIVES: During transmyocardial laser revascularization (TMLR), multiple microembolic signals (MES) can be detected in cerebral arteries. We sought to characterize composition and clinical relevance of these MES and to evaluate strategies to reduce cerebral microembolization during TMLR. STUDY DESIGN/MATERIALS AND METHODS: TMLR was performed in pigs. Laser energy was set to 4-10 J (group A) or 80 J (group B). Oxygen concentration was varied between 21 and 100%. MES were recorded in the ophthalmic artery. Brain and spinal cord were investigated histologically after 10 days. RESULTS: More MES could be detected during high- compared to low-energy laser procedures. Ventilation with 100% oxygen reduced the number of MES. No lesions were found on histology. CONCLUSIONS: The number of MES depends on the laser energy. Laser-induces cavitation-effects lead to an additional release of nitrogen bubbles. Thus, the microembolic load can be reduced by ventilation with 100% oxygen and by decreasing the laser energy.
Animals↗
Middle cerebral artery occlusion during MR-imaging: investigation of the hyperacute phase of stroke using a new in-bore occlusion model in rats.
Magnetic resonance imaging (MRI) provides insights into the dynamics of focal cerebral ischemia. Usually, experimental stroke is induced outside the magnet bore, preventing investigators from acquiring pre-ischemic images for later pixel-by-pixel comparisons and from studying the earliest changes in the hyperacute phase of ischemia. Herein, we introduce a new and easy to apply in-bore occlusion protocol based on the intraarterial embolization of ceramic macrospheres. PE-50 tubing, filled with saline and six macrospheres (0.315-0.355 mm in diameter), was placed into the internal carotid artery (ICA) of anesthetized Sprague-Dawley rats. The animals were transferred into an MRI scanner (7.0 T) and baseline diffusion-weighted imaging (DWI) and T2-imaging was performed. Then the macrospheres were injected into the internal artery to occlude the MCA. Post-ischemic DWI and T2-imaging was started immediately thereafter. The apparent diffusion coefficient (ADC) (a marker for cytotoxic brain edema) and T2-relaxation time (a marker for vasogenic brain edema) were determined in the ischemic lesions and compared to the unaffected hemisphere. ADC significantly declined within the first 5-10 min after stroke onset. T2-relaxation time increased as early as at the first T2-imaging time-point (20-35 min after embolization). After 150 min of ischemia, the lesions covered 18.0 +/- 7.4% of the hemispheres. The model failed in one out of nine animals (11%). This model allows MR-imaging from the initial minutes after permanent middle cerebral artery (MCA) occlusion. It does not permit reperfusion. This technique might provide information about the pathophysiological processes in the hyperacute phase of stroke.
Acute Disease↗
Sinus thrombosis after a jump from a small rock and a sneezing attack: minor endothelial trauma as a precipitating factor for cerebral venous thrombosis?
Cerebral venous thrombosis (CVT) associated with minor or trivial head trauma has only been described in a few cases so far. We report two patients who developed CVT after a sudden intracranial pressure increase and head acceleration. A 49-year-old woman jumped from a small rock, 1 m in height, and developed instantaneous occipital headaches. Magnetic resonance imaging (MRI) confirmed confluens sinuum thrombosis. Risk factors consisted of smoking and oral contraceptives. Our second patient, an 18-year-old woman, experienced instantaneous headaches after a sneezing attack. Superior sagittal and right-sided transverse sinus thrombosis were confirmed by venous computed tomography angiography. She took oral contraceptives as an additional risk factor. In about 20% of CVT cases the cause remains unclear. As minor head trauma may not have been recognized during history taking, this may represent a so far under-recognized precipitating factor for CVT.
Adolescent↗
Real-time MR with TrueFISP for the detection of acute pulmonary embolism: initial clinical experience.
The feasibility and diagnostic value of real-time magnetic resonance imaging (RT-MRI) for the diagnosis of acute pulmonary embolism (PE) was evaluated by comparing RT-MRI and magnetic resonance angiography (MRA). In 39 consecutive patients with suspected PE real-time true fast imaging with steady-state precession (TrueFisp) was prospectively compared with contrast-enhanced MRA on a 1.5-T MR scanner. The TrueFisp sequence used allowed acquisition of T2-weighted images at 0.4 s per image so that the pulmonary vasculature could be visualized in three orientations in <3 min without the need for breath holding or contrast media application. Results of additional scintigraphic pulmonary perfusion examinations were available from 17 patients. All 39 primary RT examinations (100%) and 30 of 39 MRA examinations (77%) were of diagnostic quality. The reasons underlying failure to achieve diagnostic quality for MRA were breathing artifacts among dyspneic patients in all 9 cases. Compared with MRA, the sensitivities and specificities of RT sequences for PE were 93 and 100% (per examination), 96 and 100% (lobar artery PE), and 97 and 100% (segmental artery PE), respectively. Compared with scintigraphy, the sensitivity and specificity of RT-MRI were 83 and 100%, respectively. The MRA reached 100% sensitivity and specificity in this subgroup. The RT-MRI proved to be very robust and undisturbed by respiratory movements and patient cooperation. Its image quality assured fast diagnostic examinations, and its sensitivity and specificity, compared with MRA and scintigraphy, were sufficient to allow the diagnosis of acute central, lobar, and segmental PE; therefore, the emergency diagnosis of PE using RT-MRI is feasible and reliable.
Acute Disease↗
The macrosphere model: evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats.
BACKGROUND AND PURPOSE: The suture middle cerebral artery occlusion (MCAO) model is widely used for the simulation of focal cerebral ischemia in rats. This technique causes hypothalamic injury resulting in hyperthermia, which can worsen outcome and obscure neuroprotective effects. Herein, we introduce a new MCAO model that avoids these disadvantages. METHODS: Permanent MCAO was performed by intraarterial embolization using six TiO(2) macrospheres (0.3-0.4 mm in diameter) or by the suture occlusion technique. Body temperature was monitored, functional and histologic outcome was assessed after 24 h. Additional 16 rats were subjected to macrosphere or suture MCAO. Lesion progression was evaluated using magnetic resonance imaging (MRI). RESULTS: The animals subjected to suture MCAO developed hyperthermia (>39 degrees C), while the temperature remained normal in the macrosphere MCAO group. Infarct size, functional outcome and model failure rate were not significantly different between the groups. Lesion size on MRI increased within the first 90 min and remained unchanged thereafter in both groups. CONCLUSIONS: The macrosphere MCAO model provides reproducible focal cerebral ischemia, similar to the established suture technique, but avoids hypothalamic damage and hyperthermia. This model, therefore, may be more appropriate for the preclinical evaluation of neuroprotective therapies and can also be used for stroke studies under difficult conditions, e.g., in awake animals or inside the MRI scanner.
Animals↗
Association between right-to-left shunts and brain lesions in sport divers.
BACKGROUND: Recent studies suggest that healthy sport divers may develop clinically silent brain damage, based on the association between a finding of multiple brain lesions on MRI and the presence of right-to-left shunt, a pathway for venous gas bubbles to enter the arterial system. METHODS: We performed echocontrast transcranial Doppler sonography in 42 sport divers to determine the presence of a right-to-left shunt. Cranial MRI was carried out using a 1.5 T magnet. A lesion was counted if it was hyperintense on both T2-weighted and T2-weighted fluid attenuated inversion recovery sequences. To test the hypothesis that the occurrence of postdive arterial gas emboli is related to brain lesions on MRI, we measured postdive intravascular bubbles in a subset of 15 divers 30 min after open water scuba dives. RESULTS: Echocontrast transcranial Doppler sonography revealed a right-to-left shunt in 16 of the divers (38%). Only one hyperintensive lesion of the central white matter was found and that was in a diver with no evidence of a right-to-left shunt. Postdive arterial gas emboli were detected in 3 out of 15 divers; they had a right-to-left shunt, but no pathologic findings on cranial magnetic resonance imaging. CONCLUSIONS: Our data support the theory that right-to-left shunts can serve as a pathway for venous gas bubbles into the arterial circulation. However, we could not confirm an association between brain lesions and the presence of a right-to-left shunt in sport divers.
Adult↗