ABSTRACT
Objective: To evaluate the effects of an outpatient clinic set-up for minor stroke/TIA using subsequent admission of patients at 'high risk' of re-stroke.Methods: A cohort study of all patients with suspected minor stroke/TIA seen in an outpatient clinic at Aarhus University Hospital, Denmark, between September 2013 and August 2014. Stroke patients were compared to historic (same hospital) and contemporary (another comparable hospital) matched, hospitalized controls on the non-prioritized outcomes: Length-of-stay, re-admissions, care quality (10 process-performance measures) and mortality. TIA patients were compared to contemporary matched, hospitalized controls.Following complete diagnostic work-up, patients with stroke/TIA were classified into 'low'/high risk' of re-stroke ≤7 days. RESULTS: We analyzed 1,076 consecutive patients of whom 253 (23.5%) were subsequently admitted to the stroke ward. Stroke/TIA was diagnosed in 215/171 patients, respectively. Fifty-six percent (121/215) of the stroke patients were subsequently admitted to the stroke ward. Comparison with the historic stroke cohort (n=191) showed a shorter acute hospital stay for the strokes (median 1 vs 3 days); adjusted length-of-stay ratio 0.49 (95% CI 0.33-0.71). Furthermore, 30-day readmission rate was 3.2% vs 11.6%; adjusted hazard ratio 0.23 (0.09-0.59); and care quality was higher with a risk ratio of 1.30 (1.15-1.47). The comparison of stroke and TIAs to contemporary controls showed similar results. Only one patient in the 'low risk' category and not admitted experienced stroke within 7 days (0.6%). CONCLUSIONS: An outpatient clinic set-up for patients with minor stroke/TIA yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a neurovascular specialist driven outpatient clinic for minor stroke/TIA patients with the ability of subsequent admission is safe and yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units.
ABSTRACT
BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Aged , Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Humans , Polypharmacy , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND AND PURPOSE: Endovascular therapy for acute ischemic stroke is often performed with the patient under conscious sedation. Emergent conversion from conscious sedation to general anesthesia is sometimes necessary. The aim of this study was to assess the functional outcome in converted patients compared with patients who remained in conscious sedation and to identify predictors associated with the risk of conversion. MATERIALS AND METHODS: Data from 368 patients, included in 3 trials randomizing between conscious sedation and general anesthesia before endovascular therapy (SIESTA, ANSTROKE, and GOLIATH) constituted the study cohort. Twenty-one (11%) of 185 patients randomized to conscious sedation were emergently converted to general anesthesia. RESULTS: Absence of hyperlipidemia seemed to be the strongest predictor of conversion to general anesthesia, albeit a weak predictor (area under curve = 0.62). Sex, hypertension, diabetes, smoking status, atrial fibrillation, blood pressure, size of the infarct, and level and side of the occlusion were not significantly associated with conversion to general anesthesia. Neither age (mean age, 71.3 ± 13.8 years for conscious sedation versus 71.6 ± 12.3 years for converters, P = .58) nor severity of stroke (mean NIHSS score, 17 ± 4 versus 18 ± 4, respectively, P = .27) were significantly different between converters and those who tolerated conscious sedation. The converters had significantly worse outcome with a common odds ratio of 2.67 (P = .015) for a shift toward a higher mRS score compared with the patients remaining in the conscious sedation group. CONCLUSIONS: Patients undergoing conversion had significantly worse outcome compared with patients remaining in conscious sedation. No factor was identified that predicted conversion from conscious sedation to general anesthesia.
Subject(s)
Anesthesia, General , Conscious Sedation , Endovascular Procedures/methods , Ischemic Stroke/surgery , Treatment Outcome , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Randomized Controlled Trials as Topic , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND AND PURPOSE: Acute endovascular reperfusion treatment (aERT) of stroke patients with large-vessel occlusions is efficacious and safe according to several clinical trials. Data on outcome and safety of aERT in daily clinical routine are warranted and, in this study, we present national data from Denmark during 2011-2017. METHODS: National data for Denmark from 2011 to 2017 on all aERT procedures in patients with acute ischaemic stroke and computed tomography angiography/magnetic resonance angiography-verified large-vessel occlusion were derived from the Danish Stroke Registry, a national clinical quality registry to which reporting is mandatory for all hospitals treating stroke patients. Outcome (modified Rankin Scale score) after 3 months, including time of death, was assessed prospectively based on clinical examination or the Danish Civil Registration System. RESULTS: During the 7 years of observation, a total of 1720 patients were treated with aERT. The annual number of procedures increased from 128 in 2011 to 409 in 2017. The median age was 70 years, 58% were males and median National Institutes of Health Stroke Scale score at baseline was 16. Median time from symptom onset to groin puncture was 238 min with a decreasing trend during the years. Successful recanalization was reported in 1306 (76%) patients. At 3-month follow-up, an modified Rankin Scale score of 0-2 was reported in 46% of patients, whereas 14% of patients had died. CONCLUSION: Routine data on aERT in acute ischaemic stroke in Denmark from 2011 to 2017 suggest that the procedure is safe and efficacious.
Subject(s)
Brain Ischemia/therapy , Endovascular Procedures/methods , Stroke/therapy , Aged , Brain Ischemia/diagnostic imaging , Denmark , Female , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Reperfusion , Stroke/diagnostic imaging , Treatment OutcomeABSTRACT
BACKGROUND: Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. METHODS: The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. RESULTS: Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. CONCLUSION: We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. CLINICAL TRIAL REGISTRATION: NCT 02317237.
Subject(s)
Blood Pressure/physiology , Brain Ischemia/surgery , Endovascular Procedures/methods , Intraoperative Care/methods , Stroke/surgery , Aged , Aged, 80 and over , Anesthesia, General/methods , Brain Ischemia/physiopathology , Brain Ischemia/rehabilitation , Cerebral Revascularization/methods , Cerebral Revascularization/rehabilitation , Conscious Sedation/methods , Disability Evaluation , Endovascular Procedures/rehabilitation , Female , Humans , Male , Middle Aged , Monitoring, Intraoperative/methods , Recovery of Function , Single-Blind Method , Stroke/physiopathology , Treatment OutcomeABSTRACT
BACKGROUND: The optimal method of anaesthesia for endovascular therapy (EVT) in acute ischaemic stroke (AIS) has not been identified. Nordic departments of anaesthesiology may handle EVT cases for AIS differently. The aim of this survey was to describe the current practice patterns of Nordic anaesthesia departments in anaesthetic management of EVT in AIS. METHODS: A survey consisting of 13 questions was sent to one qualified individual at all Nordic departments of anaesthesiology who manage anaesthesia for EVT interventions. The individual completed the questionnaire on behalf of their department. RESULTS: Response rate was 100%. The majority of departments (84%) managed all EVT cases at their respective centres. Most departments have institutional guidelines on anaesthetic management (84%) including blood pressure management (63%) and were able to provide a 24-h immediate response to an EVT request (63%). Conscious sedation was favoured by 68% of the departments using a variety of sedation protocols. Propofol and remifentanil was preferred for GA (58%). Emergent conversion to GA due to uncontrolled patient movements or loss of airway was experienced by 82% and 35% of the departments, respectively. Majority of the departments (89%) responded that non-specialist anaesthetists occasionally handle EVT cases. CONCLUSIONS: This survey indicates that the majority of Nordic anaesthesia departments who manage anaesthesia for EVT are able to provide immediate 24-h response to an EVT request. Most of these departments have institutional guidelines for EVT anaesthesia and haemodynamic management. Conscious sedation appears to be the preferred method of anaesthetic care.
Subject(s)
Anesthesia/methods , Brain Ischemia/surgery , Endovascular Procedures/methods , Stroke/surgery , Anesthetics , Anesthetics, Intravenous , Blood Pressure , Conscious Sedation , Guidelines as Topic , Health Care Surveys , Humans , Piperidines , Propofol , Remifentanil , Scandinavian and Nordic Countries , Surveys and QuestionnairesABSTRACT
OBJECTIVES: The impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is sparsely examined. We studied the association between stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-evaluated patients treated with IV-tPA. MATERIAL AND METHODS: We conducted a single-center retrospective analysis of MRI-selected stroke patients treated with IV-tPA between 2004 and 2010. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish the stroke subtype by 3 months. The outcomes of interest were a 3-month modified Rankin Scale score of 0-1 (favorable outcome), and early neurological improvement defined as complete remission of neurological deficit or improvement of ≥4 on the National Institute of Health Stroke Scale at 24 h. The outcomes among stroke subtypes were compared with multivariable logistic regression. RESULTS: Among 557 patients, 202 (36%) had large vessel disease (LVD), 153 (27%) cardioembolic stroke (CE), 109 (20%) small vessel disease, and 93 (17%) were of other or undetermined etiology. Early neurological improvement was present in 313 (56.4%) patients, and 361 (64.8%) patients achieved a favorable outcome. Early neurological improvement and favorable outcome were more likely in CE patients compared with LVD patients (odds ratio (OR), 2.1 (95% confidence interval, 1.4-3.3), and 2.0 (95% confidence interval, 1.2-3.3), respectively). CONCLUSIONS: Cardioembolic stroke patients were more likely to achieve early neurological improvement and favorable outcome compared with LVD stroke following MRI-based IV-tPA treatment. This finding may reflect a difference in the effect of IV-tPA among stroke subtypes.
Subject(s)
Brain Ischemia/drug therapy , Fibrinolytic Agents/administration & dosage , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Adult , Aged , Aged, 80 and over , Brain Ischemia/diagnostic imaging , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prospective Studies , Retrospective Studies , Stroke/diagnostic imaging , Treatment OutcomeABSTRACT
Thedomestic pig is increasingly being used as an experimental model for brain imaging studies with positron emission tomography (PET). The recording of radiotracer uptake by PET gives functional and physiological information, but with poor spatial resolution. To date, anatomical regions of interest in pig brain have been defined in MR images obtained for each individual animal, because of the lack of a standard stereotaxic coordinate system for the pig brain. In order to define a stereotaxic coordinate system, we coregistered T1-weighted MR images from 22 male Göttingen minipigs and obtained a statistically defined surface rendering of the average minipig brain in which stereotaxic zero is defined by the position of the pineal gland. The average brain is now used as a target for registration of dynamic PET data, so that time-activity curves can be extracted from standard volumes of interest. In order to define these volumes, MR images from each individual pig were manually segmented into a total of 34 brain structures, including cortical regions, white matter, caudate and putamen, ventricular system, and cerebellum. The mean volumes of these structures had variances in the range of 10-20%. The 34 brain volumes were transformed into the common coordinate system and then used to generate surface renderings with probabilistic threshold greater than 50%. This probabilistic threshold gave nearly quantitative recovery of the mean volumes in native space. The probabilistic volumes in stereotaxic space are now being used to extract time-radioactivity curves from dynamic PET recordings.
Subject(s)
Brain Mapping , Brain/anatomy & histology , Imaging, Three-Dimensional , Magnetic Resonance Imaging/statistics & numerical data , Swine, Miniature/anatomy & histology , Animals , Data Interpretation, Statistical , Dominance, Cerebral/physiology , Image Processing, Computer-Assisted , Male , Reference Values , Reproducibility of Results , Tomography, Emission-ComputedABSTRACT
OBJECTIVE: We used combined diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI to characterize hyperacute infarctions within 6 h of symptom onset with special reference to subcortical infarctions, and investigated the relation between perfusion-diffusion mismatch volume and functional outcome. MATERIAL AND METHODS: Twenty-two patients presenting with symptoms of acute stroke underwent DWI and PWI within 6 h of symptom onset, and follow-up MRI 30 days later. Twelve of these had a subcortical infarction on acute DWI. Lesion volumes were measured by acute DWI and PWI as well as chronic T(2)-weighted MRI (T2WI). Clinical severity was measured by the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI). RESULTS: In the 12 patients with subcortical infarctions, PWI and especially DWI correlated strongly with acute and chronic neurological SSS score, as well as with final infarct volume. Furthermore, a hyperacute PWI/DWI mismatch in this subgroup predicted lesion growth. There was a weaker correlation between acute DWI/PWI and neurological score among all 22 patients, and patients with a PWI/DWI mismatch larger than 100 ml had a significantly larger lesion growth and a poorer outcome than patients with a smaller mismatch. CONCLUSIONS: Subcortical infarctions may represent a sizeable subgroup of acute stroke patients. Also subcortical infarctions may have a PWI/DWI mismatch and therefore may respond to neuroprotective/thrombolytic therapy. Hyperacute DWI may reflect the acute clinical status and predict the outcome in patients with subcortical infarction.
Subject(s)
Magnetic Resonance Imaging/methods , Severity of Illness Index , Stroke/diagnosis , Stroke/physiopathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Time FactorsABSTRACT
BACKGROUND AND PURPOSE: The penumbra of ischemic stroke consists of hypoperfused, but not irreversibly damaged, tissue surrounding the ischemic core. The purpose of this study was to determine viability thresholds in the ischemic penumbra, defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of diffusion- and perfusion-weighted MRI (DWI and PWI, respectively). METHODS: DWI and PWI were performed in 11 patients =6 hours after the onset of symptoms of acute ischemic stroke. Regions of interest (ROIs) were placed covering the ischemic core (ROI 1), the penumbra that progressed to infarction on the basis of follow-up scans (ROI 2), and the penumbra that recovered (ROI 3). The ratios of relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), and apparent diffusion coefficient were calculated as lesion ROIs relative to the contralateral mirror ROIS: RESULTS: The post hoc analysis showed that the penumbra progressed to infarction at the following cutoff values: rCBF <0.59 and MTT >1.63. Higher sensitivity and accuracy in predicting outcome of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT maps. The initial rCBV and apparent diffusion coefficient ratios did not differentiate between the part of the penumbra that recovered and the part that progressed to infarction. The mean rCBF ratio was optimal in distinguishing the parts of the penumbra recovering or progressing to infarction. CONCLUSIONS: The thresholds found in this study by combined DWI/PWI might aid in the selection of patients suitable for therapeutic intervention within 6 hours. However, these hypothesized thresholds need to be prospectively tested at the voxel level on a larger patient sample before they can be applied clinically.
Subject(s)
Brain Ischemia/diagnosis , Brain Ischemia/physiopathology , Magnetic Resonance Imaging , Stroke/diagnosis , Stroke/physiopathology , Acute Disease , Adult , Aged , Aged, 80 and over , Blood Flow Velocity , Brain/blood supply , Brain/pathology , Brain/physiopathology , Brain Ischemia/complications , Cell Survival , Cerebrovascular Circulation , Diffusion , Discriminant Analysis , Disease Progression , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Perfusion , Predictive Value of Tests , ROC Curve , Sensitivity and Specificity , Severity of Illness Index , Stroke/complications , Tomography, X-Ray ComputedABSTRACT
MR is increasingly used as a diagnostic tool in stroke management, especially since new and acute treatments are now available. This article describes the new MR sequences used in the scanning of stroke patients. A scanning protocol is suggested and our preliminary experiences with acute MR scanning of stroke patients are presented. Pros and cons are discussed.
Subject(s)
Magnetic Resonance Imaging/methods , Stroke/diagnosis , Acute Disease , Cerebrovascular Circulation , Contrast Media/administration & dosage , Humans , Indicator Dilution Techniques , Stroke/pathologyABSTRACT
OBJECT: The authors tested the hypothesis that oxygen metabolism is the key factor linking the long-term viability of ischemic brain tissue to the magnitude of residual blood flow during the first 6 hours following a stroke. METHODS: Eleven anesthetized pigs underwent a series of positron emission tomography studies to measure cerebral blood flow (CBF) and metabolism before and for 7 hours after the animals were subjected to permanent middle cerebral artery (MCA) occlusion. The extent of collateral blood supply was assessed using angiography. Abnormal metabolism of the ischemic tissue progressed as a function of time in inverse proportion to the magnitude of residual CBF, and the volume of the infarct grew in inverse proportion to the residual blood supply. Ten hours after occlusion of the MCA, the infarct topographically matched the tissue with a cerebral metabolic rate of oxygen consumption below 50% of values measured on the contralateral side. This was also the threshold for the decline of the oxygen extraction fraction below normal, which was critical for the prediction of nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not reach the cerebral metabolic rate of oxygen threshold of viability during the first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12-30 m1/100 g/ min) reached the threshold of viability in 3 hours; and severely ischemic tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour. CONCLUSIONS: The relationship between the residual CBF and both oxygen metabolism and extraction is critical to the evolution of metabolic deficiency and lesion size after stroke.
Subject(s)
Brain Ischemia/physiopathology , Cerebral Arterial Diseases/diagnostic imaging , Cerebrovascular Circulation , Oxygen/metabolism , Stroke/complications , Animals , Cell Survival , Cerebral Angiography , Disease Models, Animal , Female , Magnetic Resonance Imaging , Predictive Value of Tests , Swine , Time Factors , Tomography, Emission-ComputedABSTRACT
The authors measured cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in pigs by gadodiamide bolus injections and the bolus tracking technique. Two different pulse sequences were applied and compared: gradient-echo (GE) and spin-echo (SE) echoplanar imaging (EPI). After normalization of CBF and CBV values to the area under the arterial input function (AIF), a linear relation between the two methods was found, suggesting that a previous normalization approach for determining absolute CBF by SE EPI may be extended to GE EPI measurements. The ratio between CBV values measured with GE and SE [CBV (GE)/CBV (SE)] was 2.96. Assuming that the GE acquisition reflects total CBV, our findings suggest that SE is sensitive to 34% (1/2.96) of the total vasculature. The corresponding ratio for CBF was 2.53. There was no significant difference in these two ratios, suggesting that MTT estimates derived from GE and SE EPI measurements are comparable. The findings suggest that SE and GE are equally useful in clinical measurements of functional parameters such as CBF, CBV, and MTT in the brain. J. Magn. Reson. Imaging 2000;12:411-416.
Subject(s)
Cerebrovascular Circulation , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Animals , Blood Flow Velocity/physiology , Blood Volume Determination , Brain/anatomy & histology , Brain/blood supply , Contrast Media , Disease Models, Animal , Female , Gadolinium DTPA/administration & dosage , Hypercapnia/physiopathology , Hypocapnia/physiopathology , Injections, Intravenous , Models, Biological , Perfusion , Sensitivity and Specificity , SwineABSTRACT
A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, which had been manipulated to secrete glia cell line-derived neurotrophic factor (GDNF) (approximately 2 ng GDNF/h/10(5) cells). MPTP was administered (1 mg/kg/day, SC) for 7-10 days until the pigs had developed mild parkinsonian symptoms of muscle rigidity, hypokinesia, and impaired coordination, especially of the hind limbs. Approximately 2 weeks after the last MPTP dose, animals received a T1-weighted magnetic resonance imaging (MRI) scan, and a series of dynamic PET recordings. After the first series of PET scans, four grafts of porcine embryonic mesencephalic tissue (E28 days) were placed in each striatum of some MPTP-intoxicated pigs, using MRI-based stereotactic techniques. Immunosuppression of some animals with cyclosporin and prednisolone began just prior to surgery. Two more series of PET scans were performed at 4-month intervals after surgery. After the last scans, pigs were killed and the brains were perfused for unbiased stereological examination of cytological and histochemical markers in striatum and substantial nigra. The behavioral impairment of the animals (the "Parkinson's score") had been evaluated throughout the 8-month period. Kinetic analysis of the first set of PET scans has indicated that the rate constant for the decarboxylation of FDOPA in catecholamine fibers was reduced by 33% in striatum of the mildly parkinsonian pigs. The rate of association of [11C]NS-2214 to catecholamine uptake sites was reduced by 62% in the same groups of pigs. No significant difference was found in the binding potential of [11C]raclopride to the dopamine D2-like receptors in striatum of the MPTP-intoxicated versus control pigs. These preliminary results are suggestive that the activity of DOPA decarboxylase may be upregulated in the partially denervated pig striatum.
Subject(s)
Brain Tissue Transplantation , Fetal Tissue Transplantation , MPTP Poisoning/surgery , Parkinsonian Disorders/surgery , Animals , Cell Transplantation , Corpus Striatum/diagnostic imaging , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dihydroxyphenylalanine/analogs & derivatives , Dopamine/metabolism , Dopamine Antagonists , Male , Mesencephalon/transplantation , Parkinsonian Disorders/diagnostic imaging , Parkinsonian Disorders/metabolism , Raclopride , Swine , Swine, Miniature , Tomography, Emission-Computed , Transplantation, HomologousABSTRACT
We present a new method allowing direct comparison between images obtained by present digital scanning modalities and histological sections from the same object. More specifically the paper illustrates how to orientate, embed, and section large irregular tissue blocks after magnetic resonance imaging (MRI) in such a way that accurate correlation of the digital data sets to histological sections is possible. The functionality and capability of the described procedure and slicing machine is illustrated by results from the pig brain. Accordingly, three pigs were MR-scanned, followed by perfusion fixation. The brains were removed, oriented according to the MR scans, embedded in alginate, and cut on a newly developed slicing machine. The tissue blocks were then stained to reveal grey and white matter and photographed before final sectioning on a cryostat into 80 microm thick sections which were Nissl-stained with toluidine. The results demonstrate how our method enables direct comparison between the pig brain MR images and the later obtained histological sections. The alginate embedding method and slicing machine offer the same possibilities for other parenchymateous organs and soft tissues and may, in addition, be of use in stereological analysis.
Subject(s)
Brain/cytology , Coloring Agents , Magnetic Resonance Imaging/methods , Microtomy/instrumentation , Microtomy/methods , Tissue Embedding/methods , Animals , Female , SwineABSTRACT
PURPOSE: NC100150 is a new type of ultra-small iron oxide (USPIO) blood pool agent. The aim of this study was to compare NC100150-enhanced MR angiography (MRA) to time-of-flight (TOF) MRA, phase-contrast (PC) MRA, and digital subtraction angiography (DSA) in experimental stenoses in pigs, and furthermore to determine the optimal dose of the contrast agent. MATERIAL AND METHODS: An experimental stenosis of the right and left common carotid artery (CCA) was applied surgically in 6 Yorkshire pigs. DSA was performed as the gold standard, followed by 3D-TOF, 3D-PC, and NC100150-enhanced MRA. RESULTS: Eleven stenoses of the CCA were successfully applied. The degree of the stenosis, determined by NC100150-enhanced MRA, did not differ significantly from DSA, whereas TOF and PC MRA underestimated it. The image quality of the NC100150-enhanced MRA was superior to both TOF and PC MRA. The optimal dose of NC100150 was 5-6 mg Fe/kg, since higher doses did not further increase signal-to-noise ratio or contrast-to-noise ratio. There was a linear relationship between blood relaxation rate and contrast dose. CONCLUSION: NC100150-enhanced MRA has the potential for quantification of carotid stenoses and provides an alternative to DSA. The optimal dose of NC100150 was 5-6 mg Fe/kg.
Subject(s)
Carotid Artery, Common/pathology , Carotid Stenosis/diagnosis , Contrast Media , Iron , Magnetic Resonance Angiography , Oxides , Angiography, Digital Subtraction , Animals , Carotid Artery, Common/diagnostic imaging , Carotid Stenosis/diagnostic imaging , Dextrans , Female , Ferrosoferric Oxide , Magnetic Resonance Imaging , Magnetite Nanoparticles , SwineABSTRACT
The authors measured cerebral blood flow (CBF) and cerebral blood volume (CBV) by bolus tracking of a novel ultrasmall superparamagnetic iron oxide (USPIO) contrast agent (NC100150) and compared absolute and relative perfusion measurements with those obtained by a standard gadolinium-based contrast agent. They found a linear correlation between the two methods. A dose of 0.4 mg Fe/kg body weight was found to produce a signal drop similar to that of a standard 0.2 mmol/kg gadodiamide injection using spin-echo echoplanar imaging (SE-EPI) at 1.0 T. The measurements showed a high degree of reproducibility of repeated absolute as well as relative CBF and CBV values, lending further hope to the possibility of using magnetic resonance bolus tracking for routine CBF and CBV measurements. Finally, the authors present their initial experience with high-resolution, non-EPI CBV maps obtained from steady-state levels of an intravascular superparamagnetic contrast agent.