Oliver Wittkugel

Predictors of Apparent Diffusion Coefficient Normalization in Stroke Patients

Background and Purpose— We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. Methods— Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). Results— Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. Conclusions— ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include “tissue at risk.”

Normal brain maturation characterized with age-related T2 relaxation times: An attempt to develop a quantitative imaging measure for clinical use

Objectives:We studied age-related changes in T2 relaxation times from the normal maturating human brain under routine clinical MR examination conditions. Materials and Methods:In 70 healthy subjects aged between 3 weeks and 39 years, T2 maps of the brain in which the intensity of each pixel corresponded to T2 relaxation times were generated based on magnetic resonance imaging data collected with a triple spin echo sequence. T2 relaxation times in white matter (WM) and gray matter (GM) were measured in 6 distinctive regions of interest of the T2 maps. The age dependence of the T2 values was mathematically simulated using a biexponential function. Results:T2 values were largest at the age of 3 weeks (maximum: approximately 400 milliseconds for WM and 200 milliseconds for GM) and decreased continuously with increasing age, faster in the first few months and slower thereafter, until values achieved between 95 and 110 milliseconds for WM and 88 and 95 milliseconds for GM in adults. The relationship between T2 values and age could be well simulated using a biexponential function (R2 > 0.92). Conclusions:T2 relaxation time correlates well with the progress of brain maturation. The used biexponential function reflects the dynamic development of myelination in newborns and young children as well as the maturation of myelination during adolescence and could be used to develop a “normal” reference for neuroradiological diagnoses.

Cerebral Blood Flow Predicts Lesion Growth in Acute Stroke Patients

Background and Purpose— We sought to study the role of MRI-derived cerebral blood flow (CBF) measurements for the prediction of lesion development in acute stroke patients. Methods— Thirty-two patients were treated with tissue plasminogen activator. Diffusion-weighted (DWI) and perfusion-weighted MRI, T2-weighted imaging, and MR angiography were performed before treatment (2.8±0.9 hours after symptom onset) and on follow-up (days 1 and 7). CBF thresholds (12 and 22 mL/100 g per minute) were applied to bolus tracking MRI maps to determine predictive cutoff levels. Results— In 21 patients (group A), the terminal lesion volume (T2-weighted imaging) was larger than the initial DWI lesion volume (89±93 versus 21±38 mL). In 11 patients (group B), the terminal lesion volume was smaller than the initial DWI lesion volume (7±27 versus 15±29 mL). The initial DWI lesion volume did not differ between both groups. The presence of a tissue volume ≥50 mL with a CBF value ≤12 mL/100 g per minute was predictive for lesion enlargement to day 7 in T2-weighted imaging (positive predictive value, 0.80). Conclusions— The presence of a tissue volume ≥50 mL with a CBF value ≤12 mL/100 g per minute predicts further lesion growth in hyperacute stroke patients. MRI-derived CBF values, with all their present limitations, are valuable in early estimation of prognosis of stroke patients.

Atypical focal MRI lesions in a case of juvenile Alexander's disease.

We present a juvenile case of Alexanders disease with atypical focal magnetic resonance imaging–detected lesions and elevated levels of lactate in cerebrospinal fluid. The diagnosis was based on the neuropathological finding of a diffuse accumulation of Rosenthal fibers within the brain and the spinal cord. The diagnosis was confirmed by detection of a mutation in exon 1 at nucleotide position 249 of glial fibrillary acidic protein cDNA, a finding previously reported in cases of infantile Alexanders disease.

MRI abnormalities in normal-appearing brain tissue of treated adult PKU patients.

To detect possible subclinical pathological brain changes a study on adult phenylketonuria (PKU) patients by using quantitative MRI methods was performed, since neuropsychological and cognitive deficits in treated patients with PKU have not yet been shown to correlate clearly with the brain lesions identified by conventional MRI.

Cerebral Embolism during Carotid Artery Stenting: Role of Carotid Plaque Echolucency

Background: Carotid artery stenting (CAS) is associated with the risk of intraprocedural stroke. A better understanding of specific risk factors could help to improve the procedure and to reduce the overall risk of CAS. We addressed the role of carotid plaque echolucency as potential risk factor for cerebral embolism during CAS. Methods: We prospectively evaluated carotid plaque echolucency by use of a computer-assisted measure of echogenicity, the gray scale median (GSM), in 31 consecutive patients with symptomatic high-grade carotid stenosis that were scheduled to undergo CAS. Dual-frequency transcranial Doppler ultrasound was used to detect solid cerebral microemboli during CAS. Results: 27 of the 31 patients met all inclusion/exclusion criteria.Solid cerebral microemboli were detected during 17 of 27 CAS procedures. The GSM of the target plaques was lower in subjects with intraprocedural embolism (37.9 ± 20.8) than in those without (58.2 ± 25.7) (p = 0.040). A receiver-operating characteristic analysis showed that the GSM that gave the greatest separation between plaques with a higher and a lower probability of intraprocedural embolism was 50: the proportion of subjects with intraprocedural embolism was 85% in CAS of echolucent plaques (GSM <50) and 42% in CAS of echogenic plaques (GSM ≥50) (p = 0.031). Conclusions: CAS of both echolucent and echogenic carotid plaques may be associated with cerebral embolism, particularly CAS of echolucent plaques. Plaque echolucency alone does not reliably identify patients at particularly high risk of intraprocedural embolism, but should be considered as one of a broad panel of risk factors of CAS.

Older age and greater carotid intima-media thickness predict ischemic events associated with carotid-artery stenting.

Background: Carotid-artery stenting (CAS) may be complicated by stroke. We aimed to determine predictors of procedure-related ischemic events. Methods: We analyzed new ischemic lesions in diffusion-weighted MRI (DWI) after CAS in 147 patients with symptomatic high-grade carotid stenosis. Nine covariates were assessed as potential risk factors for new lesions in DWI: age, gender, hypertension, diabetes, dyslipidemia, smoking status, severity of stenosis, side of intervention and carotid intima-media thickness (IMT). Results: From the nine covariates assessed, only age and IMT were independently associated with new DWI lesions. An age of 68 years and an IMT of 1.5 mm gave the best separation between high- and low-risk populations. The subgroup of patients <68 years who had an IMT ≤1.5 mm had the lowest rate of new DWI lesions (11.3%). This rate was greater in patients ≧68 years (30.0%; odds ratio, OR, 3.4; 95% confidence interval, CI, 1.1–10.8) and in patients with an IMT >1.5 mm (36.4%; OR 4.5; 95% CI 1.2–17.0) and was particularly high in patients aged ≧68 years with IMT >1.5 mm (69.6%; OR 18.0; 95% CI 4.8–71.9). Conclusions: Older age and greater IMT are independently associated with the risk of CAS-related ischemic events. This risk is particularly high in those patients in whom older age and greater IMT coincide.

Apparent Diffusion Coefficient, Fractional Anisotropy and T2 Relaxation Time Measurement

Background:Quantification of apparent diffusion coefficient (ADC), fractional anisotropy (FA), and T2 relaxation time are increasingly important for neuroradiologic applications. A transfer of the values established for 1.5-T to 3-T MRI must be supported by a dedicated comparison with special emphasis on possible differences in the spatial distribution.Material and Methods:In the present study, brain scans were carried out in 16 healthy volunteers at both 1.5-T and 3-T systems of the same design and gradient system. The protocol consisted of a fast spin echo (TSE) sequence, two singleshot spin echo echoplanar imaging (EPI) sequences for diffusion-weighted imaging and diffusion tensor imaging. Data from the two field strengths were compared for ADC, FA, and T2 relaxation times. The signal-to-noise ratio (SNR) was also compared for all sequences and echo times.Results:While there were no differences in ADC and FA, the T2 relaxation time was reduced by 15% at 3 T. A higher SNR at 3 T was found for both TSE and EPI sequences as expected (p < 0.05).Conclusion:Special benefits of the T2 measurement at higher field strengths are possible on certain clinical conditions due to reduced T2 relaxation time. Furthermore the results of the ADC and FA obtained from patients at different field strengths could be directly compared with each other – useful in the clinical follow-up.ZusammenfassungHintergrund:Die Quantifizierung des scheinbaren Diffusionskoeffizienten (“apparent diffusion coefficient” [ADC]), der fraktionellen Anisotropie (FA) und der T2-Relaxationszeit spielt eine zunehmend wichtige Rolle bei neuroradiologischen Anwendungen. Eine Übertragung der mit einem 1,5-T-MR-Gerät gesammelten Erfahrungen auf ein 3-T-MR-System setzt einen fundierten Vergleich voraus, insbesondere wegen des Unterschieds in den räumlichen Verteilungen.Material und Methodik:In der präsentierten Arbeit wurde anhand von Untersuchungen an 16 gesunden Probanden am 1,5-T- und 3-T-MR-System eine Vergleichsstudie durchgeführt. Das Untersuchungsprotokoll beinhaltete eine Fast-Spinechosequenz, zwei Single-Shot-Echoplanarsequenzen für die diffusionsgewichtete Bildgebung und das Diffusions-Tensor-Imaging. Die Werte für ADC, FA und T2-Relaxationszeit aus beiden Feldstärken wurden detailliert verglichen. Zusätzlich wurde das Signal-Rausch-Verhältnis (SNR) verglichen.Ergebnisse:Während sich bei ADC und FA kein Unterschied fand, war bei der höheren Feldstärke von 3 T eine 15%ige Reduktion der T2-Relaxationszeit feststellbar. Erwartungsgemäß wurde ein höheres SNR bei einer Feldstärke von 3 T gefunden (p < 0,05).Schlussfolgerung:T2-Bestimmungen bei höheren Feldstärken können unter bestimmten klinischen Bedingungen wegen der reduzierten T2-Relaxationszeit von besonderem Nutzen sein. Weiterhin können die Ergebnisse von ADC- und FA-Bestimmungen, die von Patienten bei verschiedenen Feldstärken erhalten wurden, direkt mit einander verglichen werden – ein nützlicher Aspekt bei der klinischen Verlaufskontrolle.

Kombination einer intraarteriellen rt-PA- plus intravenöser Abciximab-Therapie bei akuten thromboembolischen Verschlüssen der Arteria cerebri media Eine Dosisfindungsstudie

ZusammenfassungHintergrund: Die PROACT-II-Studie hat die Wirksamkeit der lokalen intraarteriellen Fibrinolyse (LIF) bei Verschlüssen der Arteria cerebri media bis zur 6. Stunde (Therapiebeginn) nach Beginn der Symptomatik belegt. Eine komplette Rekanalisation gelang in der Regel erst nach 2-stündiger Fibrinolyse. In unserem retrospektiv analysierten Kollektiv (LIF im vorderen Gehirnkreislauf bei 137 Patienten) betrug die durchschnittliche Rekanalisationszeit bei erfolgreicher Rekanalisation (n = 74) 91 ± 34 Minuten. Zur Beschleunigung der Rekanalisation sind neue pharmakologische Ansatzpunkte erforderlich. Die Fibrinolyse ist auf das Fibringeflecht im Thrombus ausgerichtet. Der thrombozytäre Anteil des Thrombus stellt eine weitere Angriffsfläche dar. Glykoprotein-(GP-)IIb-/IIIa-Rezeptorblocker wie der Antikörper Abciximab bewirken eine schnelle und hochwirksame Blockade der Thrombozyten-aggregation. Potentielle Wirkungen liegen in der Thrombolyse von frischen thrombozytenreichen Thrombuskompartimenten (“weißer Thrombus”), der Verhinderung einer Rethrombosierung und der Verbesserung der Mikrozirkulation. In randomisierten Studien zur Kombinationstherapie von Abciximab (i.v.) mit einem Fibrinolytikum im Vergleich zur alleinigen Fibrinolyse beim Myokardinfarkt fanden sich positive angiographische und klinische Resultate. Gegenstand der vorgestellten Dosisfindungsstudie ist die Kombination von Abciximab (i.v.) mit intraarteriell appliziertem rt-PA beim akuten Verschluss der ACM. Studiendesign: Eingeschlossen werden einwilligungsfähige Patienten (Alter 18–75 Jahre) mit nachgewiesenem (MR-, CT-Angiographie) proximalem Verschluss der ACM innerhalb des Zeitfensters (zwischen der 3. und 5. Stunde nach Schlaganfallbeginn). Primärer Endpunkt ist die Verkürzung der Rekanalisationszeit im Vergleich zu den Daten aus dem eigenem Kollektiv. Sekundäre Endpunkte sind die Rekanalisationsrate, die Rate der symptomatischen, intrakraniellen Blutungen und das neurologische Behandlungsergebnis. Die Studie ist als Multicenterstudie konzipiert.Die Abciximab-Therapie besteht aus einer intravenösen Bolusgabe von 0,25 mg/kg mit anschließender Erhaltungstherapie für 12 Studnen. Die intraarterielle rt-PA-Dosis variiert in bis zu drei Gruppen, von jeweils 15 Patienten. Begonnen wird mit einer Dosis von 10 mg/h rt-PA. Der Dosisanpassungsalgorithmus für rt-PA orientiert sich an dem Wirksamkeitskriterium (Verkürzung der Rekanalisationszeit um 50%) und dem Sicherheitskriterium (mehr als drei Patienten mit symptomatischen intrakraniellen Blutungen). Wird das Wirksamkeitskriterium nicht erfüllt, wird die rt-PA-Dosis erhöht. Sollte auch in der hohen rt-PA-Dosisstufe (20 mg/h) das Wirksamkeitskriterium nicht erfüllt werden, wird der Abciximab-Bolus zu 1/4 intraarteriell appliziert. Bei Eintreten des Sicherheitskriteriums oder des Wirksamkeitskriteriums wird die rt-PA-Dosis reduziert (5 mg/h und wenn erforderlich 2 mg/h) bis zum Erreichen des primären Endpunktes oder bis zum Studienabbruch.AbstractBackground: Local intra-arterial fibrinolysis (LIF) of middle cerebral artery stroke has been proven effective within 6 hours of symptom onset by the PROACT II trial. Complete recanalization was generally not seen before the end of 2 hours of fibrinolysis. The average time for recanalization in our retrospective study cohort of 137 patients with LIF in the carotid circulation in recanalized patients (n = 74) was 91 ± 34 minutes. In order to speed up recanalization, innovative pharmacological approaches must be sought. The fibrin formation in the clot is targeted by fibrinolytic agents. The platelet component of the clot is a second matter of concern. Glycoprotein (GP) IIb/IIIa inhibitors such as abciximab evoke a rapid and highly effective blockage of platelet aggregation. Its potential sites of action include: thrombolysis of platelet enriched compartments within the clot (“white clot”); prevention of re-thrombosis; and possible improvement of the microcirculation. A combined therapy with intravenous abciximab and tissue plasminogen activator (rt-PA) vs rt-PA alone has demonstrated positive angiographic and clinical results in myocardial infarction. The object of the present study is to improve recanalization in patients with acute middle cerebral artery stroke by combination of intravenous abciximab and intra-arterially administered rt-PA. Study Design: Inclusion criteria: A proximal middle cerebral artery occlusion established by MR or CT-angiography; treatment onset between 3 and 5 hours of symptom onset; age between 18 and 75 years; and informed consent. Primary endpoint is the time to recanalization compared with our study cohort. Secondary endpoints include evaluation of the recanalization rate, the rate of symptomatic intracranial hemorrhage and neurological outcome. The design is applicable for a multicenter study.Abciximab therapy consists of an initial intravenous bolus of 0.25 mg/kg followed by a 12-hour infusion therapy. The study is designed as dose escalation study (starting with a rt-PA dosis of 10 mg/h) in up to three study arms with 15 patients each. A pre-determined dosage adjustment algorithm is oriented towards an efficacy criterion (50% reduction of recanalization time) and a security criterion (> 3 symptmatic intracranial bleedings). In case of a neg-ative efficacy criterion, the rt-PA dosis is to be increased. If an increased rt-PA dosage (20 mg/h) does not achieve the efficacy criterion, 1/4 of the abciximab bolus will be applied i.a. Alternatively, if the security criterion is met, the rt-PA dosis will be reduced in two steps (5 mg/h first, and if necessary 2 mg/h) until the endpoint is achieved or the trial abandoned.

Bile resistance of coated transjugular intrahepatic portosystemic shunt stents in a flow-model.

Purpose:We sought to test the bile resistance of transjugular intrahepatic portosystemic shunt (TIPS) stents with 3 different coatings. Materials and Methods:Three stents with different coating materials (monolayer polyethylene terephthalate [PETP], monolayer polytetrafluoroethylene [PTFE], and double layer [PTFE]) were tested in a flow model. After testing the sealing of the system with isotonic saline solution, fresh human bile was circulated. Constant pressure was 50 cm H2O. Bile resistance of the stent membranes was analyzed. Results:Two of the 3 stents proved completely resistant to water. Only the PETP stent was resistant to bile. The PTFE-coated stents were not bile resistant. Conclusion:The bile resistance of coated TIPS stents and, thus, the dependency of TIPS shunt patency is called into question. The stent with the reported superior patency rates does not show experimental bile resistance.