Suitability of intravascular imaging for assessment of cerebrovascular diseases.

PURPOSE: Arteriosclerosis of the vascular system is associated with many accompanying diseases. Especially cerebral arteriosclerosis is a main risk factor for ischemic strokes. We want to verify the practicability of intravascular imaging like intravascular ultrasound and optical coherence tomography for the assessment of cerebral vessel walls and plaques. METHODS: We examined 18 Circuli arteriosi willisii postmortem. The data contained 48 plaques from 48 different vessel parts. The samples underwent intravascular and histological imaging to conduct a quantitative assessment of vessel wall parameters (healthy vessel wall, thinnest vessel wall, plaque thickness and vessel diameter) as well as to qualitatively evaluate the healthy vessel wall, fibrotic plaques, calcifications and cholesterol deposits in diseased vessels. RESULTS: The comparison showed statistically significant smaller measurements for thinnest vessel walls, normal vessel walls and vessel diameters in histology than in imaging. No statistically significant difference was reached for plaque diameters. Fibrotic plaques were characterized as hyper-intense with dorsal attenuation and calcifications as hypo-intense with dorsal attenuation in optical coherence tomography. In intravascular ultrasound, fibrotic plaques showed a homogeneous echogenicity without distal attenuation and calcifications were depicted as hyperechoic with dorsal sound shadows. Cholesterol deposits were hyper-intense in optical coherence tomography with strongly attenuated signals and in intravascular ultrasound; the deposits were hyper-intense with almost no attenuation. CONCLUSION: Both intravascular methods allow for plaque characterization and quantification of plaque diameter in cerebral vessel walls. When compared with histology, a statistically significant bias was obtained for the ex vivo measurements of the normal vessel wall diameters.

Fluid-Structure Simulations of a Ruptured Intracranial Aneurysm: Constant versus Patient-Specific Wall Thickness.

Computational Fluid Dynamics is intensively used to deepen the understanding of aneurysm growth and rupture in order to support physicians during therapy planning. However, numerous studies considering only the hemodynamics within the vessel lumen found no satisfactory criteria for rupture risk assessment. To improve available simulation models, the rigid vessel wall assumption has been discarded in this work and patient-specific wall thickness is considered within the simulation. For this purpose, a ruptured intracranial aneurysm was prepared ex vivo, followed by the acquisition of local wall thickness using µCT. The segmented inner and outer vessel surfaces served as solid domain for the fluid-structure interaction (FSI) simulation. To compare wall stress distributions within the aneurysm wall and at the rupture site, FSI computations are repeated in a virtual model using a constant wall thickness approach. Although the wall stresses obtained by the two approaches-when averaged over the complete aneurysm sac-are in very good agreement, strong differences occur in their distribution. Accounting for the real wall thickness distribution, the rupture site exhibits much higher stress values compared to the configuration with constant wall thickness. The study reveals the importance of geometry reconstruction and accurate description of wall thickness in FSI simulations.

Petechial bleedings in sudden infant death.

The autopsy reports of 484 cases of deceased infants (201 females, 283 males) were analysed retrospectively for the existence of external and internal petechial bleedings (PET). The cases were divided into five groups on the basis of the cause of death (sudden infant death syndrome, sepsis, airway infections, asphyxia and trauma). Internal PET (pleural, pericardial, epicardial, thymic and peritoneal) were observed in each group with a lower prevalence in cases of trauma. The highest prevalence of external (cutaneous and conjunctival) PET was detected in cases of asphyxia (38% and 31%, respectively). However, even if with low prevalence, such bleedings were detected in every group. Factors like sex, age, cardiopulmonary resuscitation and its duration did not influence the presence of PET. The detection of external PET at autopsy is a suspicious finding that suggests asphyxia. Because of the possible natural origin of these bleedings, the medicolegal investigation has to be as complete as possible and has to include histology as mandatory.

Alcohol induced region-dependent alterations of hemodynamic response: implications for the statistical interpretation of pharmacological fMRI studies.

Worldwide, ethanol abuse causes thousands of fatal accidents annually as well as innumerable social dysfunctions and severe medical disorders. Yet, few studies have used the blood oxygenation level dependent functional magnetic resonance imaging method (BOLD fMRI) to map how alcohol alters brain functions, as fMRI relies on neurovascular coupling, which may change due to the vasoactive properties of alcohol. We monitored the hemodynamic response function (HRF) with a high temporal resolution. In both motor cortices and the visual cortex, alcohol prolonged the time course of the HRF, indicating an overall slow-down of neurovascular coupling rather than an isolated reduction in neuronal activity. However, in the supplementary motor area, alcohol-induced changes to the HRF suggest a reduced neuronal activation. This may explain why initiating and coordinating complex movements, including speech production, are often impaired earlier than executing basic motor patterns. Furthermore, the present study revealed a potential pitfall associated with the statistical interpretation of pharmacological fMRI studies based on the general linear model: if the functional form of the HRF is changed between the conditions data may be erroneously interpreted as increased or decreased neuronal activation. Thus, our study not only presents an additional key to how alcohol affects the network of brain functions but also implies that potential changes to neurovascular coupling have to be taken into account when interpreting BOLD fMRI. Therefore, measuring individual drug-induced HRF changes is recommended for pharmacological fMRI.

Detection of recent ethanol intake with new markers: comparison of fatty acid ethyl esters in serum and of ethyl glucuronide and the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid in urine.

BACKGROUND: At present, recent ethanol consumption can be routinely detected with certainty only by direct measurement of ethanol concentration in blood or urine. Because ethanol is rapidly eliminated from the circulation, however, the time span for this detection is in the range of hours. Several new markers have been proposed to extend the detection interval, but their characteristics have not yet justified their use in routine clinical practice. We therefore investigated three new markers and compared their kinetics and sensitivities: (1) fatty acid ethyl esters (FAEEs) in serum, (2) ethyl glucuronide (EtG) in urine, and (3) the ratio of 5-hydroxytryptophol to 5-hydroxyindole acetic acid (5-HTOL/5-HIAA) in urine. METHODS: Seventeen healthy men participated in a drinking experiment. Blood and urine samples were collected twice daily on three consecutive days and once daily on days 4 and 5. Ethanol concentration was determined by gas chromatography, FAEE levels, by gas chromatography with mass spectrometry, EtG concentration, by liquid chromatography-tandem mass spectrometry, and 5-HTOL/5-HIAA ratio, by high-performance liquid chromatography. RESULTS: The peak serum ethanol concentrations of the subjects ranged from 5.4 to 44.7 mmol/liter (mean +/- SD, 30.1 +/- 9.1 mmol/liter). In the case of the serum ethanol determination, 100% sensitivity was reached only immediately after the end of the drinking experiment, and in the case of FAEE levels and 5-HTOL/5-HIAA ratio, it tested for 6.7 hr after the end of the ethanol intake. Thereafter, these latter parameters declined until 15.3 hr (FAEEs) and 29.4 hr (5-HTOL/5-HIAA), subsequently remaining in a stable range until 78.5 hr without further decrease. In contrast, EtG concentration showed 100% sensitivity until 39.3 hr and thereafter decreased, falling to below the limit of quantification of 0.1 mg/liter at 102.5 hr. CONCLUSION: After moderate drinking, EtG in the urine proved to be a superior marker of recent ethanol consumption in healthy subjects. This is because EtG is a direct ethanol metabolite, it occurs in the urine only when ethanol has been consumed, and its sensitivity remains at the level of 100% for 39.3 hr.

Comparative regression analysis of concurrent elimination-phase blood and breath alcohol concentration measurements to determine hourly degradation rates.

Following the introduction of limit values for blood alcohol and breath alcohol concentrations of 0.5 g/kg and 0.25 mg/L, respectively, as provided under s. 24 a of the German Road Traffic Act the question is whether also breath alcohol concentrations can be back calculated to the time of the traffic offence in cases where it is definite that the person to be examined is in the period of alcohol elimination. To this end, a study was performed in which 56 healthy volunteers consumed 0.5, 0.8 and 1.0 g of ethanol mixed with fruit juice per kilogram of body weight over a period of 10-20 min. Calculations included all 391 pairs of concurrent blood alcohol and breath alcohol concentration values obtained after 2 h following the end of drinking. All volunteers exceeded the peak value of the alcohol curve. The measured values included were above 0.1 g/kg and 0.05 mg/L. For an average intake of alcohol of 0.88 g/kg the following regression lines were calculated for the period starting 2 h after the end of drinking: blood alcohol concentration [g/kg] = 1.318 - 0.172 h and breath alcohol concentration [mg/L] = 0.589 - 0.079 h. Subtracting the simple standard deviation from the mean value yielded hourly degradation rates above 0.1 g/kg and above 0.05 mg/L, respectively. Subtracting two standard deviations, the values fell below this level in both cases. In fact, back calculation of breath alcohol concentrations based on 0.05 mg/h seems to be possible for traffic offences if certain conditions are complied with, such as the use of Evidential 7110, a calibrated breath alcohol analyser approved by the Federal Physical-Technical Laboratory for measuring the breath alcohol concentration.

Increased human polo-like kinase-1 expression in gliomas.

PLK-1 (polo-like kinase) belongs to the family of serine/threonine kinases and is involved in spindle formation, centrosome cycles and chromosome segregation. Hence, the kinase is tightly linked to cell proliferation. We could detect immunohistochemically highly expressed PLK protein in astrocytic tumours depending on the grade of anaplasia, in commercially available human glioma cell lines (U87MG, U118MG, U138MG), in one immortalized cell culture derived from a glioblastoma patient and in a primary culture derived from a glioblastoma patient. The highest labelling of PLK-1 was demonstrated in glioblastomas. There was a significant correlation between the PLK expression and the nuclear immunoreactivity of MIB-1. PLK-mRNA, found in all tumour specimens investigated emphasizes the close correlation to proliferation and growth. Furthermore, the relation of the PLK-1 expression to the Mitogen-activated Protein Kinase Cascades was studied by applying various highly specific inhibitors. While all inhibitors minimized the cell density, only the PLCy inhibitor clearly lead to a reduced PLK-1 expression in the three cell lines U87MG, U118MG, U138MG.

Determination of dopamine and dopamine-derived (R)-/(S)-salsolinol and norsalsolinol in various human brain areas using solid-phase extraction and gas chromatography/mass spectrometry.

Using a solid-phase extraction procedure and a gas chromatographic-mass spectrometric (GC/MS) method the levels of dopamine and the levels of dopamine-derived salsolinol (SAL) and norsalsolinol (NorSAL) were determined in human brain areas involved in the etiology of alcoholism, parkinsonism and other diseases. The possibility that biosynthesis of salsolinol occurs through a stereospecific enzymatic reaction was considered. Using a two-step derivatization with N-methyl-N-trimethylsilyltrifluoracetamide (MSTFA) and the chiral reagent (R)-(-)-2-phenylbutyryl chloride, baseline separated peaks of (R)- and (S)-SAL were obtained. Both enantiomers were found in human brain samples with no correlations between levels of salsolinol and dopamine. These findings do not support the hypothesis that only an enantio-selective synthesis of (R)-SAL by a putative salsolinol synthase is responsible for the in vivo formation. In our opinion, non-enzymatic formation of salsolinol via the Pictet-Spengler reaction reveals both salsolinol enantiomers and an additional enzymatic synthesis of only (R)-SAL explains the enantiomer ratio (R)-/(S)-SAL of approximately 2.