Post-mortem computed tomography is a useful tool for determining the pulmonary ventilation status in newborns

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Introduction</jats:title> <jats:p>Lung ventilation is a standard sign of life in newborns. Post-mortem computed tomography (PMCT) is highly sensitive to the presence of gas in the body including the lungs. Current standard examinations to determine the pulmonary ventilation status in newborns are the flotation test and histology. The purpose of this study was to compare the accuracy of PMCT with the flotation test for determining the lung ventilation status with histological control as reference standard. A cut-off value as CT number in Hounsfield Units (HU) determining lung ventilation of newborns in PMCT should be established.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A total of 38 infant lungs were examined of which 21 lungs were from infants deceased shortly after live birth (control group) and 17 lungs belonged to infants where live birth was in question (study group). All lungs were examined using PMCT, flotation test, and histological examination.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The control group showed an overall mean attenuation ± standard deviation of −219 HU ± 135; the study group of 45 ± 15 HU in histologically nonventilated lungs versus −192 ± 207 HU; (<jats:italic>p</jats:italic> < 0.001) in ventilated lungs. The best cut-off value for optimal discrimination of ventilated and nonventilated lungs in newborns was −35 mean HU.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>PMCT is equally well suited to determine lung ventilation as the flotation test. It provides additional information regarding pulmonary infiltration, degree of putrefaction, or signs of trauma (fractures, pneumothorax). Histology remains mandatory in ambiguous cases.</jats:p> </jats:sec&gt

Submillisievert Computed Tomography of the Chest Using Model-Based Iterative Algorithm: Optimization of Tube Voltage With Regard to Patient Size

Objective: The aim of this study was to define optimal tube potential for soft tissue and vessel visualization in dose-reduced chest CT protocols using model-based iterative algorithm in average and overweight patients. Methods: Thirty-six patients receiving chest CTaccording to 3 protocols (120 kVp/noise index [NI], 60;100 kVp/NI, 65;80 kVp/NI, 70) were included in this prospective study, approved by the ethics committee. Patients' physical parameters and dose descriptors were recorded. Images were reconstructed with model-based algorithm. Two radiologists evaluated image quality and lesion conspicuity;the protocols were intraindividually compared with preceding control CT reconstructed with statistical algorithm (120 kVp/NI, 20). Mean and standard deviation of attenuation of the muscle and fat tissues and signal-to-noise ratio of the aorta were measured. Results: Diagnostic images (lesion conspicuity, 95%-100%) were acquired in average and overweight patients at 1.34, 1.02, and 1.08 mGy and at 3.41, 3.20, and 2.88 mGy at 120, 100, and 80 kVp, respectively. Data are given as CT dose index volume values. Conclusions: Model-based algorithm allows for submillisievert chest CT in average patients;the use of 100 kVp is recommended

Analysis of the three-dimensional anatomical variance of the distal radius using 3D shape models

BACKGROUND: Various medical fields rely on detailed anatomical knowledge of the distal radius. Current studies are limited to two-dimensional analysis and biased by varying measurement locations. The aims were to 1) generate 3D shape models of the distal radius and investigate variations in the 3D shape, 2) generate and assess morphometrics in standardized cut planes, and 3) test the model's classification accuracy. METHODS: The local radiographic database was screened for CT-scans of intact radii. 1) The data sets were segmented and 3D surface models generated. Statistical 3D shape models were computed (overall, gender and side separate) and the 3D shape variation assessed by evaluating the number of modes. 2) Anatomical landmarks were assigned and used to define three standardized cross-sectional cut planes perpendicular to the main axis. Cut planes were generated for the mean shape models and each individual radius. For each cut plane, the following morphometric parameters were calculated and compared: maximum width and depth, perimeter and area. 3) The overall shape model was utilized to evaluate the predictive value (leave one out cross validation) for gender and side identification within the study population. RESULTS: Eighty-six radii (45 left, 44% female, 40 +/- 18 years) were included. 1) Overall, side and gender specific statistical 3D models were successfully generated. The first mode explained 37% of the overall variance. Left radii had a higher shape variance (number of modes: 20 female / 23 male) compared to right radii (number of modes: 6 female / 6 male). 2) Standardized cut planes could be defined using anatomical landmarks. All morphometric parameters decreased from distal to proximal. Male radii were larger than female radii with no significant side difference. 3) The overall shape model had a combined median classification probability for side and gender of 80%. CONCLUSIONS: Statistical 3D shape models of the distal radius can be generated using clinical CT-data sets. These models can be used to assess overall bone variance, define and analyze standardized cut-planes, and identify the gender of an unknown sample. These data highlight the potential of shape models to assess the 3D anatomy and anatomical variance of human bones

Die DEAD-Box RNA-Helikase DDX6 rekrutiert P-TEFb aus dem 7SK snRNP für die Inkorporation in den AF4-Superelongationskomplex

Die eukaryotische RNA-Polymerase II (RNAPII) ist der zentrale Faktor für die Umsetzung des genetischen Codes in funktionelle Proteine. Durch die Transkription wird die statische Information der DNA in ein transient nutzbares RNA-Molekül umgewandelt. Bei diesem fundamentalen Prozess der Genexpression wird ein spezifischer DNA-Abschnitt des Genoms abgelesen und in die komplementäre RNA transkribiert, die entweder direkt regulatorische bzw. funktionelle Aufgaben in der Zelle übernimmt oder als Matrize für die Proteinbiosynthese dient. Zur Erhaltung der Funktionalität eines Organismus und zur schnellen und gezielten Reaktion auf exogene Reize ist eine strikte Regulation der Transkription und der zahlreichen beteiligten Faktoren notwendig. Aufgrund der zentralen Rolle in der Genexpression ist diese Regulation äußerst vielschichtig und erfordert eine feinabgestimmte Maschinerie an Enzymen und Transkriptionsfaktoren, deren genaue Wirkungsweise und Abhängigkeit noch nicht vollständig verstanden sind. Fehler in der Transkriptionsregulation werden mit einer Reihe von schwerwiegenden metabolischen Störungen und der möglichen malignen Transformation der betroffenen Zelle in Verbindung gebracht. Während einige Regulationsmechanismen der RNAPII bereits seit längerer Zeit beschrieben sind, ist eine besondere Form der RNAPII-abhängigen Regulation erst in den letzten Jahren Gegenstand genauerer Untersuchungen geworden. So erfährt die RNAPII bei einer Vielzahl von Genen unmittelbar nach der Transkriptionsinitiation einen Arrest, der das Enzym nicht weiter über die DNA prozessieren lässt und somit die produktive Elongation des Gens blockiert. Die Aufhebung dieses promotornahen Arrests wird durch den positiven Transkriptions-Elongationsfaktor b (P-TEFb) dominiert, der durch distinkte post-translationale Modifikationen der C-terminalen Domäne der RNAPII und assoziierter Faktoren den Übergang in die produktive Transkriptionselongation ermöglicht. P-TEFb selbst unterliegt dabei einer strengen Regulation durch die Inkorporation in inhibierende Speicherkomplexe (7SK snRNPs), bestehend aus der 7SK snRNA und mehrerer assoziierter Proteine. Abseits des 7SK snRNP wurde P-TEFb als Bestandteil großer Multiproteinkomplexe identifiziert, die einen positiven Einfluss auf die Transkriptionselongation besitzen. Die Transition von P-TEFb aus dem 7SK snRNP in diese sogenannten Superelongationskomplexe (SECs) stellt einen der zentralen Regulationsmechanismen der eukaryotischen Transkription dar, ist jedoch noch nicht ausreichend verstanden. Ein zentrales Element aller SECs bilden die Mitglieder der AF4/FMR2-Proteinfamilie, darunter das AF4 Protein, dem neben der Erhaltung der strukturellen Integrität mittlerweile auch eine Funktion in der Rekrutierung von P-TEFb zugeschrieben wird. Dabei scheint AF4 jedoch auf die Hilfe bislang noch nicht charakterisierter Faktoren angewiesen zu sein. AF4 ist über diese Rolle hinaus als Bestandteil des Fusionsproteins AF4-MLL eng mit der onkogenen Zelltransformation im Falle einer durch die Translokation t(4;11)(q21;q23) bedingten, akuten lymphoblastischen Leukämie assoziiert. Das zentrale Thema dieser Arbeit stellen Untersuchungen zum Transfer von P-TEFb aus dem 7SK snRNP zum AF4-Protein dar. Dabei konnte zunächst die DEAD-Box RNA-Helikase DDX6 als Integraler Bestandteil der AF4-SECs identifiziert werden, der bereits eine Funktion in der Kontrolle des microRNA- wie auch des mRNA-Metabolismus zugeschrieben werden konnte. Aus diesem Grund wurde von uns eine mögliche Beteiligung von DDX6 an der Rekrutierung von P-TEFb zum AF4-SEC durch Modulationen der 7SK snRNA postuliert. Des Weiteren konnte eine Bindefähigkeit von DDX6 gegenüber der 7SK snRNA sowie eine direkte Korrelation zwischen des zellulären DDX6-Proteinlevel und der Akkumulation von P-TEFb im AF4-SEC nachgewiesen werden. Sowohl die Überexpression von DDX6 als auch die von AF4 resultierten in einer gesteigerten mRNA-Produktion, wobei die Ergebnisse auf einen kooperativen Mechanismus zwischen den beiden Proteinen in der Aktivierung der Transkription hindeuteten. Außerdem konnte die These einer DDX6-vermittelten Aktivierung von P-TEFb anhand von Expressionsanalysen des bekannten P-TEFb Zielgens HEXIM1, dessen Expression im Zusammenhang eines negativen Rückkopplungsmechanismus gesteigert wird, bestätigt werden. Damit konnte der DEAD-Box RNA-Helikase DDX6 in dieser Arbeit das erste Mal eine entscheidende Funktion in der Rekrutierung von P-TEFb aus dem 7SK snRNP in den AF4-SEC, und somit an der Kontrolle der eukaryotischen Transkription, zugeschrieben werden

Introduction of CTA-index as Simplified Measuring Method for Thrombus Perviousness.

PURPOSE Thrombus features on admission CT are useful imaging markers for clot characterization, stroke pathogenesis and outcome prediction. In this context, thrombus perviousness is a promising parameter, but reliable assessment in daily clinical practice is demanding. The aim of the present study was to evaluate an easy to assess measuring method for thrombus permeability at the time of admission. METHODS The CTA-index, which measures relative thrombus attenuation on admission CTA, was compared to the known perviousness parameter in a cohort of 101 patients with large-vessel occlusions of the middle cerebral artery and correlated to clinical outcome parameters (mRS after 90 days, ≤2 rated as favorable). For validation, this correlation was tested in a second independent cohort (n = 87), and possible associations between the CTA-index and outcome measurements (NIHSS/mRS/mTICI) were assessed. RESULTS In the first cohort a coherence between conventional perviousness measurements and the CTA-index was shown. The CTA-index differed significantly between favorable (-0.55 ± 0.16) and non-favorable outcomes (-0.64 ± 0.14, p = 0.01). In the validation cohort this result could be independently reproduced (-0.52 ± 0.13/-0.70 ± 0.09, p < 0.01). The CTA-index showed an association with low NIHSS at discharge (p < 0.01), favorable outcome after 90 days (p < 0.001) and with better reperfusion (measured by mTICI score, p = 0.04). CONCLUSION The CTA-index is an easy to assess imaging parameter on admission CTA in the acute stroke phase and is associated with angiographic and clinical outcome. It can be considered as a simplified measuring method for thrombus perviousness, which is known to provide useful information for further stroke progress and clinical course as well as therapeutic and rehabilitative decisions

Is It Possible to Replace Conventional Radiography (CR) with a Dose Neutral Computed Tomography (CT) of the Cervical Spine in Emergency Radiology—An Experimental Cadaver Study

The purpose of this experimental study on recently deceased human cadavers was to investigate whether (I) the radiation exposure of the cervical spine CT can be reduced comparable to a dose level of conventional radiography (CR); and (II) whether and which human body parameters can be predictive for higher dose reduction potential (in this context). Materials and Methods: Seventy serial CT scans of the cervical spine of 10 human cadavers undergoing postmortem virtual autopsy were taken using stepwise decreasing upper limits of the tube current (300 mAs, 150 mAs, 110 mAs, 80 mAs, 60 mAs, 40 mAs, and 20 mAs) at 120 kVp. An additional scan acquired at a fixed tube current of 300 mAs served as a reference. Images were reconstructed with filtered back projection and the upper (C1-4) and lower (C4-7) cervical spine were evaluated by three blinded readers for image quality, regarding diagnostic value and resolution of anatomical structures according to a semiquantitative three-point-scale. Dose values and individual physical parameters were recorded. The relationship of diagnostic IQ, dose reduction level, and patients’ physical parameters were investigated. The high-contrast resolution of the applied CT protocols was tested in an additional phantom study. Results: The IQ of the upper cervical spine was diagnostic at 1.69 ± 0.58 mGy (CTDI) corresponding to 0.20 ± 0.07 mSv (effective dose) in all cadavers. IQ of the lower cervical spine was diagnostic at 4.77 ± 1.86 mGy corresponding to 0.560 ± 0.21 mSv (effective dose) in seven cadavers and at 2.60 ± 0.93 mGy corresponding to 0.31 ± 0.11 mSv in four cadavers. Significant correlation was detected for BMI (0.8366; p = 0.002548) and the anteroposterior (a.p.) chest diameter (0.8363; p = 0.002566), shoulder positioning (0.79799; p = 0.00995), and radiation exposure. Conclusions: Conventional radiography can be replaced with a nearly dose-neutral CT scan of the cervical spine

From Perviousness to Plaque Imaging in Acute Basilar Occlusions: The Impact of Underlying Stenosis and How to Detect It.

Background and Purpose- Recent studies show that mechanical thrombectomy of acute basilar artery occlusions (BAO) results in high rates of successful recanalization and good outcomes, but predictors are not completely established yet. Varying occlusion types may benefit differently, and especially, an underlying basilar stenosis (BS) seems to have an impact. Aim of this study was to investigate angiographic and clinical differences in BAO subtypes and to test the potential of perviousness measures for a preinterventional identification of clinically relevant different occlusion types. Methods- All consecutive patients with acute BAO, endovascular treated at a single comprehensive stroke center, were included. Different occlusion patterns, especially underlying BS, were identified and analyzed in respect of angiographic and clinical (National Institutes of Health Stroke Scale/modified Rankin Scale) outcome parameters (N=115). Thrombus perviousness measures (change in thrombus attenuation Δt and corrected void fraction ε) were assessed in admission computed tomography imaging and correlated to different etiological subgroups. Results- Despite comparable rates of successful recanalization (87% for BAO with BS versus 95% without BS), the BS group showed worse clinical outcome with higher National Institutes of Health Stroke Scale/modified Rankin Scale values (P=0.002/0.003). The group of BS turned out to have lower thrombus density values in unenhanced scans (mean, 42.0 Hounsfield units) and higher perviousness measures Δt (mean, 34.6 Hounsfield units) and ε (mean, 0.23) than thrombi without an underlying BS (mean, 53.6 Hounsfield units/13.1 Hounsfield units/0.08, P=0.01/ 0.004/ 0.001). Conclusions- In agreement with previous studies, outcome of mechanical thrombectomy of BAO seems to depend on pathogenesis with less clinical benefit for underlying BS, raising the question of early identification of this subgroup. Perviousness showed a high potential to differentiate acute BAO with and without BS, possibly usable as an admission imaging marker for BS