Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain

PURPOSE Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model. METHODS Tissue responses to MRT (two orthogonal arrays (2 × 400Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR_SO2) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia. RESULTS In tumors, MR_SO2 decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (×5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR_SO2, although vessel inter-distances increased slightly. CONCLUSION We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia.

Early gene expression analysis in 9L orthotopic tumor-bearing rats identifies immune modulation in molecular response to synchrotron microbeam radiation therapy

Synchrotron Microbeam Radiation Therapy (MRT) relies on the spatial fractionation of the synchrotron photon beam into parallel micro-beams applying several hundred of grays in their paths. Several works have reported the therapeutic interest of the radiotherapy modality at preclinical level, but biological mechanisms responsible for the described efficacy are not fully understood to date. The aim of this study was to identify the early transcriptomic responses of normal brain and glioma tissue in rats after MRT irradiation (400Gy). The transcriptomic analysis of similarly irradiated normal brain and tumor tissues was performed 6 hours after irradiation of 9 L orthotopically tumor-bearing rats. Pangenomic analysis revealed 1012 overexpressed and 497 repressed genes in the irradiated contralateral normal tissue and 344 induced and 210 repressed genes in tumor tissue. These genes were grouped in a total of 135 canonical pathways. More than half were common to both tissues with a predominance for immunity or inflammation (64 and 67% of genes for normal and tumor tissues, respectively). Several pathways involving HMGB1, toll-like receptors, C-type lectins and CD36 may serve as a link between biochemical changes triggered by irradiation and inflammation and immunological challenge. Most immune cell populations were involved: macrophages, dendritic cells, natural killer, T and B lymphocytes. Among them, our results highlighted the involvement of Th17 cell population, recently described in tumor. The immune response was regulated by a large network of mediators comprising growth factors, cytokines, lymphokines. In conclusion, early response to MRT is mainly based on inflammation and immunity which appear therefore as major contributors to MRT efficacy.

State-of-the-art aortic imaging: part I - fundamentals and perspectives of CT and MRI

Over the last two decades, imaging of the aorta has undergone a clinically relevant change. As part of the change non-invasive imaging techniques have replaced invasive intra-arterial digital subtraction angiography as the former imaging gold standard for aortic diseases. Computed tomography (CT) and magnetic resonance imaging (MRI) constitute the backbone of pre- and postoperative aortic imaging because they allow for imaging of the entire aorta and its branches. The first part of this review article describes the imaging principles of CT and MRI with regard to aortic disease, shows how both technologies can be applied in every day clinical practice, offering exciting perspectives. Recent CT scanner generations deliver excellent image quality with a high spatial and temporal resolution. Technical developments have resulted in CT scan performed within a few seconds for the entire aorta. Therefore, CT angiography (CTA) is the imaging technology of choice for evaluating acute aortic syndromes, for diagnosis of most aortic pathologies, preoperative planning and postoperative follow-up after endovascular aortic repair. However, radiation dose and the risk of contrast induced nephropathy are major downsides of CTA. Optimisation of scan protocols and contrast media administration can help to reduce the required radiation dose and contrast media. MR angiography (MRA) is an excellent alternative to CTA for both diagnosis of aortic pathologies and postoperative follow-up. The lack of radiation is particularly beneficial for younger patients. A potential side effect of gadolinium contrast agents is nephrogenic systemic fibrosis (NSF). In patients with high risk of NSF unenhanced MRA can be performed with both ECG- and breath-gating techniques. Additionally, MRI provides the possibility to visualise and measure both dynamic and flow information.

Liver Remnant Regeneration in Donors After Living Donor Liver Transplantation: Long-Term Follow-Up Using CT and MR Imaging

Purpose: To assess liver remnant volume regeneration and maintenance, and complications in the long-time follow-up of donors after living donor liver transplantation using CT and MRI. Materials and Methods: 47 donors with a mean age of 33.5 years who donated liver tissue for transplantation and who were available for follow-up imaging were included in this retrospective study. Contrast-enhanced CT and MR studies were acquired for routine follow-up. Two observers evaluated pre- and postoperative images regarding anatomy and pathological findings. Volumes were manually measured on contrast-enhanced images in the portal venous phase, and potential postoperative complications were documented. Pre- and postoperative liver volumes were compared for evaluating liver remnant regeneration. Results: 47 preoperative and 89 follow-up studies covered a period of 22.4 months (range: 1 - 84). After right liver lobe (RLL) donation, the mean liver remnant volume was 522.0 ml (± 144.0; 36.1 %; n = 18), after left lateral section (LLS) donation 1,121.7 ml (± 212.8; 79.9 %; n = 24), and after left liver lobe (LLL) donation 1,181.5 ml (± 279.5; 72.0 %; n = 5). Twelve months after donation, the liver remnant volume were 87.3 % (RLL; ± 11.8; n = 11), 95.0 % (LS; ± 11.6; n = 18), and 80.1 % (LLL; ± 2.0; n = 2 LLL) of the preoperative total liver volume. Rapid initial regeneration and maintenance at 80 % of the preoperative liver volume were observed over the total follow-up period. Minor postoperative complications were found early in 4 patients. No severe or late complications or mortality occurred. Conclusion: Rapid regeneration of liver remnant volumes in all donors and volume maintenance over the long-term follow-up period of up to 84 months without severe or late complications are important observations for assessing the safety of LDLT donors. Key Points: Liver remnant volumes of LDLT donors rapidly regenerated after donation and volumes were maintained over the long-term follow-up period of up to 84 months without severe or late complications.

Virtopsy und damit verbundene rechtliche Rahmenbedingungen und Auswirkungen

Die Virtopsy ist eine progressive bildgebende Methode der Rechtsmedizin, mit welcher außergewöhnliche Todesfälle oder auch Verletzungen lebender Personen (klinisch forensische Bildgebung) untersucht werden können. Genutzt werden hierfür bildgebende Verfahren wie z. B. CT und MRT. Die Virtopsy an Verstorbenen bringt verschiedene Vorteile gegenüber einer Autopsie mit sich, wie beispielsweise die verständliche 3D-Darstellung. Demgegenüber ergeben sich aber auch Nachteile, wie etwa der Umstand, dass Organfarben nicht sichtbar sind. Per saldo überwiegen jedoch die Vorteile, insbesondere genießen bildgebende Untersuchungen bei Angehörigen aus Gründen der Pietät und der Religion eine größere Akzeptanz als konventionelle Leichenöffnungen. Die Virtopsy kann sowohl eine Autopsie ergänzen als auch eine Autopsie-Entscheidung erleichtern, indem sie Letzterer vorausgeht. David Alexander Zimmermann beschreibt in einer ersten monografischen Abhandlung zum Thema den umfassenden rechtlichen Rahmen für bildgebende Verfahren in der Forensik. Die rechtliche Diskussion umfasst dabei die Interpretation und Vergleichung rechtlicher Quellen sowohl aus verschiedenen Ländern wie z. B. Australien, Deutschland, Schweiz und USA, als auch aus unterschiedlichen Rechtsgebieten. Dabei richtet der Autor seinen Fokus auf die Festlegung gesetzlicher Grundlagen für forensische Bildgebung / Virtopsy und deren Zulässigkeit in Strafverfahren.

Risk factors associated with the longevity of multi-rooted teeth. Long-term outcomes after active and supportive periodontal therapy

AIM To investigate risk factors for the loss of multi-rooted teeth (MRT) in subjects treated for periodontitis and enrolled in supportive periodontal therapy (SPT). MATERIAL AND METHODS A total of 172 subjects were examined before (T0) and after active periodontal therapy (APT)(T1) and following a mean of 11.5 ± 5.2 (SD) years of SPT (T2). The association of risk factors with loss of MRT was analysed with multilevel logistic regression. The tooth was the unit of analysis. RESULTS Furcation involvement (FI) = 1 before APT was not a risk factor for tooth loss compared with FI = 0 (p = 0.37). Between T0 and T2, MRT with FI = 2 (OR: 2.92, 95% CI: 1.68, 5.06, p = 0.0001) and FI = 3 (OR: 6.85, 95% CI: 3.40, 13.83, p < 0.0001) were at a significantly higher risk to be lost compared with those with FI = 0. During SPT, smokers lost significantly more MRT compared with non-smokers (OR: 2.37, 95% CI: 1.05, 5.35, p = 0.04). Non-smoking and compliant subjects with FI = 0/1 at T1 lost significantly less MRT during SPT compared with non-compliant smokers with FI = 2 (OR: 10.11, 95% CI: 2.91, 35.11, p < 0.0001) and FI = 3 (OR: 17.18, 95% CI: 4.98, 59.28, p < 0.0001) respectively. CONCLUSIONS FI = 1 was not a risk factor for tooth loss compared with FI = 0. FI = 2/3, smoking and lack of compliance with regular SPT represented risk factors for the loss of MRT in subjects treated for periodontitis.

Virtopsy und damit verbundene rechtliche Rahmenbedingungen und Auswirkungen

Die Virtopsy ist eine progressive bildgebende Methode der Rechtsmedizin, mit welcher außergewöhnliche Todesfälle oder auch Verletzungen lebender Personen (klinisch forensische Bildgebung) untersucht werden können. Genutzt werden hierfür bildgebende Verfahren wie z. B. CT und MRT. Die Virtopsy an Verstorbenen bringt verschiedene Vorteile gegenüber einer Autopsie mit sich, wie beispielsweise die verständliche 3D-Darstellung. Demgegenüber ergeben sich aber auch Nachteile, wie etwa der Umstand, dass Organfarben nicht sichtbar sind. Per saldo überwiegen jedoch die Vorteile, insbesondere genießen bildgebende Untersuchungen bei Angehörigen aus Gründen der Pietät und der Religion eine größere Akzeptanz als konventionelle Leichenöffnungen. Die Virtopsy kann sowohl eine Autopsie ergänzen als auch eine Autopsie-Entscheidung erleichtern, indem sie Letzterer vorausgeht. David Alexander Zimmermann beschreibt in einer ersten monografischen Abhandlung zum Thema den umfassenden rechtlichen Rahmen für bildgebende Verfahren in der Forensik. Die rechtliche Diskussion umfasst dabei die Interpretation und Vergleichung rechtlicher Quellen sowohl aus verschiedenen Ländern wie z. B. Australien, Deutschland, Schweiz und USA, als auch aus unterschiedlichen Rechtsgebieten. Dabei richtet der Autor seinen Fokus auf die Festlegung gesetzlicher Grundlagen für forensische Bildgebung / Virtopsy und deren Zulässigkeit in Strafverfahren.

Using 18O/2H, 3H/3He, 85Kr and CFCs to determine mean residence times and water origin in the Grazer and Leibnitzer Feld groundwater bodies (Austria)

Two groundwater bodies, Grazer Feld and Leibnitzer Feld, with surface areas of 166 and 103 km2 respectively are characterised for the first time by measuring the combination of d18O/d2H, 3H/3He, 85Kr, CFC-11, CFC-12 and hydrochemistry in 34 monitoring wells in 2009/2010. The timescales of groundwater recharge have been characterised by 131 d18O measurements of well and surface water sampled on a seasonal basis. Most monitoring wells show a seasonal variation or indicate variable contributions of the main river Mur (0–30%, max. 70%) and/or other rivers having their recharge areas in higher altitudes. Combined d18O/d2H-measurements indicate that 65–75% of groundwater recharge in the unusual wet year of 2009 was from precipitation in the summer based on values from the Graz meteorological station. Monitoring wells downstream of gravel pit lakes show a clear evaporation trend. A boron–nitrate differentiation plot shows more frequent boron-rich water in the more urbanised Grazer Feld and more frequent nitrate-rich water in the more agricultural used Leibnitzer Feld indicating that a some of the nitrate load in the Grazer Feld comes from urban sewer water. Several lumped parameter models based on tritium input data from Graz and monthly data from the river Mur (Spielfeld) since 1977 yield a Mean Residence Time (MRT) for the Mur-water itself between 3 and 4 years in this area. Data from d18O, 3H/3He measurements at the Wagna lysimeter station supports the conclusion that 90% of the groundwaters in the Grazer Feld and 73% in the Leibnitzer Feld have MRTs of <5 years. Only in a few groundwaters were MRTs of 6–10 or 11–25 years as a result of either a long-distance water inflow in the basins or due to longer flow path in somewhat deeper wells (>20 m) with relative thicker unsaturated zones. The young MRT of groundwater from two monitoring wells in the Leibnitzer Feld was confirmed by 85Kr-measurements. Most CFC-11 and CFC-12 concentrations in the groundwater exceed the equilibration concentrations of modern concentrations in water and are therefore unsuitable for dating purposes. An enrichment factor up to 100 compared to atmospheric equilibrium concentrations and the obvious correlation of CFC-12 with SO4, Na, Cl and B in the ground waters of the Grazer Feld suggest that waste water in contact with CFC-containing material above and below ground is the source for the contamination. The dominance of very young groundwater (<5 years) indicates a recent origin of the contamination by nitrate and many other components observed in parts of the groundwater bodies. Rapid measures to reduce those sources are needed to mitigate against further deterioration of these waters.

Hyperammonemic encephalopathy in multiple myeloma

HISTORY AND CLINICAL FINDINGS A 54-year old man had suffered from advanced multiple myeloma for two years. After initially good response the myeloma was refractrory to treatment with dexamethasone, cyclophosphamide, bortezomibe, zoledronate and additionally doxorubicine. The patient then complained of dyspnea without clinical signs of cardiopulmonary disease. INVESTIGATIONS Arterial blood gas analysis showed hyperventilation with respiratory alkalosis and normal alveolo-arterial gradient as the reason for the dyspnea. With a normal MRI of the brain and lumbal puncture, a neurological disease could be excluded. Serum calcium, creatinine and serum viscosity were normal. Eventually, serum ammonia levels were found to be substantially elevated (144 µmol/l) and hyperammonemic encephalopathy was diagnosed. TREATMENT AND COURSE Therapy with bortezomib and high dose dexamethason was repeated, and the patient also received bendamustin. Despite this treatment, he lost consciousness and died after two weeks because of aspiration pneumonia. CONCLUSION The existence of respiratory alkalosis and multiple myeloma should prompt a search for hyperammonemia.

Magnet resonance imaging in common injuries of the wrist

Falling on the outstretched hand is a common trauma mechanism. In contrast to fractures of the distal radius, which usually are diagnosed on plain film radiographs, identifying wrist injuries requires further diagnostic methods, e.g., MRI or CT. This article provides a review of the use of MRI in the most common traumatic wrist injuries, including scaphoid fractures, TFCC lesions, and tears of the scapholunate ligament. Early and selective use of MRI as a further diagnostic method in cases of adequate clinical suspicion helps to initiate the correct treatment and, thus, prevents long-term arthrotic injuries and reduces unnecessary absence due to illness. MRI shows a high reliability in the diagnosis of scaphoid fractures and the America College of Radiology recommends MRI as method of choice after X-ray images have been made. In the diagnosis of ligament and discoid lesions, MR arthrography (MRA) using intraarticular contrast agent has considerably higher accuracy than i.v.-enhanced and especially unenhanced MRI.

Wer lenkte den PW?

Die Rekonstruktion von Verkehrsunfällen ist ein interdisziplinäres Arbeitsgebiet. Verschiedene Institutionen wie z.B. die Polizei, die Rechtsmedizin oder die Unfallanalyse befassen sich mit der Beantwortung von juristischen Fragestellungen bei Verkehrsunfällen. Die modernen 3D-Dokumentations- und Analysemethoden und der Einsatz der bildgebenden Verfahren in der Rechtsmedizin ermöglichen eine disziplinübergreifende Auswertung der vorhandenen Spuren und Befunde und eröffnen damit ganz neue Horizonte und Dimensionen. Zudem ermöglichen sie es auch dem technischen Laien, eine bildliche Vorstellung der komplexen unfalldynamischen Abläufe zu geben. Im vorliegenden Beitrag wird anhand eines Falles die interdisziplinäre Fallanalyse und morphometrische 3D-Rekonstruktion vorgestellt und erläutert. Dieser Fall wurde Jahre nach dem Ereignis in Auftrag gegeben zur Klärung der Frage, wer den PW zum Unfallzeitpunkt gelenkt hatte. Die morphometrische 3D-Rekonstruktion umfasst die Ermittlung des Unfallhergangs, des biomechanischen Verhaltens der Fahrzeuginsassen und der Entstehung ihrer Verletzungen sowie der Entstehung der Blutspuren und weiterer Spuren und Beschädigungen im Fahrzeuginneren. Die Fahrzeuginsassen werden mittels Photogrammetrie und optischem 3D-Oberflächenscanning dreidimensional dokumentiert. Von verletzten Insassen werden zusätzlich die Daten klinischer radiologischer Untersuchungen von verstorbenen die vor der Obduktion durchgeführte Computertomographie (CT) und Magnetresonanztomographie (MRT) in die 3D-Analyse integriert. Das Fahrzeug und alle unfallrelevanten Objekte werden ebenfalls mittels Photogrammetrie und 3D-Oberflächenscanning erfasst. Ein 3D- Situationsplan der Örtlichkeit mit allen Spuren wird von der Polizei mittels Photogrammetrie und Laserscanning erstellt und in die Auswertung integriert. Anhand dieser 3D-Daten, insbesondere der Spuren am Unfallort und der Beschädigungen des Fahrzeuges, wird der Unfallablauf und daraus resultierend das biomechanische Verhalten der Fahrzeuginsassen rekonstruiert und in der Animationssoftware 3DS Max Design nachgestellt. Basierend auf den gewonnenen Erkenntnissen können morphometrische Vergleiche der Verletzungen mit den relevanten Strukturen im Fahrzeuginneren durchgeführt und so ermittelt werden, wie diese Verletzungen entstanden sind und auf welchen Sitzen die Insassen während des Unfalles sassen. Neben den Verletzungen können auch die Körpergrössen der Insassen Hinweise zur Ermittlung des Lenkers geben. Die Möglichkeiten der morphometrischen Rekonstruktion mittels der 3D-Techniken sind weitreichend und können oft entscheidende Erkenntnisse für das Ermittlungsverfahren liefern.

Effects of microbeam radiation therapy on normal and tumoral blood vessels

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT.

[Diagnosis and Treatment of Spondylodiscitis/Spondylitis in Clinical Practice].

BACKGROUND The clinical presentation of spondylsodiscitis/spondylitis are manifold. This commonly leads to a period of several months from initial symptoms to final diagnosis. A standardised treatment is difficult. The purpose of this study is to investigate the treatment carried out for patients with spondylodiscitis or spondylitis to develop an individualised standard care for better treatment. PATIENTS AND METHODS Data of 90 patients were retrospective analysed. In particular documented data of the initial examination and the following treatments concerning identification of causes and systematically control of pathogens were examined. RESULTS In 91 % of patients a diagnostically conclusive MRI was conducted. The degree of spondylidiscitis/spondylitis was mainly ASA criteria I or II (86 %). In 96 % of patients different diagnostic methods for identification of pathogens were conducted and documented. RESULTS confirmed the most common pathogens mentioned in the literature. 75 % of patients were treated by surgery. In 93 % of patients an antibiotic treatment was documented. 50 patients (81 %) were successfully healed. CONCLUSION It is important to identify and treat spondylodiscitis/spondylitis as early as possible. Diagnosis by means of blood culture and MRI and treatment of the infection with antibiotics and possibly surgical interventions seem be very suitable, but need to be individualised to each and every patient.

Glenohumeral dislocation. Injury patterns and combination injuries

Hintergrund Begleitverletzungen können in bis zu 90 % der Fälle nach erstmaliger Schulterluxation auftreten. Auch wenn sie nicht immer einen Einfluss auf die Therapiewahl haben, so ist eine sorgfältige Diagnostik entscheidend. Einteilung In der Akutsituation ist eine konventionelle Bildgebung in mindestens 2 Ebenen (a.-p./Neer/evtl. axial) vor und nach Reposition zwingend. Luxationsfrakturen dürfen nicht übersehen bzw. durch das Manöver der geschlossenen Reposition sekundär disloziert werden. Bestehen ossäre glenoidale, humerale oder kombinierte Verletzungen, sollten sie gemäß Stabilitätskriterien versorgt werden. Dies kann umgehend, nach manifester Dezentrierung oder Instabilität entweder mittels Osteosythese oder als glenohumerale Stabilisation im Verlauf erfolgen. Bei einer Instabilität ist prinzipiell zur Bilanzierung einer ossären Ursache das Arthro-CT die Untersuchung der Wahl, welche auch eine Beurteilung der kapsulolabroligamentären Verletzung sowie einer traumatischen Rotatorenmanschettenläsion ermöglicht. Letztere ist jedoch besser mittels Arthro-MRT zu beurteilen. Diskussion Eine signifikante frische, meist größere oder massive, Rotatorenmanschettenläsion sollte rasch operativ angegangen werden. Medial reichende „off the track“ Hill-Sachs-Läsionen können mittels einer Hill-Sachs-Remplissage oder, wie auch glenoidale Defekte, mittels einer Kochenaugmentation versorgt werden. Langzeitresultate des Latarjet-Verfahrens zeigen 25 Jahre nach dem Eingriff die niedrigste Reluxationsrate < 4 %, eine gute Außenrotation, eine sehr hohe Patientenzufriedenheit und degenerative Veränderungen, welche vergleichbar mit der natürlichen Entwicklung nach erstmaliger Schulterluxation ohne Rezidiv sind.

Gymnasts and orienteers display better mental rotation performance than nonathletes

The aim of this study was to examine whether athletes differ from nonathletes regarding their mental rotation performance. Furthermore, it investigated whether athletes doing sports requiring distinguishable levels of mental rotation (orienteering, gymnastics, running), as well as varying with respect to having an egocentric (gymnastics) or an allocentric perspective (orienteering), differ from each other. Therefore, the Mental Rotations Test (MRT) was carried out with 20 orienteers, 20 gymnasts, 20 runners, and 20 nonathletes. The results indicate large differences in mental rotation performance, with those actively doing sports outperforming the nonathletes. Analyses for the specific groups showed that orienteers and gymnasts differed from the nonathletes, whereas endurance runners did not. Contrary to expectations, the mental rotation performance of gymnasts did not differ from that of orienteers. This study also revealed gender differences in favor of men. Implications regarding a differentiated view of the connection between specific sports and mental rotation performance are discussed.