MCI-plus: mild cognitive impairment with rapid progression Part II: Biomarkers and methods

Förstl H, Werheid K, Ulm K, et al. MCI-plus: leichte kognitive Beeinträchtigung mit rascher Progredienz Teil II: Biomarker und Untersuchungsmethoden. Deutsche Medizinische Wochenschrift - DMW . 2009;134(3):88-91.Langfristig angelegte Studien sind notwendig um die präventive und frühtherapeutische Wirksamkeit von Interventionen im Vorfeld der Demenzmanifestation zu erfassen. Wegen des hohen Aufwands an Patienten und Untersuchungen, der erwartbar hohen drop-out Raten und der geringen klinischen Progression in den Gesamtstichproben, ist der Einsatz von Biomarkern von besonderem Interesse. Die Eignung funktioneller und auch struktureller Bildgebungsverfahren wird derzeit – mit ersten positiven Ergebnissen – geprüft; ob sich konventionelle Liquormarker der Alzheimer Krankheit wie beta-Amyloid und die Tau-Proteine als hinreichend veränderungssensitiv erweisen, um die Effekte früher Interventionen zu erfassen, erscheint fraglich. Auch muss offen bleiben, ob sich ähnliche Methoden in abgewandelter Form zum Einsatz in der Praxis eignen.Long-term studies will be pivotal in order to examine the efficacy of preventive and early therapeutic interventions during the preclinical phase of dementia. Biomarkers will be of importance due to the large sample sizes and the necessary logistic efforts, high drop-out rates and slow clinical progression. The validity of functional and even structural imaging methods is currently investigated with early and promising results; it is presently unclear whether conventional csf-markers of Alzheimer’s disease (beta-amyloid and tau-proteins) are sufficiently sensitive to monitor the effects of early interventions. It also remains doubtful whether modifications of these methods will ever be useful and available for practical purposes

Prävention und TherapieMCI-plus: mild cognitive impairment with rapid progression. Part I: prevention and therapy

Förstl H, Bickel H, Frölich L, et al. MCI-plus: Leichte kognitive Beeinträchtigung mit rascher Progredienz I. Prävention und Therapie. DMW - Deutsche Medizinische Wochenschrift. 2009;134(01/02):39-44.Die leichte kognitive Beeinträchtigung (Mild Cognitive Impairment, MCI) ist im höheren Lebensalter häufig und viele Betroffene weisen Prädiktoren für eine rasche Progression zur Demenz auf („MCI-plus”). Aufgrund demografischer Veränderungen und eines anwachsenden Problembewusstseins in der Bevölkerung wird MCI-plus in den nächsten Jahren in vielen Bereichen der Medizin deutlich weiter an Bedeutung gewinnen, während sich die Möglichkeiten einer Frühdiagnose schneller entwickeln als die Einführung kausaler Interventionen gegen zugrunde liegende neurodegenerative und vaskuläre Hirnveränderungen. Bei den meisten dieser Patienten bestehen aber symptomatisch beeinflussbare oder bereits heute kausal behandelbare Grund- und Begleiterkrankungen. Wir gehen auf neuropsychologische und psychopharmakologische Therapiemöglichkeiten ein, sowie auf die Chancen einer konsequenten somatischen Behandlung relevanter internistischer und neurologischer Faktoren

Velocity mapping of the aortic flow at 9.4 T in healthy mice and mice with induced heart failure using time-resolved three-dimensional phase-contrast MRI (4D PC MRI)

Objectives: In this study, we established and validated a time-resolved three-dimensional phase-contrast magnetic resonance imaging method (4D PC MRI) on a 9.4 T small-animal MRI system. Herein we present the feasibility of 4D PC MRI in terms of qualitative and quantitative flow pattern analysis in mice with transverse aortic constriction (TAC). Materials and methods: 4D PC FLASH images of a flow phantom and mouse heart were acquired at 9.4 T using a four-point phase-encoding scheme. The method was compared with slice-selective PC FLASH and ultrasound using Bland–Altman analysis. Advanced 3D streamlines were visualized utilizing Voreen volume-rendering software. Results: In vitro, 4D PC MRI flow profiles showed the transition between laminar and turbulent flow with increasing velocities. In vivo, 4D PC MRI data of the ascending aorta and the pulmonary artery were confirmed by ultrasound, resulting in linear regressions of R2 > 0.93. Magnitude- and direction-encoded streamlines differed substantially pre- and post-TAC surgery. Conclusions: 4D PC MRI is a feasible tool for in vivo velocity measurements on high-field small-animal scanners. Similar to clinical measurement, this method provides a complete spatially and temporally resolved dataset of the murine cardiovascular blood flow and allows for three-dimensional flow pattern analysis

Micro-Injection Moulding of Polymer Microfluidic Devices

Microfluidic devices have several applications in different fields, such as chemistry, medicine and biotechnology. Many research activities are currently investigating the manufacturing of integrated microfluidic devices on a mass- production scale with relatively low costs. This is especially important for applications where disposable devices are used for medical analysis. Micromoulding of thermoplastic polymers is a developing process with great potential for producing low-cost microfluidic devices. Among different micromoulding techniques, micro-injection moulding is one of the most promising processes suitable for manufacturing polymeric disposable microfluidic devices. This review paper aims at presenting the main significant developments that have been achieved in different aspects of micro-injection moulding of microfluidic devices. Aspects covered include device design, machine capabilities, mould manufacturing, material selection and process parameters. Problems, challenges and potential areas for research are highlighted

Velocity mapping of the aortic flow at 9.4 T in healthy mice and mice with induced heart failure using time-resolved three-dimensional phase-contrast MRI (4D PC MRI)

\u3cp\u3eObjectives: In this study, we established and validated a time-resolved three-dimensional phase-contrast magnetic resonance imaging method (4D PC MRI) on a 9.4 T small-animal MRI system. Herein we present the feasibility of 4D PC MRI in terms of qualitative and quantitative flow pattern analysis in mice with transverse aortic constriction (TAC). Materials and methods: 4D PC FLASH images of a flow phantom and mouse heart were acquired at 9.4 T using a four-point phase-encoding scheme. The method was compared with slice-selective PC FLASH and ultrasound using Bland–Altman analysis. Advanced 3D streamlines were visualized utilizing Voreen volume-rendering software. Results: In vitro, 4D PC MRI flow profiles showed the transition between laminar and turbulent flow with increasing velocities. In vivo, 4D PC MRI data of the ascending aorta and the pulmonary artery were confirmed by ultrasound, resulting in linear regressions of R\u3csup\u3e2\u3c/sup\u3e > 0.93. Magnitude- and direction-encoded streamlines differed substantially pre- and post-TAC surgery. Conclusions: 4D PC MRI is a feasible tool for in vivo velocity measurements on high-field small-animal scanners. Similar to clinical measurement, this method provides a complete spatially and temporally resolved dataset of the murine cardiovascular blood flow and allows for three-dimensional flow pattern analysis.\u3c/p\u3

A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition

Over the last years, murine in vivo magnetic resonance imaging (MRI) contributed to a new understanding of tissue composition, regeneration and diseases. Due to artefacts generated by the currently used metal implants, MRI is limited in fracture healing research so far. In this study, we investigated a novel MRI-compatible, ceramic intramedullary fracture implant during bone regeneration in mice. Three-point-bending revealed a higher stiffness of the ceramic material compared to the metal implants. Electron microscopy displayed a rough surface of the ceramic implant that was comparable to standard metal devices and allowed cell attachment and growth of osteoblastic cells. MicroCT-imaging illustrated the development of the callus around the fracture site indicating a regular progressing healing process when using the novel implant. In MRI, different callus tissues and the implant could clearly be distinguished from each other without any artefacts. Monitoring fracture healing using MRI-compatible implants will improve our knowledge of callus tissue regeneration by 3D insights longitudinal in the same living organism, which might also help to reduce the consumption of animals for future fracture healing studies, significantly. Finally, this study may be translated into clinical application to improve our knowledge about human bone regeneration