Die Autoren bedanken sich bei Alexander Herbst, Jeff Killen, Charles Wells, Kathy Pearson und Vaibhav Paneri für ihre Hilfe bei dem Projekt danken in verschiedenen Stadien. Diese Arbeit wird von der UAB Fachbereich Psychologie Fakultät Anschubfinanzierung, die McNulty-Civitan Scientist Award und die CCTS Pilot Research Grant (5UL1RR025777) auf RK unterstützt.

<ol>
	<li>Friston, K. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+and+effective+connectivity+in+neuroimaging:+A+synthesis.">Functional and effective connectivity in neuroimaging: A synthesis.</a> Human Brain Mapping. 2, 56-78 (1994).</li><li>Just, M. A., Cherkassky, V. L., Keller, T. A., Minshew, N. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortical+activation+and+synchronization+during+sentence+comprehension+in+high-functioning+autism:+evidence+of+underconnectivity.">Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity.</a> Brain: a journal of neurology. 127, 1811-1821 (2004).</li><li>Kana, R. K., Keller, T. A., Cherkassky, V. A., Minshew, N. J., Just, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sentence+comprehension+in+autism:+thinking+in+pictures+with+decreased+functional+connectivity.">Sentence comprehension in autism: thinking in pictures with decreased functional connectivity.</a> Brain: a journal of neurology. 129, 2484-2493 (2006).</li><li>Koshino, H., Kana, R. K., Keller, T. A., Cherkassky, V. L., Minshew, N. J., Just, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=fMRI+Investigation+of+Working+Memory+for+Faces+in+Autism:+Visual+Coding+and+Underconnectivity+with+Frontal+Areas.">fMRI Investigation of Working Memory for Faces in Autism: Visual Coding and Underconnectivity with Frontal Areas.</a> Cerebral Cortex. 18, 289-300 (2007).</li><li>Kana, R. K., Keller, T. A., Minshew, N. J., Just, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibitory+control+in+high-functioning+autism:+decreased+activation+and+underconnectivity+in+inhibition+networks.">Inhibitory control in high-functioning autism: decreased activation and underconnectivity in inhibition networks.</a> Biological Psychiatry. 62, 196-208 (2007).</li><li>Just, M. A., Cherkassky, V. L., Keller, T. A., Kana, R. K., Minshew, N. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+and+Anatomical+Cortical+Underconnectivity+in+Autism:+Evidence+from+an+fMRI+Study+of+an+Executive+Function+Task+and+Corpus+Callosum+Morphometry.">Functional and Anatomical Cortical Underconnectivity in Autism: Evidence from an fMRI Study of an Executive Function Task and Corpus Callosum Morphometry.</a> Cerebral Cortex. 17, 951-961 (2007).</li><li>Castelli, F., Frith, C., Happe, F., Frith, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autism,+Asperger+syndrome+and+brain+mechanisms+for+the+attribution+of+mental+states+to+animated+shapes.">Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes.</a> Brain. 125, 1839-1849 (2002).</li><li>Gray, C. A., Garand, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Social+stories:+Improving+responses+of+students+with+autism+with+accurate+social+information.">Social stories: Improving responses of students with autism with accurate social information.</a> Focus on Autistic Behavior. 8, 1-10 (1993).</li><li>Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+functional+and+structural+MR+image+analysis+and+implementation+as+FSL.">Advances in functional and structural MR image analysis and implementation as FSL.</a> NeuroImage. 23, 208-219 (2004).</li><li>Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C. E., Watkins, K. E., Ciccarelli, O., Cader, M. Z., Matthews, P. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tract-based+spatial+statistics:+Voxelwise+analysis+of+multi-subject+diffusion+data.">Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data.</a> NeuroImage. 31, 1487-1505 (2006).</li><li>Li, Q., Sun, J., Guo, L., Zang, Y., Feng, Z., Huang, X., Yang, H., Lv, Y., Huang, M., Gong, Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+fractional+anisotropy+in+white+matter+of+the+right+frontal+region+in+children+with+attention-deficit/hyperactivity+disorder:+a+diffusion+tensor+imaging+study.">Increased fractional anisotropy in white matter of the right frontal region in children with attention-deficit/hyperactivity disorder: a diffusion tensor imaging study.</a> Neuro Endocrinol Lett. 31, 747-753 (2010).</li><li>Jeong, J. W., Sundaram, S. K., Kumar, A., Chugani, D. C., Chugani, H. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aberrant+diffusion+and+geometric+properties+in+the+left+arcuate+fasciculus+of+developmentally+delayed+children:+a+diffusion+tensor+imaging+study.">Aberrant diffusion and geometric properties in the left arcuate fasciculus of developmentally delayed children: a diffusion tensor imaging study.</a> AJNR Am J Neuroradiol. 32, 323-330 (2011).</li><li>Mulder, M. J., van Belle, J., van Engeland, H., Durston, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+connectivity+between+cognitive+control+regions+is+sensitive+to+familial+risk+for+ADHD.">Functional connectivity between cognitive control regions is sensitive to familial risk for ADHD.</a> Human Brain Mapping. , (2010).</li><li>Vourkas, M., Micheloyanni, S., Simos, P. G., Rezaie, R., Fletcher, J. M., Cirino, P. T., Papanicolaou, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+task-specific+brain+network+connectivity+in+children+with+severe+reading+difficulties.">Dynamic task-specific brain network connectivity in children with severe reading difficulties.</a> Neurosci Lett. 488, 123-128 (2011).</li></ol>

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Die Methoden und Verfahren in diesem Papier beschrieben werden in grundlegende Prinzipien der kognitiven Neurowissenschaft und Neuroimaging geerdet. Zusammengenommen bieten diese Methoden eine überzeugende Rahmen für die Beurteilung der Funktionsweise des Gehirns auf der Systemebene in Kinder, Erwachsene, und bei Menschen mit Störungen. Studies in diesen Methoden begründet wurden besonders einflussreich in der Charakterisierung der diskordanten Funktionsweise des Gehirns bei Menschen mit Autismus. <p class="jove...

probing the brain in autism using fmri and diffusion tensor imaging

Neu auftretende Theorien besagen, dass das Gehirn nicht als geschlossene Einheit in Autismus-Funktion, und diese Uneinigkeit in der Verhaltensauffälligkeiten von Menschen mit Autismus angezeigt wider. Während die strukturelle Bildgebung Befunde einige Einblicke in Gehirn-Anomalien bei Autismus zur Verfügung gestellt haben, ist die Konsistenz solcher Befunde fraglich. Funktionelle Bildgebung, auf der anderen Seite wurde mehr fruchtbar in dieser Hinsicht, weil Autismus ist eine Störung des dynamischen Verarbeitung und ermöglicht die Untersuchung der Kommunikation zwischen kortikalen Netzwerke, die zu sein, wo das eigentliche Problem tritt bei Autismus erscheint. Funktionelle Konnektivität ist die zeitliche Korrelation von räumlich getrennten neurologischen events1 definiert. Die Ergebnisse einer Reihe von neueren fMRI Studien haben die Vorstellung, dass es schwächer Koordinierung zwischen den verschiedenen Teilen des Gehirns, die zusammenarbeiten, um komplexe soziale oder sprachliche Probleme 2,3,4,5,6 zu erreichen, sollten unterstützt. Eines der Geheimnisse des Autismus ist die Koexistenz von Defiziten in mehreren Bereichen mit relativ intakt, manchmal erweitert, Fähigkeiten. Solche komplexen Manifestation des Autismus erfordert eine globale und umfassende Untersuchung der Störung an der neuronalen Ebene. Ein überzeugendes jüngsten Bericht über die Funktionsweise des Gehirns beim Autismus, ermöglicht die kortikale underconnectivity Theorie, 2,7 einer integrierenden Rahmen für die neurobiologischen Grundlagen von Autismus. Die kortikale underconnectivity Theorie des Autismus vermuten, dass jede Sprache, soziale oder psychologische Funktion, die abhängig von der Integration mehrerer Hirnregionen ist anfällig für Störungen, wie die Verarbeitung steigender Nachfrage ist. In Autismus, kann die Unterfunktion der integrativen Schaltungen im Gehirn verursachen weit verbreitet underconnectivity. In anderen Worten können Menschen mit Autismus Informationen auf unsystematische Weise interpretieren auf Kosten des Ganzen. Da kortikalen underconnectivity unter Hirnregionen, vor allem im frontalen Cortex und hinteren Bereiche 3,6, wurde nun relativ gut etabliert, können wir beginnen besser zu verstehen Gehirn-Konnektivität als entscheidende Komponente des Autismus Symptomatik. Ein logischer nächster Schritt in diese Richtung ist es, die anatomischen Verbindungen, die funktionelle Zusammenhänge erwähnt vermitteln untersuchen kann. Diffusion Tensor Imaging (DTI) ist eine relativ neue bildgebende Technik, die Sonde die Diffusion von Wasser in das Gehirn, um die Integrität der weißen Substanz Fasern schließen hilft. In dieser Technik wird die Diffusion von Wasser in das Gehirn in verschiedene Richtungen mit Diffusionsgradienten untersucht. Während funktionelle Konnektivität bietet Informationen über die Synchronisation der Hirnaktivität in verschiedenen Hirnregionen bei einer Aufgabe oder während der Ruhe, hilft DTI in das Verständnis der zugrunde liegenden axonalen Organisation, die die Cross-Talk zwischen den Hirnarealen erleichtern kann. Dieses Papier wird diese Techniken als wertvolle Instrumente beschreiben, in das Verständnis des Gehirns beim Autismus und die Herausforderungen in dieser Linie der Forschung beteiligt.

Watch this Scientific Journal Video about Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging at JoVE.com

Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging

Neuroimaging-Techniken, wie der funktionellen MRT und Diffusion Tensor Imaging zunehmend zur Charakterisierung der kognitiven und neuronalen Defizite bei Autismus. Eine Untersuchung der Gehirn-Konnektivität in Autismus bei einem Netzwerk-Ebene zusammen mit Anpassungen für das Scannen von Kindern mit Entwicklungsstörungen vorgestellt.

Probing the Brain in Autism mittels fMRT und Diffusion Tensor Imaging

Newly emerging theories suggest that the brain does not function as a cohesive unit in autism, and this discordance is reflected in the behavioral ...

probing-the-brain-in-autism-using-fmri-and-diffusion-tensor-imaging

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25.0K Aufrufe.  University of Alabama at Birmingham. Neuroimaging-Techniken, wie der funktionellen MRT und Diffusion Tensor Imaging zunehmend zur Charakterisierung der kognitiven und neuronalen Defizite bei Autismus. Eine Untersuchung der Gehirn-Konnektivität in Autismus bei einem Netzwerk-Ebene zusammen mit Anpassungen für das Scannen von Kindern mit Entwicklungsstörungen vorgestellt.

Serie: Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.
Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.
Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.
Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF.

Magnetic Resonance Derived Myocardial Dehnungs-Beurteilung anhand von Feature-Tracking-

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that ...

Forschung

Medizin

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness1 and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them2. This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia3. The male-to-female ratio of mutation rate is estimated at about 4&#x2013;6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males4. A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.

Molecular genetic strategy for finding de novo mutations causing common disorders such as autism and schizophrenia.

Eine Strategie, um de novo Mutationen in Common Störungen wie Autismus und Schizophrenie Identifizieren

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, ...

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a significant obstacle to pharmaceutical treatments of brain disorders as it limits the passage of molecules from the vasculature into the brain tissue to molecules less than approximately 500 Da in size6. FUS induced BBB disruption (BBBD) is temporary and reversible4 and has an advantage over chemical means of inducing BBBD by being highly localized. FUS induced BBBD provides a means for investigating the effects of a wide range of therapeutic agents on the brain, which would not otherwise be deliverable to the tissue in sufficient concentration. While a wide range of ultrasound parameters have proven successful at disrupting the BBB2,5,7, there are several critical steps in the experimental procedure to ensure successful disruption with accurate targeting. This protocol outlines how to achieve MRI-guided FUS induced BBBD in a rat model, with a focus on the critical animal preparation and microbubble handling steps of the experiment.

Microbubble-mediated focused ultrasound disruption of the blood-brain barrier (BBB) is a promising technique for non-invasive targeted drug delivery in the brain1-3. This protocol outlines the experimental procedure for MRI-guided transcranial BBB disruption in a rat model.

MRI-geführten Störung der Blut-Hirn-Schranke mit Hilfe der transkraniellen fokussiertem Ultraschall in einem Rattenmodell

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a ...

Eye Tracking Young Children with Autism

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1, promote early identification2, and inform treatment3. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8 and abnormal brain functioning9, particularly during the processing of social information1,10-11. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.

Eye tracking has long been used to study gaze patterns in typically-developing individuals, but recent technological advancements have made its use with clinical populations, including autism, more feasible. While eye-tracking young children with autism can offer insight into early symptom manifestations, it involves methodological challenges. Suggestions for best practices are provided.

Eye Tracking kleine Kinder mit Autismus

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a ...

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel underlying neurobiological mechanisms behind drug action and neurotransmitter-related disorders, such as depression and ADHD. Like most of the imaging methods (PET, SPECT, CT) it represents a progress in the investigation of brain disorders and the related function of neurotransmitter pathways in a non-invasive way with respect of the overall neuronal connectivity. Moreover it also provides the ideal tool for translation to clinical investigations. MRI, while still behind in molecular imaging strategies compared to PET and SPECT, has the great advantage to have a high spatial resolution and no need for the injection of a contrast-agent or radio-labeled molecules, thereby avoiding the repetitive exposure to ionizing radiations. Functional MRI (fMRI) is extensively used in research and clinical setting, where it is generally combined with a psycho-motor task. phMRI is an adaptation of fMRI enabling the investigation of a specific neurotransmitter system, such as serotonin (5-HT), under physiological or pathological conditions following activation via administration of a specific challenging drug.
The aim of the method described here is to assess brain 5-HT function in free-breathing animals. By challenging the 5-HT system while simultaneously acquiring functional MR images over time, the response of the brain to this challenge can be visualized. Several studies in animals have already demonstrated that drug-induced increases in extracellular levels of e.g. 5-HT (releasing agents, selective re-uptake blockers, etc) evoke region-specific changes in blood oxygenation level dependent (BOLD) MRI signals (signal due to a change of the oxygenated/deoxygenated hemoglobin levels occurring during brain activation through an increase of the blood supply to supply the oxygen and glucose to the demanding neurons) providing an index of neurotransmitter function. It has also been shown that these effects can be reversed by treatments that decrease 5-HT availability16,13,18,7. In adult rats, BOLD signal changes following acute SSRI administration have been described in several 5-HT related brain regions, i.e. cortical areas, hippocampus, hypothalamus and thalamus9,16,15. Stimulation of the 5-HT system and its response to this challenge can be thus used as a measure of its function in both animals and humans2,11.

The goal of this technique is to assess serotonin (5-HT) neurotransmitter function in the live and free-breathing animal with pharmacological magnetic resonance imaging (phMRI) and an intravenous challenge with a selective serotonin reuptake inhibitor (SSRI), fluoxetine.

Die Verwendung von pharmakologischen fMRT-Herausforderung in der präklinischen Forschung: Anwendung auf die 5-HT-System

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel ...

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls. 	
DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.	
In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.

Diffusion tensor imaging (DTI) basically serves as an MRI-based tool to identify in vivo the microstructure of the brain and pathological processes due to neurological disorders within the cerebral white matter. DTI-based analyses allow for application to brain diseases both at the group level and in single subject data.

Diffusion Tensor Magnetic Resonance Imaging in der Analyse von neurodegenerativen Erkrankungen

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present ...

MRI and PET in Mouse Models of Myocardial Infarction

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ideal model for testing novel therapeutic strategies.
In vivo magnetic resonance imaging (MRI) gives excellent views of the heart noninvasively with clear anatomical detail, which can be used for accurate functional assessment. Contrast agents can provide basic measures of tissue viability but these are nonspecific. Positron emission tomography (PET) is a complementary technique that is highly specific for molecular imaging, but lacks the anatomical detail of MRI. Used together, these techniques offer a sensitive, specific and quantitative tool for the assessment of the heart in disease and recovery following treatment.
In this paper we explain how these methods are carried out in mouse models of acute myocardial infarction. The procedures described here were designed for the assessment of putative protective drug treatments. We used MRI to measure systolic function and infarct size with late gadolinium enhancement, and PET with fluorodeoxyglucose (FDG) to assess metabolic function in the infarcted region. The paper focuses on practical aspects such as slice planning, accurate gating, drug delivery, segmentation of images, and multimodal coregistration. The methods presented here achieve good repeatability and accuracy maintaining a high throughput.

We describe how to perform MRI and PET imaging of the mouse heart. The protocol is tailored to assess treatment efficacy in models of myocardial infarction and heart failure.

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent marker. Mouse models (brain tumor and arthritis) were used to evaluate the usefulness of this method. Saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles tagged with CellVue Maroon (CVM) fluorophore were administered intravenously. Animals were then placed in the rotational holder (MARS) of the in vivo imaging system. Images were acquired in 10&#176; steps over 380&#176;. A rectangular&#160;region of interest (ROI) was placed across the full image width at the model disease site. Within the ROI, and for every image, mean fluorescence intensity was computed after background subtraction. In the mouse models studied, the labeled nanovesicles were taken up in both the orthotopic and transgenic brain tumors, and in the arthritic sites (toes and ankles). Curve analysis of the multi angle image ROIs determined the angle with the highest signal. Thus, the optimal angle for imaging each disease site was characterized. The MAROI method applied to imaging of fluorescent compounds is a noninvasive, economical, and precise tool for in vivo quantitative analysis of the disease states in the described mouse models.

In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo quantitation of a fluorescent marker delivered by saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles. Employing mouse models of cancer and arthritis, we demonstrate how the MAROI signal curve analysis can be used for the precise mapping and biological characterization of disease processes.

In Vivo Optical Imaging von Hirntumoren und Arthritis mit fluoreszierenden SapC-DOPS Nanovesicles

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent ...

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). 
The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. 
The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

We describe how to obtain parametric and vector maps of the diffusion tensor of the breast using magnetic resonance imaging. The protocol and final output following imaging processing are tailored for tracking breast architectural features and detecting breast malignancy.

Tracking der Brust architektonische Details und Erkennen von Brustkrebs mit Magnet-Resonanz-Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of ...

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

Mit Saccadometry mit Deep Brain Stimulation Normale und Pathologische Funktion des Gehirns zu studieren

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...