Die Vondriska Labor ist durch Zuschüsse aus dem National Heart, Lung and Blood Institute der NIH und der Laubisch Endowment an der UCLA unterstützt. EM ist Empfänger der Jennifer S. Buchwald Graduate Fellowship für Physiologie an der UCLA; HC ist der Empfänger einer American Heart Association Pre-Doc-Stipendium; MP ist der Empfänger einer NIH Ruth Kirschstein Post-Doktoranden-Stipendium und SF ist der Empfänger von ein NIH K99 Award.

<ol>
	<li>Li, F., Wang, X., Capasso, J. M., Gerdes, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+transition+of+cardiac+myocytes+from+hyperplasia+to+hypertrophy+during+postnatal+development.">Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development.</a> J Mol Cell Cardiol. 28, 1737-1746 (1996).</li><li>Rumyantsev, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interrelations+of+the+proliferation+and+differentiation+processes+during+cardiact+myogenesis+and+regeneration.">Interrelations of the proliferation and differentiation processes during cardiact myogenesis and regeneration.</a> Int Rev. Cytol. 51, 186-273 (1977).</li><li>Olson, E. N., Schneider, M. 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Zwei Hauptverfahren für nukleare Isolierung wurden zuvor bewertet: 27 eine ist die Technik der Behrens Homogenisieren lyophilisierten Gewebe in einem nicht-wässrigen Lösungsmittel und das zweite, eine Modifikation der wir hier von Homogenisier Gewebe in einer wäßrigen Saccharose / Salzlösung gefolgt durch differentielle oder Dichtegradientenzentrifugation. Subfraktionierung der Kerne durch saure Extraktion von Gewebeproben ist ein wichtiges Werkzeug für die Untersuchung Chr...

<table border="1"><tbody><tr><td> Name des Reagenzes </td><td> Firma </td><td> Katalog-Nummer </td></tr><tr><td> Dulbeco Modified Eagle Medium </td><td> Invitrogen </td><td> 11965 </td></tr><tr><td> Protease Pellet </td><td> Roche </td><td> 04 693 159 001 </td></tr><tr><td> 100 um Sieb </td><td> BD Falcon </td><td> 352360 </td></tr><tr><td> Ultracut Ultramikrotom </td><td> Reichert </td><td></td></tr><tr><td> 100CX Transmission Electron Mikroskop </td><td> JEOL USA, Inc. </td><td></td></tr><tr><td> Pirol </td><td> BioRad </td><td> 161-0496 </td></tr><tr><td> Histon H2A-Antikörper </td><td> Santa Cruz </td><td> sc-8648 </td></tr><tr><td> Nucleoporin p62 Antikörper </td><td> BD Biosciences </td><td> 610498 </td></tr><tr><td> Adenin nucleoFlut transporter Antikörper </td><td> Santa Cruz </td><td> sc-9299 </td></tr><tr><td> BiP-Antikörper </td><td> Santa Cruz </td><td> sc-1050 </td></tr><tr><td> Tubulin-Antikörper </td><td> Sigma </td><td> T1568 </td></tr><tr><td> Histone H3 Antikörper </td><td> Abcam </td><td> ab1791 </td></tr><tr><td> Fibrillarin Antikörper </td><td> Cell Signaling </td><td> C12C3 </td></tr><tr><td> SNRP70 Antikörper </td><td> Abcam </td><td> ab51266 </td></tr><tr><td> E2F-1-Antikörpers </td><td> Thermo Fisher </td><td> MS-879 </td></tr><tr><td> Retinoblastoma Antikörper </td><td> BD Biosciences </td><td> 554136 </td></tr><tr><td> Hypoxie-induzierbaren Faktor 1-Antikörpers </td><td> Novus Biologicals </td><td> NB100-469 </td></tr><tr><td> BCA-Protein-Assay </td><td> Thermo Scientific </td><td> 23227 </td></tr><tr><td> Umkehrphasensäule </td><td> New Objektive </td><td> PFC7515-B14-10 </td></tr><tr><td> BioWorks Browser </td><td> Thermo Scientific </td><td></td></tr></tbody></table>

quantitative analysis of chromatin proteomes in disease

Im Zellkern befinden die Proteome, deren Funktionen auf das engste mit der Genregulation verknüpft. Adulten Kardiomyozyten Kerne sind einzigartig wegen des hohen Anteils an zweikerniger Zellen, 1 die überwiegend heterochromatischen Zustand der DNA, und das nicht-teilenden Art der Herzmuskelzellen, die Erwachsenen Kerne macht in einem permanenten Zustand der Interphase. 2 Transkriptionelle Regulation während der Entwicklung und Krankheiten wurden auch in diesem Organ, 3-5 studiert, aber was bleibt relativ unerforscht ist die Rolle der nuklearen Proteine, die für DNA-Verpackung und Ausdruck gespielt, und wie diese Proteine ​​Veränderungen in der transkriptionellen Programme, die während Krankheit auftreten steuern. 6 In den Industrieländern Welt, Herzkrankheiten die häufigste Ursache der Sterblichkeit für Männer und Frauen. 7 Insight, wie nukleare Proteine ​​zusammen, um das Fortschreiten dieser Krankheit zu regeln ist entscheidend für die Förderung der aktuellen Behandlung optionen. Die Massenspektrometrie ist das ideale Werkzeug für die Bewältigung dieser Fragen, wie es für eine unvoreingenommene Annotation des nuklearen Proteom und relative Quantifizierung ermöglicht, wie die Fülle dieser Proteine ​​verändert sich mit Krankheit. Zwar gibt es mehrere proteomischen Studien für Säugetier nuklearen Proteinkomplexe, 8-13 bis vor kurzem gab es 14 nur eine Studie, die die kardiale nuklearen Proteom, und es als das gesamte Kern, anstatt Erkundung des Proteoms auf der Ebene der Fächer Nuklearteilbild . 15 In einem großen Teil ist dies Mangel an Arbeit wegen der Schwierigkeit der Isolierung Herz Kerne. Cardiac Kerne treten innerhalb einer starren und dichten Aktin-Myosin Vorrichtung, an die sie über mehrere Erweiterungen aus dem endoplasmatischen Retikulum verbunden sind, in dem Umfang, Myozyten Kontraktion verändert ihre Gesamtform. 16 Zusätzlich Kardiomyozyten 40% Mitochondrien Vol. 17, die necessitätes Anreicherung des Kernes von den anderen Organellen. Hier beschreiben wir ein Protokoll für kardiale Urananreicherung und weitere Fraktionierung in biologisch relevanten Fächern. Darüber hinaus haben wir detailliert Verfahren zur markierungsfreien quantitativen massenspektrometrischen Dissektion dieser Fraktionen-Techniken zugänglich in vivo Experimente in verschiedenen Tiermodellen und Organsysteme, wo metabolische Markierung nicht durchführbar ist.

Abbildung 4 verdeutlicht den Nutzen dieser Form der relativen Quantifizierung. Gezeigt im linken Fenster sind die einzelnen monoisotopic Peptidpeaks (überlagert von verschiedenen Mäusen), die als Angehörige der Protein HMGB1 (identifiziert über Datenbanksuche) bezeichnet wurden. Jeder Peak, im Wesentlichen eine extrahierte Ionenchromatographen für die gegebene Peptid, kommt aus einer anderen Maus. Die Gruppen repräsentieren drei verschiedene physiologische Zustände: basal, Herzhypertrophie und He...

Watch this Scientific Journal Video about Quantitative Analysis of Chromatin Proteomes in Disease at JoVE.com

Quantitative Analysis of Chromatin Proteomes in Disease

Advances in Massenspektrometrie haben die Hochdurchsatz-Analyse der Proteinexpression und Modifikation in einer Vielzahl von Geweben erlaubt. Kombiniert mit subzelluläre Fraktionierung und Krankheitsmodelle, quantitative Massenspektrometrie und der Bioinformatik neue Eigenschaften in biologischen Systemen offenbaren kann. Das hierin beschriebene Verfahren analysiert Chromatin-assoziierten Proteinen in der Einstellung von Herzerkrankungen und ist ohne weiteres auch auf andere<em&gt; In vivo</em&gt; Modelle menschlicher Erkrankungen.

Quantitative Analyse von Chromatin Proteome in Disease

In the nucleus reside the proteomes whose functions are most intimately linked with gene regulation. Adult mammalian cardiomyocyte nuclei are unique due ...

quantitative-analysis-of-chromatin-proteomes-in-disease

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JoVE Journal

Medicine

13.0K Aufrufe.  David Geffen School of Medicine at UCLA. Advances in Massenspektrometrie haben die Hochdurchsatz-Analyse der Proteinexpression und Modifikation in einer Vielzahl von Geweben erlaubt. Kombiniert mit subzelluläre Fraktionierung und Krankheitsmodelle, quantitative Massenspektrometrie und der Bioinformatik neue Eigenschaften in biologischen Systemen offenbaren kann. Das hierin beschriebene Verfahren analysiert Chromatin-assoziierten Proteinen in der Einstellung von Herzerkrankungen und ist ohne weiteres auch auf an...

Serie: Quantitative Analysis of Chromatin Proteomes in Disease

Quantitative Analysis of Cancer Metastasis using an Avian Embryo Model

During metastasis cancer cells disseminate from the primary tumor, invade into surrounding tissues, and spread to distant organs. Metastasis is a complex process that can involve many tissue types, span variable time periods, and often occur deep within organs, making it difficult to investigate and quantify. In addition, the efficacy of the metastatic process is influenced by multiple steps in the metastatic cascade making it difficult to evaluate the contribution of a single aspect of tumor cell behavior. As a consequence, metastasis assays are frequently performed in experimental animals to provide a necessarily realistic context in which to study metastasis. Unfortunately, these models are further complicated by their complex physiology. The chick embryo is a unique in vivo model that overcomes many limitations to studying metastasis, due to the accessibility of the chorioallantoic membrane (CAM), a well-vascularized extra-embryonic tissue located underneath the eggshell that is receptive to the xenografting of tumor cells (figure 1). Moreover, since the chick embryo is naturally immunodeficient, the CAM readily supports the engraftment of both normal and tumor tissues. Most importantly, the avian CAM successfully supports most cancer cell characteristics including growth, invasion, angiogenesis, and remodeling of the microenvironment. This makes the model exceptionally useful for the investigation of the pathways that lead to cancer metastasis and to predict the response of metastatic cancer to new potential therapeutics. The detection of disseminated cells by species-specific Alu PCR makes it possible to quantitatively assess metastasis in organs that are colonized by as few as 25 cells. Using the Human Epidermoid Carcinoma cell line (HEp3) we use this model to analyze spontaneous metastasis of cancer cells to distant organs, including the chick liver and lung. Furthermore, using the Alu-PCR protocol we demonstrate the sensitivity and reproducibility of the assay as a tool to analyze and quantitate intravasation, arrest, extravasation, and colonization as individual elements of metastasis.

Using quantitative PCR, we demonstrate how the well-established chick CAM model can be used to quantitatively analyze the metastasis of human tumor cells to distant organs.

Quantitative Analyse von Krebs Metastasen mit einem Vogelembryo Modell

During metastasis cancer cells disseminate from the primary tumor, invade into surrounding tissues, and spread to distant organs. Metastasis is a complex ...

Forschung

Medizin

A Simple Method of Mouse Lung Intubation

A simple procedure to intubate mice for pulmonary function measurements would have several advantages in longitudinal studies with limited numbers or expensive animal. One of the reasons that this is not done more routinely is that it is relatively difficult, despite there being several published studies that describe ways to achieve it. In this paper we demonstrate a procedure that eliminates one of the major hurdles associated with this intubation, that of visualizing the trachea during the entire time of intubation. The approach uses a 0.5 mm fiberoptic light source that serves as an introducer to direct the intubation cannula into the mouse trachea. We show that it is possible to use this procedure to measure lung mechanics in individual mice over a time course of at least several weeks. The technique can be set up with relatively little expense and expertise, and it can be routinely accomplished with relatively little training. This should make it possible for any laboratory to routinely carry out this intubation, thereby allowing longitudinal studies in individual mice, thereby minimizing the number of mice needed and increasing the statistical power by using each mouse as its own control.

This paper describes a striaghforward and efficient method of intubating mice for pulmonary function measurements or pulmonary instillation, that allows the mice to recover and be studied at later times. The procedure involves an inexpensive fiberoptic light source that directly illuminates the trachea.

Eine einfache Methode der Maus Lung Intubation

A  simple procedure to intubate mice for pulmonary function measurements would  have several advantages in longitudinal studies with limited numbers or  ...

Quantitative Analysis and Characterization of Atherosclerotic Lesions in the Murine Aortic Sinus

Atherosclerosis is a disease of the large arteries and a major underlying cause of myocardial infarction and stroke. Several different mouse models have been developed to facilitate the study of the molecular and cellular pathophysiology of this disease. In this manuscript we describe specific techniques for the quantification and characterization of atherosclerotic lesions in the murine aortic sinus and ascending aorta. The advantage of this procedure is that it provides an accurate measurement of the cross-sectional area and total volume of the lesion, which can be used to compare atherosclerotic progression across different treatment groups. This is possible through the use of the valve leaflets as an anatomical landmark, together with careful adjustment of the sectioning angle. We also describe basic staining methods that can be used to begin to characterize atherosclerotic progression. These can be further modified to investigate antigens of specific interest to the researcher. The described techniques are generally applicable to a wide variety of existing and newly created dietary and genetically-induced models of atherogenesis.

We describe procedures to quantify and characterize atherosclerotic lesions in mouse models using precision sectioning of the aortic sinus and ascending aorta combined with histochemical and immunohistochemical analysis.

Atherosclerosis is a disease of the large arteries and a major underlying cause of myocardial infarction and stroke. Several different mouse models have ...

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using non-invasive magnetic resonance imaging methods.

Quantitative Magnetresonanztomographie von Skelettmuskelerkrankung

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of ...

Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors

In-depth analyses of cancer cell proteomes are needed to elucidate oncogenic pathomechanisms, as well as to identify potential drug targets and diagnostic biomarkers. However, methods for quantitative proteomic characterization of patient-derived tumors and in particular their cellular subpopulations are largely lacking. Here we describe an experimental set-up that allows quantitative analysis of proteomes of cancer cell subpopulations derived from either liquid or solid tumors. This is achieved by combining cellular enrichment strategies with quantitative Super-SILAC-based mass spectrometry followed by bioinformatic data analysis. To enrich specific cellular subsets, liquid tumors are first immunophenotyped by flow cytometry followed by FACS-sorting; for solid tumors, laser-capture microdissection is used to purify specific cellular subpopulations. In a second step, proteins are extracted from the purified cells and subsequently combined with a tumor-specific, SILAC-labeled spike-in standard that enables protein quantification. The resulting protein mixture is subjected to either gel electrophoresis or Filter Aided Sample Preparation (FASP) followed by tryptic digestion. Finally, tryptic peptides are analyzed using a hybrid quadrupole-orbitrap mass spectrometer, and the data obtained are processed with bioinformatic software suites including MaxQuant. By means of the workflow presented here, up to 8,000 proteins can be identified and quantified in patient-derived samples, and the resulting protein expression profiles can be compared among patients to identify diagnostic proteomic signatures or potential drug targets.

In-depth analyses of cancer cell proteomes facilitate identification of novel drug targets and diagnostic biomarkers. We describe an experimental workflow for quantitative analysis of (phospho-)proteomes in cancer cell subpopulations derived from liquid and solid tumors. This is achieved by combining cellular enrichment strategies with quantitative Super-SILAC-based mass spectrometry.

Quantitative massenspektrometrische Analyse von Krebs-Zellen-Proteome Abgeleitet von Liquid und soliden Tumoren

In-depth analyses of cancer cell proteomes are needed to elucidate oncogenic pathomechanisms, as well as to identify potential drug targets and diagnostic ...

Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

Neuroinflammation is now recognized as a major etiological factor in neurodegenerative disease. Mononuclear phagocytes are innate immune cells responsible for phagocytosis and clearance of debris and detritus. These cells include CNS-resident macrophages known as microglia, and mononuclear phagocytes infiltrating from the periphery. Light microscopy has generally been used to visualize phagocytosis in rodent or human brain specimens. However, qualitative methods have not provided definitive evidence of in vivo phagocytosis. Here, we describe quantitative 3D in silico modeling (q3DISM), a robust method allowing for true 3D quantitation of amyloid-&#946; (A&#946;) phagocytosis by mononuclear phagocytes in rodent Alzheimer&#39;s Disease (AD) models. The method involves fluorescently visualizing A&#946; encapsulated within phagolysosomes in rodent brain sections. Large z-dimensional confocal datasets are then 3D reconstructed for quantitation of A&#946; spatially colocalized within the phagolysosome. We demonstrate the successful application of q3DISM to mouse and rat brains, but this methodology can be extended to virtually any phagocytic event in any tissue.

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer&#039;s Disease

We developed a methodology for quantitative 3D in silico modeling (q3DISM) of cerebral amyloid-&#946; (A&#946;) phagocytosis by mononuclear phagocytes in rodent models of Alzheimer&#39;s disease. This method can be generalized for the quantitation of virtually any phagocytic event in vivo.

Quantitative 3D<em&gt; In Silico</em&gt; Modellierung (q3DISM) zerebraler Amyloid-beta Phagozytose in Nagetiermodellen der Alzheimer-Krankheit

Neuroinflammation is now recognized as a major etiological factor in neurodegenerative disease. Mononuclear phagocytes are innate immune cells responsible ...

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment

Impaired functional connectivity in the Default Mode Network (DMN) may be involved in the progression of Alzheimer&#39;s Disease (AD). The Posterior Cingulate Cortex (PCC) is a potential imaging marker for monitoring the progression of AD. Previous studies did not focus on the functional connectivity between the PCC and nodes in regions outside the DMN, but our study is an effort to explore these overlooked functional connections. For collecting data, we used functional Magnetic Resonance Imaging (fMRI) and Granger Causality Analysis (GCA). fMRI provides a non-invasive method for studying the dynamic interactions between the different brain regions. GCA is a statistical hypothesis test for determining whether one-time series is useful in forecasting another. In simple terms, it is judged by comparing the &#34;Known all the information on the last moment, the distribution of the probability of X at this time&#34; and the &#34;Known all the information on the last moment except Y, the distribution of the probability of X at this time&#34;, to determine whether there is a causal relationship between Y and X. This definition is based on the complete information source and stationary chronological sequence. The main step of this analysis is to use X and Y to establish the regression equation and draw a causal relationship by a hypothetical test. Since GCA can measure causal effects, we used it to investigate the anisotropy of the functional connectivity and explore the hub function of the PCC. Here, we screened 116 participants for MRI scanning, and after preprocessing the data obtained from neuroimaging, we used GCA to derive the causal relationship of each node. Finally, we concluded that the directed connection is significantly different between the Mild Cognitive Impairment (MCI) and AD groups, both from the PCC to the whole brain and from the whole brain to the PCC.

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer&#039;s Disease and Mild Cognitive Impairment

Based on resting-state functional magnetic resonance imaging with Granger causality analysis, we investigated the alterations in the directed functional connectivity between the posterior cingulate cortex and whole brain in patients with Alzheimer&#39;s Disease (AD), patients with Mild Cognitive Impairment (MCI), and healthy controls.

Anwendung von Granger Kausalität Analyse des gerichteten funktionalen Zusammenhangs in der Alzheimer-Krankheit und Mild Cognitive Impairment

Impaired functional connectivity in the Default Mode Network (DMN) may be involved in the progression of Alzheimer&#39;s Disease (AD). The Posterior ...

In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Meni&#232;re's Disease Ears and Normal Hearing Ears

Analysis of neural structures in Meni&#232;re's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this patient group but has yet to be confirmed. This protocol describes a method of in vivo evaluation of neural changes especially well suitable for cranial nerve analysis using magnetic resonance imaging (MRI). MD-patients and normal hearing persons were examined in a 3-T MR-scanner using a scan protocol including strongly T2-weighted 3D gradient-echo-sequence (3D-CISS). In the patient group, MD was additionally confirmed using MRI-based assessment of endolymphatic hydrops. Morphometric analysis was performed using a freeware DICOM viewer. Evaluation of cranial nerves included measurements of cross-sectional areas (CSAs) of the nerves at different levels as well as orthogonal diametric measurements.

&lt;em&gt;In Vivo&lt;/em&gt; Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Meni&amp;#232;re&#039;s Disease Ears and Normal Hearing Ears

To evaluate morphological changes of cranial nerves such as loss of neural structures or swelling of cranial nerves in Meni&#232;re&#39;s Disease (MD) or in healthy persons in vivo, a protocol of evaluation has been developed using magnetic resonance imaging (MRI). Additional MRI-based confirmation of MD was performed.

In Vivo Morphometrische Analyse der menschlichen Hirnnerven mittels Kernspintomographie in der Menière Krankheit Ohren und Normal hörende Ohren

Analysis of neural structures in Meni&#232;re's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this ...

Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI&#8212;Application in Premanifest Huntington's Disease

Recent advances in MRI offer a variety of useful markers to identify neurodegenerative diseases. In Huntington&#39;s disease (HD), regional brain atrophy begins many years prior to the motor onset (during the &#34;premanifest&#34; period), but the spatiotemporal pattern of regional atrophy across the brain has not been fully characterized. Here we demonstrate an online cloud-computing platform, &#34;MRICloud&#34;, which provides atlas-based whole-brain segmentation of T1-weighted images at multiple granularity levels, and thereby, enables us to access the regional features of brain anatomy. We then describe a regression model that detects statistically significant inflection points, at which regional brain atrophy starts to be noticeable, i.e. the &#34;change-point&#34;, with respect to a disease progression index. We used the CAG-age product (CAP) score to index the disease progression in HD patients. Change-point analysis of the volumetric measurements from the segmentation pipeline, therefore, provides important information of the order and pattern of structural atrophy across the brain. The paper illustrates the use of these techniques on T1-weighted MRI data of premanifest HD subjects from a large multicenter PREDICT-HD study. This design potentially has wide applications in a range of neurodegenerative diseases to investigate the dynamic changes of brain anatomy.

Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI&amp;#8212;Application in Premanifest Huntington&#039;s Disease

This paper describes a statistical model for volumetric MRI data analysis, which identifies the &#34;change-point&#34; when brain atrophy begins in premanifest Huntington&#39;s disease. Whole-brain mapping of the change-points is achieved based on brain volumes obtained using an atlas-based segmentation pipeline of T1-weighted images.

Gesamte Gehirn Segmentierung und Change-Point-Analyse der anatomischen Gehirn MRI-Anwendung in Prämanifesten Huntington-Krankheit

Recent advances in MRI offer a variety of useful markers to identify neurodegenerative diseases. In Huntington&#39;s disease (HD), regional brain atrophy ...

Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. Bone is a dynamic tissue undergoing continuous remodeling with the competing activity of osteoblasts, which produce the new bone matrix, and osteoclasts, whose function is to eliminate mineralized bone. [18F]-NaF is a positron emission tomography (PET) radiotracer that enables visualization of bone metabolism. [18F]-NaF is chemically absorbed into hydroxyapatite in the bone matrix by osteoblasts and can thus noninvasively detect osteoblastic activity, which is occult to conventional imaging techniques. Kinetic modeling of dynamic [18F]-NaF-PET data provides detailed quantitative measures of bone metabolism. Conventional semi-quantitative PET data, which utilizes standardized uptake values (SUVs) as a measure of radiotracer activity, is referred to as a static technique due to its snapshot of tracer uptake in time.&#160; Kinetic modeling, however, utilizes dynamic image data where tracer levels are continuously acquired providing tracer uptake temporal resolution. From the kinetic modeling of dynamic data, quantitative values like blood flow and metabolic rate (i.e., potentially informative metrics of tracer dynamics) can be extracted, all with respect to the measured activity in the image data. When combined with dual modality PET-MRI, region-specific kinetic data can be correlated with anatomically registered high-resolution structural and pathologic information afforded by MRI. The goal of this methodological manuscript is to outline detailed techniques for performing and analyzing dynamic [18F]-NaF-PET-MRI data. The lumbar facet joint is a common site of degenerative arthritis disease and a common cause for axial low back pain.&#160; Recent studies suggest [18F]-NaF-PET may serve as a useful biomarker of painful facetogenic disease.&#160; The human lumbar facet joint will, therefore, be used as a prototypical region of interest for dynamic [18F]-NaF-PET-MRI analysis in this manuscript.

Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. We present detailed methodologies for performing and analyzing dynamic [18F]-NaF-PET-MRI data in a patient with facetogenic low back pain using the lumbar facet joints as a prototypical region of interest.

Quantitative [18F]-Naf-PET-MRI-Analyse zur Bewertung des dynamischen Knochenumsatzes bei Patienten mit facetogenen Rückenschmerzen

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. Bone is a dynamic tissue undergoing ...