وأيد هذا العمل من قبل المعاهد الوطنية للصحة منح R01 NINDS NS074388 581 (CL Limoli)، معهد كاليفورنيا للطب التجديدي (CIRM) منح RS1-00413 (CLL) ومنحة لCIRM إن الرب لدعم وثائق الفيديو. نود أيضا أن نشكر رودي ليمبورغ وإدوارد لاو من جامعة كاليفورنيا في ايرفين في آلة العلوم البيولوجية محل لدعمهم، وتقديم المشورة والمهارات الفنية الرائعة في إعداد جميع المواد حسب الطلب لإجراء تجارب سلوكية.

<ol>
	<li>Abayomi, O. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathogenesis+of+irradiation-induced+cognitive+dysfunction.">Pathogenesis of irradiation-induced cognitive dysfunction.</a> Acta. Oncol. 35, 659-663 (1996).</li><li>Anderson, V. A., Godber, T., Smibert, E., Weiskop, S., Ekert, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+and+academic+outcome+following+cranial+irradiation+and+chemotherapy+in+children:+a+longitudinal+study.">Cognitive and academic outcome following cranial irradiation and chemotherapy in children: a longitudinal study.</a> Br. J. Cancer. 82, 255-262 (2000).</li><li>Acharya, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rescue+of+radiation-induced+cognitive+impairment+through+cranial+transplantation+of+human+embryonic+stem+cells.">Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells.</a> Proc. Natl. Acad. Sci. U. S. A. 106, 19150-19155 (2009).</li><li>Mumby, D. G., Gaskin, S., Glenn, M. J., Schramek, T. E., Lehmann, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hippocampal+damage+and+exploratory+preferences+in+rats:+memory+for+objects,+places,+and+contexts.">Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts.</a> Learn. Mem. 9, 49-57 (2002).</li><li>Walf, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+the+elevated+plus+maze+as+an+assay+of+anxiety-related+behavior+in+rodents.">The use of the elevated plus maze as an assay of anxiety-related behavior in rodents.</a> Nat. Protoc. 2, 322-328 (2007).</li><li>Macleod, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cancer+chemotherapy+impairs+contextual+but+not+cue-specific+fear+memory.">Cancer chemotherapy impairs contextual but not cue-specific fear memory.</a> Behav Brain Res. 181, 168-172 (2007).</li><li>Schafe, G. E., Nadel, N. V., Sullivan, G. M., Harris, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Memory+consolidation+for+contextual+and+auditory+fear+conditioning+is+dependent+on+protein+synthesis,+PKA,+and+MAP+kinase.">Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA, and MAP kinase.</a> Learn. Mem. 6, 97-110 (1999).</li><li>Winocur, G., Wojtowicz, J. M., Sekeres, M., Snyder, J. S., Wang, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibition+of+neurogenesis+interferes+with+hippocampus-dependent+memory+function.">Inhibition of neurogenesis interferes with hippocampus-dependent memory function.</a> Hippocampus. 16, 296-304 (2006).</li><li>Phillips, R. G., LeDoux, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+contribution+of+amygdala+and+hippocampus+to+cued+and+contextual+fear+conditioning.">Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.</a> Behav. Neurosci. 106, 274-285 (1992).</li><li>D'Hooge, R., De Deyn, 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=Applications+of+the+Morris+water+maze+in+the+study+of+learning+and+memory.">Applications of the Morris water maze in the study of learning and memory.</a> Brain. Res. Brain. Res. Rev. 36, 60-90 (2001).</li><li>Morris, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Developments+of+a+water-maze+procedure+for+studying+spatial+learning+in+the+rat.">Developments of a water-maze procedure for studying spatial learning in the rat.</a> J. Neurosci. Methods. 11, 47-60 (1984).</li><li>Meyers, C. A., Brown, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+and+relevance+of+neurocognitive+assessment+in+clinical+trials+of+patients+with+CNS+tumors.">Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors.</a> J. Clin. Oncol. 24, 1305-1309 (2006).</li><li>de Ruiter, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+hyporesponsiveness+and+cognitive+impairment+10+years+after+chemotherapy+for+breast+cancer.">Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer.</a> Hum. Brain. Mapp. , (2010).</li><li>Hess, D. C., Borlongan, C. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cell-based+therapy+in+ischemic+stroke.">Cell-based therapy in ischemic stroke.</a> Expert. Rev. Neurother. 8, 1193-1201 (2008).</li></ol>

الإعلان عن أي تضارب في المصالح.

هناك حاجة ملحة لاستراتيجيات طويلة الأجل تهدف إلى قطع الطريق على تطوير الخلل المعرفي الذي أصبح شائعا بشكل متزايد في الناجيات من سرطان 12،13. العلاج بالخلايا الجذعية قد توفر وسيلة لتخفيف مجموعة من عقابيل الأنسجة الطبيعية في الجهاز العصبي المركزي، كما أنها توفر الفرصة لاستبدال الخلايا المفقودة أو التالفة من علاجات السرطان السامة للخلايا 14. للتعجيل في تحقيق هذه الجهود، اتخذنا سلسلة من التجارب الإثبات الرئيسي التي أكدت قدرة hNSCs المغروسة cranially لاستعادة الإدراك وظيفيا داخل الأنسجة السرير المشع من الجهاز العصبي المركزي 3. كان حاسما في هذا المسعى القدرة على إجراء موثوق سلسلة من الاختبارات المعرفية تسيطر عليها بعناية بطريقة استنساخه. وقد فصلنا هذه الإجراءات الحاسمة في الجهود الرامية إلى الإسراع في إمكانية متعدية من العلاج بالخلايا الجذعية في العيادة. مزيد من الاعتبارات التيويسلط الضوء المرجح أن يكون لها تأثير كبير على نوعية البيانات أدناه. اختبار المعرفي يتطلب عناية فائقة بالتفاصيل والالتزام ممارسات قياسية معينة يمكن أن تساعد في تقليل الآثار التي تعقد في تفسير النتائج. استخدام مخصص غرف منفصلة من التجارب السلوكية غرف القابضة الحيوانية والمجربون هو الأفضل. بل هو أيضا من الحكمة استخدام &quot;الضوضاء البيضاء&quot; الذي يمنع الضوضاء الخارجية في منشأة الحيوانية التي قد يصرف من الحيوانات المهمة في متناول اليد. لتقليل الضغط على الحيوانات المخصصة للاختبار المعرفي، من المهم بالنسبة لهم أن يكون على دراية المجربون من شأنها أن تؤدي الاختبارات السلوكية قبل الإدارة المهمة. بشكل عام، إذا اختبار الإناث والذكور، فمن المستحسن لاختبار الإناث الأول لأنها تميل إلى أن تكون أكثر حرصا أثناء اختبار إذا العظة رائحة الذكور البقاء في الساحات الاختبار. عندما بالإدارة بطارية المسلسل من المهام، من المهم أن تعرض الحيوانات للياالمهام المجهدة الحادي والعشرين (مثل EPM، NPR) وأكثر المهام المجهدة الأخيرة (مثل FC، MWM).

quantifying cognitive decrements caused by cranial radiotherapy

باستثناء بقاء وضعف الإدراك الناجمة عن التدبير السريري للسرطان هو أحد العوامل الرئيسية يملي نتائج علاجية. للكثير من المرضى المصابين CNS والأورام الخبيثة غير CNS، العلاج الإشعاعي والعلاج الكيميائي تقديم أفضل الخيارات المتاحة لمكافحة المرض. تأتي هذه العلاجات لكن بتكلفة، والناجيات من سرطان تقريبا كل (~ 11 مليون في الولايات المتحدة وحدها اعتبارا من 2006) تكبد بعض المخاطر لتطوير المعرفية اختلال وظيفي، مع معظم الحالات الشديدة وجدت في المرضى يتعرضون للعلاج بالأشعة في الجمجمة (~ 200،000 / سنة ) من أجل السيطرة على أورام الدماغ الأولية والمتنقل 1. إشكالية خاصة هي الحالات التي تصيب الأطفال، الذين البقاء على المدى الطويل تعاني من نتائج ملحوظة في التناقصات المعرفية أعباء اجتماعية واقتصادية كبيرة 2. حتى الآن، لا تزال هناك أي حلول مرضية لهذه المشكلة السريرية الهامة. وقد تناولنا هذا القلق الصحية الخطيرة باستخدام المزروعة الجذعية مLLS لمكافحة الإشعاع الناجم عن التدهور المعرفي لدى الجرذان يتعرضون للأشعة athymic الجمجمة 3. تفاصيل تشعيع التجسيمي ويمكن العثور على زراعة في المختبر وزرع الخلايا الجذعية العصبية البشرية (hNSCs) في ورقة رفيقنا (أشاريا وآخرون، إن الرب المرجع). بعد التشعيع وجراحة الزرع، ويتم تقييم ثم الفئران لإجراء تغييرات في الإدراك، المطعمة بقاء الخلية والتعبير التمايز علامات محددة 1 و 4 أشهر بعد التشعيع. لتقييم نقدي لنجاح أو فشل أي تدخل محتمل مصممة لتحسين الناجمة عن الاشعاع المعرفي عقابيل، سلسلة من المهام الإدراكية صارمة الكمية يجب إجراء. لتحقيق ذلك، ونحن لدينا لإخضاع الحيوانات مجموعة من نماذج اختبار المعرفية بما في ذلك الاعتراف مكان الرواية، متاهة مائية، بالإضافة إلى ارتفاع متاهة الخوف وتكييف، وذلك لتحديد التعلم قرن آمون وغير الحصين والذاكرة. لقد أثبتنا فائدةتستخدم هذه الاختبارات لقياس أنواع معينة من الحيوانات في التناقصات المعرفية المشع، ولهم لإظهار أن الحيوانات المغروسة مع hNSCs يحمل تحسينات كبيرة في وظيفة الادراك 3. فوائد المعرفية المستمدة من الخلايا الجذعية البشرية المغروسة تشير إلى أن استراتيجيات مماثلة قد تقدم يوم واحد اللجوء السريرية التي تشتد الحاجة إليها للناجين من السرطان يعانون من ضعف الادراك. وفقا لذلك، قدمنا ​​الوثائق المكتوبة والمرئية من الخطوات الهامة المستخدمة في النماذج المعرفية لدينا اختبار لتسهيل ترجمة نتائج واعدة لدينا في العيادة.

Watch this Scientific Journal Video about Quantifying Cognitive Decrements Caused by Cranial Radiotherapy at JoVE.com

Quantifying Cognitive Decrements Caused by Cranial Radiotherapy

ضعف الإدراك الناتج عن إدارة radiotherapeutic من أورام المخ يمثل حالة مستعصية سريريا أن يؤثر سلبا نوعية الحياة. القدرة على تقييم نقدي لتخفيف التدخلات المحتملة التي يسببها الإشعاع المعرفي التناقصات يعتمد في النهاية على القدرة على إجراء تقييمات كمية دقيق للمعرفة.

قياس المعرفي التناقصات التي تحدثها العلاج الإشعاعي القحف

With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For ...

quantifying-cognitive-decrements-caused-by-cranial-radiotherapy

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Medicine

12.6K Views.  University of California Irvine. ضعف الإدراك الناتج عن إدارة radiotherapeutic من أورام المخ يمثل حالة مستعصية سريريا أن يؤثر سلبا نوعية الحياة. القدرة على تقييم نقدي لتخفيف التدخلات المحتملة التي يسببها الإشعاع المعرفي التناقصات يعتمد في النهاية على القدرة على إجراء تقييمات كمية دقيق للمعرفة.

Video: Quantifying Cognitive Decrements Caused by Cranial Radiotherapy

Stem Cell Transplantation Strategies for the Restoration of Cognitive Dysfunction Caused by Cranial Radiotherapy

Radiotherapy often provides the only clinical recourse for those afflicted with primary or metastatic brain tumors. While beneficial, cranial irradiation can induce a progressive and debilitating decline in cognition that may, in part, be caused by the depletion of neural stem cells. Given the increased survival of patients diagnosed with brain cancer, quality of life in terms of cognitive health has become an increasing concern, especially in the absence of any satisfactory long-term treatments.
To address this serious health concern we have used stem cell replacement as a strategy to combat radiation-induced cognitive decline. Our model utilizes athymic nude rats subjected to cranial irradiation. The ionizing radiation is delivered as either whole brain or as a highly focused beam to the hippocampus via linear accelerator (LINAC) based stereotaxic radiosurgery. Two days following irradiation, human neural stem cells (hNSCs) were stereotaxically transplanted into the hippocampus. Rats were then assessed for changes in cognition, grafted cell survival and for the expression of differentiation-specific markers 1 and 4-months after irradiation. Our cognitive testing paradigms have demonstrated that animals engrafted with hNSCs exhibit significant improvements in cognitive function. Unbiased stereology reveals significant survival (10-40%) of the engrafted cells at 1 and 4-months after transplantation, dependent on the amount and type of cells grafted. Engrafted cells migrate extensively, differentiate along glial and neuronal lineages, and express a range of immature and mature phenotypic markers.
Our data demonstrate direct cognitive benefits derived from engrafted human stem cells, suggesting that this procedure may one day afford a promising strategy for the long-term functional restoration of cognition in individuals subjected to cranial radiotherapy. To promote the dissemination of the critical procedures necessary to replicate and extend our studies, we have provided written and visual documentation of several key steps in our experimental plan, with an emphasis on stereotaxic radiosurgey and transplantation.

Brain tumor patients routinely undergo cranial radiotherapy, and while beneficial, this treatment often results in debilitating cognitive dysfunction. This serious unresolved problem has at present, no clinical recourse, and has driven our efforts to devise stem cell based therapies for the recovery of radiation-induced cognitive decrements.

زرع الخلايا الجذعية استراتيجيات من أجل استعادة الضعف المعرفي التي تحدثها العلاج الإشعاعي القحف

Radiotherapy often provides the only clinical recourse for those afflicted with primary or metastatic brain tumors. While beneficial, cranial irradiation ...

Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment2. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure3. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 &mu;l every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without radiation.

The purpose of this article is to describe the use of an orthotopic glioblastoma model for chemoradiation studies. This article will go though cell processing, implanting, and radiotherapy of the mouse using an intracranial model.

العلاج الإشعاعي مجموعة في نموذج الفأر Orthotopic استئصال ورم من الدماغ

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the ...

High Content Screening in Neurodegenerative Diseases

The functional annotation of genomes, construction of molecular networks and novel drug target identification, are important challenges that need to be addressed as a matter of great urgency1-4. Multiple complementary 'omics' approaches have provided clues as to the genetic risk factors and pathogenic mechanisms underlying numerous neurodegenerative diseases, but most findings still require functional validation5. For example, a recent genome wide association study for Parkinson's Disease (PD), identified many new loci as risk factors for the disease, but the underlying causative variant(s) or pathogenic mechanism is not known6, 7. As each associated region can contain several genes, the functional evaluation of each of the genes on phenotypes associated with the disease, using traditional cell biology techniques would take too long. 
	There is also a need to understand the molecular networks that link genetic mutations to the phenotypes they cause. It is expected that disease phenotypes are the result of multiple interactions that have been disrupted. Reconstruction of these networks using traditional molecular methods would be time consuming. Moreover, network predictions from independent studies of individual components, the reductionism approach, will probably underestimate the network complexity8. This underestimation could, in part, explain the low success rate of drug approval due to undesirable or toxic side effects. Gaining a network perspective of disease related pathways using HT/HC cellular screening approaches, and identifying key nodes within these pathways, could lead to the identification of targets that are more suited for therapeutic intervention.
	High-throughput screening (HTS) is an ideal methodology to address these issues9-12. but traditional methods were one dimensional whole-well cell assays, that used simplistic readouts for complex biological processes. They were unable to simultaneously quantify the many phenotypes observed in neurodegenerative diseases such as axonal transport deficits or alterations in morphology properties13, 14. This approach could not be used to investigate the dynamic nature of cellular processes or pathogenic events that occur in a subset of cells. To quantify such features one has to move to multi-dimensional phenotypes termed high-content screening (HCS)4, 15-17. HCS is the cell-based quantification of several processes simultaneously, which provides a more detailed representation of the cellular response to various perturbations compared to HTS. 
	HCS has many advantages over HTS18, 19, but conducting a high-throughput (HT)-high-content (HC) screen in neuronal models is problematic due to high cost, environmental variation and human error. In order to detect cellular responses on a 'phenomics' scale using HC imaging one has to reduce variation and error, while increasing sensitivity and reproducibility. 
	Herein we describe a method to accurately and reliably conduct shRNA screens using automated cell culturing20 and HC imaging in neuronal cellular models. We describe how we have used this methodology to identify modulators for one particular protein, DJ1, which when mutated causes autosomal recessive parkinsonism21. 
	Combining the versatility of HC imaging with HT methods, it is possible to accurately quantify a plethora of phenotypes. This could subsequently be utilized to advance our understanding of the genome, the pathways involved in disease pathogenesis as well as identify potential therapeutic targets.

We describe a methodology combining automated cell culturing with high-content imaging to visualize and quantify multiple cellular processes and structures, in a high-throughput manner. Such methods can aid in the further functional annotation of genomes as well as identify disease gene networks and potential drug targets.

فحص محتوى عالية في أمراض الاعصاب

The functional annotation of genomes, construction of molecular networks and novel drug target identification, are important challenges that need to be ...

Imaging Glioma Initiation In Vivo Through a Polished and Reinforced Thin-skull Cranial Window

Glioma is the one of the most lethal forms of human cancer. The most effective glioma therapy to date-surgery followed by radiation treatment-offers patients only modest benefits, as most patients do not survive more than five years following diagnosis due to glioma relapse 1,2. The discovery of cancer stem cells in human brain tumors holds promise for having an enormous impact on the development of novel therapeutic strategies for glioma 3. Cancer stem cells are defined by their ability both to self-renew and to differentiate, and are thought to be the only cells in a tumor that have the capacity to initiate new tumors 4. Glioma relapse following radiation therapy is thought to arise from resistance of glioma stem cells (GSCs) to therapy 5-10. In vivo, GSCs are shown to reside in a perivascular niche that is important for maintaining their stem cell-like characteristics 11-14. Central to the organization of the GSC niche are vascular endothelial cells 12. Existing evidence suggests that GSCs and their interaction with the vascular endothelial cells are important for tumor development, and identify GSCs and their interaction with endothelial cells as important therapeutic targets for glioma. The presence of GSCs is determined experimentally by their capability to initiate new tumors upon orthotopic transplantation 15. This is typically achieved by injecting a specific number of GBM cells isolated from human tumors into the brains of severely immuno-deficient mice, or of mouse GBM cells into the brains of congenic host mice. Assays for tumor growth are then performed following sufficient time to allow GSCs among the injected GBM cells to give rise to new tumors-typically several weeks or months. Hence, existing assays do not allow examination of the important pathological process of tumor initiation from single GSCs in vivo. Consequently, essential insights into the specific roles of GSCs and their interaction with the vascular endothelial cells in the early stages of tumor initiation are lacking. Such insights are critical for developing novel therapeutic strategies for glioma, and will have great implications for preventing glioma relapse in patients. Here we have adapted the PoRTS cranial window procedure 16and in vivo two-photon microscopy to allow visualization of tumor initiation from injected GBM cells in the brain of a live mouse. Our technique will pave the way for future efforts to elucidate the key signaling mechanisms between GSCs and vascular endothelial cells during glioma initiation.

Imaging Glioma Initiation In Vivo Through a Polished and Reinforced Thin-skull Cranial Window

By combining a polished and reinforced thin-skull (PoRTS) cranial window and glioblastoma (GBM) cell injection, we can observe glioma initiation and growth from injected GBM cells in the brain of a live mouse longitudinally.

بدء تصوير دبقي<em&gt; في الجسم الحي</em&gt; من خلال نافذة رقيقة الجمجمة ملمع وعززت القحف

Glioma is the one of the most lethal forms of human cancer. The most effective glioma therapy to date-surgery followed by radiation treatment-offers ...

Voluntary Breath-hold Technique for Reducing Heart Dose in Left Breast Radiotherapy

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these techniques, patients hold their breath while radiotherapy is delivered, pushing the heart down and away from the radiotherapy field. Despite clear dosimetric benefits, these techniques are not yet in widespread use. One reason for this is that commercially available solutions require specialist equipment, necessitating not only significant capital investment, but often also incurring ongoing costs such as a need for daily disposable mouthpieces. The voluntary breath-hold technique described here does not require any additional specialist equipment. All breath-holding techniques require a surrogate to monitor breath-hold consistency and whether breath-hold is maintained. Voluntary breath-hold uses the distance moved by the anterior and lateral reference marks (tattoos) away from the treatment room lasers in breath-hold to monitor consistency at CT-planning and treatment setup. Light fields are then used to monitor breath-hold consistency prior to and during radiotherapy delivery.

The current priority in breast cancer radiotherapy is to reduce cardiac doses without compromising target tissue coverage. The voluntary breath-hold technique described here is a simple, inexpensive solution to this problem and capable of being instituted widely without the need for specialized equipment.

الطوعية التنفس الانتظار وتقنيات للحد من القلب جرعة العلاج الإشعاعي في اليسار الثدي

Breath-holding techniques reduce the amount of radiation received by cardiac structures during tangential-field left breast radiotherapy. With these ...

State of the Art Cranial Ultrasound Imaging in Neonates

Cranial ultrasound (CUS) is a reputable tool for brain imaging in critically ill neonates. It is safe, relatively cheap and easy to use, even when a patient is unstable. In addition it is radiation-free and allows serial imaging. CUS possibilities have steadily expanded. However, in many neonatal intensive care units, these possibilities are not optimally used. We present a comprehensive approach for neonatal CUS, focusing on optimal settings, different probes, multiple acoustic windows and Doppler techniques. This approach is suited for both routine clinical practice and research purposes. In a live demonstration, we show how this technique is performed in the neonatal intensive care unit. Using optimal settings and probes allows for better imaging quality and improves the diagnostic value of CUS in experienced hands. Traditionally, images are obtained through the anterior fontanel. Use of supplemental acoustic windows (lambdoid, mastoid, and lateral fontanels) improves detection of brain injury. Adding Doppler studies allows screening of patency of large intracranial arteries and veins. Flow velocities and indices can be obtained. Doppler CUS offers the possibility of detecting cerebral sinovenous thrombosis at an early stage, creating a window for therapeutic intervention prior to thrombosis-induced tissue damage. Equipment, data storage and safety aspects are also addressed.

Cranial ultrasound (CUS) is a valuable tool for brain imaging in critically ill neonates. This video shows a comprehensive approach for neonatal (Doppler) CUS for both clinical and research purposes, including a bedside demonstration of the technique.

حالة من الفن الجمجمة التصوير بالموجات فوق الصوتية في حديثي الولادة

Cranial ultrasound (CUS) is a reputable tool for brain imaging in critically ill neonates. It is safe, relatively cheap and easy to use, even when a ...

A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and significantly diminish the outcome. Indeed, after routine orthopedic surgery to repair a fracture, as many as 50% of elderly patients suffer from neurologic complications like delirium. Also, the capacity to heal and regenerate tissue after surgery decreases with age, and can impact the quality of fracture repair and even osseous integration of implants. Thus, a better understanding of mechanisms that drive these age-dependent changes could provide strategic targets to minimize risk for such complications and optimize outcomes. Here, we introduce a clinically relevant mouse model of tibial fracture. The postoperative changes in these mice mimic some of the cognitive impairments commonly observed after routine orthopedic surgery in humans. Briefly, an incision is performed in the right hind limb under strictly aseptic conditions. Muscles are disassociated, and a 0.38-mm stainless steel pin is inserted into the upper crest of the tibia, inside the intramedullary canal. Osteotomy is then performed, and the wound is stapled. We have used this model to investigate the effects of surgical trauma on postoperative neuroinflammation and behavioral changes. By applying this fracture model in combination with parabiosis, a surgical model in which 2 mice are anastomosed, we have studied cells and secreted factors that systemically rejuvenate organ function and tissue regeneration after injury. By following our step-by-step protocol, these models can be reproduced with high fidelity, and can be adapted to interrogate many biologic pathways that are altered by surgical trauma.

This protocol describes a mouse model of orthopedic surgery that has been used to study mechanisms of postoperative neuroinflammation and behavioral changes, and when combined with parabiosis, to study tissue regeneration during aging.

نموذج ماوس لجراحة العظام لدراسة الخلل المعرفي بعد العملية الجراحية وتجديد الأنسجة

Surgery is commonly used to improve and maintain quality of life. Unfortunately, in vulnerable patients such as the elderly, complications may occur and ...

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For inoperable patients, local ablation therapies, such as stereotactic body radiotherapy (SBRT), can provide effective local tumor control with minimal toxicity. Because of its high precision and accuracy, SBRT delivers a higher radiation dose per fraction, is more effective, and targets smaller irradiation volumes than does conventional radiotherapy. In addition, steep dose gradients from target lesions to surrounding normal tissues are achieved using SBRT; thus, SBRT provides more effective tumor control and exhibits fewer side effects than conventional radiotherapy. The use of SBRT is prevalent for treating intracranial lesions (known as stereotactic radiosurgery); however, it is now also used for treating spinal and adrenal metastases. Because of advancements in image-guided assistance and respiratory motion management, several studies have investigated the use of SBRT for treating lung or liver tumors, which move as a patient breathes. The results of these studies have suggested that SBRT favorably controls tumors in the case of moving lesions.
Four-dimensional computed tomography (4D-CT) with an abdominal compressor (AC) is clinically convenient for effective respiratory motion management. Because this method is noninvasive and allows free breathing, its use reduces complications. Furthermore, patients consider this method convenient. Moreover, it is considered more efficient than other methods of respiratory motion management by physicians and therapists. The use of 4D-CT with an AC for treating pulmonary lesions has also been widely investigated, and the technique is gaining acceptance for treating hepatic lesions. However, the protocols for using 4D-CT with an AC for treating hepatic lesions are different from those used for treating pulmonary lesions. In this article, we describe a new protocol for SBRT with 4D-CT and an AC for treating liver metastases.

Stereotactic body radiotherapy (SBRT) requires rigorous accuracy and precision for delivering high radiation doses per fraction to small treatment volumes to improve tumor control and simultaneously reduce toxicity. Herein, we present a noninvasive and clinically convenient respiratory motion management protocol for SBRT for liver metastases.

علاج الأورام الثانوية في الكبد جراء استخدام أسلوب وحدة تخزين هدف داخلي للعلاج بالمناظير باستخدام الأشعة الجسم الأشعة

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For ...

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated arc therapy (VMAT) plans for patients with head/neck cancer and 4-field box plans for patients with cervical cancer. It is a combination of specially developed in-house software that uses an application programming interface to communicate with a commercial radiotherapy treatment planning system. It also interfaces with a commercial secondary dose verification software. The necessary inputs to the system are a Treatment Plan Order, approved by the radiation oncologist, and a simulation computed tomography (CT) image, approved by the radiographer. The RPA then generates a complete radiotherapy treatment plan. For the cervical cancer treatment plans, no additional user intervention is necessary until the plan is complete. For head/neck treatment plans, after the normal tissue and some of the target structures are automatically delineated on the CT image, the radiation oncologist must review the contours, making edits if necessary. They also delineate the gross tumor volume. The RPA then completes the treatment planning process, creating a VMAT plan. Finally, the completed plan must be reviewed by qualified clinical staff.

Radiation therapy is a highly complex cancer treatment that requires multiple specialists to create a treatment plan and provide quality assurance (QA) prior to delivery to a patient. This protocol describes the use of a fully automated system, the Radiation Planning Assistant (RPA), to create high-quality radiation treatment plans.

الإشعاع تخطيط مساعد-مبسطة، مؤتمتة بالكامل نظام تخطيط العلاج بالأشعة

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated ...

Assessment of Static Graviceptive Perception in the Roll-Plane using the Subjective Visual Vertical Paradigm

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow the examination of all semicircular canals in the clinical setting. Assessment methods of the otolithic system, which is responsible for the perception of linear acceleration and perception of gravity, are far less in clinical use. There are several experimental approaches for measuring the perception of gravity. The most frequently used method is the determination of the subjective visual vertical. This is usually measured with the head in an upright position. We present here an assessment method for testing otolith function in the roll plane. The subjective visual vertical is measured in the head upright position as well as with head inclination of &#177; 15&#176; and &#177; 30&#176; in the roll plane. This extended functional paradigm is an easy-to-perform clinical test of otolith function and ensures increased information content for the detection of impaired graviceptive perception.

The perception of gravity is commonly determined by the subjective visual vertical in the head upright position. The additional assessment at head tilts of &#177; 15&#176; and &#177; 30&#176; in the roll plane ensures increased information content for the detection of impaired graviceptive perception.

تقييم التصور اللاستاتيكي في المستوى الأعلى باستخدام النموذج العمودي البصري الذاتي

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow ...