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.

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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

12.5K 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 ...

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 ...

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 ...

Digital Handwriting Analysis of Characters in Chinese Patients with Mild Cognitive Impairment

An increasing amount of evidence shows that cognitive deficits and movement dysfunctions are not separated. Patients with mild cognitive impairment (MCI) can manifest fine motor disorders of the upper extremities. Handwriting is a complex and unique human activity involving both motor and cognitive coordination. Researchers from western countries have discovered that patients with MCI have abnormal handwriting features. However, no relevant studies have been conducted in the Chinese population. Owing to the cross-culture phenomenon of handwriting, the aim of this study is to find new handwriting tasks to demonstrate the differences in handwriting features between elderly patients with MCI and age-matched healthy individuals.

This study proposed a digital handwriting analysis of characters in individuals with mild cognitive impairment to find more information than is revealed by traditional pencil&#8211;paper handwriting analysis.

تحليل رقمي للكتابة اليدوية من الأحرف في المرضى الصينيين مع ضعف الإدراك الخفيف

An increasing amount of evidence shows that cognitive deficits and movement dysfunctions are not separated. Patients with mild cognitive impairment (MCI) ...

تعزيز العلاج الإشعاعي باستخدام مساعد تخطيط الإشعاع المستند إلى الويب

Radiation Planning Assistant - A Web-based Tool to Support High-quality Radiotherapy in Clinics with Limited Resources

Access to radiotherapy worldwide is limited. The Radiation Planning Assistant (RPA) is a fully automated, web-based tool that is being developed to offer fully automated radiotherapy treatment planning tools to clinics with limited resources. The goal is to help clinical teams scale their efforts, thus reaching more patients with cancer. The user connects to the RPA via a webpage, completes a Service Request (prescription and information about the radiotherapy targets), and uploads the patient&#39;s CT image set. The RPA offers two approaches to automated planning. In one-step planning, the system uses the Service Request and CT scan to automatically generate the necessary contours and treatment plan. In two-step planning, the user reviews and edits the automatically generated contours before the RPA continues to generate a volume-modulated arc therapy plan. The final plan is downloaded from the RPA website and imported into the user&#39;s local treatment planning system, where the dose is recalculated for the locally commissioned linac; if necessary, the plan is edited prior to approval for clinical use.

تسليط الضوء على المؤلف: تحسين الوصول إلى العلاج الإشعاعي باستخدام مساعد التخطيط الإشعاعي

This protocol describes a series of automated tools designed for high-quality radiotherapy autocontouring and autoplanning that are being packaged into a web-based service to maximize robustness and scalability while minimizing operational costs.

مساعد تخطيط الإشعاع - أداة قائمة على الويب لدعم العلاج الإشعاعي عالي الجودة في العيادات ذات الموارد المحدودة

Access to radiotherapy worldwide is limited. The Radiation Planning Assistant (RPA) is a fully automated, web-based tool that is being developed to offer ...