SU-E-T-366: Estimation of Whole Body Dose From Cranial Irradiation From C and Perfexion Series Gamma Knife Units

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, S; Indiana University School of Medicine, Indianapolis, IN, University Hospitals Case Medical Center, Cleaveland, OH; Andersen, A

2015-06-15

Purpose: The Leksell Gamma Knife (GK) B & C series contains 201 Cobalt-60 sources with a helmet. The new model, Perfexion uses 192 Cobalt-60 sources without a helmet; using IRIS system for collimation and stereotactic guidance to deliver SRS to brain tumors. Relative dose to extracranial organs at risk (OARs) is measured in phantom in this study for Perfexion and C-series GK. Materials & Methods: Measurements were performed in a Rando anthropomorphic phantom on both systems using a large ion chamber (Keithley-175) for each collimator. The Keithley-175 cc ion chamber was sandwiched between phantom slices at various locations in themore » phantom to correspond to different extracranial OARs (thyroid, heart, kidney, ovary and testis, etc.) The dose measurement was repeated with OSL detectors for each position and collimator. Results: A large variation is observed in the normalized dose between these two systems. The dose beyond the housing falls off exponentially for Perfexion. Dose beyond the C-series GK housing falls off exponentially from 0–20cm then remains relatively constant from 20–40cm and again falls off with distance but less rapidly. The variation of extracranial dose with distance for each collimator is found to be parallel to each other for both systems. Conclusion: Whole body dose is found to vary significantly between these systems. It is important to measure the extracranial dose, especially for young patients. It is estimated that dose falls off exponentially from the GK housing and is about 1% for large collimators at 75 cm. The dose is two-orders of magnitude smaller for the 4mm collimator. However, this small dose for patient may be significant radiologically.« less

Efficacy and Quality of Life Outcomes in Patients With Atypical Trigeminal Neuralgia Treated With Gamma-Knife Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhople, Anil; Kwok, Young; Chin, Lawrence

2007-10-01

Purpose: To assess efficacy and quality of life (QOL) outcomes associated with gamma-knife radiosurgery (GK-RS) in treating atypical trigeminal neuralgia (ATN) compared with classic trigeminal neuralgia (CTN). Methods and Materials: Between September 1996 and September 2004, 35 cases of ATN were treated with GK-RS. Patients were categorized into two groups: Group I comprised patients presenting with ATN (57%); Group II consisted of patients presenting with CTN then progressing to ATN (43%). Median prescription dose 75 Gy (range, 70-80 Gy) was delivered to trigeminal nerve root entry zone. Treatment efficacy and QOL improvements were assessed with a standardized questionnaire. Results: Withmore » median follow-up of 29 months (range, 3-74 months), 72% reported excellent/good outcomes, with mean time to relief of 5.8 weeks (range, 0-24 weeks) and mean duration of relief of 62 weeks (range, 1-163 weeks). This rate of pain relief is similar to rate achieved in our previously reported experience treating CTN with GK-RS (p = 0.36). There was a trend toward longer time to relief (p = 0.059), and shorter duration of relief (p = 0.067) in patients with ATN. There was no difference in rate of, time to, or duration of pain relief between Groups I and II. Of the patients with ATN, 88% discontinued or decreased the use of pain medications. Among the patients with sustained pain relief, QOL improved an average of 85%. Conclusion: This is the largest reported GK-RS experience for the treatment of ATN. Patients with ATN can achieve rates of pain relief similar to those in patients with CTN. Further follow-up is necessary to assess adequately the durability of response.« less

A Simple and Efficient Methodology To Improve Geometric Accuracy in Gamma Knife Radiation Surgery: Implementation in Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karaiskos, Pantelis, E-mail: pkaraisk@med.uoa.gr; Gamma Knife Department, Hygeia Hospital, Athens; Moutsatsos, Argyris

Purpose: To propose, verify, and implement a simple and efficient methodology for the improvement of total geometric accuracy in multiple brain metastases gamma knife (GK) radiation surgery. Methods and Materials: The proposed methodology exploits the directional dependence of magnetic resonance imaging (MRI)-related spatial distortions stemming from background field inhomogeneities, also known as sequence-dependent distortions, with respect to the read-gradient polarity during MRI acquisition. First, an extra MRI pulse sequence is acquired with the same imaging parameters as those used for routine patient imaging, aside from a reversal in the read-gradient polarity. Then, “average” image data are compounded from data acquiredmore » from the 2 MRI sequences and are used for treatment planning purposes. The method was applied and verified in a polymer gel phantom irradiated with multiple shots in an extended region of the GK stereotactic space. Its clinical impact in dose delivery accuracy was assessed in 15 patients with a total of 96 relatively small (<2 cm) metastases treated with GK radiation surgery. Results: Phantom study results showed that use of average MR images eliminates the effect of sequence-dependent distortions, leading to a total spatial uncertainty of less than 0.3 mm, attributed mainly to gradient nonlinearities. In brain metastases patients, non-eliminated sequence-dependent distortions lead to target localization uncertainties of up to 1.3 mm (mean: 0.51 ± 0.37 mm) with respect to the corresponding target locations in the “average” MRI series. Due to these uncertainties, a considerable underdosage (5%-32% of the prescription dose) was found in 33% of the studied targets. Conclusions: The proposed methodology is simple and straightforward in its implementation. Regarding multiple brain metastases applications, the suggested approach may substantially improve total GK dose delivery accuracy in smaller, outlying targets.« less

The Use of Cone Beam Computed Tomography for Image Guided Gamma Knife Stereotactic Radiosurgery: Initial Clinical Evaluation.

PubMed

Li, Winnie; Cho, Young-Bin; Ansell, Steve; Laperriere, Normand; Ménard, Cynthia; Millar, Barbara-Ann; Zadeh, Gelareh; Kongkham, Paul; Bernstein, Mark; Jaffray, David A; Chung, Caroline

2016-09-01

The present study used cone beam computed tomography (CBCT) to measure the inter- and intrafraction uncertainties for intracranial stereotactic radiosurgery (SRS) using the Leksell Gamma Knife (GK). Using a novel CBCT system adapted to the GK radiosurgery treatment unit, CBCT images were acquired immediately before and after treatment for each treatment session within the context of a research ethics board-approved prospective clinical trial. Patients were immobilized in the Leksell coordinate frame (LCF) for both volumetric CBCT imaging and GK-SRS delivery. The relative displacement of the patient's skull to the stereotactic reference (interfraction motion) was measured for each CBCT scan. Differences between the pre- and post-treatment CBCT scans were used to determine the intrafraction motion. We analyzed 20 pre- and 17 post-treatment CBCT scans in 20 LCF patients treated with SRS. The mean translational pretreatment setup error ± standard deviation in the left-right, anteroposterior, and craniocaudal directions was -0.19 ± 0.32, 0.06 ± 0.27, and -0.23 ± 0.2 mm, with a maximum of -0.74, -0.53, and -0.68 mm, respectively. After an average time between the pre- and post-treatment CBCT scans of 82 minutes (range 27-170), the mean intrafraction error ± standard deviation for the LCF was -0.03 ± 0.05, -0.03 ± 0.18, and -0.03 ± 0.12 mm in the left-right, anteroposterior, and craniocaudual direction, respectively. Using CBCT on a prototype image guided GK Perfexion unit, we were able to measure the inter- and intrafraction positional changes for GK-SRS using the invasive frame. In the era of image guided radiation therapy, the use of CBCT image guidance for both frame- and non-frame-based immobilization systems could serve as a useful quality assurance tool. Our preliminary measurements can guide the application of achievable thresholds for inter- and intrafraction discrepancy when moving to a frameless approach. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The role of diffusion tensor imaging tractography for Gamma Knife thalamotomy planning.

PubMed

Gomes, João Gabriel Ribeiro; Gorgulho, Alessandra Augusta; de Oliveira López, Amanda; Saraiva, Crystian Wilian Chagas; Damiani, Lucas Petri; Pássaro, Anderson Martins; Salvajoli, João Victor; de Oliveira Siqueira, Ludmila; Salvajoli, Bernardo Peres; De Salles, Antônio Afonso Ferreira

2016-12-01

OBJECTIVE The role of tractography in Gamma Knife thalamotomy (GK-T) planning is still unclear. Pyramidal tractography might reduce the risk of radiation injury to the pyramidal tract and reduce motor complications. METHODS In this study, the ventralis intermedius nucleus (VIM) targets of 20 patients were bilaterally defined using Iplannet Stereotaxy Software, according to the anterior commissure-posterior commissure (AC-PC) line and considering the localization of the pyramidal tract. The 40 targets and tractography were transferred as objects to the GammaPlan Treatment Planning System (GP-TPS). New targets were defined, according to the AC-PC line in the functional targets section of the GP-TPS. The target offsets required to maintain the internal capsule (IC) constraint of < 15 Gy were evaluated. In addition, the strategies available in GP-TPS to maintain the minimum conventional VIM target dose at > 100 Gy were determined. RESULTS A difference was observed between the positions of both targets and the doses to the IC. The lateral (x) and the vertical (z) coordinates were adjusted 1.9 mm medially and 1.3 mm cranially, respectively. The targets defined considering the position of the pyramidal tract were more medial and superior, based on the constraint of 15 Gy touching the object representing the IC in the GP-TPS. The best strategy to meet the set constraints was 90° Gamma angle (GA) with automatic shaping of dose distribution; this was followed by 110° GA. The worst GA was 70°. Treatment time was substantially increased by the shaping strategy, approximately doubling delivery time. CONCLUSIONS Routine use of DTI pyramidal tractography might be important to fine-tune GK-T planning. DTI tractography, as well as anisotropy showing the VIM, promises to improve Gamma Knife functional procedures. They allow for a more objective definition of dose constraints to the IC and targeting. DTI pyramidal tractography introduced into the treatment planning may reduce the incidence of motor complications and improve efficacy. This needs to be validated in a large clinical series.

SU-D-BRB-04: Plan Quality Comparison of Intracranial Stereotactic Radiosurgery (SRS) for Gamma Knife and VMAT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Algan, O; Ahmad, S

2015-06-15

Purpose: To compare treatment plan quality of intracranial stereotactic radiosurgery (SRS) for VMAT (RapidArc) and Gamma Knife (GK) systems. Methods: Ten patients with 24 tumors (seven with 1–2 and three with 4–6 lesions), previously treated with GK 4C (prescription doses ranging from 14–23 Gy) were re-planned for RapidArc. Identical contour sets were kept on MRI images for both plans with tissues assigned a CT number of zero. RapidArc plans were performed using 6 MV flattening-filter-free (FFF) beams with dose rate of 1400 MU/minute using two to eight arcs with the following combinations: 2 full coplanar arcs and the rest non-coplanarmore » half arcs. Beam selection was based on target depth. Areas that penetrated more than 10 cm of tissue were avoided by creating smaller arcs or using avoidance sectors in optimization. Plans were optimized with jaw tracking and a high weighting to the normal-brain-tissue and Normal-Tissue-Objective without compromising PTV coverage. Plans were calculated on a 1 mm grid size using AAA algorithm and then normalized so that 99% of each target volume received the prescription dose. Plan quality was assessed by target coverage using Paddick Conformity Index (PCI), sparing of normal-brain-tissue through analysis of V4, V8, and V12 Gy, and integral dose. Results: In all cases critical structure dose criteria were met. RapidArc had a higher PCI than GK plans for 23 out of 24 lesions. The average PCI was 0.76±0.21 for RapidArc and 0.46±0.20 for GK plans (p≤0.001), respectively. Integral dose and normal-brain-tissue doses for all criteria were lower for RapidArc in nearly all patients. The average ratio of GK to RapidArc plans was 1.28±0.27 (p=0.018), 1.31±0.25 (p=0.017), 1.81±0.43 (p=0.005), and 1.50±0.61 (p=0.006) for V4, V8, and V12 Gy, and integral dose, respectively. Conclusion: VMAT was capable of producing higher quality treatment plans than GK when using optimal beam geometries and proper optimization techniques.« less

Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study.

PubMed

Attanasio, Roberto; Epaminonda, Paolo; Motti, Enrico; Giugni, Enrico; Ventrella, Laura; Cozzi, Renato; Farabola, Mario; Loli, Paola; Beck-Peccoz, Paolo; Arosio, Maura

2003-07-01

Stereotactic radiosurgery by gamma-knife (GK) is an attractive therapeutic option after failure of microsurgical removal in patients with pituitary adenoma. In these tumors or remnants of them, it aims to obtain the arrest of cell proliferation and hormone hypersecretion using a single precise high dose of ionizing radiation, sparing surrounding structures. The long-term efficacy and toxicity of GK in acromegaly are only partially known. Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side-effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity.

Gamma Knife radiosurgery of olfactory groove meningiomas provides a method to preserve subjective olfactory function.

PubMed

Gande, Abhiram; Kano, Hideyuki; Bowden, Gregory; Mousavi, Seyed H; Niranjan, Ajay; Flickinger, John C; Lunsford, L Dade

2014-02-01

Anosmia is a common outcome after resection of olfactory groove meningioma(s) (OGM) and for some patients represents a significant disability. To evaluate long term tumor control rates and preservation of subjective olfaction after Gamma Knife (GK) stereotactic radiosurgery (SRS) of OGM. We performed a retrospective chart review and telephone assessments of 41 patients who underwent GK SRS between 1987 and 2008. Clinical outcomes were stratified by full, partial or no subjective olfaction, whereas tumor control was assessed by changes in volume greater or lesser than 25%. The median clinical and imaging follow-up were 76 and 65 months, respectively. Prior to SRS, 19 (46%) patients had surgical resections and two (5%) had received fractionated radiation therapy. Twenty four patients (59%) reported a normal sense of smell, 12 (29%) reported a reduced sense of smell and five (12%) had complete anosmia. The median tumor volume was 8.5 cm(3) (range 0.6-56.1), the mean radiation dose at the tumor margin was 13 Gy (range 10-20) and the median estimated dose to the olfactory nerve was 5.1 Gy (range 1.1-18.1). At follow-up, 27 patients (66%) reported intact olfaction (three (7%) described return to a normal sense of smell), nine (22%) described partial anosmia, and five (12%) had complete anosmia. No patient reported deterioration in olfaction after SRS. Thirteen patients (32%) showed significant tumor regression, 26 (63%) had no further growth and two (5%) had progressed. The progression free tumor control rates were 97% at 1 year and 95% at 2, 10 and 20 years. Symptomatic adverse radiation effects occurred in three (7%) patients. Stereotactic radiosurgery provided both long term tumor control and preservation of olfaction.

Survival of melanoma patients treated with targeted therapy and immunotherapy after systematic upfront control of brain metastases by radiosurgery.

PubMed

Gaudy-Marqueste, C; Dussouil, A S; Carron, R; Troin, L; Malissen, N; Loundou, A; Monestier, S; Mallet, S; Richard, M A; Régis, J M; Grob, J J

2017-10-01

Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice. Survival after 1st GK (OS GK1 ) according to prognostic factors and treatment. Among 179 consecutive pts treated by GK, 109 received IT and/or TT after the 1st GK. Median OS GK1 was 10.95 months and 1- and 2-year survival rates were 49.5% and 27.4%, respectively, versus a median overall survival (OS) of 2.29 months (p < .001) in those who did not receive IT or TT. In pts who initially had a single BM, median OS and 1- and 2-year survival rates were 14.46 months, 66.7% and 43.4%, respectively; in pts with 2-3 BMs: 8.85 months, 46.4% and 31%, respectively; in pts with >3 BMs: 7.25 months, 37.2% and 11.9%, respectively. Multivariate analysis for OS GK1 confirmed that IT and TT were significantly and highly protective. Best OS GK1 was observed in BRAF-wild-type pts receiving anti-PD1 or in BRAF-mutated pts receiving BRAF-inhibitors and anti-PD1 (12.26 and 14.82 months, respectively). In real-life MM pts with BMs, a strategy aiming at controlling BM with GK together with TT and/or TT seems to achieve unprecedented survival rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan.

PubMed

Lin, Ching-Heng; Hsu, Kuo-Hsuan; Chang, Shih-Ni; Tsou, Hsi-Kai; Sheehan, Jason; Sheu, Meei-Ling; Pan, Hung-Chuan

2015-06-06

Whole brain irradiation (WBRT) either with or without resection has historically been the treatment for brain metastases from non-small cell lung cancer (NSCLC). The effect of gamma knife (GK) radiosurgery, chemotherapy, or the combination remains incompletely defined. In this study, we assessed the outcome of brain metastases from non-small cell lung cancer treated by WBRT followed by GK, gefitinib, or the combination of GK and gefitinib. We retrieved the records of NSCLC patients with brain metastases from the National Health Insurance Research Database (NHIRD) of Taiwan from 2004 to 2010. WBRT either with or without resection was the first line treatment for nearly all patients. The decision to add GK and/or gefitinib treatment was at the discretion of the treating physician and based upon a patient's medical records and imaging data. These patients were classified into four groups including WBRT, WBRT + gefitinib, WBRT + GK, WBRT + gefitinib + GK. These data was evaluated for difference in survival and factors that portended an extended survival from the time of brain metastasis diagnosis. Of the 60194 patients with newly diagnosed NSCLC, 23874 (39.6 %) developed brain metastases. The distribution of patients for the groups was WBRT for 20241, WBRT + gefitinib for 3379, WBRT + GK for 155, and WBRT+ gefitinib + GK for 99 patients. The median survival for the time of brain metastasis diagnosis for WBRT, WBRT+ gefitinib, WBRT+ GK, WBRT+ gefitinib + GK groups was 0.53, 1.01, 1.46, and 2.25 years, respectively (p < 0.0001). The hazard ratio (95 % CI) for survival was 1, 0.56, 0.43, and 0.40, respectively (p < 0.001). The adjusted hazard ratio (95 % CI) by age, sex and Charlson comorbidity index (CCI) was 1, 0.73, 0.49, and 0.42, respectively (p < 0.001). Patients with brain metastases from NSCLC receiving GK or gefitinib demonstrated extended survival. The improved survival seen with GK and gefitinib suggests a survival benefit in selected patients receiving the combined treatment. Further Phase II study should be conducted to assessment these influence.

Critical appraisal of RapidArc radiosurgery with flattening filter free photon beams for benign brain lesions in comparison to GammaKnife: a treatment planning study.

PubMed

Abacioglu, Ufuk; Ozen, Zeynep; Yilmaz, Meltem; Arifoglu, Alptekin; Gunhan, Basri; Kayalilar, Namik; Peker, Selcuk; Sengoz, Meric; Gurdalli, Salih; Cozzi, Luca

2014-05-21

To evaluate the role of RapidArc (RA) for stereotactic radiosurgery (SRS) of benign brain lesions in comparison to GammaKnife (GK) based technique. Twelve patients with vestibular schwannoma (VS, n = 6) or cavernous sinus meningioma (CSM, n = 6) were planned for both SRS using volumetric modulated arc therapy (VMAT) by RA. 104 MV flattening filter free photon beams with a maximum dose rate of 2400 MU/min were selected. Data were compared against plans optimised for GK. A single dose of 12.5 Gy was prescribed. The primary objective was to assess treatment plan quality. Secondary aim was to appraise treatment efficiency. For VS, comparing best GK vs. RA plans, homogeneity was 51.7 ± 3.5 vs. 6.4 ± 1.5%; Paddick conformity Index (PCI) resulted 0.81 ± 0.03 vs. 0.84 ± 0.04. Gradient index (PGI) was 2.7 ± 0.2 vs. 3.8 ± 0.6. Mean target dose was 17.1 ± 0.9 vs. 12.9 ± 0.1 Gy. For the brain stem, D(1cm3) was 5.1 ± 2.0 Gy vs 4.8 ± 1.6 Gy. For the ipsilateral cochlea, D(0.1cm3) was 1.7 ± 1.0 Gy vs. 1.8 ± 0.5 Gy. For CSM, homogeneity was 52.3 ± 2.4 vs. 12.4 ± 0.6; PCI: 0.86 ± 0.05 vs. 0.88 ± 0.05; PGI: 2.6 ± 0.1 vs. 3.8 ± 0.5; D(1cm3) to brain stem was 5.4 ± 2.8 Gy vs. 5.2 ± 2.8 Gy; D(0.1cm3) to ipsi-lateral optic nerve was 4.2 ± 2.1 vs. 2.1 ± 1.5 Gy; D(0.1cm3) to optic chiasm was 5.9 ± 3.1 vs. 4.5 ± 2.1 Gy. Treatment time was 53.7 ± 5.8 (64.9 ± 24.3) minutes for GK and 4.8 ± 1.3 (5.0 ± 0.7) minutes for RA for schwannomas (meningiomas). SRS with RA and FFF beams revealed to be adequate and comparable to GK in terms of target coverage, homogeneity, organs at risk sparing with some gain in terms of treatment efficiency.

Radiosurgery for symptomatic cavernous malformations: A multi-institutional retrospective study in Japan

PubMed Central

Kida, Yoshihisa; Hasegawa, Toshinori; Iwai, Yoshiyasu; Shuto, Takashi; Satoh, Manabu; Kondoh, Takeshi; Hayashi, Motohiro

2015-01-01

Background: A group study for symptomatic cavernous malformation (CM) treated with gamma knife (GK) surgery was performed. Methods: A total of 298 cases collected from 23 GK centers across Japan were included. Hemorrhage was the most common manifestation, followed by seizures and neurological deficits. Most of the lesions were located in the brainstem and basal ganglia, followed by the cerebral or cerebellar hemispheres. The CMs, which had a mean diameter of 14.8 mm, were treated using GK surgery with a mean marginal dose of 14.6 Gy. Results: In terms of hemorrhage-free survival (HFS), a marked dissociation was confirmed between the hemorrhage and seizure groups, while no obvious difference was noted between sexes. Superficial CMs located in cerebellum or lobar regions responded to the treatment better than deeply located CMs in the basal ganglia or brainstem. No significant difference of dose-dependent response was seen for three different ranges of marginal dose: Less than 15 Gy, between 15 and 20 Gy, and more than 20 Gy. Complications were more frequent after a marginal dose of over 15 Gy and in patients with lesions more than 15 mm in diameter. The rates of annual hemorrhage were estimated to be 7.4% during the first 2 years after radiosurgery and 2.8% thereafter. The overall hemorrhage rate after radiosurgery was 4.4%/year/patient. Conclusion: The risk of hemorrhage is considerably reduced after GK treatment. The HFS as well as annual hemorrhage rate after GK treatment was apparently superior to that after conservative treatment for symptomatic CMs. To optimize the success of GK treatment, it is important to reduce the incidence of complications. PMID:26005588

Management of brain metastases from non-small cell lung cancer.

PubMed

Baykara, Meltem; Kurt, Gokhan; Buyukberber, Suleyman; Demirci, Umut; Ceviker, Necdet; Algin, Efnan; Coskun, Ugur; Aykol, Sukru; Emmez, Hakan; Ozet, Ahmet; Benekli, Mustafa

2014-01-01

The purpose of the following study is to evaluate the treatment modalities, clinical status and prognostic factors affecting survival rates in patients with newly diagnosed brain metastasis from non-small cell lung cancer (NSCLC). NSCLC patients with a new diagnosis of one to four brain metastasis evaluated retrospectively for the effects of treatment regimens on local failure-relapse-free survival (LRFS) and overall survival (OS). The relationship between age, gender, performance status, recursive partitioning analysis (RPA) classification, the primary tumor under control, number of metastatic tumors in the brain and total volume of brain metastasis and prognosis is analyzed. Out of a total of 138 (121 male and 17 female) patients, nearly 44.2% received only gamma-knife (GK); 24.6% were received both GK and whole brain radiotherapy (WBRT), 2.9% had GK and surgery, 3.6% received GK, surgery and WBRT, 10.9% had surgery and WBRT and 12.3% received only WBRT for treatment. Median LRFS of surgery plus WBRT group was significantly higher when compared with WBRT group (P<0.0001). The OS was significantly longer for surgery plus WBRT group than the other treatment groups (P=0.037). When median survival of WBRT-only group compared with surgery plus WBRT, it was significantly higher (29.6 months vs. 16.7 months, P=0.006). Median OS of surgery plus WBRT group was significantly higher than GK plus WBRT group (29.6 months vs. 9.3 months, P=0.007). WBRT is still the most effective treatment method following surgery in selected patients according to their age, performance status and spread of the primary disease with NSCLC had limited number brain metastasis. Adding WBRT treatment after surgery significantly improved OS and LRFS.

Critical appraisal of RapidArc radiosurgery with flattening filter free photon beams for benign brain lesions in comparison to GammaKnife: a treatment planning study

PubMed Central

2014-01-01

Background To evaluate the role of RapidArc (RA) for stereotactic radiosurgery (SRS) of benign brain lesions in comparison to GammaKnife (GK) based technique. Methods Twelve patients with vestibular schwannoma (VS, n = 6) or cavernous sinus meningioma (CSM, n = 6) were planned for both SRS using volumetric modulated arc therapy (VMAT) by RA. 104 MV flattening filter free photon beams with a maximum dose rate of 2400 MU/min were selected. Data were compared against plans optimised for GK. A single dose of 12.5 Gy was prescribed. The primary objective was to assess treatment plan quality. Secondary aim was to appraise treatment efficiency. Results For VS, comparing best GK vs. RA plans, homogeneity was 51.7 ± 3.5 vs. 6.4 ± 1.5%; Paddick conformity Index (PCI) resulted 0.81 ± 0.03 vs. 0.84 ± 0.04. Gradient index (PGI) was 2.7 ± 0.2 vs. 3.8 ± 0.6. Mean target dose was 17.1 ± 0.9 vs. 12.9 ± 0.1 Gy. For the brain stem, D1cm3 was 5.1 ± 2.0 Gy vs 4.8 ± 1.6 Gy. For the ipsilateral cochlea, D0.1cm3 was 1.7 ± 1.0 Gy vs. 1.8 ± 0.5 Gy. For CSM, homogeneity was 52.3 ± 2.4 vs. 12.4 ± 0.6; PCI: 0.86 ± 0.05 vs. 0.88 ± 0.05; PGI: 2.6 ± 0.1 vs. 3.8 ± 0.5; D1cm3 to brain stem was 5.4 ± 2.8 Gy vs. 5.2 ± 2.8 Gy; D0.1cm3 to ipsi-lateral optic nerve was 4.2 ± 2.1 vs. 2.1 ± 1.5 Gy; D0.1cm3 to optic chiasm was 5.9 ± 3.1 vs. 4.5 ± 2.1 Gy. Treatment time was 53.7 ± 5.8 (64.9 ± 24.3) minutes for GK and 4.8 ± 1.3 (5.0 ± 0.7) minutes for RA for schwannomas (meningiomas). Conclusions SRS with RA and FFF beams revealed to be adequate and comparable to GK in terms of target coverage, homogeneity, organs at risk sparing with some gain in terms of treatment efficiency. PMID:24884967

P13.17STEREOTACTIC RADIOSURGERY WITH GAMMA KNIFE FOR NEUROFIBROMATOSIS 2-ASSOCIATED VESTIBULAR SCHWANNOMAS

PubMed Central

Presti, A. Lo; De Andrés, P.; Kusak, M.E.; De Campos, J.M.; Martínez, N.; Martínez, R.

2014-01-01

BACKGROUND: It is though that Stereotactic Radiosurgery (SRS) is less effective in achieving local tumor control in Neurofibromatosis 2 (NF2)-related vestibular schwannomas (VSs) compared with sporadic tumors. There is scarce literature on optimal dosing, clinical outcomes and eventual increased risk for malignant transformation among these patients. It is also possible that radiation induced tumors, in patients bearing an abnormality in a tumor suppressor gene, are misinterpreted as part of the natural history of NF2, where new tumors are expected to develop. OBJECTIVE: To evaluate the results of Gamma Knife (GK) Radiosurgery in the management of NF2-related VSs versus the sporadic VSs group treated at the same Center. METHOD: A prospectively maintained clinical database including all patients who underwent SRS for VSs was reviewed, and all subjects fulfilling the Manchester diagnostic criteria for NF2 were identified. Between 1994 and 2012, 35 patients with NF2 underwent SRS for 55 presumed VSs at our institution. The mean age at time of treatment was 30.8 years and the mean follow-up period was 4.3 years (1-14.75 years). The median margin dose used was 12 Gy and a total of 62 treatments were performed. Outcome measures, including imaging progression, hearing preservation, trigeminal and facial nerve function, were analyzed. RESULTS: Regarding tumor control 53.4% remained unchanged in size, 22.4% were smaller and 22.4% showed progression requiring further microsurgical resection or SRS. Hearing worsening occurred in 37% of tumors; 2 patients developed facial neuropathy, one of them bilateral and the other transient; trigeminal neuropathy occurred in 4 patients, one of them with previous mild impairment. No cases of malignant transformation were reported. Compared to the sporadic VSs group, NF2 patients showed lower local tumor control and higher incidence of facial and trigeminal neuropathy. CONCLUSION: NF2-related VSs treated with GK show worse clinical and imaging outcomes compared to the sporadic tumors. Although results do not seem to be as good as for patients with sporadic unilateral tumors, GK radiosurgery, using conventional doses, seems to offer acceptable local tumor control rates (75.8%), indicating that radiosurgery could be considered for primary tumor management in selected patients. In order to confirm if radiation therapy is a predisposing factor for the development of new tumors in these patients, a larger multicenter study needs to be designed.

Characterization of system-related geometric distortions in MR images employed in Gamma Knife radiosurgery applications.

PubMed

Pappas, E P; Seimenis, I; Moutsatsos, A; Georgiou, E; Nomikos, P; Karaiskos, P

2016-10-07

This work provides characterization of system-related geometric distortions present in MRIs used in Gamma Knife (GK) stereotactic radiosurgery (SRS) treatment planning. A custom-made phantom, compatible with the Leksell stereotactic frame model G and encompassing 947 control points (CPs), was utilized. MR images were obtained with and without the frame, thus allowing discrimination of frame-induced distortions. In the absence of the frame and following compensation for field inhomogeneities, measured average CP disposition owing to gradient nonlinearities was 0.53 mm. In presence of the frame, contrarily, detected distortion was greatly increased (up to about 5 mm) in the vicinity of the frame base due to eddy currents induced in the closed loop of its aluminum material. Frame-related distortion was obliterated at approximately 90 mm from the frame base. Although the region with the maximum observed distortion may not lie within the GK treatable volume, the presence of the frame results in distortion of the order of 1.5 mm at a 7 cm distance from the center of the Leksell space. Additionally, severe distortions observed outside the treatable volume could possibly impinge on the delivery accuracy mainly by adversely affecting the registration process (e.g. the position of the lower part of the N-shaped fiducials used to define the stereotactic space may be miss-registered). Images acquired with a modified version of the frame developed by replacing its front side with an acrylic bar, thus interrupting the closed aluminum loop and reducing the induced eddy currents, were shown to benefit from relatively reduced distortion. System-related distortion was also identified in patient MR images. Using corresponding CT angiography images as a reference, an offset of 1.1 mm was detected for two vessels lying in close proximity to the frame base, while excellent spatial agreement was observed for a vessel far apart from the frame base.

Characterization of system-related geometric distortions in MR images employed in Gamma Knife radiosurgery applications

NASA Astrophysics Data System (ADS)

Pappas, E. P.; Seimenis, I.; Moutsatsos, A.; Georgiou, E.; Nomikos, P.; Karaiskos, P.

2016-10-01

This work provides characterization of system-related geometric distortions present in MRIs used in Gamma Knife (GK) stereotactic radiosurgery (SRS) treatment planning. A custom-made phantom, compatible with the Leksell stereotactic frame model G and encompassing 947 control points (CPs), was utilized. MR images were obtained with and without the frame, thus allowing discrimination of frame-induced distortions. In the absence of the frame and following compensation for field inhomogeneities, measured average CP disposition owing to gradient nonlinearities was 0.53 mm. In presence of the frame, contrarily, detected distortion was greatly increased (up to about 5 mm) in the vicinity of the frame base due to eddy currents induced in the closed loop of its aluminum material. Frame-related distortion was obliterated at approximately 90 mm from the frame base. Although the region with the maximum observed distortion may not lie within the GK treatable volume, the presence of the frame results in distortion of the order of 1.5 mm at a 7 cm distance from the center of the Leksell space. Additionally, severe distortions observed outside the treatable volume could possibly impinge on the delivery accuracy mainly by adversely affecting the registration process (e.g. the position of the lower part of the N-shaped fiducials used to define the stereotactic space may be miss-registered). Images acquired with a modified version of the frame developed by replacing its front side with an acrylic bar, thus interrupting the closed aluminum loop and reducing the induced eddy currents, were shown to benefit from relatively reduced distortion. System-related distortion was also identified in patient MR images. Using corresponding CT angiography images as a reference, an offset of 1.1 mm was detected for two vessels lying in close proximity to the frame base, while excellent spatial agreement was observed for a vessel far apart from the frame base.

Comparison of full width at half maximum and penumbra of different Gamma Knife models.

PubMed

Asgari, Sepideh; Banaee, Nooshin; Nedaie, Hassan Ali

2018-01-01

As a radiosurgical tool, Gamma Knife has the best and widespread name recognition. Gamma Knife is a noninvasive intracranial technique invented and developed by Swedish neurosurgeon Lars Leksell. The first commercial Leksell Gamma Knife entered the therapeutic armamentarium at the University of Pittsburgh in the United States on August 1987. Since that time, different generation of Gamma Knife developed. In this study, the technical points and dosimetric parameters including full width at half maximum and penumbra on different generation of Gamma Knife will be reviewed and compared. The results of this review study show that the rotating gamma system provides a better dose conformity.

The gamma knife in ophthalmology. Part One--Uveal melanoma.

PubMed

Wygledowska-Promieńska, Dorota; Jurys, Małgorzata; Wilczyński, Tomasz; Drzyzga, Łukasz

2014-01-01

The Gamma Knife was designed by Lars Leksell in the early 1950's. It gave rise to a new discipline of medicine--stereotactic radiosurgery. Primarily dedicated to neurosurgery, the Gamma Knife has become an alternative, widely used surgery technique. According to Elekta's statistics, approximately 60,000 people are treated with Leksell Gamma Knife every year and it is the most extensively studied stereotactic radiosurgery system in the world. The Leksell Gamma Knife can also be used in ophthalmology. The gamma ray beam concentration enables effective treatment of uveal melanoma, choroidal hemangioma, orbital tumors or even choroidal neovascularization. The virtue of Leksell Gamma Knife is its extreme precision, non-invasiveness and the possibility of outpatient treatment, which significantly reduces costs and diminishes post-operative complications. Innovative solutions shorten a single session to a minimum, which is very comfortable and safe for both staff and patients. Advantages and possible side effects of gamma knife radiosurgery are well-documented in the professional literature. The objective of this review is to present the recognized applications of Leksell Gamma Knife in ophthalmology.

Radiosurgery for epilepsy: Systematic review and International Stereotactic Radiosurgery Society (ISRS) practice guideline.

PubMed

McGonigal, Aileen; Sahgal, Arjun; De Salles, Antonio; Hayashi, Motohiro; Levivier, Marc; Ma, Lijun; Martinez, Roberto; Paddick, Ian; Ryu, Samuel; Slotman, Ben J; Régis, Jean

2017-11-01

While there are many reports of radiosurgery for treatment of drug-resistant epilepsy, a literature review is lacking. The aim of this systematic review is to summarize current literature on the use of stereotactic radiosurgery (RS) for treatment of epilepsy. Literature search was performed using various combinations of the search terms "radiosurgery", "stereotactic radiosurgery", "Gamma Knife", "epilepsy" and "seizure", from 1990 until October 2015. Level of evidence was assessed according to the PRISMA guidelines. Fifty-five articles fulfilled inclusion criteria. Level 2 evidence (prospective studies) was available for the clinical indications of mesial temporal lobe epilepsy (MTLE) and hypothalamic hamartoma (HH) treated by Gamma Knife (GK) RS. For remaining indications including corpus callosotomy as palliative treatment, epilepsy related to cavernous malformation and extra-temporal epilepsy, only Level 4 data was available (case report, prospective observational study, or retrospective case series). No Level 1 evidence was available. Based on level 2 evidence, RS is an efficacious treatment to control seizures in MTLE, possibly resulting in superior neuropsychological outcomes and quality of life metrics in selected subjects compared to microsurgery. RS has a better risk-benefit ratio for small hypothalamic hamartomas compared to surgical methods Delayed therapeutic effect resulting in ongoing seizures is associated with morbidity and mortality risk. Lack of level 1 evidence precludes the formation of guidelines at present. Copyright © 2017 Elsevier B.V. All rights reserved.

Embolization with Gamma Knife Radiosurgery of Giant Intracranial Arteriovenous Malformations.

PubMed

Chun, Dong Hyun; Kim, Moo Seong; Kim, Sung Tae; Paeng, Sung Hwa; Jeong, Hae Woong; Lee, Won Hee

2016-01-01

Giant arteriovenous malformations (i.e., those greater than 6 cm maximum diameter or volume > 33 cc) are difficult to treat and often carry higher treatment morbidity and mortality rates. In our study, we reviewed the angiographic results and clinical outcomes for 11 patients with giant arteriovenous malformations who were treated between 1994 and 2012. The patients selected included 9 males (82%) and 2 females (18%). Their presenting symptoms were hemorrhage (n=2; 18%), seizure (n=7; 64%), and headache (n=2; 12%). Nine patients were Spetzler-Martin Grade III, 2 were Spetzler-Martin Grade IV. The mean arteriovenous malformation volume was 41 cc (33-52 cc). The mean age of the patients was 45.1 years (24-57 years) and the mean radiation dose delivered to the margin of the nidus was 14.2 Gy. Ten patients received pre-Gamma Knife radiosurgery embolization and Gamma Knife radiosurgery, 1 patient received pre-Gamma Knife radiosurgery embolization and Gamma Knife radiosurgery twice and the interval between Gamma Knife radiosurgeries was 3 months. The complete obliteration rate following Gamma Knife radiosurgery was 36%, subtotal obliteration ( > 70% decreased size of nidus) was 36%, and partial obliteration was 28%. One patient experienced a small hemorrhage after embolization. Combined embolization and Gamma Knife radiosurgery showed successful obliteration of the arteriovenous malformation nidus. The use of embolization to initially reduce nidus size followed by Gamma Knife radiosurgery improves the treatment results. Repeated Gamma Knife radiosurgery should be a treatment option when there is a small nidus remnant.

Dynamic gamma knife radiosurgery

NASA Astrophysics Data System (ADS)

Luan, Shuang; Swanson, Nathan; Chen, Zhe; Ma, Lijun

2009-03-01

Gamma knife has been the treatment of choice for various brain tumors and functional disorders. Current gamma knife radiosurgery is planned in a 'ball-packing' approach and delivered in a 'step-and-shoot' manner, i.e. it aims to 'pack' the different sized spherical high-dose volumes (called 'shots') into a tumor volume. We have developed a dynamic scheme for gamma knife radiosurgery based on the concept of 'dose-painting' to take advantage of the new robotic patient positioning system on the latest Gamma Knife C™ and Perfexion™ units. In our scheme, the spherical high dose volume created by the gamma knife unit will be viewed as a 3D spherical 'paintbrush', and treatment planning reduces to finding the best route of this 'paintbrush' to 'paint' a 3D tumor volume. Under our dose-painting concept, gamma knife radiosurgery becomes dynamic, where the patient moves continuously under the robotic positioning system. We have implemented a fully automatic dynamic gamma knife radiosurgery treatment planning system, where the inverse planning problem is solved as a traveling salesman problem combined with constrained least-square optimizations. We have also carried out experimental studies of dynamic gamma knife radiosurgery and showed the following. (1) Dynamic gamma knife radiosurgery is ideally suited for fully automatic inverse planning, where high quality radiosurgery plans can be obtained in minutes of computation. (2) Dynamic radiosurgery plans are more conformal than step-and-shoot plans and can maintain a steep dose gradient (around 13% per mm) between the target tumor volume and the surrounding critical structures. (3) It is possible to prescribe multiple isodose lines with dynamic gamma knife radiosurgery, so that the treatment can cover the periphery of the target volume while escalating the dose for high tumor burden regions. (4) With dynamic gamma knife radiosurgery, one can obtain a family of plans representing a tradeoff between the delivery time and the dose distributions, thus giving the clinician one more dimension of flexibility of choosing a plan based on the clinical situations.

Angiomatous lesion and delayed cyst formation after gamma knife surgery for intracranial meningioma: case report and review of literatures.

PubMed

Liu, Zhiyong; He, Min; Chen, Hongxu; Liu, Yi; Li, Qiang; Li, Lin; Li, Jin; Chen, Haifeng; Xu, Jianguo

2015-01-01

Gamma Knife has become a major therapeutic method for intracranial meningiomas, vascular malformations and schwannomas with exact effect. In recent years an increasing number of delayed complications after Gamma Knife surgery have been reported, such as secondary tumors, cystic changes or cyst formation. But angiomatous lesion and delayed cyst formation after Gamma Knife for intracranial lesion has rarely been reported. Here we report the first case of angiomatous lesion and delayed cyst formation following Gamma Knife for intracranial meningioma and discuss its pathogenesis.

Effect of the gamma knife treatment on the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

PubMed

Song, Zhi-Xiu; Qian, Wei; Wu, Yu-Quan; Sun, Fang-Jie; Fei, Jun; Huang, Run-Sheng; Fang, Jing-Yu; Wu, Cai-Zhen; An, You-Ming; Wang, Daxin; Yang, Jun

2014-01-01

To understand the mechanism of the gamma knife treating the trigeminal neuralgia. Using the MASEP-SRRS type gamma knife treatment system, 140 Chinese patients with trigeminal neuralgia (NT) were treated in our hospital from 2002 to 2010, in which the pain relief rate reached 95% and recurrence rate was 3% only. We investigated the effect of the gamma knife treatment on the trigeminal nerve root in 20 Chinese patients with primary trigeminal neuralgia by the magnetic resonance imager (MRI) observation. 1) The cross-sectional area of trigeminal nerve root became smaller and MRI signals were lower in the treatment side than those in the non-treatment side after the gamma knife treatment of primary trigeminal neuralgia; 2) in the treatment side, the cross-sectional area of the trigeminal nerve root decreased significantly after the gamma knife treatment; 3) there was good correlation between the clinical improvement and the MRI findings; and 4) the straight distance between the trigeminal nerve root and the brainstem did not change after the gamma knife treatment. The pain relief induced the gamma knife radiosurgery might be related with the atrophy of the trigeminal nerve root in Chinese patients with primary trigeminal neuralgia.

Gamma Knife

MedlinePlus

... equipment? How is safety ensured? What is this equipment used for? The Gamma Knife® and its associated ... in size. top of page How does the equipment work? The Gamma Knife® utilizes a technique called ...

Current gamma knife treatment for ophthalmic branch of primary trigeminal neuralgia

PubMed Central

Shan, Guo-Yong; Liang, Hao-Fang; Zhang, Jian-Hua

2011-01-01

AIM To probe into problems existing in gamma knife treatment of ophthalmic branch of primary trigeminal neuralgia (TN), and propose a safe and effective solution to the problem. METHODS Through sorting the literature reporting gamma knife treatment of refractory TN in recent years, this article analyzed the advantages and problems of gamma knife treatment of primary TN, and proposed reasonable assessment for existing problems and the possible solution. RESULTS Gamma knife treatment of TN has drawn increasing attention of clinicians due to its unique non-invasion, safety and effectiveness, but there are three related issues to be considered. The first one is the uncertainty of the optimal dose (70-90GY); the second one is the difference in radiotherapy target selection (using a single isocenter or two isocenters); and the third one is the big difference of recurrent pains (specific treatment methods need to be summarized and improved). CONCLUSION For patients with refractory TN, gamma knife treatment can be selected when the medical treatment fails or drug side effects emerge. The analysis of a large number of TN patients receiving gamma knife treatment has shown that this is a safe and effective treatment method. PMID:22553625

Comparison of penumbra regions produced by ancient Gamma knife model C and Gamma ART 6000 using Monte Carlo MCNP6 simulation.

PubMed

Banaee, Nooshin; Asgari, Sepideh; Nedaie, Hassan Ali

2018-07-01

The accuracy of penumbral measurements in radiotherapy is pivotal because dose planning computers require accurate data to adequately modeling the beams, which in turn are used to calculate patient dose distributions. Gamma knife is a non-invasive intracranial technique based on principles of the Leksell stereotactic system for open deep brain surgeries, invented and developed by Professor Lars Leksell. The aim of this study is to compare the penumbra widths of Leksell Gamma Knife model C and Gamma ART 6000. Initially, the structure of both systems were simulated by using Monte Carlo MCNP6 code and after validating the accuracy of simulation, beam profiles of different collimators were plotted. MCNP6 beam profile calculations showed that the penumbra values of Leksell Gamma knife model C and Gamma ART 6000 for 18, 14, 8 and 4 mm collimators are 9.7, 7.9, 4.3, 2.6 and 8.2, 6.9, 3.6, 2.4, respectively. The results of this study showed that since Gamma ART 6000 has larger solid angle in comparison with Gamma Knife model C, it produces better beam profile penumbras than Gamma Knife model C in the direct plane. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment of epidermoid tumors with gamma knife radiosurgery: Case series.

PubMed

Vasquez, Javier A Jacobo; Fonnegra, Julio R; Diez, Juan C; Fonnegra, Andres

2016-01-01

Epidermoid tumors (ETs) are benign lesions that are treated mainly by means of surgical resection, with overall good results. External beam radiotherapy is an alternative treatment for those recurrent tumors, in which a second surgery might not be the best choice for the patient. A little information exists about the effectiveness of gamma knife radiosurgery for the treatment of newly diagnosed and recurrent ETs. We present three cases of ETs treated with gamma knife radiosurgery. Case 1 is a 21-year-old female with an ET located in the left cerebellopontine angle (CPA) with symptoms related to VIII cranial nerve dysfunction. Symptom control was achieved and maintained after single session radiosurgery with gamma knife. Case 2 is a 59-year-old female patient with the history of trigeminal neuralgia secondary to a recurrent ET located in the left CPA. Significant pain improvement was achieved after treatment with gamma knife radiosurgery. Case 3 is a 29-year-old male patient with a CPA ET causing long lasting trigeminal neuralgia, pain relief was achieved in this patient after gamma knife radiosurgery. Long-term symptom relief was achieved in all three cases proving that gamma knife radiosurgery is a good and safe alternative for patients with recurrent or nonsurgically treated ETs.

Failure modes and effects analysis (FMEA) for Gamma Knife radiosurgery.

PubMed

Xu, Andy Yuanguang; Bhatnagar, Jagdish; Bednarz, Greg; Flickinger, John; Arai, Yoshio; Vacsulka, Jonet; Feng, Wenzheng; Monaco, Edward; Niranjan, Ajay; Lunsford, L Dade; Huq, M Saiful

2017-11-01

Gamma Knife radiosurgery is a highly precise and accurate treatment technique for treating brain diseases with low risk of serious error that nevertheless could potentially be reduced. We applied the AAPM Task Group 100 recommended failure modes and effects analysis (FMEA) tool to develop a risk-based quality management program for Gamma Knife radiosurgery. A team consisting of medical physicists, radiation oncologists, neurosurgeons, radiation safety officers, nurses, operating room technologists, and schedulers at our institution and an external physicist expert on Gamma Knife was formed for the FMEA study. A process tree and a failure mode table were created for the Gamma Knife radiosurgery procedures using the Leksell Gamma Knife Perfexion and 4C units. Three scores for the probability of occurrence (O), the severity (S), and the probability of no detection for failure mode (D) were assigned to each failure mode by 8 professionals on a scale from 1 to 10. An overall risk priority number (RPN) for each failure mode was then calculated from the averaged O, S, and D scores. The coefficient of variation for each O, S, or D score was also calculated. The failure modes identified were prioritized in terms of both the RPN scores and the severity scores. The established process tree for Gamma Knife radiosurgery consists of 10 subprocesses and 53 steps, including a subprocess for frame placement and 11 steps that are directly related to the frame-based nature of the Gamma Knife radiosurgery. Out of the 86 failure modes identified, 40 Gamma Knife specific failure modes were caused by the potential for inappropriate use of the radiosurgery head frame, the imaging fiducial boxes, the Gamma Knife helmets and plugs, the skull definition tools as well as other features of the GammaPlan treatment planning system. The other 46 failure modes are associated with the registration, imaging, image transfer, contouring processes that are common for all external beam radiation therapy techniques. The failure modes with the highest hazard scores are related to imperfect frame adaptor attachment, bad fiducial box assembly, unsecured plugs/inserts, overlooked target areas, and undetected machine mechanical failure during the morning QA process. The implementation of the FMEA approach for Gamma Knife radiosurgery enabled deeper understanding of the overall process among all professionals involved in the care of the patient and helped identify potential weaknesses in the overall process. The results of the present study give us a basis for the development of a risk based quality management program for Gamma Knife radiosurgery. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

PubMed

Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

2013-12-01

Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating patients in specific clinical situations. Copyright © 2013 Elsevier Inc. All rights reserved.

Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma.

PubMed

Jang, Chang Ki; Jung, Hyun Ho; Chang, Jong Hee; Chang, Jin Woo; Park, Yong Gou; Chang, Won Seok

2015-10-01

The predominant treatment modality for meningioma is surgical resection. However, gamma knife radiosurgery is also an important treatment modality for meningioma that is small or cannot be completely removed because of its location. In this study, we evaluated the effectiveness and long-term results of radiosurgical treatment for meningioma in our institution. We studied 628 patients (130 men and 498 women) who underwent gamma knife radiosurgery for intracranial meningioma, which is radiologically diagnosed, from Jan 2008 to Nov 2012. We included patients with single lesion meningioma, and followed up after 6 months with imaging, and then at 24 months with a clinical examination. Patients with high-grade meningioma or multiple meningiomas were excluded. We analyzed each of the factors associated with progression free survival. The median patient's age was 56.8 years. Maximal dosage was 27.8 Gy and marginal dosage was 13.9 Gy. The overall tumor control rate was 95%. Twenty-eight patients (4.4%) showed evidence of tumor recurrence. Ninety-eight patients (15%) developed peritumoral edema (PTE) after gamma-knife surgery; two of them (2%) underwent surgical resections due to PTE. Nine patients had craniotomy and tumor removal after gamma knife surgery. Gamma knife surgery for intracranial meningioma has proven to be a safe and effective treatment tool with successful long-term outcomes. Gamma knife radiosurgery can be especially effective in cases of remnant meningioma after surgical resection or where PTE is not present.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Winnie; Cho, Young-Bin; Department of Radiation Oncology, University of Toronto, Toronto, Ontario

Purpose: The present study used cone beam computed tomography (CBCT) to measure the inter- and intrafraction uncertainties for intracranial stereotactic radiosurgery (SRS) using the Leksell Gamma Knife (GK). Methods and Materials: Using a novel CBCT system adapted to the GK radiosurgery treatment unit, CBCT images were acquired immediately before and after treatment for each treatment session within the context of a research ethics board–approved prospective clinical trial. Patients were immobilized in the Leksell coordinate frame (LCF) for both volumetric CBCT imaging and GK-SRS delivery. The relative displacement of the patient's skull to the stereotactic reference (interfraction motion) was measured formore » each CBCT scan. Differences between the pre- and post-treatment CBCT scans were used to determine the intrafraction motion. Results: We analyzed 20 pre- and 17 post-treatment CBCT scans in 20 LCF patients treated with SRS. The mean translational pretreatment setup error ± standard deviation in the left-right, anteroposterior, and craniocaudal directions was −0.19 ± 0.32, 0.06 ± 0.27, and −0.23 ± 0.2 mm, with a maximum of −0.74, −0.53, and −0.68 mm, respectively. After an average time between the pre- and post-treatment CBCT scans of 82 minutes (range 27-170), the mean intrafraction error ± standard deviation for the LCF was −0.03 ± 0.05, −0.03 ± 0.18, and −0.03 ± 0.12 mm in the left-right, anteroposterior, and craniocaudual direction, respectively. Conclusions: Using CBCT on a prototype image guided GK Perfexion unit, we were able to measure the inter- and intrafraction positional changes for GK-SRS using the invasive frame. In the era of image guided radiation therapy, the use of CBCT image guidance for both frame- and non–frame-based immobilization systems could serve as a useful quality assurance tool. Our preliminary measurements can guide the application of achievable thresholds for inter- and intrafraction discrepancy when moving to a frameless approach.« less

Two-year experience with the commercial Gamma Knife Check software.

PubMed

Xu, Andy Yuanguang; Bhatnagar, Jagdish; Bednarz, Greg; Novotny, Josef; Flickinger, John; Lunsford, L Dade; Huq, M Saiful

2016-07-08

The Gamma Knife Check software is an FDA approved second check system for dose calculations in Gamma Knife radiosurgery. The purpose of this study was to evaluate the accuracy and the stability of the commercial software package as a tool for independent dose verification. The Gamma Knife Check software version 8.4 was commissioned for a Leksell Gamma Knife Perfexion and a 4C unit at the University of Pittsburgh Medical Center in May 2012. Independent dose verifications were performed using this software for 319 radiosurgery cases on the Perfexion and 283 radiosurgery cases on the 4C units. The cases on each machine were divided into groups according to their diagnoses, and an averaged absolute percent dose difference for each group was calculated. The percentage dose difference for each treatment target was obtained as the relative difference between the Gamma Knife Check dose and the dose from the tissue maximum ratio algorithm (TMR 10) from the GammaPlan software version 10 at the reference point. For treatment plans with imaging skull definition, results obtained from the Gamma Knife Check software using the measurement-based skull definition method are used for comparison. The collected dose difference data were also analyzed in terms of the distance from the treatment target to the skull, the number of treatment shots used for the target, and the gamma angles of the treatment shots. The averaged percent dose differences between the Gamma Knife Check software and the GammaPlan treatment planning system are 0.3%, 0.89%, 1.24%, 1.09%, 0.83%, 0.55%, 0.33%, and 1.49% for the trigeminal neuralgia, acoustic neuroma, arteriovenous malformation (AVM), meningioma, pituitary adenoma, glioma, functional disorders, and metastasis cases on the Perfexion unit. The corresponding averaged percent dose differences for the 4C unit are 0.33%, 1.2%, 2.78% 1.99%, 1.4%, 1.92%, 0.62%, and 1.51%, respectively. The dose difference is, in general, larger for treatment targets in the peripheral regions of the skull owing to the difference in the numerical methods used for skull shape simulation in the GammaPlan and the Gamma Knife Check software. Larger than 5% dose differences were observed on both machines for certain targets close to patient skull surface and for certain targets in the lower half of the brain on the Perfexion, especially when shots with 70 and/or 110 gamma angles are used. Out of the 1065 treatment targets studied, a 5% cutoff criterion cannot always be met for the dose differences between the studied versions of the Gamma Knife Check software and the planning system for 40 treatment targets. © 2016 The Authors.

Two‐year experience with the commercial Gamma Knife Check software

PubMed Central

Bhatnagar, Jagdish; Bednarz, Greg; Novotny, Josef; Flickinger, John; Lunsford, L. Dade; Huq, M. Saiful

2016-01-01

The Gamma Knife Check software is an FDA approved second check system for dose calculations in Gamma Knife radiosurgery. The purpose of this study was to evaluate the accuracy and the stability of the commercial software package as a tool for independent dose verification. The Gamma Knife Check software version 8.4 was commissioned for a Leksell Gamma Knife Perfexion and a 4C unit at the University of Pittsburgh Medical Center in May 2012. Independent dose verifications were performed using this software for 319 radiosurgery cases on the Perfexion and 283 radiosurgery cases on the 4C units. The cases on each machine were divided into groups according to their diagnoses, and an averaged absolute percent dose difference for each group was calculated. The percentage dose difference for each treatment target was obtained as the relative difference between the Gamma Knife Check dose and the dose from the tissue maximum ratio algorithm (TMR 10) from the GammaPlan software version 10 at the reference point. For treatment plans with imaging skull definition, results obtained from the Gamma Knife Check software using the measurement‐based skull definition method are used for comparison. The collected dose difference data were also analyzed in terms of the distance from the treatment target to the skull, the number of treatment shots used for the target, and the gamma angles of the treatment shots. The averaged percent dose differences between the Gamma Knife Check software and the GammaPlan treatment planning system are 0.3%, 0.89%, 1.24%, 1.09%, 0.83%, 0.55%, 0.33%, and 1.49% for the trigeminal neuralgia, acoustic neuroma, arteriovenous malformation (AVM), meningioma, pituitary adenoma, glioma, functional disorders, and metastasis cases on the Perfexion unit. The corresponding averaged percent dose differences for the 4C unit are 0.33%, 1.2%, 2.78% 1.99%, 1.4%, 1.92%, 0.62%, and 1.51%, respectively. The dose difference is, in general, larger for treatment targets in the peripheral regions of the skull owing to the difference in the numerical methods used for skull shape simulation in the GammaPlan and the Gamma Knife Check software. Larger than 5% dose differences were observed on both machines for certain targets close to patient skull surface and for certain targets in the lower half of the brain on the Perfexion, especially when shots with 70 and/or 110 gamma angles are used. Out of the 1065 treatment targets studied, a 5% cutoff criterion cannot always be met for the dose differences between the studied versions of the Gamma Knife Check software and the planning system for 40 treatment targets. PACS number(s): 87.55.Qr, 87.56.Fc PMID:27455470

Surgery or gamma -knife for the treatment of arteriovenous malformations?

PubMed

Shigeno, T; Atsuchi, M; Tanaka, J; Goto, K; Ogata, N

2000-09-01

Decision making for either surgery or gamma-knife for the treatment of arteriovenous malformations (AVMs) cannot be uniform. The skill of the neurosurgeon in operating on AVMs is now being compared with that of the gamma-knife. The decision varies from case to case and is to be taken by the neurosurgeon. This report presents three cases in which such decision making was not easy. Case 1 was a non-ruptured cingulate AVM of 2.5 cm diameter in the cingulate cortex. The operative field was anticipated to be very narrow between the parietal bridging veins. Case 2 was a tiny ruptured AVM in the speech-motor area which was buried underneath the cortex. Case 3 was a large ruptured thalamo-stiriate-capsular AVM with feeders from the anterior and posterior choroidal arteries. All cases were operated without serious morbidity. A combination of pre-operative intravascular surgery (cases 1 and 3) or postoperative gamma-knife (case 3) was adopted. In conclusion, there is no unitary rule to decide on surgery or gamma-knife for the treatment of AVMs. It depends on what good or harm the responsible surgeon or the gamma-knife does.

Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma

PubMed Central

Jang, Chang Ki; Jung, Hyun Ho; Chang, Jong Hee; Chang, Jin Woo; Park, Yong Gou

2015-01-01

Background The predominant treatment modality for meningioma is surgical resection. However, gamma knife radiosurgery is also an important treatment modality for meningioma that is small or cannot be completely removed because of its location. In this study, we evaluated the effectiveness and long-term results of radiosurgical treatment for meningioma in our institution. Methods We studied 628 patients (130 men and 498 women) who underwent gamma knife radiosurgery for intracranial meningioma, which is radiologically diagnosed, from Jan 2008 to Nov 2012. We included patients with single lesion meningioma, and followed up after 6 months with imaging, and then at 24 months with a clinical examination. Patients with high-grade meningioma or multiple meningiomas were excluded. We analyzed each of the factors associated with progression free survival. The median patient's age was 56.8 years. Maximal dosage was 27.8 Gy and marginal dosage was 13.9 Gy. Results The overall tumor control rate was 95%. Twenty-eight patients (4.4%) showed evidence of tumor recurrence. Ninety-eight patients (15%) developed peritumoral edema (PTE) after gamma-knife surgery; two of them (2%) underwent surgical resections due to PTE. Nine patients had craniotomy and tumor removal after gamma knife surgery. Conclusion Gamma knife surgery for intracranial meningioma has proven to be a safe and effective treatment tool with successful long-term outcomes. Gamma knife radiosurgery can be especially effective in cases of remnant meningioma after surgical resection or where PTE is not present. PMID:26605265

The current role of Gamma Knife radiosurgery in the management of intracranial haemangiopericytoma.

PubMed

Spina, Alfio; Boari, Nicola; Gagliardi, Filippo; Donofrio, Carmine A; Franzin, Alberto; Mortini, Pietro

2016-04-01

Haemangiopericytomas (HPCs) are rare tumours characterised by aggressive behaviour with tendency to local recurrence and to metastasise. WHO grade II and grade III tumours show different progression-free survival and overall survival rates. Gross total tumour resection is still considered the treatment of choice. Adjuvant radiation therapies represent an option in the treatment strategy regardless the extent of resection. Based on this consideration, Gamma Knife radiosurgery has been introduced either as a primary treatment or as an adjuvant treatment for residual or recurrent tumours. A systematic search was performed on PubMed, Web of Science and Google Scholar for clinical series reporting Gamma Knife radiosurgery, Cyberknife and Linear Accelerator (LINAC) for the management of intracranial HPCs. Fourteen studies focusing on the effects of Gamma Knife radiosurgery for intracranial HPCs were included. Four studies reported data on Cyberknife radiosurgery and LINAC. A total of 208 patients harbouring 366 tumours have been reported. Patient's features, radiosurgical treatment characteristics and follow-up data of the pertinent literature have been critically revised. Gamma Knife radiosurgery and the other radiosurgical techniques represent a feasible and effective therapy in the management of HPCs. Tumour control and survival rate are comparable to those reported for radiotherapy. Further studies should be focused to define the exact role of Gamma Knife radiosurgery in the management of HPCs.

Gamma knife radiosurgery in movement disorders: Indications and limitations.

PubMed

Higuchi, Yoshinori; Matsuda, Shinji; Serizawa, Toru

2017-01-01

Functional radiosurgery has advanced steadily during the past half century since the development of the gamma knife technique for treating intractable cancer pain. Applications of radiosurgery for intracranial diseases have increased with a focus on understanding radiobiology. Currently, the use of gamma knife radiosurgery to ablate deep brain structures is not widespread because visualization of the functional targets remains difficult despite the increased availability of advanced neuroimaging technology. Moreover, most existing reports have a small sample size or are retrospective. However, increased experience with intraoperative neurophysiological evaluations in radiofrequency thalamotomy and deep brain stimulation supports anatomical and neurophysiological approaches to the ventralis intermedius nucleus. Two recent prospective studies have promoted the clinical application of functional radiosurgery for movement disorders. For example, unilateral gamma knife thalamotomy is a potential alternative to radiofrequency thalamotomy and deep brain stimulation techniques for intractable tremor patients with contraindications for surgery. Despite the promising efficacy of gamma knife thalamotomy, however, these studies did not include sufficient follow-up to confirm long-term effects. Herein, we review the radiobiology literature, various techniques, and the treatment efficacy of gamma knife radiosurgery for patients with movement disorders. Future research should focus on randomized controlled studies and long-term effects. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Cost analysis of Gamma Knife stereotactic radiosurgery.

PubMed

Griffiths, Alison; Marinovich, Luke; Barton, Michael B; Lord, Sarah J

2007-01-01

Stereotactic radiosurgery (SRS) is used to treat intracranial lesions and vascular malformations as an addition or replacement to whole brain radiotherapy and microsurgery. SRS can be delivered by hardware and software appended to standard linear accelerators (Linacs) or by dedicated systems such as Gamma Knife, which has been proposed as a more accurate and user friendly technology. Internationally, dedicated systems have been funded, despite limitations in evidence. However, some countries including Australia have not recommended additional reimbursement for dedicated systems. This study compares the costs of Linac radiosurgery with Gamma Knife radiosurgery. Due to limited evidence on comparative effects, the economic analysis was restricted to a cost evaluation. The base-case analysis assumed a modified Linac was used only to treat SRS patients. However, because a modified Linac could be used to treat other radiotherapy patients, a second analysis assumed spare time was used to meet other radiotherapy needs, and Linac capital costs were apportioned according to SRS use. The incremental cost of Gamma Knife versus a modified Linac was estimated as AU$209 per patient. This result is sensitive to variations in assumptions. A second analysis proportioning capital costs according to SRS use showed that Gamma Knife may cost up to AU$1673 more per patient. Gamma Knife may be cost competitive only if demand for SRS services is high enough to fully use equipment working time. However, given low patient demand and competing radiotherapy needs, Gamma Knife appears more costly and further evidence of survival or quality of life advantages may be required to justify reimbursement.

Gamma knife surgery-induced ependymoma after the treatment of meningioma - a case report.

PubMed

Wang, Ke; Pan, Li; Che, Xiaoming; Lou, Meiqing

2012-01-01

Gamma knife surgery is widely used for a number of neurological disorders. However, little is known about its long-term complications such as carcinogenic risks. Here, we present a case of a radiosurgery-induced ependymoma by gamma knife surgery for the treatment of a spinal meningioma in a 7-year-old patient. In light of reviewing the previous reports, we advocate high caution in making young patients receive this treatment.

Gamma knife radiosurgery for cerebellopontine angle epidermoid tumors.

PubMed

El-Shehaby, Amr M N; Reda, Wael A; Abdel Karim, Khaled M; Emad Eldin, Reem M; Nabeel, Ahmed M

2017-01-01

Intracranial epidermoid tumors are commonly found in the cerebellopontine angle where they usually present with either trigeminal neuralgia or hemifacial spasm. Radiosurgery for these tumors has rarely been reported. The purpose of this study is to assess the safety and clinical outcome of the treatment of cerebellopontine epidermoid tumors with gamma knife radiosurgery. This is a retrospective study involving 12 patients harboring cerebellopontine angle epidermoid tumors who underwent 15 sessions of gamma knife radiosurgery. Trigeminal pain was present in 8 patients and hemifacial spasm in 3 patients. All cases with trigeminal pain were receiving medication and still uncontrolled. One patient with hemifacial spasm was medically controlled before gamma knife and the other two were not. Two patients had undergone surgical resection prior to gamma knife treatment. The median prescription dose was 11 Gy (10-11 Gy). The tumor volumes ranged from 3.7 to 23.9 cc (median 10.5 cc). The median radiological follow up was 2 years (1-5 years). All tumors were controlled and one tumor shrank. The median clinical follow-up was 5 years. The trigeminal pain improved or disappeared in 5 patients, and of these, 4 cases stopped their medication and one decreased it. The hemifacial spasm resolved in 2 patients who were able to stop their medication. Facial palsy developed in 1 patient and improved with conservative treatment. Transient diplopia was also reported in 2 cases. Gamma knife radiosurgery provides good clinical control for cerebellopontine angle epidermoid tumors.

Gamma knife radiosurgery for cerebellopontine angle epidermoid tumors

PubMed Central

El-Shehaby, Amr M. N.; Reda, Wael A.; Abdel Karim, Khaled M.; Emad Eldin, Reem M.; Nabeel, Ahmed M.

2017-01-01

Background: Intracranial epidermoid tumors are commonly found in the cerebellopontine angle where they usually present with either trigeminal neuralgia or hemifacial spasm. Radiosurgery for these tumors has rarely been reported. The purpose of this study is to assess the safety and clinical outcome of the treatment of cerebellopontine epidermoid tumors with gamma knife radiosurgery. Methods: This is a retrospective study involving 12 patients harboring cerebellopontine angle epidermoid tumors who underwent 15 sessions of gamma knife radiosurgery. Trigeminal pain was present in 8 patients and hemifacial spasm in 3 patients. All cases with trigeminal pain were receiving medication and still uncontrolled. One patient with hemifacial spasm was medically controlled before gamma knife and the other two were not. Two patients had undergone surgical resection prior to gamma knife treatment. The median prescription dose was 11 Gy (10–11 Gy). The tumor volumes ranged from 3.7 to 23.9 cc (median 10.5 cc). Results: The median radiological follow up was 2 years (1–5 years). All tumors were controlled and one tumor shrank. The median clinical follow-up was 5 years. The trigeminal pain improved or disappeared in 5 patients, and of these, 4 cases stopped their medication and one decreased it. The hemifacial spasm resolved in 2 patients who were able to stop their medication. Facial palsy developed in 1 patient and improved with conservative treatment. Transient diplopia was also reported in 2 cases. Conclusion: Gamma knife radiosurgery provides good clinical control for cerebellopontine angle epidermoid tumors. PMID:29184709

Quality assurance for gamma knives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, E.D.; Banks, W.W.; Fischer, L.E.

1995-09-01

This report describes and summarizes the results of a quality assurance (QA) study of the Gamma Knife, a nuclear medical device used for the gamma irradiation of intracranial lesions. Focus was on the physical aspects of QA and did not address issues that are essentially medical, such as patient selection or prescription of dose. A risk-based QA assessment approach was used. Sample programs for quality control and assurance are included. The use of the Gamma Knife was found to conform to existing standards and guidelines concerning radiation safety and quality control of external beam therapies (shielding, safety reviews, radiation surveys,more » interlock systems, exposure monitoring, good medical physics practices, etc.) and to be compliant with NRC teletherapy regulations. There are, however, current practices for the Gamma Knife not covered by existing, formalized regulations, standards, or guidelines. These practices have been adopted by Gamma Knife users and continue to be developed with further experience. Some of these have appeared in publications or presentations and are slowly finding their way into recommendations of professional organizations.« less

Acute necrosis after Gamma Knife surgery in vestibular schwannoma leading to multiple cranial nerve palsies.

PubMed

Kapitza, Sandra; Pangalu, Athina; Horstmann, Gerhard A; van Eck, Albert T; Regli, Luca; Tarnutzer, Alexander A

2016-08-01

We discuss a rare acute complication after Gamma Knife therapy (Elekta AB, Stockholm, Sweden) in a single patient. A 52-year-old woman presented with vertigo, facial weakness and hearing loss emerging 48hours following Gamma Knife radiosurgery for a right-sided vestibular schwannoma. Neurological examination 6days after symptom onset showed right-sided facial palsy, spontaneous left-beating nystagmus and pathologic head-impulse testing to the right. Pure-tone audiogram revealed right-sided sensorineural hearing loss. A diagnosis of acute vestibulocochlear and facial neuropathy was made. Brain MRI demonstrated focal contrast sparing within the schwannoma, likely related to acute radiation necrosis. Acute multiple cranial neuropathies of the cerebellopontine angle after Gamma Knife treatment should raise suspicion of acute tissue damage within the schwannoma and should result in urgent MRI. Treatment with steroids may be considered based on accompanying swelling and edema. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stereotaxic gamma knife surgery in treatment of critically located pilocytic astrocytoma: preliminary result

PubMed Central

Hafez, Raef FA

2007-01-01

Background Low-grade gliomas are uncommon primary brain tumors, located more often in the posterior fossa, optic pathway, and brain stem and less commonly in the cerebral hemispheres. Case presentations Two patients with diagnosed recurrent cystic pilocytic astrocytoma critically located within the brain (thalamic and brain stem) were treated with gamma knife surgery. Gamma knife surgery (GKS) did improve the patient's clinical condition very much which remained stable later on. Progressive reduction on the magnetic resonance imaging (MRI) studies of the solid part of the tumor and almost disappearance of the cystic component was achieved within the follow-up period of 36 months in the first case with the (thalamic located lesion) and 22 months in the second case with the (brain stem located lesion). Conclusion Gamma knife surgery represents an alternate tool in the treatment of recurrent and/or small postoperative residual pilocytic astrocytoma especially if they are critically located PMID:17394660

A microcosting study of microsurgery, LINAC radiosurgery, and gamma knife radiosurgery in meningioma patients

PubMed Central

van Putten, Erik; Nijdam, Wideke M.; Hanssens, Patrick; Beute, Guus N.; Nowak, Peter J.; Dirven, Clemens M.; Hakkaart-van Roijen, Leona

2010-01-01

The aim of the present study is to determine and compare initial treatment costs of microsurgery, linear accelerator (LINAC) radiosurgery, and gamma knife radiosurgery in meningioma patients. Additionally, the follow-up costs in the first year after initial treatment were assessed. Cost analyses were performed at two neurosurgical departments in The Netherlands from the healthcare providers’ perspective. A total of 59 patients were included, of whom 18 underwent microsurgery, 15 underwent LINAC radiosurgery, and 26 underwent gamma knife radiosurgery. A standardized microcosting methodology was employed to ensure that the identified cost differences would reflect only actual cost differences. Initial treatment costs, using equipment costs per fraction, were €12,288 for microsurgery, €1,547 for LINAC radiosurgery, and €2,412 for gamma knife radiosurgery. Higher initial treatment costs for microsurgery were predominantly due to inpatient stay (€5,321) and indirect costs (€4,350). LINAC and gamma knife radiosurgery were equally expensive when equipment was valued per treatment (€2,198 and €2,412, respectively). Follow-up costs were slightly, but not significantly, higher for microsurgery compared with LINAC and gamma knife radiosurgery. Even though initial treatment costs were over five times higher for microsurgery compared with both radiosurgical treatments, our study gives indications that the relative cost difference may decrease when follow-up costs occurring during the first year after initial treatment are incorporated. This reinforces the need to consider follow-up costs after initial treatment when examining the relative costs of alternative treatments. PMID:20526795

Optimal Shape of a Gamma-ray Collimator: single vs double knife edge

NASA Astrophysics Data System (ADS)

Metz, Albert; Hogenbirk, Alfred

2017-09-01

Gamma-ray collimators in nuclear waste scanners are used for selecting a narrow vertical segment in activity measurements of waste vessels. The system that is used by NRG uses tapered slit collimators of both the single and double knife edge type. The properties of these collimators were investigated by means of Monte Carlo simulations. We found that single knife edge collimators are highly preferable for a conservative estimate of the activity of the waste vessels. These collimators show much less dependence on the angle of incidence of the radiation than double knife edge collimators. This conclusion also applies to cylindrical collimators of the single knife edge type, that are generally used in medical imaging spectroscopy.

Review of the poster "Dosimetric comparison of gamma knife radiosurgery vs. 125I plaque brachytherapy in a cohort of choroidal melanomas".

PubMed

Odell, Kelly R

2009-01-01

Historically, treatment for choroidal melanomas was surgical enucleation. Currently, treatment methods such as stereotactic radiosurgery and brachytherapy are being used to spare the eye. The poster "Dosimetric Comparison of Gamma Knife Radiosurgery vs. I-125 Plaque Brachytherapy in a Cohort of Choroidal Melanomas" presented at ASTRO 2007 by Anderson et al. provides a comparison of these methods. The dose to disk, fovea and lens in 29 patients from a simulated I-125 treatment and a delivered Gamma Knife radiosurgery was compared. Thirty Gy was prescribed to the 50% Isodose line in the radiosurgery and 85 Gy was prescribed to the apex of the tumor in the I-125 simulation. It was found that the Gamma Knife spares the disk better in 59% of the tumors, including those >or=6.5 mm in height; spares the fovea better in 69% of the tumors, including those >or=5.5 mm; and spares lens better in only 30% of the tumors, with no distinction in size. Tumor location was not taken into account for this study, which could explain the variations in smaller tumors. For larger tumors, gamma knife will protect most organs at risk more effectively. This study shows how a tumor's parameters can be used in selecting treatment modality.

Correction of measured Gamma-Knife output factors for angular dependence of diode detectors and PinPoint ionization chamber.

PubMed

Hršak, Hrvoje; Majer, Marija; Grego, Timor; Bibić, Juraj; Heinrich, Zdravko

2014-12-01

Dosimetry for Gamma-Knife requires detectors with high spatial resolution and minimal angular dependence of response. Angular dependence and end effect time for p-type silicon detectors (PTW Diode P and Diode E) and PTW PinPoint ionization chamber were measured with Gamma-Knife beams. Weighted angular dependence correction factors were calculated for each detector. The Gamma-Knife output factors were corrected for angular dependence and end effect time. For Gamma-Knife beams angle range of 84°-54°. Diode P shows considerable angular dependence of 9% and 8% for the 18 mm and 14, 8, 4 mm collimator, respectively. For Diode E this dependence is about 4% for all collimators. PinPoint ionization chamber shows angular dependence of less than 3% for 18, 14 and 8 mm helmet and 10% for 4 mm collimator due to volumetric averaging effect in a small photon beam. Corrected output factors for 14 mm helmet are in very good agreement (within ±0.3%) with published data and values recommended by vendor (Elekta AB, Stockholm, Sweden). For the 8 mm collimator diodes are still in good agreement with recommended values (within ±0.6%), while PinPoint gives 3% less value. For the 4 mm helmet Diodes P and E show over-response of 2.8% and 1.8%, respectively. For PinPoint chamber output factor of 4 mm collimator is 25% lower than Elekta value which is generally not consequence of angular dependence, but of volumetric averaging effect and lack of lateral electronic equilibrium. Diodes P and E represent good choice for Gamma-Knife dosimetry. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Leksell Gamma Knife radiosurgery of the jugulotympanic glomus tumor: long-term results.

PubMed

Liscak, Roman; Urgosik, Dusan; Chytka, Tomas; Simonova, Gabriela; Novotny, Josef; Vymazal, Josef; Guseynova, Khumar; Vladyka, Vilibald

2014-12-01

Glomus tumors usually display indolent behavior, and the effectiveness of radiation in stopping their growth can be assessed after long-term follow-up. Currently only midterm results of radiosurgery are available, so the authors included patients treated by Gamma Knife at least 10 years ago in this study to obtain a perspective of long-term results. During the period from 1992 to 2003, the Gamma Knife was used to treat 46 patients with glomus tumors. The age of the patients ranged from 21 to 79 years (median 56 years). Gamma Knife radiosurgery was the primary treatment in 17 patients (37%). Open surgery preceded radiosurgery in 46% of cases, embolization in 17%, and fractionated radiotherapy in 4%. The volume of the tumor ranged from 0.2 to 24.3 cm(3) (median 3.6 cm(3)). The minimal dose to the tumor margin ranged between 10 and 30 Gy (median 20 Gy). One patient was lost for follow-up after radiosurgery. Clinical follow-up was available in 45 patients and 44 patients were followed with MRI in a follow-up period that ranged from 12 to 217 months (median 118 months). Neurological deficits improved in 19 (42%) of 45 patients and deteriorated in 2 patients (4%). Tumor size decreased in 34 (77%) of 44 patients with imaging follow-up, while an increase in volume was observed in 1 patient (2%) 182 months after radiosurgery and Gamma Knife treatment was repeated. One patient underwent another Gamma Knife treatment for secondary induced meningioma close to the glomus tumor 98 months after initial radiosurgical treatment. Seven patients died 22-96 months after radiosurgery (median 48 months), all for unrelated reasons. Radiosurgery has proved to be a safe treatment with a low morbidity rate and a reliable long-term antiproliferative effect.

Brain metastases in women with epithelial ovarian cancer: multimodal treatment including surgery or gamma-knife radiation is associated with prolonged survival.

PubMed

Niu, Xiaoyu; Rajanbabu, Anupama; Delisle, Megan; Peng, Feng; Vijaykumar, Dehannathuparambil K; Pavithran, Keechilattu; Feng, Yukuan; Lau, Susie; Gotlieb, Walter H; Press, Joshua Z

2013-09-01

To explore the impact of treatment modality on survival in patients with brain metastases from epithelial ovarian cancer. We conducted a retrospective review of cases of ovarian cancer with brain metastases treated at institutions in three countries (Canada, China, and India) and conducted a search for studies regarding brain metastases in ovarian cancer reporting survival related to treatment modality. Survival was analyzed according to treatment regimens involving (1) some form of surgical excision or gamma-knife radiation with or without other modalities, (2) other modalities without surgery or gamma-knife radiation, or (3) palliation only. Twelve patients (mean age 56 years) with detailed treatment/outcome data were included; five were from China, four from Canada, and three from India. Median time from diagnosis of ovarian cancer to brain metastasis was 19 months (range 10 to 37 months), and overall median survival time from diagnosis of ovarian cancer was 38 months (13 to 82 months). Median survival time from diagnosis of brain metastasis was 17 months (1 to 45 months). Among patients who had multimodal treatment including gamma-knife radiotherapy or surgical excision, the median survival time after the identification of brain metastasis was 25.6 months, compared with 6.0 months in patients whose treatment did not include this type of focused localized modality (P = 0.006). Analysis of 20 studies also indicated that use of gamma-knife radiotherapy and excisional surgery in multi-modal treatment resulted in improved median survival interval (25 months vs. 6.0 months, P < 0.001). In the subset of patients with brain metastases from ovarian cancer, prolonged survival may result from use of multidisciplinary therapy, particularly if metastases are amenable to localized treatments such as gamma-knife radiotherapy and surgical excision.

Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?

PubMed

Castinetti, Frederic; Brue, Thierry

2010-08-01

Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

Technical note: A 3D-printed phantom for routine accuracy check of Gamma Knife Icon HDMM system.

PubMed

Wu, Chuan; Radevic, Marlyn B; Glass, Jennifer S; Skubic, Stan E

2018-05-23

To report a novel 3D-printed device ("SH phantom") that is designed for routine accuracy check of the Gamma Knife Icon High Definition Motion Management (HDMM) system. SH phantom was designed using tinkerCAD software and printed on a commercial 3D printer. We evaluated the SH phantom on our Gamma Knife Icon unit regarding its usability and accuracy for routine HDMM QA. Single-axis and multiple-axis measurements validated the SH phantom design and implementation. An HDMM QA accuracy of 0.22 mm or better along single axis was found using SH phantom. The SH phantom proved to be a quick and simple tool to use to perform the HDMM system QA. The SH phantom was tested successfully and adopted by us as part of monthly QA for the Gamma Knife Icon. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Completion of Gamma Knife radiosurgery for AVM treatment after unplanned interruption-technical note.

PubMed

Raman, Hari S; Santanam, Lakshmi; Vellimana, Ananth K; Drzymala, Robert E; Tsien, Christina I; Zipfel, Gregory J

2018-02-17

Gamma Knife radiosurgery is an established technique for non-urgent treatment of various intracranial pathologies. Intra-procedural dislodgement of the stereotactic frame is an uncommon occurrence that could lead to abortion of ongoing treatment and necessitate more invasive treatment strategies. In this case report, we describe a novel method for resumption of Gamma Knife treatment after an unplanned intra-procedural interruption. The case example involves a radiosurgical treatment of a Spetzler-Martin grade I arteriovenous malformation. Our technique involves integration of scans and coordinate systems from two imaging sessions using the composite isodose line to resolve translational differences, thereby limiting delivery of remaining shots to the untreated region of the lesion. MRI follow-up at 13 months showed a reduction in the nidus size with no evidence of any radiation injury to the surrounding brain parenchyma. We believe this technique will allow care teams to effectively salvage interrupted Gamma Knife procedures and reduce progression to more invasive treatment options.

Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

PubMed

Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

2016-02-01

To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiosurgery with the world's first fully robotized Leksell Gamma Knife PerfeXion in clinical use: a 200-patient prospective, randomized, controlled comparison with the Gamma Knife 4C.

PubMed

Régis, Jean; Tamura, Manabu; Guillot, Cécile; Yomo, Shoji; Muraciolle, Xavier; Nagaje, Mariko; Arka, Yasser; Porcheron, Denis

2009-02-01

The world's first Leksell Gamma Knife PerfeXion (Elekta Instrument AB, Stockholm, Sweden) for radiosurgery of the head and neck became operational at Timone University Hospital in Marseille on July 10, 2006. To allow strict evaluation of the capabilities, advantages, disadvantages, and limitations of this new technology, patients were enrolled in a prospective, randomized trial. In 66 working days, between July 10 and December 20, 2006, 363 patients were treated by gamma knife surgery at Timone University Hospital, Marseille. Of these patients, 200 were eligible for the comparative prospective study (inclusion criteria were informed consent obtained, tumor or vascular indication, and no previous radiosurgery or radiotherapy). In accordance with the blinded randomization process, 100 patients were treated with the Leksell Gamma Knife 4C (Elekta Instrument AB) and Gamma Knife 100 (Elekta Instrument AB) with the Leksell Gamma Knife PerfeXion. Dose planning parameters, dosimetry measurements on the patient's body, workflow, patient comfort, quality assurance procedure, and a series of other treatment-related parameters were systematically and prospectively evaluated in both arms of the trial. No technical failure of the treatment procedure was encountered. The new dose-planning system led to the use of composite shots in 39.4% of the patients. The median number of different collimator sizes used was larger with the PerfeXion than with the 4C (2 and 1, respectively). The mean number of isocenters used was lower (10.67 and 13.08, respectively). The median total treatment time was significantly shorter with the PerfeXion (40 and 60 minutes, respectively), but there was no significant difference in the median radiation time (34.02 and 33.40 minutes, respectively). The procedure was performed using only a single run in 98.99% of the PerfeXion cases and in 42% of the 4C cases. Collision risk on the 4C forced us to change the frame gamma angle for at least 1 shot in 24% of the patients and led to treatment in manual mode for at least 1 shot in 21% of the patients. Collision risk requiring technical adaptation did not occur with the PerfeXion. In 1 patient treated with the PerfeXion, the system required a direct collision check. In terms of dose to structures outside the target area, the PerfeXion delivers 8.2 times less to the vertex, 10 times less to the thyroid, 12.9 times less to the sternum, and 15 times less to the gonads. Our prospective study indicates that procedures with the PerfeXion were collision-free, even with very eccentric lesions (e.g., multiple metastases). The duration of the surgical procedure, the amount of time required for nurse, physicist, and physician intervention on the machine, and the duration of the quality assurance procedure were all shown to be dramatically reduced with the PerfeXion gamma knife. Patient protection is greatly improved with the PerfeXion. In our experience, the technological advances of the Leksell Gamma Knife PerfeXion will make a very significant contribution to future progress in head and neck radiosurgery.

SU-E-T-86: A Systematic Method for GammaKnife SRS Fetal Dose Estimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geneser, S; Paulsson, A; Sneed, P

Purpose: Estimating fetal dose is critical to the decision-making process when radiation treatment is indicated during pregnancy. Fetal doses less than 5cGy confer no measurable non-cancer developmental risks but can produce a threefold increase in developing childhood cancer. In this study, we estimate fetal dose for a patient receiving Gamma Knife stereotactic radiosurgery (GKSRS) treatment and develop a method to estimate dose directly from plan details. Methods: A patient underwent GKSRS on a Perfexion unit for eight brain metastases (two infratentorial and one brainstem). Dose measurements were performed using a CC13, head phantom, and solid water. Superficial doses to themore » thyroid, sternum, and pelvis were measured using MOSFETs during treatment. Because the fetal dose was too low to accurately measure, we obtained measurements proximally to the isocenter, fitted to an exponential function, and extrapolated dose to the fundus of the uterus, uterine midpoint, and pubic synthesis for both the preliminary and delivered plans. Results: The R-squared fit for the delivered doses was 0.995. The estimated fetal doses for the 72 minute preliminary and 138 minute delivered plans range from 0.0014 to 0.028cGy and 0.07 to 0.38cGy, respectively. MOSFET readings during treatment were just above background for the thyroid and negligible for all inferior positions. The method for estimating fetal dose from plan shot information was within 0.2cGy of the measured values at 14cm cranial to the fetal location. Conclusion: Estimated fetal doses for both the preliminary and delivered plan were well below the 5cGy recommended limit. Due to Pefexion shielding, internal dose is primarily governed by attenuation and drops off exponentially. This is the first work that reports fetal dose for a GK Perfexion unit. Although multiple lesions were treated and the duration of treatment was long, the estimated fetal dose remained very low.« less

Clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy and their effects on EF-Tumt and EF-Tsmt expression.

PubMed

Wang, X-Q; Zhang, X-D; Han, Y-M; Shi, X-F; Lan, Z-B; Men, X-X; Pan, Y-W

2017-04-01

To study the clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy (MTLE) and their effects on EF-Tumt and EF-Tsmt expression. The data of 78 cases of MTLE patients treated in our hospital from April 2011 to March 2013 were retrospectively analyzed. The patients were divided into two groups according to the treatment methods: the surgery group (including 41 cases) and the gamma knife group (including 37 cases). The clinical efficacy, the occurrence and recurrence of complications were evaluated, respectively; meanwhile, the expression of the EF-Tumt protein and EF-Tsmt protein in brain tissue were analyzed. The difference between the efficacy rate of the two groups showed no statistical significance (χ2=0.960, p>0.05). The complication rate of the gamma knife group was significantly lower than that of the control group (χ2=6.430, p<0.05). The recurrence rate of the patients in the gamma knife group was significantly lower than that of the patients in the surgery group (p>0.05). Within the two groups, the positive expression granum of EF-Tsmt protein and EF-Tumt protein of the two groups after treatment were significantly lower than that before treatment (p<0.05). After treatment, the positive expression granum of EF-Tsmt protein of the patients in the gamma knife group was obviously more than that of the patients in the surgery group (p<0.05). The difference between the positive expression granum of EF-Tumt protein of the two groups showed no statistical significance (p>0.05). Before and after treatment within the group, the positive cell of EF-Tsmt protein and EF-Tumt protein of the two groups of patients after treatment were significantly lower than that before treatment (p<0.05). After treatment, the difference between the EF-Tsmt protein positive cell and the EF-Tumt protein positive cell of the two groups of patients showed no statistical significance (p>0.05). Both surgery and gamma knife could treat MTLE effectively, and the efficacy may be related to the ability to reduce the expression of EF-Tsmt protein and EF-Tumt protein in brain tissue.

Gamma Knife treatment of low-grade gliomas in children.

PubMed

Ekşi, Murat Şakir; Yılmaz, Baran; Akakın, Akın; Toktaş, Zafer Orkun; Kaur, Ahmet Cemil; Demir, Mustafa Kemal; Kılıç, Türker

2015-11-01

Low-grade gliomas have good overall survival rates in pediatric patients compared to adults. There are some case series that reported the effectiveness and safety of Gamma Knife radiosurgery, yet they are limited in number of patients. We aimed to review the relevant literature for pediatric low-grade glial tumors treated with stereotactic radiosurgery, specifically Gamma Knife radiosurgery, and to present an exemplary case. A 6-year-old boy was admitted to clinic due to head trauma. He was alert, cooperative, and had no obvious motor or sensorial deficit. A head CT scan depicted a hypodense zone at the right caudate nucleus. The brain magnetic resonance imaging (MRI) depicted a mass lesion at the same location. A stereotactic biopsy was performed. Histopathological diagnosis was low-grade astrocytoma (grade II, World Health Organization (WHO) classification, 2007). Gamma Knife radiosurgery was applied to the tumor bed. Tumor volume was 21.85 cm(3). Fourteen gray was given to 50% isodose segment of the lesion (maximal dose of 28 Gy). The tumor has disappeared totally in 4 months, and the patient was tumor-free 21 months after the initial treatment. The presented literature review represents mostly single-center experiences with different patient and treatment characteristics. Accordingly, a mean/median margin dose of 11.3-15 Gy with Gamma Knife radiosurgery (GKRS) is successful in treatment of pediatric and adult low-grade glial tumor patients. However, prospective studies with a large cohort of pediatric patients should be conducted to make a more comprehensive conclusion for effectiveness and safety of GKRS in pediatric low-grade glial tumors.

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery.

PubMed

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A; Sahgal, Arjun

2011-11-21

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R² = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

P11.10 Role of hydroxyurea as an adjuvant treatment after gamma knife radiosurgery for atypical (WHO grade II) meningiomas

PubMed Central

Abdel Karim, K.; El Shehaby, A.; Emad, R.; Reda, W.; El Mahdy, M.; Ghali, R.; Nabeel, A.

2016-01-01

Abstract Objective: The use of gamma knife radiosurgery in the treatment of atypical (WHO grade II) meningiomas has been reported in the past with highly variable degrees of success. The use of hydroxyurea as a radiation sensitizer as well as salvage chemotherapy in cancer patients is well established and was also used for treatment of recurrent and malignant meningiomas. In this study we investigated the effect of hydroxyurea administration after gamma knife radiosurgery for atypical (grade II) meningiomas on local tumor control and patient survival. Patients and methods: Between November 2008 and April 2014, thirty-five patients with pathologically proven atypical meningiomas were treated by gamma knife radiosurgery. We excluded patients who had received previous external beam radiotherapy. Twenty-three patients were given hydroxyurea after gamma knife treatment. The rest of the patients refused to take the treatment or were incompliant (were not included in the study). Of these 23, nineteen patients harboring 20 tumors were available for radiological and clinical follow up for a minimum of 2 years. Four patients were lost from follow up. Twenty tumors underwent 26 gamma knife procedures. Five tumors underwent staged treatment. The tumor volume was 0.6–38.3 cc (median 12.7 cc). The prescription dose/session ranged from 10 to 16 Gy (mean 14 Gy). The patients received a course of hydroxyurea (1000 mg/day) for one year after gamma knife treatment. The mean follow up period was 43 months (14–76 months). Results: Tumor control was achieved in 18 out of 20 tumors where 15 tumors shrank and 3 tumors remained stable with a tumor control rate of 90%. Tumor progression occurred in 2 patients (at 14 and 15 months). Transient edema was observed with 6 tumors which was temporary, and no G3 or G4 myelosuppression were recorded. Two patients died from progression of other tumors not included in the study after 3 and 6 years. Distant tumor progression (in another intracranial location or outside the radiation field) was observed in 5 patients. In 3 patients new tumors developed at the edge of previous craniotomy, in one patient tumor progression occurred after receiving radiosurgery alone for another lesion after the end of adjuvant treatment and in one patient progression occurred in an untreated tumor that was under observation. The actuarial progression free survival and overall survival at 3 years were 89.5% and 94% respectively. Conclusion: Preliminary results suggest good tumor control and shrinkage of atypical (grade II) meningiomas treated with Gamma Knife radiosurgery followed by one year of adjuvant hydroxyurea. Further larger randomized and double-arm studies are required to confirm the potential role of hydroxyurea in those tumors.

SU-F-P-15: Report On AAPM TG 178 Gamma Knife Dosimetry and Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goetsch, S

Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocolmore » modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers Conclusion: The full TG 178 report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics. Consultant to Elekta, Inc.« less

Stereotactic radiosurgery in hemangioblastoma: Experience over 14 years

PubMed Central

Goyal, Nishant; Agrawal, Deepak; Singla, Raghav; Kale, Shashank Sharad; Singh, Manmohan; Sharma, Bhawani Shankar

2016-01-01

Background: Although gamma knife has been advocated for hemangioblastomas, it is not used widely by neurosurgeons. Objective: We review our experience over 14 years in an attempt to define the role of stereotactic radiosurgery (SRS) in the management of hemangioblastomas. Patients and Methods: A retrospective study was conducted on all patients of hemangioblastoma who underwent SRS at our institute over a period of 14 years (1998–2011). Gamma knife plans, clinical history, and radiology were reviewed for all patients. Results: A total of 2767 patients underwent gamma knife during the study period. Of these, 10 (0.36%) patients were treated for 24 hemangioblastomas. Eight patients (80%) had von Hippel-Lindau disease while two had sporadic hemangioblastomas. The median peripheral dose (50% isodose) delivered to the tumors was 29.9 Gy. Clinical and radiological follow-up data were available for eight patients. Of these, two were re-operated for persisting cerebellar symptoms. The remaining six patients were recurrence-free at a mean follow-up of 48 months (range 19–108 months). One patient had an increase in cyst volume along with a decrease in the size of the mural nodule. Conclusions: SRS should be the first option for asymptomatic hemangioblastomas. Despite the obvious advantages, gamma knife is not widely used as an option for hemangioblastomas. PMID:26933339

Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A.; Sahgal, Arjun

2011-11-01

Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R2 = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

Successful use of Gamma Knife surgery in a distal lenticulostriate artery aneurysm intervention.

PubMed

Lan, ZhiGang; Li, Jin; You, Chao; Chen, Jing

2012-02-01

We report a case of a 21-year-old woman who underwent radiosurgical treatment of a distal lenticulostriate artery (LSA) aneurysm. Twenty-two months after treatment, repeat angiography demonstrated patency of the parent vessel and complete obliteration of the aneurysm. Our case implies that Gamma Knife surgery (GKS) might serve as an alternative microinvasive technique in the treatment of LSA aneurysms, making this procedure a potential addition to present methods.

SU-F-T-485: Independent Remote Audits for TG51 NonCompliant Photon Beams Performed by the IROC Houston QA Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alvarez, P; Molineu, A; Lowenstein, J

Purpose: IROC-H conducts external audits for output check verification of photon and electron beams. Many of these beams can meet the geometric requirements of the TG 51 calibration protocol. For those photon beams that are non TG 51 compliant like Elekta GammaKnife, Accuray CyberKnife and TomoTherapy, IROC-H has specific audit tools to monitor the reference calibration. Methods: IROC-H used its TLD and OSLD remote monitoring systems to verify the output of machines with TG 51 non compliant beams. Acrylic OSLD miniphantoms are used for the CyberKnife. Special TLD phantoms are used for TomoTherapy and GammaKnife machines to accommodate the specificmore » geometry of each machine. These remote audit tools are sent to institutions to be irradiated and returned to IROC-H for analysis. Results: The average IROC-H/institution ratios for 480 GammaKnife, 660 CyberKnife and 907 rotational TomoTherapy beams are 1.000±0.021, 1.008±0.019, 0.974±0.023, respectively. In the particular case of TomoTherapy, the overall ratio is 0.977±0.022 for HD units. The standard deviations of all results are consistent with values determined for TG 51 compliant photon beams. These ratios have shown some changes compared to values presented in 2008. The GammaKnife results were corrected by an experimentally determined scatter factor of 1.025 in 2013. The TomoTherapy helical beam results are now from a rotational beam whereas in 2008 the results were from a static beam. The decision to change modality was based on recommendations from the users. Conclusion: External audits of beam outputs is a valuable tool to confirm the calibrations of photon beams regardless of whether the machine is TG 51 or TG 51 non compliant. The difference found for TomoTherapy units is under investigation. This investigation was supported by IROC grant CA180803 awarded by the NCI.« less

Forward treatment planning techniques to reduce the normalization effect in Gamma Knife radiosurgery.

PubMed

Cheng, Hao-Wen; Lo, Wei-Lun; Kuo, Chun-Yuan; Su, Yu-Kai; Tsai, Jo-Ting; Lin, Jia-Wei; Wang, Yu-Jen; Pan, David Hung-Chi

2017-11-01

In Gamma Knife forward treatment planning, normalization effect may be observed when multiple shots are used for treating large lesions. This effect can reduce the proportion of coverage of high-value isodose lines within targets. The aim of this study was to evaluate the performance of forward treatment planning techniques using the Leksell Gamma Knife for the normalization effect reduction. We adjusted the shot positions and weightings to optimize the dose distribution and reduce the overlap of high-value isodose lines from each shot, thereby mitigating the normalization effect during treatment planning. The new collimation system, Leksell Gamma Knife Perfexion, which contains eight movable sectors, provides an additional means to reduce the normalization effect by using composite shots. We propose different techniques in forward treatment planning that can reduce the normalization effect. Reducing the normalization effect increases the coverage proportion of higher isodose lines within targets, making the high-dose region within targets more uniform and increasing the mean dose to targets. Because of the increase in the mean dose to the target after reducing the normalization effect, we can set the prescribed marginal dose at a higher isodose level and reduce the maximum dose, thereby lowering the risk of complications. © 2017 Shuang Ho Hospital-Taipei Medical University. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Brain metastases in cancer patients attending a Gamma Knife Center: A study from a single institute in Iran

PubMed Central

Azimi, Parisa; Shahzadi, Sohrab; Bitaraf, Mohammad Ali; Azar, Maziar; Alikhani, Mazdak; Zali, Alireza; Sadeghi, Sohrab; Montazeri, Ali

2017-01-01

Background: This study was aimed to explore data on brain metastases in cancer patients attending the Iranian Gamma Knife Center. Meterials and Methods: This was a retrospective study. In all 5216 case records of patients who referred to the Iranian Gamma Knife Center for treatment of brain tumors during year 2003-2011 were reviewed. Data were explored to identify patients who developed brain metastases due to cancer and assessed the information as applied to cancer patients including survival analysis. Results: Two hundred and twenty patients were identified as having brain metastases due to cancer. The mean age of patients was 54.0 (standard deviation [SD] =12.7) years. Patients were followed for an average of 7 months after treatment with gamma-knife. The median survival time for different the Graded Prognostic Assessment (GPA) was: GPA: 0-1, 4.0 ± 0.4 months; GPA: 1.5-2.5, 6.0 ± 0.7 months; GPA: 3, 9.0 ± 0.9 months; and GPA: 3.5-4.0, 12.0 ± 1.8 months and the overall median survival was 7.0 (SD = 0.6) months. Conclusion: The findings suggest that many cancer patients in Iran might develop brain metastasis. Although, this is not a very high incidence compared with the existing statistics from other countries, there is an urgent need to explore the issue further. PMID:28761536

Brain metastases in cancer patients attending a Gamma Knife Center: A study from a single institute in Iran.

PubMed

Azimi, Parisa; Shahzadi, Sohrab; Bitaraf, Mohammad Ali; Azar, Maziar; Alikhani, Mazdak; Zali, Alireza; Sadeghi, Sohrab; Montazeri, Ali

2017-01-01

This study was aimed to explore data on brain metastases in cancer patients attending the Iranian Gamma Knife Center. This was a retrospective study. In all 5216 case records of patients who referred to the Iranian Gamma Knife Center for treatment of brain tumors during year 2003-2011 were reviewed. Data were explored to identify patients who developed brain metastases due to cancer and assessed the information as applied to cancer patients including survival analysis. Two hundred and twenty patients were identified as having brain metastases due to cancer. The mean age of patients was 54.0 (standard deviation [SD] =12.7) years. Patients were followed for an average of 7 months after treatment with gamma-knife. The median survival time for different the Graded Prognostic Assessment (GPA) was: GPA: 0-1, 4.0 ± 0.4 months; GPA: 1.5-2.5, 6.0 ± 0.7 months; GPA: 3, 9.0 ± 0.9 months; and GPA: 3.5-4.0, 12.0 ± 1.8 months and the overall median survival was 7.0 (SD = 0.6) months. The findings suggest that many cancer patients in Iran might develop brain metastasis. Although, this is not a very high incidence compared with the existing statistics from other countries, there is an urgent need to explore the issue further.

Worldwide variance in the potential utilization of Gamma Knife radiosurgery.

PubMed

Hamilton, Travis; Dade Lunsford, L

2016-12-01

OBJECTIVE The role of Gamma Knife radiosurgery (GKRS) has expanded worldwide during the past 3 decades. The authors sought to evaluate whether experienced users vary in their estimate of its potential use. METHODS Sixty-six current Gamma Knife users from 24 countries responded to an electronic survey. They estimated the potential role of GKRS for benign and malignant tumors, vascular malformations, and functional disorders. These estimates were compared with published disease epidemiological statistics and the 2014 use reports provided by the Leksell Gamma Knife Society (16,750 cases). RESULTS Respondents reported no significant variation in the estimated use in many conditions for which GKRS is performed: meningiomas, vestibular schwannomas, and arteriovenous malformations. Significant variance in the estimated use of GKRS was noted for pituitary tumors, craniopharyngiomas, and cavernous malformations. For many current indications, the authors found significant variance in GKRS users based in the Americas, Europe, and Asia. Experts estimated that GKRS was used in only 8.5% of the 196,000 eligible cases in 2014. CONCLUSIONS Although there was a general worldwide consensus regarding many major indications for GKRS, significant variability was noted for several more controversial roles. This expert opinion survey also suggested that GKRS is significantly underutilized for many current diagnoses, especially in the Americas. Future studies should be conducted to investigate health care barriers to GKRS for many patients.

Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report.

PubMed

Morinaga, Nobuhiro; Tanaka, Naritaka; Shitara, Yoshinori; Ishizaki, Masatoshi; Yoshida, Takatomo; Kouga, Hideaki; Wakabayashi, Kazuki; Fukuchi, Minoru; Tsunoda, Yoshiyuki; Kuwano, Hiroyuki

2016-01-01

Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy.

SU-F-SPS-10: The Dosimetric Comparison of GammaKnife and Cyberknife Treatment Plans for Brain SRS Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanli, E; Mabhouti, H; Cebe, M

Purpose: Brain stereotactic radiosurgery (SRS) involves the use of precisely directed, single session radiation to create a desired radiobiologic response within the brain target with acceptable minimal effects on surrounding structures or tissues. In this study, the dosimetric comparison of GammaKnife perfection and Cyberknife M6 treatment plans were made. Methods: Treatment plannings were done for GammaKnife perfection unit using Gammaplan treatment planning system (TPS) on the CT scan of head and neck randophantom simulating the treatment of sterotactic treatments for one brain metastasis. The dose distribution were calculated using TMR 10 algorithm. The treatment planning for the same target weremore » also done for Cyberknife M6 machine using Multiplan (TPS) with Monte Carlo algorithm. Using the same film batch, the net OD to dose calibration curve was obtained using both machine by delivering 0- 800 cGy. Films were scanned 48 hours after irradiation using an Epson 1000XL flatbed scanner. Dose distribution were measured using EBT3 film dosimeter. The measured and calculated doses were compared. Results: The dose distribution in the target and 2 cm beyond the target edge were calculated on TPSs and measured using EBT3 film. For cyberknife treatment plans, the gamma analysis passing rates between measured and calculated dose distributions were 99.2% and 96.7% for target and peripheral region of target respectively. For gammaknife treatment plans, the gamma analysis passing rates were 98.9% and 93.2% for target and peripheral region of target respectively. Conclusion: The study shows that dosimetrically comparable plans are achievable with Cyberknife and GammaKnife. Although TMR 10 algorithm predicts the target dose.« less

SU-E-T-453: Optimization of Dose Gradient for Gamma Knife Radiosurgery.

PubMed

Sheth, N; Chen, Y; Yang, J

2012-06-01

The goals of stereotactic radiosurgery (SRS) are the ablation of target tissue and sparing of critical normal tissue. We develop tools to aid in the selection of collimation and prescription (Rx) isodose line to optimize the dose gradient for single isocenter intracranial stereotactic radiosurgery (SRS) with GammaKnife 4C utilizing the updated physics data in GammaPlan v10.1. Single isocenter intracranial SRS plans were created to treat the center of a solid water anthropomorphism head phantom for each GammaKnife collimator (4 mm, 8 mm, 14 mm, and 18 mm). The dose gradient, defined as the difference of effective radii of spheres equal to half and full Rx volumes, and Rx treatment volume was analyzed for isodoses from 99% to 20% of Rx. The dosimetric data on Rx volume and dose gradient vs. Rx isodose for each collimator was compiled into an easy to read nomogram as well as plotted graphically. The 4, 8, 14, and 18 mm collimators have the sharpest dose gradient at the 64%, 70%, 76%, and 77% Rx isodose lines, respectively. This corresponds to treating 4.77 mm, 8.86 mm, 14.78 mm, and 18.77 mm diameter targets with dose gradients radii of 1.06 mm, 1.63 mm, 2.54 mm, and 3.17 mm, respectively. We analyzed the dosimetric data for the most recent version of GammaPlan treatment planning software to develop tools that when applied clinically will aid in the selection of a collimator and Rx isodose line for optimal dose gradient and target coverage for single isocenter intracranial SRS with GammaKnife 4C. © 2012 American Association of Physicists in Medicine.

MCNP-based computational model for the Leksell gamma knife.

PubMed

Trnka, Jiri; Novotny, Josef; Kluson, Jaroslav

2007-01-01

We have focused on the usage of MCNP code for calculation of Gamma Knife radiation field parameters with a homogenous polystyrene phantom. We have investigated several parameters of the Leksell Gamma Knife radiation field and compared the results with other studies based on EGS4 and PENELOPE code as well as the Leksell Gamma Knife treatment planning system Leksell GammaPlan (LGP). The current model describes all 201 radiation beams together and simulates all the sources in the same time. Within each beam, it considers the technical construction of the source, the source holder, collimator system, the spherical phantom, and surrounding material. We have calculated output factors for various sizes of scoring volumes, relative dose distributions along basic planes including linear dose profiles, integral doses in various volumes, and differential dose volume histograms. All the parameters have been calculated for each collimator size and for the isocentric configuration of the phantom. We have found the calculated output factors to be in agreement with other authors' works except the case of 4 mm collimator size, where averaging over the scoring volume and statistical uncertainties strongly influences the calculated results. In general, all the results are dependent on the choice of the scoring volume. The calculated linear dose profiles and relative dose distributions also match independent studies and the Leksell GammaPlan, but care must be taken about the fluctuations within the plateau, which can influence the normalization, and accuracy in determining the isocenter position, which is important for comparing different dose profiles. The calculated differential dose volume histograms and integral doses have been compared with data provided by the Leksell GammaPlan. The dose volume histograms are in good agreement as well as integral doses calculated in small calculation matrix volumes. However, deviations in integral doses up to 50% can be observed for large volumes such as for the total skull volume. The differences observed in treatment of scattered radiation between the MC method and the LGP may be important in this case. We have also studied the influence of differential direction sampling of primary photons and have found that, due to the anisotropic sampling, doses around the isocenter deviate from each other by up to 6%. With caution about the details of the calculation settings, it is possible to employ the MCNP Monte Carlo code for independent verification of the Leksell Gamma Knife radiation field properties.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mihailescu, Lucian

This disclosure provides systems, methods, and apparatus related to ion beam therapy. In one aspect, a system includes a position sensitive detector and a collimator. The position sensitive detector configured to detect gamma rays generated by an ion beam interacting with a target. The collimator is positioned between the target and the position sensitive detector. The collimator includes a plurality of knife-edge slits, with a first knife-edge slit intersecting with a second knife-edge slit.

SU-F-T-593: Technical Treatment Accuracy in a Clinic of Fractionated Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bisht, R; Kale, S; Natanasabapathi, G

2016-06-15

Purpose: The purpose of this study is to estimate technical treatment accuracy in fractionated stereotactic radiosurgery (fSRS) using extend system (ES) of Gamma Knife (GK). Methods: The fSRS with GK relies on a patient specific re-locatable immobilization system. The reference treatment position is estimated using a digital probe and a repositioning check tool (RCT). The “calibration values” of RCT apertures were compared with measured values on RCT-QA tool to evaluate the standard error (SE) associated with RCT measurements. A treatment plan with single “4 mm collimator shot” was created to deliver a radiation dose of 5 Gy at the predefinedmore » plane of a newly designed in-house head-neck phantom. The plan was investigated using radiochromic EBT3 films. The stereotactic CT imaging of a designed mini CT phantom and distortion study of MR imaging, were combined to calculate imaging SE. The focal precision check for GK machine tolerance was performed using a central diode test tool. Results: Twenty observations of RCT and digital probe, shown the SE of +/−0.0186mm and +/−0.0002mm respectively. A mean positional shift of 0.2752mm (σ=0.0696mm) was observed for twenty similar treatment settings of head-neck phantom. The difference between radiological and predefined exposure point was 0.4650mm and 0.4270mm; for two independent experiments. The imaging studies showed a combined SE of +/− 0.1055mm. Twenty frequent runs of a diode test tool showed the tolerance SE of +/−0.0096mm. If, the measurements are considered to be at 95% of confidence level, an expanded uncertainty was evaluated as +/− 0.2371mm with our system. The positional shift, when combined with an expanded uncertainty, a trivial variation of 0.07mm (max) was observed in comparing resultant radiological precision through film investigations. Conclusion: The study proposes an expression of “technical treatment accuracy” within “known uncertainties” is rational in the estimation of routine fSRS quality. The research work is supported by the research section of “All India Institute of Medical Sciences” - New Delhi, India under project no A-247.« less

Effect of correlations on the polarizability of the one component plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carini, P.R.

Correlational effects on the dynamical polarizability ..cap alpha..(k,..omega..) of the one component plasma (OCP) are investigated in both the weak (..gamma.. < 1) and strong (..gamma.. < 1) coupling regions (..gamma.. is the plasma parameter, ..gamma.. = k/sup 3//4..pi..n where k/sup -1/ is the Debye length and n is the number density. In the weak coupling region a numerical solution is presented over a wide range of frequencies of the complete first order (in ..gamma..) correction to the dynamical polarizability which fully accounts for dynamical screening effects and is exact in the long wavelength and weak coupling limits (k ..-->..more » 0, ..gamma.. ..-->.. 0). This complete result is compared with a similar numerical solution for the dynamical polarizability obtained from the Golden-Kalman (GK) dynamical theory for strongly coupled plasmas. Contrary to previous results reported in the literature it was found that both theories predict the change in the dispersion of the long wavelength plasmons due to finite ..gamma.. effects to be that the slope of the plasmon dispersion curve decreases from its Bohm-Gross value as the plasma parameter increases from 0. In the strong coupling region two hydrodynamical model solutions of the GK dynamical theory for the polarizability are presented.« less

MAGAT gel and EBT2 film‐based dosimetry for evaluating source plugging‐based treatment plan in Gamma Knife stereotactic radiosurgery

PubMed Central

Vivekanandhan, S.; Kale, S.S.; Rath, G.K.; Senthilkumaran, S.; Thulkar, S.; Subramani, V.; Laviraj, M.A.; Bisht, R.K.; Mahapatra, A.K.

2012-01-01

This work illustrates a procedure to assess the overall accuracy associated with Gamma Knife treatment planning using plugging. The main role of source plugging or blocking is to create dose falloff in the junction between a target and a critical structure. We report the use of MAGAT gel dosimeter for verification of an experimental treatment plan based on plugging. The polymer gel contained in a head‐sized glass container simulated all major aspects of the treatment process of Gamma Knife radiosurgery. The 3D dose distribution recorded in the gel dosimeter was read using a 1.5T MRI scanner. Scanning protocol was: CPMG pulse sequence with 8 equidistant echoes, TR=7 s, echo step=14 ms, pixel size=0.5 mm x 0.5 mm, and slice thickness of 2 mm. Using a calibration relationship between absorbed dose and spin‐spin relaxation rate (R2), we converted R2 images to dose images. Volumetric dose comparison between treatment planning system (TPS) and gel measurement was accomplished using an in‐house MATLAB‐based program. The isodose overlay of the measured and computed dose distribution on axial planes was in close agreement. Gamma index analysis of 3D data showed more than 94% voxel pass rate for different tolerance criteria of 3%/2 mm, 3%/1 mm and 2%/2 mm. Film dosimetry with GAFCHROMIC EBT 2 film was also performed to compare the results with the calculated TPS dose. Gamma index analysis of film measurement for the same tolerance criteria used for gel measurement evaluation showed more than 95% voxel pass rate. Verification of gamma plan calculated dose on account of shield is not part of acceptance testing of Leksell Gamma Knife (LGK). Through this study we accomplished a volumetric comparison of dose distributions measured with a polymer gel dosimeter and Leksell GammaPlan (LGP) calculations for plans using plugging. We propose gel dosimeter as a quality assurance (QA) tool for verification of plug‐based planning. PACS number: 87.53.Ly, 87.55.‐x, 87.56.N‐ PMID:23149780

Gamma Knife radiosurgery for intracranial meningiomas: Do we need to treat the dural tail? A single-center retrospective analysis and an overview of the literature.

PubMed

Bulthuis, Vincent J; Hanssens, Patrick E J; Lie, Suan Te; van Overbeeke, Jacobus J

2014-01-01

The dural tail (DT) has been described as a common feature in meningiomas. There is a great variation of tumor invasion and extent of tumor cells in the DT. Therefore, the necessity to include the whole DT in Gamma Knife radiosurgery is not clear, since inclusion increases the target volume and therefore increases the risk of complications. In this analysis, we evaluated whether the complete tail should be included as part of the target in Gamma Knife radiosurgery for meningiomas. Between June 2002 and December 2010, Gamma Knife radiosurgery was performed in 160 patients with 203 meningiomas with a DT. In 105 tumors, the diagnosis was based on magnetic resonance imaging (MRI) characteristics, and in 98 tumors, the diagnosis was confirmed by histopathologic examination after surgery. The median volume of the tumors was 3.55 cc. All tumors were treated with Gamma Knife radiosurgery with a median prescribed dose of 13 Gy (range 11-15), resulting in a median marginal dose of 11 Gy (range 10-15). Only the part of the DT closely related to the tumor mass was included in the target. The median follow-up period was 41 months (range 12-123). In image-based meningiomas, the overall local control rate was 96.2% with 2- and 5-year control rates of 98.0% and 95.1%, respectively. In WHO grade I tumors, the overall local control rate was 85.9% with 2- and 5-year control rates of 94.5% and 88.0%, respectively. The overall local control rate in World Health Organization (WHO) grade II tumors was 70.6% with control rates of 83.4% and 64.4% after 2 and 5 years, respectively. The growth of all new tumors was found in the radiation target area. No tumor growth was observed in the part of the DT that had been excluded from the target volume. We found in this study that routinely excluding the DT from the target does not lead to out-of-field tumor progression. Given the possibility that the DT is infiltrated with tumor cells, regular follow-up is needed.

Multistage stereotactic radiosurgery for large cerebral arteriovenous malformations using the Gamma Knife platform.

PubMed

Ding, Chuxiong; Hrycushko, Brian; Whitworth, Louis; Li, Xiang; Nedzi, Lucien; Weprin, Bradley; Abdulrahman, Ramzi; Welch, Babu; Jiang, Steve B; Wardak, Zabi; Timmerman, Robert D

2017-10-01

Radiosurgery is an established technique to treat cerebral arteriovenous malformations (AVMs). Obliteration of larger AVMs (> 10-15 cm 3 or diameter > 3 cm) in a single session is challenging with current radiosurgery platforms due to toxicity. We present a novel technique of multistage stereotactic radiosurgery (SRS) for large intracranial arteriovenous malformations (AVM) using the Gamma Knife system. Eighteen patients with large (> 10-15 cm 3 or diameter > 3 cm) AVMs, which were previously treated using a staged SRS technique on the Cyberknife platform, were retrospectively selected for this study. The AVMs were contoured and divided into 3-8 subtargets to be treated sequentially in a staged approach at half to 4 week intervals. The prescription dose ranged from 15 Gy to 20 Gy, depending on the subtarget number, volume, and location. Gamma Knife plans using multiple collimator settings were generated and optimized. The coordinates of each shot from the initial plan covering the total AVM target were extracted based on their relative positions within the frame system. The shots were regrouped based on their location with respect to the subtarget contours to generate subplans for each stage. The delivery time of each shot for a subtarget was decay corrected with 60 Co for staging the treatment course to generate the same dose distribution as that planned for the total AVM target. Conformality indices and dose-volume analysis were performed to evaluate treatment plans. With the shot redistribution technique, the composite dose for the multistaged treatment of multiple subtargets is equivalent to the initial plan for total AVM target. Gamma Knife plans resulted in an average PTV coverage of 96.3 ± 0.9% and a PITV of 1.23 ± 0.1. The resulting Conformality indices, V 12Gy and R 50 dose spillage values were 0.76 ± 0.05, 3.4 ± 1.8, and 3.1 ± 0.5 respectively. The Gamma Knife system can deliver a multistaged conformal dose to treat large AVMs when correcting for translational setup errors of each shot at each staged treatment. © 2017 American Association of Physicists in Medicine.

Hypertrophic olivary degeneration following surgical resection or gamma knife radiosurgery of brainstem cavernous malformations: an 11-case series and a review of literature.

PubMed

Yun, Jung-Ho; Ahn, Jae Sung; Park, Jung Cheol; Kwon, Do Hoon; Kwun, Byung Duk; Kim, Chang Jin

2013-03-01

We describe 11 patients with hypertrophic olivary degeneration (HOD) after surgical resection or gamma knife radiosurgery for brainstem cavernous malformations. In addition, we statistically analyzed the predicting factors associated with the development of HOD. From January 2001 to May 2011, a total of 73 patients (30 in the surgical group and 43 in the radiosurgery group) with brainstem cavernous malformations were treated in our institute. Of them, 11 patients (incidence: 15 %) developed HOD with high signal intensity on T2-weighted MRI during follow-up. The predicting factors (location, size, age, and treatment method) associated with the development of HOD were statistically analyzed. Among the 11 HOD patients, seven patients received surgical resection and four patients received gamma knife radiosurgery. Six patients had bilateral HOD and the remaining five patients had unilateral HOD. Overall HOD-associated symptoms presented in four patients, including three palatal tremors and one ataxia. In all four patients with symptoms, these symptoms disappeared incompletely within the clinical follow-up period. The size of the cavernous malformation, age of patient, and treatment methods were not significantly correlated with the development of HOD. A significantly higher incidence of HOD was associated with midbrain cavernous malformations than with pontine or medulla cavernous malformations. HOD should be recognized as a non-infrequent complication of surgical resection or gamma knife radiosurgery within the brainstem, especially for midbrain cavernous malformations. In addition, to the best of our knowledge, this is the first report on HOD development after radiosurgery.

Mid-term prognosis of non-functioning pituitary adenomas with high proliferative potential: really an aggressive variant?

PubMed

Ogawa, Yoshikazu; Jokura, Hidefumi; Niizuma, Kuniyasu; Tominaga, Teiji

2018-05-01

Pituitary adenomas with high proliferation rate and rapid growth are well known, but the clinical characteristics, prognosis, and treatment algorithm remain unclear. The clinical characteristics and mid-term prognosis of patients with non-functioning pituitary adenomas with high proliferative potential were retrospectively investigated. This study identified 53 patients with Ki-67 labeling index of > 3% among 845 patients with non-functioning pituitary adenoma (6.3%) initially treated by surgery. Prophylactic treatment was not applied for patients with residual tumor, but salvage treatment was performed if tumor progression was identified within the follow-up period. Twenty-two patients remained progression-free, whereas 31 patients suffered tumor progression. Comparison of gross total removal (n = 22) and non-total removal (n = 31) groups showed significantly longer progression-free period in the former group (P < 0.001). As salvage treatment gamma knife radiosurgery was applied for 11 patients resulting in 10 patients remaining progression-free and regrowth in 1 patient. Fractionated irradiation was applied for 10 patients, resulting in 2 patients remaining progression-free, deaths in 5 patients including 3 of transformation to pituitary carcinoma, dementia in 1 patient caused by frontal lobe dysfunction, and progression in 2 patients requiring additional surgery and gamma knife radiosurgery. Temozolomide was administered in 2 patients, resulting in deaths in both patients including 1 transformation to pituitary carcinoma. Total removal and gamma knife radiosurgery can result in good outcome. However, the prognosis is extremely poor for patients inadequate for gamma knife radiosurgery. Development of new salvage treatments is essential.

Technical Note: PRESAGE three-dimensional dosimetry accurately measures Gamma Knife output factors

PubMed Central

Klawikowski, Slade J.; Yang, James N.; Adamovics, John; Ibbott, Geoffrey S.

2014-01-01

Small-field output factor measurements are traditionally very difficult because of steep dose gradients, loss of lateral electronic equilibrium, and dose volume averaging in finitely sized detectors. Three-dimensional (3D) dosimetry is ideal for measuring small output factors and avoids many of these potential challenges of point and two-dimensional detectors. PRESAGE 3D polymer dosimeters were used to measure the output factors for the 4 mm and 8 mm collimators of the Leksell Perfexion Gamma Knife radiosurgery treatment system. Discrepancies between the planned and measured distance between shot centers were also investigated. A Gamma Knife head frame was mounted onto an anthropomorphic head phantom. Special inserts were machined to hold 60 mm diameter, 70 mm tall cylindrical PRESAGE dosimeters. The phantom was irradiated with one 16 mm shot and either one 4 mm or one 8 mm shot, to a prescribed dose of either 3 Gy or 4 Gy to the 50% isodose line. The two shots were spaced between 30 mm and 60 mm apart and aligned along the central axis of the cylinder. The Presage dosimeters were measured using the DMOS-RPC optical CT scanning system. Five independent 4 mm output factor measurements fell within 2% of the manufacturer’s Monte Carlo simulation-derived nominal value, as did two independent 8 mm output factor measurements. The measured distances between shot centers varied by ± 0.8 mm with respect to the planned shot displacements. On the basis of these results, we conclude that PRESAGE dosimetry is excellently suited to quantify the difficult-to-measure Gamma Knife output factors. PMID:25368961

Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial.

PubMed

Jin, Hengwei; Huo, Xiaochuan; Jiang, Yuhua; Li, Xiaolong; Li, Youxiang

2017-09-01

Brain arteriovenous malformations (BAVMs) are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety), and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy). Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula), volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS). The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs.

Clinical Evaluation of Targeting Accuracy of Gamma Knife Radiosurgery in Trigeminal Neuralgia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massager, Nicolas; Abeloos, Laurence; Devriendt, Daniel

2007-12-01

Purpose: The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgical treatment with the Leksell Gamma Knife for trigeminal neuralgia. We also studied the applied radiation dose within the area of focal contrast enhancement on the trigeminal nerve root following radiosurgery. Methods and Materials: From an initial group of 78 patients with trigeminal neuralgia treated with gamma knife radiosurgery using a 90-Gy dose, we analyzed a subgroup of 65 patients for whom 6-month follow-up MRI showed focal contrast enhancement of the trigeminal nerve. Follow-up MRI was spatially coregistered to the radiosurgicalmore » planning MRI. Target accuracy was assessed from deviation of the coordinates of the intended target compared with the center of enhancement on postoperative MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was 0.91 mm in Euclidean space. The radiation doses fitting within the borders of the contrast enhancement of the trigeminal nerve root ranged from 49 to 85 Gy (median value, 77 {+-} 8.7 Gy). Conclusions: The median deviation found in clinical assessment of gamma knife treatment for trigeminal neuralgia is low and compatible with its high rate of efficiency. Focal enhancement of the trigeminal nerve after radiosurgery occurred in 83% of our patients and was not associated with clinical outcome. Focal enhancement borders along the nerve root fit with a median dose of 77 {+-} 8.7 Gy.« less

SU-F-T-252: An Investigation of Gamma Knife Frame Definition Error When Using a Pre-Planning Workflow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, P

Purpose: To determine causal factors related to high frame definition error when treating GK patients using a pre-planning workflow. Methods: 160 cases were retrospectively reviewed. All patients received treatment using a pre-planning workflow whereby stereotactic coordinates are determined from a CT scan acquired after framing using a fiducial box. The planning software automatically detects the fiducials and compares their location to expected values based on the rigid design of the fiducial system. Any difference is reported as mean and maximum frame definition error. The manufacturer recommends these values be less than 1.0 mm and 1.5 mm. In this study, framemore » definition error was analyzed in comparison with a variety of factors including which neurosurgeon/oncologist/physicist was involved with the procedure, number of post used during framing (3 or 4), type of lesion, and which CT scanner was utilized for acquisition. An analysis of variance (ANOVA) approach was used to statistically evaluate the data and determine causal factors related to instances of high frame definition error. Results: Two factors were identified as significant: number of post (p=0.0003) and CT scanner (p=0.0001). Further analysis showed that one of the four scanners was significantly different than the others. This diagnostic scanner was identified as an older model with localization lasers not tightly calibrated. The average value for maximum frame definition error using this scanner was 1.48 mm (4 posts) and 1.75 mm (3 posts). For the other scanners this value was 1.13 mm (4 posts) and 1.40 mm (3 posts). Conclusion: In utilizing a pre-planning workflow the choice of CT scanner matters. Any scanner utilized for GK should undergo routine QA at a level appropriate for radiation oncology. In terms of 3 vs 4 post, it is hypothesized that three posts provide less stability during CT acquisition. This will be tested in future work.« less

Rare case of malignant craniopharyngioma reactive to adjunctive stereotactic radiotherapy and chemotherapy; Case report and review.

PubMed

Nomura, Shunsunke; Aihara, Yasuo; Amano, Kosaku; Eguchi, Seiichiro; Chiba, Kentaro; Komori, Takashi; Kawamata, Takakazu

2018-06-19

Malignant craniopharyngioma or anaplastic craniopharyngioma was first reported in 1987 by Akachi. It has a malignant clinical and histological feature; remarkably rapid progression, atypical pathology like squamous cell carcinoma and poor prognosis. To date seventeen cases of malignant craniopharyngioma have been reported and of these cases, most were of secondary malignant tumor in nature. With respect to traditional benign craniopharyngioma, adjunctive treatment after gross total removal is not necessary, but in the case of malignant types of the tumor, adjunctive treatment is important. This paper presents the first case of malignant craniopharyngioma reactive to adjunctive Gamma knife stereotactic radiosurgery and chemotherapy. Malignant craniopharyngioma is very rare, and we report Gamma knife stereotactic radiosurgery and chemotherapy (Carboplatine and etoposide chemotherapy), as well as Temozolomide chemotherapy were effective and could control progression of the tumor temporarily. Since adjunctive Gamma knife stereotactic radiosurgery and chemotherapy of malignant craniopharyngioma cases affects follow-up strategies, we propose supporting the need to a revision to the WHO classification regarding malignancy evaluation of craniopharyngioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-Term Survival of a Patient with Brainstem and Recurrent Brain Metastasis from Stage IV Nonsmall Cell Lung Cancer Treated with Multiple Gamma Knife Radiosurgeries and Craniotomies: A Case Report and Review of the Literature

PubMed Central

Lamm, Andrew F.; Elaimy, Ameer L.; Mackay, Alexander R.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.; Taylor, Blake S.; Lamoreaux, Wayne T.

2012-01-01

The prognosis of patients diagnosed with stage IV nonsmall cell lung cancer that have brain and brainstem metastasis is very poor, with less than a third surviving a year past their initial date of diagnosis. We present the rare case of a 57-year-old man who is a long-term survivor of brainstem and recurrent brain metastasis, after aggressive treatment. He is now five and a half years out from diagnosis and continues to live a highly functional life without evidence of disease. Four separate Gamma Knife stereotactic radiosurgeries in conjunction with two craniotomies were utilized since his initial diagnosis to treat recurrent brain metastasis while chemoradiation therapy and thoracic surgery were used to treat his primary disease in the right upper lung. In his situation, Gamma Knife radiosurgery proved to be a valuable, safe, and effective tool for the treatment of multiply recurrent brain metastases within critical normal structures. PMID:23056973

WE-A-304-02: Strategies and Technologies for Cranial Radiosurgery Planning: Gamma Knife

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlesinger, D.

2015-06-15

The high fractional doses, stringent requirements for accuracy and precision, and surgical perspective characteristic of intracranial radiosurgery create considerations for treatment planning which are distinct from most other radiotherapy procedures. This session will introduce treatment planning techniques specific to two popular intracranial SRS modalities: Gamma Knife and MLC-based Linac. The basic treatment delivery characteristics of each device will be reviewed with a focus on how those characteristics determine the paradigm used for treatment planning. Basic techniques for treatment planning will be discussed, including considerations such as isodose selection, target and organ-at-risk definition, quality indices, and protection of critical structures. Futuremore » directions for SRS treatment planning will also be discussed. Learning Objectives: Introduce the basic physical principles of intracranial radiosurgery and how they are realized in the treatment planning paradigms for Gamma Knife and Linac radiosurgery. Demonstrate basic treatment planning techniques. Discuss metrics for evaluating SRS treatment plan quality. Discuss recent and future advances in SRS treatment planning. D. Schlesinger receives research support from Elekta, AB.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brezovich, I; Wu, X; Popple, R

Purpose: To test spatial and dosimetric accuracy of small cranial target irradiation based on 1.5 T MRI scans using static arcs with MLC-defined fields Methods: A plastic (PMMA) phantom simulating a small brain lesion was mounted on a GammaKnife headframe equipped with MRI localizer. The lesion was a 3 mm long, 3.175 mm diameter cylindrical cavity filled with MRI contrast. Radiochromic film passing through the cavity was marked with pin pricks at the cavity center. The cavity was contoured on an MRI image and fused with CT to simulate treatment of a lesion not visible on CT. The transfer ofmore » the target to CT involved registering the MRI contrast cannels of the localizer that were visible on both modalities. Treatments were planned to deliver 800 cGy to the cavity center using multiple static arcs with 5.0×2.4 mm MLC-defined fields. The phantom was aligned on a STx accelerator by registering the conebeam CT with the planning CT. Films from coronal and sagittal planes were scanned and evaluated using ImageJ software Results: Geographic errors in treatment based on 1.5 T scans agreed within 0.33, −0.27 and 1.21 mm in the vertical, lateral and longitudinal dimensions, respectively. The doses delivered to the cavity center were 7.2% higher than planned. The dose distributions were similar to those of a GammaKnife. Conclusion: Radiation can be delivered with an accelerator at mm accuracy to small cranial targets based on 1.5 MRI scans fused to CTs using a standard GammaKnife headframe and MRI localizer. MLC-defined static arcs produce isodose lines very similar to the GammaKnife.« less

The safety and efficacy of gamma knife surgery in management of glomus jugulare tumor

PubMed Central

2010-01-01

Background Glomus jugulare is a slowly growing, locally destructive tumor located in the skull base with difficult surgical access. The operative approach is, complicated by the fact that lesions may be both intra and extradural with engulfment of critical neurovascular structures. The tumor is frequently highly vascular, thus tumor resection entails a great deal of morbidity and not infrequent mortality. At timeslarge residual tumors are left behind. To decrease the morbidity associated with surgical resection of glomus jugulare, gamma knife surgery (GKS) was performed as an alternative in 13 patients to evaluate its safety and efficacy. Methods A retrospective review of 13 residual or unresectable glomus jagulare treated with GKS between 2004 and 2008.. Of these, 11 patients underwent GKS as the primary management and one case each was treated for postoperative residual disease and postembolization. The radiosurgical dose to the tumor margin ranged between 12-15 Gy. Results Post- gamma knife surgery and during the follow-up period twelve patients demonstrated neurological stability while clinical improvement was achieved in 5 patients. One case developed transient partial 7th nerve palsy that responded to medical treatment. In all patients radiographic MRI follow-up was obtained, the tumor size decreased in two cases and remained stable (local tumor control) in eleven patients. Conclusions Gamma knife surgery provids tumor control with a lowering of risk of developing a new cranial nerve injury in early follow-up period. This procedure can be safely used as a primary management tool in patients with glomus jugulare tumors, or in patients with recurrent tumors in this location. If long-term results with GKS are equally effective it will emerge as a good alternative to surgical resection. PMID:20819207

Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constanzo, Julie; Paquette, Benoit; Charest, Gabriel

2015-05-15

Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brainmore » were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.« less

Three-dimensional dose verification of the clinical application of gamma knife stereotactic radiosurgery using polymer gel and MRI.

PubMed

Papagiannis, P; Karaiskos, P; Kozicki, M; Rosiak, J M; Sakelliou, L; Sandilos, P; Seimenis, I; Torrens, M

2005-05-07

This work seeks to verify multi-shot clinical applications of stereotactic radiosurgery with a Leksell Gamma Knife model C unit employing a polymer gel-MRI based experimental procedure, which has already been shown to be capable of verifying the precision and accuracy of dose delivery in single-shot gamma knife applications. The treatment plan studied in the present work resembles a clinical treatment case of pituitary adenoma using four 8 mm and one 14 mm collimator helmet shots to deliver a prescription dose of 15 Gy to the 50% isodose line (30 Gy maximum dose). For the experimental dose verification of the treatment plan, the same criteria as those used in the clinical treatment planning evaluation were employed. These included comparison of measured and GammaPlan calculated data, in terms of percentage isodose contours on axial, coronal and sagittal planes, as well as 3D plan evaluation criteria such as dose-volume histograms for the target volume, target coverage and conformity indices. Measured percentage isodose contours compared favourably with calculated ones despite individual point fluctuations at low dose contours (e.g., 20%) mainly due to the effect of T2 measurement uncertainty on dose resolution. Dose-volume histogram data were also found in a good agreement while the experimental results for the percentage target coverage and conformity index were 94% and 1.17 relative to corresponding GammaPlan calculations of 96% and 1.12, respectively. Overall, polymer gel results verified the planned dose distribution within experimental uncertainties and uncertainty related to the digitization process of selected GammaPlan output data.

GammaKnife surgery: safety and the identity of users.

PubMed

Dinka, David; Nyce, James M; Timpka, Toomas

2005-01-01

In this study we investigated safety-related usability issues of an advanced medical technology, a radiosurgery system. We were interested in which criteria are important for users when a system's usability and safety is to be improved. The data collection was based on interviews and observations at three different sites where the Leksell GammaKnife is used. The analysis was qualitative. The main finding was that the user's identity or professional background has a significant impact both on how he or she views his or her role in the clinical setting, and on how he or she defines what improvements are necessary and general safety issues. In fact, the opinion even of users experienced in safety-related problems was highly influenced by how they related to the technology and its development. None of the users actually considered Leksell GammaKnife as lacking in safety, instead, their assessment was directed towards potential future system improvements. Our findings suggest that the importance of user identity or professional background cannot be neglected during the development of advanced technology. They also suggest that the user feedback should always be related to user background and identity in order to understand how important different issues are for particular users.

A simplified model of the source channel of the Leksell GammaKnife tested with PENELOPE.

PubMed

Al-Dweri, Feras M O; Lallena, Antonio M; Vilches, Manuel

2004-06-21

Monte Carlo simulations using the code PENELOPE have been performed to test a simplified model of the source channel geometry of the Leksell GammaKnife. The characteristics of the radiation passing through the treatment helmets are analysed in detail. We have found that only primary particles emitted from the source with polar angles smaller than 3 degrees with respect to the beam axis are relevant for the dosimetry of the Gamma Knife. The photon trajectories reaching the output helmet collimators at (x, v, z = 236 mm) show strong correlations between rho = (x2 + y2)(1/2) and their polar angle theta, on one side, and between tan(-1)(y/x) and their azimuthal angle phi, on the other. This enables us to propose a simplified model which treats the full source channel as a mathematical collimator. This simplified model produces doses in good agreement with those found for the full geometry. In the region of maximal dose, the relative differences between both calculations are within 3%, for the 18 and 14 mm helmets, and 10%, for the 8 and 4 mm ones. Besides, the simplified model permits a strong reduction (larger than a factor 15) in the computational time.

Gamma Knife Radiosurgery for Uveal Metastases: Report of Three Cases and a Review of the Literature.

PubMed

Ares, William J; Tonetti, Daniel; Yu, Jenny Y; Monaco, Edward A; Flickinger, John C; Lunsford, L Dade

2017-02-01

Uveal metastases are ophthalmologic tumors that have historically been treated by fractionated external beam radiation therapy or invasive brachytherapy. The need for rapid response and less invasive management options led the authors to explore the use of Gamma Knife stereotactic radiosurgery (SRS) for this common problem. Interventional case series. To prevent eye movement during the procedure, all 3 patients underwent a retrobulbar anesthetic block followed by magnetic resonance imaging to detect the target. All tumors were treated in a single procedure using the 4C or Perfexion Gamma Knife. The tumors received a minimal tumor dose of 14-20 Gy. Two patients also underwent SRS for additional intracranial metastases. At follow-up, performed between 4 and 15 months after SRS, all 3 patients demonstrated a reduction in uveal tumor volumes. One patient developed decreased visual acuity secondary to radiation retinopathy. In this early experience, SRS was found to be an effective management option for uveal metastases associated with systemic cancer. Patients can be screened and treated effectively early after diagnosis using a joint approach between ophthalmologists and neurosurgeons. Systemic oncologic care can continue without interruption. Copyright © 2016 Elsevier Inc. All rights reserved.

Stereotactic radiosurgery - discharge

MedlinePlus

Gamma knife - discharge; Cyberknife - discharge; Stereotactic radiotherapy - discharge; Fractionated stereotactic radiotherapy - discharge; Cyclotrons - discharge; Linear accelerator - discharge; Lineacs - discharge; Proton beam radiosurgery - discharge

The value of image coregistration during stereotactic radiosurgery.

PubMed

Koga, T; Maruyama, K; Igaki, H; Tago, M; Saito, N

2009-05-01

Coregistration of any neuroimaging studies into treatment planning for stereotactic radiosurgery became easily applicable using the Leksell Gamma Knife 4C, a new model of gamma knife. The authors investigated the advantage of this image processing. Since installation of the Leksell Gamma Knife 4C at the authors' institute, 180 sessions of radiosurgery were performed. Before completion of planning, coregistration of frameless images of other modalities or previous images was considered to refine planning. Treatment parameters were compared for planning before and after refinement by use of coregistered images. Coregistered computed tomography clarified the anatomical structures indistinct on magnetic resonance imaging. Positron emission tomography visualized lesions disclosing metabolically high activity. Coregistration of prior imaging distinguished progressing lesions from stable ones. Diffusion-tensor tractography was integrated for lesions adjacent to the corticospinal tract or the optic radiation. After refinement of planning in 36 sessions, excess treated volume decreased (p = 0.0062) and Paddick conformity index improved (p < 0.001). Maximal dose to the white matter tracts was decreased (p < 0.001). Image coregistration provided direct information on anatomy, metabolic activity, chronological changes, and adjacent critical structures. This gathered information was sufficiently informative during treatment planning to supplement ambiguous information on stereotactic images, and was useful especially in reducing irradiation to surrounding normal structures.

Five-year Survival After Surgical Removal and Gamma Knife Stereotactic Radiosurgery for a Cerebellar Metastasis from an Esophagogastric Junction Cancer: A Case Report and Literature Review

PubMed Central

KANAZAWA, YOSHIKAZU; FUJITA, ITSUO; KAKINUMA, DAISUKE; AOKI, YUTO; KANNO, HITOSHI; ARAI, HIROKI; MATSUNO, KUNIHIKO; SHIMODA, TOMOHIRO; MATSUTANI, TAKESHI; HAGIWARA, NOBUTOSHI; NOMURA, TSUTOMU; YAMADA, TAKESHI; KATO, SHUNJI; NAITO, ZENYA; TAKASAKI, HIDEAKI; UCHIDA, EIJI

2017-01-01

Brain metastases originating from esophageal or gastric cancer are rare, accounting for 2.1-3.3% of all brain tumors registered in Japan. There are no established therapeutic measures for brain metastases, which accordingly have a poor prognosis. We present here a patient who survived for 5 years after surgery and gamma knife treatment of a cerebellar metastasis from esophagogastric adenocarcinoma. The primary gastric cancer was treated by laparotomy with total gastrectomy, splenectomy, and D2 lymphadenectomy. It was diagnosed as a esophagogastric junction Siewert type II tumor, type 3, tub1-2, pT3 (SS), pN1, and stage IIB on histopathological examination of the surgical specimen. Five months postoperatively, a solitary cerebellar metastasis was identified and surgically removed, followed by 20 Gy administered by gamma knife stereotactic radiosurgery; the patient received no subsequent treatment such as chemotherapy. Five years after the primary surgery, there have been no recurrences and the patient has a good quality of life. There are very few case reports of long-term survival after surgical treatment of cerebellar metastases from esophagogastric junction cancer. We report our experience and review published case reports of surgical treatment of brain metastases from gastric cancer. PMID:29102948

A simplified model of the source channel of the Leksell GammaKnife® tested with PENELOPE

NASA Astrophysics Data System (ADS)

Al-Dweri, Feras M. O.; Lallena, Antonio M.; Vilches, Manuel

2004-06-01

Monte Carlo simulations using the code PENELOPE have been performed to test a simplified model of the source channel geometry of the Leksell GammaKnife®. The characteristics of the radiation passing through the treatment helmets are analysed in detail. We have found that only primary particles emitted from the source with polar angles smaller than 3° with respect to the beam axis are relevant for the dosimetry of the Gamma Knife. The photon trajectories reaching the output helmet collimators at (x, y, z = 236 mm) show strong correlations between rgr = (x2 + y2)1/2 and their polar angle thgr, on one side, and between tan-1(y/x) and their azimuthal angle phgr, on the other. This enables us to propose a simplified model which treats the full source channel as a mathematical collimator. This simplified model produces doses in good agreement with those found for the full geometry. In the region of maximal dose, the relative differences between both calculations are within 3%, for the 18 and 14 mm helmets, and 10%, for the 8 and 4 mm ones. Besides, the simplified model permits a strong reduction (larger than a factor 15) in the computational time.

Long-term effectiveness and safety of stereotactic gamma knife surgery as a primary sole treatment in the management of glomus jagulare tumor.

PubMed

Hafez, Raef F A; Morgan, Magad S; Fahmy, Osama M; Hassan, Hamdy T

2018-05-01

This study aims to report and confirm long-term effectiveness and safety of stereotactic Gamma Knife Surgery as a primary sole treatment in the management of 40 glomus jagulare tumors patients. Retrospective analysis of clinical and radiological outcomes of 40 GJTs consecutive patients treated with GKS as primary sole treatment at International Medical Center (IMC), Cairo-Egypt from the beginning of 2005 till the end of 2014,with mean follow-up period of 84 months (range 36-156 months), mean tumor volume was 6.5 cc, and mean peripheral radiation dose of 15 Gy, to mean isodose curve of 38%. The most common neurological deficit at initial evaluation was bulbar symptoms in 24 patients, followed by pulsatile tinnitus in 22, deterioration of hearing in 20 patients. The overall clinical control achieved in 92.5% of patients, while actuarial tumor size control rate post- GKS was 97.5% at 3 years, 97% at 5 years and 92% at 10 years of follow-up period. Gamma knife surgery could be used effectively and safely as a primary sole treatment tool in the management of glomus jugulare tumors. Copyright © 2018 Elsevier B.V. All rights reserved.

MR angiography fusion technique for treatment planning of intracranial arteriovenous malformations.

PubMed

McGee, Kiaran P; Ivanovic, Vladimir; Felmlee, Joel P; Meyer, Fredrick B; Pollock, Bruce E; Huston, John

2006-03-01

To develop an image fusion technique using elliptical centric contrast-enhanced (CE) MR angiography (MRA) and three-dimensional (3D) time-of-flight (TOF) acquisitions for radiosurgery treatment planning of arteriovenous malformations (AVMs). CE and 3D-TOF MR angiograms with disparate in-plane fields of view (FOVs) were acquired, followed by k-space reformatting to provide equal voxel dimensions. Spatial domain addition was performed to provide a third, fused data volume. Spatial distortion was evaluated on an MRA phantom and provided slice-dependent and global distortion along the three physical dimensions of the MR scanner. In vivo validation was performed on 10 patients with intracranial AVMs prior to their conventional angiogram on the day of gamma knife radiosurgery. Spatial distortion in the phantom within a volume of 14 x 14 x 3.2 cm(3) was less than +/-1 mm (+/-1 standard deviation (SD)) for CE and 3D-TOF data sets. Fused data volumes were successfully generated for all 10 patients. Image fusion can be used to obtain high-resolution CE-MRA images of intracranial AVMs while keeping the fiducial markers needed for gamma knife radiosurgery planning. The spatial fidelity of these data is within the tolerance acceptable for daily quality control (QC) purposes and gamma knife treatment planning. (c) 2006 Wiley-Liss, Inc.

SU-E-J-240: The Impact On Clinical Dose-Distributions When Using MR-Images Registered with Stereotactic CT-Images in Gamma Knife Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benmakhlouf, H; Kraepelien, T; Forander, P

2014-06-01

Purpose: Most Gamma knife treatments are based solely on MR-images. However, for fractionated treatments and to implement TPS dose calculations that require electron densities, CT image data is essential. The purpose of this work is to assess the dosimetric effects of using MR-images registered with stereotactic CT-images in Gamma knife treatments. Methods: Twelve patients treated for vestibular schwannoma with Gamma Knife Perfexion (Elekta Instruments, Sweden) were selected for this study. The prescribed doses (12 Gy to periphery) were delivered based on the conventional approach of using stereotactic MR-images only. These plans were imported into stereotactic CT-images (by registering MR-images withmore » stereotactic CT-images using the Leksell gamma plan registration software). The dose plans, for each patient, are identical in both cases except for potential rotations and translations resulting from the registration. The impact of the registrations was assessed by an algorithm written in Matlab. The algorithm compares the dose-distributions voxel-by-voxel between the two plans, calculates the full dose coverage of the target (treated in the conventional approach) achieved by the CT-based plan, and calculates the minimum dose delivered to the target (treated in the conventional approach) achieved by the CT-based plan. Results: The mean dose difference between the plans was 0.2 Gy to 0.4 Gy (max 4.5 Gy) whereas between 89% and 97% of the target (treated in the conventional approach) received the prescribed dose, by the CT-plan. The minimum dose to the target (treated in the conventional approach) given by the CT-based plan was between 7.9 Gy and 10.7 Gy (compared to 12 Gy in the conventional treatment). Conclusion: The impact of using MR-images registered with stereotactic CT-images has successfully been compared to conventionally delivered dose plans showing significant differences between the two. Although CTimages have been implemented clinically; the effect of the registration has not been fully investigated.« less

SU-E-T-563: Multi-Fraction Stereotactic Radiosurgery with Extend System of Gamma Knife: Treatment Verification Using Indigenously Designed Patient Simulating Multipurpose Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bisht, R; Kale, S; Gopishankar, N

2015-06-15

Purpose: Aim of the study is to evaluate mechanical and radiological accuracy of multi-fraction regimen and validate Gamma knife based fractionation using newly developed patient simulating multipurpose phantom. Methods: A patient simulating phantom was designed to verify fractionated treatments with extend system (ES) of Gamma Knife however it could be used to validate other radiotherapy procedures as well. The phantom has options to insert various density material plugs and mini CT/MR distortion phantoms to analyze the quality of stereotactic imaging. An additional thorax part designed to predict surface doses at various organ sites. The phantom was positioned using vacuum headmore » cushion and patient control unit for imaging and treatment. The repositioning check tool (RCT) was used to predict phantom positioning under ES assembly. The phantom with special inserts for film in axial, coronal and sagittal plane were scanned with X-Ray CT and the acquired images were transferred to treatment planning system (LGP 10.1). The focal precession test was performed with 4mm collimator and an experimental plan of four 16mm collimator shots was prepared for treatment verification of multi-fraction regimen. The prescription dose of 5Gy per fraction was delivered in four fractions. Each fraction was analyzed using EBT3 films scanned with EPSON 10000XL Scanner. Results: The measurement of 38 RCT points showed an overall positional accuracy of 0.28mm. The mean deviation of 0.28% and 0.31 % were calculated as CT and MR image distortion respectively. The radiological focus accuracy test showed its deviation from mechanical center point of 0.22mm. The profile measurement showed close agreement between TPS planned and film measured dose. At tolerance criteria of 1%/1mm gamma index analysis showed a pass rate of > 95%. Conclusion: Our results show that the newly developed multipurpose patient simulating phantom is highly suitable for the verification of fractionated stereotactic radiosurgery using ES of Gamma knife. The study is a part of intramural research project of Research Section, All India Institute of Medical Sciences New Delhi India (A 247)« less

SU-G-TeP2-12: IROCHouston and MDAPL SRS Anthropomorphic Phantom Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molineu, A; Kry, S; Alvarez, P

Purpose: To report the results of SRS phantom irradiations Methods: Anthropomorphic SRS head phantoms were sent to institutions participating in NCI sponsored SRS clinical trials and institutions interested in verifying SRS treatment delivery. The phantom shell was purchased from Phantom Laboratory and altered to house dosimetry and imaging inserts. The imaging insert has 1.9 cm diameter spherical target. The dosimetry insert holds two TLD capsules and radiochromic film in the coronal and sagittal planes through the center of the target. Institutions were asked to image, plan and treat the phantom as they would an SRS patient. GammaKnife, CyberKnife and c-armmore » accelerator institutions were asked to cover the target with 15 Gy, 20 Gy and 25 Gy, respectively. Following these guidelines and typical planning protocols for these three types of machines gives roughly 30 Gy to the center of the target for all units. Submission of the DICOM digital data set was required for analysis. Criteria of 5% for TLD results and 85% of pixels passing 5%/3mm gamma analysis were applied beginning in 2013. Results: The phantom was analyzed 269 times between the beginning of 2013 to present. The pass rate is 81%. Nineteen of the irradiation results failed only the TLD criteria, 19 failed only the film criteria and 12 failed both. Irradiations included 32 CyberKnife 23 GammaKnife, 3 TomoTherapy and 211 c-arm units. Planning systems included Eclipse, Ergo, GammaPlan, Hi-Art, iPlan, Monaco, MultiPlan, Pinnacle, RayStation, XiO and XKnife. Irradiations that were not accompanied with DICOM data were not included in this analysis. Conclusion: The phantom is a valuable end-to-end test used to independently verify the accuracy of SRS treatment delivery. This investigation was supported by IROC grant CA180803 awarded by the NCI.« less

[Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

PubMed

Ma, Z M; Jiang, B; Ma, J R

2001-08-28

To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P < 0.01, compared with the control group). The swelling of cells in irradiated region was observed on the 1st day; after irradiation endothelial cells degenerated and red blood cells escaped from blood vessel on the 7th day; leakage of Evans blue dye was observed in the target region on the 14th day. There was a significant decrease of specific gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

Gamma Knife radiosurgery for glomus jugulare tumors: a single-center series of 75 cases.

PubMed

Ibrahim, Ramez; Ammori, Mohannad B; Yianni, John; Grainger, Alison; Rowe, Jeremy; Radatz, Matthias

2017-05-01

OBJECTIVE Glomus jugulare tumors are rare indolent tumors that frequently involve the lower cranial nerves (CNs). Complete resection can be difficult and associated with lower CN injury. Gamma Knife radiosurgery (GKRS) has established its role as a noninvasive alternative treatment option for these often formidable lesions. The authors aimed to review their experience at the National Centre for Stereotactic Radiosurgery, Sheffield, United Kingdom, specifically the long-term tumor control rate and complications of GKRS for these lesions. METHODS Clinical and radiological data were retrospectively reviewed for patients treated between March 1994 and December 2010. Data were available for 75 patients harboring 76 tumors. The tumors in 3 patients were treated in 2 stages. Familial and/or hereditary history was noted in 12 patients, 2 of whom had catecholamine-secreting and/or active tumors. Gamma Knife radiosurgery was the primary treatment modality in 47 patients (63%). The median age at the time of treatment was 55 years. The median tumor volume was 7 cm 3 , and the median radiosurgical dose to the tumor margin was 18 Gy (range 12-25 Gy). The median duration of radiological follow-up was 51.5 months (range 12-230 months), and the median clinical follow-up was 38.5 months (range 6-223 months). RESULTS The overall tumor control rate was 93.4% with low CN morbidity. Improvement of preexisting deficits was noted in 15 patients (20%). A stationary clinical course and no progression of symptoms were noted in 48 patients (64%). Twelve patients (16%) had new symptoms or progression of their preexisting symptoms. The Kaplan-Meier actuarial tumor control rate was 92.2% at 5 years and 86.3% at 10 years. CONCLUSIONS Gamma Knife radiosurgery offers a risk-versus-benefit treatment option with very low CN morbidity and stable long-term results.

Stereotactic radiosurgery XX: ocular neuromyotonia in association with gamma knife radiosurgery

PubMed Central

McQuillan, Joe; Plowman, P Nicholas; MacDougall, Niall; Blackburn, Philip; Sabin, H Ian; Ali, Nadeem; Drake, William M

2015-01-01

Summary We report three patients who developed symptoms and signs of ocular neuromyotonia (ONM) 3–6 months after receiving gamma knife radiosurgery (GKS) for functioning pituitary tumours. All three patients were complex, requiring multi-modality therapy and all had received prior external irradiation to the sellar region. Although direct causality cannot be attributed, the timing of the development of the symptoms would suggest that the GKS played a contributory role in the development of this rare problem, which we suggest clinicians should be aware of as a potential complication. Learning points GKS can cause ONM, presenting as intermittent diplopia.ONM can occur quite rapidly after treatment with GKS.Treatment with carbamazepine is effective and improve patient's quality of life. PMID:26294961

Evaluation of stability of stereotactic space defined by cone-beam CT for the Leksell Gamma Knife Icon.

PubMed

AlDahlawi, Ismail; Prasad, Dheerendra; Podgorsak, Matthew B

2017-05-01

The Gamma Knife Icon comes with an integrated cone-beam CT (CBCT) for image-guided stereotactic treatment deliveries. The CBCT can be used for defining the Leksell stereotactic space using imaging without the need for the traditional invasive frame system, and this allows also for frameless thermoplastic mask stereotactic treatments (single or fractionated) with the Gamma Knife unit. In this study, we used an in-house built marker tool to evaluate the stability of the CBCT-based stereotactic space and its agreement with the standard frame-based stereotactic space. We imaged the tool with a CT indicator box using our CT-simulator at the beginning, middle, and end of the study period (6 weeks) for determining the frame-based stereotactic space. The tool was also scanned with the Icon's CBCT on a daily basis throughout the study period, and the CBCT images were used for determining the CBCT-based stereotactic space. The coordinates of each marker were determined in each CT and CBCT scan using the Leksell GammaPlan treatment planning software. The magnitudes of vector difference between the means of each marker in frame-based and CBCT-based stereotactic space ranged from 0.21 to 0.33 mm, indicating good agreement of CBCT-based and frame-based stereotactic space definition. Scanning 4-month later showed good prolonged stability of the CBCT-based stereotactic space definition. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

MO-F-CAMPUS-T-03: Continuous Dose Delivery with Gamma Knife Perfexion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghobadi,; Li, W; Chung, C

2015-06-15

Purpose: We propose continuous dose delivery techniques for stereotactic treatments delivered by Gamma Knife Perfexion using inverse treatment planning system that can be applied to various tumour sites in the brain. We test the accuracy of the plans on Perfexion’s planning system (GammaPlan) to ensure the obtained plans are viable. This approach introduces continuous dose delivery for Perefxion, as opposed to the currently employed step-and-shoot approaches, for different tumour sites. Additionally, this is the first realization of automated inverse planning on GammaPlan. Methods: The inverse planning approach is divided into two steps of identifying a quality path inside the target,more » and finding the best collimator composition for the path. To find a path, we select strategic regions inside the target volume and find a path that visits each region exactly once. This path is then passed to a mathematical model which finds the best combination of collimators and their durations. The mathematical model minimizes the dose spillage to the surrounding tissues while ensuring the prescribed dose is delivered to the target(s). Organs-at-risk and their corresponding allowable doses can also be added to the model to protect adjacent organs. Results: We test this approach on various tumour sizes and sites. The quality of the obtained treatment plans are comparable or better than forward plans and inverse plans that use step- and-shoot technique. The conformity indices in the obtained continuous dose delivery plans are similar to those of forward plans while the beam-on time is improved on average (see Table 1 in supporting document). Conclusion: We employ inverse planning for continuous dose delivery in Perfexion for brain tumours. The quality of the obtained plans is similar to forward and inverse plans that use conventional step-and-shoot technique. We tested the inverse plans on GammaPlan to verify clinical relevance. This research was partially supported by Elekta, Sweden (vendor of Gamma Knife Perfexion)« less

Emerging Indications for Fractionated Gamma Knife Radiosurgery.

PubMed

McTyre, Emory; Helis, Corbin A; Farris, Michael; Wilkins, Lisa; Sloan, Darrell; Hinson, William H; Bourland, J Daniel; Dezarn, William A; Munley, Michael T; Watabe, Kounosuke; Xing, Fei; Laxton, Adrian W; Tatter, Stephen B; Chan, Michael D

2017-02-01

Gamma Knife radiosurgery (GKRS) allows for the treatment of intracranial tumors with a high degree of dose conformality and precision. There are, however, certain situations wherein the dose conformality of GKRS is desired, but single session treatment is contraindicated. In these situations, a traditional pin-based GKRS head frame cannot be used, as it precludes fractionated treatment. To report our experience in treating patients with fractionated GKRS using a relocatable, noninvasive immobilization system. Patients were considered candidates for fractionated GKRS if they had one or more of the following indications: a benign tumor >10 cc in volume or abutting the optic pathway, a vestibular schwannoma with the intent of hearing preservation, or a tumor previously irradiated with single fraction GKRS. The immobilization device used for all patients was the Extend system (Leksell Gamma Knife Perfexion, Elekta, Kungstensgatan, Stockholm). We identified 34 patients treated with fractionated GKRS between August 2013 and February 2015. There were a total of 37 tumors treated including 15 meningiomas, 11 pituitary adenomas, 6 brain metastases, 4 vestibular schwannomas, and 1 hemangioma. At last follow-up, all 21 patients treated for perioptic tumors had stable or improved vision and all 4 patients treated for vestibular schwannoma maintained serviceable hearing. No severe adverse events were reported. Fractionated GKRS was well-tolerated in the treatment of large meningiomas, perioptic tumors, vestibular schwannomas with intent of hearing preservation, and in reirradiation of previously treated tumors.

Single-session Gamma Knife radiosurgery for optic pathway/hypothalamic gliomas.

PubMed

El-Shehaby, Amr M N; Reda, Wael A; Abdel Karim, Khaled M; Emad Eldin, Reem M; Nabeel, Ahmed M

2016-12-01

OBJECTIVE Because of their critical and central location, it is deemed necessary to fractionate when considering irradiating optic pathway/hypothalamic gliomas. Stereotactic fractionated radiotherapy is considered safer when dealing with gliomas in this location. In this study, the safety and efficacy of single-session stereotactic radiosurgery for optic pathway/hypothalamic gliomas were reviewed. METHODS Between December 2004 and June 2014, 22 patients with optic pathway/hypothalamic gliomas were treated by single-session Gamma Knife radiosurgery. Twenty patients were available for follow-up for a minimum of 1 year after treatment. The patients were 5 to 43 years (median 16 years) of age. The tumor volume was 0.15 to 18.2 cm 3 (median 3.1 cm 3 ). The prescription dose ranged from 8 to 14 Gy (median 11.5 Gy). RESULTS The mean follow-up period was 43 months. Five tumors involved the optic nerve only, and 15 tumors involved the chiasm/hypothalamus. Two patients died during the follow-up period. The tumors shrank in 12 cases, remained stable in 6 cases, and progressed in 2 cases, thereby making the tumor control rate 90%. Vision remained stable in 12 cases, improved in 6 cases, and worsened in 2 cases in which there was tumor progression. Progression-free survival was 83% at 3 years. CONCLUSIONS The initial results indicate that single-session Gamma Knife radiosurgery is a safe and effective treatment option for optic pathway/hypothalamic gliomas.

MRI textures as outcome predictor for Gamma Knife radiosurgery on vestibular schwannoma

NASA Astrophysics Data System (ADS)

Langenhuizen, P. P. J. H.; Legters, M. J. W.; Zinger, S.; Verheul, H. B.; Leenstra, S.; de With, P. H. N.

2018-02-01

Vestibular schwannomas (VS) are benign brain tumors that can be treated with high-precision focused radiation with the Gamma Knife in order to stop tumor growth. Outcome prediction of Gamma Knife radiosurgery (GKRS) treatment can help in determining whether GKRS will be effective on an individual patient basis. However, at present, prognostic factors of tumor control after GKRS for VS are largely unknown, and only clinical factors, such as size of the tumor at treatment and pre-treatment growth rate of the tumor, have been considered thus far. This research aims at outcome prediction of GKRS by means of quantitative texture feature analysis on conventional MRI scans. We compute first-order statistics and features based on gray-level co- occurrence (GLCM) and run-length matrices (RLM), and employ support vector machines and decision trees for classification. In a clinical dataset, consisting of 20 tumors showing treatment failure and 20 tumors exhibiting treatment success, we have discovered that the second-order statistical metrics distilled from GLCM and RLM are suitable for describing texture, but are slightly outperformed by simple first-order statistics, like mean, standard deviation and median. The obtained prediction accuracy is about 85%, but a final choice of the best feature can only be made after performing more extensive analyses on larger datasets. In any case, this work provides suitable texture measures for successful prediction of GKRS treatment outcome for VS.

Long-Term Survival after Gamma Knife Radiosurgery in a Case of Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature

PubMed Central

Thumma, Sudheer R.; Elaimy, Ameer L.; Daines, Nathan; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2012-01-01

The management of recurrent glioblastoma is highly challenging, and treatment outcomes remain uniformly poor. Glioblastoma is a highly infiltrative tumor, and complete surgical resection of all microscopic extensions cannot be achieved at the time of initial diagnosis, and hence local recurrence is observed in most patients. Gamma Knife radiosurgery has been used to treat these tumor recurrences for select cases and has been successful in prolonging the median survival by 8–12 months on average for select cases. We present the unique case of a 63-year-old male with multiple sequential recurrences of glioblastoma after initial standard treatment with surgery followed by concomitant external beam radiation therapy and chemotherapy (temozolomide). The patient was followed clinically as well as with surveillance MRI scans at every 2-3-month intervals. The patient underwent Gamma Knife radiosurgery three times for 3 separate tumor recurrences, and the patient survived for seven years following the initial diagnosis with this aggressive treatment. The median survival in patients with recurrent glioblastoma is usually 8–12 months after recurrence, and this unique case illustrates that aggressive local therapy can lead to long-term survivors in select situations. We advocate that each patient treatment at the time of recurrence should be tailored to each clinical situation and desire for quality of life and improved longevity. PMID:22548078

Acoustic Neuroma Association

MedlinePlus

... Gold Sponsor NSPC Brain & Spine Surgery Learn More Gold Sponsor University of Colorado Acoustic Neuroma Program and Rocky Mountain Gamma Knife Center Learn More Gold Sponsor USC Acoustic Neuroma Center Learn More Gold ...

In memoriam Ladislau Steiner, neurosurgeon: some people from transylvania do live forever.

PubMed

Dinca, Eduard B; Ciurea, Alexandru V; Valéry, Charles-Ambroise

2014-01-01

We review the extraordinary professional trajectory of Ladislau Steiner, a prolific neurosurgeon and radiosurgeon, who died earlier this year. Dr. Steiner trained and practiced as a neurosurgeon in his native Romania until he was 42, before moving to Stockholm. After 25 years at the Karolinska Institute, when most people consider retirement, he spent the following 25 years of his life as director of the Lars Leksell Center for Gamma Knife Radiosurgery at the University of Virginia, Charlottesville, Virginia. At 90, nostalgia for Europe made him accept the position of director of the Gamma Knife Center at the International Neuroscience Institute in Hannover, Germany. His life was dedicated to the 15,000 patients whose lives he saved in his lengthy career. Copyright © 2014 Elsevier Inc. All rights reserved.

Ladislau Steiner, 1920-2013.

PubMed

Leksell, Dan; Lindquist, Christer E H

2013-09-01

The authors commemorate the life and career of Dr. Ladislau Steiner, one of the world's most highly regarded neurosurgeons, from Stockholm and Charlottesville, Virginia, who has died at age 92. They review the events of Dr. Steiner's early life, including his early training in his native Romania, his escape with his family from East Berlin, and his postgraduate training in neurosurgery at the Karolinska Institute in Stockholm. Dr. Steiner's work in the development of microsurgery and his collaboration with Lars Leksell in the development of Gamma Knife radiosurgery are described. After his retirement from Karolinska, Dr. Steiner had a second career as head of the Lars Leksell Gamma Knife Center at the University of Virginia in Charlottesville. The authors recall their own long association with Dr. Steiner and celebrate his contributions to the field of neurosurgery.

Evaluation of dose delivery accuracy of gamma knife using MRI polymer gel dosimeter in an inhomogeneous phantom

NASA Astrophysics Data System (ADS)

Pourfallah T, A.; Alam N, Riahi; M, Allahverdi; M, Ay; M, Zahmatkesh

2009-05-01

Polymer gel dosimetry is still the only dosimetry method for directly measuring three-dimensional dose distributions. MRI Polymer gel dosimeters are tissue equivalent and can act as a phantom material. Because of high dose response sensitivity, the MRI was chosen as readout device. In this study dose profiles calculated with treatment-planning software (LGP) and measurements with the MR polymer gel dosimeter for single-shot irradiations were compared. A custom-built 16 cm diameter spherical plexiglas head phantom was used in this study. Inside the phantom, there is a cubic cutout for insertion of gel phantoms and another cutout for inserting the inhomogeneities. The phantoms were scanned with a 1.5T MRI (Siemens syngo MR 2004A 4VA25A) scanner. The multiple spin-echo sequence with 32 echoes was used for the MRI scans. Calibration relations between the spin-spin relaxation rate and the absorbed dose were obtained by using small cylindrical vials, which were filled with the PAGAT polymer gel from the same batch as for the spherical phantom. 1D and 2D data obtained using gel dosimeter for homogeneous and inhomogeneous phantoms were compared with dose obtained using LGP calculation. The distance between relative isodose curves obtained for homogeneous phantom and heterogeneous phantoms exceed the accepted total positioning error (>±2mm). The findings of this study indicate that dose measurement using PAGAT gel dosimeter can be used for verifying dose delivering accuracy in GK unit in presence of inhomogeneities.

Determination of small field synthetic single-crystal diamond detector correction factors for CyberKnife, Leksell Gamma Knife Perfexion and linear accelerator.

PubMed

Veselsky, T; Novotny, J; Pastykova, V; Koniarova, I

2017-12-01

The aim of this study was to determine small field correction factors for a synthetic single-crystal diamond detector (PTW microDiamond) for routine use in clinical dosimetric measurements. Correction factors following small field Alfonso formalism were calculated by comparison of PTW microDiamond measured ratio M Qclin fclin /M Qmsr fmsr with Monte Carlo (MC) based field output factors Ω Qclin,Qmsr fclin,fmsr determined using Dosimetry Diode E or with MC simulation itself. Diode measurements were used for the CyberKnife and Varian Clinac 2100C/D linear accelerator. PTW microDiamond correction factors for Leksell Gamma Knife (LGK) were derived using MC simulated reference values from the manufacturer. PTW microDiamond correction factors for CyberKnife field sizes 25-5 mm were mostly smaller than 1% (except for 2.9% for 5 mm Iris field and 1.4% for 7.5 mm fixed cone field). The correction of 0.1% and 2.0% for 8 mm and 4 mm collimators, respectively, needed to be applied to PTW microDiamond measurements for LGK Perfexion. Finally, PTW microDiamond M Qclin fclin /M Qmsr fmsr for the linear accelerator varied from MC corrected Dosimetry Diode data by less than 0.5% (except for 1 × 1 cm 2 field size with 1.3% deviation). Regarding low resulting correction factor values, the PTW microDiamond detector may be considered an almost ideal tool for relative small field dosimetry in a large variety of stereotactic and radiosurgery treatment devices. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

International Radiosurgery Support Association

MedlinePlus

... Tumors Brain Disorders AVMs Radiosurgery Gamma Knife Linac Radiotherapy Overview Childhood Brain Tumors Radiation Therapy Radiation Injury ... Guideline Trigeminal Neuralgia | TN Guideline ... conventional x-ray imaging procedures [New England Journal of Medicine] Read ...

Stereotactic Radiosurgery - Gamma Knife

MedlinePlus

... nerve that connects the ear to the brain ( acoustic neuroma ) Pituitary tumors Tumors that are not cancer ( ... and the A.D.A.M. Editorial team. Acoustic Neuroma Read more Brain Tumors Read more Radiation ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barrett, J C; Karmanos Cancer Institute McLaren-Macomb, Clinton Township, MI; Knill, C

Purpose: To determine small field correction factors for PTW’s microDiamond detector in Elekta’s Gamma Knife Model-C unit. These factors allow the microDiamond to be used in QA measurements of output factors in the Gamma Knife Model-C; additionally, the results also contribute to the discussion on the water equivalence of the relatively-new microDiamond detector and its overall effectiveness in small field applications. Methods: The small field correction factors were calculated as k correction factors according to the Alfonso formalism. An MC model of the Gamma Knife and microDiamond was built with the EGSnrc code system, using BEAMnrc and DOSRZnrc user codes.more » Validation of the model was accomplished by simulating field output factors and measurement ratios for an available ABS plastic phantom and then comparing simulated results to film measurements, detector measurements, and treatment planning system (TPS) data. Once validated, the final k factors were determined by applying the model to a more waterlike solid water phantom. Results: During validation, all MC methods agreed with experiment within the stated uncertainties: MC determined field output factors agreed within 0.6% of the TPS and 1.4% of film; and MC simulated measurement ratios matched physically measured ratios within 1%. The final k correction factors for the PTW microDiamond in the solid water phantom approached unity to within 0.4%±1.7% for all the helmet sizes except the 4 mm; the 4 mm helmet size over-responded by 3.2%±1.7%, resulting in a k factor of 0.969. Conclusion: Similar to what has been found in the Gamma Knife Perfexion, the PTW microDiamond requires little to no corrections except for the smallest 4 mm field. The over-response can be corrected via the Alfonso formalism using the correction factors determined in this work. Using the MC calculated correction factors, the PTW microDiamond detector is an effective dosimeter in all available helmet sizes. The authors would like to thank PTW (Friedberg, Germany) for providing the PTW microDiamond detector for this research.« less

γTools: A modular multifunction phantom for quality assurance in GammaKnife treatments.

PubMed

Calusi, Silvia; Noferini, Linhsia; Marrazzo, Livia; Casati, Marta; Arilli, Chiara; Compagnucci, Antonella; Talamonti, Cinzia; Scoccianti, Silvia; Greto, Daniela; Bordi, Lorenzo; Livi, Lorenzo; Pallotta, Stefania

2017-11-01

We present the γTools, a new phantom designed to assess geometric and dosimetric accuracy in Gamma Knife treatments, together with first tests and results of applications. The phantom is composed of two modules: the imaging module, a regular grid of 1660 control points to evaluate image distortions and image registration result and the dosimetry module for delivered dose distribution measurements. The phantom is accompanied by a MatLab routine for image distortions quantification. Dose measurement are performed with Gafchromic films fixed between two inserts and placed in various positions and orientations inside the dosimetry module thus covering a volume comparable to the full volume of a head. Tests performed to assess the accuracy and precision of the imaging module demonstrated sub-millimetric values. As an example of possible applications, the phantom was employed to measure image distortions of two MRI scanners and to perform dosimetric studies of single shots delivered to homogeneous and heterogeneous materials. Due to the phantom material, the measured absolute dose do not correspond to the planned dose; doses comparisons are thus carried out between normalized dose distributions. Finally, an end-to-end test was carried out in the treatment of a neuroma-like target which resulted in a 100% gamma passing rate (2% local, 2 mm) and a distance between the real target perimeter and the prescription isodose centroids of about 1 mm. The tests demonstrate that the proposed phantom is suitable to assess both the geometrical and relative dosimetric accuracy of Gamma Knife radiosurgery treatments. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Emerging Indications for Fractionated Gamma Knife Radiosurgery

PubMed Central

McTyre, Emory; Helis, Corbin A.; Farris, Michael; Wilkins, Lisa; Sloan, Darrell; Hinson, William H.; Bourland, J. Daniel; Dezarn, William. A.; Munley, Michael T.; Watabe, Kounosuke; Xing, Fei; Laxton, Adrian W.; Tatter, Stephen B.; Chan, Michael D.

2016-01-01

BACKGROUND Gamma Knife radiosurgery (GKRS) allows for the treatment of intracranial tumors with a high degree of dose conformality and precision. There are, however, certain situations wherein the dose conformality of GKRS is desired, but single session treatment is contraindicated. In these situations, a traditional pin-based GKRS head frame cannot be used, as it precludes fractionated treatment. OBJECTIVE To report our experience in treating patients with fractionated GKRS using a relocatable, noninvasive immobilization system. METHODS Patients were considered candidates for fractionated GKRS if they had one or more of the following indications: a benign tumor >10 cc in volume or abutting the optic pathway, a vestibular schwannoma with the intent of hearing preservation, or a tumor previously irradiated with single fraction GKRS. The immobilization device used for all patients was the Extend system (Leksell Gamma Knife Perfexion, Elekta, Kungstensgatan, Stockholm). RESULTS We identified 34 patients treated with fractionated GKRS between August 2013 and February 2015. There were a total of 37 tumors treated including 15 meningiomas, 11 pituitary adenomas, 6 brain metastases, 4 vestibular schwannomas, and 1 hemangioma. At last follow-up, all 21 patients treated for perioptic tumors had stable or improved vision and all 4 patients treated for vestibular schwannoma maintained serviceable hearing. No severe adverse events were reported. CONCLUSION Fractionated GKRS was well-tolerated in the treatment of large meningiomas, perioptic tumors, vestibular schwannomas with intent of hearing preservation, and in reirradiation of previously treated tumors. PMID:28536486

Gamma Knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part II: Differences in obliteration rates, treatment-obliteration intervals, and prognostic factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicolato, Antonio; Lupidi, Francesco; Section of Sterotactic and Functional Neurosurgery, University of Verona and University Hospital, Verona

2006-03-01

Purpose: To evaluate and compare obliteration rates (OBRs) and treatment-obliteration intervals (TOIs) for cerebral arteriovenous malformations (cAVMs) treated with Gamma Knife radiosurgery in children/adolescents and adults; and to determine factors predicting the OBR and TOI in these two populations. Methods and Materials: This study concerned 62 children/adolescents and 193 adults observed for {>=}3 years. Fisher exact two-tailed and Wilcoxon rank-sum tests, multiple logistics, and Cox proportional hazard models were used for statistical analysis. Results: The overall OBR was 85.5% in children/adolescents and 87.6% in adults (p 0.671), but children/adolescents showed higher 36-month actuarial OBRs (69.35%) and shorter median TOIs (25.7more » months) than adults (66.84% and 28.2 months; p 0.006 and p = 0.017, respectively). In children/adolescents, lower Spetzler-Martin grades (p = 0.043) and younger age (p = 0.019) correlated significantly with OBRs, and lower Spetzler-Martin grades (p 0.024) and noneloquent cAVM locations (p = 0.046) with TOIs. In adults, low flow through the cAVM and <6.2-cm{sup 3} volume were associated with both OBR and TOI (p 0.012 and p = 0.002, respectively). Conclusions: The differences in OBRs within 3 years and TOIs, although slight, seem to show that pediatric cAVMs behave differently from those in adults after Gamma Knife radiosurgery.« less

Complications Following Linear Accelerator Based Stereotactic Radiation for Cerebral Arteriovenous Malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skjoth-Rasmussen, Jane, E-mail: jane@skjoeth-rasmussen.d; Roed, Henrik; Ohlhues, Lars

2010-06-01

Purpose: Primarily, gamma knife centers are predominant in publishing results on arteriovenous malformations (AVM) treatments including reports on risk profile. However, many patients are treated using a linear accelerator-most of these at smaller centers. Because this setting is different from a large gamma knife center, the risk profile at Linac departments could be different from the reported experience. Prescribed radiation doses are dependent on AVM volume. This study details results from a medium sized Linac department center focusing on risk profiles. Method and Materials: A database was searched for all patients with AVMs. We included 50 consecutive patients with amore » minimum of 24 months follow-up (24-51 months). Results: AVM occlusion was verified in 78% of patients (39/50). AVM occlusion without new deficits (excellent outcome) was obtained in 44%. Good or fair outcome (AVM occlusion with mild or moderate new deficits) was seen in 30%. Severe complications after AVM occlusion occurred in 4% with a median interval of 15 months after treatment (range, 1-26 months). Conclusions: We applied an AVM grading score developed at the Mayo Clinic to predict probable outcome after radiosurgery in a large patient population treated with Gamma knife. A cutoff above and below a score of 1.5 could not discriminate between the likelihood of having an excellent outcome (approximately 45%). The chance of having an excellent or good outcome was slightly higher in patients with an AVM score below 1.5 (64% vs. 57%).« less

Gamma Knife Radiosurgery as a Therapeutic Strategy for Intracranial Sarcomatous Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flannery, Thomas; Department of Radiation Oncology, University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center, Pittsburgh, PA; Department of Neurosurgery, Royal Hospitals Trust, Belfast, Northern Ireland

2010-02-01

Purpose: To determine the indication and outcomes for Gamma Knife stereotactic radiosurgery (GKSRS) in the care of patients with intracranial sarcomatous metastases. Methods and Materials: Data from 21 patients who underwent radiosurgery for 60 sarcomatous intracranial metastases (54 parenchymal and 6 dural-based) were studied. Nine patients had radiosurgery for solitary tumors and 12 for multiple tumors. The primary pathology was metastatic leiomyosarcoma (4 patients), osteosarcoma (3 patients), soft-tissue sarcoma (5 patients), chondrosarcoma (2 patients), alveolar soft part sarcoma (2 patients), and rhabdomyosarcoma, Ewing's sarcoma, liposarcoma, neurofibrosarcoma, and synovial sarcoma (1 patient each). Twenty patients received multimodality management for their primarymore » tumor, and 1 patient had no evidence of systemic disease. The mean tumor volume was 6.2 cm{sup 3} (range, 0.07-40.9 cm{sup 3}), and a median margin dose of 16 Gy was administered. Three patients had progressive intracranial disease despite fractionated whole-brain radiotherapy before SRS. Results: A local tumor control rate of 88% was achieved (including patients receiving boost, up-front, and salvage SRS). New remote brain metastases developed in 7 patients (33%). The median survival after diagnosis of intracranial metastasis was 16 months, and the 1-year survival rate was 61%. Conclusions: Gamma Knife radiosurgery was a well-tolerated and initially effective therapy in the management of patients with sarcomatous intracranial metastases. However, many patients, including those who also received fractionated whole-brain radiotherapy, developed progressive new brain disease.« less

Complications following linear accelerator based stereotactic radiation for cerebral arteriovenous malformations.

PubMed

Skjøth-Rasmussen, Jane; Roed, Henrik; Ohlhues, Lars; Jespersen, Bo; Juhler, Marianne

2010-06-01

Primarily, gamma knife centers are predominant in publishing results on arteriovenous malformations (AVM) treatments including reports on risk profile. However, many patients are treated using a linear accelerator-most of these at smaller centers. Because this setting is different from a large gamma knife center, the risk profile at Linac departments could be different from the reported experience. Prescribed radiation doses are dependent on AVM volume. This study details results from a medium sized Linac department center focusing on risk profiles. A database was searched for all patients with AVMs. We included 50 consecutive patients with a minimum of 24 months follow-up (24-51 months). AVM occlusion was verified in 78% of patients (39/50). AVM occlusion without new deficits (excellent outcome) was obtained in 44%. Good or fair outcome (AVM occlusion with mild or moderate new deficits) was seen in 30%. Severe complications after AVM occlusion occurred in 4% with a median interval of 15 months after treatment (range, 1-26 months). We applied an AVM grading score developed at the Mayo Clinic to predict probable outcome after radiosurgery in a large patient population treated with Gamma knife. A cutoff above and below a score of 1.5 could not discriminate between the likelihood of having an excellent outcome (approximately 45%). The chance of having an excellent or good outcome was slightly higher in patients with an AVM score below 1.5 (64% vs. 57%). Copyright 2010 Elsevier Inc. All rights reserved.

SU-F-T-370: A Fast Monte Carlo Dose Engine for Gamma Knife

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, T; Zhou, L; Li, Y

2016-06-15

Purpose: To develop a fast Monte Carlo dose calculation algorithm for Gamma Knife. Methods: To make the simulation more efficient, we implemented the track repeating technique on GPU. We first use EGSnrc to pre-calculate the photon and secondary electron tracks in water from two mono-energy photons of 60Co. The total photon mean free paths for different materials and energies are obtained from NIST. During simulation, each entire photon track was first loaded to shared memory for each block, the incident original photon was then splitted to Nthread sub-photons, each thread transport one sub-photon, the Russian roulette technique was applied formore » scattered and bremsstrahlung photons. The resultant electrons from photon interactions are simulated by repeating the recorded electron tracks. The electron step length is stretched/shrunk proportionally based on the local density and stopping power ratios of the local material. Energy deposition in a voxel is proportional to the fraction of the equivalent step length in that voxel. To evaluate its accuracy, dose deposition in a 300mm*300mm*300mm water phantom is calculated, and compared to EGSnrc results. Results: Both PDD and OAR showed great agreements (within 0.5%) between our dose engine result and the EGSnrc result. It only takes less than 1 min for every simulation, being reduced up to ∼40 times compared to EGSnrc simulations. Conclusion: We have successfully developed a fast Monte Carlo dose engine for Gamma Knife.« less

Dose verification to cochlea during gamma knife radiosurgery of acoustic schwannoma using MOSFET dosimeter.

PubMed

Sharma, Sunil D; Kumar, Rajesh; Akhilesh, Philomina; Pendse, Anil M; Deshpande, Sudesh; Misra, Basant K

2012-01-01

Dose verification to cochlea using metal oxide semiconductor field effect transistor (MOSFET) dosimeter using a specially designed multi slice head and neck phantom during the treatment of acoustic schwannoma by Gamma Knife radiosurgery unit. A multi slice polystyrene head phantom was designed and fabricated for measurement of dose to cochlea during the treatment of the acoustic schwannoma. The phantom has provision to position the MOSFET dosimeters at the desired location precisely. MOSFET dosimeters of 0.2 mm x 0.2 mm x 0.5 μm were used to measure the dose to the cochlea. CT scans of the phantom with MOSFETs in situ were taken along with Leksell frame. The treatment plans of five patients treated earlier for acoustic schwannoma were transferred to the phantom. Dose and coordinates of maximum dose point inside the cochlea were derived. The phantom along with the MOSFET dosimeters was irradiated to deliver the planned treatment and dose received by cochlea were measured. The treatment planning system (TPS) estimated and measured dose to the cochlea were in the range of 7.4 - 8.4 Gy and 7.1 - 8 Gy, respectively. The maximum variation between TPS calculated and measured dose to cochlea was 5%. The measured dose values were found in good agreement with the dose values calculated using the TPS. The MOSFET dosimeter can be a suitable choice for routine dose verification in the Gamma Knife radiosurgery.

Stereotactic radiosurgery versus stereotactic radiotherapy for patients with vestibular schwannoma: a Leksell Gamma Knife Society 2000 debate.

PubMed

Linskey, M E

2000-12-01

By definition, the term "radiosurgery" refers to the delivery of a therapeutic radiation dose in a single fraction, not simply the use of stereotaxy. Multiple-fraction delivery is better termed "stereotactic radiotherapy." There are compelling radiobiological principles supporting the biological superiority of single-fraction radiation for achieving an optimal therapeutic response for the slowly proliferating, late-responding, tissue of a schwannoma. It is axiomatic that complication avoidance requires precise three-dimensional conformality between treatment and tumor volumes. This degree of conformality can only be achieved through complex multiisocenter planning. Alternative radiosurgery devices are generally limited to delivering one to four isocenters in a single treatment session. Although they can reproduce dose plans similar in conformality to early gamma knife dose plans by using a similar number of isocenters, they cannot reproduce the conformality of modern gamma knife plans based on magnetic resonance image-targeted localization and five to 30 isocenters. A disturbing trend is developing in which institutions without nongamma knife radiosurgery (GKS) centers are championing and/or shifting to hypofractionated stereotactic radiotherapy for vestibular schwannomas. This trend appears to be driven by a desire to reduce complication rates to compete with modern GKS results by using complex multiisocenter planning. Aggressive advertising and marketing from some of these centers even paradoxically suggests biological superiority of hypofractionation approaches over single-dose radiosurgery for vestibular schwannomas. At the same time these centers continue to use the term radiosurgery to describe their hypofractionated radiotherapy approach in an apparent effort to benefit from a GKS "halo effect." It must be reemphasized that as neurosurgeons our primary duty is to achieve permanent tumor control for our patients and not to eliminate complications at the expense of potential late recurrence. The answer to minimizing complications while maintaining maximum tumor control is improved conformality of radiosurgery dose planning and not resorting to homeopathic radiosurgery doses or hypofractionation radiotherapy schemes.

Stereotactic radiosurgery versus stereotactic radiotherapy for patients with vestibular schwannoma: a Leksell Gamma Knife Society 2000 debate.

PubMed

Linskey, Mark E

2013-12-01

By definition, the term "radiosurgery" refers to the delivery of a therapeutic radiation dose in a single fraction, not simply the use of stereotaxy. Multiple-fraction delivery is better termed "stereotactic radiotherapy." There are compelling radiobiological principles supporting the biological superiority of single-fraction radiation for achieving an optimal therapeutic response for the slowly proliferating, late-responding, tissue of a schwannoma. It is axiomatic that complication avoidance requires precise three-dimensional conformality between treatment and tumor volumes. This degree of conformality can only be achieved through complex multiisocenter planning. Alternative radiosurgery devices are generally limited to delivering one to four isocenters in a single treatment session. Although they can reproduce dose plans similar in conformality to early gamma knife dose plans by using a similar number of isocenters, they cannot reproduce the conformality of modern gamma knife plans based on magnetic resonance image--targeted localization and five to 30 isocenters. A disturbing trend is developing in which institutions without nongamma knife radiosurgery (GKS) centers are championing and/or shifting to hypofractionated stereotactic radiotherapy for vestibular schwannomas. This trend appears to be driven by a desire to reduce complication rates to compete with modern GKS results by using complex multiisocenter planning. Aggressive advertising and marketing from some of these centers even paradoxically suggests biological superiority of hypofractionation approaches over single-dose radiosurgery for vestibular schwannomas. At the same time these centers continue to use the term radiosurgery to describe their hypofractionated radiotherapy approach in an apparent effort to benefit from a GKS "halo effect." It must be reemphasized that as neurosurgeons our primary duty is to achieve permanent tumor control for our patients and not to eliminate complications at the expense of potential late recurrence. The answer to minimizing complications while maintaining maximum tumor control is improved conformality of radiosurgery dose planning and not resorting to homeopathic radiosurgery doses or hypofractionation radiotherapy schemes.

Dosimetric effects of Onyx embolization on Gamma Knife arteriovenous malformation dose distributions.

PubMed

Schlesinger, David J; Nordström, Håkan; Lundin, Anders; Xu, Zhiyuan; Sheehan, Jason P

2016-12-01

OBJECTIVE Patients with arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) subsequent to embolization suffer from elevated local failure rates and differences in adverse radiation effects. Onyx is a common embolic material for AVMs. Onyx is formulated with tantalum, a high atomic number (Z = 73) element that has been investigated as a source of dosimetric uncertainty contributing to the less favorable clinical results. However, prior studies have not modeled the complicated anatomical and beam geometries characteristic of GKRS. This study investigated the magnitude of dose perturbation that can occur due to Onyx embolization using clinically realistic anatomical and Gamma Knife beam models. METHODS Leksell GammaPlan (LGP) was used to segment the AVM nidus and areas of Onyx from postcontrast stereotactic MRI for 7 patients treated with GKRS postembolization. The resulting contours, skull surface, and clinically selected dose distributions were exported from LGP in DICOM-RT (Digital Imaging and Communications in Medicine-radiotherapy) format. Isocenter locations and dwell times were recorded from the LGP database. Contours were converted into 3D mesh representations using commercial and in-house mesh-editing software. The resulting data were imported into a Monte Carlo (MC) dose calculation engine (Pegasos, Elekta Instruments AB) with a beam geometry for the Gamma Knife Perfexion. The MC-predicted dose distributions were calculated with Onyx assigned manufacturer-reported physical constants (MC-Onyx), and then compared with corresponding distributions in which Onyx was reassigned constants for water (MC-water). Differences in dose metrics were determined, including minimum, maximum, and mean dose to the AVM nidus; selectivity index; and target coverage. Combined differences in dose magnitude and distance to agreement were calculated as 3D Gamma analysis passing rates using tolerance criteria of 0.5%/0.5 mm, 1.0%/1.0 mm, and 3.0%/3.0 mm. RESULTS Overall, the mean percentage differences in dose metrics for MC-Onyx relative to MC-water were as follows; all data are reported as mean (SD): minimum dose to AVM = -0.7% (1.4%), mean dose to AVM = 0.1% (0.2%), maximum dose to AVM = 2.9% (5.0%), selectivity = 0.1% (0.2%), and coverage = -0.0% (0.2%). The mean percentage of voxels passing at each Gamma tolerance were as follows: 99.7% (0.1%) for 3.0%/3.0 mm, 98.2% (0.7%) for 1.0%/1.0 mm, and 52.1% (4.4%) for 0.5%/0.5 mm. CONCLUSIONS Onyx embolization appears to have a detectable effect on the delivered dose distribution. However, the small changes in dose metrics and high Gamma passing rates at 1.0%/1.0 mm tolerance suggest that these changes are unlikely to be clinically significant. Additional sources of delivery and biological uncertainty should be investigated to determine the root cause of the observed less favorable postembolization GKRS outcomes.

Advanced image fusion algorithms for Gamma Knife treatment planning. Evaluation and proposal for clinical use.

PubMed

Apostolou, N; Papazoglou, Th; Koutsouris, D

2006-01-01

Image fusion is a process of combining information from multiple sensors. It is a useful tool implemented in the treatment planning programme of Gamma Knife Radiosurgery. In this paper we evaluate advanced image fusion algorithms for Matlab platform and head images. We develop nine level grayscale image fusion methods: average, principal component analysis (PCA), discrete wavelet transform (DWT) and Laplacian, filter - subtract - decimate (FSD), contrast, gradient, morphological pyramid and a shift invariant discrete wavelet transform (SIDWT) method in Matlab platform. We test these methods qualitatively and quantitatively. The quantitative criteria we use are the Root Mean Square Error (RMSE), the Mutual Information (MI), the Standard Deviation (STD), the Entropy (H), the Difference Entropy (DH) and the Cross Entropy (CEN). The qualitative are: natural appearance, brilliance contrast, presence of complementary features and enhancement of common features. Finally we make clinically useful suggestions.

Initial experience with gamma knife surgery for endocrine ophthalmopathy.

PubMed

Antico, Julio C; Crovetto, Luis; Tenca, Eduardo; Artes, Carlos

2005-01-01

The aim of this study was to evaluate both the effectiveness and safety of the treatment of endocrine ophthalmopathy with gamma knife surgery (GKS). Five patients were included in a prospective study designed to assess the results of GKS of endocrine ophthalmopathy secondary to Graves disease. All the patients completed a 2-year follow-up period. During this period, the patients were evaluated both clinically and by means of additional methods, including computerized tomography and magnetic resonance imaging studies. The minimum dose delivered to the 50% isodose line was 6.5 Gy in all the patients. In all cases, a clinical improvement was observed. The best effect was seen in symptom regression related to soft-tissue involvement. No treatment-related side effects were detected. In light of the results obtained the authors consider that GKS may be a safe and effective way to treat endocrine ophthalmopathy.

Validation of a pretreatment delivery quality assurance method for the CyberKnife Synchrony system.

PubMed

Mastella, E; Vigorito, S; Rondi, E; Piperno, G; Ferrari, A; Strata, E; Rozza, D; Jereczek-Fossa, B A; Cattani, F

2016-08-01

To evaluate the geometric and dosimetric accuracies of the CyberKnife Synchrony respiratory tracking system (RTS) and to validate a method for pretreatment patient-specific delivery quality assurance (DQA). An EasyCube phantom was mounted on the ExacTrac gating phantom, which can move along the superior-inferior (SI) axis of a patient to simulate a moving target. The authors compared dynamic and static measurements. For each case, a Gafchromic EBT3 film was positioned between two slabs of the EasyCube, while a PinPoint ionization chamber was placed in the appropriate space. There were three steps to their evaluation: (1) the field size, the penumbra, and the symmetry of six secondary collimators were measured along the two main orthogonal axes. Dynamic measurements with deliberately simulated errors were also taken. (2) The delivered dose distributions (from step 1) were compared with the planned ones, using the gamma analysis method. The local gamma passing rates were evaluated using three acceptance criteria: 3% local dose difference (LDD)/3 mm, 2%LDD/2 mm, and 3%LDD/1 mm. (3) The DQA plans for six clinical patients were irradiated in different dynamic conditions, to give a total of 19 cases. The measured and planned dose distributions were evaluated with the same gamma-index criteria used in step 2 and the measured chamber doses were compared with the planned mean doses in the sensitive volume of the chamber. (1) A very slight enlargement of the field size and of the penumbra was observed in the SI direction (on average <1 mm), in line with the overall average CyberKnife system error for tracking treatments. (2) Comparison between the planned and the correctly delivered dose distributions confirmed the dosimetric accuracy of the RTS for simple plans. The multicriteria gamma analysis was able to detect the simulated errors, proving the robustness of their method of analysis. (3) All of the DQA clinical plans passed the tests, both in static and dynamic conditions. No statistically significant differences were found between static and dynamic cases, confirming the high degree of accuracy of the Synchrony RTS. The presented methods and measurements verified the mechanical and dosimetric accuracy of the Synchrony RTS. Their method confirms the fact that the RTS, if used properly, is able to treat a moving target with great precision. By combining PinPoint ion chamber, EBT3 films, and gamma evaluation of dose distributions, their DQA method robustly validated the effectiveness of CyberKnife and Synchrony system.

Radiological aspects of gamma knife radiosurgery for arteriovenous malformations and other non-tumoural disorders of the brain.

PubMed

Guo, W Y

1993-01-01

The aims of the thesis were to investigate stereotaxic procedures in radiosurgery for cerebral arteriovenous malformations (AVMs) and radiation effects of single session high-dose irradiation delivered by gamma knife on the human brain. Investigation of gamma knife radiosurgery in 1,464 patients constitutes the data base of this thesis. High quality stereotaxic angiography is the gold standard targeting imaging in radiosurgery for cerebral AVMs, particularly for small AVMs or residual AVMs after other treatments. For medium and large size AVMs, stereotaxic MR techniques can improve targeting precision and decrease irradiation volume as compared to stereotaxic angiography in selected cases provided that proper pulse sequences are used. Combined treatments, where embolization precedes radiosurgery, can improve amenability of the treatment for large AVMs. This is on condition that the partially embolized nidi are well delineated and the volume of the residual nidi has been decreased to a level where an optimum irradiation can be safely prescribed. Radiologically, adverse radiation effects (ARE) of gamma knife radiosurgery for cerebral AVMs are observed in 16% (131/816) of the patients. The ARE are observed as a focal low attenuation on CT or as a focal high signal on MR image without enhancement in 47% (61/131), and as a peripheral or homogeneous enhancing lesion in 48% (63/131). MR imaging is more sensitive than CT in detecting the ARE. 91% of the ARE are observed within 18 months after radiosurgery and 89% are seen to regress within 18 months. Clinically, symptomatic ARE are only observed in 6% (51/816) and only in half of them, i.e. 3%, are the symptoms permanent. The risk of ARE in radiosurgery for venous angiomas is higher as compared to AVMs. Other mechanisms have probably been employed. In gamma capsulotomy, the necrotic lesions and reaction volumes created by using multiple isocentres of 4 mm collimators are less predictable as compared to that by single isocentre. Volume effects and depreciation of the steep isodose gradient are hypothesised as the leading factors of the inconsistency. Based on the in vivo assessment of the radiation effects observed on the basically normal human brain it is concluded that irradiation volume is strongly related to the radiation effects and is one of the important considerations in decision making for radiosurgery. Volume of brain tissue exposed to irradiation could be minimised and precision of targeting could be maximised provided that a proper stereotaxic imaging is used.(ABSTRACT TRUNCATED AT 400 WORDS)

Assessment of absorbed dose to thyroid, parotid and ovaries in patients undergoing Gamma Knife radiosurgery.

PubMed

Hasanzadeh, H; Sharafi, A; Allah Verdi, M; Nikoofar, A

2006-09-07

Stereotactic radiosurgery was originally introduced by Lars Leksell in 1951. This treatment refers to the noninvasive destruction of an intracranial target localized stereotactically. The purpose of this study was to identify the dose delivered to the parotid, ovaries, testis and thyroid glands during the Gamma Knife radiosurgery procedure. A three-dimensional, anthropomorphic phantom was developed using natural human bone, paraffin and sodium chloride as the equivalent tissue. The phantom consisted of a thorax, head and neck and hip. In the natural places of the thyroid, parotid (bilateral sides) and ovaries (midline), some cavities were made to place TLDs. Three TLDs were inserted in a batch with 1 cm space between the TLDs and each batch was inserted into a single cavity. The final depth of TLDs was 3 cm from the surface for parotid and thyroid and was 15 cm for the ovaries. Similar batches were placed superficially on the phantom. The phantom was gamma irradiated using a Leksell model C Gamma Knife unit. Subsequently, the same batches were placed superficially over the thyroid, parotid, testis and ovaries in 30 patients (15 men and 15 women) who were undergoing radiosurgery treatment for brain tumours. The mean dosage for treating these patients was 14.48 +/- 3.06 Gy (10.5-24 Gy) to a mean tumour volume of 12.30 +/- 9.66 cc (0.27-42.4 cc) in the 50% isodose curve. There was no significant difference between the superficial and deep batches in the phantom studies (P-value < 0.05). The mean delivered doses to the parotid, thyroid, ovaries and testis in human subjects were 21.6 +/- 15.1 cGy, 9.15 +/- 3.89 cGy, 0.47 +/- 0.3 cGy and 0.53 +/- 0.31 cGy, respectively. The data can be used in making decisions for special clinical situations such as treating pregnant patients or young patients with benign lesions who need radiosurgery for eradication of brain tumours.

SU-F-J-166: Volumetric Spatial Distortions Comparison for 1.5 Tesla Versus 3 Tesla MRI for Gamma Knife Radiosurgery Scans Using Frame Marker Fusion and Co-Registration Modes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neyman, G

Purpose: To compare typical volumetric spatial distortions for 1.5 Tesla versus 3 Tesla MRI Gamma Knife radiosurgery scans in the frame marker fusion and co-registration frame-less modes. Methods: Quasar phantom by Modus Medical Devices Inc. with GRID image distortion software was used for measurements of volumetric distortions. 3D volumetric T1 weighted scans of the phantom were produced on 1.5 T Avanto and 3 T Skyra MRI Siemens scanners. The analysis was done two ways: for scans with localizer markers from the Leksell frame and relatively to the phantom only (simulated co-registration technique). The phantom grid contained a total of 2002more » vertices or control points that were used in the assessment of volumetric geometric distortion for all scans. Results: Volumetric mean absolute spatial deviations relatively to the frame localizer markers for 1.5 and 3 Tesla machine were: 1.39 ± 0.15 and 1.63 ± 0.28 mm with max errors of 1.86 and 2.65 mm correspondingly. Mean 2D errors from the Gamma Plan were 0.3 and 1.0 mm. For simulated co-registration technique the volumetric mean absolute spatial deviations relatively to the phantom for 1.5 and 3 Tesla machine were: 0.36 ± 0.08 and 0.62 ± 0.13 mm with max errors of 0.57 and 1.22 mm correspondingly. Conclusion: Volumetric spatial distortions are lower for 1.5 Tesla versus 3 Tesla MRI machines localized with markers on frames and significantly lower for co-registration techniques with no frame localization. The results show the advantage of using co-registration technique for minimizing MRI volumetric spatial distortions which can be especially important for steep dose gradient fields typically used in Gamma Knife radiosurgery. Consultant for Elekta AB.« less

Gamma knife radiosurgery for vestibular schwannomas: tumor control and functional preservation in 70 patients.

PubMed

Arthurs, Benjamin J; Lamoreaux, Wayne T; Mackay, Alexander R; Demakas, John J; Giddings, Neil A; Fairbanks, Robert K; Cooke, Barton S; Elaimy, Ameer L; Peressini, Ben; Lee, Christopher M

2011-06-01

We present the previously unreported outcomes of 70 patients treated with Gamma knife radiosurgery for vestibular schwannoma (VS), including comprehensive analysis of clinical outcomes and the effects of lower marginal doses. We performed a retrospective study of patients treated for VS at Gamma knife of Spokane between 2003 and 2008. Endpoints measured include tumor control, hearing preservation, and facial nerve preservation, including the effect of tumor size and marginal dose. Statistical analysis was performed with Wilcoxon signed-rank test, paired Student t test, Mann-Whitney U test, Kendall's rank correlation, Fisher exact test, and Liddell's exact χ(2) test for matched pairs. With a mean follow-up of 26 months, 93.8% of tumors either shrank or remained static after receiving a mean marginal dose of 12.7 Gy. Tumor control was independent of marginal dose or tumor size. Hearing preservation was achieved in 64% of patients with serviceable function before the treatment. Hearing changes were independent of dose or tumor size. Preservation of good facial nerve function was achieved in 95% of patients. Post-treatment hydrocephalus occurred in 4.4% of patients, but no other significant morbidities were elucidated. In the treatment of VS, contemporary radiosurgical techniques and the use of marginal doses below 13 Gy offer excellent tumor control, at high rates relative to surgical intervention. These findings are independent of marginal dose and tumor size. Patients should be informed about the benefits and risks of radiosurgery and microsurgery before choosing an intervention. Further analysis of post-treatment outcomes should be encouraged as follow-up times increase and the treatment protocols continue to evolve.

Gamma knife radiosurgery for glomus jugulare tumors: therapeutic advantages of minimalism in the skull base.

PubMed

Sharma, Manish S; Gupta, A; Kale, S S; Agrawal, D; Mahapatra, A K; Sharma, B S

2008-01-01

Glomus jugulare (GJ) tumors are paragangliomas found in the region of the jugular foramen. Surgery with/without embolization and conventional radiotherapy has been the traditional management option. To analyze the efficacy of gamma knife radiosurgery (GKS) as a primary or an adjunctive form of therapy. A retrospective analysis of patients who received GKS at a tertiary neurosurgical center was performed. Of the 1601 patients who underwent GKS from 1997 to 2006, 24 patients with GJ underwent 25 procedures. The average age of the cohort was 46.6 years (range, 22-76 years) and the male to female ratio was 1:2. The most common neurological deficit was IX, X, XI cranial nerve paresis (15/24). Fifteen patients received primary GKS. Mean tumor size was 8.7 cc (range 1.1-17.2 cc). The coverage achieved was 93.1% (range 90-97%) using a mean tumor margin dose of 16.4 Gy (range 12-25 Gy) at a mean isodose of 49.5% (range 45-50%). Thirteen patients (six primary and seven secondary) were available for follow-up at a median interval of 24 months (range seven to 48 months). The average tumor size was 7.9 cc (range 1.1-17.2 cc). Using a mean tumor margin dose of 16.3 Gy (range 12-20 Gy) 93.6% coverage (range 91-97%) was achieved. Six patients improved clinically. A single patient developed transient trigeminal neuralgia. Magnetic resonance imaging follow-up was available for 10 patients; seven recorded a decrease in size. There was no tumor progression. Gamma knife radiosurgery is a safe and effective primary and secondary modality of treatment for GJ.

[The Effect of Pain Relieving Intervention During Infiltration among Gamma Knife Surgery Patients for Stereotactic Frame Fixation].

PubMed

Jang, Young Jun; Kim, Hyeon Ok

2018-04-01

This study aimed to compare the effects of three interventions on pain, blood pressure, and pulse rate during infiltration anesthesia in patients about to undergo gamma knife surgeries. The three interventions employed in a university-affiliated Hospital in J City, South Korea were as follows: EMLA cream plus Vapocoolant spray (Vapocoolant, n=30), EMLA cream plus 10.0% Lidocaine spray (Lidocaine, n=30), and EMLA cream only (EMLA, n=30). The equivalent control-group pre test - post test study design was used. Pain was assessed subjectively using the numeric rating scale (NRS) and objectively using a Galvanic Skin Response (GSR) tester. NRS scores were assessed after infiltration anesthesia and the GSR was assessed during infiltration anesthesia. Blood pressure and pulse rate were assessed twice: before and after infiltration anesthesia. Data were collected between August 3, 2016 and March 24, 2017. NRS scores after infiltration anesthesia and the GSR during infiltration anesthesia were significantly lower in the Vapocoolant group than in the Lidocaine and EMLA groups (F=13.56, p<.001 and F=14.43, p<.001, respectively). The increase in systolic blood pressure (F=4.77, p=.011) and in pulse rates (F=4.78, p=.011) before and after infiltration anesthesia were significantly smaller in the Vapocoolant group than in the Lidocaine and EMLA groups; however, no significant differences were observed in diastolic blood pressures (F=1.51, p=.227). EMLA cream plus Vapocoolant spray was the most effective intervention to relieve pain and to lower increase in systolic blood pressure and pulse rate caused by infiltration anesthesia for stereotactic frame fixation. Thus, application of Vapocoolant spray in addition to EMLA cream is highly recommended as a nursing intervention for patients undergoing gamma knife surgeries. © 2018 Korean Society of Nursing Science.

Long-term outcomes of Gamma Knife radiosurgery in patients with vestibular schwannomas.

PubMed

Murphy, Erin S; Barnett, Gene H; Vogelbaum, Michael A; Neyman, Gennady; Stevens, Glen H J; Cohen, Bruce H; Elson, Paul; Vassil, Andrew D; Suh, John H

2011-02-01

The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS). One hundred seventeen patients with VS underwent GKRS between January 1997 and February 2003. At the time of analysis, at least 5 years had passed since GKRS in all patients. The mean patient age was 60.9 years. The mean maximal tumor diameter was 1.77 ± 0.71 cm. The mean tumor volume was 1.95 ± 2.42 ml. Eighty-two percent of lesions received 1300 cGy and 14% received 1200 cGy. The median dose homogeneity ratio was 1.97 and the median dose conformality ratio was 1.78. Follow-up included MR imaging or CT scanning approximately every 6-12 months. Rates of progression to surgery were calculated using the Kaplan-Meier method. Of the 117 patients in whom data were analyzed, 103 had follow-up MR or CT images and 14 patients were lost to follow-up. Fifty-three percent of patients had stable tumors and 37.9% had a radiographically documented response. Imaging-documented tumor progression was present in 8 patients (7.8%), but in 3 of these the lesion eventually stabilized. Only 5 patients required a neurosurgical intervention. The estimated 1-, 3-, and 5-year rates of progression to surgery were 1, 4.6, and 8.9%, respectively. One patient (1%) developed trigeminal neuropathy, 4 patients (5%) developed permanent facial neuropathy, 3 patients (4%) reported vertigo, and 7 patients (18%) had new gait imbalance following GKRS. Gamma Knife radiosurgery results in excellent local control rates with minimal toxicity for patients with VS. The authors recommend standardized follow-up to gain a better understanding of the long-term effects of GKRS.

Long-term results of Gamma-knife stereotactic radiosurgery for vestibular schwannomas in patients with type 2 neurofibromatosis.

PubMed

Spatola, G; Carron, R; Delsanti, C; Thomassin, J-M; Roche, P-H; Régis, J

2016-08-12

The aim of this study was to analyze the long-term results of Gamma-knife radiosurgery treatment of vestibular schwannomas in type 2 neurofibromatosis patients. A cohort of 129 treatments for vestibular schwannomas in 103 patients was selected from a prospectively-maintained clinical database. Tumor control was assessed by volumetric analysis of the tumor at the last follow-up. Any need of a further procedure such as microsurgical removal or second treatment was regarded as a failure of tumor control. Hearing function was assessed based on Gardner-Robertson classification. Progression-free survival and functional hearing preservation rates were estimated using the Kaplan-Meier method. The median age at treatment was 34 years with no gender predominance. The median tumor volume was 1.5cm 3 . At a median clinical follow-up of 5.9 years, five patients had died, four underwent a second radiosurgical procedure and eight underwent microsurgical resection. Progression-free survival was 88 and 75% respectively at 5 and 10 years. Hearing was considered serviceable in 70 ears and remained functional in 28 ears. Kaplan-Meier estimates for 5 and 10 years functional hearing was 47 and 34%, respectively. Three patients developed new facial nerve palsy after radiosurgery at 15 days, 6 and 19 months respectively and only one partially recovered. Five patients complained of a subjective instability worsening. Four cases developed trigeminal neuropathy. No predictive factors were found to be statistically correlated with a better hearing outcome or an improved tumor growth control. Results prove less satisfying than in sporadic unilateral schwannomas. However, the lower rate of mortality and morbidity compared with microsurgical resection may support a proactive role of Gamma-knife in this pathology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Situated cognition in clinical visualization: the role of transparency in GammaKnife neurosurgery planning.

PubMed

Dinka, David; Nyce, James M; Timpka, Toomas

2009-06-01

The aim of this study was to investigate how the clinical use of visualization technology can be advanced by the application of a situated cognition perspective. The data were collected in the GammaKnife radiosurgery setting and analyzed using qualitative methods. Observations and in-depth interviews with neurosurgeons and physicists were performed at three clinics using the Leksell GammaKnife. The users' ability to perform cognitive tasks was found to be reduced each time visualizations incongruent with the particular user's perception of clinical reality were used. The main issue here was a lack of transparency, i.e. a black box problem where machine representations "stood between" users and the cognitive tasks they wanted to perform. For neurosurgeons, transparency meant their previous experience from traditional surgery could be applied, i.e. that they were not forced to perform additional cognitive work. From the view of the physicists, on the other hand, the concept of transparency was associated with mathematical precision and avoiding creating a cognitive distance between basic patient data and what is experienced as clinical reality. The physicists approached clinical visualization technology as though it was a laboratory apparatus--one that required continual adjustment and assessment in order to "capture" a quantitative clinical reality. Designers of visualization technology need to compare the cognitive interpretations generated by the new visualization systems to conceptions generated during "traditional" clinical work. This means that the viewpoint of different clinical user groups involved in a given clinical task would have to be taken into account as well. A way forward would be to acknowledge that visualization is a socio-cognitive function that has practice-based antecedents and consequences, and to reconsider what analytical and scientific challenges this presents us with.

Plan delivery quality assurance for CyberKnife: Statistical process control analysis of 350 film-based patient-specific QAs.

PubMed

Bellec, J; Delaby, N; Jouyaux, F; Perdrieux, M; Bouvier, J; Sorel, S; Henry, O; Lafond, C

2017-07-01

Robotic radiosurgery requires plan delivery quality assurance (DQA) but there has never been a published comprehensive analysis of a patient-specific DQA process in a clinic. We proposed to evaluate 350 consecutive film-based patient-specific DQAs using statistical process control. We evaluated the performance of the process to propose achievable tolerance criteria for DQA validation and we sought to identify suboptimal DQA using control charts. DQAs were performed on a CyberKnife-M6 using Gafchromic-EBT3 films. The signal-to-dose conversion was performed using a multichannel-correction and a scanning protocol that combined measurement and calibration in a single scan. The DQA analysis comprised a gamma-index analysis at 3%/1.5mm and a separate evaluation of spatial and dosimetric accuracy of the plan delivery. Each parameter was plotted on a control chart and control limits were calculated. A capability index (Cpm) was calculated to evaluate the ability of the process to produce results within specifications. The analysis of capability showed that a gamma pass rate of 85% at 3%/1.5mm was highly achievable as acceptance criteria for DQA validation using a film-based protocol (Cpm>1.33). 3.4% of DQA were outside a control limit of 88% for gamma pass-rate. The analysis of the out-of-control DQA helped identify a dosimetric error in our institute for a specific treatment type. We have defined initial tolerance criteria for DQA validations. We have shown that the implementation of a film-based patient-specific DQA protocol with the use of control charts is an effective method to improve patient treatment safety on CyberKnife. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Quality of life after gamma knife radiosurgery treatment in patients with a vestibular schwannoma: the patient’s perspective

PubMed Central

van Haren, Anniek E. P.; Mulder, Jef J. S.; Hanssens, Patrick E. J.; van Overbeeke, Jacobus J.; Cremers, Cor W. R. J.; Graamans, Kees

2009-01-01

This study evaluates the impact of gamma knife radiosurgery (GKRS) on the quality of life (QOL) of patients with a sporadic vestibular schwannoma (VS). This study pertains to 108 VS patients who had GKRS in the years 2003 through 2007. Two different QOL questionnaires were used: medical outcome study short form 36 (SF36) and Glasgow benefit inventory (GBI). Radiosurgery was performed using a Leksell 4C gamma knife. The results of the QOL questionnaires in relation to prospectively and retrospectively gathered data of the VS patients treated by GKRS. Eventually, 97 patients could be included in the study. Their mean tumor size was 17 mm (range 6–39 mm); the mean maximum dose on the tumor was 19.9 Gy (range 16–25.5 Gy) and the mean marginal dose on the tumor was 11.1 (range 9.3–12.5 Gy). SF36 scores showed results comparable to those for a normal Dutch population. GBI showed a marginal decline in QOL. No correlation was found between QOL and gender, age, tumor size, or radiation dose. Increased audiovestibular symptoms after GKRS were correlated with a decreased GBI score, and decreased symptoms were correlated with a higher QOL post-GKRS. In this study shows that GKRS for VS has little impact on the general QOL of the VS patient. However, there is a wide range in individual QOL results. Individual QOL was influenced by the audiovestibular symptoms. No predictive patient, tumor, or treatment factors for QOL outcome after GKRS could be determined. Comparison with microsurgery is difficult because of intra group variability. PMID:19894058

Novel biomarker identification using metabolomic profiling to differentiate radiation necrosis and recurrent tumor following Gamma Knife radiosurgery.

PubMed

Lu, Alex Y; Turban, Jack L; Damisah, Eyiyemisi C; Li, Jie; Alomari, Ahmed K; Eid, Tore; Vortmeyer, Alexander O; Chiang, Veronica L

2017-08-01

OBJECTIVE Following an initial response of brain metastases to Gamma Knife radiosurgery, regrowth of the enhancing lesion as detected on MRI may represent either radiation necrosis (a treatment-related inflammatory change) or recurrent tumor. Differentiation of radiation necrosis from tumor is vital for management decision making but remains difficult by imaging alone. In this study, gas chromatography with time-of-flight mass spectrometry (GC-TOF) was used to identify differential metabolite profiles of the 2 tissue types obtained by surgical biopsy to find potential targets for noninvasive imaging. METHODS Specimens of pure radiation necrosis and pure tumor obtained from patient brain biopsies were flash-frozen and validated histologically. These formalin-free tissue samples were then analyzed using GC-TOF. The metabolite profiles of radiation necrosis and tumor samples were compared using multivariate and univariate statistical analysis. Statistical significance was defined as p ≤ 0.05. RESULTS For the metabolic profiling, GC-TOF was performed on 7 samples of radiation necrosis and 7 samples of tumor. Of the 141 metabolites identified, 17 (12.1%) were found to be statistically significantly different between comparison groups. Of these metabolites, 6 were increased in tumor, and 11 were increased in radiation necrosis. An unsupervised hierarchical clustering analysis found that tumor had elevated levels of metabolites associated with energy metabolism, whereas radiation necrosis had elevated levels of metabolites that were fatty acids and antioxidants/cofactors. CONCLUSIONS To the authors' knowledge, this is the first tissue-based metabolomics study of radiation necrosis and tumor. Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for brain metastases have unique metabolite profiles that may be targeted in the future to develop noninvasive metabolic imaging techniques.

Prediction of obliteration after gamma knife surgery for cerebral arteriovenous malformations.

PubMed

Karlsson, B; Lindquist, C; Steiner, L

1997-03-01

To define the factors of importance for the obliteration of cerebral arteriovenous malformations (AVMs), thus making a prediction of the probability for obliteration possible. In 945 AVMs of a series of 1319 patients treated with the gamma knife during 1970 to 1990, the relationship between patient, AVMs, and treatment parameters on the one hand and the obliteration of the nidus on the other was analyzed. The obliteration rate increased both with increased minimum (lowest periphery) and average dose and decreased with increased AVM volume. The minimum dose to the AVMs was the decisive dose factor for the treatment result. The higher the minimum dose, the higher the chance for total obliteration. The curve illustrating this relation increased logarithmically to a value of 87%. A higher average dose shortened the latency to AVM obliteration. For the obliterated cases, the larger the malformation, the lower the minimum dose used. This prompted us to relate the obliteration rate to the product minimum dose (AVM volume)1/3 (K index). The obliteration rate increased linearly with the K index up to a value of approximately 27, and for higher K values, the obliteration rate had a constant value of approximately 80%. For the group of 273 cases treated with a minimum dose of at least 25 Gy, the obliteration rate at the study end point (defined as 2-yr latency) was 80% (95% confidence interval = 75-85%). If obliterations that occurred beyond the end point are included, the obliteration rate increased to 85% (81-89%). The probability of obliteration of AVMs after gamma knife surgery is related both to the lowest dose to the AVMs and the AVM volume, and it can be predicted using the K index.

Volumetric changes and clinical outcome for petroclival meningiomas after primary treatment with Gamma Knife radiosurgery.

PubMed

Sadik, Zjiwar H A; Lie, Suan Te; Leenstra, Sieger; Hanssens, Patrick E J

2018-01-26

OBJECTIVE Petroclival meningiomas (PCMs) can cause devastating clinical symptoms due to mass effect on cranial nerves (CNs); thus, patients harboring these tumors need treatment. Many neurosurgeons advocate for microsurgery because removal of the tumor can provide relief or result in symptom disappearance. Gamma Knife radiosurgery (GKRS) is often an alternative for surgery because it can cause tumor shrinkage with improvement of symptoms. This study evaluates qualitative volumetric changes of PCM after primary GKRS and its impact on clinical symptoms. METHODS The authors performed a retrospective study of patients with PCM who underwent primary GKRS between 2003 and 2015 at the Gamma Knife Center of the Elisabeth-Tweesteden Hospital in Tilburg, the Netherlands. This study yields 53 patients. In this study the authors concentrate on qualitative volumetric tumor changes, local tumor control rate, and the effect of the treatment on trigeminal neuralgia (TN). RESULTS Local tumor control was 98% at 5 years and 93% at 7 years (Kaplan-Meier estimates). More than 90% of the tumors showed regression in volume during the first 5 years. The mean volumetric tumor decrease was 21.2%, 27.1%, and 31% at 1, 3, and 6 years of follow-up, respectively. Improvement in TN was achieved in 61%, 67%, and 70% of the cases at 1, 2, and 3 years of follow-up, respectively. This was associated with a mean volumetric tumor decrease of 25% at the 1-year follow-up to 32% at the 3-year follow-up. CONCLUSIONS GKRS for PCMs yields a high tumor control rate with a low incidence of neurological deficits. Many patients with TN due to PCM experienced improvement in TN after radiosurgery. GKRS achieves significant volumetric tumor decrease in the first years of follow-up and thereafter.

Gamma Knife surgery for clival epidural-osseous dural arteriovenous fistulas.

PubMed

Lee, Cheng-Chia; Chen, Ching-Jen; Chen, Shao-Ching; Yang, Huai-Che; Lin, Chung Jung; Wu, Chih-Chun; Chung, Wen-Yuh; Guo, Wan-Yuo; Hung-Chi Pan, David; Shiau, Cheng-Ying; Wu, Hsiu-Mei

2018-05-01

OBJECTIVE Clival epidural-osseous dural arteriovenous fistula (DAVF) is often associated with a large nidus, multiple arterial feeders, and complex venous drainage. In this study the authors report the outcomes of clival epidural-osseous DAVFs treated using Gamma Knife surgery (GKS). METHODS Thirteen patients with 13 clival epidural-osseous DAVFs were treated with GKS at the authors' institution between 1993 and 2015. Patient age at the time of GKS ranged from 38 to 76 years (median 55 years). Eight DAVFs were classified as Cognard Type I, 4 as Type IIa, and 1 as Type IIa+b. The median treatment volume was 17.6 cm 3 (range 6.2-40.3 cm 3 ). The median prescribed margin dose was 16.5 Gy (range 15-18 Gy). Clinical and radiological follow-ups were performed at 6-month intervals. Patient outcomes after GKS were categorized as 1) complete improvement, 2) partial improvement, 3) stationary, and 4) progression. RESULTS All 13 patients demonstrated symptomatic improvement, and on catheter angiography 12 of the 13 patients had complete obliteration and 1 patient had partial obliteration. The median follow-up period was 26 months (range 14-186 months). The median latency period from GKS to obliteration was 21 months (range 8-186 months). There was no intracranial hemorrhage during the follow-up period, and no deaths occurred. Two adverse events were observed following treatment, and 2 patients required repeat GKS treatment with eventual complete obliteration. CONCLUSIONS Gamma Knife surgery offers a safe and effective primary or adjuvant treatment modality for complex clival epidural-osseous DAVFs. All patients in this case series demonstrated symptomatic improvement, and almost all patients attained complete obliteration.

Histopathology of radiation necrosis with severe peritumoral edema after gamma knife radiosurgery for parasagittal meningioma. A report of two cases.

PubMed

Chen, Chien-hua; Shen, Chiung-chyi; Sun, Ming-hsi; Ho, William L; Huang, Chuan-fu; Kwan, Po-cheung

2007-01-01

Gamma knife radiosurgery (GKS) has been an effective treatment for meningiomas. Nevertheless, it still has certain risks. We present 2 cases of parasagittal meningioma after GKS complicated with radiation necrosis and peritumoral edema. The results of histologic examination are discussed. Two cases of parasagittal meningioma received GKS. Symptomatic peritumoral edema developed 3-4 months after GKS. Both of them underwent surgical resection of their tumor afterwards. Histologic examination showed necrotic change inside the tumor and infiltration of inflammatory cells in both cases. Hyalinization of blood vessels was seen in the 2nd case. The patients had improvement of neurologic function after surgical resection. Imaging performed 3 months after surgical resection showed alleviation of brain edema. After radiosurgery peritumoral edema tends to occur in meningiomas with a parasagittal position. Radiation necrosis, infiltration of inflammatory cells, and radiation injury to the vasculature causing hyalinization of blood vessels are suggested as the underlying histopathology. (c) 2007 S. Karger AG, Basel.

Gamma Knife Radiosurgery of the Superior Laryngeal Neuralgia: A report of three cases.

PubMed

Fu, Peng; Xiong, Nan-Xiang; Abdelmaksoud, Ahmed; Huang, Yi-Zhi; Song, Guo-Bin; Zhao, Hong-Yang

2018-05-19

Superior laryngeal neuralgia (SLN) is a relatively rare disorder that is characterized by neck pain. There are only a few reported cases and treatment options for SLN to date. In this study, we reported 3 patients with SLN who were treated with gamma knife radiosurgery (GKRS) at the time of diagnosis. For all 3 patients, GKRS was administered using a 4-mm collimator to deliver a single shot of 80 Gy of radiation (the 100% isodose line). The target was set at the jugular foramen where the vagus and glossopharyngeal nerves emerge from the skull. Follow-up assessments were performed at 32 months,31 months, and 30 months after GKRS. The 3 patients described pain relief at 3 months, 2 days and 6 weeks. None of the patients developed neurological deficits during the follow-up period. This preliminary report provides encouraging evidence that GKRS represents an effective, safe and relatively durable noninvasive treatment option for patients with SLN. Copyright © 2018 Elsevier Inc. All rights reserved.

Feasibility of Multiple Repeat Gamma Knife Radiosurgeries for Trigeminal Neuralgia: A Case Report and Review of the Literature

PubMed Central

Jones, Guy C.; Elaimy, Ameer L.; Demakas, John J.; Jiang, Hansi; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Mackay, Alexander R.; Cooke, Barton S.; Lee, Christopher M.

2011-01-01

Treatment options for trigeminal neuralgia (TN) must be customized for the individual patient, and physicians must be aware of the medical, surgical, and radiation treatment modalities to prescribe optimal treatment courses for specific patients. The following case illustrates the potential for gamma knife radiosurgery (GKRS) to be repeated multiple times for the purpose of achieving facial pain control in cases of TN that have been refractory to other medical and surgical options, as well as prior GKRS. The patient described failed to achieve pain control with initial GKRS, as well as medical and surgical treatments, but experienced significant pain relief for a period of time with a second GKRS procedure and later underwent a third procedure. Only a small subset of patients have reportedly undergone more than two GKRS for TN; thus, further research and long-term clinical followup will be valuable in determining its usefulness in specific clinical situations. PMID:21904556

Clinical Positioning Accuracy for Multisession Stereotactic Radiotherapy With the Gamma Knife Perfexion

PubMed Central

Young, Lori A.; Phillips, Mark H.; Cheung, Michael; Halasz, Lia M.; Rockhill, Jason K.

2017-01-01

Multisession stereotactic radiation therapy is increasingly being seen as a preferred option for intracranial diseases in close proximity to critical structures and for larger target volumes. The objective of this study is to investigate the reproducibility of the Extend system from Elekta. A retrospective review was conducted for all patients treated with multisession Gamma Knife between July 2010 and June 2015, including both malignant and benign lesions. Eighty-four patients were treated in this 5-year span. The average residual daily setup uncertainty was 0.48 (0.19) mm. We compare measurements of setup uncertainty from the Extend system to measurements performed with a linac-based approach previously used in our center. The Extend system has significantly reduced setup uncertainty for fractionated intracranial treatments at our institution. Positive results were observed in a small population of edentulous patients. The Extend system compares favorably with other approaches to delivering intracranial stereotactic radiotherapy and is a robust, simple-to-use, and precise method for treating multisession intracranial lesions. PMID:28514899

Repeated transsphenoidal surgery or gamma knife radiosurgery in recurrent cushing disease after transsphenoidal surgery.

PubMed

Bodaghabadi, Mohammad; Riazi, Hooman; Aran, Shima; Bitaraf, Mohammad Ali; Alikhani, Mazdak; Alahverdi, Mahmud; Mohamadi, Masoumeh; Shalileh, Keivan; Azar, Maziar

2014-03-01

This study compared Gamma knife radiosurgery (GKRS) and repeated transsphenoidal adenomectomy (TSA) to find the best approach for recurrence of Cushing disease (CD) after unsuccessful first TSA. Fifty-two patients with relapse of CD after TSA were enrolled and randomly underwent a second surgery or GKRS as the next therapeutic approach. They were followed for a mean period of 3.05 ± 0.8 years by physical examination and hormone measurement as well as magnetic resonance imaging. No significant difference was observed in sex ratio, mean age, adenoma type, follow-up duration, and initial hormone level between the two groups. No significant relationship was found between preoperative 24-hour free urine cortisol and disease-free months or tumor volume among both groups. Our statistical analysis showed higher recurrence-free interval in the GKRS group compared with TSA group. With longer recurrence-free interval, GKRS could be considered a good treatment alternative to repeated TSA in recurrent CD. Georg Thieme Verlag KG Stuttgart · New York.

Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study.

PubMed

Sheehan, Jason P; Starke, Robert M; Mathieu, David; Young, Byron; Sneed, Penny K; Chiang, Veronica L; Lee, John Y K; Kano, Hideyuki; Park, Kyung-Jae; Niranjan, Ajay; Kondziolka, Douglas; Barnett, Gene H; Rush, Stephen; Golfinos, John G; Lunsford, L Dade

2013-08-01

Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

Dose calculation accuracy of the Monte Carlo algorithm for CyberKnife compared with other commercially available dose calculation algorithms.

PubMed

Sharma, Subhash; Ott, Joseph; Williams, Jamone; Dickow, Danny

2011-01-01

Monte Carlo dose calculation algorithms have the potential for greater accuracy than traditional model-based algorithms. This enhanced accuracy is particularly evident in regions of lateral scatter disequilibrium, which can develop during treatments incorporating small field sizes and low-density tissue. A heterogeneous slab phantom was used to evaluate the accuracy of several commercially available dose calculation algorithms, including Monte Carlo dose calculation for CyberKnife, Analytical Anisotropic Algorithm and Pencil Beam convolution for the Eclipse planning system, and convolution-superposition for the Xio planning system. The phantom accommodated slabs of varying density; comparisons between planned and measured dose distributions were accomplished with radiochromic film. The Monte Carlo algorithm provided the most accurate comparison between planned and measured dose distributions. In each phantom irradiation, the Monte Carlo predictions resulted in gamma analysis comparisons >97%, using acceptance criteria of 3% dose and 3-mm distance to agreement. In general, the gamma analysis comparisons for the other algorithms were <95%. The Monte Carlo dose calculation algorithm for CyberKnife provides more accurate dose distribution calculations in regions of lateral electron disequilibrium than commercially available model-based algorithms. This is primarily because of the ability of Monte Carlo algorithms to implicitly account for tissue heterogeneities, density scaling functions; and/or effective depth correction factors are not required. Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-E-T-213: Comparison of Treatment Efficiency of Gamma Knife SRS Plans for Brain Metastases with Different Planning Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Y; Huang, Z; Lo, S

2015-06-15

Purpose: To improve Gamma Knife SRS treatment efficiency for brain metastases and compare the differences of treatment time and radiobiological effects between two different planning methods of automatic filling and manual placement of shots with inverse planning. Methods: T1-weighted MRI images with gadolinium contrast from five patients with a single brain metastatic-lesion were used in this retrospective study. Among them, two were from primary breast cancer, two from primary melanoma cancer and one from primary prostate cancer. For each patient, two plans were generated in Leksell GammaPlan10.1.1 for radiosurgical treatment with a Leksell GammaKnife Perfexion machine: one with automatic filling,more » automatic sector configuration and inverse optimization (Method1); and the other with manual placement of shots, manual setup of collimator sizes, manual setup of sector blocking and inverse optimization (Method2). Dosimetric quality of the plans was evaluated with parameters of Coverage, Selectivity, Gradient-Index and DVH. Beam-on Time, Number-of-Shots and Tumor Control Probability(TCP) were compared for the two plans while keeping their dosimetric quality very similar. Relative reduction of Beam-on Time and Number-of-Shots were calculated as the ratios among the two plans and used for quantitative analysis. Results: With very similar dosimetric and radiobiological plan quality, plans created with Method 2 had significantly reduced treatment time. Relative reduction of Beam-on Time ranged from 20% to 51 % (median:29%,p=0.001), and reduction of Number-of-Shots ranged from 5% to 67% (median:40%,p=0.0002), respectively. Time of plan creation for Method1 and Method2 was similar, approximately 20 minutes, excluding the time for tumor delineation. TCP calculated for the tumors from differential DVHs did not show significant difference between the two plans (p=0.35). Conclusion: The method of manual setup combined with inverse optimization in LGP for treatment of brain metastatic lesions with the Perfexion can achieve significantly higher time efficiency without degrading treatment quality.« less

Assessment of absorbed dose to thyroid, parotid and ovaries in patients undergoing Gamma Knife radiosurgery

NASA Astrophysics Data System (ADS)

Hasanzadeh, H.; Sharafi, A.; Allah Verdi, M.; Nikoofar, A.

2006-09-01

Stereotactic radiosurgery was originally introduced by Lars Leksell in 1951. This treatment refers to the noninvasive destruction of an intracranial target localized stereotactically. The purpose of this study was to identify the dose delivered to the parotid, ovaries, testis and thyroid glands during the Gamma Knife radiosurgery procedure. A three-dimensional, anthropomorphic phantom was developed using natural human bone, paraffin and sodium chloride as the equivalent tissue. The phantom consisted of a thorax, head and neck and hip. In the natural places of the thyroid, parotid (bilateral sides) and ovaries (midline), some cavities were made to place TLDs. Three TLDs were inserted in a batch with 1 cm space between the TLDs and each batch was inserted into a single cavity. The final depth of TLDs was 3 cm from the surface for parotid and thyroid and was 15 cm for the ovaries. Similar batches were placed superficially on the phantom. The phantom was gamma irradiated using a Leksell model C Gamma Knife unit. Subsequently, the same batches were placed superficially over the thyroid, parotid, testis and ovaries in 30 patients (15 men and 15 women) who were undergoing radiosurgery treatment for brain tumours. The mean dosage for treating these patients was 14.48 ± 3.06 Gy (10.5-24 Gy) to a mean tumour volume of 12.30 ± 9.66 cc (0.27-42.4 cc) in the 50% isodose curve. There was no significant difference between the superficial and deep batches in the phantom studies (P-value < 0.05). The mean delivered doses to the parotid, thyroid, ovaries and testis in human subjects were 21.6 ± 15.1 cGy, 9.15 ± 3.89 cGy, 0.47 ± 0.3 cGy and 0.53 ± 0.31 cGy, respectively. The data can be used in making decisions for special clinical situations such as treating pregnant patients or young patients with benign lesions who need radiosurgery for eradication of brain tumours.

Time-resolved imaging of prompt-gamma rays for proton range verification using a knife-edge slit camera based on digital photon counters

NASA Astrophysics Data System (ADS)

Cambraia Lopes, Patricia; Clementel, Enrico; Crespo, Paulo; Henrotin, Sebastien; Huizenga, Jan; Janssens, Guillaume; Parodi, Katia; Prieels, Damien; Roellinghoff, Frauke; Smeets, Julien; Stichelbaut, Frederic; Schaart, Dennis R.

2015-08-01

Proton range monitoring may facilitate online adaptive proton therapy and improve treatment outcomes. Imaging of proton-induced prompt gamma (PG) rays using a knife-edge slit collimator is currently under investigation as a potential tool for real-time proton range monitoring. A major challenge in collimated PG imaging is the suppression of neutron-induced background counts. In this work, we present an initial performance test of two knife-edge slit camera prototypes based on arrays of digital photon counters (DPCs). PG profiles emitted from a PMMA target upon irradiation with a 160 MeV proton pencil beams (about 6.5   ×   109 protons delivered in total) were measured using detector modules equipped with four DPC arrays coupled to BGO or LYSO : Ce crystal matrices. The knife-edge slit collimator and detector module were placed at 15 cm and 30 cm from the beam axis, respectively, in all cases. The use of LYSO : Ce enabled time-of-flight (TOF) rejection of background events, by synchronizing the DPC readout electronics with the 106 MHz radiofrequency signal of the cyclotron. The signal-to-background (S/B) ratio of 1.6 obtained with a 1.5 ns TOF window and a 3 MeV-7 MeV energy window was about 3 times higher than that obtained with the same detector module without TOF discrimination and 2 times higher than the S/B ratio obtained with the BGO module. Even 1 mm shifts of the Bragg peak position translated into clear and consistent shifts of the PG profile if TOF discrimination was applied, for a total number of protons as low as about 6.5   ×   108 and a detector surface of 6.6 cm  ×  6.6 cm.

Recurrent Juvenile Nasopharyngeal Angiofibroma Treated with Gamma Knife Surgery

PubMed Central

Park, Chul-Kee; Paek, Sun Ha; Chung, Hyun-Tai; Jung, Hee-Won

2006-01-01

Radiosurgery has been rarely applied for juvenile nasopharyngeal angiofibroma (JNA) and cumulative reports are lacking. The authors report a case of successful treatment of recurred JNA with gamma knife surgery (GKS). A 48-yr-old man was presented with right visual acuity deterioration and brain magnetic resonance images (MRI) disclosed a 3 cm-sized intraorbital mass in the right orbit. He underwent a right fronto-temporal craniotomy and the mass was subtotally removed to preserve visual function. Histological diagnosis confirmed JNA in typical nature. However, the vision gradually worsened to fail four years after operation. MRI then showed regrowth of the tumor occupying most of the right orbit. GKS was done for the recurred lesion. A dose of 17 Gy was delivered to the 50% isodose line of tumor margin. During the following four-year follow-up period, the mass disappeared almost completely without any complications. Usually JNA can be exclusively diagnosed by radiological study alone. So this report of successful treatment of JNA with GKS may provide an important clue for the novel indication of GKS. PMID:16891831

WE-A-304-01: Strategies and Technologies for Cranial Radiosurgery Planning: MLC-Based Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, G.

2015-06-15

The high fractional doses, stringent requirements for accuracy and precision, and surgical perspective characteristic of intracranial radiosurgery create considerations for treatment planning which are distinct from most other radiotherapy procedures. This session will introduce treatment planning techniques specific to two popular intracranial SRS modalities: Gamma Knife and MLC-based Linac. The basic treatment delivery characteristics of each device will be reviewed with a focus on how those characteristics determine the paradigm used for treatment planning. Basic techniques for treatment planning will be discussed, including considerations such as isodose selection, target and organ-at-risk definition, quality indices, and protection of critical structures. Futuremore » directions for SRS treatment planning will also be discussed. Learning Objectives: Introduce the basic physical principles of intracranial radiosurgery and how they are realized in the treatment planning paradigms for Gamma Knife and Linac radiosurgery. Demonstrate basic treatment planning techniques. Discuss metrics for evaluating SRS treatment plan quality. Discuss recent and future advances in SRS treatment planning. D. Schlesinger receives research support from Elekta, AB.« less

Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery.

PubMed

Nikolaoul, Marinos; Stamenković, Srdjan; Stergiou, Christos; Skarleas, Christos; Torrens, Michael

2015-01-01

Brain metastases from epithelial ovarian cancer (EOC) are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS). A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI) scan during the work-up. The decision to perform GKRS was due to a surgical inaccessibility of intracranial lesion. Twelve weeks after the procedure, the MRI scan showed reduction in the diameter of brain metastasis and surrounding edema and the patient returned to good mental and motor performance.The patient survived for 22 months following treatment and died from a progressive intra-abdominal disease. Prognosis of ovarian cancer patients with brain metastases is generally poor regardless of treatment. Our case shows that GKRS as primary treatment modality for the control of ovarian cancer metastases to the brain was effective and can be considered as a treatment of choice if international selection criteria are followed.

Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

SU-F-J-160: Clinical Evaluation of Targeting Accuracy in Radiosurgery Using Tractography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juh, R; Han, J; Kim, C

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 males, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve. Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement. Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.« less

Gamma Knife Radiosurgery for Skull Base Meningiomas: Long-Term Radiologic and Clinical Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Jung Ho; Kim, Dong Gyu; Chung, Hyun-Tai

2008-12-01

Purpose: To analyze the long-term outcomes in patients with skull base meningiomas (SBMNGs) treated with Gamma Knife radiosurgery (GKRS). Methods and Materials: Of the 98 consecutive patients with SBMNGs treated with GKRS between 1998 and 2002, 63 were followed up for more than 48 months. The mean ({+-}SD) age of the patients was 50 {+-} 12 years, the mean tumor volume was 6.5 cm{sup 3} (range, 0.5-18.4 cm{sup 3}), the mean marginal dose was 12.6 Gy (range, 7.0-20.0 Gy), and the mean follow-up duration was 77 {+-} 18 months. The mean number of shots was 13.7 {+-} 3.8. The tumormore » volume was decreased at the last follow-up in 28 patients (44.4%) and increased in 6 (9.6%). The actuarial tumor control rate was 90.2% at 5 years. No notable prognostic factor related to tumor control was identified. Ten patients (15.9%) with a cranial neuropathy showed unfavorable outcomes. The rate of improvement in patients with a cranial neuropathy was 45.1%. Age >70 years was likely correlated with an unfavorable outcome in patients with cranial neuropathy (odds ratio = 0.027; p = 0.025; 95% confidence interval 0.001-0.632). Cavernous sinus location was significantly associated with improvement of a cranial neuropathy (odds ratio = 7.314; p = 0.007; 95% confidence interval 1.707-31.34). Conclusions: Gamma Knife radiosurgery is an effective modality for the treatment of SBMNGs and provides favorable outcomes in patients with cranial neuropathy, even in the long-term follow-up period. However, radiosurgery for patients with no or only mild symptoms should be performed cautiously because neither complication rate is low enough to be negligible, especially in elderly patients. A cranial neuropathy by MNGs involving the cavernous sinus seems to have a higher chance of improvement after radiosurgery than other SBMNGs.« less

Gamma knife radiosurgery for typical trigeminal neuralgia: An institutional review of 108 patients

PubMed Central

Elaimy, Ameer L.; Lamm, Andrew F.; Demakas, John J.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Pfeffer, Robert D.; Cooke, Barton S.; Peressini, Benjamin J.; Lee, Christopher M.

2013-01-01

Background: In this study, we present the previously unreported pain relief outcomes of 108 patients treated at Gamma Knife of Spokane for typical trigeminal neuralgia (TN) between 2002 and 2011. Methods: Pain relief outcomes were measured using the Barrow Neurological Institute (BNI) pain intensity scale. In addition, the effects gender, age at treatment, pain laterality, previous surgical treatment, repeat Gamma Knife radiosurgery (GKRS), and maximum radiosurgery dose have on patient pain relief outcomes were retrospectively analyzed. Statistical analysis was performed using Andersen 95% confidence intervals, approximate confidence intervals for log hazard ratios, and multivariate Cox proportional hazard models. Results: All 108 patients included in this study were grouped into BNI class IV or V prior to GKRS. The median clinical follow-up time was determined to be 15 months. Following the first GKRS procedure, 71% of patients were grouped into BNI class I-IIIb (I = 31%; II = 3%; IIIa = 19%; IIIb = 18%) and the median duration of pain relief for those patients was determined to be 11.8 months. New facial numbness was reported in 19% of patients and new facial paresthesias were reported in 7% of patients after the first GKRS procedure. A total of 19 repeat procedures were performed on the 108 patients included in this study. Following the second GKRS procedure, 73% of patients were grouped into BNI class I-IIIb (I = 44%; II = 6%; IIIa = 17%, IIIb = 6%) and the median duration of pain relief for those patients was determined to be 4.9 months. For repeat procedures, new facial numbness was reported in 22% of patients and new facial paresthesias were reported in 6% of patients. Conclusions: GKRS is a safe and effective management approach for patients diagnosed with typical TN. However, further studies and supporting research is needed on the effects previous surgical treatment, number of radiosurgery procedures, and maximum radiosurgery dose have on GKRS clinical outcomes. PMID:23956935

Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Vuong, D.; Volken, W.; Henzen, D.; Schmidhalter, D.; Malthaner, M.; Mueller, S.; Frei, D.; Stampanoni, M. F. M.; Dal Pra, A.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2018-01-01

This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

SU-F-T-649: Dosimetric Evaluation of Non-Coplanar Arc Therapy Using a Novel Rotating Gamma Ray System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldib, A; Chibani, O; Jin, L

2016-06-15

Purpose: Stereotactic intra and extra-cranial body radiation therapy has evolved with advances in treatment accuracy, effective radiation dose, and parameters necessary to maximize machine capabilities. Novel gamma systems with a ring type gantry were developed having the ability to perform oblique arcs. The aim of this study is to explore the dosimetric advantages of this new system. Methods: The rotating Gamma system is named CybeRay (Cyber Medical Corp., Xian, China). It has a treatment head of 16 cobalt-60 sources focused to the isocenter, which can rotate 360° on the ring gantry and swing 35° in the superior direction. Treatment plansmore » were generated utilizing our in-house Monte Carlo treatment planning system. A cylindrical phantom was modeled with 2mm voxel size. Dose inside the cylindrical phantom was calculated for coplanar and non-coplanar arcs. Dosimetric differences between CybeRay cobalt beams and CyberKnife 6MV beams were compared in a lung phantom and for previously treated SBRT patients. Results: The full width at half maxima of cross profiles in the S-I direction for the coplanar setup matched the cone sizes, while for the non-coplanar setup, FWHM was larger by 2mm for a 10mm cone and about 5mm for larger cones. In the coronal and sagittal view, coplanar beams showed elliptical shaped isodose lines, while non-coplanar beams showed circular isodose lines. Thus proper selection of the oblique angle and cone size can aid optimal dose matching to the target volume. Comparing a single 5mm cone from CybeRay to that from CyberKnife showed similar penumbra in a lung phantom but CybeRay had significant lower doses beyond lung tissues. Comparable treatment plans were obtained with CybeRay as that from CyberKnife.ConclusionThe noncoplanar multiple source arrangement of CybeRay will be of great clinical benefits for stereotactic intra and extra-cranial radiation therapy.« less

Assessment of the accuracy and stability of frameless gamma knife radiosurgery.

PubMed

Chung, Hyun-Tai; Park, Woo-Yoon; Kim, Tae Hoon; Kim, Yong Kyun; Chun, Kook Jin

2018-06-03

The aim of this study was to assess the accuracy and stability of frameless gamma knife radiosurgery (GKRS). The accuracies of the radiation isocenter and patient couch movement were evaluated by film dosimetry with a half-year cycle. Radiation isocenter assessment with a diode detector and cone-beam computed tomography (CBCT) image accuracy tests were performed daily with a vendor-provided tool for one and a half years after installation. CBCT image quality was examined twice a month with a phantom. The accuracy of image coregistration using CBCT images was studied using magnetic resonance (MR) and computed tomography (CT) images of another phantom. The overall positional accuracy was measured in whole procedure tests using film dosimetry with an anthropomorphic phantom. The positional errors of the radiation isocenter at the center and at an extreme position were both less than 0.1 mm. The three-dimensional deviation of the CBCT coordinate system was stable for one and a half years (mean 0.04 ± 0.02 mm). Image coregistration revealed a difference of 0.2 ± 0.1 mm between CT and CBCT images and a deviation of 0.4 ± 0.2 mm between MR and CBCT images. The whole procedure test of the positional accuracy of the mask-based irradiation revealed an accuracy of 0.5 ± 0.6 mm. The radiation isocenter accuracy, patient couch movement accuracy, and Gamma Knife Icon CBCT accuracy were all approximately 0.1 mm and were stable for one and a half years. The coordinate system assigned to MR images through coregistration was more accurate than the system defined by fiducial markers. Possible patient motion during irradiation should be considered when evaluating the overall accuracy of frameless GKRS. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volotskova, O; Xu, A; Jozsef, G

Purpose: To investigate the response and dose rate dependence of a scintillation detector over a wide energy range. Methods: The energy dependence of W1 scintillation detector was tested with: 1) 50–225 keV beams generated by an animal irradiator, 2) a Leksell Gamma Knife Perfexion Co-60 source, 3) 6MV, 6FFF, 10FFF and 15MV photon beams, and 4) 6–20MeV electron beams from a linac. Calibrated linac beams were used to deliver 100 cGy to the detector at dmax in water under reference conditions. The gamma-knife measurement was performed in solid water (100 cGy with 16mm collimator). The low energy beams were calibratedmore » with an ion chamber in air (TG-61), and the scintillation detector was placed at the same location as the ionization chamber during calibration. For the linac photon and electron beams, dose rate dependence was tested for 100–2400 and 100–800 MU/min. Results: The scintillation detector demonstrated strong energy dependence in the range of 50–225keV. The measured values were lower than the delivered dose and increased as the energy increased. Therapeutic photon beams showed energy independence with variations less than 1%. Therapeutic electron beams displayed the same sensitivity of ∼2–3% at their corresponding dmax depths. The change in dose-rate of photon and electron beams within the therapeutic energy range did not affect detector output (<0.5%). Measurements acquired with the gamma knife showed that the output data agreed with the delivered dose up to 3%. Conclusion: W1 scintillation detector output has a strong energy dependence in the diagnostic and orthovoltage energy range. Therapeutic photon beams exhibited energy independence with no observable dose-rate dependence. This study may aid in the implementation of a scintillation detector in QA programs by providing energy calibration factors.« less

SU-E-J-34: Clinical Evaluation of Targeting Accuracy and Tractogrphy Delineation of Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juh, R; Suh, T; Kim, Y

2014-06-01

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 male, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve . Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.« less

End-to-end test of spatial accuracy in Gamma Knife treatments for trigeminal neuralgia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brezovich, Ivan A., E-mail: ibrezovich@uabmc.edu; Wu, Xingen; Duan, Jun

2014-11-01

Purpose: Spatial accuracy is most crucial when small targets like the trigeminal nerve are treated. Although current quality assurance procedures typically verify that individual apparatus, like the MRI scanner, CT scanner, Gamma Knife, etc., are meeting specifications, the cumulative error of all equipment and procedures combined may exceed safe margins. This study uses an end-to-end approach to assess the overall targeting errors that may have occurred in individual patients previously treated for trigeminal neuralgia. Methods: The trigeminal nerve is simulated by a 3 mm long, 3.175 mm (1/8 in.) diameter MRI-contrast filled cavity embedded within a PMMA plastic capsule. Themore » capsule is positioned within the head frame such that the location of the cavity matches the Gamma Knife coordinates of an arbitrarily chosen, previously treated patient. Gafchromic EBT2 film is placed at the center of the cavity in coronal and sagittal orientations. The films are marked with a pinprick to identify the cavity center. Treatments are planned for radiation delivery with 4 mm collimators according to MRI and CT scans using the clinical localizer boxes and acquisition protocols. Shots are planned so that the 50% isodose surface encompasses the cavity. Following irradiation, the films are scanned and analyzed. Targeting errors are defined as the distance between the pinprick, which represents the intended target, and the centroid of the 50% isodose line, which is the center of the radiation field that was actually delivered. Results: Averaged over ten patient simulations, targeting errors along the x, y, and z coordinates (patient’s left-to-right, posterior-to-anterior, and head-to-foot) were, respectively, −0.060 ± 0.363, −0.350 ± 0.253, and 0.348 ± 0.204 mm when MRI was used for treatment planning. Planning according to CT exhibited generally smaller errors, namely, 0.109 ± 0.167, −0.191 ± 0.144, and 0.211 ± 0.094 mm. The largest errors along individual axes in MRI- and CT-planned treatments were, respectively, −0.761 mm in the y-direction and 0.428 mm in the x-direction, well within safe limits. Conclusions: The highly accurate dose delivery was possible because the Gamma Knife, MRI scanner, and other equipment performed within tight limits and scans were acquired using the thinnest slices and smallest pixel sizes available. Had the individual devices performed only near the limits of their specifications, the cumulative error could have left parts of the trigeminal nerve undertreated. The presented end-to-end test gives assurance that patients had received the expected high quality treatment. End-to-end tests should become part of clinical practice.« less

Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma: a Japanese multi-institutional cooperative study (JLGK1401).

PubMed

Kawabe, Takuya; Yamamoto, Masaaki; Sato, Yasunori; Yomo, Shoji; Kondoh, Takeshi; Nagano, Osamu; Serizawa, Toru; Tsugawa, Takahiko; Okamoto, Hisayo; Akabane, Atsuya; Aita, Kazuyasu; Sato, Manabu; Jokura, Hidefumi; Kawagishi, Jun; Shuto, Takashi; Kawai, Hideya; Moriki, Akihito; Kenai, Hiroyuki; Iwai, Yoshiyasu; Gondo, Masazumi; Hasegawa, Toshinori; Yasuda, Soichiro; Kikuchi, Yasuhiro; Nagatomo, Yasushi; Watanabe, Shinya; Hashimoto, Naoya

2016-12-01

OBJECTIVE In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) of the lung as a variant of large cell carcinoma, and LCNEC now accounts for 3% of all lung cancers. Although LCNEC is categorized among the non-small cell lung cancers, its biological behavior has recently been suggested to be very similar to that of a small cell pulmonary malignancy. The clinical outcome for patients with LCNEC is generally poor, and the optimal treatment for this malignancy has not yet been established. Little information is available regarding management of LCNEC patients with brain metastases (METs). This study aimed to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) for patients with brain METs from LCNEC. METHODS The Japanese Leksell Gamma Knife Society planned this retrospective study in which 21 Gamma Knife centers in Japan participated. Data from 101 patients were reviewed for this study. Most of the patients with LCNEC were men (80%), and the mean age was 67 years (range 39-84 years). Primary lung tumors were reported as well controlled in one-third of the patients. More than half of the patients had extracranial METs. Brain metastasis and lung cancer had been detected simultaneously in 25% of the patients. Before GKRS, brain METs had manifested with neurological symptoms in 37 patients. Additionally, prior to GKRS, resection was performed in 17 patients and radiation therapy in 10. A small cell lung carcinoma-based chemotherapy regimen was chosen for 48 patients. The median lesion number was 3 (range 1-33). The median cumulative tumor volume was 3.5 cm 3 , and the median radiation dose was 20.0 Gy. For statistical analysis, the standard Kaplan-Meier method was used to determine post-GKRS survival. Competing risk analysis was applied to estimate GKRS cumulative incidences of maintenance of neurological function and death, local recurrence, appearance of new lesions, and complications. RESULTS The overall median survival time (MST) was 9.6 months. MSTs for patients classified according to the modified recursive partitioning analysis (RPA) system were 25.7, 11.0, and 5.9 months for Class 1+2a (20 patients), Class 2b (28), and Class 3 (46), respectively. At 12 months after GKRS, neurological death-free and deterioration-free survival rates were 93% and 87%, respectively. Follow-up imaging studies were available in 78 patients. The tumor control rate was 86% at 12 months after GKRS. CONCLUSIONS The present study suggests that GKRS is an effective treatment for LCNEC patients with brain METs, particularly in terms of maintaining neurological status.

TH-A-BRC-02: AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goetsch, S.

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

A comparison of the convolution and TMR10 treatment planning algorithms for Gamma Knife® radiosurgery

PubMed Central

Wright, Gavin; Harrold, Natalie; Bownes, Peter

2018-01-01

Aims To compare the accuracies of the convolution and TMR10 Gamma Knife treatment planning algorithms, and assess the impact upon clinical practice of implementing convolution-based treatment planning. Methods Doses calculated by both algorithms were compared against ionisation chamber measurements in homogeneous and heterogeneous phantoms. Relative dose distributions calculated by both algorithms were compared against film-derived 2D isodose plots in a heterogeneous phantom, with distance-to-agreement (DTA) measured at the 80%, 50% and 20% isodose levels. A retrospective planning study compared 19 clinically acceptable metastasis convolution plans against TMR10 plans with matched shot times, allowing novel comparison of true dosimetric parameters rather than total beam-on-time. Gamma analysis and dose-difference analysis were performed on each pair of dose distributions. Results Both algorithms matched point dose measurement within ±1.1% in homogeneous conditions. Convolution provided superior point-dose accuracy in the heterogeneous phantom (-1.1% v 4.0%), with no discernible differences in relative dose distribution accuracy. In our study convolution-calculated plans yielded D99% 6.4% (95% CI:5.5%-7.3%,p<0.001) less than shot matched TMR10 plans. For gamma passing criteria 1%/1mm, 16% of targets had passing rates >95%. The range of dose differences in the targets was 0.2-4.6Gy. Conclusions Convolution provides superior accuracy versus TMR10 in heterogeneous conditions. Implementing convolution would result in increased target doses therefore its implementation may require a revaluation of prescription doses. PMID:29657896

Gamma knife treatment for refractory epilepsy in seizure focus localized by positron emission tomography/CT★

PubMed Central

Bai, Xia; Wang, Xuemei; Wang, Hongwei; Zhao, Shigang; Han, Xiaodong; Hao, Linjun; Wang, Xiangcheng

2012-01-01

A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The foci of 60% of the patients could be positioned using a combined positron emission tomography/CT imaging modality. Hyper- and hypometabolism foci were examined as part of this study. Patients who had abnormal metabolism in positron emission tomography/CT imaging were divided into intermittent-phase group and the seizure-phase group. The intermittent-phase group was further divided into a single-focus group and a multiple-foci group according to the number of seizure foci detected by imaging. Following gamma knife treatment, seizure frequency was significantly lower in the intermittent-phase group and the seizure-phase group. Wieser’s classification reached Grade I or II in nearly 40% of patients. Seizure frequency was significantly lower following treatment, but Wieser’s classification score was significantly higher in the seizure-phase group compared with the intermittent-phase group. Seizure frequency was significantly lower following treatment in the single-focus group, but Wieser’s classification score was significantly higher in the single-focus group as compared with the multiple-foci group. PMID:25317147

Gamma Knife radiosurgery for vestibular schwannoma: case report and review of the literature

PubMed Central

2009-01-01

Vestibular schwannomas, also called acoustic neuromas, are benign tumors of the vestibulocochlear nerve. Patients with these tumours almost always present with signs of hearing loss, and many also experience tinnitus, vertigo, and equilibrium problems. Following diagnosis with contrast enhanced MRI, patients may choose to observe the tumour with subsequent scans or seek active treatment in the form of microsurgery, radiosurgery, or radiotherapy. Unfortunately, definitive guidelines for treating vestibular schwannomas are lacking, because of insufficient evidence comparing the outcomes of therapeutic modalities. We present a contemporary case report, describing the finding of a vestibular schwannoma in a patient who presented with dizziness and a "clicking" sensation in the ear, but no hearing deficit. Audible clicking is a symptom that, to our knowledge, has not been associated with vestibular schwannoma in the literature. We discuss the diagnosis and patient's decision-making process, which led to treatment with Gamma Knife radiosurgery. Treatment resulted in an excellent radiographic response and complete hearing preservation. This case highlights an atypical presentation of vestibular schwannoma, associated with audible "clicks" and normal hearing. We also provide a concise review of the available literature on modern vestibular schwannoma treatment, which may be useful in guiding treatment decisions. PMID:20021676

Gamma Knife radiosurgery for vestibular schwannoma: case report and review of the literature.

PubMed

Arthurs, Benjamin J; Lamoreaux, Wayne T; Giddings, Neil A; Fairbanks, Robert K; Mackay, Alexander R; Demakas, John J; Cooke, Barton S; Lee, Christopher M

2009-12-18

Vestibular schwannomas, also called acoustic neuromas, are benign tumors of the vestibulocochlear nerve. Patients with these tumours almost always present with signs of hearing loss, and many also experience tinnitus, vertigo, and equilibrium problems. Following diagnosis with contrast enhanced MRI, patients may choose to observe the tumour with subsequent scans or seek active treatment in the form of microsurgery, radiosurgery, or radiotherapy. Unfortunately, definitive guidelines for treating vestibular schwannomas are lacking, because of insufficient evidence comparing the outcomes of therapeutic modalities.We present a contemporary case report, describing the finding of a vestibular schwannoma in a patient who presented with dizziness and a "clicking" sensation in the ear, but no hearing deficit. Audible clicking is a symptom that, to our knowledge, has not been associated with vestibular schwannoma in the literature. We discuss the diagnosis and patient's decision-making process, which led to treatment with Gamma Knife radiosurgery. Treatment resulted in an excellent radiographic response and complete hearing preservation. This case highlights an atypical presentation of vestibular schwannoma, associated with audible "clicks" and normal hearing. We also provide a concise review of the available literature on modern vestibular schwannoma treatment, which may be useful in guiding treatment decisions.

Clinical Outcomes of Gamma Knife Radiosurgery in the Treatment of Patients with Trigeminal Neuralgia

PubMed Central

Elaimy, Ameer L.; Hanson, Peter W.; Lamoreaux, Wayne T.; Mackay, Alexander R.; Demakas, John J.; Fairbanks, Robert K.; Cooke, Barton S.; Thumma, Sudheer R.; Lee, Christopher M.

2012-01-01

Since its introduction by Leksell, Gamma Knife radiosurgery (GKRS) has become increasingly popular as a management approach for patients diagnosed with trigeminal neuralgia (TN). For this reason, we performed a modern review of the literature analyzing the efficacy of GKRS in the treatment of patients who suffer from TN. For patients with medically refractory forms of the condition, GKRS has proven to be an effective initial and repeat treatment option. Cumulative research suggests that patients treated a single time with GKRS exhibit similar levels of facial pain control when compared to patients treated multiple times with GKRS. However, patients treated on multiple occasions with GKRS are more likely to experience facial numbness and other facial sensory changes when compared to patients treated once with GKRS. Although numerous articles have reported MVD to be superior to GKRS in achieving facial pain relief, the findings of these comparison studies are weakened by the vast differences in patient age and comorbidities between the two studied groups and cannot be considered conclusive. Questions remain regarding optimal GKRS dosing and targeting strategies, which warrants further investigation into this controversial matter. PMID:22229034

Out of field dose during Gamma Knife treatment: a paediatric case study

NASA Astrophysics Data System (ADS)

Moutrie, V.; Grace, M.; Izard, M. A.; Fuller, J. W.

2017-01-01

An 11-year-old girl with an arteriovenous malformation (AVM) was referred for Gamma Knife treatment. As this would be the first paediatric treatment in Australia, additional investigations were undertaken into out of field dose to assure the best possible long term outcome for the patient. A phantom was constructed from water equivalent materials to simulate the patient. A target volume was defined to emulate the size and location of the AVM visible in diagnostic images. An ionisation chamber and EBT3 Gafchromic film were used to record absorbed dose at strategic points both on the surface and at depth within the phantom. On the day of treatment, EBT3 Gafchromic film was used to conduct in vivo dosimetry. The pre-treatment phantom measurements matched the planning system for the cranial section (the only modelled section) and no measurable dose above background was detected in the extracranial sites. In vivo measurements of the lenses returned doses of up to 2 cGy for imaging and 8 cGy for treatment which was also consistent with the planned dose. Dose to the thyroid, chest and abdomen was not measurable above background.

TH-A-BRC-00: New Task Groups for External Beam QA: An Overview

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

TH-A-BRC-03: AAPM TG218: Measurement Methods and Tolerance Levels for Patient-Specific IMRT Verification QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miften, M.

2016-06-15

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

TH-A-BRC-01: AAPM TG-135U1 QA for Robotic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dieterich, S.

AAPM TG-135U1 QA for Robotic Radiosurgery - Sonja Dieterich Since the publication of AAPM TG-135 in 2011, the technology of robotic radiosurgery has rapidly developed. AAPM TG-135U1 will provide recommendations on the clinical practice for using the IRIS collimator, fiducial-less real-time motion tracking, and Monte Carlo based treatment planning. In addition, it will summarize currently available literature about uncertainties. Learning Objectives: Understand the progression of technology since the first TG publication Learn which new QA procedures should be implemented for new technologies Be familiar with updates to clinical practice guidelines AAPM TG-178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance -more » Steven Goetsch Purpose: AAPM Task Group 178 Gamma Stereotactic Radiosurgery Dosimetry and Quality Assurance was formed in August, 2008. The Task Group has 12 medical physicists, two physicians and two consultants. Methods: A round robin dosimetry intercomparison of proposed ionization chambers, electrometer and dosimetry phantoms was conducted over a 15 month period in 2011 and 2012 (Med Phys 42, 11, Nov, 2015). The data obtained at 9 institutions (with ten different Elekta Gamma Knife units) was analyzed by the lead author using several protocols. Results: The most consistent results were obtained using the Elekta ABS 16cm diameter phantom, with the TG-51 protocol modified as recommended by Alfonso et al (Med Phys 35, 11, Nov 2008). A key white paper (Med Phys, in press) sponsored by Elekta Corporation, was used to obtain correction factors for the ionization chambers and phantoms used in this intercomparison. Consistent results were obtained for both Elekta Gamma Knife Model 4C and Gamma Knife Perfexion units as measured with each of two miniature ionization chambers. Conclusion: The full report gives clinical history and background of gamma stereotactic radiosurgery, clinical examples and history, quality assurance recommendations and outline of possible dosimetry protocols. The report will be reviewed by the AAPM Working Group on Recommendations for Radiotherapy External Beam Quality Assurance and then by the AAPM Science Council before publication in Medical Physics Survey of possible calibration protocols for calibration of Gamma Stereotactic Radiosurgery (GSR) devices Overview of modern Quality Assurance techniques for GSR AAPM TG-218 Tolerance Levels and Methodologies for IMRT Verification QA - Moyed Miften Patient-specific IMRT QA measurement is a process designed to identify discrepancies between calculated and delivered doses. Error tolerance limits are not well-defined or consistently applied across centers. The AAPM TG-218 report has been prepared to improve the understanding and consistency of this process by providing recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Learning Objectives: Review measurement methods and methodologies for absolute dose verification Provide recommendations on delivery methods, data interpretation, the use of analysis routines and choice of tolerance limits for IMRT QA Sonja Dieterich has a research agreement with Sun Nuclear Inc. Steven Goetsch is a part-time consultant for Elekta.« less

Burn Wound gammadelta T-Cells Support a Th2 and Th17 Immune Response

DTIC Science & Technology

2014-02-01

disorder (rheumatoid arthritis), psoriasis , and graft vs host disease.24–27 Gamma-δ T-cells are functionally specialized and are involved in...Mathers AR, Ferris LK. Anti-cytokine therapy in the treatment of psoriasis . Cytokine 2013;61:704–12. 26. Greenblatt MB, Vrbanac V, Vbranac V, et al...Meglio P, Perera GK, et al. Identification of a novel proinflammatory human skin-homing V?9Vd2 T cell subset with a potential role in psoriasis . J

A fully automatic approach for multimodal PET and MR image segmentation in gamma knife treatment planning.

PubMed

Rundo, Leonardo; Stefano, Alessandro; Militello, Carmelo; Russo, Giorgio; Sabini, Maria Gabriella; D'Arrigo, Corrado; Marletta, Francesco; Ippolito, Massimo; Mauri, Giancarlo; Vitabile, Salvatore; Gilardi, Maria Carla

2017-06-01

Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [ 11 C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation. A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife ® treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTV MRI . A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without treatment response assessment, the feasibility and the clinical value of BTV integration in Gamma Knife treatment planning were considered. Therefore, a qualitative evaluation was carried out by three experienced clinicians. The achieved experimental results showed that GTV and BTV segmentations are statistically correlated (Spearman's rank correlation coefficient: 0.898) but they have low similarity degree (average Dice Similarity Coefficient: 61.87 ± 14.64). Therefore, volume measurements as well as evaluation metrics values demonstrated that MRI and PET convey different but complementary imaging information. GTV and BTV could be combined to enhance treatment planning. In more than 50% of cases the CTV was strongly or moderately conditioned by metabolic imaging. Especially, BTV MRI enhanced the CTV more accurately than BTV in 25% of cases. The proposed fully automatic multimodal PET/MRI segmentation method is a valid operator-independent methodology helping the clinicians to define a CTV that includes both metabolic and morphologic information. BTV MRI and GTV should be considered for a comprehensive treatment planning. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiosurgery alone for 5 or more brain metastases: expert opinion survey.

PubMed

Knisely, Jonathan P S; Yamamoto, Masaaki; Gross, Cary P; Castrucci, William A; Jokura, Hidefumi; Chiang, Veronica L S

2010-12-01

Oligometastatic brain metastases may be treated with stereotactic radiosurgery (SRS) alone, but no consensus exists as to when SRS alone would be appropriate. A survey was conducted at 2 radiosurgery meetings to determine which factors SRS practitioners emphasize in recommending SRS alone, and what physician characteristics are associated with recommending SRS alone for ≥ 5 metastases. All physicians attending the 8th Biennial Congress and Exhibition of the International Stereotactic Radiosurgery Society in June 2007 and the 18th Annual Meeting of the Japanese Society of Stereotactic Radiosurgery in July 2009 were asked to complete a questionnaire ranking 14 clinical factors on a 5-point Likert-type scale (ranging from 1 = not important to 5 = very important) to determine how much each factor might influence a decision to recommend SRS alone for brain metastases. Results were condensed into a single dichotomous outcome variable of "influential" (4-5) versus "not influential" (1-3). Respondents were also asked to complete the statement: "In general, a reasonable number of brain metastases treatable by SRS alone would be, at most, ___." The characteristics of physicians willing to recommend SRS alone for ≥ 5 metastases were assessed. Chi-square was used for univariate analysis, and logistic regression for multivariate analysis. The final study sample included 95 Gamma Knife and LINAC-using respondents (54% Gamma Knife users) in San Francisco and 54 in Sendai (48% Gamma Knife users). More than 70% at each meeting had ≥ 5 years experience with SRS. Sixty-five percent in San Francisco and 83% in Sendai treated ≥ 30 cases annually with SRS. The highest number of metastases considered reasonable to treat with SRS alone in both surveys was 50. In San Francisco, the mean and median numbers of metastases considered reasonable to treat with SRS alone were 6.7 and 5, while in Sendai they were 11 and 10. In the San Francisco sample, the clinical factors identified to be most influential in decision making were Karnofsky Performance Scale score (78%), presence/absence of mass effect (76%), and systemic disease control (63%). In Sendai, the most influential factors were the size of the metastases (78%), the Karnofsky Performance Scale score (70%), and metastasis location (68%). In San Francisco, 55% of respondents considered treating ≥ 5 metastases and 22% considered treating ≥ 10 metastases "reasonable." In Sendai, 83% of respondents considered treating ≥ 5 metastases and 57% considered treating ≥ 10 metastases "reasonable." In both groups, private practitioners, neurosurgeons, and Gamma Knife users were statistically significantly more likely to treat ≥ 5 metastases with SRS alone. Although there is no clear consensus for how many metastases are reasonable to treat with SRS alone, more than half of the radiosurgeons at 2 international meetings were willing to extend the use of SRS as an initial treatment for ≥ 5 brain metastases. Given the substantial variation in clinicians' approaches to SRS use, further research is required to identify patient characteristics associated with optimal SRS outcomes.

Higher dose rate Gamma Knife radiosurgery may provide earlier and longer-lasting pain relief for patients with trigeminal neuralgia.

PubMed

Lee, John Y K; Sandhu, Sukhmeet; Miller, Denise; Solberg, Timothy; Dorsey, Jay F; Alonso-Basanta, Michelle

2015-10-01

Gamma Knife radiosurgery (GKRS) utilizes cobalt-60 as its radiation source, and thus dose rate varies as the fixed source decays over its half-life of approximately 5.26 years. This natural decay results in increasing treatment times when delivering the same cumulative dose. It is also possible, however, that the biological effective dose may change based on this dose rate even if the total dose is kept constant. Because patients are generally treated in a uniform manner, radiosurgery for trigeminal neuralgia (TN) represents a clinical model whereby biological efficacy can be tested. The authors hypothesized that higher dose rates would result in earlier and more complete pain relief but only if measured with a sensitive pain assessment tool. One hundred thirty-three patients were treated with the Gamma Knife Model 4C unit at a single center by a single neurosurgeon during a single cobalt life cycle from January 2006 to May 2012. All patients were treated with 80 Gy with a single 4-mm isocenter without blocking. Using an output factor of 0.87, dose rates ranged from 1.28 to 2.95 Gy/min. The Brief Pain Inventory (BPI)-Facial was administered before the procedure and at the first follow-up office visit 1 month from the procedure (mean 1.3 months). Phone calls were made to evaluate patients after their procedures as part of a retrospective study. Univariate and multivariate linear regression was performed on several independent variables, including sex, age in deciles, diagnosis, follow-up duration, prior surgery, and dose rate. In the short-term analysis (mean 1.3 months), patients' self-reported pain intensity at its worst was significantly correlated with dose rate on multivariate analysis (p = 0.028). Similarly, patients' self-reported interference with activities of daily living was closely correlated with dose rate on multivariate analysis (p = 0.067). A 1 Gy/min decrease in dose rate resulted in a 17% decrease in pain intensity at its worst and a 22% decrease in pain interference with activities of daily living. In longer-term follow-up (mean 1.9 years), GKRS with higher dose rates (> 2.0 Gy/min; p = 0.007) and older age in deciles (p = 0.012) were associated with a lower likelihood of recurrence of pain. Prior studies investigating the role of dose rate in Gamma Knife radiosurgical ablation for TN have not used validated outcome tools to measure pain preoperatively. Consequently, differences in pain outcomes have been difficult to measure. By administering pain scales both preoperatively as well as postoperatively, the authors have identified statistically significant differences in pain intensity and pain interference with activities of daily living when comparing higher versus lower dose rates. Radiosurgery with a higher dose rate results in more pain relief at the early follow-up evaluation, and it may result in a lower recurrence rate at later follow-up.

Long-term follow-up studies of Gamma Knife surgery for patients with neurofibromatosis Type 2.

PubMed

Sun, Shibin; Liu, Ali

2014-12-01

The aim of this study was to evaluate long-term clinical outcomes after Gamma Knife surgery (GKS) for patients with neurofibromatosis Type 2 (NF2) and the role of GKS in the management of NF2. From December 1994 through December 2008, a total of 46 patients (21 male, 25 female) with NF2 underwent GKS and follow-up evaluation for at least 5 years at the Gamma Knife Center of the Beijing Neurosurgical Institute. GKS was performed using the Leksell Gamma Knife Models B and C. The mean age of the patients was 30 years (range 13-59 years). A family history of NF2 was found for 9 (20%) patients. The NF2 phenotype was thought to be Wishart for 20 (44%) and Feiling-Gardner for 26 (56%) patients. Among these 46 patients, GKS was performed to treat 195 tumors (73 vestibular schwannomas and 122 other tumors including other schwannomas and meningiomas). For vestibular schwannomas, the mean volume was 5.1 cm(3) (median 3.6 cm(3), range 0.3-27.3 cm(3)), the mean margin dose was 12.9 Gy (range 10-14 Gy), and the mean maximum dose was 27.3 Gy (range 16.2-40 Gy). For other tumors, the mean volume was 1.7 cm(3) (range 0.3-5.5 cm(3)), the mean margin dose was 13.3 Gy (range 11-14 Gy), and the mean maximum dose was 26.0 Gy (range 18.0-30.4 Gy). The median duration of follow-up was 109 months (range 8-195 months). For the 73 vestibular schwannomas that underwent GKS, the latest follow-up MR images demonstrated regression of 30 (41%) tumors, stable size for 31 (43%) tumors, and enlargement of 12 (16%) tumors. The total rate of tumor control for bilateral vestibular schwannomas in patients with NF2 was 84%. Of the 122 other types of tumors that underwent GKS, 103 (85%) showed no tumor enlargement. The rate of serviceable hearing preservation after GKS was 31.9% (15/47). The actuarial rates for hearing preservation at 3 years, 5 years, 10 years, and 15 years were 98%, 93%, 44%, and 17%, respectively. Of the 46 patients, 22 (48%) became completely bilaterally deaf, 17 (37%) retained unilateral serviceable hearing, and 7 (15%) retained bilateral serviceable hearing. The mean history of the disease course was 12 years (range 5-38 years). GKS was confirmed to provide long-term local tumor control for small- to medium-sized vestibular schwannomas and other types of tumors, although vestibular schwannomas in patients with NF2 responded less well than did unilateral sporadic vestibular schwannomas. Phenotype is the most strongly predictive factor of final outcome after GKS for patients with NF2. The risk for loss of hearing is high, whereas the risk for other cranial nerve complications is low.

Gamma Knife surgery for arteriovenous malformations in the brain: integration of time-resolved contrast-enhanced magnetic resonance angiography into dosimetry planning. Technical note.

PubMed

Taschner, Christian A; Le Thuc, Vianney; Reyns, Nicolas; Gieseke, Juergen; Gauvrit, Jean-Yves; Pruvo, Jean-Pierre; Leclerc, Xavier

2007-10-01

The aim of this study was to develop an algorithm for the integration of time-resolved contrast-enhanced magnetic resonance (MR) angiography into dosimetry planning for Gamma Knife surgery (GKS) of arteriovenous malformations (AVMs) in the brain. Twelve patients harboring brain AVMs referred for GKS underwent intraarterial digital subtraction (DS) angiography and time-resolved MR angiography while wearing an externally applied cranial stereotactic frame. Time-resolved MR angiography was performed on a 1.5-tesla MR unit (Achieva, Philips Medical Systems) using contrast-enhanced 3D fast field echo sequencing with stochastic central k-space ordering. Postprocessing with interactive data language (Research Systems, Inc.) produced hybrid data sets containing dynamic angiographic information and the MR markers necessary for stereotactic transformation. Image files were sent to the Leksell GammaPlan system (Elekta) for dosimetry planning. Stereotactic transformation of the hybrid data sets containing the time-resolved MR angiography information with automatic detection of the MR markers was possible in all 12 cases. The stereotactic coordinates of vascular structures predefined from time-resolved MR angiography matched with DS angiography data in all cases. In 10 patients dosimetry planning could be performed based on time-resolved MR angiography data. In two patients, time-resolved MR angiography data alone were considered insufficient. The target volumes showed a notable shift of centers between modalities. Integration of time-resolved MR angiography data into the Leksell GammaPlan system for patients with brain AVMs is feasible. The proposed algorithm seems concise and sufficiently robust for clinical application. The quality of the time-resolved MR angiography sequencing needs further improvement.

A comparison of two prompt gamma imaging techniques with collimator-based cameras for range verification in proton therapy

NASA Astrophysics Data System (ADS)

Lin, Hsin-Hon; Chang, Hao-Ting; Chao, Tsi-Chian; Chuang, Keh-Shih

2017-08-01

In vivo range verification plays an important role in proton therapy to fully utilize the benefits of the Bragg peak (BP) for delivering high radiation dose to tumor, while sparing the normal tissue. For accurately locating the position of BP, camera equipped with collimators (multi-slit and knife-edge collimator) to image prompt gamma (PG) emitted along the proton tracks in the patient have been proposed for range verification. The aim of the work is to compare the performance of multi-slit collimator and knife-edge collimator for non-invasive proton beam range verification. PG imaging was simulated by a validated GATE/GEANT4 Monte Carlo code to model the spot-scanning proton therapy and cylindrical PMMA phantom in detail. For each spot, 108 protons were simulated. To investigate the correlation between the acquired PG profile and the proton range, the falloff regions of PG profiles were fitted with a 3-line-segment curve function as the range estimate. Factors including the energy window setting, proton energy, phantom size, and phantom shift that may influence the accuracy of detecting range were studied. Results indicated that both collimator systems achieve reasonable accuracy and good response to the phantom shift. The accuracy of range predicted by multi-slit collimator system is less affected by the proton energy, while knife-edge collimator system can achieve higher detection efficiency that lead to a smaller deviation in predicting range. We conclude that both collimator systems have potentials for accurately range monitoring in proton therapy. It is noted that neutron contamination has a marked impact on range prediction of the two systems, especially in multi-slit system. Therefore, a neutron reduction technique for improving the accuracy of range verification of proton therapy is needed.

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

PubMed

Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

2016-09-08

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. © 2016 The Authors.

[Development of external quality control protocol for CyberKnife beams dosimetry: preliminary tests multicentre].

PubMed

Guinement, L; Marchesi, V; Veres, A; Lacornerie, T; Buchheit, I; Peiffert, D

2013-01-01

To develop an external quality control procedure for CyberKnife(®) beams. This work conducted in Nancy, has included a test protocol initially drawn by the medical physicist of Nancy and Lille in collaboration with Equal-Estro Laboratory. A head and neck anthropomorphic phantom and a water-equivalent homogeneous cubic plastic test-object, so-called "MiniCube", have been used. Powder and solid thermoluminescent dosimeters as well as radiochromic films have been used to perform absolute and relative dose studies, respectively. The comparison between doses calculated by Multiplan treatment planning system and measured doses have been studied in absolute dose. The dose distributions measured with films and treatment planning system calculations have been compared via the gamma function, configured with different tolerance criteria. This work allowed, via solid thermoluminescent dosimeter measurements, verifying the beam reliability with a reproducibility of 1.7 %. The absolute dose measured in the phantom irradiated by the seven participating centres has shown an error inferior to the standard tolerance limits (± 5 %), for most of participating centres. The relative dose measurements performed at Nancy and by the Equal-Estro laboratory allowed defining the most adequate parameters for gamma index (5 %/2mm--with at least 95 % of pixels satisfying acceptability criteria: γ<1). These parameters should be independent of the film analysis software. This work allowed defining a dosimetric external quality control for CyberKnife(®) systems, based on a reproducible irradiation plan through measurements performed with thermoluminescent dosimeters and radiochromic films. This protocol should be validated by a new series of measurement and taking into account the lessons of this work. Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Clinical features of brain metastases from hepatocellular carcinoma using gamma knife surgery.

PubMed

Ogino, Akiyoshi; Hirai, Tatsuo; Serizawa, Toru; Yoshino, Atsuo

2018-05-01

Brain metastases from hepatocellular carcinoma (HCC) are rare, but their incidence is increasing because of developments in recent therapeutic advances. The purpose of this study was to investigate the characteristics of brain metastases from HCC, to evaluate the predictive factors, and to assess the efficacy of gamma knife surgery (GKS). A retrospective study was performed on patients with brain metastases from HCC who were treated at Tokyo Gamma Unit Center from 2005 to 2014. Nineteen patients were identified. The median age at diagnosis of brain metastases was 67.0 years. Fifteen patients were male and four patients were female. Six patients were infected with hepatitis B virus (HBV). Two patients were infected with hepatitis C virus (HCV). Eleven patients were not infected with HBV or HCV. The median interval from the diagnosis of HCC to brain metastases was 32.0 months. The median number of brain metastases was two. The median Karnofsky performance score at first GKS was 70. The median survival time following brain metastases was 21.0 weeks. Six-month and 1-year survival rates were 41.2 and 0%, respectively. One month after GKS, no tumor showed progressive disease. The HBV infection (positive vs. negative) was significantly associated with survival according to univariate analysis (p = 0.002). The patients having brain metastases from HCC had poor prognosis and low performance state. Therefore, GKS is an acceptable option for controlling brain metastases from HCC because GKS is noninvasive remedy and local control is reasonable.

Multiple Comparisons of Glucokinase Activation Mechanisms of Five Mulberry Bioactive Ingredients in Hepatocyte.

PubMed

He, Hao; Yu, Wan-Guo; Yang, Jun-Peng; Ge, Sheng; Lu, Yan-Hua

2016-03-30

Glucokinase (GK) activity, which is rapidly regulated by glucokinase regulatory protein (GKRP) in the liver, is crucial for blood glucose homeostasis. In this paper, the GK activation mechanisms of 1-deoxynojrimycin (DNJ), resveratrol (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) were compared. The results revealed that DNJ, RES, C3G, and C3R could differently improve glucose consumption and enhance intracellular GK activities. DNJ and RES significantly promoted GK translocation at 12.5 μM, whereas other ingredients showed moderate effects. DNJ, C3G, and C3R could rupture intramolecular hydrogen bonds of GK to accelerate its allosteric activation at early stage. RES and OXY could bind to a "hydrophobic pocket" on GK to stabilize the active GK at the final stage. Otherwise, RES, OXY, C3G, and C3R could interact with GKRP at the F1P binding site to promote GK dissociation and translocation. Enzymatic assay showed that RES (15-50 μM) and OXY (25-50 μM) could significantly enhance GK activities, which was caused by their binding properties with GK. Moreover, the most dramatic up-regulation effects on GK expression were observed in C3G and C3R groups. This work expounded the differences between GK activation mechanisms, and the new findings would help to develop new GK activators.

Mice mutant for glucokinase regulatory protein exhibit decreased liver glucokinase: A sequestration mechanism in metabolic regulation

PubMed Central

Farrelly, Dennis; Brown, Karen S.; Tieman, Aaron; Ren, Jianming; Lira, Sergio A.; Hagan, Deborah; Gregg, Richard; Mookhtiar, Kasim A.; Hariharan, Narayanan

1999-01-01

The importance of glucokinase (GK; EC 2.7.1.12) in glucose homeostasis has been demonstrated by the association of GK mutations with diabetes mellitus in humans and by alterations in glucose metabolism in transgenic and gene knockout mice. Liver GK activity in humans and rodents is allosterically inhibited by GK regulatory protein (GKRP). To further understand the role of GKRP in GK regulation, the mouse GKRP gene was inactivated. With the knockout of the GKRP gene, there was a parallel loss of GK protein and activity in mutant mouse liver. The loss was primarily because of posttranscriptional regulation of GK, indicating a positive regulatory role for GKRP in maintaining GK levels and activity. As in rat hepatocytes, both GK and GKRP were localized in the nuclei of mouse hepatocytes cultured in low-glucose-containing medium. In the presence of fructose or high concentrations of glucose, conditions known to relieve GK inhibition by GKRP in vitro, only GK was translocated into the cytoplasm. In the GKRP-mutant hepatocytes, GK was not found in the nucleus under any tested conditions. We propose that GKRP functions as an anchor to sequester and inhibit GK in the hepatocyte nucleus, where it is protected from degradation. This ensures that glucose phosphorylation is minimal when the liver is in the fasting, glucose-producing phase. This also enables the hepatocytes to rapidly mobilize GK into the cytoplasm to phosphorylate and store or metabolize glucose after the ingestion of dietary glucose. In GKRP-mutant mice, the disruption of this regulation and the subsequent decrease in GK activity leads to altered glucose metabolism and impaired glycemic control. PMID:10588736

A minimally invasive treatment option for large metastatic brain tumors: long-term results of two-session Gamma Knife stereotactic radiosurgery

PubMed Central

2014-01-01

Background Large brain metastases (BM) remain a significant cause of morbidity and death for cancer patients despite current advances in multimodality therapies. The goal of the present study was to evaluate the efficacy and limitations of 2-session Gamma Knife stereotactic radiosurgery (SRS) for patients with large BM. Methods This is a prospective, open-label and single arm study analyzing 58 consecutive patients who received 2-session SRS for large BM (≥ 10 mL). The median age was 66 years, and the median Karnofsky performance status (KPS) score was 70. SRS was the initial treatment in 51 large tumors (84%) and was used as salvage after failed prior treatments for 10 tumors (16%). The fraction protocol was 20-30 Gy given in 2 fractions with 3–4 weeks between fractions. Overall survival (OS) and neurological death (ND), local tumor control and KPS were analyzed. Results The median follow-up time was 9.0 months. One- and 2-year OS rates were 47% and 20%, respectively. The median OS time was 11.8 months (95% CI: 5.5-15.6). The causes of death were intracranial local progression in 5 cases, meningeal carcinomatosis in 3 and progression of the primary lesion in 39. One- and 2-year ND-free survival rates were 91% and 84%, respectively. In 52 of 61 large BM (85%) with sufficient radiological follow-up data, 6- and 12-month local tumor control rates were 85% and 64%, respectively. The mean KPS improved from 70 at the 1st SRS to 82 at the 2nd; the first follow-up mean KPS was 87 (P < 0.001). Symptomatic radiation injury developed and required conservative treatment in 3 patients (5%). Conclusions Long-term follow-up showed that two-session Gamma Knife SRS achieved durable tumor control rates as well as acceptable treatment-related morbidity. This treatment method may potentially merit being offered to patients with large BM who are in poor condition or are otherwise ineligible for standard care. PMID:24917309

Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study.

PubMed

Pomeraniec, I Jonathan; Kano, Hideyuki; Xu, Zhiyuan; Nguyen, Brandon; Siddiqui, Zaid A; Silva, Danilo; Sharma, Mayur; Radwan, Hesham; Cohen, Jonathan A; Dallapiazza, Robert F; Iorio-Morin, Christian; Wolf, Amparo; Jane, John A; Grills, Inga S; Mathieu, David; Kondziolka, Douglas; Lee, Cheng-Chia; Wu, Chih-Chun; Cifarelli, Christopher P; Chytka, Tomas; Barnett, Gene H; Lunsford, L Dade; Sheehan, Jason P

2017-10-27

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

TH-CD-BRA-09: Towards Absolute Dose Measurement in MRI-Linac and Gamma-Knife: Design and Construction of An MR-Compatible Water Calorimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Entezari, N; Sarfehnia, A; Renaud, J

Purpose: The purpose of this work is to design and optimize a portable Water Calorimeter (WC) for use in a commercial MRI-linac and Gamma-knife in addition to conventional radiotherapy linacs. Water calorimeters determine absorbed dose to water at a point by measuring radiation-induced temperature rise of the volume (the two are related by the medium specific heat capacity). In this formalism, one important correction factor is heat transfer correction k-ht. It compensates for heat gain/loss due to conductive and convective effects, and is numerically calculated as ratio of temperature rise in the absence of heat loss to that in themore » presence of heat loss. Operating at 4°C ensures convection is minimal. Methods: A commercial finite element software was used to evaluate several WC designs with different insulation materials and thicknesses; channels allowing coolant to travel around WC (to sustain WC at 4°C) were modeled, and worst-case scenario variation in the temperature of the coolant was simulated for optimization purposes (2.6 mK/s). Additionally, several calorimeter vessel design parameters (front/back glass thickness/separation, diameter) were also simulated and optimized. Optimization is based on minimizing long term calorimeter drift (24h) as well as variation and magnitude of k-ht. Results: The final selected WC design reached a modest drift of 11µK/s after 15h for the worst-case coolant temperature variation. This design consists of coolant channels being encompassed on both sides by cryogel insulation. For the MRI-linac beam, glass thickness plays the largest effect on k-ht with variation of upto 0.6% in the first run for thicknesses ranging between 0.5–1.7mm. Subsequent runs vary only within 0.1% with glass thickness. Other factors such as vessel radius and top/bottom glass separation have sub 0.1% effects on k-ht. Conclusion: An MR-safe 4°C stagnant WC appropriate for dosimetry in MRI-linac and Gamma-Knife was designed, optimized, and construction is nearly completed. NSERC Discovery Grant RGPIN-435608.« less

Susceptibility of Glucokinase-MODY Mutants to Inactivation by Oxidative Stress in Pancreatic β-Cells

PubMed Central

Cullen, Kirsty S.; Matschinsky, Franz M.; Agius, Loranne; Arden, Catherine

2011-01-01

OBJECTIVE The posttranslational regulation of glucokinase (GK) differs in hepatocytes and pancreatic β-cells. We tested the hypothesis that GK mutants that cause maturity-onset diabetes of the young (GK-MODY) show compromised activity and posttranslational regulation in β-cells. RESEARCH DESIGN AND METHODS Activity and protein expression of GK-MODY and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) mutants were studied in β-cell (MIN6) and non–β-cell (H4IIE) models. Binding of GK to phosphofructo-2-kinase, fructose-2,6-bisphosphatase (PFK2/FBPase2) was studied by bimolecular fluorescence complementation in cell-based models. RESULTS Nine of 11 GK-MODY mutants that have minimal effect on enzyme kinetics in vitro showed decreased specific activity relative to wild type when expressed in β-cells. A subset of these were stable in non–β-cells but showed increased inactivation in conditions of oxidative stress and partial reversal of inactivation by dithiothreitol. Unlike the GK-MODY mutants, four of five GK-PHHI mutants had similar specific activity to wild type and Y214C had higher activity than wild type. The GK-binding protein PFK2/FBPase2 protected wild-type GK from oxidative inactivation and the decreased stability of GK-MODY mutants correlated with decreased interaction with PFK2/FBPase2. CONCLUSIONS Several GK-MODY mutants show posttranslational defects in β-cells characterized by increased susceptibility to oxidative stress and/or protein instability. Regulation of GK activity through modulation of thiol status may be a physiological regulatory mechanism for the control of GK activity in β-cells. PMID:22028181

Susceptibility of glucokinase-MODY mutants to inactivation by oxidative stress in pancreatic β-cells.

PubMed

Cullen, Kirsty S; Matschinsky, Franz M; Agius, Loranne; Arden, Catherine

2011-12-01

The posttranslational regulation of glucokinase (GK) differs in hepatocytes and pancreatic β-cells. We tested the hypothesis that GK mutants that cause maturity-onset diabetes of the young (GK-MODY) show compromised activity and posttranslational regulation in β-cells. Activity and protein expression of GK-MODY and persistent hyperinsulinemic hypoglycemia of infancy (PHHI) mutants were studied in β-cell (MIN6) and non-β-cell (H4IIE) models. Binding of GK to phosphofructo-2-kinase, fructose-2,6-bisphosphatase (PFK2/FBPase2) was studied by bimolecular fluorescence complementation in cell-based models. Nine of 11 GK-MODY mutants that have minimal effect on enzyme kinetics in vitro showed decreased specific activity relative to wild type when expressed in β-cells. A subset of these were stable in non-β-cells but showed increased inactivation in conditions of oxidative stress and partial reversal of inactivation by dithiothreitol. Unlike the GK-MODY mutants, four of five GK-PHHI mutants had similar specific activity to wild type and Y214C had higher activity than wild type. The GK-binding protein PFK2/FBPase2 protected wild-type GK from oxidative inactivation and the decreased stability of GK-MODY mutants correlated with decreased interaction with PFK2/FBPase2. Several GK-MODY mutants show posttranslational defects in β-cells characterized by increased susceptibility to oxidative stress and/or protein instability. Regulation of GK activity through modulation of thiol status may be a physiological regulatory mechanism for the control of GK activity in β-cells.

Enhancement of lymphocyte proliferation by mouse glandular kallikrein.

PubMed

Hu, Z Q; Murakami, K; Ikigai, H; Shimamura, T

1992-03-01

Mouse glandular kallikrein (mGK) strongly enhanced the spontaneous and mitogen-induced proliferation of lymphocytes. Both blast formation and 3H-TdR incorporation were dose-dependently enhanced at the same time many cells were killed. The enhancing activity was independent of EGF, because EGF-binding proteins (mGK-9 in mGK-6,9 mixture and mGK-13), renal kallikrein (mGK-6) and human kallikrein all displayed the same enhancement. A serine proteinase inhibitor, diisopropyl fluorophosphate, could block the enhancement by mGK. The new function suggests that mGK is important in the immune system as a regulatory molecule.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gopishankar, N; Agarwal, Priyanka; Bisht, Raj Kishor

Purpose: To evaluate forward and inverse planning methods for acoustic neuroma cases treated in Gamma Knife Perfexion. Methods: Five patients with acoustic neuroma tumour abutting brainstem were planned twice in LGP TPS (Version 10.1) using TMR10 algorithm. First plan was entirely based on forward planning (FP) in which each shot was chosen manually. Second plan was generated using inverse planning (IP) for which planning parameters like coverage, selectivity, gradient index (GI) and beam-on time threshold were set. Number of shots in IP was automatically selected by objective function using iterative process. In both planning methods MRI MPRAGE sequence images weremore » used for tumour localization and planning. A planning dose of 12Gy at 50% isodose level was chosen. Results and Discussion: Number of shots used in FP was greater than IP and beam-on time in FP was in average 1.4 times more than IP. One advantage of FP was that the brainstem volume subjected to 6Gy dose (25% isodose) was less in FP than IP. Our results showed use of more number of shots as in FP results in GI less than or equal to 2.55 which is close to its lower limit. Dose homogeneity index (DHI) analysis of FP and IP showed average values of 0.59 and 0.67 respectively. General trend in GK for planning in acoustic neuroma cases is to use small collimator shots to avoid dose to adjacent critical structures. More number of shots and prolonged treatment time causes inconvenience to the patients. Similarly overuse of automatic shot shaping as in IP results in increased scatter dose. A compromise is required in shot selection for these cases. Conclusion: IP method could be used in acoustic neuroma cases to decrease treatment time provided the source sector openings near brainstem are shielded or adjusted appropriately to reduce brainstem dose.« less

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

Integrable deformations of the Gk1 ×Gk2 /Gk1+k2 coset CFTs

NASA Astrophysics Data System (ADS)

Sfetsos, Konstantinos; Siampos, Konstantinos

2018-02-01

We study the effective action for the integrable λ-deformation of the Gk1 ×Gk2 /Gk1+k2 coset CFTs. For unequal levels theses models do not fall into the general discussion of λ-deformations of CFTs corresponding to symmetric spaces and have many attractive features. We show that the perturbation is driven by parafermion bilinears and we revisit the derivation of their algebra. We uncover a non-trivial symmetry of these models parametric space, which has not encountered before in the literature. Using field theoretical methods and the effective action we compute the exact in the deformation parameter β-function and explicitly demonstrate the existence of a fixed point in the IR corresponding to the Gk1-k2 ×Gk2 /Gk1 coset CFTs. The same result is verified using gravitational methods for G = SU (2). We examine various limiting cases previously considered in the literature and found agreement.

Gamma Knife surgery in patients harboring orbital cavernous hemangiomas that were diagnosed on the basis of imaging findings.

PubMed

Liu, Xiaomin; Xu, Desheng; Zhang, Yipei; Liu, Dong; Song, Guoxiang

2010-12-01

This study was undertaken to evaluate clinical outcomes and tumor control in patients harboring orbital cavernous hemangiomas (OCHs) that had been diagnosed based on findings of imaging studies and treated by Gamma Knife surgery (GKS). Between 1995 and 2008, 23 patients harboring OCHs that had been diagnosed on the basis of imaging findings were treated using GKS; complete follow-up data are available in all cases. The median treatment volume was 1.5 cm³ (range 0.15-10.10 cm³), the median tumor margin dose was 15 Gy (range 12-20 Gy), and the median follow-up period was 12 months (range 6-120 months). A decrease in tumor size was found in 20 patients, and no tumor progression was observed after GKS. Eleven of 14 patients whose visual function had been adversely affected prior to treatment had improved visual acuity at the last assessment. Side effects of the procedure included orbital pain in 3 patients and chemosis in 2 patients. In this preliminary experience, GKS proved to be an effective treatment for OCHs diagnosed on the basis of imaging findings. Additional follow-up is necessary, and the long-term side effects of the procedure still need to be determined.

Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

PubMed Central

Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2012-01-01

Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

Gamma Knife Treatment of Brainstem Metastases

PubMed Central

Peterson, Halloran E.; Larson, Erik W.; Fairbanks, Robert K.; MacKay, Alexander R.; Lamoreaux, Wayne T.; Call, Jason A.; Carlson, Jonathan D.; Ling, Benjamin C.; Demakas, John J.; Cooke, Barton S.; Peressini, Ben; Lee, Christopher M.

2014-01-01

The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control. PMID:24886816

Tolerability and efficacy of gamma knife radiosurgery on hepatocellular carcinoma with portal vein tumor thrombosis

PubMed Central

Lu, Xiao-Jie; Dong, Jing; Ji, Li-Juan; Xiao, Li-Xin; Ling, Chang-Quan; Zhou, Jun

2016-01-01

This is a retrospective study on the safety and efficacy of gamma knife radiosurgery (GKR) in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Patients with confirmed HCC and PVTT were allocated into two groups based on the treatments they received (palliative or GKR). A total of 138 patients were included (74 in the palliative group, 64 in GKR group). No significant differences in baseline characteristics existed between the two groups. Treatment-related adverse events (AEs) were recorded and compared between groups. The majority of AEs were mild to moderate and subsided naturally or after medication. There was no AE-induced death. The influences of baseline characteristics and treatment options on patients' OS were analyzed. The median OS of patients in the palliative and GKR group were 3.0 months (95% CI: 2.719-3.281) and 6.1 months (95% CI: 4.706-7.494) respectively (p = 0.003). Multivariate analysis revealed that GKR treatment, performance status 0-1, Child A, smaller tumor diameter and monolobar distribution were significant favorable prognosticators. Subgroup analyses showed OS benefit of GKR regardless of PVTT location (main or branch of PVTT). In conclusion, GKR is well tolerated in selected HCC-PVTT patients and can confer OS benefit, which needs validation in future prospective studies. PMID:26473291

Gamma Knife Radiosurgery Treatment for Metastatic Melanoma of the Trigeminal Nerve and Brainstem: A Case Report and a Review of the Literature

PubMed Central

Peterson, Halloran E.; Larson, Erik W.; Fairbanks, Robert K.; Lamoreaux, Wayne T.; Mackay, Alexander R.; Call, Jason A.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

2013-01-01

Objective and Importance. Brainstem metastases (BSMs) are uncommon but serious complications of some cancers. They cause significant neurological deficit, and options for treatment are limited. Stereotactic radiosurgery (SRS) has been shown to be a safe and effective treatment for BSMs that prolongs survival and can preserve or in some cases improve neurological function. This case illustrates the use of repeated SRS, specifically Gamma Knife radiosurgery (GKRS) for management of a unique brainstem metastasis. Clinical Presentation. This patient presented 5 years after the removal of a lentigo maligna melanoma from her left cheek with left sided facial numbness and paresthesias with no reported facial weakness. Initial MRI revealed a mass on the left trigeminal nerve that appeared to be a trigeminal schwannoma. Intervention. After only limited response to the first GKRS treatment, a biopsy of the tumor revealed it to be metastatic melanoma, not schwannoma. Over the next two years, the patient would receive 3 more GKRS treatments. These procedures were effective in controlling growth in the treated areas, and the patient has maintained a good quality of life. Conclusion. GKRS has proven in this case to be effective in limiting the growth of this metastatic melanoma without acute adverse effects. PMID:24194991

Pros, cons, and current indications of open craniotomy versus gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization.

PubMed

Surdell, Daniel L; Bhattacharjee, Sumon; Loftus, Christopher M

2002-06-01

The successful treatment of an intracranial arteriovenous malformation poses both technical and conceptual problems to the neurosurgeon. Treatment decisions are made in light of current understanding of the natural history of these lesions. It is important to understand the pros, cons and current indication of open craniotomy vs. gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization. Surgical removal of an arteriovenous malformation is indicated when the operative risk is less than the morbidity and mortality associated with its natural history. The treatment goal of complete angiographic obliteration of arteriovenous malformations is achieved most effectively by microneurosurgery in low-grade lesions. Large lesions frequently require a combination of embolization and microsurgery. Although recent advances in technology and medical management have allowed previously inoperable arteriovenous malformations to be surgically excised, there is still a small group of arteriovenous malformations that cannot be excised safely due to their size and location. Stereotactic radiosurgery is clearly an important adjunct in the multimodality treatment approach for large arteriovenous malformations. Endovascular embolization can potentially increase safety and efficacy in the treatment of arteriovenous malformations when applied to selective cases with well-defined treatment goals.

Benign orbital apex tumors treated with multisession gamma knife radiosurgery.

PubMed

Goh, Alice Siew Ching; Kim, Yoon-Duck; Woo, Kyung In; Lee, Jung-Il

2013-03-01

The orbital apex is an important anatomic landmark that hosts numerous critical neurovascular structures. Tumor resection performed at this complex region poses a therapeutic challenge to orbital surgeons and often is associated with significant visual morbidity. This article reports the efficacy and safety of multisession gamma knife radiosurgery (GKRS) in benign, well-circumscribed tumors located at the orbital apex. Retrospective interventional case series. Five patients with visual disturbances resulting from a benign, well-circumscribed orbital apex tumor (3 cases of cavernous hemangioma and 2 cases of schwannoma). Each patient treated with GKRS with a total radiation dose of 20 Gy in 4 sessions (5 Gy in each session with an isodose line of 50%) delivered to the tumor margin. Best-corrected visual acuity, visual field changes, orbital imaging, tumor growth control, and side effects of radiation. All patients demonstrated improvement in visual acuity, pupillary responses, color vision, and visual field. Tumor shrinkage was observed in all patients and remained stable until the last follow-up. No adverse events were noted during or after the radiosurgery. None of the patients experienced any radiation-related ocular morbidity. From this experience, multisession GKRS seems to be an effective management strategy to treat solitary, benign, well-circumscribed orbital apex tumors. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Gamma Knife radiosurgery for intracranial hemangioblastoma.

PubMed

Silva, Danilo; Grabowski, Mathew M; Juthani, Rupa; Sharma, Mayur; Angelov, Lilyana; Vogelbaum, Michael A; Chao, Samuel; Suh, John; Mohammadi, Alireza; Barnett, Gene H

2016-09-01

Gamma knife radiosurgery (GKRS) has become a treatment option for intracranial hemangioblastomas, especially in patients with poor clinical status and also high-risk surgical candidates. The objective of this study was to analyze clinical outcome and tumor control rates. Retrospective chart review revealed 12 patients with a total of 20 intracranial hemangioblastomas treated with GKRS from May 1998 until December 2014. Kaplan-Meier plots were used to calculate the actuarial local tumor control rates and rate of recurrence following GKRS. Univariate analysis, including log rank test and Wilcoxon test were used on the Kaplan-Meier plots to evaluate the predictors of tumor progression. Two-tailed p value of <0.05 was considered as significant. Median follow-up was 64months (2-184). Median tumor volume pre-GKRS was 946mm(3) (79-15970), while median tumor volume post-GKRS was 356mm(3) (30-5404). Complications were seen in two patients. Tumor control rates were 100% at 1year, 90% at 3years, and 85% at 5years, using the Kaplan-Meier method. There were no statistically significant univariate predictors of progression identified, although there was a trend towards successful tumor control in solid tumors (p=0.07). GKRS is an effective and safe option for treating intracranial hemangioblastoma with favorable tumor control rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic

DTIC Science & Technology

2006-12-01

acyltransferase by compound 58-035. J.Biol.Chem. 259:815-819. 5. Li,Y., Gerbod- Giannone ,M.C., Seitz,H., Cui,D., Thorp,E., Tall,A.R., Matsushima,G.K., and...differentiation of human breast cancer through PPAR gamma. Mol.Cell 1:465-470. 9. Li,Y., Schwabe,R.F., DeVries-Seimon,T., Yao,P.M., Gerbod- Giannone ...receptor. J. Cell Biol. 171:61-73. *86. Li, Y., Gerbod- Giannone , M.C., Seitz, H., Cui, D., Thorp, E., Tall, A.R., Matsushima, G.K., and Tabas

Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

NASA Astrophysics Data System (ADS)

Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

2013-12-01

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors.

PubMed

Lloyd, David J; St Jean, David J; Kurzeja, Robert J M; Wahl, Robert C; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S; Pennington, Lewis D; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H; Andrews, Kristin L; Bartberger, Michael D; Van, Gwyneth; Galbreath, Elizabeth J; Vonderfecht, Steven L; Wang, Minghan; Jordan, Steven R; Véniant, Murielle M; Hale, Clarence

2013-12-19

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

Gamma Knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part I: Differences in epidemiologic, morphologic, and clinical characteristics, permanent complications, and bleeding in the latency period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicolato, Antonio; Lupidi, Francesco; Section of Stereotactic and Functional Neurosurgery, University of Verona and University Hospital, Verona

Purpose: To compare the epidemiologic, morphologic, and clinical characteristics of 92 children/adolescents (Group A) and 362 adults (Group B) with cerebral arteriovenous malformations (cAVMs) considered suitable for radiosurgery; to correlate radiosurgery-related permanent complication and post-radiosurgery bleeding rates in the 75 children/adolescents and 297 adults available for follow-up. Methods and Materials: Radiosurgery was performed with a model C 201-source Co{sup 6} Leksell Gamma Unit (Elekta Instruments, Stockholm, Sweden). Fisher exact two-tailed, Wilcoxon rank-sum, and two-sample binomial exact tests were used for statistical analysis. Results: There were significant differences between the two populations in sex (p = 0.015), clinical presentation (p =more » 0.001), and location (p = 0.008). The permanent complication rate was lower in younger (1.3%) than in older patients (5.4%), although the difference was not significant (p = 0.213). The postradiosurgery bleeding rate was lower in Group A (1.3%) than in Group B (2.7%) (p = 0.694), with global actuarial bleeding rates of 0.56% per year and 1.15% per year, respectively. Conclusions: The different characteristics of child/adolescent and adult cAVMs suggest that they should be considered two distinct vascular disorders. The similar rates of radiosurgery-related complications and latency period bleeding in the two populations show that gamma knife radiosurgery does not expose young patients to a higher risk of sequelae than that for older patients.« less

The rice nuclear gene, VIRESCENT 2, is essential for chloroplast development and encodes a novel type of guanylate kinase targeted to plastids and mitochondria.

PubMed

Sugimoto, Hiroki; Kusumi, Kensuke; Noguchi, Ko; Yano, Masahiro; Yoshimura, Atsushi; Iba, Koh

2007-11-01

Guanylate kinase (GK) is a critical enzyme in guanine nucleotide metabolism pathways, catalyzing the phosphorylation of (d)GMP to (d)GDP. Here we show that a novel gene, VIRESCENT 2 (V2), encodes a new type of GK (designated pt/mtGK) that is localized in plastids and mitochondria. We initially identified the V2 gene by positional cloning of the rice v2 mutant. The v2 mutant is temperature-sensitive and develops chlorotic leaves at restrictive temperatures. The v2 mutation causes inhibition of chloroplast differentiation; in particular, it disrupts the chloroplast translation machinery during early leaf development [Sugimoto et al. (2004)Plant Cell Physiol. 45, 985]. In the bacterial and animal species studied to date, GK is localized in the cytoplasm and participates in maintenance of the guanine nucleotide pools required for many fundamental cellular processes. Phenotypic analysis of rice seedlings with RNAi knockdown of cytosolic GK (designated cGK) showed that cGK is indispensable for the growth and development of plants, but not for chloroplast development. Thus, rice has two types of GK, as does Arabidopsis, suggesting that higher plants have two types of GK. Our results suggest that, of the two types of GK, only pt/mtGK is essential for chloroplast differentiation.

Intracellular transport and stability of varicella-zoster virus glycoprotein K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hall, Susan L.; Govero, Jennifer L.; Heineman, Thomas C.

2007-02-20

VZV gK, an essential glycoprotein that is conserved among the alphaherpesviruses, is believed to participate in membrane fusion and cytoplasmic virion morphogenesis based on analogy to its HSV-1 homolog. However, the production of VZV gK-specific antibodies has proven difficult presumably due to its highly hydrophobic nature and, therefore, VZV gK has received limited study. To overcome this obstacle, we inserted a FLAG epitope into gK near its amino terminus and produced VZV recombinants expressing epitope-tagged gK (VZV gK-F). These recombinants grew indistinguishably from native VZV, and FLAG-tagged gK could be readily detected in VZV gK-F-infected cells. FACS analysis established thatmore » gK is transported to the plasma membrane of infected cells, while indirect immunofluorescence demonstrated that gK accumulates predominately in the Golgi. Using VZV gK-F-infected cells we demonstrated that VZV gK, like several other herpesvirus glycoproteins, is efficiently endocytosed from the plasma membrane. However, pulse-labeling experiments revealed that the half-life of gK is considerably shorter than that of other VZV glycoproteins including gB, gE and gH. This finding suggests that gK may be required in lower abundance than other viral glycoproteins during virion morphogenesis or viral entry.« less

Regulation of liver glucokinase activity in rats with fructose-induced insulin resistance and impaired glucose and lipid metabolism.

PubMed

Francini, Flavio; Castro, María C; Gagliardino, Juan J; Massa, María L

2009-09-01

We evaluated the relative role of different regulatory mechanisms, particularly 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK2/FBPase-2), in liver glucokinase (GK) activity in intact animals with fructose-induced insulin resistance and impaired glucose and lipid metabolism. We measured blood glucose, triglyceride and insulin concentration, glucose tolerance, liver triglyceride content, GK activity, and GK and PFK2 protein and gene expression in fructose-rich diet (FRD) and control rats. After 3 weeks, FRD rats had significantly higher blood glucose, insulin and triglyceride levels, and liver triglyceride content, insulin resistance, and impaired glucose tolerance. FRD rats also had significantly higher GK activity in the cytosolic fraction (18.3 +/- 0.35 vs. 11.27 +/- 0.34 mU/mg protein). Differences in GK protein concentration (116% and 100%) were not significant, suggesting a potentially impaired GK translocation in FRD rats. Although GK transcription level was similar, PFK2 gene expression and protein concentration were 4- and 5-fold higher in the cytosolic fraction of FRD animals. PFK2 immunological blockage significantly decreased GK activity in control and FRD rats; in the latter, this blockage decreased GK activity to control levels. Results suggest that increased liver GK activity might participate in the adaptative response to fructose overload to maintain glucose/triglyceride homeostasis in intact animals. Under these conditions, PFK2 increase would be the main enhancer of GK activity.

The use of fluorescent intrabodies to detect endogenous gankyrin in living cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rinaldi, Anne-Sophie; Freund, Guillaume; Desplancq, Dominique

2013-04-01

Expression of antibody fragments in mammalian cells (intrabodies) is used to probe the target protein or interfere with its biological function. We previously described the in vitro characterisation of a single-chain Fv (scFv) antibody fragment (F5) isolated from an intrabody library that binds to the oncoprotein gankyrin (GK) in solution. Here, we have isolated several other scFvs that interact with GK in the presence of F5 and tested whether they allow, when fused to fluorescent proteins, to detect by FRET endogenous GK in living cells. The binding of pairs of scFvs to GK was analysed by gel filtration and themore » ability of each scFv to mediate nuclear import/export of GK was determined. Binding between scFv-EGFP and RFP-labelled GK in living cells was detected by fluorescence lifetime imaging microscopy (FLIM). After co-transfection of two scFvs fused to EGFP and RFP, respectively, which form a tri-molecular complex with GK in vitro, FRET signal was measured. This system allowed us to observe that GK is monomeric and distributed throughout the cytoplasm and nucleus of several cancer cell lines. Our results show that pairs of fluorescently labelled intrabodies can be monitored by FLIM–FRET microscopy and that this technique allows the detection of lowly expressed endogenous proteins in single living cells. Highlights: ► Endogenous GK in living cells was targeted with pairs of fluorescently-tagged scFvs. ► Tri-molecular complexes containing two scFvs and one molecule GK were formed. ► GK was detected using fluorescence lifetime-based FRET imaging. ► GK is monomeric and homogeneously distributed in several cancer cell lines. ► This technique may have many applications in live-cell imaging of endogenous proteins.« less

7 CFR 29.1181 - Summary of standard grades.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER... B6KV 7 Mixed Grades M4F M4KR M4KM M4GK M5F M5KM M5GK 15 Grades of Green B4G B4GK C4G C4GK X4G X4GK P4G...

7 CFR 29.1181 - Summary of standard grades.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER... B6KV 7 Mixed Grades M4F M4KR M4KM M4GK M5F M5KM M5GK 15 Grades of Green B4G B4GK C4G C4GK X4G X4GK P4G...

[Glucokinase and glucokinase regulatory proteins as molecular targets for novel antidiabetic drugs].

PubMed

Rubtsov, P M; Igudin, E L; Tiulpakov, A N

2015-01-01

The impairment of glucose homeostasis leads to hyperglycemia and type-2 diabetes mellitus. Glucokinase (GK), an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate in pancreatic ß-cells, liver hepatocytes, specific hypothalamic neurons, and intestine enterocytes, is a key regulator of glucose homeostasis. In hepatocytes, GK controls the glucose uptake and glycogen synthesis and inhibits the glucose synthesis via the gluconeogenesis pathway. Glucokinase regulatory protein (GKRP) synthesized in hepatocytes acts as an endogenous GK inhibitor. During fasting, GKRP binds GK, inactivates it, and transports it into the cell nucleus, thus isolating it from the hepatocyte carbohydrate metabolism. In the beginning of the 2000s, the research was mainly focused on the development and trials of the small molecule GK activators as potential antidiabetic glucose-lowering drugs. However, the use of such substances increased the risk of hypoglycemia, and clinical studies of most synthetic GK activators are currently discontinued. Allosteric inhibitors of the GK-GKRP interaction are coming as alternative agents increasing the GK activity that can substitute GKA. In this review, we discuss the recent advances and the current state of art in the development of potential antidiabetic drugs targeted to GK as a key regulator of glucose homeostasis.

Structural basis for the mechanism and substrate specificity of glycocyamine kinase, a phosphagen kinase family member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Kap; Pullalarevu, Sadhana; Surabian, Karen Talin

2010-03-12

Glycocyamine kinase (GK), a member of the phosphagen kinase family, catalyzes the Mg{sup 2+}-dependent reversible phosphoryl group transfer of the N-phosphoryl group of phosphoglycocyamine to ADP to yield glycocyamine and ATP. This reaction helps to maintain the energy homeostasis of the cell in some multicelullar organisms that encounter high and variable energy turnover. GK from the marine worm Namalycastis sp. is heterodimeric, with two homologous polypeptide chains, {alpha} and {beta}, derived from a common pre-mRNA by mutually exclusive N-terminal alternative exons. The N-terminal exon of GK{beta} encodes a peptide that is different in sequence and is 16 amino acids longermore » than that encoded by the N-terminal exon of GK{alpha}. The crystal structures of recombinant GK{alpha}{beta} and GK{beta}{beta} from Namalycastis sp. were determined at 2.6 and 2.4 {angstrom} resolution, respectively. In addition, the structure of the GK{beta}{beta} was determined at 2.3 {angstrom} resolution in complex with a transition state analogue, Mg{sup 2+}-ADP-NO{sub 3}{sup -}-glycocyamine. Consistent with the sequence homology, the GK subunits adopt the same overall fold as that of other phosphagen kinases of known structure (the homodimeric creatine kinase (CK) and the monomeric arginine kinase (AK)). As with CK, the GK N-termini mediate the dimer interface. In both heterodimeric and homodimeric GK forms, the conformations of the two N-termini are asymmetric, and the asymmetry is different than that reported previously for the homodimeric CKs from several organisms. The entire polypeptide chains of GK{alpha}{beta} are structurally defined, and the longer N-terminus of the {beta} subunit is anchored at the dimer interface. In GK{beta}{beta} the 24 N-terminal residues of one subunit and 11 N-terminal residues of the second subunit are disordered. This observation is consistent with a proposal that the GK{alpha}{beta} amino acids involved in the interface formation were optimized once a heterodimer emerged as the physiological form of the enzyme. As a consequence, the homodimer interface (either solely {alpha} or solely {beta} chains) has been corrupted. In the unbound state, GK exhibits an open conformation analogous to that observed with ligand-free CK or AK. Upon binding the transition state analogue, both subunits of GK undergo the same closure motion that clasps the transition state analogue, in contrast to the transition state analogue complexes of CK, where the corresponding transition state analogue occupies only one subunit, which undergoes domain closure. The active site environments of the GK, CK, and AK at the bound states reveal the structural determinants of substrate specificity. Despite the equivalent binding in both active sites of the GK dimer, the conformational asymmetry of the N-termini is retained. Thus, the coupling between the structural asymmetry and negative cooperativity previously proposed for CK is not supported in the case of GK.« less

Bovine herpesvirus type-1 glycoprotein K (gK) interacts with UL20 and is required for infectious virus production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haque, Muzammel; Stanfield, Brent; Kousoulas, Kons

We have previously shown that the HSV-1 gK and UL20 proteins interact and function in virion envelopment, membrane fusion, and neuronal entry. Alignment of the predicted secondary structures of gKs encoded by BoHV-1, HSV-1, HSV-2, EHV-1 and VZV indicated a high degree of domain conservation. Two BoHV-1 gK-null mutant viruses were created by either gK gene deletion or stop codon insertion. In addition, a V5 epitope-tag was inserted at the carboxyl terminus of gK gene to detect gK. The engineered gK-null mutant viruses failed to replicate and produce viral plaques. Co-immunoprecipitation of gK and UL20 expressed via different methods revealedmore » that gK and UL20 physically interacted in the presence or absence of other viral proteins. Confocal microscopy showed that gK and UL20 colocalized in infected cells. These results indicate that BoHV-1 gK and UL20 may function in a similar manner to other alphaherpesvirus orthologues specified by HSV-1, PRV and EHV-1. -- Highlights: •Glycoprotein K(gK) is conserved among alphaherpesviruses and serves similar functions. •The bovine herpesvirus-1 gK and UL20 proteins physically interact in a similar manner to herpes simplex virus type 1 and equine herpesvirus-1. •The bovine herpesvirus-1 (BoHV-1) gK interacts with UL20 and is essential for virus replication and spread.« less

Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model

PubMed Central

SAITO, Mikako; KANEDA, Asako; SUGIYAMA, Tae; IIDA, Ryousuke; OTOKUNI, Keiko; KABURAGI, Misako; MATSUOKA, Hideaki

2015-01-01

Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk+/−) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk+/− mice ranged from 0.41–0.68 versus that in wild (Gk+/+) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95–1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk+/− strain fed the CD, and Gk+/− strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk+/− strain developed in this study. PMID:25765873

Neuropsychological outcomes after Gamma Knife radiosurgery for mesial temporal lobe epilepsy: a prospective multicenter study.

PubMed

Quigg, Mark; Broshek, Donna K; Barbaro, Nicholas M; Ward, Mariann M; Laxer, Kenneth D; Yan, Guofen; Lamborn, Kathleen

2011-05-01

To assess outcomes of language, verbal memory, cognitive efficiency and mental flexibility, mood, and quality of life (QOL) in a prospective, multicenter pilot study of Gamma Knife radiosurgery (RS) for mesial temporal lobe epilepsy (MTLE). RS, randomized to 20 Gy or 24 Gy comprising 5.5-7.5 ml at the 50% isodose volume, was performed on mesial temporal structures of patients with unilateral MTLE. Neuropsychological evaluations were performed at preoperative baseline, and mean change scores were described at 12 and 24 months postoperatively. QOL data were also available at 36 months. Thirty patients were treated and 26 were available for the final 24-month neuropsychological evaluation. Language (Boston Naming Test), verbal memory (California Verbal Learning Test and Logical Memory subtest of the Wechsler Memory Scale-Revised), cognitive efficiency and mental flexibility (Trail Making Test), and mood (Beck Depression Inventory) did not differ from baseline. QOL scores improved at 24 and 36 months, with those patients attaining seizure remission by month 24s accounting for the majority of the improvement. The serial changes in cognitive outcomes, mood, and QOL are unremarkable following RS for MTLE. RS may provide an alternative to open surgery, especially in those patients at risk of cognitive impairment or who desire a noninvasive alternative to open surgery. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Gamma Knife Treatment of Growing Vestibular Schwannoma in Norway: A Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varughese, Jobin Kotakkathu, E-mail: jobinv@gmail.com; Wentzel-Larsen, Tore; Centre for Child and Adolescent Mental Health, Eastern and Southern Norway, Oslo

2012-10-01

Purpose: Gamma Knife radiosurgery (GKRS) has been increasingly used in the treatment of vestibular schwannoma (VS). Very few studies relate tumor control and post-treatment growth rates to pretreatment growth rates. Methods and Materials: We prospectively included 45 consecutive VS patients who were initially treated conservatively and then received GKRS between 2000 and 2007 because of demonstrated tumor growth. Pretreatment and post-treatment tumor volumes were estimated. Patients underwent audiograms, reported their symptoms, and responded to the Short Form General Health Survey (SF-36) questionnaire on each visit. Results: Volume doubling times before and after treatment were 1.36 years (95% confidence intervals, 1.14-1.68)more » and -13.1 years (95% confidence intervals, -111.0 to -6.94), respectively. Tumor control, defined as a post-GKRS growth rate {<=}0, was achieved in 71.1% of patients, with highest odds for tumor control among older patients and those with larger tumors. The 5-year retreatment-free survival rate was 93.9% (95% confidence intervals, 76.5-98.5). None of the clinical endpoints investigated showed statistically significant changes after GKRS, but improvement was seen in a few SF-36 parameters. Conclusions: GKRS alters the natural course of the tumor by reducing growth. Mathematic models yield poorer tumor control rates than those found by clinical assessment. Symptoms were unaffected by treatment, but quality of life was improved.« less

Effect of beam channel plugging on the outcome of gamma knife radiosurgery for trigeminal neuralgia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massager, Nicolas; Nissim, Ouzi; Murata, Noriko

2006-07-15

Purpose: We studied the influence of using plugs for brainstem protection during gamma knife radiosurgery (GKR) of trigeminal neuralgia (TN), with special emphasis on irradiation doses delivered to the trigeminal nerve, pain outcomes, and incidence of trigeminal dysfunction. Methods and Materials: A GKR procedure for TN using an anterior cisternal target and a maximum dose of 90 Gy was performed in 109 patients. For 49 patients, customized beam channel blocking (plugs) were used to reduce the dose delivered to the brainstem. We measured the mean and integrated radiation doses delivered to the trigeminal nerve and the clinical course of patientsmore » treated with and without plugs. Results: We found that blocking increases the length of trigeminal nerve exposed to high-dose radiation, resulting in a significantly higher mean dose to the trigeminal nerve. Significantly more of the patients with blocking achieved excellent pain outcomes (84% vs. 62%), but with higher incidences of moderate and bothersome trigeminal nerve dysfunction (37% mild/10% bothersome with plugs vs. 30% mild/2% bothersome without). Conclusions: The use of plugs to protect the brainstem during GKR treatment for TN increases the dose of irradiation delivered to the intracisternal trigeminal nerve root and is associated with an important increase in the incidence of trigeminal nerve dysfunction. Therefore, beam channel blocking should be avoided for 90 Gy-GKR of TN.« less

Communicating Hydrocephalus Associated with Intracranial Schwannoma Treated by Gamma Knife Radiosurgery.

PubMed

Park, Chang Kyu; Lee, Sung Ho; Choi, Man Kyu; Choi, Seok Keun; Park, Bong Jin; Lim, Young Jin

2016-05-01

Gamma knife radiosurgery (GKRS) has been established as an effective and safe treatment for intracranial schwannoma. However, serious complications can occur after GKRS, including hydrocephalus. The pathophysiology and risk factors of this disorder are not yet fully understood. The objective of the study was to assess potential risk factors for hydrocephalus after GKRS. We retrospectively reviewed the medical radiosurgical records of 244 patients who underwent GKRS to treat intracranial schwannoma. The following parameters were analyzed as potential risk factors for hydrocephalus after GKRS: age, sex, target volume, irradiation dose, prior tumor resection, treatment technique, and tumor enhancement pattern. The tumor enhancement pattern was divided into 2 groups: group A (homogeneous enhancement) and group B (heterogeneous or rim enhancement). Of the 244 patients, 14 of them (5.7%) developed communicating hydrocephalus. Communicating hydrocephalus occurred within 2 years after GKRS in most patients (92.8%). No significant association was observed between any of the parameters investigated and the development of hydrocephalus, with the exception of tumor enhancement pattern. Group B exhibited a statistically significant difference by univariate analysis (P = 0.002); this difference was also significant by multivariate analysis (P = 0.006). Because hydrocephalus is curable, patients should be closely monitored for the development of this disorder after GKRS. In particular, patients with intracranial schwannomas with irregular enhancement patterns or cysts should be meticulously observed. Copyright © 2015 Elsevier Inc. All rights reserved.

Gamma knife surgery for brainstem arteriovenous malformations.

PubMed

Yen, Chun-Po; Steiner, Ladislau

2011-01-01

To evaluate the long-term imaging and clinical outcomes of patients with brainstem arteriovenous malformations (AVMs) treated with Gamma Knife surgery (GKS). The study included 85 patients with brainstem AVMs undergoing GKS during the period 1989-2007. The locations of the nidi were the midbrain in 42 patients, pons in 31 patients, and medulla oblongata in 12 patients. The volume of the nidi ranged from 0.1-8.9 mL (median 1.4 mL, mean 1.9 mL), and the prescription dose ranged from 5-32 Gy (median 20 Gy, mean 19.9 Gy). After the initial Gamma procedure, 18 patients had repeat GKS for AVM residuals that were still patent. Two patients had a third GKS 7 years and 16 years after a failed repeat GKS. Clinical follow-up ranged from 24-252 months with a mean of 100 months (median 102 months) after the initial GKS. GKS yielded a total angiographic obliteration in 50 (58.8%) patients and subtotal obliteration in 4 (4.7%) patients. In 22 (25.9%) patients, the AVMs remained patent. In 9 patients (10.6%), no flow voids were observed on magnetic resonance imaging (MRI), but angiographic confirmation was unavailable. A small nidus volume and a high prescription dose were significantly associated with increased AVM obliteration rate. Radiation-induced changes developed in 34 patients (40%); 24 were asymptomatic, 1 patient had only headache, and 9 patients developed neurologic deficits. One patient developed a large cyst 6 years after GKS. Given the poor surgical outcome of brainstem AVMs, the results of 59% nidus obliteration and 6% permanent neurologic deficits make GKS a reasonable management of these difficult lesions. Copyright © 2011 Elsevier Inc. All rights reserved.

Usefulness of the advanced neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state images for gamma knife radiosurgery and planning microsurgical procedures for skull base tumors.

PubMed

Hayashi, Motohiro; Chernov, Mikhail F; Tamura, Noriko; Yomo, Shoji; Tamura, Manabu; Horiba, Ayako; Izawa, Masahiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Okada, Yoshikazu; Ivanov, Pavel; Régis, Jean; Takakura, Kintomo

2013-01-01

Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images. Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures. Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts. Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

Substrate-induced Nuclear Export and Peripheral Compartmentalization of Hepatic Glucokinase Correlates with Glycogen Deposition

PubMed Central

Shiota, Masa; Knobel, Susan M.; Piston, David W.; Cherrington, Alan D.; Magnuson, Mark A.

2001-01-01

Hepatic glucokinase (GK) is acutely regulated by binding to its nuclear-anchored regulatory protein (GKRP). Although GK release by GKRP is tightly coupled to the rate of glycogen synthesis, the nature of this association is obscure. To gain insight into this coupling mechanism under physiological stimulating conditions in primary rat hepatocytes, we analyzed the subcellular distribution of GK and GKRP with immunofluorescence, and glycogen deposition with glycogen cytochemical fluorescence, using confocal microscopyand quantitative image analysis. Following stimulation, a fraction of the GK signal translocated from the nucleus to the cytoplasm. The reduction in the nuclear to cytoplasmic ratio of GK, an index of nuclear export, correlated with a >50% increase in glycogen cytochemical fluorescence over a 60min stimulation period. Furthermore, glycogen accumulation was initially deposited in a peripheral pattern in hepatocytes similar to that of GK. These data suggest that a compartmentalization exists of both active GK and the initial sites of glycogen deposition at the hepatocyte surface. PMID:12369705

The history of stereotactic radiosurgery and radiotherapy.

PubMed

Lasak, John M; Gorecki, John P

2009-08-01

Stereotactic neurosurgery originated from the pioneering work of Horsley and Clarke, who developed a stereotactic apparatus to study the monkey brain in 1908. Spiegel and Wycis applied this technology to the human brain in 1947, which ultimately lead to the development of multiple stereotactic neurosurgical devices during the 1950s. It was Lars Leksell of Sweden, however, who envisioned stereotactic radiosurgery. Leksell developed the gamma knife to treat intracranial lesions in a noninvasive fashion. His work stimulated worldwide interest and created the field of stereotactic radiosurgery.

Radiosurgery with photons or protons for benign and malignant tumours of the skull base: a review.

PubMed

Amichetti, Maurizio; Amelio, Dante; Minniti, Giuseppe

2012-12-14

Stereotactic radiosurgery (SRS) is an important treatment option for intracranial lesions. Many studies have shown the effectiveness of photon-SRS for the treatment of skull base (SB) tumours; however, limited data are available for proton-SRS.Several photon-SRS techniques, including Gamma Knife, modified linear accelerators (Linac) and CyberKnife, have been developed and several studies have compared treatment plan characteristics between protons and photons.The principles of classical radiobiology are similar for protons and photons even though they differ in terms of physical properties and interaction with matter resulting in different dose distributions.Protons have special characteristics that allow normal tissues to be spared better than with the use of photons, although their potential clinical superiority remains to be demonstrated.A critical analysis of the fundamental radiobiological principles, dosimetric characteristics, clinical results, and toxicity of proton- and photon-SRS for SB tumours is provided and discussed with an attempt of defining the advantages and limits of each radiosurgical technique.

Radiosurgery with photons or protons for benign and malignant tumours of the skull base: a review

PubMed Central

2012-01-01

Stereotactic radiosurgery (SRS) is an important treatment option for intracranial lesions. Many studies have shown the effectiveness of photon-SRS for the treatment of skull base (SB) tumours; however, limited data are available for proton-SRS. Several photon-SRS techniques, including Gamma Knife, modified linear accelerators (Linac) and CyberKnife, have been developed and several studies have compared treatment plan characteristics between protons and photons. The principles of classical radiobiology are similar for protons and photons even though they differ in terms of physical properties and interaction with matter resulting in different dose distributions. Protons have special characteristics that allow normal tissues to be spared better than with the use of photons, although their potential clinical superiority remains to be demonstrated. A critical analysis of the fundamental radiobiological principles, dosimetric characteristics, clinical results, and toxicity of proton- and photon-SRS for SB tumours is provided and discussed with an attempt of defining the advantages and limits of each radiosurgical technique. PMID:23241206

Ginkgolide K promotes astrocyte proliferation and migration after oxygen-glucose deprivation via inducing protective autophagy through the AMPK/mTOR/ULK1 signaling pathway.

PubMed

Zhang, Ying; Miao, Ju-Mei

2018-05-19

Ischemic stroke is the leading cause of death around the world. Ginkgolide K (GK) has been used to treat ischemic stroke due to its neuroprotective potential. However, the molecular mechanism underlying the neuroprotective effect of GK in ischemic stroke is still almost blank. In this study, astrocytes were divided into four groups: control group, oxygen-glucose deprivation (OGD) group, OGD + GK group and OGD + GK + Compound C (CC) group. The viability and proliferation of astrocytes were examined by Cell Counting Kit-8 assay and 5-ethynyl-20-deoxyuridine (EdU) assay, respectively. Transwell migration and wound scratch assays were conducted to evaluate astrocyte migration. The protein expression in astrocytes were determined by western blot assay. We found that GK pretreatment promoted astrocyte proliferation and migration after OGD as shown by the increase in the viability of astrocytes, glial fibrillary acidic protein level, the number of EdU positive cells and migrated cells, and the migration distance. GK pretreatment induced autophagy after OGD, as indicated by upregulation of autophagy-related protein 7, Beclin-1 protein and increase of microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I, and downregulation of p62 protein. Moreover, GK pretreatment activated the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (m-TOR)/ULK1 pathway in astrocytes following OGD. Notably, CC treatment blocked the promotory effect of GK on astrocyte proliferation and migration after OGD. Collectively, GK promoted astrocyte proliferation and migration after OGD via inducing protective autophagy through the AMPK/mTOR/ULK1 signaling pathway. Our findings suggested that GK might be a potential agent for cerebral ischemia/reperfusion injury. Copyright © 2018. Published by Elsevier B.V.

Construction of membrane-anchoring fusion protein of Thermococcus kodakaraensis glycerol kinase and its application to repetitive batchwise reactions.

PubMed

Restiawaty, Elvi; Honda, Kohsuke; Okano, Kenji; Hirota, Ryuichi; Omasa, Takeshi; Kuroda, Akio; Ohtake, Hisao

2012-04-01

We previously demonstrated the stoichiometric conversion of glycerol to glycerol-3-phosphate (G3P) using Escherichia coli recombinants producing the ATP-dependent glycerol kinase of the hyperthermophile Thermococcus kodakaraensis (TkGK) and the polyphosphate kinase of Thermus thermophilus HB27 (TtPPK). TtPPK was associated with the membrane fraction of E. coli recombinants, whereas TkGK was released from the cells during the reaction at 70°C. In this study, TkGK was fused with either TtPPK or an E. coli membrane-intrinsic protein, YedZ, to minimize the heat-induced leakage of TkGK. When the E. coli recombinants having these fusion proteins were incubated at 70°C for 2h, more than 80% of TkGK activity was retained in the heated E. coli cells. However, the yields of G3P production by E. coli having the fusion proteins of TtPPK and TkGK were only less than 35%. Polyphosphate is a strong chelator for metal ions and has an inhibitory effect on TkGK which requires magnesium. Insufficient space between TtPPK and TkGK might enhance the inhibitory effect of polyphosphate on TkGK activity of the fusion protein. The mixture of E. coli cells having TtPPK and those having TkGK fused with YedZ converted 80% of glycerol into G3P. These recombinant cells could be easily recovered from the reaction mixture by centrifugation and repeatedly used without a significant loss of enzyme activities. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhenjie; Jiang, Runxia; Yue, Qingcai

Background: In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats. Methods: MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC. IGF1 was also downregulated by siRNA in miR-29-downregulated GK MMEVC. Its effect on miR-29-associated angiogenicmore » regulation on MMEVC proliferation and migration was further investigated. Results: MiR-29 was substantially upregulated in GK MMEVC than in Wistar MMEVC. Transfection of synthetic miR-29 inhibitor successfully downregulate endogenous miR-29 in GK MMEVC, and subsequently promoted angiogenesis by increasing cell proliferation and migration. IGF1 was confirmed to be downstream target gene of miR-29 in GK MMEVC, with its gene and protein expressions both upregulated in miR-29-downregualted GK MMEVC. Conversely, siRNA-mediated IGF1 downregulation reversed the pro-angiogenic effect of miR-29 downregulation in GK MMEVC, as it decreased cell proliferation and migration. Conclusion: Our study suggests that miR-29 downregulation, through its inverse regulation on downstream target of IGF1 gene, is a pro-angiogenic factor in MMEVC in type 2 diabetic rats.« less

The significance of nerve sugar levels for the peripheral nerve impairment of spontaneously diabetic GK (Goto-Kakizaki) rats.

PubMed

Suzuki, K; Yen-Chung, H; Toyota, T; Goto, Y; Hirata, Y; Okada, K

1990-05-01

This study was carried out to clarify the relationship between the slowing of motor nerve conduction velocity and nerve levels of sorbitol, fructose, glucose and myoinositol in spontaneously diabetic GK (Goto-Kakizaki) rats. The motor nerve conduction velocity in GK rats was constantly lower than in normal controls at three and nine months of age. This constant decrease in motor nerve conduction velocity in GK rats was closely related to glucose intolerance in GK rats soon after birth. Nerve levels of sorbitol, glucose and fructose in GK rats were significantly increased as compared to normal controls at nine months old, but not (except glucose) at three months old. The increase in nerve concentrations of sugars in GK rats was progressive with age. However, levels of glucose, sorbitol and fructose in normal Wistar rats remain unchanged with age. Although nerve myo-inositol levels in GK rats were lower at three and nine months than those of normal controls, a significant difference in myo-inositol levels was observed only at nine months. On the contrary, nerve myo-inositol level in normal Wistar rats did not show age-related change. These findings suggested that both enhanced polyol pathway activity and myo-inositol depletion play important roles in the reduction of motor nerve conduction velocity.

Identification and analysis of novel R308K mutation in glucokinase of type 2 diabetic patient and its kinetic correlation.

PubMed

Yellapu, Nanda Kumar; Valasani, Koteswara Rao; Pasupuleti, Santhosh Kumar; Gopal, Sowjenya; Potukuchi Venkata Gurunadha Krishna, Sarma; Matcha, Bhaskar

2014-01-01

Glucokinase (GK) plays a critical role in glucose homeostasis and the mutations in GK gene result in pathogenic complications known as Maturity Onset Diabetes of the Young 2, an autosomal dominant form of diabetic condition. In the present study, GK was purified from human liver tissue and the pure enzyme showed single band in SDS-PAGE with a molecular weight of 50 kDa. The kinetics of pure GK showed enzyme activity of 0.423±0.02 µM glucose-6-phosphate (G6P)/mL/Min and Km value of 6.66±0.02 µM. These values were compared in the liver biopsy of a clinically proven type 2 diabetic patient, where GK kinetics showed decreased enzyme activity of 0.16±0.025 µM G6P/mL/Min and increased Km of 23±0.9 µM, indicating the hyperglycemic condition in the patient. The genetic analysis of 10th exon of GK gene from this patient showed a R308K mutation. To substantiate these results, comparative molecular dynamics and docking studies were carried out where a higher docking score (-10.218 kcal/mol) was observed in the mutated GK than wild-type GK structure (-12.593 kcal/mol) indicating affinity variations for glucose. During the simulation process, glucose was expelled out from the mutant conformation but not from wild-type GK, making glucose unavailable for phosphorylation. Therefore, these results conclusively explain hyperglycemic condition in this patient. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

Impact on cognitive functions following gamma knife radiosurgery for cerebral arteriovenous malformations.

PubMed

Raghunath, A; Bennett, Niranjana; Arimappamagan, Arivazhagan; Bhat, Dhananjaya I; Srinivas, Dwarakanath; Thennarasu, K; Jamuna, R; Somanna, Sampath

2016-01-01

Radiosurgery is an alternative to surgical resection of arteriovenous malformation (AVM). Very few studies have addressed the concern of radiation injury to the brain and its attendant adverse effects on cognitive function. This prospective study included all patients who underwent gamma knife radiosurgery (GKRS) at our institute for cerebral AVM between 2006 and December 2008 (n = 34). All patients underwent neuropsychological evaluation before the procedure. Neuropsychological evaluation was repeated in eighteen patients 2 years following GKRS. Clinical outcome, AVM obliteration, and factors influencing outcome were analyzed in these eighteen patients. Before GKRS, more than 50% had significant impairment of neuropsychological functions compared to normal population norms. 66.6% achieved the excellent radiosurgical outcome. At 2 years follow-up, patients showed varied improvement in neuropsychological function in various categories. Pretherapeutic median value for percentage perseverative responses was 26.5 and at follow-up, it reduced to 18.2 (P = 0.039). Set shifting improved in 11 patients (61.1%), remained same in 5 patients (27.7%), and deteriorated in two patients (11.1%). Patients with a higher Spetzler-Martin grade AVM demonstrated a significantly more favorable shift in follow-up test values for set shifting function (P = 0.021). Patients with postradiation imaging changes had lesser tendency to improve in neuropsychological performance at follow-up. GKRS has no clinically harmful effect on cognitive and neuropsychological functioning in patients with brain AVM. On the contrary, there is an improvement in majority of patients at 2 years following radiosurgery when nidus is obliterated.

Gamma knife surgery for refractory postherpetic trigeminal neuralgia: targeting in one session both the retrogasserian trigeminal nerve and the centromedian nucleus of the thalamus.

PubMed

Keep, Marcus F; DeMare, Paul A; Ashby, Lynn S

2005-01-01

The authors tested the hypothesis that two targets are needed to treat postherpetic trigeminal neuralgia (TN): one in the trigeminal nerve for the direct sharp pain and one in the thalamus for the diffuse burning pain. Three patients with refractory postherpetic TN were treated with gamma knife surgery (GKS) through a novel two-target approach. In a single treatment session, both the trigeminal nerve and centromedian nucleus were targeted. First, the trigeminal nerve, ipsilateral to the facial pain, was treated with 60 to 80 Gy. Second, the centromedian nucleus was localized using standard coordinates and by comparing magnetic resonance images with a stereotactic atlas. A single dose of 120 to 140 Gy was delivered to the target point with a single 4-mm isocenter. Patients were followed clinically and with neuroimaging studies. Pain relief was scored as excellent (75-100%), good (50-75%), poor (25-50%); or none (0-25%). Follow up ranged from 6 to 53 months. There were no GKS-related complications. Two patients died of unrelated medical illnesses but had good or excellent pain relief until death. One patient continues to survive with 44 months follow up and no decrease in pain intensity, but with a decreased area of pain. Combined GKS of the centromedian nucleus and trigeminal nerve in a single treatment session is feasible and safe, and the effect was promising. A larger study is required to confirm and expand these results.

Cavernomas: Outcomes after gamma-knife radiosurgery in Iran

PubMed Central

Azimi, Parisa; Shahzadi, Sohrab; Bitaraf, Mohammad Ali; Azar, Maziar; Alikhani, Mazdak; Zali, Alireza; Sadeghi, Sohrab

2015-01-01

Background: Treatment of cavernomas remains a challenge in surgically inaccessible regions. The purpose of this study was to evaluate outcomes after gamma-knife surgery (GKS) for these patients. Materials and Methods: A retrospective review of 100 patients treated between 2003 and 2011 was conducted in order to evaluate hemorrhage rates, complications, radiation effects after GKS. Dosage at the tumor margin was stratified into two groups: those that received ≤13 Gy; and those who received >13 Gy. The demographic and clinical characteristics of patients including age, gender, and hemorrhage rates were extracted from care records. Results: The median age was 32.5 years (ranging from 15 to 79). 44% were female. The median follow-up time was 42.2 months (ranging from 24 to 90). The median volume of the lesions was 1050.0 mm3 (ranging from 112.0 to 4100.0) before GKS. A reduction of 27.5% in median size of cavernomas was achieved at the last follow-up. There was 12% treatment-related morbidity after GKS. The hemorrhage rate in the first 2 years after GKS was 4.1% and 1.9% thereafter. There was no mortality due to GKS, and 93 patients were alive at the last follow-up. The radiation-related complication developed with marginal dose 13 Gy. Conclusion: The GKS for cavernomas appears to be a safe and beneficial in carefully selected patients. Low-dose GKS may be effective for the management of cavernous malformations. PMID:25767582

Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.

PubMed

Matsunaga, Shigeo; Shuto, Takashi; Sato, Mitsuru

2016-05-01

The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Reciprocal Modulation of IK1–INa Extends Excitability in Cardiac Ventricular Cells

PubMed Central

Varghese, Anthony

2016-01-01

The inwardly rectifying potassium current (IK1) and the fast inward sodium current (INa) are reciprocally modulated in mammalian ventricular myocytes. An increase in the expression of channels responsible for one of these two currents results in a corresponding increase in expression of the other. These currents are critical in the propagation of action potentials (AP) during the normal functioning of the heart. This study identifies a physiological role for IK1–INa reciprocal modulation in ventricular fiber activation thresholds and conduction. Simulations of action potentials in single cells and propagating APs in cardiac fibers were carried out using an existing model of electrical activity in cardiac ventricular myocytes. The conductances, GK1, of the inwardly rectifying potassium current, and GNa, of the fast inward sodium current were modified independently and in tandem to simulate reciprocal modulation. In single cells, independent modulation of GK1 alone resulted in changes in activation thresholds that were qualitatively similar to those for reciprocal GK1–GNa modulation and unlike those due to independent modulation of GNa alone, indicating that GK1 determines the cellular activation threshold. On the other hand, the variations in conduction velocity in cardiac cell fibers were similar for independent GNa modulation and for tandem changes in GK1–GNa, suggesting that GNa is primarily responsible for setting tissue AP conduction velocity. Conduction velocity dependence on GK1–GNa is significantly affected by the intercellular gap junction conductance. While the effects on the passive fiber space constant due to changes in both GK1 and the intercellular gap junction conductance, Ggj, were in line with linear cable theory predictions, both conductances had surprisingly large effects on fiber activation thresholds. Independent modulation of GK1 rendered cardiac fibers inexcitable at higher levels of GK1 whereas tandem GK1–GNa changes allowed fibers to remain excitable at high GK1 values. Reciprocal modulation of the inwardly rectifying potassium current and the fast inward sodium current may have a functional role in allowing cardiac tissue to remain excitable when IK1 is upregulated. PMID:27895596

[Protective effect of arctigenin in GK rats combined with hypertension macroangiopathy].

PubMed

Feng, Qin; Sun, Bao-cun; Xia, Wen-kai

2015-03-01

To study the protective effect of Arctigenin in goto-kakizaki (GK) rats combined with hypertension macroangiopathy. Six-week-old GK rats were divided randomly according to blood glucose level into four groups: the model group and low, middle and high dose arctigenin groups (12.5, 25, 50 mg x kg(-1)), with Wistar rats as the normal group. All of GK rats were given high-glucose and high-fat diet. After 16 weeks, GK rats were orally administrated with 10 mg x kg(-1) x d(-1) N-Ω-nitro-L-arginine methyl ester for eight weeks. During the modeling, all of arctigenin groups were orally administrated with different dose of arctigenin twice a day; The model group and the normal group were given solvents. At the beginning, mid-term and end of the experiment, blood glucose was measured. At the end of the experiment, efforts were made to detect blood pressure, collect abdominal aortic blood after anesthesia, fix thoracic aorta after bloodletting to make paraffin sections, observe morphological characteristics and detect the expression of VEGF by immunohistochemistry. According to the results, the blood glucose rose in all GK rats, with no significant difference between the drug group and the model group. At the end of the experiment, the blood pressure significantly increased in GK rats, indicating that Arctigenin could notably reduce the blood pressure in GK rats in a dose-dependent manner. The blood routine test showed increases in both the total white blood cell count and differential blood count, MPV and PDW, abnormal blood platelet parameters and decrease in PLT in GK rats, suggesting that Arctigenin could remarkably reduce the total white blood cell count and differential blood count, MPV and PDW. The thoracic aortic morphological observation revealed obvious endangium lesions in GK rats, demonstrating that Arctigenin could ameliorate the lesion extent. VEGF immumohistochemical staining showed a higher VEGF expression in the model group but lower expression in Arctigenin groups. In conclusion, Arctigenin had a protective effect on aorta in GK rats. Its mechanism may be related to blood pressure lowering, anti-inflammation, improvement in blood platelet function and reduction of VEGF expression.

Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain.

PubMed

Xia, Yitian; Shang, Yuan; Zhang, Rongguang; Zhu, Jinwei

2017-08-10

The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing. In the present study, we determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at 2.6-Å resolution. The complex structure reveals that, unlike a linear and elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide adopts a unique conformation with a stretch of hydrophobic residues far from each other in the primary sequence clustering and interacting with the 'hydrophobic site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117) mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD-95 GK. We demonstrate that the MAP1A peptide may undergo a conformational transition upon binding to PSD-95 GK. Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

A treatment planning comparison between a novel rotating gamma system and robotic linear accelerator based intracranial stereotactic radiosurgery/radiotherapy

NASA Astrophysics Data System (ADS)

Fareed, Muhammad M.; Eldib, Ahmed; Weiss, Stephanie E.; Hayes, Shelly B.; Li, Jinsheng; C-M Ma, Charlie

2018-02-01

To compare the dosimetric parameters of a novel rotating gamma ray system (RGS) with well-established CyberKnife system (CK) for treating malignant brain lesions. RGS has a treatment head of 16 cobalt-60 sources focused to the isocenter, which can rotate 360° on the ring gantry and swing 35° in the superior direction. We compared several dosimetric parameters in 10 patients undergoing brain stereotactic radiosurgery including plan normalization, number of beams and nodes for CK and shots for RGS, collimators used, estimated treatment time, D 2 cm and conformity index (CI) among two modalities. The median plan normalization for RGS was 56.7% versus 68.5% (p  =  0.002) for CK plans. The median number of shots from RGS was 7.5 whereas the median number of beams and nodes for CK was 79.5 and 46. The median collimator’s diameter used was 3.5 mm for RGS as compared to 5 mm for CK (p  =  0.26). Mean D 2 cm was 5.57 Gy for CyberKnife whereas it was 3.11 Gy for RGS (p  =  0.99). For RGS plans, the median CI was 1.4 compared to 1.3 for the CK treatment plans (p  =  0.98). The average minimum and maximum doses to optic chiasm were 21 and 93 cGy for RGS as compared to 32 and 209 cGy for CK whereas these were 0.5 and 364 cGy by RGS and 18 and 399 cGy by CK to brainstem. The mean V12 Gy for brain predicting for radionecrosis with RGS was 3.75 cm3 as compared to 4.09 cm3 with the CK (p  =  0.41). The dosimetric parameters of a novel RGS with a ring type gantry are comparable with CyberKnife, allowing its use for intracranial lesions and is worth exploring in a clinical setting.

Evaluation of a new disposable silicon limbal relaxing incision knife by experienced users.

PubMed

Albanese, John; Dugue, Geoffrey; Parvu, Valentin; Bajart, Ann M; Lee, Edwin

2009-12-21

Previous research has suggested that the silicon BD Atomic Edge knife has superior performance characteristics when compared to a metal knife and performance similar to diamond knife when making various incisions. This study was designed to determine whether a silicon accurate depth knife has equivalent performance characteristics when compared to a diamond limbal relaxing incision (LRI) knife and superior performance characteristics when compared to a steel accurate depth knife when creating limbal relaxing incision. Sixty-five ophthalmic surgeons with limbal relaxing incision experience created limbal relaxing incisions in ex-vivo porcine eyes with silicon and steel accurate depth knives and diamond LRI knives. The ophthalmic surgeons rated multiple performance characteristics of the knives on Visual Analog Scales. The observed differences between the silicon knife and diamond knife were found to be insignificant. The mean ratio between the performance of the silicon knife and the diamond knife was shown to be greater than 90% (with 95% confidence). The silicon knife's mean performance was significantly higher than the performance of the steel knife for all characteristics. (p-value < .05) For experienced users, the silicon accurate depth knife was found to be equivalent in performance to the diamond LRI knife and superior to the steel accurate depth knife when making limbal relaxing incisions in ex vivo porcine eyes. Disposable silicon LRI knives may be an alternative to diamond LRI knives.

Acrogigantism and facial asymmetry: McCune-Albright syndrome.

PubMed

Subbiah, Sridhar; Palikhe, Gaurav; Bhadada, Sanjay Kumar; Mukherjee, Kanchan Kumar; Bhansali, Anil

2011-01-01

McCune-Albright syndrome (MAS) is characterized by a triad of poly/monoostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies. Association of MAS with GH excess is rare, and in most of the instances somatotropinoma has not been documented. Treatment of patients of MAS with acromegaly is difficult because of thickened calvarium and dysplastic skull bone. We report a 17-year-old girl, who presented with cranio-facial fibrous dysplasia, café-au-lait macules and also had acromegaly due to pituitary macroadenoma, and treated with gamma knife radiosurgery.

Relative risk analysis of the use of radiation-emitting medical devices: A preliminary application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, E.D.

This report describes the development of a risk analysis approach for evaluating the use of radiation-emitting medial devices. This effort was performed by Lawrence Livermore National Laboratory for the US Nuclear Regulatory Commission (NRC). The assessment approach has bee applied to understand the risks in using the Gamma Knife, a gamma irradiation therapy device. This effort represents an initial step to evaluate the potential role of risk analysis for developing regulations and quality assurance requirements in the use of nuclear medical devices. The risk approach identifies and assesses the most likely risk contributors and their relative importance for the medicalmore » system. The approach uses expert screening techniques and relative risk profiling to incorporate the type, quality, and quantity of data available and to present results in an easily understood form.« less

Application of the concept of biologically effective dose (BED) to patients with Vestibular Schwannomas treated by radiosurgery

PubMed Central

Millar, William T.; Lindquist, Christer; Nordström, Håkan; Lidberg, Pär; Gårding, Jonas

2013-01-01

In the application of stereotactic radiosurgery, using the Gamma Knife, there are large variations in the overall treatment time for the same prescription dose, given in a single treatment session, for different patients. This is due to not only changes in the activity of the Cobolt-60 sources, but also to variations in the number of iso-centers used, the collimator size for a particular iso-center, and the time gap between the different iso-centers. Although frequently viewed as a single dose treatment the concept of biologically effective dose (BED), incorporating concurrent fast and a slow components of repair of sublethal damage, would imply potential variations in BED because of the influence of these different variables associated with treatment. This was investigated in 26 patients, treated for Vestibular Schwannomas, using the Series B Gamma-Knife, between 1999 and 2005. The iso-center number varied between 2 and 13, and the overall treatment time from 25.4–129.58 min. The prescription doses varied from 10–14 Gy. To obtain physical dose and dose-rates from each iso-center, in a number of locations in the region of interest, a prototype version of the Leksell GammaPlan® was used. For an individual patient, BED values varied by up to 15% for a given physical iso-dose. This was due to variation in the dose prescription at different locations on that iso-dose. Between patients there was a decline in the range of BED values as the overall treatment time increased. This increased treatment time was partly a function of the slow decline in the activity of the sources with time but predominantly due to changes in the number of iso-centers used. Thus, variations in BED values did not correlate with prescription dose but was modified by the overall treatment time. PMID:29296371

SU-E-T-492: Implementing a Method for Brain Irradiation in Rats Utilizing a Commercially Available Radiosurgery Irradiator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cates, J; Drzymala, R

2014-06-01

Purpose: The purpose of the study was to implement a method for accurate rat brain irradiation using the Gamma Knife Perfexion unit. The system needed to be repeatable, efficient, and dosimetrically and spatially accurate. Methods: A platform (“rat holder”) was made such that it is attachable to the Leskell Gamma Knife G Frame. The rat holder utilizes two ear bars contacting bony anatomy and a front tooth bar to secure the rat. The rat holder fits inside of the Leskell localizer box, which utilizes fiducial markers to register with the GammaPlan planning system. This method allows for accurate, repeatable setup.Amore » cylindrical phantom was made so that film can be placed axially in the phantom. We then acquired CT image sets of the rat holder and localizer box with both a rat and the phantom. Three treatment plans were created: a plan on the rat CT dataset, a phantom plan with the same prescription dose as the rat plan, and a phantom plan with the same delivery time as the rat plan. Results: Film analysis from the phantom showed that our setup is spatially accurate and repeatable. It is also dosimetrically accurate, with an difference between predicted and measured dose of 2.9%. Film analysis with prescription dose equal between rat and phantom plans showed a difference of 3.8%, showing that our phantom is a good representation of the rat for dosimetry purposes, allowing for +/- 3mm diameter variation. Film analysis with treatment time equal showed an error of 2.6%, which means we can deliver a prescription dose within 3% accuracy. Conclusion: Our method for irradiation of rat brain has been shown to be repeatable, efficient, and accurate, both dosimetrically and spatially. We can treat a large number of rats efficiently while delivering prescription doses within 3% at millimeter level accuracy.« less

Usefulness of a novel slim type FlushKnife-BT over conventional FlushKnife-BT in esophageal endoscopic submucosal dissection.

PubMed

Ohara, Yoshiko; Toyonaga, Takashi; Hoshi, Namiko; Tanaka, Shinwa; Baba, Shinichi; Takihara, Hiroshi; Kawara, Fumiaki; Ishida, Tsukasa; Morita, Yoshinori; Umegaki, Eiji; Azuma, Takeshi

2017-03-07

To investigated the usefulness of a novel slim type ball-tipped FlushKnife (FlushKnife-BTS) over ball-tipped FlushKnife (FlushKnife-BT) in functional experiments and clinical practice. In order to evaluate the functionality of FlushKnife-BTS, water aspiration speed, resistance to knife insertion through the scope, and waterjet flushing speed were compared between FlushKnife-BTS and BT. In clinical practice, esophageal endoscopic submucosal dissection (ESD) performed using FlushKnife-BTS or BT by an experienced endoscopist between October 2015 and January 2016 were retrospectively reviewed. The treatment speed and frequency of removing and reinserting the knife to aspirate fluid and air during ESD sessions were analyzed. Functional experiments revealed that water aspiration speed by the endoscope equipped with a 2.8-mm working channel with FlushKnife-BTS was 7.7-fold faster than that with conventional FlushKnife-BT. Resistance to knife insertion inside the scope with a 2.8-mm working channel was reduced by 40% with FlushKnife-BTS. The waterjet flushing speed was faster with the use of FlushKnife-BT. In clinical practice, a comparison of 6 and 7 ESD using FlushKnife-BT and BTS, respectively, revealed that the median treatment speed was 25.5 mm 2 /min (range 19.6-30.3) in the BT group and 44.2 mm 2 /min (range 15.5-55.4) in the BTS group ( P = 0.0633). However, the median treatment speed was significantly faster with FlushKnife-BTS when the resection size was larger than 1000 m 2 ( n = 4, median 24.2 mm 2 /min, range 19.6-27.7 vs n = 4, median 47.4 mm 2 /min, range 44.2-55.4, P = 0.0209). The frequency of knife replacement was less in the BTS group (median 1.76 times in one hour, range 0-5.45) than in the BT group (7.02 times in one hour, range 4.23-15) ( P = 0.0065). Our results indicate that FlushKnife-BTS enhances the performance of ESD, particularly for large lesions, by improving air and fluid aspiration and knife insertion during ESD and reducing the frequency of knife removal and reinsertion.

Usefulness of a novel slim type FlushKnife-BT over conventional FlushKnife-BT in esophageal endoscopic submucosal dissection

PubMed Central

Ohara, Yoshiko; Toyonaga, Takashi; Hoshi, Namiko; Tanaka, Shinwa; Baba, Shinichi; Takihara, Hiroshi; Kawara, Fumiaki; Ishida, Tsukasa; Morita, Yoshinori; Umegaki, Eiji; Azuma, Takeshi

2017-01-01

AIM To investigated the usefulness of a novel slim type ball-tipped FlushKnife (FlushKnife-BTS) over ball-tipped FlushKnife (FlushKnife-BT) in functional experiments and clinical practice. METHODS In order to evaluate the functionality of FlushKnife-BTS, water aspiration speed, resistance to knife insertion through the scope, and waterjet flushing speed were compared between FlushKnife-BTS and BT. In clinical practice, esophageal endoscopic submucosal dissection (ESD) performed using FlushKnife-BTS or BT by an experienced endoscopist between October 2015 and January 2016 were retrospectively reviewed. The treatment speed and frequency of removing and reinserting the knife to aspirate fluid and air during ESD sessions were analyzed. RESULTS Functional experiments revealed that water aspiration speed by the endoscope equipped with a 2.8-mm working channel with FlushKnife-BTS was 7.7-fold faster than that with conventional FlushKnife-BT. Resistance to knife insertion inside the scope with a 2.8-mm working channel was reduced by 40% with FlushKnife-BTS. The waterjet flushing speed was faster with the use of FlushKnife-BT. In clinical practice, a comparison of 6 and 7 ESD using FlushKnife-BT and BTS, respectively, revealed that the median treatment speed was 25.5 mm2/min (range 19.6-30.3) in the BT group and 44.2 mm2/min (range 15.5-55.4) in the BTS group (P = 0.0633). However, the median treatment speed was significantly faster with FlushKnife-BTS when the resection size was larger than 1000 m2 (n = 4, median 24.2 mm2/min, range 19.6-27.7 vs n = 4, median 47.4 mm2/min, range 44.2-55.4, P = 0.0209). The frequency of knife replacement was less in the BTS group (median 1.76 times in one hour, range 0-5.45) than in the BT group (7.02 times in one hour, range 4.23-15) (P = 0.0065). CONCLUSION Our results indicate that FlushKnife-BTS enhances the performance of ESD, particularly for large lesions, by improving air and fluid aspiration and knife insertion during ESD and reducing the frequency of knife removal and reinsertion. PMID:28321167

Design and Mechanical Stability Analysis of the Interaction Region for the Inverse Compton Scattering Gamma-Ray Source Using Finite Element Method

NASA Astrophysics Data System (ADS)

Khizhanok, Andrei

Development of a compact source of high-spectral brilliance and high impulse frequency gamma rays has been in scope of Fermi National Accelerator Laboratory for quite some time. Main goal of the project is to develop a setup to support gamma rays detection test and gamma ray spectroscopy. Potential applications include but not limited to nuclear astrophysics, nuclear medicine, oncology ('gamma knife'). Present work covers multiple interconnected stages of development of the interaction region to ensure high levels of structural strength and vibrational resistance. Inverse Compton scattering is a complex phenomenon, in which charged particle transfers a part of its energy to a photon. It requires extreme precision as the interaction point is estimated to be 20 microm. The slightest deflection of the mirrors will reduce effectiveness of conversion by orders of magnitude. For acceptable conversion efficiency laser cavity also must have >1000 finesse value, which requires a trade-off between size, mechanical stability, complexity, and price of the setup. This work focuses on advantages and weak points of different designs of interaction regions as well as in-depth description of analyses performed. This includes laser cavity amplification and finesse estimates, natural frequency mapping, harmonic analysis. Structural analysis is required as interaction must occur under high vacuum conditions.

Intracellular localization of varicella-zoster virus ORF39 protein and its functional relationship to glycoprotein K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Govero, Jennifer; Hall, Susan; Heineman, Thomas C.

2007-02-20

Varicella-zoster virus (VZV) encodes two multiply inserted membrane proteins, open reading frame (ORF) 39 protein (ORF39p) and glycoprotein K (gK). The HSV-1 homologs of these proteins are believed to act in conjunction with each other during viral egress and cell-cell fusion, and they directly influence each other's intracellular trafficking. However, ORF39p and VZV gK have received very limited study largely due to difficulties in producing antibodies to these highly hydrophobic proteins. To overcome this obstacle, we introduced epitope tags into both ORF39p and gK and examined their intracellular distributions in transfected and infected cells. Our data demonstrate that both ORF39pmore » and gK accumulate predominately in the ER of cultured cells when expressed in the absence of other VZV proteins or when coexpressed in isolation from other VZV proteins. Therefore, the transport of VZV ORF39p and gK does not exhibit the functional interdependence seen in their HSV-1 homologs. However, during infection, the primary distributions of ORF39p and gK shift from the ER to the Golgi, and they are also found in the plasma membrane indicating that their intracellular trafficking during infection depends on other VZV-encoded proteins. During infection, ORF39p and gK tightly colocalize with VZV envelope glycoproteins B, E and H; however, the coexpression of ORF39p or gK with other individual viral glycoproteins is insufficient to alter the transport of either ORF39p or gK.« less

Bioprospecting of gum kondagogu (Cochlospermum gossypium) for bioremediation of uranium (VI) from aqueous solution and synthetic nuclear power reactor effluents.

PubMed

Sashidhar, R B; Selvi, S Kalaignana; Vinod, V T P; Kosuri, Tanuja; Raju, D; Karuna, R

2015-10-01

An ecofriendly green chemistry method using a natural biopolymer, Gum Kondagogu (GK) for the removal of U (VI) from aqueous, simulated nuclear effluents was studied. The adsorption characteristic of GK towards U (VI) from aqueous solution was studied at varied pH, contact time, adsorbent dose, initial U (VI) concentration and temperature using UV-Visible spectroscopy and ICP-MS. Maximum adsorption was seen at pH 4, 0.1% GK with 60 min contact time at room temperature. The GK- U (VI) composite was characterized by FT-IR, zeta potential, TEM and SEM-EDAX. The Langmuir isotherm was found to be 487 mg of U (VI) g(-1) of GK. The adsorption capacity and (%) of U (VI) was found to be 490 ± 5.4 mg g(-1) and 98.5%. Moreover adsorption of U (VI) by GK was not influenced by other cations present in the simulated effluents. The adsorbed U (VI) was efficiently stripped from composite using 1 M HCl. Copyright © 2015 Elsevier Ltd. All rights reserved.

UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dalgaard, Louise T., E-mail: ltd@ruc.dk; Department of Science, Systems and Models, Roskilde University

2012-01-06

Highlights: Black-Right-Pointing-Pointer UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. Black-Right-Pointing-Pointer UCP2 mRNA up-regulation by glucose is dependent on glucokinase. Black-Right-Pointing-Pointer Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. Black-Right-Pointing-Pointer This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic {beta}-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was tomore » examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase mimetic, did not prevent the glucose-induced up-regulation of UCP2. Glucose-stimulated insulin secretion was increased in UCP2-/- and GK+/- islets compared with GK+/- islets and UCP2 deficiency improved glucose tolerance of GK+/- mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/- mice. Thus, the compensatory down-regulation of UCP2 is involved in preserving the insulin secretory capacity of GK mutant mice and might also be implicated in limiting disease progression in MODY2 patients.« less

Efficacy of a Novel Narrow Knife with Water Jet Function for Colorectal Endoscopic Submucosal Dissection.

PubMed

Yoshida, Naohisa; Toyonaga, Takashi; Murakami, Takaaki; Hirose, Ryohei; Ogiso, Kiyoshi; Inada, Yutaka; Rani, Rafiz Abdul; Naito, Yuji; Kishimoto, Mitsuo; Ohara, Yoshiko; Azuma, Takeshi; Itoh, Yoshito

2017-01-01

With respect to the knife's design in colorectal endoscopic submucosal dissection (ESD), diameter, water jet function, and electric power are important because these relate to efficient dissection. In this study, we analyzed a novel, narrow ball tip-typed ESD knife with water jet function (Flush knife BT-S, diameter: 2.2 mm, length: 2000 mm, Fujifilm Co., Tokyo, Japan) compared to a regular diameter knife (Flush knife BT, diameter: 2.6 mm, length: 1800 mm). In laboratory and clinical research, electric power, knife insertion time, vacuum/suction amount with knife in the endoscopic channel, and water jet function were analyzed. We used a knife 2.0 mm long for BT-S and BT knives. The BT-S showed faster mean knife insertion time (sec) and better vacuum amount (ml/min) compared to the BT (insertion time: 16.7 versus 21.6, p < 0.001, vacuum amount: 38.0 versus 14.0, p < 0.01). Additionally, the water jet function of the BT-S was not inferior. In 39 colorectal ESD cases in two institutions, there were mean 4.7 times (range: 1-28) of knife insertion. Suction under knife happened 59% (23/39) and suction of fluid could be done in 100%. Our study showed that the narrow knife allows significantly faster knife insertion, better vacuum function, and effective clinical results.

Hearing Preservation after Low-dose Gamma Knife Radiosurgery of Vestibular Schwannomas

PubMed Central

HORIBA, Ayako; HAYASHI, Motohiro; CHERNOV, Mikhail; KAWAMATA, Takakazu; OKADA, Yoshikazu

2016-01-01

The objective of the retrospective study was to evaluate the factors associated with hearing preservation after low-dose Gamma Knife radiosurgery (GKS) of vestibular schwannomas performed according to the modern standards. From January 2005 to September 2010, 141 consecutive patients underwent such treatment in Tokyo Women’s Medical University. Mean marginal dose was 11.9 Gy (range, 11–12 Gy). The doses for the brain stem, cranial nerves (V, VII, and VIII), and cochlea were kept below 14 Gy, 12 Gy, and 4 Gy, respectively. Out of the total cohort, 102 cases with at least 24 months follow-up were analyzed. Within the median follow-up of 56 months (range, 24–99 months) the crude tumor growth control was 92% (94 cases), whereas its actuarial rate at 5 years was 93%. Out of 49 patients with serviceable hearing on the side of the tumor before GKS, 28 (57%) demonstrated its preservation at the time of the last follow-up. No one evaluated factor, namely Gardner-Robertson hearing class before irradiation, Koos tumor stage, extension of the intrameatal part of the neoplasm up to fundus, nerve of tumor origin, presence of cystic changes in the neoplasm, and cochlea dose demonstrated statistically significant association with preservation of the serviceable hearing after radiosurgery. In conclusion, GKS of vestibular schwannomas performed according to the modern standards of treatment permits to preserve serviceable hearing on the side of the tumor in more than half of the patients. The actual causes of hearing deterioration after radiosurgery remain unclear. PMID:26876903

Gamma knife radiosurgery for symptomatic brainstem intra-axial cavernous malformations.

PubMed

Park, Seong-Hyun; Hwang, Sung-Kyoo

2013-12-01

The purpose of this study was to evaluate the efficacy and safety of gamma knife radiosurgery (GKRS) for the treatment of symptomatic brainstem intra-axial cavernous malformations (CMs) associated with high surgical morbidity. Twenty-one patients with symptomatic brainstem intra-axial CMs were treated by GKRS between 2005 and 2010. One patient was lost to follow-up. The median age of the patients was 39.5 years (range, 24-69 years). All patients had experienced 1 or more symptomatic hemorrhages before GKRS (range, 1-3). The median marginal radiation dose was 13 Gy, and the median volume of the malformation was 0.56 mL. The median follow-up period after radiosurgery was 32 months (range, 12-82 months; mean, 38.9 months). Before GKRS, 31 hemorrhages (1.55 per patient) were observed. The annual hemorrhage rate before GKRS was 39.5%, excluding the first hemorrhage. After GKRS, 1 hemorrhage (0.05 per patient) was identified. It occurred 6 months after radiosurgery. The patient showed complete recovery to a premorbid status with steroid medication. The annual hemorrhage rate after GKRS was 8.2% for the first 2 years. After the expected latency period, no hemorrhages were identified. One patient (5%) exhibited permanent paresthesia, which was a new neurologic symptom in absence of any hemorrhagic event, after the radiosurgery. GKRS seems to be relatively effective and safe for reducing the rebleeding rate of brainstem intra-axial CMs that have high surgical risk. Careful selection of a low marginal dose and an optimal radiosurgical technique are helpful to achieve good outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Gamma knife radiosurgery for medically and surgically refractory prolactinomas.

PubMed

Pouratian, Nader; Sheehan, Jason; Jagannathan, Jay; Laws, Edward R; Steiner, Ladislau; Vance, Mary L

2006-08-01

Experience with gamma knife radiosurgery (GKRS) for prolactinomas is limited because of the efficacy of medical and surgical intervention. Patients who are refractory to medical and/or surgical therapy may be treated with GKRS. We characterize the efficacy of GKRS for medically and surgically refractory prolactinomas. We reviewed our series of patients with prolactinomas who were treated with GKRS after failing medical and surgical intervention who had at least 1 year of follow-up. Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%). Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most.

Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study.

PubMed

Xu, Zhiyuan; Mathieu, David; Heroux, France; Abbassy, Mahmoud; Barnett, Gene; Mohammadi, Alireza M; Kano, Hideyuki; Caruso, James; Shih, Han-Hsun; Grills, Inga S; Lee, Kuei; Krishnan, Sandeep; Kaufmann, Anthony M; Lee, John Y K; Alonso-Basanta, Michelle; Kerr, Marie; Pierce, John; Kondziolka, Douglas; Hess, Judith A; Gerrard, Jason; Chiang, Veronica; Lunsford, L Dade; Sheehan, Jason P

2018-04-23

Facial pain response (PR) to various surgical interventions in patients with multiple sclerosis (MS)-related trigeminal neuralgia (TN) is much less optimal. No large patient series regarding stereotactic radiosurgery (SRS) has been published. To evaluate the clinical outcomes of MS-related TN treated with SRS. This is a retrospective cohort study. A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study. The median latency period of PR after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute [BNI] Pain Scores I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%). In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control.

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife?

PubMed

Marek, Josef; Jezková, Jana; Hána, Václav; Krsek, Michal; Bandúrová, L'ubomíra; Pecen, Ladislav; Vladyka, Vilibald; Liscák, Roman

2011-02-01

Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism. We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary <15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001-2009 (40 patients), irradiated with a mean dose to pituitary >15 Gy. Serum TSH, free thyroxine, testosterone or 17β-oestradiol, IGF1, prolactin and cortisol levels were evaluated before and every 6 months after LGK irradiation. Hypopituitarism after LGK irradiation developed only in 1 out of 45 (2.2%) patients irradiated with a mean dose to pituitary <15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose of 17 Gy. Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

Stereotactic radiosurgery for the treatment of mesial temporal lobe epilepsy.

PubMed

Feng, E-S; Sui, C-B; Wang, T-X; Sun, G-L

2016-12-01

Stereotactic radiosurgery (RS) is a potential option for some patients with temporal lobe epilepsy (TLE). The aim of this meta-analysis was to determine the pooled seizure-free rate and the time interval to seizure cessation in patients with lesions in the mesial temporal lobe, and who were eligible for either stereotactic or gamma knife RS. We searched the Medline, Cochrane, EMBASE, and Google Scholar databases using combinations of the following terms: RS, stereotactic radiosurgery, gamma knife, and TLE. We screened 103 articles and selected 13 for inclusion in the meta-analysis. Significant study heterogeneity was detected; however, the included studies displayed an acceptable level of quality. We show that approximately half of the patients were seizure free over a follow-up period that ranged from 6 months to 9 years [pooled estimate: 50.9% (95% confidence interval: 0.381-0.636)], with an average of 14 months to seizure cessation [pooled estimate: 14.08 months (95% confidence interval: 11.95-12.22 months)]. Nine of 13 included studies reported data for adverse events (AEs), which included visual field deficits and headache (the two most common AEs), verbal memory impairment, psychosis, psychogenic non-epileptic seizures, and dysphasia. Patients in the individual studies experienced AEs at rates that ranged from 8%, for non-epileptic seizures, to 85%, for headache. Our findings indicate that RS may have similar or slightly less efficacy in some patients compared with invasive surgery. Randomized controlled trials of both treatment regimens should be undertaken to generate an evidence base for patient decision-making. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact on cognitive functions following gamma knife radiosurgery for cerebral arteriovenous malformations

PubMed Central

Raghunath, A.; Bennett, Niranjana; Arimappamagan, Arivazhagan; Bhat, Dhananjaya I.; Srinivas, Dwarakanath; Thennarasu, K.; Jamuna, R.; Somanna, Sampath

2016-01-01

Background: Radiosurgery is an alternative to surgical resection of arteriovenous malformation (AVM). Very few studies have addressed the concern of radiation injury to the brain and its attendant adverse effects on cognitive function. Materials and Methods: This prospective study included all patients who underwent gamma knife radiosurgery (GKRS) at our institute for cerebral AVM between 2006 and December 2008 (n = 34). All patients underwent neuropsychological evaluation before the procedure. Neuropsychological evaluation was repeated in eighteen patients 2 years following GKRS. Clinical outcome, AVM obliteration, and factors influencing outcome were analyzed in these eighteen patients. Results: Before GKRS, more than 50% had significant impairment of neuropsychological functions compared to normal population norms. 66.6% achieved the excellent radiosurgical outcome. At 2 years follow-up, patients showed varied improvement in neuropsychological function in various categories. Pretherapeutic median value for percentage perseverative responses was 26.5 and at follow-up, it reduced to 18.2 (P = 0.039). Set shifting improved in 11 patients (61.1%), remained same in 5 patients (27.7%), and deteriorated in two patients (11.1%). Patients with a higher Spetzler-Martin grade AVM demonstrated a significantly more favorable shift in follow-up test values for set shifting function (P = 0.021). Patients with postradiation imaging changes had lesser tendency to improve in neuropsychological performance at follow-up. Conclusions: GKRS has no clinically harmful effect on cognitive and neuropsychological functioning in patients with brain AVM. On the contrary, there is an improvement in majority of patients at 2 years following radiosurgery when nidus is obliterated. PMID:26933340

Retrospective analysis of imaging techniques for treatment planning and monitoring of obliteration for gamma knife treatment of cerebral arteriovenous malformation.

PubMed

Amponsah, Kwame; Ellis, Thomas L; Chan, Michael D; Lovato, James F; Bourland, J Daniel; deGuzman, Allan F; Ekstrand, Kenneth E; Munley, Michael T; McMullen, Kevin P; Shaw, Edward G; Tatter, Stephen B

2012-10-01

It has been well established that Gamma Knife radiosurgery (GKS) is an effective treatment for brain arteriovenous malformations (AVMs). To evaluate complete obliteration rates for magnetic resonance imaging (MRI)-based GKS treatment planning performed with and without angiography and to conduct a preliminary assessment of the utility of using pulsed arterial spin labeling (PASL) magnetic resonance (MR) perfusion imaging to confirm complete obliteration. Forty-six patients were identified who had undergone GKS without embolization with a minimum follow-up of 2 years. One group was planned with integrated stereotactic angiography and MR (spoiled gradient recalled) images obtained on the day of GKS. A second technique avoided the risk of arteriography by using only axial MR images. Beginning in 2007, PASL MR perfusion imaging was routinely performed as a portion of the follow-up MRI to assess the restoration of normal blood flow of the nidus and surrounding area. The overall obliteration rate for the angiography/MRI group was 88.0% (29 of 33). Patients in the MRI-only group had an obliteration rate of 61.5% (8 of 13), with P=.092 with the Fisher exact test, which is not statistically significant. A Kaplan-Meier analysis was also not statistically significant (log rank test, P=.474). Four of 9 patients with incomplete obliteration on angiography also had shown residual abnormal blood flow on PASL imaging. This retrospective analysis shows that treatment planning technique used in GKS does not play a role in the eventual obliteration of treated AVMs. PASL may have potential in the evaluation of AVM obliteration.

Utilization of Cone-Beam Computed Tomographic Angiography in Planning for Gamma Knife Radiosurgery of Arteriovenous Malformations: A Case Series and Early Report

PubMed Central

Safain, Mina G.; Rahal, Jason P.; Raval, Ami; Rivard, Mark J.; Mignano, John; Wu, Julian; Malek, Adel M.

2014-01-01

Background The effectiveness of Gamma Knife radiosurgery (GKR) for cerebral arteriovenous malformations (AVM) is predicated on inclusion of the entire nidus while excluding normal tissue. As such, GKR may be limited by the resolution and accuracy of the imaging modality used in targeting. Objective We present the first case series to demonstrate the feasibility of utilizing ultra-high-resolution C-arm cone beam computed tomography angiography (CBCT-A) in AVM targeting. Methods From June 2009 to June 2013, CBCT-A was utilized for targeting of all patients with AVMs treated with GKR at our institution. Patients underwent Leksell stereotactic head frame placement followed by catheter-based biplane 2-D digital subtraction angiography (DSA), 3-D rotational angiography (3DRA), as well as CBCT-A. The CBCT-A dataset was used for stereotactic planning for GKR. Patients were followed up at 1, 3, 6, and 12 months, and then annually thereafter. Results CBCT-A-based targeting was used in twenty-two consecutive patients. CBCT-A provided detailed spatial resolution and sensitivity of nidal angioarchitecture enabling treatment. The average radiation dose to the margin of the AVM nidus corresponding to the 50% percent isodose line was 15.6 Gy. No patient had treatment-associated hemorrhage. At early follow-up (mean=16 months), 84% of patients had a decreasing or obliterated AVM nidus. Conclusion CBCT-A-guided radiosurgery is feasible and useful because it provides sufficient detailed resolution and sensitivity for imaging brain AVMs. PMID:24584136

Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma

PubMed Central

Larson, Erik W; Peterson, Halloran E; Lamoreaux, Wayne T; MacKay, Alexander R; Fairbanks, Robert K; Call, Jason A; Carlson, Jonathan D; Ling, Benjamin C; Demakas, John J; Cooke, Barton S; Lee, Christopher M

2014-01-01

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed. PMID:24829861

Gamma Knife radiosurgery for hemangioma of the cavernous sinus.

PubMed

Lee, Cheng-Chia; Sheehan, Jason P; Kano, Hideyuki; Akpinar, Berkcan; Martinez-Alvarez, Roberto; Martinez-Moreno, Nuria; Guo, Wan-Yuo; Lunsford, L Dade; Liu, Kang-Du

2017-05-01

OBJECTIVE Cavernous sinus hemangiomas (CSHs) are rare vascular tumors. A direct microsurgical approach usually results in massive hemorrhage and incomplete tumor resection. Although stereotactic radiosurgery (SRS) has emerged as a therapeutic alternative to microsurgery, outcome studies are few. Authors of the present study evaluated the role of SRS for CSH. METHODS An international multicenter study was conducted to review outcome data in 31 patients with CSH. Eleven patients had initial microsurgery before SRS, and the other 20 patients (64.5%) underwent Gamma Knife SRS as the primary management for their CSH. Median age at the time of radiosurgery was 47 years, and 77.4% of patients had cranial nerve dysfunction before SRS. Patients received a median tumor margin dose of 12.6 Gy (range 12-19 Gy) at a median isodose of 55%. RESULTS Tumor regression was confirmed by imaging in all 31 patients, and all patients had greater than 50% reduction in tumor volume at 6 months post-SRS. No patient had delayed tumor growth, new cranial neuropathy, visual function deterioration, adverse radiation effects, or hypopituitarism after SRS. Twenty-four patients had presented with cranial nerve disorders before SRS, and 6 (25%) of them had gradual improvement. Four (66.7%) of the 6 patients with orbital symptoms had symptomatic relief at the last follow-up. CONCLUSIONS Stereotactic radiosurgery was effective in reducing the volume of CSH and attaining long-term tumor control in all patients at a median of 40 months. The authors' experience suggests that SRS is a reasonable primary and adjuvant treatment modality for patients in whom a CSH is diagnosed.

Gamma knife radiosurgery for Cushing's disease and Nelson's syndrome.

PubMed

Marek, Josef; Ježková, Jana; Hána, Václav; Kršek, Michal; Liščák, Roman; Vladyka, Vilibald; Pecen, Ladislav

2015-06-01

This paper presents our 18 years of experience in treating ACTH secreting adenomas (Cushing's disease and Nelson's syndrome) using the Leksell gamma knife (LGK) irradiation. Twenty-six patients with Cushing's disease were followed-up after LGK irradiation for 48-216 months (median 78 months). Seventeen patients had undergone previous surgery, in nine patients LGK irradiation was the primary therapy. Furthermore, 14 patients with Nelson's syndrome were followed-up for 30-204 months (median 144 months). LGK treatment resulted in hormonal normalization in 80.7 % of patients with Cushing's disease. Time to normalization was 6-54 months (median 30 months). The volume of the adenoma decreased in 92.3% (in 30.7% disappeared completely). There was no recurrence of the disease. In all 14 patients with Nelson's syndrome ACTH levels decreased (in two patients fully normalized) their ACTH levels. When checked up 5-10 years after irradiation regrowth of the adenoma was only detected in one patient (9.1%), in 27.3% adenoma volume remained unchanged, in 45.4% adenoma volume decreased and in 18.2% adenoma completely disappeared. Hypopituitarism did not develop in any patient where the critical dose to the pituitary and distal infundibulum was respected. LGK radiation represents an effective and well-tolerated option for the treatment of patients with Cushing's disease after unsuccessful surgery and may be valuable even as a primary treatment in patients who are not suitable for, or refuse, surgery. In the case of Nelson's syndrome it is possible to impede tumorous growth and control the size of the adenoma in almost all patients.

Radiosurgery for Arteriovenous Malformations and the Impact on Headaches.

PubMed

Bowden, Greg; Cavaleri, Jonathon; Kano, Hideyuki; Monaco, Edward; Niranjan, Ajay; Flickinger, John; Dade Lunsford, L

2017-05-01

Arteriovenous malformations (AVMs) can underlie many diverse neurological signs and symptoms. Headaches are a common presentation that can have a significant impact on quality of life. The authors investigated Gamma Knife ® stereotactic radiosurgery (SRS) outcomes in patients with AVMs and associated headaches. This retrospective study analyzed 102 patients with AVMs who underwent SRS between 1995 and 2013. The patient's headache symptoms led to their AVM diagnosis or developed post hemorrhage of their AVM. Information regarding headache characteristics was obtained from the patient's medical records and at follow-up using a scripted clinical interview. The median imaging follow-up was 61.7 months and clinical follow-up was 89.7 months. The median treatment volume at SRS was 4.1 cm 3 and the median marginal dose was 20 Gy. The actuarial AVM obliteration rate was 60% at 5 years and 78% at 10 years. Patients reported that their overall headache severity decreased by -43.6% and their headache frequency was reduced by -53.4%. Headache reduction was reported in 49.1% of patients at 1 year and 69.5% at 5 years. The median time until improvement was 6.5 months. After SRS, headache medication usage decreased in 29% of patients. Permanent adverse radiation effects after SRS occurred in 3% of patients. Until obliteration was complete, the annual risk of a hemorrhage after SRS was 0.4% per year. Although recall bias related to a retrospective analysis can impact outcomes, headache symptoms associated with AVMs may potentially be decreased or eliminated in a subset of patients treated with Gamma Knife radiosurgery. © 2017 American Headache Society.

Conservative management or gamma knife radiosurgery for vestibular schwannoma: tumor growth, symptoms, and quality of life.

PubMed

Breivik, Cathrine Nansdal; Nilsen, Roy Miodini; Myrseth, Erling; Pedersen, Paal Henning; Varughese, Jobin K; Chaudhry, Aqeel Asghar; Lund-Johansen, Morten

2013-07-01

There are few reports about the course of vestibular schwannoma (VS) patients following gamma knife radiosurgery (GKRS) compared with the course following conservative management (CM). In this study, we present prospectively collected data of 237 patients with unilateral VS extending outside the internal acoustic canal who received either GKRS (113) or CM (124). The aim was to measure the effect of GKRS compared with the natural course on tumor growth rate and hearing loss. Secondary end points were postinclusion additional treatment, quality of life (QoL), and symptom development. The patients underwent magnetic resonance imaging scans, clinical examination, and QoL assessment by SF-36 questionnaire. Statistics were performed by using Spearman correlation coefficient, Kaplan-Meier plot, Poisson regression model, mixed linear regression models, and mixed logistic regression models. Mean follow-up time was 55.0 months (26.1 standard deviation, range 10-132). Thirteen patients were lost to follow-up. Serviceable hearing was lost in 54 of 71 (76%) (CM) and 34 of 53 (64%) (GKRS) patients during the study period (not significant, log-rank test). There was a significant reduction in tumor volume over time in the GKRS group. The need for treatment following initial GKRS or CM differed at highly significant levels (log-rank test, P < .001). Symptom and QoL development did not differ significantly between the groups. In VS patients, GKRS reduces the tumor growth rate and thereby the incidence rate of new treatment about tenfold. Hearing is lost at similar rates in both groups. Symptoms and QoL seem not to be significantly affected by GKRS.

Salvage Gamma Knife Stereotactic Radiosurgery for Surgically Refractory Trigeminal Neuralgia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, Andrew S.; Shetter, Andrew G.; Shetter, Mary E.

2009-06-01

Purpose: To evaluate the clinical outcome of patients with surgically refractory trigeminal neuralgia (TN) treated with rescue gamma knife radiosurgery (GKRS). Methods and Materials: Seventy-nine patients with typical TN received salvage GKRS between 1997 and 2002 at the Barrow Neurological Institute (BNI). All patients had recurrent pain following at least one prior surgical intervention. Prior surgical interventions included percutaneous destructive procedures, microvascular decompression (MVD), or GKRS. Thirty-one (39%) had undergone at least two prior procedures. The most common salvage dose was 80 Gy, although 40-50 Gy was typical in patients who had received prior radiosurgery. Pain outcome was assessed usingmore » the BNI Pain Intensity Score, and quality of life was assessed using the Brief Pain Inventory. Results: Median follow-up after salvage GKRS was 5.3 years. Actuarial analysis demonstrated that at 5 years, 20% of patients were pain-free and 50% had pain relief. Pain recurred in patients who had an initial response to GKRS at a median of 1.1 years. Twenty-eight (41%) required a subsequent surgical procedure for recurrence. A multivariate Cox proportional hazards model suggested that the strongest predictor of GKRS failure was a history of prior MVD (p=0.029). There were no instances of serious morbidity or mortality. Ten percent of patients developed worsening facial numbness and 8% described their numbness as 'very bothersome.' Conclusions: GKRS salvage for refractory TN is well tolerated and results in long-term pain relief in approximately half the patients treated. Clinicians may reconsider using GKRS to salvage patients who have failed prior MVD.« less

Long-term Auditory Symptoms in Patients With Sporadic Vestibular Schwannoma: An International Cross-Sectional Study.

PubMed

Tveiten, Oystein Vesterli; Carlson, Matthew L; Goplen, Frederik; Vassbotn, Flemming; Link, Michael J; Lund-Johansen, Morten

2015-08-01

There are limited data on the long-term auditory symptoms in patients with sporadic small- and medium-sized vestibular schwannoma (VS). The initial treatment strategy for VS is controversial. To characterize auditory symptoms in a large cohort of patients with VS. Patients with ≤3 cm VS who underwent primary microsurgery, gamma knife surgery, or observation between 1998 and 2008 at 2 independent hospitals were identified. Clinical data were extracted from existing VS databases. At a mean time of 7.7 years after initial treatment, patients were surveyed via mail with the use of the Hearing Handicap Inventory for Adults (HHIA) and the Tinnitus Handicap Inventory. The response rate was 79%; a total of 539 respondents were analyzed. Overall, the hearing prognosis was poor, because more than 75% of all patients had nonserviceable hearing at the last clinical follow-up. Good baseline hearing proved to be a strong predictor for maintained serviceable hearing. Treatment modality was independently associated with both audiometric outcome and HHIA results. Active treatment with microsurgery or gamma knife surgery did not appear to be protective, because patients who were observed had the greatest probability of durable hearing. Patients in the surgical series had the greatest hearing loss. Tinnitus Handicap Inventory results were less predictable. The only predictors of tinnitus handicap were age and HHIA score. The overall prognosis for hearing in sporadic VS is poor regardless of treatment strategy. Treatment modality was an independent predictor of hearing status; observation was associated with the highest rate of hearing preservation. .

Longitudinal assessment of quality of life and audiometric test outcomes in vestibular schwannoma patients treated with gamma knife surgery.

PubMed

Park, Sean S; Grills, Inga Siiner; Bojrab, Dennis; Pieper, Daniel; Kartush, Jack; Maitz, Ann; Martin, Arturo; Perez, Evelyn; Hahn, Yoav; Ye, Hong; Martinez, Alvaro; Chen, Peter

2011-06-01

To prospectively assess the quality of life (QOL) and hearing acuity in vestibular schwannoma (VS) patients after gamma knife surgery (GKS). Fifty-nine VS patients. GKS. Prospective follow-up algorithm included 36-item Short Form Health Survey (SF-36), Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), pure-tone average, and speech discrimination hearing scores (Gardner-Robertson and American Academy of Otolaryngology), performed before and after GKS at 1-, 3-, 6-, 12-, and 18-month posttreatment intervals. From December 2006 to November 2008, 59 VS patients were treated with a median follow-up of 15 months. At baseline, mean scores for SF-36, HHI, DHI, and THI were 73, 37, 17, and 23, respectively. Median baseline Gardner-Robertson and American Academy of Otolaryngology hearing acuity scores were 2 and B, respectively. No significant decline in SF-36 health survey was noted after GKS. Mean SF-36 score at baseline was 73, compared with a range of 70 to 77 at predetermined posttreatment intervals. Similarly, no significant changes in DHI, HHI, and THI were noted. Approximately 47% of patients with baseline serviceable hearing maintained serviceable hearing at 12 months. Significant acute and chronic worsening in hearing acuity were noted at 1 and 18 months, respectively. No correlative decline in QOL was noted as assessed by SF-36 or HHI. No significant decline in global QOL occurred after GKS with relatively short follow-up and approximately 50% survey completion. When discussing therapy options with VS patients, anticipated treatment-related QOL outcomes should be considered.

Structure based design, synthesis and biological evaluation of amino phosphonate derivatives as human glucokinase activators.

PubMed

Yellapu, Nanda Kumar; Kilaru, Ravendra Babu; Chamarthi, Nagaraju; Pvgk, Sarma; Matcha, Bhaskar

2017-06-01

Glucokinase (GK) is a potential therapeutic target of type 2 diabetes and GK activators (GKAs) represent a promising class of small organic molecules which enhance GK activity. Based on the configuration and conformation of the allosteric site of GK, we have designed a novel class of amino phosphonate derivatives in order to develop potent GKAs. The QSAR model developed using numerous descriptors revealed its potential with the best effective statistical values of RMSE=1.52 and r 2 =0.30. Moreover, application of this model on the present test set GKAs proved to be worthy to predict their activities as a better linear relationship was observed with RMSE=0.14 and r 2 =0.88. ADME studies and Lipinski filters encouraged them as safer therapeutics. The molecular dynamics and docking studies against the GK allosteric site revealed that all GKAs bind with best affinities and the complexes are strengthened by H-bonding, phosphonate salt bridges, hydrophobic and arene cat ionic interactions. Finally, in vitro evaluation with human liver GK revealed their potential to increase the GK activity by different folds. The results from QSAR, ADME, molecular docking and in vitro assays strongly suggested that the present molecules could be used as effective and safer therapeutics to control and manage type 2 diabetes. Copyright © 2017. Published by Elsevier Ltd.

Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study.

PubMed

Yellapu, Nanda Kumar; Kandlapalli, Kalpana; Valasani, Koteswara Rao; Sarma, P V G K; Matcha, Bhaskar

2013-01-01

Glucokinase (GK) is the predominant hexokinase that acts as glucose sensor and catalyses the formation of Glucose-6-phosphate. The mutations in GK gene influence the affinity for glucose and lead to altered glucose levels in blood causing maturity onset diabetes of the young type 2 (MODY2) condition, which is one of the prominent reasons of type 2 diabetic condition. In view of the importance of mutated GK resulting in hyperglycemic condition, in the present study, molecular dynamics simulations were carried out in intact and 256 E-K mutated GK structures and their energy values and conformational variations were correlated. Energy variations were observed in mutated GK (3500 Kcal/mol) structure with respect to intact GK (5000 Kcal/mol), and it showed increased γ -turns, decreased β -turns, and more helix-helix interactions that affected substrate binding region where its volume increased from 1089.152 Å(2) to 1246.353 Å(2). Molecular docking study revealed variation in docking scores (intact = -12.199 and mutated = -8.383) and binding mode of glucose in the active site of mutated GK where the involvement of A53, S54, K56, K256, D262 and Q286 has resulted in poor glucose binding which probably explains the loss of catalytic activity and the consequent prevailing of high glucose levels in MODY2 condition.

Ingenious laparoscopic knife.

PubMed

Goel, Rajiv; Modi, Pranjal

2007-06-01

Retroperitoneoscopic ureterolithotomy may be an option in selected group of patients. We present our cost effective, reliable ingenious laparoscopic knife of ureteric incision during retroperitoneoscopic ureterolithotomy. Ingenious laparoscopic knife is made by firmly tying stab knife to 5 mm laparoscopic instrument. This knife is passed through 10-mm renal angle port for making ureteric incision. Ingenious laparoscopic knife has been successfully used in 22 patients with no intraoperative and postoperative complications. Ingenious laparoscopic knife is cost effective, reliable instrument for ureteric incision during retroperitoneoscopic ureterolithotomy.

Evaluation of the National Science Foundation Graduate Teaching Fellows in K-12 Education (GK-12) Program.

ERIC Educational Resources Information Center

Mitchell, Julia; Levine, Roger; Gonzalez, Raquel; Bitter, Catherine; Webb, Norman; White, Paul

The GK-12 program of the National Science Foundation is an innovative program for enriching the value of graduate and advanced undergraduate students' education while simultaneously enriching science and mathematics teaching at the K-12 level. GK-12 is a fellowship program that offers graduate students and advanced undergraduates the opportunity…

Antibacterial effects of gum kondagogu reduced/stabilized silver nanoparticles in combination with various antibiotics: a mechanistic approach

NASA Astrophysics Data System (ADS)

Rastogi, Lori; Kora, Aruna Jyothi; Sashidhar, R. B.

2015-06-01

Gum kondagogu reduced/stabilized silver nanoparticles (GK-AgNPs) were evaluated for their increased antibacterial and antibiofilm activities in combination with various antibiotics (ciprofloxacin, streptomycin and gentamicin) against Gram-positive ( Staphylococcus aureus 25923, Staphylococcus aureus 49834) and Gram-negative ( Escherichia coli 25922, Pseudomonas aeruginosa 27853) bacteria. The micro-broth dilution assay suggested an enhanced antibacterial activity of GK-AgNPs in combination with ciprofloxacin and aminoglycosides (streptomycin and gentamicin) against tested strains. Though the antibacterial activity of GK-AgNPs was found to increase significantly in the presence of antibiotics, the % enhancement was found to depend on both types of antibiotic and bacterial strain. It was also found that GK-AgNPs (1 µg/mL) in combination with various antibiotics at sub-MIC concentrations could inhibit 70 % of the bacterial biofilm formation as compared to respective controls. The enhanced antibacterial activity was due to the increased production of intracellular reactive oxygen species in bacteria when treated with a combination of GK-AgNPs and streptomycin as compared to individual treatment. The increased oxidative stress led to increased membrane damage as assessed by live/dead assay and higher levels of potassium ion release from the cells treated with both silver nanoparticles and streptomycin. The results suggested that the combination of antibiotics with GK-AgNPs has an enhanced antibacterial action. Further, the GK-AgNPs were found to be biocompatible up to a concentration of 2.5 µg/mL as assessed with MTT assay on HeLa cell line. The results suggest that GK-AgNPs could potentially be used as in vivo antibacterial agent in combination with antibiotics to overcome the problem of antibiotic resistance.

Conformational Transition Pathway in the Activation Process of Allosteric Glucokinase

PubMed Central

Shi, Ting; Zhao, Yaxue; Chen, Yingyi; Li, Xiaobai; Liu, Xinyi; Huang, Zhimin; Zhang, Jian

2013-01-01

Glucokinase (GK) is a glycolytic enzyme that plays an important role in regulating blood glucose level, thus acting as a potentially attractive target for drug discovery in the treatment of diabetes of the young type 2 and persistent hyperinsulinemic hypoglycemia of infancy. To characterize the activation mechanism of GK from the super-open state (inactive state) to the closed state (active state), a series of conventional molecular dynamics (MD) and targeted MD (TMD) simulations were performed on this enzyme. Conventional MD simulation showed a specific conformational ensemble of GK when the enzyme is inactive. Seven TMD simulations depicted a reliably conformational transition pathway of GK from the inactive state to the active state, and the components important to the conformational change of GK were identified by analyzing the detailed structures of the TMD trajectories. In combination with the inactivation process, our findings showed that the whole conformational pathway for the activation-inactivation-activation of GK is a one-direction circulation, and the active state is less stable than the inactive state in the circulation. Additionally, glucose was demonstrated to gradually modulate its binding pose with the help of residues in the large domain and connecting region of GK during the activation process. Furthermore, the obtained energy barriers were used to explain the preexisting equilibrium and the slow binding kinetic process of the substrate by GK. The simulated results are in accordance with the recent findings from the mutagenesis experiments and kinetic analyses. Our observations reveal a complicated conformational process in the allosteric protein, resulting in new knowledge about the delicate mechanisms for allosteric biological macromolecules that will be useful in drug design for targeting allosteric proteins. PMID:23409066

Multicenter Analysis of Clinical Follow-Ups in Patients with a Star GK Cardiac Valve Replacement for More than One Year.

PubMed

Li, Mingwen; Xiao, Yingbin; Chen, Daozhong; Liu, Liming; Ma, Liming; Wang, Pingfan; Jia, Kui; Yang, Kai; Chen, Lin

2016-05-18

Star GK valves were widely used in China, and we studied the clinical follow-up results of patients with Star GK valve implants for more than one year.  Clinical data were collected from those patients who had Star GK valve implants for over one year. Patients were divided into three groups: (1) AVR group: received aortic valve replacement surgery. Based on the valve model this group was further sub-divided into two groups: 21A group, and 23A group; (2) MVR group: received mitral valve replacement surgery. Based on the valve model this group was further sub-divided into three groups: 25M group, 27M group, and 29M group; (3) DVR group: received combined replacement surgeries including AVR + MVR. According to postoperative follow-up time these patients were divided into two groups: 1-year group and 3-year group. Follow-up data were collected by telephone, outpatient visits, or correspondence. Clinical data were aggregated by professional data scientists to conduct independent analyses.  959 patients were included in the study following Star GK valve implant. Follow-up after 1 year found that thrombosis occurred in 4 cases, hemorrhage in 15 cases, left heart failure in 13 cases, paravalvular leakage in 5 cases, and death due to cardiac causes in 2 cases.  The long-term efficacy of Star GK valve implants was satisfactory with low incidence of valve-related complications, and following Star GK valve implant, valve and blood were highly compatible and blood component damage was minor. Very low incidence rate of thrombosis was observed following Star GK valve implant, however, attention should be paid to adjust the anticoagulation intensity.

Diabetic Goto-Kakizaki rats display pronounced hyperglycemia and longer-lasting cognitive impairments following ischemia induced by cortical compression.

PubMed

Moreira, T; Cebers, G; Pickering, C; Ostenson, C-G; Efendic, S; Liljequist, S

2007-02-23

Hyperglycemia has been shown to worsen the outcome of brain ischemia in several animal models but few experimental studies have investigated impairments in cognition induced by ischemic brain lesions in hyperglycemic animals. The Goto-Kakizaki (GK) rat naturally develops type 2 diabetes characterized by mild hyperglycemia and insulin resistance. We hypothesized that GK rats would display more severe cerebral damage due to hyperglycemia-aggravated brain injury and, accordingly, more severe cognitive impairments. In this study, recovery of motor and cognitive functions of GK and healthy Wistar rats was examined following extradural compression (EC) of the sensorimotor cortex. For this purpose, tests of vestibulomotor function (beam-walking) and combined tests of motor function and learning (locomotor activity from day (D) 1 to D5, operant lever-pressing from D14 to D25) were used. EC consistently reduced cerebral blood flow in both strains. Anesthesia-challenge and EC resulted in pronounced hyperglycemia in GK but not in Wistar rats. Lower beam-walking scores, increased locomotor activity, impairments in long-term habituation and learning of operant lever-pressing were more pronounced and observed at later time-points in GK rats. Fluoro-Jade, a marker of irreversible neuronal degeneration, revealed consistent degeneration in the ipsilateral cortex, hippocampus and thalamus at 2, 7 and 14 days post-compression. The amount of degeneration in these structures was considerably higher in GK rats. Thus, GK rats exhibited marked hyperglycemia during EC, as well as longer-lasting behavioral deficits and increased neurodegeneration during recovery. The GK rat is thus an attractive model for neuropathologic and cognitive studies after ischemic brain injury in hyperglycemic rats.

Anti-GK1 antibodies damage Taenia crassiceps cysticerci through complement activation.

PubMed

Núñez, Guadalupe; Villalobos, Nelly; Herrera, Cinthia P; Navarrete-Perea, José; Méndez, Adriana; Martinez-Maya, José J; Bobes, Raúl J; Fragoso, Gladis; Sciutto, Edda; Aguilar, Laura; Del Arenal, Irene P

2018-06-06

Taeniasis-cysticercosis, a zoonosis caused by Taenia solium, is prevalent in underdeveloped countries, where marginalization promotes its continued transmission. Pig cysticercosis, an essential stage for transmission, is preventable by vaccination. An efficient multiepitope vaccine against pig cysticercosis, S3Pvac, was developed. Previous studies showed that antibodies against one of the S3Pvac components, GK-1, are capable of damaging T. solium cysticerci, inhibiting their ability to transform into the adult stage in golden hamster gut. This study is aimed to evaluate one of the mechanisms that could mediate anti-GK-1 antibody-dependent protection. To this end, pig anti-GK-1 antibodies were produced and purified by using protein A. Proteomic analysis showed that the induced antibodies recognized the respective native cysticercal protein KE7 (Bobes et al. Infect Immun 85:e00395-17, 2017) and two additional T. solium proteins (endophilin B1 and Gp50). A new procedure to evaluate cysticercus viability, based on quantifying the cytochrome c released after parasite damage, was developed. Taenia crassiceps cysticerci were cultured in the presence of differing amounts of anti-GK-1 antibody and complement in a saturating concentration, along with the respective controls. Cysticercus viability was assessed by recording parasite motility, trypan blue exclusion, and cytochrome c levels in cysticercal soluble extract. Anti-GK-1 antibody significantly increased cysticercus damage as measured by all three methods. Parasite evaluation by electron microscopy after treatment with anti-GK-1 antibody plus complement demonstrated cysticercus damage as shorter, capsule-severed microtrichia; a decrease in glycocalyx length with respect to untreated cysts; and disaggregated desmosomes. These results demonstrate that anti-GK-1 antibodies damage cysticerci through classic complement activation.

Stress-strain analysis of jejunal contractility in response to flow and ramp distension in type 2 diabetic GK rats: effect of carbachol stimulation.

PubMed

Zhao, Jingbo; Chen, Pengmin; Gregersen, Hans

2013-09-27

Investigation of intestinal motility in a genetic model of GK rats abandons the possible neurotoxic effect of streptozotocin in streptozotocin-induced diabetic model. Seven GK male rats (GK group) and nine normal Wistar rats (Normal group) were used in the study. The motility experiments were carried out in an organ bath containing physiological Krebs solution. Before and after 10(-5)M carbachol application, the pressure and diameter changes of jejunum were obtained in relation to (1) basic contraction, (2) flow-induced contraction with different outlet resistance pressures and (3) contractions induced by ramp distension. The frequency and amplitude of contractions were analyzed from pressure-diameter curves. Distension-induced contraction thresholds and maximum contraction amplitude of basic and flow-induced contractions were calculated in terms of stress and strain. (1) The contraction amplitude increased to the peak value in less than 10s after adding carbachol. More than two peaks were observed in the GK group. (2) Carbachol decreased the pressure and stress threshold and Young's modulus in the GK group (P<0.01). (3) Carbachol increased the maximum pressure and stress of flow-induced contractions at most outlet pressure levels in both two groups (P<0.001). Furthermore, the flow-induced contractions were significantly bigger at low outlet pressure levels in GK group (P<0.05 and P<0.01). (4) The contraction frequency, the strain threshold and the maximum contraction strain did not differ between the two groups (P>0.05) and between before and after carbachol application (P>0.05). In GK diabetic rats, the jejunal contractility was hypersensitive to flow and distension stimulation after carbachol application. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genomic-Enabled Prediction in Maize Using Kernel Models with Genotype × Environment Interaction

PubMed Central

Bandeira e Sousa, Massaine; Cuevas, Jaime; de Oliveira Couto, Evellyn Giselly; Pérez-Rodríguez, Paulino; Jarquín, Diego; Fritsche-Neto, Roberto; Burgueño, Juan; Crossa, Jose

2017-01-01

Multi-environment trials are routinely conducted in plant breeding to select candidates for the next selection cycle. In this study, we compare the prediction accuracy of four developed genomic-enabled prediction models: (1) single-environment, main genotypic effect model (SM); (2) multi-environment, main genotypic effects model (MM); (3) multi-environment, single variance G×E deviation model (MDs); and (4) multi-environment, environment-specific variance G×E deviation model (MDe). Each of these four models were fitted using two kernel methods: a linear kernel Genomic Best Linear Unbiased Predictor, GBLUP (GB), and a nonlinear kernel Gaussian kernel (GK). The eight model-method combinations were applied to two extensive Brazilian maize data sets (HEL and USP data sets), having different numbers of maize hybrids evaluated in different environments for grain yield (GY), plant height (PH), and ear height (EH). Results show that the MDe and the MDs models fitted with the Gaussian kernel (MDe-GK, and MDs-GK) had the highest prediction accuracy. For GY in the HEL data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 9 to 32%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 9 to 49%. For GY in the USP data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 0 to 7%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 34 to 70%. For traits PH and EH, gains in prediction accuracy of models with GK compared to models with GB were smaller than those achieved in GY. Also, these gains in prediction accuracy decreased when a more difficult prediction problem was studied. PMID:28455415

Genomic-Enabled Prediction in Maize Using Kernel Models with Genotype × Environment Interaction.

PubMed

Bandeira E Sousa, Massaine; Cuevas, Jaime; de Oliveira Couto, Evellyn Giselly; Pérez-Rodríguez, Paulino; Jarquín, Diego; Fritsche-Neto, Roberto; Burgueño, Juan; Crossa, Jose

2017-06-07

Multi-environment trials are routinely conducted in plant breeding to select candidates for the next selection cycle. In this study, we compare the prediction accuracy of four developed genomic-enabled prediction models: (1) single-environment, main genotypic effect model (SM); (2) multi-environment, main genotypic effects model (MM); (3) multi-environment, single variance G×E deviation model (MDs); and (4) multi-environment, environment-specific variance G×E deviation model (MDe). Each of these four models were fitted using two kernel methods: a linear kernel Genomic Best Linear Unbiased Predictor, GBLUP (GB), and a nonlinear kernel Gaussian kernel (GK). The eight model-method combinations were applied to two extensive Brazilian maize data sets (HEL and USP data sets), having different numbers of maize hybrids evaluated in different environments for grain yield (GY), plant height (PH), and ear height (EH). Results show that the MDe and the MDs models fitted with the Gaussian kernel (MDe-GK, and MDs-GK) had the highest prediction accuracy. For GY in the HEL data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 9 to 32%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 9 to 49%. For GY in the USP data set, the increase in prediction accuracy of SM-GK over SM-GB ranged from 0 to 7%. For the MM, MDs, and MDe models, the increase in prediction accuracy of GK over GB ranged from 34 to 70%. For traits PH and EH, gains in prediction accuracy of models with GK compared to models with GB were smaller than those achieved in GY. Also, these gains in prediction accuracy decreased when a more difficult prediction problem was studied. Copyright © 2017 Bandeira e Sousa et al.

Efficacy of a Novel Narrow Knife with Water Jet Function for Colorectal Endoscopic Submucosal Dissection

PubMed Central

Inada, Yutaka; Rani, Rafiz Abdul; Naito, Yuji; Azuma, Takeshi; Itoh, Yoshito

2017-01-01

Backgrounds With respect to the knife's design in colorectal endoscopic submucosal dissection (ESD), diameter, water jet function, and electric power are important because these relate to efficient dissection. In this study, we analyzed a novel, narrow ball tip-typed ESD knife with water jet function (Flush knife BT-S, diameter: 2.2 mm, length: 2000 mm, Fujifilm Co., Tokyo, Japan) compared to a regular diameter knife (Flush knife BT, diameter: 2.6 mm, length: 1800 mm). Methods In laboratory and clinical research, electric power, knife insertion time, vacuum/suction amount with knife in the endoscopic channel, and water jet function were analyzed. We used a knife 2.0 mm long for BT-S and BT knives. Results The BT-S showed faster mean knife insertion time (sec) and better vacuum amount (ml/min) compared to the BT (insertion time: 16.7 versus 21.6, p < 0.001, vacuum amount: 38.0 versus 14.0, p < 0.01). Additionally, the water jet function of the BT-S was not inferior. In 39 colorectal ESD cases in two institutions, there were mean 4.7 times (range: 1–28) of knife insertion. Suction under knife happened 59% (23/39) and suction of fluid could be done in 100%. Conclusions Our study showed that the narrow knife allows significantly faster knife insertion, better vacuum function, and effective clinical results. PMID:29081793

Single‐fraction spine SBRT end‐to‐end testing on TomoTherapy, Vero, TrueBeam, and CyberKnife treatment platforms using a novel anthropomorphic phantom

PubMed Central

Kaufman, Isaac; Powell, Rachel; Pandya, Shalini; Somnay, Archana; Bossenberger, Todd; Ramirez, Ezequiel; Reynolds, Robert; Solberg, Timothy; Burmeister, Jay

2015-01-01

Spine SBRT involves the delivery of very high doses of radiation to targets adjacent to the spinal cord and is most commonly delivered in a single fraction. Highly conformal planning and accurate delivery of such plans is imperative for successful treatment without catastrophic adverse effects. End–to‐end testing is an important practice for evaluating the entire treatment process from simulation through treatment delivery. We performed end‐to‐end testing for a set of representative spine targets planned and delivered using four different treatment planning systems (TPSs) and delivery systems to evaluate the various capabilities of each. An anthropomorphic E2E SBRT phantom was simulated and treated on each system to evaluate agreement between measured and calculated doses. The phantom accepts ion chambers in the thoracic region and radiochromic film in the lumbar region. Four representative targets were developed within each region (thoracic and lumbar) to represent different presentations of spinal metastases and planned according to RTOG 0631 constraints. Plans were created using the TomoTherapy TPS for delivery using the Hi·Art system, the iPlan TPS for delivery using the Vero system, the Eclipse TPS for delivery using the TrueBeam system in both flattened and flattening filter free (FFF), and the MultiPlan TPS for delivery using the CyberKnife system. Delivered doses were measured using a 0.007 cm3 ion chamber in the thoracic region and EBT3 GAFCHROMIC film in the lumbar region. Films were scanned and analyzed using an Epson Expression 10000XL flatbed scanner in conjunction with FilmQAPro2013. All treatment platforms met all dose constraints required by RTOG 0631. Ion chamber measurements in the thoracic targets delivered an overall average difference of 1.5%. Specifically, measurements agreed with the TPS to within 2.2%, 3.2%, 1.4%, 3.1%, and 3.0% for all three measureable cases on TomoTherapy, Vero, TrueBeam (FFF), TrueBeam (flattened), and CyberKnife, respectively. Film measurements for the lumbar targets resulted in average global gamma index passing rates of 100% at 3%/3 mm, 96.9% at 2%/2 mm, and 61.8% at 1%/1 mm, with a 10% minimum threshold for all plans on all platforms. Local gamma analysis was also performed with similar results. While gamma passing rates were consistently accurate across all platforms through 2%/2 mm, treatment beam‐on delivery times varied greatly between each platform with TrueBeam FFF being shortest, averaging 4.4 min, TrueBeam using flattened beam at 9.5 min, TomoTherapy at 30.5 min, Vero at 19 min, and CyberKnife at 46.0 min. In spite of the complexity of the representative targets and their proximity to the spinal cord, all treatment platforms were able to create plans meeting all RTOG 0631 dose constraints and produced exceptional agreement between calculated and measured doses. However, there were differences in the plan characteristics and significant differences in the beam‐on delivery time between platforms. Thus, clinical judgment is required for each particular case to determine most appropriate treatment planning/delivery platform. PACS number: 87.53.Ly PMID:25679169

The journey from proton to gamma knife.

PubMed

Ganz, Jeremy C

2014-01-01

It was generally accepted by the early 1960s that proton beam radiosurgery was too complex and impractical. The need was seen for a new machine. The beam design had to be as good as a proton beam. It was also decided that a static design was preferable even if the evolution of that notion is no longer clear. Complex collimators were designed that using sources of cobalt-60 could produce beams with characteristics adequately close to those of proton beams. The geometry of the machine was determined including the distance of the sources from the patient the optimal distance between the sources. The first gamma unit was built with private money with no contribution from the Swedish state, which nonetheless required detailed design information in order to ensure radiation safety. This original machine was built with rectangular collimators to produce lesions for thalamotomy for functional work. However, with the introduction of dopamine analogs, this indication virtually disappeared overnight.

Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study

PubMed Central

Yellapu, Nanda Kumar; Kandlapalli, Kalpana; Valasani, Koteswara Rao; Sarma, P. V. G. K.; Matcha, Bhaskar

2013-01-01

Glucokinase (GK) is the predominant hexokinase that acts as glucose sensor and catalyses the formation of Glucose-6-phosphate. The mutations in GK gene influence the affinity for glucose and lead to altered glucose levels in blood causing maturity onset diabetes of the young type 2 (MODY2) condition, which is one of the prominent reasons of type 2 diabetic condition. In view of the importance of mutated GK resulting in hyperglycemic condition, in the present study, molecular dynamics simulations were carried out in intact and 256 E-K mutated GK structures and their energy values and conformational variations were correlated. Energy variations were observed in mutated GK (3500 Kcal/mol) structure with respect to intact GK (5000 Kcal/mol), and it showed increased γ-turns, decreased β-turns, and more helix-helix interactions that affected substrate binding region where its volume increased from 1089.152 Å2 to 1246.353 Å2. Molecular docking study revealed variation in docking scores (intact = −12.199 and mutated = −8.383) and binding mode of glucose in the active site of mutated GK where the involvement of A53, S54, K56, K256, D262 and Q286 has resulted in poor glucose binding which probably explains the loss of catalytic activity and the consequent prevailing of high glucose levels in MODY2 condition. PMID:23476789

Zidovudine Induces Downregulation of Mitochondrial Deoxynucleoside Kinases: Implications for Mitochondrial Toxicity of Antiviral Nucleoside Analogs

PubMed Central

Sun, Ren; Eriksson, Staffan

2014-01-01

Mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) catalyze the initial phosphorylation of deoxynucleosides in the synthesis of the DNA precursors required for mitochondrial DNA (mtDNA) replication and are essential for mitochondrial function. Antiviral nucleosides are known to cause toxic mitochondrial side effects. Here, we examined the effects of 3′-azido-2′,3′-dideoxythymidine (AZT) (zidovudine) on mitochondrial TK2 and dGK levels and found that AZT treatment led to downregulation of mitochondrial TK2 and dGK in U2OS cells, whereas cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) levels were not affected. The AZT effects on mitochondrial TK2 and dGK were similar to those of oxidants (e.g., hydrogen peroxide); therefore, we examined the oxidative effects of AZT. We found a modest increase in cellular reactive oxygen species (ROS) levels in the AZT-treated cells. The addition of uridine to AZT-treated cells reduced ROS levels and protein oxidation and prevented the degradation of mitochondrial TK2 and dGK. In organello studies indicated that the degradation of mitochondrial TK2 and dGK is a mitochondrial event. These results suggest that downregulation of mitochondrial TK2 and dGK may lead to decreased mitochondrial DNA precursor pools and eventually mtDNA depletion, which has significant implications for the regulation of mitochondrial nucleotide biosynthesis and for antiviral therapy using nucleoside analogs. PMID:25182642

Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

PubMed

Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

1994-11-08

Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosphoglycan (IPG) mediator, prepared from beef liver, bypassed this defect and comparably activated G3PAT in cell-free adipocyte preparations of both diabetic GK and control rats. A myo-inositol-containing IPG mediator did not activate G3PAT. Relative to control adipocytes, labeling of GPI by [3H]glucosamine was diminished by 50% and insulin failed to stimulate GPI hydrolysis in GK adipocytes. In contrast to GPI-dependent G3PAT activation, insulin-stimulated hexose transport was intact in adipocytes and soleus and gastrocnemius muscles of the GK rat, as was insulin-induced activation of mitogen-activated protein kinase and protein kinase C. We conclude that (i) chiro-inositol-containing IPG mediator activates G3PAT during insulin action, (ii) diabetic GK rats have a defect in synthesizing or releasing functional chiro-inositol-containing IPG, and (iii) defective IPG-regulated intracellular glucose metabolism contributes importantly to insulin resistance in diabetic GK rats.

Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats.

PubMed

Yoshinari, Orie; Sato, Hideyo; Igarashi, Kiharu

2009-05-01

The effects of a pumpkin paste concentrate and its components on oral glucose tolerance and serum lipid levels were determined in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. In the oral glucose tolerance test, the pumpkin paste concentrate-fed group maintained a lower glucose level than the control group between 15 and 60 min. The compounds considered to be effective in improving glucose tolerance and contained in the methanol extract of the pumpkin in relatively abundant amounts were isolated and identified as trigonelline (TRG) and nicotinic acid (NA).Feeding a diet containing TRG and NA respectively improved and tended to improve glucose tolerance. The insulin level increased after 15 min in the TRG-fed GK rats and then gradually decreased over the next 120 min. In contrast, a gradual increase was seen in the insulin level over 120 min in the control GK rats not fed with TRG, suggesting that TRG could improve the insulin resistance. The serum and liver triglyceride (TG) levels in the TRG- and NA-fed GK rats were lower than those in the control GK rats. Lower activity of liver fatty acid synthase (FAS), and higher activity of liver carnitine palmitoyl transferase (CPT) and glucokinase (GLK) in the TRG- and NA-fed GK rats than in the control GK rats were observed. This suggests that the regulation of these enzyme activities by TRG and NA was closely related to the suppression of both TG accumulation and the progression of diabetes.

Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

PubMed Central

Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

1994-01-01

Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosphoglycan (IPG) mediator, prepared from beef liver, bypassed this defect and comparably activated G3PAT in cell-free adipocyte preparations of both diabetic GK and control rats. A myo-inositol-containing IPG mediator did not activate G3PAT. Relative to control adipocytes, labeling of GPI by [3H]glucosamine was diminished by 50% and insulin failed to stimulate GPI hydrolysis in GK adipocytes. In contrast to GPI-dependent G3PAT activation, insulin-stimulated hexose transport was intact in adipocytes and soleus and gastrocnemius muscles of the GK rat, as was insulin-induced activation of mitogen-activated protein kinase and protein kinase C. We conclude that (i) chiro-inositol-containing IPG mediator activates G3PAT during insulin action, (ii) diabetic GK rats have a defect in synthesizing or releasing functional chiro-inositol-containing IPG, and (iii) defective IPG-regulated intracellular glucose metabolism contributes importantly to insulin resistance in diabetic GK rats. PMID:7972005

A new prostaglandin E1 analogue (TFC-612) improves the reduction in motor nerve conduction velocity in spontaneously diabetic GK (Goto-Kakizaki) rats.

PubMed

Suzuki, K; Saito, N; Sakata, Y; Toyota, T; Goto, Y

1990-11-01

A new prostaglandin E1 analogue, TFC-612, was given orally to 2 month-old spontaneously diabetic GK (Goto-Kakizaki) rats for 3 months to ascertain its effects on reduced motor nerve conduction velocity (MCV). A high dose of this compound (0.3 mg/kg body weight) significantly restored MCV after 2 and 3 months of administration, although the low dose (0.03 mg/kg body weight) did not. In addition, 1 month administration of TFC-612 significantly improved the reduced MCV in aged (5 month-old) GK rats only in the high dose group (0.3 mg/kg body weight), but not in the low dose group (0.03 mg/kg body weight). Although TFC-612 significantly suppressed sorbitol accumulation in the sciatic nerves of GK rats in a dose dependent manner after 3 months administration, this suppression was not observed after either 2 months administration to 2 month-old GK rats or after 1 month administration to 5 month-old GK rats. Fasting blood glucose levels of all GK rats remained high throughout the experiments, regardless of TFC-612 administration. TFC-612's improvement on reduced motor nerve conduction velocity was related partly to suppression of sorbitol accumulation, but other factors, including microcirculation, may contribute significantly to this effect. These results suggest that TFC-612 may be beneficial in the treatment of diabetic nerve impairment.

Progressive alveolar echinococcosis after discontinuation of anthelmintic therapy

PubMed Central

2013-01-01

We report a case of a female patient with alveolar echinococcosis (AE) who presented with progressive pulmonary and hepatic lesions and had a fatal outcome. AE affecting the liver, the lungs and the brain had been diagnosed 20 years ago and treated successfully with albendazole and stereotactic gamma knife therapy. Due to severe hair loss albendazole was stopped 14 years before presentation. Lesions had remained stable in imaging studies for at least 11 years, but then had started to progress. Lifelong anthelmintic maintenance therapy and regular follow-up may therefore be crucial in order to prevent such a dramatic clinical course. PMID:24289745

Asymptomatic solitary cerebral metastasis from papillary carcinoma thyroid: 131I SPECT/CT for accurate staging.

PubMed

Jain, Tarun Kumar; Karunanithi, Sellam; Sharma, Punit; Vijay, Maneesh Kumar; Ballal, Sanjana; Bal, Chandrasekhar

2014-11-01

Isolated asymptomatic brain metastasis in papillary carcinoma thyroid (PCT) is extremely rare. We here present such a case of a 48-year-old woman with PCT. SPECT/CT localized the 131I radiotracer concentration seen on whole-body scan in this patient to the right posterior parietal cortex, suggesting brain metastasis. Contrast-enhanced MRI and 18F-FDG PET/CT confirmed the diagnosis and the patient was taken for gamma-knife radiosurgery. 131I SPECT/CT in this case accurately restaged the patient by detecting asymptomatic isolated brain metastasis and correctly directed the management strategy.

Gamma Knife surgery for intracranial chordoma and chondrosarcoma: radiosurgical perspectives and treatment outcomes.

PubMed

Kim, Ji Hee; Jung, Hyun Ho; Chang, Jong Hee; Chang, Jin Woo; Park, Yong Gou; Chang, Won Seok

2014-12-01

Intracranial chordomas and chondrosarcomas are histologically low-grade, locally invasive tumors that are reported to be similar in terms of anatomical location, clinical presentation, and radiological findings but different in terms of behavior and outcomes. The purpose of this study was to investigate and compare clinical outcomes after Gamma Knife surgery (GKS) for the treatment of intracranial chordoma and chondrosarcoma. The authors conducted a retrospective review of the results of radiosurgical treatment of intracranial chordomas and chondrosarcomas. They enrolled patients who had undergone GKS for intracranial chordoma or chondrosarcoma at the Yonsei Gamma Knife Center, Yonsei University College of Medicine, from October 2000 through June 2007. Analyses included only patients for whom the disease was pathologically diagnosed before GKS and for whom more than 5 years of follow-up data after GKS were available. Rates of progression-free survival and overall survival were analyzed and compared according to tumor pathology. Moreover, the association between tumor control and the margin radiation dose to the tumor was analyzed, and the rate of tumor volume change after GKS was quantified. A total of 10 patients were enrolled in this study. Of these, 5 patients underwent a total of 8 sessions of GKS for chordoma, and the other 5 patients underwent a total of 7 sessions of GKS for chondrosarcoma. The 2- and 5-year progression-free survival rates for patients in the chordoma group were 70% and 35%, respectively, and rates for patients in the chondrosarcoma group were 100% and 80%, respectively (log-rank test, p = 0.04). The 2- and 5-year overall survival rates after GKS for patients in the chordoma group were 87.5% and 72.9%, respectively, and rates for patients in the chondrosarcoma group were 100% and 100%, respectively (log-rank test, p = 0.03). The mean rates of tumor volume change 2 years after radiosurgery were 79.64% and 39.91% for chordoma and chondrosarcoma, respectively (p = 0.05). No tumor progression was observed when margin doses greater than 16 Gy for chordoma and 14 Gy for chondrosarcoma were prescribed. Outcomes after GKS were more favorable for patients with chondrosarcoma than for those with chordoma. The data also indicated that at 2 years after GKS, the rate of volume change is significantly higher for chordomas than for chondrosarcomas. The authors conclude that radiosurgery with a margin dose of more than 16 Gy for chordomas and more than 14 Gy for chondrosarcomas seems to enhance local tumor control with relatively few complications. Further studies are needed to determine the optimal dose of GKS for patients with intracranial chordoma or chondrosarcoma.

Evaluation of fractionated radiotherapy and gamma knife radiosurgery in cavernous sinus meningiomas: treatment strategy.

PubMed

Metellus, Philipe; Regis, Jean; Muracciole, Xavier; Fuentes, Stephane; Dufour, Henry; Nanni, Isabelle; Chinot, Oliver; Martin, Pierre-Marie; Grisoli, Francois

2005-11-01

To investigate the respective role of fractionated radiotherapy (FR) and gamma knife stereotactic (GKS) radiosurgery in cavernous sinus meningioma (CSM) treatment. The authors report the long-term follow-up of two populations of patients harboring CSMs treated either by FR (Group I, 38 patients) or GKS radiosurgery (Group II, 36 patients). There were 31 females with a mean age of 53 years in Group I and 29 females with a mean age of 51.2 years in Group II. In 20 patients (Group I) and 13 patients (Group II), FR and GKS radiosurgery were performed as an adjuvant treatment. In 18 patients (Group I) and in 23 patients (Group II), FR and GKS radiosurgery were performed as first line treatment. In our early experience with GKS radiosurgery (1992, date of gamma knife availability in the department), patients with tumors greater than 3 cm, showing close relationship with the optic apparatus (<3 mm) or skull base dural spreading, were treated by FR. Secondarily, with the advent of new devices and our growing experience, these criteria have evolved. The median follow-up period was 88.6 months (range, 42-168 mo) for Group I and 63.6 months (range, 48-92 mo) for Group II. According to Sekhar's classification, 26 (68.4%) patients were Grade III to IV in Group I and 10 (27.8%) patients in Group II (P < 0.05); 23 (60.5%) patients had extensive lesions in Group I and 7 (19.4%) patients in Group II (P < 0.05). Mean tumor volume was 13.5 cm in Group I and 5.2 cm in Group II (P < 0.05). Actuarial progression-free survival was 94.7% and 94.4% in Group I and II, respectively. Clinically, improvement was seen for 24 (63.2%) patients in Group I and for 21 (53.8%) patients in Group II (P > 0.05). Radiologically, 11 (29%, Group I) patients and 19 (Group II, 52.7%) patients showed tumor shrinkage (P = 0.04). Transient morbidity was 10.5% in Group I and 2.8% in Group II. Permanent morbidity was 2.6% in Group I and 0% in Group II. FR and GKS radiosurgery are safe and efficient techniques in treatment of CSMs, affording comparable satisfactory long-term tumor control. However, GKS radiosurgery provides better radiological response, is far more convenient, and fits into most patients lives much better than FR. Therefore, in the authors' opinion, GKS radiosurgery should be advocated in first intention for patients with CSMs, whereas conventional radiotherapy should be reserved for cases that are not amenable to this technique, thus making these two therapeutic modalities not alternative but complementary tools in CS meningioma treatment strategy.

Long-term safety and efficacy of Gamma Knife surgery in classical trigeminal neuralgia: a 497-patient historical cohort study.

PubMed

Régis, Jean; Tuleasca, Constantin; Resseguier, Noémie; Carron, Romain; Donnet, Anne; Gaudart, Jean; Levivier, Marc

2016-04-01

Gamma Knife surgery (GKS) is one of the surgical alternatives for the treatment of drug-resistant trigeminal neuralgia (TN). This study aims to evaluate the safety and efficacy of GKS in a large population of patients with TN with very long-term clinical follow-up. Between July 1992 and November 2010, 737 patients presenting with TN were treated using GKS. Data were collected prospectively and were further retrospectively evaluated at Timone University Hospital. The frequency and severity of pain, as well as trigeminal nerve function, were evaluated before GKS and regularly thereafter. Radiosurgery using the Gamma Knife (model B, C, 4C, or Perfexion) was performed with the help of both MR and CT targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4-14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90 Gy) was prescribed. The safety and efficacy are reported for 497 patients with medically refractory classical TN who were never previously treated by GKS and had a follow-up of at least 1 year. The median age in this series was 68.3 years (range 28.1-93.2 years). The median follow-up period was 43.8 months (range 12-174.4 months). Overall, 456 patients (91.75%) were initially pain free in a median time of 10 days (range 1-180 days). Their actuarial probabilities of remaining pain free without medication at 3, 5, 7, and 10 years were 71.8%, 64.9%, 59.7%, and 45.3%, respectively. One hundred fifty-seven patients (34.4%) who were initially pain free experienced at least 1 recurrence, with a median delay of onset of 24 months (range 0.6-150.1 months). However, the actuarial rate of maintaining pain relief without further surgery was 67.8% at 10 years. The hypesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1%, but remained stable until 14 years with a median delay of onset of 12 months (range 1-65 months). Very bothersome facial hypesthesia was reported in only 3 patients (0.6%). Retrogasserian GKS proved to be safe and effective in the long term and in a very large number of patients. Even if the probability of long-lasting effects may be modest compared with microvascular decompression, the rarity of complications prompts discussion of using GKS as the pragmatic surgical first- or second-intention alternative for classical TN. However, a randomized trial, or at least a case-matched control study, would be required to compare with microvascular decompression.

Magnetic resonance imaging characteristics and the prediction of outcome of vestibular schwannomas following Gamma Knife radiosurgery.

PubMed

Wu, Chih-Chun; Guo, Wan-Yuo; Chung, Wen-Yuh; Wu, Hisu-Mei; Lin, Chung-Jung; Lee, Cheng-Chia; Liu, Kang-Du; Yang, Huai-Che

2017-12-01

OBJECTIVE Gamma Knife surgery (GKS) is a promising treatment modality for patients with vestibular schwannomas (VSs), but a small percentage of patients have persistent postradiosurgical tumor growth. The aim of this study was to determine the clinical and quantitative MRI features of VS as predictors of long-term tumor control after GKS. METHODS The authors performed a retrospective study of all patients with VS treated with GKS using the Leksell Gamma Knife Unit between 2005 and 2013 at their institution. A total of 187 patients who had a minimum of 24 months of clinical and radiological assessment after radiosurgery were included in this study. Those who underwent a craniotomy with tumor removal before and after GKS were excluded. Study patients comprised 85 (45.5%) males and 102 (54.5%) females, with a median age of 52.2 years (range 20.4-82.3 years). Tumor volumes, enhancing patterns, and apparent diffusion coefficient (ADC) values were measured by region of interest (ROI) analysis of the whole tumor by serial MRI before and after GKS. RESULTS The median follow-up period was 60.8 months (range 24-128.9 months), and the median treated tumor volume was 3.54 cm 3 (0.1-16.2 cm 3 ). At last follow-up, imaging studies indicated that 150 tumors (80.2%) showed decreased tumor volume, 20 (10.7%) had stabilized, and 17 (9.1%) continued to grow following radiosurgery. The postradiosurgical outcome was not significantly correlated with pretreatment volumes or postradiosurgical enhancing patterns. Tumors that showed regression within the initial 12 months following radiosurgery were more likely to have a larger volume reduction ratio at last follow-up than those that did not (volume reduction ratio 55% vs 23.6%, respectively; p < 0.001). Compared with solid VSs, cystic VSs were more likely to regress or stabilize in the initial postradiosurgical 6-12-month period and during extended follow-up. Cystic VSs exhibited a greater volume reduction ratio at last follow-up (cystic vs solid: 67.6% ± 24.1% vs 31.8% ± 51.9%; p < 0.001). The mean preradiosurgical maximum ADC (ADC max ) values of all VSs were significantly higher for those with tumor regression or stabilization at last follow-up compared with those with progression (2.391 vs 1.826 × 10 -3 mm 2 /sec; p = 0.010). CONCLUSIONS Loss of central enhancement after radiosurgery was a common phenomenon, but it did not correlate with tumor volume outcome. Preradiosurgical MRI features including cystic components and ADC max values can be helpful as predictors of treatment outcome.

Gamma Knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients.

PubMed

Boari, Nicola; Bailo, Michele; Gagliardi, Filippo; Franzin, Alberto; Gemma, Marco; del Vecchio, Antonella; Bolognesi, Angelo; Picozzi, Piero; Mortini, Pietro

2014-12-01

Since the 1990 s, Gamma Knife radiosurgery (GKRS) has become the first-line treatment option for small- to medium-size vestibular schwannomas (VSs), especially in patients without mass effect-related symptoms and with functional hearing. The aim of this study was to assess the safety and efficacy of GKRS, in terms of tumor control, hearing preservation, and complications, in a series of 379 consecutive patients treated for VS. Of 523 patients treated at the authors' institution for VS between 2001 and 2010, the authors included 379 who underwent GKRS as the primary treatment. These patients were not affected by Type 2 neurofibromatosis and had clinical follow-up of at least 36 months. Clinical follow-up (mean and median 75.7 and 69.5 months, respectively) was performed for all patients, whereas audiometric and quantitative radiological follow-up examinations were obtained for only 153 and 219 patients, respectively. The patients' ages ranged from 23 to 85 years (mean 59 years). The mean tumor volume was 1.94 ± 2.2 cm(3) (median 1.2 cm(3), range 0.013-14.3 cm(3)), and the median margin dose was 13 Gy (range 11-15 Gy). Parameters considered as determinants of the clinical outcome were long-term tumor control, hearing preservation, and complications. A statistical analysis was performed to correlate clinical outcomes with the radiological features of the tumor, dose-planning parameters, and patient characteristics. Control of the tumor with GKRS was achieved in 97.1% of the patients. In 82.7% of the patients, the tumor volume had decreased at the last follow-up, with a mean relative reduction of 34.1%. The rate of complications was very low, with most consisting of a transient worsening of preexisting symptoms. Patients who had vertigo, balance disorders, or facial or trigeminal impairment usually experienced a complete or at least significant symptom relief after treatment. However, no significant improvement was observed in patients previously reporting tinnitus. The overall rate of preservation of functional hearing at the long-term follow-up was 49%; in patients with hearing classified as Gardner-Robertson (GR) Class I, this value was 71% and reached 93% among cases of GR Class I hearing in patients younger than 55 years. Gamma Knife radiosurgery is a safe and effective treatment for VS, achieving tumor control in 97.1% of cases and resulting in a very low morbidity rate. Younger GR Class I patients had a significantly higher probability of retaining functional hearing even at the 10-year follow-up; for this reason, the time between symptom onset, diagnosis, and treatment should be shortened to achieve better outcomes in functional hearing preservation.

Draft Genome Sequence of Acinetobacter calcoaceticus Strain GK1, a Hydrocarbon-Degrading Plant Growth-Promoting Rhizospheric Bacterium.

PubMed

Gkorezis, Panagiotis; Bottos, Eric M; Van Hamme, Jonathan D; Franzetti, Andrea; Abbamondi, Gennaro Roberto; Balseiro-Romero, Maria; Weyens, Nele; Rineau, Francois; Vangronsveld, Jaco

2015-08-13

The 3.94-Mb draft genome of Acinetobacter calcoaceticus GK1, a hydrocarbonoclastic plant growth-promoting Gram-negative rhizospheric bacterium, is presented here. Isolated at the Ford Motor Company site in Genk, Belgium, from poplar trees planted on a diesel-contaminated plume, GK1 is useful for enhancing hydrocarbon phytoremediation. Copyright © 2015 Gkorezis et al.

Alternative splicing produces transcripts coding for alpha and beta chains of a hetero-dimeric phosphagen kinase.

PubMed

Ellington, W Ross; Yamashita, Daisuke; Suzuki, Tomohiko

2004-06-09

Glycocyamine kinase (GK) catalyzes the reversible phosphorylation of glycocyamine (guanidinoacetate), a reaction central to cellular energy homeostasis in certain animals. GK is a member of the phosphagen kinase enzyme family and appears to have evolved from creatine kinase (CK) early in the evolution of multi-cellular animals. Prior work has shown that GK from the polychaete Neanthes (Nereis) diversicolor exits as a hetero-dimer in vivo and that the two polypeptide chains (termed alpha and beta) are coded for by unique transcripts. In the present study, we demonstrate that the GK from a congener Nereis virens is also hetero-dimeric and is coded for by alpha and beta transcripts, which are virtually identical to the corresponding forms in N. diversicolor. The GK gene from N. diversicolor was amplified by PCR. Sequencing of the PCR products showed that the alpha and beta chains are the result of alternative splicing of the GK primary mRNA transcript. These results also strongly suggest that this gene underwent an early tandem exon duplication event. Full-length cDNAs for N. virens GKalpha and GKbeta were individually ligated into expression vectors and the resulting constructs used to transform Escherichia coli expression hosts. Regardless of expression conditions, minimal GK activity was observed in both GKalpha and GKbeta constructs. Inclusion bodies for both were harvested, unfolded in urea and alpha chains, beta chains and mixtures of alpha and beta chains were refolded by sequential dialysis. Only modest amounts of GK activity were observed when alpha and beta were refolded individually. In contrast, when refolded the alpha and beta mixture yielded highly active hetero-dimers, as validated by size exclusion chromatography, electrophoresis and mass spectrometry, with a specific activity comparable to that of natural GK. The above evidence suggests that there is a preference for hetero-dimer formation in the GKs from these two polychaetes. The evolution of the alternate splicing and an additional exon in these GKs, producing alpha and beta transcripts, can be viewed as a possible compensation for a mutation(s) in the original gene, which most likely coded for a homo-dimeric protein.

Prompt Gamma Imaging for In Vivo Range Verification of Pencil Beam Scanning Proton Therapy.

PubMed

Xie, Yunhe; Bentefour, El Hassane; Janssens, Guillaume; Smeets, Julien; Vander Stappen, François; Hotoiu, Lucian; Yin, Lingshu; Dolney, Derek; Avery, Stephen; O'Grady, Fionnbarr; Prieels, Damien; McDonough, James; Solberg, Timothy D; Lustig, Robert A; Lin, Alexander; Teo, Boon-Keng K

2017-09-01

To report the first clinical results and value assessment of prompt gamma imaging for in vivo proton range verification in pencil beam scanning mode. A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan. In 6 treatment fractions recorded over 3 weeks, the mean (± standard deviation) range shifts aggregated over all spots in 9 energy layers were -0.8 ± 1.3 mm for the lateral field, 1.7 ± 0.7 mm for the right-superior-oblique field, and -0.4 ± 0.9 mm for the vertex field. This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for in vivo proton range verification and quantification of range uncertainties. Copyright © 2017 Elsevier Inc. All rights reserved.

Feasibility Study on Applying Radiophotoluminescent Glass Dosimeters for CyberKnife SRS Dose Verification

PubMed Central

Hsu, Shih-Ming; Hung, Chao-Hsiung; Liao, Yi-Jen; Fu, Hsiao-Mei; Tsai, Jo-Ting

2017-01-01

CyberKnife is one of multiple modalities for stereotactic radiosurgery (SRS). Due to the nature of CyberKnife and the characteristics of SRS, dose evaluation of the CyberKnife procedure is critical. A radiophotoluminescent glass dosimeter was used to verify the dose accuracy for the CyberKnife procedure and validate a viable dose verification system for CyberKnife treatment. A radiophotoluminescent glass dosimeter, thermoluminescent dosimeter, and Kodak EDR2 film were used to measure the lateral dose profile and percent depth dose of CyberKnife. A Monte Carlo simulation for dose verification was performed using BEAMnrc to verify the measured results. This study also used a radiophotoluminescent glass dosimeter coupled with an anthropomorphic phantom to evaluate the accuracy of the dose given by CyberKnife. Measurements from the radiophotoluminescent glass dosimeter were compared with the results of a thermoluminescent dosimeter and EDR2 film, and the differences found were less than 5%. The radiophotoluminescent glass dosimeter has some advantages in terms of dose measurements over CyberKnife, such as repeatability, stability, and small effective size. These advantages make radiophotoluminescent glass dosimeters a potential candidate dosimeter for the CyberKnife procedure. This study concludes that radiophotoluminescent glass dosimeters are a promising and reliable dosimeter for CyberKnife dose verification with clinically acceptable accuracy within 5%. PMID:28046056

Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation

PubMed Central

Zhang, Yuebin; Niu, Huiyan; Li, Yan; Chu, Huiying; Shen, Hujun; Zhang, Dinglin; Li, Guohui

2015-01-01

Dramatic functional changes of enzyme usually require scores of alterations in amino acid sequence. However, in the case of guanylate kinase (GK), the functional novelty is induced by a single (S→P) mutation, leading to the functional transition of the enzyme from a phosphoryl transfer kinase into a phosphorprotein interaction domain. Here, by using molecular dynamic (MD) and metadynamics simulations, we provide a comprehensive description of the conformational transitions of the enzyme after mutating serine to proline. Our results suggest that the serine plays a crucial role in maintaining the closed conformation of wild-type GK and the GMP recognition. On the contrary, the S→P mutant exhibits a stable open conformation and loses the ability of ligand binding, which explains its functional transition from the GK enzyme to the GK domain. Furthermore, the free energy profiles (FEPs) obtained by metadymanics clearly demonstrate that the open-closed conformational transition in WT GK is positive correlated with the process of GMP binding, indicating the GMP-induced closing motion of GK enzyme, which is not observed in the mutant. In addition, the FEPs show that the S→P mutation can also leads to the mis-recognition of GMP, explaining the vanishing of catalytic activity of the mutant. PMID:25672880

Effects of the herbal medicine Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on insulin secretion and glucose tolerance in type 2 diabetic Goto-Kakizaki rats.

PubMed

Hirotani, Y; Ikeda, K; Myotoku, M

2010-04-01

Hachimi-jio-gan (HJ) is a Chinese medicine that has been widely used for the treatment of nephrotic syndromes, hypertension, and diabetes mellitus. We reported that HJ lowers plasma glucose in type 1 diabetic rats. We investigated the effects of HJ on diabetic hyperglycemia and insulin secretion in type 2 diabetic Goto-Kakizaki (GK) rats. Eight-week-old diabetic GK rats were given free access to pellets containing 1% HJ extract powder for 14 weeks. HJ consumption increased the food intake and body weight of these rats in comparison to control rats. HJ may control the body weight loss observed in GK rats. HJ also reduced hyperglycemia in diabetic GK rats, and it significantly increased insulin secretion in non-fasting GK rats over the experimental period. In oral glucose tolerance tests, HJ significantly improved the insulin response at 30 min and reduced the plasma glucose level at 60 min after glucose administration (p < 0.05). Ten weeks after administration, the plasma leptin levels significantly increased in the HJ group rats. These results demonstrate that in diabetic GK rats, HJ decreased the level of postprandial glucose via enhanced insulin secretion coupled with the regulation of food intake by leptin.

Mechanistic insight into the functional transition of the enzyme guanylate kinase induced by a single mutation.

PubMed

Zhang, Yuebin; Niu, Huiyan; Li, Yan; Chu, Huiying; Shen, Hujun; Zhang, Dinglin; Li, Guohui

2015-02-12

Dramatic functional changes of enzyme usually require scores of alterations in amino acid sequence. However, in the case of guanylate kinase (GK), the functional novelty is induced by a single (S→P) mutation, leading to the functional transition of the enzyme from a phosphoryl transfer kinase into a phosphorprotein interaction domain. Here, by using molecular dynamic (MD) and metadynamics simulations, we provide a comprehensive description of the conformational transitions of the enzyme after mutating serine to proline. Our results suggest that the serine plays a crucial role in maintaining the closed conformation of wild-type GK and the GMP recognition. On the contrary, the S→P mutant exhibits a stable open conformation and loses the ability of ligand binding, which explains its functional transition from the GK enzyme to the GK domain. Furthermore, the free energy profiles (FEPs) obtained by metadymanics clearly demonstrate that the open-closed conformational transition in WT GK is positive correlated with the process of GMP binding, indicating the GMP-induced closing motion of GK enzyme, which is not observed in the mutant. In addition, the FEPs show that the S→P mutation can also leads to the mis-recognition of GMP, explaining the vanishing of catalytic activity of the mutant.

Cyclic GMP-dependent protein kinase-I in the guinea pig cochlea.

PubMed

Tian, F; Fessenden, J D; Schacht, J

1999-05-01

Recent studies have begun to characterize the nitric oxide/cyclic GMP/protein kinase G pathway in the mammalian cochlea by demonstrating the presence of both the enzyme that produces nitric oxide (NO), nitric oxide synthase, and the NO receptor, soluble guanylate cyclase. The present study investigated protein kinase G (cyclic GMP-dependent protein kinase-I, cGK-I), the downstream enzyme of this pathway that frequently mediates its physiological effects. A commercial antibody to a human cGK-I sequence recognized a protein of appropriate molecular weight in Western blots of guinea pig aorta. Immunostaining of guinea pig aorta was consistent with the expected distribution of cGK-I. In lateral wall tissues of the cochlea, pericytes lining the blood vessels of the spiral ligament were strongly immunoreactive. In the organ of Corti, cGK-I was detected in Hensen's, Deiters', and pillar cells, but not in inner and outer hair cells. This distribution coincides with the localization of soluble guanylate cyclase activity and suggests that cGK-I mediates the effects of the NO/cyclic GMP pathway in the cochlea. It reinforces the hypothesis that the NO/cyclic GMP/cGK-I pathway is involved in regulation of cochlear blood flow and supporting cell physiology.

Astronomy Education through the NSF GK-12 Program

NASA Astrophysics Data System (ADS)

Jensen, A. G.

2004-05-01

The National Science Foundation's GK-12 program encourages graduate students in science to be active in public education at the middle school and high school levels. As a GK-12 fellow at the University of Colorado-Boulder (CU), I worked with a local 8th-grade science teacher and his students during the 2003-2004 school year. In the Boulder Valley School District, 8th-grade science covers Earth history, meteorology, astronomy, and oceanography. There are many special challenges for this school district and 8th-grade education in Colorado, including a large number of English as a second language (ESL) students and the administration of standardized tests during March, before students have completed much of the relevant material. As a GK-12 Fellow, my responsibilities included work with the Earth history Full Option Science System (FOSS) kit, guest lecturing, aid in hands-on exercises, and the creation of new activities and assignments. Astronomy activities accomplished through this program include sunspot viewing and a field trip to the Colorado Scale Model Solar System on the CU campus. The GK-12 program at CU will continue for at least two more years, possibly placing future GK-12 fellows who are astronomy grad students into classes that are astronomy- or physics-specific.

Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes.

PubMed

Jeng, J H; Ho, Y S; Chan, C P; Wang, Y J; Hahn, L J; Lei, D; Hsu, C C; Chang, M C

2000-07-01

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is associated with increased incidence of oral cancer and submucous fibrosis. In this study, areca nut (AN) extract (200-800 microg/ml) induced the prostaglandin E(2) (PGE(2)) production by 1. 4-3.4-fold and 6-keto-PGF(1 alpha) production by 1.1-1.7-fold of gingival keratinocytes (GK), respectively, following 24 h of exposure. Exposure of GK to AN extract (>400 microg/ml) led to cell retraction and intracellular vacuoles formation. At concentrations of 800 and 1200 microg/ml, AN extract induced cell death at 21-24 and 32-52% as detected by MTT assay and cellular lactate dehydrogenase release, respectively. Interestingly, AN-induced morphological changes of GK are reversible. GK can still proliferate following exposure to AN extract. Cytotoxicity of AN extract cannot be inhibited by indomethacin (1 microM) and aspirin (50 microM), indicating that prostaglandin (PG) production is not the major factor responsible for AN cytotoxicity. PGE(2) exhibited little effect on the growth of GK at concentrations ranging from 100-1000 pg/ml. Stimulating GK production of PGs by AN extract could be due to induction of cyclooxygenase-2 (COX-2) mRNA expression and protein production. These results suggest that AN ingredients are critical in the pathogenesis of oral submucous fibrosis and oral cancer via their stimulatory effects on the PGs, COX-2 production and associated tissue inflammatory responses. AN cytotoxicity to GK is not directly mediated by COX-2 stimulation and PG production.

Verification of Gyrokinetic codes: theoretical background and applications

NASA Astrophysics Data System (ADS)

Tronko, Natalia

2016-10-01

In fusion plasmas the strong magnetic field allows the fast gyro motion to be systematically removed from the description of the dynamics, resulting in a considerable model simplification and gain of computational time. Nowadays, the gyrokinetic (GK) codes play a major role in the understanding of the development and the saturation of turbulence and in the prediction of the consequent transport. We present a new and generic theoretical framework and specific numerical applications to test the validity and the domain of applicability of existing GK codes. For a sound verification process, the underlying theoretical GK model and the numerical scheme must be considered at the same time, which makes this approach pioneering. At the analytical level, the main novelty consists in using advanced mathematical tools such as variational formulation of dynamics for systematization of basic GK code's equations to access the limits of their applicability. The indirect verification of numerical scheme is proposed via the Benchmark process. In this work, specific examples of code verification are presented for two GK codes: the multi-species electromagnetic ORB5 (PIC), and the radially global version of GENE (Eulerian). The proposed methodology can be applied to any existing GK code. We establish a hierarchy of reduced GK Vlasov-Maxwell equations using the generic variational formulation. Then, we derive and include the models implemented in ORB5 and GENE inside this hierarchy. At the computational level, detailed verification of global electromagnetic test cases based on the CYCLONE are considered, including a parametric β-scan covering the transition between the ITG to KBM and the spectral properties at the nominal β value.

[Research progress of needles with knife-edge for carotid cardiac syndrome].

PubMed

Tan, Lingqiong; Zhao, Yanling

2015-04-01

According to topographic anatomy, pathogenesis and by retrieving, summarizing and analyzing literature regarding needle-knife and needles with knife-edge for carotid cardiac syndrome, it is found out that clinical misdiagnosis rate of carotid cardiac syndrome is considerably high. Needle-knife and needles with knife-edge could significantly improve the clinical symptoms of carotid cardiac syndrome, showing characteristic and advantage in treatment, but it is deficient in technique standard and efficacy criteria that should be united and authoritative. Researches regarding pathogenesis of carotid cardiac syndrome are not systematic. Clinical observation regarding long-term efficacy and relapse of needle-knife and needles with knife-edge treatment is rare. It is believed that the awareness on carotid cardiac syndrome should be increased to reduce misdiagnosis; scientific and standardized technique standard and efficacy criteria should be established; systematic and comprehensive researches regarding mechanism of needle-knife and needles with knife-edge for carotid cardiac syndrome should be launched; besides, clinical discussion regarding its long-term efficacy should start to provide a better clinical guideline.

[Design and application of silver needle-knife].

PubMed

Sun, Guodong; Shi, Bin; Zhang, Benwu; Xu, Haidong

2015-04-01

A silver needle-knife which has the dual function of silver needle and needle-knife is designed. The main components of this silver needle-knife are approximately 50% silver and approximately 50% nichrome. The silver needle-knife is composed of five parts, including needle-knife tail, spiral handle; steering handle, needle-knife body and needle-knife edge. It converges the advantages of needle-knife and silver needle, which can cut loose of diseased tissue and peel adhesion of lesions, but also be heated with moxa cone and thermal therapeutic instrument, and connect with electroacupuncture apparatus. It has the function of warming channel and removing coldness, dispelling wind and eliminating dampness, resolving spasm and relieving pain, dredging the channel and so on. Due to the spiral handle and the steering handle, the operation is easier, which reduces the blindness of cutting and increase the safety. It is mainly used for soft tissue injury, rheumatism and rheumatoid arthritis, as well as degenerative diseases of spine and joint, and it has obvious efficacy on some internal medical diseases.

Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

PubMed Central

García-Herrero, Carmen-María; Rubio-Cabezas, Oscar; Azriel, Sharona; Gutierrez-Nogués, Angel; Aragonés, Angel; Vincent, Olivier; Campos-Barros, Angel; Argente, Jesús; Navas, María-Angeles

2012-01-01

Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing. PMID:22291974

ImmunoPET Imaging of Murine CD4+ T Cells Using Anti-CD4 Cys-Diabody: Effects of Protein Dose on T Cell Function and Imaging.

PubMed

Freise, Amanda C; Zettlitz, Kirstin A; Salazar, Felix B; Lu, Xiang; Tavaré, Richard; Wu, Anna M

2017-08-01

Molecular imaging of CD4 + T cells throughout the body has implications for monitoring autoimmune disease and immunotherapy of cancer. Given the key role of these cells in regulating immunity, it is important to develop a biologically inert probe. GK1.5 cys-diabody (cDb), a previously developed anti-mouse CD4 antibody fragment, was tested at different doses to assess its effects on positron emission tomography (PET) imaging and CD4 + T cell viability, proliferation, CD4 expression, and function. The effect of protein dose on image contrast (lymphoid tissue-to-muscle ratio) was assessed by administering different amounts of 89 Zr-labeled GK1.5 cDb to mice followed by PET imaging and ex vivo biodistribution analysis. To assess impact of GK1.5 cDb on T cell biology, GK1.5 cDb was incubated with T cells in vitro or administered intravenously to C57BL/6 mice at multiple protein doses. CD4 expression and T cell proliferation were analyzed with flow cytometry and cytokines were assayed. For immunoPET imaging, the lowest protein dose of 2 μg of 89 Zr-labeled GK1.5 cDb resulted in significantly higher % injected dose/g in inguinal lymph nodes (ILN) and spleen compared to the 12-μg protein dose. In vivo administration of GK1.5 cDb at the high dose of 40 μg caused a transient decrease in CD4 expression in spleen, blood, lymph nodes, and thymus, which recovered within 3 days postinjection; this effect was reduced, although not abrogated, when 2 μg was administered. Proliferation was inhibited in vivo in ILN but not the spleen by injection of 40 μg GK1.5 cDb. Concentrations of GK1.5 cDb in excess of 25 nM significantly inhibited CD4 + T cell proliferation and interferon-γ production in vitro. Overall, using low-dose GK1.5 cDb minimized biological effects on CD4 + T cells. Low-dose GK1.5 cDb yields high-contrast immunoPET images with minimal effects on T cell biology in vitro and in vivo and may be a useful tool for investigating CD4 + T cells in the context of preclinical disease models. Future approaches to minimizing biological effects may include the creation of monovalent fragments or selecting anti-CD4 antibodies which target alternative epitopes.

Reciprocal Education Experiences In Two GK-12 Programs: Teachers Learning And Students Teaching In Diverse Settings

NASA Astrophysics Data System (ADS)

Mayo, M.; Williams, C.; Rodriguez, T.; Greely, T.; Pyrtle, A. J.; Rivera-Rentas, A. L.; Vilches, M.

2004-12-01

The National Science Foundation's Graduate Teaching Fellows in K-12 Education (GK-12) Program has enabled science, technology, engineering and mathematics (STEM) graduate schools across the country to become more active in local area K-12 schools. An overview of a graduate student's experiences, insights gained and lessons learned as a Fellow in the 2003-2004 Universidad Metropolitana's (UMET) environmental science and the 2004-2005 University of South Florida's (USF) ocean science GK-12 Programs is presented. The major goals of the 2003-2004 UMET GK-12 Program were 1) to enrich environmental science teaching and learning via a thematic approach in eight local public schools and 2) to provide UMET graduate students with exposure to teaching methodologies and practical teaching experience. Utilizing examples from local environments in and nearby Carolina, Puerto Rico to teach key science principles at Escuela de la Comunidad Juana Rodriguez Mundo provided numerous opportunities to relate science topics to students' daily life experiences. By 2004, the UMET GK-12 Program had successfully engaged the entire student body (primarily comprised of bilingual minority kindergarten to sixth graders), teachers and school administrators in environment-focused teaching and learning activities. Examples of such activities include tree planting projects to minimize local erosion, conducting a science fair for the first time in many years, and numerous opportunities to experience what "real scientists do" while conducting environmental science investigations. During the 2004-2005 academic year, skills, insights and lessons learned as a UMET GK-12 Fellow are being further enhanced through participation in the USF GK-12 OCEANS Program. The overall objectives of the 2004-2005 USF GK-12 OCEANS assignment at Madeira Beach Elementary School in Saint Petersburg, Florida are to 1) engage students from various ethnic backgrounds and cultures in hands-on science activities, 2) enhance the school's third grade ocean science education curriculum, and 3) foster dialog between students at Madeira Beach Elementary School and Escuela de la Comunidad Juana Rodriguez Mundo, via exchange of pictures, video recordings, letters and emails related to environment-focused learning activities being undertaken at the two schools. In addition to these objectives, during the 2004-2005 academic year several ocean science-focused activities, the majority of which were adapted and/or identified from either the UMET GK-12 or USF OCEAN GK-12 Programs, will be utilized to further stimulate Madeira Beach Elementary School third graders' critical thinking skills. Examples of such activities, including hands-on exercises, case studies, games and field trips are highlighted in this presentation.

Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Haksoo; Welford, Scott; Fabien, Jeffrey

2014-02-15

Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, withmore » radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate of 99% was measured in areas of above 40% of the prescription dose. The final inverse treatment plan was comprised of 43 beams ranging from 5 to 12.5 mm in diameter (2.5 mm size increments are available up to 15 mm in diameter collimation). Using the Xsight Spine Tracking module, the CyberKnife system could not reliably identify and track the tiny mouse spine; however, the CyberKnife system could identify and track the fiducial markers on the 3D mold.In vivo positional accuracy analysis using the 3D mold generated a mean error of 1.41 mm ± 0.73 mm when fiducial markers were used for position tracking. Analysis of the dissected brain confirmed the ability to target the correct brain volume. Conclusions: With the use of a stereotactic body mold with fiducial markers, microCT imaging, and resolution down-sampling, the CyberKnife system can successfully perform small-animal radiotherapy studies.« less

Long-term outcome of gamma knife radiosurgery for metastatic brain tumors originating from lung cancer

PubMed Central

Bir, Shyamal C.; Ambekar, Sudheer; Bollam, Papireddy; Nanda, Anil

2014-01-01

Background: Gamma knife radiosurgery (GKRS) has emerged as an important treatment option for metastasis brain tumors (MBTs). However, the long-term outcome of GKRS on MBTs originating from lung carcinoma is not well understood. The treatment of MBTs derived from lung cancer with GKRS at our institution is reviewed. Methods: We performed a retrospective review (2000-2013) of 173 patients with MBTs from lung cancer who received GKRS. Out of 173 patients, 38 patients had recurrent tumors after microsurgical resection and whole brain radiotherapy (WBT). Results: GKRS in MBTs metastasized from lung carcinoma showed significant variations in tumor growth control (decreased in 79 [45.7%] patients, arrested growth in 54 [31.2%] patients, and increased tumor size in 40 [23.1%] patients). The median survival in the study population was 14 months. Overall survival after 3 years was 25%, whereas progression-free survival after 3 years was 45%. The predictive factors for improving survival in the patients with MBTs were recursive partitioning analysis (RPA) class I (P = 0.005), absence of hydrocephalus (P = 0.001), Karnofsky performance scale (KPS) >70 (P = 0.007), age ≤65 (P = 0.041), tumor size ≤3 cm (P = 0.023), controlled primary tumor (P = 0.049), and single number of MBTS (P = 0.044). Conclusion: Long-term follow-up revealed that GKRS offers a high rate of tumor control and good overall survival period in both new and recurrent patients with MBTs originating from lung carcinoma. Thus, GKRS is an effective treatment option for new patients with MBTs from lung cancer, as well as an adjuvant therapy in patients with recurrent MBTs derived from lung cancer. PMID:25289169

Recent advances in molecular biology and treatment strategies for intracranial germ cell tumors.

PubMed

Huang, Xiang; Zhang, Rong; Mao, Ying; Zhou, Liang-Fu; Zhang, Chao

2016-08-01

Intracranial germ cell tumors (IGCTs) are a group of rare pediatric brain tumors which include various subtypes. The current understanding of the etiology of the tumors and their optimal management strategies remain controversial. The data on IGCTs were collected from articles published in the past 20 years, and the origin and etiology of IGCTs at molecular level as well as the relative roles of varied treatment strategies in different prognosis groups according to Matsutani's classification were reviewed. Recent cellular and molecular evidence suggests that IGCTs may arise from the transformation of endogenous brain cells; and findings in the molecular characterization of IGCTs suggest roles of CCND2, RB1, and PRDM14 in the pathogenesis of IGCTs and identify the KIT/RAS and AKT1/mTOR pathways as potential therapeutic targets in future. According to Matsutani's classification of IGCTs, the good prognosis group includes both germinomas and mature teratomas. For germinomas, both radiation alone and reduced-dose radiotherapy in combination with adjuvant chemotherapy are effective, while complete surgical excision is recommended for mature teratomas. In the intermediate prognosis group, immature teratoma has been successfully treated with gamma knife surgery. However, for intermediate prognosis IGCTs other than immature teratomas, gross total resection with adjuvant chemotherapy and radiotherapy or gamma knife surgery may be necessary to achieve cure. In the poor prognosis group, survival outcomes are unsatisfactory, and complete surgical resection combined with more intensive chemotherapy and radiotherapy remains the best available treatment option at this time. IGCTs should be strictly classified according to their pathological categories before administering pathology-specific treatments. Although open microsurgical excision is the traditional surgical strategy for IGCTs, recent publications also support the role of endoscopic surgical options for pineal region IGCTs.

Stereotactic radiosurgery for vestibular schwannoma: International Stereotactic Radiosurgery Society (ISRS) Practice Guideline.

PubMed

Tsao, May N; Sahgal, Arjun; Xu, Wei; De Salles, Antonio; Hayashi, Motohiro; Levivier, Marc; Ma, Lijun; Martinez, Roberto; Régis, Jean; Ryu, Sam; Slotman, Ben J; Paddick, Ian

2017-01-01

The aim of this systematic review was to develop International Stereotactic Radiosurgery Society (ISRS) consensus guideline statements for vestibular schwannoma. A systematic review of the literature was performed up to April 2015. A total of 55 full-text articles were included in the analysis. All studies were retrospective, except for 2 prospective quality of life studies. Five-year tumour control rates with Gamma Knife radiosurgery (RS), single fraction linac RS, or fractionated (either hypofractionated or conventional fractionation) stereotactic radiation therapy (FSRT) were similar at 81-100%. The single fraction RS series (linac or Gamma Knife) with tumour marginal doses between 12 and 14 Gy revealed 5-year tumour control rates of 90-99%, hearing preservation rates of 41-79%, facial nerve preservation rates of 95-100% and trigeminal preservation rates of 79-99%.There were 6 non-randomized studies comparing single fraction RS versus FSRT. There was no statistically significant difference in tumour control; HR=1.66 (95% CI 0.81, 3.42), p =0.17, facial nerve function; HR = 0.67 (95% CI 0.30, 1.49), p =0.33, trigeminal nerve function; HR = 0.80 (95% CI 0.41, 1.56), p =0.51, and hearing preservation; HR = 1.10 (95% CI 0.72, 1.68), p =0.65 comparing single fraction RS with FSRT.Nine quality of life reports yielded conflicting results as to which modality (surgery, observation, or radiation) was associated with better quality of life outcomes. There are no randomized trials to help guide management of patients with vestibular schwannoma. Within the limitations of the retrospective series, a number of consensus statements were made.

Stereotactic radiosurgery for vestibular schwannoma: International Stereotactic Radiosurgery Society (ISRS) Practice Guideline

PubMed Central

Sahgal, Arjun; Xu, Wei; De Salles, Antonio; Hayashi, Motohiro; Levivier, Marc; Ma, Lijun; Martinez, Roberto; Régis, Jean; Ryu, Sam; Slotman, Ben J.; Paddick, Ian

2017-01-01

Objectives The aim of this systematic review was to develop International Stereotactic Radiosurgery Society (ISRS) consensus guideline statements for vestibular schwannoma. Methods A systematic review of the literature was performed up to April 2015. Results A total of 55 full-text articles were included in the analysis. All studies were retrospective, except for 2 prospective quality of life studies. Five-year tumour control rates with Gamma Knife radiosurgery (RS), single fraction linac RS, or fractionated (either hypofractionated or conventional fractionation) stereotactic radiation therapy (FSRT) were similar at 81-100%. The single fraction RS series (linac or Gamma Knife) with tumour marginal doses between 12 and 14 Gy revealed 5-year tumour control rates of 90-99%, hearing preservation rates of 41-79%, facial nerve preservation rates of 95-100% and trigeminal preservation rates of 79-99%. There were 6 non-randomized studies comparing single fraction RS versus FSRT. There was no statistically significant difference in tumour control; HR=1.66 (95% CI 0.81, 3.42), p =0.17, facial nerve function; HR = 0.67 (95% CI 0.30, 1.49), p =0.33, trigeminal nerve function; HR = 0.80 (95% CI 0.41, 1.56), p =0.51, and hearing preservation; HR = 1.10 (95% CI 0.72, 1.68), p =0.65 comparing single fraction RS with FSRT. Nine quality of life reports yielded conflicting results as to which modality (surgery, observation, or radiation) was associated with better quality of life outcomes. Conclusions There are no randomized trials to help guide management of patients with vestibular schwannoma. Within the limitations of the retrospective series, a number of consensus statements were made. PMID:29296459

Stereotactic Radiosurgery for Cushing Disease: Results of an International, Multicenter Study.

PubMed

Mehta, Gautam U; Ding, Dale; Patibandla, Mohana Rao; Kano, Hideyuki; Sisterson, Nathaniel; Su, Yan-Hua; Krsek, Michal; Nabeel, Ahmed M; El-Shehaby, Amr; Kareem, Khaled A; Martinez-Moreno, Nuria; Mathieu, David; McShane, Brendan; Blas, Kevin; Kondziolka, Douglas; Grills, Inga; Lee, John Y; Martinez-Alvarez, Roberto; Reda, Wael A; Liscak, Roman; Lee, Cheng-Chia; Lunsford, L Dade; Vance, Mary Lee; Sheehan, Jason P

2017-11-01

Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge. To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management. International, multicenter, retrospective cohort analysis. Ten medical centers participating in the International Gamma Knife Research Foundation. Patients with CD with >6 months endocrine follow-up. SRS using Gamma Knife radiosurgery. The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded. In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation. SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS. Copyright © 2017 Endocrine Society

A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy

PubMed Central

Ayala-Peacock, Diandra N.; Peiffer, Ann M.; Lucas, John T.; Isom, Scott; Kuremsky, J. Griff; Urbanic, James J.; Bourland, J. Daniel; Laxton, Adrian W.; Tatter, Stephen B.; Shaw, Edward G.; Chan, Michael D.

2014-01-01

Background We review our single institution experience to determine predictive factors for early and delayed distant brain failure (DBF) after radiosurgery without whole brain radiotherapy (WBRT) for brain metastases. Materials and methods Between January 2000 and December 2010, a total of 464 patients were treated with Gamma Knife stereotactic radiosurgery (SRS) without WBRT for primary management of newly diagnosed brain metastases. Histology, systemic disease, RPA class, and number of metastases were evaluated as possible predictors of DBF rate. DBF rates were determined by serial MRI. Kaplan–Meier method was used to estimate rate of DBF. Multivariate analysis was performed using Cox Proportional Hazard regression. Results Median number of lesions treated was 1 (range 1–13). Median time to DBF was 4.9 months. Twenty-seven percent of patients ultimately required WBRT with median time to WBRT of 5.6 months. Progressive systemic disease (χ2= 16.748, P < .001), number of metastases at SRS (χ2 = 27.216, P < .001), discovery of new metastases at time of SRS (χ2 = 9.197, P < .01), and histology (χ2 = 12.819, P < .07) were factors that predicted for earlier time to distant failure. High risk histologic subtypes (melanoma, her2 negative breast, χ2 = 11.020, P < .001) and low risk subtypes (her2 + breast, χ2 = 11.343, P < .001) were identified. Progressive systemic disease (χ2 = 9.549, P < .01), number of brain metastases (χ2 = 16.953, P < .001), minimum SRS dose (χ2 = 21.609, P < .001), and widespread metastatic disease (χ2 = 29.396, P < .001) were predictive of shorter time to WBRT. Conclusion Systemic disease, number of metastases, and histology are factors that predict distant failure rate after primary radiosurgical management of brain metastases. PMID:24558022

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Mapping clinical outcomes expectations to treatment decisions: an application to vestibular schwannoma management.

PubMed

Cheung, Steven W; Aranda, Derick; Driscoll, Colin L W; Parsa, Andrew T

2010-02-01

Complex medical decision making obligates tradeoff assessments among treatment outcomes expectations, but an accessible tool to perform the necessary analysis is conspicuously absent. We aimed to demonstrate methodology and feasibility of adapting conjoint analysis for mapping clinical outcomes expectations to treatment decisions in vestibular schwannoma (VS) management. Prospective. Tertiary medical center and US-based otologists/neurotologists. Treatment preference profiles among VS stakeholders-61 younger and 74 older prospective patients, 61 observation patients, and 60 surgeons-were assessed for the synthetic VS case scenario of a 10-mm tumor in association with useful hearing and normal facial function. Treatment attribute utility. Conjoint analysis attribute levels were set in accordance to the results of a meta-analysis. Forty-five case series were disaggregated to formulate microsurgery facial nerve and hearing preservation outcomes expectations models. Attribute utilities were computed and mapped to the realistic treatment choices of translabyrinthine craniotomy, middle fossa craniotomy, and gamma knife radiosurgery. Among the treatment attributes of likelihoods of causing deafness, temporary facial weakness for 2 months, and incurable cancer within 20 years, and recovery time, permanent deafness was less important to tumor surgeons, and temporary facial weakness was more important to tumor surgeons and observation patients (Wilcoxon rank-sum, p < 0.001). Inverse mapping of preference profiles to realistic treatment choices showed all study cohorts were inclined to choose gamma knife radiosurgery. Mapping clinical outcomes expectations to treatment decisions for a synthetic clinical scenario revealed inhomogeneous drivers of choice selection among study cohorts. Medical decision engines that analyze personal preferences of outcomes expectations for VS and many other diseases may be developed to promote shared decision making among health care stakeholders and transparency in the informed consent process.

Factors Determining the Clinical Complications of Radiosurgery for AVM.

PubMed

Machnowska, Matylda; Taeshineetanakul, Patamintita; Geibprasert, Sasikhan; Menezes, Ravi; Agid, Ronit; Terbrugge, Karel G; Andrade-Souza, Yuri; Schwartz, Michael L; Krings, Timo

2013-11-01

To identify the predictors of symptomatic post-radiation T2 signal change in patients with arteriovenous malformations (AVM) treated with radiosurgery. The charts of 211 consecutive patients with arteriovenous malformations treated with either gamma knife radisurgery or linear accelerator radiosurgery between 2000-2009 were retrospectively reviewed. 168 patients had a minimum of 12 months of clinical and radiologic follow-up following the procedure and complete dosage data. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. 141 patients had no clinical symptomatic complications. 21 patients had global or focal neurological deficits attributed to symptomatic edema. Variables associated with development of symptomatic edema included a non-hemorrhagic symptomatic presentation compared to presentation with hemorrhage, p=0.001; OR (95%CI) = 6.26 (1.99, 19.69); the presence of venous rerouting compared to the lack of venous rerouting, p=0.031; OR (95% CI) = 3.25 (1.20, 8.80); radiosurgery with GKS compared to linear accelerator radiosurgery p = 0.012; OR (95% CI) = 4.58 (1.28, 16.32); and the presence of more than one draining vein compared to a single draining vein p = 0.032; OR (95% CI) = 2.82 (1.06, 7.50). We postulated that the higher maximal doses used with gamma knife radiosurgery may be responsible for the greater number of adverse radiation effects with this modality compared to linear accelerator radiosurgery. We found that AVMs with greater venous complexity and therefore instability resulted in more adverse treatment outcomes, suggesting that AVM angioarchitecture should be considered when making treatment decisions. Facteurs en cause dans les complications cliniques de la radiochirurgie pour une malformation artérioveineuse.

Experimental Comparison of Knife-Edge and Multi-Parallel Slit Collimators for Prompt Gamma Imaging of Proton Pencil Beams.

PubMed

Smeets, Julien; Roellinghoff, Frauke; Janssens, Guillaume; Perali, Irene; Celani, Andrea; Fiorini, Carlo; Freud, Nicolas; Testa, Etienne; Prieels, Damien

2016-01-01

More and more camera concepts are being investigated to try and seize the opportunity of instantaneous range verification of proton therapy treatments offered by prompt gammas emitted along the proton tracks. Focusing on one-dimensional imaging with a passive collimator, the present study experimentally compared in combination with the first, clinically compatible, dedicated camera device the performances of instances of the two main options: a knife-edge slit (KES) and a multi-parallel slit (MPS) design. These two options were experimentally assessed in this specific context as they were previously demonstrated through analytical and numerical studies to allow similar performances in terms of Bragg peak retrieval precision and spatial resolution in a general context. Both collimators were prototyped according to the conclusions of Monte Carlo optimization studies under constraints of equal weight (40 mm tungsten alloy equivalent thickness) and of the specificities of the camera device under consideration (in particular 4 mm segmentation along beam axis and no time-of-flight discrimination, both of which less favorable to the MPS performance than to the KES one). Acquisitions of proton pencil beams of 100, 160, and 230 MeV in a PMMA target revealed that, in order to reach a given level of statistical precision on Bragg peak depth retrieval, the KES collimator requires only half the dose the present MPS collimator needs, making the KES collimator a preferred option for a compact camera device aimed at imaging only the Bragg peak position. On the other hand, the present MPS collimator proves more effective at retrieving the entrance of the beam in the target in the context of an extended camera device aimed at imaging the whole proton track within the patient.

Analysis of risk factors to predict communicating hydrocephalus following gamma knife radiosurgery for intracranial schwannoma.

PubMed

Lee, Seunghoon; Seo, Seong-Wook; Hwang, Juyoung; Seol, Ho Jun; Nam, Do-Hyun; Lee, Jung-Il; Kong, Doo-Sik

2016-12-01

Communicating hydrocephalus (HCP) in vestibular schwannomas (VS) after gamma knife radiosurgery (GKRS) has been reported in the literature. However, little information about its incidence and risk factors after GKRS for intracranial schwannomas is yet available. The objective of this study was to identify the incidence and risk factors for developing communicating HCP after GKRS for intracranial schwannomas. We retrospectively reviewed a total of 702 patients with intracranial schwannomas who were treated with GKRS between January 2002 and December 2015. We investigated patients' age, gender, tumor origin, previous surgery history, tumor volume, marginal radiation dose, and presence of tumor control to identify associations with communicating HCP following GKRS. To make predictive models of communicating HCP, we performed Cox regression analyses and constructed a decision tree for risk factors. In total, 29 of the 702 patients (4.1%) developed communicating HCP following GKRS, which required ventriculo-peritoneal (VP) shunt surgery. Multivariate analyses indicated that age (P = 0.0011), tumor origin (P = 0.0438), and tumor volume (P < 0.0001) were significant predictors of communicating HCP in patients with intracranial schwannoma after GKRS. Using machine-learning methods, we fit an optimal predictive model. We found that developing communicating HCP following GKRS was most likely if the tumor was vestibular origin and had a volume ≥13.65 cm 3 . Communicating HCP is not a rare complication of GKRS for intracranial schwannomas. Under specific conditions, communicating HCP following GKRS is warranted for this patient group, and this patient group should be closely followed up. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Therapeutic Effect of Gamma Knife Radiosurgery for Multiple Brain Metastases

PubMed Central

Lee, Chul-Kyu; Lee, Sang Ryul; Cho, Jin Mo; Yang, Kyung Ah

2011-01-01

Objective The aim of this study is to evaluate the therapeutic effects of gamma knife radiosurgery (GKRS) in patients with multiple brain metastases and to investigate prognostic factors related to treatment outcome. Methods We retrospectively reviewed clinico-radiological and dosimetric data of 36 patients with 4-14 brain metastases who underwent GKRS for 264 lesions between August 2008 and April 2011. The most common primary tumor site was the lung (n=22), followed by breast (n=7). At GKRS, the median Karnofsky performance scale score was 90 and the mean tumor volume was 1.2 cc (0.002-12.6). The mean prescription dose of 17.8 Gy was delivered to the mean 61.1% isodose line. Among 264 metastases, 175 lesions were assessed for treatment response by at least one imaging follow-up. Results The overall median survival after GKRS was 9.1±1.7 months. Among various factors, primary tumor control was a significant prognostic factor (11.1±1.3 months vs. 3.3±2.4 months, p=0.031). The calculated local tumor control rate at 6 and 9 months after GKRS were 87.9% and 84.2%, respectively. Paddick's conformity index (>0.75) was significantly related to local tumor control. The actuarial peritumoral edema reduction rate was 22.4% at 6 months. Conclusion According to our results, GKRS can provide beneficial effect for the patients with multiple (4 or more) brain metastases, when systemic cancer is controlled. And, careful dosimetry is essential for local tumor control. Therefore, GKRS can be considered as one of the treatment modalities for multiple brain metastase. PMID:22102945

Postcontrast T1 Mapping for Differential Diagnosis of Recurrence and Radionecrosis after Gamma Knife Radiosurgery for Brain Metastasis.

PubMed

Wang, B; Zhang, Y; Zhao, B; Zhao, P; Ge, M; Gao, M; Ding, F; Xu, S; Liu, Y

2018-06-01

The differential diagnosis of radionecrosis and tumor recurrence in brain metastases is challenging. We investigated the diagnostic efficiency of postcontrast T1 mapping in solving this problem. Between March 2016 and June 2017, fifty-six patients with brain metastases who underwent contrast-enhanced cerebral T1 mapping were recruited for this prospective study. The findings revealed new enhancement after gamma knife radiosurgery. The subjects were assigned to radionecrosis and recurrence groups based on follow-up (median, 11.5 months) and histopathologic results. T1 values of lesions 5 (T1 5min ) and 60 (T1 60min ) minutes after administration of contrast agent and their difference (T1 differ ) were compared between the 2 groups with the 2-tailed Mann-Whitney U test. Receiver operating characteristic curves were used to determine the optimum cutoff values for differential diagnosis. There were significant differences between the 2 groups in T1 5min , T1 60min , and T1 differ values ( P = .012, P = .004, and P < .001, respectively). Relative to T1 5min and T1 60min , T1 differ exhibited greater sensitivity and specificity ( P < .001, respectively) in identifying radionecrosis. The optimum T1 differ value for differential diagnosis was 71.1 ms (area under the curve = 0.97; 95% CI, 0.93-1.00), with sensitivity and specificity of 81.5% and 96.5%, respectively. Postcontrast T1 mapping is optimal for the differential diagnosis of radionecrosis and tumor recurrence. Among T1 parameters, T1 differ is the most powerful parameter for differential diagnosis. Advantages in terms of quantitative analysis and high resolution portend the wide use of postcontrast T1 mapping in the future. © 2018 by American Journal of Neuroradiology.

Relapsed or refractory primary central nervous system lymphoma radiosurgery: Report of the International Gamma Knife Research Foundation.

PubMed

Shin, Samuel M; Silverman, Joshua S; Bowden, Greg; Mathieu, David; Yang, Huai-Che; Lee, Cheng-Chia; Tam, Moses; Szelemej, Paul; Kaufmann, Anthony M; Cohen-Inbar, Or; Sheehan, Jason; Niranjan, Ajay; Lunsford, L Dade; Kondziolka, Douglas

2017-01-01

Stereotactic radiosurgery (SRS) can be used as part of multimodality management for patients with primary central nervous system lymphoma (PCNSL). The objective of this study is to evaluate outcomes of SRS for this disease. The International Gamma Knife Research Foundation identified 23 PCNSL patients who underwent SRS for either relapsed (intracerebral in-field or out-of-field tumor recurrences) or refractory disease from 1995-2014. All 23 patients presented with RPA Class I or II PCNSL, and were initially treated with a median of 7 cycles of methotrexate-based chemotherapy regimens (range, 3-26 cycles). Ten received prior whole brain radiation (WBRT) to a median dose of 43 Gy (range, 24-55 Gy). Sixteen presented with relapsed PCNSL, and seven presented with refractory disease. Twenty-three received 26 procedures of SRS. The median tumor volume was 4 cm 3 (range, 0.1-26 cm 3 ), and the median margin dose was 15 Gy (range, 8-20 Gy). Median follow-up from SRS was 11 months (interquartile range, 5.7-33.2 months). Twenty presented with treatment response to twenty-three tumors (12 complete, 11 partial). Fourteen patients relapsed or were refractory to salvage SRS, and local control was 95%, 91%, and 75% at 3, 6, and 12 months post SRS. Intracranial (in-field and out-of-field) and distant (systemic) PFS was 86%, 81%, and 55% at 3, 6, and 12 months post SRS. Toxicity of SRS was low, with one developing an adverse radiation effect requiring no additional intervention. Although methotrexate-based chemotherapy regimens with or without WBRT is the first-line management option for PCNSL, SRS may be used as an alternative option in properly selected patients with smaller relapsed or refractory PCNSL tumors.

Evaluation of Different Score Index for Predicting Prognosis in Gamma Knife Radiosurgical Treatment for Brain Metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franzin, Alberto; Snider, Silvia; Picozzi, Piero

2009-07-01

Purpose: To assess the utility of the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and Score Index for Radiosurgery (SIR) stratification systems in predicting survival in patients with brain metastasis treated with Gamma Knife radiosurgery (GKRS). Methods and Materials: A total of 185 patients were included in the study. Patients were stratified according to RPA and SIR classes. The RPA and SIR classes, age, Karnofsky Performance Status (KPS), and systemic disease were correlated with survival. Results: Five patients were lost to follow-up. Median survival in patients in RPA Class 1 (30 patients) was 17 months; in Class 2 (140more » patients), 10 months; and in Class 3 (10 patients), 3 months. Median survival in patients in SIR Class 1 (30 patients) was 3 months; in Class 2 (135 patients), 8 months; and in Class 3 (15 patients), 20 months. In univariate testing, age younger than 65 years (p = 0.0004), KPS higher than 70 (p = 0.0001), RPA class (p = 0.0078), SIR class (p = 0.0002), and control of the primary tumor (p = 0.02) were significantly associated with improved outcome. In multivariate analysis, KPS (p < 0.0001), SIR class (p = 0.0008), and RPA class (p = 0.03) had statistical value. Conclusions: This study supports the use of GKRS as a single-treatment modality in this selected group of patients. Stratification systems are useful in the estimation of patient eligibility for GKRS. A second-line treatment was necessary in 30% of patients to achieve distal or local brain control. This strategy is useful to control brain metastasis in long-surviving patients.« less

Optimization of the prescription isodose line for Gamma Knife radiosurgery using the shot within shot technique.

PubMed

Johnson, Perry B; Monterroso, Maria I; Yang, Fei; Mellon, Eric

2017-11-25

This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larger shot at the same stereotactic coordinates (shot within shot technique). Beam profiles for the 4, 8, and 16 mm collimator settings were extracted from the treatment planning system and characterized using Gaussian fits. The characterized data were used to create over 10,000 shot within shot configurations by systematically changing collimator weighting and choice of prescription IDL. Each configuration was quantified in terms of the dose gradient, target coverage, and beam-on time. By analyzing these configurations, it was found that there are regions of overlap in target size where a higher prescription IDL provides equivalent dose fall-off to a plan prescribed at the 50% IDL. Furthermore, the data indicate that treatment times within these regions can be reduced by up to 40%. An optimization strategy was devised to realize these gains. The strategy was tested for seven patients treated for 1-4 brain metastases (20 lesions total). For a single collimator setting, the gradient in the axial plane was steepest when prescribed to the 56-63% (4 mm), 62-70% (8 mm), and 77-84% (16 mm) IDL, respectively. Through utilization of the optimization technique, beam-on time was reduced by more than 15% in 16/20 lesions. The volume of normal brain receiving 12 Gy or above also decreased in many cases, and in only one instance increased by more than 0.5 cm 3 . This work demonstrates that IDL optimization using the shot within shot technique can reduce treatment times without degrading treatment plan quality.

Long-Term Outcome of Gamma Knife Radiosurgery for Treatment of Typical Trigeminal Neuralgia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Jung Ho; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.k; Chung, Hyun-Tai

2009-11-01

Purpose: To analyze the long-term outcomes of patients with typical trigeminal neuralgia treated with gamma knife radiosurgery (GKRS). Patients and Methods: A total of 62 consecutive patients with typical trigeminal neuralgia were treated with GKRS between 1998 and 2004. Of the 62 patients, 2 were lost to follow-up; the remaining 60 patients were followed for >12 months. The mean prescribed maximal dose was 79.7 Gy (range, 75-80), using a 4-mm shot. Results: Of the 60 patients, 48 were followed for >4 years. An additional 3 patients, followed for <4 years, experienced recurrent pain after a favorable initial response and weremore » incorporated into the long-term response analysis. Of these 51 patients (mean age, 61 +- 11 years; 37 women [72.5%]; and mean follow-up duration, 58 +- 14 months), 46 (90.2%) responded to GKRS, as demonstrated by an improvement in their Barrow Neurological Institute pain intensity score. Of the 46 patients, 24 (52.2%) had pain recurrence. The actuarial recurrence-free survival rate was 84.8%, 76.1%, 69.6%, 63.0%, and 45.8% at 1, 2, 3, 4, and 5 years after radiosurgery, respectively. Patient age >70 years correlated with a favorable outcome in terms of pain recurrence after radiosurgery (hazard ratio, 0.125; 95% confidence interval, 0.016-0.975; p = .047) on multivariate analysis. Conclusion: GKRS seems to be an effective treatment modality for patients with typical trigeminal neuralgia considering the initial response rate; however, fewer than one-half of patients might continue to benefit from GKRS after long-term follow-up. Elderly patients might be good candidates for radiosurgery considering the long-term durability of efficacy.« less

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aubuchon, Adam C., E-mail: acaubuchon@gmail.com; Chan, Michael D.; Lovato, James F.

2011-11-15

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90).more » The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.« less

FoxO1 and HNF-4 Are Involved in Regulation of Hepatic Glucokinase Gene Expression by Resveratrol*

PubMed Central

Ganjam, Goutham Kumar; Dimova, Elitsa Y.; Unterman, Terry G.; Kietzmann, Thomas

2009-01-01

Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol. PMID:19740748

FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by resveratrol.

PubMed

Ganjam, Goutham Kumar; Dimova, Elitsa Y; Unterman, Terry G; Kietzmann, Thomas

2009-11-06

Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol.

The Deoxynucleoside Triphosphate Triphosphohydrolase Activity of SAMHD1 Protein Contributes to the Mitochondrial DNA Depletion Associated with Genetic Deficiency of Deoxyguanosine Kinase*

PubMed Central

Franzolin, Elisa; Salata, Cristiano; Bianchi, Vera; Rampazzo, Chiara

2015-01-01

The dNTP triphosphohydrolase SAMHD1 is a nuclear antiviral host restriction factor limiting HIV-1 infection in macrophages and a major regulator of dNTP concentrations in human cells. In normal human fibroblasts its expression increases during quiescence, contributing to the small dNTP pool sizes of these cells. Down-regulation of SAMHD1 by siRNA expands all four dNTP pools, with dGTP undergoing the largest relative increase. The deoxyguanosine released by SAMHD1 from dGTP can be phosphorylated inside mitochondria by deoxyguanosine kinase (dGK) or degraded in the cytosol by purine nucleoside phosphorylase. Genetic mutations of dGK cause mitochondrial (mt) DNA depletion in noncycling cells and hepato-cerebral mtDNA depletion syndrome in humans. We studied if SAMHD1 and dGK interact in the regulation of the dGTP pool during quiescence employing dGK-mutated skin fibroblasts derived from three unrelated patients. In the presence of SAMHD1 quiescent mutant fibroblasts manifested mt dNTP pool imbalance and mtDNA depletion. When SAMHD1 was silenced by siRNA transfection the composition of the mt dNTP pool approached that of the controls, and mtDNA copy number increased, compensating the depletion to various degrees in the different mutant fibroblasts. Chemical inhibition of purine nucleoside phosphorylase did not improve deoxyguanosine recycling by dGK in WT cells. We conclude that the activity of SAMHD1 contributes to the pathological phenotype of dGK deficiency. Our results prove the importance of SAMHD1 in the regulation of all dNTP pools and suggest that dGK inside mitochondria has the function of recycling the deoxyguanosine derived from endogenous dGTP degraded by SAMHD1 in the nucleus. PMID:26342080

Verification of Gyrokinetic codes: Theoretical background and applications

NASA Astrophysics Data System (ADS)

Tronko, Natalia; Bottino, Alberto; Görler, Tobias; Sonnendrücker, Eric; Told, Daniel; Villard, Laurent

2017-05-01

In fusion plasmas, the strong magnetic field allows the fast gyro-motion to be systematically removed from the description of the dynamics, resulting in a considerable model simplification and gain of computational time. Nowadays, the gyrokinetic (GK) codes play a major role in the understanding of the development and the saturation of turbulence and in the prediction of the subsequent transport. Naturally, these codes require thorough verification and validation. Here, we present a new and generic theoretical framework and specific numerical applications to test the faithfulness of the implemented models to theory and to verify the domain of applicability of existing GK codes. For a sound verification process, the underlying theoretical GK model and the numerical scheme must be considered at the same time, which has rarely been done and therefore makes this approach pioneering. At the analytical level, the main novelty consists in using advanced mathematical tools such as variational formulation of dynamics for systematization of basic GK code's equations to access the limits of their applicability. The verification of the numerical scheme is proposed via the benchmark effort. In this work, specific examples of code verification are presented for two GK codes: the multi-species electromagnetic ORB5 (PIC) and the radially global version of GENE (Eulerian). The proposed methodology can be applied to any existing GK code. We establish a hierarchy of reduced GK Vlasov-Maxwell equations implemented in the ORB5 and GENE codes using the Lagrangian variational formulation. At the computational level, detailed verifications of global electromagnetic test cases developed from the CYCLONE Base Case are considered, including a parametric β-scan covering the transition from ITG to KBM and the spectral properties at the nominal β value.

FOOD-INTAKE DYSREGULATION IN TYPE 2 DIABETIC GOTO-KAKIZAKI RATS: HYPOTHESIZED ROLE OF DYSFUNCTIONAL BRAINSTEM THYROTROPIN-RELEASING HORMONE AND IMPAIRED VAGAL OUTPUT

PubMed Central

Zhao, K.; Ao, Y.; Harper, R.M.; Go, V. L.W.; Yang, H.

2013-01-01

Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56–81% in GK rats. Fasting (48 h) and refeeding (2 h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. PMID:23701881

Food-intake dysregulation in type 2 diabetic Goto-Kakizaki rats: hypothesized role of dysfunctional brainstem thyrotropin-releasing hormone and impaired vagal output.

PubMed

Zhao, K; Ao, Y; Harper, R M; Go, V L W; Yang, H

2013-09-05

Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56-81% in GK rats. Fasting (48h) and refeeding (2h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. Published by Elsevier Ltd.

Bleeding Efficiency and Meat Oxidative Stability and Microbiological Quality of New Zealand White Rabbits Subjected to Halal Slaughter without Stunning and Gas Stun-killing

PubMed Central

Nakyinsige, K.; Fatimah, A. B.; Aghwan, Z. A.; Zulkifli, I.; Goh, Y. M.; Sazili, A. Q.

2014-01-01

A study was conducted to compare the effect of halal slaughter without stunning and gas stun killing followed by bleeding on residual blood content and storage stability of rabbit meat. Eighty male New Zealand white rabbits were divided into two groups of 40 animals each and subjected to either halal slaughter without stunning (HS) or gas stun-kill (GK). The volume of blood lost during exsanguination was measured. Residual blood was further quantified by determination of haemoglobin content in Longissimus lumborum (LL) muscle. Storage stability of the meat was evaluated by microbiological analysis and measuring lipid oxidation in terms of thiobarbituric acid reactive substances (TBARS). HS resulted in significantly higher blood loss than GK. HS had significantly lower residual haemoglobin in LL muscle compared to GK. Slaughter method had no effect on rabbit meat lipid oxidation at 0, 1, and 3 d postmortem. However, at 5 and 8 days of storage at 4°C, significant differences (p<0.05) were found, with meat from the GK group exhibiting significantly higher levels of MDA than that from HS. At day 3, greater growth of Pseudomonas aeroginosa and E. coli were observed in the GK group (p<0.05) with B. thermosphacta and total aerobic counts remained unaffected by slaughter method. At days 5 and 7 postmortem, bacterial counts for all tested microbes were affected by slaughter method, with GK exhibiting significantly higher growth than HS. It can be concluded that slaughter method can affect keeping quality of rabbit meat, and HS may be a favourable option compared to GK due to high bleed out. PMID:25049968

Bleeding Efficiency and Meat Oxidative Stability and Microbiological Quality of New Zealand White Rabbits Subjected to Halal Slaughter without Stunning and Gas Stun-killing.

PubMed

Nakyinsige, K; Fatimah, A B; Aghwan, Z A; Zulkifli, I; Goh, Y M; Sazili, A Q

2014-03-01

A study was conducted to compare the effect of halal slaughter without stunning and gas stun killing followed by bleeding on residual blood content and storage stability of rabbit meat. Eighty male New Zealand white rabbits were divided into two groups of 40 animals each and subjected to either halal slaughter without stunning (HS) or gas stun-kill (GK). The volume of blood lost during exsanguination was measured. Residual blood was further quantified by determination of haemoglobin content in Longissimus lumborum (LL) muscle. Storage stability of the meat was evaluated by microbiological analysis and measuring lipid oxidation in terms of thiobarbituric acid reactive substances (TBARS). HS resulted in significantly higher blood loss than GK. HS had significantly lower residual haemoglobin in LL muscle compared to GK. Slaughter method had no effect on rabbit meat lipid oxidation at 0, 1, and 3 d postmortem. However, at 5 and 8 days of storage at 4°C, significant differences (p<0.05) were found, with meat from the GK group exhibiting significantly higher levels of MDA than that from HS. At day 3, greater growth of Pseudomonas aeroginosa and E. coli were observed in the GK group (p<0.05) with B. thermosphacta and total aerobic counts remained unaffected by slaughter method. At days 5 and 7 postmortem, bacterial counts for all tested microbes were affected by slaughter method, with GK exhibiting significantly higher growth than HS. It can be concluded that slaughter method can affect keeping quality of rabbit meat, and HS may be a favourable option compared to GK due to high bleed out.

Weaning stage hyperglycemia induces glucose-insensitivity in arcuate POMC neurons and hyperphagia in type 2 diabetic GK rats.

PubMed

Ando, A; Gantulga, D; Nakata, M; Maekawa, F; Dezaki, K; Ishibashi, S; Yada, T

2018-04-01

Hyperphagia triggers and accelerates diabetes, and prevents proper dietary control of glycemia. Inversely, the impact of hyperglycemia on hyperphagia and possible mechanistic cause common for these two metabolic disorders in type 2 diabetes are less defined. The present study examined the precise developmental process of hyperglycemia and hyperphagia and explored the alterations in the hypothalamic arcuate nucleus (ARC), the primary feeding and metabolic center, in Goto-Kakizaki (GK) rats with type 2 diabetes and nearly normal body weight. At mid 3 to 4 weeks of age, GK rats first exhibited hyperglycemia, and then hyperphagia and reduced mRNA expressions for anorexigenic pro-opiomelanocortin (POMC) and glucokinase in ARC. Furthermore, [Ca 2+ ]i responses to high glucose in ARC POMC neurons were impaired in GK rats at 4 weeks. Treating GK rats from early 3 to mid 6 weeks of age with an anti-diabetic medicine miglitol not only suppressed hyperglycemia but ameliorated hyperphagia and restored POMC mRNA expression in ARC. These results suggest that the early hyperglycemia occurring in weaning period may lead to impaired glucose sensing and neuronal activity of POMC neurons, and thereby induce hyperphagia in GK rats. Correction of hyperglycemia in the early period may prevent and/or ameliorate the progression of hyperphagia in type 2 diabetes. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

No need to change the skin knife in modern arthroplasty surgery.

PubMed

Ottesen, C; Skovby, A; Troelsen, A; Specht, C; Friis-Møller, A; Husted, H

2014-08-01

Earlier studies have found varying contamination rates using separate skin and deep knives in total hip (THA) and total knee (TKA) arthroplasty surgery. Previous studies were primarily conducted in the setting of concomitant use of laminar airflow and/or plastic adhesive draping. This has lead to conflicting conclusions regarding discarding the skin knife or not. This study evaluates the prevalence of contamination of a separate skin knife using modern antiseptic technique in primary THA and TKA without laminar airflow. Three knives from each primary THA and TKA surgery in non-laminar airflow operating rooms were collected: one used for the skin, one used for deeper tissues and one control knife. A total of 831 knife blades from 277 patients were cultured 12 days. Contamination of the skin knife was found in eight patients (2.8 %), contamination of the "deep" knife in five patients (1.8 %) and contamination of the control knife in five patients (1.8 %). No patient developed an infection with 1-year follow-up. Our findings suggest a very low rate of contamination of the skin knife using modern antiseptic technique without laminar airflow and/or plastic adhesive draping and do not support the use of a separate skin knife in arthroplasty surgery.

The use of docking-based comparative intermolecular contacts analysis to identify optimal docking conditions within glucokinase and to discover of new GK activators

NASA Astrophysics Data System (ADS)

Taha, Mutasem O.; Habash, Maha; Khanfar, Mohammad A.

2014-05-01

Glucokinase (GK) is involved in normal glucose homeostasis and therefore it is a valid target for drug design and discovery efforts. GK activators (GKAs) have excellent potential as treatments of hyperglycemia and diabetes. The combined recent interest in GKAs, together with docking limitations and shortages of docking validation methods prompted us to use our new 3D-QSAR analysis, namely, docking-based comparative intermolecular contacts analysis (dbCICA), to validate docking configurations performed on a group of GKAs within GK binding site. dbCICA assesses the consistency of docking by assessing the correlation between ligands' affinities and their contacts with binding site spots. Optimal dbCICA models were validated by receiver operating characteristic curve analysis and comparative molecular field analysis. dbCICA models were also converted into valid pharmacophores that were used as search queries to mine 3D structural databases for new GKAs. The search yielded several potent bioactivators that experimentally increased GK bioactivity up to 7.5-folds at 10 μM.

Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder.

PubMed

Miguel, Euripedes C; Lopes, Antonio C; McLaughlin, Nicole C R; Norén, Georg; Gentil, André F; Hamani, Clement; Shavitt, Roseli G; Batistuzzo, Marcelo C; Vattimo, Edoardo F Q; Canteras, Miguel; De Salles, Antonio; Gorgulho, Alessandra; Salvajoli, João Victor; Fonoff, Erich Talamoni; Paddick, Ian; Hoexter, Marcelo Q; Lindquist, Christer; Haber, Suzanne N; Greenberg, Benjamin D; Sheth, Sameer A

2018-05-09

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Z; Feng, Y; Lo, S

2015-06-15

Purpose: The dose–volume histogram (DVH) has been normally accepted as a tool for treatment plan evaluation. However, spatial information is lacking in DVH. As a supplement to the DVH in three-dimensional treatment planning, the differential DVH (DDVH) provides the spatial variation, the size and magnitude of the different dose regions within a region of interest, which can be incorporated into tumor control probability model. This study was to provide a method in evaluating and improving Gamma Knife treatment planning. Methods: 10 patients with brain metastases from different primary tumors including melanoma (#1,#4,#5, #10), breast cancer (#2), prostate cancer (#3) andmore » lung cancer (#6–9) were analyzed. By using Leksell GammaPlan software, two plans were prepared for each patient. Special attention was given to the DDVHs that were different for different plans and were used for a comparison between two plans. Dose distribution inside target and tumor control probability (TCP) based on DDVH were calculated, where cell density and radiobiological parameters were adopted from literature. The plans were compared based on DVH, DDVH and TCP. Results: Using DVH, the coverage and selectivity were the same between plans for 10 patients. DDVH were different between two plans for each patient. The paired t-test showed no significant difference in TCP between the two plans. For brain metastases from melanoma (#1, #4–5), breast cancer (#2) and lung cancer (#6–8), the difference in TCP was less than 5%. But the difference in TCP was about 6.5% for patient #3 with the metastasis from prostate cancer, 10.1% and 178.7% for two patients (#9–10) with metastasis from lung cancer. Conclusion: Although DVH provides average dose–volume information, DDVH provides differential dose– volume information with respect to different regions inside the tumor. TCP provides radiobiological information and adds additional information on improving treatment planning as well as adaptive radiotherapy. Further clinical validation is necessary.« less

Vertebral body or intervertebral disc wedging: which contributes more to thoracolumbar kyphosis in ankylosing spondylitis patients?: A retrospective study.

PubMed

Liu, Hao; Qian, Bang-Ping; Qiu, Yong; Wang, Yan; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang

2016-09-01

Both vertebral body wedging and disc wedging are found in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis. However, their relative contribution to thoracolumbar kyphosis is not fully understood. The objective of this study was to compare different contributions of vertebral and disc wedging to the thoracolumbar kyphosis in AS patients, and to analyze the relationship between the apical vertebral wedging angle and thoracolumbar kyphosis.From October 2009 to October 2013, a total of 59 consecutive AS patients with thoracolumbar kyphosis with a mean age of 38.1 years were recruited in this study. Based on global kyphosis (GK), 26 patients with GK < 70° were assigned to group A, and the other 33 patients with GK ≥ 70° were included in group B. Each GK was divided into disc wedge angles and vertebral wedge angles. The wedging angle of each disc and vertebra comprising the thoracolumbar kyphosis was measured, and the proportion of the wedging angle to the GK was calculated accordingly. Intergroup and intragroup comparisons were subsequently performed to investigate the different contributions of disc and vertebra to the GK. The correlation between the apical vertebral wedging angle and GK was calculated by Pearson correlation analysis. The duration of disease and sex were also recorded in this study.With respect to the mean disease duration, significant difference was observed between the two groups (P < 0.01). The wedging angle and wedging percentage of discs were significantly higher than those of vertebrae in group A (34.8° ± 2.5° vs 26.7° ± 2.7°, P < 0.01 and 56.6% vs 43.4%, P < 0.01), whereas disc wedging and disc wedging percentage were significantly lower than vertebrae in group B (37.6° ± 7.0° vs 50.1° ± 5.1°, P < 0.01 and 42.7% vs 57.3%, P < 0.01). The wedging of vertebrae was significantly higher in group B than in group A (50.1° ± 5.1° vs 26.7° ± 2.7°, P < 0.01). Additionally, correlation analysis revealed a significant correlation between the apical vertebral wedging angle and GK (R = 0.850, P = 0.001).Various disc and vertebral wedging exist in thoracolumbar kyphosis secondary to AS. The discs wedging contributes more to the thoracolumbar kyphosis in patients with GK < 70° than vertebral wedging, whereas vertebral wedging is more conducive to the thoracolumbar kyphosis in patients with GK ≥ 70°, indicating different biomechanical pathogenesis in varied severity of thoracolumbar kyphosis secondary to AS.

Vertebral body or intervertebral disc wedging: which contributes more to thoracolumbar kyphosis in ankylosing spondylitis patients?

PubMed Central

Liu, Hao; Qian, Bang-Ping; Qiu, Yong; Wang, Yan; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang

2016-01-01

Abstract Both vertebral body wedging and disc wedging are found in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis. However, their relative contribution to thoracolumbar kyphosis is not fully understood. The objective of this study was to compare different contributions of vertebral and disc wedging to the thoracolumbar kyphosis in AS patients, and to analyze the relationship between the apical vertebral wedging angle and thoracolumbar kyphosis. From October 2009 to October 2013, a total of 59 consecutive AS patients with thoracolumbar kyphosis with a mean age of 38.1 years were recruited in this study. Based on global kyphosis (GK), 26 patients with GK < 70° were assigned to group A, and the other 33 patients with GK ≥ 70° were included in group B. Each GK was divided into disc wedge angles and vertebral wedge angles. The wedging angle of each disc and vertebra comprising the thoracolumbar kyphosis was measured, and the proportion of the wedging angle to the GK was calculated accordingly. Intergroup and intragroup comparisons were subsequently performed to investigate the different contributions of disc and vertebra to the GK. The correlation between the apical vertebral wedging angle and GK was calculated by Pearson correlation analysis. The duration of disease and sex were also recorded in this study. With respect to the mean disease duration, significant difference was observed between the two groups (P < 0.01). The wedging angle and wedging percentage of discs were significantly higher than those of vertebrae in group A (34.8° ± 2.5° vs 26.7° ± 2.7°, P < 0.01 and 56.6% vs 43.4%, P < 0.01), whereas disc wedging and disc wedging percentage were significantly lower than vertebrae in group B (37.6° ± 7.0° vs 50.1° ± 5.1°, P < 0.01 and 42.7% vs 57.3%, P < 0.01). The wedging of vertebrae was significantly higher in group B than in group A (50.1° ± 5.1° vs 26.7° ± 2.7°, P < 0.01). Additionally, correlation analysis revealed a significant correlation between the apical vertebral wedging angle and GK (R = 0.850, P = 0.001). Various disc and vertebral wedging exist in thoracolumbar kyphosis secondary to AS. The discs wedging contributes more to the thoracolumbar kyphosis in patients with GK < 70° than vertebral wedging, whereas vertebral wedging is more conducive to the thoracolumbar kyphosis in patients with GK ≥ 70°, indicating different biomechanical pathogenesis in varied severity of thoracolumbar kyphosis secondary to AS. PMID:27661026

Maintaining knife sharpness in industrial meat cutting: A matter of knife or meat cutter ability.

PubMed

Karltun, J; Vogel, K; Bergstrand, M; Eklund, J

2016-09-01

Knife sharpness is imperative in meat cutting. The aim of this study was to compare the impact of knife blade steel quality with meat cutters' individual ability to maintain the cutting edge sharp in an industrial production setting. Twelve meat cutters in two different companies using three different knives during normal production were studied in this quasi-experimental study. Methods included were measuring knife cutting force before and after knife use, time knives were used, ratings of sharpness and discomfort and interviews. Results showed that the meat cutters' skill of maintaining sharpness during work had a much larger effect on knife sharpness during work than the knife steel differences. The ability was also related to feelings of discomfort and to physical exertion. It was found that meat cutters using more knives were more likely to suffer from discomfort in the upper limbs, which is a risk for developing MSD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevention and reversal of experimental autoimmune thyroiditis (EAT) in mice by administration of anti-L3T4 monoclonal antibody at different stages of disease development.

PubMed

Stull, S J; Kyriakos, M; Sharp, G C; Braley-Mullen, H

1988-11-01

Experimental autoimmune thyroiditis (EAT) can be induced in CBA/J mice following the transfer of spleen cells from mouse thyroglobulin (MTg)-sensitized donors that have been activated in vitro with MTg. Since L3T4+ T cells are required to transfer EAT in this model, the present study was undertaken to assess the effectiveness of the anti-L3T4 monoclonal antibody (mAb) GK1.5 in preventing or arresting the development of EAT. Spleen cells from mice given mAb GK1.5 prior to sensitization with MTg and adjuvant could not transfer EAT to normal recipients and cells from these mice did not proliferate in vitro to MTg. Donor mice given GK1.5 before immunization did not develop anti-MTg autoantibody and recipients of cells from such mice also produced little anti-MTg. GK1.5 could also prevent the proliferation and activation of sensitized effector cell precursors when added to in vitro cultures. When a single injection of mAb GK1.5 was given to recipients of in vitro-activated spleen cells, EAT was reduced whether the mAb was given prior to cell transfer or as late as 19 days after cell transfer. Whereas the incidence and severity of EAT was consistently reduced by injecting recipient mice with GK1.5, the same mice generally had no reduction in anti-MTg autoantibody. Since EAT is consistently induced in control recipients by 14-19 days after cell transfer, the ability of mAb GK1.5 to inhibit EAT when injected 14 or 19 days after cell transfer indicates that a single injection of the mAb GK1.5 can cause reversal of the histopathologic lesions of EAT in mice. These studies further establish the important role of L3T4+ T cells in the pathogenesis of EAT in mice and also suggest that therapy with an appropriate mAb may be an effective treatment for certain autoimmune diseases even when the therapy is initiated late in the course of the disease.

Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus?

PubMed Central

Panveloski-Costa, Ana Carolina; Yokota, Caroline Naomi Fukusawa; Pereira, Joice Naiara Bertaglia; Filho, Jorge Mancini; Torres, Rosangela Pavan; Hirabara, Sandro Massao; Curi, Rui; Alba-Loureiro, Tatiana Carolina

2017-01-01

Type 2 Diabetes mellitus (T2DM) is an evident growing disease that affects different cultures throughout the world. T2DM occurs under the influence of three main factors: the genetic background, environmental and behavioral components. Obesity is strongly associated to the development of T2DM in the occident, while in the orient most of the diabetic patients are considered lean. Genetics may be a key factor in the development of T2DM in societies where obesity is not a recurrent public health problem. Herein, two different models of rats were used to understand their differences and reliability as experimental models to study the pathophysiology of T2DM, in two different approaches: the genetic (GK rats) and the environmental (HFD-induced obese rats) influences. GK rats were resistant to weight gain even though food/energy consumption (relative to body weight) was higher in this group. HFD, on the other hand, induced obesity in Wistar rats. White adipose tissue (WAT) expansion in this group was accompanied by immune cells infiltration, inflammation and insulin resistance. GK rats also presented WAT inflammation and insulin resistance; however, no immune cells infiltration was observed in the WAT of this group. Liver of HFD group presented fat accumulation without differences in inflammatory cytokines content, while liver of GK rats didn’t present fat accumulation, but showed an increase of IL-6 and IL-10 content and glycogen. Also, GK rats showed increased plasma GOT and GPT. Soleus muscle of HFD presented normal insulin signaling, contrary to GK rats, which presented higher content of basal phosphorylation of GSK-3β. Our results demonstrated that HFD developed a mild insulin resistance in Wistar rats, but was not sufficient to develop T2DM. In contrast, GK rats presented all the typical hallmarks of T2DM, such as insulin resistance, defective insulin production, fasting hyperglycemia/hyperinsulinemia and lipid plasma alteration. Thus, on the given time point of this study, we may conclude that only GK rats shown to be a reliable model to study T2DM. PMID:29220408

Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model of Diabetes Mellitus Type 2.

PubMed

Zambrana, Silvia; Lundqvist, Lena C E; Veliz, Virginia; Catrina, Sergiu-Bogdan; Gonzales, Eduardo; Östenson, Claes-Göran

2018-01-15

Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus ( AC ) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single oral administration of AC extract (2000 mg/kg body weight) improved glucose tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the glucose tolerance evaluated by the area under the curve (AUC) of glucose levels during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK (19.83%) and W rats (10.7%). This effect was secondary to an increase in serum insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated from treated animals, where the chronic AC exposure increased the insulin production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold in W rat islets, and the insulin secretion in perifused GK and W rat islets increased 31 and nine times, respectively. The mechanism of action of AC on insulin secretion was shown to involve calcium, PKA and PKC activation, and G-protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L-type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC inhibitor) and 20% by pertussis toxin (G-protein suppressor).

Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model of Diabetes Mellitus Type 2

PubMed Central

Zambrana, Silvia; Lundqvist, Lena C. E.; Veliz, Virginia; Catrina, Sergiu-Bogdan; Gonzales, Eduardo; Östenson, Claes-Göran

2018-01-01

Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single oral administration of AC extract (2000 mg/kg body weight) improved glucose tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the glucose tolerance evaluated by the area under the curve (AUC) of glucose levels during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK (19.83%) and W rats (10.7%). This effect was secondary to an increase in serum insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated from treated animals, where the chronic AC exposure increased the insulin production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold in W rat islets, and the insulin secretion in perifused GK and W rat islets increased 31 and nine times, respectively. The mechanism of action of AC on insulin secretion was shown to involve calcium, PKA and PKC activation, and G-protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L-type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC inhibitor) and 20% by pertussis toxin (G-protein suppressor). PMID:29342984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Haksoo; Welford, Scott; Fabien, Jeffrey

Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, withmore » radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A passing rate of 99% was measured in areas of above 40% of the prescription dose. The final inverse treatment plan was comprised of 43 beams ranging from 5 to 12.5 mm in diameter (2.5 mm size increments are available up to 15 mm in diameter collimation). Using the Xsight Spine Tracking module, the CyberKnife system could not reliably identify and track the tiny mouse spine; however, the CyberKnife system could identify and track the fiducial markers on the 3D mold.In vivo positional accuracy analysis using the 3D mold generated a mean error of 1.41 mm ± 0.73 mm when fiducial markers were used for position tracking. Analysis of the dissected brain confirmed the ability to target the correct brain volume. Conclusions: With the use of a stereotactic body mold with fiducial markers, microCT imaging, and resolution down-sampling, the CyberKnife system can successfully perform small-animal radiotherapy studies.« less

21 CFR 886.4230 - Ophthalmic knife test drum.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic knife test drum. 886.4230 Section 886...) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4230 Ophthalmic knife test drum. (a) Identification. An ophthalmic knife test drum is a device intended to test the keenness of ophthalmic surgical...

Cross-Grain Knife Planing Improves Surface Quality and Utilization of Aspen

Treesearch

Harold A. Stewart

1971-01-01

Aspen at 6 percent moisture content was planed parallel to the grain and across the grain on a cabinet planer with a 25? rake angle, 1/16- and 1/32-inch depth of cut, and 20 knife marks per inch. Aspen was also cross-grain knife planed with a 45? rake angle, 1/32-, 1/16-, and 1/8-inch depths of cut, and 20, 10, 5, and 2.5 knife marks per inch. Cross-grain knife...

Penetration tests to study the mechanical tribological properties of chisel type knife

NASA Astrophysics Data System (ADS)

Vlăduţoiu, L.; Chişiu, G.; Andrei, T.; Predescu, A.; Muraru, C.; Vlăduţ, V.

2017-02-01

The goal of this study was to analyze the behaviour of chisel knife type penetration in a certain type of sand. A series of penetration tests were carried out with chisel knife type, the answer to penetration depending mainly on nature, shape, size of knife and operating parameters such as speed, depth and working conditions. Tests were conducted in work conditions with wet sand and dry sand and determined force of resistance to penetration of the chisel knife type to a certain depth.

Effect of modified atmosphere packaging on quality and shelf life of 'Robusta' banana (Musa sp.) stored at low temperature.

PubMed

Kudachikar, V B; Kulkarni, S G; Prakash, M N Keshava

2011-06-01

Banana (Musa sp var. 'Robusta') stored under active and passive modified atmosphere packaging (MAP) at 12 ± 1°C and 85-90% RH for 2 seasons were evaluated for fruit quality and shelf-life. A steady state of about 8.6 and 8.2% of CO2 and 2.8 and 2.6% of O2 in passive MAP and MAP+GK (Green Keeper) packages, respectively, were established after 3 weeks of storage. Passive MAP and MAP+GK treatments of banana resulted in reduction in physiological loss in weight (PLW) of 0.7 and 0.8% after 5 and 7 weeks of storage, respectively as against 5% PLW in openly kept green banana after 3 weeks. Both MAP and MAP+GK treatments delayed colour, texture, pulp to peel ratio and total soluble solids (TSS) content as compared to openly kept control banana. Results indicated that the shelf life of fruits packed under MAP and MAP+GK could be extended up to 5 and 7 weeks, respectively as compared to 3 weeks for openly kept control fruits. Sensory quality of fully ripe fruits of both passive MAP and MAP+GK treatments, 5 days after ethrel dip was very good. Thus, MAP+GK at 12 ± 1°C and 85-90% RH could be commercially used for long term storage and long distance transportation of banana with maximum shelf-life of 7 weeks.

Restitution of defective glucose-stimulated insulin secretion in diabetic GK rat by acetylcholine uncovers paradoxical stimulatory effect of beta-cell muscarinic receptor activation on cAMP production.

PubMed

Dolz, Manuel; Bailbé, Danielle; Giroix, Marie-Hélène; Calderari, Sophie; Gangnerau, Marie-Noelle; Serradas, Patricia; Rickenbach, Katharina; Irminger, Jean-Claude; Portha, Bernard

2005-11-01

Because acetylcholine (ACh) is a recognized potentiator of glucose-stimulated insulin release in the normal beta-cell, we have studied ACh's effect on islets of the Goto-Kakizaki (GK) rat, a spontaneous model of type 2 diabetes. We first verified that ACh was able to restore the insulin secretory glucose competence of the GK beta-cell. Then, we demonstrated that in GK islets 1) ACh elicited a first-phase insulin release at low glucose, whereas it had no effect in Wistar; 2) total phospholipase C activity, ACh-induced inositol phosphate production, and intracellular free calcium concentration ([Ca2+]i) elevation were normal; 3) ACh triggered insulin release, even in the presence of thapsigargin, which induced a reduction of the ACh-induced [Ca2+]i response (suggesting that ACh produces amplification signals that augment the efficacy of elevated [Ca2+]i on GK exocytosis); 4) inhibition of protein kinase C did not affect [Ca2+]i nor the insulin release responses to ACh; and 5) inhibition of cAMP-dependent protein kinases (PKAs), adenylyl cyclases, or cAMP generation, while not affecting the [Ca2+]i response, significantly lowered the insulinotropic response to ACh (at low and high glucose). In conclusion, ACh acts mainly through activation of the cAMP/PKA pathway to potently enhance Ca2+-stimulated insulin release in the GK beta-cell and, in doing so, normalizes its defective glucose responsiveness.

Interfraction and intrafraction performance of the Gamma Knife Extend system for patient positioning and immobilization.

PubMed

Schlesinger, David; Xu, Zhiyuan; Taylor, Frances; Yen, Chun-Po; Sheehan, Jason

2012-12-01

The Extend system for the Gamma Knife Perfexion makes possible multifractional Gamma Knife treatments. The Extend system consists of a vacuum-monitored immobilization frame and a positioning measurement system used to determine the location of the patient's head within the frame at the time of simulation imaging and before each treatment fraction. The measurement system consists of a repositioning check tool (RCT), which attaches to the Extend frame, and associated digital measuring gauges. The purpose of this study is to evaluate the performance of the Extend system for patient repositioning before each treatment session (fraction) and patient immobilization between (interfraction) and during (intrafraction) each session in the first 10 patients (36 fractional treatments) treated at the University of Virginia. The RCT was used to acquire a set of reference measurements for each patient position at the time of CT simulation. Repositioning measurements were acquired before each fraction, and the patient position was adjusted until the residual radial difference from the reference position measurements was less than 1 mm. After treatment, patient position measurements were acquired, and the difference between those measurements and the ones obtained for patient position before the fraction was calculated as a measure of immobilization capability. Analysis of patient setup and immobilization performance included calculation of the group mean, standard deviation (SD), and distribution of systematic (components affecting all fractions) and random (per fraction) uncertainty components. Across all patients and fractions, the mean radial setup difference from the reference measurements was 0.64 mm, with an SD of 0.24 mm. The distribution of systematic uncertainty (Σ) was 0.17 mm, and the distribution of random uncertainty (σ) was 0.16 mm. The root mean square (RMS) differences for each plate of the RCT were as follows: right = 0.35 mm; left = 0.41 mm; superior = 0.28 mm; and anterior = 0.20 mm. The mean intrafractional positional difference across all treatments was 0.47 mm, with an SD of 0.30 mm. The distribution of systematic uncertainty was 0.18 mm, and the distribution of random uncertainty was 0.22 mm. The RMS differences for each plate of the RCT were 0.24 mm for the right plate, 0.22 mm for the left plate, 0.24 mm for the superior plate, and 0.34 mm for the anterior plate. Data from 1 fraction were excluded from the analysis because the vacuum-monitoring interlock detected patient motion, which in turn required repositioning in the middle of the fraction. The Extend system can be used to reposition and immobilize patients in a radiosurgical setting. However, care should be taken to acquire measurements that can implicitly account for rotations of the patient's head. Further work is required to determine the sensitivity of the vacuum interlock to detect patient motion.

Quantifying and improving the efficiency of Gamma Knife treatment plans for brain metastases: results of a 1-year audit.

PubMed

Wright, Gavin; Hatfield, Paul; Loughrey, Carmel; Reiner, Beatrice; Bownes, Peter

2014-12-01

A method for quantifying the efficiency of Gamma Knife treatment plans for metastases was previously implemented by the authors to retrospectively identify the least efficient plans and has provided insights into improved planning strategies. The aim of the current work was to ascertain whether those insights led to improved treatment plans. Following completion of the initial study, a 1-year audit of metastasis plans created at St. James's Institute of Oncology was carried out. Audited recent plans were compared with the earlier plans of the initial study, in terms of their efficiency and dosimetric quality. The statistical significance of any differences between relevant plan parameters was quantified by Mann-Whitney U-tests. Comparisons were made between all plans and repeated for a reduced set of plans from which the smallest lesions treated with a single 4-mm shot were excluded. The plan parameters compared were a plan efficiency index (PEI), the number of shots, Paddick conformity index (PCI), gradient index (GI), and percent coverage (of the lesion by the prescription isodose). A total of 157 metastatic lesions were included in the audit and were compared with 241 in the initial study. In a comparison of all cases, the audited plans achieved a higher median PEI score than did the earlier plans from the initial study (1.08 vs 1.02), indicating improved efficiency of the audited plans. When the smallest lesions (for which there was little scope for varying plan strategy) were discounted, the improvement in median PEI score was greater (1.23 vs 1.03, p < 0.001). This improvement in efficiency corresponds to an estimated mean (maximum) time saving of 15% (66%) per lesion (11 minutes [64 minutes] on the day of treatment). The modified planning strategy yielding these efficiency improvements did not rely on the use of significantly fewer shots (median 11 vs 11 shots, p = 0.924), nor did it result in significant detriment to dosimetric quality (median coverage 99% vs 99%, median PCI 0.84 vs 0.83, p = 0.449, and median GI 2.72 vs 2.67, p = 0.701, audited plans vs initial plans, respectively). Choice of planning strategy can substantially affect plan efficiency and thus strongly influence treatment time. Through increased emphasis on efficiency, resulting from the introduction of PEI combined with a modified planning strategy informed by previous work, it has been possible to reduce times for metastatic plans without compromising their dosimetric quality. Although the average time savings achieved per lesion are moderate, the potential benefits per patient are greater for those with multiple metastases. Reducing treatment times has clear benefits with regard to patient comfort and throughput. In addition, optimization of plan efficiency may potentially affect the biologically effective dose from Gamma Knife treatments and offers opportunity for further work.

Palliation of Postintubation Tracheal Stenosis Using Insulation-Tipped Diathermic Knife 2: A Case Report

PubMed Central

Yoon, Seon Bin; Park, Yong Won; Cheon, Mi Ju; Koh, Young Min; Park, Sanghoon; Kim, Se Joong; Lee, Seung Hyeun

2015-01-01

Objective To report the first case of using the insulation-tipped diathermic knife 2 (IT knife-2) for the treatment of postintubation tracheal stenosis. Clinical Presentation and Intervention A 71-year-old female patient with a history of endotracheal intubation 3 years earlier presented with throat discomfort, gross wheezing and dyspnea. Chest imaging and bronchoscopy demonstrated a strand-like tracheal stenosis in the upper trachea. The IT knife-2 was used to treat the patient and the lesion was palliated without complication. Conclusion This case was successfully treated with the IT knife-2 and thus implies a potential usefulness of the IT knife-2 as a new modality for bronchoscopic intervention. PMID:26390388

19 CFR 12.95 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... handle of the knife, or any knife with a blade which opens automatically by operation of inertia, gravity... button or device in the handle of the knife or by operation of inertia, gravity, or both; (3) Unassembled... handle of the knife or by operation of inertia, gravity, or both; or (4) Knives with a detachable blade...

19 CFR 12.95 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... handle of the knife, or any knife with a blade which opens automatically by operation of inertia, gravity... button or device in the handle of the knife or by operation of inertia, gravity, or both; (3) Unassembled... handle of the knife or by operation of inertia, gravity, or both; or (4) Knives with a detachable blade...

19 CFR 12.95 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... handle of the knife, or any knife with a blade which opens automatically by operation of inertia, gravity... button or device in the handle of the knife or by operation of inertia, gravity, or both; (3) Unassembled... handle of the knife or by operation of inertia, gravity, or both; or (4) Knives with a detachable blade...

19 CFR 12.95 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... handle of the knife, or any knife with a blade which opens automatically by operation of inertia, gravity... button or device in the handle of the knife or by operation of inertia, gravity, or both; (3) Unassembled... handle of the knife or by operation of inertia, gravity, or both; or (4) Knives with a detachable blade...

19 CFR 12.95 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... handle of the knife, or any knife with a blade which opens automatically by operation of inertia, gravity... button or device in the handle of the knife or by operation of inertia, gravity, or both; (3) Unassembled... handle of the knife or by operation of inertia, gravity, or both; or (4) Knives with a detachable blade...

Relative risk analysis in regulating the use of radiation-emitting medical devices. A preliminary application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, E.D.; Banks, W.W.; Altenbach, T.J.

1995-09-01

This report describes a preliminary application of an analysis approach for assessing relative risks in the use of radiation- emitting medical devices. Results are presented on human-initiated actions and failure modes that are most likely to occur in the use of the Gamma Knife, a gamma irradiation therapy device. This effort represents an initial step in a US Nuclear Regulatory Commission (NRC) plan to evaluate the potential role of risk analysis in regulating the use of nuclear medical devices. For this preliminary application of risk assessment, the focus was to develop a basic process using existing techniques for identifying themore » most likely risk contributors and their relative importance. The approach taken developed relative risk rankings and profiles that incorporated the type and quality of data available and could present results in an easily understood form. This work was performed by the Lawrence Livermore National Laboratory for the NRC.« less

Deoxyribonucleoside kinases in mitochondrial DNA depletion.

PubMed

Saada-Reisch, Ann

2004-10-01

Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of mitochondrial disorders, manifested by a decreased mtDNA copy number and respiratory chain dysfunction. Primary MDS are inherited autosomally and may affect a single organ or multiple tissues. Mutated mitochondrial deoxyribonucleoside kinases; deoxyguanosine kinase (dGK) and thymidine kinase 2 (TK2), were associated with the hepatocerebral and myopathic forms of MDS respectively. dGK and TK2 are key enzymes in the mitochondrial nucleotide salvage pathway, providing the mitochondria with deoxyribonucleotides (dNP) essential for mtDNA synthesis. Although the mitochondrial dNP pool is physically separated from the cytosolic one, dNP's may still be imported through specific transport. Non-replicating tissues, where cytosolic dNP supply is down regulated, are thus particularly vulnerable to dGK and TK2 deficiency. The overlapping substrate specificity of deoxycytidine kinase (dCK) may explain the relative sparing of muscle in dGK deficiency, while low basal TK2 activity render this tissue susceptible to TK2 deficiency. The precise pathophysiological mechanisms of mtDNA depletion due to dGK and TK2 deficiencies remain to be determined, though recent findings confirm that it is attributed to imbalanced dNTP pools.

Iridium-Knife: Another knife in radiation oncology.

PubMed

Milickovic, Natasa; Tselis, Nikolaos; Karagiannis, Efstratios; Ferentinos, Konstantinos; Zamboglou, Nikolaos

Intratarget dose escalation with superior conformity is a defining feature of three-dimensional (3D) iridium-192 ( 192 Ir) high-dose-rate (HDR) brachytherapy (BRT). In this study, we analyzed the dosimetric characteristics of interstitial 192 Ir HDR BRT for intrathoracic and cerebral malignancies. We examined the dose gradient sharpness of HDR BRT compared with that of linear accelerator-based stereotactic radiosurgery and stereotactic body radiation therapy, usually called X-Knife, to demonstrate that it may as well be called a Knife. Treatment plans for 10 patients with recurrent glioblastoma multiforme or intrathoracic malignancies, five of each entity, treated with X-Knife (stereotactic radiosurgery for glioblastoma multiforme and stereotactic body radiation therapy for intrathoracic malignancies) were replanned for simulated HDR BRT. For 3D BRT planning, we used identical structure sets and dose prescription as for the X-Knife planning. The indices for qualitative treatment plan analysis encompassed planning target volume coverage, conformity, dose falloff gradient, and the maximum dose-volume limits to different organs at risk. Volume coverage in HDR plans was comparable to that calculated for X-Knife plans with no statistically significant difference in terms of conformity. The dose falloff gradient-sharpness-of the HDR plans was considerably steeper compared with the X-Knife plans. Both 3D 192 Ir HDR BRT and X-Knife are effective means for intratarget dose escalation with HDR BRT achieving at least equal conformity and a steeper dose falloff at the target volume margin. In this sense, it can reasonably be argued that 3D 192 Ir HDR BRT deserves also to be called a Knife, namely Iridium-Knife. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Usefulness of IT knife nano for endoscopic submucosal dissection of large colo-rectal lesions.

PubMed

Suzuki, T; Hara, T; Kitagawa, Y; Yamaguchi, T

2016-01-01

Endoscopic submucosal dissection (ESD) is currently widely conducted for the treatment of early gastrointestinal -cancers. Due to the characteristic anatomy of the large intestine, needle- tip type devices such as Dual knife are mainly used in colorectal ESD. On the other hand, the non- needle-tip type IT knife is a unique device with an insulated tip, and has been reported to be safe, efficacious and speedy when used in gastric ESD. A new model of IT knife, IT knife nano, anticipated to be useful for esophageal and colorectal ESD has become available, but its usefulness has not been reported. Therefore, we performed this study to evaluate the usefulness of IT knife nano for ESD of large colorectal lesions. Previous studies have shown that a tumor size of 40 mm or above significantly prolongs treatment time and is a factor of treatment difficulty. We selected colorectal lesions of 40 mm and above, and compared 32 lesions treated with Dual knife alone before IT knife nano was available (No-IT group) and 40 cases treated with IT knife nano as a second knife after IT knife nano became available (IT group). We assessed en bloc resection rate, complete en bloc resection rate, complication rate and treatment time. The en bloc resection rates in No-IT group and IT group were 100% and 97.5%, respectively, with no significant difference. The respective median treatment time was 70 min and 51 min, and was significantly shortened in IT group (P < 0.05). The respective rates of procedure- related perforation were 3.1% and 0% ; in IT group suggesting a tendency of reduced incidence. Use of IT knife nano in ESD for large colorectal -lesions achieves the same levels of efficacy and safety as conventional device, with the additional merit of shortening treatment time. © Acta Gastro-Enterologica Belgica.

Prompt gamma imaging of proton pencil beams at clinical dose rate

NASA Astrophysics Data System (ADS)

Perali, I.; Celani, A.; Bombelli, L.; Fiorini, C.; Camera, F.; Clementel, E.; Henrotin, S.; Janssens, G.; Prieels, D.; Roellinghoff, F.; Smeets, J.; Stichelbaut, F.; Vander Stappen, F.

2014-10-01

In this work, we present experimental results of a prompt gamma camera for real-time proton beam range verification. The detection system features a pixelated Cerium doped lutetium based scintillation crystal, coupled to Silicon PhotoMultiplier arrays, read out by dedicated electronics. The prompt gamma camera uses a knife-edge slit collimator to produce a 1D projection of the beam path in the target on the scintillation detector. We designed the detector to provide high counting statistics and high photo-detection efficiency for prompt gamma rays of several MeV. The slit design favours the counting statistics and could be advantageous in terms of simplicity, reduced cost and limited footprint. We present the description of the realized gamma camera, as well as the results of the characterization of the camera itself in terms of imaging performance. We also present the results of experiments in which a polymethyl methacrylate phantom was irradiated with proton pencil beams in a proton therapy center. A tungsten slit collimator was used and prompt gamma rays were acquired in the 3-6 MeV energy range. The acquisitions were performed with the beam operated at 100 MeV, 160 MeV and 230 MeV, with beam currents at the nozzle exit of several nA. Measured prompt gamma profiles are consistent with the simulations and we reached a precision (2σ) in shift retrieval of 4 mm with 0.5 × 108, 1.4 × 108 and 3.4 × 108 protons at 100, 160 and 230 MeV, respectively. We conclude that the acquisition of prompt gamma profiles for in vivo range verification of proton beam with the developed gamma camera and a slit collimator is feasible in clinical conditions. The compact design of the camera allows its integration in a proton therapy treatment room and further studies will be undertaken to validate the use of this detection system during treatment of real patients.

Ketamine, propofol and low dose remifentanil versus propofol and remifentanil for ERCP outside the operating room: Is ketamine not only a “rescue drug”?

PubMed Central

Fabbri, Lea Paola; Nucera, Maria; Marsili, Massimo; Al Malyan, Mohamed; Becchi, Chiara

2012-01-01

Summary Background Endoscopic retrograde cholangiopancreatography ERCP is a painful and long procedure requiring transient deep analgesia and conscious sedation. An ideal anaesthetic that guarantees a rapid and smooth induction, good quality of maintenance, lack of adverse effects and rapid recovery is still lacking. This study aimed to compare safety and efficacy of a continuous infusion of low dose remifentanil plus ketamine combined with propofol in comparison to the standard regimen dose of remifentanil plus propofol continuous infusion during ERCP. Material/Methods 322 ASAI-III patients, 18–85 years old and scheduled for planned ERCP were randomized. Exclusion criteria were a predictable difficult airway, drug allergy, and ASA IV–V patients. We evaluated Propofol 1 mg/kg/h plus Remifentanil 0.25 μg/kg/min (GR) vs. Propofol 1 mg/kg/h plus Ketamine 5 μg/kg/min and Remifentanil 0.1 μg/kg/min (GK). Main outcome measures were respiratory depression, nausea/vomiting, quality of intraoperative conditions, and discharge time. P≤0.05 was statistically significant (95% CI). Results Respiratory depression was observed in 25 patients in the GR group compared to 9 patients in the GK group (p=0.0035). ERCP was interrupted in 9 cases of GR vs. no cases in GK; patients ventilated without any complication. Mean discharge time was 20±5 min in GK and 35±6 min in GR (p=0.0078) and transfer to the ward delayed because of nausea and vomiting in 30 patients in GR vs. 5 patients in GK (p=0.0024). Quality of intraoperative conditions was rated highly satisfactory in 92% of GK vs. 67% of GR (p=0.028). Conclusions The drug combination used in GK confers clinical advantages because it avoids deep sedation, maintains adequate analgesia with conscious sedation, and achieves lower incidence of postprocedural nausea and vomiting with shorter discharge times. PMID:22936194

cAMP-secretion coupling is impaired in diabetic GK/Par rat β-cells: a defect counteracted by GLP-1.

PubMed

Dolz, Manuel; Movassat, Jamileh; Bailbé, Danielle; Le Stunff, Hervé; Giroix, Marie-Hélène; Fradet, Magali; Kergoat, Micheline; Portha, Bernard

2011-11-01

cAMP-raising agents with glucagon-like peptide-1 (GLP-1) as the first in class, exhibit multiple actions that are beneficial for the treatment of type 2 diabetic (T2D) patients, including improvement of glucose-induced insulin secretion (GIIS). To gain additional insight into the role of cAMP in the disturbed stimulus-secretion coupling within the diabetic β-cell, we examined more thoroughly the relationship between changes in islet cAMP concentration and insulin release in the GK/Par rat model of T2D. Basal cAMP content in GK/Par islets was significantly higher, whereas their basal insulin release was not significantly different from that of Wistar (W) islets. Even in the presence of IBMX or GLP-1, their insulin release did not significantly change despite further enhanced cAMP accumulation in both cases. The high basal cAMP level most likely reflects an increased cAMP generation in GK/Par compared with W islets since 1) forskolin dose-dependently induced an exaggerated cAMP accumulation; 2) adenylyl cyclase (AC)2, AC3, and G(s)α proteins were overexpressed; 3) IBMX-activated cAMP accumulation was less efficient and PDE-3B and PDE-1C mRNA were decreased. Moreover, the GK/Par insulin release apparatus appears less sensitive to cAMP, since GK/Par islets released less insulin at submaximal cAMP levels and required five times more cAMP to reach a maximal secretion rate no longer different from W. GLP-1 was able to reactivate GK/Par insulin secretion so that GIIS became indistinguishable from that of W. The exaggerated cAMP production is instrumental, since GLP-1-induced GIIS reactivation was lost in the presence the AC blocker 2',5'-dideoxyadenosine. This GLP-1 effect takes place in the absence of any improvement of the [Ca(2+)](i) response and correlates with activation of the cAMP-dependent PKA-dependent pathway.

Ischemic preconditioning maintains the immunoreactivities of glucokinase and glucokinase regulatory protein in neurons of the gerbil hippocampal CA1 region following transient cerebral ischemia

PubMed Central

CHO, YOUNG SHIN; CHO, JUN HWI; SHIN, BICH-NA; CHO, GEUM-SIL; KIM, IN HYE; PARK, JOON HA; AHN, JI HYEON; OHK, TAEK GEUN; CHO, BYUNG-RYUL; KIM, YOUNG-MYEONG; HONG, SEONGKWEON; WON, MOO-HO; LEE, JAE-CHUL

2015-01-01

Glucokinase (GK) is involved in the control of blood glucose homeostasis. In the present study, the effect of ischemic preconditioning (IPC) on the immunoreactivities of GK and its regulatory protein (GKRP) following 5 min of transient cerebral ischemia was investigated in gerbils. The gerbils were randomly assigned to four groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the gerbils to 2 min of ischemia, followed by 1 day of recovery. In the ischemia-operated group, a significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) at 5 days post-ischemia; however, in the IPC+ischemia-operated group, the neurons in the SP were well protected. Following immunohistochemical investigation, the immunoreactivities of GK and GKRP in the neurons of the SP were markedly decreased in the CA1, but not the CA2/3, from 2 days post-ischemia, and were almost undetectable in the SP 5 days post-ischemia. In the IPC + ischemia-operated group, the immunoreactivities of GK and GKRP in the SP of the CA1 were similar to those in the sham-group. In brief, the findings of the present study demonstrated that IPC notably maintained the immunoreactivities of GK and GKRP in the neurons of the SP of CA1 following ischemia-reperfusion. This indicated that GK and GKRP may be necessary for neuron survival against transient cerebral ischemia. PMID:26134272

Development of an air knife to remove seed coat fragments during lint cleaning

USDA-ARS?s Scientific Manuscript database

An air knife is a tool commonly used to blow off debris in a manufacturing line. The knife may also be used to break the attachment force between a lint cleaner saw and a seed coat fragment (SCF) with attached fiber, and remove them. Work continued on evaluating an auxiliary air knife mounted on t...

Current transport and mass separation for an asymmetric fluctuation system with correlated noises

NASA Astrophysics Data System (ADS)

Wang, Jie; Ning, Li-Juan

2018-01-01

Not Available Projected supported by the National Natural Science Foundation of China (Grant No. 11202120) and the Fundamental Research Funds for the Central Universities of China (Grant Nos. GK201502007 and GK201701001).

NSF GK-12 Fellows as Mentors for K-12 Teachers Participating in Field Research Experiences

NASA Astrophysics Data System (ADS)

Ellins, K.; Perry, E.

2005-12-01

The University of Texas Institute for Geophysics (UTIG) recognizes the value of providing educational opportunities to K-12 teachers who play a critical role in shaping the minds of young people who are the future of our science. To that end, UTIG established the "Texas Teachers in the Field" program in 2000 to formalize the participation of K-12 teachers in field programs that included UTIG scientists. In 2002, "Texas Teachers in the Field" evolved through UTIG's involvement in a University of Texas at Austin GK-12 project led by the Environmental Sciences Institute, which enabled UTIG to partner a subset of GK-12 Fellows with teachers participating in geophysical field programs. During the three years of the GK-12 project, UTIG successfully partnered four GK-12 Fellows with five K-12 teachers. The Fellows served as mentors to the teachers, as liaisons between UTIG scientists leading field programs and teachers and their students, and as resources in science, mathematics, and technology instruction. Specifically, Fellows prepared teachers and their students for the field investigations, supervised the design of individual Teacher Research Experience (TRE) projects, and helped teachers to develop standards-aligned curriculum resources related to the field program for use in their own classrooms, as well as broader distribution. Although all but one TRE occurred during the school year, Texas school districts and principals were willing to release teachers to participate because the experience and destinations were so extraordinary (i.e., a land-based program in Tierra del Fuego, Argentina; and research cruises to the Southeast Caribbean Sea and Hess Deep in the Pacific Ocean) and carried opportunities to work with scientists from around the world. This exceptional collaboration of GK-12 Fellows, K-12 teachers and research scientists enriches K-12 student learning and promotes greater enthusiasm for science. The level of mentoring, preparation and follow-up provided by the GK-12 Fellows was important in helping teachers transfer components of a challenging field research experience to their students. Participating research scientists were able to convey the importance of their science to a wider audience. NSF GK-12 Fellows gained valuable experience in communicating scientific knowledge and field skills to K-12 teachers and students, became more knowledgeable about K-12 science education and were exposed to advances in pedagogy.

Observation of Phase Objects by Using an X-ray Microscope with a Foucault Knife-Edge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, N.; Sasaya, T.; Imai, Y.

2011-09-09

An x-ray microscope with a zone plate was assembled at the synchrotron radiation source of BL3C, Photon Factory. A Foucault knife-edge was set at the back focal plate of the objective zone plate and phase retrieval was tested by scanning the knife-edge. A preliminary result shows that scanning the knife-edge during exposure was effective for phase retrieval. Phase-contrast tomography was investigated using differential projection images calculated from two Schlieren images with the oppositely oriented knife-edges. Fairly good reconstruction images of polystyrene beads and spores could be obtained.

Combination of water-jet dissection and needle-knife as a hybrid knife simplifies endoscopic submucosal dissection.

PubMed

Lingenfelder, Tobias; Fischer, Klaus; Sold, Moritz G; Post, Stefan; Enderle, Markus D; Kaehler, Georg F B A

2009-07-01

The safety and efficacy of endoscopic submucosal dissection (ESD) is very dependent on an effective injection beneath the submucosal lamina and on a controlled cutting technique. After our study group demonstrated the efficacy of the HydroJet in needleless submucosal injections under various physical conditions to create a submucosal fluid cushion (Selective tissue elevation by pressure = STEP technique), the next step was to develop a new instrument to combine the capabilities of an IT-Knife with a high-pressure water-jet in a single instrument. In this experimental study, we compared this new instrument with a standard ESD technique. Twelve gastric ESD were performed in six pigs under endotracheal anesthesia. Square areas measuring 4-cm x 4-cm were marked out on the anterior and posterior wall in the corpus-antrum transition region. The HybridKnife was used as an standard needle knife with insulated tip (i.e., the submucosal injection was performed with an injection needle and only the radiofrequency (RF) part of the HybridKnife was used for cutting (conventional technique)) or the HybridKnife was used in all the individual stages of the ESD, making use of the HybridKnife's combined functions (HybridKnife technique). The size of the resected specimens, the operating time, the frequency with which instruments were changed, the number of bleeding episodes, and the number of injuries to the gastric wall together with the subjective overall assessment of the intervention by the operating physician were recorded. The resected specimens were the same size, with average sizes of 16.96 cm(2) and 15.85 cm(2) resp (p = 0.8125). Bleeding episodes have been less frequent in the HybridKnife group (2.83 vs. 3.5; p = 0.5625). The standard knife caused more injuries to the lamina muscularis propria (0.17 vs. 1.33; p = 0.0313). The operating times had a tendency to be shorter with the HybridKnife technique (47.18 vs. 58.32 minute; p = 0.0313). The combination of a needle-knife with high-pressure water-jet dissection improved the results of endoscopic submucosal dissection in this experimental setting. Because the frequency of complications is still high, further improvements to the instrument are necessary.

Transcatheter arterial chemoembolization (TACE) combined with γ-knife compared to TACE or γ-knife alone for hepatocellular carcinoma.

PubMed

Cai, Yeyu; Chang, Qian; Xiao, Enhua; Shang, Quan-Liang; Chen, Zhu

2018-06-01

To compare the clinical efficacies and adverse reactions between transcatheter arterial chemoembolization (TACE), γ-ray 3-dimensional fractionated stereotactic conformal radiotherapy (FSCR), and TACE combined with FSCR for primary hepatocellular carcinoma.The study was approved by the Institutional Review Board, and informed consent was waived due to the retrospective study design. About 121 patients met the inclusion criteria and were included in this study, from March 2008 to January 2010, in the Second Xiangya Hospital. Forty-six patients underwent TACE alone, 36 patients underwent γ-knife alone, and 39 were treated by γ-knife combined with TACE. Short-term effects, overall survival rates, adverse reactions, and survival times were compared between the 3 treatment groups.Short-term effects were observed in 41.3% of the TACE group, 33.3% of the γ-knife group, and 64.1% of the TACE combined γ-knife group (P = .020). Overall survival rates at 6,12, 18, and 24 months were 50%, 34.8%, 28.3%, and 21.7% for the TACE group, 36.1%, 30.6%, 16.7%, and 11.1% for γ-knife group, and 84.6%, 71.8%, 61.5%, and 30.8% for TACE combined γ-knife group, respectively. The differences in the overall survival rates at 6, 12, and 18 months between the 3 groups were statistically significant (P = 0), but the overall survival rates at 24 months in the 3 groups were not significantly different (P = .117). The median survival time was 7 months for the TACE group, 3 months for the γ-knife group, and 20 months for the TACE combined γ-knife group (P = 0). There were statistically significant differences (P = .010) of leukopenia between the 3 groups, and no statistically significant differences of (P > .05) thrombocytopenia, anemia, nausea, vomiting, and liver function lesions.TACE combined with γ-knife for primary hepatocellular carcinoma is superior to TACE or γ-knife alone in short-term and long-term effects. This procedure is a mild, safe, and effective treatment for primary hepatocellular carcinoma.

Generalized Kähler geometry and current algebras in classical N=2 superconformal WZW model

NASA Astrophysics Data System (ADS)

Parkhomenko, S. E.

2018-04-01

I examine the Generalized Kähler (GK) geometry of classical N = (2, 2) superconformal WZW model on a compact group and relate the right-moving and left-moving Kac-Moody superalgebra currents to the GK geometry data using biholomorphic gerbe formulation and Hamiltonian formalism. It is shown that the canonical Poisson homogeneous space structure induced by the GK geometry of the group manifold is crucial to provide N = (2, 2) superconformal σ-model with the Kac-Moody superalgebra symmetries. Then, the biholomorphic gerbe geometry is used to prove that Kac-Moody superalgebra currents are globally defined.

Glucosensing capacity in rainbow trout liver displays day-night variations possibly related to melatonin action.

PubMed

Conde-Sieira, Marta; Patiño, Marcos A López; Míguez, Jesús M; Soengas, José L

2012-09-01

To assess whether the glucosensing capacity in peripheral (liver and Brockmann bodies) and central (hypothalamus and hindbrain) locations of rainbow trout displays day-night variations in its response to changes in circulating glucose levels, we evaluated the response of parameters related to glucosensing [glucose, glycogen and glucose 6-phosphate levels, activities of glucokinase (GK), glycogen synthetase (GSase) and pyruvate kinase (PK), and mRNA abundance of GK, glucose transporter 2 (GLUT2), and K(ATP) channel subunits Kir6.x-like and sulfonylurea receptor (SUR)-like] in fish subjected to hyperglycemic treatment under night or day conditions. No day-night significant variations were noticed in the glucosensing capacity of the hypothalamus, hindbrain and Brockmann bodies. In contrast, a clear differential response was noticed in the liver, where glucose levels, GK activity (and mRNA levels) and GSase activity displayed increased values during the day in hyperglycemic fish compared with controls, and lower (GK mRNA levels) or non-existent (glucose, GK and GSase activities, and Kir6.x-like mRNA levels) values during the night. A similar decrease in parameters related to glucosensing in the liver was observed when fish under day conditions were treated with melatonin, suggesting a modulatory role of melatonin in day-night changes of the glucosensing response in the same tissue.

PDZ Ligand Binding-Induced Conformational Coupling of the PDZ-SH3-GK Tandems in PSD-95 Family MAGUKs.

PubMed

Zeng, Menglong; Ye, Fei; Xu, Jia; Zhang, Mingjie

2018-01-05

Discs large (DLG) MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission, and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively is largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization. Aided by sortase-mediated protein ligation and selectively labeling, we elucidated the PDZ3/SH3-GK conformational coupling mechanism using NMR spectroscopy. We further demonstrated that PSD-93, but not SAP102, can also undergo PDZ3 ligand binding-induced conformational coupling with SH3-GK and form homo-oligomers. Interestingly, PSD-95 and PSD-93 can also form ligand binding-induced hetero-oligomers, suggesting a cooperative assembly mechanism for the mega-N-methyl-d-aspartate receptor synaptic signaling complex. Finally, we provide evidence showing that ligand binding-induced conformational coupling between PDZ and SH3-GK is a common feature for other MAGUKs including CASK and PALS1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular modeling and identification of novel glucokinase activators through stepwise virtual screening.

PubMed

Behera, Pabitra Mohan; Behera, Deepak Kumar; Satpati, Suresh; Agnihotri, Geetanjali; Nayak, Sanghamitra; Padhi, Payodhar; Dixit, Anshuman

2015-04-01

The glucose phosphorylating enzyme glucokinase (GK) is a 50kD monomeric protein having 465 amino acids. It maintains glucose homeostasis inside cells, acts as a glucose sensor in pancreatic β-cells and as a rate controlling enzyme for hepatic glucose clearance and glycogen synthesis. It has two binding sites, one for binding d-glucose and the other for a putative allosteric activator named glucokinase activator (GKA). The GKAs interact with the same region of the GK enzyme that is commonly affected by naturally occurring mutations in humans. However, many GKAs do not bind to GK in the absence of glucose. Recently, it has been reported that GKAs are highly effective in patients with type 2 diabetes mellitus. In this milieu a molecular modeling study has been carried out on three natural variants of GK that lie in the GKA binding site and are known to cause maturity onset diabetes of young (MODY). Additionally, a 10ns molecular dynamics simulation was done on each of the modeled variant in order to explore the flexibility of this site. Subsequently, a systematic virtual screening study was done to identify compounds which can bind with high affinity at GKA binding site of mutant GK. Copyright © 2015 Elsevier Inc. All rights reserved.

Scissor-type knife significantly improves self-completion rate of colorectal endoscopic submucosal dissection: Single-center prospective randomized trial.

PubMed

Yamashina, Takeshi; Takeuchi, Yoji; Nagai, Kengo; Matsuura, Noriko; Ito, Takashi; Fujii, Mototsugu; Hanaoka, Noboru; Higashino, Koji; Uedo, Noriya; Ishihara, Ryu; Iishi, Hiroyasu

2017-05-01

Colorectal endoscopic submucosal dissection (C-ESD) is recognized as a difficult procedure. Recently, scissors-type knives were launched to reduce the difficulty of C-ESD. The aim of this study was to evaluate the efficacy and safety of the combined use of a scissors-type knife and a needle-type knife with a water-jet function (WJ needle-knife) for C-ESD compared with using the WJ needle-knife alone. This was a prospective randomized controlled trial in a referral center. Eighty-five patients with superficial colorectal neoplasms were enrolled and randomly assigned to undergo C-ESD using a WJ needle-knife alone (Flush group) or a scissor-type knife-supported WJ needle-knife (SB Jr group). Procedures were conducted by two supervised residents. Primary endpoint was self-completion rate by the residents. Self-completion rate was 67% in the SB Jr group, which was significantly higher than that in the Flush group (39%, P = 0.01). Even after exclusion of four patients in the SB Jr group in whom C-ESD was completed using the WJ needle-knife alone, the self-completion rate was significantly higher (63% vs 39%; P = 0.03). Median procedure time among the self-completion cases did not differ significantly between the two groups (59 vs 51 min; P = 0.14). No fatal adverse events were observed in either group. In this single-center phase II trial, scissor-type knife significantly improved residents' self-completion rate for C-ESD, with no increase in procedure time or adverse events. A multicenter trial would be warranted to confirm the validity of the present study. © 2016 Japan Gastroenterological Endoscopy Society.

Novel design and sensitivity analysis of displacement measurement system utilizing knife edge diffraction for nanopositioning stages.

PubMed

Lee, ChaBum; Lee, Sun-Kyu; Tarbutton, Joshua A

2014-09-01

This paper presents a novel design and sensitivity analysis of a knife edge-based optical displacement sensor that can be embedded with nanopositioning stages. The measurement system consists of a laser, two knife edge locations, two photodetectors, and axillary optics components in a simple configuration. The knife edge is installed on the stage parallel to its moving direction and two separated laser beams are incident on knife edges. While the stage is in motion, the direct transverse and diffracted light at each knife edge is superposed producing interference at the detector. The interference is measured with two photodetectors in a differential amplification configuration. The performance of the proposed sensor was mathematically modeled, and the effect of the optical and mechanical parameters, wavelength, beam diameter, distances from laser to knife edge to photodetector, and knife edge topography, on sensor outputs was investigated to obtain a novel analytical method to predict linearity and sensitivity. From the model, all parameters except for the beam diameter have a significant influence on measurement range and sensitivity of the proposed sensing system. To validate the model, two types of knife edges with different edge topography were used for the experiment. By utilizing a shorter wavelength, smaller sensor distance and higher edge quality increased measurement sensitivity can be obtained. The model was experimentally validated and the results showed a good agreement with the theoretically estimated results. This sensor is expected to be easily implemented into nanopositioning stage applications at a low cost and mathematical model introduced here can be used for design and performance estimation of the knife edge-based sensor as a tool.

[Infraoccipital needle-knife for cervical vertigo].

PubMed

Li, Shaofang; Huang, Manhua; Lin, Zhuopeng; Chen, Xinze; Lin, Dongna; Lu, Peng; Lu, Qu

2017-03-12

To observe the clinical effect differences between infraoccipital needle-knife and massage for cervical vertigo. A total of 366 patients with cervical vertigo were randomly assigned into a needle-knife group (186 cases) and a massage group (180 cases). With cases dropping excluded, 183 cases in the needle-knife group and 176 cases in the massage group were included. Needle-knife was used at Fengchi (GB 20), infraoccipital ashi point, etc. in the needle-knife group. The treatment was given for one course, once three days, 5 times as one course. The traditional massage was applied in the massage group for one course, including systematic stroking, kneading, and the application of pressure and plucking, etc., once every two days and 7 times as one course. The dizziness handicap inventory (DHI) score was observed before and after treatment, as well as 3, 6, and 12 months after treatment. The effects were also evaluated. The total effective rate was 92.3% (169/183) in the needle-knife group, which was better than 85.2% (150/176) in the massage group ( P <0.05). Compared with those before treatment, the DHI scores at all the observation time points after treatment were improved in the two groups (all P <0.05), with better improvements after treatment as well as 3 and 6 months after treatment in the needle-knife group (all P <0.05). There was no significant difference in the improvement of DHI scores between the two groups 12 months after treatment ( P >0.05). The recurrence rate was 10.3% (12/117) in the needle-knife group, and it was 10.7% (11/103) in the massage group 12 months after treatment ( P >0.05). Infraoccipital needle-knife achieves apparent effect for cervical vertigo, which is superior to massage in short period.

Caudal hindbrain lactate infusion alters glucokinase, SUR1, and neuronal substrate fuel transporter gene expression in the dorsal vagal complex, lateral hypothalamic area, and ventromedial nucleus hypothalamus of hypoglycemic male rats.

PubMed

Vavaiya, Kamlesh V; Briski, Karen P

2007-10-24

While in vitro studies show that the oxidizable energy substrate, lactate, is a preferred fuel for CNS neurons during states of energy crisis, and that lactate may regulate neuronal glucose uptake under those conditions, its role in neuronal function in vivo remains controversial. Glucose-excited neurons in hindbrain dorsal vagal complex (DVC) monitor both glucose and lactate, and express both the glucose sensor, glucokinase (GK), and the SUR1 subunit of the plasma membrane energy transducer, K(ATP). Fourth ventricular lactate infusion exacerbates insulin-induced hypoglycemia (IIH) and IIH-associated patterns of DVC neuronal activation. We investigated the hypothesis that during glucoprivation, lactate regulates neuronal monocarboxylate and glucose transporter gene transcription in the DVC, and adjustments in these gene profiles are correlated with altered GK and SUR1 mRNA expression. We also examined whether caudal hindbrain lactate repletion alters the impact of hypoglycemia on substrate fuel uptake and metabolic sensing functions in other characterized metabolic monitoring sites, e.g., the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA). qPCR was used to measure MCT2, GLUT3, GLUT4, GK, and SUR1 transcripts in the microdissected DVC, VMH, and LHA from groups of male rats treated by continuous infusion of aCSF or lactate into the caudal fourth ventricle (CV4), initiated prior to injection of Humulin R or saline. Blood glucose was decreased in response to insulin, a response that was significantly augmented by CV4 lactate infusion. IIH alone did not alter mean DVC MCT2, GLUT3, GLUT4, GK, or SUR1 mRNA levels, but these transcripts were increased in the lactate plus insulin group, relative to both euglycemic and aCSF-infused hypoglycemic rats. IIH decreased MCT2, GLUT3, and SUR1 gene profiles in the VMH; CV4 lactate infusion during IIH further diminished these transcripts, and suppressed GLUT4 and GK mRNA levels in this site. In LHA, IIH increased GLUT3 and SUR1 gene expression to an equal extent, with or without lactate, while GLUT4, MCT2, and GK mRNA levels were elevated only in response to lactate plus insulin. These studies show that caudal hindbrain-targeted delivery of exogenous lactate during IIH upregulates neuronal monocarboxylate and glucose transporter, GK, and SUR1 gene profiles in the DVC, and results in increased or decreased GLUT4 and GK mRNA in LHA and VMH, respectively. These data suggest that lactate and glucose utilization by DVC neurons may be enhanced in response to local lactate surfeit, alone or relative to glucose deficiency, and that increases in intracellular glucose and net energy yield may be correlated with elevated GK and SUR1 gene transcription, respectively, in local glucose sensing neurons. The results also imply that GLUT4- and GK-mediated glucose uptake and glucose sensing functions in the VMH and LHA may be reactive to DVC signaling of relative lactate abundance within the caudal hindbrain, and/or to physiological sequelae of this fuel augmentation, including amplified hypoglycemia.

A retracting wire knife for cutting fiber bundles and making sheet lesions of brain tissue.

PubMed

Shibata, M; Russell, I S

1979-07-01

A retracting knife which has two cutting wires for the transection of fiber bundles is described. The knife holds the fiber bundles of the stria terminalis between the two cutting wires and transects them by a shearing movement as the wires close. In addition, the feasability of such a knife producing a sheet lesion around the n. caudatus is also described.

Endoscopic treatment for pancreatic diseases: Needle-knife-guided cannulation via the minor papilla

PubMed Central

Wang, Wei; Gong, Biao; Jiang, Wei-Song; Liu, Lei; Bielike, Kouken; Xv, Bin; Wu, Yun-Lin

2015-01-01

AIM: To determine the efficacy and safety of meticulous cannulation by needle-knife. METHODS: Three needle-knife procedures were used to facilitate cannulation in cases when standard cannulation techniques failed. A total of 104 cannulations via the minor papilla attempted in 74 patients at our center between January 2008 and June 2014 were retrospectively reviewed. RESULTS: Standard methods were successful in 79 cannulations. Of the 25 cannulations that could not be performed by standard methods, 19 were performed by needle-knife, while 17 (89.5%) were successful. Needle-knife use improved the success rate of cannulation [76.0%, 79/104 vs 92.3%, (79 + 17)/104; P = 0.001]. When the 6 cases not appropriate for needle-knife cannulation were excluded, the success rate was improved further (80.6%, 79/98 vs 98.0%, 96/98; P = 0.000). There were no significant differences in the rates of post-endoscopic retrograde cholangiopancreatography adverse events between the group using standard methods alone and the group using needle-knife after failure of standard methods (4.7% vs 10.5%, P = 0.301). CONCLUSION: The needle-knife procedure may be an alternative method for improving the success rate of cannulation via the minor papilla, particularly when standard cannulation has failed. PMID:26019460

Pleuroscopic punch biopsy using insulated-tip diathermic knife-2 for the diagnosis of desmoplastic malignant mesothelioma.

PubMed

Masai, Kyohei; Sasada, Shinji; Izumo, Takehiro; Taniyama, Tomoko; Nakamura, Yukiko; Chavez, Christine; Sakurai, Hiroyuki; Tsuta, Koji; Tsuchida, Takaaki

2013-10-01

Desmoplastic malignant mesothelioma (DMM) is a rare subtype of malignant pleural mesothelioma (MPM) and is often difficult to distinguish from pleural fibrosis and reactive mesothelial hyperplasia, especially if the biopsy samples are small. We performed full-thickness pleural biopsy on a lesion suspected to be DMM using an insulated-tip diathermic knife-2 (IT knife-2) during flex-rigid pleuroscopy. IT knife-2 is a novel electrosurgical device for endoscopic submucosal dissection in the early gastrointestinal cancer. It consists of a needle knife with 3 short blades at the distal end attached to an insulated ceramic tip. A 54-year-old man presenting with chest wall mass and thickened pleura, in whom a computed tomography-guided percutaneous needle aspiration had remained negative, underwent flex-rigid pleuroscopy for definitive diagnosis. While applying electric current, we used the IT knife-2 to incise the pleura in a circular shape just above the endothoracic fascia. The incised pleura was removed by forceps and examined pathologically. The microscopic examination was compatible with DMM. We discovered that pleuroscopic punch biopsy using IT knife-2 can diagnose DMM. Use of IT knife-2 during flex-rigid pleuroscopy can obtain sufficient samples from densely thickened pleura, which is difficult to diagnose with small biopsies.

Endoscopic treatment for pancreatic diseases: Needle-knife-guided cannulation via the minor papilla.

PubMed

Wang, Wei; Gong, Biao; Jiang, Wei-Song; Liu, Lei; Bielike, Kouken; Xv, Bin; Wu, Yun-Lin

2015-05-21

To determine the efficacy and safety of meticulous cannulation by needle-knife. Three needle-knife procedures were used to facilitate cannulation in cases when standard cannulation techniques failed. A total of 104 cannulations via the minor papilla attempted in 74 patients at our center between January 2008 and June 2014 were retrospectively reviewed. Standard methods were successful in 79 cannulations. Of the 25 cannulations that could not be performed by standard methods, 19 were performed by needle-knife, while 17 (89.5%) were successful. Needle-knife use improved the success rate of cannulation [76.0%, 79/104 vs 92.3%, (79 + 17)/104; P = 0.001]. When the 6 cases not appropriate for needle-knife cannulation were excluded, the success rate was improved further (80.6%, 79/98 vs 98.0%, 96/98; P = 0.000). There were no significant differences in the rates of post-endoscopic retrograde cholangiopancreatography adverse events between the group using standard methods alone and the group using needle-knife after failure of standard methods (4.7% vs 10.5%, P = 0.301). The needle-knife procedure may be an alternative method for improving the success rate of cannulation via the minor papilla, particularly when standard cannulation has failed.

Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes.

PubMed

Wang, Liya; Limongelli, Anna; Vila, Maya R; Carrara, Franco; Zeviani, Massimo; Eriksson, Staffan

2005-01-01

Thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) are the two key enzymes in mitochondrial DNA (mtDNA) precursor synthesis. Deficiencies in TK2 or dGK activity, due to genetic alteration, have been shown to cause tissue-specific depletion of mtDNA. In the case of TK2 deficiency, affected individuals suffer severe myopathy and, in the case of dGK deficiency, devastating liver or multi-systemic disease. Here, we report clinical and biochemical findings from two patients with mtDNA depletion syndrome. Patient A was a compound heterozygote carrying the previously reported T77M mutation and a novel mutation (R161K) in the TK2 gene. Patient B carried a novel mutation (L250S) in the dGK gene. The clinical symptoms of patient A included muscular weakness and exercise intolerance due to a severe mitochondrial myopathy associated with a 92% reduction in mtDNA. There was minimal involvement of other organs. Patient B suffered from rapidly progressive, early onset fatal liver failure associated with profoundly decreased mtDNA levels in liver and, to a lesser extent, in skeletal muscle. Site-directed mutagenesis was used to introduce the mutations detected in patients A and B into the TK2 and dGK cDNAs, respectively. We then characterized each of these recombinant enzymes. Catalytic activities of the three mutant enzymes were reduced to about 2-4% for TK2 and 0.5% for dGK as compared to the wild-type enzymes. Altered competition between dCyd and dThd was observed for the T77M mutant. The residual activities of the two mitochondrial enzymes correlated directly with disease development.

TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models

PubMed Central

Tsushima, Yu; Tamura, Azusa; Hasebe, Makiko; Kanou, Masanobu; Kato, Hirotsugu; Kobayashi, Tsunefumi

2017-01-01

Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues. TMG-123 selectively activated GK enzyme activity without increasing Vmax. TMG-123 improved glucose tolerance without increasing plasma insulin levels in both insulin-deficient (Goto-Kakizaki rats) and insulin-resistant (db/db mice) models. The beneficial effect on glucose tolerance was greater than results observed with clinically available antidiabetic drugs such as metformin and glibenclamide in Zucker Diabetic Fatty rats. TMG-123 also improved glucose tolerance in combination with metformin. After 4 weeks of administration, TMG-123 reduced the Hemoglobin A1c levels without affecting liver and plasma triglyceride levels in Goto-Kakizaki rats and Diet-Induced Obesity mice. Moreover, TMG-123 sustained its effect on Hemoglobin A1c levels even after 24 weeks of administration without affecting triglycerides. Taken together, these data indicate that TMG-123 exerts glucose-lowering effects in both insulin-deficient and -resistant diabetes, and sustains reduced Hemoglobin A1c levels without affecting hepatic and plasma triglycerides even after chronic treatment. Therefore, TMG-123 is expected to be an antidiabetic drug that overcomes the concerns previously reported with other GK activators. PMID:28207836

TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models.

PubMed

Tsumura, Yoshinori; Tsushima, Yu; Tamura, Azusa; Hasebe, Makiko; Kanou, Masanobu; Kato, Hirotsugu; Kobayashi, Tsunefumi

2017-01-01

Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues. TMG-123 selectively activated GK enzyme activity without increasing Vmax. TMG-123 improved glucose tolerance without increasing plasma insulin levels in both insulin-deficient (Goto-Kakizaki rats) and insulin-resistant (db/db mice) models. The beneficial effect on glucose tolerance was greater than results observed with clinically available antidiabetic drugs such as metformin and glibenclamide in Zucker Diabetic Fatty rats. TMG-123 also improved glucose tolerance in combination with metformin. After 4 weeks of administration, TMG-123 reduced the Hemoglobin A1c levels without affecting liver and plasma triglyceride levels in Goto-Kakizaki rats and Diet-Induced Obesity mice. Moreover, TMG-123 sustained its effect on Hemoglobin A1c levels even after 24 weeks of administration without affecting triglycerides. Taken together, these data indicate that TMG-123 exerts glucose-lowering effects in both insulin-deficient and -resistant diabetes, and sustains reduced Hemoglobin A1c levels without affecting hepatic and plasma triglycerides even after chronic treatment. Therefore, TMG-123 is expected to be an antidiabetic drug that overcomes the concerns previously reported with other GK activators.

Thermonuclear 19F(p, {{\\boldsymbol{\\alpha }}}_{0})16O reaction rate

NASA Astrophysics Data System (ADS)

He, Jian-Jun; Lombardo, Ivano; Dell'Aquila, Daniele; Xu, Yi; Zhang, Li-Yong; Liu, Wei-Ping

2018-01-01

The thermonuclear 19F(p, {{{α }}}0)16O reaction rate in the temperature region 0.007-10 GK has been derived by re-evaluating the available experimental data, together with the low-energy theoretical R-matrix extrapolations. Our new rate deviates by up to about 30% compared to the previous results, although all rates are consistent within the uncertainties. At very low temperature (e.g. 0.01 GK) our reaction rate is about 20% lower than the most recently published rate, because of a difference in the low energy extrapolated S-factor and a more accurate estimate of the reduced mass used in the calculation of the reaction rate. At temperatures above ˜1 GK, our rate is lower, for instance, by about 20% around 1.75 GK, because we have re-evaluated the previous data (Isoya et al., Nucl. Phys. 7, 116 (1958)) in a meticulous way. The present interpretation is supported by the direct experimental data. The uncertainties of the present evaluated rate are estimated to be about 20% in the temperature region below 0.2 GK, and are mainly caused by the lack of low-energy experimental data and the large uncertainties in the existing data. Asymptotic giant branch (AGB) stars evolve at temperatures below 0.2 GK, where the 19F(p, {{α }})16O reaction may play a very important role. However, the current accuracy of the reaction rate is insufficient to help to describe, in a careful way, the fluorine over-abundances observed in AGB stars. Precise cross section (or S factor) data in the low energy region are therefore needed for astrophysical nucleosynthesis studies. Supported by National Natural Science Foundation of China (11490562, 11490560, 11675229) and National Key Research and Development Program of China (2016YFA0400503)

Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

PubMed

Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

2017-05-01

Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.

PubMed

Pérez-Torres, Armando; Vera-Aguilera, Jesús; Hernaiz-Leonardo, Juan Carlos; Moreno-Aguilera, Eduardo; Monteverde-Suarez, Diego; Vera-Aguilera, Carlos; Estrada-Bárcenas, Daniel

2013-11-01

The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal. C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 μg/100 μL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 μL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C). The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (p<0.05) in the treated mice. The overall survival rates obtained with surgical treatment at 6 months were 83.33% for group A, 40% for group B, and 0% for group C, with significant differences (p<0.05) among the groups. The GK1 peptide demonstrated therapeutic properties in a mouse melanoma model, as treatment resulted in a significant increase in the mean survival time of the treated animals (42.58%). The potential for GK1 to be used as a primary or adjuvant component of chemotherapeutic cocktails for the treatment of experimental and human cancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.

Semiquantitative Analysis Using Thallium-201 SPECT for Differential Diagnosis Between Tumor Recurrence and Radiation Necrosis After Gamma Knife Surgery for Malignant Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsunaga, Shigeo, E-mail: shigeo-m@mui.biglobe.ne.jp; Shuto, Takashi; Takase, Hajime

Purpose: Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography ({sup 201}Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. Methods and Materials: The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of {sup 201}Tl SPECT data used the early ratio (ER) and the delayedmore » ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. Results: A total of 107 tumors were analyzed with {sup 201}Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. Conclusions: Semiquantitative analysis of {sup 201}Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most valuable index for this purpose.« less

TU-D-207B-01: A Prediction Model for Distinguishing Radiation Necrosis From Tumor Progression After Gamma Knife Radiosurgery Based On Radiomics Features From MR Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Z; MD Anderson Cancer Center, Houston, TX; Ho, A

Purpose: To develop and validate a prediction model using radiomics features extracted from MR images to distinguish radiation necrosis from tumor progression for brain metastases treated with Gamma knife radiosurgery. Methods: The images used to develop the model were T1 post-contrast MR scans from 71 patients who had had pathologic confirmation of necrosis or progression; 1 lesion was identified per patient (17 necrosis and 54 progression). Radiomics features were extracted from 2 images at 2 time points per patient, both obtained prior to resection. Each lesion was manually contoured on each image, and 282 radiomics features were calculated for eachmore » lesion. The correlation for each radiomics feature between two time points was calculated within each group to identify a subset of features with distinct values between two groups. The delta of this subset of radiomics features, characterizing changes from the earlier time to the later one, was included as a covariate to build a prediction model using support vector machines with a cubic polynomial kernel function. The model was evaluated with a 10-fold cross-validation. Results: Forty radiomics features were selected based on consistent correlation values of approximately 0 for the necrosis group and >0.2 for the progression group. In performing the 10-fold cross-validation, we narrowed this number down to 11 delta radiomics features for the model. This 11-delta-feature model showed an overall prediction accuracy of 83.1%, with a true positive rate of 58.8% in predicting necrosis and 90.7% for predicting tumor progression. The area under the curve for the prediction model was 0.79. Conclusion: These delta radiomics features extracted from MR scans showed potential for distinguishing radiation necrosis from tumor progression. This tool may be a useful, noninvasive means of determining the status of an enlarging lesion after radiosurgery, aiding decision-making regarding surgical resection versus conservative medical management.« less

Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebinu, Julius O.; Lwu, Shelly; Monsalves, Eric

Purpose: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. Methods: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. Results:more » A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. Conclusions: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pino, R; Therriault-Proulx, F; Yang, J

Purpose: To perform dose profile and output factor measurements for the Exradin W1 plastic scintillation detector (PSD) for the Gamma Knife Perfexion (GKP) collimators in a Lucy phantom and to compare these values to an Exradin A16 ion chamber, EBT3 radiochromic film and treatment planning system (TPS) data. Methods: We used the Exradin W1 PSD which has a small volume, near-water equivalent sensitive element. It has also been shown to be energy independent. This new detector is manufactured and distributed by Standard Imaging, Inc. Measurements were performed for all three collimators (4 mm, 8 mm and 16 mm) for themore » GKP. The Lucy phantom with the PSD inserted was moved in small steps to acquire profiles in all three directions. EBT3 film was inserted in the Lucy phantom and exposed to a single shot for each collimator. Relative output factors were measured using the three detectors while profiles acquired with the PSD were compared to the ones measured with EBT3 radiochromic film. Results: Measured output factors relative to the largest collimator are as followsCollimator PS EBT3 A1616mm 1.000 1.000 1.0008mm 0.892 0.881 0.8834mm 0.795 0.793 0.727 The nominal (vendor) OFs for GKP are 1.000, 0.900, and 0.814, for collimators 16 mm, 8 mm and 4 mm, respectively. There is excellent agreement between all profiles measured with the PSD and EBT3 as well as with the TPS data provided by the vendor. Conclusion: Output factors measured with the W1 were consistent with the ones measured with EBT3 and A16 ion chamber. Measured profiles are in excellent agreement. The W1 detector seems well suited for beam QA for Gamma Knife due to its dosimetric characteristics. Sam Beddar would like to disclose a NIH/NCI SBIR Phase II grant (2R44CA153824-02A1) with Standard Imaging, Title: “Water-Equivalent Plastic Scintillation Detectors for Small Field Radiotherapy”.« less

A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases: research protocol CAR-study B.

PubMed

Schimmel, Wietske C M; Verhaak, Eline; Hanssens, Patrick E J; Gehring, Karin; Sitskoorn, Margriet M

2018-02-21

Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing. CAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11-20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months. Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery. Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment. Knowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups. The Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration number NCT02953717 , first received October 27, 2016, 8 patients were enrolled in this study on 31 July 2017.

Real-time inverse planning for Gamma Knife radiosurgery.

PubMed

Wu, Q Jackie; Chankong, Vira; Jitprapaikulsarn, Suradet; Wessels, Barry W; Einstein, Douglas B; Mathayomchan, Boonyanit; Kinsella, Timothy J

2003-11-01

The challenges of real-time Gamma Knife inverse planning are the large number of variables involved and the unknown search space a priori. With limited collimator sizes, shots have to be heavily overlapped to form a smooth prescription isodose line that conforms to the irregular target shape. Such overlaps greatly influence the total number of shots per plan, making pre-determination of the total number of shots impractical. However, this total number of shots usually defines the search space, a pre-requisite for most of the optimization methods. Since each shot only covers part of the target, a collection of shots in different locations and various collimator sizes selected makes up the global dose distribution that conforms to the target. Hence, planning or placing these shots is a combinatorial optimization process that is computationally expensive by nature. We have previously developed a theory of shot placement and optimization based on skeletonization. The real-time inverse planning process, reported in this paper, is an expansion and the clinical implementation of this theory. The complete planning process consists of two steps. The first step is to determine an optimal number of shots including locations and sizes and to assign initial collimator size to each of the shots. The second step is to fine-tune the weights using a linear-programming technique. The objective function is to minimize the total dose to the target boundary (i.e., maximize the dose conformity). Results of an ellipsoid test target and ten clinical cases are presented. The clinical cases are also compared with physician's manual plans. The target coverage is more than 99% for manual plans and 97% for all the inverse plans. The RTOG PITV conformity indices for the manual plans are between 1.16 and 3.46, compared to 1.36 to 2.4 for the inverse plans. All the inverse plans are generated in less than 2 min, making real-time inverse planning a reality.

Histopathological observations on vestibular schwannomas after Gamma Knife radiosurgery: the Marseille experience.

PubMed

Szeifert, G T; Figarella-Branger, D; Roche, P-H; Régis, J

2004-06-01

Radiosurgery has become a successful treatment modality in the management of vestibular schwannomas (VS) during the past four decades. Although the number of treated cases has been increasing continuously we know relatively little about the pathological effect of high dose irradiation on VS following radiosurgery. The purpose of this study was to analyze histopathological changes in VS after Leksell Gamma Knife (LGK) radiosurgery. Out of a series of 1350 VS cases treated with LGK surgery 22 patients underwent craniotomy for tumor removal in 6-92 Months interval after radiosurgery. Surgical pathology material was available in 17 cases. Routine histological and immunohistochemical investigations were performed on the tIssue samples. Histopathological findings were compared with clinical and radiological follow-up data. Coagulation necrosis in the central part of the schwannomas surrounded with a transitional zone containing loosened tIssue structure of shrunken tumor cells covered with an outer capsule of vigorous neoplastic cells was the basic histopathological lesion. Granulation tIssue proliferation with inflammatory cell infiltration, different extent of hemorrhages and scar tIssue development was usually present. Endothelial destruction or wall damage of vascular channels was a common finding. Analyzing the follow-up data it turned out that 7 patients out of the 22 were operated on because of radiological progression only without clinical deterioration and 4 of them was removed during the latency period after radiosurgery. Results of the present histopathological study suggest that radiosurgery works with double effect on VS: it seems to destroy directly tumor cells (with necrosis or inducing apoptosis), and causes vascular damages as well. The loss of central contrast enhancement on CT and MR images following radiosurgery might be consequence of necrosis and vascular impairment. From clinical-pathological point of view we think that patients should not undergo craniotomy just because of radiological progression of the tumor without clinical deterioration, mainly in the latency period. This requires consultation and common decision-making between the radiosurgical and the microsurgical team.

Gamma knife radiosurgery for skull-base meningiomas.

PubMed

Takanashi, Masami; Fukuoka, Seiji; Hojyo, Atsufumi; Sasaki, Takehiko; Nakagawara, Jyoji; Nakamura, Hirohiko

2009-01-01

The primary purpose of this study was to evaluate the efficacy of gamma knife radiosurgery (GKRS) when used as a treatment modality for cavernous sinus or posterior fossa skull-base meningiomas (SBMs), with particular attention given to whether or not intentional partial resection followed by GKRS constitutes an appropriate combination treatment method for larger SBMs. Of the 101 SBM patients in this series, 38 were classified as having cavernous sinus meningiomas (CSMs), and 63 presented with posterior fossa meningiomas (PFMs). The patients with no history of prior surgery (19 CSMs, 57 PFMs) were treated according to a set protocol. Small to medium-sized SBMs were treated by GKRS only. To minimize the risk of functional deficits, larger tumors were treated with the combination of intentional partial resection followed by GKRS. Residual or recurrent tumors in patients who had undergone extirpations prior to GKRS (19 CSMs, 6 PFMs) are not eligible for this treatment method (due to the surgeries not being performed as part of a combination strategy designed to preserve neurological function as the first priority). The mean follow-up period was 51.9 months (range, 6-144 months). The overall tumor control rates were 95.5% in CSMs and 98.4% in PFMs. Nearly all tumors treated with GKRS alone were well controlled and the patients had no deficits. Furthermore, none of the patients who had undergone prior surgeries experienced new neurological deficits after GKRS. While new neurological deficits appeared far less often in those receiving the combination of partial resection with subsequent GKRS, extirpations tended to be associated with not only a higher incidence of new deficits but also a significant increase in the worsening of already-existing deficits. Our results indicate that GKRS is a safe and effective primary treatment for SBMs with small to moderate tumor volumes. We also found that larger SBMs compressing the optic pathway or brain stem can be effectively treated, minimizing any possible functional damage, by a combination of partial resection with subsequent GKRS.

Neurological Change after Gamma Knife Radiosurgery for Brain Metastases Involving the Motor Cortex

PubMed Central

Park, Chang-Yong; Choi, Hyun-Yong; Lee, Sang-Ryul; Roh, Tae Hoon; Seo, Mi-Ra

2016-01-01

Background Although Gamma Knife radiosurgery (GKRS) can provide beneficial therapeutic effects for patients with brain metastases, lesions involving the eloquent areas carry a higher risk of neurologic deterioration after treatment, compared to those located in the non-eloquent areas. We aimed to investigate neurological change of the patients with brain metastases involving the motor cortex (MC) and the relevant factors related to neurological deterioration after GKRS. Methods We retrospectively reviewed clinical, radiological and dosimetry data of 51 patients who underwent GKRS for 60 brain metastases involving the MC. Prior to GKRS, motor deficits existed in 26 patients (50.9%). The mean target volume was 3.2 cc (range 0.001–14.1) at the time of GKRS, and the mean prescription dose was 18.6 Gy (range 12–24 Gy). Results The actuarial median survival time from GKRS was 19.2±5.0 months. The calculated local tumor control rates at 6 and 12 months after GKRS were 89.7% and 77.4%, respectively. During the median clinical follow-up duration of 12.3±2.6 months (range 1–54 months), 18 patients (35.3%) experienced new or worsened neurologic deficits with a median onset time of 2.5±0.5 months (range 0.3–9.7 months) after GKRS. Among various factors, prescription dose (>20 Gy) was a significant factor for the new or worsened neurologic deficits in univariate (p=0.027) and multivariate (p=0.034) analysis. The managements of 18 patients were steroid medication (n=10), boost radiation therapy (n=5), and surgery (n=3), and neurological improvement was achieved in 9 (50.0%). Conclusion In our series, prescription dose (>20 Gy) was significantly related to neurological deterioration after GKRS for brain metastases involving the MC. Therefore, we suggest that careful dose adjustment would be required for lesions involving the MC to avoid neurological deterioration requiring additional treatment in the patients with limited life expectancy. PMID:27867921

Toxicity of Gamma Knife Radiosurgery in the Treatment of Intracranial Tumors in Patients With Collagen Vascular Diseases or Multiple Sclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowell, Dot; Tatter, Stephen B.; Bourland, J. Daniel

Purpose: To assess toxicity in patients with either a collagen vascular disease (CVD) or multiple sclerosis (MS) treated with intracranial radiosurgery. Methods and Materials: Between January 2004 and April 2009, 6 patients with MS and 14 patients with a CVD were treated with Gamma Knife radiosurgery (GKRS) for intracranial tumors. Treated lesions included 15 total brain metastases in 7 patients, 11 benign brain tumors, 1 low grade glioma, and 1 cavernous malformation. Toxicities were graded by the Radiation Therapy Oncology Group Acute/Late Radiation Morbidity Scoring Criteria. 'Rare toxicities' were characterized as those reported in the scientific literature at an incidencemore » of <5%. Results: Median follow-up time was 16 months. Median dose to the tumor margin was 13.0 Gy (range, 12-21 Gy). Median size of tumor was 5.0 cm{sup 3} (range, 0.14-7.8 cm{sup 3}). Of the 14 patients with CVD, none experienced a Grade 3 or 4 toxicity or a toxicity characterized as rare. Of the 6 patients with MS, 3 experienced rare toxicities, and two of these were Grade 3 toxicities. Rare complications included a patient experiencing both communicating hydrocephalus and facial nerve palsy, as well as 2 additional patients with motor cranial nerve palsy. High-grade toxicities included the patient with an acoustic neuroma requiring ventriculoperitoneal shunt placement for obstructive hydrocephalus, and 1 patient with a facial nerve schwannoma who experienced permanent facial nerve palsy. Interval between radiosurgery and high-grade toxicities ranged from 1 week to 4 months. Conclusions: Our series suggests that patients with MS who receive GKRS may be at increased risk of rare and high-grade treatment-related toxicity. Given the time course of toxicity, treatment-related edema or demyelination represent potential mechanisms.« less

Long-Term Results for Trigeminal Schwannomas Treated With Gamma Knife Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasegawa, Toshinori, E-mail: h-toshi@komakihp.gr.jp; Kato, Takenori; Iizuka, Hiroshi

Purpose: Surgical resection is considered the desirable curative treatment for trigeminal schwannomas. However, complete resection without any complications remains challenging. During the last several decades, stereotactic radiosurgery (SRS) has emerged as a minimally invasive treatment modality. Information regarding long-term outcomes of SRS for patients harboring trigeminal schwannomas is limited because of the rarity of this tumor. The aim of this study was to evaluate long-term tumor control and functional outcomes in patients harboring trigeminal schwannomas treated with SRS, specifically with gamma knife surgery (GKS). Methods and Materials: Fifty-three patients harboring trigeminal schwannomas treated with GKS were evaluated. Of these, 2more » patients (4%) had partial irradiation of the tumor, and 34 patients (64%) underwent GKS as the initial treatment. The median tumor volume was 6.0 cm{sup 3}. The median maximum and marginal doses were 28 Gy and 14 Gy, respectively. Results: The median follow-up period was 98 months. On the last follow-up image, 7 patients (13%) had tumor enlargement, including the 2 patients who had partial treatment. Excluding the 2 patients who had partial treatment, the actuarial 5- and 10-year progression-free survival (PFS) rates were 90% and 82%, respectively. Patients with tumors compressing the brainstem with deviation of the fourth ventricle had significantly lower PFS rates. If those patients with tumors compressing the brainstem with deviation of the fourth ventricle are excluded, the actuarial 5- and 10-year PFS rates increased to 95% and 90%, respectively. Ten percent of patients had worsened facial numbness or pain in spite of no tumor progression, indicating adverse radiation effect. Conclusions: GKS can be an acceptable alternative to surgical resection in patients with trigeminal schwannomas. However, large tumors that compress the brainstem with deviation of the fourth ventricle should be surgically removed first and then treated with GKS when necessary.« less

Gamma knife radiosurgery in patients with persistent acromegaly or Cushing's disease: long-term risk of hypopituitarism.

PubMed

Cohen-Inbar, Or; Ramesh, Arjun; Xu, Zhiyuan; Vance, Mary Lee; Schlesinger, David; Sheehan, Jason P

2016-04-01

For patient with a recurrent or residual acromegaly or Cushing's disease (CD) after resection, gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow-up has hampered understanding of the latent risks of hypopituitarism in patients with acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for acromegaly or CD. From a prospectively created, IRB-approved database, we identified all patients with acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow-up of 60 months were included. The median follow-up is 159·5 months (60·1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Sixty patients with either acromegaly or CD were included. Median tumour volume at time of GKRS was 1·3 cm(3) (0·3-13·4), and median margin dose was 25 Gy (6-30). GKRS-induced new pituitary deficiency occurred in 58·3% (n = 35) of patients. Growth hormone deficiency was most common (28·3%, n = 17). The actuarial overall rates of hypopituitarism at 3, 5 and 10 years were 10%, 21·7% and 53·3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumour was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (P = 0·018). Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS. © 2015 John Wiley & Sons Ltd.

RT-06GAMMA KNIFE SURGERY AFTER NAVIGATION-GUIDED ASPIRATION FOR CYSTIC METASTATIC BRAIN TUMORS

PubMed Central

Chiba, Yasuyoshi; Mori, Kanji; Toyota, Shingo; Kumagai, Tetsuya; Yamamoto, Shota; Sugano, Hirofumi; Taki, Takuyu

2014-01-01

Metastatic brain tumors over 3 cm in diameter (volume of 14.1ml) are generally considered poor candidates for Gamma Knife surgery (GKS). We retrospectively assessed the method and efficacy of GKS for large cystic metastatic brain tumors after navigation-guided aspiration under local anesthesia. From September 2007 to April 2014, 38 cystic metastatic brain tumors in 32 patients (12 males, 20 females; mean age, 63.2 years) were treated at Kansai Rosai Hospital. The patients were performed navigation-guided cyst aspiration under local anesthesia, then at the day or the next day, were performed GKS and usually discharged on the day. The methods for preventing of leptomeningeal dissemination are following: 1) puncture from the place whose cerebral thickness is 1 cm or more; 2) avoidance of Ommaya reservoir implantation; and 3) placement of absorbable gelatin sponge to the tap tract. Tumor volume, including the cystic component, decreased from 25.4 ml (range 8.7-84.7 ml) to 11.4 ml (range 2.9-36.7 ml) following aspiration; the volume reduction was approximately 51.6%. Follow-up periods in the study population ranged from 0 to 24 months (median 3.5 months). The overall median survival was 6.7 months. There was no leptomeningeal dissemination related to the aspiration. One patient experienced radiation necrosis after GKS, one patient experienced re-aspiration by failure of aspiration, and two patients experienced surgical resections and one patient experienced re-aspiration by cyst regrowth after GKS. Long-term hospitalization is not desirable for the patients with brain metastases. In japan, Long-term hospitalization is required for surgical resection or whole brain radiation therapy, but only two days hospitalization is required for GKS after navigation-guided aspiration at our hospital. This GKS after navigation-guided aspiration is more effective and less invasive than surgical resection or whole brain radiation therapy.

Effect of image uncertainty on the dosimetry of trigeminal neuralgia irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jursinic, Paul A.; Rickert, Kim; Gennarelli, Thomas A.

2005-08-01

Objective: Our objective was to quantify the uncertainty in localization of the trigeminal nerve (TGN) with magnetic resonance imaging (MRI) and computed tomography (CT) and to determine the effect of this uncertainty on gamma-knife dose delivery. Methods: An MR/CT test phantom with 9, 0.6-mm diameter, copper rings was devised. The absolute ring positions in stereotactic space were determined by the angiographic module of the LGP software. The standard deviation, {sigma}, in the difference between the absolute and MR-measured or CT-measured coordinates of the rings was determined. The trigeminal nerve in 52 previously treated patients was contoured and expanded by 1{sigma}more » and 2{sigma} margins to model the uncertainty in the location of the nerve. For gamma-knife treatment, a single isocenter was used and was located at the distal cisternal portion of the trigeminal nerve root. Irradiation methods included a 4-mm collimator, 90 Gy to isocenter and a 4 and 8-mm collimator, 70 Gy to isocenter. A patient outcome survey that sampled pain relief and morbidity was done. Results: The MR coordinate {sigma} was 0.7 mm left-right, 0.8 mm anterior-posterior, and 0.6 mm superior-inferior, and the CT coordinate {sigma} was 0.4 mm left-right, 0.2 mm anterior-posterior, and 0.2 mm superior-inferior. A 45% higher dose line covered the TGN with the 4 and 8-mm method. No significant increase in pain reduction or morbidity occurred. Conclusions: The uncertainty of target location by MRI is more than twice that found in CT imaging. The 4 and 8-mm collimator method covers the trigeminal root cross section with a higher isodose line than does the 4-mm method. This higher dose did not significantly reduce pain or increase morbidity.« less

Gamma Knife Radiosurgery for Treatment of Cerebral Metastases From Non-Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Motta, Micaela, E-mail: motta.micaela@hsr.it; Vecchio, Antonella del; Attuati, Luca

2011-11-15

Purpose: To evaluate clinical and physico-dosimetric variables affecting clinical outcome of patients treated with Gamma Knife radiosurgery (GKRS) for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between 2001 and 2006, 373 patients (298 men and 75 women, median age 65 years) with brain metastases from NSCLC underwent GKRS. All of them had KPS {>=} 60%, eight or fewer brain metastases, confirmed histopathological diagnosis and recent work-up (<3 months). Thirty-five patients belonged to recursive partitioning analysis (RPA) Class I, 307 patients were in RPA Class II, 7 patients were in RPA Class III. Median tumor volume wasmore » 3.6 cm{sup 3}. Median marginal dose was 22.5 Gy at 50% isodose.; median 10 Gy and 12 Gy isodose volumes were 30.8 cm{sup 3} and 15.8 cm{sup 3}, respectively. Follow-up with MRI was performed every 3 months. Overall survival data were collected from internal database, telephone interviews, and identifying registries. Results: Mean follow-up after GKRS was 51 months (range, 6 to 96 months); mean overall survival was 14.2 months. Of 373 patients, 29 were alive at time of writing, 104 had died of cerebral progression, and 176 had died of systemic progression. In 64 cases it was not possible to ascertain the cause. Univariate and multivariate analysis were adjusted for the following: RPA class, surgery, WBRT, age, gender, number of lesions, median tumor volume, median peripheral dose, and 10 Gy and 12 Gy volumes. Identified RPA class and overall tumor volume >5 cc were the only two covariates independently predictive of overall survival in patients who died of cerebral progression. Conclusions: Global volume of brain disease should be the main parameter to consider for performing GKRS, which is a first-line therapy for patient in good general condition and controlled systemic disease.« less

A stab in the dark: Design and construction of a novel device for conducting incised knife trauma investigations and its initial test.

PubMed

Humphrey, Caitlin; Kumaratilake, Jaliya; Henneberg, Maciej

2016-05-01

Knife attacks are commonly seen in Australia and other countries. During forensic investigations the force with which a wound was inflicted is often questioned. The ability to examine resultant trauma and particular weapons at different forces with an experimental device may lead to better interpretations of knife wounds. The objective of this study is to design, construct and test a device to analyse the characteristics and forces involved in knife attacks, particularly incised wounds. The mechanical variables (e.g. force, angle, knife geometry) involved in knife attacks have been considered to design and construct a suitable device which allows these variables to be systematically controlled and varied. A device was designed and constructed from mild steel. This included a pivoting arm and instrumented knife holder. The arm has adjustable angle and weight so that knives can be operated at different calculated forces. A device was successfully constructed and the repeatability of incised knife trauma and its characteristics in skeletal tissues were investigated. A device which allows reproducible and controlled experiments with knife wounds will be advantageous to forensic investigations. In particular, in determining forces and types of weapons associated with particular wounds, identifying or eliminating suspected weapons and more accurately answering the common question: How much force would be required to cause that particular wound. This could help to characterise the perpetrator. The device can be altered to be used in the future to investigate trauma caused by other weapons. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Detecting DNA synthesis of neointimal formation after catheter balloon injury in GK and in Wistar rats: using 5-ethynyl-2'-deoxyuridine.

PubMed

Guo, Jingsheng; Li, Dongye; Bai, Shiru; Xu, Tongda; Zhou, Zhongmin; Zhang, Yanbin

2012-12-13

Neointimal formation plays an important role in the pathogenesis of coronary restenosis after percutaneous coronary intervention (PCI), especially in patients with diabetes mellitus. Recently, some studies have shown that 5-ethynyl-2'-deoxyuridine (EdU) incorporation can serve as a novel alternative to the 5-bromo-2'-deoxyuridine (BrdU) antibody detection method for detection of DNA synthesis in regenerating avian cochlea, chick embryo and the adult nervous system. However, few studies have been performed to assess the suitability of EdU for detecting DNA synthesis in vascular neointima. The carotid artery balloon injury model was established in Goto-Kakizaki (GK) and Wistar rats. A Cell-LightTM EdU Kit was used to detect EdU-labeled cell nuclei of common carotid arteries at day 7 after catheter balloon injury. Different methods of injecting EdU were tested. The protein levels of proliferating cell nuclear antigen (PCNA) and p-Akt (Ser473), as well as the mRNA levels of PCNA were evaluated by Western blotting and quantitative real-time PCR (qRT-PCR), respectively. Immunohistochemical staining was also employed to visualize PCNA-positive cells. At day 7 after catheter balloon injury, far more EdU-positive and PCNA-positive cells were observed in GK rats. When comparing groups that received different EdU doses, it was found that the percentage of EdU-positive cells at a dose of 100 mg/kg body weight was than at doses of 25 mg/kg and 50 mg/kg. The number of positive cells was significantly higher in the repeated injection group compared to the single injection group. Further, after balloon injury DNA synthesis in GK rats was more notable than in Wistar rats. Neointimal formation in GK rats was more obvious than in Wistar rats. The protein levels of PCNA and p-Akt (Ser473) and the mRNA levels of PCNA were increased in injured rats as compared to uninjured rats, and were significantly higher in GK rats than in Wistar rats. By intraperitoneal injections of EdU at a dose of 100 mg/kg three times, EdU incorporation can detect carotid arterial DNA synthesis caused by neointimal formation in GK rats and Wistar rats at day 7 after balloon injury by the EdU click reaction quickly and effectively. Moreover, more obvious DNA synthesis in the vascular neointima could be observed in GK rats than in Wistar rats.

Laparoscopic pyloromyotomy: comparing the arthrotomy knife to the Bovie blade.

PubMed

Thomas, Priscilla G; Sharp, Nicole E; St Peter, Shawn D

2014-07-01

Laparoscopic pyloromyotomy was performed at our institution using an arthrotomy knife until it became unavailable in 2010. Thus, we adapted the use of the blunt Bovie tip, which can be used with or without electrocautery to perform the myotomy. This study compared the outcomes between using the arthrotomy knife versus the Bovie blade in laparoscopic pyloromyotomies. Retrospective review was performed on all laparoscopic pyloromyotomy patients from October 2007 to September 2012. Arthrotomy knife pyloromyotomy patients were compared with those performed with the Bovie blade. Patient demographics, diagnostic measurements, electrolyte levels, length of stay, operative time, and complications were compared. A total of 381 patients were included, with 191 in the arthrotomy group and 190 in the Bovie blade group. No significant differences existed between groups in age, weight, gender, pyloric dimensions, electrolyte levels, or length of stay. Mean operative times were 15.8±5.6 min with knife and 16.4±5.3 min for Bovie blade (P=0.24). In the arthrotomy knife group, there was one incomplete pyloromyotomy and one omental herniation. There was one wound infection in each group. Readmission rate was greater in the arthrotomy knife group (5.7%) versus the Bovie blade group (3.1%). The Bovie blade appears to offer no objective disadvantages compared with the arthrotomy knife when performing laparoscopic pyloromyotomy. Copyright © 2014 Elsevier Inc. All rights reserved.

[Meta-analysis of needle-knife treatment on cervical spondylosis].

PubMed

Kan, Li-Li; Wang, Hai-Dong; Liu, An-Guo

2013-11-01

To assess the efficacy of cervical spondylosis by needle-knife treatment according to the correlated literature of RCT,to compare advantages of needle-knife treatment. Randomized Controlled Trials about needle-knife treatment of cervical spondylosis were indexed from Chinese HowNet (CNKI) and Wanfang (WF) from 2000 to 2012, then were analyzed the efficacy by Review Manager 5.1 software. A total of 13 RCT literatures and 1 419 patients were included. The methods of included studies were poor in quality evaluation because of large sample and multi-center RCT studies was lacked, randomization method was not accurate enough, diagnostic criteria and efficacy evaluation were various, only four studies described long-term efficacy, most of the literature didn't describe the adverse event and fall off,all studies did not use the blind method. The Meta analysis outcome showed overall efficiency of needle-knife therapy was better than acupuncture and traction. Needle-knife therapy compared with Acupuncture, the total RR = 0.19, 95% confidence interval was (0.15, 0.24), P < 0.000.01. Compared with traction therapy the total RR = 1.30, 95% confidence intervalwas (1.18,1.42), P < 0.00001. Compared with acupuncture therapy,the overall effectiveness of needle-knife therapy is higher;compared with traction therapy, although,needle-knife therapy has a high overall effectiveness, but because of the loss of total sample size, the outcome RCT researches to confirm.

Gyrokinetic turbulence: between idealized estimates and a detailed analysis of nonlinear energy transfers

NASA Astrophysics Data System (ADS)

Teaca, Bogdan; Jenko, Frank; Told, Daniel

2017-04-01

Using large resolution numerical simulations of gyrokinetic (GK) turbulence, spanning an interval ranging from the end of the fluid scales to the electron gyroradius, we study the energy transfers in the perpendicular direction for a proton-electron plasma in a slab equilibrium magnetic geometry. The plasma parameters employed here are relevant to kinetic Alfvén wave turbulence in solar wind conditions. In addition, we use an idealized test representation for the energy transfers between two scales, to aid our understanding of the diagnostics applicable to the nonlinear cascade in an infinite inertial range. For GK turbulence, a detailed analysis of nonlinear energy transfers that account for the separation of energy exchanging scales is performed. Starting from the study of the energy cascade and the scale locality problem, we show that the general nonlocal nature of GK turbulence, captured via locality functions, contains a subset of interactions that are deemed local, are scale invariant (i.e. a sign of asymptotic locality) and possess a locality exponent that can be recovered directly from measurements on the energy cascade. It is the first time that GK turbulence is shown to possess an asymptotic local component, even if the overall locality of interactions is nonlocal. The results presented here and their implications are discussed from the perspective of previous findings reported in the literature and the idea of universality of GK turbulence.

A quiet harvest: linkage between ritual, seed selection and the historical use of the finger-bladed knife as a traditional plant breeding tool in Ifugao, Philippines.

PubMed

Murphy, Kevin M

2017-01-13

The transverse harvest knife, also commonly called the finger or finger-bladed knife, has been utilized by rice farmers in southeast Asia for many centuries. The finger knife persisted in many traditional cultures long after the introduction of the sickle, a tool which provided farmers with the means to execute a much faster harvest. Several theories in interpretative archaeology have attempted to account for this rejection of more modern technological innovations. These theories, which include community-based social organization ideas and practical reasons for the continued use of the finger knife, are presented in this paper. Here I suggest an alternate theory based on a re-interpretation of existing research and fusion of existing theories: the primary reason for the historical and continued use of the finger knife is for seed selection through a centuries old tradition of plant breeding. Though I accept the accuracy of the practical and community-based, socio-cultural reasons for the use of the finger knife put forth by other authors, I suggest that seed selection and genetic improvement was the driving factor in the use of the finger knife. Indeed, intricate planting and harvesting rituals, which both ensured and encouraged varietal conservation and improvement co-evolved with the use of the finger knife as the primary harvest tool due to its unique ability to aid the farmer in the art and science of seed selection. When combined with previous ideas, this interpretative theory, based on the connection between ethnoagronomy and material culture, may provide a more complete picture of the story around the persistence of the finger knife in traditional rice-growing cultures in southeast Asia. I focus my theory on the terrace-building Ifugao people in the mountainous Cordillera region of northcentral Philippines; however, to put the use of the finger into a wider regional context, I draw from examples of the use of the finger knife in other traditional cultures throughout the region of southeast Asia.

Experimental study of hybrid-knife endoscopic submucosal dissection (ESD) versus standard ESD in a Western country.

PubMed

De-la-Peña, Joaquín; Calderón, Ángel; Esteban, José Miguel; López-Rosés, Leopoldo; Martínez-Ares, David; Nogales, Óscar; Orive-Calzada, Aitor; Rodríguez, Sarbelio; Sánchez-Hernández, Eloy; Vila, Juan; Fernández-Esparrach, Gloria

2014-02-01

Endoscopic submucosal dissection (ESD) is an effective but time-consuming treatment for early neoplasia that requires a high level of expertise. The objective of this study was to assess the efficacy and learning curve of gastric ESD with a hybrid knife with high pressure water jet and to compare with standard ESD. We performed a prospective non survival animal study comparing hybrid-knife and standard gastric ESD. Variables recorded were: Number of en-bloc ESD, number of ESD with all marks included (R0), size of specimens, time and speed of dissection and adverse events. Ten endoscopists performed a total of 50 gastric ESD (30 hybrid-knife and 20 standard). Forty-six (92 %) ESD were en-bloc and 25 (50 %) R0 (hybrid-knife: n = 13, 44 %; standard: n = 16, 80 %; p = 0.04). Hybrid-knife ESD was faster than standard (time: 44.6 +/- 21.4 minutes vs. 68.7 +/- 33.5 minutes; p = 0.009 and velocity: 20.8 +/- 9.2 mm(2)/min vs. 14.3 +/- 9.3 mm(2)/min (p = 0.079). Adverse events were not different. There was no change in speed with any of two techniques (hybrid-knife: From 20.33 +/- 15.68 to 28.18 +/- 20.07 mm(2)/min; p = 0.615 and standard: From 6.4 +/- 0.3 to 19.48 +/- 19.21 mm(2)/min; p = 0.607). The learning curve showed a significant improvement in R0 rate in the hybrid-knife group (from 30 % to 100 %). despite the initial performance of hybrid-knife ESD is worse than standard ESD, the learning curve with hybrid knife ESD is short and is associated with a rapid improvement. The introduction of new tools to facilitate ESD should be implemented with caution in order to avoid a negative impact on the results.

[Effect of Small Knife Needle on β-enorpin and Enkehalin Contents of Tansverse Process Syndrome of the Third Vertebra].

PubMed

Liu, Nai-gang; Guo, Chang-qing; Sun, Hong-mei; Li, Xiao-hong; Wu, Hai-xia; Xu, Hong

2016-04-01

To explore the analgesic mechanism of small knife needle for treating transverse process syndrome of the third vertebra (TPSTV) by observing peripheral and central changesof β-endorphin (β-EP) and enkephalin (ENK) contents. Totally 30 Japanese white big-ear rabbits of clean grade were divided into 5 groups according to random digit table, i.e., the normal control group, the model group, the small knife needle group, the electroacupunture (EA) group, and the small knife needle plus EA group, 6 in each group. The TPSTV model was established by inserting a piece of gelatin sponge into the left transverse process of 3rd lumbar vertebrae. Rabbits in the small knife needlegroup were intervened by small knife needle. Those in the EA group were intervened by EA at bilateralWeizhong (BL40). Those in the small knife needle plus EA group were intervened by small knife needleand EA at bilateral Weizhong (BL40). Contents of β-EP and ENK in plasma, muscle, spinal cord, and hypothalamus were determined after sample collection at day 28 after modeling. Compared with the normal control group, contents of β-EP and ENK in plasma and muscle increased significantly, and contents of β-EP and ENK in spinal cord and hypothalamus decreased significantly in the model group (P < 0.05, P < 0.01). Contents of β-EP and ENK approximated normal levels in the three treatment groups after respective treatment. Compared with the model group, the content of β-EP in muscle decreased, and contents of β-EP and ENK in hypothalamus increased in the three treatment groups after respective treatment (P < 0.05). There were no significant difference among the three treatment groups (P > 0.05). Small knife needle treatment and EA had benign regulation on peripheral and central β-EP and ENK in TPSTV rabbits. Small knife needle treatment showed better effect than that of EA.

SU-E-J-64: Feasibility Study of Surgical Clips for Fiducial Tracking in CyberKnife System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H; Yoon, J; Lee, E

Purpose: To investigate the ability of CyberKnife to track surgical clips used as fiducial markers. Methods: The Octavius 1000SRS detector and solid water (RW3) slab phantom were used with motion platform to evaluate the study. The RW3 slab phantom was set up to measure the dose distribution from coronal plane. It consists of 9 plates and the thickness of each plate is 10mm. Among them, one plate was attached with 3 surgical clips, which are orthogonally positioned on outer region of array. The length of attached clip was represented as 1cm on planning CT. The clip plate was placed onmore » the 1000SRS detector and 3 slabs were stacked up on the plate to build the measuring depth. Below the detector, 5 slabs were set. The two-axis motion platform was programmed with 1D sinusoidal movement (20mm peak-to-peak, 3s period) toward superior/inferior and left/right directions to simulate target motion. During delivery, two clips were extracted by two X-ray imagers, which led to translational error correction only. Synchrony was also used for dynamic tracking. After the irradiation, the measured dose distribution of coronal plane was compared with the planar dose distribution calculated by the CyberKnife treatment planning system (Multiplan) for cross verification. The results were assessed by comparing the absolute Gamma (γ) index. Results: The dose distributions measured by the 1000SRS detector were in good agreements with those calculated by Multiplan. In the dosimetric comparison using γ-function criteria based on the distance-to-agreement of 3mm and the local dose difference of 3%, the passing rate with γ- parameter ≤1 was 91% in coronal plane. Conclusion: The surgical clips can be considered as new fiducials for robotic radiosurgery delivery by considering the target margin with less than 5mm.« less

Cognitive Ability, Learning Approaches and Personality Correlates of General Knowledge

ERIC Educational Resources Information Center

Furnham, Adrian; Swami, Viren; Arteche, Adriane; Chamorro-Premuzic, Tomas

2008-01-01

The relationship between general knowledge (GK) and cognitive ability (IQ and abstract reasoning), learning approaches, and personality ("big five" traits and typical intellectual engagement) was investigated in a sample of 101 British undergraduates. As predicted, GK was positively correlated with cognitive ability (more so with IQ than…

Outcome of peroral endoscopic myotomy in achalasia cardia: Experience with a new triangular knife.

PubMed

Nabi, Zaheer; Ramchandani, Mohan; Chavan, Radhika; Kalapala, Rakesh; Darisetty, Santosh; Reddy, D Nageshwar

2018-01-01

Peroral endoscopic myotomy (POEM) is a technically demanding procedure. Recently, a new triangular knife with integrated water jet function (TTJ) has been introduced. The present study was aimed to analyze and compare the operating time, efficacy, and adverse events (AEs) between the conventional (TT knife) and new knife (TTJ). All patients with achalasia cardia (AC) who underwent POEM between August 2015 and November 2016 were analyzed retrospectively. Operating time (OT), technical success, and AEs were assessed and compared between TT and TTJ knife. A total of 193 patients with AC underwent POEM during the specified period. Both groups had equivalent number of different subtypes of AC (I, II, and III). There was no difference in technical success between the two groups (TT, 99% vs TT, 98.9%). OT was significantly less in the TTJ group as compared to TT group (53.8 ± 15.2 vs 66.26 ± 19.2; P = 0.0001). On subanalysis, OT taken for submucosal tunneling was significantly less with TTJ knife (34.6 ± 10.1 vs 45.83 ± 14.80), whereas OT was similar for myotomy and clipping in both the groups. Significantly fewer use of coagulation forceps and exchanges of accessories were required in TTJ knife group (2.92 ± 1.77 vs 10.5 ± 3.58; P = 0.0001). There were no major AEs. Minor AEs were noted in 21.5% and 31% of patients in TTJ and TT knife groups, respectively. New triangular knife reduces procedure time and technical difficulty with POEM. POEM is an efficacious treatment for achalasia and can be safely executed in an endoscopy unit.

Outcome of peroral endoscopic myotomy in achalasia cardia: Experience with a new triangular knife

PubMed Central

Nabi, Zaheer; Ramchandani, Mohan; Chavan, Radhika; Kalapala, Rakesh; Darisetty, Santosh; Reddy, D. Nageshwar

2018-01-01

Background and Aim: Peroral endoscopic myotomy (POEM) is a technically demanding procedure. Recently, a new triangular knife with integrated water jet function (TTJ) has been introduced. The present study was aimed to analyze and compare the operating time, efficacy, and adverse events (AEs) between the conventional (TT knife) and new knife (TTJ). Patients and Methods: All patients with achalasia cardia (AC) who underwent POEM between August 2015 and November 2016 were analyzed retrospectively. Operating time (OT), technical success, and AEs were assessed and compared between TT and TTJ knife. Results: A total of 193 patients with AC underwent POEM during the specified period. Both groups had equivalent number of different subtypes of AC (I, II, and III). There was no difference in technical success between the two groups (TT, 99% vs TT, 98.9%). OT was significantly less in the TTJ group as compared to TT group (53.8 ± 15.2 vs 66.26 ± 19.2; P = 0.0001). On subanalysis, OT taken for submucosal tunneling was significantly less with TTJ knife (34.6 ± 10.1 vs 45.83 ± 14.80), whereas OT was similar for myotomy and clipping in both the groups. Significantly fewer use of coagulation forceps and exchanges of accessories were required in TTJ knife group (2.92 ± 1.77 vs 10.5 ± 3.58; P = 0.0001). There were no major AEs. Minor AEs were noted in 21.5% and 31% of patients in TTJ and TT knife groups, respectively. Conclusion: New triangular knife reduces procedure time and technical difficulty with POEM. POEM is an efficacious treatment for achalasia and can be safely executed in an endoscopy unit. PMID:29451180

21 CFR 874.4420 - Ear, nose, and throat manual surgical instrument.

Code of Federal Regulations, 2010 CFR

2010-04-01

... device includes the esophageal dilator; tracheal bistour (a long, narrow surgical knife); tracheal dilator; tracheal hook; laryngeal injection set; laryngeal knife; laryngeal saw; laryngeal trocar...; wire ear loop; microrule; mirror; mobilizer; ear, nose, and throat punch; ear, nose and throat knife...

Management of Liver Cancer Argon-helium Knife Therapy with Functional Computer Tomography Perfusion Imaging.

PubMed

Wang, Hongbo; Shu, Shengjie; Li, Jinping; Jiang, Huijie

2016-02-01

The objective of this study was to observe the change in blood perfusion of liver cancer following argon-helium knife treatment with functional computer tomography perfusion imaging. Twenty-seven patients with primary liver cancer treated with argon-helium knife and were included in this study. Plain computer tomography (CT) and computer tomography perfusion (CTP) imaging were conducted in all patients before and after treatment. Perfusion parameters including blood flows, blood volume, hepatic artery perfusion fraction, hepatic artery perfusion, and hepatic portal venous perfusion were used for evaluating therapeutic effect. All parameters in liver cancer were significantly decreased after argon-helium knife treatment (p < 0.05 to all). Significant decrease in hepatic artery perfusion was also observed in pericancerous liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy. © The Author(s) 2014.

NEEDLE KNIFE SPHINCTEROTOMY - THE CHRIS HANI BARAGWANATH ACADEMIC HOSPITAL EXPERIENCE.

PubMed

Thomson, J T; Smith, M D; Omoshoro-Jones, J A O; Devar, J D; Khan, Z K; Jugmohan, B J

2017-06-01

Deep biliary cannulation is essential in performing a therapeutic ERCP. Cannulation can be enhanced through the utilization of a pre-cut by means of a needle knife sphincterotomy. Retrospective analysis of the Chris Hani Baragwanath Academic Hospital's ERCP database was performed. All ERCPs performed with the aid of a needle knife were identified and analysed for successful and unsuccessful deep biliary cannulation. 2830 ERCPs were performed during the study period. 369 (13%) required needle knife sphincterotomies and successful deep biliary cannulation was achieved in 229 (62%) of these patients. Repeat ERCPs were performed on 125 (34%) patients. 61 (49%) of the repeat ERCPs were performed because of previously failed cannulation. 34 (56%) of these repeat ERCPs resulted in successful deep biliary cannulation at re-attempt. 99% of successful cannulations at repeat ERCP had had a needle knife sphincterotomy at the first ERCP. Needle knife sphincterotomy improves deep biliary cannulation at initial ERCP and subsequent ERCPs with low incidences of complications.

Nasopharyngeal carcinoma presented as cavernous sinus tumour.

PubMed

Moona, Mohammad Shafi; Mehdi, Itrat

2011-12-01

A 32 year Libyan male presented with the complaints of headache and diplopia. He was diagnosed with a cavernous sinus meningioma on the basis of MRI findings but no initial biopsy was taken. Depending on the radiologic diagnosis the patient was treated with gamma knife surgery twice, abroad. During follow up he developed left ear deafness and left cervical lymph adenopathy. An ENT evaluation with biopsy from the nasopharynx and cervical lymph node was taken. The histopathologic diagnosis of the resected tumour showed a nasopharyngeal carcinoma with cervical lymph node metastasis (poorly differentiated lympho-epithelial carcinoma). The cavernous sinus tumour which was initially treated as a meningioma was in fact metastasis from the nasopharyngeal carcinoma, making this an interesting and rare occurrence.

A Long Term Follow Up After Radiosurgery Of Papillary Tumour Of The Pineal Region (Ptpr): Two Cases Report And Review Of The Literature.

PubMed

Fernández-Mateos, Cecilia; Martinez, Roberto; Vaquero, Jesús

2018-05-19

Tumours of the pineal region are rare in adulthood, accounting for approximately 1% of intracranial neoplasms in this age range. Because of their rarity, it has proven to be difficult to establish the optimal therapy. Furthermore, microsurgical total resection in this eloquent location is associated with not low rates of morbidity. We described two patients diagnosed of papillary tumours of the pineal region (PTPR) by stereotactic biopsy and referred for gamma knife radiosurgery after shunting for hydrocephalus. We are reporting a long-term follow up of 15 and 20 years respectively, showing a good response to the treatment. Copyright © 2018. Published by Elsevier Inc.

Radiosurgery of Glomus Jugulare Tumors: A Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guss, Zachary D.; Batra, Sachin; Limb, Charles J.

2011-11-15

Purpose: During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. Methods and Materials: To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data whenmore » Cochrane's statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test. Results: Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. Conclusions: The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.« less

The Effective Research-Based Characteristics of Professional Development of the National Science Foundation's GK-12 Program

ERIC Educational Resources Information Center

Cormas, Peter C.; Barufaldi, James P.

2011-01-01

This study investigates the effective research-based characteristics of professional development (ERBCPD) of the National Science Foundation's GK-12 Program--a program which partners institutions of higher education with local school districts and places science, technology, engineering, and mathematics graduates in the K-12 classroom with…

A Subacute Care Intervention for Short Stay Cancer Surgery

DTIC Science & Technology

2001-10-01

VandenBoom in "The State News," Michigan State University, East Lansing, MI. Wyatt, G.K. & Collins, C. (1999, November 10). A Yoga Program for Women following...2000," Sparrow Health System, Lansing, MI. Wyatt, G.K. (1999, November 15). Research on the Rise. Article by Elizabeth Vandenboom in "The State News

Mutations in exons 10 and 11 of human glucokinase result in conformational variations in the active site of the structure contributing to poor substrate binding - explains hyperglycemia in type 2 diabetic patients.

PubMed

Yellapu, Nandakumar; Mahto, Manoj Kumar; Valasani, Koteswara Rao; Sarma, P V G K; Matcha, Bhaskar

2015-01-01

Mutations in the glucokinase (GK) gene play a critical role in the establishment of type 2 diabetes. In our earlier study, R308K mutation in GK in a clinically proven type 2 diabetic patient showed, structural and functional variations that contributed immensely to the hyperglycemic condition. In the extension of this work, a cohort of 30 patients with established type 2 diabetic condition were chosen and the exons 10 and 11 of GK were PCR-amplified and sequenced. The sequence alignment showed A379S, D400Y, E300A, E395A, E395G, H380N, I348N, L301M, M298I, M381G, M402R, R308K, R394P, R397S, and S398R mutations in 12 different patients. The structural analysis of these mutated GKs, showed a variable number of β-α-β units, hairpins, β-bulges, strands, helices, helix-helix interactions, β-turns, and γ-turns along with the RMSD variations when compared to wild-type GK. Molecular modeling studies revealed that the substrate showed variable binding orientations and could not fit into the active site of these mutated structures; moreover, it was expelled out of the conformations. Therefore, these structural variations in GK due to mutations could be one of the strongest reasons for the hyperglycemic levels in these type 2 diabetic patients.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, J.; Chassy, B.M.; Egan, W.

A mutant of Streptococcus lactis 133 has been isolated that lacks both glucokinase and phosphoenolpyruvate-dependent mannose- phosphotransferase (mannose-PTS) activities. The double mutant S. lactis 133 mannose-PTSd GK- is unable to utilize either exogenously supplied or intracellularly generated glucose for growth. Fluorographic analyses of metabolites formed during the metabolism of (/sup 14/C)lactose labeled specifically in the glucose or galactosyl moiety established that the cells were unable to phosphorylate intracellular glucose. However, cells of S. lactis 133 mannose-PTSd GK- readily metabolized intracellular glucose 6-phosphate, and the growth rates and cell yield of the mutant and parental strains on sucrose were the same.more » During growth on lactose, S. lactis 133 mannose-PTSd GK- fermented only the galactose moiety of the disaccharide, and 1 mol of glucose was generated per mol of lactose consumed. For an equivalent concentration of lactose, the cell yield of the mutant was 50% that of the wild type. The specific rate of lactose utilization by growing cells of S. lactis 133 mannose-PTSd GK- was ca. 50% greater than that of the wild type, but the cell doubling times were 70 and 47 min, respectively. High-resolution /sup 31/P nuclear magnetic resonance studies of lactose transport by starved cells of S. lactis 133 and S. lactis 133 mannose-PTSd GK- showed that the latter cells contained elevated lactose-PTS activity. Throughout exponential growth on lactose, the mutant maintained an intracellular steady-state glucose concentration of 100 mM.« less

The Knife Machine. Module 15.

ERIC Educational Resources Information Center

South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

This module on the knife machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the knife machine (a single needle or multi-needle machine which sews and cuts at the same time). These components are provided: an introduction, directions, an objective,…

The Shoemaker's Knife

ERIC Educational Resources Information Center

Thomson, Ian

2010-01-01

Archimedes, the famous Greek mathematician, lived from 287 BCE until approximately 212 BCE. He thought that the figure of two semi-circles on a straight line enclosed by a larger semi-circle resembled a shoemaker's knife. Archimedes called this figure an "arbelos" since arbelos is the Greek word for a shoemaker's knife. The author describes the…

Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen

PubMed Central

Bobes, Raúl J.; Navarrete-Perea, José; Ochoa-Leyva, Adrián; Anaya, Víctor Hugo; Hernández, Marisela; Cervantes-Torres, Jacquelynne; Estrada, Karel; Sánchez-Lopez, Filiberto; Soberón, Xavier; Rosas, Gabriela; Nunes, Cáris Maroni; García-Varela, Martín; Sotelo-Mundo, Rogerio Rafael; López-Zavala, Alonso Alexis; Gevorkian, Goar; Acero, Gonzalo; Laclette, Juan P.; Fragoso, Gladis

2017-01-01

ABSTRACT Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps. Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Escherichia coli Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. In silico analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines. PMID:28923896

Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen.

PubMed

Bobes, Raúl J; Navarrete-Perea, José; Ochoa-Leyva, Adrián; Anaya, Víctor Hugo; Hernández, Marisela; Cervantes-Torres, Jacquelynne; Estrada, Karel; Sánchez-Lopez, Filiberto; Soberón, Xavier; Rosas, Gabriela; Nunes, Cáris Maroni; García-Varela, Martín; Sotelo-Mundo, Rogerio Rafael; López-Zavala, Alonso Alexis; Gevorkian, Goar; Acero, Gonzalo; Laclette, Juan P; Fragoso, Gladis; Sciutto, Edda

2017-12-01

Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Escherichia coli Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. In silico analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines. Copyright © 2017 American Society for Microbiology.

Gyrokinetic and kinetic particle-in-cell simulations of guide-field reconnection. I. Macroscopic effects of the electron flows

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muñoz, P. A., E-mail: munozp@mps.mpg.de; Kilian, P.; Büchner, J.

In this work, we compare gyrokinetic (GK) with fully kinetic Particle-in-Cell (PIC) simulations of magnetic reconnection in the limit of strong guide field. In particular, we analyze the limits of applicability of the GK plasma model compared to a fully kinetic description of force free current sheets for finite guide fields (b{sub g}). Here, we report the first part of an extended comparison, focusing on the macroscopic effects of the electron flows. For a low beta plasma (β{sub i} = 0.01), it is shown that both plasma models develop magnetic reconnection with similar features in the secondary magnetic islands if a sufficientlymore » high guide field (b{sub g} ≳ 30) is imposed in the kinetic PIC simulations. Outside of these regions, in the separatrices close to the X points, the convergence between both plasma descriptions is less restrictive (b{sub g} ≳ 5). Kinetic PIC simulations using guide fields b{sub g} ≲ 30 reveal secondary magnetic islands with a core magnetic field and less energetic flows inside of them in comparison to the GK or kinetic PIC runs with stronger guide fields. We find that these processes are mostly due to an initial shear flow absent in the GK initialization and negligible in the kinetic PIC high guide field regime, in addition to fast outflows on the order of the ion thermal speed that violate the GK ordering. Since secondary magnetic islands appear after the reconnection peak time, a kinetic PIC/GK comparison is more accurate in the linear phase of magnetic reconnection. For a high beta plasma (β{sub i} = 1.0) where reconnection rates and fluctuations levels are reduced, similar processes happen in the secondary magnetic islands in the fully kinetic description, but requiring much lower guide fields (b{sub g} ≲ 3)« less

Endoscopic submucosal dissection for superficial esophageal neoplasms using the stag beetle knife.

PubMed

Fujinami, H; Hosokawa, A; Ogawa, K; Nishikawa, J; Kajiura, S; Ando, T; Ueda, A; Yoshita, H; Sugiyama, T

2014-01-01

Endoscopic submucosal dissection (ESD) is an accepted standard treatment for early gastric cancer but is not widely used in the esophagus because of technical difficulties. To increase the safety of esophageal ESD, we used a scissors-type device called the stag beetle (SB) knife. The aim of this study was to determine the efficacy and safety of ESD using the SB knife. We performed a single-center retrospective, uncontrolled trial. A total of 38 lesions were excised by ESD from 35 consecutive patients who were retrospectively divided into the following two groups according to the type of knife used to perform ESD: the hook knife (hook group) was used in 20 patients (21 lesions), and the SB knife (SB group) was used in 15 patients (17 lesions). We evaluated and compared the operative time, lesion size, en bloc resection rate, pathological margins free rate, and complication rate in both groups. The operative time was shorter in the SB group (median 70.0 minutes [interquartile range, 47.5-87.0]) than in the hook group (92.0 minutes [interquartile range, 63.0-114.0]) (P = 0.019), and the rate of complications in the SB group was 0% compared with 45.0% in the hook group (P = 0.004). However, the lesion size, en bloc resection rate, and pathological margins free rate did not differ significantly between the two groups. In conclusion, ESD using the SB knife was safer than that using a conventional knife for superficial esophageal neoplasms. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Knife inflicted penetrating injuries of the maxillofacial region: a descriptive, record-based study.

PubMed

Meer, M; Siddiqi, A; Morkel, J A; Janse van Rensburg, P; Zafar, S

2010-01-01

Penetrating knife injuries of the face are more common in South Africa than the rest of the world. These injuries can be life-threatening, especially where the major blood vessels of the face are involved. The approach to treatment should be multidisciplinary, beginning with the trauma unit to provide airway maintenance and haemodynamic stabilisation. An interventional radiologist may be consulted for angiography. The aim of the present study was to retrospectively analyse all cases of knife-inflicted penetrating injuries to the maxillofacial region with the knife in situ and subsequently develop a management protocol to be used by maxillofacial surgery registrars when presented with such cases. It was a retrospective, cross-sectional and record-based study, analysing all penetrating knife injuries reported at various hospitals for a period of 11 years. In this study, 24 cases of knife injuries were analysed. Twenty-one patients (87.5%) in this series were male and three (12.5%) were female. Of these 24 patients, 13 (54.2%) were coloured and 11 (45.8%) were black. There were no white or Indian patients. Post-surgical recovery of all patients was rapid and uneventful, and there were no fatalities. Patients with knife injuries to the face with no definite signs of vascular injury can thus be safely and accurately managed on the basis of physical examination and plain-film radiography. An angiogram is mandatory if the patient presents with excessive bleeding, an expanding haematoma or if the knife blade is in the region of any large vessels.

Using the phacoemulsification crescent knife in dacryocystorhinostomy.

PubMed

Fong, K S; Koh, A H; Choo, C T

1998-04-01

Dacryocystorhinostomy is an effective treatment for nasolacrimal duct obstruction. Most techniques employ a conventional blade or knife in making the incision of the nasal mucosa and lacrimal sac. The authors describe the use of a phacoemulsification crescent knife for this purpose. This technique can be effective and at the same time safer and easier to perform.

Molecular mechanisms of mitochondrial DNA depletion diseases caused by deficiencies in enzymes in purine and pyrimidine metabolism.

PubMed

Eriksson, Staffan; Wang, Liya

2008-06-01

Mitochondrial DNA depletion syndrome (MDS), a reduction of mitochondrial DNA copy number, often affects muscle or liver. Mutations in enzymes of deoxyribonucleotide metabolism give MDS, for example, the mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) genes. Sixteen TK2 and 22 dGK alterations are known. Their characteristics and symptoms are described. Levels of five key deoxynucleotide metabolizing enzymes in mouse tissues were measured. TK2 and dGK levels in muscles were 5- to 10-fold lower than other nonproliferating tissues and 100-fold lower compared to spleen. Each type of tissue apparently relies on de novo and salvage synthesis of DNA precursors to varying degrees.

Durable fear memories require PSD-95

PubMed Central

Fitzgerald, Paul J.; Pinard, Courtney R.; Camp, Marguerite C.; Feyder, Michael; Sah, Anupam; Bergstrom, Hadley; Graybeal, Carolyn; Liu, Yan; Schlüter, Oliver; Grant, Seth G.N.; Singewald, Nicolas; Xu, Weifeng; Holmes, Andrew

2014-01-01

Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. While overly persistent fear memories underlie anxiety disorders such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Post-synaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Employing a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95GK), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95GK mice to retrieve remote cued fear memories was associated with hypoactivation of the infralimbic cortex (IL) (not anterior cingulate (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated PSD-95 virus-mediated knockdown in the IL, not ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories. PMID:25510511

Durable fear memories require PSD-95.

PubMed

Fitzgerald, P J; Pinard, C R; Camp, M C; Feyder, M; Sah, A; Bergstrom, H C; Graybeal, C; Liu, Y; Schlüter, O M; Grant, S G; Singewald, N; Xu, W; Holmes, A

2015-07-01

Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. Although overly persistent fear memories underlie anxiety disorders, such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Postsynaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Using a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95(GK)), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown (KD) approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95(GK) mice to retrieve remote cued fear memory was associated with hypoactivation of the infralimbic (IL) cortex (but not the anterior cingulate cortex (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated virus-mediated PSD-95 KD in the IL, but not the ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories.

How sharp is sharp? Towards quantification of the sharpness and penetration ability of kitchen knives used in stabbings.

PubMed

Hainsworth, S V; Delaney, R J; Rutty, G N

2008-07-01

Stabbing is the most common method for violent death in the UK. As part of their investigation, forensic pathologists are commonly asked to estimate or quantify the degree of force required to create a wound. The force required to penetrate the skin and body by a knife is a complex function of the sharpness of the knife, the area of the body and alignment with cleavage lines of the skin, the angle of attack and the relative movement of the person stabbing relative to the victim being stabbed. This makes it difficult for the forensic pathologist to give an objective answer to the question; hence, subjective estimations are often used. One area where some degree of quantification is more tractable is in assessing how sharp an implement (particularly a knife) is. This paper presents results of a systematic study of how the different aspects of knife geometry influence sharpness and presents a simple test for assessing knife sharpness using drop testing. The results show that the radius of the blunt edge at the tip is important for controlling the penetration ability of a kitchen knife. Using high-speed video, it also gives insight into the mechanism of knife penetration into the skin. The results of the study will aid pathologists in giving a more informed answer to the question of the degree of force used in stabbing.

Knife River Indian Villages National Historic Site: Teacher's Guide.

ERIC Educational Resources Information Center

National Park Service (Dept. of Interior), Washington, DC. National Register of Historic Places.

This guide provides history and social studies teachers, at all grade levels, with information and activities about the American Indians of the Northern Plains who lived in the area of the Knife River where it enters the Missouri River. Located in what is now North Dakota, this area is the Knife River Indian Villages National Historic Site. The…

Removing seed coat fragments with a lint cleaner grid bar air knife

USDA-ARS?s Scientific Manuscript database

Seed coat fragments (SCF) in ginned lint cause spinning problems at the textile mill and undesirable defects in finished goods. Work continued on developing an air knife that may help remove SCF from ginned lint. The air knife is mounted on the 1st lint cleaner grid bar of a saw-type lint cleaner,...

"Knife to skin" time is a poor marker of operating room utilization and efficiency in cardiac surgery.

PubMed

Luthra, Suvitesh; Ramady, Omar; Monge, Mary; Fitzsimons, Michael G; Kaleta, Terry R; Sundt, Thoralf M

2015-06-01

Markers of operation room (OR) efficiency in cardiac surgery are focused on "knife to skin" and "start time tardiness." These do not evaluate the middle and later parts of the cardiac surgical pathway. The purpose of this analysis was to evaluate knife to skin time as an efficiency marker in cardiac surgery. We looked at knife to skin time, procedure time, and transfer times in the cardiac operational pathway for their correlation with predefined indices of operational efficiency (Index of Operation Efficiency - InOE, Surgical Index of Operational Efficiency - sInOE). A regression analysis was performed to test the goodness of fit of the regression curves estimated for InOE relative to the times on the operational pathway. The mean knife to skin time was 90.6 ± 13 minutes (23% of total OR time). The mean procedure time was 282 ± 123 minutes (71% of total OR time). Utilization efficiencies were highest for aortic valve replacement and coronary artery bypass grafting and least for complex aortic procedures. There were no significant procedure-specific or team-specific differences for standard procedures. Procedure times correlated the strongest with InOE (r = -0.98, p < 0.01). Compared to procedure times, knife to skin is not as strong an indicator of efficiency. A statistically significant linear dependence on InOE was observed with "procedure times" only. Procedure times are a better marker of OR efficiency than knife to skin in cardiac cases. Strategies to increase OR utilization and efficiency should address procedure times in addition to knife to skin times. © 2015 Wiley Periodicals, Inc.

Diamond knife-assisted deep anterior lamellar keratoplasty to manage keratoconus.

PubMed

Vajpayee, Rasik B; Maharana, Prafulla K; Sharma, Namrata; Agarwal, Tushar; Jhanji, Vishal

2014-02-01

To evaluate the outcomes of a new surgical technique, diamond knife-assisted deep anterior lamellar keratoplasty (DALK), and compare its visual and refractive results with big-bubble DALK in cases of keratoconus. Tertiary eyecare hospital. Comparative case series. The visual and surgical outcomes of diamond knife-assisted DALK were compared with those of successful big-bubble DALK. Diamond knife-assisted DALK was performed in 19 eyes and big-bubble DALK, in 11 eyes. All surgeries were completed successfully. No intraoperative or postoperative complications occurred with diamond knife-assisted DALK. Six months after diamond knife-assisted DALK, the mean corrected distance visual acuity (CDVA) improved significantly from 1.87 logMAR ± 0.22 (SD) to 0.23 ± 0.06 logMAR, the mean keratometry improved from 65.99 ± 8.86 diopters (D) to 45.13 ± 1.16 D, and the mean keratometric cylinder improved from 7.99 ± 3.81 D to 2.87 ± 0.59 D (all P=.005). Postoperatively, the mean refractive astigmatism was 2.55 ± 0.49 D and the mean spherical equivalent was -1.97 ± 0.56 D. The mean logMAR CDVA (P = .06), postoperative keratometry (P=.64), refractive cylinder (P=.63), and endothelial cell loss (P=.11) were comparable between diamond knife-assisted DALK and big-bubble DALK. Diamond knife-assisted DALK was effective and predictable as a surgical technique for management of keratoconus cases. This technique has the potential to offer visual and refractive outcomes comparable to those of big-bubble DALK. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Bipolar plasma vaporization using plasma-cutting and plasma-loop electrodes versus cold-knife transurethral incision for the treatment of posterior urethral stricture: a prospective, randomized study.

PubMed

Cai, Wansong; Chen, Zhiyuan; Wen, Liping; Jiang, Xiangxin; Liu, Xiuheng

2016-01-01

Evaluate the efficiency and safety of bipolar plasma vaporization using plasma-cutting and plasma-loop electrodes for the treatment of posterior urethral stricture. Compare the outcomes following bipolar plasma vaporization with conventional cold-knife urethrotomy. A randomized trial was performed to compare patient outcomes from the bipolar and cold-knife groups. All patients were assessed at 6 and 12 months postoperatively via urethrography and uroflowmetry. At the end of the first postoperative year, ureteroscopy was performed to evaluate the efficacy of the procedure. The mean follow-up time was 13.9 months (range: 12 to 21 months). If re-stenosis was not identified by both urethrography and ureteroscopy, the procedure was considered "successful". Fifty-three male patients with posterior urethral strictures were selected and randomly divided into two groups: bipolar group (n=27) or cold-knife group (n=26). Patients in the bipolar group experienced a shorter operative time compared to the cold-knife group (23.45±7.64 hours vs 33.45±5.45 hours, respectively). The 12-month postoperative Qmax was faster in the bipolar group than in the cold-knife group (15.54±2.78 ml/sec vs 18.25±2.12 ml/sec, respectively). In the bipolar group, the recurrence-free rate was 81.5% at a mean follow-up time of 13.9 months. In the cold-knife group, the recurrence-free rate was 53.8%. The application of bipolar plasma-cutting and plasma-loop electrodes for the management of urethral stricture disease is a safe and reliable method that minimizes the morbidity of urethral stricture resection. The advantages include a lower recurrence rate and shorter operative time compared to the cold-knife technique.

Influence on grip of knife handle surface characteristics and wearing protective gloves.

PubMed

Claudon, Laurent

2006-11-01

Ten subjects were asked to apply maximum torques on knife handles with either their bare hand or their hand wearing a Kevlar fibre protective glove. Four knife handles (2 roughnesses, 2 hardnesses) were tested. Surface electromyograms of 6 upper limb and shoulder muscles were recorded and subject opinions on both knife handle hardness and friction in the hand were also assessed. The results revealed the significant influence of wearing gloves (p<0.0001), knife type (p<0.0005) and handle hardness (p<0.005) on the applied torque. Wearing Kevlar fibre gloves greatly increased the torque independently of the other two parameters. Under the bare hand condition, a 90 degrees ShA slightly rough handle provided the greatest torque. Subject opinion agreed with the observed effects on recorded torque values except for the hardness factor, for which a preference for the 70 degrees ShA value over the 90 degrees ShA value emerged.

Preparing Graduate Students for Teaching: Expected and Unexpected Outcomes from Participation in a GK-12 Classroom Fellowship

ERIC Educational Resources Information Center

Page, Melissa; Wilhelm, Mari S.; Regens, Nancy

2011-01-01

Graduate students in science technology, engineering, and mathematics (STEM) fields often enter degree programs focused on research or field-based experiences. Being a teaching assistant can serve two purposes: one for financial compensation and two as preparation for teaching in a future career. The GK-12 program (Graduate Teaching Fellows in…

Distributed and Focused Attention: Neuropsychological Evidence for Separate Attentional Mechanisms when Counting and Estimating

ERIC Educational Resources Information Center

Demeyere, Nele; Humphreys, Glyn W.

2007-01-01

Evidence is presented for 2 modes of attention operating in simultanagnosia. The authors examined visual enumeration in a patient, GK, who has severe impairments in serially scanning across a scene and is unable to count the numbers of items in visual displays. However, GK's ability to judge the relative magnitude of 2 displays was consistently…

Effects of Maximal Sodium and Potassium Conductance on the Stability of Hodgkin-Huxley Model

PubMed Central

Wang, Kuanquan; Yuan, Yongfeng; Zhang, Henggui

2014-01-01

Hodgkin-Huxley (HH) equation is the first cell computing model in the world and pioneered the use of model to study electrophysiological problems. The model consists of four differential equations which are based on the experimental data of ion channels. Maximal conductance is an important characteristic of different channels. In this study, mathematical method is used to investigate the importance of maximal sodium conductance g-Na and maximal potassium conductance g-K. Applying stability theory, and taking g-Na and g-K as variables, we analyze the stability and bifurcations of the model. Bifurcations are found when the variables change, and bifurcation points and boundary are also calculated. There is only one bifurcation point when g-Na is the variable, while there are two points when g-K is variable. The (g-Na,  g-K) plane is partitioned into two regions and the upper bifurcation boundary is similar to a line when both g-Na and g-K are variables. Numerical simulations illustrate the validity of the analysis. The results obtained could be helpful in studying relevant diseases caused by maximal conductance anomaly. PMID:25104970

The insulin and islet amyloid polypeptide genes contain similar cell-specific promoter elements that bind identical beta-cell nuclear complexes.

PubMed Central

German, M S; Moss, L G; Wang, J; Rutter, W J

1992-01-01

The pancreatic beta cell makes several unique gene products, including insulin, islet amyloid polypeptide (IAPP), and beta-cell-specific glucokinase (beta GK). The functions of isolated portions of the insulin, IAPP, and beta GK promoters were studied by using transient expression and DNA binding assays. A short portion (-247 to -197 bp) of the rat insulin I gene, the FF minienhancer, contains three interacting transcriptional regulatory elements. The FF minienhancer binds at least two nuclear complexes with limited tissue distribution. Sequences similar to that of the FF minienhancer are present in the 5' flanking DNA of the human IAPP and rat beta GK genes and also the rat insulin II and mouse insulin I and II genes. Similar minienhancer constructs from the insulin and IAPP genes function as cell-specific transcriptional regulatory elements and compete for binding of the same nuclear factors, while the beta GK construct competes for protein binding but functions poorly as a minienhancer. These observations suggest that the patterns of expression of the beta-cell-specific genes result in part from sharing the same transcriptional regulators. Images PMID:1549125

Global expression profiling of glucose-regulated genes in pancreatic islets of spontaneously diabetic Goto-Kakizaki rats.

PubMed

Ghanaat-Pour, Hamedeh; Huang, Zhen; Lehtihet, Mikael; Sjöholm, Ake

2007-08-01

The spontaneously diabetic Goto-Kakizaki (GK) rat is frequently used as a model for human type 2 diabetes. Selective loss of glucose-sensitive insulin secretion is an early pathogenetic event in human type 2 diabetes, and such a defect also typifies islets from the GK rat. We investigated whether expression of specific glucose-regulated genes is disturbed in islets from GK rats when compared with Wistar rats. Large-scale gene expression analysis using Affymetrix microarrays and qRT-PCR measurements of mRNA species from normal and diabetic islets were performed after 48 h of culture at 3 or 20 mM glucose. Of the 2020 transcripts differentially regulated in diabetic GK islets when compared with controls, 1033 were up-regulated and 987 were down-regulated. We identified significant changes in islet mRNAs involved in glucose sensing, phosphorylation, incretin action, glucocorticoid handling, ion transport, mitogenesis, and apoptosis that clearly distinguish diabetic animals from controls. Such markers may provide clues to the pathogenesis of human type 2 diabetes and may be of predictive and therapeutical value in clinical settings in efforts aiming at conferring beta-cell protection against apoptosis, impaired regenerative capacity and functional suppression occurring in diabetes.

A new spectroscopic calibration to determine Teff and [Fe/H] of FGK dwarfs and giants

NASA Astrophysics Data System (ADS)

Teixeira, G. D. C.; Sousa, S. G.; Tsantaki, M.; Monteiro, M. J. P. F. G.; Santos, N. C.; Israelian, G.

2017-10-01

We present a new spectroscopic calibration for a fast estimate of Teff and [Fe/H] for FGK dwarfs and GK giant stars. We used spectra from a joint sample of 708 stars, composed by 451 FGK dwarfs and 257 GK-giant stars with homogeneously determined spectroscopic stellar parameters. We have derived 322 EW line-ratios and 100 FeI lines that can be used to compute Teff and [Fe/H], respectively. We show that these calibrations are effective for FGK dwarfs and GK-giant stars in the following ranges: 4500 K < Teff < 6500 K, 2.5 < log g < 4.9 dex, and -0.8 < [Fe/H] < 0:5 dex. The new calibration has a standard deviation of 74 K for Teff and 0.07 dex for [Fe/H]. We use four independent samples of stars to test and verify the new calibration, a sample of giant stars, a sample composed of Gaia FGK benchmark stars, a sample of GK-giant stars from the DR1 of the Gaia-ESO survey, and a sample of FGK-dwarf stars. We present a new computer code, GeTCal, for automatically producing new calibration files based on any new sample of stars.

Gamma Knife® radiosurgery for trigeminal neuralgia.

PubMed

Yen, Chun-Po; Schlesinger, David; Sheehan, Jason P

2011-11-01

Trigeminal neuralgia is characterized by a temporary paroxysmal lancinating facial pain in the trigeminal nerve distribution. The prevalence is four to five per 100,000. Local pressure on nerve fibers from vascular loops results in painful afferent discharge from an injured segment of the fifth cranial nerve. Microvascular decompression addresses the underlying pathophysiology of the disease, making this treatment the gold standard for medically refractory trigeminal neuralgia. In patients who cannot tolerate a surgical procedure, those in whom a vascular etiology cannot be identified, or those unwilling to undergo an open surgery, stereotactic radiosurgery is an appropriate alternative. The majority of patients with typical facial pain will achieve relief following radiosurgical treatment. Long-term follow-up for recurrence as well as for radiation-induced complications is required in all patients undergoing stereotactic radiosurgery for trigeminal neuralgia.

Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas.

PubMed

Kruyt, Ivo J; Verheul, Jeroen B; Hanssens, Patrick E J; Kunst, Henricus P M

2018-01-01

OBJECTIVE Neurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS. METHODS The authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes. RESULTS Actuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm 3 both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients experienced worsening of trigeminal nerve function. Facial nerve function worsened in 1 patient (2.5%). No significant differences in tumor control, hearing preservation, or complications were found in comparing the results of GKRS for NF2-related VS versus GKRS for sporadic VS. CONCLUSIONS With modern GKRS, the use of low margin doses for treating growing VSs in patients with NF2 demonstrates good long-term tumor control rates. Feiling-Gardner phenotype and tumor volume smaller than 6 cm 3 seem to be independently associated with prolonged progression-free survival, highlighting the clinical importance of phenotype assessment before GKRS treatment. In addition, no significant differences in tumor control rates or complications were found in the matched-control cohort analysis comparing GKRS for VS in patients with NF2 and GKRS for sporadic VS. These results show that GKRS is a valid treatment option for NF2-related VS, in addition to being a good option for sporadic VS, particularly in patients with the Feiling-Gardner phenotype and/or tumors that are small to medium in size. Larger tumors in patients with the Wishart phenotype appear to respond poorly to radiosurgery, and other treatment modalities should therefore be considered in such cases.

Predictors of quality of life and survival following Gamma Knife surgery for lung cancer brain metastases: a prospective study.

PubMed

Bragstad, Sidsel; Flatebø, Marianne; Natvig, Gerd Karin; Eide, Geir Egil; Skeie, Geir Olve; Behbahani, Maziar; Pedersen, Paal-Henning; Enger, Per Øyvind; Skeie, Bente Sandvei

2017-08-18

OBJECTIVE Lung cancer (LC) patients who develop brain metastases (BMs) have a poor prognosis. Estimations of survival and risk of treatment-related deterioration in quality of life (QOL) are important when deciding on treatment. Although we know of several prognostic factors for LC patients with BMs, the role of QOL has not been established. Authors of this study set out to evaluate changes in QOL following Gamma Knife surgery (GKS) for BMs in LC patients and QOL as a prognostic factor for survival. METHODS Forty-four of 48 consecutive LC patients with BMs underwent GKS in the period from May 2010 to September 2011, and their QOL was prospectively assessed before and 1, 3, 6, 9, and 12 months after GKS by using the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire. A mixed linear regression model was used to identify potential predictive factors for QOL and to assess the effect of GKS and the disease course on QOL at follow-up. RESULTS Mean QOL as measured by the brain cancer subscale (BRCS) of the FACT-BR remained stable from baseline (score 53.0) up to 12 months post-GKS (57.1; p = 0.624). The BRCS score improved for 32 patients (72.3%) with a total BM volume ≤ 5 cm 3 . Mean improvement in these patients was 0.45 points each month of follow-up, compared to a decline of 0.50 points each month despite GKS treatment in patients with BM volumes > 5 cm 3 (p = 0.04). Asymptomatic BMs (p = 0.01), a lower recursive partitioning analysis (RPA) classification (p = 0.04), and a higher Karnofsky Performance Scale (KPS) score (p < 0.01) at baseline were predictors for a high, stable QOL after GKS. After multivariate analysis, a high KPS score (p < 0.01) remained the only positive predictor of a high, stable QOL post-GKS. Median survival post-GKS was 5.6 months (95% CI 1.0-10.3). A higher BRCS score (p = 0.01), higher KPS score (p = 0.01), female sex (p = 0.01), and the absence of liver (p = 0.02), adrenal (p = 0.02), and bone metastases (p = 0.03) predicted longer survival in unadjusted models. However, in multivariate analyses, a higher BRCS score (p < 0.01), female sex (p = 0.01), and the absence of bone metastases (p = 0.02) at GKS remained significant predictors. Finally, the BRCS score's predictive value for survival was compared with the values for the variables behind well-known prognostic indices: age, KPS score, extracranial disease status, and number and volume of BMs. Both BRCS score (p = 0.01) and BM volume (p = 0.05) remained significant predictors for survival in the final model. CONCLUSIONS Patient-reported QOL according to the BRCS is a predictor of survival in patients with BMs and may be helpful in deciding on the optimal treatment. Gamma Knife surgery is a safe and effective therapeutic modality that improves QOL for LC patients with a BM volume ≤ 5 cm 3 at treatment. Careful follow-up and salvage therapy on demand seem to prevent worsening of QOL due to relapse of BMs.

Objective assessment of knife sharpness over a working day cutting meat.

PubMed

Savescu, Adriana; Cuny-Guerrier, Aude; Wild, Pascal; Reno, Gilles; Aublet-Cuvelier, Agnès; Claudon, Laurent

2018-04-01

Knife sharpness is one of multiple factors involved in musculoskeletal disorders in industrial meat cutting. The aim of this study was to objectively evaluate, in real working situations, how knife sharpness changed over a working day cutting meat, and to analyse the impact of sharpening, steeling and meat-cutting activities on these variations. Twenty-two meat-cutting workers from three different companies participated in the study. The methods included measurements of knife sharpness in relation to real work situations and consideration of the way meat-cutting and sharpening operations were organised. Results showed that the type of meat-cutting activities, the steeling strategy adopted by the worker, including the types of tool used, and the overall organisation of the sharpening task all had a significant influence on how knife sharpness evolved over a 2-h period and over an entire working day. To improve MSD prevention, sharpening and steeling operations should not be considered as independent activities, but taken into account as a continuity of working actions. Appropriate assessment of knife sharpness by meat cutters affects how they organise meat-cutting and sharpening tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

The cutting edge - Micro-CT for quantitative toolmark analysis of sharp force trauma to bone.

PubMed

Norman, D G; Watson, D G; Burnett, B; Fenne, P M; Williams, M A

2018-02-01

Toolmark analysis involves examining marks created on an object to identify the likely tool responsible for creating those marks (e.g., a knife). Although a potentially powerful forensic tool, knife mark analysis is still in its infancy and the validation of imaging techniques as well as quantitative approaches is ongoing. This study builds on previous work by simulating real-world stabbings experimentally and statistically exploring quantitative toolmark properties, such as cut mark angle captured by micro-CT imaging, to predict the knife responsible. In Experiment 1 a mechanical stab rig and two knives were used to create 14 knife cut marks on dry pig ribs. The toolmarks were laser and micro-CT scanned to allow for quantitative measurements of numerous toolmark properties. The findings from Experiment 1 demonstrated that both knives produced statistically different cut mark widths, wall angle and shapes. Experiment 2 examined knife marks created on fleshed pig torsos with conditions designed to better simulate real-world stabbings. Eight knives were used to generate 64 incision cut marks that were also micro-CT scanned. Statistical exploration of these cut marks suggested that knife type, serrated or plain, can be predicted from cut mark width and wall angle. Preliminary results suggest that knives type can be predicted from cut mark width, and that knife edge thickness correlates with cut mark width. An additional 16 cut marks walls were imaged for striation marks using scanning electron microscopy with results suggesting that this approach might not be useful for knife mark analysis. Results also indicated that observer judgements of cut mark shape were more consistent when rated from micro-CT images than light microscopy images. The potential to combine micro-CT data, medical grade CT data and photographs to develop highly realistic virtual models for visualisation and 3D printing is also demonstrated. This is the first study to statistically explore simulated real-world knife marks imaged by micro-CT to demonstrate the potential of quantitative approaches in knife mark analysis. Findings and methods presented in this study are relevant to both forensic toolmark researchers as well as practitioners. Limitations of the experimental methodologies and imaging techniques are discussed, and further work is recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of holmium laser versus cold knife in optical internal urethrotomy for the management of short segment urethral stricture.

PubMed

Jain, Sudhir Kumar; Kaza, Ram Chandra Murthy; Singh, Bipin Kumar

2014-10-01

SACHSE COLD KNIFE IS CONVENTIONALLY USED FOR OPTICAL INTERNAL URETHROTOMY INTENDED TO MANAGE URETHRAL STRICTURES AND HO: YAG laser is an alternative to it. The aim of this study was to evaluate the role of urethral stricture treatment outcomes, efficacy, and complications using cold knife and Ho: YAG (Holmium laser) for optical internal urethrotomy. In this prospective study included, 90 male patients age >18 years, with diagnosis of urethral stricture admitted for internal optical urethrotomy during April 2010 to March 2012. The patients were randomized into two groups containing 45 patients each using computer generated random number. In group A (Holmium group), internal urethrotomy was done with Holmium laser and in group B (Cold knife group) Sachse cold knife was used. Patients were followed up for 6 months after surgery in Out Patient Department on 15, 30 and 180 post-operative days. At each follow up visit physical examination, and uroflowmetry was performed along with noting complaints, if any. The peak flow rates (PFR) were compared between the two groups on each follow up. At 180 days (6 month interval) the difference between mean of PFR for Holmium and Cold knife group was statistically highly significant (P < 0.001). Complications were seen in 12.22% of cases. Both modalities are effective in providing immediate relief to patients with single and short segment (<2 cm long) urethral strictures but more sustained response was attained with Cold knife urethrotomy.

The Amino Terminus of Herpes Simplex Virus 1 Glycoprotein K (gK) Is Required for gB Binding to Akt, Release of Intracellular Calcium, and Fusion of the Viral Envelope with Plasma Membranes.

PubMed

Musarrat, Farhana; Jambunathan, Nithya; Rider, Paul J F; Chouljenko, V N; Kousoulas, K G

2018-03-15

Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to the amino terminus of gB and that deletion of the amino-terminal 38 amino acids of gK prevents herpes simplex virus 1 (HSV-1) infection of mouse trigeminal ganglia after ocular infection and virus entry into neuronal axons. Recently, it has been shown that gB binds to Akt during virus entry and induces Akt phosphorylation and intracellular calcium release. Proximity ligation and two-way immunoprecipitation assays using monoclonal antibodies against gB and Akt-1 phosphorylated at S473 [Akt-1(S473)] confirmed that HSV-1(McKrae) gB interacted with Akt-1(S473) during virus entry into human neuroblastoma (SK-N-SH) cells and induced the release of intracellular calcium. In contrast, the gB specified by HSV-1(McKrae) gKΔ31-68, lacking the amino-terminal 38 amino acids of gK, failed to interact with Akt-1(S473) and induce intracellular calcium release. The Akt inhibitor miltefosine inhibited the entry of McKrae but not the gKΔ31-68 mutant into SK-N-SH cells. Importantly, the entry of the gKΔ31-68 mutant but not McKrae into SK-N-SH cells treated with the endocytosis inhibitors pitstop-2 and dynasore hydrate was significantly inhibited, indicating that McKrae gKΔ31-68 entered via endocytosis. These results suggest that the amino terminus of gK functions to regulate the fusion of the viral envelope with cellular plasma membranes. IMPORTANCE HSV-1 glycoprotein B (gB) functions in the fusion of the viral envelope with cellular membranes during virus entry. Herein, we show that a deletion in the amino terminus of glycoprotein K (gK) inhibits gB binding to Akt-1(S473), the release of intracellular calcium, and virus entry via fusion of the viral envelope with cellular plasma membranes. Copyright © 2018 American Society for Microbiology.

Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats.

PubMed

Zhou, Qian; Sun, Yan; Tan, Wangxiao; Liu, Xiao; Qian, Yuchen; Ma, Xianghui; Wang, Ting; Wang, Xiaoying; Gao, Xiumei

2017-01-01

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.

Effect of Shenmai injection on preventing the development of nitroglycerin-induced tolerance in rats

PubMed Central

Zhou, Qian; Sun, Yan; Tan, Wangxiao; Liu, Xiao; Qian, Yuchen; Ma, Xianghui; Wang, Ting; Wang, Xiaoying; Gao, Xiumei

2017-01-01

Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance. PMID:28453571

Simple Schlieren Light Meter

NASA Technical Reports Server (NTRS)

Rhodes, David B.; Franke, John M.; Jones, Stephen B.; Leighty, Bradley D.

1992-01-01

Simple light-meter circuit used to position knife edge of schlieren optical system to block exactly half light. Enables operator to check quickly position of knife edge between tunnel runs to ascertain whether or not in alignment. Permanent measuring system made part of each schlieren system. If placed in unused area of image plane, or in monitoring beam from mirror knife edge, provides real-time assessment of alignment of schlieren system.