bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic chemosensitivity of rostral ventrolateral medullary sympathetic premotor neurons in the in situ arterially perfused preparation of rats
Authors: Koganezawa Tadachika , Paton Julian F. R.
Published: July 2014

New Findings

What is the central question of this study?

Brain hypoperfusion is a key factor triggering hypertension through activation of cardiovascular sympathetic vasomotor nerves. However, mechanisms of detecting brain hypoperfusion remain unclear. We hypothesized that the sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) can sense asphyxia and cause sympathoexcitation.

What is the main finding and its importance?

Functionally identified RVLM sympathetic premotor neurons were excited by hypoxia but less so by hypercapnia, before and after blockade of synaptic transmission. The RVLM sympathetic premotor neurons can act as an important oxygen sensor during brain hypoxia/hypoperfusion, which may be important in maintaining sympathetic nerve discharge to support blood pressure and hence maintain brain perfusion.

Brainstem hypoperfusion is a major excitant of sympathetic activity triggering hypertension, but the exact mechanisms involved remain incompletely understood. A major source of excitatory drive to preganglionic sympathetic neurons originates from the ongoing activity of premotor neurons in the rostral ventrolateral medulla (RVLM sympathetic premotor neurons). The chemosensitivity profile of physiologically characterized RVLM sympathetic premotor neurons during hypoxia and hypercapnia remains unclear. We examined whether physiologically characterized RVLM sympathetic premotor neurons can sense brainstem ischaemia intrinsically. We addressed this issue in a unique in situ arterially perfused preparation before and after a complete blockade of fast excitatory and inhibitory synaptic transmission. During hypercapnic hypoxia, respiratory modulation of RVLM sympathetic premotor neurons was lost, but tonic firing of most RVLM sympathetic premotor neurons was elevated. After blockade of fast excitatory and inhibitory synaptic transmission, RVLM sympathetic premotor neurons continued to fire and exhibited an excitatory firing response to hypoxia but not hypercapnia. This study suggests that RVLM sympathetic premotor neurons can sustain high levels of neuronal discharge when oxygen is scarce. The intrinsic ability of RVLM sympathetic premotor neurons to maintain responsivity to brainstem hypoxia is an important mechanism ensuring adequate arterial pressure, essential for maintaining cerebral perfusion in the face of depressed ventilation and/or high cerebral vascular resistance.
Respiratory pump contributes to increased physiological reserve for compensation during simulated haemorrhage
Authors: Poh Paula Y. S. , Carter Robert , Hinojosa‐Laborde Carmen , Mulligan Jane , Grudic Gregory Z. , Convertino Victor A.
Published: July 2014

New Findings

What is the central question of this study?

The negative intrathoracic pressure created by inspiration (i.e. the respiratory pump) is associated with enhanced venous return, although its contribution as a potential mechanism of compensation during blood loss has not been quantified.

What is the main finding and its importance?

We demonstrated that optimizing the creation of negative intrathoracic pressure during inspiration represented a mechanism of compensation during haemorrhage that was quantifiably reflected in a reduced rate of diminution of the compensatory reserve, resulting in increased tolerance to progressive reductions in central blood volume.

Intrathoracic pressure regulation (IPR) represents a therapy for increasing systemic circulation through the creation of negative intrathoracic pressure. We hypothesized that using this ‘respiratory pump’ effect would slow the diminution of the physiological reserve to compensate during progressive reductions in central blood volume. The compensatory reserve index (CRI) algorithm was used to measure the proportion (from 100 to 0%) of reserve capacity that remained to compensate for central volume loss before the onset of cardiovascular decompensation. Continuous analog recordings of arterial waveforms were extracted from data files of seven healthy volunteers. Subjects had previously participated in experiments designed to induce haemodynamic decompensation (presyncope) by progressive reduction in central blood volume using graded lower‐body negative pressure. The lower‐body negative pressure protocol was completed while breathing spontaneously through a standard medical face mask without (placebo) and with a resistance (approximately −7 cmH2O; active IPR) applied during inspiration. At the onset of presyncope in the placebo conditions, CRI was smaller than the CRI observed at the same time point in the active IPR conditions. The CRI at the onset of presyncope during active IPR (0.08 ± 0.01) was similar to the CRI at presyncope with placebo. Kaplan–Meier and log rank tests indicated that CRI survival curves were shifted to the right by active IPR. Optimizing the respiratory pump contributed a small but significant effect of increasing tolerance to progressive reductions in central blood volume by extending the compensatory reserve.
Genesis of the characteristic pulmonary venous pressure waveform as described by the reservoir‐wave model
Authors: Bouwmeester J. Christopher , Belenkie Israel , Shrive Nigel G. , Tyberg John V.
Published: July 2014

Key points

In pressure flow data from a pulmonary vein, we use the reservoir wave model to separate the effects of an elastic venous reservoir from the effects of waves created by the heart.

Wave intensity analysis was used to separate the effects of waves generated upstream by the right ventricle from the effects of waves generated downstream by the left atrium and left ventricle.

Most waves are created by the left atrium and left ventricle and can be linked to events that occur during the cardiac cycle.

Waves transmitted through the pulmonary circulation are attenuated less when blood volume is increased but are attenuated more and delayed when the lungs are expanded.

The drainage of pulmonary arterial and venous reservoirs are responsible for substantial changes in measured pulmonary venous pressure and flow but waves are associated with the conventional landmarks of these characteristic waveforms.

Conventional haemodynamic analysis of pulmonary venous and left atrial (LA) pressure waveforms yields substantial forward and backward waves throughout the cardiac cycle; the reservoir wave model provides an alternative analysis with minimal waves during diastole. Pressure and flow in a single pulmonary vein (PV) and the main pulmonary artery (PA) were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading, and positive‐end expiratory pressure (PEEP) were observed. The reservoir wave model was used to determine the reservoir contribution to PV pressure and flow. Subtracting reservoir pressure and flow resulted in ‘excess’ quantities which were treated as wave‐related. Wave intensity analysis of excess pressure and flow quantified the contributions of waves originating upstream (from the PA) and downstream (from the LA and/or left ventricle (LV)). Major features of the characteristic PV waveform are caused by sequential LA and LV contraction and relaxation creating backward compression (i.e. pressure‐increasing) waves followed by decompression (i.e. pressure‐decreasing) waves. Mitral valve opening is linked to a backwards decompression wave (i.e. diastolic suction). During late systole and early diastole, forward waves originating in the PA are significant. These waves were attenuated less with volume loading and delayed with PEEP. The reservoir wave model shows that the forward and backward waves are negligible during LV diastasis and that the changes in pressure and flow can be accounted for by the discharge of upstream reservoirs. In sharp contrast, conventional analysis posits forward and backward waves such that much of the energy of the forward wave is opposed by the backward wave.
Assembly of AMPA receptors: mechanisms and regulation
Authors: Gan Quan , Salussolia Catherine L. , Wollmuth Lonnie P.
Published: July 2014

AMPA receptors (AMPARs) play a critical role in excitatory glutamatergic neurotransmission. The number and subunit composition of AMPARs at synapses determines the dynamics of fast glutamatergic signalling. Functional AMPARs on the cell surface are tetramers. Thus tetrameric assembly of AMPARs represents a promising target for modulating AMPAR‐mediated signalling in health and disease. Multiple structural domains within the receptor influence AMPAR assembly. In a proposed model for AMPAR assembly, the amino‐terminal domain underlies the formation of a dimer pool. The transmembrane domain facilitates the formation and enhances the stability of the tetramer. The ligand‐binding domain influences assembly through a process referred to as ‘domain swapping’. We propose that this core AMPAR assembly process could be regulated by neuronal signals and speculate on possible mechanisms for such regulation.
Osmotic activation of phospholipase C triggers structural adaptation in osmosensitive rat supraoptic neurons
Authors: Shah Love , Bansal Vimal , Rye Peter L. , Mumtaz Naima , Taherian Amir , Fisher Thomas E.
Published: July 2014

Key points

Acutely isolated rat magnocellular neurosecretory cells (MNCs) display reversible hypertrophy when exposed to hypertonic saline (325 mosmol kg−1) for tens of minutes.

Osmotically evoked hypertrophy is prevented by agents that block Na+ channels, TRPV1 channels (which mediate an osmotically evoked depolarization in these cells), L‐type Ca2+ channels, and exocytotic fusion and is associated with an increase in whole‐cell capacitance.

Exposure to hypertonic saline activates phospholipase C leading to a decrease in plasma membrane phosphatidylinositol 4,5‐bisphosphate.

Inhibition of phospholipase C or protein kinase C prevents osmotically evoked hypertrophy and activation of protein kinase C evokes hypertrophy in the absence of an increase in osmolality.

These results suggest that osmotically evoked hypertrophy is triggered by an increase in MNC action potential firing, leading to Ca2+ influx, the activation of phospholipase C, an increase in diacylglycerol, and the activation of protein kinase C.

The magnocellular neurosecretory cells of the hypothalamus (MNCs) synthesize and secrete vasopressin or oxytocin. A stretch‐inactivated cation current mediated by TRPV1 channels rapidly transduces increases in external osmolality into a depolarization of the MNCs leading to an increase in action potential firing and thus hormone release. Prolonged increases in external osmolality, however, trigger a reversible structural and functional adaptation that may enable the MNCs to sustain high levels of hormone release. One poorly understood aspect of this adaptation is somatic hypertrophy. We demonstrate that hypertrophy can be evoked in acutely isolated rat MNCs by exposure to hypertonic solutions lasting tens of minutes. Osmotically evoked hypertrophy requires activation of the stretch‐inactivated cation channel, action potential firing, and the influx of Ca2+. Hypertrophy is prevented by pretreatment with a cell‐permeant inhibitor of exocytotic fusion and is associated with an increase in total membrane capacitance. Recovery is disrupted by an inhibitor of dynamin function, suggesting that it requires endocytosis. We also demonstrate that hypertonic solutions cause a decrease in phosphatidylinositol 4,5‐bisphosphate in the plasma membranes of MNCs that is prevented by an inhibitor of phospholipase C (PLC). Inhibitors of PLC or protein kinase C (PKC) prevent osmotically evoked hypertrophy, and treatment with a PKC‐activating phorbol ester can elicit hypertrophy in the absence of changes in osmolality. These studies suggest that increases in osmolality cause fusion of internal membranes with the plasma membrane of the MNCs and that this process is mediated by activity‐dependent activation of PLC and PKC.
The contributions of filaments and cross‐bridges to sarcomere compliance in skeletal muscle
Authors: Brunello Elisabetta , Caremani Marco , Melli Luca , Linari Marco , Fernandez‐Martinez Manuel , Narayanan Theyencheri , Irving Malcolm , Piazzesi Gabriella , Lombardi Vincenzo , Reconditi Massimo
Published: July 2014

Key points

Muscle contraction is driven at the molecular level by a structural working stroke in the head domain of the myosin cross‐bridge linking the thick and thin filaments. Crystallographic models suggest that the working stroke corresponds to a relative movement of 11 nm between the attachments of the head domain to the thin and thick filaments.

The molecular mechanism of force generation depends on the relationship between cross‐bridge force and movement, which is determined by cross‐bridge and filament compliances.

Here we measured the compliance of the cross‐bridges and of the thin and thick filaments by combining mechanical and X‐ray diffraction experiments.

The results show that cross‐bridge compliance is relatively low and fully accounted for by the elasticity of the myosin head, suggesting that the myosin cross‐bridge generates isometric force by a small sub‐step of the 11 nm stroke that drives filament sliding at low load.

Force generation in the muscle sarcomere is driven by the head domain of the myosin molecule extending from the thick filament to form cross‐bridges with the actin‐containing thin filament. Following attachment, a structural working stroke in the head pulls the thin filament towards the centre of the sarcomere, producing, under unloaded conditions, a filament sliding of ∼11 nm. The mechanism of force generation by the myosin head depends on the relationship between cross‐bridge force and movement, which is determined by compliances of the cross‐bridge (Ccb) and filaments. By measuring the force dependence of the spacing of the high‐order myosin‐ and actin‐based X‐ray reflections from sartorius muscles of Rana esculenta we find a combined filament compliance (Cf) of 13.1 ± 1.2 nm MPa−1, close to recent estimates from single fibre mechanics (12.8 ± 0.5 nm MPa−1). Ccb calculated using these estimates is 0.37 ± 0.12 nm pN−1, a value fully accounted for by the compliance of the myosin head domain, 0.38 ± 0.06 nm pN−1, obtained from the intensity changes of the 14.5 nm myosin‐based X‐ray reflection in response to 3 kHz oscillations imposed on single muscle fibres in rigor. Thus, a significant contribution to Ccb from the myosin tail that joins the head to the thick filament is excluded. The low Ccb value indicates that the myosin head generates isometric force by a small sub‐step of the 11 nm stroke that drives filament sliding at low load. The implications of these results for the mechanism of force generation by myosins have general relevance for cardiac and non‐muscle myosins as well as for skeletal muscle.
Correlation between the structural and cathodoluminescence properties in InGaN/GaN multiple quantum wells with large number of quantum wells
Authors: Yang Jing , Zhao Degang , Jiang Desheng , Chen Ping , Zhu Jianjun , Liu Zongshun , Le Lingcong , He Xiaoguang , Li Xiaojing , Wang Hui , Yang Hui , Jahn Uwe
Published: July 2014

Cathodoluminescence (CL) characteristics on 30-period InGaN/GaN multiple quantum well (MQW) solar cell structures are investigated, revealing the relationship between optical and structural properties of the MQW structures with a large number of quantum wells. In the bottom MQW layers, a blueshift of CL peak along the growth direction is found and attributed to the decrease of indium content due to the compositional pulling effect. An obvious split of emission peak and a redshift of the main emission energy are found in the top MQW layers when the MQW grows above the critical layer thickness. They are attributed to the segregation of In-rich InGaN clusters rather than the increase of indium content in quantum well layer. The MQW structure is identified to consist of two regions: a strained one in the bottom, where the indium content is gradually decreased, and a partly relaxed one in the top with segregated In-rich InGaN clusters.
Preparation and bioactive properties of nanocrystalline hydroxyapatite thin films obtained by conversion of atomic layer deposited calcium carbonate
Authors: Holopainen Jani , Kauppinen Kyösti , Mizohata Kenichiro , Santala Eero , Mikkola Esa , Heikkilä Mikko , Kokkonen Hanna , Leskelä Markku , Lehenkari Petri , Tuukkanen Juha , Ritala Mikko
Published: July 2014

Nanocrystalline hydroxyapatite thin films were fabricated on silicon and titanium by atomic layer deposition (ALD) of CaCO3 and its subsequent conversion to hydroxyapatite by diammonium hydrogen phosphate (DAP) solution. The effects of conversion process parameters to crystallinity and morphology of the films were examined. DAP concentration was found to be critical in controlling the crystal size and homogeneity of the films. The hydroxyapatite phase was identified by XRD. ToF-elastic recoil detection analysis studies revealed that the films are calcium deficient in relation to hydroxyapatite with a Ca/P ratio of 1.39 for films converted with 0.2 M DAP at 95 °C. The coatings prepared on titanium conformally follow the rough surface topography of the substrate, verifying that the good step coverage of the ALD method was maintained in the conversion process. The dissolution tests revealed that the coating was nondissolvable in the cell culture medium. Annealing the coated sample at 700 °C for 1 h seemed to enhance its bonding properties to the substrate. Also, the biocompatibility of the coatings was confirmed by human bone marrow derived cells in vitro. The developed method provides a new possibility to produce thin film coatings on titanium implants with bone-type hydroxyapatite that is biocompatible with human osteoblasts and osteoclasts.
Improving mass candidate detection in mammograms via feature maxima propagation and local feature selection
Authors: Melendez Jaime , Sánchez Clara I. , van Ginneken Bram , Karssemeijer Nico
Published: July 2014

Purpose:

Mass candidate detection is a crucial component of multistep computer‐aided detection (CAD) systems. It is usually performed by combining several local features by means of a classifier. When these features are processed on a per‐image‐location basis (e.g., for each pixel), mismatching problems may arise while constructing feature vectors for classification, which is especially true when the behavior expected from the evaluated features is a peaked response due to the presence of a mass. In this study, two of these problems, consisting of maxima misalignment and differences of maxima spread, are identified and two solutions are proposed.

Methods:

The first proposed method, feature maxima propagation, reproduces feature maxima through their neighboring locations. The second method, local feature selection, combines different subsets of features for different feature vectors associated with image locations. Both methods are applied independently and together.

Results:

The proposed methods are included in a mammogram‐based CAD system intended for mass detection in screening. Experiments are carried out with a database of 382 digital cases. Sensitivity is assessed at two sets of operating points. The first one is the interval of 3.5–15 false positives per image (FPs/image), which is typical for mass candidate detection. The second one is 1 FP/image, which allows to estimate the quality of the mass candidate detector's output for use in subsequent steps of the CAD system. The best results are obtained when the proposed methods are applied together. In that case, the mean sensitivity in the interval of 3.5–15 FPs/image significantly increases from 0.926 to 0.958 (p < 0.0002). At the lower rate of 1 FP/image, the mean sensitivity improves from 0.628 to 0.734 (p < 0.0002).

Conclusions:

Given the improved detection performance, the authors believe that the strategies proposed in this paper can render mass candidate detection approaches based on image location classification more robust to feature discrepancies and prove advantageous not only at the candidate detection level, but also at subsequent steps of a CAD system.
SU‐E‐T‐412: Effect of Ingested Contrast Media On Dose Reporting for GI Malignancies Comparing Multiple Dose Calculation Algorithms
Authors: Doemer A , Miller B , Chetty I
Published: July 2014

Purpose:

Varian AcurosXB calculates dose‐to‐medium (Dm) as well as the clinically prevalent dose‐to‐water (Dw). For abdominal malignancies, ingested contrast is used during simulation to delineate the treatment volume (TV) or outline the organ at risk (OAR), but this effect is transient. The purpose of this study is to evaluate the effect of contrast media on dose reporting using AAA, Acuros(Dw) and Acuros(Dm).

Methods:

Ingested contrast was contoured and either “forced” to water density or left uncorrected. Six plans were generated for 26 patients in Eclipse using identical leaf motions and MU values. The Acuros(Dm) forced density plan was our gold standard.

Results:

For 6MV plans where contrast was in the TV, AAA underrepresented the dose to the contrast region by 3.91%±3.08% (p=0.037) and 2.51%±1.25% (p=0.005) for unforced and forced densities respectively. Acuros(Dw) plans with unforced and forced densities overrepresented the dose by 2.97%±1.23% (p=.001) and 1.66%±0.24% (p=2.5e‐4). For 6MV plans where contrast was an OAR, all plans were not statistically significantly different from the Acuros(dm) plan. For 15MV plans where contrast was in the TV, AAA overrepresented the dose to the contrast region by 0.73%±0.49% (p=0.015) and 0.95%±0.39% (p=0.002) for unforced and forced densities respectively. Acuros(Dw) plans with unforced and forced densities overrepresented the dose by 2.15%±1.20% (p=0.009) and 1.00%±0.63% (p=0.007). Plans calculated with an unforced density in Acuros dm consistently showed the closest agreement to the Acuros(Dm) plan calculated with forced densities. For all 26 plans, the difference was ‐0.25%±0.84%.

Conclusion:

The appearance of contrast media will impact dose calculation. More clinical studies are needed to determine if dw and dm reporting shows any clinical significance. Care should be taken to force the density of contrast media in the GI region to a suitable value. As a fail safe condition, the use of Acuros(Dm) is recommended for these treatments.
SU‐E‐T‐413: Experience‐Based VMAT Plan Quality Database
Authors: Bernstein K , Kalach N , Wolthuis B , Tai C , Kravchuk A , Bernstein E
Published: July 2014

Purpose:

To quantify VMAT plan quality using a retrospective study of over 200 clinical treated VMAT plans created using the Eclipse Treatment Planning System to create benchmarks of plan quality for a few categories of treatment sites.

Methods:

Using a controlled phantom geometry, various dosimetric indices were investigated to quantify dosimetric plan quality as a function of isocenter displacement from center of mass, average path length, number of arcs and PTV proximity to critical structures. Beginning with published dosimetry indices from SRS and SBRT evaluations, UDI (Unified Dosimetry Index) and modified UDI were tested before creating a new factor VMAT‐DI. VMAT‐DI was developed within boundaries of this project and it includes renormalized factors of conformity index, coverage index, modified gradient index and homogeneity index as well as indices based on routine clinical practice such as absolute dose max index. The plans were then evaluated using the VMAT‐DI such that benchmarks for planning could be created.

Results:

The majority of the plans evaluated could be assigned VMAT‐DI values within a range for each treatment site. However, the outliers were results of difficult planning parameters such as very irregular targets, inhomogeneities or difficult to achieve critical structure constraints. To effectively use VMAT‐DI for guidance, especially for prediction of the plan quality for body sites new to the practice, VMATDI database needs to be subdivided by target complexity and by body site index/average path length factor.

Conclusion:

An experienced‐based VMAT‐DI database can be used to help analyze plans before evaluation by the physician to show that it adheres to the clinical standards of previously treated VMAT plans which will make a guideline for concluding the optimization. The introduction of institution‐wide clinical planning protocols, standardizing OAR naming and constraints will make it possible to incorporate a cumulative critical structure dosimetry index such as NTCP.
SU‐E‐T‐414: TG‐129 Implementation On BrachyvisionTM
Authors: Nguyen A , Hu Y , He R , Paul T , Plowman A , Mobit P , Ma J , Packianathan S , Kanakamedala M , Yang C
Published: July 2014

Purpose:

To outline the steps taken to clinically implement TG‐129 on Brachyvision™ Treatment Planning System and to show the dosimetric differences that can be expected from the original COMS Eye Plaque model.

Methods:

The original COMS‐Eye Plaque protocol was based on the following simplification: point source model in infinite water medium, 1D geometric function, 1D radial dose function and no anisotropy. Recently, AAPM Task Group 129 had made two specific recommendations: 1> Upgrade to TG‐43U1 line source model; and 2> Report the heterogeneity corrected dose. Upgrading to line TG‐43U1 line source model was done by a creating a seed collection in Brachyvision (version 11) for each plaque size. For each seed in the collection, both end coordinates had to be entered into the software. Full line source model was followed to compute the homogeneous dose at the prescription point. This homogeneous dose was converted to heterogeneous dose using a conversion table. Dose to prescription points for five different plaque sizes, including one customized notched plaque, was calculated using the implemented TG‐129 model and compared against actual COMS derived doses from previously treated patient plans. Conversion to heterogeneous doses was done based on table 2 of TG‐129 report.

Results:

As expected, dose difference between COMS and TG‐129 was relatively minor, ranging from ‐0.15% to 1.91% at the prescription point. On the other hand, heterogeneous dose, which should be used for reporting purpose only, can be up to ∼17% lower than the corresponding homogeneous dose.

Conclusion:

Conversion to TG‐129 can be rapidly accomplished in 1–2 weeks. The initial time investment can be quickly recouped since the TPS plans created can be modified for different patient cases. Dosimetric difference between TG‐129 and the original COMS model is small, generally less than 2%.
SU‐E‐T‐415: An Ionization Chamber Array with High Spatial Resolution for External Beam Radiotherapy
Authors: Togno M , Wilkens J , Menichelli D
Published: July 2014

Purpose:

To characterize an ionization chamber array technology with high spatial resolution and high charge collection efficiency for external beam radiotherapy.

Methods:

The prototype under test is a linear array of air vented ionization chambers developed by IBA Dosimetry, consisting of 80 pixels with 3.5mm spatial resolution and 4mm3 sensitive volume. The detector was characterized in a plastic phantom with 6 0 Co radiation and MV X‐rays from an ELEKTA Agility LINAC (with flattened and unflattened beam qualities). Bias voltage was varied in order to evaluate charge collection efficiency. A commercial array of ionization chambers (MatriXX Evolution, IBA Dosimetry) and an amorphous silicon flat panel in direct conversion configuration were used as references.

Results:

Repeatability (0.4%) and stability under continuous gamma irradiation (0.3%) are very good, in spite of low active volume and sensitivity (∼200pC/Gy). Charge collection efficiency is higher than 99% already at 150V with ∼2mGy dose per pulse, leading to a ±1.1% sensitivity change with dose per pulse in the range 0.09‐2mGy (covering all flattened and unflattened applications). Measured dose profiles are in agreement with MatriXX for fields larger than 2×2cm2, in which case the linear array offers a much better characterization of the penumbra region. Down to 1×1cm2, measured profiles are in very good agreement with the flat panel.

Conclusion:

The array represents a valuable tool for the characterization of treatment fields in which high spatial resolution is required, together with the dosimetric performance of air vented ionization chambers. Such a technology would be particularly valuable in association with advanced treatment modalities such as rotational radiotherapy, stereotactic treatments (even with unflattened beam qualities) and proton therapy, due to the insensitivity of the chambers on dose per pulse. In the future, a two dimensional prototype based on this technology will be developed and tested.

This research project has been supported by a Marie Curie Early Initial Training Network Fellowship of the European Community's Seventh Framework Programme under contract number (PITN‐GA‐2011‐289198‐
SU‐E‐T‐416: VMAT Dose Calculations Using Cone Beam CT Images: A Preliminary Study
Authors: Yu S , Sehgal V , kuo J , Daroui P , Ramsinghani N , Al‐Ghazi M
Published: July 2014

Purpose:

Cone beam CT (CBCT) images have been used routinely for patient positioning throughout the treatment course. However, use of CBCT for dose calculation is still investigational. The purpose of this study is to assess the utility of CBCT images for Volumetric Modulated Arc Therapy (VMAT) plan dose calculation.

Methods:

A CATPHAN 504 phantom (The Phantom Laboratory, Salem, NY) was used to compare the dosimetric and geometric accuracy between conventional CT and CBCT (in both full and half fan modes). Hounsfield units (HU) profiles at different density areas were evaluated. A C shape target that surrounds a central avoidance structure was created and a VMAT plan was generated on the CT images and copied to the CBCT phantom images. Patient studies included three brain patients, and one head and neck (H' N) patient. VMAT plans generated on the patients treatment planning CT was applied to CBCT images obtained during the first treatment. Isodose distributions and dosevolume‐ histograms (DVHs) were compared.

Results:

For the phantom study, the HU difference between CT and CBCT is within 100 (maximum 96 HU for Teflon CBCT images in full fan mode). The impact of these differences on the calculated dose distributions was clinically insignificant. In both phantom and patient studies, target DVHs based on CBCT images were in excellent agreement with those based on planning CT images. Mean, Median, near minimum (D98%), and near maximum (D2%) doses agreed within 0‐2.5%. A slightly larger discrepancy is observed in the patient studies compared to that seen in the phantom study, (0‐1% vs. 0 – 2.5%).

Conclusion:

CBCT images can be used to accurately predict dosimetric results, without any HU correction. It is feasible to use CBCT to evaluate the actual dose delivered at each fraction. The dosimetric consequences resulting from tumor response and patient geometry changes could be monitored.
SU‐E‐T‐417: A Method for Predicting and Correcting the Dosimetric Effect of a Radiotherapy Treatment Couch in Actual Treatment Position
Authors: Duan J , Shen S , Wu X , Huang M , Benhabib S , Cardan R , Popple R , Brezovich I
Published: July 2014

Purpose:

Although radiation attenuation by the treatment couch can be included in the calculation of radiotherapy dose, difference between planned and actual treatment couch positions can generate significant dose discrepancies. We propose a method to predict and correct the dosimetric effect of the couch in actual treatment position.

Methods:

The couch transmission factor, T, varies with beam angle, G, couch lateral position, x, and vertical position, y, i.e., T=T(x,y,G). If T(x,y,G) is known for a fixed couch vertical position y=h, the transmission of central‐axis beam (CAX) T(x,y,G) can be obtained by T(x,y,G)=T(x+,h,G), where x+=x‐(y‐h)tan(G) and G is the angle between the beam and the vertical axis. Similarly, the transmission of any off‐CAX point can be obtained using a similar formula. We measured CAX couch transmission at a fixed couch vertical position over the couch lateral motion range for all gantry angles by continuously scanning rotating arc beams. A 2D couch transmission correction matrix can thus be generated from T(x,h,G) for each treatment field for the actual couch position. By applying the transmission correction matrix to the planned field dose, the couch effect can be predicted and corrected. To verify this method, we measured couch transmission T(x, y=10cm, G=225°)(225°=IEC 135°) and compared to that obtained from equivalent T(x+, y=3cm, G=225°) over the range of lateral motion with a step size of 2 cm .

Results:

The measured couch transmission factors T(x, y=10cm, G=225°) are in excellent agreement with those obtained from the equivalent T(x+, y=3cm, G=225°). The mean difference is 0.00406±0.00135.

Conclusion:

The couch transmission correction matrix for any couch position and beam angle can be obtained from one set of scanning measurements at a fixed couch vertical position. The dosimetric effect of the treatment couch can be predicted and corrected by applying the couch transmission correction to the planned dose.
SU‐E‐T‐417: The Impact of Normal Tissue Constraints On PTV Dose Homogeneity for Intensity Modulated Radiotherapy (IMRT), Volume Modulated Arc Therapy (VMAT) and Tomotherapy
Authors: Peng J , McDonald D , Ashenafi M , Ellis A , Vanek K
Published: July 2014

Purpose:

Complex intensity modulated arc therapy tends to spread low dose to normal tissue(NT)regions to obtain improved target conformity and homogeneity and OAR sparing. This work evaluates the trade‐offs between PTV homogeneity and reduction of the maximum dose(Dmax)spread to NT while planning of IMRT,VMAT and Tomotherapy.

Methods:

Ten prostate patients,previously planned with step‐and‐shoot IMRT,were selected. To fairly evaluate how PTV homogeneity was affected by NT Dmax constraints,original IMRT DVH objectives for PTV and OARs(femoral heads,and rectal and bladder wall)applied to 2 VMAT plans in Pinnacle(V9.0), and Tomotherapy(V4.2). The only constraint difference was the NT which was defined as body contours excluding targets,OARs and dose rings.NT Dmax constraint for 1st VMAT was set to the prescription dose(Dp).For 2nd VMAT(VMAT_NT)and Tomotherapy,it was set to the Dmax achieved in IMRT(~70‐80% of Dp).All NT constraints were set to the lowest priority. Three common homogeneity indices(HI),RTOG_HI=Dmax/Dp,moderated_HI=D95%/D5% and complex_HI=(D2%‐D98%)/Dp*100 were calculated.

Results:

All modalities with similar dosimetric endpoints for PTV and OARs. The complex_HI shows the most variability of indices,with average values of 5.9,4.9,9.3 and 6.1 for IMRT,VMAT,VMAT_NT and Tomotherapy,respectively.VMAT provided the best PTV homogeneity without compromising any OAR/NT sparing.Both VMAT_NT and Tomotherapy,planned with more restrictive NT constraints,showed reduced homogeneity,with VMAT_NT showing the worst homogeneity(P<0.0001)for all HI. Tomotherapy gave the lowest NT Dmax,with slightly decreased homogeneity compared to VMAT. Finally, there was no significant difference in NT Dmax or Dmean between VMAT and VMAT_NT.

Conclusion:

PTV HI is highly dependent on permitted NT constraints. Results demonstrated that VMAT_NT with more restrictive NT constraints does not reduce Dmax NT,but significantly receives higher Dmax and worse target homogeneity. Therefore, it is critical that planners do not use too restrictive NT constraints during VMAT optimization. Tomotherapy plan was not as sensitive to NT constraints,however,care shall be taken to ensure NT is not pushed too hard. These results are relevant for clinical practice. The biological effect of higher Dmax and increased target heterogeneity needs further study.
SU‐E‐T‐419: Workflow and FMEA in a New Proton Therapy (PT) Facility
Authors: Cheng C , Wessels B , Hamilton H , Difranco T , Mansur D
Published: July 2014

Purpose:

Workflow is an important component in the operational planning of a new proton facility. By integrating the concept of failure mode and effect analysis (FMEA) and traditional QA requirements, a workflow for a proton therapy treatment course is set up. This workflow serves as the blue print for the planning of computer hardware/software requirements and network flow. A slight modification of the workflow generates a process map(PM) for FMEA and the planning of QA program in PT.

Methods:

A flowchart is first developed outlining the sequence of processes involved in a PT treatment course. Each process consists of a number of sub‐processes to encompass a broad scope of treatment and QA procedures. For each subprocess, the personnel involved, the equipment needed and the computer hardware/software as well as network requirements are defined by a team of clinical staff, administrators and IT personnel.

Results:

Eleven intermediate processes with a total of 70 sub‐processes involved in a PT treatment course are identified. The number of sub‐processes varies, ranging from 2‐12. The sub‐processes within each process are used for the operational planning. For example, in the CT‐Sim process, there are 12 sub‐processes: three involve data entry/retrieval from a record‐and‐verify system, two controlled by the CT computer, two require department/hospital network, and the other five are setup procedures. IT then decides the number of computers needed and the software and network requirement. By removing the traditional QA procedures from the workflow, a PM is generated for FMEA analysis to design a QA program for PT.

Conclusion:

Significant efforts are involved in the development of the workflow in a PT treatment course. Our hybrid model of combining FMEA and traditional QA program serves a duo purpose of efficient operational planning and designing of a QA program in PT.
SU‐E‐T‐420: Impact of Different Prescription Isodose Lines On Plan Quality for Brain Metastases Using Multiplan System
Authors: Zhang Y , Li X , Li T , Ozhasoglu C , Burton S , Flickinger J , clump d , heron d , Huq M
Published: July 2014

Purpose:

With the sequential optimization algorithm in MultiPlan system, clinical objectives (homogeneity, PTV coverage, conformity, normal tissue protection) can be optimized in sequence. However, the prescription isodose line (RxIDL) varies widely among institutions, which can influence the optimized dose distribution. The aim of this study is to investigate the impact of different prescription isodose lines on plan quality for the treatment of brain metastases using CyberKnife Multiplan system.

Methods:

Ten patients with multiple metastases were selected for this study. Four plans were generated for each patient such that 100% of the target volume receives the prescribed dose of 18 Gy, which was 50%, 60%, 70%, and 80% prescription Isodose line, separately. The prescription isodose was calculated as the ratio of the prescription dose and the maximum dose in target volume. The dosimetric parameters, including PTV coverage, conformity index (CI), gradient index (GI) and the volume covered by 12 Gy (V12Gy) were analyzed. The plan Monitor Units (MU) and treatment time were also compared.

Results:

All plans can provide the same target coverage (100%) and similar conformity index (1.26, 1.30, 1.32, and 1.29 on average for 80%, 70%, 60%, and 50% RxIDL plans, separately); there was no difference in critical structure dose. The 50% RxIDL plans have much lower GI (4.21±1.79 for 50% and 5.56±2.92 for 80% RxIDL plans) and V12Gy (13.36±10.31cc for 50% and 15.87±11.85cc for 80% RxIDL plans). The variation in estimated treatment delivery time was insignificant.

Conclusion:

The dose falloff is much faster for the lower RxIDL plans in terms of GI and V12Gy. For 50% RxIDL plans, the average V12Gy decreases by 16% compared to 80% RxIDL plans, which indicates that the normal tissue can be better protected by decreasing the prescription Isodose line.
SU‐E‐T‐421: Feasibility Study of Volumetric Modulated Arc Therapy with Constant Dose Rate for Endometrial Cancer
Authors: Yang R , Wang J
Published: July 2014

Purpose:

To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT‐CDR) for whole‐pelvic radiotherapy (WPRT) of endometrial cancer.

Methods:

The nine‐Field intensity‐modulated radiotherapy (IMRT), VMAT with variable dose‐rate (VMAT‐VDR), and VMAT‐CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT‐CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA.

Results:

Compared with IMRT, the VMAT‐CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high‐dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT‐CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients.

Conclusion:

VMAT‐CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability.

This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237).
SU‐E‐T‐422: Correlation Between 2D Passing Rates and 3D Dose Differences for Pretreatment VMAT QA
Authors: Jin X , Xie C
Published: July 2014

Purpose:

Volumetric modulated arc therapy (VMAT) quality assurance (QA) is typically using QA methods and action levels taken from fixedbeam intensity‐modulated radiotherapy (IMRT) QA methods. However, recent studies demonstrated that there is no correlation between the percent gamma passing rate (%GP) and the magnitude of dose discrepancy between the planned dose and the actual delivered dose for IMRT. The purpose of this study is to investigate whether %GP is correlated with clinical dosimetric difference for VMAT.

Methods:

Twenty nasopharyngeal cancer (NPC) patients treated with dual‐arc simultaneous integrated boost VMAT and 20 esophageal cancer patients treated with one‐arc VMAT were enrolled in this study. Pretreatment VMAT QA was performed by a 3D diode array ArcCheck. Acceptance criteria of 2%/2mm, 3%/3mm, and 4%/4mm were applied for 2D %GP. Dose values below 10% of the per‐measured normalization maximum dose were ignored.Mean DVH values obtained from 3DVH software and TPS were calculated and percentage dose differences were calculated. Statistical correlation between %GP and percent dose difference was studied by using Pearson correlation.

Results:

The %GP for criteria 2%/2mm, 3%/3mm, and 4%/4mm were 82.33±4.45, 93.47±2.31, 97.13±2.41, respectively. Dose differences calculated from 3DVH and TPS for beam isocenter, mean dose of PTV, maximum dose of PTV, D2 of PTV and D98 of PTV were ‐1.04±3.24, ‐0.74±1.71, 2.92±3.62, 0.89±3.29, ‐1.46±1.97, respectively. No correction were found between %GP and dose differences.

Conclusion:

There are weak correlations between the 2D %GP and dose differences calculated from 3DVH. The %GP acceptance criteria of 3%/3mm usually applied for pretreatment QA of IMRT and VMAT is not indicating strong clinical correlation with 3D dose difference. 3D dose reconstructions on patient anatomy may be necessary for physicist to predict the accuracy of delivered dose for VMAT QA.
SU‐E‐T‐423: TrueBeam Small Field Dosimetry Using Commercial Plastic Scintillation and Other Stereotactic Detectors
Authors: Pino R , Therriault‐Proulx F , Wang X , Yang J , Beddar S
Published: July 2014

Purpose:

To perform dose profile and output factor (OF) measurements with the Exradin W1 plastic scintillation detector (PSD) for small fields made by the high‐definition multi‐leaf collimator (MLC) on the TrueBeam STx system and to compare them to values measured with an IBA CC01 ionization chamber and a Sun Nuclear Edge detector diode for 6 MV photon beams.

Methods:

The Exradin W1 is a new small volume near‐water equivalent and energy independent PSD manufactured by Standard Imaging, Inc. All measurements were performed in an IBA Blue Phantom water tank. Square MLC‐shaped fields with sides ranging from 0.5 cm to 2 cm and jawshaped fields with sides ranging from 1 cm to 40 cm were measured using an SAD setup at 10 cm depth. Dose profile and percent depth dose (PDD) measurements were also taken under the same conditions for MLC fields 0.5×0.5 and 1×1 cm2 in size with jaws at 2×2cm2. The CC01 and W1 were vertically mounted.

Results:

OFs measured with the W1 for jaw only square fields were consistent with the ones measured with a Farmers PTW TN33013 ion chamber (1.8% maximum deviation). OF and penumbra measurement results are presented below. PDDs measured for all detectors are within 1.5% for the 0.5×0.5 cm2 and within 1% for the 1×1 cm2 MLC fields.Output factors:MLC size W1 CC01 EDGE0.5cm 0.555 0.541 0.5851.0cm 0.716 0.702 0.7331.5cm 0.779 0.761 0.7772.0cm 0.804 0.785 0.796Penumbras (mm):MLC size W1 CC01 EDGE0.5cm 2.7 2.9 2.51.0cm 3.0 3.4 2.

Conclusion:

OFs measured for small MLC fields were consistent with the ones measured with the other stereotactic detectors. Measured penumbras are consistent with detector size. The Exradin W1 PSD is an excellent choice for characterizing MLC‐shaped small beam dosimetry used for stereotactic radiosurgery and body radiation therapy.

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”
SU‐E‐T‐424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases
Authors: Eldib A , Jin L , Martin J , Li J , Chibani O , Mora G , Galloway T , Ma C
Published: July 2014

Purpose:

Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC).

Methods:

We have used the MCBEAM code for treatment head simulation and for generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in‐house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations.

Results:

The eMLC allows effective treatment of scalps with multi‐lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup.

Conclusion:

MERT can improve treatment plan quality for patients with scalp cancers. Our in‐house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.