EPID-based in vivo dosimetry using Dosimetry Check™: Overview and clinical experience in a 5-yr study including breast, lung, prostate, and head and neck cancer patients.

BACKGROUND: Independent verification of the dose delivered by complex radiotherapy can be performed by electronic portal imaging device (EPID) dosimetry. This paper presents 5-yr EPID in vivo dosimetry (IVD) data obtained using the Dosimetry Check (DC) software on a large cohort including breast, lung, prostate, and head and neck (H&N) cancer patients. MATERIAL AND METHODS: The difference between in vivo dose measurements obtained by DC and point doses calculated by the Eclipse treatment planning system was obtained on 3795 radiotherapy patients treated with volumetric modulated arc therapy (VMAT) (n = 842) and three-dimensional conformal radiotherapy (3DCRT) (n = 2953) at 6, 10, and 15 MV. In cases where the dose difference exceeded ±10% further inspection and additional phantom measurements were performed. RESULTS: The mean and standard deviation ( µ ± σ ) of the percentage difference in dose obtained by DC and calculated by Eclipse in VMAT was: 0.19 ± 3.89 % in brain, 1.54 ± 4.87 % in H&N, and 1.23 ± 4.61 % in prostate cancer. In 3DCRT, this was 1.79 ± 3.51 % in brain, - 2.95 ± 5.67 % in breast, - 1.43 ± 4.38 % in bladder, 1.66 ± 4.77 % in H&N, 2.60 ± 5.35% in lung and - 3.62 ± 4.00 % in prostate cancer. A total of 153 plans exceeded the ±10% alert criteria, which included: 88 breast plans accounting for 7.9% of all breast treatments; 28 H&N plans accounting for 4.4% of all H&N treatments; and 12 prostate plans accounting for 3.5% of all prostate treatments. All deviations were found to be as a result of patient-related anatomical deviations and not from procedural errors. CONCLUSIONS: This preliminary data shows that EPID-based IVD with DC may not only be useful in detecting errors but has the potential to be used to establish site-specific dose action levels. The approach is straightforward and has been implemented as a radiographer-led service with no disruption to the patient and no impact on treatment time.

Reversible thermal switching of aqueous dispersibility of multiwalled carbon nanotubes.

Easily reversible aqueous dispersion/precipitation of multiwalled carbon nanotubes (MWNTs) has been demonstrated using small-molecule non-ionic pyrene-based surfactants, which exhibit lower critical solution temperature (LCST) phase behaviour. The MWNTs are dispersed by means of non-covalent interactions. The dispersibility can be switched "off" (i.e., MWNTs precipitated) upon heating and switched "on" (i.e., MWNTs re-dispersed) upon cooling and merely swirling the sample at room temperature, that is, under very mild conditions. This effect is also observed under high ionic strength conditions with NaCl in the aqueous phase.

Identifying the dominant prostate cancer focal lesion using image analysis and planning of a simultaneous integrated stereotactic boost.

BACKGROUND: Prostate cancer is now the only solid organ cancer in which therapy is commonly applied to the whole gland. One of the main challenges in adopting focal boost or true focal therapy is in the accurate mapping of cancer foci defined on magnetic resonance (MR) images onto the computerised tomography (CT) images used for radiotherapy planning. MATERIAL AND METHODS: Prostate cancer patients (n = 14) previously treated at the Edinburgh Cancer Centre (ECC) were selected for this study. All patients underwent MR scanning for the purpose of diagnosis and staging. Patients received three months of androgen deprivation hormone therapy followed by a radiotherapy planning CT scan. The dominant focal prostate lesions were identified on MR scans by a radiologist and a novel image analysis approach was used to map the location of the dominant focal lesion from MR to CT. An offline planning study was undertaken on suitable patients (n = 7) to investigate boosting of the radiation dose to the tumour using a stereotactic ablative body radiotherapy (SABR) technique. RESULTS: The non-rigid registration algorithm showed clinically acceptable estimates of the location of the dominant focal disease on all CT image data of patients suitable for a boost treatment. Standard rigid registration was found to produce unacceptable estimates of the dominant focal lesion on CT. A SABR boost dose of 47.5 Gy was delivered to the dominant focal lesion of all patients whilst meeting all dose-volume histogram (DVH) constraints. Normal tissue complication probability (NTCP) for the rectum decreased from 1.28% to 0.73% with this method. CONCLUSIONS: These preliminary results demonstrate the potential of this image analysis method for reliably mapping dominant focal disease within the prostate from MR images onto planning CT images. Significant dose escalation using a simultaneous integrated SABR boost was achieved in all patients.

Self-assembled multivalent RGD-peptide arrays--morphological control and integrin binding.

We report the synthesis of four different RGD peptide derivatives which spontaneously self-assemble into nanoscale architectures. Depending on the information programmed into the molecular-scale building blocks by organic synthesis, these compounds assemble into different nanoscale morphologies. This process can be fully understood using multiscale modelling which provides predictive insight into subtle differences, such as whether the compounds form spherical micelles, rod-like cylinders or tubular assemblies, and predicts experimentally observed critical aggregation concentrations (CACs). We then probe the multivalent binding of these assemblies to integrin proteins and demonstrate that the spherical micellar assemblies perform well in our solution-phase integrin binding assay as a consequence of self-assembled multivalency, with the CAC switching-on the binding. Conversely, the cylindrical assemblies do not work in this assay. As such, the nanoscale morphology controls the apparent ability to perform as a self-assembled multivalent ligand array.

A Right-Sided Approach to Anterior Communicating Artery Aneurysms: A Case Review and Technical Report.

Anterior communicating artery (ACoA) aneurysms are the most frequently encountered type of intracranial aneurysm. ACoA aneurysms may require treatment depending on clinical presentation, size, risk of rupture, and ruptured status. In patients where treatment is indicated, options entail endovascular securement or clipping. Under the clipping umbrella, surgical approaches traditionally entail a pterional craniotomy and its modifications such as the lateral supraorbital approach. Sidedness of this craniotomy has been a topic of debate. To discuss this we present a case and technical report with nuances of the approach wherein a 48-year-old female presented with the worst headache of her life. The patient was found to have a ruptured wide-necked 7.2 x 8.1 x 5.8 mm ACoA aneurysm more eccentric to the left and fed from the left A1 intertwined with a frontopolar branch, numerous perforators and the recurrent artery of Heubner. The patient underwent a successful clipping from a right-sided approach. As such, with appropriate skull base drilling, exposure, optimization of brain relaxation, and a generous opening of the Sylvian fissure bilateral internal carotid arteries, anterior cerebral arteries with both A1 and A2 segments, middle cerebral arteries, the ACoA, and the relevant anatomy can be appropriately visualized from a right-sided approach. Therefore, an approach is described to optimize exposure to allow for nearly all anterior communicating aneurysms to be clipped from a right-sided pterional approach.

Comparing dendritic and self-assembly strategies to multivalency--RGD peptide-integrin interactions.

This paper compares covalent and non-covalent approaches for the organisation of ligand arrays to bind integrins. In the covalent strategy, linear RGD peptides are conjugated to first and second generation dendrons, and using a fluorescence polarisation competition assay, the first generation compound is demonstrated to show the most effective integrin binding, with an EC(50) of 125 µM (375 µM per peptide unit). As such, this dendritic compound is significantly more effective than a monovalent ligand, which does not bind integrin, even at concentrations as high as 1 mM. However, the second generation compound is significantly less effective, demonstrating that there is an optimum ligand density for multivalency in this case. In the non-covalent approach to multivalency, the same RGD peptide is functionalised with a hydrophobic C12 chain, giving rise to a lipopeptide which is demonstrated to be capable of self-assembly. This lipopeptide is capable of effective integrin binding at concentrations of 200 µM. These results therefore demonstrate that covalent (dendritic) and non-covalent (micellar self-assembly) approaches have, in this case, comparable efficiency in terms of achieving multivalent organisation of a ligand array.

"On-off" multivalent recognition: degradable dendrons for temporary high-affinity DNA binding.

Now you bind it--now you don't! Chemical degradation of a dendritic scaffold allows multivalent interactions with DNA to be "switched off" as the multivalent array of ligands breaks down into smaller fragments, offering an approach by which a molecule can be temporarily endowed with high affinity for a biological target--an important concept in the development of new synthetic systems to intervene in biological pathways.

Formation of Two-Dimensional Micelles on Graphene: Multi-Scale Theoretical and Experimental Study.

Graphene and related two-dimensional (2D) materials possess outstanding electronic and mechanical properties, chemical stability, and high surface area. However, to realize graphene's potential for a range of applications in materials science and nanotechnology there is a need to understand and control the interaction of graphene with tailored high-performance surfactants designed to facilitate the preparation, manipulation, and functionalization of new graphene systems. Here we report a combined experimental and theoretical study of the surface structure and dynamics on graphene of pyrene-oligoethylene glycol (OEG) -based surfactants, which have previously been shown to disperse carbon nanotubes in water. Molecular self-assembly of the surfactants on graphitic surfaces is experimentally monitored and optimized using a graphene coated quartz crystal microbalance in ambient and vacuum environments. Real-space nanoscale resolution nanomechanical and topographical mapping of submonolayer surfactant coverage, using ultrasonic and atomic force microscopies both in ambient and ultrahigh vacuum, reveals complex, multilength-scale self-assembled structures. Molecular dynamics simulations show that at the nanoscale these structures, on atomically flat graphitic surfaces, are dependent upon the surfactant OEG chain length and are predicted to display a previously unseen class of 2D self-arranged "starfish" micelles (2DSMs). While three-dimensional micelles are well-known for their widespread uses ranging from microreactors to drug-delivery vehicles, these 2DSMs possess the highly desirable and tunable characteristics of high surface affinity coupled with unimpeded mobility, opening up strategies for processing and functionalizing 2D materials.