The influence of MRI scan position on patients with oropharyngeal cancer undergoing radical radiotherapy

<p>Background: The purpose of this study was to demonstrate how magnetic resonance imaging (MRI) patient position protocols influence registration quality in patients with oropharyngeal cancer undergoing radical radiotherapy and the consequences for gross tumour volume (GTV) definition and radiotherapy planning.</p> <p>Methods and materials: Twenty-two oropharyngeal patients underwent a computed tomography (CT), a diagnostic MRI (MRID) and an MRI in the radiotherapy position within an immobilization mask (MRIRT). Clinicians delineated the GTV on the CT viewing the MRID separately (GTVC); on the CT registered to MRID (GTVD) and on the CT registered to MRIRT (GTVRT). Planning target volumes (PTVs) were denoted similarly. Registration quality was assessed by measuring disparity between structures in the three set-ups. Volumetric modulated arc therapy (VMAT) radiotherapy planning was performed for PTVC, PTVD and PTVRT. To determine the dose received by the reference PTVRT, we optimized for PTVC and PTVD while calculating the dose to PTVRT. Statistical significance was determined using the two-tailed Mann–Whitney or two-tailed paired student t-tests.</p> <p>Results: A significant improvement in registration accuracy was found between CT and MRIRT versus the MRID measuring distances from the centre of structures (geometric mean error of 2.2 mm versus 6.6 mm). The mean GTVC (44.1 cm3) was significantly larger than GTVD (33.7 cm3, p value = 0.027) or GTVRT (30.5 cm3, p value = 0.014). When optimizing the VMAT plans for PTVC and investigating the mean dose to PTVRT neither the dose to 99% (58.8%) nor 95% of the PTV (84.7%) were found to meet the required clinical dose constraints of 90% and 95% respectively. Similarly, when optimizing for PTVD the mean dose to PTVRT did not meet clinical dose constraints for 99% (14.9%) nor 95% of the PTV (66.2%). Only by optimizing for PTVRT were all clinical dose constraints achieved.</p> <p>Conclusions: When oropharyngeal patients MRI scans are performed in the radiotherapy position there are significant improvements in CT-MR image registration, target definition and PTV dose coverage.</p&gt

Multi-center planning study of radiosurgery for intracranial metastases through Automation (MC-PRIMA) by crowdsourcing prior web-based plan challenge study

BACKGROUND: Planning radiosurgery to multiple intracranial metastases is complex and shows large variability in dosimetric quality among planners and treatment planning systems (TPS). This project aimed to determine whether autoplanning using the Muliple Brain Mets (AutoMBM) software can improve plan quality and reduce inter-planner variability by crowdsourcing results from prior international planning study. METHODS: Twenty-four institutions autoplanned with AutoMBM on a five metastases case from a prior international planning competition from which population statistics (means and variances) of 23 dosimetric metrics and resulting composite plan score (maximum score = 150) of other TPS (Eclipse, Monaco, RayStation, iPlan, GammaPlan, MultiPlan) were crowdsourced. Plan results of AutoMBM and each of the other TPS were compared using two sample t-tests for means and Levene's tests for variances. Plan quality of AutoMBM was correlated with the planner' experience and compared between academic and non-academic centers. RESULTS: AutoMBM produced plans with comparable composite plan score to GammaPlan, MultiPlan, Eclipse and iPlan (127.6 vs. 131.7 vs. 127.3 vs. 127.3 and 126.7; all p > 0.05) and superior to Monaco and RayStation (118.3 and 108.6; both p 0.05). CONCLUSIONS: By plan crowdsourcing prior international plan challenge, AutoMBM produces high and consistent plan quality independent of the planning experience and the institution that is crucial to addressing the technical bottleneck of SRS to intracranial metastases

Multi-center planning study of radiosurgery for intracranial metastases through Automation (MC-PRIMA) by crowdsourcing prior web-based plan challenge study

Background: Planning radiosurgery to multiple intracranial metastases is complex and shows large variability in dosimetric quality among planners and treatment planning systems (TPS). This project aimed to determine whether autoplanning using the Muliple Brain Mets (AutoMBM) software can improve plan quality and reduce inter-planner variability by crowdsourcing results from prior international planning study. Methods: Twenty-four institutions autoplanned with AutoMBM on a five metastases case from a prior international planning competition from which population statistics (means and variances) of 23 dosimetric metrics and resulting composite plan score (maximum score = 150) of other TPS (Eclipse, Monaco, RayStation, iPlan, GammaPlan, MultiPlan) were crowdsourced. Plan results of AutoMBM and each of the other TPS were compared using two sample t-tests for means and Levene\u27s tests for variances. Plan quality of AutoMBM was correlated with the planner\u27 experience and compared between academic and non-academic centers. Results: AutoMBM produced plans with comparable composite plan score to GammaPlan, MultiPlan, Eclipse and iPlan (127.6 vs. 131.7 vs. 127.3 vs. 127.3 and 126.7; all p \u3e 0.05) and superior to Monaco and RayStation (118.3 and 108.6; both p \u3c 0.05). Inter-planner variability of overall plan quality was lowest for AutoMBM among all TPS (all p \u3c 0.05). AutoMBM\u27s plan quality did not differ between academic and non-academic centers and uncorrelated with planning experience (all p \u3e 0.05). Conclusions: By plan crowdsourcing prior international plan challenge, AutoMBM produces high and consistent plan quality independent of the planning experience and the institution that is crucial to addressing the technical bottleneck of SRS to intracranial metastases

Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)n Repeats by PNA or LNA Targeting

Expansion of (GAA)n repeats in the first intron of the Frataxin gene is associated with reduced mRNA and protein levels and the development of Friedreich’s ataxia. (GAA)n expansions form non-canonical structures, including intramolecular triplex (H-DNA), and R-loops and are associated with epigenetic modifications. With the aim of interfering with higher order H-DNA (like) DNA structures within pathological (GAA)n expansions, we examined sequence-specific interaction of peptide nucleic acid (PNA) with (GAA)n repeats of different lengths (short: n=9, medium: n=75 or long: n=115) by chemical probing of triple helical and single stranded regions. We found that a triplex structure (H-DNA) forms at GAA repeats of different lengths; however, single stranded regions were not detected within the medium size pathological repeat, suggesting the presence of a more complex structure. Furthermore, (GAA)4-PNA binding of the repeat abolished all detectable triplex DNA structures, whereas (CTT)5-PNA did not. We present evidence that (GAA)4-PNA can invade the DNA at the repeat region by binding the DNA CTT strand, thereby preventing non-canonical-DNA formation, and that triplex invasion complexes by (CTT)5-PNA form at the GAA repeats. Locked nucleic acid (LNA) oligonucleotides also inhibited triplex formation at GAA repeat expansions, and atomic force microscopy analysis showed significant relaxation of plasmid morphology in the presence of GAA-LNA. Thus, by inhibiting disease related higher order DNA structures in the Frataxin gene, such PNA and LNA oligomers may have potential for discovery of drugs aiming at recovering Frataxin expression

Autonomous Meridian Sensory Response: from Internet subculture to audiovisual therapy

ASMR (Autonomous Sensory Meridian Response) is the name given to a pleasant sensation that can be felt most commonly on the scalp and can be triggered by various gentle sounds (like whispers, crinkles or tapping), smooth and repetitive visual stimuli, personal attention (like the touch of a hairdresser or a masseur) or other events. ASMR is often associated with a general feeling of relaxation and peace. Whilst academic research on the sociological, artistic, sensory and cognitive dimensions is still in its infancy ASMR has grown into a worldwide, cross-disciplinary, inter-cultural, multi-lingual social media sensation. This paper outlines the rise of ASMR as Internet subculture from its inception as ‘whispering community’ on Internet platforms and blogs, to become a truly popular (i.e. made by the people) platform for creative expression, self-made holistic therapy and in some instances true artistic audiovisual endeavours. This paper comments on the reasons behind the rise of the ASMR community as a fertile ground for creative expression. Audiences’ expectations are dictated by the attention-induced nature of the sensory experience, a factor that spawned an exceptionally perceptive viewership if one considers the inherently fragmented essence of ubiquitous streaming media and the impatient scanning and skipping modes of reception it encourages. ‘ASMRtists’ thus enjoy a privileged relationship with audiences who are not impressed with the relentless pour of energy and information from social media platforms and treasure, instead, the slow, the quiet and the subtle. Examples from various ASMR content creators will be analysed from the compositional standpoint, highlighting technical and idiomatic similarities with forms of improvisatory practices and experimental artistic languages such as Musique Concrète. The paper will also illustrate recent audiovisual projects related to ASMR carried out at Keele University and will introduce the audience to planned developments towards ASMR related content delivered through mobile platforms