Viscous Aqueous Gel Illustrating Natural Anatomy: The VAGINA method in gynaecological MRI simulation.

Accurately defining gross tumour volume (GTV) and organs at risk (OAR) is key to successful radiation therapy (RT) treatment outcomes for patients with gynaecological cancers. With improved access to magnetic resonance imaging (MRI) for RT simulation and planning, the optimisation and tailoring of proven diagnostic MRI techniques towards RT specific planning goals is fast evolving. Modifying MRI techniques for radiation oncology (RO) with the priority of anatomy visualisation and spatial location over diagnosis and disease characterisation relies heavily on successful collaboration between radiology and radiation oncology staff. This 'How I Do It' paper describes a qualitative analysis of the adaptation of a diagnostic MRI vaginal opacification technique into an RT specific MRI simulation procedure using aqueous ultrasound gel for improving natural anatomical visualisation of the vaginal canal. This technique is explained and could be introduced in other RO departments for dedicated RT planning scans in MR-Sim sessions with minimal difficulty. We found 10-15 cc of aqueous gel delivered vaginally produced optimal MRI planning images for most patients. With this small amount of gel and careful application technique, the full extent of the vaginal vault and cervix can be well visualised on T2 Weighted (T2W) imaging, while tending not to unfold the natural fornices of the collapsed vagina, representing a significant improvement in image quality from the outdated tampon procedure.

Cone beam computed tomography image guidance within a magnetic resonance imaging-only planning workflow.

Background and purpose: Magnetic Resonance Imaging (MRI)-only planning workflows offer many advantages but raises challenges regarding image guidance. The study aimed to assess the viability of MRI to Cone Beam Computed Tomography (CBCT) based image guidance for MRI-only planning treatment workflows. Materials and methods: An MRI matching training package was developed. Ten radiation therapists, with a range of clinical image guidance experience and experience with MRI, completed the training package prior to matching assessment. The matching assessment was performed on four match regions: prostate gold seed, prostate soft tissue, rectum/anal canal and gynaecological. Each match region consisted of five patients, with three CBCTs per patient, resulting in fifteen CBCTs for each match region. The ten radiation therapists performed the CBCT image matching to CT and to MRI for all regions and recorded the match values. Results: The median inter-observer variation for MRI-CBCT matching and CT-CBCT matching for all regions were within 2 mm and 1 degree. There was no statistically significant association in the inter-observer variation in mean match values and radiation therapist image guidance experience levels. There was no statistically significant association in inter-observer variation in mean match values for MRI experience levels for prostate soft tissue and gynaecological match regions, while there was a statistically significant difference for prostate gold seed and rectum match regions. Conclusion: The results of this study support the concept that with focussed training, an MRI to CBCT image guidance approach can be successfully implemented in a clinical planning workflow.

MRI sequence optimisation methods to identify cranial nerve course for radiotherapy planning.

INTRODUCTION: Magnetic resonance imaging (MRI) is being increasingly used to improve radiation therapy planning by allowing visualisation of organs at risk that cannot be well-defined on computed tomography (CT). Diagnostic sequences are increasingly being adapted for radiation therapy planning, such as the use of heavily T2-weighted 3D SPACE (Sampling Perfection with Application optimised Contrasts using different flip angle Evolution) sequence for cranial nerve identification in head and neck tumour treatment planning. METHODS: A 3D isotropic T2 SPACE sequence used for cranial nerve identification was adapted for radiation therapy purposes. Distortion was minimised using a spin-echo-based sequence, 3D distortion correction, isocentre scanning and an increased readout bandwidth. Radiation therapy positioning was accounted for by utilising two small flex, 4-channel coils. The protocol was validated for cranial nerve identification in clinical applications and distortion minimisation using an MRI QA phantom. RESULTS: Normal anatomy of the cranial nerves CI-CIX, were presented, along with a selection of clinical applications and abnormal anatomy. The usefulness of cranial nerve identification is discussed for several case studies, particularly in proximity to tumours extending into the base of skull region. In-house testing validated that higher bandwidths of 600 Hz resulted in minimal displacement well below 1 mm. CONCLUSION: The use of MRI for radiation therapy planning allows for greater individualisation and prediction of patient outcomes. Dose reduction to cranial nerves can decrease late side effects such as cranial neuropathy. In addition to current applications, future directions include further applications of this technology for radiation therapy treatments.

Knowledge, attitudes and perceived behavioral modification of chiropractic students returning to clinical training in South Africa amid the COVID-19 pandemic.

OBJECTIVE: The purpose of this study was to determine the knowledge and attitudes toward COVID-19 and perceived behavioral modification of South African chiropractic students returning to clinical training during the COVID-19 pandemic. METHODS: An online survey was administered to students registered for clinical training in South African chiropractic programs. The survey consisted of questions related to knowledge and attitudes toward COVID-19 and perceptions on behavioral modification in the form of personal protective equipment (PPE) use to prevent transmission. RESULTS: Out of 129 participants, there was a 69% response rate (n = 89), with a mean age of 25 (±2.39) years and 75% were females. They had an acceptable level of knowledge (67.9%). There was a favorable perception score about COVID-19 (98.8%) but a poor perception of the role of PPE. They expressed concern about returning to clinical training (62.9%) but were prepared to return to serve their patients during the pandemic (72%). CONCLUSION: Chiropractic students within South Africa demonstrated good attitudes, knowledge, and perception toward the measures required to return safely to the clinical environment during the COVID-19 pandemic. There was a level of stress associated with potential infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mostly for onward transmission to family members.

Validation of an MRI-only planning workflow for definitive pelvic radiotherapy.

PURPOSE: Previous work on Magnetic Resonance Imaging (MRI) only planning has been applied to limited treatment regions with a focus on male anatomy. This research aimed to validate the use of a hybrid multi-atlas synthetic computed tomography (sCT) generation technique from a MRI, using a female and male atlas, for MRI only radiation therapy treatment planning of rectum, anal canal, cervix and endometrial malignancies. PATIENTS AND METHODS: Forty patients receiving radiation treatment for a range of pelvic malignancies, were separated into male (n = 20) and female (n = 20) cohorts for the creation of gender specific atlases. A multi-atlas local weighted voting method was used to generate a sCT from a T1-weighted VIBE DIXON MRI sequence. The original treatment plans were copied from the CT scan to the corresponding sCT for dosimetric validation. RESULTS: The median percentage dose difference between the treatment plan on the CT and sCT at the ICRU reference point for the male cohort was - 0.4% (IQR of 0 to - 0.6), and - 0.3% (IQR of 0 to - 0.6) for the female cohort. The mean gamma agreement for both cohorts was > 99% for criteria of 3%/2 mm and 2%/2 mm. With dose criteria of 1%/1 mm, the pass rate was higher for the male cohort at 96.3% than the female cohort at 93.4%. MRI to sCT anatomical agreement for bone and body delineated contours was assessed, with a resulting Dice score of 0.91 ± 0.2 (mean ± 1 SD) and 0.97 ± 0.0 for the male cohort respectively; and 0.96 ± 0.0 and 0.98 ± 0.0 for the female cohort respectively. The mean absolute error in Hounsfield units (HUs) within the entire body for the male and female cohorts was 59.1 HU ± 7.2 HU and 53.3 HU ± 8.9 HU respectively. CONCLUSIONS: A multi-atlas based method for sCT generation can be applied to a standard T1-weighted MRI sequence for male and female pelvic patients. The implications of this study support MRI only planning being applied more broadly for both male and female pelvic sites. Trial registration This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) ( www.anzctr.org.au ) on 04/10/2017. Trial identifier ACTRN12617001406392.

Comparison of Synthetic Computed Tomography Generation Methods, Incorporating Male and Female Anatomical Differences, for Magnetic Resonance Imaging-Only Definitive Pelvic Radiotherapy.

PURPOSE: There are several means of synthetic computed tomography (sCT) generation for magnetic resonance imaging (MRI)-only planning; however, much of the research omits large pelvic treatment regions and female anatomical specific methods. This research aimed to apply four of the most popular methods of sCT creation to facilitate MRI-only radiotherapy treatment planning for male and female anorectal and gynecological neoplasms. sCT methods were validated against conventional computed tomography (CT), with regard to Hounsfield unit (HU) estimation and plan dosimetry. METHODS AND MATERIALS: Paired MRI and CT scans of 40 patients were used for sCT generation and validation. Bulk density assignment, tissue class density assignment, hybrid atlas, and deep learning sCT generation methods were applied to all 40 patients. Dosimetric accuracy was assessed by dose difference at reference point, dose volume histogram (DVH) parameters, and 3D gamma dose comparison. HU estimation was assessed by mean error and mean absolute error in HU value between each sCT and CT. RESULTS: The median percentage dose difference between the CT and sCT was <1.0% for all sCT methods. The deep learning method resulted in the lowest median percentage dose difference to CT at -0.03% (IQR 0.13, -0.31) and bulk density assignment resulted in the greatest difference at -0.73% (IQR -0.10, -1.01). The mean 3D gamma dose agreement at 3%/2 mm among all sCT methods was 99.8%. The highest agreement at 1%/1 mm was 97.3% for the deep learning method and the lowest was 93.6% for the bulk density method. Deep learning and hybrid atlas techniques gave the lowest difference to CT in mean error and mean absolute error in HU estimation. CONCLUSIONS: All methods of sCT generation used in this study resulted in similarly high dosimetric agreement for MRI-only planning of male and female cancer pelvic regions. The choice of the sCT generation technique can be guided by department resources available and image guidance considerations, with minimal impact on dosimetric accuracy.

Public Reporting of Adverse Events From Long-Term Care Facilities for Older Persons and People With Disability in Ireland 2013-2019: Development of an Openly Accessible Database and Descriptive Analyses.

OBJECTIVES: To describe the development of an analyzable database of statutory notifications received from long-term care facilities (LTCFs) and to describe trends in receipt of notifications from 2013 to 2019. DESIGN: Description of database development with descriptive and trend analyses. SETTING AND PARTICIPANTS: LTCFs for older persons and for people with disability in Ireland. METHODS: Data on notifications received and on centers were extracted from a system internal to the health and social services regulator and combined into an analyzable database. Variables were screened for personal information, cleaned, transformed, or redacted and combined into a database suitable for open access publication. Descriptive analyses of the volume of notifications, trends over time and breakdown by service type, notification type, and risk-rating were conducted. RESULTS: The Database of Statutory Notifications from Social Care in Ireland was developed and an open access version published in February 2021. Protection of personal data was an important consideration in publishing the data publicly. Uses of the database include examination of national trends and identification of determinants of adverse events and areas for quality improvement. The number of notifications received increased over time. Quarterly notifications contributed to the largest proportion of notifications (older persons, 36.7%; disability, 39.1%). This was followed by serious injury notifications in LTCFs for older persons (33.3%) and abuse allegation notifications in LTCFs for people with disability (36.0%). Less than 1% of individual notifications were risk-rated red (highest severity level of impact on resident welfare). The types of notifications that were collectively risk-rated highest were staff misconduct, abuse allegations, and outbreaks of infectious disease. CONCLUSIONS AND IMPLICATIONS: The methodology and findings can inform publications of notifications, planning and resourcing for receipt and submission of notifications, target areas for quality improvement initiatives, mandating of timelines for receipt of notifications, and the mandating of notifications in legislation.

Optimisation and validation of an integrated magnetic resonance imaging-only radiotherapy planning solution.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI)-only treatment planning is gaining in popularity in radiation oncology, with various methods available to generate a synthetic computed tomography (sCT) for this purpose. The aim of this study was to validate a sCT generation software for MRI-only radiotherapy planning of male and female pelvic cancers. The secondary aim of this study was to improve dose agreement by applying a derived relative electron and mass density (RED) curve to the sCT. METHOD AND MATERIALS: Computed tomography (CT) and MRI scans of forty patients with pelvic neoplasms were used in the study. Treatment plans were copied from the CT scan to the sCT scan for dose comparison. Dose difference at reference point, 3D gamma comparison and dose volume histogram analysis was used to validate the dose impact of the sCT. The RED values were optimised to improve dose agreement by using a linear plot. RESULTS: The average percentage dose difference at isocentre was 1.2% and the mean 3D gamma comparison with a criteria of 1%/1 mm was 84.0% ± 9.7%. The results indicate an inherent systematic difference in the dosimetry of the sCT plans, deriving from the tissue densities. With the adapted REDmod table, the average percentage dose difference was reduced to -0.1% and the mean 3D gamma analysis improved to 92.9% ± 5.7% at 1%/1 mm. CONCLUSIONS: CT generation software is a viable solution for MRI-only radiotherapy planning. The option makes it relatively easy for departments to implement a MRI-only planning workflow for cancers of male and female pelvic anatomy.

Derivation and Validation of a Total Fruit and Vegetable Intake Prediction Model to Identify Targets for Biomarker Discovery Using the UK National Diet and Nutrition Survey.

BACKGROUND: Dietary assessments in research and clinical settings are largely reliant on self-reported questionnaires. It is acknowledged that these are subject to measurement error and biases and that objective approaches would be beneficial. Dietary biomarkers have been purported as a complementary approach to improve the accuracy of dietary assessments. Tentative biomarkers have been identified for many individual fruits and vegetables (FVs), but an objective total FV intake assessment tool has not been established. OBJECTIVES: To derive and validate a prediction model of total FV intake (TFVpred) to inform future biomarker studies. METHODS: Data from the National Diet and Nutrition Survey (NDNS) were used for this analysis. A modeling group (MG) consisting of participants aged >11 years from the NDNS years 5-6 was created (n = 1746). Intake data for 96 FVs were analyzed by stepwise regression to derive a model that satisfied 3 selection criteria: SEE ≤80, R2 >0.7, and ≤10 predictors. The TFVpred model was validated using comparative data from a validation group (VG) created from the NDNS years 7-8 (n = 1865). Pearson's correlation coefficients were assessed between observed and predicted values in the MG and VG. Bland-Altman plots were used to assess agreement between TFVpred estimates and total FV intake. RESULTS: A TFVpred model, comprised of tomatoes, apples, carrots, bananas, pears, strawberries, and onions, satisfied the selection criteria (R2 = 0.761; SEE = 78.81). Observed and predicted total FV intake values were positively correlated in the MG (r = 0.872; P < 0.001; R2 = 0.761) and the VG (r = 0.838; P < 0.001; R2 = 0.702). In the MG and VG, 95.0% and 94.9%, respectively, of TFVpred model residuals were within the limits of agreement. CONCLUSIONS: Intakes of a concise FV list can be used to predict total FV intakes in a UK population. The individual FVs included in the TFVpred model present targets for biomarker discovery aimed at objectively assessing total FV intake.

Deformable image registration in radiation therapy.

Deformable image registration is an increasingly important method to account for soft tissue deformation between image acquisitions. This editorial discusses the clinical need and current status of deformable image registration.

Dietary dairy product intake and incident type 2 diabetes: a prospective study using dietary data from a 7-day food diary.

AIM/HYPOTHESIS: The aim of this study was to investigate the association between total and types of dairy product intake and risk of developing incident type 2 diabetes, using a food diary. METHODS: A nested case-cohort within the EPIC-Norfolk Study was examined, including a random subcohort (n = 4,000) and cases of incident diabetes (n = 892, including 143 cases in the subcohort) followed-up for 11 years. Diet was assessed using a prospective 7-day food diary. Total dairy intake (g/day) was estimated and categorised into high-fat (≥3.9%) and low-fat (<3.9% fat) dairy, and by subtype into yoghurt, cheese and milk. Combined fermented dairy product intake (yoghurt, cheese, sour cream) was estimated and categorised into high- and low-fat. Prentice-weighted Cox regression HRs were calculated. RESULTS: Total dairy, high-fat dairy, milk, cheese and high-fat fermented dairy product intakes were not associated with the development of incident diabetes. Low-fat dairy intake was inversely associated with diabetes in age- and sex-adjusted analyses (tertile [T] 3 vs T1, HR 0.81 [95% CI 0.66, 0.98]), but further adjustment for anthropometric, dietary and diabetes risk factors attenuated this association. In addition, an inverse association was found between diabetes and low-fat fermented dairy product intake (T3 vs T1, HR 0.76 [95% CI 0.60, 0.99]; p(trend) = 0.049) and specifically with yoghurt intake (HR 0.72 [95% CI 0.55, 0.95]; p(trend) = 0.017) in multivariable adjusted analyses. CONCLUSIONS/INTERPRETATION: Greater low-fat fermented dairy product intake, largely driven by yoghurt intake, was associated with a decreased risk of type 2 diabetes development in prospective analyses. These findings suggest that the consumption of specific dairy types may be beneficial for the prevention of diabetes, highlighting the importance of food group subtypes for public health messages.

The p38 MAPK inhibitor, PD169316, inhibits transforming growth factor beta-induced Smad signaling in human ovarian cancer cells.

Transforming growth factor beta (TGFbeta) can signal through a variety of Smad-independent pathways, including the p38 MAPK pathway. Recent work has shown that inhibitors of p38 MAPK, such as SB203580 and SB202190, can inhibit signaling induced by TGFbeta. Here we show that another p38 MAPK inhibitor, PD169316, abrogates signaling initiated by both TGFbeta and Activin A, but not bone morphogenetic protein (BMP) 4. Inhibition of TGFbeta signaling is dose dependent and results in reduced Smad2 and Smad3 phosphorylation, nuclear translocation, and up-regulation of the TGFbeta target gene Smad7. Reduced TGFbeta signaling is not due to abrogation of p38 MAPK activity, since blocking p38 MAPK activity with a dominant negative form of p38 MAPK has no effect on TGFbeta/Smad signaling. Our results show that use of PD169316 at 5 MICROM or higher can block TGFbeta signaling activity and thus caution must be used when attributing cellular activities exclusively to p38 MAPK signaling when these inhibitors are used experimentally.