The Influence of Fat Suppression Technique on Diffusion-weighted (DW) MRI in Lung Cancer

Purpose: To qualitatively and quantitatively investigate the effect of common vendor-related sequence variations in fat suppression techniques on the diagnostic performance of free-breathing DW protocols for lung imaging.Methods: 8 patients with malignant lung lesions were scanned in free breathing using two diffusion-weighted (DW) protocols with different fat suppression techniques: DWA used short-tau inversion recovery (STIR), and DWB used Spectral Adiabatic Inversion Recovery (SPAIR). Both techniques were obtained at two time points, between 1 hour and 1 week apart. Image quality was assessed using a 5-point scoring system. The number of lesions visible within lung, mediastinum and at thoracic inlet on the DW (b=800 s/mm2) images was compared. Signal-to-noise ratios (SNR) were calculated for lesions and para-spinal muscle. Repeatability of ADC values of the lesions was estimated for both protocols together and separately.Results: There was a signal void at the thoracic inlet in all patients with DWB but not with DWA. DWA images were rated significantly better than DWB images overall quality domains. (Cohens κ = 1). Although 8 more upper mediastinal/thoracic inlet lymph nodes were detected with DWA than DWB, this did not reach statistical significance (p = 0.23). Tumour ADC values were not significantly different between protocols (p=0.93), their ADC reproducibility was satisfactory (CoV=7.7%) and repeatability of each protocol separately was comparable (CoVDWA=3.7% (95% CI 2.5 7.1%) and CoVDWB=4.6% (95% CI 3.18.8%)).Conclusion: In a free-breathing DW-MRI protocol for lung, STIR fat suppression produced images of better diagnostic quality than SPAIR, while maintaining comparable SNR and providing repeatable quantitative ADC acceptable for use in a multicentre trial setting

Giant magnons of string theory in the lambda background

The analogues of giant magnon configurations are studied on the string world sheet in the lambda background. This is a discrete deformation of the AdS(5)xS(5) background that preserves the integrability of the world sheet theory. Giant magnon solutions are generated using the dressing method and their dispersion relation is found. This reduces to the usual dyonic giant magnon dispersion relation in the appropriate limit and becomes relativistic in another limit where the lambda model becomes the generalized sine-Gordon theory of the Pohlmeyer reduction. The scattering of giant magnons is then shown in the semi-classical limit to be described by the quantum S-matrix that is a quantum group deformation of the conventional giant magnon S-matrix. It is further shown that in the small g limit, a sector of the S-matrix is related to the XXZ spin chain whose spectrum matches the spectrum of magnon bound states.Comment: 53 pages, 6 figures, final version to appear in JHE

Development of training-related health care software by a team of clinical educators: their experience, from conception to piloting

Derfel ap Dafydd,1 Ruth Williamson,2 Philip Blunt,3 Dominic M Blunt4 1Department of Radiology, Royal Marsden NHS Foundation Trust, London, 2Imaging Department, Royal Bornemouth Hospital, Bornemouth, 3Savernake IT Ltd, Marlborough, 4Imaging Department, Imperial College Healthcare NHS Trust, London, UK Abstract: The difficulties of producing useful, bespoke, and affordable information technology systems for large health care organizations are well publicized, following several high-profile endeavors in the UK. This article describes the experience of a small group of clinical radiologists and their collaborators in producing an information technology system – from conception to piloting. This system, called Trainee Tracker, enables automated target date recalculation of trainee milestones, depending on their work patterns and other individual circumstances. It utilizes an automated email alert system to notify the educational supervisors and trainees of approaching and elapsed target dates, in order to identify trainees in difficulty early and address their training needs accordingly. The challenges and advantages, both common to and contrasting with larger-scale projects, are also considered. The benefits of the development team’s “agile” approach to software development and the lessons learned will be of interest to medical educators, particularly those with expertise in e-portfolios and other training-related software. Keywords: training, appraisal, ARCP, Annual Review of Clinical Progression, portfolio, traine

Detection and staging of radio-recurrent prostate cancer using multiparametric MRI.

OBJECTIVE: We determined the sensitivity and specificity of multiparametric magnetic resonance imaging (MP-MRI) in detection of locally recurrent prostate cancer and extra prostatic extension in the post-radical radiotherapy setting. Histopathological reference standard was whole-mount prostatectomy specimens. We also assessed for any added value of the dynamic contrast enhancement (DCE) sequence in detection and staging of local recurrence. METHODS: This was a single centre retrospective study. Participants were selected from a database of males treated with salvage prostatectomy for locally recurrent prostate cancer following radiotherapy. All underwent pre-operative prostate-specific antigen assay, positron emission tomography CT, MP-MRI and transperineal template prostate mapping biopsy prior to salvage prostatectomy. MP-MRI performance was assessed using both Prostate Imaging-Reporting and Data System v. 2 and a modified scoring system for the post-treatment setting. RESULTS: 24 patients were enrolled. Using Prostate Imaging-Reporting and Data System v. 2, sensitivity, specificity, positive predictive value and negative predictive value was 64%, 94%, 98% and 36%. MP-MRI under staged recurrent cancer in 63%. A modified scoring system in which DCE was used as a co-dominant sequence resulted in improved diagnostic sensitivity (61%-76%) following subgroup analysis. CONCLUSION: Our results show MP-MRI has moderate sensitivity (64%) and high specificity (94%) in detecting radio-recurrent intraprostatic disease, though disease tends to be under quantified and under staged. Greater emphasis on dynamic contrast images in overall scoring can improve diagnostic sensitivity. ADVANCES IN KNOWLEDGE: MP-MRI tends to under quantify and under stage radio-recurrent prostate cancer. DCE has a potentially augmented role in detecting recurrent tumour compared with the de novo setting. This has relevance in the event of any future modified MP-MRI scoring system for the irradiated gland

Paratesticular Sarcoma: Typical Presentation, Imaging Features, and Clinical Challenges.

Objective To describe the major imaging features, together with clinical data, of paratesticular sarcomas.Materials and methods A retrospective analysis was performed of available imaging and clinical data of 77 consecutive cases of paratesticular sarcoma referred to the soft tissue sarcoma center at the Royal Marsden hospital between January 2006 and January 2015.Results Of the total cases, 87% had been referred postoperatively, 43% of which had been imaged preoperatively and 24% of which required re-resection due to incomplete initial excision. On imaging, abnormal fat was present in 73% of paratesticular liposarcomas, with solid or enhancing components indicating high-grade tumors. Leiomyosarcomas and rhabdomyosarcomas were all purely solid masses.Conclusion Paratesticular sarcomas are rare, and lack of awareness may compromise treatment and outcome. They may be mistaken for common clinical problems such as inguinal hernias and epididymal cysts. Surgery for these presumed diagnoses may result in inadequate clearance and an increased risk of recurrence. A low threshold for imaging atypical paratesticular masses is needed, as this may better inform management

On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy

Background Previous studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy.Methods Analysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics.Results Low baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0–2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell’s C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell’s C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model.Conclusions NLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC

Interpretability of radiomics models is improved when using feature group selection strategies for predicting molecular and clinical targets in clear-cell renal cell carcinoma: insights from the TRACERx Renal study.

BACKGROUND: The aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability. METHODS: Contrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds. RESULTS: Classification performance was significant (p  0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage. CONCLUSIONS: Use of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance. TRIAL REGISTRATION: NCT03226886 (TRACERx Renal)

Stability of p53 Homologs

<div><p>Most proteins have not evolved for maximal thermal stability. Some are only marginally stable, as for example, the DNA-binding domains of p53 and its homologs, whose kinetic and thermodynamic stabilities are strongly correlated. Here, we applied high-throughput methods using a real-time PCR thermocycler to study the stability of several full-length orthologs and paralogs of the p53 family of transcription factors, which have diverse functions, ranging from tumour suppression to control of developmental processes. From isothermal denaturation fluorimetry and differential scanning fluorimetry, we found that full-length proteins showed the same correlation between kinetic and thermodynamic stability as their isolated DNA-binding domains. The stabilities of the full-length p53 orthologs were marginal and correlated with the temperature of their organism, paralleling the stability of the isolated DNA-binding domains. Additionally, the paralogs p63 and p73 were significantly more stable and long-lived than p53. The short half-life of p53 orthologs and the greater persistence of the paralogs may be biologically relevant.</p> </div