Histo-MRI map study protocol: a prospective cohort study mapping MRI to histology for biomarker validation and prediction of prostate cancer

Magnetic resonance imaging; Pathology; Prostate diseaseImatges per ressonància magnètica; Patologia; Malaltia de la pròstataImágenes por resonancia magnética; Patología; Enfermedad de la próstataIntroduction Multiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and a high false-positive rate, especially in men with mpMRI scored as indeterminate (3/5) or likely (4/5) to have clinically significant cancer (csPCa) (Gleason ≥3+4). Advanced MRI techniques have emerged which seek to improve this characterisation and could predict biopsy results non-invasively. Before these techniques are translated clinically, robust histological and clinical validation is required. Methods and analysis This study aims to clinically validate two advanced MRI techniques in a prospectively recruited cohort of men suspected of prostate cancer. Histological analysis of men undergoing biopsy or prostatectomy will be used for biological validation of biomarkers derived from Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours and Luminal Water imaging. In particular, prostatectomy specimens will be processed using three-dimension printed patient-specific moulds to allow for accurate MRI and histology mapping. The index tests will be compared with the histological reference standard to derive false positive rate and true positive rate for men with mpMRI scores which are indeterminate (3/5) or likely (4/5) to have clinically significant prostate cancer (csPCa). Histopathological validation from both biopsy and prostatectomy samples will provide the best ground truth in validating promising MRI techniques which could predict biopsy results and help avoid unnecessary biopsies in men suspected of prostate cancer. Ethics and dissemination Ethical approval was granted by the London—Queen Square Research Ethics Committee (19/LO/1803) on 23 January 2020. Results from the study will be presented at conferences and submitted to peer-reviewed journals for publication. Results will also be available on ClinicalTrials.gov.This work is supported by Engineering and Physical Sciences Research Council (EPSRC), grant reference (EP/R006032/1) and EP/M020533/1

Histo-MRI map study protocol: a prospective cohort study mapping MRI to histology for biomarker validation and prediction of prostate cancer

INTRODUCTION: Multiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and a high false-positive rate, especially in men with mpMRI scored as indeterminate (3/5) or likely (4/5) to have clinically significant cancer (csPCa) (Gleason ≥3+4). Advanced MRI techniques have emerged which seek to improve this characterisation and could predict biopsy results non-invasively. Before these techniques are translated clinically, robust histological and clinical validation is required. METHODS AND ANALYSIS: This study aims to clinically validate two advanced MRI techniques in a prospectively recruited cohort of men suspected of prostate cancer. Histological analysis of men undergoing biopsy or prostatectomy will be used for biological validation of biomarkers derived from Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours and Luminal Water imaging. In particular, prostatectomy specimens will be processed using three-dimension printed patient-specific moulds to allow for accurate MRI and histology mapping. The index tests will be compared with the histological reference standard to derive false positive rate and true positive rate for men with mpMRI scores which are indeterminate (3/5) or likely (4/5) to have clinically significant prostate cancer (csPCa). Histopathological validation from both biopsy and prostatectomy samples will provide the best ground truth in validating promising MRI techniques which could predict biopsy results and help avoid unnecessary biopsies in men suspected of prostate cancer. ETHICS AND DISSEMINATION: Ethical approval was granted by the London-Queen Square Research Ethics Committee (19/LO/1803) on 23 January 2020. Results from the study will be presented at conferences and submitted to peer-reviewed journals for publication. Results will also be available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04792138

Injury epidemiology in professional ballet: a five-season prospective study of 1596 medical attention injuries and 543 time-loss injuries

OBJECTIVES: To describe the incidence rate, severity, burden and aetiology of medical attention and time-loss injuries across five consecutive seasons at a professional ballet company. METHODS: Medical attention injuries, time-loss injuries and dance exposure hours of 123 professional ballet dancers (women: n=66, age: 28.0+/-8.3 years; men: n=57, age: 27.9+/-8.5 years) were prospectively recorded between the 2015/2016 and 2019/2020 seasons. RESULTS: The incidence rate (per 1000 hours) of medical attention injury was 3.9 (95% CI 3.3 to 4.4) for women and 3.1 (95% CI 2.6 to 3.5) for men. The incidence rate (per 1000 hours) of time-loss injury was 1.2 (95% CI 1.0 to 1.5) for women and 1.1 (95% CI 0.9 to 1.3) for men. First Soloists and Principals experienced between 2.0-2.2 additional medical attention injuries per 1000 hours and 0.9-1.1 additional time-loss injuries per 1000 hours compared with Apprentices (p</=0.025). Further, intraseason differences were observed in medical attention, but not time-loss, injury incidence rates with the highest incidence rates in early (August and September) and late (June) season months. Thirty-five per cent of time-loss injuries resulted in over 28 days of modified dance training. A greater percentage of time-loss injuries were classified as overuse (women: 50%; men: 51%) compared with traumatic (women: 40%; men: 41%). CONCLUSION: This is the first study to report the incidence rate of medical attention and time-loss injuries in professional ballet dancers. Incidence rates differed across company ranks and months, which may inform targeted injury prevention strategies

Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1-13 C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade

BACKGROUND: Three-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) 13 C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa). PURPOSE: To validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP 13 C-MRI in patients. To evaluate the metabolism in PCa measured by ME-bSSFP. STUDY TYPE: Retrospective single-center cohort study. PHANTOMS/POPULATION: Phantoms containing aqueous solutions of [1-13 C] lactate (2.3 M) and [13 C] urea (8 M). Eight patients (mean age 67 ± 6 years) with biopsy-confirmed Gleason 3 + 4 (n = 7) and 4 + 3 (n = 1) PCa. FIELD STRENGTH/SEQUENCES: 1 H MRI at 3 T with T2 -weighted turbo spin-echo sequence used for spatial localization and spoiled dual gradient-echo sequence used for B0 -field measurement. ME-bSSFP sequence for 13 C MR spectroscopic imaging with retrospective multipoint IDEAL metabolite separation. ASSESSMENT: The primary endpoint was the analysis of pyruvate-to-lactate conversion in PCa and healthy prostate regions of interest (ROIs) using model-free area under the curve (AUC) ratios and a one-directional kinetic model (kP ). The secondary objectives were to investigate the correlation between simulated and experimental ME-bSSFP metabolite signals for HP 13 C-MRI parameter optimization. STATISTICAL TESTS: Pearson correlation coefficients with 95% confidence intervals and paired t-tests. The level of statistical significance was set at P  0.96). Therefore, the simulation framework was used for sequence optimization. Whole prostate metabolic HP 13 C-MRI, observing the conversion of pyruvate into lactate, with a temporal resolution of 6 seconds was demonstrated using ME-bSSFP. Both assessed metrics resulted in significant differences between PCa (mean ± SD) (AUC = 0.33 ± 012, kP  = 0.038 ± 0.014) and healthy (AUC = 0.15 ± 0.10, kP  = 0.011 ± 0.007) ROIs. DATA CONCLUSION: Metabolic HP 13 C-MRI in the prostate using ME-bSSFP allows for differentiation between aggressive PCa and healthy tissue. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1

First-in-human in-vivo depiction of paraganglioma metabolism by hyperpolarised 13C-magnetic resonance

Phaeochromocytomas (PCC) and paragangliomas (PGL), cumulatively referred to as PPGLs, are neuroendocrine tumours arising from neural crest-derived cells in the sympathetic and parasympathetic nervous systems. Predicting future tumour behaviour and the likelihood of metastatic disease remains problematic as genotype–phenotype correlations are limited, the disease has variable penetrance and, to date, no reliable molecular, cellular or histological markers have emerged. Tumour metabolism quantification can be considered as a method to delineating tumour aggressiveness by utilising hyperpolarised 13 C-MR (HP-MR). The technique may provide an opportunity to non-invasively characterise disease behaviour. Here, we present the first instance of the analysis of PPGL metabolism via HP-MR in a single case

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.Peer reviewe

Autonomous control of an ultrasound probe for intra-operative ultrasonography using vision-based shape sensing of pneumatically attachable flexible rails.

PURPOSE: In robotic-assisted minimally invasive surgery, surgeons often use intra-operative ultrasound to visualise endophytic structures and localise resection margins. This must be performed by a highly skilled surgeon. Automating this subtask may reduce the cognitive load for the surgeon and improve patient outcomes. METHODS: We demonstrate vision-based shape sensing of the pneumatically attachable flexible (PAF) rail by using colour-dependent image segmentation. The shape-sensing framework is evaluated on known curves ranging from r = 30 to r = 110 mm, replicating curvatures in a human kidney. The shape sensing is then used to inform path planning of a collaborative robot arm paired with an intra-operative ultrasound probe. We execute 15 autonomous ultrasound scans of a tumour-embedded kidney phantom and retrieve viable ultrasound images, as well as seven freehand ultrasound scans for comparison. RESULTS: The vision-based sensor is shown to have comparable sensing accuracy with FBGS-based systems. We find the RMSE of the vision-based shape sensing of the PAF rail compared with ground truth to be 0.4975 ± 0.4169 mm. The ultrasound images acquired by the robot and by the human were evaluated by two independent clinicians. The median score across all criteria for both readers was '3-good' for human and '4-very good' for robot. CONCLUSION: We have proposed a framework for autonomous intra-operative US scanning using vision-based shape sensing to inform path planning. Ultrasound images were evaluated by clinicians for sharpness of image, clarity of structures visible, and contrast of solid and fluid areas. Clinicians evaluated that robot-acquired images were superior to human-acquired images in all metrics. Future work will translate the framework to a da Vinci surgical robot

openpreserve/jpylyzer: Jpylyzer 2.2.0

&lt;h2&gt;What's Changed since 2.1&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;Added support for High Throughput JPEG 2000 (JPH and JHC formats)&lt;/li&gt; &lt;li&gt;Added support for CAP, PRF and CPF marker segments&lt;/li&gt; &lt;li&gt;Improved reporting and validation of Rsiz property, added Capability property&lt;/li&gt; &lt;li&gt;Added reporting of warnings to output file&lt;/li&gt; &lt;li&gt;Added reporting of compression ratio for codestreams&lt;/li&gt; &lt;li&gt;Output and extraction options are now callable from API&lt;/li&gt; &lt;li&gt;Removed Python 2.7 fallbacks&lt;/li&gt; &lt;li&gt;Removed legacy wrapper and legacyout options&lt;/li&gt; &lt;li&gt;New XSD schema&lt;/li&gt; &lt;li&gt;Various bug fixes and improvements&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;&lt;strong&gt;Full Changelog&lt;/strong&gt;: https://github.com/openpreserve/jpylyzer/compare/2.1.0...2.2.0&lt;/p&gt