The Importance Of Multi-Reader Assessment For External Validation Of Prostate Lesion Classification Models Using Quantitative MpMRI

Machine learning for classifying prostate mpMRI lesions may help reduce unnecessary biopsies. However, external validation with multiple scanners and readers is required before the clinical adoption of such models can be considered. Two readers validated a previously published and well-performing logistic regression model on an external cohort. The model performance was not generalisable and offered no advantage to using PSAd cut-offs, and there was marked variation in model score related to contour differences from different readers. This potential variability should be investigated in future models which use quantitative MRI

The ReIMAGINE prostate cancer risk study protocol: A prospective cohort study in men with a suspicion of prostate cancer who are referred onto an MRI-based diagnostic pathway with donation of tissue, blood and urine for biomarker analyses

INTRODUCTION: The ReIMAGINE Consortium was conceived to develop risk-stratification models that might incorporate the full range of novel prostate cancer (PCa) diagnostics (both commercial and academic). METHODS: ReIMAGINE Risk is an ethics approved (19/LO/1128) multicentre, prospective, observational cohort study which will recruit 1000 treatment-naive men undergoing a multi-parametric MRI (mpMRI) due to an elevated PSA (≤20ng/ml) or abnormal prostate examination who subsequently had a suspicious mpMRI (score≥3, stage ≤T3bN0M0). Primary outcomes include the detection of ≥Gleason 7 PCa at baseline and time to clinical progression, metastasis and death. Baseline blood, urine, and biopsy cores for fresh prostate tissue samples (2 targeted and 1 non-targeted) will be biobanked for future analysis. High-resolution scanning of pathology whole-slide imaging and MRI-DICOM images will be collected. Consortium partners will be granted access to data and biobanks to develop and validate biomarkers using correlation to mpMRI, biopsy-based disease status and long-term clinical outcomes. RESULTS: Recruitment began in September 2019(n = 533). A first site opened in September 2019 (n = 296), a second in November 2019 (n = 210) and a third in December 2020 (n = 27). Acceptance to the study has been 65% and a mean of 36.5ml(SD+/-10.0), 12.9ml(SD+/-3.7) and 2.8ml(SD+/-0.7) urine, plasma and serum donated for research, respectively. There are currently 4 academic and 15 commercial partners spanning imaging (~9 radiomics, artificial intelligence/machine learning), fluidic (~3 blood-based and ~2urine-based) and tissue-based (~1) biomarkers. CONCLUSION: The consortium will develop, or adjust, risk models for PCa, and provide a platform for evaluating the role of novel diagnostics in the era of pre-biopsy MRI and targeted biopsy

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

MIF Participates in Toxoplasma gondii-Induced Pathology Following Oral Infection

BACKGROUND: Macrophage migration inhibitory factor (MIF) is essential for controlling parasite burden and survival in a model of systemic Toxoplasma gondii infection. Peroral T. gondii infection induces small intestine necrosis and death in susceptible hosts, and in many aspects resembles inflammatory bowel disease (IBD). Considering the critical role of MIF in the pathogenesis of IBD, we hypothesized that MIF participates in the inflammatory response induced by oral infection with T. gondii. METHODOLOGY/PRINCIPAL FINDINGS: Mif deficient (Mif(-/-)) and wild-type mice in the C57Bl/6 background were orally infected with T. gondii strain ME49. Mif(-/-) mice had reduced lethality, ileal inflammation and tissue damage despite of an increased intestinal parasite load compared to wt mice. Lack of MIF caused a reduction of TNF-α, IL-12, IFN-γ and IL-23 and an increased expression of IL-22 in ileal mucosa. Moreover, suppressed pro-inflammatory responses at the ileal mucosa observed in Mif(-/-) mice was not due to upregulation of IL-4, IL-10 or TGF-β. MIF also affected the expression of matrix metalloproteinase-9 (MMP-9) but not MMP-2 in the intestine of infected mice. Signs of systemic inflammation including the increased concentrations of inflammatory cytokines in the plasma and liver damage were less pronounced in Mif(-/-) mice compared to wild-type mice. CONCLUSION/SIGNIFICANCE: In conclusion, our data suggested that in susceptible hosts MIF controls T. gondii infection with the cost of increasing local and systemic inflammation, tissue damage and death

Arrhythmias in Dilated Cardiomyopathy: Diagnosis and Treatment

In patients with dilated cardiomyopathy (DCM), it is possible to find a broad range of bradyrhythmias and tachyarrhythmias. Bradyrhythmias and supraventricular arrhythmias can frequently occur in some familial forms such as lamin A/C mutations. Nonsustained ventricular arrhythmias (VA) are observed in about 40% of patients with DCM, but their prognostic role is not clear, and conflicting data have been published in the last 30 years. Multiple mechanisms can explain atrial and ventricular tachyarrhythmias in DCM. Reentry is associated with slow conduction across surviving muscle bundles within regions of interstitial fibrosis, but other mechanisms can be involved, as nonuniform anisotropy of impulse propagation, ion channel dysfunction, and reduced gap junction function

Non linear dynamic behaviour of a motorcycle forecarriage during braking

An experimental and numerical experience was carried out to investigate the nonlinear dynamic response of the forecarriage of a motorcycle, paying attention to a particular type of vibration that occurs during the braking. In fact, it was found that, in particular conditions of load on the handlebar, braking pressure, speed and temperature, the first flexural mode of the front fork is strongly excited. Thanks to the numerical model, solutions to these undesired vibrations were identified. Experimental tests were carried out modifying the design parameters of the motorcycles and of the braking system as suggested by the numerical model thus verifying that the purposed solutions were effective

US/TOF-PET endorectal probe compatible with MR, for diagnosis and staging of the prostate cancer

Prostate Cancer (PCa) is one of the most prevalent cancers worldwide. Early and accurate diagnosis of PCa is crucial for effective and successful treatment. Our project aims at developing a unique, highly performing flexible geometry multi-modality imaging system for diagnosis and staging of PCa. The imager will have the form of an endorectal probe combining high-resolution (0.1 mm) ultrasound (US) with a very high-resolution Positron Emission Tomography (PET) probe (1 mm spatial resolution) with exceptional Time-of-Flight (TOF) capability (100 ps FWHM targeted) compatible with Magnetic Resonance Imaging (MRI), in coincidence with a set of external PET panels. While standard multiparametric MRI (mpMR) has drawbacks, diagnosis will be improved significantly by the introduction of PSPMA-PET as well as the simultaneous PET/MR imaging. The system will be capable of morphological visualization instantly and continuously combined with biological and metabolic activity, offering crucial improvement with respect to standard systems (detection of ∼ 2 mm lesions vs. ∼ 6 mm lesions) in spatial resolution, efficiency, signal-to-noise ratio (SNR), scanning time and/or lowering injected dose

Influence of input reflectance values on climate-based daylight metrics using sensitivity analysis

This paper is published by Taylor & Francis as Gold Open Access under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).The insertion of climate-based daylight metrics as a requirement in several design guidelines calls for a better understanding of their effectiveness. This paper draws attention to the sensitivity of annual daylight metrics to changes in input reflectance values. The uncertainties related to the choice of guidelines and of simulation techniques were also considered. Total Annual Illumination (TAI) showed the most consistent correlation and the highest sensitivity to variations in reflectance (up to ±60% from the benchmark), independently of the geometrical characteristics of the space. Other annual metrics were less sensitive, or showed a poorer correlation. The deviations among different simulation techniques varied with the chosen metric too (NRMSD≤ 15% for TAI), but all techniques were equally affected by variations in reflectance. The results highlighted the importance of selecting appropriate metrics for annual climate-based daylight evaluations