We provide an assessment of the energy dependence of key measurements within the scope of the machine parameters for a US based electron-ion collider (EIC) outlined in the EIC White Paper. We first ...examine the importance of the physics underlying these measurements in the context of the outstanding questions in nuclear science. We then demonstrate, through detailed simulations of the measurements, that the likelihood of transformational scientific insights is greatly enhanced by making the energy range and reach of the EIC as large as practically feasible.
Purpose
In this article we take a critical look at the key changes of the newest edition of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 (v2.1) and indicate future directions ...for further development of the system.
Conclusion
PI-RADS v2.1 addresses some of the shortcomings of its widely embraced precursor version 2, largely to simplify interpretation and improve interobserver agreement without changing the fundamental acquisition and scoring guidelines. Biparametric MRI is acknowledged in the newest version, but multiparametric MRI including dynamic contrast-enhanced imaging is still recommended for most scenarios. Management recommendations and guidance on evaluation of follow-up MRI’s are still not included in the system.
•Readout-segmented multi-shot echo-planar imaging (rs-EPI) and parallel transmit (ptx)-EPI showed a significantly higher contrast intensity between prostate cancer (PCa) and benign PZ or TZ compared ...single-shot (ss)-EPI.•Subjective IQ was significantly higher for rs-EPI.•Single PCa lesions could only be recognized and correlated on rs-EPI.
This study evaluates objective and subjective image quality (IQ) of three different diffusion weighted imaging (DWI) sequences in prostate MRI at 3.0 Tesla within the same patients.
Thirty-six consecutive patients (70 ± 8 years) with multi-parametric prostate MRI (mp-MRI; 3 T) and subsequently verified prostate cancer (PCa) by targeted plus systematic MR/US-fusion biopsy from 03/2016 to 12/2017 were included. Readout-segmented (rs) multi shot echo-planar imaging (EPI), parallel transmit (ptx) EPI, and single-shot (ss) EPI with b-values of 0, (500,) 1,000 s/mm² and calculated b1,500 were prospectively acquired of every patient. Signal intensities (SI) of PCa and benign tissue (peripheral and transition zone; PZ and TZ) in ADC, b1,000, and calculated b1,500 images were analyzed. Endpoints were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and subjective IQ on a 5-point scale by two blinded readers.
For ss-EPI ADC, b-values of 1,000, and calculated 1,500 s/mm² images showed a higher SNR compared to rs-EPI and ptx-EPI (p < 0.01). CNR of PCa and benign tissue was significantly higher for rs-EPI in high b value images compared to ptx-EPI and ss-EPI (p < 0.01). Subjective IQ was significantly higher for rs-EPI (p < 0.01). Significantly higher ADC reduction combined with signal increase on high b value images for PCa compared to the surrounding healthy tissue in PZ and TZ (PCa contrast intensity) was detected for rs-EPI (p < 0.01). Single PCa lesions could only be recognized and correlated on rs-EPI.
Rs-EPI and ptx-EPI were superior to ss-EPI regarding contrast intensity of PCA, but inferior regarding SNR. Subjective imaging parameters were superior for rs-EPI. Especially rs-EPI, but also ptx-EPI might improve and faciliate prostate cancer detection, rs-EPI at the expense of a longer acquisition time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. The prognosis of SCLC patients is devastating and no biologically targeted therapeutics are active in this tumor type. To ...develop a framework for development of specific SCLC-targeted drugs we conducted a combined genomic and pharmacological vulnerability screen in SCLC cell lines. We show that SCLC cell lines capture the genomic landscape of primary SCLC tumors and provide genetic predictors for activity of clinically relevant inhibitors by screening 267 compounds across 44 of these cell lines. We show Aurora kinase inhibitors are effective in SCLC cell lines bearing MYC amplification, which occur in 3-7% of SCLC patients. In MYC-amplified SCLC cells Aurora kinase inhibition associates with G2/M-arrest, inactivation of PI3-kinase (PI3K) signaling, and induction of apoptosis. Aurora dependency in SCLC primarily involved Aurora B, required its kinase activity, and was independent of depletion of cytoplasmic levels of MYC. Our study suggests that a fraction of SCLC patients may benefit from therapeutic inhibition of Aurora B. Thus, thorough chemical and genomic exploration of SCLC cell lines may provide starting points for further development of rational targeted therapeutic intervention in this deadly tumor type.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Electron-Ion Collider: The next QCD frontier Accardi, A.; Albacete, J. L.; Anselmino, M. ...
The European physical journal. A, Hadrons and nuclei,
2016/9, Volume:
52, Issue:
9
Journal Article
Peer reviewed
Open access
.
This White Paper presents the science case of an Electron-Ion Collider (EIC), focused on the structure and interactions of gluon-dominated matter, with the intent to articulate it to the broader ...nuclear science community. It was commissioned by the managements of Brookhaven National Laboratory (BNL) and Thomas Jefferson National Accelerator Facility (JLab) with the objective of presenting a summary of scientific opportunities and goals of the EIC as a follow-up to the 2007 NSAC Long Range plan. This document is a culmination of a community-wide effort in nuclear science following a series of workshops on EIC physics over the past decades and, in particular, the focused ten-week program on “Gluons and quark sea at high energies” at the Institute for Nuclear Theory in Fall 2010. It contains a brief description of a few golden physics measurements along with accelerator and detector concepts required to achieve them. It has been benefited profoundly from inputs by the users’ communities of BNL and JLab. This White Paper offers the promise to propel the QCD science program in the US, established with the CEBAF accelerator at JLab and the RHIC collider at BNL, to the next QCD frontier.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Electron-Ion Collider: The next QCD frontier Accardi, A; Albacete, J L; Anselmino, M ...
European physical journal. A, Hadrons and nuclei,
09/2016, Volume:
52, Issue:
9
Journal Article
Peer reviewed
Open access
This White Paper presents the science case of an Electron-Ion Collider (EIC), focused on the structure and interactions of gluon-dominated matter, with the intent to articulate it to the broader ...nuclear science community. It was commissioned by the managements of Brookhaven National Laboratory (BNL) and Thomas Jefferson National Accelerator Facility (JLab) with the objective of presenting a summary of scientific opportunities and goals of the EIC as a follow-up to the 2007 NSAC Long Range plan. This document is a culmination of a community-wide effort in nuclear science following a series of workshops on EIC physics over the past decades and, in particular, the focused ten-week program on “Gluons and quark sea at high energies” at the Institute for Nuclear Theory in Fall 2010. It contains a brief description of a few golden physics measurements along with accelerator and detector concepts required to achieve them. It has been benefited profoundly from inputs by the users’ communities of BNL and JLab. This White Paper offers the promise to propel the QCD science program in the US, established with the CEBAF accelerator at JLab and the RHIC collider at BNL, to the next QCD frontier.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors and initiate the angiogenic switch in tumors remain poorly defined. By combining chemical genetics ...with multimodal imaging, we have identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal. Disruption of this feed-forward loop by chemical perturbation or knockdown of VEGFR2 in tumor cells dramatically inhibited production of VEGF in vitro and in vivo. This disruption was sufficient to prevent tumor growth in vivo. In patients with lung cancer, we found that this VEGF:VEGFR2 feed-forward loop was active, as the level of VEGF/VEGFR2 binding in tumor cells was highly correlated to tumor angiogenesis. We further demonstrated that inhibition of tumor cell VEGFR2 induces feedback activation of the IRS/MAPK signaling cascade. Most strikingly, combined pharmacological inhibition of VEGFR2 (ZD6474) and MEK (PD0325901) in tumor cells resulted in dramatic tumor shrinkage, whereas monotherapy only modestly slowed tumor growth. Thus, a tumor cell-autonomous VEGF:VEGFR2 feed-forward loop provides signal amplification required for the establishment of fully angiogenic tumors in lung cancer. Interrupting this feed-forward loop switches tumor cells from an angiogenic to a proliferative phenotype that sensitizes tumor cells to MAPK inhibition.
To evaluate if follow-up mpMRI scans of patients in PI-RADS category 3 are safe enough to omit or delay prostate biopsy in the future and to determine an optimal control interval. This retrospective ...single center study includes consecutive PI-RADS category 3 patients with one or more follow-up mpMRI (T2WI, DWI, DCE) and subsequent MRI-targeted and systematic TRUS-guided biopsy between 2012 and 2018. Primary study objective was the verification of a significant PI-RADS category upgrade in follow-up mpMRI in patients with subsequent PCA positive biopsy versus patients with negative biopsy. Further objectives were development of the PI-RADS category and clinical parameters between initial and follow-up mpMRI in the context of histopathologic results and time interval. Eighty-nine patients (median PSA 6.6 ng/ml; PSAD 0.13 ng/ml/ml) were finally included (follow-up period 31 ± 18 months). 19 cases had PCA (median PSA 7.8 ng/ml; PSAD 0.14 ng/ml/ml). 4 cases had csPCA (median PSA 5.4 ng/ml; PSAD 0.13 ng/ml/ml) for which there was a significant PI-RADS upgrade after 12-24 months (mean 3.75; p = 0.01) compared to patients without PCA (mean 2.74). Without PCA the mean PI-RADS category decreased after 25-36 months (mean 2.74; p = 0.02). Clinical parameters did not change significantly except a PSAD increase for PCA patients after 24 months. Patients within PI-RADS category 3 may not need prompt biopsy since those with PCA reliably demonstrate a PI-RADS category upgrade in follow-up mpMRI after 12-24 months. PI-RADS 3 patients with negative biopsy do not benefit from follow-up mpMRI earlier than 24 months.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
T o evaluate the value of multiparametric MRI (mpMRI) for the prediction of prostate cancer (PCA) aggressiveness.
Methods
In this single center cohort study, consecutive patients with ...histologically confirmed PCA were retrospectively enrolled. Four different ISUP grade groups (1, 2, 3, 4–5) were defined and fifty patients per group were included. Several clinical (age, PSA, PSAD, percentage of PCA infiltration) and mpMRI parameters (ADC value, signal increase on high b-value images, diameter, extraprostatic extension EPE, cross-zonal growth) were evaluated and correlated within the four groups. Based on combined descriptors, MRI grading groups (mG1–mG3) were defined to predict PCA aggressiveness.
Results
In total, 200 patients (mean age 68 years, median PSA value 8.1 ng/ml) were analyzed. Between the four groups, statistically significant differences could be shown for age, PSA, PSAD, and for MRI parameters cross-zonal growth, high b-value signal increase, EPE, and ADC (
p
< 0.01). All examined parameters revealed a significant correlation with the histopathologic biopsy ISUP grade groups (
p
< 0.01), except PCA diameter (
p
= 0.09). A mixed linear model demonstrated the strongest prediction of the respective ISUP grade group for the MRI grading system (
p
< 0.01) compared to single parameters.
Conclusions
MpMRI yields relevant pre-biopsy information about PCA aggressiveness. A combination of quantitative and qualitative parameters (MRI grading groups) provided the best prediction of the biopsy ISUP grade group and may improve clinical pathway and treatment planning, adding useful information beyond PI-RADS assessment category. Due to the high prevalence of higher grade PCA in patients within mG3, an early re-biopsy seems indicated in cases of negative or post-biopsy low-grade PCA.
Key Points
•
MpMRI yields relevant pre-biopsy information about prostate cancer aggressiveness.
•
MRI grading in addition to PI-RADS classification seems to be helpful for a size independent early prediction of clinically significant PCA.
•
MRI grading groups may help urologists in clinical pathway and treatment planning, especially when to consider an early re-biopsy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Highlights • Objective IQ for T2WI was at 1.5T under optimized parameters comparable to 3T. • SNR and CNR of DWI were significantly higher at 3T. • Subjective IQ on was significantly better at 3T. • ...PI-RADS v2 scores were similar at 3T and 1.5T.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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