Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

First Probe of Sub-GeV Dark Matter beyond the Cosmological Expectation with the COHERENT CsI Detector at the SNS.

The COHERENT Collaboration searched for scalar dark matter particles produced at the Spallation Neutron Source with masses between 1 and 220 MeV/c^{2} using a CsI[Na] scintillation detector sensitive to nuclear recoils above 9 keV_{nr}. No evidence for dark matter is found and we thus place limits on allowed parameter space. With this low-threshold detector, we are sensitive to coherent elastic scattering between dark matter and nuclei. The cross section for this process is orders of magnitude higher than for other processes historically used for accelerator-based direct-detection searches so that our small, 14.6 kg detector significantly improves on past constraints. At peak sensitivity, we reject the flux consistent with the cosmologically observed dark-matter concentration for all coupling constants α_{D}<0.64, assuming a scalar dark-matter particle. We also calculate the sensitivity of future COHERENT detectors to dark-matter signals which will ambitiously test multiple dark-matter spin scenarios.

Measurement of the Coherent Elastic Neutrino-Nucleus Scattering Cross Section on CsI by COHERENT.

We measured the cross section of coherent elastic neutrino-nucleus scattering (CEvNS) using a CsI[Na] scintillating crystal in a high flux of neutrinos produced at the Spallation Neutron Source at Oak Ridge National Laboratory. New data collected before detector decommissioning have more than doubled the dataset since the first observation of CEvNS, achieved with this detector. Systematic uncertainties have also been reduced with an updated quenching model, allowing for improved precision. With these analysis improvements, the COHERENT Collaboration determined the cross section to be (165_{-25}^{+30})×10^{-40} cm^{2}, consistent with the standard model, giving the most precise measurement of CEvNS yet. The timing structure of the neutrino beam has been exploited to compare the CEvNS cross section from scattering of different neutrino flavors. This result places leading constraints on neutrino nonstandard interactions while testing lepton flavor universality and measures the weak mixing angle as sin^{2}θ_{W}=0.220_{-0.026}^{+0.028} at Q^{2}≈(50 MeV)^{2}.

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon.

We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.

Applications of PET imaging with the proliferation marker [18F]-FLT.

[18F]-3'-fluoro-3'-deoxythymidine (FLT) is a nucleoside-analog imaging agent for quantifying cellular proliferation that was first reported in 1998. It accumulates during the S-phase of the cell cycle through the action of cytosolic thymidine kinase, TK1. Since TK1 is primarily expressed in dividing cells, FLT uptake is essentially limited to dividing cells. Thus FLT is an effective measure of cell proliferation. FLT uptake has been shown to correlate with the more classic proliferation marker, the monoclonal antibody to Ki-67. Increased cellular proliferation is known to correlate with worse outcome in many cancers. However, the Ki-67 binding assay is performed on a sampled preparation, ex vivo, whereas FLT can be quantitatively measured in vivo using positron emission tomography (PET). FLT is an effective and quantitative marker of cell proliferation, and therefore a useful prognostic predictor in the setting of neoplastic disease. This review summarizes clinical studies from 2011 forward that used FLT-PET to assess tumor response to therapy. The paper focuses on our recommendations for a standardized clinical trial protocol and components of a report so multi center studies can be effectively conducted, and different studies can be compared. For example, since FLT is glucuronidated by the liver, and the metabolite is not transported into the cell, the plasma fraction of FLT can be significantly changed by treatment with particular drugs that deplete this enzyme, including some chemotherapy agents and pain medications. Therefore, the plasma level of metabolites should be measured to assure FLT uptake kinetics can be accurately calculated. This is important because the flux constant (KFLT) is a more accurate measure of proliferation and, by inference, a better discriminator of tumor recurrence than standardized uptake value (SUVFLT). This will allow FLT imaging to be a specific and clinically relevant prognostic predictor in the treatment of neoplastic disease.

Regional P-glycoprotein activity and inhibition at the human blood-brain barrier as imaged by positron emission tomography.

We used positron emission tomography (PET) to evaluate the contribution of P-glycoprotein (P-gp), present at the human blood-brain barrier (BBB), to regional drug distribution in the brain. Eleven healthy volunteers underwent PET imaging with [(11)C]-verapamil before and during cyclosporine A infusion. Regional P-gp inhibition was expressed as cyclosporine A-induced percentage change in the distributional clearance of verapamil (K(1)) in the brain, normalized to the regional blood flow (rCBF). K(1) estimates were similar across gray-matter regions of the brain and lower in the white matter regions, but all these estimates were considerably lower than rCBF. Normalization of K(1) by rCBF diminished the differences in estimates related to gray matter and white matter. In contrast, the K(1) for the pituitary, which is situated outside the BBB, approximated the rCBF. The magnitude of P-gp inhibition was comparable across BBB-protected brain structures. Our results indicate that P-gp and its inhibition equally affect the distribution of drugs (and therefore their neuro-efficacy and toxicity) in the various brain regions protected by the BBB.

Positron emission tomography imaging of tissue P-glycoprotein activity during pregnancy in the non-human primate.

BACKGROUND AND PURPOSE: Changes in tissue P-glycoprotein (P-gp) activity during pregnancy could affect the pharmacokinetics and thus the efficacy and toxicity of many drugs. Therefore, using positron emission tomography (PET) imaging, we tested whether gestational age affects tissue P-gp activity in the pregnant non-human primate, Macaca nemestrina. EXPERIMENTAL APPROACH: Mid-gestational (day 75 +/- 13, n= 7) and late-gestational (day 150 +/- 10, n= 5) age macaques were imaged after administration of a prototypic P-gp substrate, (11)C-verapamil (13.7-75.4 MBq.kg(-1)), before and during intravenous infusion of a P-gp inhibitor, cyclosporin A (CsA) (12 or 24 mg.kg(-1).h(-1)). Accumulation of radioactivity in the fetal liver served as a reporter of placental P-gp activity. P-gp activity was expressed as CsA-induced percent change in the ratio of the area (0-9 min) under the (11)C-radioactivity concentration-time curve in the tissue (AUC(tissue)) to that in the maternal plasma (AUC(plasma)). KEY RESULTS: The CsA-induced change in AUC(fetal liver)/AUC(maternal)(plasma) of (11)C-radioactivity significantly increased from mid- (35 +/- 25%) to late gestation (125 +/- 66%). Likewise, the CsA-induced change in AUC(maternal brain)/AUC(plasma) increased from mid- (172 +/- 80%) to late gestation (337 +/- 148%). The AUC ratio for the other maternal tissues was not significantly affected. Neither the CsA blood concentrations nor the level of circulating (11)C-verapamil metabolites were significantly affected by gestational age. CONCLUSIONS AND IMPLICATIONS: P-gp activity at the blood-brain barrier and the placental barrier in the macaque increased with gestational age. If replicated in humans, the exposure of the fetus and maternal brain to P-gp substrate drugs, and therefore their efficacy and toxicity, will change during pregnancy.

Search for muon neutrino and antineutrino disappearance in MiniBooNE.

The MiniBooNE Collaboration reports a search for nu_{micro} and nu[over]_{micro} disappearance in the Deltam;{2} region of 0.5-40 eV;{2}. These measurements are important for constraining models with extra types of neutrinos, extra dimensions, and CPT violation. Fits to the shape of the nu_{micro} and nu[over]_{micro} energy spectra reveal no evidence for disappearance at the 90% confidence level (C.L.) in either mode. The test of nu[over]_{micro} disappearance probes a region below Deltam;{2} = 40 eV;{2} never explored before.

Measurement of the ratio of the numu charged-current single-pion production to quasielastic scattering with a 0.8 GeV neutrino beam on mineral oil.

Using high statistics samples of charged-current numu interactions, the MiniBooNE [corrected] Collaboration reports a measurement of the single-charged-pion production to quasielastic cross section ratio on mineral oil (CH2), both with and without corrections for hadron reinteractions in the target nucleus. The result is provided as a function of neutrino energy in the range 0.4 GeV

Measurement of numicro and nue events in an off-axis horn-focused neutrino beam.

We report the first observation of off-axis neutrino interactions in the MiniBooNE detector from the NuMI beam line at Fermilab. The MiniBooNE detector is located 745 m from the NuMI production target, at 110 mrad angle (6.3 degrees) with respect to the NuMI beam axis. Samples of charged-current quasielastic numicro and nue interactions are analyzed and found to be in agreement with expectation. This provides a direct verification of the expected pion and kaon contributions to the neutrino flux and validates the modeling of the NuMI off-axis beam.

Unexplained excess of electronlike events from a 1-GeV neutrino beam.

The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20} protons on target, 544 electronlike events are observed in this energy range, compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of 128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either nu_{e} and nu[over ]_{e} charged-current scattering or nu_{mu} neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9+/-35.7 events.

Measurement of muon neutrino quasielastic scattering on carbon.

The observation of neutrino oscillations is clear evidence for physics beyond the standard model. To make precise measurements of this phenomenon, neutrino oscillation experiments, including MiniBooNE, require an accurate description of neutrino charged current quasielastic (CCQE) cross sections to predict signal samples. Using a high-statistics sample of nu_(mu) CCQE events, MiniBooNE finds that a simple Fermi gas model, with appropriate adjustments, accurately characterizes the CCQE events observed in a carbon-based detector. The extracted parameters include an effective axial mass, M_(A)(eff)=1.23+/-0.20 GeV, that describes the four-momentum dependence of the axial-vector form factor of the nucleon, and a Pauli-suppression parameter, kappa=1.019+/-0.011. Such a modified Fermi gas model may also be used by future accelerator-based experiments measuring neutrino oscillations on nuclear targets.

Search for electron neutrino appearance at the Delta m2 approximately 1 eV2 scale.

The MiniBooNE Collaboration reports first results of a search for nu e appearance in a nu mu beam. With two largely independent analyses, we observe no significant excess of events above the background for reconstructed neutrino energies above 475 MeV. The data are consistent with no oscillations within a two-neutrino appearance-only oscillation model.

Measurement of the D(s)+ lifetime.

A high statistics measurement of the D(s)+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis of the two decay modes, D(s)+ --> phi(1020)pi+ and D(s)+ -->K*(892)0K+, used for the measurement. The measured lifetime is 507.4 +/- 5.5(stat) +/- 5.1(syst) fs using 8961 +/- 105 D(s)+ --> phi(1020)pi+ and 4680 +/- 90 D(s)+ --> K*(892)0K+ decays. This is a significant improvement over the present world average.

A high statistics measurement of the Lambda(+)(c) lifetime.

A high statistics measurement of the Lambda(+)(c) lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat) +/- 2.5 (syst) fs from 8034 +/- 122 Lambda(+)(c)-->pK(-)pi(+) decays represents a significant improvement over the present world average.

Search for CP violation in the decays D+--> K(S)pi+ and D+-->K(S)K+.

A high-statistics sample of photoproduced charm from the FOCUS experiment has been used to search for direct CP violation in the decay rates for D+-->K(S)pi+ and D+-->K(S)K+. We have measured the following asymmetry parameters relative to D+-->K-pi+pi+: A(CP)(K(S)pi+) = (-1.6+/-1.5+/-0.9)%, A(CP)(K(S)K+) = (+6.9+/-6.0+/-1.5)%, and A(CP)(K(S)K+) = (+7.1+/-6.1+/-1.2)% relative to D+-->K(S)pi+. We have also measured the relative branching ratios and found Gamma(D+-->K(0)pi+)/Gamma(D+-->K-pi+pi+) = (30.60+/-0.46+/-0.32)%, Gamma(D+-->K(0)K+)/Gamma(D+-->K-pi+pi+) = (6.04+/-0.35+/-0.30)%, and Gamma(D+-->K(0)K+)/Gamma(D+-->K(0)pi+) = (19.96+/-1.19+/-0.96)%.

Measurement of the branching ratios of D(+) and D(+)(s) hadronic decays to four-body final states containing a K(S).

We have studied hadronic four-body decays of D(+) and D(+)(s) mesons with a K(S) in the final state using data recorded during the 1996-1997 fixed-target run of the Fermilab high energy photoproduction experiment FOCUS. We report a new branching ratio measurement of gamma(D(+)-->K(S)K-pi(+)pi(+))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0768+/-0.0041+/-0.0032. We make the first observation of three new decay modes with branching ratios gamma(D(+)-->K(S)K+pi(+)pi(-))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0562+/-0.0039+/-0.0040, gamma(D(+)-->K(S)K+K-pi(+))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0077+/-0.0015+/-0.0009, and gamma(D(+)(s)-->K(S)K+pi(+)pi(-))/gamma(D(+)(s)-->K(S)K-pi(+)pi(+)) = 0.586+/-0.052+/-0.043, where in each case the first error is statistical and the second error is systematic.

Cardiac receptor physiology and its application to clinical imaging: present and future.

Both gamma imaging and positron emission tomography (PET) imaging of cell surface receptors have become possible through the development of agonists and antagonists with high specific radioactivity and high specificity for the receptors. An understanding of the physiology of the cardiac receptor system is essential to comprehending receptor imaging. The complexity of the physiologic information developed over the past decade has been compounded by the concomitant discovery of additional receptor subtypes. The following is a review of a select group of cardiac receptors and their regulation-namely, adrenergic, muscarinic-cholinergic, adenosine, and angiotensin I and II receptors. The role of imaging regional receptor localization and function in providing new insights into cardiac pathology and therapeutic avenues is explored.

[18F]fluoroestradiol radiation dosimetry in human PET studies.

UNLABELLED: [18F]16alpha-fluoroestradiol (FES) is a PET imaging agent useful for the study of estrogen receptors in breast cancer. We estimated the radiation dosimetry for this tracer using data obtained in patient studies. METHODS: Time-dependent tissue concentrations of radioactivity were determined from blood samples and PET images in 49 patients (52 studies) after intravenous injection of FES. Radiation absorbed doses were calculated using the procedures of the MIRD committee, taking into account the variation in dose based on the distribution of activities observed in the individual patients. Effective dose equivalent was calculated using International Commission on Radiological Protection Publication 60 weights for the standard woman. RESULTS: The effective dose equivalent was 0.022 mSv/MBq (80 mrem/mCi). The organ that received the highest dose was the liver (0.13 mGy/MBq [470 mrad/mCi]), followed by the gallbladder (0.10 mGy/MBq [380 mrad/mCi]) and the urinary bladder (0.05 mGy/MBq [190 mrad/mCi]). CONCLUSION: The organ doses are comparable to those associated with other commonly performed nuclear medicine tests. FES is a useful estrogen receptor-imaging agent, and the potential radiation risks associated with this study are well within accepted limits.