Roadmap on nanoscale magnetic resonance imaging.

The field of nanoscale magnetic resonance imaging (NanoMRI) was started 30 years ago. It was motivated by the desire to image single molecules and molecular assemblies, such as proteins and virus particles, with near-atomic spatial resolution and on a length scale of 100 nm. Over the years, the NanoMRI field has also expanded to include the goal of useful high-resolution nuclear magnetic resonance (NMR) spectroscopy of molecules under ambient conditions, including samples up to the micron-scale. The realization of these goals requires the development of spin detection techniques that are many orders of magnitude more sensitive than conventional NMR and MRI, capable of detecting and controlling nanoscale ensembles of spins. Over the years, a number of different technical approaches to NanoMRI have emerged, each possessing a distinct set of capabilities for basic and applied areas of science. The goal of this roadmap article is to report the current state of the art in NanoMRI technologies, outline the areas where they are poised to have impact, identify the challenges that lie ahead, and propose methods to meet these challenges. This roadmap also shows how developments in NanoMRI techniques can lead to breakthroughs in emerging quantum science and technology applications. .

Strong on-Chip Microwave Photon-Magnon Coupling Using Ultralow-Damping Epitaxial Y3Fe5O12 Films at 2 K.

Y3Fe5O12 is arguably the best magnetic material for magnonic quantum information science (QIS) because of its extremely low damping. We report ultralow damping at 2 K in epitaxial Y3Fe5O12 thin films grown on a diamagnetic Y3Sc2Ga3O12 substrate that contains no rare-earth elements. Using these ultralow damping YIG films, we demonstrate for the first time strong coupling between magnons in patterned YIG thin films and microwave photons in a superconducting Nb resonator. This result paves the road toward scalable hybrid quantum systems that integrate superconducting microwave resonators, YIG film magnon conduits, and superconducting qubits into on-chip QIS devices.

Enhancing Perpendicular Magnetic Anisotropy in Garnet Ferrimagnet by Interfacing with Few-Layer WTe2.

Engineering magnetic anisotropy in a ferro- or ferrimagnetic (FM) thin film is crucial in a spintronic device. One way to modify the magnetic anisotropy is through the surface of the FM thin film. Here, we report the emergence of a perpendicular magnetic anisotropy (PMA) induced by interfacial interactions in a heterostructure comprised of a garnet ferrimagnet, Y3Fe5O12 (YIG), and a low-symmetry, high spin-orbit coupling (SOC) transition metal dichalcogenide, WTe2. At the same time, we also observed an enhancement in Gilbert damping in the WTe2-covered YIG area. Both the magnitude of interface-induced PMA and the Gilbert damping enhancement have no observable WTe2 thickness dependence down to a single quadruple layer, indicating that the interfacial interaction plays a critical role. The ability of WTe2 to enhance the PMA in FM thin film, combined with its previously reported capability to generate out-of-plane damping like spin torque, makes it desirable for magnetic memory applications.

Relevance of biopsy-derived pancreatic organoids in the development of efficient transcriptomic signatures to predict adjuvant chemosensitivity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) patients are frequently treated by chemotherapy. Even if personalized therapy based on molecular analysis can be performed for some tumors, PDAC regimens selection is still mainly based on patients' performance status and expected efficacy. Therefore, the establishment of molecular predictors of chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. We have recently developed an RNA-based signature that predicts the efficacy of adjuvant gemcitabine using 38 PDAC primary cell cultures. While demonstrated its efficiency, a significant association with the classical/basal-like PDAC spectrum was observed. We hypothesized that this flaw was due to the basal-like biased phenotype of cellular models used in our strategy. To overcome this limitation, we generated a prospective cohort of 27 consecutive biopsied derived pancreatic organoids (BDPO) and include them in the signature identification strategy. As BDPO's do not have the same biased phenotype as primary cell cultures we expect they can compensate one with each other and cover a broader range of molecular phenotypes. We then obtained an improved signature predicting gemcitabine sensibility that was validated in a cohort of 300 resected PDAC patients that have or have not received adjuvant gemcitabine. We demonstrated a significant association between the improved signature and the overall and disease-free survival in patients predicted as sensitive and treated with adjuvant gemcitabine. We propose then that including BDPO along primary cell cultures represent a powerful strategy that helps to overcome primary cell cultures limitations producing unbiased RNA-based signatures predictive of adjuvant treatments in PDAC.

Spin-Orbit Torque Nano-oscillators by Dipole-Field-Localized Spin Wave Modes.

We demonstrate a high-quality spin-orbit torque nano-oscillator comprised of spin wave modes confined by the magnetic field by the strongly inhomogeneous dipole field of a nearby micromagnet. This approach enables variable spatial confinement and systematic tuning of magnon spectrum and spectral separations for studying the impact of multimode interactions on auto-oscillations. We find these dipole-field-localized spin wave modes exhibit good characteristic properties as auto-oscillators─narrow line width and large amplitude─while persisting up to room temperature. We find that the line width of the lowest-lying localized mode is approximately proportional to temperature in good agreement with theoretical analysis of the impact of thermal fluctuations. This demonstration of a clean oscillator with tunable properties provides a powerful tool for understanding the fundamental limitations and line width contributions to improve future spin-Hall oscillators.

A transcriptomic signature to predict adjuvant gemcitabine sensitivity in pancreatic adenocarcinoma.

BACKGROUND: Chemotherapy is the only systemic treatment approved for pancreatic ductal adenocarcinoma (PDAC), with a selection of regimens based on patients' performance status and expected efficacy. The establishment of a potent stratification associated with chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. PATIENTS AND METHODS: Concomitant chemosensitivity and genome-wide RNA profiles were carried out on preclinical models (primary cell cultures and patient-derived xenografts) derived from patients with PDAC included in the PaCaOmics program (NCT01692873). The RNA-based stratification was tested in a monocentric cohort and validated in a multicentric cohort, both retrospectively collected from resected PDAC samples (67 and 368 patients, respectively). Forty-three (65%) and 203 (55%) patients received adjuvant gemcitabine in the monocentric and the multicentric cohorts, respectively. The relationships between predicted gemcitabine sensitivity and patients' overall survival (OS) and disease-free survival were investigated. RESULTS: The GemPred RNA signature was derived from preclinical models, defining gemcitabine sensitive PDAC as GemPred+. Among the patients who received gemcitabine in the test and validation cohorts, the GemPred+ patients had a higher OS than GemPred- (P = 0.046 and P = 0.00216). In both cohorts, the GemPred stratification was not associated with OS among patients who did not receive gemcitabine. Among gemcitabine-treated patients, GemPred+ patients had significantly higher OS than the GemPred-: 91.3 months [95% confidence interval (CI): 61.2-not reached] versus 33 months (95% CI: 24-35.2); hazard ratio 0.403 (95% CI: 0.221-0.735, P = 0.00216). The interaction test for gemcitabine and GemPred+ stratification was significant (P = 0.0245). Multivariate analysis in the gemcitabine-treated population retained an independent predictive value. CONCLUSION: The RNA-based GemPred stratification predicts the benefit of adjuvant gemcitabine in PDAC patients.

Broadband multi-magnon relaxometry using a quantum spin sensor for high frequency ferromagnetic dynamics sensing.

Development of sensitive local probes of magnon dynamics is essential to further understand the physical processes that govern magnon generation, propagation, scattering, and relaxation. Quantum spin sensors like the NV center in diamond have long spin lifetimes and their relaxation can be used to sense magnetic field noise at gigahertz frequencies. Thus far, NV sensing of ferromagnetic dynamics has been constrained to the case where the NV spin is resonant with a magnon mode in the sample meaning that the NV frequency provides an upper bound to detection. In this work we demonstrate ensemble NV detection of spinwaves generated via a nonlinear instability process where spinwaves of nonzero wavevector are parametrically driven by a high amplitude microwave field. NV relaxation caused by these driven spinwaves can be divided into two regimes; one- and multi-magnon NV relaxometry. In the one-magnon NV relaxometry regime the driven spinwave frequency is below the NV frequencies. The driven spinwave undergoes four-magnon scattering resulting in an increase in the population of magnons which are frequency matched to the NVs. The dipole magnetic fields of the NV-resonant magnons couple to and relax nearby NV spins. The amplitude of the NV relaxation increases with the wavevector of the driven spinwave mode which we are able to vary up to 3 × 106 m-1, well into the part of the spinwave spectrum dominated by the exchange interaction. Increasing the strength of the applied magnetic field brings all spinwave modes to higher frequencies than the NV frequencies. We find that the NVs are relaxed by the driven spinwave instability despite the absence of any individual NV-resonant magnons, suggesting that multiple magnons participate in creating magnetic field noise below the ferromagnetic gap frequency which causes NV spin relaxation.

Nonlocal Uniform-Mode Ferromagnetic Resonance Spin Pumping.

Nonlocal spin transport using lateral structures is attractive for spintronic devices. Typically, a spin current is generated by a ferromagnetic (FM) or a heavy metal (HM) electrode in a nonlocal structure, which can be detected by another FM or HM electrode. Here, we report a new nonlocal spin injection scheme using uniform-mode ferromagnetic resonance (FMR) spin pumping in Pt/Y3Fe5O12 (YIG) lateral structures. This scheme is enabled by well-separated resonant fields of Pt/YIG and bare YIG due to substantial change of anisotropy in YIG films induced by a Pt overlayer, allowing for clearly distinguishable local and nonlocal spin pumping. Our results show that the spin decay length of nonlocal uniform-mode spin pumping in 20 nm YIG films is 2.1 µm at room temperature.

Interfacial Rashba-Effect-Induced Anisotropy in Nonmagnetic-Material-Ferrimagnetic-Insulator Bilayers.

Interfacial magnetic anisotropy in magnetic insulators has been largely unexplored. Recently, interface-induced skyrmions and electrical control of magnetization have been discovered in insulator-based heterostructures, which demand a thorough understanding of interfacial interactions in these materials. We observe a substantial, tunable interfacial magnetic anisotropy between Tm_{3}Fe_{5}O_{12} epitaxial thin films and fifteen nonmagnetic materials spanning a significant portion of the periodic table, which we attribute to Rashba spin-orbit coupling. Our results show a clear distinction between nonmagnetic capping layers from the d block and the p block. This work offers a new path for controlling magnetic phases in magnetic insulators for low-loss spintronic applications.

Fundamental Spin Interactions Underlying the Magnetic Anisotropy in the Kitaev Ferromagnet CrI_{3}.

We lay the foundation for determining the microscopic spin interactions in two-dimensional (2D) ferromagnets by combining angle-dependent ferromagnetic resonance (FMR) experiments on high quality CrI_{3} single crystals with theoretical modeling based on symmetries. We discover that the Kitaev interaction is the strongest in this material with K∼-5.2 meV, 25 times larger than the Heisenberg exchange J∼-0.2 meV, and responsible for opening the ∼5 meV gap at the Dirac points in the spin-wave dispersion. Furthermore, we find that the symmetric off-diagonal anisotropy Γ∼-67.5 µeV, though small, is crucial for opening a ∼0.3 meV gap in the magnon spectrum at the zone center and stabilizing ferromagnetism in the 2D limit. The high resolution of the FMR data further reveals a µeV-scale quadrupolar contribution to the S=3/2 magnetism. Our identification of the underlying exchange anisotropies opens paths toward 2D ferromagnets with higher T_{C} as well as magnetically frustrated quantum spin liquids based on Kitaev physics.

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib.

BACKGROUND: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER: NCT02184195.

Spin-Hall Topological Hall Effect in Highly Tunable Pt/Ferrimagnetic-Insulator Bilayers.

Electrical detection of topological magnetic textures such as skyrmions is currently limited to conducting materials. Although magnetic insulators offer key advantages for skyrmion technologies with high speed and low loss, they have not yet been explored electrically. Here, we report a prominent topological Hall effect in Pt/Tm3Fe5O12 bilayers, where the pristine Tm3Fe5O12 epitaxial films down to 1.25 unit cell thickness allow for tuning of topological Hall stability over a broad range from 200 to 465 K through atomic-scale thickness control. Although Tm3Fe5O12 is insulating, we demonstrate the detection of topological magnetic textures through a novel phenomenon: "spin-Hall topological Hall effect" (SH-THE), where the interfacial spin-orbit torques allow spin-Hall-effect generated spins in Pt to experience the unique topology of the underlying skyrmions in Tm3Fe5O12. This novel electrical detection phenomenon paves a new path for utilizing a large family of magnetic insulators in future skyrmion technologies.

Prognostic factors in patients treated with second-line chemotherapy for advanced gastric cancer: results from the randomized prospective phase III FFCD-0307 trial.

AIM: The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2. METHODS: In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model. RESULTS: Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0-1: 90.4% versus 79.7%; p = 0.0002), more frequent GEJ localization (40.8% versus 27.6%; p = 0.005), and lower platelet count (median: 298000 versus 335000/mm3; p = 0.02). In multivariate analyses, age < 60 years at diagnosis (HR 1.49, 95% CI 1.09-2.03, p = 0.013) and ECOG score 2 before L2 (HR 2.62, 95% CI 1.41-4.84, p = 0.005) were the only significant poor prognostic factors for OS. CONCLUSION: Age ≥ 60 years at diagnosis and ECOG score 0/1 before L2 were the only favorable prognostic factors for OS.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

Sporadic pancreatic neuroendocrine tumor: Surgery of the primary tumor.

The management of patients with sporadic pancreatic neuroendocrine tumors (PNET) is multi-disciplinary and often, multimodal. Surgery has a large part in treatment because it is the only potentially curative therapeutic modality if resection can be complete. The update reviews the operative indications and the different surgical techniques available (including parenchymal-sparing surgery) to treat the primary lesion according to patient status, preoperative work-up and whether the tumor is functioning or not. The place of observation for "small" non-functional sporadic PNET is also discussed.

Voltage-driven, local, and efficient excitation of nitrogen-vacancy centers in diamond.

Magnetic sensing technology has found widespread application in a diverse set of industries including transportation, medicine, and resource exploration. These uses often require highly sensitive instruments to measure the extremely small magnetic fields involved, relying on difficult-to-integrate superconducting quantum interference devices and spin-exchange relaxation-free magnetometers. A potential alternative, nitrogen-vacancy (NV) centers in diamond, has shown great potential as a high-sensitivity and high-resolution magnetic sensor capable of operating in an unshielded, room-temperature environment. Transitioning NV center-based sensors into practical devices, however, is impeded by the need for high-power radio frequency (RF) excitation to manipulate them. We report an advance that combines two different physical phenomena to enable a highly efficient excitation of the NV centers: magnetoelastic drive of ferromagnetic resonance and NV-magnon coupling. Our work demonstrates a new pathway that combine acoustics and magnonics that enables highly energy-efficient and local excitation of NV centers without the need for any external RF excitation and, thus, could lead to completely integrated, on-chip, atomic sensors.

[Role of radiation therapy in the management of pancreatic cancer]. / Quelle place pour la radiothérapie dans la prise en charge des cancers du pancréas localisés ?

At diagnosis, about 15% of patients with pancreatic cancer present with a resectable tumour, 50% have a metastatic tumour, and 25% a locally advanced tumor (non-metastatic but unresectable due to vascular invasion) or borderline resectable. Despite the technical progress made in the field of radiation therapy and the improvement of the efficacy of chemotherapy, the prognosis of these patients remains very poor. Recently, the role of radiation therapy in the management of pancreatic cancer has been much debated. This review aims to evaluate the role of radiation therapy for these patients.

Preoperative imaging and pathologic classification for pancreatic neuroendocrine tumors.

The management of patients with pancreatic neuroendocrine tumor (PNET), whether hormonally secretory or not, is multidisciplinary and often multimodal. Surgical treatment plays a central role because complete resection is the only potentially curative treatment. The choice of the therapeutic plan for a PNET requires precise localization of the primary tumor (which may sometimes be multiple in case of genetic predisposition), confirmation of the diagnosis of PNET, a search for metastases (mainly hepatic), and identification of the main histoprognostic factors. This update focuses on the WHO 2017 histological classification and recent innovations in the preoperative assessment of PNET using conventional and isotopic imaging. The aim is to not only allow the mapping of primary and metastatic lesions but also to predict tumor aggressiveness.

Metallic ferromagnetic films with magnetic damping under 1.4 × 10-3.

Low-damping magnetic materials have been widely used in microwave and spintronic applications because of their low energy loss and high sensitivity. While the Gilbert damping constant can reach 10-4 to 10-5 in some insulating ferromagnets, metallic ferromagnets generally have larger damping due to magnon scattering by conduction electrons. Meanwhile, low-damping metallic ferromagnets are desired for charge-based spintronic devices. Here, we report the growth of Co25Fe75 epitaxial films with excellent crystalline quality evident by the clear Laue oscillations and exceptionally narrow rocking curve in the X-ray diffraction scans as well as from scanning transmission electron microscopy. Remarkably, the Co25Fe75 epitaxial films exhibit a damping constant <1.4 × 10-3, which is comparable to the values for some high-quality Y3Fe5O12 films. This record low damping for metallic ferromagnets offers new opportunities for charge-based applications such as spin-transfer-torque-induced switching and magnetic oscillations.Owing to their conductivity, low-damping metallic ferromagnets are preferred to insulating ferromagnets in charge-based spintronic devices, but are not yet well developed. Here the authors achieve low magnetic damping in CoFe epitaxial films which is comparable to conventional insulating ferromagnetic YIG films.

Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study.

BACKGROUND: In a phase III trial in patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumors, sunitinib 37.5 mg/day improved investigator-assessed progression-free survival (PFS) versus placebo (11.4 versus 5.5 months; HR, 0.42; P < 0.001). Here, we present PFS using retrospective blinded independent central review (BICR) and final median overall survival (OS), including an assessment highlighting the impact of patient crossover from placebo to sunitinib. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled study, cross-sectional imaging from patients was evaluated retrospectively by blinded third-party radiologists using a two-reader, two-time-point lock, followed by a sequential locked-read, batch-mode paradigm. OS was summarized using the Kaplan-Meier method and Cox proportional hazards model. Crossover-adjusted OS effect was derived using rank-preserving structural failure time (RPSFT) analyses. RESULTS: Of 171 randomized patients (sunitinib, n = 86; placebo, n = 85), 160 (94%) had complete scan sets/time points. By BICR, median (95% confidence interval [CI]) PFS was 12.6 (11.1-20.6) months for sunitinib and 5.8 (3.8-7.2) months for placebo (HR, 0.32; 95% CI 0.18-0.55; P = 0.000015). Five years after study closure, median (95% CI) OS was 38.6 (25.6-56.4) months for sunitinib and 29.1 (16.4-36.8) months for placebo (HR, 0.73; 95% CI 0.50-1.06; P = 0.094), with 69% of placebo patients having crossed over to sunitinib. RPSFT analysis confirmed an OS benefit for sunitinib. CONCLUSIONS: BICR confirmed the doubling of PFS with sunitinib compared with placebo. Although the observed median OS improved by nearly 10 months, the effect estimate did not reach statistical significance, potentially due to crossover from placebo to sunitinib. TRIAL REGISTRATION NUMBER: NCT00428597.