Monte Carlo and experimental evaluation of a Timepix4 compact gamma camera for coded aperture nuclear medicine imaging with depth resolution

Purpose: We designed a prototype compact gamma camera (MediPROBE4) for nuclear medicine tasks, including radio-guided surgery and sentinel lymph node imaging with a 99mTc radiotracer. We performed Monte Carlo (MC) simulations for image performance assessment, and first spectroscopic imaging tests with a 300 μm thick silicon detector. Methods: The hand-held camera (1 kg weight) is based on a Timepix4 readout circuit for photon-counting, energy-sensitive, hybrid pixel detectors (24.6 × 28.2 mm2 sensitive area, 55 μm pixel pitch), developed by the Medipix4 Collaboration. The camera design adopts a CdTe detector (1 or 2 mm thick) bump-bonded to a Timepix4 readout chip and a coded aperture collimator with 0.25 mm diameter round holes made of 3D printed 1-mm thick tungsten. Image reconstruction is performed via autocorrelation deconvolution. Results: Geant4 MC simulations showed that, for a 99mTc source in air, at 50 mm source-collimator distance, the estimated collimator sensitivity (4 × 10-4) is 292 times larger than that of a single hole in the mask; the system sensitivity is 0.22 cps/kBq (2 mm CdTe); the lateral spatial resolution is 1.7 mm FWHM. The estimated axial longitudinal resolution is 8.2 mm FWHM at 40 mm distance. First experimental tests with a 300 μm thick Silicon pixel detector bump-bonded to a Timepix4 chip and a high-resolution coded aperture collimator showed time-over-threshold and time-of-arrival capabilities with 241Am and 133Ba gamma-ray sources. Conclusions: MC simulations and validation lab tests showed the expected performance of the MediPROBE4 compact gamma camera for gamma-ray 3D imaging

Effective Neutralizing Antibody Response Against SARS-CoV-2 Virus and Its Omicron BA.1 Variant in Fully Vaccinated Hematological Patients

SARS-CoV-2 and its variants cause CoronaVIrus Disease 19 (COVID-19), a pandemic disease. Hematological malignancies increase susceptibility to severe COVID-19 due to immunosuppression. Anti-SARS-CoV-2 neutralizing antibodies protect against severe COVID-19. This retrospective real-life study aimed to evaluate seropositivity and neutralizing antibody rates against SARS-CoV-2 and its Omicron BA.1 variant in hematological patients. A total of 106 patients with different hematologic malignancies, who have mostly received three or more vaccine doses (73%), were included in this study. Serum was collected between May and June 2022. The primary endpoint was anti-SARS-CoV-2 antibody response against ancestral (wild type; wt) and Omicron BA.1 virus, defined as a neutralizing antibody titer ≥ 1:10. Adequate neutralizing antibody response was observed in 75 (71%) and 87 (82%) of patients for wt and Omicron BA.1 variants, respectively.However, patients with B-cell lymphoproliferative disorders and/or those treated with anti-CD20 monoclonal antibodies in the prior 12 months showed a lower seropositivity rate compared to other patients against both Omicron BA.1 variant (73% vs 91%; P = 0.02) and wt virus (64% vs 78%; P = 0.16). Our real-life experience confirmed that full vaccination against SARS-CoV-2 induces adequate neutralizing antibody protection for both the wt virus and Omicron BA.1 variants, even in hematological frail patients. However, protective measures should be maintained in hematological patients, especially those with B-cell lymphoproliferative diseases treated with anti-CD20 monoclonal antibodies, because these subjects could have a reduced neutralizing antibody production

BriXs ultra high fluxinverse compton source based on modified push-pull energy recovery linacs

We present a conceptual design for a compact X-ray Source BriXS (Bright and compact X-ray Source). BriXS, the first stage of the Marix project, is an Inverse Compton Source (ICS) of X-ray based on superconducting cavities technology for the electron beam with energy recirculation and on a laser system in Fabry-Pérot cavity at a repetition rate of 100 MHz, producing 20–180 keV monochromatic X-Rays devoted mainly to medical applications. An energy recovery scheme based on a modified folded push-pull CW-SC twin Energy Recovery Linac (ERL) ensemble allows us to sustain an MW-class beam power with almost one hundred kW active power dissipation/consumption

Prophylactic letermovir decreases cytomegalovirus reactivation after stem cell transplantation: a single-center real-world evidence study

Cytomegalovirus (CMV) reactivation is a major cause of morbidity and mortality after organ or hematopoietic stem cell transplantation (HSCT). Letermovir (LTV) is a novel antiviral agent approved for CMV prophylaxis after allogeneic transplantation. In this single-center real-world study, we evidenced the efficacy and safety of LTV for CMV prophylaxis in allogeneic HSCT recipients. A total of 133 consecutive patients who underwent autologous or allogeneic HSCT were included in the study, and a subgroup of 13 allogeneic HSCT recipients received CMV prophylaxis with LTV 240 mg/daily from day +7 to +100 (allo-LTV cohort). All patients in the allo-LTV cohort were at moderate or high risk of reactivation based on donor/recipient serology status, and 62% also received haploidentical HSCT and cyclophosphamide which further increased the CMV reactivation risk. CMV infection rate was also compared to that observed in allogeneic HSCT patients without CMV prophylaxis and autologous recipients who have the lowest reported CMV infection incidence and were used as a control cohort. In our experience, patients receiving LTV showed a significant decline in CMV reactivation incidence to similar rates described in autologous HSCT recipients (7.7% of allogeneic LTV-treated vs 68% of allogeneic recipients without prophylaxis vs 15% of autologous patients; p> 0.0001). The only patient in the allo-LTV cohort with CMV reactivation was a 25-year-old female with a diagnosis of very high-risk acute lymphoblastic leukemia who received a haploidentical HSCT after ex vivo T cell depletion. CMV reactivation occurred beyond LTV course, at +187 days from transplantation. In addition, we confirmed efficacy and safety of valganciclovir 450 mg/daily as pre-emptive therapy or for treatment of CMV disease in allogeneic and autologous HSCT recipients who experienced CMV reactivation even after LTV prophylaxis. However, further clinical trials in larger populations and longer follow-up are required to confirm our preliminary results

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

The serum free light-chain (FLC) ratio is a sensitive tool for the differential diagnosis of plasma cell disorders and is biomarker of multiple myeloma (MM) progression from premalignant conditions. Here, we investigate the potential role of FLC ratio at diagnosis in identifying early renal damage in MM patients and other correlations with clinical, laboratory, and molecular findings. A total of 34 MM patients who had undergone autologous stem cell transplantation were included in this retrospective case series study, and FLC quantification was performed with nephelometric assays. In our study, sFLC ratio was significantly associated with light-chain MM and β-2 microglobulin levels, likely indicating a high disease burden at diagnosis, especially in patients without heavy chain M-protein at serum electrophoresis. Moreover, the sFLC ratio was inversely correlated with glomerular filtration rate, possibly identifying early renal damage in MM patients. Our preliminary results confirm the importance of early sFLC evaluation, especially in patients with the light-chain MM type and low disease burden, to minimize the risk of late renal failure

The MariX source (Multidisciplinary Advanced Research Infrastructure with X-rays)

MariX (Multidisciplinary advanced research infra-structure with X-rays) is a joint project of INFN and University of Milan, aiming at developing a twin X-ray Source of advanced characteristics for the future Sci-entific Campus of the University of Milan. Presently in its design study phase, it will be built in the post Expo area located in north-west Milan district. The first component of the X-source MariX is BriXS (Bright and compact X-ray Source), a Compton X-ray source based on superconducting cavities technology for the electron beam with energy recirculation and on a laser system in Fabry-Pérot cavity at a repetition rate of 100 MHz, producing 20-180 keV radiation for medical applications. The BriXS accelerator is also serving as injector of a 3.8 GeV superconductive linac, driving a X-ray FEL at 1 MHz, for providing coherent, moderate flux radiation at 0.3-10 KeV at 1 MHz. Scientific case, layout and typical parameters of MariX will be discussed

BriXs Ultra High Flux Inverse Compton Source Based on Modified Push-Pull Energy Recovery Linacs

We present a conceptual design for a compact X-ray Source BriXS (Bright and compact X-ray Source). BriXS, the first stage of the Marix project, is an Inverse Compton Source (ICS) of X-ray based on superconducting cavities technology for the electron beam with energy recirculation and on a laser system in Fabry-Pérot cavity at a repetition rate of 100 MHz, producing 20–180 keV monochromatic X-Rays devoted mainly to medical applications. An energy recovery scheme based on a modified folded push-pull CW-SC twin Energy Recovery Linac (ERL) ensemble allows us to sustain an MW-class beam power with almost one hundred kW active power dissipation/consumption