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

Gliomatosis cerebri type II: two case reports

Two types of gliomatosis cerebri exist: Type I and Type II. We report the results of a histological and genetic study of two cases of gliomatosis cerebri Type II, correlating these results with therapy and prognosis. Case presentation Two patients, a 52-year-old man (Patient 1) and a 76-year-old man (Patient 2) with gliomatosis cerebri II were admitted to our institution; they underwent surgical treatment and received radiotherapy and chemotherapy. At the 24-month follow-up, Patient 1 was still alive, while Patient 2 had died. The poor prognosis of Patient 2 was underlined by molecular analysis which showed that the angiogenesis related genes VCAM1 and VEGF were overexpressed, reflecting the high degree of neovascularization. Conclusion Genes involved in drug resistance and metallothioneins were highly expressed in Patient 2 and this, associated with unmethylated O6-methylguanine methyltransferase, can explain the lack of response to chemotherapy

Untargeted and Targeted LC-MS/MS Based Metabolomics Study on In Vitro Culture of Phaeoacremonium Species

Grapevine (Vitis vinifera L.) can be affected by many different biotic agents, including tracheomycotic fungi such as Phaeomoniella chlamydospora and Phaeoacremonium minimum, which are the main causal agent of Esca and Petri diseases. Both fungi produce phytotoxic naphthalenone polyketides, namely scytalone and isosclerone, that are related to symptom development. The main objective of this study was to investigate the secondary metabolites produced by three Phaeoacremonium species and to assess their phytotoxicity by in vitro bioassay. To this aim, untargeted and targeted LC-MS/MS-based metabolomics were performed. High resolution mass spectrometer UHPLC-Orbitrap was used for the untargeted profiling and dereplication of secondary metabolites. A sensitive multi reaction monitoring (MRM) method for the absolute quantification of scytalone and isosclerone was developed on a UPLC-QTrap. Different isolates of P. italicum, P. alvesii and P. rubrigenum were grown in vitro and the culture filtrates and organic extracts were assayed for phytotoxicity. The toxic effects varied within and among fungal isolates. Isosclerone and scytalone were dereplicated by matching retention times and HRMS and MS/MS data with pure standards. The amount of scytalone and isosclerone differed within and among fungal species. To our best knowledge, this is the first study that applies an approach of LC-MS/MS-based metabolomics to investigate differences in the metabolic composition of organic extracts of Phaeoacremonium species culture filtrates

Extralymphatic Disease Is an Independent Prognostic Factor in Hodgkin Lymphoma

A retrospective study was performed of 341 cases of extralymphatic Hodgkin lymphoma (HL) to identify its characteristics and outcomes. Sites were lung in 29 patients (44%), bone in 22 (33%), and liver in 5 (18%). Extralymphatic HL is a rare occurrence (16%) associated with poor clinical outcome. Purpose: To identify the characteristics and outcomes of patients with extralymphatic Hodgkin lymphoma. Patients and Methods: We performed a retrospective single-institution study of 341 cases comprising 207 male (61%) and 134 female (39%) subjects with a median follow-up of 44 months. Results: Fifty-five patients (16%) had extralymphatic disease. The sites were lung in 29 patients (44%), bone in 22 (33%), liver in 12 (18%), and kidney in 3 (5%). In 46 patients (86%) only one organ was involved, while in 7 patients (13%) extralymphatic disease was present in 2 sites and in 2 patients (3%) in 3 sites. The extralymphatic disease group had a poorer prognosis than the lymphatic disease group. Complete remission rates in the extralymphatic and lymphatic patient subsets were 65% and 82% (P =.043), respectively. Conclusion: Extralymphatic disease in patients with Hodgkin lymphoma is a rare occurrence (16%) associated with poor clinical outcome

Cardiovascular Risk in Patients With Takayasu Arteritis Directly Correlates With Diastolic Dysfunction and Inflammatory Cell Infiltration in the Vessel Wall: A Clinical, ex vivo and in vitro Analysis

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Atherosclerosis leads to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched atherosclerotic patients (Controls). In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical changes of the vessel wall were evaluated as well. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. The degree of dysfunction appears associated with uric acid levels. A significant increase in aortic stiffness was also observed and associated with levels of peripheral T lymphocytes. CD3+ CD4+ cell infiltrates were detected in the vessel wall samples of TAK patients, whose mean percentage of Tregs was lower than Controls at T0, but increased significantly at T18. Opposite behavior was observed for Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms underlie vessel damage, including atherosclerosis, in TAK patients compared with Controls. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants