MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies

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Persistent modification of forebrain networks and metabolism in rats following adolescent exposure to a 5-HT7 receptor agonist

RATIONALE: The serotonin 7 receptor (5-HT7-R) is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive or sleep regulation. OBJECTIVES: We investigated long-term consequences of sub-chronic treatment, during adolescence (43-45 to 47-49 days old) in rats, with a novel 5-HT7-R agonist (LP-211, 0 or 0.250 mg/kg/day). METHODS: We evaluated behavioural changes as well as forebrain structural/functional modifications by in vivo magnetic resonance (MR) in a 4.7 T system, followed by ex vivo histology. RESULTS: Adult rats pre-treated during adolescence showed reduced anxiety-related behaviour, in terms of reduced avoidance in the light/dark test and a less fragmented pattern of exploration in the novel object recognition test. Diffusion tensor imaging (DTI) revealed decreased mean diffusivity (MD) in the amygdala, increased fractional anisotropy (FA) in the hippocampus (Hip) and reduced axial (D||) together with increased radial (D⊥) diffusivity in the nucleus accumbens (NAcc). An increased neural dendritic arborization was confirmed in the NAcc by ex vivo histology. Seed-based functional MR imaging (fMRI) identified increased strength of connectivity within and between "limbic" and "cortical" loops, with affected cross-correlations between amygdala, NAcc and Hip. The latter displayed enhanced connections through the dorsal striatum (dStr) to dorso-lateral prefrontal cortex (dl-PFC) and cerebellum. Functional connection also increased between amygdala and limbic elements such as NAcc, orbito-frontal cortex (OFC) and hypothalamus. MR spectroscopy (1H-MRS) indicated that adolescent LP-211 exposure increased glutamate and total creatine in the adult Hip. CONCLUSIONS: Persistent MR-detectable modifications indicate a rearrangement within forebrain networks, accounting for long-lasting behavioural changes as a function of developmental 5-HT7-R stimulatio

Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions

Mapping of the longitudinal relaxation time (T1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson- Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field. Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions. Available from: https://www.researchgate.net/publication/317548806_Towards_accurate_and_precise_T1_and_extracellular_volume_mapping_in_the_myocardium_a_guide_to_current_pitfalls_and_their_solutions [accessed Jun 13, 2017]

Outcomes after intensive chemotherapy for secondary and myeloid-related changes acute myeloid leukemia patients aged 60 to 75 years old: a retrospective analysis from the PETHEMA registry

© 2024 Ferrata Storti Foundation Published under a CC BY-NC license.Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval [CI]: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.This study was partially supported by the Jazz Pharmaceuticals and Cooperative Research Thematic Network (RTICC) grant RD12/0036/014 (ISCIII & ERDF).Peer reviewe

Outcomes after intensive chemotherapy for secondary and myeloid-related changes acute myeloid leukemia patients aged 60 to 75 years old: a retrospective analysis from the PETHEMA registry

Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval [CI]: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351

Pixel-based parametric source depth map for Cerenkov luminescence imaging

Optical tomography represents a challenging problem in optical imaging because of the intrinsically ill-posed inverse problem due to photon diffusion. Cerenkov luminescence tomography (CLT) for optical photons produced in tissues by several radionuclides (i.e.: 32P, 18F, 90Y), has been investigated using both 3D multispectral approach and multiviews methods. Difficult in convergence of 3D algorithms can discourage to use this technique to have information of depth and intensity of source. For these reasons, we developed a faster 2D corrected approach based on multispectral acquisitions, to obtain source depth and its intensity using a pixel-based fitting of source intensity. Monte Carlo simulations and experimental data were used to develop and validate the method to obtain the parametric map of source depth. With this approach we obtain parametric source depth maps with a precision between 3% and 7% for MC simulation and 5\u20136% for experimental data. Using this method we are able to obtain reliable information about the source depth of Cerenkov luminescence with a simple and flexible procedure

Monte Carlo feasibility study for image guided surgery: from direct beta minus detection to Cerenkov luminescence imaging

The goal of this work is to compare the performances of different beta minus detection strategies for image guided surgery or ex vivo tissue analysis. In particular we investigated Cerenkov luminescence imaging (CLI) with and without the use of a radiator, direct and indirect beta detection and bremsstrahlung imaging using beta emitters commonly employed in Nuclear Medicine. Monte Carlo simulations were implemented using the GAMOS plug-in for GEANT4 considering a slab of muscle and a radioactive source (32P or 90Y) placed at 0.5 mm depth. We estimated the gain that can be obtained in terms of produced photons using different materials placed on the slab used as Cerenkov radiators, we then focused on the number of exiting photons and their spatial distribution for the different strategies. The use of radiator to enhance Cerenkov signal reduces the spatial resolution because of the increased optical spread. We found that direct beta detection and CLI are best approaches in term of resolution while the use of a thin scintillator increases the signal but the spatial resolution is degraded. Bremsstrahlung presents lower signal and it does not represent the best choice for image guided surgery. CLI represents a more flexible approach for image guided surgery using or ex vivo tissue analysis using beta-emitter imaging

Dosimetric and radiation cancer risk evaluation of high resolution thorax CT during COVID-19 outbreak

Purpose: The aim of this work was to evaluate the dosimetric impact of high-resolution thorax CT during COVID-19 outbreak in the University Hospital of Parma. In two months we have performed a huge number of thorax CT scans collecting effective and equivalent organ doses and evaluating also the lifetime attributable risk (LAR) of lung and other major cancers. Materials and Method: From February 24th to April 28th, 3224 high-resolution thorax CT were acquired. For all patients we have examined the volumetric computed tomography dose index (CTDIvol), the dose length product (DLP), the size-specific dose estimate (SSDE) and effective dose (E103) using a dose tracking software (Radimetrics Bayer HealthCare). From the equivalent dose to organs for each patient, LAR for lung and major cancers were estimated following the method proposed in BEIR VII which considers age and sex differences. Results: Study population included 3224 patients, 1843 male and 1381 female, with an average age of 67 years. The average CTDIvol, SSDE and DLP, and E103 were 6.8 mGy, 8.7 mGy, 239 mGy·cm and 4.4 mSv respectively. The average LAR of all solid cancers was 2.1 cases per 10,000 patients, while the average LAR of leukemia was 0.2 cases per 10,000 patients. For both male and female the organ with a major cancer risk was lung. Conclusions: Despite the impressive increment in thoracic CT examinations due to COVID-19 outbreak, the high resolution low dose protocol used in our hospital guaranteed low doses and very low risk estimation in terms of LAR