Neuroscienze e lettura

La cosiddetta neurolettura, ossia l'indagine dell'attività del leggere alla luce delle neuroscienze, può dirsi iniziata già alla fine dell'Ottocento, tuttavia solo in tempi recenti si sono compiute importanti scoperte grazie alle tecniche di neuroimaging. Esaminando alcune ricerche neuroscientifiche, da una parte emerge con forza l'estrema complessità dell'atto del leggere, che dal punto di vista filogenetico parrebbe il frutto di una sorta di riciclaggio neuronale (il nostro cervello non è fatto per la lettura, ma in un modo o nell'altro vi si riconverte grazie alla sua innata plasticità); dall'altra si delinea un'universalità delle basi cerebrali della lettura per cui, qualunque sia la lingua in cui si legge, una sola e medesima area cerebrale viene coinvolta, la regione occipito-temporale sinistra. Tale universalità non pare essere messa in discussione neppure dalla rivoluzione digitale in atto: se è vero che la lettura digitale apre nuove prospettive e nuove frontiere, offrendo vantaggi soprattutto in sede di apprendimento, essa non pare al momento avere una significativa incidenza sui meccanismi cerebrali sottesi alla prima fase del leggere (quella della decodifica), mentre potrebbe avere delle ricadute maggiori sui due momenti successivi, la comprensione di un testo e la nostra risposta ad esso, per quanto in quest'ambito le ricerche siano solo all'inizio

Effect of image registration on 3D absorbed dose calculations in 177 Lu-DOTATOC Peptide Receptor Radionuclide Therapy

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with 177Lu or 90Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation. A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of 177Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code. The similarity analysis demonstrated the superiority of the deformable registrations (p < .001). Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [−19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [−67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL. Image based 3D dosimetry for 177Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans

Labelling of

In spite of the hazard due to the radiation exposure, preparation of 90Y- and 177Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177Lu- and 90Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617) was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90Y- and 177Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90Y-DOTATOC were 96.2±4.9%, 90.3±5.6%, and 82.0±8.4%, while for 177Lu-DOTATOC they were 98.3%  ± 0.6, 90.8%  ± 8.3, and 83.1±5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15±0.4 mSv/GBq, 0.04±0.1 mSv/GBq, and 0.11±0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02±0.008 mSv/GBq, 0.01±0.03 mSv/GBq, and 0.01±0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system

Effetti della lettura sulle abilità sociali e l’identità

The acquisition of reading skills is a key step in the learning process. Nonetheless the role of reading does not end in school age but recurs throughout life, stimulating creativity, intellectual processes and social skills. Why this close correlation between ficition and social abilities? The simulation of social experiences required by the reading of fiction engages the same socio-cognitive processes put in place during comprehension in the real world; such simulation would lead to the refinement of social and empathic processes, which in turn could be applied outside the storywold (Social-Improvement Hypothesis). Another possibility is that the reader of fiction acquires a greater knowledge about the mind – his own as that of others – by gaining access to a better understanding of himself (Self-Improvement Hypothesis). Therefore from an educational point of view the use of reading and narrative methodologies is fundamental, which activate interpretative and reflective processes capable of developing not only expressiveness and communicative empowerment but also socio-cognitive skills connected to empathy. and the theory of mind.L’acquisizione dell’abilità di lettura è una tappa fondamentale nel processo di apprendimento. Nondimeno, il ruolo della lettura non si esaurisce in età scolare, ma si ripropone durante tutta la vita, stimolando la creatività, i processi intellettivi e le competenze sociali. In particolare, è provato che i lettori di testi narrativi tendono ad avere migliori abilità di risonanza empatica e di teoria della mente. Quali sono le cause di questa forte correlazione tra fiction e abilità sociali? La simulazione di esperienze sociali richiesta dalla lettura di opere narrative impegna i medesimi processi socio-cognitivi messi in atto durante la comprensione nel mondo reale; tale simulazione porterebbe all’affinamento di processi sociali ed empatici, che a loro volta potrebbero essere applicati a contesti esterni alla lettura (Social-Improvement Hypothesis). Un’altra possibilità è quella che il lettore di fiction acquisisca una maggior conoscenza in merito alla psiche umana, propria e altrui, accedendo a una miglior comprensione di sé (Self-Improvement Hypothesis). Dunque, da un punto di vista educativo appare fondamentale l’uso della lettura e di metodologie narrative, le quali attivino processi interpretativi e riflessivi in grado di sviluppare non solo espressività ed empowerment comunicativo, ma anche abilità socio-cognitive connesse all’empatia e alla teoria della mente

Skin dose saving of the staff in 90Y/177Lu peptide receptor radionuclide therapy with the automatic dose dispenser

OBJECTIVE: When handling Y-labelled and Lu-labelled radiopharmaceuticals, skin exposure is mainly due to β-particles. This study aimed to investigate the equivalent dose saving of the staff when changing from an essentially manual radiolabelling procedure to an automatic dose dispenser (ADD). MATERIALS AND METHODS: The chemist and physician were asked to wear thermoluminescence dosimeters on their fingertips to evaluate the quantity of Hp(0.07) on the skin. Data collected were divided into two groups: before introducing ADD (no ADD) and after introducing ADD. RESULTS: For the chemist, the mean values (95th percentile) of Hp(0.07) for no ADD and ADD are 0.030 (0.099) and 0.019 (0.076) mSv/GBq, respectively, for Y, and 0.022 (0.037) and 0.007 (0.023) mSv/GBq, respectively, for Lu. The reduction for ADD was significant (t-test with P<0.05) for both isotopes. The relative differences before and after ADD collected for every finger were treated using the Wilcoxon test, proving a significantly higher reduction in extremity dose to each fingertip for Lu than for Y (P<0.05). For the medical staff, the mean values of Hp(0.07) (95th percentile) for no ADD and ADD are 0.021 (0.0762) and 0.0143 (0.0565) mSv/GBq, respectively, for Y, and 0.0011 (0.00196) and 0.0009 (0.00263) mSv/GBq, respectively, for Lu. The t-test provided a P-value less than 0.05 for both isotopes, making the difference between ADD and no ADD significant. CONCLUSION: ADD positively affects the dose saving of the chemist in handling both isotopes. For the medical staff not directly involved with the introduction of the ADD system, the analysis shows a learning curve of the workers over a 5-year period. Specific devices and procedures allow staff skin dose to be limited

Comparison of different calculation techniques for absorbed dose assessment in patient specific peptide receptor radionuclide therapy.

AimThe present work concerns the comparison of the performances of three systems for dosimetry in RPT that use different techniques for absorbed dose calculation (organ-level dosimetry, voxel-level dose kernel convolution and Monte Carlo simulations). The aim was to assess the importance of the choice of the most adequate calculation modality, providing recommendations about the choice of the computation tool.MethodsThe performances were evaluated both on phantoms and patients in a multi-level approach. Different phantoms filled with a 177Lu-radioactive solution were used: a homogeneous cylindrical phantom, a phantom with organ-shaped inserts and two cylindrical phantoms with inserts different for shape and volume. A total of 70 patients with NETs treated by PRRT with 177Lu-DOTATOC were retrospectively analysed.ResultsThe comparisons were performed mainly between the mean values of the absorbed dose in the regions of interest. A general better agreement was obtained between Dose kernel convolution and Monte Carlo simulations results rather than between either of these two and organ-level dosimetry, both for phantoms and patients. Phantoms measurements also showed the discrepancies mainly depend on the geometry of the inserts (e.g. shape and volume). For patients, differences were more pronounced than phantoms and higher inter/intra patient variability was observed.ConclusionThis study suggests that voxel-level techniques for dosimetry calculation are potentially more accurate and personalized than organ-level methods. In particular, a voxel-convolution method provides good results in a short time of calculation, while Monte Carlo based computation should be conducted with very fast calculation systems for a possible use in clinics, despite its intrinsic higher accuracy. Attention to the calculation modality is recommended in case of clinical regions of interest with irregular shape and far from spherical geometry, in which Monte Carlo seems to be more accurate than voxel-convolution methods

Partial volume effect of SPECT images in PRRT with 177Lu labelled somatostatin analogues: A practical solution

Background At present activity quantification is one of the most critical step in dosimetry calculation, and Partial Volume Effect (PVE) one of the most important source of error. In recent years models based upon phantoms that incorporate hot spheres have been used to establish recovery models. In this context the goal of this study was to point out the most critical issues related to PVE and to establish a model closer to a biological imaging environment. Methods Two different phantoms, filled with a 177Lu solution, were used to obtain the PVE Recovery Coefficients (RCs): a phantom with spherical inserts and a phantom with organ-shaped inserts. Two additional phantoms with inserts of various geometrical shapes and an anthropomorphic phantom were acquired to compare the real activities to predicted values after PVE correction. Results The RCs versus volume of the inserts produced two different curves, one for the spheres and one for the organs. After PVE correction, accuracy on activity quantification averaged over all inserts of three test phantoms passed from −26% to 1.3% (from 26% to 10% for absolute values). Conclusion RCs is a simple method for PVE correction easily applicable in clinical routine. The use of two different models for organs and lesions has permitted to closely mimic the situation in a living subject. A marked improvement in the quantification of activity was observed when PVE correction was adopted, even if further investigations should be performed for more accurate models of PVE corrections

Predictive and Prognostic Role of Pre-Therapy and Interim 68Ga-DOTATOC PET/CT Parameters in Metastatic Advanced Neuroendocrine Tumor Patients Treated with PRRT

Peptide receptor radionuclide therapy (PRRT) is an effective therapeutic option in patients with metastatic neuroendocrine tumor (NET). However, PRRT fails in about 15&ndash;30% of cases. Identification of biomarkers predicting the response to PRRT is essential for treatment tailoring. We aimed to evaluate the predictive and prognostic role of semiquantitative and volumetric parameters obtained from the 68Ga-DOTATOC PET/CT before therapy (bPET) and after two cycles of PRRT (iPET). A total of 46 patients were included in this retrospective analysis. The primary tumor was 78% gastroenteropancreatic (GEP), 13% broncho-pulmonary and 9% of unknown origin. 35 patients (76.1%) with stable disease or partial response after PRRT were classified as responders and 11 (23.9%) as non-responders. Logistic regression analysis identified that baseline total volume (bTV) was associated with therapy outcome (OR 1.17; 95%CI 1.02&ndash;1.32; p = 0.02). No significant association with PRRT response was observed for other variables. High bTV was confirmed as the only variable independently associated with OS (HR 12.76, 95%CI 1.53&ndash;107, p = 0.01). In conclusion, high bTV is a negative predictor for PRRT response and is associated with worse OS rates. Early iPET during PRRT apparently does not provide information useful to change the management of NET patients