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Bontempi, L.

Publications and source records attributed to Bontempi, L..

2 recordsLinked to original sources

Aortic annuloplasty FSI digital twin of 3D-printed phantoms with 4D-flow MRI comparison

BackgroundAortic annuloplasty, involving the implantation of an external ring around the aortic root to reduce annular dimensions, is a promising treatment for aortic valve insufficiency. However, its hemodynamic effects remain underexplored due to the absence of computational models validated by experimental and clinical data. MethodsThis study introduces a computational fluid-structure interaction (FSI) model of supra valvular aortic annuloplasty using 4D-flow magnetic resonance imaging (MRI). Native and post-annuloplasty conditions of idealized aortic root phantoms, including the aortic valve, were CAD-modelled and 3D-printed with elastic resin. These phantoms were tested in a mock circulatory flow-loop providing normal pulsatile physiologic conditions using a glycerol-water mixture to simulate blood viscosity. Flow and pressure data collected from sensors were used as boundary conditions for FSI simulations. Experimental velocity fields from 4D-flow MRI were compared to computational results to assess model accuracy. ResultsMRI scans of the annuloplasty model showed an increased peak systolic velocity (up to 145.4 cm/s) and localized flow alterations, corresponding to a higher pressure gradient across the valve. During regurgitation, the annuloplasty model showed broader velocity distributions compared to the native condition. The FSI simulations closely matched 4D-flow MRI data, with strong correlation coefficients (r > 0.93) and minimal Bland-Altman differences, particularly during systolic phases. ConclusionsThis study establishes an integrative methodology combining in-vitro, in-silico, and clinical imaging techniques to evaluate aortic annuloplasty hemodynamics. The validated digital twin framework offers a pathway for patient-specific modelling, enabling prediction of surgical outcomes and optimization of aortic valve repair strategies.

bioengineering↗

Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

Ketamines role in providing a rapid and sustained antidepressant response, particularly for patients unresponsive to conventional treatments, is increasingly recognized. A core symptom of depression, anhedonia, or the loss of enjoyment or interest in previously pleasurable activities, is known to be significantly alleviated by ketamine. While several hypotheses have been proposed regarding the mechanisms by which ketamine alleviates anhedonia, the specific circuits and synaptic changes responsible for its sustained therapeutic effects are not yet understood. Here, we show that the nucleus accumbens (NAc), a major hub of the reward circuitry, is essential for ketamines effect in rescuing anhedonia in mice subjected to chronic stress, a critical risk factor in the genesis of depression in humans. Specifically, a single exposure to ketamine rescues stress-induced decreased strength of excitatory synapses on NAc D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs). By using a novel cell-specific pharmacology method, we demonstrate that this cell-type specific neuroadaptation is necessary for the sustained therapeutic effects of ketamine. To test for causal sufficiency, we artificially mimicked ketamine-induced increase in excitatory strength on D1-MSNs and found that this recapitulates the behavioral amelioration induced by ketamine. Finally, to determine the presynaptic origin of the relevant glutamatergic inputs for ketamine-elicited synaptic and behavioral effects, we used a combination of opto- and chemogenetics. We found that ketamine rescues stress-induced reduction in excitatory strength at medial prefrontal cortex and ventral hippocampus inputs to NAc D1-MSNs. Chemogenetically preventing ketamine-evoked plasticity at those unique inputs to the NAc reveals a ketamine-operated input-specific control of hedonic behavior. These results establish that ketamine rescues stress-induced anhedonia via cell-type-specific adaptations as well as information integration in the NAc via discrete excitatory synapses.

neuroscience↗