A fully automatic method for vascular tortuosity feature extraction in the supra-aortic region: unraveling possibilities in stroke treatment planning.

Vascular tortuosity of supra-aortic vessels is widely considered one of the main reasons for failure and delays in endovascular treatment of large vessel occlusion in patients with acute ischemic stroke. Characterization of tortuosity is a challenging task due to the lack of objective, robust and effective analysis tools. We present a fully automatic method for arterial segmentation, vessel labelling and tortuosity feature extraction applied to the supra-aortic region. A sample of 566 computed tomography angiography scans from acute ischemic stroke patients (aged 74.8 ± 12.9, 51.0% females) were used for training, validation and testing of a segmentation module based on a U-Net architecture (162 cases) and a vessel labelling module powered by a graph U-Net (566 cases). Successively, 30 cases were processed for testing of a tortuosity feature extraction module. Measurements obtained through automatic processing were compared to manual annotations from two observers for a thorough validation of the method. The proposed feature extraction method presented similar performance to the inter-rater variability observed in the measurement of 33 geometrical and morphological features of the arterial anatomy in the supra-aortic region. This system will contribute to the development of more complex models to advance the treatment of stroke by adding immediate automation, objectivity, repeatability and robustness to the vascular tortuosity characterization of patients.

3D dynamical ultrasonic model of pulsating vessel walls.

The aim of this work is to introduce a novel 3-D model of pulsating vessels, through which the dynamic acoustic response of arterial regions can be predicted. Blood flow is numerically simulated by considering the fluid-dynamic displacements of the scatterers (erythrocytes), while a mechanical model calculates the wall displacement due to fluid pressure. The acoustic characteristics of each region are simulated through the FIELD software. Two numerical phantoms of a carotid artery surrounded by elastic tissue have been developed to illustrate the model. One of them includes a plaque involving a 50% stenosis. B-mode and M-mode images are produced and segmented to obtain the wall displacement profile. A cylindrical holed phantom made of cryogel mimicking material has been constructed for the model validation. In pulsatile flow conditions, fluid and wall displacements have been measured by Doppler ultrasound methods and quantitatively compared to simulated M-mode images, showing a fairly good agreement.

Retinoic acid increases insulin-like growth factor-binding protein-4 expression in cultured rat hepatocytes.

Hepatic insulin-like growth factor binding protein (IGFBP) expression is controlled by diverse factors including thyroid hormone, which enhances IGFBP-4 production in hepatocytes. In the present work, we have investigated whether hepatic IGFBP-4 expression is regulated by retinoic acid (RA), which acts via nuclear receptors belonging to the steroid/thyroid hormone receptor superfamily. Primary cultures of adult rat hepatocytes were incubated with two natural stereoisomers of RA, all-trans RA and 9-cis RA (atRA and 9cRA), and with the synthetic RA receptor (RAR)-selective agonist TTNPB. IGFBP-4 mRNA abundance was measured by Northern blot and protein production was evaluated by Ligand blot on hepatocyte-conditioned culture media. Our results indicate that atRA, 9cRA, and TTNPB increase IGFBP-4 expression by cultured hepatocytes, both at the mRNA and protein level. The RARs play a definite role in this regulation, which is independent from ongoing protein synthesis but dependent on active transcription. AtRA and thyroid hormone act synergistically in increasing hepatic IGFBP-4 expression. Our data establish a role for hormonal factors such as thyronines and retinoids in regulating the hepatic IGF system directly at the IGFBP-4 level.

Poly(ADP-ribose) polymerase is affected early by thyroid state during liver regeneration in rats.

Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme involved in DNA synthesis, DNA repair, and cell replication and transformation, also plays a role in the early steps of liver regeneration induced by partial hepatectomy (PH). PARP and DNA topoisomerase I (Topo I) activities and de novo DNA synthesis were studied during liver regeneration in rats with altered thyroid state. Hepatic PARP activity, evaluated as [(32)P]NAD incorporated into isolated liver nuclei, was inhibited in hyperthyroid rats and increased in hypothyroid animals. In both euthyroid and hyperthyroid rats PARP activity was rapidly stimulated, peaking 6 h after PH. In hypothyroid animals, an early decrease in activity was found, at a minimum of 6 h after PH, followed by an early onset of DNA synthesis. An inverse relationship between PARP and Topo I activities was a shared feature among euthyroid, hypothyroid, and hyperthyroid rats. Together these data show that, in replicating hepatocytes, thyroid hormones exert a regulatory role on PARP activity, which reflects the control of a number of nuclear proteins involved in DNA metabolism.

Increased insulin-like growth factor binding protein-4 expression after partial hepatectomy in the rat.

The insulin-like growth factor (IGF) binding proteins (IGFBPs) are important regulators of cell growth produced by different tissues. The IGFBPs regulate cell growth by modulating the activity and bioavailability of IGFs. The evidence that IGFBP-1 is a liver-specific immediate-early gene highly induced after 70% partial hepatectomy (PHx) suggests a role for the IGF-IGFBP system in hepatic regeneration. In this work we analyzed the effect of PHx on the expression of IGFBP-4, which is highly produced by the liver and very abundant in rat serum. Our results show a marked increase in hepatic IGFBP-4 mRNA levels 6-12 h after PHx and no significant change in sham-operated control animals. A parallel rise in IGFBP-4 transcript abundance was observed in the kidneys of PHx rats but not in sham-operated animals. Moreover, ligand blot analysis demonstrated that serum IGFBP-4 levels began to increase 12-24 h after surgery, consistent with the rise in the corresponding mRNA. This enhancement in IGFBP-4 production after PHx could be part of a fine regulatory mechanism to modulate IGF activity during liver regeneration.