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In the last decade, Ultrafast ultrasound localisation microscopy has taken non-invasive deep vascular imaging down to the microscopic level. By imaging diluted suspensions of circulating microbubbles in the blood stream at kHz frame rate and localizing the center of their individual point spread function with a sub-resolution precision, it enabled to break the unvanquished trade-off between depth of imaging and resolution by microscopically mapping the microbubbles flux and velocities deep into tissue. However, ULM also suffers limitations. Many small vessels are not visible in the ULM images due to the noise level in areas dimly explored by the microbubbles. Moreover, as the vast majority of studies are performed using 2D imaging, quantification is limited to in-plane velocity or flux measurements which hinders the accurate velocity determination and quantification. Here we show that the backscattering amplitude of each individual microbubble can also be exploited to produce backscattering images of the vascularization with a higher sensitivity compared to conventional ULM images. By providing valuable information about the relative distance of the microbubble to the 2D imaging plane in the out-of-plane direction, backscattering ULM images introduces a physically relevant 3D rendering perception in the vascular maps. It also retrieves the missing information about the out-of-plane motion of microbubbles and provides a way to improve 3D flow and velocity quantification using 2D ULM. These results pave the way to improved visualization and quantification for 2D and 3D ULM. [ABSTRACT FROM AUTHOR]

Fifty million people worldwide are affected by dementia, a heterogeneous neurodegenerative condition encompassing diseases such as Alzheimer's, vascular dementia, and Parkinson's. For them, cognitive decline is often the first marker of the pathology after irreversible brain damage has already occurred. Researchers now believe that structural and functional alterations of the brain vasculature could be early precursors of the diseases and are looking at how functional imaging could provide an early diagnosis years before irreversible clinical symptoms. In this preclinical pilot study, we proposed using functional ultrasound (fUS) on the retina to assess neurovascular alterations non-invasively, bypassing the skull limitation. We demonstrated for the first time the use of functional ultrasound in the retina and applied it to characterize the retinal hemodynamic response function in vivo in rats following a visual stimulus. We then demonstrated that retinal fUS could measure robust neurovascular coupling alterations between wild-type rats and TgF344-AD rat models of Alzheimer's disease. We observed an average relative increase in blood volume of 21% in the WT versus 37% for the TG group (p = 0.019). As a portable, non-invasive and inexpensive technique, rfUS is a promising functional screening tool in clinics for dementia years before symptoms. [ABSTRACT FROM AUTHOR]

Calcific aortic stenosis (CAS) is associated with advanced age and comorbidities, therefore a non-invasive therapy for it would be beneficial. We previously demonstrated that ultrasound therapy improved calcified bioprosthetic valve function in an open chest model. For translational applications, we tested non-invasive ultrasound therapy (NIUT) transthoracically on swine aortic valves and investigated the need for antithrombotic treatment as a follow-up. Primary objective: feasibility and safety of NIUT. Secondary objectives: occurrence, severity and evolution of side effects during therapy and at 1 month follow-up. The device (Valvosoft, Cardiawave) consisted of an electronically steered multi-element transducer and a 2D echocardiographic probe. Three groups of swine received treatment on aortic valves: NIUT (group 1; n = 10); NIUT and 1 month antithrombotic treatment (group 2; n = 5); sham group (group 3; n = 4). Feasibility was successfully reached in all treated swine (n = 15) and no life-threatening arrhythmia were detected. Non-sustained ventricular tachycardia occurred during the procedure in seven swine. Decrease or interruption of NIUT ended arrhythmia. Histopathology revealed no valve or surrounding tissue damage and echocardiography revealed no valvular dysfunction. Only one animal had side effects [right ventricle (RV) dilatation], but the RV normalized after therapy cessation with no sequelae at follow-up. No disturbance in biological markers nor valve thrombosis were observed at follow-up. Antithrombotic treatment did not demonstrate any advantage. Survival at 30 d was 100%. We demonstrated, in vivo, the feasibility and safety of transthoracic NIUT on aortic valves in a swine model without serious adverse events. We expect this first-time transthoracic delivery of NIUT to pave the way towards a new non-invasive approach to valve softening in human CAS to restore valve function. [ABSTRACT FROM AUTHOR]

Ultrafast acoustoelectric imaging (UAI) is a novel method for the mapping of biological current densities, which may improve the diagnosis and monitoring of cardiac activation diseases such as arrhythmias. This paper evaluates the feasibility of performing UAI in beating rat hearts. A previously described system based on a 256-channel ultrasound research platform fitted with a 5-MHz linear array was used for simultaneous UAI, ultrafast B-mode, and electrocardiogram (ECG) recordings. In this paper, rat hearts (n = 4) were retroperfused within a Langendorff isolated heart system. A pair of Ag/Cl electrodes were positioned on the epicardium to simultaneously record ECG and UAI signals for imaging frame rates of up to 1000 Hz and a mechanical index of 1.3. To account for the potential effect of motion on the UAI maps, acquisitions for n = 3 hearts were performed with and without suppression of the mechanical contraction using 2,3-butanedione monoxime. Current densities were detected for all four rats in the region of the atrio-ventricular node, with an average contrast-to-noise ratios of 12. The UAI signals’ frequency matched the sinus rhythm, even without mechanical contraction, suggesting that the signals measured correspond to physiological electrical activation. UAI signals appeared at the apex and within the ventricular walls with a delay estimated at 29 ms. Finally, the signals from different electrode positions along the myocardium wall showed the possibility of mapping the electrical activation throughout the heart. These results show the potential of UAI for cardiac activation mapping in vivo and in real time. [ABSTRACT FROM AUTHOR]

Background: The peptide hepcidin plays a central role in regulating dietary iron absorption and body iron distribution. This 25-amino acid hormone is produced and secreted predominantly by hepatocytes. Hepcidin has been suggested as a promising diagnostic marker for iron-related disorders. However, its accurate quantification for clinical use remains so far challenging. In this report we describe a highly specific and quantitative serum hepcidin method using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Material: The analytical validation included the determination of the limit of detection, of quantification, repeatability, reproducibility and linearity. This assay was developed for human and mouse hepcidin. The human assay was performed on serum patients with unexplained microcytic anemia. We applied our LC-MS/MS method for quantifying hepcidin-1 in mouse in various conditions: inflammation, hemolytic anemia, Hamp-1, Hjv and Hfe KO mice. Results: We show that the LC-MS/MS is suitable for accurate determination of hepcidin-25 in clinical samples, thereby representing a useful tool for the clinical diagnosis and follow-up of iron-related diseases. In mouse, a strong correlation between hepatic Hamp-1 mRNA expression and serum hepcidin-1 levels was found (r = 0.88; p = 0.0002) and the expected variations in mouse models of iron disorders were observed. Conclusions: Therefore, we propose this adaptive LC-MS/MS method as a suitable method for accurate determination of hepcidin-25 in clinical samples and as a major tool contributing to the clinical diagnosis, follow-up and management of iron-related disorders. It also opens new avenues to measure hepcidin in animal models without interspecies antigenic limitations. [ABSTRACT FROM AUTHOR]