Ultrasound and microbubbles for the treatment of ocular diseases : From preclinical research towards clinical application

The unique anatomy of the eye and the presence of various biological barriers make efficacious ocular drug delivery challenging, particularly in the treatment of posterior eye diseases. This review focuses on the combination of ultrasound and microbubbles (USMB) as a minimally invasive method to improve the efficacy and targeting of ocular drug delivery. An extensive overview is given of the in vitro and in vivo studies investigating the mechanical effects of ultrasound-driven microbubbles aiming to: (i) temporarily disrupt the blood–retina barrier in order to enhance the delivery of systemically administered drugs into the eye, (ii) induce intracellular uptake of anticancer drugs and macromolecules and (iii) achieve targeted delivery of genes, for the treatment of ocular malignancies and degenerative diseases. Finally, the safety and tolerability aspects of USMB, essential for the translation of USMB to the clinic, are discussed.Peer reviewe

The Focused Ultrasound Myoma Outcome Study (FUMOS); a retrospective cohort study on long-term outcomes of MR-HIFU therapy

Objectives: Since 2004, uterine fibroids have been treated with MR-HIFU, but there are persevering doubts on long-term efficacy to date. In the Focused Ultrasound Myoma Outcome Study (FUMOS), we evaluated long-term outcomes after MR-HIFU therapy, primarily to assess the reintervention rate. Methods: Data was retrospectively collected from 123 patients treated with MR-HIFU at our hospital from 2010 to 2017. Follow-up duration and baseline (MRI) characteristics were retrieved from medical records. Treatment failures, adverse events, and the nonperfused volume percentage (NPV%) were determined. Patients received a questionnaire about reinterventions, recovery time, satisfaction, and pregnancy outcomes. Restrictive treatment protocols were compared with unrestrictive (aiming for complete ablation) treatments. Subgroups were analyzed based on the achieved NPV < 50 or ≥ 50%. Results: Treatment failures occurred in 12.1% and the number of adverse events was 13.7%. Implementation of an unrestrictive treatment protocol significantly (p = 0.006) increased the mean NPV% from 37.4% [24.3–53.0] to 57.4% [33.5–76.5]. At 63.5 ± 29.0 months follow-up, the overall reintervention rate was 33.3% (n = 87). All reinterventions were performed within 34 months follow-up, but within 21 months in the unrestrictive group. The reintervention rate significantly (p = 0.002) decreased from 48.8% in the restrictive group (n = 43; follow-up 87.5 ± 7.3 months) to 18.2% in the unrestrictive group (n = 44; follow-up 40.0 ± 22.1 months). The median recovery time was 2.0 [1.0–7.0] days. Treatment satisfaction rate was 72.4% and 4/11 women completed family planning after MR-HIFU. Conclusions: The unrestrictive treatment protocol significantly increased the NPV%. Unrestrictive MR-HIFU treatments led to acceptable reintervention rates comparable to other reimbursed uterine-sparing treatments, and no reinterventions were reported beyond 21 months follow-up. Key Points: • All reinterventions were performe

Estimation of In Vivo Water Content of the Stratum Corneum from Electrical Measurements

In vivo water content in the epidermal stratum corneum can be estimated by means of low frequency susceptance measurements. In the in vitro calibration necessary to find the in vivo water content, the stratum corneum will have a uniform distribution of water across its thickness. However, in vivo stratum corneum has an increasing water concentration profile from the outermost towards the innermost parts. This paper will investigate the possibility of estimating the equilibrium water content in the in vivo stratum corneum non-invasively from electrical susceptance measurements. Given a known shape of the water concentration profile in the in vivo stratum corneum and the dependence of susceptance on the water content, it is possible to calculate the water content in vivo based on analytically derived expressions for the water concentration profile. A correspondence between in vivo and in vitro water content needed for this purpose is also established

Exploring label dynamics of velocity-selective arterial spin labeling in the kidney

Purpose: Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR). Methods: Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior–posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported. Results: In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P .05) with good correlations on subject level. Conclusion: Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

Ultrasound and Microbubbles for the Treatment of Ocular Diseases: From Preclinical Research towards Clinical Application

The unique anatomy of the eye and the presence of various biological barriers make efficacious ocular drug delivery challenging, particularly in the treatment of posterior eye diseases. This review focuses on the combination of ultrasound and microbubbles (USMB) as a minimally invasive method to improve the efficacy and targeting of ocular drug delivery. An extensive overview is given of the in vitro and in vivo studies investigating the mechanical effects of ultrasound-driven microbubbles aiming to: (i) temporarily disrupt the blood-retina barrier in order to enhance the delivery of systemically administered drugs into the eye, (ii) induce intracellular uptake of anticancer drugs and macromolecules and (iii) achieve targeted delivery of genes, for the treatment of ocular malignancies and degenerative diseases. Finally, the safety and tolerability aspects of USMB, essential for the translation of USMB to the clinic, are discussed

Ultrasound and Microbubbles for the Treatment of Ocular Diseases: From Preclinical Research towards Clinical Application

The unique anatomy of the eye and the presence of various biological barriers make efficacious ocular drug delivery challenging, particularly in the treatment of posterior eye diseases. This review focuses on the combination of ultrasound and microbubbles (USMB) as a minimally invasive method to improve the efficacy and targeting of ocular drug delivery. An extensive overview is given of the in vitro and in vivo studies investigating the mechanical effects of ultrasound-driven microbubbles aiming to: (i) temporarily disrupt the blood-retina barrier in order to enhance the delivery of systemically administered drugs into the eye, (ii) induce intracellular uptake of anticancer drugs and macromolecules and (iii) achieve targeted delivery of genes, for the treatment of ocular malignancies and degenerative diseases. Finally, the safety and tolerability aspects of USMB, essential for the translation of USMB to the clinic, are discussed

Evaluation of respiration-induced magnetic field disturbance correction of MR thermometry in volunteers and in patients for MR-HIFU ablation of breastcancer: the effects of conscious sedation

International audienc

Growth assessment in down syndrome after cardiac surgery

Abstract Objective To assess the effect of cardiac surgery on growth catch-up of Down syndrome (DS) children with failure to thrive (FTT) and congenital heart disease (CHD) and investigate other causes of FTT in DS children. Method We conducted a retrospective observational study in tertiary cardiac center from 2015 to 2018. We included all cases of DS diagnosed with CHD and FTT who completed a 1-year follow-up after cardiac surgery. We divided the cases into two groups; “normalize group” includes children who normalized their growth parameters and “underweight group” includes those who remained in FTT category during the follow-up period. We compared both groups for multiple risk factors. Result Most of DS had FTT upon surgery. Fifty percent of cases completed 1-year follow-up including 29 (60%) in the normalized group and 19 (40%) in underweight group. Within 6 months post-surgery, the normalized group though did not reach yet normalization of growth parameters, demonstrated statically significant improvement in weight for age, weight Z-score in compared to underweight group. Within 12 months post-surgery, the normalized group achieved normalization of growth parameters and continue to show more statistically significant differences in growth parameters. Both groups had comparable post-operation course. Univariate analysis of possible peri-operative risk factors showed no difference between both groups except for presence of untreated subclinical hypothyroidism in 58% of the underweight group versus 17% in control group (p = 0.005). Conclusion FTT in DS patient is multifactorial which needs thorough investigation and work up by multidisciplinary team. Cardiac surgery may not guarantee the improvement of growth parameters

Performance analysis of a dedicated breast MR-HIFU system for tumor ablation in breast cancer patients

International audienc