Theranostics in the vasculature: bioeffects of ultrasound and microbubbles to induce vascular shutdown.

Ultrasound-triggered microbubbles destruction leading to vascular shutdown have resulted in preclinical studies in tumor growth delay or inhibition, lesion formation, radio-sensitization and modulation of the immune micro-environment. Antivascular ultrasound aims to be developed as a focal, targeted, non-invasive, mechanical and non-thermal treatment, alone or in combination with other treatments, and this review positions these treatments among the wider therapeutic ultrasound domain. Antivascular effects have been reported for a wide range of ultrasound exposure conditions, and evidence points to a prominent role of cavitation as the main mechanism. At relatively low peak negative acoustic pressure, predominantly non-inertial cavitation is most likely induced, while higher peak negative pressures lead to inertial cavitation and bubbles collapse. Resulting bioeffects start with inflammation and/or loose opening of the endothelial lining of the vessel. The latter causes vascular access of tissue factor, leading to platelet aggregation, and consequent clotting. Alternatively, endothelium damage exposes subendothelial collagen layer, leading to rapid adhesion and aggregation of platelets and clotting. In a pilot clinical trial, a prevalence of tumor response was observed in patients receiving ultrasound-triggered microbubble destruction along with transarterial radioembolization. Two ongoing clinical trials are assessing the effectiveness of ultrasound-stimulated microbubble treatment to enhance radiation effects in cancer patients. Clinical translation of antivascular ultrasound/microbubble approach may thus be forthcoming.

Focused Ultrasound for Pediatric Diseases.

Focused ultrasound (FUS) is a noninvasive therapeutic technology with multiple pediatric clinical applications. The ability of focused ultrasound to target tissues deep in the body without exposing children to the morbidities associated with conventional surgery, interventional procedures, or radiation offers significant advantages. In 2021, there are 10 clinical pediatric focused ultrasound studies evaluating various musculoskeletal, oncologic, neurologic, and vascular diseases of which 8 are actively recruiting and 2 are completed. Pediatric musculoskeletal applications of FUS include treatment of osteoid osteoma and bone metastases using thermal ablation and high-intensity FUS. Pediatric oncologic applications of FUS include treatment of soft tissue tumors including desmoid tumors, malignant sarcomas, and neuroblastoma with high-intensity FUS ablation alone, or in combination with targeted chemotherapy delivery. Pediatric neurologic applications include treatment of benign tumors such as hypothalamic hamartomas with thermal ablation and malignant diffuse intrinsic pontine glioma with low-intensity FUS for blood brain barrier opening and targeted drug delivery. Additionally, low-intensity FUS can be used to treat seizures. Pediatric vascular applications of FUS include treatment of arteriovenous malformations and twin-twin transfusion syndrome using ablation and vascular occlusion. FUS treatment appears safe and efficacious in pediatric populations across many subspecialties. Although there are 7 Food and Drug Administration-approved indications for adult applications of FUS, the first Food and Drug Administration approval for pediatric patients with osteoid osteoma was obtained in 2020. This review summarizes the preclinical and clinical research on focused ultrasound of potential benefit to pediatric populations.

Mindfulness with paced breathing reduces blood pressure.

Elevated blood pressure (BP) is a major avoidable cause of premature morbidity and mortality in the United States (US) and worldwide, due primarily to increased risks of stroke as well as myocardial infarction. While there are therapeutic lifestyle changes and adjunctive pharmacologic medications of proven benefit, recent interest has increasingly focused on Complementary and Alternative Medicine, in particular, Mind-Body Interventions. With respect to BP, it is tempting to speculate that mindfulness with paced breathing will have beneficial effects in the short run that may translate into lowered risks of stroke in the long run. Paced breathing is deep diaphragmatic breathing with typical rates equal to or less than 5-7 breaths per minute compared with the usual rate of 12-14. One plausible mechanism of benefit is that paced breathing stimulates the parasympathetic nervous system which alters neuronal function in specific areas of the brain and reduces stress chemicals. The hypothesis that mindfulness with paced slow breathing reduces BP could be directly tested in randomized trials designed a priori to do so. Subsequently, a finding that mindfulness with paced breathing reduces BP would also lead to direct tests in randomized trials of reductions of carotid atherosclerosis and, if so, a larger scale trial to test whether there is a direct impact of mindfulness with paced breathing on reducing the risks of stroke and MI. If rigorous testing of this medical hypothesis led to positive results this would have large and important clinical and policy implications in the US and worldwide.