Assessment of the biodistribution of an [ 18 F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97497/1/cmmi1532.pd

(−)‐[ 18 F]Flubatine: evaluation in rhesus monkeys and a report of the first fully automated radiosynthesis validated for clinical use

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101867/1/jlcr3069.pd

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

Control of Fibroblast Differentiation in Acoustically-Responsive Scaffolds using Ultrasound-Induced Matrix Stiffening

Cells respond to biochemical and biomechanical cues (e.g., stiffness) from the surrounding extracellular matrix (ECM). Cellular differentiation into more specialized cell types is a common cellular response intimately related to these cues. Regenerative medicine often employs implantable hydrogel scaffolds as surrogates of the native ECM and as carriers of biomolecules and cells. The mechanical properties of hydrogels are conventionally designed a priori and are often static and uniform. That is to say, the mechanical properties cannot be dynamically controlled following implantation in a user-defined, on demand manner. The Fabiilli lab utilizes specialized composite hydrogel scaffolds that have mechanical characteristics that can be modulated when focused ultrasound (FUS) is applied. These scaffolds, termed acoustically-responsive scaffolds (ARSs), consist of a phase-shift emulsions (PSE) embedded within a polymerized fibrin matrix. PSE is non-thermally vaporized when FUS is applied, and expands into a gas bubble, thereby causing localized compaction and significant increases in stiffness of the matrix surrounding the bubble.1 In this in vitro study, we investigate how these localized increases in matrix stiffness can be used to control the differentiation of fibroblasts into myofibroblasts, a transition which occurs at high stiffnesses.2 Findings indicated that vaporized PSE generated stable bubbles as well as bubbles that recondensed within the ARS, and that ɑSMA intensity was qualitatively higher at locations proximal to vaporized PSE compared to distal locations. Quantitatively, the normalized aSMA signal intensity was significantly increased in regions proximal to the vaporized PSE (p = 0.0007 and p = 0.0478).http://deepblue.lib.umich.edu/bitstream/2027.42/169560/1/Honors_Capstone_Myofibroblast_Differentiation_Under_Ultrasound.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169560/2/Honors_Capstone_Myofibroblast_Differentiation_Using_Ultrasound.pptxhttp://deepblue.lib.umich.edu/bitstream/2027.42/169560/3/Easton_Farrell_Capstone.mp

Increased capillary tortuosity and pericapillary basement membrane thinning in skeletal muscle of mice undergoing running wheel training.

To work out which microvascular remodeling processes occur in murine skeletal muscle during endurance exercise, we subjected C57BL/6-mice to voluntary running wheel training for 1 week (1wk-t) or 6 weeks (6wks-t). By means of morphometry, the capillarity as well as the compartmental and sub-compartmental structure of the capillaries were quantitatively described at the light microscopy and at the electron microscopy level, respectively, in the plantaris muscle (PLNT) of the exercising mice in comparison to untrained littermates. In the early phase of the training (1wk-t), angiogenesis (32%-higher capillary-fiber (CF)-ratio; P0.05), further reduction of CBMT (16.5%; P<0.05) and additional shortening of the intraluminal protrusion length (23%; P<0.05), all compared to controls. Other structural indicators such as capillary profile sizes, profile area densities, perimeters of the capillary compartments and concentrations of endothelium-pericyte peg-socket junctions were not significantly different between the mouse groups. Besides angiogenesis, increase of capillary tortuosity and reduction of CBMT represent the most striking microvascular remodeling processes in skeletal muscle of mice that undergo running wheel training

Ultrasound-Induced Mechanical Compaction in Acoustically Responsive Scaffolds Promotes Spatiotemporally Modulated Signaling in Triple Negative Breast Cancer

Cancer cells continually sense and respond to mechanical cues from the extracellular matrix (ECM). Interaction with the ECM can alter intracellular signaling cascades, leading to changes in processes that promote cancer cell growth, migration, and survival. The present study used a recently developed composite hydrogel composed of a fibrin matrix and phase-shift emulsion, termed an acoustically responsive scaffold (ARS), to investigate effects of local mechanical properties on breast cancer cell signaling. Treatment of ARSs with focused ultrasound drives acoustic droplet vaporization (ADV) in a spatiotemporally controlled manner, inducing local compaction and stiffening of the fibrin matrix adjacent to the matrix–bubble interface. Combining ARSs and live single cell imaging of triple-negative breast cancer cells, it is discovered that both basal and growth-factor stimulated activities of protein kinase B (also known as Akt) and extracellular signal-regulated kinase (ERK), two major kinases driving cancer progression, negatively correlate with increasing distance from the ADV-induced bubble both in vitro and in a mouse model. Together, these data demonstrate that local changes in ECM compaction regulate Akt and ERK signaling in breast cancer and support further applications of the novel ARS technology to analyze spatial and temporal effects of ECM mechanics on cell signaling and cancer biology.The study uses a smart hydrogel system with focused ultrasound for precise temporal and spatial control of tissue compaction. Incorporating breast cancer cells into this hydrogel system reveals that ultrasound-triggered increases in compaction of extracellular matrix promotes signaling through pathways known to drive proliferation and aggressive features in breast cancer and other malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172808/1/adhm202101672_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172808/2/adhm202101672.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172808/3/adhm202101672-sup-0001-SuppMat.pd

Evaluation of Imaging Strategy to Optimize and Improve Outcome of Transcatheter Aortic Valvular Implantation

International audienceCardiac computed tomography (CT) provides additional information with ultrasound in the transcatheter heart valve (THV) size selection. However, the influence of these incremental data on outcomes has not been evaluated in a randomized study. A single-center prospective, randomized, and open study was performed. Patients referred for transfemoral transcatheter aortic valve implantation with a balloon-expandable endoprothesis were included. THV size selection was performed using either transthoracic and transesophageal echocardiography data (control group) or ultrasound and CT results (CT group). The primary composite end point included the occurrence of stroke, major vascular complications, and moderate or severe paravalvular aortic regurgitation (PAR) at 1 year. Fifty patients (n = 25 in the control and CT groups) were enrolled. The primary composite end point occurred in 40% and 8% of patients from the control and CT groups, respectively (p = 0.008). The Kaplan-Meier analysis revealed a pejorative association with not performing the CT (p = 0.007). A decrease in the occurrence of PAR was observed in the CT group compared with the control group (PAR 28% vs 4%, p = 0.04; major vascular complications 12% vs 4%, p = 0.6; all-cause death 16% vs. 4%, p = 0.34; no stroke). In conclusion, the use of cardiac CT in addition to ultrasound data in THV size selection reduced the long-term occurrence of cardiovascular events

4‑[¹⁸F]Fluoro‑<i>m</i>‑hydroxyphenethylguanidine: A Radiopharmaceutical for Quantifying Regional Cardiac Sympathetic Nerve Density with Positron Emission Tomography

4-[¹⁸F]­Fluoro-<i>m</i>-hydroxyphenethylguanidine ([¹⁸F]­4F-MHPG, [¹⁸F]<b>1</b>) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [¹⁸F]<b>1</b> was developed in which the intermediate 4-[¹⁸F]­fluoro-<i>m</i>-tyramine ([¹⁸F]<b>16</b>) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [¹⁸F]­fluorination. In PET imaging studies in rhesus macaque monkeys, [¹⁸F]<b>1</b> demonstrated high quality cardiac images with low uptake in lungs and the liver. Compartmental modeling of [¹⁸F]<b>1</b> kinetics provided net uptake rate constants <i>K</i>_i (mL/min/g wet), and Patlak graphical analysis of [¹⁸F]<b>1</b> kinetics provided Patlak slopes <i>K</i>_p (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [¹⁸F]<b>1</b> can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET