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Lumason

Manufactured by Bracco
Sourced in Italy

Lumason is a contrast agent used in ultrasound imaging. It is composed of stabilized microbubbles that enhance the visibility of blood flow and blood-containing structures during ultrasound examinations.

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9 protocols using lumason

1

Ultrasound Contrast and Oxygen Scavenging

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The effect of the ultrasound contrast agent Lumason® (Bracco Diagnostics, Inc., Milan, Italy) on the ADV transition efficiency and oxygen scavenging was studied by comparing measurements with and without Lumason® co-administered with droplets. Lumason® was activated according to the manufacturer’s package insert and used within 48 h of activation. A 19 G needle (Hamilton, Reno, NV, USA) connected to a 25 µL gas-tight syringe (Becton Dickinson, Franklin Lakes, NJ, USA) was used to withdraw 24 µL of Lumason®. Lumason® was transferred to a 60 mL syringe (Becton Dickinson, Franklin Lakes, NJ, USA) containing 60 mL of 95% DI water and perfluorocarbon droplets (4.8 × 10−4 ± 0.6 × 10−4 mL/mL final concentration). The Lumason® dose was based on the package insert dose per weight (0.03 mL/kg). Co-diluted Lumason® and droplets were infused through the coolant delivery port of an EkoSonic® catheter with a Harvard Apparatus Elite syringe pump (Harvard Apparatus, Holliston, MA, USA) and exposed to ultrasound, as described in Section 2.3.
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2

Quantifying Cerebrospinal Fluid Flow

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The cranial pressure catheter was disconnected from the transducer and used to introduce into the CSF a suspension of approximately 2.0 × 109 artificial (sulfur hexafluoride) microspheres in 5 ml of saline (Lumason; Bracco Diagnostics, Monroe Township, NJ, USA). Doppler ultrasonographic records of CSF flow were quantified using an ultrasonography machine (Mindray M7; Nanshan, Shenzhen, P.R. China). A linear array probe (Mindary L12-4) was placed contralateral to the exposed suboccipital muscles and pulsed-wave Doppler ultrasonography used to detect the spread of the introduced microspheres in the CSF. The recordings presented were all taken prior to stimulation of the myodural bridge, and thus represent the resting or baseline flow condition. CSF flow velocity was quantified relative to the internally calibrated zero baseline of the ultrasonography machine. Data were collected from five of the alligators.
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3

Contrast-Enhanced Transrectal Ultrasound for Prostate Imaging

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After the TRUS transducer was inserted in the patients’ rectum, image settings were optimized. The contrast-enhanced TRUS examination started with conventional TRUS B-mode imaging followed by color or power Doppler imaging. A dual-scan, split-screen mode (simultaneous contrast-enhanced TRUS and B-mode imaging) using low mechanical index settings was used for contrast. Prior to the procedure, the off-label use of microbubble contrast agent for evaluation of the prostate was discussed with the patients. Lumason (Bracco Diagnostic, Inc, Monroe Township, NJ), a sulfur hexafluoride microsphere US contrast agent, was manually agitated for 20 seconds. A 2.5-mL bolus dose of the contrast agent was injected intravenously, followed immediately by a 10-mL normal saline flush. Complete, real-time, 2-minute continuous video clips of the contrast-enhanced TRUS examination, starting from the saline flush, were stored. The contrast-enhanced TRUS video clips were acquired at the base, mid, and apex of the prostate on an axial view. Depending on availability, the US units used were GE LOGIQ E9(GE Healthcare, Buckinghamshire, England) or Philips EPIQ 7 (Philips Healthcare, Bothell, WA). For the GE LOGIQ E9 unit, a GE iC5–9-D transducer was used. For the Philips EPIQ 7 unit, a C10–3v transducer was used. For both systems, a low– mechanical index mode with a frequency of 8 MHz was used.
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4

Intraoperative CEUS for Femoral Head Perfusion

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Intraoperative CEUS was performed to assess the perfusion of the cartilaginous femoral head before and after surgical reduction. Pre-reduction imaging was done in a coronal plane, while post-reduction imaging was conducted in a transperineal transverse plane after spica cast placement [Figure 1]. All CEUS examinations were conducted by an experienced sonographer, using a GE Logiq E10 US unit (General Electric, Boston, MA) equipped with the C3–10 curved array transducer with frequncey broadband of 3–10MHz.
Prior to the imaging procedure, the ultrasound contrast agent Lumason® (sulfur hexafluoride lipid-type A microsphere) (Bracco Diagnostic Inc Monroe Township, NJ) was constituted according to the manufacter’s instructions. A bolus intravenous injection of 2 mL of the ultrasound contrast agent was followed by 3 mL saline flush. The dose was selected based on previous study. [12 (link)]. CEUS clips were acquired for approximately 2 minutes. The imaging parameters remained consistent both pre and post-reduction,.
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5

Ultrasound-Mediated Doxorubicin Delivery

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Doxorubicin was used as the chemotherapeutic drug as it is detectable using fluorescent imaging. Although clinically, the liposomal formulation of doxorubicin, Doxil, is favored over the free drug, we chose to use free doxorubicin for simplicity, and note that it could be easily replaced by a wide variety of other small molecule drugs. Furthermore, the benefits of using Doxil over doxorubicin (ie, limiting cardiotoxicity) would not be relevant in the current study due to the acute timeline of the experiments. Doxorubicin HCl was purchased and dissolved in sterile saline at a concentration of 10 mg/ml and mice received a dosing level of 30 mg/kg (Li et al., 2015 (link)). Sonovue®, marketed in the US as Lumason® (Bracco Suisse SA, Geneva, Switzerland), was the contrast agent used for these studies and was resuspended according to the manufacturer’s instructions. Microbubble concentration was measured using a Multisizer 3 (Beckman Coulter, Brea, CA, USA) and found to consistently be between 1 and 5 × 108 microbubbles/ml. Microbubble dosing was evaluated through preliminary experiments in which it was observed that 50-μl injections gave adequate contrast without acoustic shadowing (Keller et al., 2019 (link)) and therefore that dosing regimen was used for all further experiments.
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6

Ultrafast Plane Wave Imaging of Chicken Embryo Vasculature

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Data were collected as reported in [22 (link)] and as recounted briefly here. The CEUS images were taken from the chorioallantoic membrane (CAM) of chicken embryos. This model is attractive due to the long microbubble recirculation times, small bulk tissue motions, and the ability to directly compare the US images with high resolution optical microscopy images of the vasculature. A bolus injection of microbubbles (Lumason, Bracco Diagnostics Inc., Monroe Township, NJ) at 1.8 × 109 microbubbles per milliliter, and imaging acquisitions were performed at the microbubble concentration plateau after the injection.
CEUS images were obtained with a Verasonics Vantage 256 ultrasound system (Verasonics Inc., Kirkland, WA, USA) with a 25 MHz linear array transducer (L35–16vX, Verasonics Inc.). Ultrafast plane wave imaging (15 angles, − 7° to 7°) was performed at 500 compounded frames per second, with 5 V transmit excitation. At each location, 5 successive acquisitions of 720 frames each (total acquisition length 3600 frames over 7.2 seconds) were captured. The IQ data were stored and post-processed with custom MATLAB scripts on a standard desktop computer (4 cores at 2.8 GHz, 16 GB RAM).
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7

Transcranial Focused Ultrasound Sonication

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The sonication procedure was performed using a pre-clinical LIPU device (SonoCloud® technology) manufactured by CarThera (Paris, France). Mice were anesthetized with ketamine/xylazine (K/X) cocktail (Ketamine 100mg/kg, Xylazine 10mg/kg, i.p.). MB (Lumason®, Bracco) were reconstituted according to manufacturer instructions and injected at a dose of 7.5 ml/kg through the retro-orbital route. Shortly after MB administration, mice were quickly (<10s) placed supine upon the US transducer holder and sonications began. A 1 MHz, 10-mm diameter flat US transducer was fixed in a holder filled with degassed water and sonications were performed transcranially (Figure S1A). Sonications were performed for 120 s using a 25,000 cycle burst at a 1 Hz pulse repetition frequency and an acoustic pressure of 0.3 MPa as measured in water. After sonications, mice were moved to a clean cage, placed upon a heating pad, and monitored until they recovered from anesthesia.
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8

Ultrasound-Mediated Blood-Brain Barrier Opening

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The LIPU preclinical platform (SonoCloud® technology, CarThera, France) consists of an ultrasound transducer placed in a small cylinder surrounded by a compartment of degassed water to ensure acoustic coupling. A laser is vertically aligned on the center of the transducer. To enhance reproducibility of the sonicated areas of the brain, the mouse’s shaved head is placed in contact with the surface of the degassed water and the area of tumor implantation is aligned with the laser dot. Head stabilization allows for motionless sonication to the CNS (Fig. 1A). The transducer used a center frequency of 1-MHz, pulse-repetition frequency of 1 Hz, pulse length of 25,000 cycles (2.5% duty cycle) and in situ acoustic pressure level of 0.3 MPa for a duration of 120 seconds. A 200 μl bolus of microbubbles (Lumason®, Bracco Diagnostics) were injected through the tail vein just prior to the start of sonications. These were safe parameters as determined in previous experiments in mice (11 (link)).
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9

Focused Ultrasound Mediated Drug Delivery

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The LIPU preclinical platform (SonoCloud Technology, CarThera) consists of an ultrasound transducer placed in a small cylinder surrounded by a compartment of degassed water to ensure acoustic coupling. A laser is vertically aligned on the center of the transducer. To enhance reproducibility of the sonicated areas of the brain, the mouse's shaved head is placed in contact with the surface of the degassed water and the area of tumor implantation is aligned with the laser dot. Head stabilization allows for motionless sonication to the CNS (Fig. 1A). The transducer used a center frequency of 1-MHz, pulse-repetition frequency of 1 Hz, pulse length of 25,000 cycles (2.5% duty cycle), and in situ acoustic pressure level of 0.3 MPa for a duration of 120 seconds. A 200-μL bolus of microbubbles (Lumason, Bracco Diagnostics) was injected through the tail vein just prior to the start of sonications. These were safe parameters as determined in previous experiments in mice (11 (link)).
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