Journal: Pharmaceutics

Article Title: Novel Developments to Enable Treatment of CNS Diseases with Targeted Drug Delivery

doi: 10.3390/pharmaceutics15041100

Figure Lengend Snippet: Clinical Studies Utilizing FUS with Microbubbles to Disrupt the BBB.

Article Snippet: 1 day 1 , January 2015–July 2021 , Definity ® microbubbles , InSightec ® , Haifa, Israel , Brain tumors , NCT02343991.

Techniques: Enzyme-linked Immunosorbent Assay

Journal: Ultrasound in medicine & biology

Article Title: Accelerated clearance of ultrasound contrast agents containing polyethylene glycol is associated with the generation of anti-polyethylene glycol antibodies

doi: 10.1016/j.ultrasmedbio.2018.02.006

Figure Lengend Snippet: Timeline detailing experiment 2. Free PEG competition to recover circulatory persistence of house-MBs. On days 0, 7, 22, and 24, animals underwent contrast ultrasound imaging to quantify microbubble circulatory persistence. On days 1, 2, and 3, animals received a dose of house-MBs without imaging to induce the ABC effect. On days 7 and 24, free PEG (or saline) was administered prior to the house-MB dose and contrast imaging.

Article Snippet: Commercially available microbubbles Definity (Lantheus Medical Imaging, Billerica, MA, USA) and Optison (GE Healthcare, Princeton, NJ, USA) used throughout this study were purchased from the Hospital Pharmacy at the University of North Carolina at Chapel Hill.

Techniques: Imaging, Saline

Journal: Ultrasound in medicine & biology

Article Title: Accelerated clearance of ultrasound contrast agents containing polyethylene glycol is associated with the generation of anti-polyethylene glycol antibodies

doi: 10.1016/j.ultrasmedbio.2018.02.006

Figure Lengend Snippet: Competition with 2,200 mpk free PEG20 kDa prolongs house-MB circulation in animals exhibiting the ABC effect. (A) Initial time intensity curve of house-MBs (red) shows slow clearance compared to that of control animals on day 24 (grey). When animals were pre-dosed with 2,200 mpk free PEG, the microbubble time intensity curve (black) showed a long circulation profile similar to that seen on day 0, indicating successful competition of binding between anti-PEG antibodies and microbubbles. (B-D) After competition on day 24, ke and t1/2 values were not statistically different from their respective initial values. After competition on day 24, AUC was still significantly lower than the initial value, however, competition did significantly increase AUC compared to control animals that received saline injections on day 24. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001

Article Snippet: Commercially available microbubbles Definity (Lantheus Medical Imaging, Billerica, MA, USA) and Optison (GE Healthcare, Princeton, NJ, USA) used throughout this study were purchased from the Hospital Pharmacy at the University of North Carolina at Chapel Hill.

Techniques: Control, Binding Assay, Saline

Journal: Ultrasound in medicine & biology

Article Title: Accelerated clearance of ultrasound contrast agents containing polyethylene glycol is associated with the generation of anti-polyethylene glycol antibodies

doi: 10.1016/j.ultrasmedbio.2018.02.006

Figure Lengend Snippet: (A) Average time intensity curves obtained from animals receiving multiple injections of Definity over 30 d. Curve labels (D0-D30) indicate time in days since the initial dose. (B) Average time intensity curves from animals receiving multiple injections of Optison over 30 d.

Article Snippet: Commercially available microbubbles Definity (Lantheus Medical Imaging, Billerica, MA, USA) and Optison (GE Healthcare, Princeton, NJ, USA) used throughout this study were purchased from the Hospital Pharmacy at the University of North Carolina at Chapel Hill.

Techniques:

Journal: Ultrasound in medicine & biology

Article Title: Accelerated clearance of ultrasound contrast agents containing polyethylene glycol is associated with the generation of anti-polyethylene glycol antibodies

doi: 10.1016/j.ultrasmedbio.2018.02.006

Figure Lengend Snippet: Change in areas under the curves (A), half-lives (B), elimination rates (C) through time for Definity when administered repeatedly over a 30-d period. Change in areas under the curves (D), half-lives (E), elimination rates (F) through time for Optison when administered repeatedly over a 30-d period. * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; **** p ≤ 0.0001

Article Snippet: Commercially available microbubbles Definity (Lantheus Medical Imaging, Billerica, MA, USA) and Optison (GE Healthcare, Princeton, NJ, USA) used throughout this study were purchased from the Hospital Pharmacy at the University of North Carolina at Chapel Hill.

Techniques:

Journal: Ultrasound in medicine & biology

Article Title: Accelerated clearance of ultrasound contrast agents containing polyethylene glycol is associated with the generation of anti-polyethylene glycol antibodies

doi: 10.1016/j.ultrasmedbio.2018.02.006

Figure Lengend Snippet: Enzyme-linked immunosorbent assay detection of serum anti-PEG IgM (A) and anti-PEG IgG (B) antibodies for animals repeatedly dosed with Definity or Optison over 30 d. PEG = polyethylene glycol; Ig = immunoglobulin

Article Snippet: Commercially available microbubbles Definity (Lantheus Medical Imaging, Billerica, MA, USA) and Optison (GE Healthcare, Princeton, NJ, USA) used throughout this study were purchased from the Hospital Pharmacy at the University of North Carolina at Chapel Hill.

Techniques: Enzyme-linked Immunosorbent Assay

Journal: Cellular and Molecular Life Sciences: CMLS

Article Title: Ultrasonic technologies in imaging and drug delivery

doi: 10.1007/s00018-021-03904-9

Figure Lengend Snippet: Conceptual diagram showing the use of FUS exposure in the presence of MBs to open the BBB in CNS

Article Snippet: To test the application of MB-ultrasound BBB opening to treat Parkinson’s disease dementia, Gasca-Salas et al. conducted a single-arm non-randomized BBB opening clinical trial ( NCT03608553 ) using a MR-guided FUS system (Exablate Neuro, Insightec; Microbubble: Definity (Bristol-Myers Squibb)).

Techniques:

Journal: Pharmaceutics

Article Title: Novel Developments to Enable Treatment of CNS Diseases with Targeted Drug Delivery

doi: 10.3390/pharmaceutics15041100

Figure Lengend Snippet: Clinical Studies Utilizing FUS with Microbubbles to Disrupt the BBB.

Article Snippet: 1 day , August 2019–January 2027 , Definity ® microbubbles , Neurological Assoc., BrainSonix Corp, Sherman Oaks, CA, USA , Low Grade Glioma , NCT04063514.

Techniques: Enzyme-linked Immunosorbent Assay

Journal: Physics in medicine and biology

Article Title: A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

doi: 10.1088/0031-9155/61/24/8476

Figure Lengend Snippet: (a) Lateral (top row) and axial (bottom row) images of microbubble clouds located near the array's geometric focus reconstructed at 306 kHz (0.53 MPa estimated in-situ pressure), 612 kHz (0.27 MPa estimated in-situ pressure), and 1.224 MHz (0.23 MPa estimated in-situ pressure), respectively, through an ex-vivo human skullcap using source-based aberration corrections. Please note that the scale bars used in each sub plot in figure 10(a) are different. (b) Frequency spectrum of the beamformed signal at the point of maximum intensity is given for each of the cases in (a). (c) Normalized maximum pixel projection images of the tube phantom obtained through an ex-vivo human skullcap. Images were captured at both the half-harmonic (612 kHz transmit frequency, 0.53 MPa estimated in-situ pressure) and the second-harmonic (306 kHz transmit frequency, 0.27 MPa estimated in-situ pressure), and were reconstructed with and without the use of source-based aberration corrections on receive. The cross-sectional images (bottom row) were generated by taking the maximum pixel projection over the range of [−1,1] mm in Y.

Article Snippet: C. Receiver Array Characterization: Passive Microbubble Imaging The receiving capabilities of the array were investigated by imaging ultrasound-stimulated microbubbles (Definity™, Lantheus Medical Imaging, North Billerica, MA, USA) flowing through thin-walled tube phantoms (Cole-Parmer, Vernon Hills, IL, USA).

Techniques: In Situ, Ex Vivo, Generated

Journal: Physics in medicine and biology

Article Title: A multi-frequency sparse hemispherical ultrasound phased array for microbubble-mediated transcranial therapy and simultaneous cavitation mapping

doi: 10.1088/0031-9155/61/24/8476

Figure Lengend Snippet: (a). Contrast-enhanced T1-weighted MR image of the rat taken with contrast following FUS+microbubbles (MBs). (b). Corresponding passive acoustic maps from the burst 30 s into the sonication for sonications with MBs and BBB opening. The lateral plane of maximum intensity pixel projection is shown. (c) Frequency spectrum of the beamformed signal at the point of maximum intensity in (b) is given.

Article Snippet: C. Receiver Array Characterization: Passive Microbubble Imaging The receiving capabilities of the array were investigated by imaging ultrasound-stimulated microbubbles (Definity™, Lantheus Medical Imaging, North Billerica, MA, USA) flowing through thin-walled tube phantoms (Cole-Parmer, Vernon Hills, IL, USA).

Techniques: Sonication

Journal: Scientific Reports

Article Title: A new safety index based on intrapulse monitoring of ultra-harmonic cavitation during ultrasound-induced blood-brain barrier opening procedures

doi: 10.1038/s41598-020-66994-8

Figure Lengend Snippet: ( A ) Representation of a typical ultrasound sequence for BBB opening. In general, multiple bursts of 3–10 ms are repeated at a pulse repetition frequency of 5–10 Hz, for a total exposure time ranging from 0.5 to 5 minutes. ( B ) The ultrasound backscattered signal originated from the cavitation of microbubbles is decomposed into n temporal windows for comparative frequency analysis.

Article Snippet: Commercial ultrasound contrast agents currently available for BBB opening in humans consist of lipid-stabilized microbubbles ( e.g ., Definity, Lantheus Medical Imaging; SonoVue, Bracco Imaging).

Techniques: Sequencing

Journal: Scientific Reports

Article Title: A new safety index based on intrapulse monitoring of ultra-harmonic cavitation during ultrasound-induced blood-brain barrier opening procedures

doi: 10.1038/s41598-020-66994-8

Figure Lengend Snippet: Representative frequency responses of a microbubble cavitation signal measured at different periods (before and after 3.3 ms) following ultrasound bursts. Transcranial ultrasound was emitted at 0.5 MHz into the NHP brain, and the cavitation signal was measured using a PCD transducer centered at 1.5 MHz. The occurrence of ultra-harmonic frequency components (1.5 f 0 , 2.5 f 0 , 3.5 f 0 ) is a very sudden event (<256 µs), which can occur over the burst period.

Article Snippet: Commercial ultrasound contrast agents currently available for BBB opening in humans consist of lipid-stabilized microbubbles ( e.g ., Definity, Lantheus Medical Imaging; SonoVue, Bracco Imaging).

Techniques: