Ultrasound Imaging and Therapeutics Research Laboratory

Focused Ultrasound Delivery of US/PA Contrast Agents for In Vivo, Longitudinal Imaging

Summary

Focused ultrasound (FUS) is a non-invasive, therapeutic technology used to treat various medical conditions. In the area of neuroscience, FUS, in conjunction with microbubbles, can be used to transiently open the blood-brain barrier (BBB), a semipermeable barrier that prevents large molecule drugs or contrast agents from leaving blood vessels and entering into the brain tissue.1 Over the past two decades, microbubble-assisted FUS has been developed to safely and effectively deliver therapeutics and contrast agents to the brain and is used in both pre-clinical and clinical studies.2

This project employs FUS to open the BBB and deliver photoacoustic (PA) contrast agents for ultrasound and photoacoustic (US/PA) imaging of the brain. Delivery of PA contrast such as gold nanorods (AuNRs) allows for localized US/PA imaging of the brain (Fig. 1).3 Further, these contrast agents can be functionalized to target specific diseases or disorders of the brain (Fig. 2).4,5 Targeted PA contrast agents could thus be used to monitor disease state in the brain over time using US/PA imaging techniques. One example of targeted US/PA imaging of the brain is through β-amyloid functionalized AuNRs.6 These targeted nanoparticles could be used in the monitoring of Alzheimer’s Disease (AD), which is characterized by pathogenic protein plaques composed of β-amyloid.4 Through the development of targeted PA contrast agents, progression of AD can be monitored non-invasively, through US/PA imaging.

Fig 1
Fig. 1 Setup of ultrasound and photoacoustic (US/PA) imaging system combined with focused ultrasound (FUS) used to open the blood-brain barrier (FUS and microbbbules), deliver PA contrast agents (gold nanorods) and image the brain (US/PA imaging system).^
Fig 2
Fig. 2 Ultrasound and photoacoustic (US/PA) imaging of a murine brain with gold nanorod (AuNR) contrast agent delivered via microbubble-assisted focused ultrasound (FUS). 2(a) and 2(b) show PA signal received from in vivo and ex vivo imaging, respectively. In 2(c-g) and 2(d-h), in vivo and ex vivo PA signal from blood and the FUS delivered AuNRs is separated using spectroscopic analysis. ^

Further Reading

  • R.K. Hartman, K.A. Hallam, E.M. Donnelly, S.Y. Emelianov, “Photoacoustic imaging of gold nanorods in the brain delivered via microbubble-assisted focused ultrasound: a tool for in vivo molecular neuroimaging,” Laser Physics Letters, 16, 025603 (2019)

References

  1. Vykhodtseva, N., McDannold, N. & Hynynen, K. Progress and problems in the application of focused ultrasound for blood-brain barrier disruption. Ultrasonics 48, 279-296, doi:10.1016/j.ultras.2008.04.004 (2008) ^
  2. Hynynen, K., McDannold, N., Vykhodtseva, N. & Jolesz, F. A. Non-invasive opening of BBB by focused ultrasound. Acta Neurochir Suppl 86, 555-558 (2003) ^
  3. Hartman, R.K., Hallam, K.A., Donnelly, E.M., Emelianov, S.Y. “Photoacoustic imaging of gold nanorods in the brain delivered via microbubble-assisted focused ultrasound: a tool for in vivo molecular neuroimaging,” Laser Physics Letters, 16, 025603 (2019) ^
  4. Lahiri, D. K. et al. A critical analysis of new molecular targets and strategies for drug developments in Alzheimer’s disease. Current Drug Targets 4, 97-112 (2003) ^
  5. Kumar, S., J. Aaron, and K. Sokolov, Directional conjugation of antibodies to nanoparticles for synthesis of multiplexed optical contrast agents with both delivery and targeting moieties. Nat Protoc, 2008. 3(2): p. 314-20 ^
  6. Hartman, R.K. Applications of Ultrasound and Photoacoustics in the Central Nervous System. The University of Texas at Austin. Dissertation. 2017. ^