Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo

D. E. Kruse, M. A. Mackanos, C. E. O'Connell-Rodwell, C. H. Contag, K. W. Ferrara

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The development of transgenic reporter mice and advances in in vivo optical imaging have created unique opportunities to assess and analyze biological responses to thermal therapy directly in living tissues. Reporter mice incorporating the regulatory regions from the genes encoding the 70 kDa heat-shock proteins (Hsp70) and firefly luciferase (luc) as reporter genes can be used to non-invasively reveal gene activation in living tissues in response to thermal stress. High-intensity-focused ultrasound (HIFU) can deliver measured doses of acoustic energy to highly localized regions of tissue at intensities that are sufficient to stimulate Hsp70 expression. We report activation of Hsp70-luc expression using 1 s duration HIFU heating to stimulate gene expression in the skin of the transgenic reporter mouse. Hsp70 expression was tracked for 96 h following the application of 1.5 MHz continuous-wave ultrasound with spatial peak intensities ranging from 53 W cm-2 up to 352 W cm-2. The results indicated that peak Hsp70 expression is observed 6-48 h post-heating, with significant activity remaining at 96 h. Exposure durations were simulated using a finite-element model, and the predicted temperatures were found to be consistent with the observed Hsp70 expression patterns. Histological evaluation revealed that the thermal damage starts at the stratum corneum and extends deeper with increasing intensity. These results indicated that short-duration HIFU may be useful for inducing heat-shock expression, and that the period between treatments needs to be greater than 96 h due to the protective properties of Hsp70.

Original languageEnglish (US)
Pages (from-to)3641-3660
Number of pages20
JournalPhysics in Medicine and Biology
Volume53
Issue number13
DOIs
StatePublished - Jul 7 2008

Fingerprint

stimulation
Hot Temperature
Ultrasonics
Tissue
genes
Heating
Transgenic Mice
mice
Genes
Chemical activation
Firefly Luciferases
Gene encoding
HSP70 Heat-Shock Proteins
Nucleic Acid Regulatory Sequences
Optical Imaging
Regulator Genes
Luciferases
shock
Reporter Genes
fireflies

ASJC Scopus subject areas

  • Biomedical Engineering
  • Physics and Astronomy (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Kruse, D. E., Mackanos, M. A., O'Connell-Rodwell, C. E., Contag, C. H., & Ferrara, K. W. (2008). Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo. Physics in Medicine and Biology, 53(13), 3641-3660. https://doi.org/10.1088/0031-9155/53/13/017

Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo. / Kruse, D. E.; Mackanos, M. A.; O'Connell-Rodwell, C. E.; Contag, C. H.; Ferrara, K. W.

In: Physics in Medicine and Biology, Vol. 53, No. 13, 07.07.2008, p. 3641-3660.

Research output: Contribution to journalArticle

Kruse, DE, Mackanos, MA, O'Connell-Rodwell, CE, Contag, CH & Ferrara, KW 2008, 'Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo', Physics in Medicine and Biology, vol. 53, no. 13, pp. 3641-3660. https://doi.org/10.1088/0031-9155/53/13/017
Kruse DE, Mackanos MA, O'Connell-Rodwell CE, Contag CH, Ferrara KW. Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo. Physics in Medicine and Biology. 2008 Jul 7;53(13):3641-3660. https://doi.org/10.1088/0031-9155/53/13/017
Kruse, D. E. ; Mackanos, M. A. ; O'Connell-Rodwell, C. E. ; Contag, C. H. ; Ferrara, K. W. / Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo. In: Physics in Medicine and Biology. 2008 ; Vol. 53, No. 13. pp. 3641-3660.
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