Effect of High-Intensity Ultrasound–Targeted Microbubble Destruction on Perfusion and Function of the Rat Heart Assessed by Pinhole-Gated SPECT

Hernot, Sophie; Cosyns, Bernard; Droogmans, Steven; Garbar, Christian; Couck, Pedro; Vanhove, Christian; Caveliers, Vicky; Camp, Guy Van; Bossuyt, Axel; Lahoutte, Tony

doi:10.1016/j.ultrasmedbio.2009.08.011

Cited by 7 publications

(5 citation statements)

References 42 publications

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“…The images were reconstructed using a modified version of the ordered-subsets expectation maximization algorithm, previously described by Vanhove et al (16,17). Corrections were made for attenuation and scatter (15,17,18).…”

Section: Micro-spect and Micro-ct Acquisition And Data Analysismentioning

confidence: 99%

Serial Semiquantitative Imaging of Brain Damage Using Micro-SPECT and Micro-CT After Endothelin-1–Induced Transient Focal Cerebral Ischemia in Rats

Ceulemans¹,

Hernot

Zgavc³

et al. 2011

J Nucl Med

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In this study, we validated the use of 99m Tc-hexamethylpropyleneamine oxime ( 99m Tc-HMPAO) micro-SPECT combined with micro-CT for semiquantification of the infarct size after an experimental stroke in rats and compared our observations with those obtained from histology. This imaging strategy was applied to measure the longitudinal effect of mild hypothermia on the progression of brain damage after stroke in rats. Methods: The endothelin-1 model was used to elicit a transient focal cerebral ischemia in rats. This resulted in a reproducible insult in which the core is represented by the striatum and the penumbra by the cortex. Micro-SPECT and micro-CT images were taken at 1, 3, and 7 d after infusion of endothelin-1 and compared with those taken before the insult. After the last acquisition, rats were sacrificed and the infarct volume was determined via Nissl staining. The results obtained with micro-SPECT and micro-CT were compared with histology at the same time points. Mild hypothermia (33°C) was induced for 2 h, starting 20 min after the insult. Results: Brain damage was estimated using micro-SPECT and micro-CT and was reproducible with minimal interobserver variability. Normothermic stroke rats had reduced 99m Tc-HMPAO uptake at 1 and 3 d after the insult, whereas hypothermia improved damage after stroke. These findings corroborate with histology at the same time points. At 1 wk after the insult, no reduction of radioactive uptake was observed in any treatment group. Conclusion: Micro-SPECT and micro-CT allow quick and reproducible semiquantification of brain damage as an interesting alternative to histology to measure the extent of infarcted tissue in small animals after stroke.

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Section: Micro-spect and Micro-ct Acquisition And Data Analysismentioning

confidence: 99%

Serial Semiquantitative Imaging of Brain Damage Using Micro-SPECT and Micro-CT After Endothelin-1–Induced Transient Focal Cerebral Ischemia in Rats

Ceulemans¹,

Hernot

Zgavc³

et al. 2011

J Nucl Med

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“…This leads to transiently increased capillary and cell membrane permeability in the near vicinity of the ruptured MBs that may be due to the formation of micropores in cell membrane. 41,42 Furthermore, it has been shown that the conditions for UTMD-mediated gene delivery are different for different animals and tissues. In a specific time and space, we can crush the MBs within the target tissue to enhance the target effect of the genes.…”

Section: Discussionmentioning

confidence: 99%

“…Studies from clinical and animal studies have shown that high-intensity UTMD can induce biomarker release and transient histologically definable extravasation. 41,42 Furthermore, it has been shown that the conditions for UTMD-mediated gene delivery are different for different animals and tissues. Therefore, it is particularly important to determine the threshold between therapeutic and toxic effects of UTMD.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound‐Targeted Microbubble Destruction Enhances Gene Expression of microRNA‐21 in Swine Heart via Intracoronary Delivery

Liu

et al. 2015

Echocardiography

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“…The same ROI was transposed to the contralateral side to determine radioactivity counts in the brain region without probe implant (Figure S1E). Corrections were made for attenuation and scatter (Meikle et al ., 2005; Vanhove et al ., 2009; Hernot et al ., 2010). 99m Tc‐Nb_An33 and 99m Tc‐Sestamibi brain uptake was calculated as the counts in the tissue divided by the IA and normalized for the ROI size (%IA·cm −3 ).…”

Section: Methodsmentioning

confidence: 99%

Using microdialysis to analyse the passage of monovalent nanobodies through the blood–brain barrier

Caljon

Caveliers

Lahoutte

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSE Nanobodies are promising antigen‐binding moieties for molecular imaging and therapeutic purposes because of their favourable pharmacological and pharmacokinetic properties. However, the capability of monovalent nanobodies to reach targets in the CNS remains to be demonstrated. EXPERIMENTAL APPROACH We have assessed the blood–brain barrier permeability of Nb_An33, a nanobody against the Trypanosoma brucei brucei variant‐specific surface glycoprotein (VSG). This analysis was performed in healthy rats and in rats that were in the encephalitic stage of African trypanosomiasis using intracerebral microdialysis, single photon emission computed tomography (SPECT) or a combination of both methodologies. This enabled the quantification of unlabelled and 99mTc‐labelled nanobodies using, respectively, a sensitive VSG‐based nanobody‐detection elisa, radioactivity measurement in collected microdialysates and SPECT image analysis. KEY RESULTS The combined read‐out methodologies showed that Nb_An33 was detected in the brain of healthy rats following i.v. injection, inflammation‐induced damage to the blood–brain barrier, as in the late encephalitic stage of trypanosomiasis, significantly increased the efficiency of passage of the nanobody through this barrier. Complementing SPECT analyses with intracerebral microdialysis improved analysis of brain disposition. There is clear value in assessing penetration of the blood–brain barrier by monovalent nanobodies in models of CNS inflammation. Our data also suggest that rapid clearance from blood might hamper efficient targeting of specific nanobodies to the CNS. CONCLUSIONS AND IMPLICATIONS Nanobodies can enter the brain parenchyma from the systemic circulation, especially in pathological conditions where the blood–brain barrier integrity is compromised.

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Effect of High-Intensity Ultrasound–Targeted Microbubble Destruction on Perfusion and Function of the Rat Heart Assessed by Pinhole-Gated SPECT

Cited by 7 publications

References 42 publications

Serial Semiquantitative Imaging of Brain Damage Using Micro-SPECT and Micro-CT After Endothelin-1–Induced Transient Focal Cerebral Ischemia in Rats

Serial Semiquantitative Imaging of Brain Damage Using Micro-SPECT and Micro-CT After Endothelin-1–Induced Transient Focal Cerebral Ischemia in Rats

Ultrasound‐Targeted Microbubble Destruction Enhances Gene Expression of microRNA‐21 in Swine Heart via Intracoronary Delivery

Using microdialysis to analyse the passage of monovalent nanobodies through the blood–brain barrier

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