High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection
Low-intensity transcranial focused ultrasound (FUS) has gained momentum as a non-/minimally-invasive modality that facilitates the delivery of various pharmaceutical agents to the brain. With the additional ability to modulate regional brain tissue excitability, FUS is anticipated to confer potentia...
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| Format: | Article |
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Multidisciplinary Digital Publishing Institute
2022
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| Online Access: | https://hdl.handle.net/1721.1/145824 |
| _version_ | 1826201687946166272 |
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| author | Kim, Evgenii Van Reet, Jared Kim, Hyun-Chul Kowsari, Kavin Yoo, Seung-Schik |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Kim, Evgenii Van Reet, Jared Kim, Hyun-Chul Kowsari, Kavin Yoo, Seung-Schik |
| author_sort | Kim, Evgenii |
| collection | MIT |
| description | Low-intensity transcranial focused ultrasound (FUS) has gained momentum as a non-/minimally-invasive modality that facilitates the delivery of various pharmaceutical agents to the brain. With the additional ability to modulate regional brain tissue excitability, FUS is anticipated to confer potential neurotherapeutic applications whereby a deeper insight of its safety is warranted. We investigated the effects of FUS applied to the rat brain (Sprague-Dawley) shortly after an intracortical injection of fluorescent interstitial solutes, a widely used convection-enhanced delivery technique that directly (i.e., bypassing the blood–brain-barrier (BBB)) introduces drugs or interstitial tracers to the brain parenchyma. Texas Red ovalbumin (OA) and fluorescein isothiocyanate-dextran (FITC-d) were used as the interstitial tracers. Rats that did not receive sonication showed an expected interstitial distribution of OA and FITC-d around the injection site, with a wider volume distribution of OA (21.8 ± 4.0 µL) compared to that of FITC-d (7.8 ± 2.7 µL). Remarkably, nearly half of the rats exposed to the FUS developed intracerebral hemorrhaging (ICH), with a significantly higher volume of bleeding compared to a minor red blood cell extravasation from the animals that were not exposed to sonication. This finding suggests that the local cerebrovascular injury inflicted by the micro-injection was further exacerbated by the application of sonication, particularly during the acute stage of injury. Smaller tracer volume distributions and weaker fluorescent intensities, compared to the unsonicated animals, were observed for the sonicated rats that did not manifest hemorrhaging, which may indicate an enhanced degree of clearance of the injected tracers. Our results call for careful safety precautions when ultrasound sonication is desired among groups under elevated risks associated with a weakened or damaged vascular integrity. |
| first_indexed | 2024-09-23T11:55:27Z |
| format | Article |
| id | mit-1721.1/145824 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:55:27Z |
| publishDate | 2022 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | mit-1721.1/1458242023-06-28T20:18:20Z High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection Kim, Evgenii Van Reet, Jared Kim, Hyun-Chul Kowsari, Kavin Yoo, Seung-Schik Massachusetts Institute of Technology. Department of Mechanical Engineering Low-intensity transcranial focused ultrasound (FUS) has gained momentum as a non-/minimally-invasive modality that facilitates the delivery of various pharmaceutical agents to the brain. With the additional ability to modulate regional brain tissue excitability, FUS is anticipated to confer potential neurotherapeutic applications whereby a deeper insight of its safety is warranted. We investigated the effects of FUS applied to the rat brain (Sprague-Dawley) shortly after an intracortical injection of fluorescent interstitial solutes, a widely used convection-enhanced delivery technique that directly (i.e., bypassing the blood–brain-barrier (BBB)) introduces drugs or interstitial tracers to the brain parenchyma. Texas Red ovalbumin (OA) and fluorescein isothiocyanate-dextran (FITC-d) were used as the interstitial tracers. Rats that did not receive sonication showed an expected interstitial distribution of OA and FITC-d around the injection site, with a wider volume distribution of OA (21.8 ± 4.0 µL) compared to that of FITC-d (7.8 ± 2.7 µL). Remarkably, nearly half of the rats exposed to the FUS developed intracerebral hemorrhaging (ICH), with a significantly higher volume of bleeding compared to a minor red blood cell extravasation from the animals that were not exposed to sonication. This finding suggests that the local cerebrovascular injury inflicted by the micro-injection was further exacerbated by the application of sonication, particularly during the acute stage of injury. Smaller tracer volume distributions and weaker fluorescent intensities, compared to the unsonicated animals, were observed for the sonicated rats that did not manifest hemorrhaging, which may indicate an enhanced degree of clearance of the injected tracers. Our results call for careful safety precautions when ultrasound sonication is desired among groups under elevated risks associated with a weakened or damaged vascular integrity. 2022-10-14T12:57:59Z 2022-10-14T12:57:59Z 2022-10-06 2022-10-13T15:25:50Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/145824 Pharmaceutics 14 (10): 2120 (2022) PUBLISHER_CC http://dx.doi.org/10.3390/pharmaceutics14102120 Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf Multidisciplinary Digital Publishing Institute Multidisciplinary Digital Publishing Institute |
| spellingShingle | Kim, Evgenii Van Reet, Jared Kim, Hyun-Chul Kowsari, Kavin Yoo, Seung-Schik High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection |
| title | High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection |
| title_full | High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection |
| title_fullStr | High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection |
| title_full_unstemmed | High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection |
| title_short | High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection |
| title_sort | high incidence of intracerebral hemorrhaging associated with the application of low intensity focused ultrasound following acute cerebrovascular injury by intracortical injection |
| url | https://hdl.handle.net/1721.1/145824 |
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