{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T01:11:26Z","timestamp":1793841086794,"version":"4.6.1"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["16lm0103007j0005"],"award-info":[{"award-number":["16lm0103007j0005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17lk1403011h0001"],"award-info":[{"award-number":["17lk1403011h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Ultrasonics"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We previously developed a novel therapy with low-intensity pulsed ultrasound (LIPUS) that ameliorates cognitive decline through upregulation of endothelial nitric oxide synthase (eNOS) in mouse models of Alzheimer\u2019s disease (AD). In a randomized, double-blind, placebo-controlled pilot trial, we demonstrated that whole-brain LIPUS therapy is safe and tends to suppress the cognitive decline in early AD patients. We herein report the findings of our basic experiments that we performed for the pilot trial in order to apply whole-brain LIPUS therapy to humans, as well.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>First, we examined the relationship between bone density\/thickness and ultrasound transmittance using human temporal bone. Next, based on the results of ultrasound transmittance, we further examined mRNA expression of VEGF, FGF2, and eNOS in response to variable ultrasound frequencies, duty cycles, and sound pressures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There was a significant correlation between bone thickness and transmittance (1.0\u00a0MHz, P\u2009&lt;\u20090.001), while there was no significant correlation between bone density and transmittance (1.0\u00a0MHz, P\u2009=\u20090.421). At a frequency of 0.5\u00a0MHz, the optimum duty cycle was considered to be up to 20%. When the tissue amplitude was in the range of 0.05\u20130.5\u00a0MPa, VEGF, FGF2, and eNOS were significantly upregulated by LIPUS. Thus, the conditions necessary for LIPUS therapy for the human brain were identified as sound pressure just below the probe 1.3\u00a0MPa (tissue amplitude 0.15\u00a0MPa), duty cycle 5%, and frequency 0.5\u00a0MHz.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We successfully identified the optimal treatment conditions for LIPUS therapy for patients with AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10396-024-01461-9","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T12:02:39Z","timestamp":1714651359000},"page":"419-427","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Optimal treatment conditions for low-intensity pulsed ultrasound therapy for Alzheimer\u2019s disease: applications from mice to humans"],"prefix":"10.1007","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3420-9999","authenticated-orcid":false,"given":"Tomohiko","family":"Shindo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Eguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Monma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-4826","authenticated-orcid":false,"given":"Hiroaki","family":"Shimokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"1461_CR1","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1093\/eurheartj\/eht544","volume":"35","author":"ZS Katusic","year":"2014","unstructured":"Katusic ZS, Austin SA. Endothelial nitric oxide: protector of a healthy mind. Eur Heart J. 2014;35:888\u201394.","journal-title":"Eur Heart J"},{"key":"1461_CR2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104863","volume":"9","author":"K Hanawa","year":"2014","unstructured":"Hanawa K, Ito K, Aizawa K, et al. Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia. PLoS ONE. 2014;9: e104863.","journal-title":"PLoS ONE"},{"key":"1461_CR3","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1161\/ATVBAHA.115.306477","volume":"36","author":"T Shindo","year":"2016","unstructured":"Shindo T, Ito K, Ogata T, et al. Low-intensity pulsed ultrasound enhances angiogenesis and ameliorates left ventricular dysfunction in a mouse model of acute myocardial infarction. 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All of the patients included in this study gave written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statements"}}]}}