# US 12,109,441 B2 · Extracorporeal therapeutic ultrasound for promoting vasodilation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,109,441 B2 - Document ID: US12109441B2 - Status: Granted - Kind: B2 - Application number: 18/310,450 - Filed: 2023-05-01 - Published: 2023-10-05 - Granted: 2024-10-08 - Earliest claimed: 2016-10-16 - Assignees: Vibrato Medical, Inc. - Applicants: Vibrato Medical, Inc. - Inventors: Babak Nazer; John For Migliazza - Web page: https://patentgrep.com/patent/US12109441B2 ## CPC - A61N 7/02: Localised ultrasound hyperthermia - A61N 7/00: Ultrasound therapy (lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 {; using ultrasound for introducing media into the body A61M37/0092}) - A61N 2007/0056: {Beam shaping elements} - A61N 2007/0078: {with multiple treatment transducers} - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract Systems and methods can include wearable, non-invasive ultrasound modalities for treating a variety of medical conditions, including but not limited to peripheral vascular disease. The modality could be therapeutic ultrasound (TUS), and be configured to promote angiogenesis within a patient via stimulation of cavitation and shear stress, among other mechanisms. ## Claims ### Claim 1 A method of treating peripheral vascular disease by stimulating vasodilation within a patient, comprising: providing a wearable non-invasive device comprising a flexible housing material and an array of ultrasound transducers operably attached to the flexible housing material; positioning the device and the array of transducers proximate a skin surface of a patient above at least one target site angiosome below the knee where vasodilation is desired, and such that the flexible housing material and the array of ultrasound transducers conforms to the skin surface of one or more of the calf, ankle, and foot of the patient; and causing a therapeutically effective amount of therapeutic ultrasonic energy to be directed toward the target site angiosome without delivering a drug, to stimulate cavitation and shear stress within tissue at the target site angiosome, to stimulate the production and/or release of growth factors, angiogenic factors, tissue vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), basic fibroblast growth factor (bFGF), or adenosine triphosphate (ATP) and to stimulate vasodilation within the patient, and assessing acoustic or electrical parameters of individual transducers of the array of ultrasound transducers during therapy to determine the presence of bone or air in a near-field, and thereby reducing or ceasing power to one or more of the individual transducers if bone or air is found to be present in the near-field, wherein said causing the therapeutically effective amount of therapeutic ultrasonic energy to be directed toward the target site angiosome occurs for at least 15 minutes per treatment session and for at least five treatment sessions, wherein the therapeutic ultrasonic energy has a mechanical index in the range of 2 to 6, wherein the therapeutic ultrasonic energy has a peak negative pressure between 1 MPa and 4 MPa, wherein the therapeutic ultrasonic energy has a derated spatial-peak pulse-average intensity (Isppa) between 190 W/cm2 and 1,000 W/cm2, and wherein each transducer of the array of ultrasound transducers is operated at a duty cycle of no more than 1%. ### Claim 2 (depends on 1) The method of claim 1, wherein the therapeutic ultrasonic energy has a frequency of between 250 kHz and 5 MHz. ### Claim 3 (depends on 1) The method of claim 1, wherein the therapeutic ultrasonic energy has a frequency of between 400 kHz and 1.5 MHz. ### Claim 4 (depends on 1) The method of claim 1, each transducer of the array of ultrasound transducers is operated at a duty cycle of no more than 0.10%. ### Claim 5 (depends on 1) The method of claim 1, wherein each transducer of the array of ultrasound transducers is operated at a duty cycle of no more than 0.05%. ### Claim 6 A method of stimulating vasodilation within a patient, comprising: providing a wearable non-invasive device comprising at least one ultrasound transducer; positioning the at least one ultrasound transducer or an array of transducers proximate a skin surface of a patient above a target site below the skin surface where vasodilation is desired; causing a therapeutically effective amount of therapeutic ultrasonic energy over a set time period to be directed toward the target site, thereby stimulating cavitation and shear stress within tissue at the target site, and stimulating vasodilation within the patient, wherein the therapeutic ultrasonic energy has a mechanical index in the range of 2 to 6, wherein the therapeutic ultrasonic energy has a peak negative pressure of between 1 MPa and 4 MPa, wherein each transducer is operated at a duty cycle of no more than 1%, and wherein the therapeutic ultrasonic energy has a derated spatial-peak pulse-average intensity (Isppa) between 190 W/cm2 and 1,000 W/cm2. ### Claim 7 (depends on 6) The method of claim 6, wherein the transducer comprises a therapeutic ultrasound (TUS) transducer. ### Claim 8 (depends on 6) The method of claim 6, wherein the wearable device is circumferentially wrapped around a portion of an extremity of the patient. ### Claim 9 (depends on 8) The method of claim 8, wherein the extremity is a lower extremity. ### Claim 10 (depends on 6) The method of claim 6, wherein the skin surface is on at least one of a thigh, a calf, an ankle, and a foot of a patient. ### Claim 11 (depends on 6) The method of claim 6, for treating peripheral vascular disease. ### Claim 12 (depends on 6) The method of claim 6, wherein positioning the at least one ultrasound transducer proximate a skin surface comprises positioning the at least one ultrasound transducer on the posterior surface of the patient's calf, the patient's ankle, or the patient's foot. ### Claim 13 (depends on 6) The method of claim 6, further comprising measuring blood flow at the target site. ### Claim 14 (depends on 6) The method of claim 6, further comprising sensing the temperature at the skin surface, and decreasing or terminating the therapeutic ultrasonic energy delivery if the temperature is above a pre-determined level. ### Claim 15 (depends on 6) The method of claim 6, further comprising assessing acoustic or electrical parameters of at least one of the individual transducers during therapy to determine the presence of bone or air in a near-field, and thereby reducing or ceasing power to the one or more of the individual transducers if bone or air is found to be present in the near-field. ### Claim 16 (depends on 15) The method of claim 15, further comprising adjusting a parameter of the therapeutic ultrasonic energy such that the target site is in a near-field, and bony structures of the patient are in a far-field. ### Claim 17 (depends on 6) The method of claim 6, wherein the target site is selected from the group consisting of: a gastrocnemius muscle, a soleus muscle, and a posterior tibial artery. ### Claim 18 (depends on 6) The method of claim 6, wherein the set time period is at least 15 minutes. ### Claim 19 (depends on 18) The method of claim 18, wherein the set time period is at least 30 minutes. ### Claim 20 (depends on 6) The method of claim 6, wherein the set time period comprises at least five treatment sessions. ### Claim 21 A system for stimulating vasodilation within a patient, comprising: a wearable non-invasive device comprising an elastic sleeve comprising at least one therapeutic ultrasound (TUS) transducer configured to be positioned proximate a skin surface of a patient above a target site below the skin surface where vasodilation is desired, wherein the ultrasound transducer is configured to cause a therapeutically effective amount of therapeutic ultrasonic energy over a set time period to be directed toward the target site, thereby stimulating cavitation and shear stress within tissue at the target site, and wherein the ultrasound transducer is further configured to stimulate vasodilation within the patient at the target site, wherein the therapeutic ultrasonic energy has a frequency of between 400 kHz and 1.5 MHz, wherein each transducer is operated at a duty cycle of no more than 1%, wherein the therapeutic ultrasonic energy has a mechanical index in the range of 2 to 6, wherein the therapeutic ultrasonic energy has a peak negative pressure of between 1 MPa and 4 MPa, and wherein the therapeutic ultrasonic energy has a derated spatial-peak pulse-average intensity (Isppa) between 190 W/cm2 and 1,000 W/cm2; a portable power supply operably attached to the sleeve; and an adhesive gel pack positionable between (a) the skin surface and (b) the at least one ultrasound transducer and the elastic sleeve. ### Claim 22 (depends on 21) The system of claim 21, wherein the at least one TUS transducer is configured to deliver the therapeutic ultrasonic energy at a pulse duration of between 1 ms and 10 ms. ### Claim 23 (depends on 21) The system of claim 21, comprising an array of TUS transducers, wherein the array of TUS transducers comprises solid piezoelectric materials and a backing material. ### Claim 24 (depends on 21) The system of claim 21, wherein the set time period is at least 15 minutes. ### Claim 25 (depends on 21) The system of claim 21, wherein the set time period is at least 30 minutes. ### Claim 26 (depends on 21) The system of claim 21, wherein the set time period comprises at least five treatment sessions.