SBIR-STTR Award

?Stress urinary incontinence (SUI) in women is an increase of pelvic floor compliance which results in decrease of urethral pressure, typically through childbirth, and presents as urine leakage during exertion. SUI has significant impact on women's health, including an association with increased levels of depression. Curative options are limited to the invasive surgical insertion of a tape implant which limits the mobility of the urethra. Bulking agents injected in the peri-urethral tissue are a longstanding effective but temporary treatment. Pharmaceuticals are relatively new, prohibitively expensive, and there is no track record of long term efficacy. The remaining 14 million women are relegated to the palliative approaches of wearing absorptive pads or diapers. A substantial clinical need exists for a noninvasive alternative to traditional surgical approaches with the promise of less morbidity and recovery time, faster procedure time, and lower cost. Recent clinical investigations of minimally-invasive thermal techniques have demonstrated targeted thermal modification of tissue can reduce symptoms of SUI. These techniques have shown promise, but are more invasive than the current surgical options and are less effective. Therapeutic and interstitial ultrasound devices are an innovative technology under development by our group for delivering thermal therapy for treating cancer, as well as uterine fibroids, with demonstrated capabilities to provide dynamic spatial control of selective heating patterns, greater radial thermal penetration, and fast treatment times. We propose to develop this ultrasound technology specifically for the treatment of SUI; this technology has potential to provide a superior minimally-invasive heating technique for treating SUI with the promise of more accurate and thorough targeting, protection of critical non-targeted tissue (e.g., urethra, vaginal wall), more accessibility to a larger numbe of SUI patients, and faster procedure times. The objective of this Phase I research plan is to extend existing technology and develop transurethral therapeutic ultrasound applicators specific for selective and conformal thermal therapy of specific tissue structures required for successful treatment of SUI. Empirical design, bench experiments, biothermal and acoustic modeling, together with experimental testing in both ex-vivo tissues and a pilot in-vivo study in older ewes GU tract will be used for design feedback and to characterize device performance, as well as assess the technical and potential clinical feasibility. These results will be applied to the development and understanding of refined devices and potential treatment approaches in preparation for the ultimate goal of product development and clinical implementation during Phase II.

Public Health Relevance Statement:


Public Health Relevance:
Stress urinary incontinence (SUI) is a condition which affects more than 15 million American women. Those who seek treatment results in close to 250,000 surgical and other therapeutic interventions each year. The condition presents as inadvertent urinary leakage during exertion, such as exercise, lifting, or laughing. The curative interventions currently available are either invasive surgery/implants or too expensive. The vast majority seek palliative therapies, such as absorptive pads and diapers, as their only alternative. The problems associated with SUI extend beyond the apparent symptoms of inadvertent urinary leakage. The associated effects on freedom of activity, embarrassment, self-esteem, and mental health (SUI has a direct association with depression in sufferers) are significant. There is a strong need for a noninvasive and relatively inexpensive method to address the condition in these women's lives. This proposed new high intensity ultrasound treatment would address both of those issues. Therapeutic ultrasound requires no incisions and may be performed with topical anesthetic. The proposed design of the delivery device will be inexpensive, outpatient/office based, quick and simple 2 minute single treatment procedure allowing many women to receive a curative treatment for a lower payment than they spend annually on palliative absorptive pads and diapers. Moreover, the proposed technique aims to treat SUI using the concept of personalized medicine where treatment energy pattern is administered according to the respective anatomy of the patient. As such, this treatment will provide a potential cure for the nearly 15 million women who remain untreated.

NIH Spending Category:
Bioengineering; Diagnostic Radiology; Urologic Diseases

Project Terms:
Ablation; Acoustics; Address; Adult; Adverse effects; Affect; American; Anatomy; Anesthetics; Animal Model; Animals; Asthma; base; Cadaver; Catheters; Childbirth; Chronic; Chronic Bronchitis; Clinical; clinical investigation; clinically relevant; Connective Tissue; cost; Coughing; Coupling; Data; Data Set; design; Development; Device Designs; Device or Instrument Development; Devices; Dose; dosimetry; Economics; Electric Stimulation; Evaluation; Exercise; Exertion; Expenditure; Extravasation; falls; Fascia; FDA approved; Feedback; Female; Female urethral structure; flexibility; Freedom; Frequencies (time pattern); Genitourinary system; Goals; Heating; Human; image guided; Implant; in vivo; innovative technologies; International; interstitial; Intervention; Lifting; Ligaments; Literature; Local anesthesia; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Mental Depression; Mental Health; Methods; minimally invasive; model design; Modeling; Modification; Morbidity - disease rate; Mucous Membrane; Operative Surgical Procedures; Outpatients; palliative; Palliative Care; Patients; Pattern; payment; Pelvic floor structure; Pelvis; Penetration; Performance; personalized medicine; Pharmacologic Substance; Phase; Physicians; Pilot Projects; Positioning Attribute; Preparation; pressure; Procedures; product development; Production; Property; public health relevance; Radial; Recovery; Research; Research Design; research study; Risk; Safety; self esteem; Severities; Shapes; Sheep; simulation; Sneezing; Societies; Specimen; Sphincter; stem cell therapy; Stress Urinary Incontinence; Structure; success; Surgical incisions; symptomatic improvement; Symptoms; System; Systems Development; Techniques; Technology; Testing; Theoretical model; Therapeutic; Therapeutic Intervention; three-dimensional modeling; Time; Tissues; Transducers; Ultrasonic Therapy; Ultrasonography; Urethra; urinary; urinary bladder neck; Urinary Incontinence; Urine; Uterine Fibroids; Vagina; Validation; Woman; Women's Health; Work

Stress urinary incontinence (SUI) in women is an increase of pelvic floor compliance which results in decrease of urethral pressure, typically through childbirth, and presents as urine leakage during exertion. SUI has significant impact on women's health, including an association with increased levels of depression. Curative options are limited to the invasive surgical insertion of a tape implant which limits the mobility of the urethra. Bulking agents injected in the peri-urethral tissue are a longstanding effective but temporary treatment. Pharmaceuticals are relatively new, prohibitively expensive, and there is no track record of long term efficacy. The remaining 14 million women are relegated to the palliative approaches of wearing absorptive pads or diapers. A substantial clinical need exists for a noninvasive alternative to traditional surgical approaches with the promise of less morbidity and recovery time, faster procedure time, and lower cost. Recent clinical investigations of minimally-invasive thermal techniques have demonstrated targeted thermal modification of tissue can reduce symptoms of SUI. These techniques have shown promise, but are more invasive than the current surgical options and are less effective. Therapeutic and interstitial ultrasound devices are an innovative technology under development by our group for delivering thermal therapy for treating cancer, as well as uterine fibroids, with demonstrated capabilities to provide dynamic spatial control of selective heating patterns, greater radial thermal penetration, and fast treatment times. We propose to develop this ultrasound technology specifically for the treatment of SUI; this technology has potential to provide a superior minimally-invasive heating technique for treating SUI with the promise of more accurate and thorough targeting, protection of critical non-targeted tissue (e.g., urethra, vaginal wall), more accessibility to a larger numbe of SUI patients, and faster procedure times. The objective of this Phase I research plan is to extend existing technology and develop transurethral therapeutic ultrasound applicators specific for selective and conformal thermal therapy of specific tissue structures required for successful treatment of SUI. Empirical design, bench experiments, biothermal and acoustic modeling, together with experimental testing in both ex-vivo tissues and a pilot in-vivo study in older ewes GU tract will be used for design feedback and to characterize device performance, as well as assess the technical and potential clinical feasibility. These results will be applied to the development and understanding of refined devices and potential treatment approaches in preparation for the ultimate goal of product development and clinical implementation during Phase II.

Public Health Relevance Statement:


Public Health Relevance:
Stress urinary incontinence (SUI) is a condition which affects more than 15 million American women. Those who seek treatment results in close to 250,000 surgical and other therapeutic interventions each year. The condition presents as inadvertent urinary leakage during exertion, such as exercise, lifting, or laughing. The curative interventions currently available are either invasive surgery/implants or too expensive. The vast majority seek palliative therapies, such as absorptive pads and diapers, as their only alternative. The problems associated with SUI extend beyond the apparent symptoms of inadvertent urinary leakage. The associated effects on freedom of activity, embarrassment, self-esteem, and mental health (SUI has a direct association with depression in sufferers) are significant. There is a strong need for a noninvasive and relatively inexpensive method to address the condition in these women's lives. This proposed new high intensity ultrasound treatment would address both of those issues. Therapeutic ultrasound requires no incisions and may be performed with topical anesthetic. The proposed design of the delivery device will be inexpensive, outpatient/office based, quick and simple 2 minute single treatment procedure allowing many women to receive a curative treatment for a lower payment than they spend annually on palliative absorptive pads and diapers. Moreover, the proposed technique aims to treat SUI using the concept of personalized medicine where treatment energy pattern is administered according to the respective anatomy of the patient. As such, this treatment will provide a potential cure for the nearly 15 million women who remain untreated.

NIH Spending Category:
Bioengineering; Diagnostic Radiology; Urologic Diseases

Project Terms:
Ablation; Acoustics; Address; Adult; Adverse effects; Affect; American; Anatomy; Anesthetics; Animal Model; Animals; Asthma; base; Cadaver; Catheters; Childbirth; Chronic; Chronic Bronchitis; Clinical; clinical investigation; clinically relevant; Connective Tissue; cost; Coughing; Coupling; curative treatments; Data; Data Set; design; Development; Device Designs; Device or Instrument Development; Devices; Dose; dosimetry; Economics; Electric Stimulation Therapy; Evaluation; Exercise; Exertion; Expenditure; Extravasation; falls; Fascia; FDA approved; Feedback; Female; Female urethral structure; flexibility; Freedom; Frequencies; Genitourinary system; Goals; Health; Heating; Human; image guided; Implant; in vivo; innovative technologies; International; interstitial; Lifting; Ligaments; Literature; Local anesthesia; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Mental Depression; Mental Health; Methods; minimally invasive; model design; Modeling; Modification; Morbidity - disease rate; Mucous Membrane; Operative Surgical Procedures; Outpatients; palliative; Palliative Care; Patients; Pattern; payment; Pelvic floor structure; Pelvis; Penetration; Performance; personalized medicine; Pharmacologic Substance; Phase; Physicians; Pilot Projects; Positioning Attribute; Preparation; pressure; Procedures; product development; Production; Property; Radial; Recovery; reduce symptoms; Research; Research Design; research study; Risk; Safety; self esteem; Severities; Shapes; Sheep; simulation; Sneezing; Societies; Specimen; Sphincter; stem cell therapy; Stress Urinary Incontinence; Structure; success; Surgical incisions; symptomatic improvement; Symptoms; System; Systems Development; Techniques; Technology; Testing; Theoretical model; Therapeutic; Therapeutic Intervention; three-dimensional modeling; Time; Tissues; Transducers; Ultrasonic Therapy; Ultrasonography; Urethra; urinary; urinary bladder neck; Urinary Incontinence; Urine; Uterine Fibroids; Vagina; Validation; Woman; Women's Health; Work