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0044: Challenges and Advances in Medical Ultrasound Metrology - 100 MHz, Spatial Averaging Free Ultrasonic Hydrophone Probes for Theragnostic Applications
S8
Ultrasound in Medicine and Biology
this limitation include vector Doppler systems, transverse Doppler systems, speckle tracking systems and multiple beam methods. 2) The frame rate problem. In general Doppler frame rates are much lower than imaging frame rates because in order to get a reliable estimate of velocity it is necessary to sample each region of interest several (often between 8 and 16) times, whereas to generate a pulse-echo image it is only necessary to sample once. One potential solution to this is to use synthetic aperture techniques which greatly speed up image acquisition. 3) Axial resolution. The axial resolution of some Doppler systems is limited by the transmitted pulse length. A solution which has previously been applied to pulse echo systems is to use coded excitation. It now appears that a similar solution can be used for Doppler signals without introducing the serious artifacts that might be anticipated. 0041 Ultrasound Enhanced Thrombolysis Christy K Holland, University of Cincinnati, United States Azzdine Y Ammi, University of Oregon, United States Saurabh Datta, Siemens Medical Solutions USA Inc., United States Stephen R Perrin Jr, University of Cincinnati, United States Shauna L Beiler, University of Cincinnati, United States Christian R Beiler, University of Cincinnati, United States Kenneth R Wagner, University of Cincinnati, United States Ultrasound (US) acts synergistically with thrombolytic agents, such as recombinant tissue plasminogen activator (rt-PA), to accelerate thrombolysis. Stable cavitation is highly correlated with sonothrombolytic efficacy for rt-PA-mediated thrombolysis. A review of in vitro sonothrombolysis studies utilizing a commercial US contrast agent or echogenic liposomes loaded with rt-PA to nucleate stable cavitation will be presented. Ultraharmonic signals, broadband emissions, and harmonics of the fundamental were measured acoustically using a focused hydrophone as a passive cavitation detector and utilized to quantify the level of cavitation activity. The thrombolytic efficacy of rt-PA in combination with 120-kHz US was also explored in vivo using a porcine intracerebral hemorrhagic stroke model. Clots were formed by gently infusing 3 ml of autologous blood into the frontal white matter of 28 mixed-bred Yorkshire pigs (20.5 ⫾ 3.1 kg) and incubated for 3 hr. For these nonsurvival studies, 6 pig received rt-PA only (0.3 cc of 0.107 g/ml), 6 received 120-kHz pulsed US alone, 6 received rt-PA plus 120-kHz pulsed US exposure, and 6 were reserved as controls (saline injection, no rt-PA and no 120-kHz US exposure). Clots treated with rt-PA alone exhibit a volume loss of 55.0% and clots treated with rt-PA and 120-kHz US have a significantly higher volume loss of 72.5% and a higher penetration of rt-PA. Thus 120-kHz pulsed US enhancement of thrombolysis has been demonstrated both in vitro and in an in vivo porcine hemorrhagic stroke model. This work was supported by NIH 1RO1 NS047603. 0043 Visualization of Microstructure of the Skin by 3D Ultrasound Microscope Yoshifumi Saijo, Tohoku University, Japan Kazuto Kobayashi, Honda Electronics Co. Ltd., Japan Naohiro Hozumi, Aichi Institute of Technology, Japan Akira Tanaka, Fukushima University, Japan Non-invasive imaging technique capable of visualizing microstructure of the skin is strongly desired for dermatological and cosmetic purposes. In the present study, three-dimensional (3D) ultrasound microscope with the central frequency of 100 MHz was developed and applied for imaging of 3D structure of human skin.
Volume 35, Number 8S, 2009 A PVDF ultrasonic transducer with the central frequency of 100 MHz and the focal length of 3.2 mm was mechanically scanned over the objects by two linear servo motors controlled by a personal computer. Conventional echo gel was used as the coupling medium between transducer and skin surface. Reflected ultrasound was digitized by a fast digitizer card at the sampling frequency of 1 GHz and the resolution of 8-bits. Each RF line consisted of 2000 points and a single B-mode image consisted of 300 lines which corresponded 1.5 mm in depth and 2.4 mm in width. Serial B-mode imaging was made with 8-micron intervals. Finally, 3D ultrasound data of 1.5x2.4x2.4 mm space was obtained. In each B-mode image, surface of skin, hair-follicle and microvessel was registered and 3D reconstructed image was obtained. Stratum corneum, epidermis and dermis were clearly classified by the echo intensity. Small, round, low echo region was continuously observed in the serial sections in the dermis and it was considered as the microvessel. 3D image visualized 3D structure of hair-follicle from the skin surface to the bud of hair-follicle in dermis. The 3D ultrasound microscope noninvasively showed microstructure of the skin. 0044 Challenges and Advances in Medical Ultrasound Metrology - 100 MHz, Spatial Averaging Free Ultrasonic Hydrophone Probes for Theragnostic Applications Peter A Lewin, Drexel University, Philadelphia, United States Sumet Umchid, King Mongkut’s University of Technology, North Bangkok 10800, Thailand Rupa Gopinath, Drexel University, Philadelphia, United States Karthik Srinivasan, Drexel University, Philadelphia, United States Khushali Manseta, Drexel University, Philadelphia, United States Mahmoud El-Sherif, 3Photonics Laboratories, Inc. Philadelphia, United States The primary objective of this work was to develop spatial averaging free fiber optic (FO) hydrophone probe suitable for measurements of theragnostic (i.e. diagnostic and therapeutic, including HITU) ultrasound fields in the frequency range 1-100 MHz. The innovative elements of this research include implementation and testing of a prototype FO sensor with an active diameter of about 7 m (half wavelength at 100 MHz) that exhibits unprecedented and exceptionally high conversion factor of 2000 mV/MPa or 2V/MPa and development of novel calibration approach, which allows the sensitivity of the hydrophone probes to be determined as a virtually continuous function of frequency. The near continuous frequency calibration approach allowed the uniformity of the FO sensor frequency response to be verified. As anticipated, the overall uncertainty of the calibration was dependent on frequency and determined to be about ⫾12% (⫾1 dB) up to 40 MHz, ⫾20% (⫾1.5 dB) from 40 to 60 MHz and ⫾25% (⫾2 dB) from 60 to 100 MHz. The outcome of this research indicates that once fully developed and calibrated, the combined acousto-optic system will constitute a universal reference tool in the wide, 100 MHz bandwidth. Also, because the sensitivity of the FO probes is frequency independent their phase shift is zero in the whole frequency range considered; that feature makes them particularly suitable to determine phase shift of other ultrasonic hydrophone probes, so if needed, deconvolution of the pressure-time waveform can be performed. This work was supported by the NIH grant 5 RO1 EB007117. 0045 A Single-Element Ultrasonic Vessel Locator and Ablator Chung-Ting Ko, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taiwan Wen-Shiang Chen, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taiwan
Ultrasound in Medicine and Biology
this limitation include vector Doppler systems, transverse Doppler systems, speckle tracking systems and multiple beam methods. 2) The frame rate problem. In general Doppler frame rates are much lower than imaging frame rates because in order to get a reliable estimate of velocity it is necessary to sample each region of interest several (often between 8 and 16) times, whereas to generate a pulse-echo image it is only necessary to sample once. One potential solution to this is to use synthetic aperture techniques which greatly speed up image acquisition. 3) Axial resolution. The axial resolution of some Doppler systems is limited by the transmitted pulse length. A solution which has previously been applied to pulse echo systems is to use coded excitation. It now appears that a similar solution can be used for Doppler signals without introducing the serious artifacts that might be anticipated. 0041 Ultrasound Enhanced Thrombolysis Christy K Holland, University of Cincinnati, United States Azzdine Y Ammi, University of Oregon, United States Saurabh Datta, Siemens Medical Solutions USA Inc., United States Stephen R Perrin Jr, University of Cincinnati, United States Shauna L Beiler, University of Cincinnati, United States Christian R Beiler, University of Cincinnati, United States Kenneth R Wagner, University of Cincinnati, United States Ultrasound (US) acts synergistically with thrombolytic agents, such as recombinant tissue plasminogen activator (rt-PA), to accelerate thrombolysis. Stable cavitation is highly correlated with sonothrombolytic efficacy for rt-PA-mediated thrombolysis. A review of in vitro sonothrombolysis studies utilizing a commercial US contrast agent or echogenic liposomes loaded with rt-PA to nucleate stable cavitation will be presented. Ultraharmonic signals, broadband emissions, and harmonics of the fundamental were measured acoustically using a focused hydrophone as a passive cavitation detector and utilized to quantify the level of cavitation activity. The thrombolytic efficacy of rt-PA in combination with 120-kHz US was also explored in vivo using a porcine intracerebral hemorrhagic stroke model. Clots were formed by gently infusing 3 ml of autologous blood into the frontal white matter of 28 mixed-bred Yorkshire pigs (20.5 ⫾ 3.1 kg) and incubated for 3 hr. For these nonsurvival studies, 6 pig received rt-PA only (0.3 cc of 0.107 g/ml), 6 received 120-kHz pulsed US alone, 6 received rt-PA plus 120-kHz pulsed US exposure, and 6 were reserved as controls (saline injection, no rt-PA and no 120-kHz US exposure). Clots treated with rt-PA alone exhibit a volume loss of 55.0% and clots treated with rt-PA and 120-kHz US have a significantly higher volume loss of 72.5% and a higher penetration of rt-PA. Thus 120-kHz pulsed US enhancement of thrombolysis has been demonstrated both in vitro and in an in vivo porcine hemorrhagic stroke model. This work was supported by NIH 1RO1 NS047603. 0043 Visualization of Microstructure of the Skin by 3D Ultrasound Microscope Yoshifumi Saijo, Tohoku University, Japan Kazuto Kobayashi, Honda Electronics Co. Ltd., Japan Naohiro Hozumi, Aichi Institute of Technology, Japan Akira Tanaka, Fukushima University, Japan Non-invasive imaging technique capable of visualizing microstructure of the skin is strongly desired for dermatological and cosmetic purposes. In the present study, three-dimensional (3D) ultrasound microscope with the central frequency of 100 MHz was developed and applied for imaging of 3D structure of human skin.
Volume 35, Number 8S, 2009 A PVDF ultrasonic transducer with the central frequency of 100 MHz and the focal length of 3.2 mm was mechanically scanned over the objects by two linear servo motors controlled by a personal computer. Conventional echo gel was used as the coupling medium between transducer and skin surface. Reflected ultrasound was digitized by a fast digitizer card at the sampling frequency of 1 GHz and the resolution of 8-bits. Each RF line consisted of 2000 points and a single B-mode image consisted of 300 lines which corresponded 1.5 mm in depth and 2.4 mm in width. Serial B-mode imaging was made with 8-micron intervals. Finally, 3D ultrasound data of 1.5x2.4x2.4 mm space was obtained. In each B-mode image, surface of skin, hair-follicle and microvessel was registered and 3D reconstructed image was obtained. Stratum corneum, epidermis and dermis were clearly classified by the echo intensity. Small, round, low echo region was continuously observed in the serial sections in the dermis and it was considered as the microvessel. 3D image visualized 3D structure of hair-follicle from the skin surface to the bud of hair-follicle in dermis. The 3D ultrasound microscope noninvasively showed microstructure of the skin. 0044 Challenges and Advances in Medical Ultrasound Metrology - 100 MHz, Spatial Averaging Free Ultrasonic Hydrophone Probes for Theragnostic Applications Peter A Lewin, Drexel University, Philadelphia, United States Sumet Umchid, King Mongkut’s University of Technology, North Bangkok 10800, Thailand Rupa Gopinath, Drexel University, Philadelphia, United States Karthik Srinivasan, Drexel University, Philadelphia, United States Khushali Manseta, Drexel University, Philadelphia, United States Mahmoud El-Sherif, 3Photonics Laboratories, Inc. Philadelphia, United States The primary objective of this work was to develop spatial averaging free fiber optic (FO) hydrophone probe suitable for measurements of theragnostic (i.e. diagnostic and therapeutic, including HITU) ultrasound fields in the frequency range 1-100 MHz. The innovative elements of this research include implementation and testing of a prototype FO sensor with an active diameter of about 7 m (half wavelength at 100 MHz) that exhibits unprecedented and exceptionally high conversion factor of 2000 mV/MPa or 2V/MPa and development of novel calibration approach, which allows the sensitivity of the hydrophone probes to be determined as a virtually continuous function of frequency. The near continuous frequency calibration approach allowed the uniformity of the FO sensor frequency response to be verified. As anticipated, the overall uncertainty of the calibration was dependent on frequency and determined to be about ⫾12% (⫾1 dB) up to 40 MHz, ⫾20% (⫾1.5 dB) from 40 to 60 MHz and ⫾25% (⫾2 dB) from 60 to 100 MHz. The outcome of this research indicates that once fully developed and calibrated, the combined acousto-optic system will constitute a universal reference tool in the wide, 100 MHz bandwidth. Also, because the sensitivity of the FO probes is frequency independent their phase shift is zero in the whole frequency range considered; that feature makes them particularly suitable to determine phase shift of other ultrasonic hydrophone probes, so if needed, deconvolution of the pressure-time waveform can be performed. This work was supported by the NIH grant 5 RO1 EB007117. 0045 A Single-Element Ultrasonic Vessel Locator and Ablator Chung-Ting Ko, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taiwan Wen-Shiang Chen, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taiwan