Publications by authors named "Hiroshi Furuhata"

22 Publications

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[Subacute Pseudoaneurysm Formation after Sutureless Repair for Postinfarction Left Ventricular Rupture:Report of a Case].

Kyobu Geka 2021 Sep;74(9):697-700

Department of Cardiovascular Surgery, Jichi Medical University Saitama Medical Center, Saitama, Japan.

A 71-year-old woman was admitted for cardiac tamponade due to left ventricular free wall rupture after acute myocardial infarction. Sutureless repair was performed for bleeding from the inferior wall. Fifteen days later, computed tomography demonstrated enlargement of a left ventricular pseudoaneurysm. Patch closure using a vascular prosthesis was performed through left thoracotomy. No recurrence of the left ventricular aneurysm has been observed since.
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September 2021

Perioperative factors associated with aneurysm sac size changes after endovascular aneurysm repair.

Surg Today 2019 Feb 12;49(2):130-136. Epub 2018 Sep 12.

Department of Cardiovascular Surgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Japan.

Purpose: To identify the perioperative factors associated with aneurysm size changes after endovascular aortic aneurysm repair (EVAR).

Methods: Between August, 2008 and December, 2014, 187 patients underwent EVAR treatment in our institution. The subjects of this study were 135 of these patients without peripheral artery disease, who were followed up with computed tomography (CT) for 3 years. Significant aneurysm size change was defined as sac size change of more than 5 mm from the baseline.

Results: Sac enlargement was identified in 25 patients (18.5%) and sac shrinkage was identified in 59 (43.7%) patients. The factors associated with sac enlargement were postoperative pulse wave velocity (OR: odds ratio 3.80, p = 0.047), prevalence of a type 2 endoleak 1 week after surgery (OR 4.26, p = 0.022), inner diameter (OR 1.10, p = 0.005), and distance from the lower renal artery to the terminal aorta (OR 1.05, p = 0.017). The factors associated with sac shrinkage were prevalence of a type 2 endoleak (OR 0.09, p < 0.001) and preoperative pulse wave velocity (OR 0.32, p = 0.022). The factors independently associated with type 2 endoleak were the use of an Excluder device (OR 3.99, p = 0.002) and the length of the aneurysm (OR 1.02, p = 0.027).

Conclusion: Inner diameter, treatment length, perioperative pulse wave velocity, and type 2 endoleak were associated with sac size changes after EVAR.
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http://dx.doi.org/10.1007/s00595-018-1714-zDOI Listing
February 2019

Transcranial color flow imaging can evaluate the severity of periventricular hyperintensity.

J Stroke Cerebrovasc Dis 2015 Jan 16;24(1):112-6. Epub 2014 Oct 16.

Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan.

Background: The goal of this study was to investigate the relationship between white matter lesions on magnetic resonance imaging and flow parameters in the middle cerebral artery (MCA) measured by transcranial color flow imaging.

Methods: Patients with acute ischemic stroke or transient ischemic attack were included. The relationship between severities of periventricular hyperintensity (PVH) and ultrasonographic parameters in the MCA was investigated. The frequency of PVH was calculated for different categories according to the presence or absence of 2 considerable parameters according to the value of area under the receiver operating characteristic curve.

Results: MCA flow was successfully measured in 203 temporal windows among 124 patients. After determining the cutoff value of end-diastolic velocity (EDV) and pulsatility index (PI) for the presence of PVH, 4 different categories were established: Category A, EDV more than 40 cm/second and PI less than .7; Category B, EDV more than 40 cm/second and PI more than .7; Category C, EDV less than 40 cm/second and PI less than .7; and Category D, EDV less than 40 cm/second and PI more than .7. The prevalence of PVH gradually increased along with category (P < .01).

Conclusions: The evaluation of MCA parameters using the combination of PI and EDV may be useful for the prediction of PVH.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.07.027DOI Listing
January 2015

Stiffness parameter β of cardioembolism measured by carotid ultrasound was lower than other stroke subtypes.

J Stroke Cerebrovasc Dis 2014 Jul 3;23(6):1391-5. Epub 2014 Jan 3.

Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan.

Background: We estimated the stiffness parameter β (β value), which is useful in the assessment of premature atherosclerosis, among patients with different subtypes of cerebral infarction (CI; eg, small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined and undetermined etiologies) to determine the clinical utility of the β value in classification of stroke patients into CI subtypes.

Methods: Carotid ultrasonography (ALOKA ProSound SSD-alpha10) was performed in 31 CI patients and 38 control subjects, and the β value of the bilateral common carotid artery at 2.0 cm proximal to the bifurcation was measured using the echo-tracking method. The relationship between β value and age was examined, and the β value was compared among the different CI subtypes.

Results: Positive β value correlated with age in control subjects (R=.69, P<.001) but not in CI patients (R=-.01, P=.996). There was no significant difference in the β value when comparing control patients and patients with cardioembolic stroke (P=.106), but the β value were lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke (eg, small-vessel occlusion, large-artery atherosclerosis, and others, P=.009).

Conclusions: The β value was lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke. The β value may be useful for estimating the risk of different stroke subtypes.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.11.015DOI Listing
July 2014

Comparative study of standing wave reduction methods using random modulation for transcranial ultrasonication.

Ultrasound Med Biol 2013 Aug 4;39(8):1440-50. Epub 2013 Jun 4.

Medical Engineering Laboratory, The Jikei University School of Medicine, Tokyo, Japan.

Various transcranial sonotherapeutic technologies have risks related to standing waves in the skull. In this study, we present a comparative study on standing waves using four different activation methods: sinusoidal (SIN), frequency modulation by noise (FMN), periodic selection of random frequency (PSRF), and random switching of both inverse carriers (RSBIC). The standing wave was produced and monitored by the schlieren method using a flat plane and a human skull. The minimum ratio RSW, which is defined by the ratio of the mean of the difference between local maximal value and local minimal value of amplitude to the average value of the amplitude, was 36% for SIN, 24% for FMN, 13% for PSRF, and 4%for RSBIC for the flat reflective plate, and it was 25% for SIN, 11% for FMN, 13% for PSRF, and 5% for RSBIC for the inner surface of the human skull. This study is expected to have a role in the development of safer therapeutic equipment.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.11.011DOI Listing
August 2013

Ultrasound safety with midfrequency transcranial sonothrombolysis: preliminary study on normal macaca monkey brain.

Ultrasound Med Biol 2012 Jun 3;38(6):1040-50. Epub 2012 Apr 3.

Medical Engineering Laboratory, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan; Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan.

We investigated the safety of transcranial-targeting midfrequency (0.1 to 1 MHz) ultrasonic thrombolysis for acute ischemic stroke. We applied a new therapeutic and imaging transducer to healthy Macaca monkey brains via sonication of the ipsilateral middle cerebral artery through an acoustic temporal window. Young adult cynomolgus monkeys (Macaca fascicularis) were assigned to a group without sonication (control), a group maintained for 1 d after sonication (C1) and a group maintained for 7 d after sonication (C7; n = 3 for each). Two elder rhesus monkeys (Macaca mulatta) were ultrasonicated under transvenous injection of the recombinant tissue plasminogen activator alteplase (0.9 mg/kg), and maintained for 7 d (R). An automatic switching circuit alternately operated a therapeutic ultrasound beam (T-beam) generator for thrombolysis (frequency = 490 kHz; intensity = 0.72 W/cm(2)) and a diagnostic color-flow imaging ultrasound beam (D-beam; frequency = 2.5 MHz; intensity = 0.20 W/cm(2)). A 15-min protocol, comprising four repeats of a sequence of 120-s T-beam activation followed by 30-s D-beam activation and then 5-min T-beam deactivation together with D-beam activation, was repeated four times over 60 min. After confirmation of neurologic deficits, the brains were removed and investigated histologically and immunohistochemically. Three skull samples were subjected to 494-kHz continuous waveform ultrasound, the transcranial intensity was measured and the mechanical index was calculated. None of the monkeys showed neurologic deficits after ultrasonication. The transskull ultrasound intensity rate was 48 ± 12%. The intracranial mechanical index value was 0.15. The novel system did not cause tissue damage in the primate brain and no cavitation effect was detected intracranially.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2012.02.009DOI Listing
June 2012

Safety of low-frequency transcranial ultrasound in permanent middle cerebral artery occlusion in spontaneously hypertensive rats.

Cerebrovasc Dis 2012 30;33(1):23-9. Epub 2011 Nov 30.

Medical Engineering Laboratory, Jikei University School of Medicine, Tokyo, Japan.

Background: Some studies suggest that low-frequency transcranial ultrasound (LFTUS) can enhance thrombolysis, but other studies suggest that it may have adverse effects on intracranial tissues. We previously reported that LFTUS with appropriate parameters was effective and safe in a normotensive rat model of thromboembolic middle cerebral artery occlusion (MCAO) stroke. The goal of this study was to test the safety of this strategy in a spontaneously hypertensive rat (SHR) model of permanent MCAO.

Methods: Right MCAO was achieved in male SHRs using intraluminal nylon sutures. Rats exhibiting left hemiparesis were randomly assigned to one of four different groups: (1) normal saline (NS) group (n = 8), intravenous administration of NS as placebo at 3 h after MCAO; (2) NS+LFTUS group (n = 10), NS administration with simultaneous application of LFTUS (480.4 kHz, continuous wave, at an intensity of 0.3 W/cm(2)) for 1 h; (3) tissue plasminogen activator (tPA) group (n = 11), intravenous administration of alteplase (10 mg/kg body weight) over 1 h instead of NS; or (4) tPA+LFTUS group (n = 11), tPA administration and application of LFTUS. Twenty-four hours after treatment, neurological change was evaluated, and brains were removed and examined histologically.

Results: There was no significant difference (p > 0.09) when comparing changes in neurologic status and body weight, infarct ratio, edema ratio, or hemorrhagic transformation among the four groups.

Conclusions: Our findings suggest that sonothrombolytic treatment with LFTUS with appropriate parameters is safe when used for the treatment of ischemic stroke in hypertensive rats under the undesired permanent MCAO condition.
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http://dx.doi.org/10.1159/000332034DOI Listing
May 2012

A facile preparation method of a PFC-containing nano-sized emulsion for theranostics of solid tumors.

Int J Pharm 2011 Dec 15;421(2):379-87. Epub 2011 Oct 15.

Medical Engineering Laboratory, Research Center for Medical Science, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.

Theranostics means a therapy conducted in a diagnosis-guided manner. For theranostics of solid tumors by means of ultrasound, we designed a nano-sized emulsion containing perfluoropentane (PFC5). This emulsion can be delivered into tumor tissues through the tumor vasculatures owing to its nano-size, and the emulsion is transformed into a micron-sized bubble upon sonication through phase transition of PFC5. The micron-sized bubbles can more efficiently absorb ultrasonic energy for better diagnostic images and can exhibit more efficient ultrasound-driven therapeutic effects than nano-sized bubbles. For more efficient tumor delivery, smaller size is preferable, yet the preparation of a smaller emulsion is technically more difficult. In this paper, we used a bath-type sonicator to successfully obtain small PFC5-containing emulsions in a diameter of ca. 200nm. Additionally, we prepared these small emulsions at 40°C, which is above the boiling temperature of PFC5. Accordingly, we succeeded in obtaining very small nano-emulsions for theranostics through a very facile method.
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http://dx.doi.org/10.1016/j.ijpharm.2011.10.006DOI Listing
December 2011

Dual-frequency ultrasound imaging and therapeutic bilaminar array using frequency selective isolation layer.

IEEE Trans Ultrason Ferroelectr Freq Control 2010 May;57(5):1211-24

Hitachi Central Research Laboratory, Tokyo, Japan.

A new ultrasound array transducer with two different optimal frequencies designed for diagnosis and therapy integration in Doppler imaging-based transcranial sonothrombolysis is described. Previous studies have shown that respective frequencies around 0.5 and 2 MHz are suitable for sonothrombolysis and Doppler imaging. Because of the small acoustic window available for transcranial ultrasound exposure, it is highly desirable that both therapeutic and diagnostic ultrasounds pass through the same aperture with high efficiency. To achieve such a dual-frequency array transducer, we propose a bilaminar array, having an array for imaging and another for therapy, with a frequency selective isolation layer between the two arrays. The function of this layer is to isolate the imaging array from the therapy array at 2 MHz without disturbing the 0.5-MHz ultrasound transmission. In this study, we first used a 1-D model including two lead zirconate titanate (PZT) layers separated by an isolation layer for intuitive understanding of the phenomena. After that, we optimized the acoustic impedance and thickness of the isolation layer by analyzing pulse propagation in a 2-D model by conducting a numerical simulation with commercially available software. The optimal acoustic impedance and thickness are 3 to 4 MRayI and lambda/10, respectively. On the basis of the optimization, a prototype array transducer was fabricated, and the spatial resolutions of the Doppler images it obtained were found to be practically the same as those obtained through conventional imaging array transducers.
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http://dx.doi.org/10.1109/TUFFC.2010.1534DOI Listing
May 2010

[Transcranial sonothrombolysis].

Authors:
Hiroshi Furuhata

Rinsho Shinkeigaku 2009 Nov;49(11):804-6

ME Lab. Research Center for Medical Science, The Jikei University School of Medicine.

Transcranial ultrasonic diagnostic equipment has been approved to enhance the thrombolytic effect of IVrt-PA. Moreover, transcranial sonothrombolysis with low frequency ultrasound has a great advantage in lytic effect of IVrt-PA. It is remarkable to choose a optimal ultrasonic condition for transcranial sonothrombolysis. We are developing a new transcranial targeting Low Frequency Ultrasonic Thrombolysis system (TCT-LoFUT). This system is anticipated to be a useful therapeutic equipment to realize a early recanalization in the acute ischemic stroke treatment.
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http://dx.doi.org/10.5692/clinicalneurol.49.804DOI Listing
November 2009

Experimental evaluation of a new antithrombogenic stent using ion beam surface modification.

Artif Organs 2009 Jun;33(6):456-63

Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

A new antithrombogenic stent using ion beam surface modification nanotechnology was evaluated. The ion stent is being developed to inhibit acute and chronic stent-related thrombosis. Thirty self-expanding mesh stents were fabricated from Ti-Ni metal wires with a dimension of 4 mm (diameter) x 25 mm (length) x 0.15 mm (thickness). Twenty stents were coated with type I collagen and irradiated with a He(+) ion beam at an energy of 150 keV with fluences of 1 x 10(14) ions/cm(2) (ion stent group). Ten stents had no treatment (non-ion stent group). The self-expanding stents were implanted into the right and left peripheral femoral arteries of 15 beagle dogs (vessel diameter approximately 3 mm) via a 6Fr catheter under fluoroscopic guidance. Heparin (100 units/kg) was administered intravenously before implantation. Following stent implantation, no antiplatelet or anticoagulant drugs were administered. The 1-month patency rate for the non-ion stent group was 10% (1/10), and for the ion stent group it was 80% (16/20) with no anticoagulant or antiplatelet drugs given after stent implantation (P = 0.0004 by Fisher's exact test). Ten stents remain patent after 2 years in vivo with no anticoagulant or antiplatelet drugs. These results indicate that He(+) ion-implanted collagen-coated Ti-Ni self-expanding stents have excellent antithrombogenicity and biocompatibility. This ion stent is promising for coronary and cerebral stent applications.
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http://dx.doi.org/10.1111/j.1525-1594.2009.00747.xDOI Listing
June 2009

Application of therapeutic insonation to malignant glioma cells and facilitation by echo-contrast microbubbles of levovist.

Anticancer Res 2009 Jan;29(1):235-42

Department of Molecular Cell Biology, Institute of DNA Medicine, Research Center for Medical Sciences, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan.

Background: Malignancies affecting the central nervous system are intractable to conventional therapies thereby requiring an alternative strategy, such as ultrasound irradiation.

Materials And Methods: We originally designed a transducer for intracranial insonation and investigated the effect of 210.4 kHz ultrasound on malignant glioma cells.

Results: The insonation of 2.61 W/cm2 effectively disrupted the malignant cells. This effect was reinforced by the echo-contrast agent, Levovist. The condition was applied to tumor-bearing animals and external insonation inhibited subcutaneous tumor growth. It also repressed the growth of intracranially implanted tumors and prolonged survival of the animals. When Levovist was stereotactically injected into the tumors, the effect of insonation was significantly enhanced.

Conclusion: A neuronavigation system or stereotactic device has been used commonly for patients with brain tumor. Administration of combination therapy consisting of insonation and a local echo-contrast agent will have a role in improving the treatment for malignant gliomas.
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January 2009

Accelerating effects of ultrasonic thrombolysis with bubble liposomes.

J Med Ultrason (2001) 2008 Mar 15;35(1):5-10. Epub 2008 Mar 15.

Medical Engineering Laboratory, Research Center for Medical Science, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan.

Purpose: The accelerating effect on thrombolysis by combined use of 500-kHz low-frequency ultrasound (US), recombinant tissue plasminogen activator (rt-PA), and bubble liposomes (BLs) was verified in vitro.

Methods: A fibrin clot was formed by adding thrombin to bovine plasma. It was enclosed in a pressurized container, the pressure and temperature of which were maintained at 150 mmHg and 37°C, respectively. Ultrasonic conditions were set at a continuous wave, a frequency of 500 kHz, an intensity of 0.7 W/cm(2), and a sonication time of 60 s. We derived the rate of reduction in clot weight from the decreased clot weight and the weight before sonication. We compared the rate of reduction in groups combining physiological saline, rt-PA, BLs, and US.

Results: Only the rt-PA+US+BL group showed a significantly accelerated thrombolytic effect compared with any other group or with any combination of two factors in the 60-s period (0.001 < P < 0.027).

Conclusion: BLs have great potential to accelerate the thrombolytic effect of rt-PA with low-frequency, 500-kHz, continuous-wave ultrasound.
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http://dx.doi.org/10.1007/s10396-007-0163-xDOI Listing
March 2008

Effective and safe conditions of low-frequency transcranial ultrasonic thrombolysis for acute ischemic stroke: neurologic and histologic evaluation in a rat middle cerebral artery stroke model.

Stroke 2008 Mar 31;39(3):1007-11. Epub 2008 Jan 31.

Department of Neurosurgery, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.

Background And Purpose: Transcranial ultrasound (TUS) enhances thrombolysis and is expected to be useful for the treatment of ischemic stroke. However, neither its effectiveness in improving neurologic outcome nor its safety in living tissue has been fully established. We examined the efficacy and safety of low-frequency TUS under appropriate conditions of ultrasound for thrombolytic treatment in a rat middle cerebral artery stroke model.

Methods: Sixty-five male Wistar rats were used. Rats with right middle cerebral artery stroke exhibiting left hemiparesis were blindly selected and randomly assigned to 1 of 3 groups: (1) control, no therapy; (2) tPA, intravenous administration of tissue plasminogen activator 3 hours after middle cerebral artery stroke, or (3) TUS, tPA administration and application of TUS (490 kHz, continuous wave, at an intensity of 0.8 W/cm(2)). Twenty-four hours after the onset of stroke, neurologic improvement was evaluated and brains were then removed. Thrombolysis at the origin of the right middle cerebral artery was examined. Thrombolysis ratio, cerebral infarct ratio, and rate of histologic evidence of hemorrhage were compared in the 3 groups.

Results: Significantly better neurologic improvement (P=0.008), a higher thrombolysis ratio (P=0.041), and a reduction of cerebral infarct volume (P=0.047) were obtained in the TUS group compared with the tPA group, without an increase in hemorrhagic transformation.

Conclusions: Our findings suggest that thrombolytic treatment with low-frequency TUS under appropriate conditions could be an effective and safe method of treatment for ischemic stroke.
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http://dx.doi.org/10.1161/STROKEAHA.107.496117DOI Listing
March 2008

Nitric oxide generation directly responds to ultrasound exposure.

Ultrasound Med Biol 2008 Mar 15;34(3):487-93. Epub 2007 Oct 15.

Medical Engineering Laboratory, Jikei University School of Medicine, Tokyo, Japan.

Recently, several reports have been published on ultrasonic vascular dilation produced with relatively low-frequency ultrasound. It has been speculated that nitric oxide (NO) is an important factor for this ultrasonic vascular dilation. However, a quantitative relationship between the ultrasound intensity and NO generation was not clarified in these reports. We investigated the quantity of NO generated by various ultrasonic intensities by means of real-time measurement of NO concentration in the adductor muscles of the thigh of New Zealand white rabbits exposed to a continuous-wave ultrasound (490 kHz). In the quantitative relationship between NO generation and ultrasonic intensity, the percent increase in NO concentration was 1.25% +/- 1.25%, 10.6% +/- 2.9% and 20.1% +/- 3.5%, with the maximum muscle temperature increase 0.5 +/- 0.2 degrees C, 0.7 +/- 0.2 degrees C, and 0.8 +/- 0.3 degrees C at the ultrasonic intensity (SPTA) of 0.21, 0.35 and 0.48 W/cm(2), respectively. The effect of ultrasound on NO generation was intensity-dependent with a progressive increase from 0.21 W/cm(2) to 0.48 W/cm(2) without significant thermal effect. Ultrasonic NO generation was partially reduced by NOS inhibitor of L-NMMA, clarifying that ultrasound can activate both NOS-dependent and NOS-independent NO generation. These new findings provided scientific basis for ultrasonic vasodilatation and support the potentiality of a new ultrasonic technology for the treatment and prevention of the ischemic tissue based on the new concept of NO generated angiogenesis. (E-mail: [email protected]).
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http://dx.doi.org/10.1016/j.ultrasmedbio.2007.08.008DOI Listing
March 2008

In vitro evaluation of dual mode ultrasonic thrombolysis method for transcranial application with an occlusive thrombosis model.

Ultrasound Med Biol 2008 Jan 14;34(1):96-102. Epub 2007 Sep 14.

Medical Engineering Laboratory, Research Center for Medical Science, Jikei University School of Medicine, Tokyo, Japan.

A recent clinical trial of transcranial low-frequency ultrasound-mediated tPA thrombolysis (LFUT) showed cerebral hemorrhages associated with high spatial peak pulse average intensity (I(SPPA)), wide beam and long pulse duration. We developed an alternative approach to LFUT wherein diagnostic power M-mode Doppler (PMD) ultrasound is combined with LFUT, with a goal of increased safety. The effectiveness of such a dual mode ultrasonic thrombolysis (DMUT) was explored in vitro. The DMUT system emitted PMD (2 MHz) and LFUT (550 kHz) beams in alternating fashion from a small 12 mm diameter probe. The LFUT had a low I(SPPA) (2 W/cm(2)) and a short pulse duration (55 micros). Occlusive clots made in plastic tips from bovine plasma and thrombin were placed in flow models pressurized to 800 mH(2)O, with 600 IU/mL monteplase injected upstream. Recanalization times were then compared among three groups: the control (monteplase alone), PMD (monteplase + PMD) and DMUT (monteplase + PMD + LFUT). The capability of the DMUT device to monitor recanalization was demonstrated by observing with Doppler the degree of flow of a blood-mimicking fluid in the vicinity of the clot. Recanalization times were 37.9 +/- 22.9, 38.9 +/- 12.4 and 18.5 +/- 8.0 min, respectively, for the control, PMD and DMUT. There were significant differences between DMUT and the control (p = 0.0004) and between DMUT and PMD (p = 0.0004). Recanalization flows were clearly detected. It is anticipated that this DMUT method presents a safer and more efficient approach than normal LFUT.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2007.07.010DOI Listing
January 2008

Does long-term continuous transcranial Doppler monitoring require a pause for safer use?

Cerebrovasc Dis 2007 22;24(1):27-34. Epub 2007 May 22.

Department of Anesthesiology, ME Laboratory, Research Center for Medical Science, Jikei University School of Medicine, Tokyo, Japan.

Background: Transcranial Doppler sonography (TCD) has been used widely for long-term monitoring of cerebral blood flow without adverse reports. However, attention has not been adequately paid to the fact that an increase in the time period of TCD insonation causes brain temperature to rise due to ultrasound absorption by tissue and the skull. We measured the actual temperature rise in local brain tissue induced by TCD insonation over a long time period during in vivo animal experiments in order to verify whether or not a pause is required in long-term, continuous TCD monitoring.

Methods: We inserted thermocouples into the skull-brain interface (SBI) of 15 New Zealand White rabbits (10: TCD application group; 5: control group, TCD non-application group). The TCD probe was placed on the parietal bone, and changes in SBI temperature (SBIT) were measured for 90 min. TCD was set at maximum output level (0.2 W, 2 MHz).

Results: SBIT in the TCD group increased rapidly to 3.47 degrees C within 25 min and then reached a plateau. The maximum time for safe continuous TCD application is estimated to be 33 min.

Conclusions: Even though there are large differences in factors, such as brain volume and environmental conditions, between rabbits and humans, there is less difference in their cerebral blood flow per brain weight, which is the parameter that is mainly associated with heat reduction. Accordingly, the findings of the present experiment suggest that long-term TCD monitoring in clinical use should include a pause after every 30 min of insonation to avoid thermal damage to the brain surface.
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http://dx.doi.org/10.1159/000103113DOI Listing
August 2007

Overexpression of heat shock proteins in pallido-nigral axonal spheroids of nonhuman aged primates.

Acta Neuropathol 2005 Aug 22;110(2):145-50. Epub 2005 Jun 22.

Division of Neuropathology, Department of Neuroscience, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, 105-8461, Tokyo, Japan.

The occurrence of spheroids has been described in the globus pallidus (GP) and substantia nigra pars reticulata (SNr) of aged rhesus monkeys. Opinions vary as to the origin of spheroids. Ultrastructural and immunohistochemical analysis suggested that spheroids originate from degenerating axons or astroglia. In the present study, we have investigated the GP and SNr of aged monkeys (Macaca fascicularis and Macaca mulatta). Although immunoreactive for microtubule-associated protein (MAP) 1A, tau, amyloid precursor protein, synaptophysin and phosphorylated neurofilament, spheroids were not immunoreactive for MAP1B and MAP2. We confirmed the axonal nature of pallido-nigral spheroids in aged rhesus monkeys. Pallido-nigral spheroids have been reported to overexpress stress proteins, such as ubiquitin, alphaB-crystallin, and heat shock protein (Hsp) 27. We further evaluated the expression of Hsps in pallido-nigral spheroids. As well as being intensely immunoreactive for ubiquitin, alphaB-crystallin, Hsp27, and Hsp70, spheroids were immunoreactive for Hsp32 (heme oxygenase-1), Hsp40, Hsp60, and Hsp90. On the basis of these findings, we speculate that Hsp32-immunoreactive spheroids might be expressed as an oxidative stress response. Induction of other Hsps might play a role in protection of axons from the aggregation of neurofilament, MAPs and other proteins, and failure to protect degenerating axons might result in their proteolysis by the ubiquitin-proteasome system.
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http://dx.doi.org/10.1007/s00401-005-1030-8DOI Listing
August 2005

Insonation facilitates plasmid DNA transfection into the central nervous system and microbubbles enhance the effect.

Ultrasound Med Biol 2005 May;31(5):693-702

Department of Molecular Cell Biology, Institute of DNA Medicine, Research Center for Medical Science, Jikei University School of medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, Japan 105-8461.

Many of the diseases which affect the central nervous system are intractable to conventional therapies and therefore require alternative treatments such as gene therapy. Therapy requires safety, since the central nervous system is a critical organ. Choice of nonviral vectors such as naked plasmid DNA may have merit. However, transfection efficiencies of these vectors are low. We have investigated the use of 210.4 kHz ultrasound and found that 5.0 W/cm(2) of insonation for 5 s most effectively transfected a plasmid DNA into culture slices of mouse brain (147.68-fold increase compared with 0 W/cm(2) of insonation for 5 s). The effect was reinforced by combination with echo contrast agent, Levovist. One hundred fifty mg/mL of Levovist significantly increased gene transfection by ultrasound (5.23-fold when insonated at 5.0 W/cm(2) for 5 s). When DNA was intracranially injected, Levovist also enhanced gene transfection in newborn mice (4.49-fold increase when insonated at 5.0 W/cm(2) for 5 s). Since ultrasound successfully transfected naked plasmid DNA into the neural tissue and Levovist enhanced the effect, this approach may have a significant role in gene transfer to the central nervous system.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2005.01.015DOI Listing
May 2005

Comparison of transcranial brain tissue perfusion images between ultraharmonic, second harmonic, and power harmonic imaging.

Stroke 2004 Mar 12;35(3):687-93. Epub 2004 Feb 12.

Department of Clinical Neurosciences, Kyoto Takeda Hospital, Minamikinuta-cho 11, Nishinanajo, Shimogyo-ku, Kyoto 600-8884, Japan.

Background And Purpose: To clarify optimal brain tissue perfusion images visualized by transcranial ultrasound harmonic imaging, we compared gray-scale integrated backscatter (IBS) images of new ultraharmonic imaging (UHI) and conventional second harmonic imaging (SHI) with power harmonic imaging (PHI) (harmonic B-mode with harmonic power Doppler images) in 10 patients with and 4 without a temporal skull.

Methods: Using a SONOS 5500 (Philips), we evaluated transient response images taken after a bolus Levovist injection at a horizontal diencephalic plane via temporal windows. Based on transmitting/receiving frequencies (MHz), 4 imaging procedures using an S3 transducer (SHI2.6 [1.3/2.6], UHI [1.3/3.6], PHI2.6 [1.3/2.6], and PHI3.2 [1.6/3.2]) and 2 imaging procedures using an S4 transducer (SHI3.6 [1.8/3.6] and PHI3.6 [1.8/3.6]) were compared in terms of size and location, peak intensity (PI), contrast area demarcation, and background image quality.

Results: In intact skull cases, gray-scale imaging tended to show larger contrast areas than PHI. A large contrast area was most frequently observed in SHI2.6 images, despite there being more high-PI cases in UHI. No contrast area with unclear background was observed in a few cases. In craniectomized cases, all contrast images tended to have large and high PI compared with the intact skull cases. PHI, particularly PHI3.6, demonstrated sharper demarcation and a clearer background than gray-scale imaging.

Conclusions: Transcranial gray-scale SHI using a low receiving frequency of 2.6 MHz is the superior method. PHI identifies contrast area localization better than gray-scale imaging and is particularly suitable for intraoperative and postoperative cases.
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http://dx.doi.org/10.1161/01.STR.0000116102.15636.65DOI Listing
March 2004

Effect of ultrasound application on fat mobilization.

Pathophysiology 2002 Oct;9(1):13

Miwa Science Laboratory Inc., 6-7-10 Miyazaki, Miyamae-ku, Kawasaki, 216-0033, Kanagawa, Japan

The aim of this experimental trial was to study the effect of ultrasound application on the lipolysis in adipose tissue. Rats were administered to pentobarbital (Nembutal) anesthesia and their abdomens were shaved. Rat abdomen was subjected to 24 kHz-1 MHz ultrasound for 10 min to investigate frequency and power-intensity dependency for fat mobilization. Blood was taken from the tail vein to estimate plasma free fatty acids (FFA). For frequency dependency two regions around 100 kHz and 300-500 kHz were effective for fat mobilization. For power-intensity dependency, effective regions were found to be from 24 to 1090 kHz. In the effective regions on frequency and power-intensity, application of ultrasound caused increases in plasma FFA and norepinephrine concentration of extra-cellular fluid of perirenal adipose tissue. These results suggest that ultrasound application stimulates fat mobilization through a local increase in norepinephrine secretion under the conditions of effective frequency and intensity.
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http://dx.doi.org/10.1016/s0928-4680(02)00017-2DOI Listing
October 2002

Can transcranial ultrasonication increase recanalization flow with tissue plasminogen activator?

Stroke 2002 May;33(5):1399-404

Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan.

Background And Purpose: In thrombolytic therapy for acute ischemic stroke, it is essential to obtain rapid thrombolysis before ischemic neuronal injury occurs. To develop a new technique of thrombolysis for acute ischemic stroke, the effect of transcranially applied ultrasound (TUS) on thrombolysis was examined.

Methods: An occlusion model of rabbit femoral artery was produced with thrombin after establishment of stenotic flow and endothelial damage. After stable occlusion was confirmed, monteplase (mtPA) was administered intravenously, and ultrasound (490 kHz, 0.13 W/cm2) was applied through a piece of temporal bone (TUS group; n=9). The control group received mtPA alone (tissue plasminogen activator [tPA] group; n=12). To verify the efficacy of TUS, femoral artery flow was measured during the procedure.

Results: The recanalization ratio was 16.7% (2 of 12) in the tPA group and 66.7% (6 of 9) in the TUS group. The recanalization ratio in the TUS group was higher than that in the tPA group (P=0.03). Patency flow ratio, which was defined as recanalization flow divided by baseline flow, of the TUS group (44.6+/-13.9%) was significantly greater than that of the tPA group (9.9+/-6.8%) at 60 minutes (P=0.025). Patency flow ratio became higher in the TUS group than in the tPA group between 20 and 30 minutes from the start of thrombolysis.

Conclusions: Low-frequency and low-intensity TUS enhanced thrombolysis by mtPA in a rabbit femoral artery occlusion model. This technique should be clinically useful for thrombolysis in acute ischemic stroke.
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http://dx.doi.org/10.1161/01.str.0000013789.15436.42DOI Listing
May 2002
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