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1.  Transthoracic needle biopsy of thoracic tumours by a colour Doppler ultrasound puncture guiding device. 
Thorax  1995;50(12):1258-1263.
BACKGROUND--Ultrasound guided transthoracic needle aspiration biopsy has recently been used to obtain specimens for histological diagnosis of pulmonary and mediastinal tumours. Conventional real time, grey scale puncture guiding devices cannot differentiate vascular structures, and clear visualisation of the needle shaft or tip within a desired target is not always possible. This study describes a new built-in colour Doppler ultrasound puncture guiding device and assesses the relative safety of transthoracic needle aspiration biopsy of thoracic tumours by grey scale or colour Doppler ultrasound guidance. METHODS--Thirty patients with radiographic evidence of pulmonary (22 patients) or mediastinal tumours (eight patients) underwent ultrasonographic evaluation and transthoracic needle aspiration biopsy by using the colour Doppler ultrasound puncture guiding device (Aloka UST 5045P-3.5). These tumours were initially examined by grey scale ultrasound, and colour Doppler imaging was then used to evaluate the number of blood vessels surrounding and within the target tumour and the possibility of visualisation of the needle shaft or needle tip during the aspiration biopsy procedure. RESULTS--The colour Doppler ultrasound guiding device was far superior to the grey scale device for identification of the number of vessels surrounding or within the target tumour (83% v 20%) and for visualisation of the needle shaft or needle tip (80% v 17%). CONCLUSIONS--By using the colour Doppler ultrasound puncture device, vascular structures surrounding or within the target tumour can be verified. Visualisation of the needle shaft or tip is also better. Biopsy routes can be selected to avoid puncturing vessels. This approach should be particularly helpful for guiding biopsies of mediastinal tumours, where puncturing the heart or great vessels is a potential complication.
PMCID: PMC1021347  PMID: 8553297
2.  Color Doppler Imaging of Cardiac Catheters Using Vibrating Motors 
Ultrasonic imaging  2008;30(4):247-250.
We attached a miniature motor rotating at 11,000 rpm onto the proximal end of cardiac electrophysiological (EP) catheters in order to produce vibrations at the tip which were then visualized by color Doppler on ultrasound scanners. We imaged the catheter tip within a vascular graft submerged in a water tank using the Volumetrics Medical Imaging 3D scanner, the Siemens Sonoline Antares 2D scanner, and the Philips ie33 3D ultrasound scanner with TEE probe. The vibrating catheter tip was visualized in each case though results varied with the color Doppler properties of the individual scanner.
PMCID: PMC2804844  PMID: 19514134
Color flow Doppler; device guidance; cardiac electrophysiology catheters
3.  Real-Time 3D Intracranial Ultrasound with an Endoscopic Matrix Array Transducer 
Ultrasound in medicine & biology  2007;33(8):1277-1284.
A transducer originally designed for Transesophageal Echocardiography (TEE) was adapted for real-time volumetric endoscopic imaging of the brain. The transducer consists of a 36 × 36 array with an interelement spacing of 0.18 mm. There are 504 transmitting and 252 receive channels placed in a regular pattern in the array. The operating frequency is 4.5 MHz with a −6 dB bandwidth of 30%. The transducer is fabricated on a 10 layer flexible circuit from MicroConnex (Snoqualmie, WA). The purpose of this study is to evaluate the clinical feasibility of real-time 3D intracranial ultrasound with this device. The Volumetrics Medical Imaging (Durham, NC) 3D scanner was used to obtain images in a canine model. A transcalvarial acoustic window was created under general anesthesia in the animal laboratory by placing a 10 mm burr hole in the high parietal calvarium of a 50 kg canine subject. The burr-hole was placed in a left para-sagittal location to avoid the sagittal sinus, and the transducer was placed against the intact dura mater for ultrasound imaging. Images of the lateral ventricles were produced, including real-time 3D guidance of a needle puncture of one ventricle. In a second canine subject, contrast (Optison™, Amersham Health, Inc., Princeton, NJ) enhanced 3D Doppler color flow images were made of the cerebral vessels including the complete Circle of Willis. Clinical applications may include real-time 3D guidance of cerebral spinal fluid extraction from the lateral ventricles and bedside evaluation of critically ill patients where CT and MR imaging techniques are unavailable.
PMCID: PMC2755488  PMID: 17478032
Real-Time 3D Imaging; 2D Array Transducer; Intraoperative Guidance
4.  Real-Time 3-D Ultrasound Guidance of Interventional Devices 
We have previously developed 2-D array transducers for many real-time volumetric imaging applications. These applications include transducers operating up to 7 MHz for transthoracic imaging, up to 15 MHz for intracardiac echocardiography (ICE), 5 MHz for transesophageal echocardiography (TEE) and intracranial imaging, and 7 MHz for laparoscopic ultrasound imaging (LUS). Now we have developed a new generation of miniature ring-array transducers integrated into the catheter deployment kits of interventional devices to enable real-time 3-D ultrasound scanning for improved guidance of minimally invasive procedures. We have constructed 3 new ring transducers. The first consists of 54 elements operating at 5 MHz. Typical measured transducer element bandwidth was 25%, and the 50 Ohm round trip insertion loss was −65 dB. Average nearest neighbor cross talk was −23.8 dB. The second is a prototype 108-element transducer operating at 5 MHz. The third is a prototype 108-element ring array with a transducer center frequency of 8.9 MHz and a −6 dB bandwidth of 25%. All transducers were integrated with an 8.5 French catheter sheath of a Cook Medical, Inc. vena cava filter deployment device.
PMCID: PMC2656286  PMID: 18986903
5.  Novel Applications of Ultrasound Technology to Visualize and Characterize Myofascial Trigger Points and Surrounding Soft Tissue 
Apply ultrasound (US) imaging techniques to better describe the characteristics of myofascial trigger points (MTrPs) and the immediately adjacent soft tissue.
Descriptive (exploratory) study.
Biomedical research center.
9 subjects meeting Travell and Simons’s criteria for MTrPs in a taut band in the upper trapezius.
Main Outcome Measures
MTrPs were evaluated by 1) physical examination, 2) pressure algometry, and 3) three types of ultrasound imaging including grayscale (2D US), vibration sonoelastography (VSE), and Doppler.
Four sites in each patient were labeled based on physical examination as either active MTrP (spontaneously-painful, A-MTrP), latent MTrP (non-painful, L-MTrP), or normal myofascial tissue. US examination was performed on each subject by a team blinded to the physical findings. A 12-5 MHz US transducer was used. VSE was performed by color Doppler variance imaging while simultaneously inducing vibrations (~92Hz) with a handheld massage vibrator. Each site was assigned a tissue imaging score (TIS) as follows: 0 = uniform echogenicity and stiffness; 1 = focal hypoechoic region with stiff nodule; 2 = multiple hypoechoic regions with stiff nodules. Blood flow in the neighborhood of MTrPs was assessed using Doppler imaging. Each site was assigned a blood flow waveform score (BFS) as follows: 0 = normal arterial flow in muscle; 1 = elevated diastolic flow; 2 = high-resistance flow waveform with retrograde diastolic flow.
MTrPs appeared as focal, hypoechoic regions on 2D US, indicating local changes in tissue echogenicity, and as focal regions of reduced vibration amplitude on VSE, indicating a localized stiff nodule. MTrPs were elliptical in shape, with a size of 0.16 ± 0.11 cm2. There were no significant differences in size between A-MTrPs and L-MTrPs. Sites containing MTrPs were more likely to have higher TIS compared to normal myofascial tissue (p<0.002). Small arteries (or enlarged arterioles) near A-MTrPs showed retrograde flow in diastole indicating a highly resistive vascular bed. A-MTrP sites were more likely to have higher BFS compared to L-MTrPs (p<0.021).
Preliminary findings show that, under the conditions of this investigation, US imaging techniques can be used to distinguish myofascial tissue containing MTrPs from normal myofascial tissue (lacking trigger points). Ultrasound enables visualization and some characterization of MTrPs and adjacent soft tissue.
PMCID: PMC2774893  PMID: 19887205
Ultrasonography; Sonoelastography; Rehabilitation; Myofascial Pain Syndromes; Trigger Points; Myofascia
6.  Measurements of attenuation coefficient for evaluating the hardness of a cataract lens by a high-frequency ultrasonic needle transducer 
Physics in medicine and biology  2009;54(19):5981-5994.
A cataract is a clouding of the lens in the eye that affects vision. Phacoemulsification is the mostly common surgical method for treating cataracts, and determining that the optimal phacoemulsification energy is dependent on measuring the hardness of the lens. This study explored the use of an ultrasound needle transducer for invasive measurements of ultrasound attenuation coefficient to evaluate the hardness of the cataract lens. A 47 MHz high-frequency needle transducer with a diameter of 0.9 mm was fabricated by a polarized PMN-33%PT single crystal in the present study. The attenuation coefficients at different stages of an artificial porcine cataract lens were measured using the spectral shift approach. The hardness of the cataract lens was also evaluated by mechanical measurement of its elastic properties. The results demonstrated that the ultrasonic attenuation coefficient was increased from 0.048 ± 0.02 to 0.520 ± 0.06 dB mm−1 MHz−1 corresponding to an increase in Young’s modulus from 6 ± 0.4 to 96 ± 6.2 kPa as the cataract further developed. In order to evaluate the feasibility of combining needle transducer and phacoemulsification probe for real-time measurement during cataract surgery, the needle transducer was mounted on the phacoemulsification probe for a vibration test. The results indicated that there was no apparent damage to the tip of the needle transducer and the pulse–echo test showed that a good performance in sensitivity was maintained after the vibration test.
PMCID: PMC2843554  PMID: 19759408
7.  Ring Array Transducers for Real-Time 3D Imaging of an Atrial Septal Occluder 
Ultrasound in medicine & biology  2012;38(8):1483-1487.
We developed new miniature ring array transducers integrated into interventional device catheters such as used to deploy atrial septal occluders. Each ring array consisted of 55 elements operating near 5 MHz with interelement spacing of 0.20 mm. It was constructed on a flat piece of copper-clad polyimide and then wrapped around an 11 French O.D. catheter. We used a braided cabling technology from Tyco Electronics Corp to connect the elements to the Volumetrics Medical Imaging (VMI) real-time 3D ultrasound scanner. Transducer performance yielded a –6 dB fractional bandwidth of 20% centered at 4.7 MHz without a matching layer versus average bandwidth of 60% centered at 4.4 MHz with a matching layer. Real time 3D rendered images of an en face view of a Gore Helex septal occluder in a water tank showed a finer texture of the device surface from the ring array with the matching layer.
PMCID: PMC3434960  PMID: 22698504
2D array transducer; real-time 3D imaging; septal occluder
8.  High-intensity focused ultrasound ablation assisted using color Doppler imaging for the treatment of hepatocellular carcinomas 
Abdominal Imaging  2013;38(6):1263-1268.
We evaluated the usefulness of color Doppler flow imaging to compensate for the inadequate resolution of the ultrasound (US) monitoring during high-intensity focused ultrasound (HIFU) for the treatment of hepatocellular carcinoma (HCC).
Materials and methods
US-guided HIFU ablation assisted using color Doppler flow imaging was performed in 11 patients with small HCC (<3 lesions, <3 cm in diameter). The HIFU system (Chongqing Haifu Tech) was used under US guidance. Color Doppler sonographic studies were performed using an HIFU 6150S US imaging unit system and a 2.7-MHz electronic convex probe.
The color Doppler images were used because of the influence of multi-reflections and the emergence of hyperecho. In 1 of the 11 patients, multi-reflections were responsible for the poor visualization of the tumor. In 10 cases, the tumor was poorly visualized because of the emergence of a hyperecho. In these cases, the ability to identify the original tumor location on the monitor by referencing the color Doppler images of the portal vein and the hepatic vein was very useful. HIFU treatments were successfully performed in all 11 patients with the assistance of color Doppler imaging.
Color Doppler imaging is useful for the treatment of HCC using HIFU, compensating for the occasionally poor visualization provided by B-mode conventional US imaging.
PMCID: PMC3827892  PMID: 23728304
High-intensity focused ultrasound; Hepatocellular carcinoma; Ultrasound; Color Doppler imaging
9.  Ultrasound-Mediated Release of Hydrophilic and Lipophilic Agents From Echogenic Liposomes 
To achieve ultrasound-controlled drug delivery using echogenic liposomes (ELIPs), we assessed ultrasound-triggered release of hydrophilic and lipophilic agents in vitro using color Doppler ultrasound delivered with a clinical 6-MHz compact linear array transducer.
Calcein, a hydrophilic agent, and papaverine, a lipophilic agent, were each separately loaded into ELIPs. Calcein-loaded ELIP (C-ELIP) and papaverine-loaded ELIP (P-ELIP) solutions were circulated in a flow model and treated with 6-MHz color Doppler ultrasound or Triton X-100. Treatment with Triton X-100 was used to release the encapsulated calcein or papaverine content completely. The free calcein concentration in the solution was measured directly by spectrofluorimetry. The free papaverine in the solution was separated from liposome-bound papaverine by spin column filtration, and the resulting papaverine concentration was measured directly by absorbance spectrophotometry. Dynamic changes in echogenicity were assessed with low-output B-mode ultrasound (mechanical index, 0.04) as mean digital intensity.
Color Doppler ultrasound caused calcein release from C-ELIPs compared with flow alone (P < .05) but did not induce papaverine release from P-ELIPs compared with flow alone (P > .05). Triton X-100 completely released liposome-associated calcein and papaverine. Initial echogenicity was higher for C-ELIPs than P-ELIPs. Color Doppler ultrasound and Triton X-100 treatments reduced echogenicity for both C-ELIPs and P-ELIPs (P < .05).
The differential efficiency of ultrasound-mediated pharmaceutical release from ELIPs for water- and lipid-soluble compounds suggests that water-soluble drugs are better candidates for the design and development of ELIP-based ultrasound-controlled drug delivery systems.
PMCID: PMC2860106  PMID: 18946099
calcein; Doppler ultrasound; drug release; echogenic liposomes; papaverine; ultrasound
10.  Forward-Looking Intracardiac Ultrasound Imaging Using a 1-D CMUT Array Integrated With Custom Front-End Electronics 
Minimally invasive catheter-based electrophysiological (EP) interventions are becoming a standard procedure in diagnosis and treatment of cardiac arrhythmias. As a result of technological advances that enable small feature sizes and a high level of integration, nonfluoroscopic intracardiac echocardiography (ICE) imaging catheters are attracting increasing attention. ICE catheters improve EP procedural guidance while reducing the undesirable use of fluoroscopy, which is currently the common catheter guidance method. Phased-array ICE catheters have been in use for several years now, although only for side-looking imaging. We are developing a forward-looking ICE catheter for improved visualization. In this effort, we fabricate a 24-element, fine-pitch 1-D array of capacitive micromachined ultrasonic transducers (CMUT), with a total footprint of 1.73 mm × 1.27 mm. We also design a custom integrated circuit (IC) composed of 24 identical blocks of transmit/receive circuitry, measuring 2.1 mm × 2.1 mm. The transmit circuitry is capable of delivering 25-V unipolar pulses, and the receive circuitry includes a transimpedance preamplifier followed by an output buffer. The CMUT array and the custom IC are designed to be mounted at the tip of a 10-Fr catheter for high-frame-rate forward-looking intracardiac imaging. Through-wafer vias incorporated in the CMUT array provide access to individual array elements from the back side of the array. We successfully flip-chip bond a CMUT array to the custom IC with 100% yield. We coat the device with a layer of polydimethylsiloxane (PDMS) to electrically isolate the device for imaging in water and tissue. The pulse-echo in water from a total plane reflector has a center frequency of 9.2 MHz with a 96% fractional bandwidth. Finally, we demonstrate the imaging capability of the integrated device on commercial phantoms and on a beating ex vivo rabbit heart (Langendorff model) using a commercial ultrasound imaging system.
PMCID: PMC2730563  PMID: 19126489
11.  Ultrasound-triggered Release of Recombinant Tissue-type Plasminogen Activator from Echogenic Liposomes 
Ultrasound in medicine & biology  2010;36(1):145-157.
Echogenic liposomes (ELIP) were developed as ultrasound-triggered targeted drug or gene delivery vehicles (Lanza et al., 1997; Huang et al., 2001). Recombinant tissue-type Plasminogen Activator (rt-PA), a thrombolytic, has been loaded into ELIP (Tiukinhoy-Laing et al., 2007). These vesicles have the potential to be used for ultrasound-enhanced thrombolysis in the treatment of acute ischemic stroke, myocardial infarction, deep vein thrombosis, or pulmonary embolus. A clinical diagnostic ultrasound scanner (Philips HDI 5000) equipped with a linear array transducer (L12-5) was employed for in vitro studies using rt-PA-loaded ELIP (T-ELIP). The goal of this study was to quantify ultrasound-triggered drug release from rt-PA-loaded echogenic liposomes. T-ELIP samples were exposed to 6.9-MHz B-mode pulses at a low pressure amplitude (600 kPa) to track the echogenicity over time under four experimental conditions: 1) flow alone to monitor gas diffusion from the T-ELIP, 2) pulsed 6.0-MHz color Doppler exposure above the acoustically driven threshold (0.8 MPa) to force gas out of the liposome gently, 3) pulsed 6.0-MHz color Doppler above the rapid fragmentation threshold (2.6 MPa), or 4) Triton X-100 to rupture the T-ELIP chemically as a positive control. Release of rt-PA for each ultrasound exposure protocol was assayed spectrophotometrically. T-ELIP were echogenic in the flow model (5 ml/min) for thirty minutes. The thrombolytic drug remained associated with the liposome when exposed to low-amplitude B-mode pulses over 60 min and was released when exposed to color Doppler pulses or Triton X-100. The rt-PA released from the liposomes had similar enzymatic activity as the free drug. These T-ELIP are robust and echogenic during continuous fundamental 6.9-MHz B-mode imaging at a low exposure output level (600 kPa). Furthermore, a therapeutic concentration of rt-PA can be released by fragmenting the T-ELIP with pulsed 6.0-MHz color Doppler ultrasound above the rapid fragmentation threshold (1.59 MPa).
PMCID: PMC3037723  PMID: 19900755
ultrasound-enhanced thrombolysis; drug delivery; therapeutic ultrasound; echogenic liposomes; ultrasound contrast agents; destruction thresholds
12.  Ultrasound-guided rectus sheath block in children with umbilical hernia: Case series 
Saudi Journal of Anaesthesia  2013;7(4):432-435.
Umbilical hernia repair, a common day-case surgery procedure in children, is associated with a significant postoperative pain. The most popular peripheral nerve blocks used in umbilical hernia repair are rectus sheath infiltration and caudal block. The rectus sheath block may offer improved pain relief following umbilical hernia repair with no undesired effects such as lower limb motor weakness or urinary retention seen with caudal block which might delay discharge from the hospital. Ultrasound guidance of peripheral nerve blocks has reduced the number of complications and improved the quality of blocks. The aim of this case series is to assess the post rectus sheath block pain relief in pediatric patients coming for umbilical surgery.
Twenty two (22) children (age range: 1.5-8 years) scheduled for umbilical hernia repair were included in the study. Following the induction of general anesthesia, the ultrasonographic anatomy of the umbilical region was studied with a 5-16 MHz 50 mm linear probe. An ultrasound-guided posterior rectus sheath block of both rectus abdominis muscles (RMs) was performed (total of 44 punctures). An in-plain technique using Stimuplex A insulated facet tip needle 22G 50mm. Surgical conditions, intraoperative hemodynamic parameters, and postoperative analgesia by means of the modified CHEOPS scale were evaluated.
ultrasonograghic visualization of the posterior sheath was possible in all patients. The ultrasound guided rectus sheath blockade provided sufficient analgesia in all children with no need for additional analgesia except for one patient who postoperatively required morphine 0.1 mg/kg intravenously. There were no complications.
Ultrasound guidance enables performances of an effective rectus sheath block for umbilical hernia. Use of the Stimuplex A insulated facet tip needle 22G 50mm provides easy, less traumatic skin and rectus muscle penetration and satisfactory needle visualiza.
PMCID: PMC3858695  PMID: 24348296
Anesthesia; analgesia; anesthetic techniques; peripheral nerve block; postoperative; regional; rectus sheath block; surgery; umbilical hernia; ultrasonography; umbilical
13.  Avoiding Unnecessary Fine-Needle Aspiration Cytology by Accuractely Predicting the Benign Nature of Thyroid Nodules Using Ultrasound 
The objective of this study was to describe a reliable ultrasound based index scoring system based on ultraound characteristics to identify benign thyroid nodules and avoid unnecessary fine needle aspiration cytology.
Materials and Methods:
Patients undergoing ultrasound-guided fine-needle aspiration cytology (FNAC) for thyroid nodules were evaluated prospectively. A total of 284 patients were evaluated from November 2005 to November 2011. There were 284 nodules. Any solid or partly solid focal nodule in the thyroid gland was included in the study. Cysts with no solid component were excluded. We used LOGIQ 9 (GE Healthcare) scanner equipped with a 10--14 MHz linear matrix transducer with color and power Doppler capability. Four US characteristics were evaluated, i.e., nodule margins, echo texture, vascularity, and calcification. Fine needle aspiration (FNA) was performed on all nodules. The nodules were labeled benign or suspicious using an ultrasound index score and the results compared with FNAC. Follicular neoplasms on fine-needle aspiration cytology were further assessed by excision biopsy and histology. Cytology/histology was used as the final diagnosis.
In total 284 nodules were analyzed. All the 234 nodules in US labeled benign category were proven to be benign on cytology/histology. Therefore the specificity of ultrasound in labeling a nodule benign was 100%. Twenty of the 50 nodules that were suspicious on US were malignant. The most significant US differentiating characteristics were nodule margins, vascularity, and microcalcification.
Our results show that US can accurately characterize benign thyroid nodules using an index scoring system and therefore preclude FNAC in these patients.
PMCID: PMC3352615  PMID: 22616040
Fine needle aspiration cytology; thyroid; ultrasound; benign thyroid nodule
14.  Novel Epidural Needle with Embedded High-frequency Ultrasound Transducer—Epidural Access in Porcine Model 
Anesthesiology  2011;114(6):1320-1324.
Epidural needle insertion is usually a blind technique where the rate of adverse events depends on the experience of the operator. A novel ultrasound method to guide epidural catheter insertion is described.
An ultrasound transducer (40 MHz, a −6 dB fractional bandwidth of 50%) was placed into the hollow chamber of an 18-gauge Tuohy needle. The single crystal was polished to a thickness of 50 µm, with a width of 0.5 mm. Tissue planes were identified from the reflected signals in an A-mode display. The device was inserted three times into both the lumbar and thoracic regions of five pigs (average weight, 20 kg) using a paramedian approach at an angle of 35–4°. The epidural space was identified using signals from the ligamentum flavum and dura mater. Epidural catheters were placed with each attempt and placement confirmed by contrast injection.
The ligamentum flavum was identified in 83.3% of insertions and the dura mater in all insertions. The dura mater signal was stronger than that of the ligamentum flavum and served as a landmark in all epidural catheter insertions. Contrast studies confirmed correct placement of the catheter in the epidural space of all study animals.
This is the first study to introduce a new ultrasound probe embedded in a standard epidural needle. It is anticipated that this technique could reduce failed epidural blocks and complications caused by dural puncture.
PMCID: PMC3104409  PMID: 21519228
15.  Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results 
Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap.
Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm2 for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to in vivo studies on pig esophagi.
Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases.
This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.
PMCID: PMC2430546  PMID: 18533990
16.  Feasibility and Safety of Transthoracic Echocardiography-Guided Transcatheter Closure of Atrial Septal Defects with Deficient Superior-Anterior Rims 
PLoS ONE  2012;7(12):e51117.
Although previous studies showed that transthoracic echocardiography (TTE) can be used to guide transcatheter closure of atrial septal defect (ASD), whether TTE can be used to guide transcatheter closure of secundum ASD with a deficient superior-anterior rim is unknown and this critical issue was addressed in the present study. A total of 280 patients with secundum ASD who underwent transcatheter ASD closure were recruited and divided into groups A and B depending on ASD superior-anterior rim>4 mm (n = 118) or ≤4 mm (n = 162). TTE was used to guide Amplatzer-type septal occluder (ASO) positioning and assess residual shunt. Procedure success was defined as no, trivial and small residual shunt immediately after the procedure as assessed by color Doppler flow imaging. Group A and group B did not differ in complication rate (8.55% vs.7.55%), procedure success rate (98.3% vs. 95.0%) or complete closure rate immediately after the procedure (89.7% vs. 89.3%) or at 6-month follow-up (98.3% vs. 96.8%). The mean procedure and fluoroscopy time in group B were much longer than those in group A. In conclusion, the absence of a sufficient superior-anterior rim in patients undergoing percutaneous closure of secundum-type ASDs using fluoroscopic and TTE guidance is associated with slightly greater device malposition and migration as well as increased procedural and fluoroscopic times, but the overall complication rate did not differ with TTE guidance when compared to historical controls that used TEE guidance.
PMCID: PMC3524244  PMID: 23284660
17.  Acoustic Techniques for Assessing the Optison Destruction Threshold 
The purpose of this study was to identify the pressure threshold for the destruction of Optison (octafluoropropane contrast agent; Amersham Health, Princeton, NJ) using a laboratory-assembled 3.5-MHz pulsed ultrasound system and a clinical diagnostic ultrasound scanner.
A 3.5-MHz focused transducer and a linear array with a center frequency of 6.9 MHz were positioned confocally and at 90° to each other in a tank of deionized water. Suspensions of Optison (5–8 × 104 microbubbles/mL) were insonated with 2-cycle pulses from the 3.5-MHz transducer (peak rarefactional pressure, or Pr, from 0.0, or inactive, to 0.6 MPa) while being interrogated with fundamental B-mode imaging pulses (mechanical index, or MI, = 0.04). Scattering received by the 3.5-MHz transducer or the linear array was quantified as mean backscattered intensity or mean digital intensity, respectively, and fit with exponential decay functions (Ae−kt + N, where A + N was the amplitude at time 0; N, background echogenicity; and k, decay constant). By analyzing the decay constants statistically, a pressure threshold for Optison destruction due to acoustically driven diffusion was identified.
The decay constants determined from quantified 3.5-MHz radio frequency data and B-mode images were in good agreement. The peak rarefactional pressure threshold for Optison destruction due to acoustically driven diffusion at 3.5 MHz was 0.15 MPa (MI = 0.08). Furthermore, the rate of Optison destruction increased with increasing 3.5-MHz exposure pressure output.
Optison destruction was quantified with a laboratory-assembled 3.5-MHz ultrasound system and a clinical diagnostic ultrasound scanner. The pressure threshold for acoustically driven diffusion was identified, and 3 distinct mechanisms of ultrasound contrast agent destruction were observed with acoustic techniques.
PMCID: PMC1939689  PMID: 17121946
acoustically driven diffusion; Optison; rapid fragmentation; static diffusion; ultrasound contrast agent destruction
18.  Ultrasonic Characterization of the Upper Trapezius Muscle in Patients with Chronic Neck Pain 
Ultrasonic imaging  2013;35(2):173-187.
Myofascial trigger points (MTrPs) are palpable, tender nodules in taut bands of skeletal muscle that are painful on compression. MTrPs are characteristic findings in myofascial pain syndrome (MPS). The role of MTrPs in the pathophysiology of MPS is unknown. Localization, diagnosis, and clinical outcome measures of painful MTrPs can be improved by objectively characterizing and quantitatively measuring their properties. The goal of this study was to evaluate whether ultrasound imaging and elastography can differentiate symptomatic (active) MTrPs from normal muscle. Patients with chronic (>3 months) neck pain with spontaneously painful, palpable (i.e., active) MTrPs and healthy volunteers without spontaneous pain (having palpably normal muscle tissue) were recruited for this study. The upper trapezius muscles in all subjects were imaged, and the echotexture was analyzed using entropy filtering of B-mode images. Vibration elastography was performed by vibrating the muscle externally at 100 Hz. Color Doppler variance imaging was used to quantify the regions of color deficit exhibiting low vibration amplitude. The imaging measures were compared against the clinical findings of a standardized physical exam. We found that sites with active MTrPs (n = 14) have significantly lower entropy (p < 0.05) and significantly larger nonvibrating regions (p < 0.05) during vibration elastography compared with normal, uninvolved muscle (n = 15). A combination of both entropy analysis and vibration elastography yielded 69% sensitivity and 81% specificity in discriminating active MTrPs from normal muscle. These results suggest that active MTrPs have more homogeneous texture and heterogeneous stiffness when compared with normal, unaffected muscle. Our methods enabled us to improve the imaging contrast between suspected MTrPs and surrounding muscle. Our results indicate that in subjects with chronic neck pain and active MTrPs, the abnormalities are not confined to discrete isolated nodules but instead affect the milieu of the muscle surrounding palpable MTrPs. With further refinement, ultrasound imaging can be a promising objective method for characterizing soft tissue abnormalities associated with active MTrPs and elucidating the role of MTrPs in the pathophysiology of MPS.
PMCID: PMC4332887  PMID: 23493615
ultrasound; superficial muscle; texture image analysis; myofascial trigger point; tissue differentiation; tissue characterization; ultrasonic imaging; entropy filtering
19.  Imaging investigation of pancreatic cystic lesions and proposal for therapeutic guidelines 
World Journal of Radiology  2012;4(8):372-378.
AIM: To propose a diagnostic algorithm for preoperatively predicting the need for surgical intervention.
METHODS: The study included 56 patients (27 men and 29 women) with a final diagnosis of cystic pancreatic lesions. The following materials were used: ultrasonic equipment with 3.5 and 7 MHz linear, convex and biopsical transducers. Multidetector computed tomography (MDCT) investigations were performed using a 16-slice scanner. Images were obtained following the oral administration of 200 mL water and 100 mL intravenous iopamidol (300 mg/mL) administered by pump injector at a rate of 3 mL/s (40 and 60 s post-injection, respectively) using 0.5 mm detectors, reconstructed at 1 mm (pancreatic phase) or 2 mm (portal venous phase) increments. The table feed was 10 mm per rotation. Images were acquired in the pancreatic and portal venous phases of contrast enhancement. The “Chiba” needles 18, 20, 22, 23 G and an automatic aspiration system were used in conjunction with the following methods of guiding the interventional procedures: (1)“free-hand” biopsy and puncture method under ultrasound (US) or computed tomography (CT) control; (2) guiding method using biopsical transducer.
RESULTS: All 56 patients in this study underwent at least two cuts imaging survey methods, such as US, CT or magnetic resonance imaging (MRI). The most common preoperative diagnostic examination was US scan - 56 patients (100%). MDCT studies were conducted in 49 (87.50%) and MRI in 13 (23.21%). More than half of patients surveyed (37) underwent some type of interventional procedure: 25-fine-needle aspiration and 29-fine needle aspiration biopsy (FNAB), as part of the examination. Thirty-four patients of all 56 patients underwent surgery because of histological evidence of malignancy after the FNAB for cystic lesions of the pancreas. Distal pancreatectomy with splenectomy was the most common operative approach in 13 patients, followed by Whipple resection in 11 and distal pancreatectomy without splenectomy in 7. Three patients were treated with total pancreatectomy due to the presence of a multifocal mucinous neoplasm. Comparing the diagnostic results of US examination with those of MDCT examination and histological verification true positive results were found in 31 patients, true negative in 11 patients, false positive in 5 and false negative in 9 patients. Accordingly we estimated the power of the diagnostic imaging methods for cystic lesions of the pancreas. A specificity of 68.75%, sensitivity of 79.48%, accuracy of 75.00%, positive predictive value of 86.11% and negative predictive value of 55% were obtained. The power increased after applying invasive procedures with immunohistochemical analysis of CEA and P-53 (Fig. 4). In 15 patients with cytological feature of malignant tumour cells, the tumour markers were positive. In our opinion the higher the percentage of reacting cells the higher the percent of malignancy. In patients with clear symptoms and/or clear imaging features of malignant or premalignant cystic neoplasm, the need for surgery was confirmed by histological verification in 34 (60.71%) of cases.
CONCLUSION: By using the proposed algorithm, cystic mucinous tumors of the pancreas were detected and proper operative interventions would have been rendered with fewer diagnostic examinations.
PMCID: PMC3430734  PMID: 22937216
Pancreatic cystic neoplasm; Diagnostic intervention; Fine-needle biopsy
20.  Ultrasound Enhanced Thrombolysis: Applications in Acute Cerebral Ischemia 
Intravenous tissue plasminogen activator (TPA) improves patient chances to recover from stroke by inducing mostly partial recanalization of large intracranial thrombi. TPA activity can be enhanced with ultrasound including 2 MHz transcranial Doppler (TCD). TCD identifies residual blood flow signals around thrombi, and, by delivering mechanical pressure waves, exposes more thrombus surface to circulating TPA. The international multi-center CLOTBUST trial showed that ultrasound enhances thrombolytic activity of a drug in humans thereby confirming multi-disciplinary experimental research conducted worldwide for the past 30 years.
In the CLOTBUST trial, the dramatic clinical recovery from stroke coupled with complete recanalization within 2 hours after TPA bolus occurred in 25% of patients treated with TPA+TCD compared to 8% who received TPA alone (p=0.02). Complete clearance of a thrombus and dramatic recovery of brain functions during treatment are feasible goals for ultrasound-enhanced thrombolysis that can lead to sustained recovery. An early boost in brain perfusion seen in the Target CLOTBUST group resulted in a trend of 13% more patients achieving favorable outcome at 3 months, subject for a pivotal trial. However, different results were achieved in a small TRUMBI trial and another study that used Transcranial Color-Coded Duplex Sonography (TCCD). Adverse bio-effects of mid-KHz (300) ultrasound promote bleeding, including brain areas not-affected by ischemia while exposure to multi-frequency / multi-element duplex ultrasound resulted in a trend towards higher risk of hemorrhagic transformations.
To further enhance the ability of TPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Enhancement of intra-arterial TPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter). Multi-national dose escalation studies of microspheres and the development of an operator independent ultrasound device are underway.
PMCID: PMC2686927  PMID: 19513336
TPA; Transcranial Doppler; Stroke; Thrombolysis; Outcomes
21.  Dual-mode Intracranial Catheter Integrating 3D Ultrasound Imaging & Hyperthermia for Neuro-oncology: Feasibility Study 
Ultrasonic imaging  2009;31(2):81-100.
In this study, we investigated the feasibility of an intracranial catheter transducer with dual-mode capability of real-time 3D (RT3D) imaging and ultrasound hyperthermia, for application in the visualization and treatment of tumors in the brain. Feasibility is demonstrated in two ways: first by using a 50-element linear array transducer (17 mm × 3.1 mm aperture) operating at 4.4 MHz with our Volumetrics diagnostic scanner and custom electrical impedance matching circuits to achieve a temperature rise over 4°C in excised pork muscle, and second by designing and constructing a 12 Fr, integrated matrix and linear array catheter transducer prototype for combined RT3D imaging and heating capability. This dual-mode catheter incorporated 153 matrix array elements and 11 linear array elements diced on a 0.2 mm pitch, with a total aperture size of 8.4 mm × 2.3 mm. This array achieved a 3.5°C in vitro temperature rise at a 2 cm focal distance in tissue-mimicking material. The dual-mode catheter prototype was compared with a Siemens 10 Fr AcuNav™ catheter as a gold standard in experiments assessing image quality and therapeutic potential, and both probes were used in a canine brain model to image anatomical structures and color Doppler blood flow and to attempt in vivo heating.
PMCID: PMC2810199  PMID: 19630251
catheter transducer; real-time 3D imaging; ultrasound hyperthermia; dual-mode array
22.  Blood-Brain Barrier (BBB) Disruption Using a Diagnostic Ultrasound Scanner and Definity® in Mice 
Ultrasound in medicine & biology  2009;35(8):1298-1308.
The objective of this work was to determine whether diagnostic ultrasound and contrast agent could be used to transcranially and nondestructively disrupt the blood-brain barrier (BBB) in mice under ultrasound image guidance, and to quantify that disruption using MRI and MR contrast agent. Each mouse was placed under isoflurane anesthesia and the hair on top of its skull was removed before treatment. A diagnostic ultrasound transducer was placed in a water bag coupled with gel to the mouse skull. Definity (US contrast) and Magnevist (MR contrast) were injected concurrent with the start of a custom ultrasound transmission sequence. The transducer was translated along the rostral-caudal axis to insonify three spatial locations (2 mm apart) along one half of the brain for each sequence. T1-weighted MR images were used to quantify the volume of tissue over which the BBB disruption allowed Magnevist to enter the brain, based upon increases in MR contrast-to-noise ratio (CNR) as compared to the noninsonified portions of the brain. Ultrasonic frequency, pressure, and pulse duration, as well as Definity dose and injection time were varied. Preliminary results suggest that a threshold exists for BBB opening dependent upon both pressure and pulse duration (consistent with reports in the literature performed at lower frequencies). A range of typical diagnostic frequencies (e.g., 5.0-8.0 MHz) generated BBB disruption. Comparable BBB opening was noted with varied delays between Definity injection and insonification (0-2 min) for a range of Definity concentrations (400-2400 μL/kg). The low-pressure, custom sequences (MI≤0.65) had minimal blood cell extravasation as determined by histological evaluation. This study has shown the ability of a diagnostic ultrasound system, in conjunction with Definity, to open the BBB transcranially in a mouse model for molecules approximately 0.5 kDa in size. Opening was achieved at higher frequencies than previously reported and was localized under ultrasound image guidance. A typical, ultrasound imaging mode (PW Doppler) with specific settings (transmit frequency=5.7 MHz, gate size=15 mm, pulse repetition frequency=100 Hz, system power=15%) successfully opened the BBB, which facilitates implementation using the majority of commercially available clinical diagnostic scanners. Localized opening of the BBB may have potential clinical utility for the delivery of diagnostic or therapeutic agents to the brain.
PMCID: PMC2729364  PMID: 19545939
Ultrasound; Contrast agent; Blood-brain barrier; Drug delivery; Magnetic resonance imaging
23.  Characterization of a Broadband All-Optical Ultrasound Transducer—From Optical and Acoustical Properties to Imaging 
A broadband all-optical ultrasound transducer has been designed, fabricated, and evaluated for high-frequency ultrasound imaging. The device consists of a 2-D gold nanostructure imprinted on top of a glass substrate, followed by a 3 μm PDMS layer and a 30 nm gold layer. A laser pulse at the resonance wavelength of the gold nanostructure is focused onto the surface for ultrasound generation, while the gold nanostructure, together with the 30 nm thick gold layer and the PDMS layer in between, forms an etalon for ultrasound detection, which uses a CW laser at a wavelength far from resonance as the probing beam. The center frequency of a pulse-echo signal recorded in the far field of the transducer is 40 MHz with -6 dB bandwidth of 57 MHz. The signal to noise ratio (SNR) from a 70 μm diameter transmit element combined with a 20 μm diameter receive element probing a near perfect reflector positioned 1.5 mm from the transducer surface is more than 10 dB and has the potential to be improved by at least another 40 dB. A high-frequency ultrasound array has been emulated using multiple measurements from the transducer while mechanically scanning an imaging target. Characterization of the device’s optical and acoustical properties, as well as preliminary imaging results, strongly suggest that all-optical ultrasound transducers can be used to build high-frequency arrays for real-time high-resolution ultrasound imaging.
PMCID: PMC2760086  PMID: 18986929
24.  Ultrasonic Doppler measurements of blood flow velocity of rabbit retinal vessels using a 45-MHz needle transducer 
The purpose of this study is to measure blood flow velocity of rabbit retinal vessels using a 45-MHz ultrasonic Doppler system with a needle transducer.
A high-frequency pulsed Doppler system that utilizes a 45-MHz PMN-PT needle transducer was developed to measure retinal blood flow velocity in situ. The pulsed Doppler allowed the differentiation of retinal from choroidal blood flow velocity. The needle transducer was inserted into the vitreous cavity through a 20-gauge incision port to access the retinal vessels. The first phase of the experiment evaluated the reproducibility of the measurements. The second phase measured velocities at four positions from the optic disc edge to the distal part of each vessel in nine eyes for the temporal and six eyes for the nasal portions. The angle between the transducer and the retinal vessel at each site was measured in enucleated rabbit eyes to estimate and compensate for measurement errors.
In the first phase, the average measurement error was 5.97±1.34%. There was no significant difference comparing all eyes. In the second phase, the velocities gradually slowed from the disc edge to the distal part, and temporal velocities were faster than nasal velocities at all measurement sites.
This study demonstrated the feasibility of reliably measuring retinal blood flow velocity using a 45-MHz ultrasonic Doppler system with a needle transducer.
PMCID: PMC2847001  PMID: 20162299
Blood flow velocity; Rabbit; Retina; High-frequency Doppler system; Intraocular transducer
25.  Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney 
Ultrasound in medicine & biology  2010;36(10):1691-1703.
Acoustic droplet vaporization (ADV) shows promise for spatially and temporally targeted tissue occlusion. In this study, substantial tissue occlusion was achieved in operatively exposed and transcutaneous canine kidneys by generating ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were anesthetized, among which 10 underwent laparotomy to externalize the left kidney and 5 were undisturbed for transcutaneous ADV. The microbubbles were generated by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid shells in the blood. A 3.5 MHz single-element therapy transducer was aligned with an imaging array in a water tank with direct access to the renal artery or a segmental artery. In vivo color flow and spectral Doppler imaging were used to identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency with 0.25% duty cycle vaporized the droplets during bolus passage. Both intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent with this in two cases was the detection by pulse wave Doppler of blood flow reversal, along with a narrowing of the waveform. Localized cortex occlusion was achieved with 87% regional flow reduction in one case using IC injections. Vaporization from IV injections resulted in a substantial echogenicity increase with an average half-life of 8 minutes per droplet dose. Gas bubbles sufficient to produce some shadowing were generated by transcutaneous vaporization of intra renal artery or IV administered droplets, with a tissue path up to 5.5 cm.
PMCID: PMC2951622  PMID: 20800939
Acoustic droplet vaporization; embolization; blood flow reduction; canine kidney; transcutaneous vaporization; ultrasound

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