Novel treatment system using endoscopic ultrasound-guided high-intensity focused ultrasound: A proof-of-concept study.

AIM: High-intensity focused ultrasound (HIFU) is a novel minimally invasive local treatment of solid tumors. Endoscopic ultrasound-guided HIFU (EUS-HIFU) using mechanical effects would have potential benefits, including precise detection of target lesions and enhance drug delivery. The aim of this study is to develop EUS-HIFU device and to prove our concept in porcine model using a locally injected phase change nano droplet (PCND) as the sensitizer. METHOD: A phospholipid PCND contained volatile perfluoro-carbon liquids. The prototype HIFU apparatus comprised a small (20 × 20 mm) transducer with center frequency of 2.1 MHz, attachable to a linear EUS transducer. Under general anesthetic, a single porcine received EUS-guided injection of PCND. The HIFU transducer was placed laparotomically in the stomach, and the liver was ablated through the gastric wall. RESULTS: PCND was injected successfully and a distinct lesion was generated at the HIFU transducer focus only in injected areas that received HIFU exposure at 4.7 kW/cm2 at a duty cycle of 5 % (mean temporal intensity, 0.245 kW/cm2) for 30 s. The generated lesions were mechanically fractionated in macroscopic view. CONCLUSION: The concept of transluminal HIFU ablation using novel EUS-HIFU system was proved in a porcine animal model. This novel treatment system has great potential for future cancer treatment although further investigation in more animals and different organs are warranted.

Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF. METHODS AND RESULTS: Patients with HFpEF (n = 198) had measurements of baPWV and PVR by right heart catheterization, and were prospectively followed-up for <96 months or until the occurrence of a composite of all-cause death, hospitalization with worsening HF, and nonfatal acute coronary syndrome. RESULTS: Multivariate logistic analysis showed that baPWV was independently associated with PH with increased PVR (P < .001). During the follow-up period, 46 clinical events occurred. Multivariate Cox proportional hazards analysis showed that PH with increased PVR was a significant predictor of adverse outcomes after adjustment for conventional risk factors (HR 1.96, 95% CI 1.03-3.76, P = .04). CONCLUSIONS: PH with increased PVR was associated with increased baPWV and adverse clinical outcomes in HFpEF. Thus, increased arterial stiffness may contribute to increased risk predictability of PVR for patients with HFpEF.

Echolucency of carotid plaque is useful for assessment of residual cardiovascular risk in patients with chronic coronary artery disease who achieve LDL-C goals on statin therapy.

BACKGROUND: Ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of the carotid artery provides prognostic information on coronary events. This study examined the hypothesis that IMT and plaque echolucency of the carotid artery may remain useful for prediction of coronary events in patients with coronary artery disease (CAD) after achievement of LDL-C goals on statin therapy. METHODS AND RESULTS: Ultrasound assessment of carotid maximum IMT (maxIMT) and plaque echolucency with integrated backscatter (IBS) analysis was performed in 357 chronic CAD patients with LDL-C <100mg/dl on statin therapy. All patients were prospectively followed up until the occurrence of one of the following coronary events: cardiac death, non-fatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. During a mean follow-up of 32±18 months, 33 coronary events occurred. On multivariate Cox proportional hazards analysis, plaque echolucency (lower IBS value) was a significant predictor of coronary events (HR, 0.44; 95% CI: 0.29-0.73; P=0.009), whereas maxIMT was not. The addition of plaque echolucency to traditional risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI; NRI, 0.59; P=0.0013; and IDI, 0.075; P=0.0009). CONCLUSIONS: Measurement of echolucency of the carotid artery was useful for assessment of residual coronary risk in CAD patients after LDL-C goal attainment on statin treatment.

In-stent restenosis is inhibited in a bare metal stent implanted distal to a sirolimus-eluting stent to treat a long de novo coronary lesion with small distal vessel diameter.

OBJECTIVES: This study examined whether sirolimus-eluting stent (SES) implantation exerts an antiproliferative action on a bare metal stent (BMS) placed distally in the same coronary artery. BACKGROUND: Diffusion of sirolimus into flowing coronary blood may cause accumulation of this drug in the coronary bed beyond the distal edge of an SES. METHODS: We analyzed data from 115 consecutive patients with ischemic heart disease who were treated with two overlapping stents without a gap in the same coronary artery for a long de novo lesion. The distal stent was a 2.25 mm BMS in all patients, and the proximal stent was an SES in 73 patients (SES-BMS group) and a BMS in 42 patients (BMS-BMS group). Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) were performed at stent implantation and 8 months later. RESULTS: Clinical and procedural variables were comparable between the two groups. QCA and IVUS showed that the SES-BMS group had less luminal late loss and a lower percent of in-stent volume obstruction in the distal BMS compared with the BMS-BMS group. Furthermore, compared with the BMS-BMS group, the SES-BMS group had less in-stent restenosis (23.3 vs. 54.8%, P < 0.0005) and target lesion revascularization (21.9 vs. 50.0%, P < 0.005). CONCLUSIONS: SES implantation just proximal to a BMS inhibits neointimal proliferation in the BMS, when both stents are implanted in the same coronary artery to treat a de novo lesion.

Contrast-enhanced ultrasound imaging of carotid plaque neovascularization is useful for identifying high-risk patients with coronary artery disease.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) in the carotid artery has potential as a technique for imaging plaque neovascularization. This study examined whether CEUS could provide information on the severity and instability of coronary artery disease (CAD). METHODS AND RESULTS: A total of 304 patients with CAD and carotid plaque underwent CEUS examination of the carotid artery. Intraplaque neovascularization was identified on the basis of microbubbles within the plaque and graded as: G0, not visible; G1, moderate; or G2, extensive microbubbles. The complexity and extent of the coronary lesions were assessed angiographically. A higher grade of CEUS-assessed plaque neovascularization of the carotid artery was associated significantly with greater complexity (ρ=0.48 by Spearman's rank correlation test) and extent (ρ=0.51) of coronary lesions. G2 plaque neovascularization was a risk for acute coronary syndrome, independent of traditional risk factors (odds ratio 1.91, 95% confidence interval 1.04-3.53, P<0.01). Subgroup analysis showed that carotid CEUS-assessed neovascularization regressed in 12 (46%) of 26 plaques in patients during 6 months of statin treatment, whereas regression occurred in 2 (14%) of 14 plaques in patients not taking a statin (P=0.04, Chi-square test). CONCLUSIONS: CEUS examination of the carotid artery may provide valuable information on the severity and instability of CAD and also the efficacy of antiatherosclerotic treatment.

Usefulness of a collateral channel dilator for antegrade treatment of chronic total occlusion of a coronary artery.

OBJECTIVES: The aim of this study was to clarify the effectiveness of a collateral channel dilator microcatheter in antegrade percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) of a coronary artery. BACKGROUND: The Corsair microcatheter, which was originally developed as a collateral channel dilator, has been reported to be useful for retrograde CTO-PCI. METHODS: We compared the success rate of the Corsair microcatheter collateral channel dilator for antegrade CTO-PCI with a previously available microcatheter. We analyzed the data from 27 patients (32 CTOs) using the FinecrossMG (Finecross group) and the data from 31 patients (34 CTOs) using the Corsair (Corsair group). RESULTS: There were no significant differences in the clinical or lesion characteristics between the 2 groups. The success rate for crossing the CTO by the microcatheter was 62.5% in the Finecross group and 85.3% in the Corsair group (P < 0.05). After the Corsair crossed the CTO, a 2-mm diameter balloon catheter crossed the lesion in all the cases, but it crossed the lesion in only 17 of 20 cases in the Finecross group (85.0%, P < 0.05). The number of balloon catheters used for predilation was significantly less in the Corsair group compared with the Finecross group (P < 0.05). CONCLUSIONS: The success rate for crossing of the microcatheters and the balloon catheters through the occlusion in antegrade CTO-PCI was better with the Corsair than with the FinecrossMG. In addition, the use of the Corsair reduced the number of balloon catheters used for predilation in antegrade CTO-PCI.

Early improvement in carotid plaque echogenicity by acarbose in patients with acute coronary syndromes.

BACKGROUND: The resolution of hyperglycemia is associated with suppression of in-hospital cardiac complications in patients with acute coronary syndromes (ACS). This study evaluated carotid artery plaque echolucency using ultrasound in patients with ACS and type 2 diabetes mellitus (DM) to determine whether acarbose, an α-glucosidase inhibitor, may rapidly stabilize unstable atherosclerotic plaques. METHODS AND RESULTS: ACS patients with type 2 DM and carotid plaques (n=44) were randomly assigned to treatment with acarbose (150 or 300 mg/day, n=22) or a control group (no acarbose, n=22). Acarbose treatment was initiated within 5 days after the onset of ACS. Unstable carotid plaques were assessed by measuring plaque echolucency using carotid ultrasound with integrated backscatter (IBS) before, and at 2 weeks, 1 and 6 months after the initiation of treatment. An increase in the IBS value reflected an increase in carotid plaque echogenicity. As results, the IBS value of echolucent carotid plaques showed a significant increase at 1 month and a further increase at 6 months after treatment in the acarbose group, but there was minimal change in the control group. The increase in IBS values was significantly correlated with a decrease in C-reactive protein levels. CONCLUSIONS: Acarbose rapidly improved carotid plaque echolucency within 1 month of therapy in patients with ACS and type 2 DM.

Comparative study of bezafibrate and pravastatin in patients with coronary artery disease and high levels of remnant lipoprotein.

BACKGROUND: Remnant lipoproteinemia is a strong risk factor for cardiovascular (CV) diseases. This study examined which of 2 common lipid-lowering drugs (fibrates and statins) is more effective in patients with remnant lipoproteinemia and if lowering remnant lipoprotein levels can reduce CV risk. METHODS AND RESULTS: Remnant lipoprotein levels were measured by an immunoseparation method (remnant-like lipoprotein particles cholesterol: RLP-C) in 274 patients with coronary artery disease and high RLP-C levels (>or=5.0 mg/dl). They were randomly assigned to receive bezafibrate (200-400 mg/day) or pravastatin (10-20 mg/day), and were prospectively followed-up for 1 year or until the occurrence of CV events. Complete follow-up data were obtained in 180 patients. RLP-C levels at 1 year of treatment were reduced more by bezafibrate than pravastatin (37% and 25% from baseline, respectively). During follow-up, bezafibrate-treated patients had 3 CV events, compared with 12 events in pravastatin-treated patients (P<0.01). In multivariate logistic regression analysis, a decrease in RLP-C level was significantly associated with a reduction in CV events after adjustment for treatment group and changes in levels of other lipids. CONCLUSIONS: Bezafibrate therapy decreased RLP-C levels to a greater extent than pravastatin and a decrease in RLP-C level may be associated with a reduction in CV events in patients with high RLP-C levels.

Inhibition of secretory phospholipase A2 activity attenuates lipopolysaccharide-induced acute lung injury in a mouse model.

This study evaluated the hypothesis that LY374388, an inhibitor of secretory phospholipase A(2) (sPLA(2)) activity, may exert a protective effect on lipopolysaccharide (LPS)-induced acute lung injury in male C57BL/6J mice. Intratracheal administration of LPS increased histopathological changes in lung tissue, lung wet to dry ratios, and the bronchoalveolar lavage fluid levels of neutrophil numbers, sPLA(2) activity, leukotriene B(4), and thromboxane B(2). However, a simultaneous intraperitoneal treatment with LY374388 significantly attenuated these LPS-induced changes. Thus, inhibition of sPLA(2) activity significantly attenuated the acute lung injury induced by LPS. sPLA(2) played an important role in the pathogenesis of LPS-induced acute lung injury in mice.

Ultrasound Sub-pixel Motion-tracking Method with Out-of-plane Motion Detection for Precise Vascular Imaging.

Ultrasound vascularity imaging provides important information for differential diagnosis of tumors. Peak-hold (PH) is a useful technique for precisely imaging small vessels by selecting a maximum brightness in each pixel through the frames obtained sequentially. To use PH successfully one needs motion compensation to reduce image blur, but out-of-plane motion cannot be avoided. To address this problem, we developed a sub-pixel motion-tracking method with out-of-plane motion detection (OPMD). It is a combination of the sum of the absolute differences (SAD) method and the Kanade-Lucas-Tomasi method and can be accurately applied to various motions. The value from OPMD (γ) is defined as a statistical value obtained from the distribution of residual values in the SAD procedure with the obtained frames. The value is ideally 0, and the frames having large γ are removed from the PH procedure. The accuracy of the proposed tracking method was found by a simulation study to be approximately 20 µm. We also found, through a phantom experiment, that the value of γ sensitively increased enough to detect out-of-plane motion. Most important, γ begins to increase before tracking errors occur. This suggests that OPMD can be used to predict tracking errors and effectively remove frames from the PH procedure. An in vivo experiment with a rabbit showed that the PH image obtained with motion tracking clearly revealed peripheral vessels that were blurred in the PH image obtained without motion tracking. We also found that the image quality becomes better when OPMD was used to remove frames including out-of-plane motion.

Reduction in myocardial ischemia/reperfusion injury in group X secretory phospholipase A2-deficient mice.

BACKGROUND: Group X secretory phospholipase A(2) (sPLA(2)-X) has the most potent hydrolyzing activity toward phosphatidylcholine and elicits a marked release of arachidonic acid among several types of sPLA(2). sPLA(2)-X is expressed in neutrophils, but its pathogenic role remains unclear. METHODS AND RESULTS: We generated mice that lack sPLA(2)-X and studied their response to myocardial ischemia/reperfusion. The sPLA(2)-X(-/-) mice had a significant reduction in myocardial infarct size and a decrease in myocardial myeloperoxidase activity compared with sPLA(2)-X(+/+) mice. Myocardial infarct size was also significantly reduced in lethally irradiated sPLA(2)-X(+/+) mice reconstituted with sPLA(2)-X(-/-) bone marrow compared with sPLA(2)-X(+/+) bone marrow. The extent of myocardial ischemia/reperfusion injury was comparable between sPLA(2)-X(-/-) and sPLA(2)-X(+/+) mice in Langendorff experiments using isolated hearts and blood-free perfusion buffer, supporting a potential role of sPLA(2)-X in blood in myocardial ischemia/reperfusion injury. In the infarcted myocardium of sPLA(2)-X(+/+) mice, sPLA(2)-X was released from neutrophils but not myocardial tissues and platelets and was undetectable in the peripheral serum. The sPLA(2)-X(-/-) mice had lower accumulation of neutrophils in ischemic myocardium, and the isolated sPLA(2)-X(-/-) neutrophils had lower release of arachidonic acid and attenuated cytotoxic activities including respiratory burst compared with sPLA(2)-X(+/+) neutrophils. The attenuated functions of sPLA(2)-X(-/-) neutrophils were reversible by the exogenous addition of sPLA(2)-X protein. Furthermore, administration of a sPLA(2) inhibitor reduced myocardial infarct size and suppressed the cytotoxic activity of sPLA(2)-X(+/+) neutrophils. CONCLUSIONS: Myocardial ischemia/reperfusion injury was attenuated in sPLA(2)-X(-/-) mice partly through the suppression of neutrophil cytotoxic activities.

Measurement of the platelet retention rate in a column of collagen-coated beads is useful for the assessment of efficacy of antiplatelet therapy.

INTRODUCTION: A simple, validated method to measure platelet function is unavailable for bedside use. Measurement of platelet retention rate using a column of collagen-coated beads and whole blood is a new, simple assay that reflects platelet aggregation. This study was aimed to examine the utility of this assay to assess efficacy of antiplatelet drug therapy. METHODS: Citrated whole blood (1.5 ml) in a syringe was passed through a polyvinyl tube packed with collagen-coated beads for 40 seconds using a syringe pump. Platelet retention rate in the column was calculated from platelet counts in blood before and after passage. An increase in the retention rate reflects an increase in platelet activity. This new platelet retention assay and the traditional optical aggregometry assay were performed in 331 patients with stable coronary artery disease (CAD). RESULTS: The retention rate was significantly reduced in patients taking dual antiplatelet therapy (aspirin plus clopidogrel or ticlopidine) compared with aspirin alone. There was a significant linear correlation between the platelet retention rate and platelet aggregability measured by the traditional method (r=0.44, p<0.001). In multivariate Cox proportional hazards analysis, higher platelet retention rate was an independent predictor of future cardiovascular events in patients on dual antiplatelet therapy (hazard ratio 3.9, 95% CI 1.6 to 9.5, p=0.003). CONCLUSIONS: Measurement of the platelet retention rate in a column of collagen-coated beads may be useful for monitoring the efficacy of antiplatelet drug therapy in patients with CAD.

Correction to: Accuracy and limitations of vector flow mapping: left ventricular phantom validation using stereo particle image velocimetory.

The original version of this article unfortunately contained a mistake. The conflict of interest statement was missing in the article. The CoI statement is given below.

Transluminal Approach with Bubble-Seeded Histotripsy for Cancer Treatment with Ultrasonic Mechanical Effects.

Bubble-seeded histotripsy (BSH) is a newly developed ultrasound-based mechanical fractionation technique using locally injected phase change nanodroplets (PCNDs) as sensitizers. The PCNDs are a kind of microbubble precursor compressed into submicron-size in droplets form, which were designed for local administration and will expand into microbubbles under ultrasound exposure. Previously, we reported that a combination of PCNDs injection and pulsed high-intensity focused ultrasound (pHIFU) with an acoustic intensity as low as about 3 kW/cm2 at 1.1 MHz, which is similar to the acoustic intensity of currently available HIFU coagulation therapy, was enough to induce tissue fractionation after significant antitumor effects in an in vivo study. Toward therapeutic application of BSH to deep-seated tissues such as the pancreas, the transluminal approach, using endoscopic ultrasound was thought to be ideal. Therefore, for a preliminary examination, we developed a new transducer with a small aperture (20- × 20-mm square) and long focal length (35 mm), operating at 2.1 MHz that could be attached to an EUS-mimicking probe. With the newly developed transducer and locally injected PCNDs, predictable tissue mechanical fractionation was observed in both ex vivo and in vivo studies at acoustic intensities that were too low to induce any significant bioeffects (around 4 kW/cm2) without using PCNDs. For in situ monitoring of the treatment site during a procedure, the degree of attenuation of microbubble motions after exposing the microbubbles to pHIFU was monitored, using ultrafast echographic imaging. Microbubble movements were observed to be largest at 25-30 s after pHIFU exposure. On the contrary, after 40 s, the movement of microbubbles decreased to the same level as at the start of the procedure, suggesting that an overdose of pHIFU exposure causes coagulation attributable to the thermal effect caused by absorption of the energy. Those results were promising for expanding the application of BSH for a transluminal approach, using a small transducer under real-time monitoring.

Association of low serum levels of apolipoprotein A-I with adverse outcomes in patients with nonischemic heart failure.

BACKGROUND: There is extensive evidence that low serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) predict a worse prognosis in patients with ischemic heart disease. This study examined whether apoA-I levels may also provide prognostic information in patients with nonischemic heart failure. METHODS AND RESULTS: A prospective follow-up study was performed in 117 consecutive patients with nonischemic heart failure for a period of < or = 36 months until the first occurrence of 1 of the following clinical events: all-cause death, cardiac death, and hospitalization with worsening heart failure. Serum levels of apoA-I were measured by immunoturbidimetry. A clinical event occurred during follow-up in 28 (24%) patients. A multivariate Cox proportional hazards analysis showed that lower apoA-I levels (< 103 mg/dL: determined by a receiver-operating characteristic analysis) were significantly associated with an adverse outcome that was independent of creatinine clearance, HDL cholesterol levels, and brain natriuretic peptide levels. ApoA-I was inversely correlated with levels of C-reactive protein and fibrinogen, known inflammatory predictors of poor prognosis in heart failure. CONCLUSIONS: Low levels of apoA-I are independently associated with an adverse prognosis in patients with nonischemic heart failure. ApoA-I may play a beneficial role in nonischemic heart failure partly through an anti-inflammatory action.

Accuracy and limitations of vector flow mapping: left ventricular phantom validation using stereo particle image velocimetory.

BACKGROUND: The accuracy of vector flow mapping (VFM) was investigated in comparison to stereo particle image velocimetry (stereo-PIV) measurements using a left ventricular phantom. VFM is an echocardiographic approach to visualizing two-dimensional flow dynamics by estimating the azimuthal component of flow from the mass-conservation equation. VFM provides means of visualizing cardiac flow, but there has not been a study that compared the flow estimated by VFM to the flow data acquired by other methods. METHODS: A reproducible three-dimensional cardiac blood flow was created in an optically and acoustically transparent left-ventricle phantom, that allowed color-flow mapping (CFM) data and stereo-PIV to be simultaneously acquired on the same plane. A VFM algorithm was applied to the CFM data, and the resulting VFM estimation and stereo-PIV data were compared to evaluate the accuracy of VFM. RESULTS: The velocity fields acquired by VFM and stereo-PIV were in excellent agreement in terms of the principle flow features and time-course transitions of the main vortex characteristics, i.e., the overall correlation of VFM and PIV vectors was R = 0.87 (p < 0.0001). The accuracy of VFM was suggested to be influenced by both CFM signal resolution and the three-dimensional flow, which violated the algorithm's assumption of planar flow. Statistical analysis of the vectors revealed a standard deviation of discrepancy averaging at 4.5% over the CFM velocity range for one cardiac cycle, and that value fluctuated up to 10% depending on the phase of the cardiac cycle. CONCLUSIONS: VFM provided fairly accurate two-dimensional-flow information on cardio-hemodynamics. These findings on VFM accuracy provide the basis for VFM-based diagnosis.

A posteriori accuracy estimation of ultrasonic vector-flow mapping (VFM).

ABSTRACT: A novel method, called a posteriori "VFM accuracy estimation" (VAE), for resolving an intrinsic VFM problem is proposed. The problem is that VFM uncertainty can easily vary according to blood flows through an echocardiographic imaged plane (i.e., "through-plane" flows), and it is unknown. Knowing the VFM uncertainty for each patient will make it possible to refine the quality of VFM-based diagnosis. In the present study, VAE was derived on the basis of an error-propagation analysis and a statistical analysis. The accuracy of VAE with a pulsatile left-ventricle phantom was experimentally investigated for realistic cases with through-plane flows. VAE was validated by comparing VFM uncertainty (S.D.) estimated by VAE with VFM uncertainty measured by particle-image velocimetry (PIV) for different imaged planes. VAE accurately estimated the S.D. of VFM uncertainty measured by PIV for all cases with different image planes (R > 0.6 and p < 0.001). These findings on VFM accuracy will provide the basis for widespread clinical application of VFM-based diagnosis.

Endothelial vasomotor dysfunction in the brachial artery is associated with late in-stent coronary restenosis.

OBJECTIVES: This study examined whether endothelial dysfunction in the brachial artery might be associated with late in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). BACKGROUND: Simple and noninvasive identification of late ISR might help to select patients who require further angiographic evaluation. METHODS: Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was measured before (initial FMD) and at six months (follow-up FMD) after PCI in 141 consecutive patients who had elective and successful PCI with bare metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease. Follow-up angiography was performed at six months after PCI in all patients. RESULTS: With multivariate logistic regression analysis, the impairment (< or = 4.8% dilation from baseline diameter) of FMD at follow-up showed the strongest association with late ISR (defined as > 50% diameter stenosis, n = 46) independently of other clinical and angiographic variables known to be associated with ISR (odds ratio 7.4, 95% confidence interval 2.8 to 19.2, p < 0.001), whereas the initial FMD did not have the association. The sensitivity of impaired FMD at follow-up (69%) in detecting ISR was higher than chest pain during the follow-up period (45%), with comparable specificity. The impaired FMD in combination with the chest pain increased the sensitivity to 90%. CONCLUSIONS: The impairment of FMD in the brachial artery at the time of follow-up was independently and closely associated with late ISR in native coronary arteries. The noninvasive assessment of FMD at the time of follow-up might be useful for identification of late ISR.

Effect of echo-guided high-intensity focused ultrasound ablation on localized experimental tumors.

We fabricated a prototype 3.25-MHz split-focus therapeutic transducer combined with a small 6.5-MHz imaging ultrasonic probe for transrectal treatment of prostate cancer and evaluated the feasibility of using split-focus high-intensity focused ultrasound (HIFU) to ablate localized tumor tissue without injuring the surrounding organs. We therefore established a localized tumor model by inoculating VX2 tumor into rabbit livers. The localized VX2 tumors of nine rabbits were transdermally treated with split-focus ablation at a peak intensity in water of 6 kW/cm2 for 4 s (6 shots) under the guidance of ultrasonic B-mode imaging. Necropsy a day after treatment found the surface of the livers and gastrointestinal tracts to be grossly normal. The VX2 tumors were completely coagulated and were surrounded by ablated liver tissue. The six shots of split-focus HIFU destroyed the VX2 tumors without injuring the liver surfaces or the surrounding organs. These results suggest that split-focus HIFU ablation could be an effective treatment of localized tumors.

Chronic effect of transrectal split-focus ultrasonic ablation on canine prostatic tissue.

The treatment time needed for high-intensity focused ultrasound (HIFU) ablation might be decreased substantially by using the split-focus approach, so we made a prototype 4.2-MHz split-focus therapeutic transducer combined with a small 6.5-MHz imaging ultrasonic probe for transrectally treatment of canine prostatic cancer and used it to experimentally evaluate the feasibility of using split-focus transrectal HIFU to ablate canine prostatic tissue without injuring surrounding tissues. The prostates of 5 dogs were transrectally treated with split-focus ablation at a peak intensity in the water of 1.7 kW/cm(2) for 4 s (4 shots) under the guidance of ultrasonic B-mode imaging. After ultrasonic exposure, the prostates became stiff because of thermal effect of HIFU. For the first 3-5 days after treatment, dogs were catheterized daily for urinary management and treated with oral antibiotics to prevent urinary tract infection. The dogs were able to urinate normally by a week after. Within two weeks a large centrally located cystic cavity had formed in the prostate by replacing the necrotic parenchyma around the prostatic urethra. Necropsy three months after treatment found the rectum and prostate capsule to be normal grossly and histologically. The 4 shots of split-focus HIFU destroyed the prostatic parenchyma and created a prostatic cavity 0.34-0.45 cm(3) in volume without injuring surrounding tissues. These results suggest that split-focus HIFU ablation could be used for noninvasive treatment of prostatic cancer in dogs.