Search

ObjectiveThe aim of the study was to investigate the effectiveness and safety of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in patients with poststroke aphasia.MethodWe comprehensively searched for eligible studies from 11 electronic medical databases from their inception to February 20, 2019. Randomized controlled trials reporting the effectiveness of LF-rTMS for patients with poststroke aphasia were included. The primary outcome was language ability. The secondary outcomes were functional communication and adverse events. The methodological quality of the randomized controlled trials was evaluated by the Cochrane Back Review Group Risk of Bias Assessment Criteria.ResultsOf the 567 records retrieved, 18 studies with a total of 536 participants were included. All the included studies were of relatively acceptable methodological quality. All studies but one used LF-rTMS + speech and language therapy (SLT), not LF-rTMS alone. The meta-analysis showed that LF-rTMS had beneficial effects for patients with aphasia after a stroke in terms of naming, repetition, comprehension, written language, and functional communication. The subgroup analyses of language performance showed positive effects of LF-rTMS among stroke patients with chronic aphasia and acute aphasia. LF-rTMS + SLT had effects on language performance that were superior to the sham rTMS + SLT and SLT alone. A shorter LF-rTMS duration benefited language performance more than a longer duration. Additionally, 20 min of LF-rTMS per session produced a positive effect on language ability for patients with aphasia after a stroke. No adverse events were reported.ConclusionsLF-rTMS + SLT is an effective and safe method for patients with poststroke aphasia to improve their language performance. Additionally, the most commonly used LF-rTMS protocol for patients with aphasia after a stroke was 90% of the resting motor threshold 20 min per day, 5 days per week, for 2 weeks.

Background Spasticity is a common post-stroke complication, and it results in substantial deterioration in the quality of life of patients. Although potential positive effects of warm-needle moxibustion on spasticity after stroke have been observed, evidence on its definitive effect remains uncertain. Objectives This study aimed to summarize clinical evidence pertaining to therapeutic effects and safety of warm-needle moxibustion for treating spasticity after stroke. Design Randomized controlled trials were reviewed systematically on the basis of the Cochrane Handbook for Systematic Reviews of Interventions. The report follows the PRISMA statement. Methods Ten electronic databases (PubMed, CENTRAL, EMBASE, AMED, CINAHL, Web of Science, CBM, CNKI, WanFang, and VIP) were explored, and articles were retrieved manually from two Chinese journals ( The Journal of Traditional Chinese Medicine and Zhong Guo Zhen Jiu ) through retrospective search. Randomized controlled trials with warm-needle moxibustion as treatment intervention for patients with limb spasm after stroke were included in this review. The risk of bias assessment tool was utilized in accordance with Cochrane Handbook 5.1.0. All included studies reported spasm effect as primary outcome. Effect size was estimated using relative risk, standardized mean difference, or mean difference with a corresponding 95% confidence interval. Review Manager 5.3 was utilized for meta-analysis. Results Twelve randomized controlled trials with certain methodological flaws and risk of bias were included, and they involved a total of 878 participants. Warm-needle moxibustion was found to be superior to electroacupuncture or acupuncture in reducing spasm and in promoting motor function and daily living activities. Pooled results for spasm effect and motor function were significant when warm-needle moxibustion was compared with electroacupuncture or acupuncture. A comparison of daily living activities indicated significant differences between warm-needle moxibustion and electroacupuncture. However, no difference was observed between warm-needle moxibustion and acupuncture. Conclusions Warm-needle moxibustion may be a promising intervention to reduce limb spasm as well as improve motor function and daily living activities for stroke patients with spasticity. However, evidence was not conclusive. Rigorously designed randomized controlled trials with sample sizes larger than that in the included trials should be conducted for verification.

Apelin plays important roles in cardiovascular homeostasis. However, its effects on the mechanoenergetics of heart failure (HF) are unavailable. We attempted to investigate the effects of apelin on the left ventricular-arterial coupling (VAC) and mechanical efficiency in rats with HF. HF was induced in rats by the ligation of the left coronary artery. The ischemic HF rats were treated with apelin or saline for 12 weeks. The sham-operated animals served as the control. The left ventricular (LV) afterload and the systolic and diastolic functions, as well as the mechanoenergetic indices were estimated from the pressure-volume loops. Myocardial fibrosis by Masson’s trichrome staining, myocardial apoptosis by TUNEL, and collagen content in the aorta as well as media area in the aorta and the mesenteric arteries were determined. Our data indicated that HF rats manifested an increased arterial load (Ea), a declined systolic function (reduced ejection fraction, +dP/dtmax, end-systolic elastance, and stroke work), an abnormal diastolic function (elevated end-diastolic pressure, τ, and declined −dP/dtmax), and decreased mechanical efficiency. Apelin treatment improved those indices. Concomitantly, increased fibrosis in the LV myocardium and the aorta and enhanced apoptosis in the LV were partially restored by apelin treatment. A declined wall-to-lumen ratio in the mesenteric arteries of the untreated HF rats was further reduced in the apelin-treated group. We concluded that the rats with ischemic HF were characterized by deteriorated LV mechanoenergetics. Apelin improved mechanical efficiency, at least in part, due to the inhibiting cardiac fibrosis and apoptosis in the LV myocardium, reducing collagen deposition in the aorta and dilating the resistant artery.

Objectives To investigate the use of contrast-enhanced ultrasound imaging (US) for detection of secondary lymph nodes (LNs) in a naturally occurring melanoma swine model compared to surgery and pathologic assessment. Methods Twenty-seven Sinclair swine were studied. The perfluorobutane microbubble contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was administered (1.0 mL total dose) around the melanoma, and contrast-enhanced US was used to localize contrast-enhanced sentinel lymph nodes (SLNs). Then Sonazoid (dose, 0.25–1.0 mL) was injected into the SLNs to detect contrast-enhanced efferent lymphatic channels and secondary LNs. After peritumoral injection of blue dye, a surgeon (blinded to the contrast-enhanced US results) performed a radical LN dissection. Contrast-enhanced US was used to guide removal of any enhanced secondary LNs left after radical LN dissection. Clustered conditional logistic regression analyzed the benefit of contrast-enhanced US–directed secondary LN dissection over radical LN dissection using pathologic findings as the reference standard. Results A total of 268 secondary LNs were resected, with 59 (22%) containing metastases. Contrast-enhanced US detected 92 secondary LNs; 248 were identified by radical LN dissection; and 68 were identified by both methods. Metastases were detected in 20% (51 of 248) and 40% (37 of 92) of the secondary LNs identified by radical LN dissection and contrast-enhanced US, respectively. Thus, secondary LNs detected by contrast-enhanced US were nearly 5 times more likely to contain metastases than secondary LNs removed by radical LN dissection (odds ratio, 4.8; P < .0001). Twenty-two of the 180 secondary LNs (12%) identified only by radical LN dissection contained metastases, whereas contrast-enhanced US identified 20 secondary LNs after the surgeon completed the radical LN dissection, of which 8 (40%) contained metastases. Conclusions Secondary LNs can be detected by using contrast-enhanced US after injection of Sonazoid into SLNs. Secondary LNs detected with contrast-enhanced US are significantly more likely to contain metastases than those removed by radical LN dissection.

OBJECTIVES The ability to estimate tissue perfusion (in milliliter per minute per gram) in vivo using contrast-enhanced 3-dimensional (3D) harmonic and subharmonic ultrasound imaging was investigated. MATERIALS AND METHODS A LOGIQ™ 9 scanner (GE Healthcare, Milwaukee, WI) equipped with a 4D10L probe was modified to perform 3D harmonic imaging (HI; f(transmit), 5 MHz and f(receive), 10 MHz) and subharmonic imaging (SHI; f(transmit), 5.8 MHz and f(receive), 2.9 MHz). In vivo imaging was performed in the lower pole of both kidneys in 5 open-abdomen canines after injection of the ultrasound contrast agent (UCA) Definity (Lantheus Medical Imaging, N Billerica, MA). The canines received a 5-μL/kg bolus injection of Definity for HI and a 20-μL/kg bolus for SHI in triplicate for each kidney. Ultrasound data acquisition was started just before the injection of UCA (to capture the wash-in) and continued until washout. A microvascular staining technique based on stable (nonradioactive) isotope-labeled microspheres (Biophysics Assay Laboratory, Inc, Worcester, MA) was used to quantify the degree of perfusion in each kidney (the reference standard). Ligating a surgically exposed branch of the renal arteries induced lower perfusion rates. This was followed by additional contrast-enhanced imaging and microsphere injections to measure post-ligation perfusion. Slice data were extracted from the 3D ultrasound volumes and used to generate time-intensity curves offline in the regions corresponding to the tissue samples used for microvascular staining. The midline plane was also selected from the 3D volume (as a quasi-2-dimensional [2D] image) and compared with the 3D imaging modes. Perfusion was estimated from the initial slope of the fractional blood volume uptake (for both HI and SHI) and compared with the reference standard using linear regression analysis. RESULTS Both 3D HI and SHI were able to provide visualization of flow and, thus, perfusion in the kidneys. However, SHI provided near-complete tissue suppression and improved visualization of the UCA flow. Microsphere perfusion data were available for 4 canines (1 was excluded because of an error with the reference blood sample) and showed a mean (SD) perfusion of 9.30 (6.60) and 5.15 (3.42) mL/min per gram before and after the ligation, respectively. The reference standard showed significant correlation with the overall 3D HI perfusion estimates (r = 0.38; P = 0.007), but it correlated more strongly with 3D SHI (r = 0.62; P < 0.001). In addition, these results showed an improvement over the quasi-2D HI and SHI perfusion estimates (r = -0.05 and r = 0.14) and 2D SHI perfusion estimates previously reported by our group (r = 0.57). CONCLUSIONS In this preliminary study, 3D contrast-enhanced nonlinear ultrasound was able to quantify perfusion in vivo. Three-dimensional SHI resulted in better overall agreement with the reference standard than 3D HI did and was superior to previously reported 2D SHI results. Three-dimensional SHI outperforms the other methods for estimating blood perfusion because of the improved visualization of the complete perfused vascular networks.

Rationale and Objectives Although contrast-enhanced ultrasound imaging techniques such as harmonic imaging (HI) have evolved to reduce tissue signals using the nonlinear properties of the contrast agent, levels of background suppression have been mixed. Subharmonic imaging (SHI) offers near complete tissue suppression by centering the receive bandwidth at half the transmitting frequency. The aims of this study were to demonstrate the feasibility of three-dimensional (3D) SHI and to compare it to 3D HI. Materials and Methods Three-dimensional HI and SHI were implemented on a Logiq 9 ultrasound scanner with a 4D10L probe. Four-cycle SHI was implemented to transmit at 5.8 MHz and receive at 2.9 MHz, while two-cycle HI was implemented to transmit at 5 MHz and receive at 10 MHz. The ultrasound contrast agent Definity was imaged within a flow phantom and the lower pole of two canine kidneys in both HI and SHI modes. Contrast-to-tissue ratios and rendered images were compared offline. Results SHI resulted in significant improvement in contrast-to-tissue ratios relative to HI both in vitro (12.11 ± 0.52 vs 2.67 ± 0.77, P P = .04). Rendered 3D subharmonic images provided better tissue suppression and a greater overall view of vessels in a flow phantom and canine renal vasculature. Conclusions The successful implementation of SHI in 3D allows imaging of vascular networks over a heterogeneous sample volume and should improve future diagnostic accuracy. Additionally, 3D SHI provides improved contrast-to-tissue ratios relative to 3D HI.

Objective. The purpose of this study was to evaluate the contrast-enhanced ultrasonographic (CEUS) characteristics of metastatic lymph nodes (LNs) and to determine the correlation of CEUS parameters with the tumor aggressiveness in patients with breast cancer. Methods. Real-time gray scale CEUS of axillary LNs was preoperatively performed in 51 consecutive patients with breast carcinoma who were scheduled for axillary lymph node dissection. The CEUS characteristics assessed by a direct visualization method and quantification software were compared with pathologic findings. Expression of human epidermal growth factor receptor 2 (HER-2/neu) in the primary tumor was detected by immunohistochemical analysis. Correlation analysis of CEUS parameters with HER-2/neu expression and the LN stage was performed. Results. Of the LNs examined, 27 were metastatic, and 25 were diagnosed as reactive hyperplasia. Lymph nodes with metastasis were characterized by centripetal progress (66.7%) and a heterogeneous pattern (55.6%) or no or scarce perfusion (25.9%). However, LNs with nonmetastases were characterized by with centrifugal enhancement (56.0%) and a homogeneous pattern (80.0%). The difference between the hyperintense and hypointense regions was higher in metastatic LNs than nonmetastatic ones (P < .001). No significant differences were found in the arrival time, time to peak intensity, and peak intensity between the two groups. A histopathologic diagnosis could be predicted with sensitivity, specificity, and accuracy of 92.6%, 76.0%, and 84.6% respectively, by a standardized difference between maximum and minimum signal intensity (SI max –SI min ) value of 28. Human epidermal growth factor receptor 2 expression and the LN histopathologic stage were significantly associated with the SI max –SI min . In metastatic LNs, the relationship between the diagnostic sensitivity of CEUS and the transverse diameter of LNs remained statistically significant (P < .05). Conclusions. Noninvasive CEUS can play a role in discriminating metastatic from nonmetastatic LNs and predicting the aggressiveness in patients with breast cancer. Key words: breast neoplasm; contrast-enhanced ultrasonography; human epidermal growth factor receptor 2; lymph node metastasis; reactive hyperplasia lymph node. Abbreviations

To evaluate the significance of contrast-enhanced ultrasound (CEUS) examination in differential diagnosis of malignant and benign breast lesions.Seventy-one patients with seventy-six breast tumors are selected randomly. CEUS examinations were performed before and after bolus injection of the contrast agent SonoVue (Bracco, Milan, Italy). Specific sonographic quantification software, Qontrast, was adopted to determine the morphology of vessels. Wash-in and wash-out parameters of each lesion were assessed for both procedures.The final histopathological findings distinguished 45 malignant and 31 benign from all of the lesions. Following SonoVue administration different perfusion phases could be identified: early (0-1min), mid (1-4min) and late (4-6min) phases. In the early phase, CEUS identified 91.1% of malignant tumors characterized by a claw-shaped enhancement, while 83.9% of benign tumors had a homogeneous enhancement, with a statistically significant difference between the two enhancement patterns (chi(2)=43.16, P0.01). Moreover, contrast medium persistence in the late phase was helpful in the identification of benign and malignant tumors (chi(2)=46.88, P0.01): contrast medium was present in 88.9% of malignant tumors, while in only 9.7% of the benign tumors. The study showed that various parametric imaging color maps for peak intensity and time to peak were mostly suggestive of malignancy, while quite uniform peak intensity and time to peak of color maps were the characteristic of benign tumors. The study also found that malignant lesions presented with a higher maximum intensity signal than benign ones (P0.05) on the time-intensity curves.CEUS cooperating with conventional US shows improved accuracy in differentiating between malignant and benign breast tumors. It could be a reliable diagnostic method of breast lesions.

Background Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. Objective To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). Methods Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. Results The EA group had significantly decreased neurological deficit scores compared to the IR group (pConclusions These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression.

Effective animal models are needed to evaluate the feasibility of new techniques to assess portal hypertension (PH). Here we developed 2 canine models of acute PH by increasing intrasinusoidal resistance and by increasing the portal vein (PV) flow volume to test the efficacy of a noninvasive technique to evaluate PH. The acute low-flow PH model was based on embolization of liver circulation by using a gelatin sponge material. The acute high-flow PH model was based on increasing the PV flow volume by using an arteriovenous (A-V) shunt from the femoral artery and saline infusion. PV pressures and diameters were assessed before and after inducing PH. Pressure values and diameters were obtained from the inferior vena cava in 3 unmanipulated controls. The low-flow model of PH was repeatable and successfully increased PV pressure by an average of 16.5 mm Hg within 15 min. The high-flow model of PH failed to achieve increased PV pressures. However, saline supplementation of the portal circulation in the high-flow model led to mean increases in PV pressures of 12.8 mm Hg within 20 min. Pulsatility in the PV was decreased in the low-flow model and increased in the high-flow model relative to baseline. No changes in PV diameter were noted in either model. These acute PH models are relatively straightforward to implement and may facilitate the evaluation of new techniques to assess PH.

Incident acoustic output (IAO) dependent subharmonic signal amplitudes from ultrasound contrast agents can be categorized into occurrence, growth or saturation stages. Subharmonic aided pressure estimation (SHAPE) is a technique that utilizes growth stage subharmonic signal amplitudes for hydrostatic pressure estimation. In this study, we developed an automated IAO optimization algorithm to identify the IAO level eliciting growth stage subharmonic signals and also studied the effect of pulse length on SHAPE. This approach may help eliminate the problems of acquiring and analyzing the data offline at all IAO levels as was done in previous studies and thus, pave the way for real-time clinical pressure monitoring applications. The IAO optimization algorithm was implemented on a Logiq 9 (GE Healthcare, Milwaukee, WI) scanner interfaced with a computer. The optimization algorithm stepped the ultrasound scanner from 0 to 100 % IAO. A logistic equation fitting function was applied with the criterion of minimum least squared error between the fitted subharmonic amplitudes and the measured subharmonic amplitudes as a function of the IAO levels and the optimum IAO level was chosen corresponding to the inflection point calculated from the fitted data. The efficacy of the optimum IAO level was investigated for in vivo SHAPE to monitor portal vein (PV) pressures in 5 canines and was compared with the performance of IAO levels, below and above the optimum IAO level, for 4, 8 and 16 transmit cycles. The canines received a continuous infusion of Sonazoid microbubbles (1.5 μl/kg/min; GE Healthcare, Oslo, Norway). PV pressures were obtained using a surgically introduced pressure catheter (Millar Instruments, Inc., Houston, TX) and were recorded before and after increasing PV pressures. The experiments showed that optimum IAO levels for SHAPE in the canines ranged from 6 to 40 %. The best correlation between changes in PV pressures and in subharmonic amplitudes (r = -0.76; p = 0.24), and between the absolute PV pressures and the subharmonic amplitudes (r = -0.89; p < 0.01) were obtained for the optimized IAO and 4 transmit cycles. Only for the optimized IAO and 4 transmit cycles did the subharmonic amplitudes differ significantly (p < 0.01) before and after increasing PV pressures. A new algorithm to identify optimum IAO levels for SHAPE has been developed and validated with the best results being obtained for 4 transmit cycles. The work presented in this study may pave the way for real-time clinical applications of estimating pressures using the subharmonic signals from ultrasound contrast agents.