Device-assisted enteroscopy performance measures in the United Kingdom: DEEP-UK quality improvement project.

BACKGROUND: Device-assisted enteroscopy (DAE) has become a well-established diagnostic and therapeutic tool for the management of small-bowel pathology. We aimed to evaluate the performance measures for DAE across the UK against the quality benchmarks proposed by the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We retrospectively collected data on patient demographics and DAE performance measures from electronic endoscopy records of consecutive patients who underwent DAE for diagnostic and therapeutic purposes across 12 enteroscopy centers in the UK between January 2017 and December 2022. RESULTS: A total of 2005 DAE procedures were performed in 1663 patients (median age 60 years; 53% men). Almost all procedures (98.1%) were performed for appropriate indications. Double-balloon enteroscopy was used for most procedures (82.0%), followed by single-balloon enteroscopy (17.2%) and spiral enteroscopy (0.7%). The estimated depth of insertion was documented in 73.4% of procedures. The overall diagnostic yield was 70.0%. Therapeutic interventions were performed in 42.6% of procedures, with a success rate of 96.6%. Overall, 78.0% of detected lesions were marked with a tattoo. Patient comfort was significantly better with the use of deep sedation compared with conscious sedation (99.7% vs. 68.5%; P<0.001). Major adverse events occurred in only 0.6% of procedures. CONCLUSIONS: Performance measures for DAE in the UK meet the ESGE quality benchmarks, with high diagnostic and therapeutic yields, and a low incidence of major adverse events. However, there is room for improvement in optimizing sedation practices, standardizing the depth of insertion documentation, and adopting marking techniques to aid in the follow-up of detected lesions.

3D Super-Resolution US Imaging of Rabbit Lymph Node Vasculature in Vivo by Using Microbubbles.

Background Variations in lymph node (LN) microcirculation can be indicative of metastasis. The identification and quantification of metastatic LNs remains essential for prognosis and treatment planning, but a reliable noninvasive imaging technique is lacking. Three-dimensional super-resolution (SR) US has shown potential to noninvasively visualize microvascular networks in vivo. Purpose To study the feasibility of three-dimensional SR US imaging of rabbit LN microvascular structure and blood flow by using microbubbles. Materials and Methods In vivo studies were carried out to image popliteal LNs of two healthy male New Zealand white rabbits aged 6-8 weeks. Three-dimensional, high-frame-rate, contrast material-enhanced US was achieved by mechanically scanning with a linear imaging probe. Individual microbubbles were identified, localized, and tracked to form three-dimensional SR images and super-resolved velocity maps. Acoustic subaperture processing was used to improve image contrast and to generate enhanced power Doppler and color Doppler images. Vessel size and blood flow velocity distributions were evaluated and assessed by using Student paired t test. Results SR images revealed microvessels in the rabbit LN, with branches clearly resolved when separated by 30 µm, which is less than half of the acoustic wavelength and not resolvable by using power or color Doppler. The apparent size distribution of most vessels in the SR images was below 80 µm and agrees with micro-CT data, whereas most of those detected with Doppler techniques were larger than 80 µm in the images. The blood flow velocity distribution indicated that most of the blood flow in rabbit popliteal LN was at velocities lower than 5 mm/sec. Conclusion Three-dimensional super-resolution US imaging using microbubbles allows noninvasive nonionizing visualization and quantification of lymph node microvascular structures and blood flow dynamics with resolution below the wave diffraction limit. This technology has potential for studying the physiologic functions of the lymph system and for clinical detection of lymph node metastasis. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Quantification of Vaporised Targeted Nanodroplets Using High-Frame-Rate Ultrasound and Optics.

Molecular targeted nanodroplets that can extravasate beyond the vascular space have great potential to improve tumor detection and characterisation. High-frame-rate ultrasound, on the other hand, is an emerging tool for imaging at a frame rate one to two orders of magnitude higher than those of existing ultrasound systems. In this study, we used high-frame-rate ultrasound combined with optics to study the acoustic response and size distribution of folate receptor (FR)-targeted versus non-targeted (NT)-nanodroplets in vitro with MDA-MB-231 breast cancer cells immediately after ultrasound activation. A flow velocity mapping technique, Stokes' theory and optical microscopy were used to estimate the size of both floating and attached vaporised nanodroplets immediately after activation. The floating vaporised nanodroplets were on average more than seven times larger than vaporised nanodroplets attached to the cells. The results also indicated that the acoustic signal of vaporised FR-targeted-nanodroplets persisted after activation, with 70% of the acoustic signals still present 1 s after activation, compared with the vaporised NT-nanodroplets, for which only 40% of the acoustic signal remained. The optical microscopic images revealed on average six times more vaporised FR-targeted-nanodroplets generated with a wider range of diameters (from 4 to 68 µm) that were still attached to the cells, compared with vaporised NT-nanodroplets (from 1 to 7 µm) with non-specific binding after activation. The mean size of attached vaporised FR-targeted-nanodroplets was on average about threefold larger than that of attached vaporised NT-nanodroplets. Taking advantage of high-frame-rate contrast-enhanced ultrasound and optical microscopy, this study offers an improved understanding of the vaporisation of the targeted nanodroplets in terms of their size and acoustic response in comparison with NT-nanodroplets. Such understanding would help in the design of optimised methodology for imaging and therapeutic applications.

Power Doppler Quantification in Assessing Gestational Trophoblastic Neoplasia.

PURPOSE: The FIGO score cannot accurately stratify low-risk gestational trophoblastic neoplasia (GTN) patients who develop chemoresistance to single agent methotrexate chemotherapy. Tumour vascularisation is a key risk factor and its quantification may provide non-invasive way of complementing risk assessment. MATERIALS AND METHODS: 187 FIGO-staged, low-risk GTN patients were prospectively recruited. Power Doppler ultrasound was analysed using a quantification program. Four diagnostic indicators were obtained comprising the number of colour pixels (NCP), mean dB, power Doppler quantification (PDQ), and percentage of colour pixels (%CP). Each indicator performance was assessed to determine if they could distinguish the subset of low-risk patients who became chemoresistant. RESULTS: There were 111 non-resistant and 76 resistant patients. NCP performed best at distinguishing these two groups where the non-resistant group had an average 3435 (±â€Š2060) pixels and the resistant group 6151 (±â€Š3192) pixels (p < 0.001). PDQ and %CP showed significant differences (p < 0.001) but had poorer performance (area under ROC curves were 72 % and 67 % respectively compared with 75 % for NCP). The mean dB index was not significantly different (p = 0.133). CONCLUSION: Power Doppler ultrasound quantification shows potential for non-invasive assessment of tumour vascularity and can distinguish low-risk GTN patients who become chemoresistant from those who have an uncomplicated course with first line treatment.

3-D In Vitro Acoustic Super-Resolution and Super-Resolved Velocity Mapping Using Microbubbles.

Standard clinical ultrasound (US) imaging frequencies are unable to resolve microvascular structures due to the fundamental diffraction limit of US waves. Recent demonstrations of 2-D super-resolution both in vitro and in vivo have demonstrated that fine vascular structures can be visualized using acoustic single bubble localization. Visualization of more complex and disordered 3-D vasculature, such as that of a tumor, requires an acquisition strategy which can additionally localize bubbles in the elevational plane with high precision in order to generate super-resolution in all three dimensions. Furthermore, a particular challenge lies in the need to provide this level of visualization with minimal acquisition time. In this paper, we develop a fast, coherent US imaging tool for microbubble localization in 3-D using a pair of US transducers positioned at 90°. This allowed detection of point scatterer signals in 3-D with average precisions equal to [Formula: see text] in axial and elevational planes, and [Formula: see text] in the lateral plane, compared to the diffraction limited point spread function full-widths at half-maximum of 488, 1188, and [Formula: see text] of the original imaging system with a single transducer. Visualization and velocity mapping of 3-D in vitro structures was demonstrated far beyond the diffraction limit. The capability to measure the complete flow pattern of blood vessels associated with disease at depth would ultimately enable analysis of in vivo microvascular morphology, blood flow dynamics, and occlusions resulting from disease states.

Prospects for enhancement of targeted radionuclide therapy of cancer using ultrasound.

Ultrasound-mediated drug delivery is a promising means of enhancing delivery, distribution and effectiveness of drugs within tumours. In this review, prospects for exploiting ultrasound to improve the tumour delivery and distribution of radiolabelled antibodies for radioimmunotherapy and to overcome barriers imposed by tumour microenvironment are discussed.

Shear wave elasticity imaging based on acoustic radiation force and optical detection.

Tissue elasticity is closely related to the velocity of shear waves within biologic tissue. Shear waves can be generated by an acoustic radiation force and tracked by, e.g., ultrasound or magnetic resonance imaging (MRI) measurements. This has been shown to be able to noninvasively map tissue elasticity in depth and has great potential in a wide range of clinical applications including cancer and cardiovascular diseases. In this study, a highly sensitive optical measurement technique is proposed as an alternative way to track shear waves generated by the acoustic radiation force. A charge coupled device (CCD) camera was used to capture diffuse photons from tissue mimicking phantoms illuminated by a laser source at 532 nm. CCD images were recorded at different delays after the transmission of an ultrasound burst and were processed to obtain the time of flight for the shear wave. A differential measurement scheme involving generation of shear waves at two different positions was used to improve the accuracy and spatial resolution of the system. The results from measurements on both homogeneous and heterogeneous phantoms were compared with measurements from other instruments and demonstrate the feasibility and accuracy of the technique for imaging and quantifying elasticity. The relative error in estimation of shear wave velocity can be as low as 3.3% with a spatial resolution of 2 mm, and increases to 8.8% with a spatial resolution of 1 mm for the medium stiffness phantom. The system is shown to be highly sensitive and is able to track shear waves propagating over several centimetres given the ultrasound excitation amplitude and the phantom material used in this study. It was also found that the reflection of shear waves from boundaries between regions with different elastic properties can cause significant bias in the estimation of elasticity, which also applies to other shear wave tracking techniques. This bias can be reduced at the expense of reduced spatial resolution.

The influence of gas saturation on microbubble stability.

Accurate acoustic characterisation is an essential component of any experimental investigation concerning the use and development of microbubble contrast agents. It is of increasing importance as applications such as therapy and molecular and quantitative imaging are investigated. Such characterisation is generally conducted in the laboratory in the form of bulk acoustic studies or optical observation of single bubbles using high speed photography in a water tank containing "out-gassed" water. The approach is widely used in acoustics to prevent inaccurate measurements being made due to the presence of gas bubbles settling on instrumentation, however, the term is often used to cover a range of water preparation techniques and the final gas content of the water is not usually stated. This technical note demonstrates the influence of gas content on the stability of microbubble contrast agents and concludes that characterisation should always be conducted in equilibrated, gas-saturated water to ensure accurate and repeatable measurements are made.

Effects of acoustic radiation force and shear waves for absorption and stiffness sensing in ultrasound modulated optical tomography.

Ultrasound-modulated optical tomography (UOT) combines optical contrast with ultrasound spatial resolution and has great potential for soft tissue functional imaging. One current problem with this technique is the weak optical modulation signal, primarily due to strong optical scattering in diffuse media and minimal acoustically induced modulation. The acoustic radiation force (ARF) can create large particle displacements in tissue and has been shown to be able to improve optical modulation signals. However, shear wave propagation induced by the ARF can be a significant source of nonlocal optical modulation which may reduce UOT spatial resolution and contrast. In this paper, the time evolution of shear waves was examined on tissue mimicking-phantoms exposed to 5 MHz ultrasound and 532 nm optical radiation and measured with a CCD camera. It has been demonstrated that by generating an ARF with an acoustic burst and adjusting both the timing and the exposure time of the CCD measurement, optical contrast and spatial resolution can be improved by ~110% and ~40% respectively when using the ARF rather than 5 MHz ultrasound alone. Furthermore, it has been demonstrated that this technique simultaneously detects both optical and mechanical contrast in the medium and the optical and mechanical contrast can be distinguished by adjusting the CCD exposure time.

Ultrasound-mediated optical tomography: a review of current methods.

Ultrasound-mediated optical tomography (UOT) is a hybrid technique that is able to combine the high penetration depth and high spatial resolution of ultrasound imaging to overcome the limits imposed by optical scattering for deep tissue optical sensing and imaging. It has been proposed as a method to detect blood concentrations, oxygenation and metabolism at depth in tissue for the detection of vascularized tumours or the presence of absorbing or scattering contrast agents. In this paper, the basic principles of the method are outlined and methods for simulating the UOT signal are described. The main detection methods are then summarized with a discussion of the advantages and disadvantages of each. The recent focus on increasing the weak UOT signal through the use of the acoustic radiation force is explained, together with a summary of our results showing sensitivity to the mechanical shear stiffness and optical absorption properties of tissue-mimicking phantoms.

Measurement of the reflectivity of the intima-medial layer of the common carotid artery improves the discriminatory value of intima-medial thickness measurement as a predictor of risk of atherosclerotic disease.

Our aim was to assess the predictive value of a measurement of intima-medial layer (IML) reflectivity in the differentiation of pathological from physiological increases in intima-medial thickness (IMT). Both common carotid arteries (CCA) of familial hypercholesterolemia (FH) patients and age- and sex-matched controls (no cardiovascular risk factors) were imaged using a 10- to 15-MHz linear array transducer (n = 30). Images of the CCA far wall were analyzed in the IMT "plug-in" of "HDI Lab." The IML reflectivity, averaged over an 8- to 12-mm length of arterial wall, was expressed as a ratio of reflectivity at a point 0.21-mm deep to the intima-medial interface divided by the reflectivity at the intima-medial interface, termed the intima-medial reflectivity index (IMRI). The risk of atherosclerosis was assessed in terms of IMT alone and IMT coupled with IMRI. Defining high risk of atherosclerosis in FH, in terms of both IMT alone and IMT coupled with IMRI, produced an appropriate, when compared with cholesterol-years score, statistically significant stratification (p < 0.01 and p < 0.005). Analysis of the low-risk subjects revealed a tendency to define a subject as "high risk" based on a physiological increase in IMT, but when IMRI is included in the assessment, all controls are correctly identified as low risk. This method of quantifying the reflectivity of the IML improved the discriminatory performance of IMT increase as an indicator of atherosclerotic risk by enabling a smaller, therefore earlier, increase in IMT to be considered pathologic when accompanied by an increase in IMRI.

Hepatic vein transit time of SonoVue: a comparative study with Levovist.

PURPOSE: To prospectively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Forty patients and 25 healthy volunteers were examined. Subjects fasted, a bolus of SonoVue (0.6 mL) was injected into a cubital fossa vein, and hepatic venous time-intensity profiles were measured with spectral Doppler tracing. This was repeated with two injections of Levovist (2 g) and another injection of SonoVue. Time-intensity curves of spectral Doppler signals of right and middle hepatic veins were analyzed. A sustained signal intensity increase of 10% above baseline levels indicated hepatic vein transit time (HVTT). Carotid artery audio intensity was measured in volunteers. Analysis of variance and t tests were used for statistical analysis. RESULTS: Twelve patients had mild hepatitis; 18, moderate or severe hepatitis; and 10, cirrhosis. Mean HVTTs in control, mild hepatitis, moderate or severe hepatitis, and cirrhosis groups were 38.3 seconds +/- 2.4 (standard error), 47.5 seconds +/- 6.5, 29.5 seconds +/- 10.8, and 17.6 seconds +/- 5.0, respectively, with Levovist (P < .001) and 29.4 seconds +/- 6.9, 27.4 seconds +/- 9.3, 22.9 seconds +/- 4.7, and 16.4 seconds +/- 4.9, respectively, with SonoVue (P < .001). HVTT decreased as severity increased at imaging with both contrast agents. There was no significant difference in HVTT between mild and moderate hepatitis groups with SonoVue; however, there were significant differences in HVTT between all patient groups with Levovist. HVTT of SonoVue was shorter than that of Levovist in all groups (P < .001) except the cirrhosis group; in this group, HVTT of the two contrast agents was similar (P = .05). No difference was observed in mean cardiopulmonary transit time for SonoVue or Levovist (9.1 seconds +/- 2.4 [standard error] and 8.4 seconds +/- 2.5, respectively, P = .18). CONCLUSION: HVTT was significantly shorter with SonoVue than with Levovist; there was no significant difference in cardiopulmonary transit time.

Can Doppler sonography grade the severity of hepatitis C-related liver disease?

OBJECTIVE: Many authors have claimed that Doppler sonography indexes are of value in grading and assessing diffuse liver disease. However, there is much controversy regarding the reliability and reproducibility of these techniques. We performed a prospective study to evaluate whether these methods can grade disease in a well-stratified cohort of patients with hepatitis C virus (HCV)-related liver disease. SUBJECTS AND METHODS: Sixty-five patients with biopsy-proven HCV-related liver disease were recruited, and Doppler sonography was performed by one operator. The patients were classified into one of the following three groups on the basis of the Ishak-modified histologic activity index (HAI) fibrosis (F) and necroinflammatory (NI) scores: mild hepatitis (F < or = 2 and NI < or = 3), moderate or severe hepatitis (3 < or = F < 6 or NI > or = 4), or cirrhosis (F = 6/6). We measured the following Doppler indexes: main hepatic artery peak velocity (Vmax) and resistive index, main portal vein peak velocity (Vmax), and maximal portal vein diameter and circumference that allowed calculation of the portal vein congestive index (portal vein area and portal vein velocity). The ratio of the hepatic artery velocity (Vmax) to the portal vein velocity (Vmax) was also calculated, and the phasicity (triphasic, biphasic, or monophasic) of the hepatic veins of each patient was recorded. We also measured the maximal spleen length longitudinally. RESULTS: A total of 65 patients with liver disease (mild hepatitis, n = 20; moderate or severe hepatitis, n = 25; cirrhosis, n = 20) with biopsy-proven HCV-related liver disease were studied. Optimal hepatic arterial traces were obtained in only 30 patients and portal vein circumference in 18 patients. No significant differences were observed in the Doppler indexes with increasing severity of liver disease. Five (29%) of 17 patients with mild hepatitis had an abnormal hepatic vein trace (i.e., biphasic or monophasic) compared with 11 (55%) of 20 patients with moderate or severe hepatitis and 12 (60%) of 20 patients with cirrhosis. The only index to show a significant intergroup difference was splenic length (analysis of variance, p < 0.001), but there was still overlap between the groups. CONCLUSION: Doppler-derived indexes, which have previously been recommended for the assessment of severity in chronic liver disease, are difficult to reproduce reliably and therefore have a limited clinical role in the noninvasive assessment of hepatic fibrosis or inflammation.

Quantitative microbubble enhanced transrectal ultrasound as a tool for monitoring hormonal treatment of prostate carcinoma.

BACKGROUND: We quantified changes in prostate carcinoma vascularity treated with anti-androgens using color Doppler and power transrectal ultrasound in combination with microbubble contrast agent Levovist. METHODS: Thirty-six men with prostate carcinoma were studied at baseline and at intervals during treatment. At each attendance, Levovist((R)) (10 ml, 300 mg/ml) was given as an iv bolus. Using quantitative analysis, we calculated the pre-enhancement scores, arrival time, time to peak, peak value, and area under the time-enhancement curve (AUC). These were compared to pre-treatment values and serial PSA measurements. RESULTS: The pre-enhancement, peak value, and AUC each showed a marked response with reductions within one week. The average AUC declined to 68% +/- 9% (mean +/- standard error) by week 1, 56% +/- 9% by week 3, and 20% +/- 4% by week 6. A strong correlation with changes in the mean PSA (r = 0.95, P < 0.001) was also measured. In four patients, Doppler indices did not fall with PSA: two patients with the most marked discrepancy relapsed at 6 months. CONCLUSION: The vascular enhancement declined with therapy, similar to PSA. Microbubble enhanced ultrasound can show early response to treatment.

Which continuous US scanning mode is optimal for the detection of vascularity in liver lesions when enhanced with a second generation contrast agent?

OBJECTIVES: Microbubble echo-enhancers help in the assessment of focal liver masses by enhancing the signal from blood vessels. A variety of linear and nonlinear scanning modes are now available, but it is unclear which is optimal. A controlled comparison was performed during the infusion of such an agent (SonoVue: Bracco, Milan, Italy). METHODS AND MATERIALS: Ten patients with known focal liver lesions were studied. The diagnoses, confirmed on dual phase helical computed tomography (CT) at the same attendance were metastasis (n = 7), haemangioma (n = 2) and focal nodular hyperplasia FNH (n = 1). A dose of 12 ml SonoVue concentrated at 5 mg/ml was infused intravenously at a rate of 1 ml/min. The enhancement level was monitored with a continuous wave (CW) Doppler probe over the right radial artery and the intensity of the signal was registered at 1 s intervals. When a plateau of enhancement was reached, a single lesion in each patient was imaged using five different continuous scanning modes, fundamental grey scale (FGS); fundamental colour Doppler (FCD); fundamental power Doppler (FPD); second harmonic grey scale (HGS); and pulse inversion mode (Pim) using an HDI5000 scanner and C5-2 probe (ATL, Bothell, WA). The order of scanning modes was varied between patients using a predefined randomisation protocol. The videos (super video home system (SVHS)) were analysed offsite by two blinded readers, both experienced in contrast ultrasound of the liver. The readers were asked to score each mode in terms of its ability to detect vessels within/around the lesion at optimal enhancement. This was done using a ranking system (1, worst; 5, best) for each patient. RESULTS: Both observers scored FPD as the optimal imaging method, followed by Pim. (Scores summed across all patients, observer 1: FPD 48, Pim 42, FCD 37, HGS 21, FGS 10; observer 2: FPD 49, Pim 40, FCD 38, HGS 21, FGS 10). The differences from FPD were significant for FCD, HGS and FGS using a unpaired analysis of variance (ANOVA) comparison, with Bonferroni multiple corrections, (P<0.01, both observers). The differences between FPD and Pim were also significant both for observer 2 and for both observers combined (P<0.01), but did not reach significance for observer 1 (P = 0.19). CONCLUSIONS: In this study, FPD performed best, and the non-linear modes, performed continuously (pulse inversion and second HGS), showed no clear advantage.