Multi-contrast high spatial resolution black blood inner volume three-dimensional fast spin echo MR imaging in peripheral vein bypass grafts

The purpose of this study is to primarily evaluate the lumen area and secondarily evaluate wall area measurements of in vivo lower extremity peripheral vein bypass grafts patients using high spatial resolution, limited field of view, cardiac gated, black blood inner volume three-dimensional fast spin echo MRI. Fifteen LE-PVBG patients prospectively underwent ultrasound followed by T1-weighted and T2-weighted magnetic resonance (MR) imaging. Lumen and vessel wall areas were measured by direct planimetry. For graft lumen areas, T1- and T2-weighted measurements were compared with ultrasound. For vessel wall areas, differences between T1- and T2-weighted measurements were evaluated. There was no significant difference between ultrasound and MR lumen measurements, reflecting minimal MR blood suppression artifact. Graft wall area measured from T1-weighted images was significantly larger than that measured from T2-weighted images (P < 0.001). The mean of the ratio of T1- versus T2-weighted vessel wall areas was 1.59 (95% CI: 1.48–1.69). The larger wall area measured on T1-weighted images was due to a significantly larger outer vessel wall boundary. Very high spatial resolution LE-PVBG vessel wall MR imaging can be performed in vivo, enabling accurate measurements of lumen and vessel wall areas and discerning differences in those measures between different tissue contrast weightings. Vessel wall area differences suggest that LE-PVBG vessel wall tissues produce distinct signal characteristics under T1 and T2 MR contrast weightings.     

Quantitative measurements in IVUS images

IntraVascular UltraSound (IVUS) is a catheter-based technique which provides real-time high resolution tomographic images of both the lumen and arterial wall of a coronary segment, this in contrast to X-ray arteriography that provides a shadow image (luminogram) of the entire lumen. Nowadays the lumen and vessel parameters are measured manually, which is very time consuming and suffers from high inter- and intra-obser variability. With the continuing improvement in IVUS imaging, it is now feasible to develop and clinically apply automated methods of three-dimensional quantitative analysis of the coronary vessel morphology in an objective and reproducible way with automated contour detection techniques (QCU). Quantification, in 2D and 3D, as well as volume rendering for visualization of the IVUS images requires segmentation of the images (contour detection). The 3D contour detection system described in this article is based on the combination of contour detection in the transversal and sagital view. This article provides some of the basic principles of IVUS, the IVUS image quantification, the three-dimensional reconstruction and the contour detection and quantification in three-dimensional IVUS images.     

Automatic segmentation of the lumen region in intravascular images of the coronary artery

Image assessment of the arterial system plays an important role in the diagnosis of cardiovascular diseases. The segmentation of the lumen and media-adventitia in intravascular (IVUS) images of the coronary artery is the first step towards the evaluation of the morphology of the vessel under analysis and the identification of possible atherosclerotic lesions. In this study, a fully automatic method for the segmentation of the lumen in IVUS images of the coronary artery is presented. The proposed method relies on the K-means algorithm and the mean roundness to identify the region corresponding to the potential lumen. An approach to identify and eliminate side branches on bifurcations is also proposed to delimit the area with the potential lumen regions. Additionally, an active contour model is applied to refine the contour of the lumen region. In order to evaluate the segmentation accuracy, the results of the proposed method were compared against manual delineations made by two experts in 326 IVUS images of the coronary artery. The average values of the Jaccard measure, Hausdorff distance, percentage of area difference and Dice coefficient were 0.88 ± 0.06, 0.29 ± 0.17  mm, 0.09 ± 0.07 and 0.94 ± 0.04, respectively, in 324 IVUS images successfully segmented. Additionally, a comparison with the studies found in the literature showed that the proposed method is slight better than the majority of the related methods that have been proposed. Hence, the new automatic segmentation method is shown to be effective in detecting the lumen in IVUS images without using complex solutions and user interaction.     

Automated segmentation of outer retinal layers in macular OCT images of patients with retinitis pigmentosa

To provide a tool for quantifying the effects of retinitis pigmentosa (RP) seen on spectral domain optical coherence tomography images, an automated layer segmentation algorithm was developed. This algorithm, based on dual-gradient information and a shortest path search strategy, delineates the inner limiting membrane and three outer retinal boundaries in optical coherence tomography images from RP patients. In addition, an automated inner segment (IS)/outer segment (OS) contour detection method based on the segmentation results is proposed to quantify the locus of points at which the OS thickness goes to zero in a 3D volume scan. The segmentation algorithm and the IS/OS contour were validated with manual segmentation data. The segmentation and IS/OS contour results on repeated measures showed good within-day repeatability, while the results on data acquired on average 22.5 months afterward demonstrated a possible means to follow disease progression. In particular, the automatically generated IS/OS contour provided a possible objective structural marker for RP progression.     

三维增强MR血管成像在主动脉瘤诊治中的临床价值

目的评价三维增强MR血管成像（3D CE-MRA）在主动脉瘤诊治中的临床价值。材料与方法 925例主动脉瘤患者行3D CE-MRA检查,工作站上三维重建,探讨图像在制定治疗方案中的作用。结果 925例主动脉瘤中,真性动脉瘤479例（胸段138例,胸腹段29例,腹段312例）,主动脉夹层407例（Stanford A型84例,B型232例,主动脉壁内血肿91例）,假性动脉瘤39例（胸段21例,腹段18例）。3D CE-MRA立体显示各种动脉瘤类型、形态、部位、病变细节及其与邻近动脉分支的关系,与行腔内隔绝术的DSA比较,3D CE-MRA所测参数与DSA高度一致（P〉0.05）,对临床治疗方案的制定具有重要指导作用。925例中,352例行腔内隔绝术（真性动脉瘤195例,主动脉夹层126例,假性动脉瘤31例）,115例行手术治疗（真性动脉瘤47例,主动脉夹层63例,假性动脉瘤5例）。结论 3D CEMRA能无创、快速、有效诊断主动脉瘤,为手术或腔内隔绝术提供较为全面的信息,可作为主动脉瘤患者,尤其是伴有肾功能不全患者的首选诊断方法。     

Detecting Regional Stiffness Changes in Aortic Aneurysmal Geometries Using Pressure-Normalized Strain

Transabdominal ultrasound elasticity imaging could improve the assessment of rupture risk for abdominal aortic aneurysms by providing information on the mechanical properties and stress or strain states of vessel walls. We implemented a non-rigid image registration method to visualize the pressure-normalized strain within vascular tissues and adapted it to measure total strain over an entire cardiac cycle. We validated the algorithm's performance with both simulated ultrasound images with known principal strains and anatomically accurate heterogeneous polyvinyl alcohol cryogel vessel phantoms. Patient images of abdominal aortic aneurysm were also used to illustrate the clinical feasibility of our imaging algorithm and the potential value of pressure-normalized strain as a clinical metric. Our results indicated that pressure-normalized strain could be used to identify spatial variations in vessel tissue stiffness. The results of this investigation were sufficiently encouraging to warrant a clinical study measuring abdominal aortic pressure-normalized strain in a patient population with aneurysmal disease.     

Finding parametric representations of the cortical sulci using an active contour model

The cortical sulci are brain structures resembling thin convoluted ribbons embedded in three dimensions. The importance of the sulci lies primarily in their relation to the cytoarchitectonic and functional organization of the underlying cortex and in their utilization as features in non-rigid registration methods. This paper presents a methodology for extracting parametric representations of the cerebral sulci from magnetic resonance images. The proposed methodology is based on deformable models utilizing characteristics of the cortical shape. Specifically, a parametric representation of a sulcus is determined by the motion of an active contour along the medial surface of the corresponding cortical fold. The active contour is initialized along the outer boundary of the brain and deforms toward the deep root of a sulcus under the influence of an external force field, restricting it to lie along the medial surface of the particular cortical fold. A parametric representation of the medial surface of the sulcus is obtained as the active contour traverses the sulcus. Based on the first fundamental form of this representation, the location and degree of an interruption of a sulcus can be readily quantified; based on its second fundamental form, shape properties of the sulcus can be determined. This methodology is tested on magnetic resonance images and it is applied to three medical imaging problems: quantitative morphological analysis of the central sulcus; mapping of functional activation along the primary motor cortex and non-rigid registration of brain images.     

A variational framework for integrating segmentation and registration through active contours

Traditionally, segmentation and registration have been solved as two independent problems, even though it is often the case that the solution to one impacts the solution to the other. In this paper, we introduce a geometric, variational framework that uses active contours to simultaneously segment and register features from multiple images. The key observation is that multiple images may be segmented by evolving a single contour as well as the mappings of that contour into each image.     

Semi-automatic segmentation and detection of aorta dissection wall in MDCT angiography

Aorta dissection is a serious vascular disease produced by a rupture of the tunica intima of the vessel wall that can be lethal to the patient. The related diagnosis is strongly based on images, where the multi-detector CT is the most generally used modality. We aim at developing a semi-automatic segmentation tool for aorta dissections, which will isolate the dissection (or flap) from the rest of the vascular structure. The proposed method is based on different stages, the first one being the semi-automatic extraction of the aorta centerline and its main branches, allowing an subsequent automatic segmentation of the outer wall of the aorta, based on a geodesic level set framework. This segmentation is then followed by an extraction the center of the dissected wall as a 3D mesh using an original algorithm based on the zero crossing of two vector fields. Our method has been applied to five datasets from three patients with chronic aortic dissection. The comparison with manually segmented dissections shows an average absolute distance value of about half a voxel. We believe that the proposed method, which tries to solve a problem that has attracted little attention to the medical image processing community, provides a new and interesting tool to isolate the intimal flap that can provide very useful information to the clinician.     

High resolution carotid black-blood 3T MR with parallel imaging and dedicated 4-channel surface coils

Background

Most of the carotid plaque MR studies have been performed using black-blood protocols at 1.5 T without parallel imaging techniques. The purpose of this study was to evaluate a multi-sequence, black-blood MR protocol using parallel imaging and a dedicated 4-channel surface coil for vessel wall imaging of the carotid arteries at 3 T.

Materials and methods

14 healthy volunteers and 14 patients with intimal thickening as proven by duplex ultrasound had their carotid arteries imaged at 3 T using a multi-sequence protocol (time-of-flight MR angiography, pre-contrast T1w-, PDw- and T2w sequences in the volunteers, additional post-contrast T1w- and dynamic contrast enhanced sequences in patients). To assess intrascan reproducibility, 10 volunteers were scanned twice within 2 weeks.

Results

Intrascan reproducibility for quantitative measurements of lumen, wall and outer wall areas was excellent with Intraclass Correlation Coefficients >0.98 and measurement errors of 1.5%, 4.5% and 1.9%, respectively. Patients had larger wall areas than volunteers in both common carotid and internal carotid arteries and smaller lumen areas in internal carotid arteries (p < 0.001). Positive correlations were found between wall area and cardiovascular risk factors such as age, hypertension, coronary heart disease and hypercholesterolemia (Spearman''s r = 0.45-0.76, p < 0.05). No significant correlations were found between wall area and body mass index, gender, diabetes or a family history of cardiovascular disease.

Conclusion

The findings of this study indicate that high resolution carotid black-blood 3 T MR with parallel imaging is a fast, reproducible and robust method to assess carotid atherosclerotic plaque in vivo and this method is ready to be used in clinical practice.     

Advanced contour detection for three-dimensional intracoronary ultrasound: a validation--in vitro and in vivo

Intracoronary ultrasound (ICUS) provides high-resolution transmural images of the arterial wall. By performing a pullback of the ICUS transducer and three-dimensional reconstruction of the images, an advanced assessment of the lumen and vessel wall morphology can be obtained. To reduce the analysis time and the subjectivity of boundary tracing, automated segmentation of the image sequence must be performed. The Quantitative Coronary Ultrasound – Clinical Measurement Solutions (QCU-CMS) (semi)automated analytical software package uses a combination of transversal and longitudinal model and knowledge-guided contour detection techniques. On multiple longitudinal sections through the pullback stack, the external vessel contours are detected simultaneously, allowing mutual guidance of the detection in difficult areas. Subsequently, luminal contours are detected on these longitudinal sections. Vessel and luminal contour points are transformed to the individual cross-sections, where they guide the vessel and lumen contour detection on these transversal images. The performance of the software was validated stepwise. A set of phantoms was used to determine the systematic and random errors of the contour detection of external vessel and lumen boundaries. Subsequently, the results of the contour detection as obtained in in vivo image sets were compared with expert manual tracing, and finally the contour detection in in vivo image sequences was compared with results obtained from another previously validated ICUS quantification system. The phantom lumen diameters were underestimated by 0.1 mm, equally by the QCU-CMS software and by manual tracing. Comparison of automatically detected contours and expert manual contours, showed that lumen contours correspond very well (systematic and random radius difference: –0.025 ± 0.067 mm), while automatically detected vessel contours slightly overestimated the expert manual contours (radius difference: 0.061 ± 0.037 mm). The cross-sectional vessel and lumen areas as detected with our system and with the second computerized system showed a high correlation (r = 0.995 and 0.978, respectively). Thus, use of the new QCU-CMS analytical software is feasible and the validation data suggest its application for the analysis of clinical research.     

Accuracy of quantitative MR vessel wall imaging applying a semi-automated gradient detection algorithm--a validation study.

Magnetic resonance imaging (MRI) is uniquely suited to study the pathophysiology of arteriosclerosis. So far, magnetic resonance (MR) measurements of vessel dimensions have mainly been done by manual tracing of vessel wall contours. However, such data postprocessing is very time-consuming and has limited accuracy due to difficulties in precise tracing of the thin vessel wall. PURPOSE: To assess the accuracy and reproducibility of quantitative vascular MR imaging applying a data analysis method based on (1) vessel wall unwrapping, followed by (2) a gradient detection algorithm for MR data postprocessing. Vascular MR imaging studies were done both in vessel phantoms and in healthy volunteers (n=29) on a clinical 1.5 T MR scanner. A dark blood double-inversion turbo spin echo sequence with fat suppression was applied, with proton-density-weighted and breath-hold acquisition for aortic imaging and T2-weighted acquisition for carotid imaging. Intraobserver and interobserver variability were systematically evaluated by two independent observers. A repeat study within 10 days of the first MRI was performed in 10 of these subjects for assessment of interstudy reproducibility. RESULTS: The semiautomated edge detection software revealed a clear view of the inner and outer vessel wall boundaries both in the phantoms and in the volunteers studied. There was close agreement between MR-derived measurements and phantom dimensions (mean difference of 1.1+/-16.9 mm2, 8.0+/-19.9 mm2, 9.0+/-12.1 mm2 for vessel wall cross-sectional area, inner vessel area, and total vessel area, respectively). Quantification of vessel dimensions was feasible in all 29 healthy volunteers studied. Semiautomated quantification of cross-sectional vessel wall area (mean+/-SD, 253.6+/-208.4 mm2) revealed close correlation for repeated measurements by one or two observers (r=0.99 each). Both intraobserver and interobserver variability of vessel wall area MR measurements were low (mean difference 7.5+/-16.7 mm2 and 14.4+/-24.6 mm2 , respectively). In the repeat study of 10 volunteers, MRI with semiautomated postprocessing quantitation revealed a high correlation and agreement of vessel dimensions between the two scans (r=0.994, mean difference 2.6+/-25.1 mm2). CONCLUSION: Semiautomated analysis methods can provide approaches that benefit from the human understanding of the image and the computer's ability to measure precisely and rapidly. Thus, by combining the latest MRI methods and semiautomated image analysis methods, we are now able to reproducibly determine the geometric parameters of blood vessels.     

Optimization of ex vivo CT- and MR- Imaging of Atherosclerotic Vessel Wall Changes

OBJECTIVE: To optimize a methodology for ex vivo imaging of atherosclerotic vessel wall changes using multidetector-row computed tomography (MDCT) and multi-contrast magnetic resonance imaging (MRI). METHODS: In phantom studies and studies on intact ex vivo porcine and human hearts, various filling mixtures of MDCT and MRI contrast agents have been evaluated, to enable filling and distension of the coronary arteries for optimal visualization of atherosclerotic vessel wall changes with both techniques. Various proportions of methyl cellulose, iodine-containing CT contrast agent and paramagnetic MR contrast agent containing iron-oxide particles have been tested. Imaging parameters have been optimized for high resolution plaque imaging using a four detector-row CT scanner and a 1.5 T MR system. RESULTS: Phantom studies and studies on ex vivo porcine and human hearts demonstrated optimal proportion of methyl cellulose and CT contrast agent to be 98% vs. 2%, and 75% vs. 25% of methyl cellulose vs. MR contrast agent, respectively. These proportions provided optimal opacification of the vessel lumen in the MDCT images with 250 Hounsfield Units, and good signal suppression within the vessel lumen in the MR images, resembling in vivo imaging techniques. After retrospective matching with histopathology, atherosclerotic lesions of the human ex vivo specimens could be identified on MRI and MDCT images. CONCLUSION: Using an optimized mixture of methyl cellulose, MDCT and MRI contrast agents, visualization of atherosclerotic vessel wall changes is feasible, and applicable to various ex vivo models.     

Aortic compliance in healthy subjects: evaluation of tissue Doppler imaging

Increased compliance of abdominal aortic aneurysms at maximum diameter over time might be related to rupture. Compliance could, therefore, be valuable in their management. However, such measurement requires a sophisticated system. An original arterial wall-motion measurement technique, based on tissue Doppler imaging (TDI) and providing segmental exploration, was applied to the study of aorta walls. We report its validation in healthy subjects. Technical feasibility was reliable. The time required for sequence acquisition and transfer was suitable for routine clinical use and the quality of the sequences provided precise identification of the aorta wall/lumen interface and accurate segmentation. The values characterising normal aortic compliance were similar to those previously published, and the initial results concerning reproducibility were appropriate for clinical studies. Further refinements may improve it. This study validates the TDI system for measurement of abdominal aortic compliance in healthy subjects. Study of application to aneurysm compliance is in progress.     

Semiautomatic carotid lumen segmentation for quantification of lumen geometry in multispectral MRI

Quantitative information about the geometry of the carotid artery bifurcation is relevant for investigating the onset and progression of atherosclerotic disease. This paper proposes an automatic approach for quantifying the carotid bifurcation angle, carotid area ratio, carotid bulb size and the vessel tortuosity from multispectral MRI. First, the internal and external carotid centerlines are determined by finding a minimum cost path between user-defined seed points where the local costs are based on medialness and intensity. The minimum cost path algorithm is iteratively applied after curved multi-planar reformatting to refine the centerline. Second, the carotid lumen is segmented using a topology preserving geodesic active contour which is initialized by the extracted centerlines and steered by the MR intensities. Third, the bifurcation angle and vessel tortuosity are automatically extracted from the segmented lumen. The methods for centerline tracking and lumen segmentation are evaluated by comparing their accuracy to the inter- and intra-observer variability on 48 datasets (96 carotid arteries) acquired as part of a longitudinal population study. The evaluation reveals that 94 of 96 carotid arteries are segmented successfully. The distance between the tracked centerlines and the reference standard (0.33mm) is similar to the inter-observer variation (0.32mm). The lumen segmentation accuracy (average DSC=0.89, average mean absolute surface distance=0.31mm) is close to the inter-observer variation (average dice=0.92, average mean surface distance=0.23mm). The correlation coefficient of manually and automaticly derived bifurcation angle, carotid proximal area ratio, carotid proximal bulb size and vessel totuosity quantifications are close to the correlation of these measures between observers. This demonstrates that the automated method can be used for replacing manual centerline annotation and manual contour drawing for lumen segmentation in MRIs data prior to quantifying the carotid bifurcation geometry.     

螺旋CT血管造影在腹主动脉瘤诊断中的应用

目的:评价螺旋CT血管造影在腹主动脉瘤诊断中的价值。方法:回顾性分析30例腹主动脉瘤病人行螺旋CT增强检查后进行各种重建如最大密度投影(MIP)、表面阴影显示(SSD)的临床资料。结果:本组腹主动脉瘤患者均合并附壁血栓,其中10例合并单侧髂总动脉瘤,4例出现动脉瘤破裂。SSD明确显示动脉瘤的范围和周围血管的关系;MIP对瘤壁的钙化及管腔各段可较精确测量。结论:螺旋CT血管造影操作简单、安全,诊断明确,能帮助和指导手术。     

Interactive segmentation of abdominal aortic aneurysms in CTA images

A model-based approach to interactive segmentation of abdominal aortic aneurysms from CTA data is presented. After manual delineation of the aneurysm sac in the first slice, the method automatically detects the contour in subsequent slices, using the result from the previous slice as a reference. If an obtained contour is not sufficiently accurate, the user can intervene and provide an additional manual reference contour. The method is inspired by the active shape model (ASM) segmentation scheme (), in which a statistical shape model, derived from corresponding landmark points in manually labeled training images, is fitted to the image in an iterative manner. In our method, a shape model of the contours in two adjacent image slices is progressively fitted to the entire volume. The contour obtained in one slice thus constrains the possible shapes in the next slice. The optimal fit is determined on the basis of multi-resolution gray level models constructed from gray value patches sampled around each landmark. We propose to use the similarity of adjacent image slices for this gray level model, and compare these to single-slice features that are more generally used with ASM. The performance of various image features is evaluated in leave-one-out experiments on 23 data sets. Features that use the similarity of adjacent image slices outperform measures based on single-slice features in all cases. The average number of slices in our datasets is 51, while on average eight manual initializations are required, which decreases operator segmentation time by a factor of 6.     

3.0T MRI观察兔腹主动脉粥样硬化斑块演变过程

目的 探讨MRI在识别兔动脉粥样硬化斑块中的诊断价值.方法 20只新西兰白兔,随机设置实验组16只,对照组4只,结合球囊拉伤腹主动脉和间断高脂饲料喂养,建立动脉粥样硬化模型;在建模后2、3、4个月分别行高分辨MR成像.通过测量腹主动脉管壁厚度和面积、管腔面积、管壁信号增强程度等指标,观察腹主动脉壁的重构过程,并对模型最终的斑块成分进行MRI和组织病理结果对照研究.结果 对17只兔(实验组14只,对照组3只)完成3次MR检查,并获得组织病理学结果.MRI显示,实验组腹主动脉管壁厚度和面积逐渐增厚,且与同期对照组相比差异均有统计学意义(P＜0.01);实验组腹主动脉管腔进行性扩张,管壁强化程度较对照组增加明显,但演变过程不明显.另外,MRI对兔腹主动脉硬化斑块的成分判别限制在纤维、脂质和钙化斑块,对纤维斑块、脂质斑块识别率较高.结论 高分辨MRI可以无创性地观察动脉粥样硬化动物模型腹主动脉管壁重构的演变过程,有助于对动脉硬化斑块的预后和药物干预进行探索.     

彩色多普勒在腹部及周围血管动脉瘤诊断中的应用

目的：总结腹部及周围血管动脉瘤的彩色多普勒超声表现。方法：对我科经彩色多普勒超声诊断的8例动脉瘤进行回顾性分析。结果：8例中腹主动脉真性动脉瘤4例，均位于肾动脉水平以下，表现为腹主动脉局部扩张。腹主动脉夹层动脉瘤1例，CDFI可识别夹层瘤的真腔和假腔。肱动脉及股动脉假性动脉瘤各1例，CDFI见动脉有破口与肿块相通，肿块内有彩色和频谱血流信号。胰头周围假性动脉瘤1例，有胰腺炎病史，CDFI见肿块中有局部动脉型高速血流。8例均经CT、MRA或手术证实。结论：彩色多普勒可准确诊断腹部及周围血管动脉瘤，它是首选的无创伤性的诊断方法。     

Quantification of atherosclerosis with MRI and image processing in spontaneously hyperlipidemic rabbits.

The need for a quantitative method to assess atherosclerosis in vivo is well known. This study tested, in a familiar animal model of atherosclerosis, a combination of magnetic resonance imaging (MRI) and image processing. Six spontaneously hyperlipidemic (Watanabe) rabbits were examined with a knee coil in a 1.5-T clinical MRI scanner. Inflow angio (2DI) and proton density weighted (PDW) images were acquired to examine 10 cm of the aorta immediately cranial to the aortic bifurcation. Examination of the thoracic aorta was added in four animals. To identify the inner and outer boundary of the arterial wall, a dynamic contour algorithm (Gradient Vector Flow snakes) was applied to the 2DI and PDW images, respectively, after which the vessel wall area was calculated. The results were compared with histopathological measurements of intima and intima-media cross-sectional area. The correlation coefficient between wall area measurements with MRI snakes and intima-media area was 0.879 when computed individual-wise for abdominal aortas, 0.958 for thoracic aortas, and 0.834 when computed segment-wise. When the algorithm was applied to the PDW images only, somewhat lower correlations were obtained. The MRI yielded significantly higher values than histopathology, which excludes the adventitia. Magnetic resonance imaging, in combination with dynamic contours, may be a suitable technique for quantitative assessment of atherosclerosis in vivo. Using two sequences for the measurement seems to be superior to using a single sequence.