Hristo N. Nikolov

PIV-Measured Versus CFD-Predicted Flow Dynamics in Anatomically Realistic Cerebral Aneurysm Models

Computational fluid dynamics (CFD) modeling of nominally patient-specific cerebral aneurysms is increasingly being used as a research tool to further understand the development, prognosis, and treatment of brain aneurysms. We have previously developed virtual angiography to indirectly validate CFD-predicted gross flow dynamics against the routinely acquired digital subtraction angiograms. Toward a more direct validation, here we compare detailed, CFD-predicted velocity fields against those measured using particle imaging velocimetry (PIV). Two anatomically realistic flow-through phantoms, one a giant internal carotid artery (ICA) aneurysm and the other a basilar artery (BA) tip aneurysm, were constructed of a clear silicone elastomer. The phantoms were placed within a computer-controlled flow loop, programed with representative flow rate waveforms. PIV images were collected on several anterior-posterior (AP) and lateral (LAT) planes. CFD simulations were then carried out using a well-validated, in-house solver, based on micro-CT reconstructions of the geometries of the flow-through phantoms and inlet/outlet boundary conditions derived from flow rates measured during the PIV experiments. PIV and CFD results from the central AP plane of the ICA aneurysm showed a large stable vortex throughout the cardiac cycle. Complex vortex dynamics, captured by PIV and CFD, persisted throughout the cardiac cycle on the central LAT plane. Velocity vector fields showed good overall agreement. For the BA, aneurysm agreement was more compelling, with both PIV and CFD similarly resolving the dynamics of counter-rotating vortices on both AP and LAT planes. Despite the imposition of periodic flow boundary conditions for the CFD simulations, cycle-to-cycle fluctuations were evident in the BA aneurysm simulations, which agreed well, in terms of both amplitudes and spatial distributions, with cycle-to-cycle fluctuations measured by PIV in the same geometry. The overall good agreement between PIV and CFD suggests that CFD can reliably predict the details of the intra-aneurysmal flow dynamics observed in anatomically realistic in vitro models. Nevertheless, given the various modeling assumptions, this does not prove that they are mimicking the actual in vivo hemodynamics, and so validations against in vivo data are encouraged whenever possible.

A quality assurance phantom for the performance evaluation of volumetric micro-CT systems.

Small-animal imaging has recently become an area of increased interest because more human diseases can be modeled in transgenic and knockout rodents. As a result, micro-computed tomography (micro-CT) systems are becoming more common in research laboratories, due to their ability to achieve spatial resolution as high as 10 microm, giving highly detailed anatomical information. Most recently, a volumetric cone-beam micro-CT system using a flat-panel detector (eXplore Ultra, GE Healthcare, London, ON) has been developed that combines the high resolution of micro-CT and the fast scanning speed of clinical CT, so that dynamic perfusion imaging can be performed in mice and rats, providing functional physiological information in addition to anatomical information. This and other commercially available micro-CT systems all promise to deliver precise and accurate high-resolution measurements in small animals. However, no comprehensive quality assurance phantom has been developed to evaluate the performance of these micro-CT systems on a routine basis. We have designed and fabricated a single comprehensive device for the purpose of performance evaluation of micro-CT systems. This quality assurance phantom was applied to assess multiple image-quality parameters of a current flat-panel cone-beam micro-CT system accurately and quantitatively, in terms of spatial resolution, geometric accuracy, CT number accuracy, linearity, noise and image uniformity. Our investigations show that 3D images can be obtained with a limiting spatial resolution of 2.5 mm(-1) and noise of +/-35 HU, using an acquisition interval of 8 s at an entrance dose of 6.4 cGy.

Virtual angiography for visualization and validation of computational models of aneurysm hemodynamics

It has recently become possible to simulate aneurysmal blood flow dynamics in a patient-specific manner via the coupling of three-dimensional (3-D) X-ray angiography and computational fluid dynamics (CFD). Before such image-based CFD models can be used in a predictive capacity, however, it must be shown that they indeed reproduce the in vivo hemodynamic environment. Motivated by the fact that there are currently no techniques for adequately measuring complex blood velocity fields in vivo, in this paper we describe how cine X-ray angiograms may be simulated for the purpose of indirectly validating patient-specific CFD models. Mimicking the radiological procedure, a virtual angiogram is constructed by first simulating the time-varying injection of contrast agent into a precomputed, patient-specific CFD model. A time-series of images is then constructed by simulating the attenuation of X-rays through the computed 3-D contrast-agent flow dynamics. Virtual angiographic images and residence time maps, here derived from an image-based CFD model of a giant aneurysm, are shown to be in excellent agreement with the corresponding clinical images and residence time maps, but only when the interaction between the quasisteady contrast agent injection and the pulsatile flow are properly accounted for. These virtual angiographic techniques pave the way for validating image-based CFD models against routinely available clinical data, and provide a means of visualizing complex, 3-D blood flow dynamics in a clinically relevant manner. They also clearly show how the contrast agent injection perturbs the normal blood flow patterns, further highlighting the potential utility of image-based CFD as a window into the true aneurysmal hemodynamics.

Prospective respiratory-gated micro-CT of free breathing rodents.

Microcomputed tomography (Micro-CT) has the potential to noninvasively image the structure of organs in rodent models with high spatial resolution and relatively short image acquisition times. However, motion artifacts associated with the normal respiratory motion of the animal may arise when imaging the abdomen or thorax. To reduce these artifacts and the accompanying loss of spatial resolution, we propose a prospective respiratory gating technique for use with anaesthetized, free-breathing rodents. A custom-made bed with an embedded pressure chamber was connected to a pressure transducer. Anaesthetized animals were placed in the prone position on the bed with their abdomens located over the chamber. During inspiration, the motion of the diaphragm caused an increase in the chamber pressure, which was converted into a voltage signal by the transducer. An output voltage was used to trigger image acquisition at any desired time point in the respiratory cycle. Digital radiographic images were acquired of anaesthetized, free-breathing rats with a digital radiographic system to correlate the respiratory wave form with respiration-induced organ motion. The respiratory wave form was monitored and recorded simultaneously with the x-ray radiation pulses, and an imaging window was defined, beginning at end expiration. Phantom experiments were performed to verify that the respiratory gating apparatus was triggering the micro-CT system. Attached to the distensible phantom were 100μm diameter copper wires and the measured full width at half maximum was used to assess differences in image quality between respiratory-gated and ungated imaging protocols. This experiment allowed us to quantify the improvement in the spatial resolution, and the reduction of motion artifacts caused by moving structures, in the images resulting from respiratory-gated image acquisitions. The measured wire diameters were 0.135mm for the stationary phantom image, 0.137mm for the image gated at end deflation, 0.213mm for the image gated at peak inflation, and 0.406mm for the ungated image. Micro-CT images of anaesthetized, free-breathing rats were acquired with a General Electric Healthcare eXplore RS in vivo micro-CT system. Images of the thorax were acquired using the respiratory cycle-based trigger for the respiratory-gated mode. Respiratory gated-images were acquired at inspiration and end expiration, during a period of minimal respiration-induced organ motion. Gated images were acquired with a nominal isotropic voxel spacing of 44μm in 20-25min (80kVp, 113mAs, 300ms imaging window per projection). The equivalent ungated acquisitions were 11min in length. We observed improved definition of the diaphragm boundary and increased conspicuity of small structures within the lungs in the gated images, when compared to the ungated acquisitions. In this work, we have characterized the externally monitored respiratory wave form of free-breathing, anaesthetized rats and correlated the respiration-induced organ motion to the respiratory cycle. We have shown that the respiratory pressure wave form is an excellent surrogate for the radiographic organ motion. This information facilitates the definition of an imaging window at any phase of the breathing cycle. This approach for prospectively gated micro-CT can provide high quality images of anaesthetized free-breathing rodents.

Clinical Doppler ultrasound for the assessment of plaque ulceration in the stenosed carotid bifurcation by detection of distal turbulence intensity: A matched model study

The assessment of flow disturbances due to carotid plaque ulceration may provide added diagnostic information to Doppler ultrasound (DUS) of the carotid stenosis, and indicate whether the associated hemodynamics are a potential thromboembolic source. We evaluated the effect of ulceration in a moderately stenosed carotid bifurcation on distal turbulence intensity (TI) measured using clinical DUS in matched anthropomorphic models. Several physiologically relevant ulcer geometries (hemispherical, mushroom-shaped, and ellipsoidal pointing distally and proximally) and sizes (2-mm, 3-mm and 4-mm diameter hemispheres) were investigated. An offline analysis was performed to determine several velocity-based parameters from ensemble-averaged spectral data, including TI. Significant elevations in TI were observed in the post-stenotic flow field of the stenosed carotid bifurcation by the inclusion of ulceration (P < 0.001) in a region two common carotid artery diameters distal to the site of ulceration during the systolic peak and the diastolic phase of the cardiac cycle. Both the size and shape of ulceration had a significant effect on TI in the distal region (P < 0.001). Due to the use of a clinical system, this method provides the means to evaluate for plaque ulcerations in patients with carotid atherosclerosis using DUS.

Doppler Ultrasound Compatible Plastic Material for Use in Rigid Flow Models

A technique for the rapid but accurate fabrication of multiple flow phantoms with variations in vascular geometry would be desirable in the investigation of carotid atherosclerosis. This study demonstrates the feasibility and efficacy of implementing numerically controlled direct-machining of vascular geometries into Doppler ultrasound (DUS)-compatible plastic for the easy fabrication of DUS flow phantoms. Candidate plastics were tested for longitudinal speed of sound (SoS) and acoustic attenuation at the diagnostic frequency of 5 MHz. Teflon was found to have the most appropriate SoS (1376 +/- 40 m s(-1) compared with 1540 m s(-1) in soft tissue) and thus was selected to construct a carotid bifurcation flow model with moderate eccentric stenosis. The vessel geometry was machined directly into Teflon using a numerically controlled milling technique. Geometric accuracy of the phantom lumen was verified using nondestructive micro-computed tomography. Although Teflon displayed a higher attenuation coefficient than other tested materials, Doppler data acquired in the Teflon flow model indicated that sufficient signal power was delivered throughout the depth of the vessel and provided comparable velocity profiles to that obtained in the tissue-mimicking phantom. Our results indicate that Teflon provides the best combination of machinability and DUS compatibility, making it an appropriate choice for the fabrication of rigid DUS flow models using a direct-machining method.

Metrology test object for dimensional verification in additive manufacturing of metals for biomedical applications.

Additive manufacturing continues to increase in popularity and is being used in applications such as biomaterial ingrowth that requires sub-millimeter dimensional accuracy. The purpose of this study was to design a metrology test object for determining the capabilities of additive manufacturing systems to produce common objects, with a focus on those relevant to medical applications. The test object was designed with a variety of features of varying dimensions, including holes, cylinders, rectangles, gaps, and lattices. The object was built using selective laser melting, and the produced dimensions were compared to the target dimensions. Location of the test objects on the build plate did not affect dimensions. Features with dimensions less than 0.300 mm did not build or were overbuilt to a minimum of 0.300 mm. The mean difference between target and measured dimensions was less than 0.100 mm in all cases. The test object is applicable to multiple systems and materials, tests the effect of location on the build, uses a minimum of material, and can be measured with a variety of efficient metrology tools (including measuring microscopes and micro-CT). Investigators can use this test object to determine the limits of systems and adjust build parameters to achieve maximum accuracy.

Multisite trial of MR flow measurement: Phantom and protocol design

To describe a portable, easily assembled phantom with well‐defined bore geometry together with a series of tests that will form the basis of a standardized quality assurance protocol in a multicenter trial of flow measurement by the MR phase mapping technique.

Correction of XRII geometric distortion using a liquid-filled grid and image subtraction

X-ray image intensifier (XRII) geometric distortion reduces the accuracy of image-guided procedures and quantitative image reconstructions. Due to the dependence of this error on the earths magnetic field, the required correction is angle dependent, and calibration data should ideally be acquired simultaneously with clinical image data, at a specific orientation. We describe a technique to correct XRII geometric image distortion at any angular position during a stereotactic procedure. This approach uses a machined plastic grid, which contains channels that can be filled with iodinated contrast agent and subsequently flushed with water, providing contrast and mask images, respectively, of a geometric calibration grid. The standard image subtraction capabilities of conventional digital subtraction angiography devices can then be used to create a subtraction image of the iodine-filled channels, without any confounding anatomical structure. Grid-line intersection points are used to determine the control points that are required for a global polynomial correction algorithm, creating a correction map that is specific to the current angular position and XRII field of view (FOV). Tests with a clinical C-arm based XRII show that control points can be obtained with a precision of +/-0.053 mm, resulting in geometric correction accuracy of +/-0.152 mm, at a nominal FOV of 40 cm. While the precision and accuracy are both poorer than that achieved with a high-contrast steel-bead grid, the fact that the liquid grid can remain rigidly attached to the XRII during an entire procedure results in the establishment of an absolute detector coordinate system (referenced to the liquid-filled correction grid). The design of the liquid-filled channels allows the required control points to be introduced into the image or removed in about 30 s, avoiding the appearance of obscuring or confounding markers during clinical image acquisition, with a concurrent increase in patient dose of about 8% in the current design. Applications for this technique include stereotactic surgery, radiosurgery, x-ray stereogrammetry, and other image-guided procedures.

In Vitro Doppler Ultrasound Investigation of Turbulence Intensity in Pulsatile Flow With Simulated Cardiac Variability

An in vitro investigation of turbulence intensity (TI) associated with a severe carotid stenosis in the presence of physiological cardiac variability is described. The objective of this investigation was to determine if fluctuations due to turbulence could be quantified with conventional Doppler ultrasound (DUS) in the presence of normal physiological cycle-to-cycle cardiac variability. An anthropomorphic model of a 70% stenosed carotid bifurcation was used in combination with a programmable flow pump to generate pulsatile flow with a mean flow rate of 6 mL/s. Utilizing the pump, we studied normal, nonrepetitive cycle-to-cycle cardiac variability (+/-3.9%) in flow, as well as waveform shapes with standard deviations equal to 0, 2 and 3 times the normal variation. Eighty cardiac cycles of Doppler data were acquired at two regions within the model, representing either laminar or turbulent flow; each measurement was repeated six times. Turbulence intensity values were found to be 11 times higher (p < 0.001), on average, in the turbulent region than in the laminar region, with a mean difference of 24 cm/s. Twenty cardiac cycles were required for confidence in TI values. In conclusion, these results indicate that it is possible to quantify TI in vitro, even in the presence of normal and exaggerated cycle-to-cycle cardiac variability.