Multi-angled simultaneous biplane High-Speed Angiography (HSA) of patient-specific 3D-printed aneurysm phantoms using 1000 fps CdTe Photon-Counting Detectors (PCD's).

1000 fps HSA enables visualization of flow details, which may be important in accurately guiding interventional procedures; however, single-plane imaging may lack clear visualization of vessel geometry and flow detail. The previously presented high-speed orthogonal biplane imaging may overcome these limitations but may still result in foreshortening of vessel morphology. In certain morphologies, acquiring two non-orthogonal biplane projections at multiple angles can provide better flow detail rather than a standard orthogonal biplane acquisition. Flow studies of aneurysm models were performed, where simultaneous biplane acquisitions at various angles separating the two detector views allowed for better evaluation of morphology and flow. 3D-printed, patient-specific internal carotid artery aneurysm models were imaged with various non-orthogonal angles between the two high-speed photon-counting detectors (7.5 cm x 5 cm FOV) to provide frame-correlated simultaneous 1000-fps image sequences. Fluid dynamics were visualized in multi-angled planes of each model using automated injections of iodine contrast media. The resulting dual simultaneous frame-correlated 1000-fps acquisitions from multiple planes of each aneurysm model provided improved visualization of complex aneurysm geometries and flow streamlines. Multi-angled biplane acquisitions with frame correlation allows for further understanding of aneurysm morphology and flow details: additionally, the ability to recover fluid dynamics at depth enables accurate analysis of 3D flow streamlines, and it is expected that multiple-planar views will enable better volumetric flow visualization and quantification. Such better visualization has the potential to improve interventional procedures.

Determining 3D Distributions of Pulsatile Blood Flow Using Orthogonal Simultaneous Biplane High-Speed Angiography (SB-HSA) with 1000 fps CdTe Photon Counting Detectors for 3D X-ray Particle Image Velocimetry (3D-XPIV) compared to Results Using Computational Fluid Dynamics (CFD).

3D hemodynamic distributions are useful for the diagnosis and treatment of aneurysms. Detailed blood-flow patterns and derived velocity maps can be obtained using 1000 fps High Speed Angiography (HSA). The novel orthogonal Simultaneous Biplane High-Speed Angiography (SB-HSA) system enables flow information to be quantified in multiple planes, and with additional components of flow at depth, accurate 3D flow distributions are available. Computational Fluid Dynamics (CFD) is the current standard for derivation of volumetric flow distributions, but obtaining solution convergence is computationally expensive and time intensive. More importantly, matching in-vivo boundary conditions is non-trivial. Therefore, an experimentally derived 3D flow distribution method could offer realistic results with less computation time. Using SB-HSA image sequences, 3D X-Ray Particle Image Velocimetry (3D-XPIV) was explored as a new method for assessing 3D flow. 3D-XPIV was demonstrated using an in-vitro setup, where a patient-specific internal carotid artery aneurysm model was attached to a flow loop, and an automated injection of iodinated microspheres was used as a flow tracer. Two 1000 fps photon-counting detectors were placed orthogonally with the aneurysm model in the FOV of both planes. Frame-synchronization of the two detectors made correlation of single-particle velocity components at a given timepoint possible. With frame-rates of 1000 fps, small particle displacements between frames resolved realistic time varying flow, where accurate velocity distributions depended on near-instantaneous velocities. 3D-XPIV velocity distributions were compared to CFD velocity distributions, where the simulation boundary conditions matched the in-vitro setup. Results showed similar velocity distributions between CFD and 3D-XPIV.

Derivation of vascular wall shear stress from 1000 fps high-speed angiography (HSA) velocity distributions.

Pathological changes in blood flow lead to altered hemodynamic forces, which are responsible for a number of conditions related to the remodeling and regeneration of the vasculature. More specifically, wall shear stress (WSS) has been shown to be a significant hemodynamic parameter with respect to aneurysm growth and rupture, as well as plaque activation leading to increased risk of stroke. In-vivo measurement of shear stress is difficult due to the stringent requirements on spatial resolution near the wall boundaries, as well as the deviation from the commonly assumed parabolic flow behavior at the wall. In this work, we propose an experimental method of in-vitro WSS calculations from high-temporal resolution velocity distributions, which are derived from 1000 fps high-speed angiography (HSA). The high-spatial and temporal resolution of our HSA detector makes such high-resolution velocity gradient measurements feasible. Presented here is the methodology for calculation of WSS in the imaging plane, as well as initial results for a variety of vascular geometries at physiologically realistic flow rates. Further, the effect of spatial resolution on the gradient calculation is explored using CFD-derived velocity data. Such angiographic-based analysis with HSA has the potential to provide critical hemodynamic feedback in an interventional setting, with the overarching objective of supporting clinical decision-making and improving patient outcomes.

Characterization of velocity patterns produced by pulsatile and constant flows using 1000 fps high-speed angiography (HSA).

In order to accurately quantify rapidly changing blood flow velocities, as typically seen in the neurovasculature, high temporal resolution is necessary. Current methods to extract velocity data from angiographic image sequences are generally limited to 30 fps or less. High-speed angiography (HSA) with a maximal frame rate of 1000 fps can be used to evaluate time-dependent flow details normally averaged out with lower frame rates. For new HSA image sequences, two different quantitative methods were utilized to extract high-temporal resolution velocity changes: X-Ray Particle Image Velocimetry (X-PIV) and optical flow (OF). A variety of flow conditions were examined in a range of patient-specific 3D-printed phantoms. Both pulsatile and constant flow settings were investigated. X-PIV was performed using radiopaque sub-millimeter microspheres, which were tracked throughout the image sequence to provide accurate, but limited sampling of the velocity field within the 3D-printed models. Also, an open source optical flow algorithm, OpenOpticalFlow, was used to perform velocity estimation based on the spatio-temporal intensity changes of iodinated contrast wavefronts. Periodic changes in velocity within each phantom ROI can be illustrated throughout the pulsatile cycle capture by the high-speed detector. In the constant flow sequences, changes in velocity across the phantom geometry can be seen. The ability to accurately measure detailed velocity distributions and velocity changes throughout various flow conditions at high temporal resolution enables further insight into the evaluation and treatment of neurovascular disease states.

High-Definition Zoom Mode, a High-Resolution X-Ray Microscope for Neurointerventional Treatment Procedures: A Blinded-Rater Clinical-Utility Study.

BACKGROUND AND PURPOSE: Quality of visualization of treatment devices during critical stages of endovascular interventions, can directly impact their safety and efficacy. Our aim was to compare the visualization of neurointerventional procedures and treatment devices using a 194-µm pixel flat panel detector mode and a 76-µm pixel complementary metal oxide semiconductor detector mode (high definition) of a new-generation x-ray detector system using a blinded-rater study. MATERIALS AND METHODS: Deployment of flow-diversion devices for the treatment of internal carotid artery aneurysms was performed under flat panel detector and high-definition-mode image guidance in a neurointerventional phantom simulating patient cranium and tissue attenuation, embedded with 3D-printed intracranial vascular models, each with an aneurysm in the ICA segment. Image-sequence pairs of device deployments for each detector mode, under similar exposure and FOV conditions, were evaluated by 2 blinded experienced neurointerventionalists who independently selected their preferred image on the basis of visualization of anatomic features, image noise, and treatment device. They rated their selection as either similar, better, much better, or substantially better than the other choice. Inter- and intrarater agreement was calculated and categorized as poor, moderate, and good. RESULTS: Both raters demonstrating good inter- and intrarater agreement selected high-definition-mode images with a frequency of at least 95% each and, on average, rated the high-definition images as much better than flat panel detector images with a frequency of 73% from a total of 60 image pairs. CONCLUSIONS: Due to their higher resolution, high-definition-mode images are sharper and visually preferred compared with the flat panel detector images. The improved imaging provided by the high-definition mode can potentially provide an advantage during neurointerventional procedures.

Flow-Pattern Details in an Aneurysm Model Using High-Speed 1000-Frames-per-Second Angiography.

Traditional digital subtraction angiography provides rather limited evaluation of contrast flow dynamics when studying and treating intracranial brain aneurysms. A 1000-frames-per-second photon-counting x-ray detector was used to image detailed iodine-contrast flow patterns in an internal carotid artery aneurysm of a 3D-printed vascular phantom. High-speed imaging revealed differences in vortex and inflow patterns with and without a Pipeline Embolization Device flow diverter in more detail and clarity than could be seen in standard pulsed angiography. Improved temporal imaging has the potential to impact the outcomes of endovascular interventions by allowing clinicians to better understand and act on flow dynamics in real-time.

A Patient Dose-Reduction Technique for Neuroendovascular Image-Guided Interventions: Image-Quality Comparison Study.

BACKGROUND AND PURPOSE: The ROI-dose-reduced intervention technique represents an extension of ROI fluoroscopy combining x-ray entrance skin dose reduction with spatially different recursive temporal filtering to reduce excessive image noise in the dose-reduced periphery in real-time. The aim of our study was to compare the image quality of simulated neurointerventions with regular and reduced radiation doses using a standard flat panel detector system. MATERIALS AND METHODS: Ten 3D-printed intracranial aneurysm models were generated on the basis of a single patient vasculature derived from intracranial DSA and CTA. The incident dose to each model was reduced using a 0.7-mm-thick copper attenuator with a circular ROI hole (10-mm diameter) in the middle mounted inside the Infinix C-arm. Each model was treated twice with a primary coiling intervention using ROI-dose-reduced intervention and regular-dose intervention protocols. Eighty images acquired at various intervention stages were shown twice to 2 neurointerventionalists who independently scored imaging qualities (visibility of aneurysm-parent vessel morphology, associated vessels, and/or devices used). Dose-reduction measurements were performed using an ionization chamber. RESULTS: A total integral dose reduction of 62% per frame was achieved. The mean scores for regular-dose intervention and ROI dose-reduced intervention images did not differ significantly, suggesting similar image quality. Overall intrarater agreement for all scored criteria was substantial (Kendall τ = 0.62887; P < .001). Overall interrater agreement for all criteria was fair (κ = 0.2816; 95% CI, 0.2060-0.3571). CONCLUSIONS: Substantial dose reduction (62%) with a live peripheral image was achieved without compromising feature visibility during neuroendovascular interventions.

A CMOS-based high resolution fluoroscope (HRF) detector prototype with 49.5 µm pixels for use in endovascular image guided interventions (EIGI).

X-ray detectors to meet the high-resolution requirements for endovascular image-guided interventions (EIGIs) are being developed and evaluated. A new 49.5-micron pixel prototype detector is being investigated and compared to the current suite of high-resolution fluoroscopic (HRF) detectors. This detector featuring a 300-micron thick CsI(Tl) scintillator, and low electronic noise CMOS readout is designated the HRF-CMOS50. To compare the abilities of this detector with other existing high resolution detectors, a standard performance metric analysis was applied, including the determination of the modulation transfer function (MTF), noise power spectra (NPS), noise equivalent quanta (NEQ), and detective quantum efficiency (DQE) for a range of energies and exposure levels. The advantage of the smaller pixel size and reduced blurring due to the thin phosphor was exemplified when the MTF of the HRF-CMOS50 was compared to the other high resolution detectors, which utilize larger pixels, other optical designs or thicker scintillators. However, the thinner scintillator has the disadvantage of a lower quantum detective efficiency (QDE) for higher diagnostic x-ray energies. The performance of the detector as part of an imaging chain was examined by employing the generalized metrics GMTF, GNEQ, and GDQE, taking standard focal spot size and clinical imaging parameters into consideration. As expected, the disparaging effects of focal spot unsharpness, exacerbated by increasing magnification, degraded the higher-frequency performance of the HRF-CMOS50, while increasing scatter fraction diminished low-frequency performance. Nevertheless, the HRF-CMOS50 brings improved resolution capabilities for EIGIs, but would require increased sensitivity and dynamic range for future clinical application.

Focal spot size reduction using asymmetric collimation to enable reduced anode angles with a conventional angiographic x-ray tube for use with high resolution detectors.

The high-resolution requirements for neuro-endovascular image-guided interventions (EIGIs) necessitate the use of a small focal-spot size; however, the maximum tube output limits for such small focal-spot sizes may not enable sufficient x-ray fluence after attenuation through the human head to support the desired image quality. This may necessitate the use of a larger focal spot, thus contributing to the overall reduction in resolution. A method for creating a higher-output small effective focal spot based on the line-focus principle has been demonstrated and characterized. By tilting the C-arm gantry, the anode-side of the x-ray field-of-view is accessible using a detector placed off-axis. This tilted central axis diminishes the resultant focal spot size in the anode-cathode direction by the tangent of the effective anode angle, allowing a medium focal spot to be used in place of a small focal spot with minimal losses in resolution but with increased tube output. Images were acquired of two different objects at the central axis, and with the C-arm tilted away from the central axis at 1° increments from 0°-7°. With standard collimation settings, only 6° was accessible, but using asymmetric extended collimation a maximum of 7° was accessed for enhanced comparisons. All objects were positioned perpendicular to the anode-cathode direction and images were compared qualitatively. The increasing advantage of the off-axis focal spots was quantitatively evidenced at each subsequent angle using the Generalized Measured-Relative Object Detectability metric (GM-ROD). This anode-tilt method is a simple and robust way of increasing tube output for a small field-of-view detector without diminishing the overall apparent resolution for neuro-EIGIs.

Quantitative comparison using Generalized Relative Object Detectability (G-ROD) metrics of an amorphous selenium detector with high resolution Microangiographic Fluoroscopes (MAF) and standard flat panel detectors (FPD).

A novel amorphous selenium (a-Se) direct detector with CMOS readout has been designed, and relative detector performance investigated. The detector features include a 25µm pixel pitch, and 1000µm thick a-Se layer operating at 10V/µm bias field. A simulated detector DQE was determined, and used in comparative calculations of the Relative Object Detectability (ROD) family of prewhitening matched-filter (PWMF) observer and non-prewhitening matched filter (NPWMF) observer model metrics to gauge a-Se detector performance against existing high resolution micro-angiographic fluoroscopic (MAF) detectors and a standard flat panel detector (FPD). The PWMF-ROD or ROD metric compares two x-ray imaging detectors in their relative abilities in imaging a given object by taking the integral over spatial frequencies of the Fourier transform of the detector DQE weighted by an object function, divided by the comparable integral for a different detector. The generalized-ROD (G-ROD) metric incorporates clinically relevant parameters (focal-spot size, magnification, and scatter) to show the degradation in imaging performance for detectors that are part of an imaging chain. Preliminary ROD calculations using simulated spheres as the object predicted superior imaging performance by the a-Se detector as compared to existing detectors. New PWMF-G-ROD and NPWMF-G-ROD results still indicate better performance by the a-Se detector in an imaging chain over all sphere sizes for various focal spot sizes and magnifications, although a-Se performance advantages were degraded by focal spot blurring. Nevertheless, the a-Se technology has great potential to provide breakthrough abilities such as visualization of fine details including of neuro-vascular perforator vessels and of small vascular devices.

Comparison of modern stroke thrombectomy approaches using an in vitro cerebrovascular occlusion model.

BACKGROUND AND PURPOSE: A new in vitro cerebrovascular occlusion model of the intracranial circulation was developed recently for testing thrombectomy devices. Using this model, we compared recanalization success associated with different modern endovascular thrombectomy approaches. MATERIALS AND METHODS: Model experiments were performed in 4 thrombectomy test groups: 1) primary or direct Stentriever thrombectomy with a conventional guide catheter (control group), 2) primary Stentriever thrombectomy with a balloon-guide catheter, 3) combined Stentriever-continuous aspiration approach, and 4) direct aspiration alone. Successful recanalization was defined as a TICI score of 2b or 3. RESULTS: Seventy-one thrombectomy experiments were conducted. Similar rates of TICI 2b-3 scores were achieved with balloon-guide and conventional guide catheters (P = .34). The combined Stentriever plus aspiration approach and the primary aspiration thrombectomy resulted in significantly higher rates of TICI 2b or 3 than the conventional guide-catheter approach in the control group (P = .008 and P = .0001, respectively). The primary Stentriever thrombectomy with the conventional guide catheter showed the highest rate of embolization to new territories (53%). CONCLUSIONS: Data from our in vitro model experiments show that the Stentriever thrombectomy under continuous aspiration and primary aspiration thrombectomy approaches led to the highest degree of recanalization.

Treatment Planning for Image-Guided Neuro-Vascular Interventions Using Patient-Specific 3D Printed Phantoms.

Minimally invasive endovascular image-guided interventions (EIGIs) are the preferred procedures for treatment of a wide range of vascular disorders. Despite benefits including reduced trauma and recovery time, EIGIs have their own challenges. Remote catheter actuation and challenging anatomical morphology may lead to erroneous endovascular device selections, delays or even complications such as vessel injury. EIGI planning using 3D phantoms would allow interventionists to become familiarized with the patient vessel anatomy by first performing the planned treatment on a phantom under standard operating protocols. In this study the optimal workflow to obtain such phantoms from 3D data for interventionist to practice on prior to an actual procedure was investigated. Patient-specific phantoms and phantoms presenting a wide range of challenging geometries were created. Computed Tomographic Angiography (CTA) data was uploaded into a Vitrea 3D station which allows segmentation and resulting stereo-lithographic files to be exported. The files were uploaded using processing software where preloaded vessel structures were included to create a closed-flow vasculature having structural support. The final file was printed, cleaned, connected to a flow loop and placed in an angiographic room for EIGI practice. Various Circle of Willis and cardiac arterial geometries were used. The phantoms were tested for ischemic stroke treatment, distal catheter navigation, aneurysm stenting and cardiac imaging under angiographic guidance. This method should allow for adjustments to treatment plans to be made before the patient is actually in the procedure room and enabling reduced risk of peri-operative complications or delays.

Micro-Computed tomography (CT) based assessment of dental regenerative therapy in the canine mandible model.

High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine's jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custom-built micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (p<0.005). Regenerative material NCS showed an average 63.15% bone yield improvement over the control sample, NCS+alg showed 55.55% and NanoGen showed 37.5%. The bone regeneration process and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non-destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor in-vivo bone regeneration studies for greater regenerative process understanding.