A target containing phantom for accuracy assessment of cone-beam CT-guided histotripsy.

PURPOSE: Histotripsy is a nonionizing, noninvasive, and nonthermal focal tumor therapy. Cone-beam computed tomography (CBCT) guidance was developed for targeting tumors not visible on ultrasound. This approach assumes cavitation is formed at the geometrical focal point of the therapy transducer. In practice, the exact location might vary slightly between transducers. In this study, we present a phantom with an embedded target to evaluate CBCT-guided histotripsy accuracy and assess the completeness of treatments. METHODS: Spherical (2.8 cm) targets with alternating layers of agar and radiopaque barium were embedded in larger phantoms with similar layers. The layer geometry was designed so that targets were visible on pre-treatment CBCT scans. The actual histotripsy treatment zone was visualized via the mixing of adjacent barium and agar layers in post-treatment CBCT images. CBCT-guided histotripsy treatments of the targets were performed in six phantoms. Offsets between planned and actual treatment zones were measured and used for calibration refinement. To measure targeting accuracy after calibration refinement, six additional phantoms were treated. In a separate investigation, two groups (N = 3) of phantoms were treated to assess visualization of incomplete treatments ("undertreatment" group: 2 cm treatment within 2.8 cm tumor, "mistarget" group: 2.8 cm treatment intentionally shifted laterally). Treatment zones were segmented (3D Slicer 5.0.3), and the centroid distance between the prescribed target and actual treatment zones was quantified. RESULTS: In the calibration refinement group, a 2 mm offset in the direction of ultrasound propagation (Z) was measured. After calibration refinement, the centroid-to-centroid distance between prescribed and actual treatment volumes was 0.5 ± 0.2 mm. Average difference between the prescribed and measured treatment sizes in the incomplete treatment groups was 0.5 ± 0.7 mm. In the mistarget group, the distance between prescribed and measured shifts was 0.2 ± 0.1 mm. CONCLUSION: The proposed prototype phantom allowed for accurate measurement of treatment size and location, and the CBCT visible target provided a simple way to detect misalignments for preliminary quality assurance of CBCT-guided histotripsy.

Topology observing 3D device reconstruction from continuous-sweep limited angle fluoroscopy.

BACKGROUND: Minimally invasive procedures usually require navigating a microcatheter and guidewire through endoluminal structures such as blood vessels and airways to sites of the disease. For numerous clinical applications, two-dimensional (2D) fluoroscopy is the primary modality used for real-time image guidance during navigation. However, 2D imaging can pose challenges for navigation in complex structures. Real-time 3D visualization of devices within the anatomic context could provide considerable benefits for these procedures. Continuous-sweep limited angle (CLA) fluoroscopy has recently been proposed to provide a compromise between conventional rotational 3D acquisitions and real-time fluoroscopy. PURPOSE: The purpose of this work was to develop and evaluate a noniterative 3D device reconstruction approach for CLA fluoroscopy acquisitions, which takes into account endoluminal topology to avoid impossible paths between disconnected branches. METHODS: The algorithm relies on a static 3D roadmap (RM) of vessels or airways, which may be generated from conventional cone beam CT (CBCT) acquisitions prior to navigation. The RM is converted to a graph representation describing its topology. During catheter navigation, the device is segmented from the live 2D projection images using a deep learning approach from which the centerlines are extracted. Rays from the focal spot to detector pixels representing 2D device points are identified and intersections with the RM are computed. Based on the RM graph, a subset of line segments is selected as candidates to exclude device paths through disconnected branches of the RM. Depth localization for each point along the device is then performed by finding the point closest to the previous 3D reconstruction along the candidate segments. This process is repeated as the projection angle changes for each CLA image frame. The approach was evaluated in a phantom study in which a catheter and guidewire were navigated along five pathways within a complex vessel phantom. The result was compared to static cCBCT acquisitions of the device in the final position. RESULTS: The average root mean squared 3D distance between CLA reconstruction and reference centerline was 1.87 ± 0.30 $1.87 \pm 0.30$ mm. The Euclidean distance at the device tip was 2.92 ± 2.35 $2.92 \pm 2.35$ mm. The correct pathway was identified during reconstruction in 100 % $100\%$ of frames ( n = 1475 $n=1475$ ). The percentage of 3D device points reconstructed inside the 3D roadmap was 91.83 ± 2.52 % $91.83 \pm 2.52\%$ with an average distance of 0.62 ± 0.30 $0.62 \pm 0.30$ mm between the device points outside the roadmap and the nearest point within the roadmap. CONCLUSIONS: This study demonstrates the feasibility of reconstructing curvilinear devices such as catheters and guidewires during endoluminal procedures including intravascular and transbronchial interventions using a noniterative reconstruction approach for CLA fluoroscopy. This approach could improve device navigation in cases where the structure of vessels or airways is complex and includes overlapping branches.

Motion-compensation approach for quantitative digital subtraction angiography and its effect on in-vivo blood velocity measurement.

Purpose: Quantitative monitoring of flow-altering interventions has been proposed using algorithms that quantify blood velocity from time-resolved two-dimensional angiograms. These algorithms track the movement of contrast oscillations along a vessel centerline. Vessel motion may occur relative to a statically defined vessel centerline, corrupting the blood velocity measurement. We provide a method for motion-compensated blood velocity quantification. Approach: The motion-compensation approach utilizes a vessel segmentation algorithm to perform frame-by-frame vessel registration and creates a dynamic vessel centerline that moves with the vasculature. Performance was evaluated in-vivo through comparison with manually annotated centerlines. The method was also compared to a previous uncompensated method using best- and worst-case static centerlines chosen to minimize and maximize centerline placement accuracy. Blood velocities determined through quantitative DSA (qDSA) analysis for each centerline type were compared through linear regression analysis. Results: Centerline distance errors were 0.3±0.1 mm relative to gold standard manual annotations. For the uncompensated approach, the best- and worst-case static centerlines had distance errors of 1.1±0.6 and 2.9±1.2 mm, respectively. Linear regression analysis found a high R-squared between qDSA-derived blood velocities using gold standard centerlines and motion-compensated centerlines (R2=0.97) with a slope of 1.15 and a small offset of -0.6 cm/s. The use of static centerlines resulted in low coefficients of determination for the best case (R2=0.35) and worst-case (R2=0.20) scenarios, with slopes close to zero. Conclusions: In-vivo validation of motion-compensated qDSA analysis demonstrated improved velocity quantification accuracy in vessels with motion, addressing an important clinical limitation of the current qDSA algorithm.

Interleaved x-ray imaging: A method for simultaneous acquisition of quantitative and diagnostic digital subtraction angiography.

BACKGROUND: Flow altering angiographic procedures suffer from ill-defined, qualitative endpoints. Quantitative digital subtraction angiography (qDSA) is an emerging technology that aims to address this issue by providing intra-procedural blood velocity measurements from time-resolved, 2D angiograms. To date, qDSA has used 30 frame/s DSA imaging, which is associated with high radiation dose rate compared to clinical diagnostic DSA (up to 4 frame/s). PURPOSE: The purpose of this study is to demonstrate an interleaved x-ray imaging method which decreases the radiation dose rate associated with high frame rate qDSA while simultaneously providing low frame rate diagnostic DSA images, enabling the acquisition of both datasets in a single image sequence with a single injection of contrast agent. METHODS: Interleaved x-ray imaging combines low radiation dose image frames acquired at a high rate with high radiation dose image frames acquired at a low rate. The feasibility of this approach was evaluated on an x-ray system equipped with research prototype software for x-ray tube control. qDSA blood velocity quantification was evaluated in a flow phantom study for two lower dose interleaving protocols (LD1: 3.7 ± 0.02 mGy / s $3.7 \pm 0.02\ {\mathrm{mGy}}/{\mathrm{s}}$ and LD2: 1.7 ± 0.04 mGy / s $1.7 \pm 0.04{\mathrm{\ mGy}}/{\mathrm{s}}$ ) and one conventional (full dose) protocol ( 11.4 ± 0.04 mGy / s ) $11.4 \pm 0.04{\mathrm{\ mGy}}/{\mathrm{s}})$ . Dose was measured at the interventional reference point. Fluid velocities ranging from 24 to 45 cm/s were investigated. Gold standard velocities were measured using an ultrasound flow probe. Linear regression and Bland-Altman analysis were used to compare ultrasound and qDSA. RESULTS: The LD1 and LD2 interleaved protocols resulted in dose rate reductions of -67.7% and -85.5%, compared to the full dose qDSA scan. For the full dose protocol, the Bland-Altman limits of agreement (LOA) between qDSA and ultrasound velocities were [0.7, 6.7] cm/s with a mean difference of 3.7 cm/s. The LD1 interleaved protocol results were similar (LOA: [0.3, 6.9] cm/s, bias: 3.6 cm/s). The LD2 interleaved protocol resulted in slightly larger LOA: [-2.5, 5.5] cm/s with a decrease in the bias: 1.5 cm/s. Linear regression analysis showed a strong correlation between ultrasound and qDSA derived velocities using the LD1 protocol, with a R 2 ${R}^2$ of 0.96 $0.96$ , a slope of 1.05 $1.05$ and an offset of 1.9 $1.9$  cm/s. Similar values were also found for the LD2 protocol, with a R 2 ${R}^2$ of 0.93 $0.93$ , a slope of 0.98 $0.98$ and an offset of 2.0 $2.0$  cm/s. CONCLUSIONS: The interleaved method enables simultaneous acquisition of low-dose high-rate images for intra-procedural blood velocity quantification (qDSA) and high-dose low-rate images for vessel morphology evaluation (diagnostic DSA).

Spatiotemporal frequency domain analysis for blood velocity measurement during embolization procedures.

BACKGROUND: Currently, determining procedural endpoints and treatment efficacy of vascular interventions is largely qualitative and relies on subjective visual assessment of digital subtraction angiography (DSA) images leading to large interobserver variabilities and poor reproducibility. Quantitative metrics such as the residual blood velocity in embolized vessel branches could help establish objective and reproducible endpoints. Recently, velocity quantification techniques based on a contrast enhanced X-ray sequence such as qDSA and 4D DSA have been proposed. These techniques must be robust, and, to avoid radiation dose concerns, they should be compatible with low dose per frame image acquisition. PURPOSE: To develop and evaluate a technique for robust blood velocity quantification from low dose contrast enhanced X-ray image sequences that leverages the oscillating signal created by pulsatile blood flow. METHODS: The proposed spatiotemporal frequency domain (STF) approach quantifies velocities from time attenuation maps (TAMs) representing the oscillating signal over time for all points along a vessel centerline. Due to the time it takes a contrast bolus to travel along the vessel centerline, the resulting TAM resembles a sheared sine wave. The shear angle is related to the velocity and can be determined in the spatiotemporal frequency domain after applying the 2D Fourier transform to the TAM. The approach was evaluated in a straight tube phantom using three different radiation dose levels and compared to ultrasound transit-time-based measurements. The STF velocity results were also compared to previously published approaches for the measurement of blood velocity from contrast enhanced X-ray sequences including shifted least squared (SLS) and phase shift (PHS). Additionally, an in vivo porcine study (n = 8) was performed where increasing amounts of embolic particles were injected into a hepatic or splenic artery with intermittent velocity measurements after each injection to monitor the resulting reduction in velocity. RESULTS: At the lowest evaluated dose level (average air kerma rate 1.3 mGy/s at the interventional reference point), the Pearson correlation between ultrasound and STF velocity measurements was 99 % $99\%$ . This was significantly higher ( p < 0.0001 $p < 0.0001$ ) than corresponding correlation results between ultrasound and the previously published SLS and PHS approaches ( 91 $\hskip.001pt 91$ and 93 % $93\%$ , respectively). In the in vivo study, a reduction in velocity was observed in 85.7 % $85.7\%$ of cases after injection of 1 mL, 96.4 % $96.4\%$ after 3 mL, and 100.0 % $100.0\%$ after 4 mL of embolic particles. CONCLUSIONS: The results show good agreement of the spatiotemporal frequency domain approach with ultrasound even in low dose per frame image sequences. Additionally, the in vivo study demonstrates the ability to monitor the physiological changes due to embolization. This could provide quantitative metrics during vascular procedures to establish objective and reproducible endpoints.

Introduction to concept inventories for medical physics education.

Concept inventories are multiple choice exams designed with the intention to test core concepts on specific subjects and evaluate common misconceptions. These tests serve as a useful tool in the classroom to assess value added by the instructor's educational methods and to better understand how students learn. They can provide educators with a method to evaluate their current teaching strategies and to make modifications that enhance student learning and ultimately elevate the quality of medical physics education. The use of concept inventories in introductory college physics courses revealed important gaps in conceptual understanding of physics by undergraduate students and motivated a shift of physics teaching towards more effective methods, such as active learning techniques. The goal of this review is to introduce medical physicists to concept inventories as educational evaluation tools and discuss potential applications to medical physics education by development through multi-institutional collaboration.

In silico simulation of hepatic arteries: An open-source algorithm for efficient synthetic data generation.

BACKGROUND: In silico testing of novel image reconstruction and quantitative algorithms designed for interventional imaging requires realistic high-resolution modeling of arterial trees with contrast dynamics. Furthermore, data synthesis for training of deep learning algorithms requires that an arterial tree generation algorithm be computationally efficient and sufficiently random. PURPOSE: The purpose of this paper is to provide a method for anatomically and physiologically motivated, computationally efficient, random hepatic arterial tree generation. METHODS: The vessel generation algorithm uses a constrained constructive optimization approach with a volume minimization-based cost function. The optimization is constrained by the Couinaud liver classification system to assure a main feeding artery to each Couinaud segment. An intersection check is included to guarantee non-intersecting vasculature and cubic polynomial fits are used to optimize bifurcation angles and to generate smoothly curved segments. Furthermore, an approach to simulate contrast dynamics and respiratory and cardiac motion is also presented. RESULTS: The proposed algorithm can generate a synthetic hepatic arterial tree with 40 000 branches in 11 s. The high-resolution arterial trees have realistic morphological features such as branching angles (MAD with Murray's law = 1.2 ± 1 . 2 o $ = \;1.2 \pm {1.2^o}$ ), radii (median Murray deviation = 0.08 $ = \;0.08$ ), and smoothly curved, non-intersecting vessels. Furthermore, the algorithm assures a main feeding artery to each Couinaud segment and is random (variability = 0.98 ± 0.01). CONCLUSIONS: This method facilitates the generation of large datasets of high-resolution, unique hepatic angiograms for the training of deep learning algorithms and initial testing of novel 3D reconstruction and quantitative algorithms designed for interventional imaging.

An X-Ray C-Arm Guided Automatic Targeting System for Histotripsy.

OBJECTIVE: Histotripsy is an emerging noninvasive, nonionizing and nonthermal focal cancer therapy that is highly precise and can create a treatment zone of virtually any size and shape. Current histotripsy systems rely on ultrasound imaging to target lesions. However, deep or isoechoic targets obstructed by bowel gas or bone can often not be treated safely using ultrasound imaging alone. This work presents an alternative x-ray C-arm based targeting approach and a fully automated robotic targeting system. METHODS: The approach uses conventional cone beam CT (CBCT) images to localize the target lesion and 2D fluoroscopy to determine the 3D position and orientation of the histotripsy transducer relative to the C-arm. The proposed pose estimation uses a digital model and deep learning-based feature segmentation to estimate the transducer focal point relative to the CBCT coordinate system. Additionally, the integrated robotic arm was calibrated to the C-arm by estimating the transducer pose for four preprogrammed transducer orientations and positions. The calibrated system can then automatically position the transducer such that the focal point aligns with any target selected in a CBCT image. RESULTS: The accuracy of the proposed targeting approach was evaluated in phantom studies, where the selected target location was compared to the center of the spherical ablation zones in post-treatment CBCTs. The mean and standard deviation of the Euclidean distance was 1.4 ±0.5 mm. The mean absolute error of the predicted treatment radius was 0.5 ±0.5 mm. CONCLUSION: CBCT-based histotripsy targeting enables accurate and fully automated treatment without ultrasound guidance. SIGNIFICANCE: The proposed approach could considerably decrease operator dependency and enable treatment of tumors not visible under ultrasound.

Three-dimensional catheter navigation of airways using continuous-sweep limited angle fluoroscopy on a C-arm.

Purpose: To develop an imaging-based 3D catheter navigation system for transbronchial procedures including biopsy and tumor ablation using a single-plane C-arm x-ray system. The proposed system provides time-resolved catheter shape and position as well as motion compensated 3D airway roadmaps. Approach: A continuous-sweep limited angle (CLA) imaging mode where the C-arm continuously rotates back and forth within a limited angular range while acquiring x-ray images was used for device tracking. The catheter reconstruction was performed using a sliding window of the most recent x-ray images, which captures information on device shape and position versus time. The catheter was reconstructed using a model-based approach and was displayed together with the 3D airway roadmap extracted from a pre-navigational cone-beam CT (CBCT). The roadmap was updated in regular intervals using deformable registration to tomosynthesis reconstructions based on the CLA images. The approach was evaluated in a porcine study (three animals) and compared to a gold standard CBCT reconstruction of the device. Results: The average 3D root mean squared distance between CLA and CBCT reconstruction of the catheter centerline was 1 ± 0.5 mm for a stationary catheter and 2.9 ± 1.1 mm for a catheter moving at ∼ 1 cm / s . The average tip localization error was 1.3 ± 0.7 mm and 2.7 ± 1.8 mm , respectively. Conclusions: The results indicate catheter navigation based on the proposed single plane C-arm imaging technique is feasible with reconstruction errors similar to the diameter of a typical ablation catheter.

Real-time respiratory motion compensated roadmaps for hepatic arterial interventions.

PURPOSE: During hepatic arterial interventions, catheter or guidewire position is determined by referencing or overlaying a previously acquired static vessel roadmap. Respiratory motion leads to significant discrepancies between the true position and configuration of the hepatic arteries and the roadmap, which makes navigation and accurate catheter placement more challenging and time consuming. The purpose of this work was to develop a dynamic respiratory motion compensated device guidance system and evaluate the accuracy and real-time performance in an in vivo porcine liver model. METHODS: The proposed device navigation system estimates a respiratory motion model for the hepatic vasculature from prenavigational X-ray image sequences acquired under free-breathing conditions with and without contrast enhancement. During device navigation, the respiratory state is tracked based on live fluoroscopic images and then used to estimate vessel deformation based on the previously determined motion model. Additionally, guidewires and catheters are segmented from the fluoroscopic images using a deep learning approach. The vessel and device information are combined and shown in a real-time display. Two different display modes are evaluated within this work: (1) a compensated roadmap display, where the vessel roadmap is shown moving with the respiratory motion; (2) an inverse compensated device display, where the device representation is compensated for respiratory motion and overlaid on a static roadmap. A porcine study including seven animals was performed to evaluate the accuracy and real-time performance of the system. In each pig, a guidewire and microcatheter with a radiopaque marker were navigated to distal branches of the hepatic arteries under fluoroscopic guidance. Motion compensated displays were generated showing real-time overlays of the vessel roadmap and intravascular devices. The accuracy of the motion model was estimated by comparing the estimated vessel motion to the motion of the X-ray visible marker. RESULTS: The median (minimum, maximum) error across animals was 1.08 mm (0.92 mm, 1.87 mm). Across different respiratory states and vessel branch levels, the odds of the guidewire tip being shown in the correct vessel branch were significantly higher (odds ratio = 3.12, p < 0.0001) for motion compensated displays compared to a noncompensated display (median probabilities of 86 and 69%, respectively). The average processing time per frame was 17 ms. CONCLUSIONS: The proposed respiratory motion compensated device guidance system increased the accuracy of the displayed device position relative to the hepatic vasculature. Additionally, the provided display modes combine both vessel and device information and do not require the mental integration of different displays by the physician. The processing times were well within the range of conventional clinical frame rates.

Pseudo-Enhancement in Intracranial Aneurysms on Black-Blood MRI: Effects of Flow Rate, Spatial Resolution, and Additional Flow Suppression.

BACKGROUND: Vessel-wall enhancement (VWE) on black-blood MRI (BB MRI) has been proposed as an imaging marker for a higher risk of rupture and associated with wall inflammation. Whether VWE is causally linked to inflammation or rather induced by flow phenomena has been a subject of debate. PURPOSE: To study the effects of slow flow, spatial resolution, and motion-sensitized driven equilibrium (MSDE) preparation on signal intensities in BB MRI of patient-specific aneurysm flow models. STUDY TYPE: Prospective. SUBJECTS/FLOW ANEURYSM MODEL/VIRTUAL VESSELS: Aneurysm flow models based on 3D rotational angiography datasets of three patients with intracranial aneurysms were 3D printed and perfused at two different flow rates, with and without Gd-containing contrast agent. FIELD STRENGTH/SEQUENCE: Variable refocusing flip angle 3D fast-spin echo sequence at 3 T with and without MSDE with three voxel sizes ((0.5 mm)3 , (0.7 mm)3 , and (0.9 mm)3 ); time-resolved with phase-contrast velocity-encoding 3D spoiled gradient echo sequence (4D flow MRI). ASSESSMENT: Three independent observers performed a qualitative visual assessment of flow patterns and signal enhancement. Quantitative analysis included voxel-wise evaluation of signal intensities and magnitude velocity distributions in the aneurysm. STATISTICAL TESTS: Kruskal-Wallis test, potential regressions. RESULTS: A hyperintense signal in the lumen and adjacent to the aneurysm walls on BB MRI was colocalized with slow flow. Signal intensities increased by a factor of 2.56 ± 0.68 (P < 0.01) after administering Gd contrast. After Gd contrast administration, the signal was suppressed most in conjunction with high flows and with MSDE (2.41 ± 2.07 for slow flow without MSDE, and 0.87 ± 0.99 for high flow with MSDE). A clear result was not achieved by modifying the spatial resolution . DATA CONCLUSIONS: Slow-flow phenomena contribute substantially to aneurysm enhancement and vary with MRI parameters. This should be considered in the clinical setting when assessing VWE in patients with an unruptured aneurysm. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Technical and clinical study of x-ray-based surface echo probe tracking using an attached fiducial apparatus.

PURPOSE: Several types of structural heart intervention (SHI) use information from multiple imaging modalities to complete an interventional task. For example, in transcatheter aortic valve replacement (TAVR), placement and deployment of a bioprosthetic aortic valve in the aorta is primarily guided by x-ray fluoroscopy (XRF), and echocardiography provides visualization of cardiac anatomy and blood flow. However, simultaneous interpretation of independent x-ray and echo displays remains a challenge for the interventionalist. The purpose of this work was to develop a novel echo/x-ray co-registration solution in which volumetric transthoracic echo (TTE) is transformed to the x-ray coordinate system by tracking the three-dimensional (3D) pose of a probe fiducial attachment from its appearance in two-dimensional (2D) x-ray images. METHODS: A fiducial attachment for a commercial TTE probe consisting of rings of high-contrast ball bearings was designed and fabricated. The 3D pose (position and orientation) of the fiducial attachment is estimated from a 2D x-ray image using an algorithm in which a virtual point cloud model of the attachment is iteratively rotated, translated, and forward-projected onto the image until the average sum-of-squares of grayscale values at the projected points is minimized. Fiducial registration error (FRE) and target registration error (TRE) of this approach were evaluated in phantom studies using TAVR-relevant gantry orientations and four standard acoustic windows for the TTE probe. A patient study was conducted to assess the clinical suitability of the fiducial attachment prototype during TTE imaging of patients undergoing SHI. TTE image quality for the task of guiding a transcatheter procedure was evaluated in a reviewer study. RESULTS: The 3D FRE ranged from 0.32 ± 0.03 mm (mean ± SD) to 1.31 ± 0.05 mm, depending on C-arm orientation and probe acoustic window. The 3D TRE ranged from 1.06 ± 0.03 mm to 2.42 ± 0.06 mm. Fiducial pose estimation was stable when >75% of the fiducial markers were visible in the x-ray image. A panel of reviewers graded the presentation of heart valves in TTE images from 48 SHI patients. While valve presentation did not differ significantly between acoustic windows (P > 0.05), the mitral valve did achieve a significantly higher image quality compared to the aortic and tricuspid valves (P < 0.001). Overall, reviewers perceived sufficient image quality in 76.5% of images of the mitral valve, 54.9% of images of the aortic valve, and 48.6% of images of the tricuspid valve. CONCLUSIONS: Fiducial-based tracking of a commercial TTE probe is compatible with clinical SHI workflows and yields 3D target registration error of less than 2.5 mm for a variety of x-ray gantry geometries and echo probe acoustic windows. Although TTE image quality with respect to target valve anatomy was sufficient for the majority of cases examined, prescreening of patients for sufficient TTE quality would be helpful.

A technique for intra-procedural blood velocity quantitation using time-resolved 2D digital subtraction angiography.

BACKGROUND: 2D digital subtraction angiography (DSA) is utilized qualitatively to assess blood velocity changes that occur during arterial interventions. Quantitative angiographic metrics, such as blood velocity, could be used to standardize endpoints during angiographic interventions. PURPOSE: To assess the accuracy and precision of a quantitative 2D DSA (qDSA) technique and to determine its feasibility for in vivo measurements of blood velocity. MATERIALS AND METHODS: A quantitative DSA technique was developed to calculate intra-procedural blood velocity. In vitro validation was performed by comparing velocities from the qDSA method and an ultrasonic flow probe in a bifurcation phantom. Parameters of interest included baseline flow rate, contrast injection rate, projection angle, and magnification. In vivo qDSA analysis was completed in five different branches of the abdominal aorta in two 50 kg swine and compared to 4D Flow MRI. Linear regression, Bland-Altman, Pearson's correlation coefficient and chi squared tests were used to assess the accuracy and precision of the technique. RESULTS: In vitro validation showed strong correlation between qDSA and flow probe velocities over a range of contrast injection and baseline flow rates (slope = 1.012, 95% CI [0.989,1.035], Pearson's r = 0.996, p < .0001). The application of projection angle and magnification corrections decreased variance to less than 5% the average baseline velocity (p = 0.999 and p = 0.956, respectively). In vivo validation showed strong correlation with a small bias between qDSA and 4D Flow MRI velocities for all five abdominopelvic arterial vessels of interest (slope = 1.01, Pearson's r = 0.880, p = <.01, Bias = 0.117 cm/s). CONCLUSION: The proposed method allows for accurate and precise calculation of blood velocities, in near real-time, from time resolved 2D DSAs.

A Quantitative Digital Subtraction Angiography Technique for Characterizing Reduction in Hepatic Arterial Blood Flow During Transarterial Embolization.

OBJECTIVE: There is no standardized and objective method for determining the optimal treatment endpoint (sub-stasis) during transarterial embolization. The objective of this study was to demonstrate the feasibility of using a quantitative digital subtraction angiography (qDSA) technique to characterize intra-procedural changes in hepatic arterial blood flow velocity in response to transarterial embolization in an in vivo porcine model. MATERIALS AND METHODS: Eight domestic swine underwent bland transarterial embolizations to partial- and sub-stasis angiographic endpoints with intraprocedural DSA acquisitions. Embolized lobes were assessed on histopathology for ischemic damage and tissue embolic particle density. Analysis of target vessels used qDSA and a commercially available color-coded DSA (ccDSA) tool to calculate blood flow velocities and time-to-peak, respectively. RESULTS: Blood flow velocities calculated using qDSA showed a statistically significant difference (p < 0.01) between partial- and sub-stasis endpoints, whereas time-to-peak calculated using ccDSA did not show a significant difference. During the course of embolizations, the average correlation with volume of particles delivered was larger for qDSA (- 0.86) than ccDSA (0.36). There was a statistically smaller mean squared error (p < 0.01) and larger coefficient of determination (p < 0.01) for qDSA compared to ccDSA. On pathology, the degree of embolization as calculated by qDSA had a moderate, positive correlation (p < 0.01) with the tissue embolic particle density of ischemic regions within the embolized lobe. CONCLUSIONS: qDSA was able to quantitatively discriminate angiographic embolization endpoints and, compared to a commercially available ccDSA method, improve intra-procedural characterization of blood flow changes. Additionally, the qDSA endpoints correlated with tissue-level changes.

Optimization of quantitative time-resolved 3D (4D) digital subtraction angiography in a porcine liver model.

BACKGROUND: Time-resolved three-dimensional digital subtraction angiography (4D-DSA) can be used to quantify blood velocity. Contrast pulsatility, a major discriminant on 4D-DSA, is yet to be optimized. We investigated the effects of different imaging and injection parameters on sideband ratio (SBR), a measure of contrast pulsatile strength, within the hepatic vasculature of an in vivo porcine model. METHODS: Fifty-nine hepatic 4D-DSA procedures were performed in three female domestic swine (mean weight 54 kg). Contrast injections were performed in the common hepatic artery with different combinations of imaging duration (6 s or 12 s), injection rates (from 1.0 to 2.5 mL/s), contrast concentration (50% or 100%), and catheter size (4 Fr or 5 Fr). Reflux was recorded. SBR and vessel cross-sectional areas were calculated in 289 arterial segments. Multiple linear mixed-effects models were estimated to determine the effects of parameters on SBR and cross-sectional vessel area. RESULTS: Twelve-second acquisitions yielded a SBR higher than 6 s (p < 0.001). No significant differences in SBR were seen between different catheter sizes (p = 0.063) or contrast concentration (p = 0.907). For higher injection rates (2.5 mL/s), SBR was lower (p = 0.007) and cross-sectional area was higher (p < 0.001). Reflux of contrast does not significantly affect SBR (p = 0.087). CONCLUSIONS: The strength of contrast pulsatility used for flow quantitation with 4D-DSA can be increased by adjusting injection rates and using longer acquisition times. Reduction of contrast concentration to 50% is feasible and reflux of contrast does not significantly hinder contrast pulsatility.

Quantitative 4D-Digital Subtraction Angiography to Assess Changes in Hepatic Arterial Flow during Transarterial Embolization: A Feasibility Study in a Swine Model.

PURPOSE: To determine the feasibility of using time-resolved 3D-digital subtraction angiography (4D-DSA) for quantifying changes in hepatic arterial blood flow and velocity during transarterial embolization. MATERIALS AND METHODS: Hepatic arteriography and selective transarterial embolization were performed in 4 female domestic swine (mean weight, 54 kg) using 100-300-µm microspheres. Conventional 2D and 4D-DSA were performed before, during, and after each embolization. From the 4D-DSA reconstructions, blood flow and velocity values were calculated for hepatic arterial branches using a pulsatility-based algorithm. 4D-DSA velocity values were compared to those measured using an intravascular Doppler wire with a linear regression analysis. Paired t-tests were used to compare data before and after embolization. RESULTS: There was a weak-to-moderate but statistically significant correlation of flow velocities measured with 4D-DSA and the Doppler wire (r = 0.35, n = 39, P = .012). For vessels with high pulsatility, the correlation was higher (r = 0.64, n = 11, P = .034), and the relationship between 4D-DSA and the Doppler wire fit a linear model with a positive bias toward the Doppler wire (failed to reject at 95% confidence level, P = .208). 4D-DSA performed after partial embolization showed a reduction in velocity in the embolized hepatic arteries compared to pre-embolization (mean, 3.96 ± 0.74 vs 11.8 2± 2.15 cm/s, P = .006). CONCLUSION: Quantitative 4D-DSA can depict changes in hepatic arterial blood velocity during transarterial embolization in a swine model. Further work is needed to optimize 4D-DSA acquisitions and to investigate its applicability in humans.

Mechanical Contact Spectroscopy: Characterizing Nanoscale Adhesive Contacts via Thermal Forces.

The adhesion of micro- and nanoparticles to solid substrates immersed in liquids is a problem of great scientific and technological importance. However, the quantitative characterization of such nanoscale adhesive contacts without rupturing them still presents a major experimental challenge. In this article, we introduce mechanical contact spectroscopy (MCS), an experimental technique for the nondestructive probing of particle adhesion in liquid environments. With MCS, the strength of adhesive contacts is inferred from residual position fluctuations of adherent particles excited by thermal forces. In particular, the strength of adhesion is correlated with the standard deviation of the particle lateral position x, with smaller position standard deviations [Formula: see text] indicating higher adhesive strength. For a given combination of particles, substrate, and immersion medium, the adhesion is characterized by the mechanical contact spectrum, which is a histogram of ξ values obtained from tracking an ensemble of adherent particles. Because the energy of thermal excitation at room temperature is very small in comparison to the typical total energy of adhesive contacts, the studied contacts remain in equilibrium during the measurement. Using MCS, we study the adhesion of micrometer-sized particles to planar solid substrates under a wide range of environmental conditions, including liquid immersion media of varying ionic strength and adhesion substrates with different chemical functionality of their surfaces. These experiments provide evidence that MCS is capable of reproducibly detecting minute changes in the particle-substrate work of adhesion while at the same time covering the range of adhesive contact strength relevant in the context of surface chemistry, biology, and microfabrication.

Prototype system for interventional dual-energy subtraction angiography.

Dual-energy subtraction angiography (DESA) using fast kV switching has received attention for its potential to reduce misregistration artifacts in thoracic and abdominal imaging where patient motion is difficult to control; however, commercial interventional solutions are not currently available. The purpose of this work was to adapt an x-ray angiography system for 2D and 3D DESA. The platform for the dual-energy prototype was a commercially available x-ray angiography system with a flat panel detector and an 80 kW x-ray tube. Fast kV switching was implemented using custom x-ray tube control software that follows a user-defined switching program during a rotational acquisition. Measurements made with a high temporal resolution kV meter were used to calibrate the relationship between the requested and achieved kV and pulse width. To enable practical 2D and 3D imaging experiments, an automatic exposure control algorithm was developed to estimate patient thickness and select a dual-energy switching technique (kV and ms switching) that delivers a user-specified task CNR at the minimum air kerma to the interventional reference point. An XCAT-based simulation study conducted to evaluate low and high energy image registration for the scenario of 30-60 frame/s pulmonary angiography with respiratory motion found normalized RMSE values ranging from 0.16% to 1.06% in tissue-subtracted DESA images, depending on respiratory phase and frame rate. Initial imaging in a porcine model with a 60 kV, 10 ms, 325 mA / 120 kV, 3.2 ms, 325 mA switching technique demonstrated an ability to form tissue-subtracted images from a single contrast-enhanced acquisition.

Multicenter Assessment of Radiation Exposure during Pediatric Cardiac Catheterizations Using a Novel Imaging System.

OBJECTIVES: To quantify radiation exposure during pediatric cardiac catheterizations performed by multiple operators on a new imaging platform, the Artis Q.zen (Siemens Healthcare, Forchheim, Germany), and to compare these data to contemporary benchmark values. BACKGROUND: The Artis Q.zen has been shown to achieve significant radiation reduction during select types of pediatric cardiac catheterizations in small single-center studies. No large multicenter study exists quantifying patient dose exposure for a broad spectrum of procedures. METHODS: Retrospective collection of Air Kerma (AK) and dose area product (DAP) for all pediatric cardiac catheterizations performed on this new imaging platform at four institutions over a two-year time period. RESULTS: A total of 1,127 pediatric cardiac catheterizations were analyzed. Compared to dose data from earlier generation Artis Zee imaging systems, this study demonstrates 70-80% dose reduction (AK and DAP) for similar patient and procedure types. Compared to contemporary benchmark data for common interventional procedures, this study demonstrates an average percent reduction in AK and DAP from the lowest dose saving per intervention of 39% for AK and 27% for DAP for transcatheter pulmonary valve implantation up to 77% reduction in AK and 70% reduction in DAP for atrial septal defect closure. CONCLUSION: Use of next-generation imaging platforms for pediatric cardiac catheterizations can substantially decrease patient radiation exposure. This multicenter study defines new low-dose radiation measures achievable on a novel imaging system.

Measuring blood velocity using 4D-DSA: A feasibility study.

PURPOSE: Four-dimensional (4D) DSA reconstruction provides three-dimensional (3D) time-resolved visualization of contrast bolus passage through arterial vasculature in the interventional setting. The purpose of this study was to evaluate the feasibility of using these data in measuring blood velocity and flow. METHODS: The pulsatile signals in the time concentration curves (TCCs) measured at different points along a vessel are markers of the movement of a contrast bolus and thus of blood flow. When combined with the spatial content, that is, geometry of the vasculature, this information then provides the data required to determine blood velocity. A Fourier-based algorithm was used to identify and follow the pulsatility signal. A Side Band Ratio (SBR) metric was used to reduce uncertainty in identifying the pulsatility in regions where the signal was weak. We tested this method using 4D-DSA reconstructions from vascular phantoms as well as from human studies. RESULTS: In five studies using 3D printed patient-specific cerebrovascular phantoms, velocities calculated from the 4D-DSAs were found to be within 10% of velocities measured with a flow meter. Calculated velocity and flow values from three human studies were within the range of those reported in the literature. CONCLUSIONS: 4D-DSA provides temporal and spatial information about blood flow and vascular geometry. This information is obtained using conventional rotational angiographic systems. In this small feasibility study, these data allowed calculations of velocity values that correlated well with measured values. The availability of velocity and blood flow information in the interventional setting would support a more quantitative approach to diagnosis, treatment planning and post-treatment evaluations of a variety of cerebrovascular diseases.