Quantitative 2D Digital Subtraction Venography for Venous Interventions: Validation in Phantom and In Vivo Porcine Models.

PURPOSE: To determine the feasibility of using a 2D quantitative digital subtraction venography (qDSV) technique that employs a temporally modulated contrast injection to quantify blood velocity in phantom, normal, and stenotic porcine iliac vein models. MATERIALS AND METHODS: Blood velocity was calculated using qDSV following temporally-modulated, pulsed injections of iodinated contrast medium, and compared to Doppler ultrasound (US) measurements (phantom: in-line sensor, in vivo: diagnostic linear probe). Phantom evaluation was performed in a compliant polyethylene tube phantom with simulated venous flow. In vivo evaluation of qDSV was performed in normal (n=7) and stenotic (n=3) iliac vein models. Stenoses were created using endovenous radiofrequency ablation and blood velocities were determined at baseline, post-stenosis, post-venoplasty and post-stent placement. RESULTS: In the phantom model, qDSV-calculated blood velocities (12-50 cm/s) had very strong correlations with US-measured velocities (13-51 cm/s) across a range of baseline blood velocities and injection protocols (slope=[1.01-1.13], R2=[0.96-0.99]). qDSV velocities were similar to US regardless of injection method: custom injector, commercial injector, or hand injection. In the normal in vivo model, qDSV-calculated velocities (5-18 cm/s) had strong correlation (slope=1.22, R2=0.90) with US (3-20 cm/s). In the stenosis model, blood velocity at baseline, post-stenosis, post-venoplasty, and post-stent placement were similar on qDSV and US at all time points. CONCLUSION: Venous blood velocity was accurately quantified in a venousphantom and in vivo porcine models using qDSV. Intra-procedural changes in porcine iliac vein blood velocity were quantified with qDSV after creation of a stenosis and subsequently treating it with venoplasty and stent placement.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

Multimodality image fusion to guide peripheral artery chronic total arterial occlusion recanalization in a swine carotid artery occlusion model: unblinding the interventionalist.

OBJECTIVES: To demonstrate the feasibility of magnetic resonance imaging (MRI) to X-ray fluoroscopy (XRF) image fusion to guide peripheral artery chronic total occlusion (CTO) recanalization. BACKGROUND: Endovascular peripheral artery CTO revascularization is minimally invasive, but challenging, because the occlusion is poorly visualized under XRF. Devices may steer out of the artery, which can lead to severe perforation. Merging preacquired MRI of the CTO to the live XRF display may permit upfront use of aggressive devices and improve procedural outcomes. METHODS: Swine carotid artery CTOs were created using a balloon injury model. Up to 8 weeks later, MRI of the carotid arteries was acquired and segmented to create three-dimensional surface models, which were then registered onto live XRF. CTO recanalization was performed using incrementally aggressive CTO devices (group A) or an upfront aggressive directed laser approach (group B). Procedural success was defined as luminal or subintimal device position without severe perforation. RESULTS: In this swine model, MRI to XRF fusion guidance resulted in a procedural success of 57% in group A and 100% in group B, which compared favorably to 33% using XRF alone. Fluoroscopy time was significantly less for group B (8.5 ± 2.6 min) compared to group A (48.7 ± 23.9 min), P < 0.01. Contrast dose used was similar between groups A and B. CONCLUSIONS: MRI to XRF fusion-guided peripheral artery CTO recanalization is feasible. Multimodality image fusion may permit upfront use of aggressive CTO devices with improved procedural outcomes compared to XRF-guided procedures.

Feasibility of low-dose single-view 3D fiducial tracking concurrent with external beam delivery.

PURPOSE: In external-beam radiation therapy, existing on-board x-ray imaging chains orthogonal to the delivery beam cannot recover 3D target trajectories from a single view in real-time. This limits their utility for real-time motion management concurrent with beam delivery. To address this limitation, the authors propose a novel concept for on-board imaging based on the inverse-geometry Scanning-Beam Digital X-ray (SBDX) system and evaluate its feasibility for single-view 3D intradelivery fiducial tracking. METHODS: A chest phantom comprising a posterior wall, a central lung volume, and an anterior wall was constructed. Two fiducials were placed along the mediastinal ridge between the lung cavities: a 1.5 mm diameter steel sphere superiorly and a gold cylinder (2.6 mm length × 0.9 mm diameter) inferiorly. The phantom was placed on a linear motion stage that moved sinusoidally. Fiducial motion was along the source-detector (z) axis of the SBDX system with ±10 mm amplitude and a programmed period of either 3.5 s or 5 s. The SBDX system was operated at 15 frames per second, 100 kVp, providing good apparent conspicuity of the fiducials. With the stage moving, detector data were acquired and subsequently reconstructed into 15 planes with a 12 mm plane-to-plane spacing using digital tomosynthesis. A tracking algorithm was applied to the image planes for each temporal frame to determine the position of each fiducial in (x,y,z)-space versus time. A 3D time-sinusoidal motion model was fit to the measured 3D coordinates and root mean square (RMS) deviations about the fitted trajectory were calculated. RESULTS: Tracked motion was sinusoidal and primarily along the source-detector (z) axis. The RMS deviation of the tracked z-coordinate ranged from 0.53 to 0.71 mm. The motion amplitude derived from the model fit agreed with the programmed amplitude to within 0.28 mm for the steel sphere and within -0.77 mm for the gold seed. The model fit periods agreed with the programmed periods to within 7%. CONCLUSIONS: Three dimensional fiducial tracking with approximately 1 mm or better accuracy and precision appears to be feasible with SBDX, supporting its use to guide radiotherapy.

Noise spatial nonuniformity and the impact of statistical image reconstruction in CT myocardial perfusion imaging.

PURPOSE: To achieve high temporal resolution in CT myocardial perfusion imaging (MPI), images are often reconstructed using filtered backprojection (FBP) algorithms from data acquired within a short-scan angular range. However, the variation in the central angle from one time frame to the next in gated short scans has been shown to create detrimental partial scan artifacts when performing quantitative MPI measurements. This study has two main purposes. (1) To demonstrate the existence of a distinct detrimental effect in short-scan FBP, i.e., the introduction of a nonuniform spatial image noise distribution; this nonuniformity can lead to unexpectedly high image noise and streaking artifacts, which may affect CT MPI quantification. (2) To demonstrate that statistical image reconstruction (SIR) algorithms can be a potential solution to address the nonuniform spatial noise distribution problem and can also lead to radiation dose reduction in the context of CT MPI. METHODS: Projection datasets from a numerically simulated perfusion phantom and an in vivo animal myocardial perfusion CT scan were used in this study. In the numerical phantom, multiple realizations of Poisson noise were added to projection data at each time frame to investigate the spatial distribution of noise. Images from all datasets were reconstructed using both FBP and SIR reconstruction algorithms. To quantify the spatial distribution of noise, the mean and standard deviation were measured in several regions of interest (ROIs) and analyzed across time frames. In the in vivo study, two low-dose scans at tube currents of 25 and 50 mA were reconstructed using FBP and SIR. Quantitative perfusion metrics, namely, the normalized upslope (NUS), myocardial blood volume (MBV), and first moment transit time (FMT), were measured for two ROIs and compared to reference values obtained from a high-dose scan performed at 500 mA. RESULTS: Images reconstructed using FBP showed a highly nonuniform spatial distribution of noise. This spatial nonuniformity led to large fluctuations in the temporal direction. In the numerical phantom study, the level of noise was shown to vary by as much as 87% within a given image, and as much as 110% between different time frames for a ROI far from isocenter. The spatially nonuniform noise pattern was shown to correlate with the source trajectory and the object structure. In contrast, images reconstructed using SIR showed a highly uniform spatial distribution of noise, leading to smaller unexpected noise fluctuations in the temporal direction when a short scan angular range was used. In the numerical phantom study, the noise varied by less than 37% within a given image, and by less than 20% between different time frames. Also, the noise standard deviation in SIR images was on average half of that of FBP images. In the in vivo studies, the deviation observed between quantitative perfusion metrics measured from low-dose scans and high-dose scans was mitigated when SIR was used instead of FBP to reconstruct images. CONCLUSIONS: (1) Images reconstructed using FBP suffered from nonuniform spatial noise levels. This nonuniformity is another manifestation of the detrimental effects caused by short-scan reconstruction in CT MPI. (2) Images reconstructed using SIR had a much lower and more uniform noise level and thus can be used as a potential solution to address the FBP nonuniformity. (3) Given the improvement in the accuracy of the perfusion metrics when using SIR, it may be desirable to use a statistical reconstruction framework to perform low-dose dynamic CT MPI.

Targeted transendocardial therapeutic delivery guided by MRI-x-ray image fusion.

OBJECTIVES: To validate a multi-modality image fusion approach to guide catheter-based, targeted transendocardial therapeutic delivery in a swine myocardial infarction (MI) model. BACKGROUND: Biologic agents such as stem cells may curb post MI adverse ventricular remodeling if delivered by a transendocardial catheter directly into the infarct border. 3D visualization of the infarct and other cardiac surfaces is required to perform this task. We propose registering and overlaying magnetic resonance imaging (MRI) roadmaps onto live x-ray fluoroscopy (XRF) to guide targeted transendocardial delivery. METHODS: Custom software was used to register and overlay MRI models of the endocardium and infarct on live XRF by aligning common endocardial border features. In a swine MI model, transendocardial injections of co-localizing imaging labels were performed, targeting a 20 mm perimeter around the infarct. Directed targeting error (DTE) was defined as the difference between the predicted injection site-to-infarct distance calculated by the image fusion system, to the actual distance determined by postprocedure in vivo MRI. The mobile image fusion system was designed to be vendor-independent for imaging systems and transendocardial catheters. RESULTS: Transendocardial injections were performed in all animals without complications. Mean DTE was 0.9 ± 5.0 mm (n = 8 swine). Time to register the images and establish a high quality roadmap was less than 12 min in all animals. Custom imaging tools to display injection sites and distribution were useful adjuncts during targeted injection procedures. CONCLUSIONS: Multi-modality image fusion is a feasible and accurate platform technology to guide transendocardial injections precisely to the discrete infarct border.

Calibration of GafChromic XR-RV3 radiochromic film for skin dose measurement using standardized x-ray spectra and a commercial flatbed scanner.

PURPOSE: In this study, newly formulated XR-RV3 GafChromic film was calibrated with National Institute of Standards and Technology (NIST) traceability for measurement of patient skin dose during fluoroscopically guided interventional procedures. METHODS: The film was calibrated free-in-air to air kerma levels between 15 and 1100 cGy using four moderately filtered x-ray beam qualities (60, 80, 100, and 120 kVp). The calibration films were scanned with a commercial flatbed document scanner. Film reflective density-to-air kerma calibration curves were constructed for each beam quality, with both the orange and white sides facing the x-ray source. A method to correct for nonuniformity in scanner response (up to 25% depending on position) was developed to enable dose measurement with large films. The response of XR-RV3 film under patient backscattering conditions was examined using on-phantom film exposures and Monte Carlo simulations. RESULTS: The response of XR-RV3 film to a given air kerma depended on kVp and film orientation. For a 200 cGy air kerma exposure with the orange side of the film facing the source, the film response increased by 20% from 60 to 120 kVp. At 500 cGy, the increase was 12%. When 500 cGy exposures were performed with the white side facing the x-ray source, the film response increased by 4.0% (60 kVp) to 9.9% (120 kVp) compared to the orange-facing orientation. On-phantom film measurements and Monte Carlo simulations show that using a NIST-traceable free-in-air calibration curve to determine air kerma in the presence of backscatter results in an error from 2% up to 8% depending on beam quality. The combined uncertainty in the air kerma measurement from the calibration curves and scanner nonuniformity correction was +/- 7.1% (95% C.I.). The film showed notable stability. Calibrations of film and scanner separated by 1 yr differed by 1.0%. CONCLUSIONS: XR-RV3 radiochromic film response to a given air kerma shows dependence on beam quality and film orientation. The presence of backscatter slightly modifies the x-ray energy spectrum; however, the increase in film response can be attributed primarily to the increase in total photon fluence at the sensitive layer. Film calibration curves created under free-in-air conditions may be used to measure dose from fluoroscopic quality x-ray beams, including patient backscatter with an error less than the uncertainty of the calibration in most cases.

Calibration-free device sizing using an inverse geometry x-ray system.

PURPOSE: Quantitative coronary angiography (QCA) can be used to support device size selection for cardiovascular interventions. The accuracy of QCA measurements using conventional x-ray fluoroscopy depends on proper calibration using a reference object and avoiding vessel foreshortening. The authors have developed a novel interventional device sizing method using the inverse geometry scanning-beam digital x-ray (SBDX) fluoroscopy system. The proposed method can measure the diameter and length of vessel segments without imaging a reference object and when vessels appear foreshortened. METHODS: SBDX creates multiple tomosynthetic x-ray images corresponding to planes through the patient volume. The structures that lie in the plane are in focus and the features above and below the plane are blurred. Three-dimensional localization of the vessel edges was performed by examining the degree of blurring at each image plane. A 3D vessel centerline was created and used to determine vessel magnification and angulation relative to the image planes. Diameter measurements were performed using a model-based method and length measurements were calculated from the 3D centerline. Phantom validation was performed by measuring the diameter and length of vessel segments with nominal diameters ranging from 0.5 to 2.8 mm and nominal lengths of 42 mm. The phantoms were imaged at a range of positions between the source and the detector (+/- 16 cm relative to isocenter) and with a range of foreshortening angles (0 degrees-75 degrees). RESULTS: Changes in vessel phantom position created magnifications ranging from 87% to 118% relative to isocenter magnification. Average diameter errors were less than 0.15 mm. Average length measurements were within 1% (0.3 mm) of the true length. No trends were observed between measurement accuracy and magnification. Changes in vessel phantom orientation resulted in decreased apparent length down to 28% of the original nonforeshortened length. Average diameter errors were less than 0.25 mm across all vessel angulations; errors were less than 0.1 mm for smaller diameter vessels and low to moderate vessel angles. Diameter errors increased with true diameter and vessel angle relative to the image plane. Average length measurement errors were also within 1% (0.3 mm) for each angulation. CONCLUSIONS: Tomosynthetic imaging with SBDX can accurately measure dimensions of vessels in various magnifications and angulations without calibration. This method may be more accurate and convenient than conventional QCA techniques.

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.