Quantitative Digital Subtraction Angiography Measurement of Arterial Velocity at Low Radiation Dose Rates.

PURPOSE: Quantitative digital subtraction angiography (qDSA) has been proposed to quantify blood velocity for monitoring treatment progress during blood flow altering interventions. The method requires high frame rate imaging [~ 30 frame per second (fps)] to capture temporal dynamics. This work investigates performance of qDSA in low radiation dose acquisitions to facilitate clinical translation. MATERIALS AND METHODS: Velocity quantification accuracy was evaluated at five radiation dose rates in vitro and in vivo. Angiographic technique ranged from 30 fps digital subtraction angiography ( 29.3 ± 1.7 mGy / s at the interventional reference point) down to a 30 fps protocol at 23% higher radiation dose per frame than fluoroscopy ( 1.1 ± 0.2 mGy / s ). The in vitro setup consisted of a 3D-printed model of a swine hepatic arterial tree connected to a pulsatile displacement pump. Five different flow rates (3.5-8.8 mL/s) were investigated in vitro. Angiography-based fluid velocity measurements were compared across dose rates using ANOVA and Bland-Altman analysis. The experiment was then repeated in a swine study (n = 4). RESULTS: Radiation dose rate reductions for the lowest dose protocol were 99% and 96% for the phantom and swine study, respectively. No significant difference was found between angiography-based velocity measurements at different dose rates in vitro or in vivo. Bland-Altman analysis found little bias for all lower-dose protocols (range: [- 0.1, 0.1] cm/s), with the widest limits of agreement ([- 3.3, 3.5] cm/s) occurring at the lowest dose protocol. CONCLUSIONS: This study demonstrates the feasibility of quantitative blood velocity measurements from angiographic images acquired at reduced radiation dose rates.

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.

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).

Normative Cerebral Hemodynamics in Middle-aged and Older Adults Using 4D Flow MRI: Initial Analysis of Vascular Aging.

Background Characterizing cerebrovascular hemodynamics in older adults is important for identifying disease and understanding normal neurovascular aging. Four-dimensional (4D) flow MRI allows for a comprehensive assessment of cerebral hemodynamics in a single acquisition. Purpose To establish reference intracranial blood flow and pulsatility index values in a large cross-sectional sample of middle-aged (45-65 years) and older (>65 years) adults and characterize the effect of age and sex on blood flow and pulsatility. Materials and Methods In this retrospective study, patients aged 45-93 years (cognitively unimpaired) underwent cranial 4D flow MRI between March 2010 and March 2020. Blood flow rates and pulsatility indexes from 13 major arteries and four venous sinuses and total cerebral blood flow were collected. Intraobserver and interobserver reproducibility of flow and pulsatility measures was assessed in 30 patients. Descriptive statistics (mean ± SD) of blood flow and pulsatility were tabulated for the entire group and by age and sex. Multiple linear regression and linear mixed-effects models were used to assess the effect of age and sex on total cerebral blood flow and vessel-specific flow and pulsatility, respectively. Results There were 759 patients (mean age, 65 years ± 8 [SD]; 506 female patients) analyzed. For intra- and interobserver reproducibility, median intraclass correlation coefficients were greater than 0.90 for flow and pulsatility measures across all vessels. Regression coefficients ß ± standard error from multiple linear regression showed a 4 mL/min decrease in total cerebral blood flow each year (age ß = -3.94 mL/min per year ± 0.44; P < .001). Mixed effects showed a 1 mL/min average annual decrease in blood flow (age ß = -0.95 mL/min per year ± 0.16; P < .001) and 0.01 arbitrary unit (au) average annual increase in pulsatility over all vessels (age ß = 0.011 au per year ± 0.001; P < .001). No evidence of sex differences was observed for flow (ß = -1.60 mL/min per male patient ± 1.77; P = .37), but pulsatility was higher in female patients (sex ß = -0.018 au per male patient ± 0.008; P = .02). Conclusion Normal reference values for blood flow and pulsatility obtained using four-dimensional flow MRI showed correlations with age. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Steinman in this issue.

Automated hemodynamic assessment for cranial 4D flow MRI.

Cranial 4D flow MRI post-processing typically involves manual user interaction which is time-consuming and associated with poor repeatability. The primary goal of this study is to develop a robust quantitative velocity tool (QVT) that utilizes threshold-based segmentation techniques to improve segmentation quality over prior approaches based on centerline processing schemes (CPS) that utilize k-means clustering segmentation. This tool also includes an interactive 3D display designed for simplified vessel selection and automated hemodynamic visualization and quantification. The performances of QVT and CPS were compared in vitro in a flow phantom and in vivo in 10 healthy participants. Vessel segmentations were compared with ground-truth computed tomography in vitro (29 locations) and manual segmentation in vivo (13 locations) using linear regression. Additionally, QVT and CPS MRI flow rates were compared to perivascular ultrasound flow in vitro using linear regression. To assess internal consistency of flow measures in vivo, conservation of flow was assessed at vessel junctions using linear regression and consistency of flow along vessel segments was analyzed by fitting a Gaussian distribution to a histogram of normalized flow values. Post-processing times were compared between the QVT and CPS using paired t-tests. Vessel areas segmented in vitro (CPS: slope = 0.71, r = 0.95 and QVT: slope = 1.03, r = 0.95) and in vivo (CPS: slope = 0.61, r = 0.96 and QVT: slope = 0.93, r = 0.96) were strongly correlated with ground-truth area measurements. However, CPS (using k-means segmentation) consistently underestimated vessel areas. Strong correlations were observed between QVT and ultrasound flow (slope = 0.98, r = 0.96) as well as flow at junctions (slope = 1.05, r = 0.98). Mean and standard deviation of flow along vessel segments was 9.33e-16 ± 3.05%. Additionally, the QVT demonstrated excellent interobserver agreement and significantly reduced post-processing by nearly 10 min (p < 0.001). By completely automating post-processing and providing an easy-to-use 3D visualization interface for interactive vessel selection and hemodynamic quantification, the QVT offers an efficient, robust, and repeatable means to analyze cranial 4D flow MRI. This software is freely available at: https://github.com/uwmri/QVT.

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.

Quantitative cerebrovascular 4D flow MRI at rest and during hypercapnia challenge.

UNLABELLED: Non-invasive measurement of cerebral blood flow (CBF) in humans is fraught with technologic, anatomic, and accessibility issues, which has hindered multi-vessel hemodynamic analysis of the cranial vasculature. Recent developments in cardiovascular MRI have allowed for the measurement of cine velocity vector fields over large imaging volumes in a single acquisition with 4D flow MRI. The purpose of this study was to develop an imaging protocol to simultaneously measure pulsatile flow in the circle of Willis as well as the carotid and vertebrate arteries at rest and during increased CO2 (hypercapnia). METHODS: 8 healthy adults (3 women, 26±0.4years) completed this study. Heart rate (pulse oximetry), arterial oxygen saturation (pulse oximetry), blood pressure (MAP, sphygmomanometry), and end-tidal CO2 (capnograph) were measured at rest (baseline) and during hypercapnia. Hypercapnia was induced via breathing a mixed gas of 3% CO2 and 21% O2 (balance N2) in the MR magnet. CBF and vessel cross-sectional area were quantified in 11 arteries using a 4D flow MRI scan, lasting 5-6min with a radially undersampled acquisition and an isotropic spatial resolution of 0.7mm. RESULTS: Baseline total CBF was 665±54ml • min(-1). Hypercapnia increased total CBF 9±3% to 721±61ml • min(-1). Hypercapnic increases in CBF ranged from 7 to 36% by artery, with the largest increases in the left anterior cerebral artery. Increases in artery cross-sectional area were observed in basilar and vertebral arteries. CONCLUSION: 4D flow MRI methods are sensitive enough to detect non-uniform changes in CBF and cross-sectional area to a mild yet clinically relevant CO2 stimulus. 4D flow MRI is a non-invasive reliable tool providing high spatio-temporal resolution in clinically feasible scan times without contrast agent. This approach can be used to interrogate regional cerebrovascular control in health and disease.