Enhancing cerebral vasculature analysis with pathlength-corrected 2D angiographic parametric imaging: A feasibility study.

BACKGROUND: 2D angiographic parametric imaging (API) quantitatively extracts imaging biomarkers related to contrast flow and is conventionally applied to 2D digitally subtracted angiograms (DSA's). In the interventional suite, API is typically performed using 1-2 projection views and is limited by vessel overlap, foreshortening, and depth-integration of contrast motion. PURPOSE: This work explores the use of a pathlength-correction metric to overcome the limitations of 2D-API: the primary objective was to study the effect of converting 3D contrast flow to projected contrast flow using a simulated angiographic framework created with computational fluid dynamics (CFD) simulations, thereby removing acquisition variability. METHODS: The pathlength-correction framework was applied to in-silico angiograms, generating a reference (i.e., ground-truth) volumetric contrast distribution in four patient-specific intracranial aneurysm geometries. Biplane projections of contrast flow were created from the reference volumetric contrast distributions, assuming a cone-beam geometry. A Parker-weighted reconstruction was performed to obtain a binary representation of the vessel structure in 3D. Standard ray tracing techniques were then used to track the intersection of a ray from the focal spot with each voxel of the reconstructed vessel wall to a pixel in the detector plane. The lengths of each ray through the 3D vessel lumen were then projected along each ray-path to create a pathlength-correction map, where the pixel intensity in the detector plane corresponds to the vessel width along each source-detector ray. By dividing the projection sequences with this correction map, 2D pathlength-corrected in-silico angiograms were obtained. We then performed voxel-wise (3D) API on the ground-truth contrast distribution and compared it to pixel-wise (2D) API, both with and without pathlength correction for each biplane view. The percentage difference (PD) between the resultant API biomarkers in each dataset were calculated within the aneurysm region of interest (ROI). RESULTS: Intensity-based API parameters, such as the area under the curve (AUC) and peak height (PH), exhibited notable changes in magnitude and spatial distribution following pathlength correction: these now accurately represent conservation of mass of injected contrast media within each arterial geometry and accurately reflect regions of stagnation and recirculation in each aneurysm ROI. Improved agreement was observed between these biomarkers in the pathlength-corrected biplane maps: the maximum PD within the aneurysm ROI is 3.3% with pathlength correction and 47.7% without pathlength correction. As expected, improved agreement with ROI-averaged ground-truth 3D counterparts was observed for all aneurysm geometries, particularly large aneurysms: the maximum PD for both AUC and PH was 5.8%. Temporal parameters (mean transit time, MTT, time-to-peak, TTP, time-to-arrival, TTA) remained unaffected after pathlength correction. CONCLUSIONS: This study indicates that the values of intensity-based API parameters obtained with conventional 2D-API, without pathlength correction, are highly dependent on the projection orientation, and uncorrected API should be avoided for hemodynamic analysis. The proposed metric can standardize 2D API-derived biomarkers independent of projection orientation, potentially improving the diagnostic value of all acquired 2D-DSA's. Integration of a pathlength correction map into the imaging process can allow for improved interpretation of biomarkers in 2D space, which may lead to improved diagnostic accuracy during procedures involving the cerebral vasculature.

Use of high-speed angiography HSA-derived boundary conditions and Physics Informed Neural Networks (PINNs) for comprehensive estimation of neurovascular hemodynamics.

Purpose: Physics-informed neural networks (PINNs) and computational fluid dynamics (CFD) have both demonstrated an ability to derive accurate hemodynamics if boundary conditions (BCs) are known. Unfortunately, patient-specific BCs are often unknown, and assumptions based upon previous investigations are used instead. High speed angiography (HSA) may allow extraction of these BCs due to the high temporal fidelity of the modality. We propose to investigate whether PINNs using convection and Navier-Stokes equations with BCs derived from HSA data may allow for extraction of accurate hemodynamics in the vasculature. Materials and Methods: Imaging data generated from in vitro 1000 fps HSA, as well as simulated 1000 fps angiograms generated using CFD were utilized for this study. Calculations were performed on a 3D lattice comprised of 2D projections temporally stacked over the angiographic sequence. A PINN based on an objective function comprised of the Navier-Stokes equation, the convection equation, and angiography-based BCs was used for estimation of velocity, pressure and contrast flow at every point in the lattice. Results: Imaging-based PINNs show an ability to capture such hemodynamic phenomena as vortices in aneurysms and regions of rapid transience, such as outlet vessel blood flow within a carotid artery bifurcation phantom. These networks work best with small solution spaces and high temporal resolution of the input angiographic data, meaning HSA image sequences represent an ideal medium for such solution spaces. Conclusions: The study shows the feasibility of obtaining patient-specific velocity and pressure fields using an assumption-free data driven approach based purely on governing physical equations and imaging data.

Identification of infarct core and ischemic penumbra using computed tomography perfusion and deep learning.

Purpose: The size and location of infarct and penumbra are key to decision-making for acute ischemic stroke (AIS) management. CT perfusion (CTP) software estimate infarct and penumbra volume using contralateral hemisphere relative thresholding. This approach is not robust and widely contested by the scientific community. In this study, we investigate the use of deep learning-based algorithms to efficiently locate infarct and penumbra tissue on CTP hemodynamic maps. Approach: CTP scans were retrospectively collected for 60 and 59 patients in the infarct only and infarct + penumbra substudies respectively. Commercial CTP software was used to generate cerebral blood flow, cerebral blood volume, mean transit time, time to peak, and delay time maps. U-Net-shaped architectures were trained to segment infarct or infarct + penumbra. Test-time-augmentation, ensembling, and watershed segmentation were used as postprocessing techniques. Segmentation performance was evaluated using Dice coefficients (DC) and mean absolute volume errors (MAVE). Results: The algorithm segmented infarct tissue resulted in DC of 0.64 ± 0.03 (0.63, 0.65), and MAVE of 4.91 ± 0.94 (4.5, 5.32) mL. In comparison, the commercial software predicted infarct with a DC of 0.31 ± 0.17 (0.26, 0.36) and MAVE of 9.77 ± 8.35 (7.12, 12.42) mL. The algorithm was able to segment infarct + penumbra with a DC of 0.61 ± 0.04 (0.6, 0.63), and MAVE of 6.51 ± 1.37 (5.91, 7.11) mL. In comparison, the commercial software predicted infarct + penumbra with a DC of 0.3 ± 0.19 (0.25, 0.35) and MAVE of 9.18 ± 7.55 (7.25, 11.11) mL. Conclusions: Use of deep learning algorithms to assess severity of AIS in terms of infarct and penumbra volume is precise and outperforms current relative thresholding methods. Such an algorithm would enhance the reliability of CTP in guiding treatment decisions.

Recovery of complete time density curves from incomplete angiographic data using recurrent neural networks.

Quantitative angiography is a 2D/3D x-ray imaging modality that summarizes hemodynamic information using time density curve (TDC) based parameters. Estimation of the TDC parameters are susceptible to errors due to various factors including, patient motion, incomplete temporal data, imaging trigger errors etc. In this study, we tested the feasibility of using recurrent neural networks (RNN) to recover complete TDC temporal information from incomplete sequences and evaluate quantitative parameters generated from the corrected TDCs. Digital subtraction angiograms (DSAs) were collected from patients undergoing endovascular treatments and angiographic parametric imaging (API) parameters were calculated from each DSA. Each set of API parameters was used to simulate a TDC resulting in a dataset of 760 TDCs. One-third of each TDC was continuously masked from pseudo-random points past the peak height (PH) point to simulate missing/artifact information. An RNN was developed, trained and tested to generate completed/corrected TDCs. The RNN recovered complete TDC temporal information with an average mean squared error of 0.0086±0.002. Average mean absolute errors were calculated between each API parameter generated from the ground truth TDCs and RNN corrected TDCs, these were 11.02%±0.91 for time to peak, 10.97%±0.69 for mean transit time, 5.65%±0.76 for PH, and 15.08%±0.98 for area under the TDC. The change in API parameters was not clinically significant and the predictive power of the API parameters was retained. This study proved the feasibility of using RNNs to mitigate motion artifacts and incomplete angiographic acquisitions to extract accurate quantitative parameters.

Initial investigation of the use of angiographic parametric imaging for early prognosis of delayed cerebral ischemia in patients with subarachnoid hemorrhage.

Purpose: Subarachnoid Hemorrhage (SAH) is a lethal hemorrhagic stroke that account for 25% of cerebrovascular deaths. As a result of the initial bleed, a chain of physiological events are initiated which may lead to Delayed Cerebral Ischemia (DCI). As of now we have no diagnostic capability to identify patients which may present DCI a few weeks after initial presentation. We propose to investigate whether a data driven approach using angiographic parametric imaging (API) may predict occurrence of the DCI. Materials and Methods: Digital Subtraction Angiographic (DSA) sequences from 125 SAH patients were used retrospectively to perform API assessment of the entire brain hemisphere where the hemorrhage was detected. Four Regions of Interests (ROIs) were placed to extract five average API biomarkers in the lateral and AP DSAs. Data driven analysis using Logistic Regression was performed for various API parameters and ROIs to find the optimal configuration to maximize the prognosis accuracy. Each model performance was evaluated using area under the curve of the receiver operator characteristic (AUROC). Results: Data driven approach with API has a 60% accuracy predicting DCI occurrence. We determined that location of the ROI for extraction of the API parameters is very important for the data driven model performance. Normalizing the values using the inlet velocities for each patient yield higher and more consistent results. Single API biomarkers models had poor prediction accuracies, barely better than chance. Conclusions: This effectiveness exploratory study demonstrates for the first time, that prognosis of the DCI in SAH patients, is feasible and warrants a more in-depth investigation.

Comparison of fluid dynamics changes due to physical activity in 3D printed patient specific coronary phantoms with the Windkessel equivalent model of coronary flow.

BACKGROUND: 3D printing (3DP) used to replicate the geometry of normal and abnormal vascular pathologies has been demonstrated in many publications; however, reproduction of hemodynamic changes due to physical activities, such as rest versus moderate exercise, need to be investigated. We developed a new design for patient specific coronary phantoms, which allow adjustable physiological variables such as coronary distal resistance and coronary compliance in patients with coronary artery disease. The new design was tested in precise benchtop experiments and compared with a theoretical Windkessel electrical circuit equivalent, that models coronary flow and pressure using arterial resistance and compliance. METHODS: Five phantoms from patients who underwent clinically indicated elective invasive coronary angiography were built from CCTA scans using multi-material 3D printing. Each phantom was used in a controlled flow system where patient specific flow conditions were simulated by a programmable cardiac pump. To simulate the arteriole and capillary beds flow resistance and the compliance for various physical activities, we designed a three-chamber outlet system which controls the outflow dynamics of each coronary tree. Benchtop pressure measurements were recorded using sensors embedded in each of the main coronary arteries. Using the Windkessel model, patient specific flow equivalent electrical circuit models were designed for each coronary tree branch, and flow in each artery was determined for known inflow conditions. Local flow resistances were calculated through Poiseuille's Law derived from the radii and lengths of the coronary arteries using CT angiography based multi-planar reconstructions. The coronary stenosis flow rates from the benchtop and the electrical models were compared to the localized flow rates calculated from invasive pressure measurements recorded in the angio-suites. RESULTS: The average Pearson correlations of the localized flow rates at the location of the stenosis between each of the models (Benchtop/Electrical, Benchtop/Angio, Electrical/Angio) are 0.970, 0.981, and 0.958 respectively. CONCLUSIONS: 3D printed coronary phantoms can be used to replicate the human arterial anatomy as well as blood flow conditions. It displays high levels of correlation when compared to hemodynamics calculated in electrically-equivalent coronary Windkessel models as well as invasive angio-suite pressure measurements.

Use of patient specific 3D printed neurovascular phantoms to simulate mechanical thrombectomy.

BACKGROUND: The ability of the patient specific 3D printed neurovascular phantoms to accurately replicate the anatomy and hemodynamics of the chronic neurovascular diseases has been demonstrated by many studies. Acute occurrences, however, may still require further development and investigation and therefore we studied acute ischemic stroke (AIS). The efficacy of endovascular procedures such as mechanical thrombectomy (MT) for the treatment of large vessel occlusion (LVO), can be improved by testing the performance of thrombectomy devices and techniques using patient specific 3D printed neurovascular models. METHODS: 3D printed phantoms were connected to a flow loop with physiologically relevant flow conditions, including input flow rate and fluid temperature. A simulated blood clot was introduced into the model and placed in the proximal Middle Cerebral Artery (MCA) region. Clot location, composition, length, and arterial angulation were varied and MTs were simulated using stent retrievers. Device placement relative to the clot and the outcome of the thrombectomy were recorded for each situation. Digital subtraction angiograms (DSA) were captured before and after LVO simulation. Recanalization outcome was evaluated using DSA as either 'no recanalization' or 'recanalization'. Forty-two 3DP neurovascular phantom benchtop experiments were performed. RESULTS: Clot angulation within the MCA region had the most significant impact on the MT outcome, with a p-value of 0.016. Other factors such as clot location, clot composition, and clot length correlated weakly with the MT outcome. CONCLUSIONS: This project allowed us to gain knowledge of how such characteristics influence thrombectomy success and can be used in making clinical decisions when planning the procedure and selecting specific thrombectomy tools and approaches.

Evaluation of challenges and limitations of mechanical thrombectomy using 3D printed neurovascular phantoms.

The mechanical thrombectomy (MT) efficacy, for large vessel occlusion (LVO) treatment in patients with stroke, could be improved if better teaching and practicing surgical tools were available. We propose a novel approach that uses 3D printing (3DP) to generate patient anatomical vascular variants for simulation of diverse clinical scenarios of LVO treated with MT. 3DP phantoms were connected to a flow loop with physiologically relevant flow conditions, including input flow rate and fluid temperature. A simulated blood clot was introduced into the model and placed in the Middle Cerebral Artery region. Clot location, composition (hard or soft clot), length, and arterial angulation were varied and MTs were simulated using stent retrievers. Device placement relative to the clot and the outcome of the thrombectomy were recorded for each situation. Angiograms were captured before and after LVO simulation and after the MT. Recanalization outcome was evaluated using the Thrombolysis in Cerebral Infarction (TICI) scale. Forty-two 3DP neurovascular phantom benchtop experiments were performed. Clot mechanical properties, hard versus soft, had the highest impact on the MT outcome, with 18/42 proving to be successful with full or partial clot retrieval. Other factors such as device manufacturer and the tortuosity of the 3DP model correlated weakly with the MT outcome. We demonstrated that 3DP can become a comprehensive tool for teaching and practicing various surgical procedures for MT in LVO patients. This platform can help vascular surgeons understand the endovascular devices limitations and patient vascular geometry challenges, to allow surgical approach optimization.

The Aneurysm Occlusion Assistant, an AI platform for real time surgical guidance of intracranial aneurysms.

PURPOSE: In recent years, endovascular treatment has become the dominant approach to treat intracranial aneurysms (IAs). Despite tremendous improvement in surgical devices and techniques, 10-30% of these surgeries require retreatment. Previously, we developed a method which combines quantitative angiography with data-driven modeling to predict aneurysm occlusion within a fraction of a second. This is the first report on a semi-autonomous system, which can predict the surgical outcome of an IA immediately following device placement, allowing for therapy adjustment. Additionally, we previously reported various algorithms which can segment IAs, extract hemodynamic parameters via angiographic parametric imaging, and perform occlusion predictions. METHODS: We integrated these features into an Aneurysm Occlusion Assistant (AnOA) utilizing the Kivy library's graphical instructions and unique language properties for interface development, while the machine learning algorithms were entirely developed within Keras, Tensorflow and skLearn. The interface requires pre- and post-device placement angiographic data. The next steps for aneurysm segmentation, angiographic analysis and prediction have been integrated allowing either autonomous or interactive use. RESULTS: The interface allows for segmentation of IAs and cranial vasculature with a dice index of ~0.78 and prediction of aneurysm occlusion at six months with an accuracy 0.84, in 6.88 seconds. CONCLUSION: This is the first report on the AnOA to guide endovascular treatment of IAs. While this initial report is on a stand-alone platform, the software can be integrated in the angiographic suite allowing direct communication with the angiographic system for a completely autonomous surgical guidance solution.

Use of biplane quantitative angiographic imaging with ensemble neural networks to assess reperfusion status during mechanical thrombectomy.

Digital subtraction angiography (DSA) is the main imaging modality used to assess reperfusion during mechanical thrombectomy (MT) when treating large vessel occlusion (LVO) ischemic strokes. To improve this visual and subjective assessment, hybrid models combining angiographic parametric imaging (API) with deep learning tools have been proposed. These models use convolutional neural networks (CNN) with single view individual API maps, thus restricting use of complementary information from multiple views and maps resulting in loss of relevant clinical information. This study investigates use of ensemble networks to combine hemodynamic information from multiple bi-plane API maps to assess level of reperfusion. Three-hundred-eighty-three anteroposterior (AP) and lateral view DSAs were retrospectively collected from patients who underwent MTs of anterior circulation LVOs. API peak height (PH) and area under time density curve (AUC) maps were generated. CNNs were developed to classify maps as adequate/inadequate reperfusion as labeled by two neuro-interventionalists. Outputs from individual networks were combined by weighting each output, using a grid search algorithm. Ensembled, AP-AUC, AP-PH, lateral-AUC, and lateral-PH networks achieved accuracies of 83.0% (95% confidence-interval: 81.2%-84.8%), 74.4% (72.0%-76.7%), 74.2% (72.8%-75.7%), 74.9% (72.2%-77.7%), and 76.9% (74.4%-79.5%); area under receiver operating characteristic curves of 0.86 (0.84-0.88), 0.81 (0.79-0.83), 0.83 (0.81-0.84), 0.82 (0.8-0.84), and 0.84 (0.82-0.87); and Matthews correlation coefficients of 0.66 (0.63-0.70), 0.48 (0.43-0.53), 0.49 (0.46-0.52), 0.51 (0.45-0.56), and 0.54 (0.49-0.59) respectively. Ensembled network performance was significantly better than individual networks (McNemar's p-value<0.05). This study proved feasibility of using ensemble networks to combine hemodynamic information from multiple bi-plane API maps to assess level of reperfusion during MTs.

Enhancing performance of a computed tomography perfusion software for improved prediction of final infarct volume in acute ischemic stroke patients.

Computed tomography perfusion (CTP) is crucial for acute ischemic stroke (AIS) patient diagnosis. To improve infarct prediction, enhanced image processing and automated parameter selection have been implemented in Vital Images' new CTP+ software. We compared CTP+ with its previous version, commercially available software (RAPID and Sphere), and follow-up diffusion-weighted imaging (DWI). Data from 191 AIS patients between March 2019 and January 2020 was retrospectively collected and allocated into endovascular intervention (n = 81) and conservative treatment (n = 110) cohorts. Intervention patients were treated for large vessel occlusion, underwent mechanical thrombectomy, and achieved successful reperfusion of thrombolysis in cerebral infarction 2b/2c/3. Conservative treatment patients suffered large or small vessel occlusion and did not receive intravenous thrombolysis or mechanical thrombectomy. Infarct and penumbra were assessed using intervention and conservative treatment patients, respectively. Infarct and penumbra volumes were segmented from CTP+ and compared with 24-h DWI along with RAPID, Sphere, and Vitrea. Mean infarct differences (95% confidence intervals) and Spearman correlation coefficients (SCCs) between DWI and each CTP software product for intervention patients are: CTP+ = (5.8 ± 5.9 ml, 0.62), RAPID = (10.0 ± 5.2 ml, 0.73), Sphere = (3.0 ± 6.0 ml, 0.56), Vitrea = (7.2 ± 4.9 ml, 0.66). For conservative treatment patients, mean infarct differences and SCCs are: CTP+ = (-8.0 ± 5.4 ml, 0.64), RAPID = (-25.6 ± 11.5 ml, 0.60), Sphere = (-25.6 ± 8.0 ml, 0.66), Vitrea = (1.3 ± 4.0 ml, 0.72). CTP+ performed similarly to RAPID and Sphere in addition to its semi-automated predecessor, Vitrea, when assessing intervention patient infarct volumes. For conservative treatment patients, CTP+ outperformed RAPID and Sphere in assessing penumbra. Semi-automated Vitrea remains the most accurate in assessing penumbra, but CTP+ provides an improved workflow from its predecessor.

Effect of computed tomography perfusion post-processing algorithms on optimal threshold selection for final infarct volume prediction.

In acute ischemic stroke (AIS) patients, eligibility for endovascular intervention is commonly determined through computed tomography perfusion (CTP) analysis by quantifying ischemic tissue using perfusion parameter thresholds. However, thresholds are not uniform across all analysis methods due to dependencies on patient demographics and computational algorithms. This study aimed to investigate optimal perfusion thresholds for quantifying infarct and penumbra volumes using two post-processing CTP algorithms: Vitrea Bayesian and singular value decomposition plus (SVD+). We utilized 107 AIS patients (67 non-intervention patients and 40 successful reperfusion of thrombolysis in cerebral infarction (2b/3) patients). Infarct volumes were predicted for both post-processing algorithms through contralateral hemisphere comparisons using absolute time-to-peak (TTP) and relative regional cerebral blood volume (rCBV) thresholds ranging from +2.8 seconds to +9.3 seconds and -0.23 to -0.56 respectively. Optimal thresholds were determined by minimizing differences between predicted CTP and 24-hour fluid-attenuation inversion recovery magnetic resonance imaging infarct. Optimal thresholds were tested on 60 validation patients (30 intervention and 30 non-intervention) and compared using RAPID CTP software. Among the 67 non-intervention and 40 intervention patients, the following optimal thresholds were determined: intervention Bayesian: TTP = +4.8 seconds, rCBV = -0.29; intervention SVD+: TTP = +5.8 seconds, rCBV = -0.29; non-intervention Bayesian: TTP = +5.3 seconds, rCBV = -0.32; non-intervention SVD+: TTP = +6.3 seconds, rCBV = -0.26. When comparing SVD+ and Bayesian post-processing algorithms, optimal thresholds for TTP were significantly different for intervention and non-intervention patients. rCBV optimal thresholds were equal for intervention patients and significantly different for non-intervention patients. Comparison with commercially utilized software indicated similar performance.