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Background and purpose: Previous studies predicting the rupture risk of intracranial aneurysms (IAs) have predominantly utilized static imaging data, overlooking the dynamic blood flow and biomechanical properties of the aneurysm wall. Irregular pulsation detected by 4D-CTA is a potential predictor of aneurysm rupture, albeit with uncertain clinical significance. This study aimed to analyze the changes in morpho-hemodynamic characteristics of IAs during the cardiac cycle to elucidate the dynamic changes and the associated hemodynamic mechanisms. Methods: A retrospective review was conducted on the 4D-CTA data of IA patients between January 2017 and September 2019. R-R intervals were segmented into 20-time phases, reconstructing 20 CT datasets to identify irregular pulsation and extract 3D aneurysm models. Computational fluid dynamics (CFD) simulations analyzed hemodynamic parameters such as oscillatory shear index (OSI) and relative residence time (RRT). Changes in morpho-hemodynamic characteristics were quantified in terms of the absolute change (parameter*) and relative change rate (parameter%). Rupture risk was assessed using the rupture resemblance model (RRS). Results: Eleven UIAs from 10 patients were finally included, with five aneurysms showing irregular pulsation (45.45%). No significant differences in morpho-hemodynamic characteristics were observed between aneurysms with or without irregular pulsation. More remarkable changes in aneurysm size (size*: 0.59  ±  0.14  mm vs. 0.32  ±  0.12  mm, p  =  0.010; size%: 10.49%  ±  1.43% vs. 3.95%  ±  1.79%, p  <  0.001), volume (volume%: 13.72% vs. 6.39%, p  =  0.009), OSI (OSI*: 0.02  ±  0.01 vs. 0.004  ±  0.005, p  =  0.004; OSI%: 200% vs. 12.50%, p  =  0.004) and RRT (RRT%: 97.14% vs. 43.95, p  =  0.052) over the cardiac cycle were significantly linked to irregular pulsation. Aneurysms with irregular pulsation demonstrated a more unfavorable hemodynamic environment during the cardiac cycle, irrespective of the predicted rupture risk. Furthermore, irregular pulsation at the aneurysm dome exhibited higher hemodynamic instability than at the sidewall. Conclusion: Irregular pulsation may indicate hemodynamic instability within the aneurysm, leading to an increased rupture risk in the area where irregular pulsation occurs. This proof-of-concept study could enhance understanding of dynamic changes in UIAs during the cardiac cycle and the underlying hemodynamic mechanisms. [ABSTRACT FROM AUTHOR]

Background and purpose: Irregular pulsation of the aneurysmal wall has been suggested as a novel predictor for aneurysm rupture. Aneurysm volume variations during the cardiac cycle and the association between irregular pulsation and morphological features have been discussed, but the clinical significance remains unclear. The purpose of this study was to quantify changes in morphological characteristics over the cardiac cycle and examine their correlation with irregular pulsation to facilitate comprehension of aneurysm dynamics. Materials and methods: Fourteen unruptured intracranial aneurysms (UIAs) from 11 patients were included in this study, and each of them underwent 4D-CTA after diagnosis by DSA. The R-R intervals were divided into 20-time phases at 5% intervals to determine whether an aneurysm had irregular pulsation throughout the cardiac cycle. CT images from the 20-time phases were used to reconstruct 3D aneurysm models, measure 14 morphological parameters, and quantify each parameter's absolute change and relative rates of change during the cardiac cycle. Results: Seven of 14 UIAs exhibited irregular pulsation over the cardiac cycle by 4D-CTA, 5 of which were small aneurysms (< 7 mm). The UIAs with irregular pulsation exhibited greater changes in morphological characteristics. As aneurysm size increased, the absolute change in aneurysm volume increased (p = 0.035), but the relative rates of change in aneurysm size (p = 0.013), height (p = 0.014), width (p = 0.008), height-to-width ratio (p = 0.009), dome-to-neck ratio (p = 0.019) and bottleneck factor (p = 0.012) decreased. Conclusion: Although the larger the aneurysm, the greater the amplitude of its volumetric variation, small aneurysms are prone to irregular pulsation during the cardiac cycle and have more pronounced and dramatic morphological changes during the cardiac cycle that may increase the risk of rupture. This proof-ofconcept study could help to explain the importance of dynamic changes using 4D-CTA in assessing the rupture risk of UIAs. [ABSTRACT FROM AUTHOR]

Objective To investigate the value of 4D-CTA combined with SDF-1a/CXCR4 signaling pathway in evaluating the risk of intracranial aneurysm rupture. Methods Fifty patients with unruptured intracranial posterior communicating aneurysms and 50 patients with ruptured intracranial posterior communicating aneurysms were divided into unruptured group 1 and ruptured group 1. All patients underwent 4D-CTA examination and serum SDF-1a level was detected. Non-ruptured group 1 was followed up for 12 months ( After conservative treatment), on this basis, patients with ruptured posterior communicating aneurysms were included in ruptured group 2, and patients with unruptured posterior communicating aneurysms were included in non-ruptured group 2. Results The AUC values of Wn, AR, L, SR, SDF-1a and their combinations in diagnosing ruptured intracranial posterior communicating aneurysms were all greater than 0.70.The AUC values of Wn, AR, L, SR, SDF-1a and their combinations in predicting ruptured intracranial posterior communicating aneurysms in ruptured group 2 were all greater than 0.70. Conclusion 4D-CTA combined with SDF-1acan effectively distinguish ruptured intracranial posterior communicating aneurysms and predict the risk of rupture. [ABSTRACT FROM AUTHOR]

Objective　To explore the correlation between 4D-CTA imaging and the risk factors for the rupture of anterior communicating aneurysms. Methods　A total of 100 patients with anterior communicating aneurysms in the Department of Radiology of Yan’an Hospital of Kunming City from June 2020 to March 2023 were selected as the study objects. The patients were divided into ruptured group and unruptured group based on whether the aneurysm had ruptured（with 50 cases in each group）. The unruptured group（50 cases） received conservative treatment and follow-up observation for 1-12 months. The measurements included the aneurysm neck width（Wn）， aneurysm height（ H）， average diameter of the carrying artery（ DA）， aneurysm length（ L）， aneurysm neck ratio（AR），the ratio of aneurysm height to carrying artery diameter（ SR），aneurysm volume to aneurysm base area（ VOR）， and the search for the pulsation point of the aneurysm, analyzing the correlation between these measurements and aneurysm rupture. Results　Wn，AR，L and SR in ruptured group 1 were higher than those in non-ruptured group 1（P < 0.05）. Wn，AR，L and SR in fracture group 2 were higher than those in non-fracture group 2（P < 0.05）. The CT values of internal carotid artery and middle cerebral artery, and the CT values and noise of brain parenchyma in 4D-CTA were higher than those in 3D-CTA（P < 0.05）. Conclusion The use of 4D-CTA imaging for quantitative analysis of anterior communicating aneurysms can not only predict the risk of rupture，but also provide better image quality compared to 3D imaging while reducing radiation dosage. 4D-CTA imaging has a positive impact on the diagnosis and treatment of clinical aneurysms. [ABSTRACT FROM AUTHOR]

Determine the effect of a multiphase fusion deep-learning model with automatic phase selection in detection of intracranial aneurysm (IA) from computed tomography angiography (CTA) images. CTA images of intracranial arteries from patients at Ningbo First Hospital were retrospectively analyzed. Images were randomly classified as training data, internal validation data, or test data. CTA images from cases examined by digital subtraction angiography (DSA) were examined for independent validation. A deep-learning model was constructed by automatic phase selection of multiphase fusion, and compared to the single-phase algorithm to evaluate algorithm sensitivity. We analyzed 1110 patients (1493 aneurysms) as training data, 139 patients (174 aneurysms) as internal validation data, and 134 patients (175 aneurysms) as test data. The sensitivity of the multiphase analysis of the internal validation data, test data, and independent validation data were greater than from the single-phase analysis. The recall of the multiphase selection was greater or equal to that of single-phase selection in the aneurysm position, shape, size, and rupture status. Use of the test data to determine the presence and absence of aneurysm rupture led to a recall from multiphase selection of 94.8% and 87.6% respectively; both of these values were greater than those from single-phase selection (89.6% and 79.4%). A multiphase fusion deep learning model with automatic phase selection provided automated detection of IAs with high sensitivity. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the relationship between the rate of morphological changes and intracranial aneurysm rupture during the cardiac cycle. Methods: Eighty-four patients with intracranial aneurysms were retrospectively analyzed and divided into the rupture (42 cases) and unruptured (42 cases) groups. Four-dimensional computed tomography angiography (4D-CTA) was performed to collect quantitative parameters of aneurysm morphology and calculate the morphological change rate. The potential factors associated with aneurysm rupture were determined by comparing the general clinical data and rate of change in the location and morphology of the aneurysm between the two groups. Results: Each morphological change rate in the rupture group was generally higher than that of the unruptured group. The rate of dome height change and aneurysm volume change were independent factors associated with aneurysm rupture. ROC curve analysis revealed that the diagnostic accuracy of the aneurysm volume change rate was higher. When the volume change rate was 12.33%, the sensitivity and specificity of rupture were 90.5 and 55.8%, respectively. Conclusion: The rate of change in dome height and volume of intracranial aneurysms during one cardiac cycle were independent factors associated with aneurysm rupture. [ABSTRACT FROM AUTHOR]

To investigate the change of cortical venous flow in acute ischemic stroke patients with large vessel occlusion (LVO-AIS) and its clinical value. Baseline whole-brain 4D-CTA/CTP and clinical data of LVO-AIS and a control group were collected from June 2020 to October 2021. Venous inflow time (VIT), venous peak time (VPT), and venous outflow time (VOT) were analyzed on both sides of patients and normal controls. The VIT/VPT/VOT were statistically described and compared between the patient group and normal controls, then, in patients with different collateral circulation and prognoses. Next, the correlation between cortical venous drainage time and collateral circulation grading was analyzed. Finally, logistic regression analysis was used to explore the relationship between the three venous times and prognosis, and receiver operating characteristic (ROC) curves were plotted to assess the value of delayed cortical venous imaging in predicting prognosis. 149 LVO-AIS and 73 normal controls were collected. VIT, VPT, and VOT were significantly delayed on the affected side in the patient group compared with the healthy side (p <0.05) and the controls (p <0.05); VIT and VPT were also significantly delayed on the healthy side of patients compared with the controls (p <0.05). Delayed VIT and VPT on the affected side in the patient group were more significant in patients with poor collateral circulation (p <0.05), and VIT and VPT on the affected side in the patient group were negatively correlated with arterial collateral scores. VIT and VPT were significantly delayed in both sides of patients in the poor prognosis group compared with the good prognosis group (p <0.05). logistic regression showed that patients' affected VPT, arterial collateral scores, and NIHSS were independent predictors of poor prognosis, with an accuracy of 79.6% in predicting poor prognosis. The affected VPT and NIHSS were independent predictors of poor prognosis for patients presenting within 24 hours, with an accuracy of 79.6% in predicting poor prognosis. Cortical venous flow was significantly slowed in both sides of LVO-AIS patients. delayed ipsilateral VPT in LVO-AIS patients can be used as an imaging indicator to determine poor collateral circulation and predict poor prognosis. [ABSTRACT FROM AUTHOR]

Cerebral proliferative angiopathy is a rare cerebrovascular disorder characterized by diffuse abnormal vessels with intermingled brain parenchyma fed by many arteries and draining into many veins without high-flow arteriovenous shunts, which is usually confirmed by conventional digital subtraction angiography. However, dilution of the contrast medium due to the markedly increased blood flow and volume in cerebral proliferative angiopathy leads to low-contrast angiography. We report a 53-year-old man with cerebral proliferative angiopathy who underwent CT, MR imaging, MR angiography, digital subtraction angiography and 4D-CTA. The 4D-CTA exhibited abnormal vessels without early venous filling between the atrophic brain parenchyma in higher contrast than the angiography due to high spatial and time resolution, whereas the left external carotid angiography visualized the characteristic transdural supply more clearly than the 4D-CTA due to high vascular selectivity. Therefore, novel 4D-CTA and conventional angiography plays a complementary role in the accurate diagnosis of cerebral proliferative angiopathy. Taking invasiveness into account, 4D-CTA may be advantageous for the diagnosis of cerebral proliferative angiopathy based on the characteristic imaging findings.

Recent studies have suggested that irregular pulsation of intracranial aneurysm during the cardiac cycle may be potentially associated with aneurysm rupture risk. However, there is a lack of quantification method for irregular pulsations. This study aims to quantify irregular pulsations by the displacement and strain distribution of the intracranial aneurysm surface during the cardiac cycle using four-dimensional CT angiographic image data. Four-dimensional CT angiography was performed in 8 patients. The image data of a cardiac cycle was divided into approximately 20 phases, and irregular pulsations were detected in four intracranial aneurysms by visual observation, and then the displacement and strain of the intracranial aneurysm was quantified using coherent point drift and finite element method. The displacement and strain were compared between aneurysms with irregular and normal pulsations in two different ways (total and stepwise). The stepwise first principal strain was significantly higher in aneurysms with irregular than normal pulsations (0.20 ± 0.01 vs 0.16 ± 0.02 , p = 0.033). It was found that the irregular pulsations in intracranial aneurysms usually occur during the consecutive ascending or descending phase of volume changes during the cardiac cycle. In addition, no statistically significant difference was found in the aneurysm volume changes over the cardiac cycle between the two groups. Our method can successfully quantify the displacement and strain changes in the intracranial aneurysm during the cardiac cycle, which may be proven to be a useful tool to quantify intracranial aneurysm deformability and aid in aneurysm rupture risk assessment. [ABSTRACT FROM AUTHOR]

We aimed to build a deep learning-based, objective, fast, and accurate collateral circulation assessment model. We included 92 patients who had suffered acute ischemic stroke (AIS) with large vessel occlusion in the anterior circulation in this study, following their admission to our hospital from June 2020 to August 2021. We analyzed their baseline whole-brain four-dimensional computed tomography angiography (4D-CTA)/CT perfusion. The images of the arterial, arteriovenous, venous, and late venous phases were extracted from 4D-CTA according to the perfusion time–density curve. The subtraction images of each phase were created by subtracting the non-contrast CT. Each patient was marked as having good or poor collateral circulation. Based on the ResNet34 classification network, we developed a single-image input and a multi-image input network for binary classification of collateral circulation. The training and test sets included 65 and 27 patients, respectively, and Monte Carlo cross-validation was employed for five iterations. The network performance was evaluated based on its precision, accuracy, recall, F1-score, and AUC. All the five performance indicators of the single-image input model were higher than those of the other model. The single-image input processing network, combining multiphase CTA images, can better classify AIS collateral circulation. This automated collateral assessment tool could help to streamline clinical workflows, and screen patients for reperfusion therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Previous studies predicting the rupture risk of intracranial aneurysms (IAs) have predominantly utilized static imaging data, overlooking the dynamic blood flow and biomechanical properties of the aneurysm wall. Irregular pulsation detected by 4D-CTA is a potential predictor of aneurysm rupture, albeit with uncertain clinical significance. This study aimed to analyze the changes in morpho-hemodynamic characteristics of IAs during the cardiac cycle to elucidate the dynamic changes and the associated hemodynamic mechanisms., Methods: A retrospective review was conducted on the 4D-CTA data of IA patients between January 2017 and September 2019. R-R intervals were segmented into 20-time phases, reconstructing 20 CT datasets to identify irregular pulsation and extract 3D aneurysm models. Computational fluid dynamics (CFD) simulations analyzed hemodynamic parameters such as oscillatory shear index (OSI) and relative residence time (RRT). Changes in morpho-hemodynamic characteristics were quantified in terms of the absolute change (parameter*) and relative change rate (parameter%). Rupture risk was assessed using the rupture resemblance model (RRS)., Results: Eleven UIAs from 10 patients were finally included, with five aneurysms showing irregular pulsation (45.45%). No significant differences in morpho-hemodynamic characteristics were observed between aneurysms with or without irregular pulsation. More remarkable changes in aneurysm size (size*: 0.59 ± 0.14 mm vs. 0.32 ± 0.12 mm, p  = 0.010; size%: 10.49% ± 1.43% vs. 3.95% ± 1.79%, p  < 0.001), volume (volume%: 13.72% vs. 6.39%, p  = 0.009), OSI (OSI*: 0.02 ± 0.01 vs. 0.004 ± 0.005, p  = 0.004; OSI%: 200% vs. 12.50%, p  = 0.004) and RRT (RRT%: 97.14% vs. 43.95, p  = 0.052) over the cardiac cycle were significantly linked to irregular pulsation. Aneurysms with irregular pulsation demonstrated a more unfavorable hemodynamic environment during the cardiac cycle, irrespective of the predicted rupture risk. Furthermore, irregular pulsation at the aneurysm dome exhibited higher hemodynamic instability than at the sidewall., Conclusion: Irregular pulsation may indicate hemodynamic instability within the aneurysm, leading to an increased rupture risk in the area where irregular pulsation occurs. This proof-of-concept study could enhance understanding of dynamic changes in UIAs during the cardiac cycle and the underlying hemodynamic mechanisms., Competing Interests: GW was employed by Shanghai HeartCare Medical Technology Corporation Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhang, Cheng, Wang and Lv.)

We aimed to build a deep learning-based, objective, fast, and accurate collateral circulation assessment model. We included 92 patients who had suffered acute ischemic stroke (AIS) with large vessel occlusion in the anterior circulation in this study, following their admission to our hospital from June 2020 to August 2021. We analyzed their baseline whole-brain four-dimensional computed tomography angiography (4D-CTA)/CT perfusion. The images of the arterial, arteriovenous, venous, and late venous phases were extracted from 4D-CTA according to the perfusion time–density curve. The subtraction images of each phase were created by subtracting the non-contrast CT. Each patient was marked as having good or poor collateral circulation. Based on the ResNet34 classification network, we developed a single-image input and a multi-image input network for binary classification of collateral circulation. The training and test sets included 65 and 27 patients, respectively, and Monte Carlo cross-validation was employed for five iterations. The network performance was evaluated based on its precision, accuracy, recall, F1-score, and AUC. All the five performance indicators of the single-image input model were higher than those of the other model. The single-image input processing network, combining multiphase CTA images, can better classify AIS collateral circulation. This automated collateral assessment tool could help to streamline clinical workflows, and screen patients for reperfusion therapy.

Background and Purpose: Irregular pulsation of the aneurysmal wall has been suggested as a novel predictor for aneurysm rupture. Aneurysm volume variations during the cardiac cycle and the association between irregular pulsation and morphological features have been discussed, but the clinical significance remains unclear. The purpose of this study was to quantify changes in morphological characteristics over the cardiac cycle and examine their correlation with irregular pulsation to facilitate comprehension of aneurysm dynamics., Materials and Methods: Fourteen unruptured intracranial aneurysms (UIAs) from 11 patients were included in this study, and each of them underwent 4D-CTA after diagnosis by DSA. The R-R intervals were divided into 20-time phases at 5% intervals to determine whether an aneurysm had irregular pulsation throughout the cardiac cycle. CT images from the 20-time phases were used to reconstruct 3D aneurysm models, measure 14 morphological parameters, and quantify each parameter's absolute change and relative rates of change during the cardiac cycle., Results: Seven of 14 UIAs exhibited irregular pulsation over the cardiac cycle by 4D-CTA, 5 of which were small aneurysms ( < 7 mm). The UIAs with irregular pulsation exhibited greater changes in morphological characteristics. As aneurysm size increased, the absolute change in aneurysm volume increased ( p  = 0.035), but the relative rates of change in aneurysm size ( p  = 0.013), height ( p  = 0.014), width ( p  = 0.008), height-to-width ratio ( p  = 0.009), dome-to-neck ratio ( p  = 0.019) and bottleneck factor ( p  = 0.012) decreased., Conclusion: Although the larger the aneurysm, the greater the amplitude of its volumetric variation, small aneurysms are prone to irregular pulsation during the cardiac cycle and have more pronounced and dramatic morphological changes during the cardiac cycle that may increase the risk of rupture. This proof-of-concept study could help to explain the importance of dynamic changes using 4D-CTA in assessing the rupture risk of UIAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Lv, Qian, Zhang, Zhang and Cheng.)

Purpose: Delayed cerebral ischemia represents a significant cause of poor functional outcome for patients with vasospasm after subarachnoid hemorrhage. We investigated whether delayed cerebral ischemia could be detected by the arterial opacification of internal carotid artery at the level of the skull base. Methods: In this exploratory, nested retrospective cohort diagnostic accuracy study, patients with clinical and/or transcranial Doppler suspicion of vasospasm who underwent four-dimensional computed tomography angiography were included. They were split into two groups for the main endpoint analysis, according to the actually adopted morphological (cerebral infarction) and clinical criteria (neurologic deterioration) of delayed cerebral ischemia. Opacification with a temporal resolution of 0.15 s of both internal carotid arteries at the skull base level was obtained through a semi-automated segmentation method based on skeletonization, and analyzed by a wavelet transform (rbio2.2, level 1). The results obtained by k-means clustering were analyzed with regard to the state of delayed cerebral infarction. Results: Over ten patients included and analyzed, five patients presented a delayed cerebral ischemia, two of them in both side. The semi-automated processing and analysis clustered two different types of opacification curves. The obtaining of a nonlinear opacification pattern was associated (p < 0.001) with delayed cerebral ischemia. Conclusions: The analysis of arterial opacification of internal carotid arteries at skull base by the proposed processing is feasible and leads to cluster two types of opacification that may help to early detect and prevent delayed cerebral ischemia, in particularly when examinations are artifacted by aneurysm treatment materials. [ABSTRACT FROM AUTHOR]

• A novel approach for aneurysm surface deformation estimation. • Transforms the deformation estimation into a constrained problem. • Sparse data point displacements from the 4D-CTA imaging data. Intracranial aneurysms are relatively common life-threatening diseases, and assessing aneurysm rupture risk and identifying the associated risk factors is essential. Parameters such as the Oscillatory Shear Index, Pressure Loss Coefficient, and Wall Shear Stress are reliable indicators of intracranial aneurysm development and rupture risk, but aneurysm surface irregular pulsation has also received attention in aneurysm rupture risk assessment. The present paper proposed a new approach to estimate aneurysm surface deformation. This method transforms the estimation of aneurysm surface deformation into a constrained optimization problem, which minimizes the error between the displacement estimated by the model and the sparse data point displacements from the four-dimensional CT angiography (4D-CTA) imaging data. The effect of the number of sparse data points on the results has been discussed in both simulation and experimental results, and it shows that the proposed method can accurately estimate the surface deformation of intracranial aneurysms when using sufficient sparse data points. Due to a potential association between aneurysm rupture and surface irregular pulsation, the estimation of aneurysm surface deformation is needed. This paper proposed a method based on 4D-CTA imaging data, offering a novel solution for the estimation of intracranial aneurysm surface deformation. [ABSTRACT FROM AUTHOR]

The flow dynamics of the intracranial venous channels are fundamentally important for understanding intracranial physiology and pathophysiology. However, the method clinically applicable to the evaluation of the flow dynamics of the intracranial venous system has not been well described in the reported data. We have developed a new method to evaluate intracranial venous flow direction and velocity using 4-dimensional (4D) computed tomography angiography (CTA). The aim of the present study was to verify the accuracy and validity of 4D-CTA in a clinical setting. We retrospectively analyzed 97 veins from 26 patients (16 cases of arteriovenous shunt disease, 9 intracranial tumor cases, and 1 cerebral aneurysm case) who had undergone both 4D-CTA and conventional digital subtraction angiography (DSA). Using 4D-CTA, we analyzed the time-density curve with gamma distribution extrapolation and obtained the direction of the flow and flow velocity of each vein. The direction of the flow in 4D-CTA was also collated with that obtained using conventional DSA to verify the experimental method. The direction of the flow determined by 4D-CTA was consistent with that of conventional DSA in 94.8% of cases. The average venous flow velocity was 64.3 mm/second and 81.8 mm/second, respectively, in the antegrade and retrograde channels affected by arteriovenous shunts. The present flow analysis using 4D-CTA enabled us to evaluate the direction and velocity of intracranial venous flow. Other than some limitations, the presented method is reliable and its potential for application in clinical settings is promising. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the relationship between the rate of morphological changes and intracranial aneurysm rupture during the cardiac cycle., Methods: Eighty-four patients with intracranial aneurysms were retrospectively analyzed and divided into the rupture (42 cases) and unruptured (42 cases) groups. Four-dimensional computed tomography angiography (4D-CTA) was performed to collect quantitative parameters of aneurysm morphology and calculate the morphological change rate. The potential factors associated with aneurysm rupture were determined by comparing the general clinical data and rate of change in the location and morphology of the aneurysm between the two groups., Results: Each morphological change rate in the rupture group was generally higher than that of the unruptured group. The rate of dome height change and aneurysm volume change were independent factors associated with aneurysm rupture. ROC curve analysis revealed that the diagnostic accuracy of the aneurysm volume change rate was higher. When the volume change rate was 12.33%, the sensitivity and specificity of rupture were 90.5 and 55.8%, respectively., Conclusion: The rate of change in dome height and volume of intracranial aneurysms during one cardiac cycle were independent factors associated with aneurysm rupture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Shen, Su, Nie, Zhao, Qiu and Li.)

Introduction The present study aimed to evaluate the accuracy of time-resolved-computed tomographic angiography (TR-CTA) on a 128-slice CT scanner vis-à-vis cerebral digital subtraction angiography (DSA) in defining the morphological and haemodynamic characteristics of cerebral arteriovenous malformation (AVM). Methods Twenty-one patients (age range 10–46, mean 24.8 years) with clinical suspicion of AVM and three patients (age range 23–35, mean 24.3 years) with diagnosed AVM who were on follow-up underwent DSA and TR-CTA, on average 1.5 days apart. Three independent neuroradiologists analysed both studies in a blinded fashion based on the following parameters: AVM location, arterial feeder territories, venous drainage pattern, nidus flow characteristics, venous outflow obstruction, arterial feeder enlargement, external carotid artery feeder, location of aneurysm if any, leptomeningeal and transdural recruitment, neoangiogenesis, and pseudophlebitic pattern. Results The TR-CTA correctly demonstrated AVM in all 21 positive cases. It concordantly detected location (21/21), venous drainage pattern (21/21), nidus flow characteristics (21/21), and the venous outflow obstruction (9/9). However, discordance was seen in the demonstration of the arterial feeder (2/45) (p = 0.49), arterial enlargement (13/17) (p = 0.103), external carotid artery feeder (0/1), aneurysmal location (3/5) (p = 0.40), leptomeningeal recruitment (1/3) (p = 0.40), neoangiogenesis (0/4) (p = 0.028) and in the pseudophlebitic pattern (2/5) (p = 0.167) demonstration. Conclusions The results suggest that TR-CTA can provide the important features of cerebral AVM which are required in patient management. [ABSTRACT FROM AUTHOR]

Background and purpose Digital subtraction angiography is the current gold standard for diagnosing as well as the follow-up of cerebral arteriovenous malformations. However, as it is invasive, relatively expensive and time-consuming, a non-invasive alternative is of interest. We aimed to evaluate the feasibility of time resolved computed tomography angiography (TR-CTA) in a series of five diagnosed cranial arteriovenous malformation patients, demonstrated by conventional digital subtraction angiography with respect to acquisition, depiction of angiographic phases and radiation exposure. Materials and methods Five patients demonstrating a cranial arteriovenous malformation on digital subtraction angiography were studied with TR-CTA. The TR-CTA imaging was done by using a 128-detector computed tomography scanner. Digital subtraction angiography and TR-CTA studies were independently read by two blinded observers, by using a standardised scoring sheet. TR-CTA results were analysed with digital subtraction angiography as the criterion standard. Results TR-CTA generated comparable angiographic phases. In all five cases, there was complete agreement between digital subtraction angiography and TR-CTA regarding the size, arterial feeders, nidal morphology and venous drainage of the arteriovenous malformation. Conclusions TR-CTA imaging as a technique is feasible, providing images with good temporal and spatial resolution at an acceptable radiation dose. It appears to be a promising non-invasive adjunct to digital subtraction angiography. [ABSTRACT FROM AUTHOR]

Background Localization of the arteriovenous fistula (AVF) is a crucial step in the diagnosis and treatment of spinal vascular malformations (VMs). Noninvasive angiographic techniques such as dynamic magnetic resonance angiography and three-dimensional computed tomography angiography (CTA) have been used as standard modalities to localize AVF. With the increasing prevalence of high-specification computed tomography scanners, four-dimensional (4D) CTA is being increasingly used in the evaluation of cerebrovascular disorders. However, application of 4D-CTA in spinal lesions has been limited. The position and role of 4D-CTA, among various modalities, in the evaluation of spinal VMs has not been elucidated. Methods We retrospectively review our clinical experience with 4D-CTA used for spinal AVFs. 4D-CTA images were acquired in 10 cases of spinal VMs consisting of 8 dural/epidural AVFs and 2 perimedullary AVFs. Imaging findings of 4D-CTA and digital subtraction angiography were reviewed to validate the usefulness of 4D-CTA. Results In 9 of 10 cases, 4D-CTA accurately localized the AVF. The scan visualized direction of flow in the perimedullary veins in all cases. Regarding perimedullary AVFs, 4D-CTA showed dynamic images of feeding arteries, AVF, and perimedullary drainage. Information provided by 4D-CTA was beneficial as a reference in subsequent DSA. Conclusions In the diagnostic process of spinal VMs, the position of 4D-CTA is the third choice for noninvasive angiography, after dynamic MRA and three-dimensional CTA. However, the role of 4D-CTA might be decisive in difficult-to-find spinal dural AVFs. We believe that this novel imaging technique can be applied in spinal VMs. [ABSTRACT FROM AUTHOR]

Background: Differentiation between true acute tandem occlusion involving the extracranial internal carotid artery (ICA) from pseudotandem occlusion with a patent extracranial ICA has important prognostic and therapeutic implications. We explored the utility of perfusion-derived 4-dimensional CT angiogram (4D-CTA) in identifying carotid pseudo-occlusion in a single-center pilot study.Methods: Acute stroke patients with delayed antegrade ICA flow on 4D-CTA despite an apparent tandem occlusion on conventional single-phase CTA were prospectively identified over a 2.5-year period (2013-2015).Results: Eight patients were identified. Delayed antegrade intracranial flow from the apparently occluded ICA was detected up to 50 seconds after contrast administration on 4D-CTA. The distal intracranial ICA was the most common site of true occlusion. Reconstruction of the 4D-CTA images required an additional processing time of 2-3 minutes.Conclusions: 4D-CTA is a novel noninvasive technique that can identify carotid pseudo-occlusion in the acute stroke setting. Our preliminary findings suggest that 4D-CTA can be easily incorporated into an existing acute stroke neuroimaging protocol. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate whether advanced patient motion correction (APMC) can reduce the misregistration of pixels between the different X-ray tube positions in four-dimensional CT angiography (4D-CTA).Materials and Methods: Eight patients with intracranial aneurysms were included in this retrospective study. We compared the CTA images with APMC reconstruction and half-scan reconstruction with regard to the following 3 items: (1) bone misalignment area; (2) image noise; and (3) aneurysm volume change.Results: The bone misalignment area and image noise were significantly reduced in the APMC images, as compared to that in the half-scan reconstruction images (bone misalignment area: 33.0 ± 18.1 cm(3) vs 152.0 ± 72.2 cm(3), respectively; p < 0.001) (image noise at pons: 9.70 ± 2.58 vs 15.16 ± 5.02, respectively, p < 0.001). The aneurysm volume and volume variance were significantly smaller in the APMC reconstruction than those in the half-scan reconstruction (volume: 1107.2 ± 1813.8 mm(3) vs 1135.1 ± 1853.8 mm(3); p < 0.05; coefficient of variation: 0.0291 ± 0.014 vs 0.0463 ± 0.026, p < 0.05, respectively).Conclusion: Our results show that APMC reduces the reconstruction related misregistration between the cardiac phases compared to half-scan reconstruction. [ABSTRACT FROM AUTHOR]

Objectives: Automated image-level detection of large vessel occlusions (LVO) could expedite patient triage for mechanical thrombectomy. A few studies have previously attempted LVO detection using artificial intelligence (AI) on CT angiography (CTA) images. To our knowledge this is the first study to detect LVO existence and location on raw 4D-CTA/ CT perfusion (CTP) images using neural network (NN) models.Materials and Methods: Retrospective study using data from a level-I stroke center was performed. A total of 306 (187 with LVO, and 119 without) patients were evaluated. Image pre-processing included co-registration, normalization and skull stripping. Five consecutive time-points for each patient were selected to provide variable contrast density in data. Additional data augmentation included rotation and horizonal image flipping. Our model architecture consisted of two neural networks, first for classification (based on hemispheric asymmetry), followed by second model for exact site of LVO detection. Only cases deemed positive by the classification model were routed to the detection model, thereby reducing false positives and improving specificity. The results were compared with expert annotated LVO detection.Results: Using a 80:20 split for training and validation, the combination of both classification and detection model achieved a sensitivity of 86.5%, a specificity of 89.5%, and an accuracy of 87.5%. A 5-fold cross-validation using the entire data achieved a mean sensitivity of 82.7%, a specificity of 89.8%, and an accuracy of 85.5% and a mean AUC of 0.89 (95% CI: 0.85-0.93).Conclusion: Our findings suggest that accurate image-level LVO detection is feasible on CTP raw images. [ABSTRACT FROM AUTHOR]

• We quantitatively assessed the geometry variation of endovascular cavity which captured by 4D-CTA images. The pulsating characteristics of cavity volume and internal blood vessel wall surface can be observed from morphological parameters. • The computational fluid dynamic (CFD) simulation is based on deforming models of aneurysms during cardiac cycle. We quantitatively evaluated the influence of arteries' deformation on simulation results and reproduced the hemodynamic situation during cardiac cycle. Muscular arteries and related aneurysms keep deforming during the cardiac cycle. However, current patient-specific computational fluid dynamics (CFD) analyses of aneurysms are usually based on individual cardiac phase images. The cardiac deformation and displacement characteristics of muscle arteries and aneurysms, as well as their impact on CFD results, have not been adequately explored. The present study tried to illustrate the cardiac morphological variation of visceral muscular arteries (VMAs) & aneurysms (VAAs) and evaluate its influence on the hemodynamic situation at lesion locations. Four-dimensional computed tomography angiogram (4D-CTA) images of six patients with VAAs were acquired. Medical image registration is used to capture cardiac variations of VMAs. The steady-state CFD simulation is performed on twelve different time-phase geometries. Deformation, displacement, wall shear stress (WSS), velocity, and pressure values at pathological locations are compared to illustrate the deforming characteristics of VAAs and their influence on CFD simulation results. The deformation and displacement characteristics of lesion locations for six specific patients show a pulsatile pattern. Maximum displacements are always less than 4 mm. The ratio fluctuations of endovascular cavity volume and vascular inner wall surface area, which were employed to depict cardiac deformation, are always less than 20%. According to CFD simulations based on deformed VMAs, WSS has a larger coefficient of variation (COV) than velocity and pressure. Except for one patient's WSS, the COVs of different hemodynamic parameters obtained from simulation results are always less than 10%. Based on 4D-CTA images, we confirmed that cardiovascular circulation has a periodic impact on the morphologic characteristics of VMAs. A wave that has extended throughout the studied region is observed. It has a dominant influence on the displacement of VMAs. According to CFD results, the influence of the VMAs' deformation and displacement on different hemodynamic parameters is distinct. The variance in WSS is more prominent compared to pressure and velocity. On most occasions, the influence of the VMAs' periodic deformation and displacement on simulation results is insignificant. However, the variant simulation results induced by deforming VMAs cannot be simply ignored. [ABSTRACT FROM AUTHOR]

Purpose: Many epidemiological studies on unruptured cerebral aneurysms have reported that the larger the aneurysm, the higher the risk of rupture. However, many ruptured aneurysms are not large. Electrocardiography (ECG)-gated 3D-computed tomography angiography (4D-CTA) was used to detect pulsation in unruptured cerebral aneurysms. The differences in the clinical course of patients in whom pulsation was or was not detected were then evaluated. Methods: Forty-two patients with 62 unruptured cystiform cerebral aneurysms who underwent 4D-CTA and follow-up 3D-CTA more than 120 days later were studied. The tube voltage, tube current, and rotation speed were 120 kV, 270 mA, and 0.35 s/rot., respectively. ECG-gated reconstruction was performed, with the cardiac cycle divided into 20 phases. Patients with heart rates higher than 80 bpm were excluded, so 37 patients with 56 aneurysms were analyzed. Results: Pulsation was detected in 20 of the 56 unruptured aneurysms. Of these 20 aneurysms, 6 showed a change in shape at the time of follow-up. Of the 36 aneurysms in which pulsation was not detected, 2 showed a change in shape at follow-up. There was no significant difference in the follow-up interval between the two groups. The aneurysms in which pulsation was detected were significantly more likely to show a change in shape ( P = 0.04), with a higher odds ratio of 7.286. Conclusion: Unruptured aneurysms in which pulsation was detected by 4D-CTA were more likely to show a change in shape at follow-up, suggesting that 4D-CTA may be useful for identifying aneurysms with a higher risk of rupture. [ABSTRACT FROM AUTHOR]

In time-resolved CT angiography (4D-CTA), it is of substantial merit to detect the veins and sinuses of the whole brain with the simultaneous demonstration of the natural drain­age flow in order to find occlusion or stenosis of the dural sinuses with collateral pathways. As preoperative information for patients with brain tumors, it is important to detect feeding arteries, incidentally found aneurysms or other vascular lesions, and to detect patency of the dural sinuses and the important cortical veins, whether they are compressed by tumors or not. On the other hand, cerebral venous thrombosis (CVT) may occur in patients due to various causes, which has not been unusual in recent years. For patients with acute symptomatic or chronic non-symptomatic CVT, identification of dural sinus occlusion (DSO) or dural sinus stenosis (DSS) and compensatory col­lateral pathways is necessary for suitable thrombolytic therapy or careful investigation to avoid further CVT. This study reviews our experiences in 116 cases of 4D-CTA for 90 patients with brain tumors and 26 other patients including 11 with arteriovenous malformation, and four with acute CVT and other conditions. 4D-CTA presented DSO/DSS with compensatory venous collateral path­ways, which was helpful to detect the severity of the venous abnormality, and see whether it was compressed by brain tumors, or due to other causes in patients with symptomatic or non-sympto­matic CVT. 4D-CTA is a useful non-invasive diagnostic tool to detect cerebral venous abnormalities as an alternative to DSA. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate the usefulness of CT digital subtraction angiography (CTDSA) by using 320-detector row CT in the diagnosis and classification of cerebral dural arteriovenous fistula (dAVF) and comparing it with DSA as the standard reference. Methods: A total of 29 CTDSA/DSA from 25 patients with dAVF were retrospectively evaluated by two neuroradiologists. The presence, Cognard classification, and feeding arteries of dAVFs on CTDSA were assessed according to DSA. Results: DSA depicted 33 dAVFs in 28 cases. By consensus reading, CTDSA correctly detected 32 dAVFs in 27 cases and properly graded 31 lesions. The intermodality agreement for the presence and classification of dAVFs was excellent (kappa = 0.955 and 0.921, respectively). CTDSA detected 77 of 109 feeding arteries (70.6 %) in 25 cases. The intermodality agreement for the feeding arteries was good (kappa = 0.713). Conclusion: Although CTDSA is limited in temporal and spatial resolution in comparison with DSA, it is an effective non-invasive tool for the detection and classification of dAVF. [ABSTRACT FROM AUTHOR]

• Patients with intracranial anterior circulation arterial occlusions were detected with a sensitivity of 95% and a specificity of 92%. • Deep learning accurately detects intracranial anterior circulation arterial occlusions in high-resolution 4D-CTA. • The first deep learning approach to automatically detect intracranial anterior circulation artery occlusions in 4D-CTA of acute ischemic stroke at image-level is presented. • Normalized Time-to-Signal maps show an intuitive representation of the arrival time in the brain. The triage of acute stroke patients is increasingly dependent on four-dimensional CTA (4D-CTA) imaging. In this work, we present a convolutional neural network (CNN) for image-level detection of intracranial anterior circulation artery occlusions in 4D-CTA. The method uses a normalized 3D time-to-signal (TTS) representation of the input image, which is sensitive to differences in the global arrival times caused by the potential presence of vascular pathologies. The TTS map presents the time within the cranial cavity at which the signal reaches a percentage of the maximum signal intensity, corrected for the baseline intensity. The method was trained and validated on (n = 214) patient images and tested on an independent set of (n = 279) patient images. This test set included all consecutive suspected-stroke patients admitted to our hospital in 2018. The accuracy, sensitivity, and specificity were 92%, 95%, and 92%. The area under the receiver operating characteristics curve was 0.98 (95% CI: 0.95- 0.99). These results show the feasibility of automated stroke triage in 4D-CTA. [ABSTRACT FROM AUTHOR]

Time resolved whole brain CT angiography (4D-CTA) is a novel imaging technology providing information regarding blood flow. One of the factors that influence the diagnostic value of this examination is the temporal resolution, which is affected by the gantry rotation speed during acquisition and the reconstruction interval during post-processing. Post-processing determines the time spacing between two reconstructed volumes and, unlike rotation speed, does not affect radiation burden. The data sets of six patients who underwent a cranial 4D-CTA were used for this study. Raw data was acquired using a 320-slice scanner with a rotation speed of 2 Hz. The arterial to venous passage of an intravenous contrast bolus was captured during a 15 s continuous scan. The raw data was reconstructed using four different reconstruction-intervals: 0.2, 0.3, 0.5 and 1.0 s. The results were rated by two observers using a standardized score sheet. The appearance of each lesion was rated correctly in all readings. Scoring for quality of temporal resolution revealed a stepwise improvement from the 1.0 s interval to the 0.3 s interval, while no discernable improvement was noted between the 0.3 s and 0.2 s interval. An increase in temporal resolution may improve the diagnostic quality of cranial 4D-CTA. Using a rotation speed of 0.5 s, the optimal reconstruction interval appears to be 0.3 s, beyond which, changes can no longer be discerned. [ABSTRACT FROM AUTHOR]

Correct identification of symptomatic high-grade internal carotid artery stenosis from low-grade or total chronic occlusion is critical for patient selection for urgent carotid endarterectomy. Carotid pseudo-occlusion is a flow-related artifact on noninvasive imaging that can lead to an incorrect diagnosis of total internal carotid artery occlusion, thereby denying an eligible patient for appropriate surgical treatment. We present an 82-year-old man with a symptomatic critical internal carotid artery, which was detected on time-resolved 4-dimensional computed-tomography angiography, whereas single-phase computed-tomography angiography, magnetic resonance angiography, and Doppler ultrasonography suggested apparent occlusion. To our understanding, the use of 4-dimensional computed-tomography angiography to identify carotid pseudo-occlusion has not been previously reported. [ABSTRACT FROM AUTHOR]

Background In case of carotid artery occlusion, the risk and extent of ischemic cerebral damage are highly dependent on the pathways of collateral flow including the anatomy of the circle of Willis. In this report, cases are presented to illustrate that 4-dimensional computed tomography angiography (4D-CTA) can be considered as a noninvasive alternative to digital subtraction angiography for the evaluation of circle of Willis collateral flow. Case Description Five patients with unilateral internal carotid artery (ICA) occlusion underwent 4D-CTA for the evaluation of intracranial hemodynamics. Next to a visual evaluation of 4D-CTA, temporal information was visualized using a normalized color scale on the cerebral vasculature, which enabled quantification of the contrast bolus arrival time. In these patients, 4D-CTA demonstrated dominant middle cerebral artery blood supply on the side of ICA occlusion originating from either the contralateral ICA or posterior circulation via the communicating arteries. Conclusions Temporal dynamics of collateral flow in the circle of Willis can be depicted with 4D-CTA in patients with a unilateral carotid artery occlusion. [ABSTRACT FROM AUTHOR]

Background Spontaneous intracerebral hemorrhage may arise from underlying abnormalities, including aneurysms. Computed tomography angiography (CTA) is widely used for the detection of possible underlying causes, which is important because it may have immediate therapeutic consequences. In addition, CTA is used to detect the so-called spot sign, indicating active hemorrhage, which carries a worse prognosis. However, CTA is a snapshot in time. Four-dimensional (4D) CTA is a dynamic type of imaging and has emerged as a valuable imaging technique for different neurovascular disorders. Case Description Two patients with intracerebral hemorrhage both showed an assumed spot sign on CTA, suggesting active hemorrhage. Additional 4D-CTA showed true active hemorrhage in one patient and a distal intracranial aneurysm in the other. This aneurysm was initially falsely interpreted as a spot sign on conventional CTA. Conclusions Our case findings show how 4D-CTA can discern active bleeding from aneurysmal hemorrhage in cases with hemorrhagic stroke. This finding proves the additional value of this relatively new technique, because the detected underlying disorders have different therapeutic consequences in the acute setting. [ABSTRACT FROM AUTHOR]

A 61-year-old woman suffered a pronounced subarachnoid hemorrhage. Conventional computed tomography angiography (CTA) showed no enhancement of the intracranial vasculature, whereas there was normal contrast enhancement of bilateral external carotid artery branches. Subsequent four-dimensional computed tomography angiography (4D-CTA) demonstrated active contrast leakage out of a ruptured basilar tip aneurysm, whereas there was no enhancement of the anterior circulation at any time point, consistent with intracranial anterior circulation arrest. This case illustrates that 4D-CTA is superior to conventional CTA for the evaluation of intracranial flow dynamics and delayed intracranial vascular contrast filling. [ABSTRACT FROM AUTHOR]

The rupture of dural arteriovenous fistula (DAVF) is a serious complication endangering the lives of patients. It is difficult to treat such ruptured DAVF with large intracranial hematoma since lacking of early diagnostic methods. Meanwhile, there was no consensus of how to surgically treat these patients in early stage. In this study, we tried to use 4D-CTA to diagnose DAVF and guide surgical treatment. Based on the result of 4D-CTA, we attempted to eliminate DAVF at the same time we removed hematoma. The result was encouraging. 7 patients with ruptured DAVF presented as large spontaneous intracranial hemorrhage were included in this research between May, 2010 and August, 2012 in our hospital. 4D-CTA was performed in all cases. All results of 4D-CTA inspections were studied by both neurosurgeon and neuroradiologist. The therapeutic options were evaluated based on the clinical and angiographic results. All fistulas of seven patients were eliminated at the same time the hematoma being evacuated. 4D-CTA was sufficient for detecting and recognizing basic vessel angioarchitecture of DAVF to guide surgical treatment. Main arterial supplies, fistula location and CVDs found during surgery are consistent with the results 4D-CTA. All seven cases achieved completely fistula occlusion in operation without new neurological complication. We favor one stage surgical treatment for ruptured DAVF with large intracranial hemorrhage. 4D-CTA plays an important role in preoperative emergent inspection for its safety, rapidity and accuracy. However, it still needs further and larger investigations to optimize such treatment methods and to find out other potential risks.

Background and Purpose: Digital subtraction angiography (DSA) is the current imaging 'gold standard' for diagnosis of arteriovenous malformation (AVM). The latest technique, four-dimensional computed tomography (4D-CT), offers a new diagnostic method for assessing AVM in real time. This study used a 320-detector-row CT scanner to compare the value of 4D-CT angiography (4D-CTA) with DSA in the diagnosis of untreated AVM patients., Methods: Seventeen patients diagnosed with AVM by DSA were included in this study. Two independent readers blind to the results of all examinations evaluated the findings of DSA and 4D-CTA in each patient. All results were then documented using a standardized scoring sheet., Results: The results of 4D-CTA in all 17 cases were fully consistent with DSA for AVM location, size and vascular structures. 4D-CTA had the same ability as DSA to distinguish the main feeding arteries in all cases, although in the identification of smaller and specific arterial branches, there were discrepancies in one patient between the two methods. In the diagnosis of draining veins, however, 4D-CTA successfully displayed all of the vessels found by DSA., Conclusion: 4D-CTA was able to detect all AVM lesions, including their size, location, feeding arteries and draining veins. Thus, 4D-CTA has a value similar to that of DSA in the diagnosis and assessment of AVM., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The introduction of computed tomography (CT) scanning in the 1970s revolutionized the way clinicians could diagnose and treat stroke. Subsequent advances in CT technology significantly reduced radiation dose, reduced metallic artifact, and achieved speeds that enable dynamic functional studies. The recent addition of whole-brain volumetric CT perfusion technology has given clinicians a powerful tool to assess parenchymal perfusion parameters as well as visualize dynamic changes in blood vessel flow throughout the brain during a single cardiac cycle. This article reviews clinical applications of volumetric multimodal CT that helped to guide and manage care., (Copyright © 2014 Elsevier Inc. All rights reserved.)