MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma.

BACKGROUND: In pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT). MATERIALS AND METHODS: Ten randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position. RESULTS: The median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from - 3.5 to 5.8 Gy for the pancreatic tail and - 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation. CONCLUSION: Inter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.

Gating and intrafraction drift correction on a 1.5 T MR-Linac: Clinical dosimetric benefits for upper abdominal tumors.

This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen.

Detection of Cardioembolic Sources With Nongated Cardiac Computed Tomography Angiography in Acute Stroke: Results From the ENCLOSE Study.

BACKGROUND: Identifying cardioembolic sources in patients with acute ischemic stroke is important for the choice of secondary prevention strategies. We prospectively investigated the yield of admission (spectral) nongated cardiac computed tomography angiography (CTA) to detect cardioembolic sources in stroke. METHODS: Participants of the ENCLOSE study (Improved Prediction of Recurrent Stroke and Detection of Small Volume Stroke) with transient ischemic attack or acute ischemic stroke with assessable nongated head-to-heart CTA at the University Medical Center Utrecht were included between June 2017 and March 2022. The presence of cardiac thrombus on cardiac CTA was based on a Likert scale and dichotomized into certainly or probably absent versus possibly, probably, or certainly present. The diagnostic certainty of cardiac thrombus was evaluated again on spectral computed tomography reconstructions. The likelihood of a cardioembolic source was determined post hoc by an expert panel in patients with cardiac thrombus on CTA. Parametric and nonparametric tests were used to compare the outcome groups. RESULTS: Forty four (12%) of 370 included patients had a cardiac thrombus on admission CTA: 35 (9%) in the left atrial appendage and 14 (4%) in the left ventricle. Patients with cardiac thrombus had more severe strokes (median National Institutes of Health Stroke Scale score, 10 versus 4; P=0.006), had higher clot burden (median clot burden score, 9 versus 10; P=0.004), and underwent endovascular treatment more often (43% versus 20%; P<0.001) than patients without cardiac thrombus. Left atrial appendage thrombus was present in 28% and 6% of the patients with and without atrial fibrillation, respectively (P<0.001). The diagnostic certainty for left atrial appendage thrombus was higher for spectral iodine maps compared with the conventional CTA (P<0.001). The presence of cardiac thrombus on CTA increased the likelihood of a cardioembolic source according to the expert panel (P<0.001). CONCLUSIONS: Extending the stroke CTA to cover the heart increases the chance of detecting cardiac thrombi and helps to identify cardioembolic sources in the acute stage of ischemic stroke with more certainty. Spectral iodine maps provide additional value for detecting left atrial appendage thrombus. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04019483.

Probability maps classify ischemic stroke regions more accurately than CT perfusion summary maps.

OBJECTIVES: To compare single parameter thresholding with multivariable probabilistic classification of ischemic stroke regions in the analysis of computed tomography perfusion (CTP) parameter maps. METHODS: Patients were included from two multicenter trials and were divided into two groups based on their modified arterial occlusive lesion grade. CTP parameter maps were generated with three methods-a commercial method (ISP), block-circulant singular value decomposition (bSVD), and non-linear regression (NLR). Follow-up non-contrast CT defined the follow-up infarct region. Conventional thresholds for individual parameter maps were established with a receiver operating characteristic curve analysis. Probabilistic classification was carried out with a logistic regression model combining the available CTP parameters into a single probability. RESULTS: A total of 225 CTP data sets were included, divided into a group of 166 patients with successful recanalization and 59 with persistent occlusion. The precision and recall of the CTP parameters were lower individually than when combined into a probability. The median difference [interquartile range] in mL between the estimated and follow-up infarct volume was 29/23/23 [52/50/52] (ISP/bSVD/NLR) for conventional thresholding and was 4/6/11 [31/25/30] (ISP/bSVD/NLR) for the probabilistic classification. CONCLUSIONS: Multivariable probability maps outperform thresholded CTP parameter maps in estimating the infarct lesion as observed on follow-up non-contrast CT. A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions. KEY POINTS: • Combining CTP parameters with a logistic regression model increases the precision and recall in estimating ischemic stroke regions. • Volumes following from a probabilistic analysis predict follow-up infarct volumes better than volumes following from a threshold-based analysis. • A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions.

Fully automated quantification method (FQM) of coronary calcium in an anthropomorphic phantom.

OBJECTIVE: Coronary artery calcium (CAC) score is a strong predictor for future adverse cardiovascular events. Anthropomorphic phantoms are often used for CAC studies on computed tomography (CT) to allow for evaluation or variation of scanning or reconstruction parameters within or across scanners against a reference standard. This often results in large number of datasets. Manual assessment of these large datasets is time consuming and cumbersome. Therefore, this study aimed to develop and validate a fully automated, open-source quantification method (FQM) for coronary calcium in a standardized phantom. MATERIALS AND METHODS: A standard, commercially available anthropomorphic thorax phantom was used with an insert containing nine calcifications with different sizes and densities. To simulate two different patient sizes, an extension ring was used. Image data were acquired with four state-of-the-art CT systems using routine CAC scoring acquisition protocols. For interscan variability, each acquisition was repeated five times with small translations and/or rotations. Vendor-specific CAC scores (Agatston, volume, and mass) were calculated as reference scores using vendor-specific software. Both the international standard CAC quantification methods as well as vendor-specific adjustments were implemented in FQM. Reference and FQM scores were compared using Bland-Altman analysis, intraclass correlation coefficients, risk reclassifications, and Cohen's kappa. Also, robustness of FQM was assessed using varied acquisitions and reconstruction settings and validation on a dynamic phantom. Further, image quality metrics were implemented: noise power spectrum, task transfer function, and contrast- and signal-to-noise ratio among others. Results were validated using imQuest software. RESULTS: Three parameters in CAC scoring methods varied among the different vendor-specific software packages: the Hounsfield unit (HU) threshold, the minimum area used to designate a group of voxels as calcium, and the usage of isotropic voxels for the volume score. The FQM was in high agreement with vendor-specific scores and ICC's (median [95% CI]) were excellent (1.000 [0.999-1.000] to 1.000 [1.000-1.000]). An excellent interplatform reliability of κ = 0.969 and κ = 0.973 was found. TTF results gave a maximum deviation of 3.8% and NPS results were comparable to imQuest. CONCLUSIONS: We developed a fully automated, open-source, robust method to quantify CAC on CT scans in a commercially available phantom. Also, the automated algorithm contains image quality assessment for fast comparison of differences in acquisition and reconstruction parameters.

Non-contrast dual-energy CT virtual ischemia maps accurately estimate ischemic core size in large-vessel occlusive stroke.

Dual-energy CT (DECT) material decomposition techniques may better detect edema within cerebral infarcts than conventional non-contrast CT (NCCT). This study compared if Virtual Ischemia Maps (VIM) derived from non-contrast DECT of patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are superior to NCCT for ischemic core estimation, compared against reference-standard DWI-MRI. Only patients whose baseline ischemic core was most likely to remain stable on follow-up MRI were included, defined as those with excellent post-thrombectomy revascularization or no perfusion mismatch. Twenty-four consecutive AIS-LVO patients with baseline non-contrast DECT, CT perfusion (CTP), and DWI-MRI were analyzed. The primary outcome measure was agreement between volumetric manually segmented VIM, NCCT, and automatically segmented CTP estimates of the ischemic core relative to manually segmented DWI volumes. Volume agreement was assessed using Bland-Altman plots and comparison of CT to DWI volume ratios. DWI volumes were better approximated by VIM than NCCT (VIM/DWI ratio 0.68 ± 0.35 vs. NCCT/DWI ratio 0.34 ± 0.35; P < 0.001) or CTP (CTP/DWI ratio 0.45 ± 0.67; P < 0.001), and VIM best correlated with DWI (rVIM = 0.90; rNCCT = 0.75; rCTP = 0.77; P < 0.001). Bland-Altman analyses indicated significantly greater agreement between DWI and VIM than NCCT core volumes (mean bias 0.60 [95%AI 0.39-0.82] vs. 0.20 [95%AI 0.11-0.30]). We conclude that DECT VIM estimates the ischemic core in AIS-LVO patients more accurately than NCCT.

Virtual monochromatic dual-energy CT reconstructions improve detection of cerebral infarct in patients with suspicion of stroke.

PURPOSE: Early infarcts are hard to diagnose on non-contrast head CT. Dual-energy CT (DECT) may potentially increase infarct differentiation. The optimal DECT settings for differentiation were identified and evaluated. METHODS: One hundred and twenty-five consecutive patients who presented with suspected acute ischemic stroke (AIS) and underwent non-contrast DECT and subsequent DWI were retrospectively identified. The DWI was used as reference standard. First, virtual monochromatic images (VMI) of 25 patients were reconstructed from 40 to 140 keV and scored by two readers for acute infarct. Sensitivity, specificity, positive, and negative predictive values for infarct detection were compared and a subset of VMI energies were selected. Next, for a separate larger cohort of 100 suspected AIS patients, conventional non-contrast CT (NCT) and selected VMI were scored by two readers for the presence and location of infarct. The same statistics for infarct detection were calculated. Infarct location match was compared per vascular territory. Subgroup analyses were dichotomized by time from last-seen-well to CT imaging. RESULTS: A total of 80-90 keV VMI were marginally more sensitive (36.3-37.3%) than NCT (32.4%; p > 0.680), with marginally higher specificity (92.2-94.4 vs 91.1%; p > 0.509) for infarct detection. Location match was superior for VMI compared with NCT (28.7-27.4 vs 19.5%; p < 0.010). Within 4.5 h from last-seen-well, 80 keV VMI more accurately detected infarct (58.0 vs 54.0%) and localized infarcts (27.1 vs 11.9%; p = 0.004) than NCT, whereas after 4.5 h, 90 keV VMI was more accurate (69.3 vs 66.3%). CONCLUSION: Non-contrast 80-90 keV VMI best differentiates normal from infarcted brain parenchyma.

Improving the Quality of Cerebral Perfusion Maps With Monoenergetic Dual-Energy Computed Tomography Reconstructions.

OBJECTIVE: We compared 40- to 70-keV virtual monoenergetic to conventional computed tomography (CT) perfusion reconstructions with respect to quality of perfusion maps. METHODS: Conventional CT perfusion (CTP) images were acquired at 80 kVp in 25 patients, and 40- to 70-keV images were acquired with a dual-layer CT at 120 kVp in 25 patients. First, time-attenuation-curve contrast-to-noise ratio was assessed. Second, the perfusion maps of both groups were qualitatively analyzed by observers. Last, the monoenergetic reconstruction with the highest quality was compared with the clinical standard 80-kVp CTP acquisitions. RESULTS: Contrast-to-noise ratio was significantly better for 40 to 60 keV as compared with 70 keV and conventional images (P < 0.001). Visually, the difference between the blood volume maps among reconstructions was minimal. The 50-keV perfusion maps had the highest quality compared with the other monoenergetic and conventional maps (P < 0.002). CONCLUSIONS: The quality of 50-keV CTP images is superior to the quality of conventional 80- and 120-kVp images.

Image Quality of Virtual Monochromatic Reconstructions of Noncontrast CT on a Dual-Source CT Scanner in Adult Patients.

RATIONALE AND OBJECTIVES: To evaluate the image quality of virtual monochromatic images (VMI) reconstructed from dual-energy dual-source noncontrast head CT with different reconstruction kernels. MATERIALS AND METHODS: Twenty-five consecutive adult patients underwent noncontrast dual-energy CT. VMI were retrospectively reconstructed at 5-keV increments from 40 to 140 keV using quantitative and head kernels. CT-number, noise levels (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the gray and white matter and artifacts using the posterior fossa artifact index (PFAI) were evaluated. RESULTS: CT-number increased with decreasing VMI energy levels, and SD was lowest at 85 keV. SNR was maximized at 80 keV and 85 keV for the head and quantitative kernels, respectively. CNR was maximum at 40 keV; PFAI was lowest at 90 (head kernel) and 100 (quantitative kernel) keV. Optimal VMI image quality was significantly better than conventional CT. CONCLUSION: Optimal image quality of VMI energies can improve brain parenchymal image quality compared to conventional CT but are reconstruction kernel dependent and depend on indication for performing noncontrast CT.

Collateral Status in Ischemic Stroke: A Comparison of Computed Tomography Angiography, Computed Tomography Perfusion, and Digital Subtraction Angiography.

OBJECTIVE: To compare assessment of collaterals by single-phase computed tomography (CT) angiography (CTA) and CT perfusion-derived 3-phase CTA, multiphase CTA and temporal maximum-intensity projection (tMIP) images to digital subtraction angiography (DSA), and relate collateral assessments to clinical outcome in patients with acute ischemic stroke. METHODS: Consecutive acute ischemic stroke patients who underwent CT perfusion, CTA, and DSA before thrombectomy with occlusion of the internal carotid artery, the M1 or the M2 segments were included. Two observers assessed all CT images and one separate observer assessed DSA (reference standard) with static and dynamic (modified American Society of Interventional and Therapeutic Neuroradiology) collateral grading methods. Interobserver agreement and concordance were quantified with Cohen-weighted κ and concordance correlation coefficient, respectively. Imaging assessments were related to clinical outcome (modified Rankin Scale, ≤ 2). RESULTS: Interobserver agreement (n = 101) was 0.46 (tMIP), 0.58 (3-phase CTA), 0.67 (multiphase CTA), and 0.69 (single-phase CTA) for static assessments and 0.52 (3-phase CTA) and 0.54 (multiphase CTA) for dynamic assessments. Concordance correlation coefficient (n = 80) was 0.08 (3-phase CTA), 0.09 (single-phase CTA), and 0.23 (multiphase CTA) for static assessments and 0.10 (3-phase CTA) and 0.27 (multiphase CTA) for dynamic assessments. Higher static collateral scores on multiphase CTA (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7) and tMIP images (OR, 2.0; 95% CI, 1.1-3.4) were associated with modified Rankin Scale of 2 or less as were higher modified American Society of Interventional and Therapeutic Neuroradiology scores on 3-phase CTA (OR, 1.5; 95% CI, 1.1-2.2) and multiphase CTA (OR, 1.7; 95% CI, 1.1-2.6). CONCLUSIONS: Concordance between assessments on CT and DSA was poor. Collateral status evaluated on 3-phase CTA and multiphase CTA, but not on DSA, was associated with clinical outcome.

Early detection of small volume stroke and thromboembolic sources with computed tomography: Rationale and design of the ENCLOSE study.

BACKGROUND: Computed tomography is the most frequently used imaging modality in acute stroke imaging protocols. Detection of small volume infarcts in the brain and cardioembolic sources of stroke is difficult with current computed tomography protocols. Furthermore, the role of computed tomography findings to predict recurrent ischemic stroke is unclear. With ENCLOSE, we aim to improve (1) the detection of small volume infarcts with thin slice computed tomography perfusion (CTP) images and thromboembolic source with cardiac computed tomography techniques in the acute stage of ischemic stroke and (2) prediction of recurrent ischemic stroke with computed tomography-derived predictors.Methods/design: ENCLOSE is a prospective multicenter observational cohort study, which will be conducted in three Dutch stroke centers (ClinicalTrials.gov Identifier: NCT04019483). Patients (≥18 years) with suspected acute ischemic stroke who undergo computed tomography imaging within 9 h after symptom onset are eligible. Computed tomography imaging includes non-contrast CT, CTP, and computed tomography angiography (CTA) from base of the heart to the top of the brain. Dual-energy CT data will be acquired when possible, and thin-slice CTP reconstructions will be obtained in addition to standard 5 mm CTP data. CTP data will be processed with commercially available software and locally developed model-based methods. The post-processed thin-slice CTP images will be compared to the standard CTP images and to magnetic resonance diffusion-weighted imaging performed within 48 h after admission. Detection of cardioembolic sources of stroke will be evaluated on the CTA images. Recurrence will be evaluated 90 days and two years after the index event. The added value of imaging findings to prognostic models for recurrent ischemic stroke will be evaluated. CONCLUSION: The aim of ENCLOSE is to improve early detection of small volume stroke and thromboembolic sources and to improve prediction of recurrence in patients with acute ischemic stroke.

Computed Tomography Perfusion Data for Acute Ischemic Stroke Evaluation Using Rapid Software: Pitfalls of Automated Postprocessing.

Computed tomography perfusion (CTP) is increasingly used to determine treatment eligibility for acute ischemic stroke patients. Automated postprocessing of raw CTP data is routinely used, but it can fail. In reviewing 176 consecutive acute ischemic stroke patients, failures occurred in 20 patients (11%) during automated postprocessing by the RAPID software. Failures were caused by motion (n = 11, 73%), streak artifacts (n = 2, 13%), and poor contrast bolus arrival (n = 2, 13%). Stroke physicians should review CTP results with care before they are being integrated in their decision-making process.

Effect of prolonged acquisition intervals for CT-perfusion analysis methods in patients with ischemic stroke.

INTRODUCTION: The limited axial coverage of many computed tomography (CT) scanners poses a high risk on false negative findings in cerebral CT-perfusion (CTP) imaging. Axial coverage may be increased by moving the table back and forth during image acquisition. However, this method often increases the acquisition interval between CT frames, which may influence the CTP analysis. In this study, we evaluated the influence of different acquisition intervals on quantitative perfusion maps and infarct volumes by analyzing patient data with three CTP analysis methods. METHODS: CT-perfusion data from 25 patients with ischemic stroke were used for this study. The acquisition interval was synthetically reduced from 1 to 5 s before calculating perfusion values, which included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The color scaling of the perfusion was scaled such that the mean perfusion value had the same color-coding as the mean perfusion in the 1 s reference. Also, infarct core and penumbra volumes (summary map) were calculated using default thresholds of CBV and relative MTT (rMTT). The original, 1 s acquisition interval scan served as the reference standard. A commercial block-circulant singular value decomposition (bSVD) based method (ISP; Philips Healthcare), a non-commercial bSVD method, and a non-linear regression (NLR) model-based method were evaluated. RESULTS: Cerebral blood volume values generated with bSVD and NLR were not significantly different from the reference standard, while ISP showed significant differences for acquisition intervals of 3 and 4 s. MTT and CBF values generated with bSVD and ISP were significantly different for all acquisition intervals, whereas NLR did not show any significant differences. Calibrated perfusion maps were able to distinguish healthy from infarcted tissue up to an acquisition interval of 5 s for all methods. The infarct core volumes were significantly different for acquisition intervals of 2 (NLR) and 3 s (bSVD and ISP) or greater. For the penumbra volumes, NLR showed no significant differences, while bSVD and ISP showed significant differences for the 5 s interval and for all intervals, respectively. Visual inspection of the summary maps indicated minor differences between the reference standard and acquisition intervals of 4 s or less (ISP) and 5 s or less (bSVD and NLR). CONCLUSION: Altering the acquisition interval may introduce a bias in the perfusion parameters. Calibration of the visualization of the perfusion maps with increasing acquisition intervals allowed distinction between healthy and infarcted tissue. Infarct volumes based on relative MTT can be influenced by the acquisition interval, but visual inspection of the summary maps indicated minor differences between the reference standard and acquisition intervals up to 4 (ISP) and 5 s (bSVD and NLR). Taken together, axial coverage can be increased by prolonging the acquisition interval up to 5 s depending on the perfusion analysis.

Image quality of conventional images of dual-layer SPECTRAL CT: A phantom study.

PURPOSE: Spectral CT using a dual layer detector offers the possibility of retrospectively introducing spectral information to conventional CT images. In theory, the dual-layer technology should not come with a dose or image quality penalty for conventional images. In this study, we evaluate the influence of a dual-layer detector (IQon Spectral CT, Philips Healthcare) on the image quality of conventional CT images, by comparing these images with those of a conventional but otherwise technically comparable single-layer CT scanner (Brilliance iCT, Philips Healthcare), by means of phantom experiments. METHODS: For both CT scanners, conventional CT images were acquired using four adult scanning protocols: (a) body helical, (b) body axial, (c) head helical, and (d) head axial. A CATPHAN 600 phantom was scanned to conduct an assessment of image quality metrics at equivalent (CTDI) dose levels. Noise was characterized by means of noise power spectra (NPS) and standard deviation (SD) of a uniform region, and spatial resolution was evaluated with modulation transfer functions (MTF) of a tungsten wire. In addition, contrast-to-noise ratio (CNR), image uniformity, CT number linearity, slice thickness, slice spacing, and spatial linearity were measured and evaluated. Additional measurements of CNR, resolution and noise were performed in two larger phantoms. RESULTS: The resolution levels at 50%, 10%, and 5% MTF of the iCT and IQon showed small, but significant differences up to 0.25 lp/cm for body scans, and up to 0.2 lp/cm for head scans in favor of the IQon. The iCT and IQon showed perfect CT linearity for body scans, but for head scans both scanners showed an underestimation of the CT numbers of materials with a high opacity. Slice thickness was slightly overestimated for both scanners. Slice spacing was comparable and reconstructed correctly. In addition, spatial linearity was excellent for both scanners, with a maximum error of 0.11 mm. CNR was higher on the IQon compared to the iCT for both normal and larger phantoms with differences up to 0.51. Spatial resolution did not change with phantom size, but noise levels increased significantly. For head scans, IQon had a noise level that was significantly lower than the iCT, on the other hand IQon showed noise levels significantly higher than the iCT for body scans. Still, these differences were well within the specified range of performance of iCT scanners. CONCLUSIONS: At equivalent dose levels, this study showed similar quality of conventional images acquired on iCT and IQon for medium-sized phantoms and slightly degraded image quality for (very) large phantoms at lower tube voltages on the IQon. Accordingly, it may be concluded that the introduction of a dual-layer detector neither compromises image quality of conventional images nor increases radiation dose for normal-sized patients, and slightly degrades dose efficiency for large patients at 120 kVp and lower tube voltages.