Author Correction: White Matter and Gray Matter Segmentation in 4D Computed Tomography.

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Observer variability of reference tissue selection for relativecerebral blood volume measurements in glioma patients.

OBJECTIVES: To assess observer variability of different reference tissues used for relative CBV (rCBV) measurements in DSC-MRI of glioma patients. METHODS: In this retrospective study, three observers measured rCBV in DSC-MR images of 44 glioma patients on two occasions. rCBV is calculated by the CBV in the tumour hotspot/the CBV of a reference tissue at the contralateral side for normalization. One observer annotated the tumour hotspot that was kept constant for all measurements. All observers annotated eight reference tissues of normal white and grey matter. Observer variability was evaluated using the intraclass correlation coefficient (ICC), coefficient of variation (CV) and Bland-Altman analyses. RESULTS: For intra-observer, the ICC ranged from 0.50-0.97 (fair-excellent) for all reference tissues. The CV ranged from 5.1-22.1 % for all reference tissues and observers. For inter-observer, the ICC for all pairwise observer combinations ranged from 0.44-0.92 (poor-excellent). The CV ranged from 8.1-31.1 %. Centrum semiovale was the only reference tissue that showed excellent intra- and inter-observer agreement (ICC>0.85) and lowest CVs (<12.5 %). Bland-Altman analyses showed that mean differences for centrum semiovale were close to zero. CONCLUSION: Selecting contralateral centrum semiovale as reference tissue for rCBV provides the lowest observer variability. KEY POINTS: • Reference tissue selection for rCBV measurements adds variability to rCBV measurements. • rCBV measurements vary depending on the choice of reference tissue. • Observer variability of reference tissue selection varies between poor and excellent. • Centrum semiovale as reference tissue for rCBV provides the lowest observer variability.

White Matter and Gray Matter Segmentation in 4D Computed Tomography.

Modern Computed Tomography (CT) scanners are capable of acquiring contrast dynamics of the whole brain, adding functional to anatomical information. Soft tissue segmentation is important for subsequent applications such as tissue dependent perfusion analysis and automated detection and quantification of cerebral pathology. In this work a method is presented to automatically segment white matter (WM) and gray matter (GM) in contrast- enhanced 4D CT images of the brain. The method starts with intracranial segmentation via atlas registration, followed by a refinement using a geodesic active contour with dominating advection term steered by image gradient information, from a 3D temporal average image optimally weighted according to the exposures of the individual time points of the 4D CT acquisition. Next, three groups of voxel features are extracted: intensity, contextual, and temporal. These are used to segment WM and GM with a support vector machine. Performance was assessed using cross validation in a leave-one-patient-out manner on 22 patients. Dice coefficients were 0.81 ± 0.04 and 0.79 ± 0.05, 95% Hausdorff distances were 3.86 ± 1.43 and 3.07 ± 1.72 mm, for WM and GM, respectively. Thus, WM and GM segmentation is feasible in 4D CT with good accuracy.

Interleaving cerebral CT perfusion with neck CT angiography. Part II: clinical implementation and image quality.

OBJECTIVES: Feasibility evaluation of the One-Step Stroke Protocol, which is an interleaved cerebral computed tomography perfusion (CTP) and neck volumetric computed tomography angiography (vCTA) scanning technique using wide-detector computed tomography, and to assess the image quality of vCTA. METHODS: Twenty patients with suspicion of acute ischaemic stroke were prospectively scanned and evaluated with a head and neck CTA and with the One-Step Stroke Protocol. Arterial enhancement and contrast-to-noise ratio (CNR) in the carotid arteries was assessed. Three observers scored artefacts and image quality of the cervical arteries. The total z-coverage was evaluated. RESULTS: Mean enhancement in the carotid bifurcation was rated higher in the vCTA (595 ± 164 HU) than CTA (441 ± 117 HU). CNR was rated higher in vCTA. Image quality scores showed no significant difference in the region of the carotid bifurcation between vCTA and CTA. Lower neck image quality scores were slightly lower for vCTA due to artefacts, although not rated as diagnostically relevant. In ten patients, the origin of the left common carotid artery was missed by 1.6 ± 0.8 cm. Mean patient height was 1.8 ± 0.09 m. Carotid bifurcation and origin of vertebral arteries were covered in all patients. CONCLUSIONS: The One-Step Stroke Protocol is feasible with good diagnostic image quality of vCTA, although full z-coverage is limited in tall patients. KEY POINTS: • Interleaving cerebral CTP with neck CTA (One-Step Stroke Protocol) is feasible • Diagnostic quality of One-Step Stroke Protocol neck CTA is similar to conventional CTA • One-Step Stroke Protocol neck CTA suffers from streak artefacts in the lower neck • A limitation of One-Step Stroke Protocol CTA is lack of coverage in tall patients • Precise planning of One-Step Stroke Protocol neck CTA is necessary in tall patients.

Interleaving cerebral CT perfusion with neck CT angiography part I. Proof of concept and accuracy of cerebral perfusion values.

OBJECTIVES: We present a novel One-Step-Stroke protocol for wide-detector CT scanners that interleaves cerebral CTP with volumetric neck CTA (vCTA). We evaluate whether the resulting time gap in CTP affects the accuracy of CTP values. METHODS: Cerebral CTP maps were retrospectively obtained from 20 patients with suspicion of acute ischemic stroke and served as the reference standard. To simulate a 4 s gap for interleaving CTP with vCTA, we eliminated one acquisition at various time points of CTP starting from the bolus-arrival-time(BAT). Optimal timing of the vCTA was evaluated. At the time point with least errors, we evaluated elimination of a second time point (6 s gap). RESULTS: Mean absolute percentage errors of all perfusion values remained below 10 % in all patients when eliminating any one time point in the CTP sequence starting from the BAT. Acquiring the vCTA 2 s after reaching a threshold of 70HU resulted in the lowest errors (mean <3.0 %). Eliminating a second time point still resulted in mean errors <3.5 %. CBF/CBV showed no significant differences in perfusion values except MTT. However, the percentage errors were always below 10 % compared to the original protocol. CONCLUSION: Interleaving cerebral CTP with neck CTA is feasible with minor effects on the perfusion values. KEY POINTS: • Removing a single CTP acquisition has minor effects on calculated perfusion values • Calculated perfusion values errors depend on timing of skipping a CTP acquisition • Qualitative evaluation of CTP was not influenced by removing two time points • Neck CTA is optimally timed in the upslope of arterial enhancement.

Quantitative Dose Dependency Analysis of Whole-Brain CT Perfusion Imaging.

PURPOSE: To quantitatively assess whether decreasing total radiation dose of the image acquisition protocol has an effect on cerebral CT perfusion values in patients with acute stroke. MATERIALS AND METHODS: This retrospective study was approved by the institutional ethics committee, and informed consent was waived. Twenty consecutive patients with ischemic stroke who underwent CT perfusion imaging with a 320-detector row CT scanner were included. A standard acquisition protocol was used, which was started 5 seconds after injection of a contrast agent, with a scan at 200 mAs, followed after 4 seconds by 13 scans, one every 2 seconds, at 100 mAs, and then five scans, one every 5 seconds, at 75 mAs. The total examination had an average effective dose of 5.0 mSv. For each patient, a patient-specific digital perfusion phantom was constructed to simulate the same protocol at a lower total dose (0.5-5.0 mSv, with stepped doses of 0.5 mSv). The lowest setting for which the maximum mean difference remained within 5% of the reference standard (at 5.0 mSv) was marked as the optimal setting. At the optimal setting, Pearson correlation coefficients were calculated to assess correlations with the reference values, and paired t tests were performed to compare the means. RESULTS: At 2.5 mSv, the maximum mean differences in values from those of the reference standard were 4.5%, 5.0%, and 1.9%, for cerebral blood flow, cerebral blood volume, and mean transit time, respectively. Pearson correlation coefficients of perfusion values for white matter and gray matter were 0.864-0.917, and all differences were significant (P < .0001). Paired t tests showed no significant differences between the reference standard and optimal settings (P = .089-.923). CONCLUSION: The total dose of a clinical cerebral CT perfusion protocol can be lowered to 2.5 mSv, with only minor quantitative effects on perfusion values. Dose reduction beyond this point resulted in overestimation of perfusion values.

A 4D digital phantom for patient-specific simulation of brain CT perfusion protocols.

PURPOSE: Optimizing CT brain perfusion protocols is a challenge because of the complex interaction between image acquisition, calculation of perfusion data, and patient hemodynamics. Several digital phantoms have been developed to avoid unnecessary patient exposure or suboptimum choice of parameters. The authors expand this idea by using realistic noise patterns and measured tissue attenuation curves representing patient-specific hemodynamics. The purpose of this work is to validate that this approach can realistically simulate mean perfusion values and noise on perfusion data for individual patients. METHODS: The proposed 4D digital phantom consists of three major components: (1) a definition of the spatial structure of various brain tissues within the phantom, (2) measured tissue attenuation curves, and (3) measured noise patterns. Tissue attenuation curves were measured in patient data using regions of interest in gray matter and white matter. By assigning the tissue attenuation curves to the corresponding tissue curves within the phantom, patient-specific CTP acquisitions were retrospectively simulated. Noise patterns were acquired by repeatedly scanning an anthropomorphic skull phantom at various exposure settings. The authors selected 20 consecutive patients that were scanned for suspected ischemic stroke and constructed patient-specific 4D digital phantoms using the individual patients' hemodynamics. The perfusion maps of the patient data were compared with the digital phantom data. Agreement between phantom- and patient-derived data was determined for mean perfusion values and for standard deviation in de perfusion data using intraclass correlation coefficients (ICCs) and a linear fit. RESULTS: ICCs ranged between 0.92 and 0.99 for mean perfusion values. ICCs for the standard deviation in perfusion maps were between 0.86 and 0.93. Linear fitting yielded slope values between 0.90 and 1.06. CONCLUSIONS: A patient-specific 4D digital phantom allows for realistic simulation of mean values and standard deviation in perfusion data and makes it possible to retrospectively study how the interaction of patient hemodynamics and scan parameters affects CT perfusion values.

Hepatocellular carcinoma: perfusion quantification with dynamic contrast-enhanced MRI.

OBJECTIVE: The objective of our study was to report our initial experience with dynamic contrast-enhanced MRI (DCE-MRI) for perfusion quantification of hepatocellular carcinoma (HCC) and surrounding liver. SUBJECTS AND METHODS: DCE-MRI of the liver was prospectively performed on 31 patients with HCC (male-female ratio, 26:5; mean age, 61 years; age range, 41-83 years). A dynamic coronal 3D FLASH sequence was performed at 1.5 T before and after injection of gadolinium-based contrast agent with an average temporal resolution of 3.8 seconds. Regions of interest were drawn on the abdominal aorta, portal vein, liver parenchyma, and HCC lesions by two observers in consensus. Time-activity curves were analyzed using a dual-input single-compartment model. The following perfusion parameters were obtained: arterial flow, portal venous flow, arterial fraction, distribution volume, and mean transit time (MTT). RESULTS: Thirty-three HCCs (mean size, 3.9 cm; range, 1.1-12.6 cm) were evaluated in 26 patients. When compared with liver parenchyma, HCC showed significantly higher arterial hepatic blood flow and arterial fraction (p < 0.0001) and significantly lower distribution volume and portal venous hepatic blood flow (p < 0.0001-0.023), with no difference in MTT. Untreated HCCs (n = 16) had a higher arterial fraction and lower portal venous hepatic blood flow value than chemoembolized HCCs (n = 17, p < 0.04). CONCLUSION: DCE-MRI can be used to quantify perfusion metrics of HCC and liver parenchyma and to assess perfusion changes after HCC chemoembolization.