Evert-Jan Vonken

Measuring the arterial input function with gradient echo sequences.

The measurement of the arterial input function by use of gradient echo sequences was investigated by in vitro and in vivo experiments. First, calibration curves representing the influence of the concentration of Gd‐DTPA on both the phase and the amplitude of the MR signal were measured in human blood by means of a slow‐infusion experiment. The results showed a linear increase in the phase velocity and a quadratic increase in ΔR  *2 as a function of the Gd‐DTPA concentration. Next, the resultant calibration curves were incorporated in a partial volume correction algorithm for the arterial input function determination. The algorithm was tested in a phantom experiment and was found to substantially improve the accuracy of the concentration measurement. Finally, the reproducibility of the arterial input function measurement was estimated in 16 patients by considering the input function of the left and the right sides as replicate measurements. This in vivo study showed that the reproducibility of the arterial input function determination using gradient echo sequences is improved by employing a partial volume correction algorithm based on the calibration curve for the contrast agent used. Magn Reson Med 49:1067–1076, 2003.

Pulmonary Vein Ostium Geometry Analysis by Magnetic Resonance Angiography

Background—During a catheter ablation procedure for selective electrical isolation of pulmonary vein (PV) ostia, the size of these ostia is usually estimated using fluoroscopic angiography. This measurement may be misleading, however, because only the projected supero/inferior ostium diameters can be measured. In this study, we analyzed 3-dimensional magnetic resonance angiographic (MRA) images to measure the minimal and maximal cross-sectional diameter of PV ostia in relation to the diameter that would have been projected on fluoroscopic angiograms during a catheter ablation procedure. Methods and Results—In 42 patients with idiopathic atrial fibrillation who were scheduled for selective electrical isolation of PV ostia, the minimal and maximal diameters of these ostia were measured from 3-dimensional MRA images. Thereafter, these images were oriented in a 45° right or left anterior oblique direction and the projected diameter of the PV ostia were measured again. The average ratio between maximal and minimal diameter was 1.5±0.4 for the left and 1.2±0.1 for the right pulmonary vein ostia. Because of the orientation and oval shape of especially the left pulmonary vein ostia, their minimal diameters were significantly smaller than the projected diameters. Conclusion—Pulmonary vein ostia, especially those at the left, are oval with the short axis oriented approximately in the antero/posterior direction. Consequently, PV ostia may sometimes be very narrow despite a rather normal appearance on angiographic images obtained during a catheter ablation procedure.

Correcting partial volume artifacts of the arterial input function in quantitative cerebral perfusion MRI

To quantify cerebral perfusion with dynamic susceptibility contrast MRI (DSC‐MRI), one needs to measure the arterial input function (AIF). Conventionally, one derives the contrast concentration from the DSC sequence by monitoring changes in either the amplitude or the phase signal on the assumption that the signal arises completely from blood. In practice, partial volume artifacts are inevitable because a compromise has to be reached between the temporal and spatial resolution of the DSC acquisition. As the concentration of the contrast agent increases, the vector of the complex blood signal follows a spiral‐like trajectory. In the case of a partial‐volume voxel, the spiral is located around the static contribution of the surrounding tissue. If the static contribution of the background tissue is disregarded, estimations of the contrast concentration will be incorrect. By optimizing the correspondence between phase information and amplitude information one can estimate the origin of the spiral, and thereupon correct for partial volume artifacts. This correction is shown to be accurate at low spatial resolutions for phantom data and to improve the AIF determination in a clinical example. Magn Reson Med 45:477–485, 2001.

Simultaneous quantitative cerebral perfusion and Gd-DTPA extravasation measurement with dual-echo dynamic susceptibility contrast MRI.

Quantification of cerebral perfusion using dynamic susceptibility contrast MRI generally relies on the assumption of an intact blood–brain barrier. The present study proposes a method to correct the tissue response function that does not require this assumption, thus, allowing perfusion studies in, for example, high‐grade brain tumors. The correction for contrast extravasation in the tissue during the bolus passage is based on a two‐compartment kinetic model. The method separates the intravascular hemodynamic response and the extravascular component and returns the corrected tissue response function for perfusion quantification as well as the extravasation rate constant of the vasculature. Results of simulation experiments with different degrees of contrast extravasation are presented. The clinical potential is illustrated by determination of the perfusion and extravasation of a glioblastoma multiforme. The correction scheme proves to be fast and reliable even in cases of low signal‐to‐noise ratio. It is applicable whether extravasation occurs or not. When extravasation is present, application of the proposed method is mandatory for accurate cerebral blood volume measurements. Magn Reson Med 43:820–827, 2000.

Maximum likelihood estimation of cerebral blood flow in dynamic susceptibility contrast MRI.

For quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast magnetic resonance imaging (DSC‐MRI), knowledge of the tissue response function is necessary. To obtain this, the tissue contrast passage measurement must be corrected for the arterial input. This study proposes an iterative maximum likelihood expectation maximization (ML‐EM) algorithm for this correction, which takes into account the noise in T2‐ or T*2‐weighted image sequences. The ML‐EM algorithm does not assume a priori knowledge of the shape of the response function; it automatically corrects for arrival time offsets and inherently yields positive response values. The results on synthetic image sequences are presented, for which the recovered flow values and the response functions are in good agreement with their expectation values. The method is illustrated by calculating the gray and white matter flow in a clinical example. Magn Reson Med 41:343–350, 1999.

Automatic Image-Driven Segmentation of the Ventricles in Cardiac Cine MRI

To propose and to evaluate a novel method for the automatic segmentation of the hearts two ventricles from dynamic (“cine”) short‐axis “steady state free precession” (SSFP) MR images. This segmentation task is of significant clinical importance. Previously published automated methods have various disadvantages for routine clinical use.

Contrast agent concentration measurements affecting quantification of bolus-tracking perfusion MRI

Measurement of the concentration of the contrast agent using dynamic susceptibility contrast MRI relies on field inhomogeneities caused by the presence of the paramagnetic agent. The usual method for calculation of the concentration from dynamic T  2* ‐weighted images is based on two key assumptions: 1) a linear relation between the change in R  2* and the contrast agent concentration, and 2) a negligible effect on the MR signal due to concurrent T1 changes. In this study the effect of inaccuracies in these two assumptions on perfusion measurements was investigated using simulations and in vivo data. The results of the simulations provide a quantitative characterization of the magnitude of these effects for various experimental conditions (e.g., when a 1‐sec TR is used with TE = 20 ms, the T1 effects can introduce up to 40% cerebral blood flow underestimation depending on the flip angle). These findings can be used as a guide to estimate the errors in specific practical implementaions, as well as to optimize the sequence parameters to minimize their effect. In summary, this study shows that the arterial input function measurement should be corrected for nonlinear R  2* effects and that care should be taken in the study design to avoid introducing significant T1 effects in perfusion quantification. Magn Reson Med 58:544–553, 2007.

Eligibility for percutaneous renal denervation: the importance of a systematic screening.

Objective: Percutaneous renal denervation (pRDN) is a new and promising therapy for resistant hypertension. Among patients suspected of having resistant hypertension, the actual presence of this condition needs to be well established; pseudoresistant hypertension and significant white-coat effect (WCE) should be excluded. This analysis presents the results of a standardized screening programme for patients referred for pRDN. Methods: All patients referred to our centre for pRDN underwent a standardized stepwise screening and were subsequently discussed in a multidisciplinary team. The screening included a 24-h ambulatory blood pressure measurement (ABPM), collection of plasma, urine and saliva, and finally imaging of the renal arteries. Results: From August 2010 till October 2012, 181 patients were referred for pRDN. Mean blood pressure (BP) was 182/100 mmHg, and median use was three antihypertensives. Ultimately, 121 patients (67%) were excluded from pRDN. Main reasons for exclusion were BP-related. Twenty-three patients (19%) had an office SBP less than 160 mmHg and 26 patients (22%) showed a WCE. Fourteen patients (12%) had a so far undetected underlying cause of hypertension, the majority being primary aldosteronism (n = 11). Nine patients had an ineligible renal anatomy. Conclusion: A high percentage of patients were excluded from treatment with pRDN due to secondary causes of hypertension, WCE or a BP below the currently advised thresholds. Treatment of these excluded patients would lead to inappropriate use of pRDN, leading most likely to little benefit for the patients and a burden to healthcare. Therefore, it is recommended to use a standardized screening before treatment with pRDN.

Timing-Invariant Imaging of Collateral Vessels in Acute Ischemic Stroke

Background and Purpose— Although collateral vessels have been shown to be an important prognostic factor in acute ischemic stroke, patients with lack of collaterals on standard imaging techniques may still have good clinical outcome. We postulate that in these cases collateral vessels are present though not visible on standard imaging techniques that are based on a single time frame. Methods— This study included 40 consecutive patients with acute ischemic stroke with a large-vessel occlusion. Standard computed tomography angiography (CTA, single time frame) and CT perfusion (multiple time frames) were obtained at admission and timing-invariant (TI)-CTA was created from the CT perfusion data. Clinical outcome data (modified Rankin Scale) were assessed at 3-month follow-up. Four experienced observers independently assessed collateral status twice on both standard CTA and TI-CTA in an independent, blinded, randomized manner. Collateral status was rated as good if ≥50% and poor if <50% of collaterals were present compared with the contralateral hemisphere. Results— Collateral status was rated higher on TI-CTA (good in 84%) compared with standard CTA (good in 49%; P<0.001). Thirty-one percent of patients with poor collateral status on standard CTA still had good clinical outcome. All of those patients, however, showed good collaterals on TI-CTA. All cases with poor collateral status rated on TI-CTA had poor clinical outcome. Conclusions— Collateral vessels may not always be visible on standard single time-frame CTA because of delayed contrast arrival. Future prognostic studies in acute stroke should consider delay-insensitive techniques, such as TI-CTA, instead of standard single time-frame imaging, such as standard CTA.

TIPS bilateral noise reduction in 4D CT perfusion scans produces high-quality cerebral blood flow maps

Cerebral computed tomography perfusion (CTP) scans are acquired to detect areas of abnormal perfusion in patients with cerebrovascular diseases. These 4D CTP scans consist of multiple sequential 3D CT scans over time. Therefore, to reduce radiation exposure to the patient, the amount of x-ray radiation that can be used per sequential scan is limited, which results in a high level of noise. To detect areas of abnormal perfusion, perfusion parameters are derived from the CTP data, such as the cerebral blood flow (CBF). Algorithms to determine perfusion parameters, especially singular value decomposition, are very sensitive to noise. Therefore, noise reduction is an important preprocessing step for CTP analysis. In this paper, we propose a time-intensity profile similarity (TIPS) bilateral filter to reduce noise in 4D CTP scans, while preserving the time-intensity profiles (fourth dimension) that are essential for determining the perfusion parameters. The proposed TIPS bilateral filter is compared to standard Gaussian filtering, and 4D and 3D (applied separately to each sequential scan) bilateral filtering on both phantom and patient data. Results on the phantom data show that the TIPS bilateral filter is best able to approach the ground truth (noise-free phantom), compared to the other filtering methods (lowest root mean square error). An observer study is performed using CBF maps derived from fifteen CTP scans of acute stroke patients filtered with standard Gaussian, 3D, 4D and TIPS bilateral filtering. These CBF maps were blindly presented to two observers that indicated which map they preferred for (1) gray/white matter differentiation, (2) detectability of infarcted area and (3) overall image quality. Based on these results, the TIPS bilateral filter ranked best and its CBF maps were scored to have the best overall image quality in 100% of the cases by both observers. Furthermore, quantitative CBF and cerebral blood volume values in both the phantom and the patient data showed that the TIPS bilateral filter resulted in realistic mean values with a smaller standard deviation than the other evaluated filters and higher contrast-to-noise ratios. Therefore, applying the proposed TIPS bilateral filtering method to 4D CTP data produces higher quality CBF maps than applying the standard Gaussian, 3D bilateral or 4D bilateral filter. Furthermore, the TIPS bilateral filter is computationally faster than both the 3D and 4D bilateral filters.