Matthias J.P. van Osch

Recommended implementation of arterial spin-labeled Perfusion mri for clinical applications: A consensus of the ISMRM Perfusion Study group and the European consortium for ASL in dementia

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade‐offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo‐continuous labeling, background suppression, a segmented three‐dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102–116, 2015.

Probabilistic segmentation of white matter lesions in MR imaging.

A new method has been developed for fully automated segmentation of white matter lesions (WMLs) in cranial MR imaging. The algorithm uses information from T1-weighted (T1-w), inversion recovery (IR), proton density-weighted (PD), T2-weighted (T2-w) and fluid attenuation inversion recovery (FLAIR) scans. It is based on the K-Nearest Neighbor (KNN) classification technique that builds a feature space from voxel intensities and spatial information. The technique generates images representing the probability per voxel being part of a WML. By application of thresholds on these probability maps, binary segmentations can be obtained. ROC curves show that the segmentations achieve both high sensitivity and specificity. A similarity index (SI), overlap fraction (OF) and extra fraction (EF) are calculated for additional quantitative analysis of the result. The SI is also used for determination of the optimal probability threshold for generation of the binary segmentation. Using probabilistic equivalents of the SI, OF and EF, the probability maps can be evaluated directly, providing a powerful tool for comparison of different classification results. This method for automated WML segmentation reaches an accuracy that is comparable to methods for multiple sclerosis (MS) lesion segmentation and is suitable for detection of WMLs in large and longitudinal population studies.

Probabilistic segmentation of brain tissue in MR imaging.

A new method has been developed for probabilistic segmentation of five different types of brain structures: white matter, gray matter, cerebro-spinal fluid without ventricles, ventricles and white matter lesion in cranial MR imaging. The algorithm is based on information from T1-weighted (T1-w), inversion recovery (IR), proton density-weighted (PD), T2-weighted (T2-w) and fluid attenuation inversion recovery (FLAIR) scans. It uses the K-Nearest Neighbor classification technique that builds a feature space from spatial information and voxel intensities. The technique generates for each tissue type an image representing the probability per voxel being part of it. By application of thresholds on these probability maps, binary segmentations can be obtained. A similarity index (SI) and a probabilistic SI (PSI) were calculated for quantitative evaluation of the results. The influence of each image type on the performance was investigated by alternately leaving out one of the five scan types. This procedure showed that the incorporation of the T1-w, PD or T2-w did not significantly improve the segmentation results. Further investigation indicated that the combination of IR and FLAIR was optimal for segmentation of the five brain tissue types. Evaluation with respect to the gold standard showed that the SI-values for all tissues exceeded 0.8 and all PSI-values exceeded 0.7, implying an excellent agreement.

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.

Estimation of labeling efficiency in pseudocontinuous arterial spin labeling

Pseudocontinuous arterial spin labeling MRI is a new arterial spin labeling technique that has the potential of combining advantages of continuous arterial spin labeling and pulsed arterial spin labeling. However, unlike continuous arterial spin labeling, the labeling process of pseudocontinuous arterial spin labeling is not strictly an adiabatic inversion and the efficiency of labeling may be subject specific. Here, three experiments were performed to study the labeling efficiency in pseudocontinuous arterial spin labeling MRI. First, the optimal labeling position was determined empirically to be approximately 84 mm below the anterior commissure‐posterior commissure line in order to achieve the highest sensitivity. Second, an experimental method was developed to utilize phase‐contrast velocity MRI as a normalization factor and to estimate the labeling efficiency in vivo, which was founded to be 0.86 ± 0.06 (n = 10, mean ± standard deviation). Third, we compared the labeling efficiency of pseudocontinuous arterial spin labeling MRI under normocapnic and hypercapnic (inhalation of 5% CO2) conditions and showed that a higher flow velocity in the feeding arteries resulted in a reduction in the labeling efficiency. In summary, our results suggest that labeling efficiency is a critical parameter in pseudocontinuous arterial spin labeling MRI not only in terms of achieving highest sensitivity but also in quantification of absolute cerebral blood flow in milliliters per minute per 100 g. We propose that the labeling efficiency should be estimated using phase‐contrast velocity MRI on a subject‐specific basis. Magn Reson Med 63:765–771, 2010.

Can Arterial Spin Labeling Detect White Matter Perfusion Signal

Since the invention of arterial spin labeling (ASL) it has been acknowledged that ASL does not allow reliable detection of a white matter (WM) perfusion signal. However, recent developments such as pseudo‐continuous labeling and background suppression have improved the quality. The goal of this research was to study the ability of these newer ASL sequences to detect WM perfusion signal. Background suppressed pseudo‐continuous ASL was implemented at 3T with multislice 2D readout after 1525 ms. In five volunteers it was shown that 10 min scanning resulted in significant perfusion signal in 70% of WM voxels. Increasing the labeling and delay time did not lead to a higher percentage. In 27 normal volunteers it was found that 35 averages are necessary to detect significant WM signal, but 150 averages are needed to detect signal in the deep WM. Finally, it was shown in a patient with a cerebral arteriovenous malformation that pseudo‐continuous ASL enabled the depiction of hypointense WM perfusion signal, although dynamic susceptibility contrast MRI showed that this region was merely showing delayed arrival of contrast agent than hypoperfusion. It can be concluded that, except within the deep WM, ASL is sensitive enough to detect WM perfusion signal and perfusion deficits. Magn Reson Med, 2009.

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.

Functional MRI of human hypothalamic responses following glucose ingestion.

The hypothalamus is intimately involved in the regulation of food intake, integrating multiple neural and hormonal signals. Several hypothalamic nuclei contain glucose-sensitive neurons, which play a crucial role in energy homeostasis. Although a few functional magnetic resonance imaging (fMRI) studies have indicated that glucose consumption has some effect on the neuronal activity levels in the hypothalamus, this matter has not been investigated extensively yet. For instance, dose-dependency of the hypothalamic responses to glucose ingestion has not been addressed. We measured the effects of two different glucose loads on neuronal activity levels in the human hypothalamus using fMRI. After an overnight fast, the hypothalamus of 15 normal weight men was scanned continuously for 37 min. After 7 min, subjects ingested either water or a glucose solution containing 25 or 75 g of glucose. We observed a prolonged decrease of the fMRI signal in the hypothalamus, which started shortly after subjects began drinking the glucose solution and lasted for at least 30 min. Moreover, the observed response was dose-dependent: a larger glucose load resulted in a larger signal decrease. This effect was most pronounced in the upper anterior hypothalamus. In the upper posterior hypothalamus, the signal decrease was similar for both glucose loads. No effect was found in the lower hypothalamus. We suggest a possible relation between the observed hypothalamic response and changes in the blood insulin concentration.

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.

Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI

In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.