André Ahlgren

Idiopathic normal pressure hydrocephalus : cerebral perfusion measured with pCASL before and repeatedly after CSF removal

Pseudo-continuous arterial spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.

Quantification of microcirculatory parameters by joint analysis of flow-compensated and non-flow-compensated intravoxel incoherent motion (IVIM) data

The aim of this study was to improve the accuracy and precision of perfusion fraction and blood velocity dispersion estimates in intravoxel incoherent motion (IVIM) imaging, using joint analysis of flow‐compensated and non‐flow‐compensated motion‐encoded MRI data. A double diffusion encoding sequence capable of switching between flow‐compensated and non‐flow‐compensated encoding modes was implemented. In vivo brain data were collected in eight healthy volunteers and processed using the joint analysis. Simulations were used to compare the performance of the proposed analysis method with conventional IVIM analysis. With flow compensation, strong rephasing was observed for the in vivo data, approximately cancelling the IVIM effect. The joint analysis yielded physiologically reasonable perfusion fraction maps. Estimated perfusion fractions were 2.43 ± 0.81% in gray matter, 1.81 ± 0.90% in deep gray matter, and 1.64 ± 0.72% in white matter (mean ± SD, n = 8). Simulations showed improved accuracy and precision when using joint analysis of flow‐compensated and non‐flow‐compensated data, compared with conventional IVIM analysis. Double diffusion encoding with flow compensation was feasible for in vivo imaging of the perfusion fraction in the brain. The strong rephasing implied that blood flowing through the cerebral microvascular system was closer to the ballistic limit than the diffusive limit.

Dynamic susceptibility contrast MRI with a prebolus contrast agent administration design for improved absolute quantification of perfusion.

Arterial partial‐volume effects (PVEs) often hamper reproducible absolute quantification of cerebral blood flow (CBF) and cerebral blood volume (CBV) obtained by dynamic susceptibility contrast MRI (DSC‐MRI). The aim of this study was to examine whether arterial PVEs in DSC‐MRI data can be minimized by rescaling the arterial input function (AIF) using a sagittal‐sinus venous output function obtained following a prebolus administration of a low dose of contrast agent.

Partial volume correction of brain perfusion estimates using the inherent signal data of time-resolved arterial spin labeling.

Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross‐contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high‐resolution T1‐weighted morphological image volume that is coregistered to the low‐resolution ASL data, making the result sensitive to errors in the segmentation and coregistration. In this work, we present a methodology for partial volume estimation and correction, using only low‐resolution ASL data acquired with the QUASAR sequence. The methodology consists of a T1‐based segmentation method, with no spatial priors, and a modified PVC method based on linear regression. The presented approach thus avoids prior assumptions about the spatial distribution of brain compartments, while also avoiding coregistration between different image volumes. Simulations based on a digital phantom as well as in vivo measurements in 10 volunteers were used to assess the performance of the proposed segmentation approach. The simulation results indicated that QUASAR data can be used for robust partial volume estimation, and this was confirmed by the in vivo experiments. The proposed PVC method yielded probable perfusion maps, comparable to a reference method based on segmentation of a high‐resolution morphological scan. Corrected gray matter (GM) perfusion was 47% higher than uncorrected values, suggesting a significant amount of PVEs in the data. Whereas the reference method failed to completely eliminate the dependence of perfusion estimates on the volume fraction, the novel approach produced GM perfusion values independent of GM volume fraction. The intra‐subject coefficient of variation of corrected perfusion values was lowest for the proposed PVC method. As shown in this work, low‐resolution partial volume estimation in connection with ASL perfusion estimation is feasible, and provides a promising tool for decoupling perfusion and tissue volume. Copyright

A novel approach to measure local cerebral haematocrit using MRI.

The percentage blood volume occupied by red blood cells is known as haematocrit. While it is straightforward to measure haematocrit in large arteries, it is very challenging to do it in microvasculature (cerebral haematocrit). Currently, this can only be done using invasive methods (e.g. PET), but their use is very limited. Local variations in cerebral haematocrit have been reported in various brain abnormalities (e.g. stroke, tumours). We propose a new approach to image cerebral haematocrit using MRI, which relies on combining data from two measurements: one that provides haematocrit-weighted and other one haematocrit-independent values of the same parameter, thus providing an easily obtainable measurement of this important physiological parameter. Four different implementations are described, with one illustrated as proof-of-concept using data from healthy subjects. Cerebral haematocrit measurements were found to be in general agreement with literature values from invasive techniques (e.g. cerebral/arterial ratios of 0.88 and 0.86 for sub-cortical and cortical regions), and showed good test–retest reproducibility (e.g. coefficient-of-variation: 15% and 13% for those regions). The method was also able to detect statistically significant haematocrit gender differences in cortical regions (p < 0.01). The proposed MRI technique should have important applications in various neurological diseases, such as in stroke and brain tumours.

Reduction of arterial partial volume effects for improved absolute quantification of DSC-MRI perfusion estimates: Comparison between tail scaling and prebolus administration.

To evaluate and mutually compare the tail‐scaling approach and the prebolus administration concept for reduction of arterial partial volume effects (PVEs), because reproducible absolute quantification of cerebral blood flow (CBF) by dynamic susceptibility contrast magnetic resonance imaging (MRI) is often hampered by PVEs in the arterial input function (AIF) registration.

Separating Blood and Water: Perfusion and Free Water Elimination from Diffusion MRI in the Human Brain.

&NA; The assessment of the free water fraction in the brain provides important information about extracellular processes such as atrophy and neuroinflammation in various clinical conditions as well as in normal development and aging. Free water estimates from diffusion MRI are assumed to account for freely diffusing water molecules in the extracellular space, but may be biased by other pools of molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM) of blood, where water molecules perfuse in the randomly oriented capillary network. The goal of this work was to separate the signal contribution of the perfusing blood from that of free‐water and of other brain diffusivities. The influence of the vascular compartment on the estimation of the free water fraction and other diffusivities was investigated by simulating perfusion in diffusion MRI data. The perfusion effect in the simulations was significant, especially for the estimation of the free water fraction, and was maintained as long as low b‐value data were included in the analysis. Two approaches to reduce the perfusion effect were explored in this study: (i) increasing the minimal b‐value used in the fitting, and (ii) using a three‐compartment model that explicitly accounts for water molecules in the capillary blood. Estimation of the model parameters while excluding low b‐values reduced the perfusion effect but was highly sensitive to noise. The three‐compartment model fit was more stable and additionally, provided an estimation of the volume fraction of the capillary blood compartment. The three‐compartment model thus disentangles the effects of free water diffusion and perfusion, which is of major clinical importance since changes in these components in the brain may indicate different pathologies, i.e., those originating from the extracellular space, such as neuroinflammation and atrophy, and those related to the vascular space, such as vasodilation, vasoconstriction and capillary density. Diffusion MRI data acquired from a healthy volunteer, using multiple b‐shells, demonstrated an expected non‐zero contribution from the blood fraction, and indicated that not accounting for the perfusion effect may explain the overestimation of the free water fraction evinced in previous studies. Finally, the applicability of the method was demonstrated with a dataset acquired using a clinically feasible protocol with shorter acquisition time and fewer b‐shells. HighlightsPerfusing capillary blood affects the estimation of diffusivities.Other fast diffusing components such as the free water fraction are overestimated.A three‐compartment model including tissue, free water and blood is proposed.Separating perfusing blood signal from water diffusion improves freewater estimation.Clinical feasibility is demonstrated with simulations and real data.

Arterial spin-labeling perfusion MR imaging demonstrates regional cbf decrease in idiopathic normal pressure hydrocephalus

The authors assessed regional CBF in patients with idiopathic normal pressure hydrocephalus compared with healthy controls using the noninvasive quantitative arterial spin-labeling MR imaging technique. Twenty-one consecutive patients with NPH and 21 age- and sex-matched randomly selected healthy controls from a population registry were prospectively included. In patients with idiopathic NPH, perfusion was reduced in the periventricular white matter,lentiform nucleus, and thalamus compared with controls. They conclude that using pseudocontinuous ASL, they confirmed the findings of reduced perfusion in the periventricular white matter, basal ganglia, and thalamus in patients with idiopathic NPH previously observed with other imaging techniques. BACKGROUND AND PURPOSE: Regional cerebral blood flow has previously been studied in patients with idiopathic normal pressure hydrocephalus with imaging methods that require an intravenous contrast agent or expose the patient to ionizing radiation. The purpose of this study was to assess regional CBF in patients with idiopathic normal pressure hydrocephalus compared with healthy controls using the noninvasive quantitative arterial spin-labeling MR imaging technique. A secondary aim was to compare the correlation between symptom severity and CBF. MATERIALS AND METHODS: Differences in regional cerebral perfusion between patients with idiopathic normal pressure hydrocephalus and healthy controls were investigated with pseudocontinuous arterial spin-labeling perfusion MR imaging. Twenty-one consecutive patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched randomly selected healthy controls from the population registry were prospectively included. The controls did not differ from patients with respect to selected vascular risk factors. Twelve different anatomic ROIs were manually drawn on coregistered FLAIR images. The Holm-Bonferroni correction was applied to statistical analyses. RESULTS: In patients with idiopathic normal pressure hydrocephalus, perfusion was reduced in the periventricular white matter (P < .001), lentiform nucleus (P < .001), and thalamus (P < .001) compared with controls. Cognitive function in patients correlated with CBF in the periventricular white matter (r = 0.60, P < .01), cerebellum (r = 0.63, P < .01), and pons (r = 0.71, P < .001). CONCLUSIONS: Using pseudocontinuous arterial spin-labeling, we could confirm findings of a reduced perfusion in the periventricular white matter, basal ganglia, and thalamus in patients with idiopathic normal pressure hydrocephalus previously observed with other imaging techniques.

Perfusion quantification by model-free arterial spin labeling using nonlinear stochastic regularization deconvolution.

Quantification of cerebral blood flow can be accomplished by model‐free arterial spin labeling using the quantitative STAR labeling of arterial regions (QUASAR) sequence. The required deconvolution is normally based on block‐circulant singular value decomposition (cSVD)/oscillation SVD (oSVD), an algorithm associated with nonphysiological residue functions and potential effects of arterial dispersion. The aim of this work was to amend this by implementing nonlinear stochastic regularization (NSR) deconvolution, previously used to retrieve realistic residue functions in dynamic susceptibility contrast MRI.

Visual Assessment of Brain Perfusion MRI Scans in Dementia: A Pilot Study.

Functional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG‐PET data.