Arterial spin labeling signal in the CSF: Implications for partial volume correction and blood-CSF barrier characterization.

For better quantification of perfusion with arterial spin labeling (ASL), partial volume correction (PVC) is used to disentangle the signals from gray matter (GM) and white matter within any voxel. Based on physiological considerations, PVC algorithms typically assume zero signal in the cerebrospinal fluid (CSF). Recent measurements, however, have shown that CSF-ASL signal can exceed 10% of GM signal, even when using recommended ASL labeling parameters. CSF signal is expected to particularly affect PVC results in the choroid plexus. This study aims to measure the impact of CSF signal on PVC perfusion measurements, and to investigate the potential use of PVC to retrieve pure CSF-ASL signal for blood-CSF barrier characterization. In vivo imaging included six pCASL sequences with variable label duration and post-labeling delay (PLD), and an eight-echo 3D-GRASE readout. A dataset was simulated to estimate the effect of CSF-PVC with known ground-truth parameters. Differences between the results of CSF-PVC and non-CSF-PVC were estimated for regions of interest (ROIs) based on GM probability, and a separate ROI isolating the choroid plexus. In vivo, the suitability of PVC-CSF signal as an estimate of pure CSF was investigated by comparing its time course with the long-TE CSF signal. Results from both simulation and in vivo data indicated that including the CSF signal in PVC improves quantification of GM CBF by approximately 10%. In simulated data, this improvement was greater for multi-PLD (model fitting) quantification than for single PLD (~1-5% difference). In the choroid plexus, the difference between CSF-PVC and non-CSF-PVC was much larger, averaging around 30%. Long-TE (pure) CSF signal could not be estimated from PVC CSF signal as it followed a different time course, indicating the presence of residual macrovascular signal in the PVC. The inclusion of CSF adds value to PVC for more accurate measurements of GM perfusion, and especially for quantification of perfusion in the choroid plexus and study of the glymphatic system.

Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans.

The study of brain clearance mechanisms is an active area of research. While we know that the cerebrospinal fluid (CSF) plays a central role in one of the main existing clearance pathways, the exact processes for the secretion of CSF and the removal of waste products from tissue are under debate. CSF is thought to be created by the exchange of water and ions from the blood, which is believed to mainly occur in the choroid plexus. This exchange has not been thoroughly studied in vivo. We propose a modified arterial spin labeling (ASL) MRI sequence and image analysis to track blood water as it is transported to the CSF, and to characterize its exchange from blood to CSF. We acquired six pseudo-continuous ASL sequences with varying labeling duration (LD) and post-labeling delay (PLD) and a segmented 3D-GRASE readout with a long echo train (8 echo times (TE)) which allowed separation of the very long-T2 CSF signal. ASL signal was observed at long TEs (793 ms and higher), indicating presence of labeled water transported from blood to CSF. This signal appeared both in the CSF proximal to the choroid plexus and in the subarachnoid space surrounding the cortex. ASL signal was separated into its blood, gray matter and CSF components by fitting a triexponential function with T2s taken from literature. A two-compartment dynamic model was introduced to describe the exchange of water through time and TE. From this, a water exchange time from the blood to the CSF (Tbl->CSF) was mapped, with an order of magnitude of approximately 60 s.

Combining T2 measurements and crusher gradients into a single ASL sequence for comparison of the measurement of water transport across the blood-brain barrier.

PURPOSE: Arterial spin labeling can be used to assess the transition time of water molecules across the blood-brain barrier when combined with sequence modules, which allow a separation of intravascular from tissue signal. The bipolar gradient technique measures the intravascular fraction by removing flowing spins. The T2 -relaxation-under-spin-tagging (TRUST) technique modulates the TE to differentiate between intravascular and extravascular spins based on T2 . These modules were combined into a single time-encoded pseudo-continuous arterial spin labeling sequence to compare their mechanisms of action as well as their assessment of water transition across the blood-brain barrier. METHODS: This protocol was acquired on a scanner with 9 healthy volunteers who provided written, informed consent. The sequence consisted of a Hadamard-encoded pseudo-continuous arterial spin labeling module, followed by the TRUST module (effective TEs of 0, 40, and 80 ms) and bipolar flow-crushing gradients (2, 4, and ∞ cm/s). An additional experiment was performed with TRUST and a 3D gradient and spin-echo readout. RESULTS: Gradients imperfectly canceled the intravascular signal, as evidenced by the presence of residual signal in the arteries at early postlabeling delays as well as the underestimation of the intravascular fraction as compared with the TRUST method. The TRUST module allowed us to detect the transport of water deeper into the vascular tree through changes in T2 than the used crusher gradients could, with their limited b-value. CONCLUSION: Of the implemented techniques, TRUST allowed us to follow intravascular signal deeper into the vascular tree than the approach with (relatively weak) crusher gradients when quantifying the transport time of water across the blood-brain barrier.

MRI cine-tagging of cardiac-induced motion for noninvasive staging of liver fibrosis.

BACKGROUND: MR elastography is a noninvasive technique that provides high diagnostic accuracy for the staging of liver fibrosis; however, it requires external hardware and mainly assesses the right lobe. PURPOSE: To evaluate the diagnostic performance of MRI cine-tagging for staging fibrosis in the left liver lobe, using biopsy as the reference standard. STUDY TYPE: Institutional Review Board (IRB)-approved two-center prospective study. POPULATION: Seventy-six patients with chronic liver disease who underwent an MRI cine-tagging examination and a liver biopsy within a 6-week interval. FIELD STRENGTH/SEQUENCE: 2D-GRE multislice sequence at 3.0T with spatial modulation of the magnetization preparation sequence and peripheral pulse-wave triggering on two coronal slices chosen underneath the heart apex to capture maximal deformation with consecutive breath-holds adapted to patient cardiac frequency. ASSESSMENT: A region of interest was selected in the liver close to the heart apex. Maximal strain was evaluated with the harmonic phase (HARP) technique. STATISTICAL TESTS: Spearman's correlation, Kruskal-Wallis test, Mann-Whitney U-test, and receiver operating characteristic (ROC) analysis were performed. RESULTS: Liver strain measured on tagged images decreased with higher histological fibrosis stage (ρ = -0.68, P < 0.0001). Strain values were significantly different between all fibrosis stages (P < 0.0001), and between groups of fibrosis stages ≤F3 vs. F4 (P < 0.05). Areas under the ROC curves were 0.95 (95% confidence interval: 0.89-1.00) to distinguish fibrosis stages F0 vs. F4, 0.81 (0.70-0.92) for stages F0 vs. ≥F1, 0.84 (0.76-0.93) for stages ≤F1 vs. ≥F2, 0.86 (0.78-0.94) for stages ≤F2 vs. ≥F3, and 0.87 (0.77-0.96) for stages ≤F3 vs. F4. DATA CONCLUSION: MRI cine-tagging is a promising technique for measuring liver strain without additional elastography hardware. It could be used to assess the left liver lobe as a complement to current techniques assessing the right lobe. LEVEL OF EVIDENCE: 1 Technical Efficacy: 3 J. Magn. Reson. Imaging 2020;51:1570-1580.

Liver fibrosis: Review of current imaging and MRI quantification techniques.

Liver fibrosis is characterized by the accumulation of extracellular matrix proteins such as collagen in the liver interstitial space. All causes of chronic liver disease may lead to fibrosis and cirrhosis. The severity of liver fibrosis influences the decision to treat or the need to monitor hepatic or extrahepatic complications. The traditional reference standard for diagnosis of liver fibrosis is liver biopsy. However, this technique is invasive, associated with a risk of sampling error, and has low patient acceptance. Imaging techniques offer the potential for noninvasive diagnosis, staging, and monitoring of liver fibrosis. Recently, several of these have been implemented on ultrasound (US), computed tomography, or magnetic resonance imaging (MRI). Techniques that assess changes in liver morphology, texture, or perfusion that accompany liver fibrosis have been implemented on all three imaging modalities. Elastography, which measures changes in mechanical properties associated with liver fibrosis-such as strain, stiffness, or viscoelasticity-is available on US and MRI. Some techniques assessing liver shear stiffness have been adopted clinically, whereas others assessing strain or viscoelasticity remain investigational. Further, some techniques are only available on MRI-such as spin-lattice relaxation time in the rotating frame (T1 ρ), diffusion of water molecules, and hepatocellular function based on the uptake of a liver-specific contrast agent-remain investigational in the setting of liver fibrosis staging. In this review, we summarize the key concepts, advantages and limitations, and diagnostic performance of each technique. The use of multiparametric MRI techniques offers the potential for comprehensive assessment of chronic liver disease severity. LEVEL OF EVIDENCE: 5 J. MAGN. RESON. IMAGING 2017;45:1276-1295.

Dynamic contrast-enhanced MRI to assess hepatocellular carcinoma response to Transarterial chemoembolization using LI-RADS criteria: A pilot study.

PURPOSE: To identify quantitative dynamic contrast-enhanced (DCE)-MRI perfusion parameters indicating tumor response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE). MATERIALS AND METHODS: This prospective pilot study was approved by our institutional review board; written and informed consent was obtained for each participant. Patients underwent DCE-MRI examinations before and after TACE. A variable flip-angle unenhanced 3D mDixon sequence was performed for T1 mapping. A dynamic 4D mDixon sequence was performed after contrast injection for assessing dynamic signal enhancement. Nonparametric analysis was conducted on the time-intensity curves. Parametric analysis was performed on the time-concentration curves using a dual-input single-compartment model. Treatment response according to Liver Reporting and Data System (LI-RADS) v2018 was used as the reference standard. The comparisons within groups (before vs. after treatment) and between groups (nonviable vs. equivocal or viable tumor) were performed using nonparametric bootstrap taking into account the clustering effect of lesions in patients. RESULTS: Twenty-eight patients with 52 HCCs (size: 10-104 mm) were evaluated. For nonviable tumors (n = 27), time to peak increased from 62.5 ±â€¯18.2 s before to 83.3 ±â€¯12.8 s after treatment (P< 0.01). For equivocal or viable tumors (n = 25), time to peak and mean transit time significantly increased (from 54.4 ±â€¯24.1 s to 69.5 ±â€¯18.9 s, P < 0.01 and from 14.2 ±â€¯11.8 s to 33.9 ±â€¯36.8 s, P= 0.01, respectively) and the transfer constant from the extracellular and extravascular space to the central vein significantly decreased from 14.8 ±â€¯14.1 to 8.1 ±â€¯9.1 s-1 after treatment (P= 0.01). CONCLUSION: This prospective pilot DCE-MRI study showed that time to peak significantly changed after TACE treatment for both groups (nonviable tumors and equivocal or viable tumors). In our cohort, several perfusion parameters may provide an objective marker for differentiation of treatment response after TACE in HCC patients.

Liver Fibrosis Quantification by Magnetic Resonance Imaging.

Liver fibrosis is a hallmark of chronic liver disease characterized by the excessive accumulation of extracellular matrix proteins. Although liver biopsy is the reference standard for diagnosis and staging of liver fibrosis, it has some limitations, including potential pain, sampling variability, and low patient acceptance. Hence, there has been an effort to develop noninvasive imaging techniques for diagnosis, staging, and monitoring of liver fibrosis. Many quantitative techniques have been implemented on magnetic resonance imaging (MRI) for this indication. The most widely validated technique is magnetic resonance elastography, which aims to measure viscoelastic properties of the liver and relate them to fibrosis stage. Several additional MRI methods have been developed or adapted to liver fibrosis quantification. Diffusion-weighted imaging measures the Brownian motion of water molecules which is restricted by collagen fibers. Texture analysis assesses the changes in the texture of liver parenchyma associated with fibrosis. Perfusion imaging relies on signal intensity and pharmacokinetic models to extract quantitative perfusion parameters. Hepatocellular function, which decreases with increasing fibrosis stage, can be estimated by the uptake of hepatobiliary contrast agents. Strain imaging measures liver deformation in response to physiological motion such as cardiac contraction. T1ρ quantification is an investigational technique, which measures the spin-lattice relaxation time in the rotating frame. This article will review the MRI techniques used in liver fibrosis staging, their advantages and limitations, and diagnostic performance. We will briefly discuss future directions, such as longitudinal monitoring of disease, prediction of portal hypertension, and risk stratification of hepatocellular carcinoma.