Implementation and validation of ASL perfusion measurements for population imaging

Purpose: Pseudocontinuous arterial spin labeling (pCASL) allows for noninvasive measurement of regional cerebral blood flow (CBF), which has the potential to serve as biomarker for neurodegenerative and cardiovascular diseases. This work aimed to implement and validate pCASL on the dedicated MRI system within the population-based Rotterdam Study, which was installed in 2005 and for which software and hardware configurations have remained fixed. Methods: Imaging was performed on two 1.5T MRI systems (General Electric); (I) the Rotterdam Study system, and (II) a hospital-based system with a product pCASL sequence. An in-house implementation of pCASL was created on scanner I. A flow phantom and three healthy volunteers (<27 years) were scanned on both systems for validation purposes. The data of the first 30 participants (86 ± 4 years) of the Rotterdam Study undergoing pCASL scans on scanner I only were analyzed with and without partial volume correction for gray matter. Results: The validation study showed a difference in blood flow velocity, sensitivity, and spatial coefficient of variation of the perfusion-weighted signal between the two scanners, which was accounted for during post-processing. Gray matter CBF for the Rotterdam Study participants was 52.4 ± 8.2 ml/100 g/min, uncorrected for partial volume effects of gray matter. In this elderly cohort, partial volume correction for gray matter had a variable effect on measured CBF in a range of cortical and sub-cortical regions of interest. Conclusion: Regional CBF measurements are now included to investigate novel biomarkers in the Rotterdam Study. This work highlights that when it is not feasible to purchase a novel ASL sequence, an in-house implementation is valuable

Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T

Objective: Amide proton transfer (APT) weighted chemical exchange saturation transfer (CEST) imaging is increasingly used to investigate high-grade, enhancing brain tumours. Non-enhancing glioma is currently less studied, but shows heterogeneous pathophysiology with subtypes having equally poor prognosis as enhancing glioma. Here, we investigate the use of CEST MRI to best differentiate non-enhancing glioma from healthy tissue and image tumour heterogeneity. Materials & Methods: A 3D pulsed CEST sequence was applied at 3 Tesla with whole tumour coverage and 31 off-resonance frequencies (+6 to -6 ppm) in 18 patients with non-enhancing glioma. Magnetisation transfer ratio asymmetry (MTRasym)

Recommendations for quantitative cerebral perfusion MRI using multi‐timepoint arterial spin labeling: Acquisition, quantification, and clinical applications

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article

Arterial spin labelling MRI for brain tumour surveillance:do we really need cerebral blood flow maps?

OBJECTIVES: Arterial spin labelling (ASL) perfusion MRI is one of the available advanced MRI techniques for brain tumour surveillance. The first aim of this study was to investigate the correlation between quantitative cerebral blood flow (CBF) and non-quantitative perfusion weighted imaging (ASL-PWI) measurements. The second aim was to investigate the diagnostic accuracy of ASL-CBF and ASL-PWI measurements as well as visual assessment for identifying tumour progression.METHODS: A consecutive cohort of patients who underwent 3-T MRI surveillance containing ASL for treated brain tumours was used. ROIs were drawn in representative parts of tumours in the ASL-CBF maps and copied to the ASL-PWI. ASL-CBF ratios and ASL-PWI ratios of the tumour ROI versus normal appearing white matter (NAWM) were correlated (Pearson correlation) and AUCs were calculated to assess diagnostic accuracy. Additionally, lesions were visually classified as hypointense, isointense, or hyperintense. We calculated accuracy at two thresholds: low threshold (between hypointense-isointense) and high threshold (between isointense-hyperintense).RESULTS: A total of 173 lesions, both enhancing and non-enhancing, measured in 115 patients (93 glioma, 16 metastasis, and 6 lymphoma) showed a very high correlation of 0.96 (95% CI: 0.88-0.99) between ASL-CBF ratios and ASL-PWI ratios. AUC was 0.76 (95%CI: 0.65-0.88) for ASL-CBF ratios and 0.72 (95%CI: 0.58-0.85) for ASL-PWI ratios. Diagnostic accuracy of visual assessment for enhancing lesions was 0.72.CONCLUSION: ASL-PWI ratios and ASL-CBF ratios showed a high correlation and comparable AUCs; therefore, quantification of ASL-CBF could be omitted in these patients. Visual classification had comparable diagnostic accuracy to the ASL-PWI or ASL-CBF ratios.CLINICAL RELEVANCE STATEMENT: This study shows that CBF quantification of ASL perfusion MRI could be omitted for brain tumour surveillance and that visual assessment provides the same diagnostic accuracy. This greatly reduces the complexity of the use of ASL in routine clinical practice.KEY POINTS: • Arterial spin labelling MRI for clinical brain tumour surveillance is undervalued and underinvestigated. • Non-quantitative and quantitative arterial spin labelling assessments show high correlation and comparable diagnostic accuracy. • Quantification of arterial spin labelling MRI could be omitted to improve daily clinical workflow.</p

Micro- to macroscale magnetic resonance imaging of glioma

Radiolog

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1-2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity

Correction to:3D APT and NOE CEST-MRI of healthy volunteers and patients with non-enhancing glioma at 3 T

The original version of this article unfortunately contained a mistake. The following author names were incorrectly structured. Tobias C. Wood Gareth J. Barker Juan A. Hernandez-Tamames Esther A. H. Warnert The original article has been corrected

Improved postprocessing of dynamic glucose-enhanced CEST MRI for imaging brain metastases at 3 T

Abstract Background Dynamic glucose-enhanced (DGE) chemical exchange saturation transfer (CEST) has the potential to characterize glucose metabolism in brain metastases. Since the effect size of DGE CEST is small at 3 T (< 1%), measurements of signal-to-noise ratios are challenging. To improve DGE detection, we developed an acquisition pipeline and extended image analysis for DGE CEST on a hybrid 3-T positron emission tomography/magnetic resonance imaging system. Methods This cross-sectional study was conducted after local ethical approval. Static Z-spectra (from -100 to 100 ppm) were acquired to compare the use of 1.2 versus 2 ppm to calculate static glucose-enhanced (glucoCEST) maps in 10 healthy volunteers before and after glucose infusion. Dynamic CEST images were acquired during glucose infusion. Image analysis was optimized using motion correction, dynamic B 0 correction, and principal component analysis (PCA) to improve the detection of DGE CEST in the sagittal sinus, cerebrospinal fluid, and grey and white matter. The developed DGE CEST pipeline was applied to four patients diagnosed with brain metastases. Results GlucoCEST was strongest in healthy tissues at 2 ppm. Correcting for motion, B 0, and use of PCA locally improved DGE maps. A larger contrast between healthy tissues and enhancing regions in brain metastases was found when dynamic B 0 correction and PCA denoising were applied. Conclusion We demonstrated the feasibility of DGE CEST with our developed acquisition and analysis pipeline at 3 T in patients with brain metastases. This work enables a direct comparison of DGE CEST to 18F-fluoro-deoxy-D-glucose positron emission tomography of glucose metabolism in patients with brain metastases. Relevance statement Contrast between brain metastasis and healthy brain tissue in DGE CEST MR images is improved by including principle component analysis and dynamic magnetic field correction during postprocessing. This approach enables the detection of increased DGE CEST signal in brain metastasis, if present. Key points • Despite the low signal-to-noise ratio, dynamic glucose-enhanced CEST MRI is feasible at 3 T. • Principal component analyses and dynamic magnetic field correction improve DGE CEST MRI. • DGE CEST MRI does not consequently show changes in brain metastases compared to healthy brain tissue. • Increased DGE CEST MRI in brain metastases, if present, shows overlap with contrast enhancement on T1-weighted images. Graphical Abstrac

Multi-delay pseudo-continuous arterial spin labeling to measure blood flow in the head and neck

Perfusion MRI is promising for the assessment, prediction, and monitoring of radiation toxicity in organs at risk in head and neck cancer. Arterial spin labeling (ASL) may be an attractive alternative for conventional perfusion MRI, that does not require administration of contrast agents. However, currently, little is known about the characteristics and performance of ASL in healthy tissues in the head and neck region. Therefore, the purpose of this study was to optimize and evaluate multi-delay pseudo-continuous ASL (pCASL) for the head and neck region and to explore nominal values and measurement repeatability for the blood flow (BF), and transit time and T1 values needed for BF quantification in healthy tissues. Twenty healthy volunteers underwent a scan session containing 4 repeats of multi-delay pCASL (Post-label delays (PLDs): 1000, 1632, 2479 ms). ROIs were defined in the parotid glands, submandibular glands, tonsils, and cerebellum (as reference). Nominal values of BF were calculated as the average over 4 repeats per volunteer. The repeatability coefficient and within subject coefficient of repeatability (wCV) of BF were calculated. The effect of T1 (map versus cohort average) and transit time correction on BF was investigated. The mean BF (±SE) was 55.7±3.1 ml/100 g/min for the parotid glands, 41.2±2.8 ml/100 g/min for the submandibular glands, and 32.3±2.2 ml/100 g/min for the tonsils. The best repeatability was found in the parotid glands (wCV = 13.3%-16.1%), followed by the submandibular glands and tonsils (wCV=20.0-24.6%). On average the effect of T1 and transit time correction on BF was limited, although substantial bias occurred in individual acquisitions. In conclusion, we demonstrated the feasibility of BF measurements in the head and neck region using multi-delay pCASL and reported on nominal BF values, BF repeatability, the effect of T1, and transit time in various tissues in the head and neck region

MR Vascular Fingerprinting with Hybrid Gradient–Spin Echo Dynamic Susceptibility Contrast MRI for Characterization of Microvasculature in Gliomas

Characterization of tumor microvasculature is important in tumor assessment and studying treatment response. This is possible by acquiring vascular biomarkers with magnetic resonance imaging (MRI) based on dynamic susceptibility contrast (DSC). We propose magnetic resonance vascular fingerprinting (MRVF) for hybrid echo planar imaging (HEPI) acquired during the first passage of the contrast agent (CA). The proposed approach was evaluated in patients with gliomas, and we simultaneously estimated vessel radius and relative cerebral blood volume. These parameters were also compared to the respective values estimated using the previously introduced vessel size imaging (VSI) technique. The results of both methods were found to be consistent. MRVF was also found to be robust to noise in the estimation of the parameters. DSC-HEPI-based MRVF provides characterization of microvasculature in gliomas with a short acquisition time and can be further improved in several ways to increase our understanding of tumor physiology