Arterial spin labeling (ASL) is a magnetic resonance (MR) imaging technique used to assess cerebral blood flow noninvasively by magnetically labeling inflowing blood. In this article, the main ...labeling techniques, notably pulsed and pseudocontinuous ASL, as well as emerging clinical applications will be reviewed. In dementia, the pattern of hypoperfusion on ASL images closely matches the established patterns of hypometabolism on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images due to the close coupling of perfusion and metabolism in the brain. This suggests that ASL might be considered as an alternative for FDG, reserving PET to be used for the molecular disease-specific amyloid and tau tracers. In stroke, ASL can be used to assess perfusion alterations both in the acute and the chronic phase. In arteriovenous malformations and dural arteriovenous fistulas, ASL is very sensitive to detect even small degrees of shunting. In epilepsy, ASL can be used to assess the epileptogenic focus, both in peri- and interictal period. In neoplasms, ASL is of particular interest in cases in which gadolinium-based perfusion is contraindicated (eg, allergy, renal impairment) and holds promise in differentiating tumor progression from benign causes of enhancement. Finally, various neurologic and psychiatric diseases including mild traumatic brain injury or posttraumatic stress disorder display alterations on ASL images in the absence of visualized structural changes. In the final part, current limitations and future developments of ASL techniques to improve clinical applicability, such as multiple inversion time ASL sequences to assess alterations of transit time, reproducibility and quantification of cerebral blood flow, and to measure cerebrovascular reserve, will be reviewed.
RSNA, 2016 Online supplemental material is available for this article.
Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal ...studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF).
Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test–retest study across sites from around the world, dubbed “The QUASAR reproducibility study”. Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well.
Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87±0.95 mm and rotations of 1.56±0.66°. Mean gray matter CBF was 47.4±7.5 ml/100 g/min with a between-subject standard variation SDb=5.5 ml/100 g/min and a within-subject standard deviation SDw=4.7 ml/100 g/min. The corresponding repeatability was 13.0 ml/100 g/min and was found to be within the range of previous studies.
Summary The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in ...preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood–brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.
Purpose
Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange ...saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations.
Methods
Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (
B
1rms
= 2μT,
T
sat
= 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3–4 ppm, amines: 1.5–2.5 ppm, amide/amine ratio) were calculated with two models: ‘asymmetry-based’ (AB) and ‘fluid-suppressed’ (FS). The presence of T2/FLAIR mismatch was noted.
Results
IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19q
codel
(
p
< 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (
p
< 0.0045) and from IDH-mutant_1p/19q
ret
(
p
< 0.021). IDH-mutant_1p/19q
ret
had higher amides and amines than IDH-mutant_1p/19q
codel
(
p
< 0.035). IDH-mutant_1p/19q
ret
with AB/FS mismatch had higher amines than IDH-mutant_1p/19q
ret
without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19q
ret
, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (
p
= 0.014).
Conclusions
CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.
Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. We developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic ...resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities. We show that our technique, named glucose chemical exchange saturation transfer (glucoCEST), is sensitive to tumor glucose accumulation in colorectal tumor models and can distinguish tumor types with differing metabolic characteristics and pathophysiologies. The results of this study suggest that glucoCEST has potential as a useful and cost-effective method for characterizing disease and assessing response to therapy in the clinic.
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•CEST contrast results from selective saturation of molecules containing exchangeable protons.•CEST signal is related to pH, temperature, ion concentration, buffer concentration and ...composition.•CEST signal is affected by direct water saturation and magnetization transfer of immobile molecules.•Recent developments in CEST point towards quantitative measurements of the chemical exchange rate.•CEST is applied in the fields of neurology, neuro-oncology and psychiatry.
Within the field of NMR spectroscopy, the study of chemical exchange processes through saturation transfer techniques has a long history. In the context of MRI, chemical exchange techniques have been adapted to increase the sensitivity of imaging to small fractions of exchangeable protons, including the labile protons of amines, amides and hydroxyls. The MR contrast is generated by frequency-selective irradiation of the labile protons, which results in a reduction of the water signal associated with transfer of the labile protons’ saturated magnetization to the protons of the surrounding free water. The signal intensity depends on the rate of chemical exchange and the concentration of labile protons as well as on the properties of the irradiation field. This methodology is referred to as CEST (chemical exchange saturation transfer) imaging. Applications of CEST include imaging of molecules with short transverse relaxation times and mapping of physiological parameters such as pH, temperature, buffer concentration and chemical composition due to the dependency of this chemical exchange effect on all these parameters. This article aims to describe these effects both theoretically and experimentally. In depth analysis and mathematical modelling are provided for all pulse sequences designed to date to measure the chemical exchange rate. Importantly, it has become clear that the background signal from semi-solid protons and the presence of the Nuclear Overhauser Effect (NOE), either through direct dipole-dipole mechanisms or through exchange-relayed signals, complicates the analysis of CEST effects. Therefore, advanced methods to suppress these confounding factors have been developed, and these are also reviewed. Finally, the experimental work conducted both in vitro and in vivo is discussed and the progress of CEST imaging towards clinical practice is presented.
•Partial volume effects influence studies of brain perfusion.•Systematic and random effects on perfusion can occur within and between groups.•Partial volume correction strategies are available, but ...underused.
The mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent.
In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption.
We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, ‘uncorrected’, images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods.
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Motion can induce pseudo CEST effects that can be misinterpreted as uptake. This artifact is studied and discussed herein. Dynamic CEST studies without motion correction are ill-advised.
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•Motion during dynamic CEST experiments can lead to false positive effects.•Even small rotations lead to a pseudo uptake in grey matter and tumor areas.•Motion is the dominant perturbation, yet motion induced B0 alterations lead to artifacts as well.
Dynamic CEST studies such as dynamic glucose enhanced imaging, have gained a lot of attention recently. The expected CEST effects after injection are rather small in tissue especially at clinical field strengths (0.5–2%). Small movements during the dynamic CEST measurement together with a subtraction-based evaluation can lead to pseudo CEST effects of the same order of magnitude. These artifacts are studied herein.
A brain tumor patient 3D-CEST baseline scan without glucose injection performed at 3 T is used to generate a virtual dynamic measurement introducing different kinds of simulated motion and B0 shifts.
Minor motion (0.6 mm translations) and B0 artifacts (7 Hz shift) can lead to pseudo effects in the order of 1% in dynamic CEST imaging. Especially around tissue interfaces such as CSF borders or tumor affected areas, the pseudo effect patterns are non-intuitive and can be mistaken as dynamic agent uptake.
Correction or mitigation for small motions is crucial for dynamic CEST imaging, especially in subjects with lesions. Concomitant B0 alterations can as well induce pseudo CEST effects at 3 T.
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