Esben T. Petersen

Pulsed Star Labeling of Arterial Regions (PULSAR): A Robust Regional Perfusion Technique for High Field Imaging

Regional perfusion imaging (RPI) has recently been introduced as a potentially powerful technique to map the perfusion territories of patients with vascular diseases in a fully noninvasive manner. However, this technique suffers from the problems of the transfer insensitive labeling technique upon which it is based. In particular, RPI is very sensitive to magnetic field inhomogeneities, and therefore the definition of the labeled bolus can deteriorate at field strength higher than 1.5 T. Furthermore, the slab‐selective triple‐pulse postsaturation sequence used originally will also be impaired due to the same problem, rendering RPI unusable at higher field. In this work, an adiabatic‐based signal targeting with alternating radiofrequency pulses sequence is proposed as a labeling scheme to solve the problems related to variations in local magnetic field, together with an improved four‐pulse water suppression enhanced through T1 effects technique as a presaturation scheme. Magn Reson Med 53:15–21, 2005.

Territorial Arterial Spin Labeling in the Assessment of Collateral Circulation Comparison With Digital Subtraction Angiography

Background and Purpose— Collateral circulation plays a vital role in patients with steno-occlusive disease, in particular for predicting stroke outcome. Digital subtraction angiography (DSA) is the gold standard for the assessment of collateral circulation, despite its invasive nature. Recently, the development of a new class of arterial spin labeling (ASL) methods allowed independent measurement of territorial flow information without the need for contrast media injection. Here, we compared combined territorial ASL (TASL) and MR angiography (MRA) against DSA in the assessment of collateral circulation. Methods— Eighteen patients presenting with extra- or intracranial arterial steno-occlusive disease were recruited. All DSA studies were performed using a biplane angiography unit. MR imaging consisted of time-of-flight MRA and TASL, performed at 3T. Collateral circulation on both modalities was evaluated in consensus in a double-blinded manner by 3 neuroradiologists. Results— Good agreement was found between DSA and TASL in the assessment of collateral flow: Cramer coefficient, V=0.53 (P<0.0001) and Contingency coefficient, C=0.67, with kappa=0.70 and kappa=0.72 in the assessment of flow and collaterals, respectively. TASL and DSA successfully evaluated 89% and 98% of the vessels, respectfully. Failure was linked to motion-related artifacts in TASL, and highly tortuous vessels in DSA. Generally, combined MRA–TASL was comparable to DSA in diagnostic quality. Conclusions— TASL provided radiological information comparable to DSA on collateral flow, with the advantage that it could be performed during routine MRI studies. TASL may provide insight on collateral perfusion in patients who may not otherwise be candidates for DSA, and may potentially replace it.

Chronic Pain: Lost Inhibition?

Human brain imaging has revealed that acute pain results from activation of a network of brain regions, including the somatosensory, insular, prefrontal, and cingulate cortices. In contrast, many investigations report little or no alteration in brain activity associated with chronic pain, particularly neuropathic pain. It has been hypothesized that neuropathic pain results from misinterpretation of thalamocortical activity, and recent evidence has revealed altered thalamocortical rhythm in individuals with neuropathic pain. Indeed, it was suggested nearly four decades ago that neuropathic pain may be maintained by a discrete central generator, possibly within the thalamus. In this investigation, we used multiple brain imaging techniques to explore central changes in subjects with neuropathic pain of the trigeminal nerve resulting in most cases (20 of 23) from a surgical event. Individuals with chronic neuropathic pain displayed significant somatosensory thalamus volume loss (voxel-based morphometry) which was associated with decreased thalamic reticular nucleus and primary somatosensory cortex activity (quantitative arterial spin labeling). Furthermore, thalamic inhibitory neurotransmitter content was significantly reduced (magnetic resonance spectroscopy), which was significantly correlated to the degree of functional connectivity between the somatosensory thalamus and cortical regions including the primary and secondary somatosensory cortices, anterior insula, and cerebellar cortex. These data suggest that chronic neuropathic pain is associated with altered thalamic anatomy and activity, which may result in disturbed thalamocortical circuits. This disturbed thalamocortical activity may result in the constant perception of pain.

In vivo blood T1 measurements at 1.5 T, 3 T, and 7 T

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal‐to‐noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B0), its in vivo value is well established; at ultra‐high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look‐Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ∼ 2.1 s which translates to an anticipated 33% gain in the signal‐to‐noise ratio in arterial spin labeling experiments due to T1 relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B0 was confirmed. Magn Reson Med, 70:1082–1086, 2013.

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: A head-to-head comparison with 15O H2O positron emission tomography

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. (15)O H₂O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with (15)O H₂O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to (15)O H₂O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings.

A method for rapid in vivo measurement of blood T1

We present a technique to measure the longitudinal relaxation time constant of venous blood (T1b) in vivo in a few seconds. The MRI sequence consists of a thick‐slab adiabatic inversion, followed by a series of slice‐selective excitations and single‐shot echo planar imaging readouts. The time intervals between excitations were chosen so that blood in macroscopic vessels is fully refreshed between excitations, making the blood signal follow an unperturbed inversion recovery curve. Static tissue, which experiences the inversion and all excitation pulses, quickly reaches a steady state at a low signal as a result of partial saturation. This allows blood‐filled voxels to be discriminated from those containing static tissue, and to be fitted voxel‐by‐voxel to a simple inversion recovery model. The sequence was tested on a flow phantom with the proposed method, yielding T1 values consistent to within 3% of those obtained using a conventional inversion recovery sequence with a spin‐echo readout. The method was applied to seven adult volunteers and 18 neonates. The blood T1 of the neonates (1799 ± 206 ms; range, 1393–2035 ms) was found to be more variable than that of adults (1717 ± 39 ms; range, 1662–1779 ms). A linear correlation between the inverse of T1b and the haematocrit was established in 12 neonates (R2 = 0.90). Copyright

Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling

PURPOSE To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs). METHODS CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus. RESULTS In GM, the average DSC-MRI CBF estimate was 150+/-45 ml/(min 100 g) (mean+/-SD) while the corresponding ASL CBF was 44+/-10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions. CONCLUSIONS A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.

Dual vessel arterial spin labeling scheme for regional perfusion imaging

Regional perfusion imaging (RPI) based on pulsed arterial spin labeling and angulated inversion slabs has been recently proposed. The technique allows mapping of individual brain perfusion territories of the major feeding arteries and could become a valuable clinical tool for evaluation of patients with cerebrovascular diseases. Here we propose a new labeling scheme for RPI where lateral and posterior circulations are labeled simultaneously. Two scans instead of three are sufficient to obtain the same perfusion territories as in the original approach, allowing for a 33% reduction in the total RPI protocol time. Moreover, the position of the inversion slabs with respect to vascular anatomy facilitates the planning and allows potentially better labeling efficiency. The new approach was tested on seven healthy volunteers and compared to the original labeling scheme. The results showed that the same perfusion territories and regional CBF values can be obtained. Magn Reson Med, 2006.

Mapping of cerebral perfusion territories using territorial arterial spin labeling: techniques and clinical application

A knowledge of the exact cerebral perfusion territory which is supplied by any artery is of great importance in the understanding and diagnosis of cerebrovascular disease. The development and optimization of territorial arterial spin labeling (T‐ASL) MRI techniques in the past two decades have made it possible to visualize and determine the cerebral perfusion territories in individual patients and, more importantly, to do so without contrast agents or otherwise invasive procedures. This review provides an overview of the development of ASL techniques that aim to visualize the general cerebral perfusion territories or the territory of a specific artery of interest. The first efforts of T‐ASL with pulsed, continuous and pseudo‐continuous techniques are summarized and subsequent clinical studies using T‐ASL are highlighted. In the healthy population, the perfusion territories of the brain‐feeding arteries are highly variable. This high variability requires special consideration in specific patient groups, such as patients with cerebrovascular disease, stroke, steno‐occlusive disease of the large arteries and arteriovenous malformations. In the past, catheter angiography with selective contrast injection was the only available method to visualize the cerebral perfusion territories in vivo. Several T‐ASL methods, sometimes referred to as regional perfusion imaging, are now available that can easily be combined with conventional brain MRI examinations to show the relationship between the cerebral perfusion territories, vascular anatomy and brain infarcts or other pathology. Increased availability of T‐ASL techniques on clinical MRI scanners will allow radiologists and other clinicians to gain further knowledge of the relationship between vasculature and patient diagnosis and prognosis. Treatment decisions, such as surgical revascularization, may, in the near future, be guided by information provided by T‐ASL MRI in close correlation with structural MRI and quantitative perfusion information. Copyright

Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates.

PURPOSE The purpose of this study was to evaluate if non-invasive Arterial Spin Labeling MR imaging can be used to assess changes in brain perfusion with age which reflect neonatal brain development. For this purpose regional perfusion values obtained with ASL MR imaging were evaluated as a function of postmenstrual age. MATERIALS AND METHODS Pulsed ASL imaging was performed in 33 neonates with a postmenstrual age from 30 to 53 weeks. Whole brain cerebral blood flow (wbCBF), CBF in the basal ganglia and thalamus (BGT-CBF), in the occipital cortex (OC-CBF) and the frontal cortex (FC-CBF) were measured. Regional CBF values were expressed quantitatively (in ml/100 g min) and relative as a percentage of the wbCBF. RESULTS Mean wbCBF increased significantly from 7±2 ml/100 g min (mean±sd) at 31±2 weeks postmenstrual age to 12±3 ml/100 g min at term-equivalent age (TEA) and 29±9 ml/100 g min at 52±1 weeks postmenstrual age. Relative regional CBF was highest in the BGT at all time-points. Relative OC-and FC-CBF increased significantly from 31±2 weeks postmentrual age to TEA. A significant difference in relative BGT-CBF and OC-CBF was shown between infants at 31±2 weeks postmenstrual age and infants scanned at 52±1 weeks postmenstrual age. Relative perfusion in the BGT measured at TEA was significant different compared to 52±1 weeks postmenstrual age. CONCLUSION In conclusion, regional differences in CBF and changes with postmenstrual age could be detected with ASL in neonates. This suggests that ASL can be used as a non-invasive tool to investigate brain maturation in neonates.