Thomas W. Okell

Quantitative measurement of cerebral physiology using respiratory-calibrated MRI.

Functional magnetic resonance imaging typically measures signal increases arising from changes in the transverse relaxation rate over small regions of the brain and associates these with local changes in cerebral blood flow, blood volume and oxygen metabolism. Recent developments in pulse sequences and image analysis methods have improved the specificity of the measurements by focussing on changes in blood flow or changes in blood volume alone. However, FMRI is still unable to match the physiological information obtainable from positron emission tomography (PET), which is capable of quantitative measurements of blood flow and volume, and can indirectly measure resting metabolism. The disadvantages of PET are its cost, its availability, its poor spatial resolution and its use of ionising radiation. The MRI techniques introduced here address some of these limitations and provide physiological data comparable with PET measurements. We present an 18-minute MRI protocol that produces multi-slice whole-brain coverage and yields quantitative images of resting cerebral blood flow, cerebral blood volume, oxygen extraction fraction, CMRO(2), arterial arrival time and cerebrovascular reactivity of the human brain in the absence of any specific functional task. The technique uses a combined hyperoxia and hypercapnia paradigm with a modified arterial spin labelling sequence.

The dorsal posterior insula subserves a fundamental role in human pain

Several brain regions have been implicated in human painful experiences, but none have been proven to be specific to pain. We exploited arterial spin-labeling quantitative perfusion imaging and a newly developed procedure to identify a specific role for the dorsal posterior insula (dpIns) in pain. Tract tracing studies in animals identify a similar region as fundamental to nociception, which suggests the dpIns is its human homolog and, as such, a potential therapeutic target.

Comparison of cerebral blood flow acquired by simultaneous [15O]water positron emission tomography and arterial spin labeling magnetic resonance imaging.

Until recently, no direct comparison between [15O]water positron emission tomography (PET) and arterial spin labeling (ASL) for measuring cerebral blood flow (CBF) was possible. With the introduction of integrated, hybrid magnetic resonance (MR)-PET scanners, such a comparison becomes feasible. This study presents results of CBF measurements recorded simultaneously with [15O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [15O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant (P<0.05) correlation was observed between the two modalities; the whole-brain CBF values determined with PET and pCASL were 43.3 ±6.1 mL and 51.9 ± 7.1 mL per 100 g per minute, respectively. The gray/white matter (GM/WM) ratio of CBF was 3.0 for PET and 3.4 for pCASL. A paired t-test revealed differences in regional CBF between ASL and PET with higher ASL-CBF than PET-CBF values in cortical areas. Using an integrated, hybrid MR-PET a direct simultaneous comparison between ASL and [15O]water PET became possible for the first time so that temporal, physiologic, and functional variations were avoided. Regional and individual differences were found despite the overall similarity between ASL and PET, requiring further detailed investigations.

Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging

Harston et al. establish proof of principle for clinical use of pH-weighted MRI in patients with acute ischaemic stroke. Detailed tissue-level analysis reveals that cerebral intracellular pH, a marker of metabolic stress, is associated with eventual tissue outcome, and complements established imaging modalities.

Visual activation of extra-striate cortex in the absence of V1 activation.

Research highlights ▶ Gray matter of V1 shows abnormal T1 characteristics and its perfusion is reduced. ▶ Damage is confined to gray matter with no adjacent white matter involvement. ▶ BOLD activation levels in the calcarine sulcus are drastically reduced. ▶ Activation of extrastriate regions to visual stimulation is preserved. ▶ Pathway between LGN and V1 shows degeneration; between LGN and V5/MT is intact.

Comparing different analysis methods for quantifying the MRI amide proton transfer (APT) effect in hyperacute stroke patients.

Amide proton transfer (APT) imaging is a pH mapping method based on the chemical exchange saturation transfer phenomenon that has potential for penumbra identification following stroke. The majority of the literature thus far has focused on generating pH‐weighted contrast using magnetization transfer ratio asymmetry analysis instead of quantitative pH mapping. In this study, the widely used asymmetry analysis and a model‐based analysis were both assessed on APT data collected from healthy subjects (n = 2) and hyperacute stroke patients (n = 6, median imaging time after onset = 2 hours 59 minutes). It was found that the model‐based approach was able to quantify the APT effect with the lowest variation in grey and white matter (≤ 13.8 %) and the smallest average contrast between these two tissue types (3.48 %) in the healthy volunteers. The model‐based approach also performed quantitatively better than the other measures in the hyperacute stroke patient APT data, where the quantified APT effect in the infarct core was consistently lower than in the contralateral normal appearing tissue for all the patients recruited, with the group average of the quantified APT effect being 1.5 ± 0.3 % (infarct core) and 1.9 ± 0.4 % (contralateral). Based on the fitted parameters from the model‐based analysis and a previously published pH and amide proton exchange rate relationship, quantitative pH maps for hyperacute stroke patients were generated, for the first time, using APT imaging.

Vessel-encoded dynamic magnetic resonance angiography using arterial spin labeling.

A new noninvasive MRI method for vessel‐selective angiography is presented. The technique combines vessel‐encoded pseudocontinuous arterial spin labeling with a two‐dimensional dynamic angiographic readout and was used to image the cerebral arteries in healthy volunteers. Time‐of‐flight angiograms were also acquired prior to vessel‐selective dynamic angiography acquisitions in axial, coronal, and/or sagittal planes, using a 3‐T MRI scanner. The latter consisted of a vessel‐encoded pseudocontinuous arterial spin labeling pulse train of 300 or 1000 ms followed by a two‐dimensional thick‐slab flow‐compensated fast low‐angle shot readout combined with a segmented Look‐Locker sampling strategy (temporal resolution = 55 ms). Selective labeling was performed at the level of the neck to generate individual angiograms for both right and left internal carotid and vertebral arteries. Individual vessel angiograms were reconstructed using a bayesian inference method. The vessel‐selective dynamic angiograms obtained were consistent with the time‐of‐flight images, and the longer of the two vessel‐encoded pseudocontinuous arterial spin labeling pulse train durations tested (1000 ms) was found to give better distal vessel visibility. This technique provides highly selective angiograms quickly and noninvasively that could potentially be used in place of intra‐arterial x‐ray angiography for larger vessels. Magn Reson Med, 2010.

Cerebral blood flow quantification using vessel-encoded arterial spin labeling.

Arterial spin labeling (ASL) techniques are gaining popularity for visualizing and quantifying cerebral blood flow (CBF) in a range of patient groups. However, most ASL methods lack vessel-selective information, which is important for the assessment of collateral flow and the arterial supply to lesions. In this study, we explored the use of vessel-encoded pseudocontinuous ASL (VEPCASL) with multiple postlabeling delays to obtain individual quantitative CBF and bolus arrival time maps for each of the four main brain-feeding arteries and compared the results against those obtained with conventional pseudocontinuous ASL (PCASL) using matched scan time. Simulations showed that PCASL systematically underestimated CBF by up to 37% in voxels supplied by two arteries, whereas VEPCASL maintained CBF accuracy since each vascular component is treated separately. Experimental results in healthy volunteers showed that there is no systematic bias in the CBF estimates produced by VEPCASL and that the signal-to-noise ratio of the two techniques is comparable. Although more complex acquisition and image processing is required and the potential for motion sensitivity is increased, VEPCASL provides comparable data to PCASL but with the added benefit of vessel-selective information. This could lead to more accurate CBF estimates in patients with a significant collateral flow.

A general framework for the analysis of vessel encoded arterial spin labeling for vascular territory mapping.

Vessel encoded arterial spin labeling provides a way to perform non‐invasive vascular territory imaging. By uniquely encoding the blood within feeding arteries over a number of images, the territories of each can be identified. Here, a new approach for the analysis of vessel encoded arterial spin labeling data is presented. The method includes a full description of how the geometry of arteries and spatial label modulation affects the measured signal. It also incorporates an artery‐based classification that considers multiple arteries in each class, explicitly permitting a voxel to be supplied by multiple arteries. The developed framework is cast within a Bayesian inference procedure allowing both flow contributions and the locations of the arteries in the labeling plane to be inferred. By using simulated data, the method was shown to provide more accurate estimates of blood contribution in areas of mixed supply, such as would be found in watershed regions, than conventional methods. It was also able to estimate the location of arteries within the labeling plane, accounting for motion between sequence prescription and acquisition. Similar performance was found for data acquired using a pseudo‐continuous labeling scheme both in the neck and above the Circle of Willis. Magn Reson Med, 2010.

Optimization and reliability of multiple postlabeling delay pseudo-continuous arterial spin labeling during rest and stimulus-induced functional task activation.

Arterial spin labeling (ASL) sequences that incorporate multiple postlabeling delay (PLD) times allow estimation of when arterial blood signal arrives within a region of interest. Sequences that account for such variability may improve the reliability of ASL and therefore make the technique well suited for future clinical and experimental investigations of cerebral perfusion. This study assessed the within- and between-session reproducibility of an optimized pseudo-continuous ASL (pCASL) functional magnetic resonance imaging (FMRI) sequence that incorporates multiple postlabeling delays (multi-PLD pCASL). Healthy subjects underwent four identical scans separated by 30 minutes, 1 week, and 1 month using multi-PLD pCASL to image absolute perfusion (cerebral blood flow (CBF) and arterial arrival time (AAT)) during both rest and a visual-cued motor task. We show good test-retest reliability, with strong consistency across subjects and sessions during rest (inter-session within-subject coefficient of variation: gray matter (GM) CBF = 6.44%; GM AAT = 2.20%). We also report high sensitivity and reproducibility during the functional task, where we show robust task-related decreases in AAT corresponding with regions of increased CBF. Importantly, these results give insight into optimal PLD selection for future investigations using single-PLD ASL to image different brain regions, and highlight the necessity of multi-PLD ASL when imaging perfusion in the whole brain.