Partial volume correction for quantitative CEST imaging of acute ischemic stroke.

PURPOSE: Contributions of cerebrospinal fluid (CSF) have not been previously taken into account in the quantification of APT CEST effects, and correction for the dilution of CEST effects by CSF may allow for more robust measurement of CEST signals. The objective of this study was to compare the robustness of a partial volume (PV) correction model against a standard (4-pool) multi-pool model as far as their ability to quantify CEST effects in healthy, normal, and pathological tissue. METHODS: MRI data from 12 patients presenting with ischemic stroke, and 6 healthy subjects, were retrospectively analyzed. CEST signals derived from a 4-pool model and a PV correction model were compared for repeatability and pathological tissue contrast. The effect of PV correction (PVC) was assessed within 3 ranges of tissue PV estimate (PVE): high PVE voxels, low PVE voxels, and the whole slice. RESULTS: In voxels with a high tissue PVE, PV correction did not make a significant difference to absolute APTR* . In low PVE voxels, the PVC model exhibited a significantly decreased ischemic core signal. The PVC measures exhibited higher repeatability between healthy subjects (4 pools: 3.4%, PVC: 2.4%) while maintaining a similar ischemic core CNR (0.7) to the 4-pool model. In whole slice analysis it was found that both models exhibited similar results. CONCLUSIONS: PV correction yielded a measure of APT effects that was more repeatable than standard 4-pool analysis while achieving a similar CNR in pathological tissue, suggesting that PV-corrected analysis was more robust at low values of tissue PVE.

Quantitative CEST imaging of amide proton transfer in acute ischaemic stroke.

BACKGROUND: Amide proton transfer (APT) imaging may help identify the ischaemic penumbra in stroke patients, the classical definition of which is a region of tissue around the ischaemic core that is hypoperfused and metabolically stressed. Given the potential of APT imaging to complement existing imaging techniques to provide clinically-relevant information, there is a need to develop analysis techniques that deliver a robust and repeatable APT metric. The challenge to accurate quantification of an APT metric has been the heterogeneous in-vivo environment of human tissue, which exhibits several confounding magnetisation transfer effects including spectrally-asymmetric nuclear Overhauser effects (NOEs). The recent literature has introduced various model-free and model-based approaches to analysis that seek to overcome these limitations. OBJECTIVES: The objective of this work was to compare quantification techniques for CEST imaging that specifically separate APT and NOE effects for application in the clinical setting. Towards this end a methodological comparison of different CEST quantification techniques was undertaken in healthy subjects, and around clinical endpoints in a cohort of acute stroke patients. METHODS: MRI data from 12 patients presenting with ischaemic stroke were retrospectively analysed. Six APT quantification techniques, comprising model-based and model-free techniques, were compared for repeatability and ability for APT to distinguish pathological tissue in acute stroke. RESULTS: Robustness analysis of six quantification techniques indicated that the multi-pool model-based technique had the smallest contrast between grey and white matter (2%), whereas model-free techniques exhibited the highest contrast (>30%). Model-based techniques also exhibited the lowest spatial variability, of which 4-pool APTR∗ was by far the most uniform (10% coefficient of variation, CoV), followed by 3-pool analysis (20%). Four-pool analysis yielded the highest ischaemic core contrast-to-noise ratio (0.74). Four-pool modelling of APT effects was more repeatable (3.2% CoV) than 3-pool modelling (4.6% CoV), but this appears to come at the cost of reduced contrast between infarct growth tissue and normal tissue. CONCLUSION: The multi-pool measures performed best across the analyses of repeatability, spatial variability, contrast-to-noise ratio, and grey matter-white matter contrast, and might therefore be more suitable for use in clinical imaging of acute stroke. Addition of a fourth pool that separates NOEs and semisolid effects appeared to be more biophysically accurate and provided better separation of the APT signal compared to the 3-pool equivalent, but this improvement appeared be accompanied by reduced contrast between infarct growth tissue and normal tissue.

Feasibility of Flat Panel Detector CT in Perfusion Assessment of Brain Arteriovenous Malformations: Initial Clinical Experience.

The different results from flat panel detector CT in various pathologies have provoked some discussion. Our aim was to assess the role of flat panel detector CT in brain arteriovenous malformations, which has not yet been assessed. Five patients with brain arteriovenous malformations were studied with flat panel detector CT, DSC-MR imaging, and vessel-encoded pseudocontinuous arterial spin-labeling. In glomerular brain arteriovenous malformations, perfusion was highest next to the brain arteriovenous malformation with decreasing values with increasing distance from the lesion. An inverse tendency was observed in the proliferative brain arteriovenous malformation. Flat panel detector CT, originally thought to measure blood volume, correlated more closely with arterial spin-labeling-CBF and DSC-CBF than with DSC-CBV. We conclude that flat panel detector CT perfusion depends on the time point chosen for data collection, which is triggered too early in these patients (ie, when contrast agent appears in the superior sagittal sinus after rapid shunting through the brain arteriovenous malformation). This finding, in combination with high data variability, makes flat panel detector CT inappropriate for perfusion assessment in brain arteriovenous malformations.

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.

Non-invasive imaging of cartilage in early osteoarthritis.

Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition.

Hemodynamic alterations in vertebrobasilar large artery disease assessed by arterial spin-labeling MR imaging.

BACKGROUND AND PURPOSE: VB artery stenosis is associated with a high risk of recurrent ischemic events, and knowledge about the hemodynamic relevance of VB stenosis is important for clinical decision making. In this study, multiple inflow pulsed ASL MR imaging was assessed for its ability to measure CBF and ATT in patients with VB disease. MATERIALS AND METHODS: ASL was performed on a 3T MR imaging scanner in 41 participants. Twenty-one patients had a history of ischemic events in the VB circulation (14 men, 7 women, age 66 ± 11 years). Clinical data and CE-MRA were used to classify VB disease severity. Twenty age-matched adults were controls. Group and within-VB analyses were performed. Mean CBF and ATT values in the ROIs were adjusted by excluding voxels that did not produce a reliable ASL estimate. RESULTS: CBF was reduced (P < .003) in patients compared with controls, which was significant after excluding voxels with a poor fit. Differences in ATT between patients and controls were not significant after voxel correction. There was a strong correlation between CBF and ATT among patients. Finally, ATT was significantly correlated with VB disease severity (P = .026). CONCLUSIONS: Multiple inflow ASL distinguished patients with VB disease from age matched-controls. VB disease rating was associated with prolonged ATT downstream. ASL may have diagnostic potential among patients in whom risk of intervention is high.

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.

Partial volume correction of multiple inversion time arterial spin labeling MRI data.

The accuracy of cerebral blood flow (CBF) estimates from arterial spin labeling (ASL) is affected by the presence of both gray matter (GM) and white matter within any voxel. Recently a partial volume (PV) correction method for ASL has been demonstrated (Asllani et al. Magn Reson Med 2008; 60:1362-1371), where PV estimates were used with a local linear regression to separate the GM and white matter ASL signal. Here a new PV correction method for multi-inversion time ASL is proposed that exploits PV estimates within a spatially regularized kinetic curve model analysis. The proposed method exploits both PV estimates and the different kinetics of the ASL signal arising from GM and white matter. The new correction method is shown, on both simulated and real data, to provide correction of GM CBF comparable to a linear regression approach, whilst preserving greater spatial detail in the CBF image. On real data corrected GM CBF values were found to be largely independent of GM PV, implying that the correction had been successful. Increases of mean GM CBF after correction of 69-80% were observed.

Multiple inflow pulsed arterial spin-labeling reveals delays in the arterial arrival time in minor stroke and transient ischemic attack.

Our purpose was to use multiple inflow pulsed ASL to investigate whether hemodynamic AAT information is sensitive to hemispheric asymmetry in acute ischemia. The cohorts included 15 patients with acute minor stroke or TIA and 15 age-matched controls. Patients were scanned by using a stroke MR imaging protocol at a median time of 74 hours. DWI lesion volumes were small and functional impairment was low; however, perfusion abnormalities were evident. Prolonged AAT values were more likely to reside in the affected hemisphere (significant when compared with controls, P < .048). An advantage of this ASL technique is the ability to use AAT information in addition to CBF to characterize ischemia.

Lack of effect of citalopram on magnetic resonance spectroscopy measures of glutamate and glutamine in frontal cortex of healthy volunteers.

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide localised measures of brain chemistry in vivo. We previously found that healthy volunteers receiving the selective serotonin reuptake inhibitor, citalopram, daily for 1 week showed higher levels of a combined measure of glutamate and glutamine (Glx) in occipital cortex than those receiving placebo. The aim of this study was to assess if a similar effect could be detected in the frontal brain region. Twenty-three healthy volunteers randomised to receive either citalopram 20 mg or a placebo capsule daily for 7-10 days were studied and scanned using a 3T Varian INOVA system before and at the end of treatment. Standard short-TE (echo time) PRESS (Point-resolved spectroscopy) (TE = 26 ms) and PRESS-J spectra were acquired from a single 8-cm(3) voxel in a frontal region incorporating anterior cingulate cortex. Glutamate and total Glx levels were quantified both relative to creatine and as absolute levels. Relative to placebo, citalopram produced no change in Glx or glutamate alone at the end of the study. Similarly, no effect was seen on other MRS measures studied: myo-inositol, choline, N-acetylaspartate and creatine. These data suggest that the effects of serotonin reuptake to modify cortical glutamatergic MRS measures may be regionally specific. This supports the potential for MRS in assessing neuroanatomically specific serotonin-glutamate interactions in the human brain.

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy.

Continuous theta burst stimulation (cTBS) is a novel transcranial stimulation technique that causes significant inhibition of synaptic transmission for

Functional changes in CSF volume estimated using measurement of water T2 relaxation.

Cerebrospinal fluid (CSF) provides hydraulic suspension for the brain. The general concept of bulk CSF production, circulation, and reabsorption is well established, but the mechanisms of momentary CSF volume variation corresponding to vasoreactive changes are far less understood. Nine individuals were studied in a 3T MR scanner with a protocol that included visual stimulation using a 10-Hz reversing checkerboard and administration of a 5% CO(2) mix in air. We acquired PRESS-localized spin-echoes (TR = 12 sec, TE = 26 ms to 1.5 sec) from an 8-mL voxel located in the visual cortex. Echo amplitudes were fitted to a two-compartmental model of relaxation to estimate the partial volume of CSF and the T(2) relaxation times of the tissues. CSF signal contributed 10.7 +/- 3% of the total, with T(2,csf) = 503.0 +/- 64.3 [ms], T(2,brain) = 61.0 +/- 2 [ms]. The relaxation time of tissue increased during physiological stimulation, while the fraction of signal contributed by CSF decreased significantly by 5-6% with visual stimulation (P < 0.03) and by 3% under CO(2) inhalation (P < 0.08). The CSF signal fraction is shown to represent well the volume changes under viable physiological scenarios. In conclusion, CSF plays a significant role in buffering the changes in cerebral blood volume, especially during rapid functional stimuli.

Differential effects of citalopram and reboxetine on cortical Glx measured with proton MR spectroscopy.

The pharmacological effects of monoamine potentiating antidepressants are likely to be expressed ultimately on cortical pyramidal neurones that use glutamate as a neurotransmitter. However, there are few data on the effects of antidepressant treatment on cortical glutamate levels in humans. The aim of the present study was to use proton magnetic resonance spectroscopy (MRS) to assess the effects of short-term administration of the selective serotonin re-uptake inhibitor, citalopram and the selective noradrenaline re-uptake inhibitor, reboxetine, on a composite measure of glutamate and glutamine (Glx) in occipital cortex in healthy volunteers using a parallel group, placebo-controlled design. We found that relative both to placebo and reboxetine, seven days treatment with citalopram significantly increased cortical Glx. Our data suggest that short-term treatment with citalopram, but not reboxetine, increases occipital Glx in healthy subjects. Further studies are needed to find out if similar effects occur in anterior brain regions and whether they reflect changes in glutamate or glutamine or both.

Simultaneous recording of laser-evoked brain potentials and continuous, high-field functional magnetic resonance imaging in humans.

Simultaneous recording of event-related electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) responses has the potential to provide information on how the human brain reacts to an external stimulus with unique spatial and temporal resolution. However, in most studies combining the two techniques, the acquisition of functional MR images has been interleaved with the recording of evoked potentials. In this study we investigated the feasibility of recording pain-related evoked potentials during continuous and simultaneous collection of blood oxygen level-dependent (BOLD) functional MR images at 3 T. Brain potentials were elicited by selective stimulation of cutaneous Adelta and C nociceptors using brief radiant laser pulses (laser-evoked potentials, LEPs). MR-induced artifacts on EEG data were removed using a novel algorithm. Latencies, amplitudes, and scalp distribution of LEPs recorded during fMRI were not significantly different from those recorded in a control session outside of the MR scanner using the same equipment and experimental design. Stability tests confirmed that MR-image quality was not impaired by the evoked potential recording, beyond signal loss related to magnetic susceptibility differences local to the electrodes. fMRI results were consistent with our previous studies of brain activity in response to nociceptive stimulation. These results demonstrate the feasibility of recording reliable pain-related LEPs and fMRI responses simultaneously. Because LEPs collected during fMRI and those collected in a control session show remarkable similarity, for many experimental designs the integration of LEP and fMRI data collected in separate, single-modality acquisitions may be appropriate. Truly simultaneous recording of LEPs and fMRI is still desirable in specific experimental conditions, such as single-trial, learning, and pharmacological studies.

Functional magnetic resonance imaging.

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful approach to defining activity in the healthy and diseased human brain. BOLD fMRI detects local increases in relative blood oxygenation that are most probably a direct consequence of neurotransmitter action and thus reflect local neuronal signalling. The method allows localisation to volumes of the order of a few to several cubic millimetres and can be used in serial studies of individual subjects. Basic approaches to experimental design and analysis are reviewed briefly, as well as potential clinical applications. The latter include three broad areas: anatomical characterisation of normal or pathological patterns of brain functioning; distinguishing pathological traits; and monitoring treatment responses. New research is emphasising the integration of fMRI with other techniques, particularly electrophysiological. In conjunction with MRI methods for characterising pathological load, fMRI promises a refined understanding of when disease processes begin and how they can be modified by new treatments.

Thalamic neurodegeneration in relapsing-remitting multiple sclerosis.

OBJECTIVE: To define the extent of neuronal injury and loss in thalamic gray matter in patients with relapsing-remitting (RR) MS and to characterize how these neuronal pathologic changes are related to disease duration. METHODS: The authors studied 14 patients with RRMS (Expanded Disability Status Scale score, mean 3.25, range 2.0 to 6.0) and 14 (8 men, 6 women) age-matched healthy controls. Structural MR and MRS studies were performed in a single scanning session using a 3T MR system. RESULTS: N-acetylaspartate (NAA) concentrations (a measure of the apparent neuronal density) were decreased approximately 11% in the thalami of the patients with RRMS relative to controls (p < 0.05). The patients with RRMS also had an almost 25% lower mean normalized thalamic volume than controls (p < 0.005). Decreases in thalamic NAA concentration correlated strongly with thalamic volume loss for individual patients (r = 0.85, p < 0.01). Both the NAA concentration (r = -0.48, p = 0.044) and normalized thalamic volume (r = -0.60, p = 0.01) were correlated inversely with disease duration. There was a trend for a correlation between the thalamic NAA/creatine (Cr) ratio and the NAA/Cr in the frontal normal-appearing white matter (r = 0.56, p < 0.08). CONCLUSIONS: The reduction of both NAA concentration and thalamic volume suggests that a neurodegenerative component may contribute to the pathology of MS even in the earlier RR stage. The trend toward a relationship between thalamic NAA/Cr and distant normal-appearing white matter changes implies that there may be a common mechanism for the white matter axonal loss and thalamic neuronal injury.

Radio frequency magnetic field mapping of a 3 Tesla birdcage coil: experimental and theoretical dependence on sample properties.

The RF B(1) distribution was studied, theoretically and experimentally, in phantoms and in the head of volunteers using a 3 T MRI system equipped with a birdcage coil. Agreement between numerical simulation and experiment demonstrates that B(1) distortion at high field can be explained with 3D full-Maxwell calculations. It was found that the B(1) distribution in the transverse plane is strongly dependent on the dielectric properties of the sample. We show that this is a consequence of RF penetration effects combined with RF standing wave effects. In contrast, along the birdcage coil z-axis the B(1) distribution is determined mainly by the coil geometry. In the transverse plane, the region of B(1) uniformity (within 10% of the maximum) was 15 cm with oil, 6 cm with distilled water, 11 cm with saline, and 10 cm in the head. Along z the B(1) uniformity was 9 cm with phantoms and 7 cm in the head.

Rapid T(1) mapping using multislice echo planar imaging.

Determination of neurological pathology in white matter disease can be made in a semiquantitative way from T(1)- or T(2)-weighted images. A higher level of quantification based on measured T(1) or T(2) values has been either limited to specific regions of interest or to low-resolution maps. Higher-resolution T(1) maps have proved difficult to obtain due to the excessively long scan times required using conventional techniques. In this study, clinically acceptable images are obtained by using single-shot echo planar imaging (EPI) with an acquisition scheme that maximizes signal-to-noise while minimizing the scan time. Magn Reson Med 45:630-634, 2001.

Compensating for B(1) inhomogeneity using active transmit power modulation.

The effect of poor B(1) homogeneity on MRI images not only affects the appearance of the images, but produces difficulty in automated segmentation and in certain quantification methods. While improved RF coil design is the first line in reducing such artifact, compensation methods can significantly improve the quality of images. Existing methods of compensation typically apply a filter during the image reconstruction. Here a method is presented that compensates for part of the inhomogeneity by actively modulating the RF transmit power as a function of slice position. The method is demonstrated both quantitatively on a phantom and qualitatively on a human brain.