Safety and performance of TCI pumps in a magnetic resonance imaging environment.

Target controlled infusion (TCI) devices can be associated with significant safety concerns when used during magnetic resonance imaging (MRI). We tested the safety and compatibility of newer TCI systems in a 3-Tesla MRI environment. Two Asena PK and two Agilia TCI pumps were used to administer TCI propofol (at target blood concentrations of 0.5 and 6.0 µg.ml⁻¹) using the Marsh model under magnetic fields of up to 50 G with a T2-weighted sequence. We assessed the devices for projectile risk, accuracy of drug delivery, alarm function and effects on MR image quality. Both devices did not demonstrate any significant deflection at the tested field strengths, and performed within acceptable limits (cumulative error in total delivered volume < 3%; maximum 10-min interval error < 10%). The Asena pump caused minor artefacts on MR images. The TCI pumps tested perform well and safely implement pharmacokinetic software in a high magnetic field.

Altered functional connectivity in the motor network after traumatic brain injury.

BACKGROUND: A large proportion of survivors of traumatic brain injury (TBI) have persistent cognitive impairments, the profile of which does not always correspond to the size and location of injuries. One possible explanation could be that TBI-induced damage extends beyond obvious lesion sites to affect remote brain networks. We explored this hypothesis in the context of a simple and well-characterized network, the motor network. The aim of this cross-sectional study was to establish the residual integrity of the motor network as an important proof of principle of abnormal connectivity in TBI. METHODS: fMRI data were obtained from 12 right-handed patients and 9 healthy controls while they performed the finger-thumb opposition task with the right hand. We used both conventional and psychophysiologic interaction (PPI) analyses to examine the integrity of functional connections from brain regions we found to be activated in the paradigm we used. RESULTS: As expected, the analysis showed significant activations of the left primary motor cortex (M1), right cerebellum (Ce), and bilateral supplementary motor area (SMA) in controls. However, only the activation of M1 survived robust statistical thresholding in patients. In controls, the PPI analysis revealed that left M1, SMA, and right Ce positively interacted with the left frontal cortex and negatively interacted with the right supramarginal gyrus. In patients, we observed no negative interaction and reduced interhemispheric interactions from these seed regions. CONCLUSIONS: These observations suggest that patients display compromised activation and connectivity patterns during the finger-thumb opposition task, which may imply functional reorganization of motor networks following TBI.

Preliminary evaluation of a combined microPET-MR system.

There are many motivations for adding simultaneously acquired MR images to PET scanning. The most straight forward are, superior registration of MR and PET images, the addition of morphological detail when there is non-rigid motion and for pre-clinical studies simultaneous imaging could lead to a significant reduction in the time that animals are required to be anesthetised. In addition simultaneous MR has the potential to provide accurate motion correction for PET image reconstruction. For functional imaging simultaneous acquisition is required to assess the subject in the same physiological state, such as acute stroke studies. The elimination of the additional radiation associated with combining CT with PET, by providing anatomic detail with MR, would be a crucial advantage for cancer screening. Combining the two instruments necessitates some engineering tradeoffs, especially associated with the use of the highly developed photomultiplier tube (PMT) used for light amplification, because of its incompatibility with strong magnetic fields. Our approach is to provide a split in the magnet and gradients to locate the magnetic sensitive components, the PMTs, in regions of low magnetic field, leaving only the essential PET components, the scintillator blocks, in the strong magnetic field region. The crystals are coupled to the PMTs by extending the optical fibres. A further advantage accrues by moving the PET electronics out of the region seen by the MR radio-frequency (RF) and gradient coils as electromagnetic interference effects between the PET and MR systems, which could cause artefacts in either modality, are eliminated. Here we describe a preliminary evaluation of the system, which is essentially a microPET Focus-120 located in a 1T split magnet, and compare its performance to previous microPET instruments.

T2*-weighted MRI versus oxygen extraction fraction PET in acute stroke.

BACKGROUND: Mapping high oxygen extraction fraction (OEF) in acute stroke is of considerable interest to depict the at-risk tissue. Being sensitive to deoxyhemoglobin, T2*-weighted MRI has been suggested as a potential marker of high OEF. METHODS: We compared T2*-weighted images from pre-contrast arrival perfusion scans against quantitative positron emission tomography in 5 patients studied 7-21 h after onset of carotid territory stroke. OEF and T2* signal were obtained in the voxels with significantly high OEF. RESULTS: All patients showed increased OEF. No significant relationship between OEF and T2*-weighted signal was found either within or between subjects. CONCLUSION: We found no indication that T2*-weighted MRI in the way implemented in this investigation was sensitive to high OEF in acute stroke.

Use of magnetic resonance imaging for anatomical phenotyping of the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is a fatal, inherited neurodegenerative CAG disorder characterized by marked brain atrophy. We used magnetic resonance imaging (MRI) with manual volumetry for three dimensional (3D) morphological phenotyping of ex vivo brains of R6/2 mice, the most commonly used model of HD. High resolution 3D images were acquired for 18 week old wild-type (WT) and R6/2 mice. Although overall brain volumes were the same between genotypes, decreases in volumes were found in the cortex and striatum of R6/2 mice, with significant volume increases in the lateral ventricles and globus pallidus. There was no change in the volume of the amygdala, internal capsule or hippocampal formation. There was a significant increase in signal intensity in the globus pallidus, amygdala, cortex and striatum in R6/2 mice that may reflect neuronal atrophy. This study clearly shows the potential of MRI for morphological phenotyping of rodent models of HD and other neurological diseases. Having obtained proof-of-principle for the technique using ex vivo tissue, it is now our intention to carry out in vivo measurement of developing pathology in HD transgenic mice, and correlate this with behavioral deficits.

Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry.

The R6/2 mouse is the most common mouse model used for Huntington's disease (HD), a fatal, inherited neurodegenerative CAG disorder characterized by marked brain atrophy. We scanned 47 R6/2 transgenic and 42 wildtype (WT) ex vivo mouse brains at 18 weeks of age using high resolution, three-dimensional magnetic resonance imaging (MRI) for automated voxel-based morphometry (VBM) analysis. We found differences between genotypes in specific brain structures. Many of these changes were bilateral and were found in regions known to be involved in the behavioral deficits present in both R6/2 mice and HD patients. In particular, changes were evident in the basal ganglia, hippocampus, cortex and hypothalamus. In the striatum, changes were heterogenous and reminiscent of striosomal distribution. Changes were also seen in the cerebellum, as might be expected in a mouse carrying a repeat length typical of juvenile onset HD. Many of these changes were not detected by manual 2D morphometry from the same MR images. These data indicate that VBM will be a valuable technique for in vivo measurement of developing pathology in HD transgenic mice, and may be particularly useful for correlating histologically undetectable changes with behavioral deficits.

Mapping the involvement of BA 4a and 4p during Motor Imagery.

Motor Imagery (MI) is an attractive but intriguing means to access the motor network. There are marked inconsistencies in the functional imaging literature regarding the degree, extent and distribution of the primary motor cortex (BA 4) involvement during MI as compared to Executed Movement (EM), which may in part be related to the diverse role of BA 4 and its two subdivisions (i.e., 4a and 4p) in motor processes as well as to methodological issues. Here we used fMRI with monitoring of compliance to show that in healthy volunteers optimally screened for their ability to perform MI the contralateral BA 4 is involved during MI of a finger opposition sequence (2, 3, 4, 5; paced at 1 Hz), albeit less than during EM of the same sequence, and in a location sparing the hand area. Furthermore, both 4a and 4p subdivisions were found to be involved in MI, but the relative involvement of BA 4p appeared more robust and closer to that seen with EM. We suggest that during MI the role of BA 4 and its subdivisions may be non-executive, perhaps related to spatial encoding, though clearly further studies are needed. Finally, we report a similar hemispheric activation balance within BA 4 with both tasks, which extends the commonalities between EM and MI.

Analysis of acute traumatic axonal injury using diffusion tensor imaging.

Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity following traumatic brain injury (TBI), but is poorly characterized by conventional imaging techniques. Diffusion tensor imaging (DTI) may provide better detection as well as insights into the mechanisms of white matter injury. DTI data from 33 patients with moderate-to-severe TBI, acquired at a median of 32 h postinjury, were compared with data from 28 age-matched controls. The global burden of whole brain white matter injury (GB(WMI)) was quantified by measuring the proportion of voxels that lay below a critical fractional anisotropy (FA) threshold, identified from control data. Mechanisms of change in FA maps were explored using an Eigenvalue analysis of the diffusion tensor. When compared with controls, patients showed significantly reduced mean FA (p < 0.001) and increased apparent diffusion coefficient (ADC; p = 0.017). GB(WMI) was significantly greater in patients than in controls (p < 0.01), but did not distinguish patients with obvious white matter lesions seen on structural imaging. It predicted classification of DTI images as head injury with a high degree of accuracy. Eigenvalue analysis showed that reductions in FA were predominantly the result of increases in radial diffusivity (p < 0.001). DTI may help quantify the overall burden of white matter injury in TBI and provide insights into underlying pathophysiology. Eigenvalue analysis suggests that the early imaging changes seen in white matter are consistent with axonal swelling rather than axonal truncation. This technique holds promise for examining disease progression, and may help define therapeutic windows for the treatment of diffuse brain injury.

Improved delineation of glioma margins and regions of infiltration with the use of diffusion tensor imaging: an image-guided biopsy study.

BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of treatment for malignant gliomas, is limited by our inability to accurately determine tumor margins. As a result, despite recent advances, the prognosis remains appalling. Because gliomas preferentially infiltrate along white matter tracks, methods that show white matter disruption should improve this delineation. In this study, results of histologic examination from samples obtained from image-guided brain biopsies were correlated with diffusion tensor images. METHODS: Twenty patients requiring image-guided biopsies for presumed gliomas were imaged preoperatively. Patients underwent image-guided biopsies with multiple biopsies taken along a single track that went into normal-appearing brain. Regions of interest were determined from the sites of the biopsies, and diffusion tensor imaging findings were compared with glioma histology. RESULTS: Using diffusion tissue signatures, it was possible to differentiate gross tumor (reduction of the anisotropic component, q > 12% from contralateral region), from tumor infiltration (increase in the isotropic component, p > 10% from contralateral region). This technique has a sensitivity of 98% and specificity of 81%. T2-weighted abnormalities failed to identify the margin in half of all specimens. CONCLUSION: Diffusion tensor imaging can better delineate the tumor margin in gliomas. Such techniques can improve the delineation of the radiation therapy target volume for gliomas and potentially can direct local therapies for tumor infiltration.

Development of a combined microPET-MR system.

As evidenced by the success of PET-CT, there are many benefits from combining imaging modalities into a single scanner. The combination of PET and MR offers potential advantages over PET-CT, including improved soft tissue contrast, access to the multiplicity of contrast mechanisms available to MR, simultaneous imaging and fast MR sequences for motion correction. In addition, PET-MR is more suitable than PET-CT for cancer screening due to the elimination of the radiation dose from CT. A key issue associated with combining PET and MR is the fact that the performance of the photomultiplier tubes (PMTs) used in conventional PET detectors is degraded in the magnetic field required for MR. Two approaches have been adopted to circumvent that issue: retention of conventional, magnetic field-sensitive PMT-based PET detectors by modification of other features of the MR or PET system, or the use of new, magnetic field-insensitive devices in the PET detectors including avalanche photo-diodes (APDs) and silicon photomultipliers (SiPMs). Taking the former approach, we are assembling a modified microPET Focus 120 within a gap in a novel, 1T superconducting magnet. The PMTs are located in a low magnetic field (approximately 30mT) through a combination of magnet design and the use of fiber optic 'bundles'. Two main features of the modified PET system have been tested, namely the effect of using long fiber optic bundles in the PET detector, and the impact of magnetic field upon the performance of the position sensitive PMTs. The design of a modified microPET-MR system for small animal imaging is completed, and assembly and testing is underway.

Does healthy aging affect the hemispheric activation balance during paced index-to-thumb opposition task? An fMRI study.

Normal aging is generally associated with declining performance in cognitive and fine motor tasks. Previous functional imaging studies have been inconsistent regarding the effect of aging on primary motor cortex (M1) activation during finger movement, showing increased, unchanged or decreased activation contralaterally, and more consistently increased activation ipsilaterally. Furthermore, no study has addressed the effect of age on M1 hemispheric activation balance. We studied 18 optimally healthy right-handed subjects, age range 18-79 years (mean +/- SD: 47 +/- 17) using 3 T fMRI and right index finger-thumb tapping auditory-paced at 1.25 Hz. The weighted Laterality Index (wLI) for M1 was obtained according to Fernandez et al. (2001) [Fernandez, G., de Greiff, A., von Oertzen, J., Reuber, M., Lun, S., Klaver, P., et al. 2001. Language mapping in less than 15 min: real-time functional MRI during routine clinical investigation. Neuroimage 14 585-594], with some modifications. The wLI, as well as the total activation on each side, were assessed against age using non-parametric correlation. There was a highly significant negative correlation between age and wLI such that the older the subjects, the lower the wLI. Furthermore, there was a highly significant positive correlation between total activation for ipsilateral M1 and age, and a nearly significant trend for contralateral M1. This study documents that during execution of a simple paced motor task, the older the subject the less lateralized the M1 activation balance as a result of increasing amount of activation on both sides, more significantly so ipsilaterally. Thus, in aging, enhanced M1 recruitment bilaterally is required to produce the same motor performance, suggesting a compensatory process. These findings are in line with cognitive studies indicating a tendency for the aging brain to reduce its functional lateralization, perhaps from less efficient transcallosal connections.

Diffusion tensor imaging of benign intracranial hypertension: absence of cerebral oedema.

Cerebral oedema, it has been suggested, may have a role in the pathophysiology of benign intracranial hypertension (BIH). We applied diffusion tensor MR imaging (DTI), a technique able to detect cerebral oedema, to the study of patients with BIH. A quantitative regional analysis of diffusion parameters (trace and relative anisotropy) was conducted by comparing five BIH patients and six healthy controls. A small but significant increase in anisotropy accompanied by a small but significant decrease in trace was found in the putamen and head of the caudate nucleus. No significant changes were demonstrated in the thalamus, cerebral white matter or cortical regions. Our findings support other recent work that suggests cerebral oedema is not a factor in the pathogenesis of BIH.

Enhanced visualization and quantification of magnetic resonance diffusion tensor imaging using the p:q tensor decomposition.

Many scalar measures have been proposed to quantify magnetic resonance diffusion tensor imaging (MR DTI) data in the brain. However, only two parameters are commonly used in the literature: mean diffusion (D) and fractional anisotropy (FA). We introduce a visualization technique which permits the simultaneous analysis of an additional five scalar measures. This enhanced diversity is important, as it is not known a priori which of these measures best describes pathological changes for brain tissue. The proposed technique is based on a tensor transformation, which decomposes the diffusion tensor into its isotropic (p) and anisotropic (q) components. To illustrate the use of this technique, diffusion tensor imaging was performed on a healthy volunteer, a sequential study in a patient with recent stroke, a patient with hydrocephalus and a patient with an intracranial tumour. Our results demonstrate a clear distinction between different anatomical regions in the normal volunteer and the evolution of the pathology in the patients. In the normal volunteer, the brain parenchyma values for p and q fell into a narrow band with 0.976

Metallic neurosurgical implants for cranial reconstruction and fixation: assessment of magnetic field interactions, heating and artefacts at 3.0 Tesla.

The objective of this study was to evaluate the magnetic resonance imaging (MRI) compatibility of metallic neurosurgical implants commonly used for cranial reconstruction and fixation, in association with a 3.0 Tesla (T) MR system. Ten metallic neurosurgical implants used for cranioplasty operations were evaluated. The implants were tested ex vivo for magnetic field interactions (translational attraction and torque), heating (using saline and gel phantoms), and artefact production [using dual echo spin echo (DSE) and gradient echo (GRE) sequences] at 3.0 Tesla. None of the implants displayed translational attraction or torque, and heating was physiologically insignificant (maximal temperature elevation was 0.5 degrees C). MR artefacts were minimal with spin echo sequences; gradient echo sequences produced much larger artefacts. The neurosurgical implants evaluated in this study should not present a risk to patients undergoing MRI in the 3.0 T MR system. Although the implants do produce susceptibility artefacts, especially with gradient echo sequences, useful imaging should still be possible.

Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury.

Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral blood flow (CBF) and cerebral oxygen utilization (CMRO(2)) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with (15)O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO(2) and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO(2) and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO(2) and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 mumol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, Mann-Whitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO(2) threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.

Imaging of cerebral blood flow and metabolism in brain injury in the ICU.

The heterogeneity of the initial insult and subsequent pathophysiology has made both the study of human head injury and design of randomised controlled trials exceptionally difficult. The combination of multimodality bedside monitoring and functional brain imaging positron emission tomography (PET) and magnetic resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides the resource required to study critically ill patients after brain injury from initial ictus through recovery from coma and rehabilitation to final outcome. Methods to define cerebral ischemia in the context of altered cerebral oxidative metabolism have been developed, traditional therapies for intracranial hypertension re-evaluated and bedside monitors cross-validated. New modelling and analytical approaches have been developed.

Evaluation of an MRI-based protocol for cell implantation in four patients with Huntington's disease.

The purpose of this study was to evaluate our surgical protocol for the preparation and delivery of suspensions of fetal tissue into the diseased human brain. We implanted suspensions of human fetal striatal anlage into the right caudate and putamen of four patients with Huntington's disease. Postoperative 3 tesla MR imaging confirmed accurate graft placement. Variability in graft survival was noted and the MR signal changes over 6 months revealed persistent hyperintense signal on T2-weighted images. Our results are consistent with those described by other groups and indicate that our surgical protocol is safe, accurate, and reproducible.

Stereotactic MR imaging for planning neural transplantation: a reliable technique at 3 Tesla?

The purpose of this study was to assess the accuracy of high field (3 Tesla) MR in target localization for stem cell transplantation. Three patients with Huntington's disease were imaged with a stereotactic frame in place for both MRI and CT. Quality assurance procedures and manual shimming were performed before each MRI study to minimize image distortion. The images were fused using multi-modality rigid body image registration software. Image fusion demonstrated the MR images to be in agreement with CT to within 1.5 mm, as assessed by measuring the coordinates of markers on the frame and on the shape and size of the lateral ventricles. Target coordinates for transplantation were selected from the MR images. Postoperative imaging confirmed accurate graft placement.

Serial MRI, functional recovery, and long-term infarct maturation in a non-human primate model of stroke.

We have examined the effects of permanent middle cerebral artery occlusion (pMCAO) in marmoset monkeys over 5 months, using behavioural and magnetic resonance imaging (MRI) techniques. Three marmosets were trained on behavioural tests before pMCAO. Shortly after surgery, these marmosets were scanned with T2-weighted (T2W) and diffusion-weighted (DW) MRI. Three, 10 and 20 weeks after surgery, these marmosets were re-tested on the behavioural tasks and had further MRI sessions to monitor lesion development. This was followed by histological analysis. All these marmosets had a persistent contralesional motor deficit and a spatial neglect which resolved over the 20 weeks of testing. Percentage infarct volume assessed by MRI on the day of surgery and at 20 weeks matched the percentage infarct volume measured histologically at 20 weeks. However, the apparent infarct size at 3 weeks was considerably less than that measured by histological analysis or that measured at the other MRI time points. Additional histological analysis of the brains of two further marmosets removed 3 weeks after pMCAO found considerable infiltration by lipid filled macrophages into the ischaemic zone which may have caused an MRI "fogging" effect leading to an apparent reduction in infarct volume.

Influence of baseline hematocrit on between-subject BOLD signal change using gradient echo and asymmetric spin echo EPI.

The dependence of BOLD signal change (BSC) on baseline hematocrit is in the process of being characterized, primarily using conventional Gradient Echo (GE) echo planar imaging (EPI). We describe the first empiric exploration of this relationship using, in addition to GE, Spin Echo (SE) and two Asymmetric Spin Echo EPI sequences (ASE10 and ASE20), which are less susceptible to large vessel noise. Motor cortex BSC was measured (N = 17) and regressed against hematocrit and hemoglobin concentration using linear and non-linear functions. GE measurements of BSC yielded a positive linear relationship (r(2) = 0.240, p = 0.0459) whereas a positive non-linear relationship was observed using ASE10 (r(2) = 0.571, p = 0.0146). Results suggest that between-subjects BSC is significantly dependent on baseline hematocrit. The nature of dependence, and implications for quantitative studies vary with the vessel size selectivity of the imaging sequence, and with the effect of hematocrit on blood viscosity in the imaged vessels.