Simultaneous intracranial EEG-fMRI in humans: protocol considerations and data quality.

We have recently performed simultaneous intracranial EEG and fMRI recordings (icEEG-fMRI) in patients with epilepsy. In this technical note, we examine limited thermometric data for potential electrode heating during our protocol and found that heating was ≤0.1 °C in-vitro at least 10 fold less than in-vivo limits. We quantify EEG quality, which can be degraded by MRI scanner-induced artefacts, and fMRI image (gradient echo echo-planar imaging: GE-EPI) signal quality around the electrodes, which can be degraded by electrode interactions with B1 (radiofrequency) and B0 (static) magnetic fields. We recorded EEG outside and within the MRI scanner with and without scanning. EEG quality was largely preserved during scanning and in particular heartbeat-related artefacts were small compared to epileptic events. To assess the GE-EPI signal reduction around the electrodes, we compared image signal intensity along paths into the brain normal to its surface originating from the individual platinum-iridium electrode contacts. GE-EPI images were obtained at 1.5 T with an echo time (TE) of 40 ms and repetition time (TR) of 3000 ms and a slice thickness of 2.5 mm. We found that GE-EPI signal intensity reduction was confined to a 10 mm radius and that it was reduced on average by less than 50% at 5mm from the electrode contacts. The GE-EPI image signal reduction also varied with electrode orientation relative to the MRI scanner axes; in particular, cortical grid contacts with a normal along the scanner's main magnetic field (B(0)) axis have higher artefact levels relative to those with a normal perpendicular to the z-axis. This suggests that the artefacts were predominantly susceptibility-related rather than due to B1 interactions. This information can be used to guide interpretation of results of icEEG-fMRI experiments proximal to the electrodes, and to optimise artefact reduction strategies.

High resolution MR anatomy of the subthalamic nucleus: imaging at 9.4 T with histological validation.

Using conventional MRI the subthalamic nucleus (STN) is not clearly defined. Our objective was to define the anatomy of the STN using 9.4 T MRI of post mortem tissue with histological validation. Spin-echo (SE) and 3D gradient-echo (GE) images were obtained at 9.4 T in 8 post mortem tissue blocks and compared directly with corresponding histological slides prepared with Luxol Fast Blue/Cresyl Violet (LFB/CV) in 4 cases and Perl stain in 3. The variability of the STN anatomy was studied using internal reference points. The anatomy of the STN and surrounding structures was demonstrated in all three anatomical planes using 9.4 T MR images in concordance with LFB/CV stained histological sections. Signal hypointensity was seen in 6/8 cases in the anterior and medial STN that corresponded with regions of more intense Perl staining. There was significant variability in the volume, shape and location of the borders of the STN. Using 9.4 T MRI, the internal signal characteristics and borders of the STN are clearly defined and significant anatomical variability is apparent. Direct visualisation of the STN is possible using high field MRI and this is particularly relevant, given its anatomical variability, for planning deep brain stimulation.

Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps.

The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B(1)) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B(1) information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two-pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot-Marie-Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within-subject and between-subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram- and region-of-interest-based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B(1) data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle.

Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies.

MRI may provide treatment outcome measures in neuromuscular conditions. The authors assessed MRI magnetisation transfer ratios (MTRs) in lower-limb musculature as markers of pathology in peripheral neuropathies and compared the findings with associated clinical data. Ten patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were compared with 10 healthy subjects. The MTR in the calf muscles was significantly lower than controls in the two patient groups (both p<0.001). The median MTRs (IQR) were 50.5(1.6) percentage units (p.u.) (control), 41.5(10.6) p.u. (CMT1A) and 39.3(8.7) p.u. (CIDP). Moreover, anterior lower leg MTR correlated strongly with strength of ankle dorsiflexion, measured with the Medical Research Council scale, in CIDP (ρ=0.88, p<0.001) and also in CMT1A (ρ=0.50, p<0.05), where MTR also showed an association with disease duration (ρ=-0.86, p<0.001). Short tau inversion recovery MRI of the same muscles showed abnormalities associated with regions of reduced MTR (p<0.001), and MTR was also reduced in other muscles otherwise deemed normal appearing (p<0.001), indicating that MTR may be more sensitive to muscle damaged by denervation than conventional MRI. The significant reductions in muscle MTR in peripheral neuropathies and the associated correlations with clinical measures indicate that MTR has potential as an imaging outcome measure in future therapeutic trials.

MRI shows increased sciatic nerve cross sectional area in inherited and inflammatory neuropathies.

Measurements of the cross sectional area of the sciatic nerve are described in a group of 10 patients with genetically confirmed Charcot-Marie-Tooth disease type 1A (CMT1A), nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 10 healthy controls using MRI. One mid-thigh of each individual was imaged using a short tau inversion recovery sequence and the nerve appearance evaluated radiologically with respect to the signal intensity and visibility of the internal neural structure. The cross sectional area of the sciatic nerve of each individual was measured by defining irregular enclosing regions of interest on the MRI images. The sciatic nerve area was enlarged in both CMT1A (p<0.001) and CIDP (p=0.008) compared with controls and in CMT1A compared with CIDP (p<0.001). Median (interquartile range) areas were 67.6 (16.2) mm(2) for the CIDP group, 135.9 (46.5) mm(2) for the CMT1A group and 43.3 (19.9) mm(2) for the control group. The critical upper value for discriminating pathologically enlarged nerves from normal controls with p<0.05 was 64.4 mm(2). Quantification of sciatic nerve hypertrophy on MRI may be of assistance in cases where the diagnosis is still in doubt, providing an objective pathological marker complimenting other clinical investigations.

FLAIR-only joint volumetric analysis of brain lesions and atrophy in clinically isolated syndrome (CIS) suggestive of multiple sclerosis.

BACKGROUND: MRI assessment in multiple sclerosis (MS) focuses on the presence of typical white matter (WM) lesions. Neurodegeneration characterised by brain atrophy is recognised in the research field as an important prognostic factor. It is not routinely reported clinically, in part due to difficulty in achieving reproducible measurements. Automated MRI quantification of WM lesions and brain volume could provide important clinical monitoring data. In general, lesion quantification relies on both T1 and FLAIR input images, while tissue volumetry relies on T1. However, T1-weighted scans are not routinely included in the clinical MS protocol, limiting the utility of automated quantification. OBJECTIVES: We address an aspect of this important translational challenge by assessing the performance of FLAIR-only lesion and brain segmentation, against a conventional approach requiring multi-contrast acquisition. We explore whether FLAIR-only grey matter (GM) segmentation yields more variability in performance compared with two-channel segmentation; whether this is related to field strength; and whether the results meet a level of clinical acceptability demonstrated by the ability to reproduce established biological associations. METHODS: We used a multicentre dataset of subjects with a CIS suggestive of MS scanned at 1.5T and 3T in the same week. WM lesions were manually segmented by two raters, 'manual 1' guided by consensus reading of CIS-specific lesions and 'manual 2' by any WM hyperintensity. An existing brain segmentation method was adapted for FLAIR-only input. Automated segmentation of WM hyperintensity and brain volumes were performed with conventional (T1/T1 + FLAIR) and FLAIR-only methods. RESULTS: WM lesion volumes were comparable at 1.5T between 'manual 2' and FLAIR-only methods and at 3T between 'manual 2', T1 + FLAIR and FLAIR-only methods. For cortical GM volume, linear regression measures between conventional and FLAIR-only segmentation were high (1.5T: α = 1.029, R2 = 0.997, standard error (SE) = 0.007; 3T: α = 1.019, R2 = 0.998, SE = 0.006). Age-associated change in cortical GM volume was a significant covariate in both T1 (p = 0.001) and FLAIR-only (p = 0.005) methods, confirming the expected relationship between age and GM volume for FLAIR-only segmentations. CONCLUSIONS: FLAIR-only automated segmentation of WM lesions and brain volumes were consistent with results obtained through conventional methods and had the ability to demonstrate biological effects in our study population. Imaging protocol harmonisation and validation with other MS phenotypes could facilitate the integration of automated WM lesion volume and brain atrophy analysis as clinical tools in radiological MS reporting.

Short-term adaptation to a simple motor task: a physiological process preserved in multiple sclerosis.

Short-term adaptation indicates the attenuation of the functional MRI (fMRI) response during repeated task execution. It is considered to be a physiological process, but it is unknown whether short-term adaptation changes significantly in patients with brain disorders, such as multiple sclerosis (MS). In order to investigate short-term adaptation during a repeated right-hand tapping task in both controls and in patients with MS, we analyzed the fMRI data collected in a large cohort of controls and MS patients who were recruited into a multi-centre European fMRI study. Four fMRI runs were acquired for each of the 55 controls and 56 MS patients at baseline and 33 controls and 26 MS patients at 1-year follow-up. The externally cued (1 Hz) right hand tapping movement was limited to 3 cm amplitude by using at all sites (7 at baseline and 6 at follow-up) identically manufactured wooden frames. No significant differences in cerebral activation were found between sites. Furthermore, our results showed linear response adaptation (i.e. reduced activation) from run 1 to run 4 (over a 25 minute period) in the primary motor area (contralateral more than ipsilateral), in the supplementary motor area and in the primary sensory cortex, sensory-motor cortex and cerebellum, bilaterally. This linear activation decay was the same in both control and patient groups, did not change between baseline and 1-year follow-up and was not influenced by the modest disease progression observed over 1 year. These findings confirm that the short-term adaptation to a simple motor task is a physiological process which is preserved in MS.

9.4 T MR microscopy of the substantia nigra with pathological validation in controls and disease.

BACKGROUND: The anatomy of the substantia nigra on conventional MRI is controversial. Even using histological techniques it is difficult to delineate with certainty from surrounding structures. We sought to define the anatomy of the SN using high field spin-echo MRI of pathological material in which we could study the anatomy in detail to corroborate our MRI findings in controls and Parkinson's disease and progressive supranuclear palsy. METHODS: 23 brains were selected from the Queen Square Brain Bank (10 controls, 8 progressive supranuclear palsy, 5 Parkinson's disease) and imaged using high field 9.4 Tesla spin-echo MRI. Subsequently brains were cut and stained with Luxol fast blue, Perls stain, and immunohistochemistry for substance P and calbindin. Once the anatomy was defined on histology the dimensions and volume of the substantia nigra were determined on high field magnetic resonance images. RESULTS: The anterior border of the substantia nigra was defined by the crus cerebri. In the medial half it was less distinct due to the deposition of iron and the interdigitation of white matter and the substantia nigra. The posterior border was flanked by white matter bridging the red nucleus and substantia nigra and seen as hypointense on spin-echo magnetic resonance images. Within the substantia nigra high signal structures corresponded to confirmed nigrosomes. These were still evident in Parkinson's disease but not in progressive supranuclear palsy. The volume and dimensions of the substantia nigra were similar in Parkinson's disease and controls, but reduced in progressive supranuclear palsy. CONCLUSIONS: We present a histologically validated anatomical description of the substantia nigra on high field spin-echo high resolution magnetic resonance images and were able to delineate all five nigrosomes. In accordance with the pathological literature we did not observe changes in the nigrosome structure as manifest by volume or signal characteristics within the substantia nigra in Parkinson's disease whereas in progressive supranuclear palsy there was microarchitectural destruction.

High field MRI correlates of myelin content and axonal density in multiple sclerosis--a post-mortem study of the spinal cord.

Different MRI techniques are used to investigate multiple sclerosis (MS) in vivo. The pathological specificity of these techniques is poorly understood, in particular their relationship to demyelination and axonal loss. The aim of this study was to evaluate the pathological substrate of high field MRI in post-mortem (PM) spinal cord (SC) of patients with MS. MRI was performed in PMSCs of four MS patients and a healthy subject on a 7 Tesla machine. Quantitative MRI maps (PD; T2; T1; magnetization transfer ratio, MTR; diffusion weighted imaging) were obtained. After scanning, the myelin content and the axonal density of the specimens were evaluated neuropathologically using quantitative techniques. Myelin content and axonal density correlated strongly with MTR, T1, PD, and diffusion anisotropy, but only moderately with T2 and weakly with the apparent diffusion coefficient. Quantitative MR measures provide a promising tool to evaluate components of MS pathology that are clinically meaningful. Further studies are warranted to investigate the potential of new quantitative MR measures to enable a distinction between axonal loss and demyelination and between demyelinated and remyelinated lesions.

Anisotropic water diffusion in white and gray matter of the neonatal piglet brain before and after transient hypoxia-ischaemia.

Measurements of tissue water apparent diffusion coefficient (ADC) performed with diffusion sensitization applied separately along the x, y, and z axes revealed significant diffusion anisotropy in both cerebral white and gray matter in six newborn (< 24 h old) piglets. Mean baseline white matter ADC for a particular region of interest was 125.8% (SD 32.0%; p < .001) greater when the diffusion gradients were applied along the y axis as compared to along the x. For the cortical gray matter region considered, the situation was reversed, the mean ADC value measured along x exceeding that along y by 15.2% (SD 6.1%; p < .01). Forty-three hours subsequent to a transient cerebral hypoxic-ischaemic insult, phosphorous MRS measurements indicated that the animals had suffered severe secondary cerebral energy failure. This was accompanied by a significant (p < .01) decrease in the white matter anisotropy, such that the mean y direction ADC now exceeded that along the x by only 70.9% (SD 29.4%; p < .03). There was no change in the gray matter anisotropy. The average of the ADC values measured in the x, y, and z directions had decreased by 35.3% (SD 18.5%; p < .01) in white matter and 31.4% (SD 21.9%; p < .05) in cortical gray matter. Diffusion anisotropy measurements may provide additional information useful in the characterisation of hypoxic-ischaemic injury in the neonatal brain, and must be considered if tissue water ADC values are to be unambiguously interpreted in this context.

Cerebral tissue water spin-spin relaxation times in human neonates at 2.4 tesla: methodology and the effects of maturation.

Using a 4-echo spin-echo sequence, cerebral T2 was measured in specific anatomic regions in eleven healthy newborn infants, whose gestational plus postnatal ages (GPAs) lay between 37 and 42 weeks. For a region in the pons, T2 was 141+/-9 ms (mean +/- standard deviation), and no significant dependence upon GPA was seen. In the thalamus mean T2 was 136+/-13 ms, and T2 demonstrated a significant negative linear dependence upon age (r = 0.690; p < 0.02). In periventricular and frontal regions, mean T2 were 217+/-33, and 228+/-32 ms respectively, and more marked negative linear correlations with age were observed (r = 0.833; p < 0.001 and r = 0.722; p < 0.02). For these regions, the rate of T2 decrease with age appeared to be related to known patterns of myelination. For the parietal region studied, mean T2 was 204+/-34 ms, no significant dependence upon GPA being seen. T2 shows promise as an objective measure of cerebral development in the perinatal period.

Pain relief for acute soft-tissue injuries.

Treating the pain that accompanies a soft-tissue sports injury sometimes requires a delicate balancing act: making the patient comfortable enough to comply with rehabilitation - or, in some instances, to return to play - without nullifying pain's protective function. The first step is to minimize swelling and related discomfort by using rest, ice, compression, and elevation immediately after injury. In the postacute stage, the patient's symptoms and activity level will guide the choice of pain-control options.

Feast or Famine: Eating Disorders in Athletes.

Losing weight to improve performance is common-even accepted-among sports competitors. When weight loss gets out of hand, though, coaches and others close to the athlete may have to intervene to help stave off a serious eating disorder.

Hypothermia Shouldn't Freeze Out Cold-Weather Athletes.

Bone-chilling cold is not a necessary ingredient for hypothermia. The deadly condition can occur in even moderately cold temperatures-unless athletes follow some simple preventive guidelines.

How Can You Tell When an Athlete Is Too Thin?

Leanness in athletes is often a natural state of being, but in some cases it can pose a long-term liability to an athlete's performance and/or overall health. The challenge to the physician is determining when leanness is or isn't a cause for clinical concern.

Playing in Pain: When Should an Athlete Stop?

Athletes sometimes need help in deciding how much pain they should endure before they taper off or quit the offending sport. A key to counseling patients about pain is to find out how it's affecting their everyday life.

Common Concerns About the Common Cold.

Intense exercise may reduce healthy athletes' immunity or open the door to serious illness in athletes who already have a cold. Generally however, your patients can safely exercise with colds-and may even feel better-if some commonsense rules are followed.

Sexual Activity and Athletic Performance: Is There a Relationship?

Sexual abstinence before an athletic event It has been advocated by crusty football coaches, Olympic athletes, and even Muhammad Ali in his prime. The truth is no one really knows how the practice got started or whether it is in the athlete's best interest, but everyone has an opinion about it.

Carboloading and Endurance: A New Look.

Some athletes remember when carboloading seemed akin to torture. Now studies show that it can be a relatively painless process and that the less rigorous form will still enhance performance. Researchers are continuing their look at this and other dietary approaches to improving endurance.