Analysis of brain and spinal MRI measures in a common domain to investigate directional neurodegeneration in motor neuron disease.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back. METHODS: In this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z-scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z-scores, with gradients hypothesised to represent directionality of neurodegeneration. RESULTS: At group-level, z-scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient - 0.24, [95% CI - 0.62, 0.14], p = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p < 0.001), and between C5 and C6 cord levels (0.98, [95% CI 0.58, 1.38], p < 0.001). DISCUSSION: Analysis of brain and cervical spinal MRI data in a common domain enabled investigation of pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, and requires further investigation in larger cohorts.

Reduced vitamin D levels in painful diabetic peripheral neuropathy.

AIM: Recent studies have reported an association between low vitamin D levels and diabetic peripheral neuropathy. However, many of these did not differentiate between people with painful diabetic peripheral neuropathy and those with painless diabetic peripheral neuropathy, or assess major confounding factors including sunlight exposure and daily activity. Our study addressed these limitations and evaluated vitamin D levels in people with carefully phenotyped diabetic peripheral neuropathy and controls. METHODS: Forty-five white Europeans with Type 2 diabetes and 14 healthy volunteers underwent clinical and neurophysiological assessments. People with Type 2 diabetes were then divided into three groups (17 with painful diabetic peripheral neuropathy, 14 with painless diabetic peripheral neuropathy and 14 with no diabetic peripheral neuropathy). All had seasonal sunlight exposure and daily activity measured, underwent a lower limb skin biopsy and had 25-hydroxyvitamin D measured during the summer months, July to September. RESULTS: After adjusting for age, BMI, activity score and sunlight exposure, 25-hydroxyvitamin D levels (nmol/l) (se) were significantly lower in people with painful diabetic peripheral neuropathy [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05 (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to assess the impact of seven independent variables on painful diabetic peripheral neuropathy. Vitamin D was the only independent variable to make a statistically significant contribution to the model with an inverted odds ratio of 1.11. Lower 25-hydroxyvitamin D levels also correlated with lower cold detection thresholds (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01). CONCLUSIONS: We have demonstrated a significant difference in 25-hydroxyvitamin D levels in well-characterized people with painful diabetic peripheral neuropathy, while accounting for the main confounding factors. This suggests a possible role for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy. Further prospective and intervention trials are required to prove causality between low vitamin D levels and painful diabetic peripheral neuropathy.

Motion artifacts in standard clinical setting obscure disease-specific differences in quantitative susceptibility mapping.

As quantitative susceptibility mapping (QSM) is maturing, more clinical applications are being explored. With this comes the question whether QSM is sufficiently robust and reproducible to be directly used in a clinical setting where patients are possibly not cooperative and/or unable to suppress involuntary movements sufficiently. Twenty-nine patients with Alzheimer's disease, 31 patients with mild cognitive impairment and 41 healthy controls were scanned on a 3 T scanner, including a multi-echo gradient-echo sequence for QSM and an inversion-prepared segmented gradient-echo sequence (T1-TFE, MPRAGE). The severity of motion artifacts (excessive/strong/noticeable/invisible) was categorized via visual inspection by two independent raters. Quantitative susceptibility was reconstructed using 'joint background-field removal and segmentation-enhanced dipole inversion', based on segmented subcortical gray-matter regions, as well as using 'morphology enabled dipole inversion'. Statistical analysis of the susceptibility maps was performed per region. A large fraction of the data showed motion artifacts, visible in both magnitude images and susceptibility maps. No statistically significant susceptibility differences were found between groups including motion-affected data. Considering only subjects without visible motion, significant susceptibility differences were observed in caudate nucleus as well as in putamen. Motion-effects can obscure statistically significant differences in QSM between patients and controls. Additional measures to restrict and/or compensate for subject motion should be taken for QSM in standard clinical settings to avoid risk of false findings.

MR spectroscopy and atrophy in Gluten, Friedreich's and SCA6 ataxias.

BACKGROUND: Previous work using proton MR spectroscopy ((1)H-MRS) of the cerebellum in the ataxias suggested that (1)H-MRS abnormalities and atrophy do not necessarily occur concurrently. AIMS: To investigate the spectroscopic features of different types of ataxias. METHODS: Using a clinical MR system operating at 1.5T, we performed (1)H-MRS with a single voxel placed over the right dentate nucleus in 22 patients with gluten ataxia (GA), six patients with Friedreich's ataxia (FA), six patients with spinocerebellar ataxia type 6 (SCA6) and 21 healthy volunteers. Atrophy of the vermis and hemispheres on standard MRI was rated by a neuroradiologist. Any interaction between atrophy and (1)H-MRS was analysed for the three groups of patients and controls. RESULTS: Patients with GA had significant atrophy of the vermis and hemispheres as well as abnormal (1)H-MRS. Patients with SCA6 had more severe overall atrophy of the vermis and hemispheres, but relatively preserved N-acetyl-aspartate/creatine (NAA/Cr). The FA group showed significant atrophy of only the superior vermis with normal (1)H-MRS. CONCLUSIONS: This study suggests that (1)H-MRS of the cerebellum in patients with ataxia provides information in addition to the presence of atrophy. There are significant (1)H-MRS differences amongst different types of ataxia with interesting correlations between atrophy and NAA/Cr.

Magnetic resonance for assessment of axillary lymph node status in early breast cancer: a systematic review and meta-analysis.

INTRODUCTION: Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients. METHODS: Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard. RESULTS: Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78-96%; range 65-100%) and mean specificity 90% (95% CI: 75-96%; range 54-100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61-100%) and mean specificity 96% (95% CI: 72-100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78-94%) and mean specificity 73% (95% CI: 63-81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38-86%) and specificity 100% (95% CI: 69-100%). CONCLUSIONS: USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary lymph node metastases in early breast cancer: systematic review and economic evaluation.

BACKGROUND: Breast cancer is the most common type of cancer in women. Evaluation of axillary lymph node metastases is important for breast cancer staging and treatment planning. OBJECTIVES: To evaluate the diagnostic accuracy, cost-effectiveness and effect on patient outcomes of positron emission tomography (PET), with or without computed tomography (CT), and magnetic resonance imaging (MRI) in the evaluation of axillary lymph node metastases in patients with newly diagnosed early-stage breast cancer. DATA SOURCES: A systematic review of literature and an economic evaluation were carried out. Key databases (including MEDLINE, EMBASE and nine others) plus research registers and conference proceedings were searched for relevant studies up to April 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK. REVIEW METHODS: One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. Discrepancies were resolved by discussion. Quality of included studies was assessed using the quality assessment of diagnostic accuracy studies (QUADAS) checklist, applied by one reviewer and checked by a second. RESULTS: Forty-five citations relating to 35 studies were included in the clinical effectiveness review: 26 studies of PET and nine studies of MRI. Two studies were included in the cost-effectiveness review: one of PET and one of MRI. Of the seven studies evaluating PET/CT (n = 862), the mean sensitivity was 56% [95% confidence interval (CI) 44% to 67%] and mean specificity 96% (95% CI 90% to 99%). Of the 19 studies evaluating PET only (n = 1729), the mean sensitivity was 66% (95% CI 50% to 79%) and mean specificity 93% (95% CI 89% to 96%). PET performed less well for small metastases; the mean sensitivity was 11% (95% CI 5% to 22%) for micrometastases (≤ 2 mm; five studies; n = 63), and 57% (95% CI 47% to 66%) for macrometastases (> 2 mm; four studies; n = 111). The smallest metastatic nodes detected by PET measured 3 mm, while PET failed to detect some nodes measuring > 15 mm. Studies in which all patients were clinically node negative showed a trend towards lower sensitivity of PET compared with studies with a mixed population. Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), the mean sensitivity was 98% (95% CI 61% to 100%) and mean specificity 96% (95% CI 72% to 100%). Across three studies of gadolinium-enhanced MRI (n = 187), the mean sensitivity was 88% (95% CI 78% to 94%) and mean specificity 73% (95% CI 63% to 81%). In the single study of in vivo proton magnetic resonance spectroscopy (n = 27), the sensitivity was 65% (95% CI 38% to 86%) and specificity 100% (95% CI 69% to 100%). USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity than gadolinium-enhanced MRI. Results of the decision modelling suggest that the MRI replacement strategy is the most cost-effective strategy and dominates the baseline 4-node sampling (4-NS) and sentinel lymph node biopsy (SLNB) strategies in most sensitivity analyses undertaken. The PET replacement strategy is not as robust as the MRI replacement strategy, as its cost-effectiveness is significantly affected by the utility decrement for lymphoedema and the probability of relapse for false-negative (FN) patients. LIMITATIONS: No included studies directly compared PET and MRI. CONCLUSIONS: Studies demonstrated that PET and MRI have lower sensitivity and specificity than SLNB and 4-NS but are associated with fewer adverse events. Included studies indicated a significantly higher mean sensitivity for MRI than for PET, with USPIO-enhanced MRI providing the highest sensitivity. However, sensitivity and specificity of PET and MRI varied widely between studies, and MRI studies were relatively small and varied in their methods; therefore, results should be interpreted with caution. Decision modelling based on these results suggests that the most cost-effective strategy may be MRI rather than SLNB or 4-NS. This strategy reduces costs and increases quality-adjusted life-years (QALYs) because there are fewer adverse events for the majority of patients. However, this strategy leads to more FN cases at higher risk of cancer recurrence and more false- positive (FP) cases who would undergo unnecessary axillary lymph node dissection. Adding MRI prior to SLNB or 4-NS has little effect on QALYs, though this analysis is limited by lack of available data. Future research should include large, well-conducted studies of MRI, particularly using USPIO; data on the long-term impacts of lymphoedema on cost and patient utility; studies of the comparative effectiveness and cost-effectiveness of SLNB and 4-NS; and more robust UK cost data for 4-NS and SLNB as well as the cost of MRI and PET techniques. FUNDING: This study was funded by the Health Technology Assessment programme of the National Institute of Health Research.

Positron emission tomography (PET) for assessment of axillary lymph node status in early breast cancer: A systematic review and meta-analysis.

PURPOSE: Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are used to assess axillary nodal status in breast cancer, but are invasive procedures associated with morbidity, including lymphoedema. This systematic review evaluates the diagnostic accuracy of positron emission tomography (PET), with or without computed tomography (CT), for assessment of axillary nodes in early breast cancer. METHODS: Eleven databases including MEDLINE, EMBASE and the Cochrane Library, plus research registers and conference proceedings, were searched in April 2009. Study quality was assessed using the QUality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. Sensitivity and specificity were meta-analysed using a bivariate random effects approach. RESULTS: Across 26 studies evaluating PET or PET/CT (n = 2591 patients), mean sensitivity was 63% (95% CI: 52-74%; range 20-100%) and mean specificity 94% (95% CI: 91-96%; range 75-100%). Across 7 studies of PET/CT (n = 862), mean sensitivity was 56% (95% CI: 44-67%) and mean specificity 96% (90-99%). Across 19 studies of PET-only (n = 1729), mean sensitivity was 66% (50-79%) and mean specificity 93% (89-96%). Mean sensitivity was 11% (5-22%) for micrometastases (≤2 mm; five studies; n = 63), and 57% (47-66%) for macrometastases (>2 mm; four studies; n = 111). CONCLUSIONS: PET had lower sensitivity and specificity than SLNB. Therefore, replacing SLNB with PET would avoid the adverse effects of SLNB, but lead to more false negative patients at risk of recurrence and more false positive patients undergoing unnecessary ALND. The present evidence does not support the routine use of PET or PET-CT for the assessment of the clinically negative axilla.

The Anatomy of the Medial Lemniscus within the Brainstem Demonstrated at 3 Tesla with High Resolution Fat Suppressed T1-Weighted Images and Diffusion Tensor Imaging.

The medial lemniscus is part of the main somatosensory pathways ascending within the brainstem. It is formed by the heavily myelinated axons of the second order neurones of the dorsal column nuclei. This pathway ascends through the rostral medulla, pons and mesencephalon to finally terminate by synapsing with third order neurones in the ventral posterior nucleus of the thalamus. The medial lemniscus conveys proprioception and fine tactile discrimination as part of the somatosensory system. Conventional MRI studies of the brainstem have been relatively poor in demonstrating these fibre pathways. Diffusion tensor imaging and tractography may demostrated fibre pathways in the brainstem. These techniques do however suffer from relatively poor spatial resolution and some degree of image distortion - especially if based on echo planar imaging techniques. Knowledge of the anatomical relationships of the medial lemniscus is important for the understanding of clinical manifestations of disease processes affecting the somatosensory pathways and also to demonstrate important adjacent structures. Specifically, the pedunculopontine nucleus (PPN) lies in close anatomical relationship to the medial lemniscus and the decussation of the superior cerebellar peduncle. This nucleus is a promising target for deep brain stimulator placement for alleviation of non-dopamine responsive dystonias. Six healthy male volunteers (mean age 33 years) were imaged at 3 Tesla. Imaging protocols consisted of thin section, high resolution, fat suppressed T1-weighted sequences as well as thin section, high isotropic resolution diffusion tensor imaging (DTI), which was analysed to generate colour fractional anisotropy (FA) maps. These were correlated with the fat suppressed T1 weighted images. In all volunteers the medial lemniscus was seen as a pair of bands of low signal on axial, high resolution, fat suppressed T1-weighted images. They were indentified through the upper medulla, pons and mesencephalon. They correlated well with the head to foot orientated fibres on the colour FA maps generated from the DTI data. This study of normal volunteers has illustrated the value of high resolution, fat suppressed T1-weighted images in demonstrating the anatomy of the heavily myelinated medial lemniscus within the brainstem. These high resolution images with good spatial accuracy can potentially be used to aid the localisation of other nuclei, such as the PPN.

The state of tranquility: subjective perception is shaped by contextual modulation of auditory connectivity.

In this study, we investigated brain mechanisms for the generation of subjective experience from objective sensory inputs. Our experimental construct was subjective tranquility. Tranquility is a mental state more likely to occur in the presence of objective sensory inputs that arise from natural features in the environment. We used functional magnetic resonance imaging to examine the neural response to scenes that were visually distinct (beach images vs. freeway images) and experienced as tranquil (beach) or non-tranquil (freeway). Both sets of scenes had the same auditory component because waves breaking on a beach and vehicles moving on a freeway can produce similar auditory spectral and temporal characteristics, perceived as a constant roar. Compared with scenes experienced as non-tranquil, we found that subjectively tranquil scenes were associated with significantly greater effective connectivity between the auditory cortex and medial prefrontal cortex, a region implicated in the evaluation of mental states. Similarly enhanced connectivity was also observed between the auditory cortex and posterior cingulate gyrus, temporoparietal cortex and thalamus. These findings demonstrate that visual context can modulate connectivity of the auditory cortex with regions implicated in the generation of subjective states. Importantly, this effect arises under conditions of identical auditory input. Hence, the same sound may be associated with different percepts reflecting varying connectivity between the auditory cortex and other brain regions. This suggests that subjective experience is more closely linked to the connectivity state of the auditory cortex than to its basic sensory inputs.

Corpus callosum morphology and microstructure assessed using structural MR imaging and diffusion tensor imaging: initial findings in adults with neurofibromatosis type 1.

BACKGROUND AND PURPOSE: Imaging studies have shown that children with NF-1 have increased brain volumes compared with age-matched controls and the CCs are disproportionately large. The purpose of this study was to determine if the CC in adults with NF-1 differed from that in matched controls by using DTI and volumetric imaging. MATERIALS AND METHODS: MR imaging with DTI was performed in 10 adults with NF-1 and in 10 age-, sex-, and handedness-matched controls by using a 3T system. Total brain volumes and the areas and central lengths of the CC were calculated, along with the radial width of callosal subdivisions, in the 2 groups. RESULTS: Our results showed that the total brain volume was not significantly different between adults with NF-1 and matched controls. The length and total cross-sectional area of the CC were statistically larger in adults with NF-1 compared with controls (approximately 10% longer and 20% greater area). On DTI we found a preservation of the primary eigenvalue with increases in the minor eigenvalues at the genu. CONCLUSIONS: We have shown that the increased size of the CC found in children with NF-1 is also present in adults with the syndrome, whereas no difference in total brain volume was found.

The high incidence and bioethics of findings on magnetic resonance brain imaging of normal volunteers for neuroscience research.

BACKGROUND: We were finding volunteers for functional magnetic resonance imaging studies with abnormalities requiring referral surprisingly frequently. The bioethics surrounding the incidental findings are not straightforward and every imaging institution will encounter this situation in their normal volunteers. Yet the implications for the individuals involved may be profound. Should all participants have review of their imaging by an expert and who should be informed? METHODS: The normal volunteers that were imaged with magnetic resonance (MR) which were reviewed by a consultant neuroradiologist. All participants completed a volunteer consent form in addition to a standard departmental MR safety screening form. The volunteer screening form requires the general practitioner details to be completed and asks the participant to consider closely the possibility and implications of finding an unexpected but potentially serious abnormality before signing. RESULTS: 525 different individuals were scanned as normal volunteers, the mean age was 35-years and 330 were males. Of these 525, 46 had definite significant abnormalities (8.8%), mean age 50-years. CONCLUSION: We have found a high rate of incidental abnormalities amongst individuals participating in imaging studies at our institution. It is our current practice to inform the research study participant of the findings, counsel them and inform their primary care physician. We think that it is advisable for researchers utilising MR imaging of the brain to have access to trained neuroradiologists, a protocol in place to deal with this problem and take consent in a way that allows the participant to realise the possibility of an abnormal finding.

Thalamic neuronal dysfunction and chronic sensorimotor distal symmetrical polyneuropathy in patients with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Although clear peripheral nerve pathological abnormalities have been demonstrated in diabetic peripheral neuropathy (DPN), there is little information with regard to brain involvement. Our aim was to use in vivo proton magnetic resonance specroscopy (H-MRS) in patients with DPN in order to assess the neuro-chemical status of the thalamus, which acts as the gateway to the brain for somatosensory information. METHODS: Participants included 18 type 1 diabetic men (eight without DPN, ten with DPN) and six non-diabetic healthy volunteers, who all underwent detailed clinical and neurophysiological assessments yielding a Neuropathy Composite Score (NCS) derived from Neuropathy Impairment Score of the Lower Limbs plus seven tests of nerve function prior to investigation via a single-voxel H-MRS technique, which was used to sample ventral posterior thalamic parenchyma. Spectroscopic resonances including those due to N-acetyl aspartate (NAA) were assessed at both short and long echo-time, providing putative indicators of neuronal function and integrity, respectively. RESULTS: At long echo-time we observed significantly lower NAA:creatine (p = 0.04) and NAA:choline (p = 0.02) ratios in DPN patients than in the other groups. No group differences were detected at short echo-time. We found a significant positive association between both sural amplitude (rho = 0.61, p = 0.004) and nerve conduction velocity (r = 0.58, p = 0.006) and NAA:creatine signal among participants with diabetes. Vibration detection threshold (rho = -0.70, p = 0.004) was significantly related to NAA:choline ratio. Heart rate variability with deep breathing (rho = -0.46, p = 0.05) and NCS (rho = -0.53, p = 0.03) were significantly related to NAA:creatine ratio. CONCLUSIONS/INTERPRETATION: The significantly lower NAA:creatine ratio in DPN is suggestive of thalamic neuronal dysfunction, while the lack of difference in short echo-time between the groups does not suggest neuronal loss. Taken together with the observed correlations between NAA and neurophysiological assessments, these findings provide evidence for thalamic neuronal involvement in DPN.

Comparison of manual direct and automated indirect measurement of hippocampus using magnetic resonance imaging.

PURPOSE: Objective quantification of brain structure can aid diagnosis and therapeutic monitoring in several neuropsychiatric disorders. In this study, we aimed to compare direct and indirect quantification approaches for hippocampal formation changes in patients with mild cognitive impairment and Alzheimer's disease (AD). METHODS AND MATERIALS: Twenty-one healthy volunteers (mean age: 66.2), 21 patients with mild cognitive impairment (mean age: 66.6), and 10 patients with AD (mean age: 65.1) were enrolled. All subjects underwent extensive neuropsychological testing and were imaged at 1.5T (Vision, Siemens, Germany; T1w coronal TR=4 ms, Flip=13 degrees , FOV=250 mm, Matrix=256 x 256, 128 contiguous slices, 1.8mm). Direct measurement of the hippocampal formation was performed on coronal slices using a standardized protocol, while indirect temporal horn volume (THV) was calculated using a watershed algorithm-based software package (MeVis, Germany). Manual tracing took about 30 min, semi-automated measurement less than 3 min time. RESULTS: Successful direct and indirect quantification was performed in all subjects. A significant volume difference was found between controls and AD patients (p<0.001) with both the manual and the semi-automated approach. Group analysis showed a slight but not significant decrease of hippocampal volume and increase in temporal horn volume (THV) for subjects with mild cognitive impairment compared to volunteers (p<0.07). A significant correlation (p<0.001) of direct and indirect measurement was found. CONCLUSION: The presented indirect approach for hippocampus volumetry is equivalent to the direct approach and offers the advantages of observer independency, time reduction and thus usefulness for clinical routine.

Magnetic resonance perfusion imaging in malformations of cortical development.

BACKGROUND: Malformations of cortical development vary in neuronal maturity and level of functioning. PURPOSE: To characterize regional relative cerebral blood volume (rCBV) and difference in first moment transit time (TTfm) in polymicrogyria and cortical tubers using magnetic resonance (MR) perfusion imaging. MATERIAL AND METHODS: MR imaging and dynamic T2*-weighted MR perfusion imaging were performed in 13 patients with tuberous sclerosis complex, 10 with polymicrogyria, and 18 controls with developmental delay but no macroscopic brain abnormality. Regions of interest were placed in cortical tubers or polymicrogyric cortex and in the contralateral normal-appearing side in patients with malformations. In "control" subjects, regions of interest were placed in the frontal and parietal lobes in both hemispheres. The rCBV and TTfm of the tuber/contralateral side (rCBV(R)TSC and DeltaTT(FM)TSC) as well as those of the polymicrogyria/contralateral side (rCBV(R)PMG and DeltaTT(FM)PMG) were assessed. The right-to-left asymmetry of rCBV and TTfm in the control group was also assessed (rCBV(R)Controls and DeltaTT(FM)Controls). RESULTS: There was no significant asymmetry between right and left rCBV or TTfm (P>0.05) in controls. There was significant reduction in rCBV(R)TSC compared to rCBV(R)Controls (P<0.05), but no significant difference in DeltaTT(FM)TSC compared to DeltaTT(FM)Controls (P>0.05). There were no significant differences between rCBV(R)PMG and rCBV(R)Controls (P>0.05) or DeltaTT(FM)PMG and DeltaTT(FM)Controls (P>0.05). CONCLUSION: Our findings imply that cerebral blood volume of polymicrogyria is similar to normal cortex, but there is reduced cerebral blood volume in cortical tubers. The lower rCBV ratio of cortical tubers may be related to known differences in pathogenetic timing of the underlying abnormalities during brain development or the presence of gliosis.

Proton spectroscopy and imaging at 3T in ataxia-telangiectasia.

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with characteristic neurodegeneration of the cerebellum. We used MR spectroscopy to test the hypothesis that cerebellar metabolism in A-T patients would be abnormal relative to healthy controls. METHODS: Twelve adults with A-T and 12 healthy control subjects underwent MR imaging and long-echo time (1)H-MR spectroscopy at 3T. Voxels were acquired in the region of the dentate nucleus of the cerebellum and in parietooccipital white matter, and ratios for N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were calculated. RESULTS: All of the A-T patients showed marked cerebellar atrophy of the vermis and hemispheres. Two patients showed multiple small foci of hypointensity on T2*-weighted images throughout their brain suggestive of capillary telangiectasia. A further 2 patients had single low-signal-intensity foci. One patient had a tumor, thought to be meningioma radiologically, that was not suspected clinically. No group differences were found in the cerebral spectra, but analysis of the cerebellum revealed significantly lower NAA/Cho and higher Cho/Cr ratios in the A-T patients compared with the controls. There was no difference between groups for the NAA/Cr ratio. CONCLUSION: The findings suggest increased Cho signal intensity in the cerebellum of adult A-T patients. If this finding is shown through the course of the disease, it may assist in the differentiation of early A-T from other forms of ataxia and provide a marker for monitoring treatment efficacy.

Sequential dynamic gadolinium magnetic resonance perfusion-weighted imaging: effects on transit time and cerebral blood volume measurements.

PURPOSE: To evaluate if two gadolinium perfusion studies can be performed during the same table occupancy without degradation of the derived data in the second study. MATERIAL AND METHODS: Magnetic resonance (MR) perfusion studies of the whole brain were performed on 12 patients during the administration of two gadolinium boluses separated by 8 min. In six patients, gadolinium was given as two 20-ml administrations of standard 0.5 M chelate (Magnevist), whilst the other six patients received two 10-ml administrations of 1.0 M chelate (Gadovist). RESULTS: There were no significant differences in subjective quality between the time-intensity curves of the first and second perfusion studies using either the 0.5 M or 1.0 M gadolinium chelate. The objective measurements in quality of the time-intensity curves (maximum signal change and full width at half maximum) changed by less than 5% of the original values on the second perfusion study. The first-moment mean transit times did not change significantly on the sequential studies. The regional cerebral blood volume tended to increase on the second study (by 15% on average), but this did not reach statistical significance. CONCLUSION: The results from two sequential dynamic gadolinium-based perfusion studies can be compared in a meaningful manner using the technique described.

Misrepresentation of surface rendering of pediatric brain malformations performed following spatial normalization.

PURPOSE: To evaluate the effects of spatial normalization on volume rendering in cases of pediatric brain malformation. MATERIAL AND METHODS: Three-dimensional (3D) T1-weighted volume datasets were acquired in three children, one with pachygyria, one with a Dandy-Walker malformation associated with polymicrogyria, and one with dysgenesis of the corpus callosum. On the non-normalized datasets, the skull margins were cropped and the remainder stripped with the brain extraction technique (BET). The data were also normalized into standard anatomic reference space using pediatric templates prior to the BET script. The surface constructions obtained by both techniques were then compared for geometric distortions. RESULTS: Normalization of 3D datasets resulted in significant distortions in the shape of the brain, with increased anterior-posterior dimensions and narrower transverse diameter in all three cases. In two cases, there were alterations in the appearance of the gyri and sulci, leading to a potential misinterpretation of the volume-rendered surface when the gyri and sulci were in fact normal. CONCLUSION: In pediatric brain, particularly those with congenital brain anomalies, normalization as a post-processing step should be avoided as this may lead to misrepresentation of brain morphometry.

Stereotactic radiosurgery for brain arteriovenous malformations: quantitative MR assessment of nidal response at 1 year and angiographic factors predicting early obliteration.

INTRODUCTION: We investigated the role of magnetic resonance angiography (MRA) in the early follow-up of patients after stereotactic radiosurgery (STRS) for cerebral arteriovenous malformations (AVMs) and determined the influence of individual morphological factors of AVMs in early response to treatment. METHODS: A group of 40 patients (41 AVMs) consented to a dedicated 1.5-T MR protocol 12 months after receiving STRS for a brain AVM. In addition to standard spin echo sequences, 3-D contrast-enhanced sliding interleaved Ky MRA (CE-SLINKY) and dynamic time-resolved subtraction angiography (MR-DSA) were performed. Nidal volumes were calculated using CE-SLINKY data in patients with a persisting arteriovenous shunt. Planning angiographic data was investigated in all 40 patients. The following AVM factors were used in the statistical analysis to determine their role in nidus obliteration: (1) maximum linear dimension, (2) nidal volume, (3) AVM location (4) nidal morphology, (5) venous drainage, (6) "high-flow angiographic change", (7) prior embolization, and (8) dose reduction. RESULTS: Complete nidal obliteration was found in 9 patients, 26 showed greater than 50% nidal reduction and 6 had less than 50%. Two AVM factors, venous drainage and AVM location, were found to significantly correlate with rate of obliteration. CONCLUSION: We successfully demonstrated the use of MRA to quantitatively assess the response of AVMs to STRS. Two AVM factors, venous drainage and AVM location were found to correlate with rate of obliteration prior to the application of the Bonferroni correction, but if this more rigorous statistical test was applied then none of the factors was found to be significant.

Idiopathic generalised epilepsy: a pilot study of memory and neuronal dysfunction in the temporal lobes, assessed by magnetic resonance spectroscopy.

BACKGROUND: The memory deficits in patients with temporal lobe epilepsy (TLE) are associated with epileptogenic lesions of the temporal lobes, especially hippocampal sclerosis. Memory deficits have been extensively studied in TLE, but the presence of pre-existing temporal lobe abnormality has confounded studies on the relationship between memory dysfunction and seizure activity. Idiopathic generalised epilepsy (IGE) is characterised by primary generalised seizures and is found to occur in the absence of any macroscopic brain abnormalities. IGE is therefore ideal for investigations on the effects of seizure activity on memory and cognition. AIM AND METHODS: Magnetic resonance spectroscopy (MRS) and neuropsychological testing were used to investigate the relationship between epileptic seizures, memory performance and neuronal dysfunction in the temporal lobes of a group of patients with IGE. 30 patients and 15 healthy controls participated in the study. RESULTS: Patients with IGE were found to perform worse than controls on tests of speed of information processing, general cognitive performance and a range of memory tests, including face recognition, word recognition, verbal recall and complex figure recall. The performance of the patient group on the visual recognition and verbal recall sections of the Doors and People Test was found to correlate with MRS ratios of N-acetyl aspartate:choline and N-acetyl aspartate:creatine in the temporal lobes. CONCLUSION: This result supports the hypothesis that memory deficits in epilepsy may be due to neuronal dysfunction secondary to epileptic activity itself in the absence of any macroscopic lesions in the temporal lobes.