Deep Gray Matter Structures Research Articles

Human brain atlas for automated region of interest selection in quantitative susceptibility mapping: Application to determine iron content in deep gray matter structures

The purpose of this paper is to extend the single-subject Eve atlas from Johns Hopkins University, which currently contains diffusion tensor and T1-weighted anatomical maps, by including contrast based on quantitative susceptibility mapping. The new atlas combines a “deep gray matter parcellation map” (DGMPM) derived from a single-subject quantitative susceptibility map with the previously established “white matter parcellation map” (WMPM) from the same subject's T1-weighted and diffusion tensor imaging data into an MNI coordinate map named the “Everything Parcellation Map in Eve Space,” also known as the “EvePM.” It allows automated segmentation of gray matter and white matter structures. Quantitative susceptibility maps from five healthy male volunteers (30 to 33years of age) were coregistered to the Eve Atlas with AIR and Large Deformation Diffeomorphic Metric Mapping (LDDMM), and the transformation matrices were applied to the EvePM to produce automated parcellation in subject space. Parcellation accuracy was measured with a kappa analysis for the left and right structures of six deep gray matter regions. For multi-orientation QSM images, the Kappa statistic was 0.85 between automated and manual segmentation, with the inter-rater reproducibility Kappa being 0.89 for the human raters, suggesting “almost perfect” agreement between all segmentation methods. Segmentation seemed slightly more difficult for human raters on single-orientation QSM images, with the Kappa statistic being 0.88 between automated and manual segmentation, and 0.85 and 0.86 between human raters. Overall, this atlas provides a time-efficient tool for automated coregistration and segmentation of quantitative susceptibility data to analyze many regions of interest. These data were used to establish a baseline for normal magnetic susceptibility measurements for over 60 brain structures of 30- to 33-year-old males. Correlating the average susceptibility with age-based iron concentrations in gray matter structures measured by Hallgren and Sourander (1958) allowed interpolation of the average iron concentration of several deep gray matter regions delineated in the EvePM.

Effect of Age on MRI Phase Behavior in the Subcortical Deep Gray Matter of Healthy Individuals

It has been demonstrated that increased levels of iron in the brain occur with aging. In this study we investigated the nature of the association between age and SWI-filtered phase values, indicative of iron content, in the subcortical deep gray matter of healthy individuals. A total of 210 healthy individuals (men: n = 89, women: n = 121), mean age, 39.8 years (standard deviation = 15.5; range = 6-76 years), were imaged on a 3T scanner. Mean MRI phase, mean phase of low-phase voxels, and normalized volumes were determined for total subcortical deep gray matter, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus, hippocampus, amygdala, nucleus accumbens, red nucleus, and substantia nigra. Linear and nonlinear regression models were used to explore the relationship between phase and volume measures, and aging. Mean phase values of subcortical deep gray matter structures showed a quadratic relationship, with individuals in late middle age (40-59 years) having the lowest mean phase values, followed by a reversal of this trend in the elderly. In contrast, mean phase of low-phase voxel measurements showed strong negative linear relationships with aging. Significantly lower phase values were detected in women compared with men (P < .001), whereas no sex differences were observed for mean phase of low-phase voxels. Normalized volume measurements were also linearly related to aging, and women showed smaller normalized volumes of subcortical deep gray matter structures than men (P < .001). Lower mean phase of low-phase voxels was related to decreased volume measures. A strong association between phase (quadratic effect; phase decreases are followed by increases), mean phase of low-phase voxels (linear effect), volume (linear effect), and age was observed. Low phase was related to brain atrophy.

Multicenter mapping in the healthy brain

The R2* relaxation rate constant has been suggested as a sensitive measure for iron accumulation. The aim of this multi-center study was to assess the inter-scanner and inter-subject variability of R2* mapping and to investigate the relationship between brain volume and R2* in specific structures. R2* mapping was performed in 81 healthy subjects in seven centers using different 3 T systems. R2* was calculated from a dual-echo gradient echo sequence and was assessed in several deep gray matter structures. The inter-scanner and inter-subject variability of R2* was calculated by means of the coefficient of variation before and after correcting for age. Significant center effects were seen in some regions which get lost after age correction. The coefficient of variation for the inter-center variability was much lower (<5.6%) than for the intra-subject variability (6.7%-11.7%). R2* in the putamen and red nucleus scaled with cortical volume while R2* in the globus pallidus and the substantia nigra was negatively associated with white matter volume. R2* is a robust and reproducible measure in a multicenter setting provided that a standardized MRI protocol is used. The relationship between iron concentration in deep gray matter and volume of specific brain compartments needs further investigation.

Toluene Dependency, Psychosis, and Cerebellar Syndrome

Back to table of contents Previous article Next article LettersFull AccessToluene Dependency, Psychosis, and Cerebellar SyndromeMohd Fadzli Mohd Isa, M.B.B.S., Norzaini Rose Mohd Zain, M.Med., F.R.C.R., Francesco Gaillard, M.Med., FRANZCR, and Kok-Yoon Chee, M.D., M.Med.Mohd Fadzli Mohd IsaSearch for more papers by this author, M.B.B.S., Norzaini Rose Mohd ZainSearch for more papers by this author, M.Med., F.R.C.R., Francesco GaillardSearch for more papers by this author, M.Med., FRANZCR, and Kok-Yoon CheeSearch for more papers by this author, M.D., M.Med.Published Online:1 Apr 2013https://doi.org/10.1176/appi.neuropsych.12050111AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We report on a 22-year-old man who has a 9-year history of glue-sniffing that evolved into a full-blown picture of psychological dependency that was characterized by craving and tolerance, which was subsequently followed by agitation, irritability, and physical struggle. It gradually ended with period of low mood, lack of motivation, and social withdrawal. The disturbance was punctuated by episodes of florid psychosis during intoxication, which included visual hallucination and disorganized behavior. After 6 years of chronic glue-sniffing, there was an insidious onset of bilateral, low-frequency intention tremors involving the upper limbs that gradually worsened and was accompanied by unstable gait, stuttering of speech, and blurring of vision. There was no history to suggest seizure disorder or any infection of the central nervous system. There was a 1-year delay before presentation to medical services due to shame and guilt feelings about coming out of the house because of the physical problems. Mental state examination (MSE) revealed presence of scanning speech and impairment of abstract thinking. He scored 26/30 on Mini-Mental State Exam (MMSE). He had bilateral, persistent, horizontal, pendular nystagmus, and bilateral intention tremors of the hands, broad-based gait, past pointing and dysdiadokinesia of the upper limbs, which were more prominent on the right side. Further examination revealed optic atrophy of the right eye, but sensorimotor functions were normal, and muscle wasting was absent.Blood and urine biochemistry that included measurements of serum lactate and ceruloplasmin were negative, as was the screening for other commonly abused substances. Magnetic resonance imaging (MRI) of the brain demonstrated extensive increased T2 signal in the white matter extending from the centrum semiovale, down the posterior limb of the internal capsule, and through the anterolateral pons, as well as the white matter of the cerebellar hemispheres (Figure 1). Low signal is seen in the deep gray-matter structures, particularly involving the thalami, globus pallidi, and dentate nuclei, as well as the red nuclei and substantia nigra (Figure 2). Widespread cerebral and cerebellar volume loss is also present, with marked thinning of the corpus callosum, without T2 signal change.FIGURE 1. There was extensive increased T2 signal in the white matter, extending from the centrum semiovale, down the posterior limb of the internal capsule, and through the anterolateral pons, as well as the white matter of the cerebellar hemispheres.FIGURE 2. Low signal is seen in the deep gray-matter structures, particularly involving the thalami, globus pallidi, and dentate nuclei, as well as the red nuclei and substantia nigra.T: thalamus; SN: substantia nigra; RN: red nuclei; DN: dentate nuclei; GP: globus pallidus.Treatment was initiated with propranolol 40 mg bid. This was discontinued after 3 months because of lack of efficacy, and he was started on treatment with amantadine 100 mg nightly, primidone 250 mg nightly, and supplemented with thiamine. Despite 6 months of the above treatments, there has been no improvement. He continues to sniff glue, albeit at a much lower frequency and amount.Peripheral neuropathy, cerebellar dysfunction, cranial nerve damage, cortical atrophy, encephalopathy, and dementia have all been attributed to result from prolonged and heavy exposure to inhalants.1,2 N-hexane and toluene adhere to lipid-laden myelin sheaths and neuronal membranes to start the demyelinating process.3 Cerebellar damage due to toluene was first reported three decades ago, and it commonly presents with tremors and ataxia, which correlate to the extent of sulci enlargement.1Dept. of Psychiatry and Mental Health, Hospital Kuala Lumpur, MalaysiaDept. of Diagnostic Imaging, Hospital Kuala Lumpur, MalaysiaDept. of Radiology, Royal Melbourne Hospital, AustraliaCorrespondence: Dr. Kok-Yoon Chee; e-mail: [email protected]comReferences1 Fornazzari L, Wilkinson DA, Kapur BM, et al.: Cerebellar, cortical, and functional impairment in toluene abusers. Acta Neurol Scand 1983; 67:319–329Crossref, Medline, Google Scholar2 Maruff P, Burns CB, Tyler P, et al.: Neurological and cognitive abnormalities associated with chronic petrol sniffing. Brain 1998; 121:1903–1917Crossref, Medline, Google Scholar3 Lolin Y: Chronic neurological toxicity associated with exposure to volatile substances. Hum Toxicol 1989; 8:293–300Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByDrugs of abuse and ocular effects15 March 2021 | Clinical and Experimental Optometry, Vol. 104, No. 5Schizophrenia Research, Vol. 201The American Journal on Addictions, Vol. 27, No. 8Psychopharmacology, Vol. 232, No. 17Toluene related leukoencephalopathy15 March 2012 Volume 25Issue 2 Spring 2013Pages E42-E43 Metrics PDF download History Published online 1 April 2013 Published in print 1 April 2013

Iron accumulation in multiple sclerosis: an early pathogenic event

Evaluation of: Al-Radaideh AM, Wharton SJ, Lim SY et al. Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in clinically isolated syndrome. Mult. Scler. doi:10.1177/1352458512465135 (2012) (Epub ahead of print).Iron has been shown to accumulate in deep gray matter structures in many forms of multiple sclerosis (MS), but detecting its presence early in the disease course (e.g., clinically isolated syndrome [CIS]) has been less clear. Here, we review a recent study where MRI scanning at 7 T together with susceptibility mapping was performed to assess iron deposition in CIS and control subjects. Susceptibility indicative of iron deposition was found to be increased in the globus pallidus, caudate, putamen and pulvinar of CIS patients compared with controls. The findings suggest that iron deposition is a pathological change that occurs early in the development of MS. Identifying the mechanisms of iron accumulation and determining whether iron promotes pathogenesis in MS are important areas of future research.

Microglia Activation in Clinically Isolated Syndrome: 11C11195PK-PET Change within Normal Appearing White Matter and Deep Grey Matter Structures (P06.109)

Microglia Activation in Clinically Isolated Syndrome: 11C11195PK-PET Change within Normal Appearing White Matter and Deep Grey Matter Structures (P06.109)

Subcortical structural abnormalities in juvenile myoclonic epilepsy (JME): MR volumetry and vertex based analysis

PurposeImaging studies in juvenile myoclonic epilepsy (JME) have shown abnormalities of the thalamus and frontal cortex. The purpose of this study was to systematically investigate the morphological changes in the deep gray matter (GM) structures using techniques of voxel based morphometry (VBM), MR volumetry and shape analysis. MethodologyThe study included 40 patients with JME (M:F=21:19; age 22.8±5.3 years) and 19 matched controls (M:F=13:6; age 24.5±4.2 years). All subjects underwent MRI using standard protocol that included T1-3D TFE (Turbo Field Echo) images with 1mm thickness. VBM analysis and MR volumetry were performed. The volumes of deep subcortical GM structures were extracted and vertex-wise shape analysis was performed using FSL-FIRST (FSL-Integrated Registration and Segmentation Toolbox) software. ResultsVBM analysis with a thalamic mask revealed focal thalamic alterations in the anteromedial aspect of the thalamus (p<0.05, false discovery rate (FDR) corrected) which remained significant after adjusting for age, gender and intracranial volume (ICV). Significant volume loss was noted in both the thalami. Vertex-wise shape analysis showed significant focal surface reductions in the thalami bilaterally in patients that were predominantly seen in the medial as well as lateral aspects of the thalamus (p<0.05, FDR corrected). The disease duration correlated with left hippocampus volume while age of onset correlated with right hippocampus volume. ConclusionsThis study confirms the presence of thalamic alterations in patients with JME. Shape analysis technique provided complementary information and disclosed the presence of focal atrophic changes in patients’ thalami. The striatum and hippocampus did not show any significant alterations.

Anatomical patterns and correlated MRI findings of non-perinatal hypoxic–ischaemic encephalopathy

Non-perinatal hypoxic-ischaemic encephalopathy (HIE) has varying anatomical patterns dependent on the type of insult, the degree and duration of cerebral hypoxia, or presence and degree of hypoperfusion. Profound insults can affect the entire cerebral cortex or just the perirolandic cortex, the cerebellum and the deep grey matter structures. Less severe insults may affect only the watershed regions. The objective of this article is to review the anatomical patterns of non-perinatal HIEs by MRI.

Patterns of Dysgraphia in Primary Progressive Aphasia Compared to Post-Stroke Aphasia

We report patterns of dysgraphia in participants with primary progressive aphasia that can be explained by assuming disruption of one or more cognitive processes or representations in the complex process of spelling. These patterns are compared to those described in participants with focal lesions (stroke). Using structural imaging techniques, we found that damage to the left extrasylvian regions, including the uncinate, inferior fronto-occipital fasciculus, and sagittal stratum (including geniculostriate pathway and inferior longitudinal fasciculus), as well as other deep white and grey matter structures, was significantly associated with impairments in access to orthographic word forms and semantics (with reliance on phonology-to-orthography to produce a plausible spelling in the spelling to dictation task). These results contribute not only to our understanding of the patterns of dysgraphia following acquired brain damage but also the neural substrates underlying spelling.

Patterns of dysgraphia in primary progressive aphasia compared to post-stroke aphasia.

We report patterns of dysgraphia in participants with primary progressive aphasia that can be explained by assuming disruption of one or more cognitive processes or representations in the complex process of spelling. These patterns are compared to those described in participants with focal lesions (stroke). Using structural imaging techniques, we found that damage to the left extrasylvian regions, including the uncinate, inferior fronto-occipital fasciculus, and sagittal stratum (including geniculostriate pathway and inferior longitudinal fasciculus), as well as other deep white and grey matter structures, was significantly associated with impairments in access to orthographic word forms and semantics (with reliance on phonology-to-orthography to produce a plausible spelling in the spelling to dictation task). These results contribute not only to our understanding of the patterns of dysgraphia following acquired brain damage but also the neural substrates underlying spelling.

Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride

Neurodegeneration is the main cause for permanent disability in multiple sclerosis. The effect of current immunomodulatory treatments on neurodegeneration is insufficient. Therefore, direct neuroprotection and myeloprotection remain an important therapeutic goal. Targeting acid-sensing ion channel 1 (encoded by the ASIC1 gene), which contributes to the excessive intracellular accumulation of injurious Na(+) and Ca(2+) and is over-expressed in acute multiple sclerosis lesions, appears to be a viable strategy to limit cellular injury that is the substrate of neurodegeneration. While blockade of ASIC1 through amiloride, a potassium sparing diuretic that is currently licensed for hypertension and congestive cardiac failure, showed neuroprotective and myeloprotective effects in experimental models of multiple sclerosis, this strategy remains untested in patients with multiple sclerosis. In this translational study, we tested the neuroprotective effects of amiloride in patients with primary progressive multiple sclerosis. First, we assessed ASIC1 expression in chronic brain lesions from post-mortem of patients with progressive multiple sclerosis to identify the target process for neuroprotection. Second, we tested the neuroprotective effect of amiloride in a cohort of 14 patients with primary progressive multiple sclerosis using magnetic resonance imaging markers of neurodegeneration as outcome measures of neuroprotection. Patients with primary progressive multiple sclerosis underwent serial magnetic resonance imaging scans before (pretreatment phase) and during (treatment phase) amiloride treatment for a period of 3 years. Whole-brain volume and tissue integrity were measured with high-resolution T(1)-weighted and diffusion tensor imaging. In chronic brain lesions of patients with progressive multiple sclerosis, we demonstrate an increased expression of ASIC1 in axons and an association with injury markers within chronic inactive lesions. In patients with primary progressive multiple sclerosis, we observed a significant reduction in normalized annual rate of whole-brain volume during the treatment phase, compared with the pretreatment phase (P = 0.018, corrected). Consistent with this reduction, we showed that changes in diffusion indices of tissue damage within major clinically relevant white matter (corpus callosum and corticospinal tract) and deep grey matter (thalamus) structures were significantly reduced during the treatment phase (P = 0.02, corrected). Our results extend evidence of the contribution of ASIC1 to neurodegeneration in multiple sclerosis and suggest that amiloride may exert neuroprotective effects in patients with progressive multiple sclerosis. This pilot study is the first translational study on neuroprotection targeting ASIC1 and supports future randomized controlled trials measuring neuroprotection with amiloride in patients with multiple sclerosis.

Evolution of Hypoxic–Ischemic Injury

A 21-year-old man had pulseless electrical activity (PEA) arrest after cocaine overdose. Resuscitation initiated 40 minutes after the arrest led to a perfusing rhythm after 20 minutes. He remained comatose. Hypothermia was not instituted. Magnetic resonance imaging of the brain revealed symmetric reduced diffusivity and abnormal T2 hyperintensity in the cortex and deep gray matter structures, stigmata of hypoxic–ischemic injury portending poor prognosis (Figure 1A–C).1 After 28 months in a persistent vegetative state, he was reevaluated for tremulous activity, ultimately found to be rigors caused by urosepsis. Computed tomography of the head at that time demonstrated the dramatic evolution of his severe hypoxic–ischemic injury, a rarely seen phenomenon (Figure 1D–F). Figure 1. Axial diffusion weighted (A), apparent diffusion coefficient (B), and fluid-attenuated inversion recovery (C) magnetic resonance images demonstrate diffuse cytotoxic edema. Axial (D, E) and coronal (F) computed tomography reveal widespread parenchymal ...

Subcortical Volumetric Reductions in Adult Niemann-Pick Disease Type C: A Cross-Sectional Study

Voxel-based analysis has suggested that deep gray matter rather than cortical regions is initially affected in adult Niemann-Pick type C. We sought to examine a range of deep gray matter structures in adults with NPC and relate these to clinical variables. Ten adult patients with NPC (18-49 years of age) were compared with 27 age- and sex-matched controls, and subcortical structures were automatically segmented from normalized T1-weighted MR images. Absolute volumes (in cubic millimeters) were generated for a range of deep gray matter structures and were compared between groups and correlated with illness variables. Most structures were smaller in patients with NPC compared with controls. The thalamus, hippocampus, and striatum showed the greatest and most significant reductions, and left hippocampal volume correlated with symptom score and cognition. Vertex analysis of the thalamus, hippocampus, and caudate implicated regions involved in memory, executive function, and motor control. Thalamic and hippocampal reductions may underpin the memory and executive deficits seen in adult NPC. Volume losses in other subcortical regions may also be involved in the characteristic range of motor, psychiatric, and cognitive deficits seen in the disease.

Cognitive Impairment and Its Relation to Imaging Measures in Multiple Sclerosis: A Study Using a Computerized Battery

Cognitive impairment (CI) is an important component of multiple sclerosis (MS) disability. A complex biological interplay between white matter (WM) and gray matter (GM) disease likely sustains CI. This study aims to address this issue by exploring the association between the extent of normal WM and GM disease and CI. Cognitive function of 24 MS patients and 24 healthy volunteers (HVs) was studied using the Automated Neuropsychological Assessment Metrics (ANAM) battery. WM focal lesions and normal appearing WM (NAWM) volume in patients, cortical thickness (CTh) and deep GM structure volumes in both patients and HVs were measured by high field strength (3.0-Tesla; 3T) imaging. An analysis of covariance showed that patients performed worse than HVs on Code Substitution Delayed Memory (P = .04) and Procedural Reaction Time (P = .05) indicative of reduced performance in memory, cognitive flexibility, and processing speed. A summary score (Index of Cognitive Efficiency) indicating global test battery performance was also lower for the patient group (P = .04). Significant associations, as determined by the Spearman rank correlation tests, were noted between each of these 3 cognitive scores and measures of NAWM volume [CDD-TP1(r = .609; P = .0035), PRO-TP1 (r = .456; P = .029) and ICE (r = .489; P = .0129)], CTh (r = .5; P ≤ .05) and volume of subcortical normal appearing GM (NAGM) structures (r = .4; P≤ .04), but not WM lesions. Both NAWM and NAGM volumes are related to CI in MS. The results highlight once again the urgent need to develop pharmacological strategies protecting patients from widespread neurodegeneration as possible preventive strategies of CI development.

Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study

BackgroundMacro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two.Methods40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean-, radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others.ResultsMacrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05).ConclusionThe highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects.

Reduced Hippocampal Volume in Healthy Young ApoE4 Carriers: An MRI Study

The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer's disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20–38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB's Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4−), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties.

Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in Clinically Isolated Syndrome

Objective: To determine, using ultra-high field magnetic resonance imaging (MRI), whether changes in iron content occur in the earliest phases of demyelinating disease, by quantifying the magnetic susceptibility of deep grey matter structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive of multiple sclerosis (MS), as compared with age-matched healthy subjects. Methods: We compared 19 CIS patients to 20 age-matched, healthy controls. Scanning of the study subjects was performed on a 7T Philips Achieva system, using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were first high-pass filtered, using a dipole fitting method, and then inverted to produce magnetic susceptibility maps. Region of interest (ROI) analysis was used to estimate magnetic susceptibility values for deep grey matter structures (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar). Results: Significantly increased relative susceptibilities were found in the CIS group, compared with controls, for the caudate nucleus (p = < 0.01), putamen (p < 0.01), globus pallidus (p < 0.01) and pulvinar (p < 0.05). We found no significant nor consistent trends in the relationship between susceptibility and age for either the study controls or CIS patients, in any ROI (r 2 < 0.5; p > 0.05). In CIS patients, the time elapsed since the clinical event and the Expanded Disability Status Scale (EDSS) scores were not correlated with iron levels in any ROI (r 2 < 0.5; p > 0.05); however, a moderate correlation (r 2 = 0.3; p < 0.01) was found between the T1 lesion load and the mean susceptibility of the caudate nucleus. Conclusion: CIS patients showed an increased iron accumulation, as measured using susceptibility mapping of the deep grey matter, suggesting that iron changes did occur at the earlier stages of CIS disease.

Subcortical structures in progressive supranuclear palsy: vertex‐based analysis

To study the abnormalities of deep grey matter (GM) structures in patients with progressive supranuclear palsy (PSP) using MR volumetry and shape analysis techniques. Twenty-eight patients with PSP and 25 matched controls (all were right handed) were evaluated using standard clinical scales. MRI was performed on a 3 tesla MRI scanner using standard protocol which included T1-3D Turbo Field-Echo images with 1-mm slice thickness. The volumes of GM and white matter, total brain and the deep subcortical GM structures, including hippocampus, amygdala, caudate, putamen, globus pallidus and thalamus were extracted using a fully automated tool. Univariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences. Shape analysis was also performed using automated software with age, sex and total brain volume as covariates of no interest in the statistical design at P<0.05 (FDR corrected). The patients with PSP had significantly lower volumes of bilateral thalami, hippocampus, pallidum and brainstem. Shape analysis of GM structures showed significant surface reduction in bilateral thalami and head of right caudate nucleus. MR volumetry showed abnormalities of various deep GM structures. Shape analysis also revealed focal surface contractions in multiple subcortical structures. Our study highlights the usefulness of this novel technique in detecting abnormalities of deep GM structures.

222 Brain Volumetry in Infants with Congenital Heart Disease: pre- and Post-Surgery Assessments Compared to Healthy Controls

Background and aimsMRI studies in neonates with congenital heart disease (CHD) have demonstrated delayed brain maturation and mostly focal brain injury. To better define the distribution of cerebral injuries and...

Toward in vivo histology: A comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2⁎-imaging at ultra-high magnetic field strength

Quantitative magnetic susceptibility mapping (QSM) has recently been introduced to provide a novel quantitative and local MRI contrast. However, the anatomical contrast represented by in vivo susceptibility maps has not yet been compared systematically and comprehensively with gradient (recalled) echo (GRE) magnitude, frequency, and R(2)(*) images. Therefore, this study compares high-resolution quantitative susceptibility maps with conventional GRE imaging approaches (magnitude, frequency, R(2)(*)) in healthy individuals at 7 T with respect to anatomic tissue contrast. Volumes-of-interest were analyzed in deep and cortical gray matter (GM) as well as in white matter (WM) on R(2)(*) and susceptibility maps. High-resolution magnetic susceptibility maps of the human brain exhibited superb contrast that allowed the identification of substructures of the thalamus, midbrain and basal ganglia, as well as of the cerebral cortex. These were consistent with histology but not generally visible on magnitude, frequency or R(2)(*)-maps. Common target structures for deep brain stimulation, including substantia nigra pars reticulata, ventral intermediate nucleus, subthalamic nucleus, and the substructure of the internal globus pallidus, were clearly distinguishable from surrounding tissue on magnetic susceptibility maps. The laminar substructure of the cortical GM differed depending on the anatomical region, i.e., a cortical layer with increased magnetic susceptibility, corresponding to the Stria of Gennari, was found in the GM of the primary visual cortex, V1, whereas a layer with reduced magnetic susceptibility was observed in the GM of the temporal cortex. Both magnetic susceptibility and R(2)(*) values differed substantially in cortical GM depending on the anatomic regions. Regression analysis between magnetic susceptibility and R(2)(*) values of WM and GM structures suggested that variations in myelin content cause the overall contrast between gray and white matter on susceptibility maps and that both R(2)(*) and susceptibility values provide linear measures for iron content in GM. In conclusion, quantitative magnetic susceptibility mapping provides a non-invasive and spatially specific contrast that opens the door to the assessment of diseases characterized by variation in iron and/or myelin concentrations. Its ability to reflect anatomy of deep GM structures with superb delineation may be useful for neurosurgical applications.