T1-weighted Volumetric Magnetic Resonance Imaging Research Articles

Changes in the volumes and asymmetry of subcortical structures in healthy individuals according to gender.

In recent years, with the development of technology, three-dimensional software has entered our lives. Volumetric measurements made with Magnetic Resonance Imaging (MRI) are essential in the morphometry of the brain and subcortical structures. In this study, we aim to share the volume and asymmetry of the hippocampus, its sub-branches, and other subcortical structures and their interaction with age/sex using volBrain, a web-based automated software.1.5T T1-weighted volumetric MRI, of 90 healthy individuals (51 females, 39 males) of both genders were included in our study. Pallidum, hippocampus, Cornu Ammonis1 (CA1), Cornu Ammonis2-3 (CA2-CA3), and Cornu Ammonis4-Dentate Gyrus (CA4-DG) measurements in females and males had a statistically higher mean in the right region (p < 0.05). In addition, females' hippocampus, CA1, CA2-CA3, and CA4-DG averages decreased more rapidly in the right region than in the left region. Subiculum measurement had a higher mean in the left region in both males and females (p < 0.05).The mean subiculum of males decreased more rapidly in the right region than in the left region. When the total values of the subcortical region in males and females were compared according to age categories, amygdala, pallidum, putamen, hippocampus, CA2-CA3, and subiculum values did not differ to gender in individuals aged 50 and over (p > 0.05). In individuals under 50years old, the mean of females was statistically lower than the mean of males (p < 0.05).The Stratum radiatum (SR), Stratum lacunosum (SL), and Stratum molecuare (SM) asymmetry values of males in the examined subcortical regions had a higher mean than females (p = 0.039). In other regions, there was no statistically asymmetrical difference (p > 0.05). Studies evaluating the volumetric analysis and asymmetry of hippocampus subbranches and other subcortical structures in adults are very limited. As a result, the morphometry of the hippocampus subbranches and other subcortical structures was examined in detail. It was determined that the structures differed according to age, gender and body side.

Longitudinal Brain Atrophy Rates in Presymptomatic Carriers of Genetic Frontotemporal Dementia.

It is important to identify at what age brain atrophy rates in genetic frontotemporal dementia (FTD) start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We investigated longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD using normative brain volumetry software. Presymptomatic GRN, MAPT, and C9orf72 pathogenic variant carriers underwent longitudinal volumetric T1-weighted magnetic resonance imaging of the brain as part of a prospective cohort study. Images were automatically analyzed with Quantib® ND, which consisted of volume measurements (CSF and sum of gray and white matter) of lobes, cerebellum, and hippocampus. All volumes were compared with reference centile curves based on a large population-derived sample of nondemented individuals (n = 4,951). Mixed-effects models were fitted to analyze atrophy rates of the different gene groups as a function of age. Thirty-four GRN, 8 MAPT, and 14 C9orf72 pathogenic variant carriers were included (mean age = 52.1, standard deviation = 7.2; 66% female). The mean follow-up duration of the study was 64 ± 33 months (median = 52; range 13-108). GRN pathogenic variant carriers showed a faster decline than the reference centile curves for all brain areas, though relative volumes remained between the 5th and 75th percentiles between the ages of 45 and 70 years. In MAPT pathogenic variant carriers, frontal lobe volume was already at the 5th percentile at age 45 years and showed a further decline between the ages 50 and 60 years. Temporal lobe volume started in the 50th percentile at age 45 years but showed fastest decline over time compared with other brain structures. Frontal, temporal, parietal, and cerebellar volume already started below the 5th percentile compared with the reference centile curves at age 45 years for C9orf72 pathogenic variant carriers, but there was minimal decline over time until the age of 60 years. We provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease tracking and staging biomarkers in genetic FTD. These techniques could help in identifying the optimal time window for starting treatment and monitoring treatment response.

The Revised Self-Monitoring Scale detects early impairment of social cognition in genetic frontotemporal dementia within the GENFI cohort

BackgroundAlthough social cognitive dysfunction is a major feature of frontotemporal dementia (FTD), it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts.MethodsWe used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. All participants underwent the standardised GENFI clinical assessment including the ‘CDR® plus NACC FTLD’ scale and RSMS. The RSMS total score and its two subscores, socioemotional expressiveness (EX score) and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis.ResultsThe RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the C9orf72 (for the total score and both subscores) and GRN (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum.ConclusionsThe RSMS indexes socioemotional impairment at an early stage of genetic FTD and may be a suitable outcome measure in forthcoming trials.

Voxel-based morphometric magnetic resonance imaging postprocessing in non-lesional pediatric epilepsy patients using pediatric normal databases.

Pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy and negative (non-lesional) magnetic resonance imaging (MRI) is particularly challenging. Focal cortical dysplasia (FCD), a frequent pathological substrate in such setting, may be subtle on MRI and evade detection. The aim of this study was to use voxel-based MRI postprocessing to improve the detection of subtle FCD in pediatric surgical candidates. A consecutive cohort of pediatric patients undergoing pre-surgical evaluation with a negative MRI by visual analysis was included. MRI postprocessing was performed using a voxel-based morphometric analysis program (MAP) on T1-weighted volumetric MRI, with comparison to an age-specific normal pediatric database. The pertinence of MAP-positive areas was confirmed by surgical outcome and pathology. A total of 78 patients were included. Forty-four patients (56%) had positive MAP regions. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome compared with the no/partial resection group (P < 0.001). Patients with no/partial resection of the MAP-positive regions had worse seizure outcomes than the MAP-negative group (P = 0.002). The MAP-positive rate was 100%, 77%, 63% and 40% in the 3-5, 5-10, 10-15 and 15-21 year age groups, respectively. MAP-positive rates were 45% in patients with temporal resection and 63% in patients with extratemporal resection. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome in the extratemporal group (P = 0.001) but not in the temporal group (P = 0.070). Our data suggest the importance of using MRI postprocessing in the pre-surgical evaluation process of pediatric epilepsy patients with apparently normal MRI.

Amygdala subnuclei are differentially affected in the different genetic and pathological forms of frontotemporal dementia

IntroductionFrontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with multiple genetic and pathological causes. It is characterized by both cortical and subcortical atrophies, with previous studies showing early involvement of the amygdala. However, no prior study has specifically investigated the atrophy of different subnuclei of the amygdala. MethodsUsing an automated segmentation tool for T1-weighted volumetric magnetic resonance imaging, we investigated amygdalar subnuclei (AS) involvement in a cohort of 132 patients with genetic or pathologically confirmed FTD (age: mean = 61 years (standard deviation = 8); disease duration: 5 (3) years) compared with 107 age-matched controls. ResultsAS were affected in all genetic and pathological forms of FTD. MAPT mutations/FTDP-17, Pick's disease, and transactive response DNA binding protein 43 kDa type C were the forms with the smallest amygdala (35%–50% smaller than controls in the most affected hemisphere, P < .0005). In most FTD groups, medial subnuclei (particularly the superficial, accessory basal and basal/paralaminar subnuclei) tended to be affected more than the lateral subnuclei, except for the progressive supranuclear palsy group, in which the corticoamygdaloid transition area was the least-affected area. DiscussionDifferential involvement of the AS was seen in the different genetic and pathological forms of FTD. In general, the most affected subnuclei were the superficial, accessory basal and basal/paralaminar subnuclei, which form part of a network of regions that control reward and emotion regulation, functions known to be particularly affected in FTD.

Tumor Surface Regularity at MR Imaging Predicts Survival and Response to Surgery in Patients with Glioblastoma.

Purpose To evaluate the prognostic and predictive value of surface-derived imaging biomarkers obtained from contrast material-enhanced volumetric T1-weighted pretreatment magnetic resonance (MR) imaging sequences in patients with glioblastoma multiforme. Materials and Methods A discovery cohort from five local institutions (165 patients; mean age, 62 years ± 12 [standard deviation]; 43% women and 57% men) and an independent validation cohort (51 patients; mean age, 60 years ± 12; 39% women and 61% men) from The Cancer Imaging Archive with volumetric T1-weighted pretreatment contrast-enhanced MR imaging sequences were included in the study. Clinical variables such as age, treatment, and survival were collected. After tumor segmentation and image processing, tumor surface regularity, measuring how much the tumor surface deviates from a sphere of the same volume, was obtained. Kaplan-Meier, Cox proportional hazards, correlations, and concordance indexes were used to compare variables and patient subgroups. Results Surface regularity was a powerful predictor of survival in the discovery (P = .005, hazard ratio [HR] = 1.61) and validation groups (P = .05, HR = 1.84). Multivariate analysis selected age and surface regularity as significant variables in a combined prognostic model (P < .001, HR = 3.05). The model achieved concordance indexes of 0.76 and 0.74 for the discovery and validation cohorts, respectively. Tumor surface regularity was a predictor of survival for patients who underwent complete resection (P = .01, HR = 1.90). Tumors with irregular surfaces did not benefit from total over subtotal resections (P = .57, HR = 1.17), but those with regular surfaces did (P = .004, HR = 2.07). Conclusion The surface regularity obtained from high-resolution contrast-enhanced pretreatment volumetric T1-weighted MR images is a predictor of survival in patients with glioblastoma. It may help in classifying patients for surgery.

Cognitive impairment in early onset epilepsy is associated with reduced left thalamic volume

ObjectiveThe objective of this study was to investigate whether reduction of thalamic volumes in children with early onset epilepsy (CWEOE) is associated with cognitive impairment. MethodsThis is a nested case–control study including a prospectively recruited cohort of 76 children with newly-diagnosed early onset epilepsy (onset <5years age) and 14 healthy controls presenting to hospitals within NHS Lothian and Fife. Quantitative volumetric analysis of subcortical structures was performed using volumetric T1-weighted magnetic resonance imaging (MRI) and correlated with the results of formal neurocognitive and clinical assessment. False discovery rate was used to correct for multiple comparisons as appropriate with q<0.05 used to define statistical significance. ResultsAge, gender, and intracranial volume (ICV)-adjusted left thalamic volumes were significantly reduced in CWEOE with cognitive impairment compared to CWEOE without impairment (5295mm3 vs 6418mm3, q=0.008) or healthy controls (5295mm3 vs 6410mm3, q<0.001). The differences in left thalamic volume remained if gray matter or cortical/cerebellar volumes were used as covariates rather than ICV (q<0.05). The degree of volume reduction correlated with the severity of cognitive impairment (q=0.048). SignificanceReduced left thalamic volume may be a biomarker for cognitive impairment in CWEOE and could help inform the need for further formal cognitive evaluations and interventions.

Cognitive reserve and TMEM106B genotype modulate brain damage in presymptomatic frontotemporal dementia: a GENFI study.

Frontotemporal dementia is a heterogeneous neurodegenerative disorder with around a third of cases having autosomal dominant inheritance. There is wide variability in phenotype even within affected families, raising questions about the determinants of the progression of disease and age at onset. It has been recently demonstrated that cognitive reserve, as measured by years of formal schooling, can counteract the ongoing pathological process. The TMEM106B genotype has also been found to be a modifier of the age at disease onset in frontotemporal dementia patients with TDP-43 pathology. This study therefore aimed to elucidate the modulating effect of environment (i.e. cognitive reserve as measured by educational attainment) and genetic background (i.e. TMEM106B polymorphism, rs1990622 T/C) on grey matter volume in a large cohort of presymptomatic subjects bearing frontotemporal dementia-related pathogenic mutations. Two hundred and thirty-one participants from the GENFI study were included: 108 presymptomatic MAPT, GRN, and C9orf72 mutation carriers and 123 non-carriers. For each subject, cortical and subcortical grey matter volumes were generated using a parcellation of the volumetric T1-weighted magnetic resonance imaging brain scan. TMEM106B genotyping was carried out, and years of education recorded. First, we obtained a composite measure of grey matter volume by graph-Laplacian principal component analysis, and then fitted a linear mixed-effect interaction model, considering the role of (i) genetic status; (ii) educational attainment; and (iii) TMEM106B genotype on grey matter volume. The presence of a mutation was associated with a lower grey matter volume (P = 0.002), even in presymptomatic subjects. Education directly affected grey matter volume in all the samples (P = 0.02) with lower education attainment being associated with lower volumes. TMEM106B genotype did not influence grey matter volume directly on its own but in mutation carriers it modulated the slope of the correlation between education and grey matter volume (P = 0.007). Together, these results indicate that brain atrophy in presymptomatic carriers of common frontotemporal dementia mutations is affected by both genetic and environmental factors such that TMEM106B enhances the benefit of cognitive reserve on brain structure. These findings should be considered in evaluating outcomes in future disease-modifying trials, and support the search for protective mechanisms in people at risk of dementia that might facilitate new therapeutic strategies.

Morphometric MRI changes in intracranial hypertension due to cerebral venous thrombosis: a retrospective imaging study

To evaluate whether some magnetic resonance imaging (MRI) signs suggesting idiopathic intracranial hypertension (IIH) could also be found in intracranial hypertension (IH) due to cerebral venous thrombosis (CVT) and to assess their possible contribution to diagnosing this disorder. Thirty-one patients with IH due to CVT were evaluated prospectively using MRI. A group of 33 age- and sex-matched healthy volunteers served as controls. The optic nerve and sheath, pituitary gland, and ventricles were assessed. The prevalence of each imaging feature was compared between the two groups. Optic nerve sheath (ONS) dilatation and decreased pituitary gland height were the most valid signs suggesting IH in CVT patients: sensitivity 70.97% and 87.1%, respectively; specificity 96.97% and 72.73%, respectively; area under the curve 0.840 and 0.809, respectively. The MRI finding that showed the strongest association with IH in CVT patients was ONS dilatation (odds ratio 78.5). The combination of T1-weighted volumetric MRI and magnetic resonance venography could be helpful for diagnosing IH with CVT. Abnormalities of the ONS and the pituitary gland were reliable diagnostic signs for IH due to CVT.

Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals.

We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures.

Volumetric alterations following severe traumatic brain injury even in the absence of focal lesions

Traumatic brain injury (TBI) frequently leads to cognitive and behavioural disorders interfering with everyday life and work, despite the absence of focal lesions on clinical images acquired after injury. The aim of this study is to use magnetic resonance imaging (MRI) to examine whether volumetric alterations measured voxel by voxel in the whole brain could explain these cognitive and behavioural disorders. Eight adults with severe TBI (GCS ≤ 8) but without focal lesions on the CT scan were included. Patients had normal intellectual abilities (PM38) but abnormal behaviour (Lhermitte's scale). These 8 patients and 17 age-matched controls performed an episodic memory task (RL-RI-16 items) as well as classical and ecological executive tasks. All participants also underwent a volumetric T1-weighted MRI at 1.5 T. Grey and white matter volumes were compared between patients and controls using the Voxel Based Morphometry (VBM5) toolbox in the Statistical Parametric Mapping (SPM) software. Patients exhibited abnormal results on both the episodic memory and executive tasks. Regarding brain volume, between-group comparisons ( P < 0.001, uncorrected for multiple comparisons, k = 200) showed significant grey matter atrophy in the cerebellum, thalami, caudate nuclei and in the right parahippocampal gyrus in patients compared with controls. White matter atrophy was found in the corpus callosum, corona radiata, fornix, midbrain and pons. The cerebral cortex was relatively spared, even in the frontal regions. Despite the absence of cerebral brain lesions on CT scans, TBI patients with behavioural disorders show episodic memory disorders and executive dysfunctions associated with grey and white matter atrophy in subcortical and cerebellar regions. Alterations of nodes and connections of the frontal-subcortical circuits (but not systematically of the frontal cortex) following severe TBI may thus explain subsequent behavioural dysexecutive disorders.

Association between idiopathic intracranial hypertension and sigmoid sinus dehiscence/diverticulum with pulsatile tinnitus: a retrospective imaging study.

The mechanism of occurrence of sigmoid sinus dehiscence/diverticulum (SSDD) in pulsatile tinnitus (PT) patients remains under debate. Its association with idiopathic intracranial hypertension (IIH) lacks evidence, which is important for therapeutic planning and improving the clinical outcome. This study aimed to evaluate the association between SSDD and IIH by comparing the prevalence of several established imaging features of IIH between PT patients with SSDD and healthy volunteers. Thirty-three unilateral PT patients with SSDD identified on CT images and 33 age- and sex-matched healthy volunteers underwent T1-weighted volumetric magnetic resonance imaging (MRI). The optic nerve, pituitary gland, transverse sinus, and ventricles were assessed. The prevalence of established IIH imaging features was compared between the two groups. Furthermore, the PT patients were divided into two subgroups: PT patients with dehiscence only and PT patients with diverticulum. The same statistical analysis was performed on each pathophysiologic entity respectively. The PT patients with SSDD showed a significantly higher prevalence of empty sella (P < 0.001), flattened posterior sclera (P = 0.001), vertical tortuosity of the optic nerve (P = 0.001), protrusion of the optic nerve (P = 0.006), transverse sinus stenosis (P = 0.011), and distension of the optic nerve sheath (P = 0.000). There were no significant differences between the PT and control groups in the maximum widths of the third and fourth ventricles and the lateral ventricle size. In contrast to controls, the imaging findings persisted in both of pathophysiologic entities, except for transverse sinus stenosis. Several IIH imaging features occur more frequently in PT patients with SSDD than in healthy individuals, which suggests a potential correlation between SSDD with PT and IIH.

Relationship Between Brain Volumetric Changes and Interim Drinking at Six Months in Alcohol‐Dependent Patients

Chronic alcohol consumption results in brain damage potentially reversible with abstinence. It is however difficult to gauge the degree of recovery of brain tissues with abstinence since changes are subtle and a significant portion of patients relapse. State-of-the-art morphometric methods are increasingly used in neuroimaging studies to detect subtle brain changes at a voxel level. Our aim was to use the most refined morphometric methods to observe in alcohol dependence the relationship between volumetric changes and interim drinking over a 6-month follow-up. Overall, 19 patients with alcohol dependence received volumetric T1-weighted magnetic resonance imaging (MRI) after detoxification. A 6-month follow-up study was then conducted, during which 11 of them received a second MRI scan. First, correlations were conducted between gray matter (GM) and white matter (WM) volumes of patients at alcohol treatment entry and the amount of alcohol consumed between treatment entry and follow-up. Second, longitudinal analyses were performed from pairs of MRI scans using tensor-based morphometry in the 11 patients, and correlations were computed between the resultant Jacobian maps of GM and WM and interim drinking. Our preliminary results showed that, among others, alcoholics with smaller thalamus at alcohol treatment entry tended to resume with heavy alcohol consumption (p<0.005uncorrected [unc.]). Our longitudinal study revealed an overall inverse relationship between recovery of brain structures like the cerebellum, striatum, and cingulate gyrus, and the amount of alcohol consumed over the 6-month follow-up (p<0.005unc.). The recovery could be observed not only with strict abstinence but also in cases of moderate resumption of alcohol consumption, when there had been no drastic relapse into alcohol dependence. Those preliminary findings indicate that the volume of the thalamus at treatment entry may have an influence on subsequent interim drinking. There is recovery of certain brain regions even when patients resume with moderate, but not drastic, alcohol consumption.

Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults

The apolipoprotein E (APOE) ε4 allele increases the risk for late-onset Alzheimer's disease (AD) and age-related cognitive decline. We investigated whether ε4 carriers show reductions in gray matter volume compared with ε4 non-carriers decades before the potential onset of AD dementia or healthy cognitive aging. Fourteen cognitively normal ε4 carriers, aged 26 to 45 years, were compared with 10 age-matched, ε4 non-carriers using T1-weighted volumetric magnetic resonance imaging (MRI) scans. All had reported first- or second-degree family histories of dementia. Group differences in gray matter were tested using voxel-based morphometry (VBM) and a multivariate model of regional covariance, the Scaled Subprofile Model (SSM). A combination of the first two SSM MRI gray matter patterns distinguished the APOE ε4 carriers from non-carriers. This combined pattern showed gray matter reductions in bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and lateral temporal cortices with covarying relative increases in cerebellum, occipital, fusiform, and hippocampal regions. With these gray matter differences occurring decades before the potential onset of dementia or cognitive aging, the results suggest longstanding, gene-associated differences in brain morphology that may lead to preferential vulnerability for the later effects of late-onset AD or healthy brain aging.

Cortical stimulation for language mapping in focal epilepsy: Correlations with tractography of the arcuate fasciculus

Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (fractional anisotropy, FA) of water diffusion and allows visualization of major white matter tracts. The arcuate fasciculus (AF) connects anterior (Broca's) and posterior (Wernicke's) language areas. We hypothesized that essential language areas identified by direct cortical stimulation would colocalize with areas revealing subcortical connectivity via the AF. Fourteen patients with pharmacoresistant left hemispheric epilepsy and left hemisphere language dominance underwent invasive evaluations for localization of epileptogenicity and functional mapping. DTI and T1-weighted volumetric magnetic resonance imaging (MRI) scans were coregistered, and subdural grid electrodes identified on postimplantation computed tomography (CT) scans were also coregistered to the MRI scans. The AF was reconstructed from a region lateral to the corona radiata on the FA map. Colocalization, defined as <1 cm between the AF and the electrode positions delineating language cortex, was visually assessed with excellent reliability (Cronbach's alpha = 0.98). A total of 71 subdural grid contacts were overlying language cortex. Nineteen contacts in eight patients were over Broca's area, 16 of which (84.2%) colocalized with the AF. Fifty-two contacts in 10 patients were over Wernicke's area, with colocalization in 29 patients (55.8%). Colocalization was significantly greater in anterior regions than in posterior regions [chi(2)(1) = 4.850, p < 0.05]. The AF, as visualized with DTI, colocalized well with anterior language areas, but less so with posterior language areas, inferring that the latter are more spatially dispersed.

MRI measures show significant cerebellar gray matter volume loss in multiple sclerosis and are associated with cerebellar dysfunction

Background Regional atrophy measures may offer useful information about the causes of specific clinical deficits in multiple sclerosis (MS). Objective To determine the magnitude of cerebellar gray and white matter (GM and WM) atrophy in patients with clinically isolated syndromes (CIS) and MS, and their role in clinical manifestations of cerebellar damage. Methods T1-weighted volumetric magnetic resonance imaging (MRI) of 73 patients [29 CIS, 33 relapsing–remitting MS (RRMS), 11 secondary progressive MS (SPMS)] was compared with 25 controls. GM and WM regions were generated using SPM5 and cerebellar regions delineated. Linear regression was used to investigate differences in tissue-specific cerebellar volumes between groups and the association with clinical measures. Results Mean cerebellar GM volume (CGMV) was 100.1 cm3 in controls, 96.4 cm3 in CIS patients, 91.8 cm3 in RRMS patients, and 88.8 cm3 in SPMS patients. Mean cerebellar WM volumes (CWMV) were 21.3 cm3, 20.4 cm3, 19.9 cm3, and 18.8 cm3, respectively. CGMV was reduced by 4.8 cm3 (P = 0.054) in RRMS patients, and 8.5 cm3 (P = 0.012) in SPMS patients, relative to controls. Only patients with SPMS showed a borderline significant reduction in CWMV compared with controls (mean 2.1 cm3, P = 0.053). CGMV was significantly smaller in patients assessed as having cerebellar dysfunction compared with patients who had normal cerebellar function. Significant associations of CGMV and CWMV with performance on the nine-hole peg test were also observed. Conclusion Clinically relevant GM atrophy occurs in the cerebellum of MS patients and is more prominent than WM atrophy. As such, it may provide complementary data to other regional atrophy and intrinsic tissue measures.

Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease

Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimer's disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T1-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimer's disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%, sensitivity 90%, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of Alzheimer's disease, these three measures demonstrated an area under the curve of 1.0. The three magnetic resonance imaging measures demonstrated significant correlations with clinical and neuropsychological assessments as well as with cerebrospinal fluid levels of tau, hyperphosphorylated tau and abeta 42 proteins. These results demonstrate that automated magnetic resonance imaging measures can serve as an in vivo surrogate for disease severity, underlying neuropathology and as a non-invasive diagnostic method for mild cognitive impairment and Alzheimer's disease.

Amygdala in Stroke/Transient Ischemic Attack Patients and Its Relationship to Cognitive Impairment and Psychopathology: The Sydney Stroke Study

To examine the structural abnormalities in the amygdala in stroke patients and see what contribution the amygdala may make to psychopathology and cognitive dysfunction related to stroke, because the amygdala has important roles in the processing of emotions, cognitive function, and psychiatric disorders. The authors assessed 47 stroke/transient ischemic attack (TIA) patients 3-6 months after the event and 54 comparison healthy subjects, using neuropsychological tests, medical and psychiatric examination and magnetic resonance imaging (MRI) brain scans. Volumetric T1-weighted MRI was used to obtain amygdala volumes by manual tracing. Stroke/TIA patients had smaller right amygdalar volume, more white matter hyperintensities (WMHs), and larger lateral ventricles. The amygdala was smaller in stroke/TIA patients with cognitive impairment compared to those without impairment. The right amygdala volume was negatively correlated with visual new learning and not related to depression, anxiety, irritability, agitation or apathy at baseline or 12-month follow-up. However, baseline amygdala volume was negatively correlated with Hamilton depression scores at 12 months in healthy comparison subjects. Hypertension and atrial fibrillation, and to a lesser extent WMHs, were predictors of amygdala volume. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment. This may partly be accounted for by hypertension, white matter lesions, and atrial fibrillation. It is not related to psychopathology except that small amygdalae may increase vulnerability to depression.

Correlations Between Apolipoprotein E ε4 Gene Dose and Whole Brain Atrophy Rates

Objective: The purpose of this study was to characterize the relationship between whole brain atrophy rates and three levels of genetic risk for Alzheimer’s disease in cognitively normal persons. The authors previously found accelerated whole brain atrophy rates in patients with probable Alzheimer’s disease by computing changes in brain volume from sequential magnetic resonance images (MRIs). Methods: The authors assessed 36 late-middle-aged persons from three genetic groups: those with two, one, and no copies of the apolipoprotein E (APOE) ε4 allele, a common Alzheimer’s disease susceptibility gene. The participants had clinical ratings, neuropsychological tests, and volumetric T1-weighted MRIs during a baseline visit and again approximately 2 years later. Two different image-analysis techniques, brain boundary shift integration and iterative principal component analysis, were used to compute whole brain atrophy rates. Results: While there were no baseline, follow-up, or between-visit differences in the clinical ratings or neuropsychological test scores among the three subject groups, whole brain atrophy rates were significantly greater in the ε4 homozygote group than in noncarriers and were significantly correlated with ε4 gene dose (i.e., the number of ε4 alleles in a person’s APOE genotype). Conclusion: Since APOE ε4 gene dose is associated with an increased risk of Alzheimer’s disease and a younger median age at dementia onset, this study suggests an association between the risk of Alzheimer’s disease and accelerated brain atrophy rates before the onset of cognitive impairment.

Correlations Between Apolipoprotein E ε4 Gene Dose and Whole Brain Atrophy Rates

The purpose of this study was to characterize the relationship between whole brain atrophy rates and three levels of genetic risk for Alzheimer's disease in cognitively normal persons. The authors previously found accelerated whole brain atrophy rates in patients with probable Alzheimer's disease by computing changes in brain volume from sequential magnetic resonance images (MRIs). The authors assessed 36 late-middle-aged persons from three genetic groups: those with two, one, and no copies of the apolipoprotein E (APOE) epsilon4 allele, a common Alzheimer's disease susceptibility gene. The participants had clinical ratings, neuropsychological tests, and volumetric T1-weighted MRIs during a baseline visit and again approximately 2 years later. Two different image-analysis techniques, brain boundary shift integration and iterative principal component analysis, were used to compute whole brain atrophy rates. While there were no baseline, follow-up, or between-visit differences in the clinical ratings or neuropsychological test scores among the three subject groups, whole brain atrophy rates were significantly greater in the epsilon4 homozygote group than in noncarriers and were significantly correlated with epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE genotype). Since APOE epsilon4 gene dose is associated with an increased risk of Alzheimer's disease and a younger median age at dementia onset, this study suggests an association between the risk of Alzheimer's disease and accelerated brain atrophy rates before the onset of cognitive impairment.