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1.
Am J Psychiatry ; : appiajp201919060583, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32046535

RESUMO

OBJECTIVE: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. METHODS: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female). RESULTS: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. CONCLUSIONS: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

2.
Addict Biol ; : e12830, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746534

RESUMO

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

3.
Psychiatry Res Neuroimaging ; 291: 1-8, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31330407

RESUMO

We aimed to investigate the relationship between striatal morphology in Huntington disease (HD) and measures of motor and cognitive dysfunction. MRI scans, from the IMAGE-HD study, were obtained from 36 individuals with pre-symptomatic HD (pre-HD), 37 with early symptomatic HD (symp-HD), and 36 healthy matched controls. The neostriatum was manually segmented and a surface-based parametric mapping protocol derived two pointwise shape measures: thickness and surface dilation ratio. Significant shape differences were detected between all groups. Negative associations were detected between lower thickness and surface area shape measure and CAG repeats, disease burden score, and UHDRS total motor score. In symp-HD, UPSIT scores were correlated with higher thickness in left caudate tail and surface dilation ratio in left posterior putamen; Stroop scores were positively correlated with the thickness of left putamen head and body. Self-paced tapping (slow) was correlated with higher thickness and surface dilation ratio in the right caudate in symp-HD and with bilateral putamen in pre-HD. Self-paced tapping (fast) was correlated with higher surface dilation ratio in the right anterior putamen in symp-HD. Shape changes correlated with functional measures subserved by corticostriatal circuits, suggesting that the neostriatum is a potentially useful structural basis for characterisation of endophenotypes of HD.

4.
J Alzheimers Dis ; 71(1): 141-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31356202

RESUMO

BACKGROUND: It is increasingly recognized that the complex functions of human cognition are not accurately represented by arbitrarily-defined anatomical brain regions. Given the considerable functional specialization within such regions, more fine-grained studies of brain structure could capture such localized associations. However, such analyses/studies in a large community-dwelling population are lacking. OBJECTIVE: To perform a fine-mapping of cognitive ability to cortical and subcortical grey matter on magnetic resonance imaging (MRI). METHODS: In 3,813 stroke-free and non-demented persons from the Rotterdam Study (mean age 69.1 (±8.8) years; 55.8% women) with cognitive assessments and brain MRI, we performed voxel-based morphometry and subcortical shape analysis on global cognition and separate tests that tapped into memory, information processing speed, fine motor speed, and executive function domains. RESULTS: We found that the different cognitive tests significantly associated with grey matter density in differential but also overlapping brain regions, primarily in the left hemisphere. Clusters of significantly associated voxels with global cognition were located within multiple anatomic regions: left amygdala, hippocampus, parietal lobule, superior temporal gyrus, insula and posterior temporal lobe. Subcortical shape analysis revealed associations primarily within the head and tail of the caudate nucleus, putamen, ventral part of the thalamus, and nucleus accumbens, more equally distributed among the left and right hemisphere. Within the caudate nucleus both positive (head) as well as negative (tail) associations were observed with global cognition. CONCLUSIONS: In a large population-based sample, we mapped cognitive performance to cortical and subcortical grey matter density using a hypothesis-free approach with high-dimensional neuroimaging. Leveraging the power of our large sample size, we confirmed well-known associations as well as identified novel brain regions related to cognition.

5.
IEEE/ACM Trans Comput Biol Bioinform ; 16(5): 1508-1514, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31135366

RESUMO

Genome-wide association studies (GWAS) link full genome data to a handful of traits. However, in neuroimaging studies, there is an almost unlimited number of traits that can be extracted for full image-wide big data analyses. Large populations are needed to achieve the necessary power to detect statistically significant effects, emphasizing the need to pool data across multiple studies. Neuroimaging consortia, e.g., ENIGMA and CHARGE, are now analyzing MRI data from over 30,000 individuals. Distributed processing protocols extract harmonized features at each site, and pool together only the cohort statistics using meta analysis to avoid data sharing. To date, such MRI projects have focused on single measures such as hippocampal volume, yet voxelwise analyses (e.g., tensor-based morphometry; TBM) may help better localize statistical effects. This can lead to $10^{13}$1013 tests for GWAS and become underpowered. We developed an analytical framework for multi-site TBM by performing multi-channel registration to cohort-specific templates. Our results highlight the reliability of the method and the added power over alternative options while preserving single site specificity and opening the doors for well-powered image-wide genome-wide discoveries.

6.
Neuroimage Clin ; 23: 101810, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31029050

RESUMO

Alterations in subcortical brain structures have been reported in adults with HIV and, to a lesser extent, pediatric cohorts. The extent of longitudinal structural abnormalities in children with perinatal HIV infection (PaHIV) remains unclear. We modeled subcortical morphometry from whole brain structural magnetic resonance imaging (1.5 T) scans of 43 Thai children with PaHIV (baseline age = 11.09±2.36 years) and 50 HIV- children (11.26±2.80 years) using volumetric and surface-based shape analyses. The PaHIV sample were randomized to initiate combination antiretroviral treatment (cART) when CD4 counts were 15-24% (immediate: n = 22) or when CD4 < 15% (deferred: n = 21). Follow-up scans were acquired approximately 52 weeks after baseline. Volumetric and shape descriptors capturing local thickness and surface area dilation were defined for the bilateral accumbens, amygdala, putamen, pallidum, thalamus, caudate, and hippocampus. Regression models adjusting for clinical and demographic variables examined between and within group differences in morphometry associated with HIV. We assessed whether baseline CD4 count and cART status or timing associated with brain maturation within the PaHIV group. All models were adjusted for multiple comparisons using the false discovery rate. A pallidal subregion was significantly thinner in children with PaHIV. Regional thickness, surface area, and volume of the pallidum was associated with CD4 count in children with PaHIV. Longitudinal morphometry was not associated with HIV or cART status or timing, however, the trajectory of the left pallidum volume was positively associated with baseline CD4 count. Our findings corroborate reports in adult cohorts demonstrating a high predilection for HIV-mediated abnormalities in the basal ganglia, but suggest the effect of stable PaHIV infection on morphological aspects of brain development may be subtle.

7.
Neuroimage Clin ; 22: 101744, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30852398

RESUMO

Apolipoprotein E (APOE) e4 is the major genetic risk factor for late-onset Alzheimer's disease (AD). The dose-dependent impact of this allele on hippocampal volumes has been documented, but its influence on general hippocampal morphology in cognitively unimpaired individuals is still elusive. Capitalizing on the study of a large number of cognitively unimpaired late middle aged and older adults with two, one and no APOE-e4 alleles, the current study aims to characterize the ability of our automated surface-based hippocampal morphometry algorithm to distinguish between these three levels of genetic risk for AD and demonstrate its superiority to a commonly used hippocampal volume measurement. We examined the APOE-e4 dose effect on cross-sectional hippocampal morphology analysis in a magnetic resonance imaging (MRI) database of 117 cognitively unimpaired subjects aged between 50 and 85 years (mean = 57.4, SD = 6.3), including 36 heterozygotes (e3/e4), 37 homozygotes (e4/e4) and 44 non-carriers (e3/e3). The proposed automated framework includes hippocampal surface segmentation and reconstruction, higher-order hippocampal surface correspondence computation, and hippocampal surface deformation analysis with multivariate statistics. In our experiments, the surface-based method identified APOE-e4 dose effects on the left hippocampal morphology. Compared to the widely-used hippocampal volume measure, our hippocampal morphometry statistics showed greater statistical power by distinguishing cognitively unimpaired subjects with two, one, and no APOE-e4 alleles. Our findings mirrored previous studies showing that APOE-e4 has a dose effect on the acceleration of brain structure deformities. The results indicated that the proposed surface-based hippocampal morphometry measure is a potential preclinical AD imaging biomarker for cognitively unimpaired individuals.


Assuntos
Alelos , Apolipoproteína E4/genética , Cognição/fisiologia , Dosagem de Genes/genética , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Brain Imaging Behav ; 13(2): 377-388, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29564659

RESUMO

In a recent manuscript, our group demonstrated shape differences in the thalamus, nucleus accumbens, and amygdala in a cohort of U.S. Service Members with mild traumatic brain injury (mTBI). Given the significant role these structures play in cognitive function, this study directly examined the relationship between shape metrics and neuropsychological performance. The imaging and neuropsychological data from 135 post-deployed United States Service Members from two groups (mTBI and orthopedic injured) were examined. Two shape features modeling local deformations in thickness (RD) and surface area (JD) were defined vertex-wise on parametric mesh-representations of 7 bilateral subcortical gray matter structures. Linear regression was used to model associations between subcortical morphometry and neuropsychological performance as a function of either TBI status or, among TBI patients, subjective reporting of initial concussion severity (CS). Results demonstrated several significant group-by-cognition relationships with shape metrics across multiple cognitive domains including processing speed, memory, and executive function. Higher processing speed was robustly associated with more dilation of caudate surface area among patients with mTBI who reported more than one CS variables (loss of consciousness (LOC), alteration of consciousness (AOC), and/or post-traumatic amnesia (PTA)). These significant patterns indicate the importance of subcortical structures in cognitive performance and support a growing functional neuroanatomical literature in TBI and other neurologic disorders. However, prospective research will be required before exact directional evolution and progression of shape can be understood and utilized in predicting or tracking cognitive outcomes in this patient population.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Encéfalo/diagnóstico por imagem , Militares , Adulto , Encéfalo/fisiopatologia , Cognição , Estudos de Coortes , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Inconsciência , Estados Unidos
9.
Proc IEEE Int Symp Biomed Imaging ; 2017: 1226-1230, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29201284

RESUMO

Optimal representations of the genetic structure underlying complex neuroimaging phenotypes lie at the heart of our quest to discover the genetic code of the brain. Here, we suggest a strategy for achieving such a representation by decomposing the genetic covariance matrix of complex phenotypes into maximally heritable and genetically independent components. We show that such a representation can be approximated well with eigenvectors of the genetic covariance based on a large family study. Using 520 twin pairs from the QTIM dataset, we estimate 500 principal genetic components of 54,000 vertex-wise shape features representing fourteen subcortical regions. We show that our features maintain their desired properties in practice. Further, the genetic components are found to be significantly associated with the CLU and PICALM genes in an unrelated Alzheimer's Disease (AD) dataset. The same genes are not significantly associated with other volume and shape measures in this dataset.

10.
Med Image Anal ; 41: 32-39, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28487128

RESUMO

We present a continuous model for structural brain connectivity based on the Poisson point process. The model treats each streamline curve in a tractography as an observed event in connectome space, here the product space of the gray matter/white matter interfaces. We approximate the model parameter via kernel density estimation. To deal with the heavy computational burden, we develop a fast parameter estimation method by pre-computing associated Legendre products of the data, leveraging properties of the spherical heat kernel. We show how our approach can be used to assess the quality of cortical parcellations with respect to connectivity. We further present empirical results that suggest that "discrete" connectomes derived from our model have substantially higher test-retest reliability compared to standard methods. In this, the expanded form of this paper for journal publication, we also explore parcellation free analysis techniques that avoid the use of explicit partitions of the cortical surface altogether. We provide an analysis of sex effects on our proposed continuous representation, demonstrating the utility of this approach.


Assuntos
Encéfalo/diagnóstico por imagem , Conectoma , Algoritmos , Encéfalo/anatomia & histologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Nat Commun ; 8: 13624, 2017 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-28098162

RESUMO

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.


Assuntos
Hipocampo/crescimento & desenvolvimento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Criança , Estudos de Coortes , Dipeptidil Peptidase 4/genética , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Glicoproteínas/genética , Humanos , Masculino , Metionina Sulfóxido Redutases/genética , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Tamanho do Órgão , Proteínas Serina-Treonina Quinases/genética , Adulto Jovem
12.
Neuroimage ; 145(Pt B): 389-408, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-26658930

RESUMO

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.


Assuntos
Encefalopatias , Estudo de Associação Genômica Ampla , Transtornos Mentais , Estudos Multicêntricos como Assunto , Encefalopatias/diagnóstico por imagem , Encefalopatias/genética , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Humanos , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/genética , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia
13.
Mach Learn Med Imaging ; 10541: 371-378, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30035274

RESUMO

As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.

14.
Proc IEEE Int Symp Biomed Imaging ; 2017: 502-506, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30713592

RESUMO

Patients with major depressive disorder (MDD) who do not achieve full symptomatic recovery after antidepressant treatment have a higher risk of relapse. Compared to pharmacotherapies, electroconvulsive therapy (ECT) more rapidly produces a greater extent of response in severely depressed patients. However, prediction of which candidates are most likely to improve after ECT remains challenging. Using structural MRI data from 42 ECT patients scanned prior to ECT treatment, we developed a random forest classifier based on data-driven shape cluster selection and cortical thickness features to predict remission. Right hemisphere hippocampal shape and right inferior temporal cortical thickness was most predictive of remission, with the predicted probability of recovery decreasing when these regions were thicker prior to treatment. Remission was predicted with an average 73% balanced accuracy. Classification of MRI data may help identify treatment-responsive patients and aid in clinical decision-making. Our results show promise for the development of personalized treatment strategies.

15.
Nat Commun ; 7: 13738, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27976715

RESUMO

The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures.


Assuntos
Encéfalo/anatomia & histologia , Tamanho do Órgão/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Núcleo Caudado/anatomia & histologia , Núcleo Caudado/diagnóstico por imagem , Feminino , Genótipo , Globo Pálido/anatomia & histologia , Globo Pálido/diagnóstico por imagem , Hipocampo/anatomia & histologia , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/anatomia & histologia , Núcleo Accumbens/diagnóstico por imagem , Putamen/diagnóstico por imagem , Putamen/fisiologia , Reprodutibilidade dos Testes , Tálamo/anatomia & histologia , Tálamo/diagnóstico por imagem , Adulto Jovem
16.
Proc IEEE Int Symp Biomed Imaging ; 2016: 14-18, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27499828

RESUMO

Alzheimers disease (AD) is a progressive neurodegenerative disease most prevalent in the elderly. Distinguishing disease-related memory decline from normal age-related memory decline has been clinically difficult due to the subtlety of cognitive change during the preclinical stage of AD. In contrast, sensitive biomarkers derived from in vivo neuroimaging data could improve the early identification of AD. In this study, we employed a morphometric analysis in the hippocampus and lateral ventricle. A novel group-wise template-based segmentation algorithm was developed for ventricular segmentation. Further, surface multivariate tensor-based morphometry and radial distance on each surface point were computed. Using Hotellings T2 test, we found significant morphometric differences in both hippocampus and lateral ventricle between stable and clinically declining subjects. The left hemisphere was more severely affected than the right during this early disease stage. Hippocampal and ventricular morphometry has significant potential as an imaging biomarker for onset prediction and early diagnosis of AD.

17.
Proc IEEE Int Symp Biomed Imaging ; 2016: 646-650, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27499829

RESUMO

Alzheimer's disease (AD) is a progressive brain disease. Accurate diagnosis of AD and its prodromal stage, mild cognitive impairment, is crucial for clinical trial design. There is also growing interests in identifying brain imaging biomarkers that help evaluate AD risk presymptomatically. Here, we applied a recently developed multivariate tensor-based morphometry (mTBM) method to extract features from hippocampal surfaces, derived from anatomical brain MRI. For such surface-based features, the feature dimension is usually much larger than the number of subjects. We used dictionary learning and sparse coding to effectively reduce the feature dimensions. With the new features, an Adaboost classifier was employed for binary group classification. In tests on publicly available data from the Alzheimers Disease Neuroimaging Initiative, the new framework outperformed several standard imaging measures in classifying different stages of AD. The new approach combines the efficiency of sparse coding with the sensitivity of surface mTBM, and boosts classification performance.

18.
J Neurol ; 263(10): 2065-79, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27435967

RESUMO

Mild traumatic brain injury (mTBI) is a significant health concern. The majority who sustain mTBI recover, although ~20 % continue to experience symptoms that can interfere with quality of life. Accordingly, there is a critical need to improve diagnosis, prognostic accuracy, and monitoring (recovery trajectory over time) of mTBI. Volumetric magnetic resonance imaging (MRI) has been successfully utilized to examine TBI. One promising improvement over standard volumetric approaches is to analyze high-dimensional shape characteristics of brain structures. In this study, subcortical shape and volume in 76 Service Members with mTBI was compared to 59 Service Members with orthopedic injury (OI) and 17 with post-traumatic stress disorder (PTSD) only. FreeSurfer was used to quantify structures from T1-weighted 3 T MRI data. Radial distance (RD) and Jacobian determinant (JD) were defined vertex-wise on parametric mesh-representations of subcortical structures. Linear regression was used to model associations between morphometry (volume and shape), TBI status, and time since injury (TSI) correcting for age, sex, intracranial volume, and level of education. Volumetric data was not significantly different between the groups. JD was significantly increased in the accumbens and caudate and significantly reduced in the thalamus of mTBI participants. Additional significant associations were noted between RD of the amygdala and TSI. Positive trend-level associations between TSI and the amygdala and accumbens were observed, while a negative association was observed for third ventricle. Our findings may aid in the initial diagnosis of mTBI, provide biological targets for functional examination, and elucidate regions that may continue remodeling after injury.


Assuntos
Concussão Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Adulto , Concussão Encefálica/epidemiologia , Progressão da Doença , Feminino , Lateralidade Funcional , Humanos , Imagem Tridimensional , Imagem por Ressonância Magnética , Masculino , Militares , Doenças Musculoesqueléticas/diagnóstico por imagem , Estados Unidos/epidemiologia , Adulto Jovem
19.
J Acquir Immune Defic Syndr ; 73(4): 426-432, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27228100

RESUMO

BACKGROUND: There are contradicting reports on the associations between Apolipoprotein E4 (ApoE ε4) and brain outcomes in HIV with some evidence that relationships may be greatest in older age groups. METHODS: We assessed cognition in 76 clinically stable HIV-infected participants over age 60 and genotyped ApoE. Sixty-one of these subjects underwent structural brain magnetic resonance imaging and diffusion tensor imaging. RESULTS: The median age of the participants was 64 years (range: 60-84) and the median estimated duration of HIV infection was 22 years. Apo ε4 carriers (n = 19) were similar to noncarriers (n = 57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE ε4 carriers demonstrated greater deficits in cognitive performance in the executive domain (P = 0.045) and had reduced fractional anisotropy and increased mean diffusivity throughout large white matter tracts within the brain compared with noncarriers. Tensor-based morphometry analyses revealed ventricular expansion and atrophy in the posterior corpus callosum, thalamus, and brainstem among HIV-infected ApoE ε4 carriers compared with ε4 noncarriers. CONCLUSIONS: In this sample of older HIV-infected individuals, having at least 1 ApoE ε4 allele was associated with decreased cognitive performance in the executive functioning domain, reduced brain white matter integrity, and brain atrophy. Brain atrophy was most prominent in the posterior corpus callosum, thalamus, and brainstem. This pattern of cognitive deficit, atrophy, and damage to white matter integrity was similar to that described in HIV, suggesting an exacerbation of HIV-related pathology; although emergence of other age-associated neurodegenerative disorders cannot be excluded.


Assuntos
Apolipoproteínas E/metabolismo , Atrofia/patologia , Encefalopatias/patologia , Encéfalo/patologia , Cognição/fisiologia , Infecções por HIV/complicações , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Encefalopatias/metabolismo , Regulação da Expressão Gênica , Genótipo , Infecções por HIV/genética , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos
20.
PLoS One ; 11(4): e0152901, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27065111

RESUMO

The apolipoprotein E (APOE) e4 genotype is a powerful risk factor for late-onset Alzheimer's disease (AD). In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, we previously reported significant baseline structural differences in APOE e4 carriers relative to non-carriers, involving the left hippocampus more than the right--a difference more pronounced in e4 homozygotes than heterozygotes. We now examine the longitudinal effects of APOE genotype on hippocampal morphometry at 6-, 12- and 24-months, in the ADNI cohort. We employed a new automated surface registration system based on conformal geometry and tensor-based morphometry. Among different hippocampal surfaces, we computed high-order correspondences, using a novel inverse-consistent surface-based fluid registration method and multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance. At each time point, using Hotelling's T(2) test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the full cohort as well as in the non-demented (pooled MCI and control) subjects at each follow-up interval. In the complete ADNI cohort, we found greater atrophy of the left hippocampus than the right, and this asymmetry was more pronounced in e4 homozygotes than heterozygotes. These findings, combined with our earlier investigations, demonstrate an e4 dose effect on accelerated hippocampal atrophy, and support the enrichment of prevention trial cohorts with e4 carriers.


Assuntos
Doença de Alzheimer/genética , Apolipoproteína E4/genética , Atrofia/genética , Hipocampo/patologia , Idoso , Doença de Alzheimer/patologia , Atrofia/patologia , Estudos de Casos e Controles , Feminino , Genótipo , Heterozigoto , Homozigoto , Humanos , Estudos Longitudinais , Masculino , Fatores de Tempo
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