Laboratory of Neuroimaging

Los Angeles, CA, United States

Laboratory of Neuroimaging

Los Angeles, CA, United States
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Stonnington C.M.,Mayo Medical School | Stonnington C.M.,University College London | Chu C.,University College London | Chu C.,U.S. National Institutes of Health | And 6 more authors.
NeuroImage | Year: 2010

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3. months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P< 0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome. © 2010 Elsevier Inc.


Hayashi K.,Laboratory of NeuroImaging | Klunder A.,Laboratory of NeuroImaging | Braskie M.N.,Laboratory of NeuroImaging | Braskie M.N.,Ahmanson Lovelace Brain Mapping Center | And 3 more authors.
NeuroImage | Year: 2010

Objectives: To assess quantitatively the cortical pattern profile of regional FDDNP binding to beta-amyloid and neurofibrillary tangles on MR derived cortical maps, FDDNP PET images were corrected for movement and partial volume (PV), and optimized for kernel size. Methods: FDDNP DVR PET images from 23 subjects (7 with Alzheimer's disease (AD), 6 with mild cognitive impairment and 10 controls) were obtained from Logan analysis using cerebellum as reference. A hemispheric cortical surface model for each subject was extracted from the MRI. The same transformations were applied to the FDDNP DVR PET images to map them into the same space. The cortical map with PV correction was calculated as the ratio of the DVR cortical surface and that of the simulated map, created from the mask derived from MRI and smoothed to the PET resolution. Discriminant analysis was used to order the FDDNP DVR cortical surfaces based on subjects' disease state. Linear regression was used to assess the rate of change of DVR vs. MMSE for each hemispheric cortical surface point. Results: The FDDNP DVR cortical surface corrected for movement and PV had less hemispheric asymmetry. Optimal kernel size was determined to be 9 mm. The corrected cortical surface map of FDDNP DVR showed clear spatial pattern that was consistent with the known pathological progression of AD. Conclusion: Correcting for movement, PV as well as optimizing kernel size provide sensitive statistical analysis of FDDNP distribution which confirms in the living brain known pathology patterns earlier observed with cognitive decline with brain specimens. © 2009 Elsevier Inc. All rights reserved.


Bartzokis G.,University of California at Los Angeles | Bartzokis G.,Laboratory of Neuroimaging | Bartzokis G.,Greater Los Angeles VA Healthcare System
Neuropharmacology | Year: 2012

Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer's disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and non-invasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases. © 2011 Elsevier Ltd. All rights reserved.


Szeszko P.R.,Feinstein Institute for Medical Research | Szeszko P.R.,Zucker Hillside Hospital | Szeszko P.R.,Yeshiva University | Narr K.L.,Laboratory of Neuroimaging | And 12 more authors.
Schizophrenia Bulletin | Year: 2012

Identifying neurobiological predictors of response to antipsychotics in patients with schizophrenia is a critical goal of translational psychiatry. Few studies, however, have investigated the relationship between indices of brain structure and treatment response in the context of a controlled clinical trial. In this study, we sought to identify magnetic resonance (MR) imaging measures of the brain that predict treatment response in patients experiencing a first-episode of schizophrenia. Structural MR imaging scans were acquired in 39 patients experiencing a first-episode of schizophrenia with minimal or no prior exposure to antipsychotics participating in a double-blind 16-week clinical trial comparing the efficacy of risperidone vs olanzapine. Twenty-five patients were classified as responders by meeting operationally defined treatment response criteria on 2 consecutive study visits. Fourteen patients never responded to antipsychotic medication at any point during the clinical trial. MR imaging scans were also acquired in 45 age-and sex-matched healthy volunteers. Cortical pattern matching methods were used to compare cortical thickness and asymmetry measures among groups. Statistical mapping results, confirmed by permutation testing, indicated that responders had greater cortical thickness in occipital regions and greater frontal cortical asymmetry compared with nonresponders. Moreover, among responders, greater thickness in temporal regions was associated with less time to respond. Our findings are consistent with the hypothesis that plasticity and cortical thickness may be more preserved in responders and that MR imaging may assist in the prediction of antipsychotic drug response in patients experiencing a first-episode of schizophrenia. © 2010 The Author.


Lopes S.L.P.C.,São Paulo State University | Costa A.L.F.,City University of Sao Paulo | Cruz A.D.,Federal University of Fluminense | Li L.M.,Laboratory of Neuroimaging | De Almeida S.M.,University of Campinas
Dentomaxillofacial Radiology | Year: 2012

Objective: The aim of the present study was to describe the clinical and MRI findings of the temporomandibular joint (TMJ) in patients with major depressive disorders (MDDs) of the non-psychotic type. Methods: 40 patients (80 TMJs) who were diagnosed as having MDDs were selected for this study. The clinical examination of the TMJs was conducted according to the research diagnostic criteria and temporomandibular disorders (TMDs). The MRIs were obtained bilaterally in each patient with axial, parasagittal and paracoronal sections within a real-time dynamic sequence. Two trained oral radiologists assessed all images. For statistical analyses, Fisher's exact test and χ 2 test were applied (α 5 0.05). Results: Migraine was reported in 52.5% of subjects. Considering disc position, statistically significant differences between opening patterns with and without alteration (p=0.00) and between present and absent joint noises (p=0.00) were found. Regarding muscular pain, patients with and without abnormalities in disc function and patients with and without abnormalities in disc position were not statistically significant (p=0.42 and p=0.40, respectively). Significant differences between mandibular pathway with and without abnormalities (p50.00) and between present and absent joint noises (p=0.00) were observed. Conclusion: Based on the preliminary results observed by clinical and MRI examination of the TMJ, no direct relationship could be determined between MDDs and TMDs. © 2012 The British Institute of Radiology.


Altshuler L.L.,West Los Angeles Healthcare Center | Altshuler L.L.,University of California at Los Angeles | Abulseoud O.A.,University of Southern California | Foland-Ross L.,Laboratory of Neuroimaging | And 7 more authors.
Bipolar Disorders | Year: 2010

Objectives: Several magnetic resonance imaging studies have found changes in amygdala volumes in adults with mood disorders. The cellular basis for these changes has not been explored in detail. Specifically, it is not known whether differences in the density and/or volume of neurons or glial cells contribute to tissue volume changes seen on magnetic resonance images. Methods: Postmortem amygdala samples were obtained from the Stanley Foundation Neuropathology Consortium from subjects diagnosed with bipolar disorder (n = 10), major depressive disorder (n = 11), and schizophrenia (n = 9), and from normal controls (n = 14). Samples were first stained with glial fibrillary acidic protein (GFAP) and counter-stained with hematoxylin to ascertain neuron and glia (astrocyte) densities. Results: No significant differences in neuronal densities were found between groups. However, a reduction in the density of GFAP immunoreactive astrocytes was observed in the amygdala of subjects with major depressive disorder compared to the bipolar disorder, schizophrenia, and normal control postmortem samples. Conclusions: A decrease in density of GFAP immunoreactive astrocytes in the amygdala of depressed subjects is consistent with prior histologic reports and might contribute to amygdala volume reductions reported in several in vivo neuroimaging studies. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.


Bartzokis G.,University of California at Los Angeles | Bartzokis G.,Laboratory of Neuroimaging | Bartzokis G.,Greater Los Angeles VA Healthcare System | Lu P.H.,University of California at Los Angeles | And 11 more authors.
Schizophrenia Research | Year: 2011

Context: Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. Objectives: Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. Design: Two groups of SZ subjects (RLAI, N = 11; and RisO, N = 13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. Main outcome measure: WM volume change scores. Results: WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. Conclusions: The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions. © 2011.


Raven E.P.,University of California at Los Angeles | Lu P.H.,University of California at Los Angeles | Tishler T.A.,University of California at Los Angeles | Heydari P.,University of California at Los Angeles | And 3 more authors.
Journal of Alzheimer's Disease | Year: 2013

Background: Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain gray matter regions and may contribute to the risk of developing age-related diseases such as Alzheimer's disease (AD). Prior MRI studies demonstrated increased iron deposits in basal ganglia regions; however, the hippocampus (Hipp), which is heavily damaged in AD, and comparator regions that are resistant to AD damage, such as thalamus (Th), have rarely been examined. Objective: To assess iron levels and evidence of tissue damage in Hipp and Th of AD subjects and healthy controls. Methods: Thirty-one AD and sixty-eight healthy control subjects participated in this study. High-and low-field strength MRI instruments were used in combination to quantify iron content of ferritin molecules (ferritin iron) using the field dependent relaxation rate increase (FDRI) method. Decreased transverse relaxation rate (R2) was used as an index of tissue damage. Results: Compared with healthy controls, AD subjects had increased ferritin iron in Hipp (p = 0.019) but not Th (p = 0.637), and significantly decreased R2 in Hipp (p < 0.001) but not Th (p = 0.37). In the entire sample, FDRI and R2 were negatively correlated. Conclusion: The data shows that in AD, Hipp damage occurs in conjunction with ferritin iron accumulation. Prospective studies are needed to evaluate how increasing iron levels may influence the trajectory of tissue damage and cognitive and pathologic manifestations of AD. © 2013-IOS Press and the authors. All rights reserved.


Apostolova L.G.,Laboratory of NeuroImaging | Mosconi L.,New York University | Thompson P.M.,Laboratory of NeuroImaging | Green A.E.,Laboratory of NeuroImaging | And 5 more authors.
Neurobiology of Aging | Year: 2010

Atrophic changes of the hippocampus are typically regarded as an early sign of Alzheimer's dementia (AD). Using the radial distance atrophy mapping approach, we compared the longitudinal MRI data of 10 cognitively normal elderly subjects who remained normal at 3-year and 6-year follow-up (NL-NL) and 7 cognitively normal elderly subjects who were diagnosed with mild cognitive impairment (MCI) 2.8 (range 2.0-3.9) and with AD 6.8 years (range 6.1-8.2) after baseline (NL-MCIAD). 3D statistical maps revealed greater hippocampal atrophy in the NL-MCIAD relative to the NL-NL group at baseline (left p=0.05; right p=0.06) corresponding to 10-15% CA1, and 10-25% subicular atrophy, and bilateral differences at 3-year follow-up (left p=0.001, right p<0.02) corresponding to 10-30% subicular, 10-20% CA1, and 10-20% newly developed CA2-3 atrophy. This preliminary study suggests that excess CA1 and subicular atrophy is present in cognitively normal individuals predestined to decline to amnestic MCI, while progressive involvement of the CA1 and subiculum, and atrophy spreading to the CA2-3 subfield in amnestic MCI, suggests future diagnosis of AD. © 2008 Elsevier Inc.


Bartzokis G.,University of California at Los Angeles | Bartzokis G.,Laboratory of Neuroimaging | Bartzokis G.,Greater Los Angeles VA Healthcare System | Lu P.H.,University of California at Los Angeles | And 13 more authors.
Neuropsychopharmacology | Year: 2011

Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON) vs noncarrier (IRON) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON vs IRON status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r0.50, p0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRON group (r0.49, p0.005) but not in the IRON group. Between-group interactions (p0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups. © 2011 American College of Neuropsychopharmacology. All rights reserved.

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