Publications by authors named "Nazanin Makkinejad"

6 Publications

  • Page 1 of 1

ARTS: A novel In-vivo classifier of arteriolosclerosis for the older adult brain.

Neuroimage Clin 2021 24;31:102768. Epub 2021 Jul 24.

Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Dept. of Diagnostic Radiology & Nuc Med, Rush University Medical Center, Chicago, IL, USA. Electronic address:

Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for ARTerioloSclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from arteriolosclerosis. The performance of ARTS in predicting the presence of arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/.
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http://dx.doi.org/10.1016/j.nicl.2021.102768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329541PMC
September 2021

Neuropathologic and Cognitive Correlates of Enlarged Perivascular Spaces in a Community-Based Cohort of Older Adults.

Stroke 2020 09 6;51(9):2825-2833. Epub 2020 Aug 6.

Department of Biomedical Engineering, Illinois Institute of Technology, Chicago (C.J.P., N.M., K.A.).

Background And Purpose: Enlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function, and vascular dementia. However, the relationship of EPVS with age-related neuropathologies is not well understood. Therefore, the purpose of this study was to assess the neuropathologic correlates of EPVS in a large community-based cohort of older adults. The cognitive correlates of EPVS over and beyond those of other pathologies were also assessed.

Methods: This study included 654 older deceased and autopsied participants of 3 longitudinal community-based studies of aging that had available data on cognition, ex vivo brain magnetic resonance imaging, and detailed neuropathologic examination. EPVS seen on ex vivo magnetic resonance imaging were histologically validated. Experienced observers rated EPVS burden in ex vivo magnetic resonance imaging using a semiquantitative 4-level scale. Elastic-net regularized ordinal logistic regression was used to investigate associations of EPVS burden with age-related neuropathologies. Mixed-effects models of cognition controlling for neuropathologies, demographics, and clinical factors, were used to determine whether EPVS burden has additional contributions to cognitive decline.

Results: EPVS burden in the whole group was associated with gross infarcts (odds ratio=1.67, =0.0017) and diabetes mellitus (odds ratio=1.73, =0.004). When considering only nondemented participants (with mild or no cognitive impairment), EPVS burden was associated with gross infarcts (odds ratio=1.74, =0.016) and microscopic infarcts (odds ratio=1.79, =0.013). EPVS burden was associated with faster decline in visuospatial abilities (estimate=-0.009, =0.028), in the whole group, as well as lower levels of semantic memory (estimate=-0.13, =0.048) and visuospatial abilities (estimate=-0.11, =0.016) at the time of death.

Conclusions: EPVS and infarcts may share similar neurobiological pathways regardless of dementia status. EPVS burden is linked to diabetes mellitus independently of neuropathologies, extending recent findings in animal studies implicating diabetes mellitus in impairment of the glymphatic system. Finally, EPVS burden may reflect additional brain tissue injury that may contribute to cognitive decline, not captured with traditional neuropathologic measures.
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http://dx.doi.org/10.1161/STROKEAHA.120.029388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484322PMC
September 2020

Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report.

Brain 2019 06;142(6):1503-1527

University of California, San Diego, CA, USA.

We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, ∼25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-β plaques and tauopathy. Given that the 'oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.
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http://dx.doi.org/10.1093/brain/awz099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536849PMC
June 2019

Associations of amygdala volume and shape with transactive response DNA-binding protein 43 (TDP-43) pathology in a community cohort of older adults.

Neurobiol Aging 2019 05 31;77:104-111. Epub 2019 Jan 31.

Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Diagnostic Radiology, Rush University Medical Center, Chicago, IL, USA. Electronic address:

Transactive response DNA-binding protein 43 (TDP-43) pathology is common in old age and is strongly associated with cognitive decline and dementia above and beyond contributions from other neuropathologies. TDP-43 pathology in aging typically originates in the amygdala, a brain region also affected by other age-related neuropathologies such as Alzheimer's pathology. The purpose of this study was two-fold: to determine the independent effects of TDP-43 pathology on the volume, as well as shape, of the amygdala in a community cohort of older adults, and to determine the contribution of amygdala volume to the variance of the rate of cognitive decline after accounting for the contributions of neuropathologies and demographics. Cerebral hemispheres from 198 participants of the Rush Memory and Aging Project and the Religious Orders Study were imaged with MRI ex vivo and underwent neuropathologic examination. Measures of amygdala volume and shape were extracted for all participants. Regression models controlling for neuropathologies and demographics showed an independent negative association of TDP-43 with the volume of the amygdala. Shape analysis revealed a unique pattern of amygdala deformation associated with TDP-43 pathology. Finally, mixed-effects models showed that amygdala volume explained an additional portion of the variance of the rate of decline in global cognition, episodic memory, semantic memory, and perceptual speed, above and beyond what was explained by demographics and neuropathologies.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486844PMC
May 2019

Quantitative radiology: automated measurement of polyp volume in computed tomography colonography using Hessian matrix-based shape extraction and volume growing.

Quant Imaging Med Surg 2015 Oct;5(5):673-84

1 Department of Radiology, The University of Chicago, Chicago, IL, USA ; 2 Department of Radiology, University of New Mexico, Albuquerque, NM, USA ; 3 Department of Radiology, Loyola University Medical Center, Maywood, IL, USA ; 4 Medical Imaging Research Center & Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago, IL, USA ; 5 School of Electronics Engineering and Computer Science, Beijing University, Beijing 100871, China.

Background: Current measurement of the single longest dimension of a polyp is subjective and has variations among radiologists. Our purpose was to develop a computerized measurement of polyp volume in computed tomography colonography (CTC).

Methods: We developed a 3D automated scheme for measuring polyp volume at CTC. Our scheme consisted of segmentation of colon wall to confine polyp segmentation to the colon wall, extraction of a highly polyp-like seed region based on the Hessian matrix, a 3D volume growing technique under the minimum surface expansion criterion for segmentation of polyps, and sub-voxel refinement and surface smoothing for obtaining a smooth polyp surface. Our database consisted of 30 polyp views (15 polyps) in CTC scans from 13 patients. Each patient was scanned in the supine and prone positions. Polyp sizes measured in optical colonoscopy (OC) ranged from 6-18 mm with a mean of 10 mm. A radiologist outlined polyps in each slice and calculated volumes by summation of volumes in each slice. The measurement study was repeated 3 times at least 1 week apart for minimizing a memory effect bias. We used the mean volume of the three studies as "gold standard".

Results: Our measurement scheme yielded a mean polyp volume of 0.38 cc (range, 0.15-1.24 cc), whereas a mean "gold standard" manual volume was 0.40 cc (range, 0.15-1.08 cc). The "gold-standard" manual and computer volumetric reached excellent agreement (intra-class correlation coefficient =0.80), with no statistically significant difference [P (F≤f) =0.42].

Conclusions: We developed an automated scheme for measuring polyp volume at CTC based on Hessian matrix-based shape extraction and volume growing. Polyp volumes obtained by our automated scheme agreed excellently with "gold standard" manual volumes. Our fully automated scheme can efficiently provide accurate polyp volumes for radiologists; thus, it would help radiologists improve the accuracy and efficiency of polyp volume measurements in CTC.
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http://dx.doi.org/10.3978/j.issn.2223-4292.2015.10.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671965PMC
October 2015
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