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Malekzadeh, M.

Publications and source records attributed to Malekzadeh, M..

7 recordsLinked to original sources

Structural Directional Brain Behavior Asymmetry Across Cortical and Non-Cortical Regions

A substantial body of research suggests that the left and right cerebral hemispheres play differential roles in shaping human behavior. However, due to methodological considerations, most studies in this field have relied primarily on psychological methods. Here, we present exploratory neurobiological evidence suggesting that brain volume across numerous cortical and non-cortical homotopic regions may display consistent directional asymmetry in relation to a wide range of behavioral measures. Of particular note, such asymmetry recurred between contralateral homotopic areas across many behavioral parameters. The asymmetric behavioral directionality is distributed across most regions of the human brain, especially in the frontal and temporal cortices, which are particularly developed in humans. This may add a new dimension to previously described aspects of hemispheric asymmetry. In addition, it may help to understand why a marked functional asymmetry can be observed even when structural asymmetry is subtle. Moreover, these findings may shed light on how the brain modulates behavior in health and disease and may contribute to understanding processes involved in neurological and psychiatric disorders.

neuroscience↗

Quantitative MRI Reveals Bone Marrow Regeneration Following Targeted Marrow Irradiation and Transplantation in a Sickle Cell Disease Model

Sickle cell disease (SCD) is associated with chronic bone marrow stress, altered hematopoiesis, and reduced adiposity. Whether marrow-selective conditioning followed by transplantation normalizes these abnormalities remains unclear. We investigated bone marrow remodeling in Townes mice by comparing SCD control (SCD-Con) with mice that received total marrow irradiation (TMI) followed by bone marrow transplantation (SCD-TMI-BMT). Multiparametric micro-MRI at 7 T quantified proton density water fraction (PDWF), proton density fat fraction (PDFF), and R2*(1/T2*), and micro-CT assessed trabecular structure in the femur. SCD-Con marrow showed higher water content (elevated PDWF), reduced adiposity (lower PDFF), and imaging features consistent with erythroid hyperplasia and elevated iron burden (shorter T2* with reciprocal increase in R2*). In contrast, SCD-TMI-BMT mice demonstrated smaller R2*, reduced PDWF, and partial restoration of adiposity, accompanied by reciprocal shifts in R2*, consistent with decreased cellular iron and marrow remodeling. Micro-CT revealed an improved trabecular architecture after BMT compared to SCD control. MRI imaging biomarkers aligned with histologic evidence of reduced cellularity and larger adipocyte voids. In conclusion, a TMI-BMT SCD model promotes partial normalization of the marrow microenvironment. Multiparametric MRI with micro-CT provides a practical, non-invasive framework for monitoring marrow remodeling and skeletal health after curative therapy.

bioengineering↗

Development of Proton Density Fat Fraction Micro-MRI for Non-Invasive Quantitative Assessment of Bone Marrow Changes with Age and Radiation in Mouse Models

Background/ObjectivesBone marrow (BM) adipocytes are critical in progressing solid tumor metastases and hematological malignancies across pediatric to aging populations. Single-point biopsies remain the gold standard for monitoring BM diseases, including hematologic malignancies, but are limited in capturing the full complexity of loco-regional and global BM microenvironments. Non-invasive imaging techniques like Magnetic Resonance Imaging (MRI), could offer valuable alternatives for real-time evaluation of BM diseases in both preclinical translational and clinical studies. MethodsWe developed a preclinical proton density fat fraction (PDFF) MRI technique for quantitative BM composition assessment, focusing on fat fraction (FF) within mouse femurs. We validated this method using aging mice and young mice subjected to 10 Gy X-ray irradiation, compared with young unirradiated mice as controls. Water-fat phantoms (0% to 100% fat content) were used to optimize the imaging sequence, and immunohistochemical (IHC) staining with H&E validates equivalent adipose content in the femur BM regions. ResultsSignificant differences in FF were observed across age groups (p = 0.001 for histology and p = 0.0002 for PDFF) and between irradiated and control mice (p = 0.005 for histology and p = 0.002 for PDFF). A strong correlation (R2 [~] 0.84) between FF values from PDFF and histology validates the accuracy of the technique. ConclusionsThese findings demonstrate the potential of PDFF MRI as a non-invasive real-time imaging biomarker for quantifying BM fat fraction in preclinical mice model studies, particularly in evaluating the effects of aging, disease progression, and irradiation therapy in pediatric and translational oncology research.

biophysics↗

A transformer model for predicting cognitive impairment from sleep

Sleep disturbances are known to be aggravated with normal aging. Additionally, sleep disruptions have a potentially bidirectional causal relationship with dementia due to neurodegenerative diseases like Alzheimers disease. Predictive techniques that can automatically detect cognitive impairment from an individuals sleep data have broad clinical and biological significance. Here, we present a deep learning approach based on a transformer architecture to predict cognitive status from sleep electroencephalography (EEG) data. This work uses data from N = 1, 502 subjects from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Our transformer model achieves 70.22% accuracy at the binary classification task for distinguishing cognitively normal and impaired subjects based on their sleep EEG. Our method outperforms traditional feature handcrafting, which has an overall accuracy of 57.61% for the same task. We use a sparse regression model to understand and interpret the information captured by each learned feature from our transformer model. To our knowledge, this is the first effort to use deep learning to predict cognitive impairment from sleep metrics.

neuroscience↗

An in-vivo digital atlas of the spatially reliable cerebral vasculature in mice

Cerebral vascular abnormalities can have a large impact on brain function and have been frequently detected as a comorbidity in various neuropathologies. The mouse is the most common pre-clinical animal model used to investigate neuropathologies and thus cerebral vascular atlases of this species are indispensable. In particular, an atlas derived from multiple animals and that can address inter-subject variability is still absent. The current study presents a mouse cerebral vascular atlas developed from MR 2D-TOF angiograms acquired from a relatively high number (N=21) of 12 weeks old male C57BL/6 mice. The vascular atlas we present depicts large arteries, veins and sinuses that are more spatially reliable across animals than smaller vessels. The atlas is available for download and contains multiple datasets: i) a cerebral vascular atlas; ii) a digital segmentation of large vessels (arteries and veins); iii) a high resolution T2 anatomical background aligned to the atlas; iv) a skeletonized vascular atlas; and v) a vascular graph model. We suggest that these components provide a very potent analysis tool for mouse fMRI data and that the atlas can be used as a template for multimodal brain imaging studies. To this end, we also demonstrate an explicit application of the atlas for the investigation of vascular influences in resting-state fMRI.

neuroscience↗

Asymmetry Map of Human Brain in Young Adults

Although, asymmetry is a central organizational aspect of human brain, it has not been clearly described yet. Here, we have studied structural brain asymmetry in 1113 young adults using data obtained from Human Connectome Project. A significant rightward asymmetry in mean global cerebral cortical thickness, surface area and gray matter volume as well as volumes of cerebral white matter, cerebellar cortex and white matter, hippocampus, putamen, caudate nucleus, nucleus accumbens and amygdala was observed. Thalamus showed a leftward asymmetry. Regionally, most cerebral cortical regions show a significant rightward asymmetry in thickness. However, cortical surface area and gray matter volume are more evenly distributed between two hemispheres with almost half of the regions showing a leftward asymmetry. In addition, a strong correlation between cortical surface area and gray matter volume as well as their asymmetry indices was noted which results in concordant asymmetry patterns between cortical surface area and gray matter volume in most cortical regions.

neuroscience↗

Bottom-up sensory processing can decrease activity and functional connectivity in the default mode like network in rats.

The default mode network is a large-scale brain network that is active during rest and internally focused states and deactivates as well as desynchronizes during externally oriented (top-down) attention demanding cognitive tasks. However, it is not sufficiently understood if unpredicted salient stimuli, able to trigger bottom-up attentional processes, could also result in similar reduction of activity and functional connectivity in the DMN. In this study, we investigated whether bottom-up sensory processing could influence the default mode like network (DMLN) in rats. DMLN activity was examined using block-design visual functional magnetic resonance imaging (fMRI) while its synchronization was investigated by comparing functional connectivity during a resting versus a continuously stimulated brain state by unpredicted light flashes. We demonstrated that activity in DMLN regions was decreased during visual stimulus blocks and increased during blanks. Furthermore, decreased inter-network functional connectivity between the DMLN and visual networks as well as decreased intra-network functional connectivity within the DMLN was observed during the continuous visual stimulation. These results suggest that triggering of bottom-up attention mechanisms in anesthetized rats can lead to a cascade similar to top-down orienting of attention in humans and is able to deactivate and desynchronize the DMLN.

neuroscience↗