Keywords: Aging, Aging

Motivation: Understanding age-associated changes in cerebral metabolism may provide mechanistic insights into the physiology of cognitive decline.

Goal(s): The goal of the study was to explore the effect of normal aging on neurometabolite levels in different brain regions using proton magnetic resonance spectroscopy (1H-MRS).

Approach: We performed 1H-MRS in brain regions associated with executive function, memory, and motor coordination in individuals without known disease recruited from the community and ranging from 19-57 years of age. 

Results: We found a steady decline in markers of neuronal health and neurotransmission and an increase in markers of gliosis and/or neuroinflammation in the dorsolateral prefrontal cortex with age.

Impact: This study will inform future studies using 1H-MRS based normative brain metabolic data by mapping metabolic levels in healthy brain regions involved with executive function, memory, and motor coordination.

Keywords: Alzheimer's Disease, Brain, Morphometry; Spectroscopy; cell-free DNA; Biomarkers;

Motivation: There is a lack of biomarkers in elderly people with ongoing subjective or clinical cognitive decline that indicate evolution to Alzheimer’s disease, necessary for the timely identification of candidate for pharmacological treatment or cognitive rehabilitation.

Goal(s): Our goal was to determine whether combining MR, neuropsychological and biological data could provide robust biomarkers for this purpose.

Approach: We evaluated patients with subjective cognitive decline, mild cognitive impairment, Alzheimer’s disease and healthy individuals, using a multimodal approach.

Results: We identified candidate biomarkers of condition worsening at early stages of the disease among alterations possibly explained by ongoing neurodegeneration.

Impact: Our results support the combined investigation of imaging, biological and neuropsychological data to detect patients in the early stages of the Alzheimer’s disease spectrum, who may undergo active neurodegeneration and worsening of the condition.

Keywords: Alzheimer's Disease, Metabolism, 1H-[13C]-NMR, cognition, amyloid-beta plaque, glutamate, GABA, glucose

Motivation: Alzheimer’s Disease (AD) is the major form of dementia but there is no biomarker(s) and treatment available.

Goal(s): This study aimed to investigate how decline in cognitive function is manifested in neurometabolic activity with the progression of AD.

Approach: 5xFAD mice (6- and 12-month) were subjected to memory assessment using the Morris Water Maze test followed by neurometabolic analysis using ¹H-[¹³C]-NMR spectroscopy in conjunction with an infusion of [1,6-¹³C₂]glucose or [2-¹³C]acetate. 

Results: The findings of the study suggest enhanced neuroinflammation, and reduced glutamatergic and GABAergic neurotransmission in 5xFAD mice. 

Impact: ¹³C NMR based assessment of neuronal and astroglial metabolic activity may help get an insight into AD pathology, thus providing biomarker(s) for the diagnosis of AD.

Keywords: Other Neurodegeneration, Neurodegeneration, Progressive supranuclear palsy

Motivation: The subthalamic nucleus (STN) volumes have not been fully assessed in progressive supranuclear palsy (PSP) and Parkinson’s disease (PD).

Goal(s): Our goal was to explore diagnostic accuracy of STN volumes in PSP and PD.

Approach: We measured the volumes of the STN, brainstem, and superior cerebellar peduncle in PSP and PD patients.

Results: The STN volumes in patients with PSP were significantly reduced compared to those with PD patients. Furthermore, there was a significant negative correlation between the STN volume and disease duration in PSP patients.

Impact: The use of high-spatial-resolution QSM to measure the STN volume has potential as a diagnostic marker for PSP, as well as for monitoring the progression of the disease.

Keywords: Other Neurodegeneration, Neurodegeneration

Motivation:  Brain iron deposition and analysis of risk factors in cerebral small vessel disease patients with different total cerebral small vessel disease (CSVD) scores

Goal(s): Our study compares brain iron deposition in gray matter (GM) nuclei between CSVD patients and healthy controls (HCs), exploring factors that affect iron deposition and cognitive function.

Approach: Brain iron load was assessed using quantitative susceptibility mapping.
 

Results: Age, diabetes, and smoking may increase iron deposition in the basal ganglia, associated with cognitive decline. The mean susceptibility values of the neostriatum played a mediating role in the association between hypertension and cognitive scores.

Impact: Age, diabetes and smoking history could exacerbate local brain iron deposition. The iron deposition in the neostriatum plays a mediating role in the association between hypertension and executive function.

Keywords: Other Neurodegeneration, Quantitative Susceptibility mapping, Brain, biomarker, degenerative, neuro, susceptibility

Motivation: Idiopathic REM Sleep Behavior Disorder (iRBD) is the prodromal syndrome of α-synucleinopathies whose conversion is difficult to predict.  

Goal(s): The goal was to study iron accumulation in the brains of patients and its clinical correlation with neuropsychological test. 
 

Approach: 20 patients underwent MRI protocol that included a QSM and a neuropsychological evaluation. The susceptibility values were compared with a group of healthy volunteers and correlated with neuropsychological tests. 

Results: Significant increase of iron deposition resulted in brainstem and in gray matter nuclei and positive correlation resulted between deterioration of visual-constructive and executive functions and magnetic susceptibility in substantia nigra and red nuclei.

Impact: Iron accumulation in the brain can serve as an early warning sign for neurodegenerative diseases linked to idiopathic REM Sleep Behavior Disorder (iRBD), indicating cognitive decline and behavioral issues. This may offer a non-invasive means to identify individuals at risk.

Keywords: Other Neurodegeneration, Neurodegeneration, Amyotrophic Lateral Sclerosis

Motivation: There is a need to understand the metabolic effects of Amyotrophic lateral sclerosis(ALS) in more brain regions, including globus pallidus that has a role in controlling conscious and proprioceptive movement.

Goal(s): To evaluate metabolic differences  of  ALS patients and healthy controls(HC) at the white matter(WM) and globus pallidus(GP).

Approach: LCModel was used to quantify multivoxel MR spectral data of ALS patients and HC. Metabolite peak ratios of these groups were compared at WM and GP regions.

Results: Lower Glu/tCr ratio at left WM than right side, lower GSH/tCr ratio at GP, and lower tNAA/tCr ratio at WM of ALS patients were observed.

Impact: Glu/tCr, GSH/tCr and tNAA/tCr ratio differences were identified at globus pallidus and white matter as possible biomarkers of ALS disease, which might affect treatment planning in ALS patients in the future.

Keywords: Other Neurodegeneration, Neuro, Denoise, Sodium MRI, MP-PCA

Motivation: Sodium MRI, a valuable imaging modality for various clinical applications, faces challenges related to signal-to-noise ratio (SNR). This study aims to enhance sodium MRI image quality through innovative denoising techniques.

Goal(s): Evaluate and compare novel denoising methods to improve sodium MRI quality and diagnostic potential.

Approach:  The study assesses denoising techniques in sodium MRI data, utilizing a 3T clinical scanner and a unique denoising algorithm MPPCA with reduced input requirements. Evaluation metrics include residual distributions, SNR and mean-square-error comparisons.

Results: MPPCA consistently outperforms other methods, showing its effectiveness in reducing noise and maintaining data fidelity.

Impact: The study demonstrates the potential of MPPCA as a powerful tool for enhancing sodium imaging, with broader implications for healthcare diagnostics and research.

Keywords: Aging, Aging, QSM, ASL

Motivation: Recognizing the crucial role of iron accumulation and CSF clearance in neurodegenerative diseases, this study aimed to address gaps in measuring these factors simultaneously, which may enhance our understanding of neurodegenerative diseases.

Goal(s): To employ a multiparametric approach integrating Quantitative Susceptibility Mapping (QSM) with non-contrast CSF outflow measurements in a single study.

Approach: Utilize QSM and Time-SLIP techniques on a small cohort to measure and correlate iron levels in the hippocampus and CSF outflow dynamics.

Results: We observed a correlation between iron deposition and age, though no significant age-related changes in CSF outflow were detected, underscoring the need for larger-scale studies.

Impact: This study offers researchers a new perspective on the relationship between iron accumulation CSF dynamics and aging, potentially opening pathways for deeper investigation into the mechanisms of neurodegenerative diseases.

Keywords: Aging, Quantitative Susceptibility mapping, Parkinson's disease, Aging, Deep-learning

Motivation: Quantitative susceptibility imaging (QSM) has demonstrated its potential in clinical applications. In patients with Parkinson’s disease, stroke, etc., a shorter acquisition time is desired. 

Goal(s): Here we aim to validate the accuracy of a deep learning (DL) based method for accelerating QSM in human volunteers.

Approach: We enrolled 59 participants from communities and acquired both routine QSM and DL-QSM images. We measured iron deposition in deep brain nucleus and studied the influence of different acceleration factors (3,4, and 5). 

Results: Results showed that susceptibility values from DL-QSM are highly consistent with routine parallel imaging accelerated images, and they also correlated well with age.

Impact: As we validated the reliability and accuracy of deep-learning accelerated quantitative susceptibility imaging, future clinical studies can use this method on patients who cannot tolerate long scan time.

Keywords: Aging, Nervous system, Cortical inhibition

Motivation: The effect of short-term physical activity on brain metabolism has been widely studied in young population, but less is known about metabolic plasticity induced by strength training over a long range among elderly adults. 

Goal(s): This study examined the modulatory potential of long-term strength training on metabolism in elderly population. 

Approach: Using 7 tesla magnetic resonance spectroscopy (MRS), we assessed concentrations of γ-Aminobutyric acid (GABA), glutamate (Glu), and a number of other metabolites in the sensorimotor cortex. 

Results: We found that three-months of strength learning significantly reduced lactate levels in the sensorimotor cortex compared to a passive control group.

Impact: This study systematically examined brain metabolic plasticity induced by strength training in the elderly population. The reduction in lactate indicates that strength training may facilitate oxidation of lactate to meet increased energy demands for learning.

Keywords: Aging, Brain

Motivation: The increasing evidence suggests a connection between presbycusis and cognitive impairment, yet the neurochemical mechanisms remain largely unexplored.

Goal(s): To compare auditory cortex metabolite levels and brain functional connectivity strength between presbycusis patients and healthy controls, and explore their potential associations with cognitive function and hearing.

Approach: We used Magnetic Resonance Spectroscopy (MRS) and resting-state functional Magnetic Resonance Imaging (rs-fMRI).

Results: We found reduced GABA levels in the auditory cortex (AC), and decreased connectivity between the AC and the ACC in presbycusis. Furthermore, the changes jointly mediated the association between hearing loss and declines in verbal memory and information processing speed.

Impact: These findings support the sensory deprivation hypothesis and highlight the role of GABA-induced inhibitory reduction and the dysconnectivity of AC and ACC in presbycusis-related cognitive impairment, providing new insights into the neurochemical mechanisms of hearing loss-associated cognitive impairment.

Keywords: Aging, Brain, Macromolecule

Motivation: Macromolecular (MM) signals overlap with metabolite signals and hinder accurate quantification of lower concentration metabolites, but MM content differences across age and brain region have remained elusive.

Goal(s): This study assesses MM differences linked to specific brain regions and age by analyzing metabolite signals in the M1 and thalamus.

Approach: We created age- and region-specific MM basis sets and evaluated quantification differences that arose from using matched and unmatched basis sets on the quantification of normal short-echo time spectra.

Results: We found significant differences in metabolite quantification between young and older adults, emphasizing the importance of age-specific MM basis sets for accurate results.

Impact: The research highlights the impact of age-related MM differences on metabolite quantification and emphasizes the need for tailored MM basis sets in spectroscopic studies.

Keywords: Aging, Aging, Alzheimer’s disease, Ex-vivo applications, Neuropathology

Motivation: High iron levels in the brain of older adults have been linked to age-related neuropathologies and cognitive impairment. It is not yet known how iron levels relate to brain MRI characteristics above and beyond the effects of neuropathologies.

Goal(s): To investigate the association of brain iron levels with R₂ and white matter hyperintensities (WMH) independent of the effects of age-related neuropathologies in community-based older adults.

Approach: Ex-vivo MRI, detailed neuropathologic evaluation, and inductively coupled plasma mass spectrometry were combined in 437 community-based older adults.

Results: Higher iron levels are independently associated with higher R₂ and WMH levels controlling for other metals and neuropathologies.

Impact: We demonstrated that brain iron levels in older adults are associated with higher R₂ and WMH independent of age-related neuropathologies and other metals, suggesting the presence of additional mechanisms of iron accumulation.

Keywords: Aging, Heart, Brain, Iron, Cognition, fMRI, women with INOCA, high resolution QSM Aging, Dementia

Motivation: Women with ischemia and non-obstructive coronary arteries (INOCA) may experience cognitive decline due to non-heme iron accumulation causing oxidative stress and cell death, but underlying mechanism is still unknown.

Goal(s): This study aims to understand how iron affects brain function and cognitive performance in women with suspected INOCA.

Approach: By combining high-resolution Quantitative Susceptibility Mapping and resting-state fMRI, the research focused on thalamic iron and its association with brain connectivity and cognitive metrics.

Results: Results indicated that thalamic iron impacts cognitive outcomes, particularly executive functions and processing speed, in women with suspected INOCA, with these effects partly mediated by changes in functional connectivity.

Impact: This study's insights into iron's cognitive effects may guide early interventions, influence therapeutic strategies for INOCA patients, and prompt further research into the systemic impact of iron on brain connectivity and cognitive health.

Keywords: Other Neurodegeneration, Quantitative Susceptibility mapping

Motivation: Iron accumulation is central to multiple system atrophy (MSA) pathogenesis, and promising compounds targeting iron dysregulation are being developed. Biomarkers for quantifying iron deposition are needed to improve diagnosis and demonstrate target engagement.

Goal(s): To assess the utility of iron quantification for early MSA diagnosis and progression monitoring.

Approach: We enrolled patients with MSA and employed quantitative susceptibility mapping (QSM) and a novel histogram analysis to quantify the topography of subcortical iron accumulation. 

Results: Our study revealed distinctive iron accumulation patterns in early MSA stages, highlighting the significance of iron quantification for differential diagnosis and progression assessment in MSA patients.

Impact: Quantitative susceptibility mapping (QSM) provides valuable insights into the pathological alterations associated with iron dysregulation in patients with multiple system atrophy (MSA) and could serve as a valuable tool for improving early diagnosis and evaluating novel treatments.