Structural Magnetic Resonance Imaging Changes Research Articles

Magnetic resonance imaging characterization of an α‐synuclein model of Parkinson's disease

AbstractParkinson's disease (PD) is primarily characterized by three histological hallmarks: dopaminergic neuronal degeneration, α‐synuclein accumulation and iron deposition. Over the last years, neuroimaging, particularly magnetic resonance imaging (MRI) has provided invaluable insights into the mechanisms underlying the disease. However, no imaging method has yet been able to translate α‐synuclein protein accumulation and spreading. Amongst the animal models mimicking the disease, the α‐synuclein rat, generated through the injection of human α‐synuclein, has been characterized in terms of behavioural and histological aspects but not thoroughly explored in MRI. The aim of this study is, therefore, to identify the radiological signature from several MRI sequences, while controlling for histological and behavioural characteristics. Rats were assessed for motor and cognitive functions over a 4‐month period. During this time, three MRI sessions, including both morphological and functional sequences, were conducted. Histological studies evaluated the three main hallmarks of PD. The progressive dopaminergic neurodegeneration and the spread of human α‐synuclein corresponded to the level of sensorimotor, attentional and learning deficits observed in this PD model. MRI analyses showed progressive structural abnormalities in the midbrain, diencephalon and several cortical structures, as well as a pattern of hyperconnectivity in the basal ganglia and cortical networks. The regions affected in imaging demonstrated the highest load of human α‐synuclein. This model's structural and functional MRI changes could serve as indirect indicators of α‐synuclein accumulation and its association with impaired non‐motor functions.

Gait Analysis and Magnetic Resonance Imaging Characteristics in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

Isolated rapid eye movement sleep behavioral disorder (iRBD) can precede neurodegenerative diseases. There is an urgent need for biomarkers to aid early intervention and neuroprotection. The aim is to assess quantitative motor, cognitive, and brain magnetic resonance imaging (MRI) characteristics in iRBD patients. Thirty-eight polysomnography-confirmed iRBD patients and 28 age- and sex-matched healthy controls underwent clinical, cognitive, and motor functional evaluations, along with brain MRI. Motor tasks included nine-hole peg test, five-times-sit-to-stand test, timed-up-and-go test, and 4-meter walking test with and without cognitive dual task. Quantitative spatiotemporal gait parameters were obtained using an optoelectronic system. Brain MRI analysis included functional connectivity (FC) of the main resting-state networks, gray matter (GM) volume using voxel-based morphometry, cortical thickness, and deep GM and brainstem volumes using FMRIB's Integrated Registration and Segmentation Tool and FreeSurfer. iRBD patients relative to healthy subjects exhibited a poorer performance during the nine-hole peg test and five-times-sit-to-stand test, and greater asymmetry of arm-swing amplitude and stride length variability during dual-task gait. Dual task significantly worsened the walking performance of iRBD patients more than healthy controls. iRBD patients exhibited nonmotor symptoms, and memory, abstract reasoning, and visuospatial deficits. iRBD patients exhibited decreased FC of pallidum and putamen within the basal ganglia network and occipital and temporal areas within the visuo-associative network, and a reduced volume of the supramarginal gyrus. Brain functional alterations correlated with gait changes. Subtle motor and nonmotor alterations were identified in iRBD patients, alongside brain structural and functional MRI changes. These findings may represent early signs of neurodegeneration and contribute to the development of predictive models for progression to parkinsonism. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Can basic magnetic resonance imaging along with neuropsychological assessment be used as a cost-effective means for the detection of early dementia in the Indian sub-continent?

ABSTRACT Introduction: The mild cognitive impairment (MCI) stage occurs sporadically between healthy aging and the onset of Alzheimer’s disease (AD). MCI shows significant defacement in magnetic resonance imaging (MRI) of the brain along with neuropsychological and behavioral parameters. Aim: Assessment of neuropsychological, behavioral, and structural MRI changes in MCI and their relation with each other. Methodology: Seventy-eight participants in the MCI group and healthy controls (HC) were assessed using Addenbrooke’s Cognitive Examination (ACE), Mini-Mental Status Examination (MMSE), Clinical Dementia Rating Scale (CDR); and behavioral assessment by using Behavioral Pathology In AD (BEHAVE-AD). MRI brain volumetric analysis was performed using the software MYRIAN. Statistical analysis was performed using the Mann–Whitney U test, unpaired t-test (P = <0.05), and Spearman’s rank correlation. Results: MCI group showed significant impairments in ACE, MMSE, and CDR and significantly higher behavioral symptoms on BEHAVE-AD. Episodic memory had a significant positive correlation with normalized right hippocampal volume and total intracranial volume (TICV). Remote memory had a significant negative correlation with normalized left hippocampal volumes. Global CDR score had a moderately negative correlation with normalized right and left hippocampal volumes. Affective disturbances were negatively correlated with TICV. Conclusions: Comparable analysis of correctly scaled neuropsychological assessments may provide unbiased proxies for MRI-based measures of dementia risk.

Antipsychotics and structural brain changes: could treatment adherence explain the discrepant findings?

Progressive structural brain changes are well documented in schizophrenia and have been linked to both illness progression and the extent of antipsychotic treatment exposure. Literature reporting longitudinal changes in brain structure in individuals with schizophrenia is selectively reviewed to assess the roles of illness, antipsychotic treatment, adherence and other factors in the genesis of these changes. This narrative review considers literature investigating longitudinal changes in brain structure in individuals with schizophrenia. The review focusses on structural changes in the cortex, basal ganglia and white matter. It also examines effects of medication non-adherence and relapse on the clinical course of the illness and on structural brain changes. Studies investigating structural magnetic resonance imaging changes in patients treated with long-acting injectable antipsychotics are reviewed. Temporal changes in brain structure in schizophrenia can be divided into those that are associated with antipsychotic treatment and those that are not. Changes associated with treatment include increases in basal ganglia and white matter volumes. Relapse episodes may be a critical factor in illness progression and brain volume reductions. Medication adherence may be an important factor that could explain the findings that brain volume reductions are associated with poor treatment response, higher intensity of antipsychotic treatment exposure and more time spent in relapse. Improved adherence via long-acting injectable antipsychotics and adherence focussed psychosocial interventions could maximize protective effects of antipsychotics against illness progression.

Longitudinal resting-state functional connectivity and regional brain atrophy-based biomarkers of preclinical cognitive impairment in healthy old adults.

Intervention against age-related neurodegenerative diseases may be difficult once extensive structural and functional deteriorations have already occurred in the brain. Investigating 6-year longitudinal changes and implications of regional brain atrophy and functional connectivity in the triple-network model as biomarkers of preclinical cognitive impairment in healthy aging. We acquired longitudinal cognitive scores and magnetic resonance imaging (MRI) data from 74 healthy old adults. Resting-state functional MRI (rs-fMRI) analysis was conducted using FSL6.0.1 to examine functional connectivity changes and regional brain morphometries were quantified using FreeSurfer5.3. Finally, we cross-validated and compared two support vector machine (SVM) regression models to predict future 6-year cognition score from the baseline regional brain atrophy and resting-state functional connectivity (rs-FC) measures. After a 6-year follow-up, our results (P < 0.05-corrected) indicated significant connectivity reduction within all the three brain networks, significant differences in regional brain volumes and cortical thickness. We also observed significant improvement in episodic memory and significant decline in executive functions. Finally, comparing the two models, we observed that regional brain atrophy predictors were more efficient in approximating future 6-year cognitive scores (R = 0.756, P < 0.0001) than rs-FC predictors (R = 0.6, P < 0.0001). This study used longitudinal data to keep subject variability low and to increase the validity of the results. We demonstrated significant changes in structural and functional MRI over 6years. Our findings present a potential neuroimaging-based biomarker to detect cognitive impairment and prevent risks of neurodegenerative diseases in healthy old adults.

Trauma-focused psychotherapy response in youth with posttraumatic stress disorder is associated with changes in insula volume

Randomized controlled trials have shown efficacy of trauma-focused psychotherapies in youth with posttraumatic stress disorder (PTSD), but little is known about the relationship between treatment response and alternations in brain structures associated with PTSD. In this study, we longitudinally examined the association between treatment response and pre-to posttreatment changes in structural magnetic resonance imaging (MRI) scans using a voxel-based morphometry approach. We analyzed MRI scans of 35 patients (ages 8–18 years, 21 female) with PTSD (80%) or partial PTSD (20%) before and after eight weekly sessions of trauma-focused psychotherapy. PTSD severity was assessed longitudinally using the Clinician-Administered PTSD scale for Children and Adolescents to divide participants into responders and non-responders. Group by time interaction analysis showed significant differences in grey-matter volume in the bilateral insula due to volume reductions over time in non-responders compared to responders. Despite the significant group by time interaction, there were no significant group differences at baseline or follow-up. As typical development is associated with insula volume increase, these longitudinal MRI findings suggest that treatment non-response is associated with atypical neurodevelopment of the insula, which may underlie persistence of PTSD in youth. The absence of structural MRI changes in treatment responders, while in need of replication, suggest that successful trauma-focused psychotherapy may not directly normalize brain abnormalities associated with PTSD.

Working memory training and brain structure and function in extremely preterm or extremely low birth weight children.

This study in children born extremely preterm (EP; <28 weeks’ gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety‐one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45‐min sessions, 5 days a week over 5–7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task‐based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level‐dependent (BOLD) signal during an n‐back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n‐back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group‐by‐time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training‐induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, http://anzctr.org.au; ACTRN12612000124831.

Beyond clinical changes: Rehabilitation-induced neuroplasticity in MS

Background: Neural plasticity represents the substrate by which the damaged central nervous system (CNS) re-learns lost behaviors in response to rehabilitation. In persons with multiple sclerosis (MS), rehabilitation can therefore exploit the potential of neural plasticity to restore CNS functions beyond the spontaneous mechanisms of recovery from MS-related damage. Methods: Here, we reviewed the currently available evidence on the occurrence of mechanisms of structural and functional plasticity following rehabilitation, motor, and/or cognitive training. We presented both data gained from basic laboratory research on animal models and data on persons with MS obtained by advanced magnetic resonance imaging (MRI) techniques. Results: Studies on physical and environmental enrichment in experimental MS models showed beneficial effects mediated by both immune modulation and activity-dependent plasticity, lowering tissue destruction and restoring of CNS network function. Translational researches in MS people demonstrated structural and/or functional MRI changes after various interventions, but their heterogeneity and small sample sizes (5–42 patients) raise concerns about the interpretation and generalization of the obtained results. Discussion: We highlighted the limitations of published studies, focusing on the knowledge gaps to be filled in terms of neuropathological correlations between changes detected in animal models and changes detected in vivo by neuroimaging.

P2‐340: LASTING CONSEQUENCES OF CONCUSSION: BRAIN FINDINGS FROM THE BALTIMORE LONGITUDINAL STUDY OF AGING

While recent studies have reported alterations in the structure and function of the brain following a concussive event, few have examined the long-term impact of concussions on the aging brain. Here, we examine these long-term effects, 20+ years after the incident. We used neuroimaging and neuropsychological data from 51 participants (mean age at neuroimaging baseline=65.1, SD=11.23) in the Baltimore Longitudinal Study of Aging (BLSA) who reported a concussion in their medical history an average of 22 years prior to first visit, and compared them to 150 age, sex, and race matched BLSA participants with no history of concussion. Participants underwent structural magnetic resonance imaging (MRI) over a mean of 5.17 years (SD=6.14) and diffusion tensor imaging (DTI) over a mean of 2.92 years (SD=2.22) to measure brain structure, as well as 15O-water Positron Emission Tomography (PET) over a mean of 5.33 years (SD=2.19) to measure brain function. A battery of neuropsychological tests was also administered over a mean of 11.62 years (SD=7.41). Structural MRI changes indicating brain atrophy were seen in temporal lobe white matter and hippocampus at first visit, and in the occipital pole during longitudinal follow-up. Structural differences in white matter integrity using DTI were seen with increased radial and axial diffusivity in the fornix/stria terminalis, and internal capsule at first visit, and in fractional anisotropy in the corona radiata during longitudinal follow-up. Functional differences were seen in 15O-PET resting cerebral blood flow at first visit and longitudinal follow-up in regions including the frontal, temporal, and parietal cortices. No significant differences in neuropsychological performance were seen between groups, but within the concussion group itself, there was a correlation between age at concussive event and visuospatial performance, with concussion sustained at older ages associated with lower performance levels at first visit. These findings indicate that a single concussion can produce subtle, long-lasting structural and functional changes to brain. As many of these regions are susceptible to age-related neuropathologic changes, these findings also suggest that individuals with a history of concussion may be more vulnerable to further dysfunction in these brain regions with advancing age.

What does imaging reveal about the pathology of amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is now recognised to be a heterogeneous neurodegenerative syndrome of the motor system and its frontotemporal cortical connections. The development and application of structural and functional imaging over the last three decades, in particular magnetic resonance imaging (MRI), has allowed traditional post mortem histopathological and emerging molecular findings in ALS to be placed in a clinical context. Cerebral grey and white matter structural MRI changes are increasingly being understood in terms of brain connectivity, providing insights into the advancing degenerative process and producing candidate biomarkers. Such markers may refine the prognostic stratification of patients and the diagnostic pathway, as well as providing an objective assessment of changes in disease activity in response to future therapeutic agents. Studies are being extended to the spinal cord, and the application of neuroimaging to unaffected carriers of highly penetrant genetic mutations linked to the development of ALS offers a unique window to the pre-symptomatic landscape.

Neuropathologic Correlates of Hippocampal Atrophy in the Elderly: A Clinical, Pathologic, Postmortem MRI Study

The volume of the hippocampus measured with structural magnetic resonance imaging (MRI) is increasingly used as a biomarker for Alzheimer's disease (AD). However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study. First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6×10−7) or mild cognitive impairment (P = 9.6×10−7). Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018) and hippocampal sclerosis (P = 4.2×10−7). Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal volume in old age, though the impacts of each pathology on the shape of the hippocampus may differ.

Longitudinal Volume Reductions in People at High Genetic Risk of Schizophrenia as They Develop Psychosis

Structural differences between the brains of people with schizophrenia and control subjects are highly replicated but the timing and clinical correlates are unclear. In the Edinburgh High Risk Study, we have followed up 162 individuals at high genetic risk of schizophrenia and 36 healthy control subjects over 10 years. Participants received detailed clinical and up to five structural magnetic resonance imaging (MRI) assessments at 2-year intervals. All 436 MRI scans acquired were parcellated and adjusted for between-scanner differences. The trajectory of any structural MRI changes was then investigated using mixed effects analysis of variance. Seventeen of the 146 high-risk subjects who were scanned developed schizophrenia over the 8 years of the study. People at high genetic risk of schizophrenia had significantly greater reductions over time than the control group for whole brain volume and left and right prefrontal and temporal lobes. Greater prefrontal reductions were shown in high-risk subjects who subsequently became unwell compared with those who did not. These changes were significantly associated with increasing severity of psychotic symptoms. Individuals at high genetic risk of schizophrenia exhibited reductions in cerebral volume that were not found in control subjects. Changes in brain structure were also associated with increasing psychotic symptom severity as people developed schizophrenia. The progressive reductions found in those who went on to develop schizophrenia suggest an additional brain insult near to the time of onset.

Validation of Definitions for Structural Lesions Detected by Magnetic Resonance Imaging in the Spine of Patients with Spondyloarthritis

<h3>Objective.</h3> Assessment of structural features of spondyloarthritis (SpA) on magnetic resonance imaging (MRI) has proven to be no more reliable than plain radiography, which may reflect a lack of standardization and application of rigorous definitions. The Canada-Denmark MRI Working Group has developed a comprehensive list of definitions for the structural MRI changes in the spine of patients with SpA. We conducted a systematic evaluation of the frequency and reliability of detection of structural lesions. <h3>Methods.</h3> Chronic lesions were independently recorded dichotomously (present/absent) from lower C2 to the upper sacrum on T1-weighted MRI scans of 20 patients with ankylosing spondylitis by 4 readers. Prior to the exercise, a series of reference images was developed in which structural lesions were assigned by consensus. We tested a method for scoring new bone formation based on assigning a score of 2 for a bone spur and a score of 6 for intervertebral ankylosis [Canada-Denmark Spur and Ankylosis score (CanDen SAS)]. <h3>Results.</h3> Focal fat infiltration and non-corner vertebral endplate erosions were observed in the majority of patients and were reliably detected. Vertebral corner erosions were not reliably detected. New bone lesions were also detected in almost all patients, and intervertebral ankylosis was detected with good reliability. Bone spurs were not reliably detected. The CanDen SAS demonstrated excellent interobserver reliability (ICC = 0.93) across 4 readers. <h3>Conclusion.</h3> Definitions for focal fat infiltration, non-corner vertebral erosions, and intervertebral ankylosis function well as regards reliability. Despite rigorous standardization of definitions, substantial calibration is required for vertebral corner erosions and bone spurs.

Magnetic resonance imaging of sacroiliac joints in patients with seronegative spondyloarthritides

Objective. To study diagnostic possibilities of magnetic resonance imaging (MRI) of sacroiliac joints (SIJ) in pts with seronegative spondyloarthritides (SS). Material and methods. MRI and radiological examination was performed in 15 pts: 10 with ankylosing spondylitis (AS) and 5 with undifferentiated SS. MRI was done with Magnetom Symphony apparatus (Siemens, Germany) with magnetic-field strength 1,5 tesla. Tl, T2 and T2-FS weighted were used. Tl-FS weighted performed in 3-4 minutes after intravenous infusion of gadolinium were additionally used in 5 pts. Inflammatory and structural (erosions, subchondral sclerosis) MRI changes of SIJ were studied. Inflammatory changes of SIJ were analyzed in subchondral bone, bone marrow, joint capsule, joint cavity, interosseous ligaments. SS activity was assessed with BASDAI. Results. Median age of pts was 24 years, median SS duration — 3 years. HLA-B27 was revealed in 13 from 15 pts. All pts had radiological signs of sacroiliitis: 13 - bilateral (12 - II or III stage and 1 — I and III stage according to Kellgren), 2 — unilateral (II stage). So radiological signs of inflammation were revealed in 28 from 30 examined SIJ. MRI signs of sacroiliitis were present in the same 28 SIJ. Subchondral edema of sacrum and/or huckle-bone was revealed in 23 SIJ of 13 pts, bone marrow edema — in 20 SIJ of 13 pts, joint cavity edema - in 21 SIJ of 14 pts, capsule edema — in 12 SIJ of 8 pts, interosseous ligaments inflammation signs — in 3 SIJ of 2 pts. Inflammatory changes of all 5 examined anatomic structures were present in 1, 4 — in 9, 3 — in 13 SIJ. In 1 SIJ inflammation was localized in capsule only. Structural changes were revealed in 22 (73%) SIJ of 14 pts. Structural MRI changes of SIJ at II radiological stage of sacroiliitis were noted in 67% and at III stage — in 83%. Combination of inflammatory and structural changes was present in 22 from 30 SIJ (73%). Frequency of such combination was similar at different radiological stages of sacroiliitis. Isolated inflammatory signs without structural changes were present in 3 SIJ of 3 pts. Gadolinium administration allowed to reveal 5 additional edema zones in SIJ region of 4 from 5 pts. Inflammatory changes of SIJ were revealed with similar frequency in presence (81%) or absence (88%) of pain in this region. Pts with high (BASDAI>40) or not high (BASDAK40) general activity of the disease had about the same mean number of SIJ inflammatory changes (7,6 and 7,8 respectively). Conclusion. MRI is highly sensitive method for revealing SIJ changes in pts with SS. Inflammatory MRI changes were present in all joints with radiological changes irrespectively from radiological stage.