Structural Magnetic Resonance Imaging Abnormalities Research Articles

Cognitive function in primary and secondary progressive multiple sclerosis: a multiparametric MRI study.

The differences in cognitive function between primary progressive (PP) and secondary progressive (SP) multiple sclerosis (MS) remain unclear. We compared cognitive performance between PPMS and SPMS, and explored the structural and functional MRI correlates of their cognitive functions. Seventy-five healthy controls and 183 MS patients (60 PPMS and 123 SPMS) underwent 3.0T MRI. MS patients were administered the Brief Repeatable Battery of Neuropsychological Tests; cognitive domain z-scores were calculated and then averaged to obtain a measure of global cognition. Using hierarchical linear regression analysis, the contribution of lesion volumes, normalized brain volumes, white matter fractional anisotropy (FA) and mean diffusivity abnormalities, and resting state (RS) functional connectivity (FC) alterations to global cognition in PPMS and SPMS was investigated. PPMS and SPMS had similar z-scores in all investigated cognitive domains. Poor global cognitive function resulted associated with decreased FA of the medial lemniscus (ΔR2 =0.11; p=0.011) and lower normalized gray matter volume (ΔR2 =0.29; p<0.001) in PPMS, and with decreased FA of the fornix (ΔR2 =0.35; p<0.001) and lower normalized white matter volume (ΔR2 =0.05; p=0.034) in SPMS. PPMS and SPMS had similar neuropsychological performance. Cognitive dysfunction in PPMS and SPMS was related to distinct patterns of structural MRI abnormalities and involvement of different white matter tracts, while RS FC alterations did not contribute to explain their global cognitive functioning.

Deep Learning for Brain MRI Confirms Patterned Pathological Progression in Alzheimer's Disease.

Deep learning (DL) on brain magnetic resonance imaging (MRI) data has shown excellent performance in differentiating individuals with Alzheimer's disease (AD). However, the value of DL in detecting progressive structural MRI (sMRI) abnormalities linked to AD pathology has yet to be established. In this study, an interpretable DL algorithm named the Ensemble of 3-dimensional convolutional neural network (Ensemble 3DCNN) with enhanced parsing techniques is proposed to investigate the longitudinal trajectories of whole-brain sMRI changes denoting AD onset and progression. A set of 2369 T1-weighted images from the multi-centre Alzheimer's Disease Neuroimaging Initiative and Open Access Series of Imaging Studies cohorts are applied to model derivation, validation, testing, and pattern analysis. An Ensemble-3DCNN-based P-score is generated, based on which multiple brain regions, including amygdala, insular, parahippocampal, and temporal gyrus, exhibit early and connected progressive neurodegeneration. Complex individual variability in the sMRI is also observed. This study combining non-invasive sMRI and interpretable DL in detecting patterned sMRI changes confirmed AD pathological progression, shedding new light on predicting AD progression using whole-brainsMRI.

Neurophysiologic Profiling of At-Risk Low and Very Low Birth-Weight Infants Using Magnetic Resonance Imaging.

Low birth-weight (LBW) and very low birth-weight (VLBW) newborns have increased risks of brain injuries, growth failure, motor difficulties, developmental coordination disorders or delay, and adult-onset vascular diseases. However, relatively little is known of the neurobiologic underpinnings. To clarify the pathophysiologic vulnerabilities of such neonates, we applied several advanced techniques for assessing brain physiology, namely T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI) and phase-contrast (PC) MRI. This enabled quantification of oxygen extraction fraction (OEF), global cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2). A total of 50 neonates (LBW-VLBW, 41; term controls, 9) participated in this study. LBW-VLBW neonates were further stratified as those with (LBW-VLBW-a, 24) and without (LBW-VLBW-n, 17) structural MRI (sMRI) abnormalities. TRUST and PC MRI studies were undertaken to determine OEF, CBF, and CMRO2. Ultimately, CMRO2 proved significantly lower (p = 0.01) in LBW-VLBW (vs term) neonates, both LBW-VLBW-a and LBW-VLBW-n subsets showing significantly greater physiologic deficits than term controls (p = 0.03 and p = 0.04, respectively). CMRO2 and CBF in LBW-VLBW-a and LBW-VLBW-n subsets did not differ significantly (p > 0.05), although OEF showed a tendency to diverge (p = 0.15). However, OEF values in the LBW-VLBW-n subset differed significantly from those of term controls (p = 0.02). Compared with brain volume or body weight, these physiologic parameters yield higher area-under-the-curve (AUC) values for distinguishing neonates of the LBW-VLBW-a subset. The latter displayed distinct cerebral metabolic and hemodynamic, whereas changes were marginal in the LBW-VLBW-n subset (i.e., higher OEF and lower CBF and CMRO2) by comparison. Physiologic imaging may therefore be useful in identifying LBW-VLBW newborns at high risk of irreversible brain damage.

Magnetic resonance imaging abnormalities as a marker of multiple system atrophy in isolated rapid eye movement sleep behavior disorder.

Patients with isolated rapid eye movement (REM) sleep behavior disorder (IRBD) develop Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA). Magnetic resonance imaging (MRI) is abnormal in MSA showing abnormalities in the putamen, cerebellum, and brainstem. Our objective was to evaluate the usefulness of MRI to detect MRI abnormalities in IRBD and predict development of MSA and not PD and DLB. In IRBD patients that eventually developed PD, DLB, and MSA, we looked for the specific structural MRI abnormalities described in manifest MSA (e.g. hot cross-bun sign, putaminal rim, and cerebellar atrophy). We compared the frequency of these MRI changes among groups of converters (PD, DLB, and MSA) and analyzed their ability to predict development of MSA. The clinical and radiological features of the IRBD patients that eventually converted to MSA are described in detail. A total of 61 IRBD patients who underwent MRI phenoconverted to PD (n = 30), DLB (n = 26), and MSA (n = 5) after a median follow-up of 2.4 years from neuroimaging. MRI changes typical of MSA were found in four of the five (80%) patients who converted to MSA and in three of the 56 (5.4%) patients who developed PD or DLB. MRI changes of MSA had sensitivity of 80.0%, specificity of 94.6%, positive likelihood ratio of 14.9 (95% CI 4.6-48.8), and negative likelihood ratio of 0.2 (95% CI 0.04-1.2) to predict MSA. In IRBD, conventional brain MRI is helpful to predict conversion to MSA. The specific MRI abnormalities of manifest MSA may be detected in its premotor stage.

Environmental Risk Factors and Psychotic-like Experiences in Children Aged 9–10

Research implicates environmental risk factors, including correlates of urbanicity, deprivation, and environmental toxins, in psychotic-like experiences (PLEs). The current study examined associations between several types of environmental risk factors and PLEs in school-age children, whether these associations were specific to PLEs or generalized to other psychopathology, and examined possible neural mechanisms for significant associations. The current study used cross-sectional data from 10,328 children 9-10 years old from the Adolescent Brain Cognitive Development (ABCD) Study. Hierarchical linear models examined associations between PLEs and geocoded environmental risk factors and whether associations generalized to internalizing/externalizing symptoms. Mediation models examined evidence of structural magnetic resonance imaging abnormalities (eg, intracranial volume) potentially mediating associations between PLEs and environmental risk factors. Specific types of environmental risk factors, namely, measures of urbanicity (eg, drug offense exposure, less perception of neighborhood safety), deprivation (eg, overall deprivation, poverty rate), and lead exposure risk, were associated with PLEs. These associations showed evidence of stronger associations with PLEs than internalizing/externalizing symptoms (especially overall deprivation, poverty, drug offense exposure, and lead exposure risk). There was evidence that brain volume mediated between 11% and 25% of associations of poverty, perception of neighborhood safety, and lead exposure risk with PLEs. Although in the context of cross-sectional analyses, this evidence is consistent with neural measures partially mediating the association between PLEs and environmental exposures. This study also replicated and extended recent findings of associations between PLEs and environmental exposures, finding evidence for specific associations with correlates of urbanicity, deprivation, and lead exposure risk.

Are Patellofemoral Joint Alignment and Shape Associated With Structural Magnetic Resonance Imaging Abnormalities and Symptoms Among People With Patellofemoral Pain?

Background: Patellofemoral malalignment has been observed among people with patellofemoral pain (PFP) and may be associated with the presence of imaging features of osteoarthritis, symptoms, and function. Purpose: To determine whether patellofemoral joint alignment and bony shape are associated with (1) cartilage, bone, and soft tissue morphological abnormalities defined on magnetic resonance imaging (MRI) and (2) reported symptoms and function among people with PFP. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Participants (mean ± SD age, 30.2 ± 9.5 years; range, 14-50 years; 78 females, 58.6%) completed questionnaires regarding demographics, pain, symptoms, and function and underwent a 3-T MRI scan of their more symptomatic eligible knee. Structural MRI abnormalities were scored with the MOAKS (Magnetic Resonance Imaging Osteoarthritis Knee Score), and MRI alignment and shape were measured with standardized methods. Associations among MOAKS features, PFP symptoms, and alignment and shape measures were evaluated with regression analyses (α = .05). Results: Minor cartilage defects were present in 22 (16.5%) participants, patellar osteophytes in 83 (62.4%), anterior femur osteophytes in 29 (21.8%), Hoffa synovitis in 81 (60.9%), and prefemoral fat pad synovitis in 49 (36.8%). A larger Insall-Salvati ratio was significantly associated with the presence of patellar osteophytes (odds ratio [OR], 51.82; 95% CI, 4.20-640.01), Hoffa synovitis (OR, 60.37; 95% CI, 4.66-782.61), and prefemoral fat pad synovitis (OR, 43.31; 95% CI, 4.28-438.72) in the patellofemoral joint. A larger patellar tilt angle was significantly associated with the presence of minor cartilage defects (OR, 1.10; 95% CI, 1.00-1.20), the presence of patellar osteophytes (OR 1.12; 95%CI 1.02-1.22), and prefemoral fat pad synovitis (OR, 1.11; 95% CI, 1.03-1.20) in the patellofemoral joint. Finally, a larger bisect offset was significantly associated with the presence of minor cartilage defects (OR, 1.05; 95% CI, 1.00-1.11) and patellar osteophytes (OR, 1.07; 95% CI, 1.01-1.14) in the patellofemoral joint. The majority of patellofemoral alignment measures were not associated with symptoms or function. Conclusion: For people with PFP, the presence of morphological abnormalities defined on MRI appears to be related to particular patellofemoral alignment measures, including higher Insall-Salvati ratio (indicating patella alta), larger patellar tilt angle (indicating greater lateral tilt), and larger bisect offset (indicating greater lateral displacement). Hardly any associations were found with symptoms or function. So there might be a distinct subgroup of PFP that is more prone to developing patellofemoral osteoarthritis later in life, as particular alignment measures seem to be associated with the presence of patellar osteophytes. Prospective studies are required to investigate the longitudinal relationship between alignment or bony shape and morphological abnormalities defined on MRI in this patient population.

Structural Magnetic Resonance Imaging in Huntington's Disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by expansion of the CAG repeat in the huntingtin gene. HD is characterized clinically by progressive motor, cognitive and neuropsychiatric symptoms. There are currently no disease modifying treatments available for HD, and there is a great need for biomarkers to monitor disease progression and identify new targets for therapeutic intervention. Neuroimaging techniques provide a powerful tool for assessing disease pathology and progression in premanifest stages, before the onset of overt motor symptoms. Structural magnetic resonance imaging (MRI) is non-invasive imaging techniques which have been employed to study structural and microstructural changes in premanifest and manifest HD gene carriers. This chapter described structural imaging techniques and analysis methods employed across HD MRI studies. Current evidence for structural MRI abnormalities in HD, and associations between atrophy, structural white matter changes, iron deposition and clinical performance are discussed; together with the use of structural MRI measures as a diagnostic tool, to assess longitudinal changes, and as potential biomarkers and endpoints for clinical trials.

Compulsivity in opioid dependence

ObjectiveThis study aimed to investigate the relationship between compulsivity versus impulsivity and structural MRI abnormalities in opioid dependence. MethodWe recruited 146 participants: i) patients with a history of opioid dependence due to chronic heroin use (n=24), ii) heroin users stabilised on methadone maintenance treatment (n=48), iii) abstinent participants with a history of opioid dependence due to heroin use (n=24) and iv) healthy controls (n=50). Compulsivity was measured using Intra/Extra-Dimensional (IED) Task and impulsivity was measured using the Cambridge Gambling Task (CGT). Structural Magnetic Resonance Imaging (MRI) data were also obtained. ResultsAs hypothesised, compulsivity was negatively associated with impulsivity (p<0.02). Testing for the neural substrates of compulsivity versus impulsivity, we found a higher compulsivity/impulsivity ratio associated with significantly decreased white matter adjacent to the nucleus accumbens, bed nucleus of stria terminalis and rostral cingulate in the abstinent group, compared to the other opioid dependent groups. In addition, self-reported duration of opioid exposure correlated negatively with bilateral globus pallidus grey matter reductions. ConclusionOur findings are consistent with Volkow & Koob's addiction models and underline the important role of compulsivity versus impulsivity in opioid dependence. Our results have implications for the treatment of opioid dependence supporting the assertion of different behavioural and biological phenotypes in the opioid dependence and abstinence syndromes.

Improved Measurement of Brain Phenylalanine and Tyrosine Related to Neuropsychological Functioning in Phenylketonuria.

Researchers hypothesized that in phenylketonuria (PKU) high brain phenylalanine (Phe) levels and low brain tyrosine (Tyr) levels affect neuropsychological functioning. However, traditional magnetic resonance spectroscopy (MRS) yielded uncertain results of brain Phe and could not adequately measure brain Tyr. This pilot study examined the potential of correlated spectroscopy (COSY) to quantify these biomarkers and explain variability in neuropsychological functioning. Nine adults with early treated classic PKU received magnetic resonance imaging (MRI) with COSY and a battery of neuropsychological tests. Brain Phe and Tyr in parietal white matter (PWM) were compared to results in gray matter of the posterior cingulate gyrus (PCG). Brain Phe ranged from 101 to 182 (mean = 136.76 ± 23.77) μmol/L in PCG and 76 to 185 (mean = 130.11 ± 37.88) μmol/L in PWM. Brain Tyr ranged from 4.0 to 7.4 (mean = 5.44 ± 1.01) μmol/L in PCG and 4.1 to 8.4 (mean = 5.90 ± 1.48) μmol/L in PWM. Correlation coefficients were largest for brain Phe PWM and measures of auditory memory (rho = -0.79), anxiety (rho = 0.79), and executive functioning (rho = 0.69). Associations were in the expected direction, with higher brain Phe and lower brain Tyr related to poorer functioning. The two participants with severe structural MRI abnormalities had low brain Tyr levels in PCG and 3/5 of the participants with moderate to severe MRI abnormalities had higher than average brain Phe levels. COSY has the potential to quantify brain Phe and Tyr at low concentrations and in specific brain regions. In this pilot study, these biomarkers were associated with indices of neuropsychological functioning. Additional studies are needed to validate the COSY results.

Cerebral Blood Flow Abnormalities in Children With Sickle Cell Disease: A Systematic Review

A systematic review was performed to assess whether cerebral blood flow with different imaging modalities could identify brain abnormalities in children with sickle cell disease where structural magnetic resonance imaging and transcranial Doppler velocity appeared normal. A total of 11 studies were identified which reported cerebral blood flow abnormalities alongside structural magnetic resonance imaging or transcranial Doppler velocity abnormalities in patients with sickle cell disease. Potential for bias was assessed with the quality assessment of diagnostic accuracy studies scale in addition to treatment bias. Subjects of each study were categorized into patients with and without stroke. The prevalence of abnormalities for each modality was then separately calculated in each group. The included studies had mostly moderate degrees of bias. The prevalence of blood flow abnormalities compared with structural magnetic resonance imaging abnormalities was equal to or lower in patients with stroke and equal to or greater in patients without stroke. Blood flow abnormalities were more prevalent than transcranial Doppler abnormalities in four studies of patients without stroke and in one study of patients with stroke. The studies suggest that the assessment of cerebral blood flow in sickle cell disease can be of potential value in addressing brain abnormalities at the tissue level; however, further studies are warranted.

Quantitative Assessment of Brain Networks in Children With Sturge-Weber Syndrome Using Resting State Functional Magnetic Resonance Imaging (MRI)

In this study, we examined whether topologic network analysis, using resting state functional magnetic resonance imaging (MRI), can detect abnormalities of functional brain connectivity in children with unilateral brain injury due to Sturge-Weber syndrome. Three children with Sturge-Weber syndrome (ages 1, 3, and 10 years) underwent structural and resting state functional MRI, glucose metabolism positron emission tomography (PET), and neurocognitive evaluation. Eight different resting state networks were compared between the affected and unaffected hemispheres by quantitatively accessing communication efficiency measures. Significantly reduced efficiency values were found in all 3 patients. Visual network deficiency was present in both children with a visual field defect; frontal network abnormalities were associated with fine motor impairment. Location of network abnormalities corresponded to and, in some cases, extended beyond structural MRI and glucose PET abnormalities. The presented approach can detect early functional abnormalities of specific brain networks in children with Sturge-Weber syndrome.

Correlation between quantitative EEG and MRI in idiopathic generalized epilepsy

The objective of this study was to investigate the relationship between the focal discharges sometimes observed in the electroencephalogram of patients with idiopathic generalized epilepsies and subtle structural magnetic resonance imaging abnormalities. The main hypothesis to be assessed is that focal discharges may arise from areas of structural abnormality which can be detected by quantitative neuroimaging. Focal discharges were used for quantitative electroencephalogram source detection. Neuroimaging investigations consisted of voxel-based morphometry and region of interest volumetry. For voxel-based morphometry, volumetric MRI were acquired and processed. The images of each patient were individually compared with a control group. Statistical analysis was used to detect differences in gray matter volumes. Region of interest-based morphometry was automatically performed and used essentially to confirm voxel-based morphometry findings. The localization of the focal discharges on the electroencephalogram was compared to the neuroimaging results. Twenty-two patients with idiopathic generalized epilepsies were evaluated. Gray matter abnormalities were detected by voxel-based morphometry analysis in 77% of the patients. There was a good concordance between EEG source detection and voxel-based morphometry. On average, the nearest voxels detected by these methods were 19 mm (mm) apart and the most statistically significant voxels were 34 mm apart. This study suggests that in some cases subtle gray matter abnormalities are associated with focal epileptiform discharges observed in the electroencephalograms of patients with idiopathic generalized epilepsies.

Idiopathic REM Sleep Behavior Disorder and Parkinson's Disease—Two Sides of One Coin?

Idiopathic REM Sleep Behavior Disorder and Parkinson's Disease—Two Sides of One Coin?

Patterns of Structural MRI Abnormalities in Deficit and Nondeficit Schizophrenia

Negative symptoms of schizophrenia have generally been found in association with ventricular enlargement and prefrontal abnormalities. These relationships, however, have not been observed consistently, most probably because negative symptoms are heterogeneous and result from different pathophysiological mechanisms. The concept of deficit schizophrenia (DS) was introduced by Carpenter et al to identify a clinically homogeneous subgroup of patients characterized by the presence of primary and enduring negative symptoms. Findings of brain structural abnormalities reported by magnetic resonance imaging (MRI) studies focusing on DS have been mixed. The present study included 34 patients with DS, 32 with nondeficit schizophrenia (NDS), and 31 healthy comparison subjects, providing the largest set of MRI findings in DS published so far. The Schedule for the Deficit Syndrome was used to categorize patients as DS or NDS patients. The 2 patient groups were matched on age and gender and did not differ on clinical variables, except for higher scores on the negative dimension and more impaired interpersonal relationships in DS than in NDS subjects. Lateral ventricles were larger in NDS than in control subjects but were not enlarged in patients with DS. The cingulate gyri volume was smaller in NDS but not in DS patients as compared with healthy subjects. Both groups had smaller dorsolateral prefrontal cortex and temporal lobes than healthy subjects, but DS patients had significantly less right temporal lobe volume as compared with NDS patients. These findings do not support the hypothesis that DS is the extreme end of a severity continuum within schizophrenia.

Correlation of cognitive status, MRI‐ and SPECT‐imaging in CADASIL patients

Although there is evidence for correlations between disability and magnetic resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of structural MRI abnormalities for cognitive dysfunction remains controversial. We performed detailed neuropsychological testing, high resolution MRI, and Tc-99m-ethyl cysteinate-dimer SPECT in three CADASIL patients. MR-images were rated independently by two investigators for the presence of white matter lesions, lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was quantified by the use of automatic morphometric assessment of the cortical thickness. In addition, laboratory and patients' history data were collected in order to assess the individual vascular risk factor profile. The differences in cognitive performance between the three patients are neither explained by structural-, or functional neuroimaging, nor by the patient-specific vascular risk factor profiles. The neuroradiologically least affected patient met criteria for dementia, whereas the most severely affected patient was in the best clinical and cognitive state. Conventional structural and functional neuroimaging is important for the diagnosis of CADASIL, but it is no sufficient surrogate marker for the associated cognitive decline. Detailed neuropsychological assessment seems to be more useful, particularly with respect to the implementation of reliable outcome parameters in possible therapeutic trials.

Correlations between clinical and historical variables, and cerebral structural variables in people with mild intellectual disability and schizophrenia.

The increased prevalence of schizophrenia in the population with mildly intellectual disability (ID) remains unexplained. The present study explores several possibilities by examining historical/clinical findings in relation to structural neuroimaging findings in three groups: (1) comorbid mild ID and schizophrenia; (2) schizophrenia alone; and (3) mild ID alone. Information about clinical and historical variables was obtained from 101 subjects (39 with comorbidity, 34 with schizophrenia and 28 with mild ID), out of whom 68 (23, 25 and 20, respectively) had had a cerebral magnetic resonance imaging (MRI) scan. Although a number of significant correlations exist between clinical variables and structural MRI abnormalities in all three groups, no clearly predictive inter- or between-group differences emerged. More striking was the finding that showed small amygdalo-hippocampal size to be associated with a history of central nervous system injury, especially meningitis. These findings provide support for the view that cognitive impairment and comorbid psychosis can result from a common cause, such as meningitis or obstetric complications, possibly interacting with other factors, such as family history.

Structural magnetic resonance imaging abnormalities in men with severe chronic schizophrenia and an early age at clinical onset.

Early age at onset of schizophrenia often signifies a more severe form of the illness. However, the relationship between age at onset and brain abnormalities has not been established. We assessed temporal-limbic morphometry in severely ill men with chronic schizophrenia who had a relatively early onset of illness and examined the relationships among regional brain volumes, clinical symptoms, and age at illness onset. Temporal lobe, superior temporal gyrus, hippocampus, temporal horn, lateral ventricles, third ventricle, and frontoparietal volumes were measured on magnetic resonance imaging data from 56 schizophrenic men (mean [SD] age at illness onset, 16.6 [4.2] years) recruited from a state hospital and 52 age- and range-matched healthy control men. Patients had significantly smaller gray matter volumes in the temporal lobe, superior temporal gyrus, and frontoparietal regions; smaller temporal lobe white matter volumes; and larger cerebrospinal fluid volumes for temporal lobe sulci and the 3 ventricular measures. There were no group differences in hippocampal volumes. Psychotic symptom subscores from the Brief Psychiatric Rating Scale were selectively correlated with smaller left posterior superior temporal gyrus gray matter volumes. None of the brain measurements were significantly correlated with age at illness onset. Data from this unique sample of severely ill schizophrenic men emphasize a pattern of structural abnormalities involving the cortex, but not the hippocampus, in schizophrenia. Furthermore, these data support theories suggesting that superior temporal gyrus abnormalities contribute selectively to psychotic symptoms and that the extent of structural abnormalities is unrelated to age of clinical symptom onset.