Gray Matter Research Articles

Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on adolescent brain morphology.

Children born to mothers with gestational hypo- or hyperthyroidism may have increased risk of adverse neurodevelopmental outcomes. However, the effects of maternal thyroid status on offspring brain development are unclear. To establish whether adolescent brain morphology is affected by suboptimal gestational thyroid function (SGTF). The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from ∼12 weeks' gestation. At age 9, children born to mothers who were over-treated with levothyroxine had a higher risk of conduct and hyperactivity traits. For the current CATS III study, children underwent neuroimaging studies, including T1-weighted structural magnetic resonance imaging (MRI). A total of 85 children aged 11-16 years had usable T1-weighted MRI data (exposed to untreated SGTF (n=21), normal GTF (n=24), or treated SGTF (optimally-treated (n=21), over-treated (n=20)). Primary outcome: to examine the association of SGTF and its treatment with global brain volumes. Secondary and exploratory outcomes: to investigate the association of maternal TSH and free T4 levels with global and subregional brain volumes. Results were adjusted for age, sex and pubertal scores. There were no significant differences in global brain volumetric measures between groups, including total gray matter volume (p=0.373). Weak positive correlations were found between maternal TSH, but not FT4, levels and several brain volumes, but these did not survive testing for multiple comparisons. We found no evidence that SGTF was associated with differences in adolescent brain morphology, and no impact of levothyroxine supplementation.

Diabetes mellitus in older persons with neurocognitive disorder: overtreatment prevalence and associated structural brain MRI findings

BackgroundTight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes.MethodsRetrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated.ResultsAmong 161 patients included (median age 76.8 years, range 60.8–93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj β coeff: -0.217, 95%CI: [-0.416 to -0.018], p = .033), the precentral gyri (adj βcoeff:-0.277, 95%CI: [-0.482 to -0.073], p = .009), the superior frontal gyri (adj βcoeff: -0.244, 95%CI: [-0.458 to -0.030], p = .026), the calcarine cortex (adj βcoeff:-0.193, 95%CI: [-0.386 to -0.001], p = .049), the superior occipital gyri (adj βcoeff: -0.291, 95%CI: [-0.521 to -0.061], p = .014) and the inferior occipital gyri (adj βcoeff: -0.236, 95%CI: [-0.456 to – 0.015], p = .036).ConclusionA significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample.

Thyroid hormone analogues: Promising therapeutic avenues to improve the neurodevelopmental outcomes of intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a pregnancy complication impairing fetal growth and development. The compromised development is often attributed to disruptions of oxygen and nutrient supply from the placenta, resulting in a number of unfavourable physiological outcomes with impaired brain and organ growth. IUGR is associated with compromised development of both grey and white matter, predisposing the infant to adverse neurodevelopmental outcomes, including long-lasting cognitive and motor difficulties. Cerebral thyroid hormone (TH) signalling, which plays a crucial role in regulating white and grey matter development, is dysregulated in IUGR, potentially contributing to the neurodevelopmental delays associated with this condition. Notably, one of the major TH transporters, monocarboxylate transporter-8 (MCT8), is deficient in the fetal IUGR brain. Currently, no effective treatment to prevent or reverse IUGR exists. Management strategies involve close antenatal monitoring, management of maternal risk factors if present and early delivery if IUGR is found to be severe or worsening in utero. The overall goal is to determine the most appropriate time for delivery, balancing the risks of preterm birth with further fetal compromise due to IUGR. Drug candidates have shown either adverse effects or little to no benefits in this vulnerable population, urging further preclinical and clinical investigation to establish effective therapies. In this review, we discuss the major neuropathology of IUGR driven by uteroplacental insufficiency and the concomitant long-term neurobehavioural impairments in individuals born IUGR. Importantly, we review the existing clinical and preclinical literature on cerebral TH signalling deficits, particularly the impaired expression of MCT8 and their correlation with IUGR. Lastly, we discuss the current evidence on MCT8-independent TH analogues which mimic the brain actions of THs by being metabolised in a similar manner as promising, albeit underappreciated approaches to promote grey and white matter development and improve the neurobehavioural outcomes following IUGR.

Children with Congenital Heart Diseases Exhibit Altered Deep Gray Matter Structures.

Children with congenital heart diseases (CHDs) have an increased risk of developing neurologic deficits, even in the absence of apparent brain pathology. The aim of this work was to compare quantitative macro- and microstructural properties of subcortical gray matter structures of pediatric CHD patients with normal appearing brain magnetic resonance imaging to healthy controls. We retrospectively reviewed children with coarctation of the aorta (COA) and hypoplastic left heart syndrome (HLHS) admitted to our hospital. We identified 24pediatric CHD patients (17COA, 7HLHS) with normal-appearing brain MRI. Using an atlas-based approach, the volume and apparent diffusion coefficient (ADC) were determined for the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, cerebral white matter, cerebral cortex, and brainstem. Multivariate statistics were used to compare the extracted values to reference values from 100 typically developing children without any known cardiac or neurological diseases. Multivariate analysis of covariance using the regional ADC and volume values as dependent variables and age and sex as co-variates revealed asignificant difference between pediatric CHD patients and healthy controls (p < 0.001). Post-hoc comparisons demonstrated significantly reduced brain volumes in most subcortical brain regions investigated and elevated ADC values in the thalamus for children with CHD. No significant differences were found comparing children with COA and HLHS. Despite normal appearing brain MRI, children with CHD exhibit wide-spread macro-structural and regional micro-structural differences of subcortical brain structures compared to healthy controls, which could negatively impact neurodevelopment, leading to neurological deficits in childhood and beyond.

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Striatal brain volume linked to severity of substance use in high-risk incarcerated youth.

Substance use disorders among juveniles are a major public health concern and are often intertwined with other psychosocial risk factors including antisocial behavior. Identifying etiological risks and mechanisms promoting substance use disorders remains a high priority for informing more focused interventions in high-risk populations. The present study examined brain gray matter structure in relation to substance use severity among n = 152 high-risk, incarcerated boys (aged 14-20). Substance use severity was positively associated with gray matter volume across several frontal/striatal brain regions including amygdala, pallidum, putamen, insula, and orbitofrontal cortex. Effects were apparent when using voxel-based-morphometric analysis, as well as in whole-brain, data-driven, network-based approaches (source-based morphometry). These findings support the hypothesis that elevated gray matter volume in striatal reward circuits may be an endogenous marker for vulnerability to severe substance use behaviors among youth.

Long-lasting negativity in the left motoric brain structures during word memory inhibition in the Think/No-Think paradigm

In this study, we investigated the electrical brain responses in a high-density EEG array (64 electrodes) elicited specifically by the word memory cue in the Think/No-Think paradigm in 46 participants. In a first step, we corroborated previous findings demonstrating sustained and reduced brain electrical frontal and parietal late potentials elicited by memory cues following the No-Think (NT) instructions as compared to the Think (T) instructions. The topographical analysis revealed that such reduction was significant 1000 ms after memory cue onset and that it was long-lasting for 1000 ms. In a second step, we estimated the underlying brain generators with a distributed method (swLORETA) which does not preconceive any localization in the gray matter. This method revealed that the cognitive process related to the inhibition of memory retrieval involved classical motoric cerebral structures with the left primary motor cortex (M1, BA4), thalamus, and premotor cortex (BA6). Also, the right frontal-polar cortex was involved in the T condition which we interpreted as an indication of its role in the maintaining of a cognitive set during remembering, by the selection of one cognitive mode of processing, Think, over the other, No-Think, across extended periods of time, as it might be necessary for the successful execution of the Think/No-Think task.

Non-Cartesian 3D-SPARKLING vs Cartesian 3D-EPI encoding schemes for functional Magnetic Resonance Imaging at 7 Tesla.

The quest for higher spatial and/or temporal resolution in functional MRI (fMRI) while preserving a sufficient temporal signal-to-noise ratio (tSNR) has generated a tremendous amount of methodological contributions in the last decade ranging from Cartesian vs. non-Cartesian readouts, 2D vs. 3D acquisition strategies, parallel imaging and/or compressed sensing (CS) accelerations and simultaneous multi-slice acquisitions to cite a few. In this paper, we investigate the use of a finely tuned version of 3D-SPARKLING. This is a non-Cartesian CS-based acquisition technique for high spatial resolution whole-brain fMRI. We compare it to state-of-the-art Cartesian 3D-EPI during both a retinotopic mapping paradigm and resting-state acquisitions at 1mm3 (isotropic spatial resolution). This study involves six healthy volunteers and both acquisition sequences were run on each individual in a randomly-balanced order across subjects. The performances of both acquisition techniques are compared to each other in regards to tSNR, sensitivity to the BOLD effect and spatial specificity. Our findings reveal that 3D-SPARKLING has a higher tSNR than 3D-EPI, an improved sensitivity to detect the BOLD contrast in the gray matter, and an improved spatial specificity. Compared to 3D-EPI, 3D-SPARKLING yields, on average, 7% more activated voxels in the gray matter relative to the total number of activated voxels.

Kinetic modeling of the monoamine oxidase-B radioligand [18F]SMBT-1 in human brain with positron emission tomography.

This paper describes pharmacokinetic analyses of the monoamine-oxidase-B (MAO-B) radiotracer [18F](S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([18F]SMBT-1) for positron emission tomography (PET) brain imaging. Brain MAO-B expression is widespread, predominantly within astrocytes. Reactive astrogliosis in response to neurodegenerative disease pathology is associated with MAO-B overexpression. Fourteen elderly subjects (8 control, 5 mild cognitive impairment, 1 Alzheimer's disease) with amyloid ([11C]PiB) and tau ([18F]flortaucipir) imaging assessments underwent dynamic [18F]SMBT-1 PET imaging with arterial input function determination. [18F]SMBT-1 showed high brain uptake and a retention pattern consistent with the known MAO-B distribution. A two-tissue compartment (2TC) model where the K1/k2 ratio was fixed to a whole brain value best described [18F]SMBT-1 kinetics. The 2TC total volume of distribution (VT) was well identified and highly correlated (r2∼0.8) with post-mortem MAO-B indices. Cerebellar grey matter (CGM) showed the lowest mean VT of any region and is considered the optimal pseudo-reference region. Simplified analysis methods including reference tissue models, non-compartmental models, and standard uptake value ratios (SUVR) agreed with 2TC outcomes (r2 > 0.9) but with varying bias. We found the CGM-normalized 70-90 min SUVR to be highly correlated (r2 = 0.93) with the 2TC distribution volume ratio (DVR) with acceptable bias (∼10%), representing a practical alternative for [18F]SMBT-1 analyses.

Alteration of multilayer network perspective on gray and white matter connectivity in obstructive sleep apnea.

The objective of this research was to examine changes in the neural networks of both gray and white matter in individuals with obstructive sleep apnea (OSA) in comparison to those without the condition, employing a comprehensive multilayer network analysis. Patients meeting the criteria for OSA were recruited through polysomnography, while a control group of healthy individuals matched for age and sex was also assembled. Utilizing T1-weighted imaging, a morphometric similarity network was crafted to represent gray matter, while diffusion tensor imaging provided structural connectivity for constructing a white matter network. A multilayer network analysis was then performed, employing graph theory methodologies. We included 40 individuals diagnosed with OSA and 40 healthy participants in our study. Analysis revealed significant differences in various global network metrics between the two groups. Specifically, patients with OSA exhibited higher average degree overlap and average multilayer clustering coefficient (28.081 vs. 23.407, p < 0.001; 0.459 vs. 0.412, p = 0.004), but lower multilayer modularity (0.150 vs. 0.175, p = 0.001) compared to healthy controls. However, no significant differences were observed in average multiplex participation, average overlapping strength, or average weighted multiplex participation between the patients with OSA and healthy controls. Moreover, several brain regions displayed notable differences in degree overlap at the nodal level between patients with OSA and healthy controls. Remarkable alterations in the multilayer network, indicating shifts in both gray and white matter, were detected in patients with OSA in contrast to their healthy counterparts. Further examination at the nodal level unveiled notable changes in regions associated with cognition, underscoring the effectiveness of multilayer network analysis in exploring interactions across brain layers.

Focal Cortical Dysplasia: Diagnosis, Classification, and Treatment Options

AbstractFocal cortical dysplasias (FCDs) include a spectrum of anomalies of cortical development that consist in one or more areas with altered lamination and in some cases, neurons of abnormal morphology. Clinically, these structural anomalies led to arise of epilepsy, which is more often a focal, drug-resistant type with onset in pediatric or adolescent age. Occasionally, other symptoms have been reported in patients with FCDs, such as headache, movement disorders, and cognitive impairment. According to International League against Epilepsy scheme of 2011, three main subtypes of FCD can be distinguished, based of anatomopathological feature, radiological signs, and clinical expression. Magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography, and neurophysiology are the cornerstones of diagnosis, although their negativity cannot exclude FCD in symptomatic patients, especially in FCD type I which often is elusive. In MRI, the main finding is the irregularity of the cortical–subcortical signal, specifically reduction of cortical thickness and absence of clear demarcation between gray and white matters, which is strongly diagnostic for FCD. Epilepsy related to FCD is difficult to manage and until now there is not a clear direction for treatment's rules. FCD shows poor response to antiepileptic drugs (AEDs), and there is no evidence of some AED that has proved more efficacy than others in patients with FCDs. Considering genetical and pathophysiological recent acquisitions, mammalian target of rapamycin inhibitors may play a fundamental role in future treatment of FCDs, but nowadays, surgery still remains the main weapon, with 50% of patients who undergo neurosurgery.

A straightforward procedure to build a non-toxic relaxometry phantom with desired T1 and T2 times at 3T.

To prepare and analyze soy-lecithin-agar gels for non-toxic relaxometry phantoms with tissue-like relaxation times at 3T. Phantoms mimicking the relaxation times of various tissues (gray and white matter, kidney cortex and medulla, spleen, muscle, liver) were built and tested with a clinical 3T whole-body MR scanner. Simple equations were derived to calculate the appropriate concentrations of soy lecithin and agar in aqueous solutions to achieve the desired relaxation times. Phantoms were tested for correspondence between measurements and calculated T1 and T2 values, reproducibility, spatial homogeneity, and temporal stability. T1 and T2 mapping techniques and a 3D T1-weighted sequence with high spatial resolution were applied. Except for the liver relaxation phantom, all phantoms were successfully and reproducibly produced. Good agreement was found between the targeted and measured relaxation times. The percentage deviations from the targeted relaxation times were less than 3% for T1 and less than 6.5% for T2. In addition, the phantoms were homogeneous and had little to no air bubbles. However, the phantoms were unstable over time: after a storage period of 4weeks, mold growth and also changes in relaxation times were detected in almost all phantoms. Soy-lecithin-agar gels are a non-toxic material for the construction of relaxometry phantoms with tissue-like relaxation times. They are easy to prepare, inexpensive and allow independent adjustment of T1 and T2. However, there is still work to be done to improve the long-term stability of the phantoms.

Anomalies of Midbrain/Hindbrain Development: Malformations of Cerebellum: Diagnosis, Classification, and Rehabilitative Hypothesis

AbstractExtensive research has been conducted on the cerebellum, making it one of the most thoroughly investigated regions of the brain. It plays a fundamental role not only in motor control but also in motor learning and cognition. The development of the cerebellum is a lengthy process, beginning during the embryonic period up to the first years of life. This slow and protracted process makes it a vulnerable organ liable to different insults, responsible for many developmental disorders such as Dandy–Walker syndrome, medulloblastoma, dystroglicanopathy, pontocerebellar hypoplasia, thubulinopathies, and Jubert syndrome. Due to several factors, the true prevalence of cerebellar malformations is not known in most cases. The cerebellum undergoes development through following four fundamental stages:(1) Identification of the cerebellar region at the boundary between the midbrain and hindbrain.(2) Establishment of two cell proliferation compartments: firstly, Purkinje cells and deep cerebellar nuclei emerge from the ventricular zone of the metencephalic alar plate; secondly, granule cell precursors are generated from a separate proliferation compartment known as the upper rhombic lip.(3) Migration of granule cells toward the interior: granule precursor cells constitute the external granular layer (EGL), and during the initial postnatal year, granule cells migrate inward to their final position in the internal granular layer.(4) Formation of cerebellar circuitry and subsequent differentiation.Based on different types of involvement of the structures detected in the brain magnetic resonance, the classification of brainstem and cerebellar anomalies is divided into three categories: (1) mainly the cerebellum, (2) mainly the brain stem, and (3) both involved. This review will outline the developmental processes of the cerebellum and delve into common developmental disorders associated with it, including the Dandy–Walker syndrome, cerebellar hypoplasia, rhomboencephalosynapsis, lissencephaly, and gray matter heterotopias.

Temperature-Switch-Controlled Second Harmonic Mode Sensor for Brain-Tissue Detection

Identifying brain-tissue types holds significant research value in the biomedical field of non-contact brain-tissue measurement applications. In this paper, a layered metastructure is proposed, and the second harmonic generation (SHG) in a multilayer metastructure is derived using the transfer matrix method. With the SHG conversion efficiency (CE) as the measurement signal, the refractive index ranges that can be distinguished are 1.23~1.31 refractive index unit (RIU) and 1.38~1.44 RIU, with sensitivities of 0.8597 RIU−1 and 1.2967 RIU−1, respectively. It can distinguish various brain tissues, including gray matter, white matter, and low-grade glioma, achieving the function of a second harmonic mode sensor (SHMS). Furthermore, temperature has a significant impact on the SHG CE, which can be used to define the switch signal indicating whether the SHMS is functioning properly. When the temperature range is 291.4~307.9 Kelvin (K), the temperature switch is in the “open” state, and the optimal SHG CE is higher than 0.298%, indicating that the SHMS is in the working state. For other temperature ranges, the SHG CE will decrease significantly, indicating that the temperature switch is in the “off” state, and the SHMS is not working. By stimulating temperature and using the response of SHG CE, the temperature-switch function is achieved, providing a new approach for temperature-controlled second harmonic detection.

Schizencephaly: Etiopathogenesis, Classification, Therapeutic, and Rehabilitative Approach

AbstractSchizencephaly is an uncommon anomaly in neuronal migration characterized by complete clefts that extend from the pia mater to the ependymal surface of the ventricular system. These clefts are encompassed by displaced gray matter and filled with cerebrospinal fluid. Typically, they are found most often in the frontal lobe or the area around the lateral sulcus and can occur on one or both sides. The size, location, and type of these clefts carry significant clinical and prognostic implications. Moreover, they are frequently associated with other central nervous system malformations, including the absence of the septum pellucidum, septo-optic dysplasia, optic nerve hypoplasia, pachygyria, polymicrogyria, cortical dysplasia, heterotopia, and dysplasia of the corpus callosum. Occurrence of schizencephaly is almost always sporadic but its etiopathogenesis is yet to be fully understood. Most likely environmental factors, including exposure to teratogens, viral infections, and maternal factors, operate jointly with genetic defects. To date COL4A1, EMX2, SHH, and SIX3 are the genes identified as possible pathogenetic target. It is interesting to notice that schizencephaly is commonly seen in abandoned or adopted children, as proof of causative effect of intrautero insults. Clinical presentations widely vary and symptoms include a spectrum of cognitive impairment, limb paresis/tetraparesis, and epileptic seizures either with early or late onset; anyway, none of these symptoms is ever-present and patients with schizencephaly can also have normal neurocognitive and motor development. Diagnostic gold standard for schizencephaly is magnetic resonance imaging, which allows to identify and characterize typical clefts. Treatment of schizencephaly is symptomatic and supportive and depends on the severity of morbidity resulting from the malformation. Therapy includes antiepileptic drugs, psychomotor rehabilitation, and in selected cases surgical approach.

Disrupted single-subject gray matter networks are associated with cognitive decline and cortical atrophy in Alzheimer’s disease

BackgroundResearch has shown disrupted structural network measures related to cognitive decline and future cortical atrophy during the progression of Alzheimer’s disease (AD). However, evidence regarding the individual variability of gray matter network measures and the associations with concurrent cognitive decline and cortical atrophy related to AD is still sparse.ObjectiveTo investigate whether alterations in single-subject gray matter networks are related to concurrent cognitive decline and cortical gray matter atrophy during AD progression.MethodsWe analyzed structural MRI data from 185 cognitively normal (CN), 150 mild cognitive impairment (MCI), and 153 AD participants, and calculated the global network metrics of gray matter networks for each participant. We examined the alterations of single-subject gray matter networks in patients with MCI and AD, and investigated the associations of network metrics with concurrent cognitive decline and cortical gray matter atrophy.ResultsThe small-world properties including gamma, lambda, and sigma had lower values in the MCI and AD groups than the CN group. AD patients had reduced degree, clustering coefficient, and path length than the CN and MCI groups. We observed significant associations of cognitive ability with degree in the CN group, with gamma and sigma in the MCI group, and with degree, connectivity density, clustering coefficient, and path length in the AD group. There were significant correlation patterns between sigma values and cortical gray matter volume in the CN, MCI, and AD groups.ConclusionThese findings suggest the individual variability of gray matter network metrics may be valuable to track concurrent cognitive decline and cortical atrophy during AD progression. This may contribute to a better understanding of cognitive decline and brain morphological alterations related to AD.

Effects of Photon versus Carbon-Ion Irradiation in the Rat Cervical Spinal Cord - a Serial T2 and Diffusion-weighted Magnetic Resonance Imaging Study.

Carbon-ion irradiation is increasingly used at the skull base and spine near the radiation-sensitive spinal cord. To better characterize the invivo radiation response of the cervical spinal cord, radiogenic changes in the high-dose area were measured in rats using magnetic resonance imaging (MRI) diffusion measurements in comparison to conventional photon irradiations. In this longitudinal MRI study, we examined the gray matter (GM) of the cervical spinal cord in 16 female Sprague-Dawley rats after high-dose photon (n = 8) or carbon-ion (12C) irradiation (n = 8) and in 6 sham-exposed rats until myelopathy occurred. The differences in the diffusion pattern of the GM of the cervical spinal cord were examined until the endpoint of the study, occurrence of paresis grade II of both forelimbs was reached. In both radiation techniques, the same order of the occurrence of MR-morphological pathologies was observed - from edema formation to a blood spinal cord barrier (BSCB) disruption to paresis grade II of both forelimbs. However, carbon-ion irradiation showed a significant increase of the mean apparent diffusion coefficient (ADC; P = 0.031) with development of a BSCB disruption in the GM. Animals with paresis grade II as a late radiation response had a highly significant increase in mean ADC (P = 0.0001) after carbon-ion irradiation. At this time, a tendency was observed for higher mean ADC values in the GM after 12C irradiation as compared to photon irradiation (P = 0.059). These findings demonstrated that carbon-ion irradiation leads to greater structural damage to the GM of the rat cervical spinal cord than photon irradiation due to its higher linear energy transfer (LET) value.

Single-shot diffusion trace spectroscopic imaging using radial echo planar trajectories.

Demonstrate the feasibility and evaluate the performance of single-shot diffusion trace-weighted radial echo planar spectroscopic imaging (Trace DW-REPSI) for quantifying the trace ADC in phantom and in vivo using a 3T clinical scanner. Trace DW-REPSI datasets were acquired in 10 phantom and 10 healthy volunteers, with a maximum b-value of 1601 s/mm2 and diffusion time of 10.75 ms. The self-navigation properties of radial acquisitions were used for corrections of shot-to-shot phase and frequency shift fluctuations of the raw data. In vivo trace ADCs of total NAA (tNAA), total creatine (tCr), and total choline (tCho) extrapolated to pure gray and white matter fractions were compared, as well as trace ADCs estimated in voxels within white or gray matter-dominant regions. Trace ADCs in phantom show excellent agreement with reported values, and in vivo ADCs agree well with the expected differences between gray and white matter. For tNAA, tCr, and tCho, the trace ADCs extrapolated to pure gray and white matter ranged from 0.18-0.27 and 0.26-0.38 μm2/ms, respectively. In sets of gray and white matter-dominant voxels, the values ranged from 0.21 to 0.27 and 0.24 to 0.31 μm2/ms, respectively. The overestimated trace ADCs from this sequence can be attributed to the short diffusion time. This study presents the first demonstration of the single-shot diffusion trace-weighted spectroscopic imaging sequence using radial echo planar trajectories. The Trace DW-REPSI sequence could provide an estimate of the trace ADC in a much shorter scan time compared to conventional approaches that require three separate measurements.

Brain structure comparison among Parkinson disease, essential tremor, and healthy controls using 7T MRI.

Both Parkinson disease (PD) and Essential tremor (ET) are movement disorders causing tremors in elderly individuals. Although PD and ET are different disease, they often present with similar initial symptoms, making their differentiation challenging with magnetic resonance imaging (MRI) techniques. This study aimed to identify structural brain differences among PD, ET, and health controls (HCs) using 7-Tesla (T) MRI. We assessed the whole-brain parcellation in gray matter volume, thickness, subcortical volume, and small regions of basal ganglia in PD (n = 18), ET (n = 15), and HCs (n = 18), who were matched for age and sex. Brain structure analysis was performed automatic segmentation through Freesurfer software. Small regions of basal ganglia were manually segmented by ITK-SNAP. Additionally, we examined the associations between clinical indicators (symptom duration, unified Parkinson diseases rating scale (UPDRS), and clinical rating scale for tremor (CRST)) and brain structure. PD showed a significant reduction in gray matter volume in the postcentral region compared to ET. ET showed a significant reduction in cerebellum volume compared to HCs. There was a negative correlation between CRST scores (B and C) and gray matter thickness in right superior frontal in ET. This study demonstrated potential of 7T MRI in differentiating brain structure differences among PD, ET, and HCs. Specific findings, such as parietal lobe atrophy in PD compared to ET and cerebellum atrophy in ET compared to HCs, the importance of advanced imaging techniques in accurately diagnosing and distinguishing between movement disorders that present with similar initial symptoms.

Unsupervised multimodal modeling of cognitive and brain health trajectories for early dementia prediction

Predicting the course of neurodegenerative disorders early has potential to greatly improve clinical management and patient outcomes. A key challenge for early prediction in real-world clinical settings is the lack of labeled data (i.e., clinical diagnosis). In contrast to supervised classification approaches that require labeled data, we propose an unsupervised multimodal trajectory modeling (MTM) approach based on a mixture of state space models that captures changes in longitudinal data (i.e., trajectories) and stratifies individuals without using clinical diagnosis for model training. MTM learns the relationship between states comprising expensive, invasive biomarkers (β-amyloid, grey matter density) and readily obtainable cognitive observations. MTM training on trajectories stratifies individuals into clinically meaningful clusters more reliably than MTM training on baseline data alone and is robust to missing data (i.e., cognitive data alone or single assessments). Extracting an individualized cognitive health index (i.e., MTM-derived cluster membership index) allows us to predict progression to AD more precisely than standard clinical assessments (i.e., cognitive tests or MRI scans alone). Importantly, MTM generalizes successfully from research cohort to real-world clinical data from memory clinic patients with missing data, enhancing the clinical utility of our approach. Thus, our multimodal trajectory modeling approach provides a cost-effective and non-invasive tool for early dementia prediction without labeled data (i.e., clinical diagnosis) with strong potential for translation to clinical practice.