Biology subjects

Hammers, A.

Publications and source records attributed to Hammers, A..

7 recordsLinked to original sources

bioRxiv2025

Open-access template and database approaches for pseudo-CT generation in brain PET/MRI attenuation correction

Positron emission tomography (PET) provides high-sensitivity molecular information in neuroimaging. However, its quantitative accuracy critically depends on attenuation correction (AC). Unlike PET/CT, hybrid PET/MRI systems cannot directly measure photon attenuation, necessitating alternative AC strategies. While several MRI-based AC tools exist, they often raise concerns regarding data privacy, long-term accessibility and reproducibility. We present an open-access framework for PET AC using pseudo-CT (pCT) methods. A database of 60 paired MRI-CT scans was curated and normalized to stereotactic MNI space. Three established pCT approaches (Boston, MaxProb, UCL) were adapted to enable their use with the normalized database. Method performance was assessed by comparison with a CT-based AC reference in an independent validation sample of 28 subjects, using the Jaccard index and [11C]DASB PET-derived serotonin transporter quantification as evaluation metrics. Boston and MaxProb demonstrated consistent performance across database subsets, while the UCL achieved the closest agreement with CT-derived AC and yielded the lowest quantification error (mean relative error <0.5%). This work demonstrates the feasibility of different pCT approaches using a database in MNI space thereby introducing an openly available reference database to support fast, reproducible and continued integration of MRI-based AC into PET reconstruction pipelines.

neuroscience↗

bioRxiv2025

Inter-individual variability of neurotransmitter receptor and transporter density in the human brain

Neurotransmitter receptors guide the propagation of signals between brain regions. Mapping receptor distributions in the brain is therefore necessary for understanding how neurotransmitter systems mediate the link between brain structure and function. Normative receptor density can be estimated using group averages from Positron Emission Tomography (PET) imaging. However, the generalizability and reliability of group-average receptor maps depends on the inter-individual variability of receptor density, which is currently unknown. Here we collect group standard deviation brain maps of PET-estimated protein abundance for 12 different neurotransmitter receptors and transporters across 7 neurotransmitter systems, including dopamine, serotonin, acetylcholine, glutamate, GABA, cannabinoid, and opioid. We illustrate how cortical and subcortical inter-individual variability of receptor and transporter density varies across brain regions and across neurotransmitter systems. We complement inter-individual variability with inter-regional variability, and show that receptors that vary more across brain regions than across individuals also demonstrate greater out-of-sample spatial consistency. Altogether, this work quantifies how receptor systems vary in healthy individuals, and provides a means of assessing the generalizability of PET-derived receptor density quantification.

neuroscience↗

bioRxiv2025

Motifs of brain cortical folding from birth to adulthood: structural asymmetry and folding-functional links

Cortical folding of brain is widely regarded as an interplay between genetic programming and biomechanical forces, closely linked to cytoarchitectonic regionalisation. Abnormal folding patterns are frequently observed in neurodevelopmental conditions and psychiatric disorders. However, significant inter-individual variability of secondary and tertiary folds obscures detection of shape biomarkers and confounds investigation of folding-functional relationships. Here we investigate cortical folding heterogeneity at fine scale, using novel hierarchical surface registration (MSM-HT) to parse cortical folding patterns into a representative family of distinct anatomical templates. By applying this technique both to young adults from the Human Connectome Project (HCP) and neonates in the Developing HCP and Brain Imaging in Babies (BIBS) cohorts, we identify and characterize common lobe-wise folding patterns: observing consistency across both age groups, with neonatal samples showing less variation. Crucially, we highlight significant hemispheric asymmetry within the temporal lobe for both adults and neonates, and show that improved correspondence of shape does not translate to improved areal correspondence, affirming previous studies that have pointed to dissociation of folding and functional organisation. This study provides a critical step towards understanding brain asymmetry and complex relationships between folding and function, offering a robust framework to generalise the uncovered cortical folding motifs across datasets and developmental stages.

neuroscience↗

bioRxiv2024

Connecting the Dots: Approaching a Standardized Nomenclature for Molecular Connectivity Combining Data and Literature

PET-based connectivity computation is a molecular approach that complements fMRI-derived functional connectivity. However, the diversity of methodologies and terms employed in PET connectivity analysis has resulted in ambiguities and confounded interpretations, highlighting the need for a standardized nomenclature. Drawing parallels from other imaging modalities, we propose "molecular connectivity" as an umbrella term to characterize statistical dependencies between PET signals across brain regions at the individual level (within-subject). Like fMRI resting-state functional connectivity, "molecular connectivity" leverages temporal associations in the PET signal to derive brain network associations. Another within-subject approach evaluates regional similarities of tracer kinetics, which are unique in PET imaging, thus referred to as "kinetic connectivity". On the other hand, "molecular covariance" denotes group-level computations of covariance matrices across-subject. Further specification of the terminology can be achieved by including the employed radioligand, such as "metabolic connectivity/covariance" for [18F]FDG as well as "tau/amyloid covariance" for [18F]flutemetamol / [18F]flortaucipir. To augment these distinctions, high-temporal resolution functional [18F]FDG PET scans from 17 healthy participants were analysed with common techniques of molecular connectivity and covariance, allowing for a data-driven support of the above terminology. Our findings demonstrate that temporal band-pass filtering yields structured network organization, whereas other techniques like 3rd order polynomial fitting, spatio-temporal filtering and baseline normalization require further methodological refinement for high-temporal resolution data. Conversely, molecular covariance from across-subject data provided a simple means to estimate brain region interactions through regularized or sparse inverse covariance estimation. A standardized nomenclature in PET-based connectivity research can reduce ambiguity, enhance reproducibility, and facilitate interpretability across radiotracers and imaging modalities. Via a data-driven approach, this work provides a transparent framework for categorizing and comparing PET-derived connectivity and covariance metrics, laying the foundation for future investigations in the field.

neuroscience↗

bioRxiv2024

Thalamic blood flow and EEG frequency band power during hyperventilation in idiopathic generalized epilepsy

Absence seizures in idiopathic generalised epilepsy (IGE) involve thalamo-cortical circuits. Hyperventilation (HV) is a standard technique to trigger epileptiform discharges and absence seizures in IGE. HV also increases electroencephalography (EEG) delta band power and decreases global cerebral blood flow (CBF). The relationships between HV, EEG band power, and regional CBF have not been investigated in the same patients at the same time. We compared the effects of hyperventilation between 13 individuals with IGE and 18 healthy controls on thalamic CBF assessed with pseudo-continuous Arterial Spin Labelling (pCASL) simultaneously to EEG frequency band power during three periods of hyperventilation interleaved with three periods of rest, normalised to each participants pre-HV values. Pre-HV, there were no differences between patients and controls. During the three rest periods combined, patients had higher normalised respiratory rates but no difference in CBF or EEG band power compared with controls. During HV, CBF decreases were similar in controls and IGE patients in cortical gray matter (37.1{+/-}1.3% in controls, 37.9{+/-}2.0% in patients) and basal ganglia (35.6{+/-}2.0% in controls, 33.3{+/-}2.3% in patients). In the thalamus, CBF decreased by 35.5{+/-}1.9% in controls, but only by 27.1{+/-}2.5% in patients (p=0.011). Delta band power increased by 42% in patients, but only by 27% in patients (p<0.045). Both controls and patients thalamic CBF significantly decreased as a function of respiratory rate, but the relationship was weaker in patients (rho -0.38 [0.95 confidence interval lower limit -0.629; upper limit -0.059] vs -0.51 [-0.698; -0.255] in controls). Delta power correlated with thalamic CBF only in controls (rho -0.21 [-0.388; -0.017]) but not in patients (rho -0.1 [-0.345; 0.157]). EEG power and respiratory rate were not significantly correlated in either group. This first study of the interrelationships between HV, blood flow, and EEG band power suggests that regional thalamic abnormalities of blood flow regulation, or a neurophysiological abnormality leading to smaller reactive blood flow changes, may underlie HV-associated EEG activation. Graphical abstract textIn this first investigation of combined hyperventilation, blood flow and EEG band power measurements in idiopathic generalised epileptic patients and healthy subjects, we revealed that localized thalamic blood flow regulatory problems or neurophysiological disorders caused minor reactive blood flow variations and may cause hyperventilation-associated EEG activation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/586742v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@12a5ebeorg.highwire.dtl.DTLVardef@b22944org.highwire.dtl.DTLVardef@b335dforg.highwire.dtl.DTLVardef@195c5e2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

CERMEP-IDB-MRXFDG: A database of 37 normal adult human brain FDG PET, T1 and FLAIR MRI, and CT images available for research

We present a database of cerebral PET FDG and anatomical MRI for 37 normal adult human subjects (CERMEP-IDB-MRXFDG). Thirty-nine participants underwent [18F]FDG PET/CT and MRI, resulting in [18F]FDG PET, T1 MPRAGE MRI, FLAIR MRI, and CT images. Two participants were excluded after visual quality control. We describe the acquisition parameters, the image processing pipeline and provide participants individual demographics (mean age 38 {+/-} 11.5 years, range 23-65, 20 women). Volumetric analysis of the 37 T1 MRIs showed results in line with the literature. A leave-one-out assessment of the 37 FDG images using Statistical Parametric Mapping (SPM) yielded a low number of false positives after exclusion of artefacts. The database is stored in three different formats, following the BIDS common specification: 1) DICOM (data not processed), 2) NIFTI (multimodal images coregistered to PET subject space), 3) NIFTI normalized (images normalized to MNI space). Bona fide researchers can request access to the database via a short form.

neuroscience↗

bioRxiv2020

Electrophysiological receptor mapping of GABA-A receptors

The non-invasive study of cortical oscillations provides a window onto neuronal processing. Temporal correlation of these oscillations between distinct anatomical regions is considered a marker of functional connectedness. As the most abundant inhibitory neurotransmitter in the mammalian brain, {gamma}-aminobutyric acid (GABA) is thought to play a crucial role in shaping the frequency and amplitude of oscillations, which thereby suggests a role for GABA in shaping the topography of functional activity and connectivity. This study explored the effects of pharmacologically blocking the reuptake of GABA (increasing local concentrations) through oral administration of the GABA transporter 1 (GAT1) blocker tiagabine (15 mg). We show that the spatial distribution of tiagabine-induced activity changes, across the brain, corresponds to group-average flumazenil PET maps of GABAA receptor distribution. In a placebo-controlled crossover design, we collected resting magnetoencephalography (MEG) recordings from 15 healthy male individuals prior to, and at 1-, 3- and 5- hours post, administration of tiagabine and placebo pill. Using leakage-corrected amplitude envelope correlations (AECs), we quantified the functional connectivity in discrete frequency bands across the whole brain, using the 90-region Automatic Anatomical Labelling atlas (AAL90), as well as quantifying the average oscillatory activity across the brain. Analysis of variance in connectivity using a drug-by-session (2x4) design revealed interaction effects, accompanied by main effects of drug and session. Post-hoc permutation testing of each post-drug recording against the respective pre-drug baseline revealed consistent reductions of a bilateral occipital network spanning theta, alpha and beta frequencies, and across 1- 3- and 5- hour recordings following tiagabine, but not placebo. The same analysis applied to activity, across the brain, also revealed a significant interaction, with post-hoc permutation testing demonstrating significant increases in activity across frontal regions, coupled with reductions in activity in posterior regions, across the delta, theta, alpha and beta frequency bands. Crucially, we show that the spatial distribution of tiagabine-induced changes in oscillatory activity overlap significantly with group-averaged maps of the estimated distribution of GABAA receptors, derived from scaled flumazenil volume-of-distribution (FMZ-VT) PET, hence demonstrating a possible mechanistic link between GABA availability, GABAA receptor distribution, and low-frequency network oscillations. We therefore propose that electrophysiologically-derived maps of oscillatory connectivity and activity can be used as sensitive, time-resolved, and targeted receptor-mapping tools for pharmacological imaging at the group level, providing direct measures of target engagement and pharmacodynamics.

neuroscience↗