Small Brain Research Articles

Multimodal tract-based MRI metrics outperform whole brain markers in determining cognitive impact of small vessel disease-related brain injury

In cerebral small vessel disease (cSVD), whole brain MRI markers of cSVD-related brain injury explain limited variance to support individualized prediction. Here, we investigate whether considering abnormalities in brain tracts by integrating multimodal metrics from diffusion MRI (dMRI) and structural MRI (sMRI), can better capture cognitive performance in cSVD patients than established approaches based on whole brain markers. We selected 102 patients (73.7 ± 10.2 years old, 59 males) with MRI-visible SVD lesions and both sMRI and dMRI. Conventional linear models using demographics and established whole brain markers were used as benchmark of predicting individual cognitive scores. Multi-modal metrics of 73 major brain tracts were derived from dMRI and sMRI, and used together with established markers as input of a feed-forward artificial neural network (ANN) to predict individual cognitive scores. A feature selection strategy was implemented to reduce the risk of overfitting. Prediction was performed with leave-one-out cross-validation and evaluated with the R2 of the correlation between measured and predicted cognitive scores. Linear models predicted memory and processing speed with R2 = 0.26 and R2 = 0.38, respectively. With ANN, feature selection resulted in 13 tract-specific metrics and 5 whole brain markers for predicting processing speed, and 28 tract-specific metrics and 4 whole brain markers for predicting memory. Leave-one-out ANN prediction with the selected features achieved R2 = 0.49 and R2 = 0.40 for processing speed and memory, respectively. Our results show proof-of-concept that combining tract-specific multimodal MRI metrics can improve the prediction of cognitive performance in cSVD by leveraging tract-specific multi-modal metrics.

Scalability of Large Neural Network Simulations via Activity Tracking With Time Asynchrony and Procedural Connectivity.

We present a new algorithm to efficiently simulate random models of large neural networks satisfying the property of time asynchrony. The model parameters (average firing rate, number of neurons, synaptic connection probability, and postsynaptic duration) are of the order of magnitude of a small mammalian brain or of human brain areas. Through the use of activity tracking and procedural connectivity (dynamical regeneration of synapses), computational and memory complexities of this algorithm are proved to be theoretically linear with the number of neurons. These results are experimentally validated by sequential simulations of millions of neurons and billions of synapses running in a few minutes using a single thread of an equivalent desktop computer.

Application of motion-sensitized driven equilibrium based black blood 3D TSE sequence in the detection of brain metastases

PurposeTo investigate the value of contrast-enhanced motion-sensitized driven equilibrium (MSDE) based black blood three-dimensional (3D) turbo spin echo (TSE) sequence in the detection of brain metastases compared with 3D Turbo Field Echo (TFE) sequence. Material and methods53 patients with suspected brain metastases were included in this study between November 2021 and February 2022. Contrast-enhanced cranial 3D TFE and MSDE-based 3D black blood TSE MR imaging were performed for each patient. Two senior neuroradiologists independently evaluated all contrast-enhanced 3D TFE and 3D black blood TSE images to detect brain metastases. The images were divided into two groups: the TFE group and the black blood TSE group. Agreement between the two reviewers for detection of the brain metastases in each group was performed using the kappa test. The two reviewers determined the final result for brain metastasis in the two groups by consensus. A paired t-test was performed for the final detection of brain metastases between the black blood TSE group and the TFE group. ResultsThere was a very good agreement between the two reviewers for the TSE group (kappa = 0.823) and a good agreement for the TFE group (kappa = 0.663). There was a statistical difference in the detection of small cortical and subcortical metastases between the TFE and the black blood TSE groups (t = 5.039, P = 0.000 < 0.05). There was no statistical difference in the detection of small supratentorial deep lesions and subtentorial lesions between the two groups. ConclusionCompared with conventional 3D TFE sequence, MSDE-based black blood 3D TSE sequence was superior for visualizing small brain metastases, especially small cortical and subcortical metastases.

Measuring resident/faculty contour concordance as a potential tool for quantitative assessment of residents' performance in target volume delineation: a feasibility study

<h3>Background</h3> Accurate target delineation/contouring is essential for radiation treatment planning and the clinical efficacy of radiation therapy. Clinical trial data has demonstrated the importance of quality contouring and treatment planning for optimal survival outcomes. As a result, improving the quality of target delineation is an important goal in the education of radiation oncology residents. However, there is limited quantitative data on the quality of residents' contours. Therefore, it would be beneficial to track performance and improvement in resident target delineation during residency. The purpose of this study was to determine if it was feasible to track the concordance of radiation oncology residents' contours with faculty physicians' contours. <h3>Methods</h3> Residents were asked to contour target volumes (GTV, CTV, ITV, PTV, etc.) based on patient history, physical exam, clinical stage and fused diagnostic imaging and were allowed to use any available outside resources, including textbooks, review articles, consensus guidelines, and online atlases. Resident contours were saved as separate structures. Finalized, faculty physician-approved contours were also saved. Saved contour structures and data from October 2019 through June 2020 were reviewed for feasibility. <h3>Results</h3> In total, 209 structures had both resident and faculty versions saved within Eclipse and were available for analysis. The Boolean Operations Tool in Eclipse (Varian Medical Systems, Palo Alto, CA, USA) was used to create an intersection volume of the resident/faculty contours. Separately, the Boolean Operations Tool was used to create a union volume of the resident/faculty contours. Based on these two volumes, the Jaccard Concordance Index (JCI) was calculated by dividing the intersection volume (in cubic centimeters [cc]) by the union volume (cc). The JCI could be successfully calculated for 203 (97.1%) of the 209 structures. For 6 structures (2.9%), both the intersection and union volumes could not be calculated because the volumes were too small for Eclipse to determine. All 6 of these structures were small brain metastases. <h3>Discussion</h3> Tracking and comparing the concordance of resident contours and faculty physician contours is feasible using available tools in Eclipse. Additional data collection and assessment is necessary before this technique can be more widely utilized.

Curative Embolization of Small Brain Arteriovenous Malformations by Ethyl Vinyl Alcohol Copolymer: A Systematic Review and Meta-Analysis.

The right choice in treating small (Spetzler-Ponce grade A) brain arteriovenous malformations (AVMs) is a matter of debate with varying views from neurology, neurosurgery, and interventional neuroradiology points of view. The Spetzler-Martin 1 and 2 brain AVMs, especially those in eloquent and deep areas that are difficult to access by micro-neurosurgery, are most suitable for a complete cure by endovascular embolization with ethyl vinyl alcohol (EVOH)-based agents.A literature search was done with keywords such as endovascular embolization of small brain AVM. Data from 13 articles are included in the study based on predetermined inclusion and exclusion criteria.Meta-analysis for the complete cure rate was done, publication bias was removed, and regression analysis showed a 76% cure rate with a 95% confidence interval (CI). Major complications were hemorrhage and neurological deficit, which ranged from 0-20% and 0-16% with a mean proportion of 0.11 and 0.09, respectively. Long-term (3-6 months) follow-up data showed 0-4% recurrence at three months, 0-8% recurrence at six months, and 2-10% permanent disability. The mortality rate ranged from 3% to 4%. Three illustrative cases with data from the author’s institute are included in the article. To conclude, endovascular embolization for small brain AVMs is a satisfactory treatment modality, however, prospective registries and randomized controlled trials involving embolization versus neurosurgery and/or stereotactic radiosurgery (SRS) may validate the role of embolization in small brain AVMs as curative treatment.

A novel weight optimized dynamic conformal arcs with TrueBeam™ Linac for very small tumors (≤1 cc) with single isocenter of multiple brain metastases (2≤, ≥4) in stereotactic radiosurgery: A comparison with volumetric modulated arc therapy.

We evaluated whether improved increase delivery efficiency of weight optimized dynamic conformal arc (WO-DCA) therapy in comparison to volumetric modulated arc therapy (VMAT) with single isocenter for SRS treatment of very small volume and multiple brain metastases (BMs). 20 patients having a less than 1 cc volume and 2≤, ≥4 of multiple BMs, redesigned for 20 Gy in 1 fraction using WO-DCA and VMAT techniques with double full coplanar and three partial noncoplanar arcs. Plan qualities were compared using tumor coverage, conformity index (CI), gradient index (GI), V4Gy, V10Gy, and V12Gy volumes of brain, monitor units (MUs), and percent of quality assurance pass rate (QA%). Both techniques satisfied clinical requirements in coverage and CI. VMAT had a significantly higher MU and mean GI than WO-DCA (for MUs; 2330 vs. 1991; P < 0.001, and for GI; 4.72 vs. 3.39; P < 0.001). WO-DCA was found significantly lower V4Gy (171.11 vs. 232.80 cm3, P < 0.001), V10Gy (25.82 vs. 29.71 cm3, P < 0.05), and V12Gy (14.35 vs. 17.28 cm3, P < 0.05) volumes than VMAT. WO-DCA was associated with markedly increase QA pass rates for all plans (97.65% vs. 92.64%, P < 0.001). WO-DCA may be the first choice compared to the VMAT in reducing the dose in the brain and minimizing small-field dosimetric errors for very small SRS treatment of brain metastases in the range of ≤ 1 cc and 2≤, ≥4.

The relationship between prior psychiatric diagnosis and brain cancer diagnosis in the U.S. military health system.

Prior research suggested the increased likelihood of brain cancer diagnosis following certain psychiatric diagnoses. This association may result from detection bias or suggest an early sign for brain cancer. This study investigated whether psychiatric illness may be an early manifestation of brain cancer while considering potential effects of detection bias. This case-control study used the data from the Department of Defense's Central Cancer Registry and the Military Health System Data Repository. Four cancer-free controls and one negative-outcome control (cancers not associated with psychiatric illness) were matched to each brain cancer case diagnosed from 1998 to 2013 by age, sex, race, and military status. The groups were compared in the likelihood of having a pre-existing psychiatric diagnosis using conditional logistic regression. We found a significant association of psychiatric illnesses with brain cancer (Odds Ratio (OR) = 2.63, 95% confidence interval (CI) = 2.18-3.16) and other cancers (OR = 1.80, 95% CI = 1.49-2.19), compared to non-cancer controls. The association was stronger for psychiatric diagnoses within three months before cancer (brain cancer: OR = 26.77, 95% CI = 15.40-46.53; other cancers: OR = 4.12, 95% CI = 1.96-8.65). The association with psychiatric disorders within 3months were higher for small brain tumors (OR = 128.32, 95% CI = 17.28-952.92 compared to non-cancer controls) while the OR was 2.79 for other cancers (95% CI = 0.86-8.99 compared to non-cancer controls). Our findings suggest an association between diagnosed psychiatric illnesses and subsequent brain cancer diagnosis, which may not be solely explained by detection bias. Psychiatric illness might be a sign for early detection of brain cancer beyond the potential effects of detection bias.

Impacts of development and adult sex on brain cell numbers in the Black Soldier Fly, Hermetia illucens L. (Diptera: Stratiomyidae)

The Black Soldier Fly (Hermetia illucens, Diptera: Stratiomyidae) has been introduced across the globe, with numerous industry applications predicated on its tremendous growth during the larval stage. However, basic research on H. illucens biology (for example, studies of their central nervous system) are lacking. Despite their small brain volumes, insects are capable of complex behaviors; understanding how these behaviors are completed with such a small amount of neural tissue requires understanding processing power (e.g. number of cells) within the brain. Brain cell counts have been completed in only a few insect species (mostly Hymenoptera), and almost exclusively in adults. This limits the taxonomic breadth of comparative analyses, as well as any conclusions about how development and body size growth may impact brain cell populations. Here, we present the first images and cell counts of the H. illucens brain at four time points across development (early, mid, and late larval stages, and both male and female adults) using immunohistochemistry and isotropic fractionation. To assess sexual dimorphism in adults, we quantified the number of cells in the central brain vs. optic lobes of males and females separately. To assess if increases in body size during development might independently affect different regions of the CNS, we quantified the larval ventral nerve cord and central brain separately at all three stages. Together, these data provide the first description of the nervous system of a popular, farmed invertebrate and the first study of brain cell numbers using IF across developmental stages in any insect.

Regional hypothalamic, amygdala, and midbrain periaqueductal gray matter recruitment during acute pain in awake humans: A 7-Tesla functional magnetic resonance imaging study

Over the past two decades, magnetic resonance imaging (MRI) studies have explored brain activation patterns during acute noxious stimuli. Whilst these human investigations have detailed changes in primarily cortical regions, they have generally not explored discrete changes within small brain areas that are critical in driving behavioural, autonomic, and endocrine responses to pain, such as within subregions of the hypothalamus, amygdala, and midbrain periaqueductal gray matter (PAG). Ultra-high field (7-Tesla) MRI provides enough signal-to-noise at high spatial resolutions to investigate activation patterns within these small brain regions during acute noxious stimulation in awake humans. In this study we used 7T functional MRI to concentrate on hypothalamic, amygdala, and PAG signal changes during acute noxious orofacial stimuli. Noxious heat stimuli were applied in three separate fMRI scans to three adjacent sites on the face in 16 healthy control participants (7 females). Images were processed using SPM12 and custom software, and blood oxygen level dependent signal changes within the hypothalamus, amygdala, and PAG assessed. We identified altered activity within eight unique subregions of the hypothalamus, four unique subregions of the amygdala, and a single region in the lateral PAG. Specifically, within the hypothalamus and amygdala, signal intensity largely decreased during noxious stimulation, and increased in the lateral PAG. Furthermore, we found sex-related differences in discrete regions of the hypothalamus and amygdala. This study reveals that the activity of discrete nuclei during acute noxious thermal stimulation in awake humans.

Predation impacts brain allometry in female guppies (Poecilia reticulata)

Cognitive and sensory abilities are vital in affecting survival under predation risk, leading to selection on brain anatomy. However, how exactly predation and brain evolution are linked has not yet been resolved, as current empirical evidence is inconclusive. This may be due to predation pressure having different effects across life stages and/or due to confounding factors in ecological comparisons of predation pressure. Here, we used adult guppies (Poecilia reticulata) to experimentally test how direct predation during adulthood would impact the relative brain size and brain anatomy of surviving individuals to examine if predators selectively remove individuals with specific brain morphology. To this end, we compared fish surviving predation to control fish, which were exposed to visual and olfactory predator cues but could not be predated on. We found that predation impacted the relative size of female brains. However, this effect was dependent on body size, as larger female survivors showed relatively larger brains, while smaller survivors showed relatively smaller brains when compared to control females. We found no differences in male relative brain size between survivors and controls, nor for any specific relative brain region sizes for either sex. Our results corroborate the important, yet complex, role of predation as an important driver of variation in brain size.

Allometry in the corpus callosum in neonates: Sexual dimorphism.

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult‐like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex‐differences in lateralization have prenatal origins.

An End-To-End Pipeline for Fully Automatic Morphological Quantification of Mouse Brain Structures From MRI Imagery.

Segmentation of mouse brain magnetic resonance images (MRI) based on anatomical and/or functional features is an important step towards morphogenetic brain structure characterization of murine models in neurobiological studies. State-of-the-art image segmentation methods register image volumes to standard presegmented templates or well-characterized highly detailed image atlases. Performance of these methods depends critically on the quality of skull-stripping, which is the digital removal of tissue signal exterior to the brain. This is, however, tedious to do manually and challenging to automate. Registration-based segmentation, in addition, performs poorly on small structures, low resolution images, weak signals, or faint boundaries, intrinsic to in vivo MRI scans. To address these issues, we developed an automated end-to-end pipeline called DeepBrainIPP (deep learning-based brain image processing pipeline) for 1) isolating brain volumes by stripping skull and tissue from T2w MRI images using an improved deep learning-based skull-stripping and data augmentation strategy, which enables segmentation of large brain regions by atlas or template registration, and 2) address segmentation of small brain structures, such as the paraflocculus, a small lobule of the cerebellum, for which DeepBrainIPP performs direct segmentation with a dedicated model, producing results superior to the skull-stripping/atlas-registration paradigm. We demonstrate our approach on data from both in vivo and ex vivo samples, using an in-house dataset of 172 images, expanded to 4,040 samples through data augmentation. Our skull stripping model produced an average Dice score of 0.96 and residual volume of 2.18%. This facilitated automatic registration of the skull-stripped brain to an atlas yielding an average cross-correlation of 0.98. For small brain structures, direct segmentation yielded an average Dice score of 0.89 and 5.32% residual volume error, well below the tolerance threshold for phenotype detection. Full pipeline execution is provided to non-expert users via a Web-based interface, which exposes analysis parameters, and is powered by a service that manages job submission, monitors job status and provides job history. Usability, reliability, and user experience of DeepBrainIPP was measured using the Customer Satisfaction Score (CSAT) and a modified PYTHEIA Scale, with a rating of excellent. DeepBrainIPP code, documentation and network weights are freely available to the research community.

Tapered fibertrodes for optoelectrical neural interfacing in small brain volumes with reduced artefacts.

Deciphering the neural patterns underlying brain functions is essential to understanding how neurons are organized into networks. This deciphering has been greatly facilitated by optogenetics and its combination with optoelectronic devices to control neural activity with millisecond temporal resolution and cell type specificity. However, targeting small brain volumes causes photoelectric artefacts, in particular when light emission and recording sites are close to each other. We take advantage of the photonic properties of tapered fibres to develop integrated 'fibertrodes' able to optically activate small brain volumes with abated photoelectric noise. Electrodes are positioned very close to light emitting points by non-planar microfabrication, with angled light emission allowing the simultaneous optogenetic manipulation and electrical read-out of one to three neurons, with no photoelectric artefacts, in vivo. The unconventional implementation of two-photon polymerization on the curved taper edge enables the fabrication of recoding sites all around the implant, making fibertrodes a promising complement to planar microimplants.

Tapered fibertrodes for optoelectrical neural interfacing in small brain volumes with reduced artefacts

Tapered fibertrodes for optoelectrical neural interfacing in small brain volumes with reduced artefacts

Generation of FLAG-tagged Arx knock-in mouse model.

The Aristaless-related homeobox (ARX) is a paired-like homeodomain transcription factor playing important roles in brain development. Patients with mutations in ARX have a spectrum of neurodevelopmental disorders such as epilepsy, intellectual disability, and autism spectrum disorder, with or without structural abnormalities of the brain such as lissencephaly (smooth brain), microcephaly (small brain), and/or agenesis of the corpus callosum. Mouse models have provided important clues on the pathophysiologic roles of ARX in these disorders. However, successfully isolating specific in vivo complexes of ARX, with DNA and proteins, has remained as a challenge. To facilitate in vivo detection of ARX complexes, we generated a mouse line containing one epitope of FLAG-tag (1 × FLAG) targeted at the translational start site of the endogenous Arx gene using CRSPR/Cas9 strategy. Homozygous Flag-Arx mice are viable and fertile without gross abnormality, suggesting that the FLAG-tag does not perturb the normal function of ARX. Using a FLAG antibody, we successfully detected ARX with immunofluorescent staining and pulled down ARX in embryonic brain tissues. This Flag-Arx mouse line will be a useful tool to isolate ARX complexes from mouse tissues for many applications.

Gefitinib plus chemotherapy versus gefitinib alone in untreated patients with EGFR-mutated non–small cell lung cancer and brain metastases (GAP Brain): An open-label, randomized, multicenter, phase 3 study.

9095 Background: Combination of tyrosine kinase inhibitor (TKI) and chemotherapy has shown improved clinical outcomes in advanced epidermal growth factor receptor ( EGFR) mutated non-small cell lung cancer (NSCLC) patients. We conducted this phase 3, randomized, controlled trial to further investigate the clinical efficacy and safety of gefitinib combined with chemotherapy in EGFR mutated NSCLC patients with brain metastases. Methods: Treatment-naïve, confirmed brain metastases and EGFR sensitive mutated NSCLC patients were screened from six centers in China. The eligible patients were randomly assigned (1:1) to receive gefitinib alone or gefitinib plus pemetrexed-platinum chemotherapy until intracranial progressive diseases, unacceptable adverse, or any cause of death. Theprimary endpoint was intracranial progression-free survival (iPFS), secondary endpoints were PFS, overall survival, intracranial objective response rate, overall objective response rate, and safety. This study is registered at ClinicalTrials. gov, number NCT01951469. Results: From January 2017 to June 2021, 161 patients were randomly assigned to receive gefitinib (n = 81) or gefitinib plus pemetrexed-platinum chemotherapy (n = 80), the median follow-up time was 18.2 (IQR 11.8-29.7) months. The median intracranial PFS was 15.6 (14.3-16.9) months in gefitinib plus chemotherapy group versus 9.1 (8.0-10.2) months in gefitinib group (HR = 0.36, 95% CI, 0.25-0.53, P &lt; 0.001). Similarly, the median PFS was also significantly longer in gefitinib plus chemotherapy than gefitinib alone (16.3 months vs 9.5 months, P &lt; 0.001). In addition, gefitinib plus chemotherapy had better intracranial objective response rate (85.0% versus 63.0%, P = 0.002) and overall objective response rate (80.0% versus 64.2%, P = 0.035) than gefitinib alone. At the data cutoff, 50.3% of patients (35 patients in gefitinib plus chemotherapy group and 46 patients in gefitinib group) had died. The 3-year OS rate was significantly higher in gefitinib plus chemotherapy group (47.4%, 95% CI 36.3-58.7) than in gefitinib group (24.9%, 95% CI 15.1-34.3, P = 0.003). And median overall survival was 35.0 months (95% CI, 28.8-41.3 months) in gefitinib plus chemotherapy group versus 28.9 months (95% CI, 23.4-34.4 months) in gefitinib group (HR = 0.66, 95% CI, 0.42-1.03, P = 0.065). Grade 3 or worse adverse events were more common in gefitinib plus chemotherapy group (40.0% versus 21.0%, P = 0.010), but most of them were manageable. Conclusions: Inuntreated EGFR mutated NSCLC patients with brain metastases, gefitinib plus chemotherapy significantly improved intracranial PFS, PFS and a tendency of OS than gefitinib alone, and could be the optional first-line treatment. Clinical trial information: NCT01951469.

Altered patterning of trisomy 21 interneuron progenitors.

SummaryIndividuals with Down syndrome (DS; Ts21), the most common genetic cause of intellectual disability, have smaller brains that reflect fewer neurons at pre- and post-natal stages, implicating impaired neurogenesis during development. Our stereological analysis of adult DS cortex indicates a reduction of calretinin-expressing interneurons. Using Ts21 human induced pluripotent stem cells (iPSCs) and isogenic controls, we find that Ts21 progenitors generate fewer COUP-TFII+ progenitors with reduced proliferation. Single-cell RNA sequencing of Ts21 progenitors confirms the altered specification of progenitor subpopulations and identifies reduced WNT signaling. Activation of WNT signaling partially restores the COUP-TFII+ progenitor population in Ts21, suggesting that altered WNT signaling contributes to the defective development of cortical interneurons in DS.

Brain partial volume correction with point spreading function reconstruction in high-resolution digital PET: comparison with an MR-based method in FDG imaging

ObjectiveIn quantitative positron emission tomography (PET) of the brain, partial volume effect due mainly to the finite spatial resolution of the PET scanner (> 3 mm full width at half maximum [FWHM]) is a primary source of error in the measurement of tracer uptake, especially in small structures such as the cerebral cortex (typically < 3 mm thickness). The aim of this study was to evaluate the partial volume correction (PVC) performance of point spread function-incorporated reconstruction (PSF reconstruction) in combination with the latest digital PET scanner. This evaluation was performed through direct comparisons with magnetic resonance imaging (MR)-based PVC (used as a reference method) in a human brain study.MethodsTen healthy subjects underwent brain 18F-FDG PET (30-min acquisition) on a digital PET/CT system (Siemens Biograph Vision, 3.5-mm FWHM scanner resolution at the center of the field of view) and anatomical T1-weighted MR imaging for MR-based PVC. PSF reconstruction was applied with a wide range of iterations (4 to 256; 5 subsets). FDG uptake in the cerebral cortex was evaluated using the standardized uptake value ratio (SUVR) and compared between PSF reconstruction and MR-based PVC.ResultsCortical structures were visualized by PSF reconstruction with several tens of iterations and were anatomically well matched with the MR-derived cortical segments. Higher numbers of iterations resulted in higher cortical SUVRs, which approached those of MR-based PVC (1.76), although even with the maximum number of iterations they were still smaller by 16% (1.47), corresponding to approximately 1.5-mm FWHM of the effective spatial resolution.ConclusionWith the latest digital PET scanner, PSF reconstruction can be used as a PVC technique in brain PET, albeit with suboptimal resolution recovery. A relative advantage of PSF reconstruction is that it can be applied not only to cerebral cortical regions, but also to various small structures such as small brain nuclei that are hardly visualized on anatomical T1-weighted imaging, and thus hardly recovered by MR-based PVC.

The costs and benefits of larger brains in fishes.

The astonishing diversity of brain sizes observed across the animal kingdom is typically explained in the context of trade-offs: the benefits of a larger brain, such as enhanced cognitive ability, are balanced against potential costs, such as increased energetic demands. Several hypotheses have been formulated in this framework, placing different emphasis on ecological, behavioural, or physiological aspects of trade-offs in brain size evolution. Within this body of work, there exists considerable taxonomic bias towards studies of birds and mammals, leaving some uncertainty about the generality of the respective arguments. Here, we test three of the most prominent such hypotheses, the 'expensive tissue', 'social brain' and 'cognitive buffer' hypotheses, in a large dataset of fishes, derived from a publicly available resource (FishBase). In accordance with predictions from the 'expensive tissue' and the 'social brain' hypothesis, larger brains co-occur with reduced fecundity and increased sociality in at least some Classes of fish. Contrary to expectations, however, lifespan is reduced in large-brained fishes, and there is a tendency for species that perform parental care to have smaller brains. As such, it appears that some potential costs (reduced fecundity) and benefits (increased sociality) of large brains are near universal to vertebrates, whereas others have more lineage-specific effects. We discuss our findings in the context of fundamental differences between the classically studied birds and mammals and the fishes we analyse here, namely divergent patterns of growth, parenting and neurogenesis. As such, our work highlights the need for a taxonomically diverse approach to any fundamental question in evolutionary biology.

High-resolution and high-sensitivity PET for quantitative molecular imaging of the monoaminergic nuclei: A GATE simulation study.

Quantitative in vivo molecular imaging of fine brain structures requires high-spatial resolution and high-sensitivity. Positron emission tomography (PET) is an attractive candidate to introduce molecular imaging into standard clinical care due to its highly targeted and versatile imaging capabilities based on the radiotracer being used. However, PET suffers from relatively poor spatial resolution compared to other clinical imaging modalities, which limits its ability to accurately quantify radiotracer uptake in brain regions and nuclei smaller than 3 mm in diameter. Here we introduce a new practical and cost-effective high-resolution and high-sensitivity brain-dedicated PET scanner, using our depth-encoding Prism-PET detector modules arranged in a conformal decagon geometry, to substantially reduce the partial volume effect and enable accurate radiotracer uptake quantification in small subcortical nuclei. Two Prism-PET brain scanner setups were proposed based on our 4-to-1 and 9-to-1 coupling of scintillators to readout pixels using mm3 and mm3 crystal columns, respectively. Monte Carlo simulations of our Prism-PET scanners, Siemens Biograph Vision, and United Imaging EXPLORER were performed using Geant4 application for tomographic emission (GATE). National Electrical Manufacturers Association (NEMA) standard was followed for the evaluation of spatial resolution, sensitivity, and count-rate performance. An ultra-micro hot spot phantom was simulated for assessing image quality. A modified Zubal brain phantom was utilized for radiotracer imaging simulations of 5-HT1A receptors, which are abundant in the raphe nuclei (RN), and norepinephrine transporters, which are highly concentrated in the bilateral locus coeruleus (LC). The Prism-PET brain scanner with 1.5 mm crystals is superior to that with 1 mm crystals as the former offers better depth-of-interaction (DOI) resolution, which is key to realizing compact and conformal PET scanner geometries. We achieved uniform 1.3 mm full-width-at-half-maximum (FWHM) spatial resolutions across the entire transaxial field-of-view (FOV), a NEMA sensitivity of 52.1 kcps/MBq, and a peak noise equivalent count rate (NECR) of 957.8 kcps at 25.2 kBq/mL using 450-650 keV energy window. Hot spot phantom results demonstrate that our scanner can resolve regions as small as 1.35 mm in diameter at both center and 10 cm away from the center of the transaixal FOV. Both 5-HT1A receptor and norepinephrine transporter brain simulations prove that our Prism-PET scanner enables accurate quantification of radiotracer uptake in small brain regions, with a 1.8-fold and 2.6-fold improvement in the dorsal RN as well as a 3.2-fold and 4.4-fold improvement in the bilateral LC compared to the Biograph Vision and EXPLORER, respectively. Based on our simulation results, the proposed high-resolution and high-sensitivity Prism-PET brain scanner is a promising cost-effective candidate to achieve quantitative molecular neuroimaging of small but important brain regions with PET clinicallyviable.