Region-Specific Brain Volume Changes Emerge in Adolescence in the Valproic Acid Model of Autism and Parallel Human Findings.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, cognitive dysfunction, and stereotyped repetitive behaviors. Regional volume changes are commonly observed in individuals with ASD. To examine volumetric dysregulation across adolescence, the valproic acid (VPA) model was used to induce ASD-like phenotypes in rats. METHOD: Regional volumes were obtained via magnetic resonance imaging at either postnatal day 28 or postnatal day 40 (P40), which correspond to early and late adolescence, respectively. RESULTS: Consistent with prior research, VPA animals had reduced total brain volume compared to control animals. A novel outcome was that VPA animals had overgrown right hippocampi at P40. Differences in the pattern of development of the anterior cingulate cortex were also observed in VPA animals. Differences for the posterior cingulate were only observed in males, but not females. CONCLUSION: These results demonstrate differences in region-specific developmental trajectories between control and VPA animals and suggest that the VPA model may capture regional volume changes consistent with human ASD.

System for delivering microwave ablation to subcutaneous tumors in small-animals under high-field MRI thermometry guidance.

PURPOSE: Bio-effects following thermal treatments are a function of the achieved temperature profile in tissue, which can be estimated across tumor volumes with real-time MRI thermometry (MRIT). Here, we report on expansion of a previously developed small-animal microwave hyperthermia system integrated with MRIT for delivering thermal ablation to subcutaneously implanted tumors in mice. METHODS: Computational models were employed to assess suitability of the 2.45 GHz microwave applicators for delivering ablation to subcutaneous tumor targets in mice. Phantoms and ex-vivo tissues were heated to temperatures in the range 47-67 °C with custom-made microwave applicators for validating MRIT with the proton resonance frequency shift method against fiberoptic thermometry. HAC15 tumors implanted in nude mice (n = 6) were ablated in vivo and monitored with MRIT in multiple planes. One day post ablation, animals were euthanized, and excised tumors were processed for viability assessment. RESULTS: Average absolute error between temperatures from fiberoptic sensors and MRIT was 0.6 °C across all ex-vivo ablations. During in-vivo experiments, tumors with volumes ranging between 5.4-35.9 mm3 (mean 14.2 mm3) were ablated (duration: 103-150 s) to achieve 55 °C at the tumor boundary. Thermal doses ≥240 CEM43 were achieved across 90.7-98.0% of tumor volumes for four cases. Ablations were incomplete for remaining cases, attributed to motion-affected thermometry. Thermal dose-based ablative tumor coverage agreed with viability assessment of excised tumors. CONCLUSIONS: We have developed a system for delivering microwave ablation to subcutaneous tumors in small animals under MRIT guidance and demonstrated its performance in-vivo.

Glyco-nanotechnology: A biomedical perspective.

Glycans govern cellular signaling through glycan-protein and glycan-glycan crosstalk. Disruption in the crosstalk initiates 'rogue' signaling and pathology. Nanomaterials supply platforms for multivalent displays of glycans, mediate 'rogue' signal correction, and provide disease treatment modalities (therapeutics). The decorated glycans also target overexpressed lectins on unhealthy cells and direct metal nanoparticles such as gold, iron oxide, and quantum dots to the site of infection. The nanoparticles inform us about the state of the disease (diagnosis) through their distinct optical, magnetic, and electronic properties. Glyco-nanoparticles can sense disease biomarkers, report changes in protein-glycan interactions, and safeguard quality control (analysis). Here we review the current state of glyco-nanotechnology focusing on diagnosis, therapeutics, and analysis of human diseases. We highlight how glyco-nanotechnology could aid in improving diagnostic methods for the detection of disease biomarkers with magnetic resonance imaging (MRI) and fluorescence imaging (FLI), enhance therapeutics such as anti-adhesive treatment of cancer and vaccines against pneumonia, and advance analysis such as the rapid detection of pharmaceutical heparin contaminant and recombinant SARS-COV-2 spike protein. We illustrate these progressions and outline future potentials of glyco-nanotechnology in advancing human health.

Aerobic exercise improves cognitive flexibility and modulates regional volume changes in a rat model of autism.

Gestational exposure to valproic acid (VPA) is a risk factor for autism spectrum disorder (ASD). Rodents exposed to VPA in utero display common features of ASD, including volumetric dysregulation in higher-order cognitive regions like the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus. Exercise has been shown in elderly populations to boost cognition and to buffer against brain volume losses with age. This study employed an adolescent treadmill exercise intervention to facilitate cognitive flexibility and regional brain volume regulation in rats exposed to VPA during gestation. It was found that exercise improved performance on extra-dimensional shifts of attention on a set-shifting task, which is indicative of improved cognitive flexibility. Exercise decreased frontal cortex volume in females, whereas in males exercise increased the ventral hippocampus. These findings suggest that aerobic exercise may be an effective intervention to counteract the altered development of prefrontal and hippocampal regions often observed in ASD.

T1-mapping characterization of two tumor types.

T1 mapping is a quantitative method to characterize tissues with magnetic resonance imaging in a quick and efficient manner. It utilizes the relaxation rate of protons to depict the underlying structures within the imaging frame. While T1-mapping techniques are used with some frequency in areas such as cardiac imaging, their application for understanding malignancies and identifying tumor structures has yet to be thoroughly investigated. Utilizing a saturation recovery method to acquire T1 maps for two different tumor models has revealed that longitudinal relaxation mapping is sensitive enough to distinguish between normal and malignant tissue. This is seen even with decreased signal/noise ratios using small voxel sizes to obtain high-resolution images. In both tumor models, it was revealed that relaxation mapping recorded significantly different relaxation values between regions encapsulating the tumor, muscle, kidney, or spleen, as well as between the cell lines themselves. This indicates a potential future application of relaxation mapping as a method to fingerprint various stages of tumor development and may prove a useful measure to identify micro-metastases.

Super-resolution reconstruction in ultrahigh-field MRI.

Magnetic resonance imaging (MRI) is a highly significant imaging platform for a variety of medical and research applications. However, the low spatiotemporal resolution of conventional MRI limits its applicability toward rapid acquisition of ultrahigh-resolution scans. Current aims at high-resolution MRI focus on increasing the accuracy of tissue delineation, assessments of structural integrity, and early identification of malignancies. Unfortunately, high-resolution imaging often leads to decreased signal/noise (SNR) and contrast/noise (CNR) ratios and increased time cost, which are unfeasible in many clinical and academic settings, offsetting any potential benefits. In this study, we apply and assess the efficacy of super-resolution reconstruction (SRR) through iterative back-projection utilizing through-plane voxel offsets. SRR allows for high-resolution imaging in condensed time frames. Rat skulls and archerfish samples, typical models in academic settings, were used to demonstrate the impact of SRR on varying sample sizes and applicability for translational and comparative neuroscience. The SNR and CNR increased in samples that did not fully occupy the imaging probe and in instances where the low-resolution data were acquired in three dimensions, while the CNR was found to increase with both 3D and 2D low-resolution data reconstructions when compared with directly acquired high-resolution images. Limitations to the applied SRR algorithm were investigated to determine the maximum ratios between low-resolution inputs and high-resolution reconstructions and the overall cost effectivity of the strategy. Overall, the study revealed that SRR could be used to decrease image acquisition time, increase the CNR in nearly all instances, and increase the SNR in small samples.

Adolescent female valproic acid rats have impaired extra-dimensional shifts of attention and enlarged anterior cingulate cortices.

In order to develop better treatments for autism spectrum disorder (ASD) it is critical to understand the developmental trajectory of the disorder and the accompanying brain changes. This study used the valproic acid (VPA) model to induce ASD-like symptoms in rodents. Prior studies have demonstrated that VPA animals are impaired on executive function tasks, paralleling results in humans with ASD. Here, VPA adolescent female rats were impaired on a set-shifting task and had enlarged frontal cortices compared to control females. The deficits observed in the VPA female rats mirrors results in females with ASD. In addition, adolescent VPA females with enlarged frontal cortices performed the worst across the entire task. These brain changes in adolescence are also found in adolescent humans with ASD. These novel findings highlight the importance of studying the brain at different developmental stages.

Iron-Based Magnetic Nanosystems for Diagnostic Imaging and Drug Delivery: Towards Transformative Biomedical Applications.

The advancement of biomedicine in a socioeconomically sustainable manner while achieving efficient patient-care is imperative to the health and well-being of society. Magnetic systems consisting of iron based nanosized components have gained prominence among researchers in a multitude of biomedical applications. This review focuses on recent trends in the areas of diagnostic imaging and drug delivery that have benefited from iron-incorporated nanosystems, especially in cancer treatment, diagnosis and wound care applications. Discussion on imaging will emphasise on developments in MRI technology and hyperthermia based diagnosis, while advanced material synthesis and targeted, triggered transport will be the focus for drug delivery. Insights onto the challenges in transforming these technologies into day-to-day applications will also be explored with perceptions onto potential for patient-centred healthcare.

Increased volumes of lobule VI in a valproic acid model of autism are associated with worse set-shifting performance in male Long-Evan rats.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a skewed sex-based diagnostic ratio. While males are at a higher risk for ASD, it is critical to understand the neurobiology of the disorder to develop better treatments for both males and females. Our prior work has demonstrated that VPA (valproic acid) treated offspring had impaired performance on an attentional set-shifting task. The current study used MRI and regions of interest analyses to measure the volumes of cerebellar subregions in VPA and controls rats that had participated in the attentional set-shifting task. VPA males had significantly more volume in lobule VI compared to male controls. VPA female rats had significantly less volume in lobules I, IV and X compared to female controls. In addition, it was revealed that decreases in volume for VPA females was associated with worse performance. Males with increases in lobule VI were also impaired on the set-shifting task. Similar volumetric differences within the cerebellum have been observed in humans with ASD, which suggests that the VPA model is capturing some of the same brain changes observed in humans with ASD, and that these changes in volume may be impacting cognition.

Direct treatment versus indirect: Thermo-ablative and mild hyperthermia effects.

Hyperthermia is a rapidly growing field in cancer therapy and many advances have been made in understanding and applying the mechanisms of hyperthermia. Secondary effects of hyperthermia have been increasingly recognized as important in therapeutic effects and multiple studies have started to elucidate their implications for treatment. Immune effects have especially been recognized as important in the efficacy of hyperthermia treatment of cancer. Both thermo-ablative and mild hyperthermia activate the immune system, but mild hyperthermia seems to be more effective at doing so. This may suggest that mild hyperthermia has some advantages over thermo-ablative hyperthermia and research into immune effects of mild hyperthermia should continue. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery.