Biopsy Artifact in Laser Interstitial Thermal Therapy: A Technical Note

PurposeThe safety and effectiveness of laser interstitial thermal therapy (LITT) relies critically on the ability to continuously monitor the ablation based on real-time temperature mapping using magnetic resonance thermometry (MRT). This technique uses gradient recalled echo (GRE) sequences that are especially sensitive to susceptibility effects from air and blood. LITT for brain tumors is often preceded by a biopsy and is anecdotally associated with artifact during ablation. Thus, we reviewed our experience and describe the qualitative signal dropout that can interfere with ablation.MethodsWe retrospectively reviewed all LITT cases performed in our intraoperative MRI suite for tumors between 2017 and 2020. We identified a total of 17 LITT cases. Cases were reviewed for age, sex, pathology, presence of artifact, operative technique, and presence of blood/air on post-operative scans.ResultsWe identified six cases that were preceded by biopsy, all six had artifact present during ablation, and all six were noted to have air/blood on their post-operative MRI or CT scans. In two of those cases, the artifactual signal dropout qualitatively interfered with thermal damage thresholds at the borders of the tumor. There was no artifact in the 11 non-biopsy cases and no obvious blood or air was noted on the post-ablation scans.ConclusionAdditional consideration should be given to pre-LITT biopsies. The presence of air/blood caused an artifactual signal dropout effect in cases with biopsy that was severe enough to interfere with ablation in a significant number of those cases. Additional studies are needed to identify modifying strategies.

Functional Activities Detected in the Olfactory Bulb and Associated Olfactory Regions in the Human Brain Using T2-Prepared BOLD Functional MRI at 7T

Olfaction is a fundamental sense that plays a vital role in daily life in humans, and can be altered in neuropsychiatric and neurodegenerative diseases. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) using conventional echo-planar-imaging (EPI) based sequences can be challenging in brain regions important for olfactory processing, such as the olfactory bulb (OB) and orbitofrontal cortex, mainly due to the signal dropout and distortion artifacts caused by large susceptibility effects from the sinonasal cavity and temporal bone. To date, few studies have demonstrated successful fMRI in the OB in humans. T2-prepared (T2prep) BOLD fMRI is an alternative approach developed especially for performing fMRI in regions affected by large susceptibility artifacts. The purpose of this technical study is to evaluate T2prep BOLD fMRI for olfactory functional experiments in humans. Olfactory fMRI scans were performed on 7T in 14 healthy participants. T2prep BOLD showed greater sensitivity than GRE EPI BOLD in the OB, orbitofrontal cortex and the temporal pole. Functional activation was detected using T2prep BOLD in the OB and associated olfactory regions. Habituation effects and a bi-phasic pattern of fMRI signal changes during olfactory stimulation were observed in all regions. Both positively and negatively activated regions were observed during olfactory stimulation. These signal characteristics are generally consistent with literature and showed a good intra-subject reproducibility comparable to previous human BOLD fMRI studies. In conclusion, the methodology demonstrated in this study holds promise for future olfactory fMRI studies in the OB and other brain regions that suffer from large susceptibility artifacts.

Immunogenetic Epidemiology of Motor Neuron Diseases in 14 Continental Western European Countries

Very few studies have evaluated associations of human leukocyte antigen (HLA) with motor neuron diseases (MND). Using an immunogenetic epidemiological approach, we identified a population-level HLA profile for MND by evaluating the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of MND in 14 Continental Western European countries. The results demonstrated that significantly more HLA alleles, particularly for Class I, were negatively associated with the population prevalence of MND, suggesting a preponderance of protective vs susceptibility effects. The findings add to the limited literature implicating HLA in MND and considering the role of HLA in immune system responses to pathogens, suggest a potential influence of pathogens in MND.

Large parental differences in chromatin organization in pancreatic beta cell line explaining diabetes susceptibility effects

Previous GWAS studies identified non-coding loci with parent-of-origin-specific effects on Type 2 diabetes susceptibility. Here we report the molecular basis for one such locus near the KRTAP5-6 gene on chromosome 11. We determine the pattern of long-range contacts between an enhancer in this locus and the human INS promoter 460 kb away, in the human pancreatic β-cell line, EndoC-βH1. 3C long range contact experiments distinguish contacts on the two sister chromosomes. Coupling with allele-specific SNPs allows construction of maps revealing marked differences in organization of the two sister chromosomes in the entire region between KRTAP5-6 and INS. Further mapping distinguishes maternal and paternal alleles. This reveals a domain of parent-of-origin-specific chromatin structure extending in the telomeric direction from the INS locus. This suggests more generally that imprinted loci may extend their influence over gene expression beyond those loci through long range chromatin structure, resulting in parent-of-origin-biased expression patterns over great distances.

Respiratory Motion Mitigation and Repeatability of Two Diffusion-Weighted MRI Methods Applied to a Murine Model of Spontaneous Pancreatic Cancer

Respiratory motion and increased susceptibility effects at high magnetic fields pose challenges for quantitative diffusion-weighted MRI (DWI) of a mouse abdomen on preclinical MRI systems. We demonstrate the first application of radial k-space-sampled (RAD) DWI of a mouse abdomen using a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) on a 4.7 T preclinical scanner equipped with moderate gradient capability. RAD DWI was compared with the echo-planar imaging (EPI)-based DWI method with similar voxel volumes and acquisition times over a wide range of b-values (0.64, 535, 1071, 1478, and 2141 mm2/s). The repeatability metrics are assessed in a rigorous test–retest study (n = 10 for each DWI protocol). The four-shot EPI DWI protocol leads to higher signal-to-noise ratio (SNR) in diffusion-weighted images with persisting ghosting artifacts, whereas the RAD DWI protocol produces relatively artifact-free images over all b-values examined. Despite different degrees of motion mitigation, both RAD DWI and EPI DWI allow parametric maps of apparent diffusion coefficients (ADC) to be produced, and the ADC of the PDAC tumor estimated by the two methods are 1.3 ± 0.24 and 1.5 ± 0.28 × 10−3 mm2/s, respectively (p = 0.075, n = 10), and those of a water phantom are 3.2 ± 0.29 and 2.8 ± 0.15 × 10−3 mm2/s, respectively (p = 0.001, n = 10). Bland-Altman plots and probability density function reveal good repeatability for both protocols, whose repeatability metrics do not differ significantly. In conclusion, RAD DWI enables a more effective respiratory motion mitigation but lower SNR, while the performance of EPI DWI is expected to improve with more advanced gradient hardware.

Fine-scale spatial patterns of wildlife disease are common and understudied

All pathogens are heterogeneous in space, yet little is known about the prevalence and scale of this spatial variation, particularly in wild animal systems. To address this question, we conducted a broad literature search to identify datasets involving diseases of wild mammals in spatially distributed contexts. Across 31 such final datasets featuring 89 replicates and 71 host-parasite combinations, only 51% had previously been used to test spatial hypotheses. We analysed these datasets for spatial dependence within a standardised modelling framework using Bayesian linear models. We detected spatial autocorrelation in 44/89 model replicates (54%) across 21/31 datasets (68%), spread across parasites of all groups and transmission modes. Surprisingly, although larger sampling areas more easily detected spatial patterns, even some very small study areas (under 0.01km2) exhibited substantial spatial heterogeneity. Parasites of all transmission modes had easily detectable spatial patterns, implying that structured contact networks and susceptibility effects are likely as important in spatially structuring disease as are environmental drivers of transmission efficiency. Our findings imply that fine-scale spatial patterns of infection often manifest in wild animal systems, whether or not the aim of the study is to examine environmentally varying processes. Given the widespread nature of these findings, studies should more frequently record and analyse spatial data, facilitating development and testing of spatial hypotheses in disease ecology.

Characterization of Induced Susceptibility Effects of Soybean Aphid on Soybean

ABSTRACTSoybean aphid (SBA) is one of the major pests of soybean (Glycine max) in the United States of America. The main objective of this research was to characterize interactions between two different biotypes of soybean aphids in susceptible and resistant soybean cultivars. Demographic and transcriptomic responses of susceptible and resistant (Rag1) soybean cultivars to aphid feeding were investigated in soybean plants colonized by aphids (biotype 1) in the presence or absence of inducer population (biotype 2) at day 1 and day 11. Leaves tissues collected at day 1 and day 11 post infestation were used for RNA sequencing, and ten RNA datasets with 266,535,654 sequence reads were analyzed. In the presence of inducer population, we found 746 and 243 differentially expressed genes (DEGs) in susceptible and resistant cultivars, respectively at day 1, whereas 981 and 377 DEGs were found in susceptible and resistant cultivars, respectively at day 11. Enrichment analysis showed a response to chitin, lignin catabolic and metabolic process, asparagine metabolic process, response to chemical unique to treatment with no inducer population, whereas, response to reactive oxygen species, photosynthesis, regulation of endopeptidase activity unique to treatment with inducer population. Furthermore, 14 DEGs were observed in Rag QTLs regions, particularly six DEGs in Rag1 containing QTL. The identified DEGs in the experiment in both resistant and susceptible cultivars during the interaction of soybean and SBA are potential candidates for furthering investigation into induced susceptibility.

Sex effects across the lifespan in women with multiple sclerosis

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.