The quorum-sensing peptidic inhibitor rescues host immune system eradication: A novel infectivity mechanism.

Subverting the host immune system is a major task for any given pathogen to assure its survival and proliferation. For the opportunistic human pathogen Bacillus cereus (Bc), immune evasion enables the establishment of potent infections. In various species of the Bc group, the pleiotropic regulator PlcR and its cognate cell-cell signaling peptide PapR7 regulate virulence gene expression in response to fluctuations in population density, i.e., a quorum-sensing (QS) system. However, how QS exerts its effects during infections and whether PlcR confers the immune evading ability remain unclear. Herein, we report how interception of the QS communication in Bc obliterates the ability to affect the host immune system. Here, we designed a peptide-based QS inhibitor that suppresses PlcR-dependent virulence factor expression and attenuates Bc infectivity in mouse models. We demonstrate that the QS peptidic inhibitor blocks host immune system-mediated eradication by reducing the expression of PlcR-regulated major toxins similarly to the profile that was observed for isogenic strains. Our findings provide evidence that Bc infectivity is regulated by QS circuit-mediated destruction of host immunity, thus reveal a interesting strategy to limit Bc virulence and enhance host defense. This peptidic quorum-quenching agent constitutes a readily accessible chemical tool for studying how other pathogen QS systems modulate host immunity and forms a basis for development of anti-infective therapeutics.

Disrupting the epileptogenic network with stereoelectroencephalography-guided radiofrequency thermocoagulation.

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is a treatment option for focal drug-resistant epilepsy. In previous studies, this technique has shown seizure reduction by ≥50% in 50% of patients at 1 year. However, the relationship between the location of the ablation within the epileptogenic network and clinical outcomes remains poorly understood. Seizure outcomes were analyzed for patients who underwent SEEG-guided RF-TC and across subgroups depending on the location of the ablation within the epileptogenic network, defined as SEEG sites involved in seizure generation and spread. Eighteen patients who had SEEG-guided RF-TC were included. SEEG-guided seizure-onset zone ablation (SEEG-guided SOZA) was performed in 12 patients, and SEEG-guided partial seizure-onset zone ablation (SEEG-guided P-SOZA) in 6 patients. The early spread was ablated in three SEEG-guided SOZA patients. Five patients had ablation of a lesion. The seizure freedom rate in the cohort ranged between 22% and 50%, and the responder rate between 67% and 85%. SEEG-guided SOZA demonstrated superior results for both outcomes compared to SEEG-guided P-SOZA at 6 months (seizure freedom p = .294, responder rate p = .014). Adding the early spread ablation to SEEG-guided SOZA did not increase seizure freedom rates but exhibited comparable effectiveness regarding responder rates, indicating a potential network disruption.

Spinal Nerve Root Stimulation for Chronic Pain: A Systematic Review.

OBJECTIVE: Spinal cord stimulation (SCS) has been used as a minimally invasive and effective treatment modality for various chronic pain disorders, with the main target being stimulation of the dorsal columns; however, certain neuropathic pain areas involve dermatomes that are suboptimally covered by SCS. Stimulation of the spinal nerve roots has the advantage of targeting one or several dermatomes at the same time. The aim of this systematic review is to investigate the efficacy of spinal nerve root stimulation (SNRS) for chronic pain disorders. MATERIALS AND METHODS: A detailed literature review was performed through the Ovid Embase and MEDLINE data bases in addition to reference searching. Gray literature was included by searching through common search engines using a simplified search strategy. Studies included were focused on adult patients (aged >18 years), diagnosis of chronic pain syndrome (including but not limited to complex regional pain syndrome, persistent spinal pain syndrome, neuropathic pain secondary to trauma or infection, postherpetic pain, and cancer pain). Patients must have undergone SNRS insertion, with ≥six months of documented pain intensity scores on follow-up. RESULTS: A total of 40 studies underwent full text review, and 13 articles were included in final analysis. Mean preoperative pain intensity was 8.14 ± 0.74 on the visual analog scale, whereas mean postoperative pain intensity at one year was 3.18 ± 1.44. Of 119 patients, 83 (70%) achieved ≥50% reduction in pain intensity after SNRS, whereas 36 (30%) achieved <50% reduction in pain intensity. Only three studies assessed changes in analgesia medication dose and reported morphine equivalent doses varied by case series. Overall, there was a trend toward a reduction in analgesia medications in the postoperative period. CONCLUSIONS: SNRS led to a mean 44% reduction in pain intensity, with a low level of certainty. In addition, there is some evidence to suggest that using SNRS is associated with reduced use of analgesics, including morphine and gabapentin.

Antibacterial efficacy of an ultra-short palmitoylated random peptide mixture in mouse models of infection by carbapenem-resistant Klebsiella pneumoniae.

Indiscriminate use of antibiotics has imposed a selective pressure for the rapid rise in bacterial resistance, creating an urgent need for novel therapeutics for managing bacterial infectious diseases while counteracting bacterial resistance. Carbapenem-resistant Klebsiella pneumoniae strains have become a major challenge in modern medicine due to their ability to cause an array of severe infections. Recently, we have shown that the 20-mer random peptide mixtures are effective therapeutics against three ESKAPEE pathogens. Here, we evaluated the toxicity, biodistribution, bioavailability, and efficacy of the ultra-short palmitoylated 5-mer phenylalanine:lysine (FK5P) random peptide mixtures against multiple clinical isolates of carbapenem-resistant K. pneumoniae and K. oxytoca. We demonstrate the FK5P rapidly and effectively killed various strains of K. pneumoniae, inhibited the formation of biofilms, and disrupted mature biofilms. FK5P displayed strong toxicity profiles both in vitro and in mice, with prolonged favorable biodistribution and a long half-life. Significantly, FK5P reduced the bacterial burden in mouse models of acute pneumonia and bacteremia and increased the survival rate in a mouse model of bacteremia. Our results demonstrate that FK5P is a safe and promising therapy against Klebsiella species as well as other ESKAPEE pathogens.

PROTEUS Study: A Prospective Randomized Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

BACKGROUND: Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS: PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION: This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199.

Convex Optimization for Nonequilibrium Steady States on a Hybrid Quantum Processor.

Finding the transient and steady state properties of open quantum systems is a central problem in various fields of quantum technologies. Here, we present a quantum-assisted algorithm to determine the steady states of open system dynamics. By reformulating the problem of finding the fixed point of Lindblad dynamics as a feasibility semidefinite program, we bypass several well-known issues with variational quantum approaches to solving for steady states. We demonstrate that our hybrid approach allows us to estimate the steady states of higher dimensional open quantum systems and discuss how our method can find multiple steady states for systems with symmetries.

Surgical Interventions Targeting the Nucleus Caudalis for Craniofacial Pain: A Systematic and Historical Review.

INTRODUCTION: Craniofacial pain is a prevalent group of conditions, and when refractory to conventional treatments, it poses a significant burden. The last decade has seen a renewed interest in the multimodal management of pain. Interventions targeting the nucleus caudalis (NC) of the trigeminocervical complex have been available as a treatment option since the 1930s, yet evidence for efficacy remains limited. MATERIALS AND METHODS: We present a systematic review of the literature providing a historical perspective on interventions targeting the NC leading up to the present. We examine the various intervention techniques, clinical indications, and procedural efficacy. A novel outcome-reporting scheme was devised to enable comparison among studies owing to historically variable reporting methods. RESULTS: A review of the literature revealed 33 retrospective studies published over the last 80 years, reporting on 827 patients. The most common technique was the open NC dorsal root entry zone nucleotomy/tractotomy; however, there has been an emergence of novel approaches such as endoscopic and spinal cord stimulation in the last ten years. Regardless of intervention technique or preoperative diagnosis, 87% of patients showed improvement with treatment. CONCLUSIONS: The literature surrounding NC intervention techniques is reviewed. Recent advancements and the wide range of craniofacial pain syndromes for which these interventions show potential efficacy are discussed. New and less invasive techniques continue to emerge as putative therapeutic options. However, prospective studies are lacking. Furthermore, the evidence supporting even well-established techniques remains of poor quality. Future work should be prospective, use standard outcome reporting, and address efficacy comparisons between intervention type and preoperative diagnosis.

Mapping the subcortical connectome using in vivo diffusion MRI: Feasibility and reliability.

Tractography combined with regions of interest (ROIs) has been used to non-invasively study the structural connectivity of the cortex as well as to assess the reliability of these connections. However, the subcortical connectome (subcortex to subcortex) has not been comprehensively examined, in part due to the difficulty of performing tractography in this complex and compact region. In this study, we performed an in vivo investigation using tractography to assess the feasibility and reliability of mapping known connections between structures of the subcortex using the test-retest dataset from the Human Connectome Project (HCP). We further validated our observations using a separate unrelated subjects dataset from the HCP. Quantitative assessment was performed by computing tract densities and spatial overlap of identified connections between subcortical ROIs. Further, known connections between structures of the basal ganglia and thalamus were identified and visually inspected, comparing tractography reconstructed trajectories with descriptions from tract-tracing studies. Our observations demonstrate both the feasibility and reliability of using a data-driven tractography-based approach to map the subcortical connectome in vivo.

Non-canonical nematode endogenous retroviruses resulting from RNA virus glycoprotein gene capture by a metavirus.

Reverse-transcribing retroviruses exist as horizontally transmitted infectious agents or vertically transmitted endogenous retroviruses (ERVs) resident in eukaryotic genomes, and they are phylogenetically related to the long terminal repeat (LTR) class of retrotransposons. ERVs and retrotransposons are often distinguished only by the presence or absence of a gene encoding the envelope glycoprotein (env). Endogenous elements of the virus family Metaviridae include the insect-restricted Errantivirus genus of ERVs, for which some members possess env, and the pan-eukaryotic Metavirus genus that lacks an envelope glycoprotein gene. Here we report a novel Nematoda endogenous retrovirus (NERV) clade with core retroviral genes arranged uniquely as a continuous gag-env-pro-pol ORF. Reverse transcriptase sequences were phylogenetically related to metaviruses, but envelope glycoprotein sequences resembled those of the Nyamiviridae and Chrysoviridae RNA virus families, suggesting env gene capture during host cell infection by an RNA virus. NERVs were monophyletic, restricted to the nematode subclass Chromadoria, and included additional ORFs for a small hypothetical protein or a large Upf1-like RNA-dependent AAA-ATPase/helicase indicative of viral transduction of a host gene. Provirus LTR identity, low copy number, ORF integrity and segregation of three loci in Meloidogyne incognita, taken together with detection of NERV transcriptional activity, support potential infectivity of NERVs, along with their recent emergence and integration. Altogether, NERVs constitute a new and distinct Metaviridae lineage demonstrating retroviral evolution through sequential heterologous gene capture events.

Effects of MP2RAGE B1+ sensitivity on inter-site T1 reproducibility and hippocampal morphometry at 7T.

Most neuroanatomical studies are based on T1-weighted MR images, whose intensity profiles are not solely determined by the tissue's longitudinal relaxation times (T1), but also affected by varying non-T1 contributions, hampering data reproducibility. In contrast, quantitative imaging using the MP2RAGE sequence, for example, allows direct characterization of the brain based on the tissue property of interest. Combined with 7 Tesla (7T) MRI, this offers unique opportunities to obtain robust high-resolution brain data characterized by a high reproducibility, sensitivity and specificity. However, specific MP2RAGE parameter choices - e.g., to emphasize intracortical myelin-dependent contrast variations - can substantially impact image quality and cortical analyses through remnants of B1+-related intensity variations, as illustrated in our previous work. To follow up on this: we (1) validate this protocol effect using a dataset acquired with a particularly B1+ insensitive set of MP2RAGE parameters combined with parallel transmission excitation; and (2) extend our analyses to evaluate the effects on hippocampal morphometry. The latter remained unexplored initially, but can provide important insights related to generalizability and reproducibility of neurodegenerative research using 7T MRI. We confirm that B1+ inhomogeneities have a considerably variable effect on cortical T1 estimates, as well as on hippocampal morphometry depending on the MP2RAGE setup. While T1 differed substantially across datasets initially, we show the inter-site T1 comparability improves after correcting for the spatially varying B1+ field using a separately acquired Sa2RAGE B1+ map. Finally, removal of B1+ residuals affects hippocampal volumetry and boundary definitions, particularly near structures characterized by strong intensity changes (e.g. cerebral spinal fluid). Taken together, we show that the choice of MP2RAGE parameters can impact T1 comparability across sites and present evidence that hippocampal segmentation results are modulated by B1+ inhomogeneities. This calls for careful (1) consideration of sequence parameters when setting acquisition protocols, as well as (2) acquisition of a B1+ map to correct MP2RAGE data for potential B1+ variations to allow comparison across datasets.

Direct visualization and characterization of the human zona incerta and surrounding structures.

The zona incerta (ZI) is a small gray matter region of the deep brain first identified in the 19th century, yet direct in vivo visualization and characterization has remained elusive. Noninvasive detection of the ZI and surrounding region could be critical to further our understanding of this widely connected but poorly understood deep brain region and could contribute to the development and optimization of neuromodulatory therapies. We demonstrate that high resolution (submillimetric) longitudinal (T1) relaxometry measurements at high magnetic field strength (7 T) can be used to delineate the ZI from surrounding white matter structures, specifically the fasciculus cerebellothalamicus, fields of Forel (fasciculus lenticularis, fasciculus thalamicus, and field H), and medial lemniscus. Using this approach, we successfully derived in vivo estimates of the size, shape, location, and tissue characteristics of substructures in the ZI region, confirming observations only previously possible through histological evaluation that this region is not just a space between structures but contains distinct morphological entities that should be considered separately. Our findings pave the way for increasingly detailed in vivo study and provide a structural foundation for precise functional and neuromodulatory investigation.

ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations.

We investigated the proposal that ankylosing spondylitis (AS) is associated with unusual ERAP1 genotypes. ERAP1 haplotypes were constructed for 213 AS cases and 46 rheumatoid arthritis controls using family data. Haplotypes were generated from five common ERAP1 single nucleotide polymorphisms (SNPs)-rs2287987 (M349V), rs30187 (K528R), rs10050860 (D575N), rs17482078 (R725Q), and rs27044 (Q730E). Haplotype frequencies were compared using Fisher's exact test. ERAP1 haplotypes imputed from the International Genetics of AS Consortium (IGAS) Immunochip study were also studied. In the family study, we identified only four common ERAP1 haplotypes ("VRNQE," "MKDRQ," "MRDRE," and "MKDRE") in both AS cases and controls apart from two rare (<0.5%) previously unreported haplotypes. There were no examples of the unusual ERAP1 haplotype combination ("*001/*005") previously reported by others in 53% of AS cases. As expected, K528-bearing haplotypes were increased in the AS family study (AS 43% vs. control 35%), due particularly to an increase in the MKDRQ haplotype (AS 35% vs. control 25%, P = 0.01). This trend was replicated in the imputed Immunochip data for the two K528-bearing haplotypes MKDRQ (AS 33% vs. controls 27%, P = 1.2 × 10-24) and MKDRE (AS 8% vs. controls 7%, P = 0.004). The ERAP1 association with AS is therefore predominantly attributable to common ERAP1 haplotypes and haplotype combinations.

A framework for evaluating correspondence between brain images using anatomical fiducials.

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point-based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.

A Putative Protein O-Fucosyltransferase Facilitates Pollen Tube Penetration through the Stigma-Style Interface.

During pollen-pistil interactions in angiosperms, the male gametophyte (pollen) germinates to produce a pollen tube. To fertilize ovules located within the female pistil, the pollen tube must physically penetrate specialized tissues. Whereas the process of pollen tube penetration through the pistil has been anatomically well described, the genetic regulation remains poorly understood. In this study, we identify a novel Arabidopsis (Arabidopsis thaliana) gene, O-FUCOSYLTRANSFERASE1 (AtOFT1), which plays a key role in pollen tube penetration through the stigma-style interface. Semi-in vivo growth assays demonstrate that oft1 mutant pollen tubes have a reduced ability to penetrate the stigma-style interface, leading to a nearly 2,000-fold decrease in oft1 pollen transmission efficiency and a 5- to 10-fold decreased seed set. We also demonstrate that AtOFT1 is localized to the Golgi apparatus, indicating its potential role in cellular glycosylation events. Finally, we demonstrate that AtOFT1 and other similar Arabidopsis genes represent a novel clade of sequences related to metazoan protein O-fucosyltransferases and that mutation of residues that are important for O-fucosyltransferase activity compromises AtOFT1 function in vivo. The results of this study elucidate a physiological function for AtOFT1 in pollen tube penetration through the stigma-style interface and highlight the potential importance of protein O-glycosylation events in pollen-pistil interactions.

Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Énoncé de position quant à l'utilisation du cannabis médical dans le traitement de l'épilepsie. L'utilisation du cannabis à des fins récréatives a été légalisée au Canada en octobre 2018. Parallèlement à ce changement de politique, de récentes publication visant à évaluer l'efficacité du cannabis dans le traitement de l'épilepsie, de même qu'une sensibilisation médiatique accrue en ce qui concerne son utilisation, ont eu pour effet d'augmenter l'intérêt du grand public à son égard. Le Comité médical thérapeutique de la Ligue canadienne contre l'épilepsie (LCCE), de concert avec un groupe multidisciplinaire d'experts et des représentants de l'Alliance canadienne de l'épilepsie, a ainsi élaboré un énoncé de position en ce qui regarde l'utilisation du cannabis médical dans le traitement de l'épilepsie. Cet article entend donc aborder le cadre légal qui prévaut actuellement au Canada et examiner de récentes publications s'étant penchées sur le profil sécuritaire et sur l'efficacité du cannabis. De plus, nous voulons apporter un éclairage au sujet des aspects cliniques dont il faudrait tenir compte au moment d'envisager l'utilisation du cannabis à des fins médicales.

Radiology reporting of low-grade glioma growth underestimates tumor expansion.

BACKGROUND: An important aspect in the management of patients with diffuse low-grade gliomas (LGGs) involves monitoring the lesions via serial magnetic resonance imaging (MRI). However, radiological interpretations of LGG interval scans are often qualitative and thus difficult to use clinically. METHODS: To contextualize these assessments, we retrospectively compared radiological interpretations of LGG growth or stability to volume change measured by manual segmentation. Tumor diameter was also measured in one, two, and three dimensions to evaluate reported methods for assessment of glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumor diameter/ellipsoid method. RESULTS: Tumors evaluated as stable by radiologists grew a median volume of 5.1 mL (11.1%) relative to the comparison scan, and those evaluated as having grown had a median volume increase of 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate gold standard segmented volumes. In addition, agreement with segmented volume measurements improved from 17.6 ± 8.0 to 4.5 ± 5.8 to 3.9 ± 3.6 mm for diameter and from 104.0 ± 96.6 to 25.3 ± 36.8 to 15.9 ± 21.3 mL for volume with radiological measurements in one, two, and three dimensions, respectively. Measurement overestimation increased with tumor size. CONCLUSIONS: Given accumulating evidence that LGG volume and growth are prognostic factors, there is a need for objective lesion measurement. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. While volumetric analysis remains the gold standard for assessment of growth, careful diametric measurements in three dimensions may be an acceptable alternative.

Unfolding the hippocampus: An intrinsic coordinate system for subfield segmentations and quantitative mapping.

The hippocampus, like the neocortex, has a morphological structure that is complex and variable in its folding pattern, especially in the hippocampal head. The current study presents a computational method to unfold hippocampal grey matter, with a particular focus on the hippocampal head where complexity is highest due to medial curving of the structure and the variable presence of digitations. This unfolding was performed on segmentations from high-resolution, T2-weighted 7T MRI data from 12 healthy participants and one surgical patient with epilepsy whose resected hippocampal tissue was used for histological validation. We traced a critical image feature composed of the hippocampal sulcus and stratum radiatum lacunosum-moleculare, (SRLM) in these images, then employed user-guided semi-automated techniques to detect and subsequently unfold the surrounding hippocampal grey matter. This unfolding was performed by solving Laplace's equation in three dimensions of interest (long-axis, proximal-distal, and laminar). The resulting 'unfolded coordinate space' provides an intuitive way of mapping the hippocampal subfields in 2D space (long-axis and proximal-distal), such that similar borders can be applied in the head, body, and tail of the hippocampus independently of variability in folding. This unfolded coordinate space was employed to map intracortical myelin and thickness in relation to subfield borders, which revealed intracortical myelin differences that closely follow the subfield borders used here. Examination of a histological resected tissue sample from a patient with epilepsy reveals that our unfolded coordinate system has biological validity, and that subfield segmentations applied in this space are able to capture features not seen in manual tracing protocols.

Quantification of local geometric distortion in structural magnetic resonance images: Application to ultra-high fields.

Ultra-high field magnetic resonance imaging (MRI) provides superior visualization of brain structures compared to lower fields, but images may be prone to severe geometric inhomogeneity. We propose to quantify local geometric distortion at ultra-high fields in in vivo datasets of human subjects scanned at both ultra-high field and lower fields. By using the displacement field derived from nonlinear image registration between images of the same subject, focal areas of spatial uncertainty are quantified. Through group and subject-specific analysis, we were able to identify regions systematically affected by geometric distortion at air-tissue interfaces prone to magnetic susceptibility, where the gradient coil non-linearity occurs in the occipital and suboccipital regions, as well as with distance from image isocenter. The derived displacement maps, quantified in millimeters, can be used to prospectively evaluate subject-specific local spatial uncertainty that should be taken into account in neuroimaging studies, and also for clinical applications like stereotactic neurosurgery where accuracy is critical. Validation with manual fiducial displacement demonstrated excellent correlation and agreement. Our results point to the need for site-specific calibration of geometric inhomogeneity. Our methodology provides a framework to permit prospective evaluation of the effect of MRI sequences, distortion correction techniques, and scanner hardware/software upgrades on geometric distortion.

Novel connectivity map normalization procedure for improved quantitative investigation of structural thalamic connectivity in temporal lobe epilepsy patients.

BACKGROUND: Connectivity studies targeting the thalamus have revealed patterns of atrophy and deafferentiation in temporal lobe epilepsy (TLE). The thalamus can be parcellated using probabilistic tractography to demonstrate regions of cortical connectivity; however, sensitivity to smaller or less connected regions is low. PURPOSE/HYPOTHESIS: To investigate thalamic structural connectivity in a wider range of cortical and limbic structures in TLE patients using a novel connectivity map normalization procedure. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: Patients (N = 23) with medication-resistant TLE and 34 healthy age-matched controls. FIELD STRENGTH/SEQUENCE: For T1 and diffusion weighting a spoiled gradient sequence was used (41 gradient directions [b = 1000]). For T2 mapping balanced steady-state free precession was used. Images were acquired at 3T. ASSESSMENT: Probabilistic tractography and a novel normalization procedure allowed comparison of groups with respect to thalamic connected volume, quantitative MRI, and diffusion tensor imaging (DTI) metrics. STATISTICAL TESTS: Independent samples t-test, Cohen's d, and Mann-Whitney tests. RESULTS: Following normalization, significant differences in thalamic connected volumes were found in left TLE vs. controls bilaterally within the posterior parahippocampal gyrus (L: P = 0.007, confidence interval [CI]: [173.306,1044.41], effect size [ES] = 1.072; R: P = 0.017, CI: [98.677,947.653], ES = 0.945), and contralaterally in the anterior temporal neocortex (P = 0.01, CI: (-2348.09, -333.719), ES = -1.021). This procedure revealed differences in thalamic connected volumes, where previously published procedures could not, and provided a basis for exploratory analysis of quantitative MRI and DTI metrics. DATA CONCLUSION: The novel connectivity map normalization scheme proposed here successfully allowed comparison between a wider range of cortical and limbic structures. Multiple volumetric and quantitative MRI and DTI-related differences between TLE patients and controls were revealed following normalization. With validation from a larger cohort, thalamo-temporal connection aberrancies may become useful biomarkers of disease states and probabilistic tractography as a procedure for identification of thalamic targets in modulatory therapies for TLE. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1529-1539.

Tumor growth dynamics in serially-imaged low-grade glioma patients.

BACKGROUND: Diffuse low-grade gliomas (LGGs) are infiltrative, slow-growing primary brain tumors that remain relatively asymptomatic for long periods of time before progressing into aggressive and fatal high-grade gliomas. METHODS: We retrospectively identified LGG patients with numerous (≥ 8) serial magnetic resonance imaging (MRI) studies. Tumor volumes were measured by manual segmentation on serial imaging to study the natural history and growth of the lesion. Patient demographic information, tumor characteristics, and histological data were collected from electronic medical records and paper charts. RESULTS: Out of 74 LGG patients, 10 patients (13.5%) were identified to meet the study criteria with number of MRIs acquired ranging from 8 to 18 (median, 11.5) over a median of 79.7 months (range 39.8-113.8 months). Tumor diameter increased at a median of 2.17 mm/year in a linear trajectory. Cox regression analysis revealed that initial tumor volume was an independent predictor of time to clinical intervention, and Mann-Whitney U test found that patients younger than 50 years old had significantly slower-growing tumors. Clinical intervention was more likely for tumors above a volume threshold of 73.6 mL. CONCLUSION: We retrospectively analyzed the natural history of LGGs of patients managed at a single institution with numerous serial MRI scans. Comparisons of our cohort to the literature suggest that this is a subset of particularly slow-growing and low-risk tumors.