Effectiveness and Safety of Endoanchors in Abdominal and Thoracic Endovascular Aneurysm Repair: A Systematic Review and Meta-analysis.

PURPOSE: This systematic review aimed to summarize the effectiveness and safety of endoanchor, a stabilizing device for the proximal endograft designed to prevent endoleak and stent migration in endovascular aneurysm repair (EVAR) and thoracic endovascular aneurysm repair (TEVAR). MATERIALS AND METHODS: A systematic review and meta-analysis was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. Literature up to May 31, 2023 was searched and independently screened from 4 databases. Data were pooled for meta-analysis. Primary outcomes included intraoperative and follow-up endoleak, stent migration, and reintervention rates; sac regression; and 30-day all-cause mortality. RESULTS: Sixteen EVAR (n=1145) and 6 TEVAR studies (n=163) using the Heli-Fx EndoAnchor system were included from 2225 retrieved records. For EVAR patients (mean follow-up=11.9 months), the endoleak, graft migration, and reintervention rates were 3.97% (95% confidence interval [CI]=0.36%-1.99%), 0.004% (95% CI=0.00%-0.76%), and 5.43% (95% CI=0.86%-12.54%), respectively. The endoleak rates for primary and revision EVAR were 0.16% (95% CI=0.00%-1.65%) and 3.60% (95% CI=0.14%-9.72%), respectively. Only 4 cases of 30-day mortality (n=4) were reported in the literature. For TEVAR patients, the endoleak, stent migration, and reintervention rates were 7.4% (95% CI=0.03%-0.13%), 0.2% (95% CI=0.00%-0.06%), and 17.1% (95% CI=0.01%-0.45%), respectively. The 30-day mortality was 0.9% (95% CI=0%-0.12%). CONCLUSIONS: Endoanchor fixation in EVAR and TEVAR is effective and safe in preventing and treating endoleak and stent migration. The mortality is minimal in EVAR but higher in TEVAR. CLINICAL IMPACT: Endoleak, graft migration, and reintervention in EVAR and TEVAR with endoanchor use were rare. Mortality in EVAR was low. The adjunctive deployment of endoanchors is an effective and safe means to prevent and treat endoleak and stent migration in EVAR and TEVAR. Yet, long-term efficacy and safety data and randomized controlled trials would be required to definitively recommend endoanchor use in routine clinical practice.

Should trigeminal neuralgia be considered a clinically isolated syndrome?

The association between trigeminal neuralgia (TN) and multiple sclerosis (MS) is well established. Many MS patients with TN have magnetic resonance imaging (MRI) evidence of a symptomatic demyelinating lesion. Although infratentorial presentations are included in the diagnostic criteria for MS, there remains confusion in clinical practice as to whether TN should be considered a clinically isolated syndrome for the application of McDonald criteria. In this case series, we discuss this diagnostic quandary in patients presenting with TN and additional MRI findings suggestive of MS and highlight the unmet need for data in such patients to optimally guide their care.

Toward global availability of low-cost, patient-specific cranial implants: creation and validation of automated CranialRebuild freeware application.

PURPOSE: Financial restrictions limit the options for hermetically precise, patient-specific cranial implants (PSCIs) after decompressive hemicraniectomy (DHC) in low-income countries. Use of image segmentation, modeling software, and 3D printers has lowered costs associated with PSCIs. However, requirements of time and technical expertise have prevented widespread utilization. Our objective was to create a fully automated software algorithm that is able to generate a virtual model (.STL) of a negative of an implant using CT imaging following DHC. METHODS: A freeware algorithm (CranialRebuild) was constructed with the following capabilities: (1) after the upload of digital imaging and communications in medicine files, the normal side is analyzed in reference to the side of DHC, (2) Boolean subtraction is used to obtain a virtual image of the desired implant, and (3) a two-piece virtual model (.STL) of the PSCI mold is generated. In four cadaveric specimens, a standard DHC was performed. Post-DHC CT imaging was used to obtain a .STL of the negative of the implant, which was then printed using poly-lactic acid (PLA). Methylmethacrylate cement was used to generate a PSCI from the mold. The PSCIs were implanted into the index specimens; cosmesis was subjectively evaluated using a 5-point Likert scale. RESULTS: Two specimens were graded as 4/5, indicating that minor post-processing modification was needed for optimal cosmesis. Two specimens were graded as 3/5, indicating that optimal cosmesis could be obtained following moderate post-processing modification. CONCLUSIONS: CranialRebuild can be used to create hermetically precise PSCIs at a fraction of the price of third-party vendors. Validation of this technology has significant implications for the accessibility of customized cranial implants worldwide.

Reproducibility of global and segmental myocardial strain using cine DENSE at 3 T: a multicenter cardiovascular magnetic resonance study in healthy subjects and patients with heart disease.

BACKGROUND: While multiple cardiovascular magnetic resonance (CMR) methods provide excellent reproducibility of global circumferential and global longitudinal strain, achieving highly reproducible segmental strain is more challenging. Previous single-center studies have demonstrated excellent reproducibility of displacement encoding with stimulated echoes (DENSE) segmental circumferential strain. The present study evaluated the reproducibility of DENSE for measurement of whole-slice or global circumferential (Ecc), longitudinal (Ell) and radial (Err) strain, torsion, and segmental Ecc at multiple centers. METHODS: Six centers participated and a total of 81 subjects were studied, including 60 healthy subjects and 21 patients with various types of heart disease. CMR utilized 3 T scanners, and cine DENSE images were acquired in three short-axis planes and in the four-chamber long-axis view. During one imaging session, each subject underwent two separate DENSE scans to assess inter-scan reproducibility. Each subject was taken out of the scanner and repositioned between the scans. Intra-user, inter-user-same-site, inter-user-different-site, and inter-user-Human-Deep-Learning (DL) comparisons assessed the reproducibility of different users analyzing the same data. Inter-scan comparisons assessed the reproducibility of DENSE from scan to scan. The reproducibility of whole-slice or global Ecc, Ell and Err, torsion, and segmental Ecc were quantified using Bland-Altman analysis, the coefficient of variation (CV), and the intraclass correlation coefficient (ICC). CV was considered excellent for CV ≤ 10%, good for 10% < CV ≤ 20%, fair for 20% < CV ≤ 40%, and poor for CV > 40. ICC values were considered excellent for ICC > 0.74, good for ICC 0.6 < ICC ≤ 0.74, fair for ICC 0.4 < ICC ≤ 0.59, poor for ICC < 0.4. RESULTS: Based on CV and ICC, segmental Ecc provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL reproducibility and good-excellent inter-scan reproducibility. Whole-slice Ecc and global Ell provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL and inter-scan reproducibility. The reproducibility of torsion was good-excellent for all comparisons. For whole-slice Err, CV was in the fair-good range, and ICC was in the good-excellent range. CONCLUSIONS: Multicenter data show that 3 T CMR DENSE provides highly reproducible whole-slice and segmental Ecc, global Ell, and torsion measurements in healthy subjects and heart disease patients.

Sex-differences in network level brain dynamics associated with pain sensitivity and pain interference.

Neural dynamics can shape human experience, including pain. Pain has been linked to dynamic functional connectivity within and across brain regions of the dynamic pain connectome (consisting of the ascending nociceptive pathway (Asc), descending antinociceptive pathway (Desc), salience network (SN), and the default mode network (DMN)), and also shows sex differences. These linkages are based on fMRI-derived slow hemodynamics. Here, we utilized the fine temporal resolution of magnetoencephalography (MEG) to measure resting state functional coupling (FCp) related to individual pain perception and pain interference in 50 healthy individuals (26 women, 24 men). We found that pain sensitivity and pain interference were linked to within- and cross-network broadband FCp across the Asc and SN. We also identified sex differences in these relationships: (a) women exhibited greater within-network static FCp, whereas men had greater dynamic FCp within the dynamic pain connectome; (b) relationship between pain sensitivity and pain interference with FCp in women was commonly found in theta, whereas in men, these relationships were predominantly in the beta and low gamma bands. These findings indicate that dynamic interactions of brain networks underlying pain involve fast brain communication in men but slower communication in women.

IM ketorolac vs diclofenac potassium powder for oral solution for the acute treatment of severe migraine: a randomized controlled trial.

BACKGROUND: Diclofenac potassium for oral solution (CAMBIA®) may be an alternative for patients who would otherwise need to be seen in a healthcare setting for parenteral ketorolac. CAMBIA® is FDA-approved for the abortive treatment of migraine and has demonstrated superiority over generic diclofenac tablets with rapid migraine reduction. This study assessed for efficacy of CAMBIA® as an alternative outpatient treatment for refractory migraine to parenteral ketorolac. METHODS: We performed an exploratory, single-center, double-blind, double-dummy randomized controlled trial comparing CAMBIA® with IM ketorolac. Participants were randomized to receive either ketorolac 60 mg IM with dummy oral solution or CAMBIA® 50 mg, together with IM injection of normal saline. The primary endpoint was headache severity, self-rated on a scale 0-3. Secondary endpoints included self-rated nausea, disability, and photo- or phonophobia, as well as presence of side effects and need for additional rescue therapy. RESULTS: A total of 23 patients were enrolled. Ten patients received the study drug and 13 patients received IM ketorolac as the control. There were no major differences observed with respect to the primary outcome of mean headache severity at successive time points over a 24-h follow-up period. No major differences were found with respect to average disability, nausea, and photo- or phonophobia ratings. No major adverse events were reported. CONCLUSION: In treatment of refractory migraine headache, CAMBIA® may provide similar benefits as IM ketorolac without increasing the risk of treatment failure, major bleeding, or cardiovascular events. However, larger studies are needed to confirm this finding. TRIAL REGISTRATION: Clinicaltrials.gov: NCT # 02664116, Titled "IM Ketorolac vs Diclofenac Potassium Powder for Oral Solution (CAMBIA®) for the Acute Treatment of Severe Migraine". Registered 26 January 2016, https://clinicaltrials.gov/ct2/show/NCT02664116?term=02664116&rank=1.

Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach.

Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). Moreover, we examined whether there were sex-specific attributes of these functional brain abnormalities and whether functional brain abnormalities in patients is related to pain intensity characteristics on different time scales. We acquired resting-state functional MRI and quantified frequency-specific regional LFOs in chronic pain patients with ankylosing spondylitis. We found that patients exhibit frequency-specific aberrations in LFOs. Specifically, lower-frequency (slow-5) abnormalities were restricted to the ascending pain pathway (thalamus and S1), whereas higher-frequency abnormalities also included the default mode (i.e., posterior cingulate cortex; slow-3, slow-4) and salience (i.e., mid-cingulate cortex) networks (slow-4). Using a machine learning approach, we found that these abnormalities, in particular within higher frequencies (slow-3), can be used to make generalizable inferences about patients' average pain ratings (trait-like pain) but not current (i.e., state-like) pain levels. Furthermore, we identified sex differences in LFOs in patients that were not present in healthy controls. These novel findings reveal mechanistic brain abnormalities underlying the longer-lasting symptoms (trait pain intensity) in chronic pain.SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.

Brain Dynamics and Temporal Summation of Pain Predicts Neuropathic Pain Relief from Ketamine Infusion.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Ketamine is an N-methyl-D-aspartate receptor antagonist that reduces temporal summation of pain and modulates antinociception. Ketamine infusions can produce significant relief of neuropathic pain, but the treatment is resource intensive and can be associated with adverse effects. Thus, it is crucial to select patients who might benefit from this treatment. The authors tested the hypothesis that patients with enhanced temporal summation of pain and the capacity to modulate pain via the descending antinociceptive brain pathway are predisposed to obtain pain relief from ketamine. METHODS: Patients with refractory neuropathic pain (n = 30) and healthy controls underwent quantitative sensory testing and resting-state functional magnetic resonance imaging and then completed validated questionnaires. Patients then received outpatient intravenous ketamine (0.5 to 2 mg · kg · h; mean dose 1.1 mg · kg · h) for 6 h/day for 5 consecutive days. Pain was assessed 1 month later. Treatment response was defined as greater than or equal to 30% pain relief (i.e., reduction in pain scores). We determined the relationship between our primary outcome measure of pain relief with pretreatment temporal summation of pain and with brain imaging measures of dynamic functional connectivity between the default mode network and the descending antinociceptive brain pathway. RESULTS: Approximately 50% of patients achieved pain relief (mean ± SD; Responders, 61 ± 35%; Nonresponders, 7 ± 14%). Pretreatment temporal summation was associated with the effect of ketamine (ρ = -0.52, P = 0.003) and was significantly higher in Responders (median [25th, 75th] = 200 [100, 345]) compared with Nonresponders (44 [9, 92]; P = 0.001). Pretreatment dynamic connectivity was also associated with the clinical effect of ketamine (ρ = 0.51, P = 0.004) and was significantly higher in Responders (mean ± SD, 0.55 ± 0.05) compared with Nonresponders (0.51 ± 0.03; P = 0.006). Finally, the dynamic engagement of the descending antinociceptive system significantly mediated the relationship between pretreatment pain facilitation and pain relief (95% CI, 0.005 to 0.065). CONCLUSIONS: These findings suggest that brain and behavioral measures have the potential to prognosticate and develop ketamine-based personalized pain therapy.

A comparison of both DENSE and feature tracking techniques with tagging for the cardiovascular magnetic resonance assessment of myocardial strain.

BACKGROUND: Myocardial strain is increasingly recognized as an important assessment for myocardial function. In addition, it also improves outcome prediction. However, there is lack of standardization in strain evaluation by cardiovascular magnetic resonance (CMR). In this study we compared strain values using multiple techniques and multiple vendor products. METHODS: Prospectively recruited patients with cardiomyopathy of diverse etiology (N = 77) and healthy controls (N = 10) underwent CMR on a 1.5 T scanner. Tagging, displacement encoding with stimulated echoes (DENSE) and balanced stead state free precession cine imaging were acquired on all subjects. A single matched mid left ventricular (LV) short axis plane was used for the comparisons of peak circumferential (Ecc) and radial strain (Err) and a 4-chamber view for longitudinal strain (Ell). Tagging images were analyzed using harmonic phase (HARP) and displacement encoding with stimulated echoes (DENSE) images using a proprietary program. Feature tracking (FT) was evaluated using 3 commercially available software from Tomtec Imaging Systems, Cardiac Image Modeller (CIM), and Circle Cardiovascular Imaging. Tagging data were used as reference. Statistic analyses were performed using paired t-test, intraclass correlation coefficient (ICC), Bland Altman limits of agreement and coefficient of variations. RESULTS: Average LV ejection fraction was 50% (range 32 to 62%). Regional LV wall motion abnormalities were present in 48% of the analyzed planes. The average Ecc was - 13 ± 4%, - 13 ± 4%, - 16 ± 6%, - 10 ± 3% and - 14 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively, with the best agreement seen in DENSE and Circle with tagging. The Err was highly varied with poor agreement across the techniques, 32 ± 24%, 40 ± 28%, 47 ± 26%, 64 ± 33% and 23 ± 9% for tagging, DENSE, Tomtec, CIM and Circle, respectively. The average Ell was - 14 ± 4%, - 8 ± 3%, - 13 ± 5%, - 11 ± 3% and - 12 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively with the best agreement seen in Tomtec and Circle with tagging. In the intra- and inter-observer agreement analysis the reproducibility of each technique was good except for Err by HARP. CONCLUSIONS: Small but important differences are evident in Ecc and Ell comparisons among vendors while large differences are seen in Err assessment. Our findings suggest that CMR strain values are technique and vendor dependent. Hence, it is essential to develop reference standard from each technique and analytical product for clinical use, and to sequentially compare patient data using the same software.

Individual Differences in Temporal Summation of Pain Reflect Pronociceptive and Antinociceptive Brain Structure and Function.

Temporal summation of pain (TSP), the perception of increasingly greater pain evoked by repetitive noxious stimuli, is highly variable between individuals. Individuals with facilitated pain processing and/or reduced pain-modulatory capabilities are regarded as pronociceptive, whereas individuals with reduced pain processing capacity are characterized as antinociceptive. Brodmann area (BA) 3a of the primary somatosensory cortex is part of an ascending pathway from the sensory thalamus that mediates TSP. Descending pain modulation involves projections from the subgenual anterior cingulate cortex (sgACC) to the periaqueductal gray to the rostral ventromedial medulla (RVM). Here, we tested the hypothesis that pronociceptive individuals have an enhanced TSP response compared with antinociceptive individuals, marked by facilitated ascending nociceptive processing and/or reduced capacity for descending pain modulation. Eighty healthy humans were tested with a TSP protocol and underwent structural and resting-state functional magnetic resonance imaging. We found large interindividual differences in TSP responses, which were positively correlated with functional connectivity (FC) between individuals' right sensory thalamus with their BA 3a (thal-BA 3a), and with cortical thickness in their insula and medial prefrontal cortex. In contrast, TSP was negatively correlated with FC between individuals' RVM with their sgACC (RVM-sgACC). When subjects were grouped as pronociceptive or antinociceptive based on whether they had greater thal-BA 3a or RVM-sgACC FC respectively, pronociceptive subjects showed greater TSP responses. Furthermore, TSP was positively correlated with the extent of imbalance toward ascending nociceptive processing. Our study indicates that individuals with enhanced TSP have facilitated ascending nociceptive processing and reduced pain-modulatory capacities. SIGNIFICANCE STATEMENT: This study provides novel evidence that an individual's propensity to experience amplified pain with repeated stimuli [i.e., temporal summation of pain (TSP)] reflects attributes of their "pain connectome," namely stronger ascending nociceptive and weaker descending pain-modulatory components. Understanding the individual neural mechanisms underlying TSP within individuals has implications for developing personalized pain-management strategies for chronic pain.

Dynamic and opposing adjustment of movement cancellation and generation in an oculomotor countermanding task.

Adaptive adjustments of strategies help optimize behavior in a dynamic and uncertain world. Previous studies in the countermanding (or stop-signal) paradigm have detailed how reaction times (RTs) change with trial sequence, demonstrating adaptive control of movement generation. Comparatively little is known about the adaptive control of movement cancellation in the countermanding task, mainly because movement cancellation implies the absence of an outcome and estimates of movement cancellation require hundreds of trials. Here, we exploit a within-trial proxy of movement cancellation based on recordings of neck muscle activity while human subjects attempted to cancel large eye-head gaze shifts. On a subset of successfully cancelled trials where gaze remains stable, small head-only movements to the target are actively braked by a pulse of antagonist neck muscle activity. The timing of such antagonist muscle recruitment relative to the stop signal, termed the "antagonist latency," tended to decrease or increase after trials with or without a stop-signal, respectively. Over multiple time scales, fluctuations in the antagonist latency tended to be the mirror opposite of those occurring contemporaneously with RTs. These results provide new insights into the adaptive control of movement cancellation at an unprecedented resolution, suggesting it can be as prone to dynamic adjustment as movement generation. Adaptive control in the countermanding task appears to be governed by a dynamic balance between movement cancellation and generation: shifting the balance in favor of movement cancellation slows movement generation, whereas shifting the balance in favor of movement generation slows movement cancellation.

Pretreatment Brain White Matter Integrity Associated With Neuropathic Pain Relief and Changes in Temporal Summation of Pain Following Ketamine.

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP. We used a fixel-based analysis of diffusion-weighted imaging data to evaluate WM microstructure (fiber density [FD]) and macrostructure (fiber bundle cross-section) within the DMN and mPFC-PAG pathways in 70 individuals who underwent magnetic resonance imaging and TSP testing; 35 with NP who underwent ketamine treatment and 35 age- and sex-matched pain-free individuals. Individuals with NP were assessed before and 1 month after treatment; those with ≥30% pain relief were considered responders (n = 18), or otherwise as nonresponders (n = 17). We found that WM structure within the DMN and mPFC-PAG pathways did not differentiate responders from nonresponders. However, pretreatment FD in the anterior limb of the internal capsule correlated with pain relief (r=.48). Moreover, pretreatment FD in the DMN (left mPFC-precuneus/posterior cingulate cortex; r=.52) and mPFC-PAG (r=.42) negatively correlated with changes in TSP. This suggests that WM microstructure in the DMN and mPFC-PAG pathway is associated with the degree to which ketamine reduces central sensitization. Thus, fixel metrics of WM structure may hold promise to predict ketamine NP treatment outcomes. PERSPECTIVE: We used advanced fixel-based analyses of MRI diffusion-weighted imaging data to identify pretreatment WM microstructure associated with ketamine outcomes, including analgesia and markers of attenuated central sensitization. Exploring associations between brain structure and treatment outcomes could contribute to a personalized approach to treatment for individuals with NP.

Inversion recovery and saturation recovery pulmonary vein MR angiography using an image based navigator fluoro trigger and variable-density 3D cartesian sampling with spiral-like order.

Contrast enhanced pulmonary vein magnetic resonance angiography (PV CE-MRA) has value in atrial ablation pre-procedural planning. We aimed to provide high fidelity, ECG gated PV CE-MRA accelerated by variable density Cartesian sampling (VD-CASPR) with image navigator (iNAV) respiratory motion correction acquired in under 4 min. We describe its use in part during the global iodinated contrast shortage. VD-CASPR/iNAV framework was applied to ECG-gated inversion and saturation recovery gradient recalled echo PV CE-MRA in 65 patients (66 exams) using .15 mmol/kg Gadobutrol. Image quality was assessed by three physicians, and anatomical segmentation quality by two technologists. Left atrial SNR and left atrial/myocardial CNR were measured. 12 patients had CTA within 6 months of MRA. Two readers assessed PV ostial measurements versus CTA for intermodality/interobserver agreement. Inter-rater/intermodality reliability, reproducibility of ostial measurements, SNR/CNR, image, and anatomical segmentation quality was compared. The mean acquisition time was 3.58 ± 0.60 min. Of 35 PV pre-ablation datasets (34 patients), mean anatomical segmentation quality score was 3.66 ± 0.54 and 3.63 ± 0.55 as rated by technologists 1 and 2, respectively (p = 0.7113). Good/excellent anatomical segmentation quality (grade 3/4) was seen in 97% of exams. Each rated one exam as moderate quality (grade 2). 95% received a majority image quality score of good/excellent by three physicians. Ostial PV measurements correlated moderate to excellently with CTA (ICCs range 0.52-0.86). No difference in SNR was observed between IR and SR. High quality PV CE-MRA is possible in under 4 min using iNAV bolus timing/motion correction and VD-CASPR.

Relationship of phasic left atrial volume and emptying function to left ventricular filling pressure: a cardiovascular magnetic resonance study.

BACKGROUND: Left atrial volume (LAV) and emptying fraction (LAEF) are phasic during cardiac cycle. Their relationships to left ventricular end diastolic pressure (LVEDP) have not been fully defined. METHODS: Forty one patients undergoing clinically indicated left heart catheterization were recruited for same day cardiovascular magnetic resonance (CMR). LAV and LAEF were assessed in cine images using biplane area and length method. Three phasic LAV was assessed at LV end systole (LAV(max)), LV end diastole (LAV(min)) and late LV diastole prior to LA contraction (LAV(ac)). LAEF was assessed as global LAEF (LAEF(Total)), passive (LAEF(Passive)) and active LAEF (LAEF(Contractile)). The relationships of phasic LAV and LAEF to LVEDP were assessed using Receiver operating characteristic comparing areas under the curves (AUC). RESULTS: The mean age of the patients was 59 years. A history of heart failure was present in 16 (39%) with NYHA functional class III or IV in 8 (20%) patients. Average LV ejection fraction was 49 ± 16% ranging from 10% to 74% and LVEDP by catheterization 14 ± 8 mmHg ranging from 4 mmHg to 32 mmHg. LAV(min) had the strongest association with LVEDP elevation (>12 mmHg) (AUC 0.765, p = 0.002), as compared to LAV(max) (AUC 0.677, p = 0.074) and LAV(ac) (AUC 0.735, p = 0.008). Among three phasic LAEF assessed, LAEF(Total) had the closest association with LVEDP elevation (AUC 0.780, p = 0.001), followed by LAEF(Contractile) (AUC 0.698, p = 0.022) and LAEF(Passive) (AUC 0.656, p = 0.077). CONCLUSIONS: Increased LAV(min) and decreased LAEF(Total) have the best performance in identifying elevated LVEDP among three phasic LAV and LAEF analyzed. Future studies should further characterize LA phasic indices in clinical outcomes.

Can we characterize A-P/IAP behavioural phenotypes in people with chronic pain?

Two behavioural phenotypes in healthy people have been delineated based on their intrinsic attention to pain (IAP) and whether their reaction times (RT) during a cognitively-demanding task are slower (P-type) or faster (A-type) during experimental pain. These behavioural phenotypes were not previously studied in chronic pain populations to avoid using experimental pain in a chronic pain context. Since pain rumination (PR) may serve as a supplement to IAP without needing noxious stimuli, we attempted to delineate A-P/IAP behavioural phenotypes in people with chronic pain and determined if PR can supplement IAP. Behavioural data acquired in 43 healthy controls (HCs) and 43 age-/sex-matched people with chronic pain associated with ankylosing spondylitis (AS) was retrospectively analyzed. A-P behavioural phenotypes were based on RT differences between pain and no-pain trials of a numeric interference task. IAP was quantified based on scores representing reported attention towards or mind-wandering away from experimental pain. PR was quantified using the pain catastrophizing scale, rumination subscale. The variability in RT was higher during no-pain trials in the AS group than HCs but was not significantly different in pain trials. There were no group differences in task RTs in no-pain and pain trials, IAP or PR scores. IAP and PR scores were marginally significantly positively correlated in the AS group. RT differences and variability were not significantly correlated with IAP or PR scores. Thus, we propose that experimental pain in the A-P/IAP protocols can confound testing in chronic pain populations, but that PR could be a supplement to IAP to quantify attention to pain.

Resilience is associated with cortical gray matter of the antinociceptive pathway in people with chronic pain.

Resilience is an important personal characteristic that influences health and recovery. Previous studies of chronic pain suggest that highly resilient people may be more effective at modulating their pain. Since brain gray matter in the antinociceptive pathway has also been shown to be abnormal in people with chronic pain, we examined whether resilience is related to gray matter in regions of interest (ROIs) of the antinociceptive pathway (rostral and subgenual anterior cingulate cortex (rACC, sgACC), anterior insula (aINS), dorsolateral prefrontal cortex (dlPFC)) normally and in people who are experiencing chronic pain. We extracted gray matter volume (GMV) and cortical thickness (CT) from 3T MRIs of 88 people with chronic pain (half males/females) and 86 healthy controls (HCs), who completed The Resilience Scale and Brief Pain Inventory. We found that resilience scores were significantly lower in people with chronic pain compared to HCs, whereas ROI GMV and CT were not different between groups. Resilience negatively correlated with average pain scores and positively correlated with GMV in the bilateral rACC, sgACC, and left dlPFC of people with chronic pain. Mediation analyses revealed that GMV in the right rACC and left sgACC partially co-mediated the relationship between resilience and average pain in people with chronic pain. The resilience-pain and some resilience-GMV relationships were sex-dependent. These findings suggest that the antinociceptive pathway may play a role in the impact of resilience on one's ability to modulate chronic pain. A better understanding of the brain-resilience relationship may help advance evidence-based approaches to pain management.

StrainNet: Improved Myocardial Strain Analysis of Cine MRI by Deep Learning from DENSE.

Purpose: To develop a three-dimensional (two dimensions + time) convolutional neural network trained with displacement encoding with stimulated echoes (DENSE) data for displacement and strain analysis of cine MRI. Materials and Methods: In this retrospective multicenter study, a deep learning model (StrainNet) was developed to predict intramyocardial displacement from contour motion. Patients with various heart diseases and healthy controls underwent cardiac MRI examinations with DENSE between August 2008 and January 2022. Network training inputs were a time series of myocardial contours from DENSE magnitude images, and ground truth data were DENSE displacement measurements. Model performance was evaluated using pixelwise end-point error (EPE). For testing, StrainNet was applied to contour motion from cine MRI. Global and segmental circumferential strain (Ecc) derived from commercial feature tracking (FT), StrainNet, and DENSE (reference) were compared using intraclass correlation coefficients (ICCs), Pearson correlations, Bland-Altman analyses, paired t tests, and linear mixed-effects models. Results: The study included 161 patients (110 men; mean age, 61 years ± 14 [SD]), 99 healthy adults (44 men; mean age, 35 years ± 15), and 45 healthy children and adolescents (21 males; mean age, 12 years ± 3). StrainNet showed good agreement with DENSE for intramyocardial displacement, with an average EPE of 0.75 mm ± 0.35. The ICCs between StrainNet and DENSE and FT and DENSE were 0.87 and 0.72, respectively, for global Ecc and 0.75 and 0.48, respectively, for segmental Ecc. Bland-Altman analysis showed that StrainNet had better agreement than FT with DENSE for global and segmental Ecc. Conclusion: StrainNet outperformed FT for global and segmental Ecc analysis of cine MRI.Keywords: Image Postprocessing, MR Imaging, Cardiac, Heart, Pediatrics, Technical Aspects, Technology Assessment, Strain, Deep Learning, DENSE Supplemental material is available for this article. © RSNA, 2023.

Carpal tunnel surgery dampens thalamocortical and normalizes corticocortical functional connectivity.

Carpal tunnel syndrome is the most common entrapment neuropathy and is associated with altered brain function and structure. However, little is understood of the central mechanisms associated with its pain, symptom presentation, and treatment-related resolution. This longitudinal study evaluated carpal tunnel syndrome-related alterations in brain network communication and relationships to behavioural signs of central sensitization before and after carpal tunnel release surgery. We tested the hypothesis that carpal tunnel syndrome is associated with condition- and treatment-related plasticity in brain regions involved in somatosensation. We used quantitative sensory testing and clinical and pain questionnaires to assess sensory and pain function in 25 patients with carpal tunnel syndrome before (18 women, 7 men) and after (n = 16) surgery, and 25 sex- and age-matched healthy controls. We also acquired resting-state functional MRI to determine functional connectivity of two key nodes in the somatosensory system, the thalamus and primary somatosensory cortex. Seed-to-whole brain resting-state static functional connectivity analyses revealed abnormally low functional connectivity for the hand area of the primary somatosensory cortex with the contralateral somatosensory association cortex (supramarginal gyrus) before surgery (P < 0.01). After clinically effective surgery: (i) Primary somatosensory functional connectivity was normalized with the contralateral somatosensory association cortex and reduced with the dorsolateral prefrontal cortex (a region associated with cognitive and emotional modulation of pain) and primary visual areas (P < 0.001) from pre-op levels; and (ii) Functional connectivity of the thalamus with the primary somatosensory and motor cortices was attenuated from pre-op levels (P < 0.001) but did not correlate with temporal summation of pain (a behavioural measure of central sensitization) or clinical measures. This study is the first to reveal treatment-related neuroplasticity in resting-state functional connectivity of the somatosensory system in carpal tunnel syndrome. The findings of dysfunctional resting-state functional connectivity point to aberrant neural synchrony between the brain's representation of the hand with regions involved in processing and integrating tactile and nociceptive stimuli and proprioception in carpal tunnel syndrome. Aberrant neural communication between the primary somatosensory hand area and the dorsolateral prefrontal cortex could reflect increased attention to pain, paraesthesia, and altered sensation in the hand. Finally, reduced thalamocortical functional connectivity after surgery may reflect central plasticity in response to the resolution of abnormal sensory signals from the periphery. Our findings support the concept of underlying brain contributions to this peripheral neuropathy, specifically aberrant thalamocortical and corticocortical communication, and point to potential central therapeutic targets to complement peripheral treatments.

Exploring sex differences in alpha brain activity as a potential neuromarker associated with neuropathic pain.

ABSTRACT: Alpha oscillatory activity (8-13 Hz) is the dominant rhythm in the awake brain and is known to play an important role in pain states. Previous studies have identified alpha band slowing and increased power in the dynamic pain connectome (DPC) of people with chronic neuropathic pain. However, a link between alpha-band abnormalities and sex differences in brain organization in healthy individuals and those with chronic pain is not known. Here, we used resting-state magnetoencephalography to test the hypothesis that peak alpha frequency (PAF) abnormalities are general features across chronic central and peripheral conditions causing neuropathic pain but exhibit sex-specific differences in networks of the DPC (ascending nociceptive pathway [ANP], default mode network, salience network [SN], and subgenual anterior cingulate cortex). We found that neuropathic pain (N = 25 men and 25 women) was associated with increased PAF power in the DPC compared with 50 age- and sex-matched healthy controls, whereas slower PAF in nodes of the SN (temporoparietal junction) and the ANP (posterior insula) was associated with higher trait pain intensity. In the neuropathic pain group, women exhibited lower PAF power in the subgenual anterior cingulate cortex and faster PAF in the ANP and SN than men. The within-sex analyses indicated that women had neuropathic pain-related increased PAF power in the ANP, SN, and default mode network, whereas men with neuropathic pain had increased PAF power restricted to the ANP. These findings highlight neuropathic pain-related and sex-specific abnormalities in alpha oscillations across the DPC that could underlie aberrant neuronal communication in nociceptive processing and modulation.

Dynamic Functional Brain Connectivity Underlying Temporal Summation of Pain in Fibromyalgia.

OBJECTIVE: Abnormal central pain processing is a leading cause of pain in fibromyalgia (FM) and is perceptually characterized with the psychophysical measure of temporal summation of pain (TSP). TSP is the perception of increasingly greater pain in response to repetitive or tonic noxious stimuli. Previous neuroimaging studies have used static (i.e., summary) measures to examine the functional magnetic resonance imaging (fMRI) correlates of TSP in FM. However, functional brain activity rapidly and dynamically reorganizes over time, and, similarly, TSP is a temporally evolving process. This study was undertaken to demonstrate how a complete understanding of the neural circuitry supporting TSP in FM thus requires a dynamic measure that evolves over time. METHODS: We utilized novel methods for analyzing dynamic functional brain connectivity in patients with FM in order to examine how TSP-associated fluctuations are linked to the dynamic functional reconfiguration of the brain. In 84 FM patients and age- and sex-matched healthy controls, we collected high-temporal-resolution fMRI data during a resting state and during a state in which sustained cuff pressure pain was applied to the leg. RESULTS: FM patients experienced greater TSP than healthy controls (mean ± SD TSP score 17.93 ± 19.24 in FM patients versus 9.47 ± 14.06 in healthy controls; P = 0.028), but TSP scores varied substantially between patients. In the brain, the presence versus absence of TSP in patients with FM was marked by more sustained enmeshment between sensorimotor and salience networks during the pain period. Furthermore, dynamic enmeshment was noted solely in FM patients with high TSP, as interactions with all other brain networks were dampened during the pain period. CONCLUSION: This study elucidates the dynamic brain processes underlying facilitated central pain processing in FM. Our findings will enable future investigation of dynamic symptoms in FM.