Modulations in high-density EEG during the suppression of phantom-limb pain with neurostimulation in upper limb amputees.

Phantom limb pain (PLP) is a distressing and persistent sensation that occurs after the amputation of a limb. While medication-based treatments have limitations and adverse effects, neurostimulation is a promising alternative approach whose mechanism of action needs research, including electroencephalographic (EEG) recordings for the assessment of cortical manifestation of PLP relieving effects. Here we collected and analyzed high-density EEG data in 3 patients (P01, P02, and P03). Peripheral nerve stimulation suppressed PLP in P01 but was ineffective in P02. In contrast, transcutaneous electrical nerve stimulation was effective in P02. In P03, spinal cord stimulation was used to suppress PLP. Changes in EEG oscillatory components were analyzed using spectral analysis and Petrosian fractal dimension. With these methods, changes in EEG spatio-spectral components were found in the theta, alpha, and beta bands in all patients, with these effects being specific to each individual. The changes in the EEG patterns were found for both the periods when PLP level was stationary and the periods when PLP was gradually changing after neurostimulation was turned on or off. Overall, our findings align with the proposed roles of brain rhythms in thalamocortical dysrhythmia or disruption of cortical excitation and inhibition which has been linked to neuropathic pain. The individual differences in the observed effects could be related to the specifics of each patient's treatment and the unique spectral characteristics in each of them. These findings pave the way to the closed-loop systems for PLP management where neurostimulation parameters are adjusted based on EEG-derived markers.

rs12411980 single-nucleotide polymorphism related to PRTFDC1 expression is significantly associated with phantom tooth pain.

Phantom tooth pain (PTP) is one type of non-odontogenic neuropathic toothache, which rarely occurs after appropriate pulpectomy or tooth extraction. The cause of PTP is unknown. We investigated pain-related genetic factors that are associated with PTP. Four pain-associated genes, including G protein-coupled receptor 158 (GPR158) and phosphoribosyl transferase domain containing 1 (PRTFDC1), are adjacent to each other on the human genome. Some of these four genes or their genomic region may be related to PTP. We statistically analyzed associations between single-nucleotide polymorphisms (SNPs) in the genomic region and PTP in patients with PTP (PTP group), other orofacial pain (OFP group), and healthy control subjects. We then performed a database search of expression quantitative trait loci (eQTLs). For the seven SNPs that were significantly associated with PTP even after Bonferroni correction, we focused on the rs12411980 tag SNP (P = 9.42 × 10-4). Statistical analyses of the PTP group and healthy subject groups (group labels: NOC and TD) revealed that the rate of the GG genotype of the rs12411980 SNP was significantly higher in the PTP group than in the healthy subject groups (PTP group vs. NOC group: P = 2.92 × 10-4, PTP group vs. TD group: P = 5.46 × 10-4; percentage of GG: 30% in PTP group, 12% in NOC group, 11% in TD group). These results suggest that the GG genotype of the rs12411980 SNP is more susceptible to PTP. The rs2765697 SNP that is in strong linkage disequilibrium with the rs12411980 SNP is an eQTL that is associated with higher PRTFDC1 expression in the minor allele homozygotes in the healthy subject groups of the rs2765697 SNP. Thus, PRTFDC1 expression similarly increases in the minor allele homozygotes (GG genotype) in the healthy subject groups of the rs12411980 SNP, which would lead to greater susceptibility to PTP.

Novel pore size-controlled, susceptibility matched, 3D-printed MRI phantoms.

PURPOSE: We report the design concept and fabrication of MRI phantoms, containing blocks of aligned microcapillaires that can be stacked into larger arrays to construct diameter distribution phantoms or fractured, to create a "powder-averaged" emulsion of randomly oriented blocks for vetting or calibrating advanced MRI methods, that is, diffusion tensor imaging, AxCaliber MRI, MAP-MRI, and multiple pulsed field gradient or double diffusion-encoded microstructure imaging methods. The goal was to create a susceptibility-matched microscopically anisotropic but macroscopically isotropic phantom with a ground truth diameter that could be used to vet advanced diffusion methods for diameter determination in fibrous tissues. METHODS: Two-photon polymerization, a novel three-dimensional printing method is used to fabricate blocks of capillaries. Double diffusion encoding methods were employed and analyzed to estimate the expected MRI diameter. RESULTS: Susceptibility-matched microcapillary blocks or modules that can be assembled into large-scale MRI phantoms have been fabricated and measured using advanced diffusion methods, resulting in microscopic anisotropy and random orientation. CONCLUSION: This phantom can vet and calibrate various advanced MRI methods and multiple pulsed field gradient or diffusion-encoded microstructure imaging methods. We demonstrated that two double diffusion encoding methods underestimated the ground truth diameter.

A 3D-printed phantom for quality-controlled reproducibility measurements of arterial spin labeled perfusion.

PURPOSE: To develop a portable MR perfusion phantom for quality-controlled assessment and reproducibility of arterial spin labeled (ASL) perfusion measurement. METHODS: A 3D-printed perfusion phantom was developed that mimics the branching of arterial vessels, capillaries, and a chamber containing cellulose sponge representing tissue characteristics. A peristaltic pump circulated distilled water through the phantom, and was first evaluated at 300, 400, and 500 mL/min. Longitudinal reproducibility of perfusion was performed using 2D pseudo-continuous ASL at 20 post-label delays (PLDs, ranging between 0.2 and 7.8 s at 0.4-s intervals) over a period of 16 weeks, with three repetitions each week. Multi-PLD data were fitted into a general kinetic model for perfusion quantification (f) and arterial transit time (ATT). Intraclass correlation coefficient was used to assess intersession reproducibility. RESULTS: MR perfusion signals acquired in the 3D-printed perfusion phantom agreed well with the experimental conditions, with progressively increasing signal intensities and decreasing ATT for pump flow rates from 300 to 500 mL/min. The perfusion signal at 400 mL/min and the general kinetic model-derived f and ATT maps were similar across all PLDs for both intrasession and intersession reproducibility. Across all 48 experimental time points, the average f was 75.55 ± 3.83 × 10-3 mL/mL/s, the corresponding ATT was 2.10 ± 0.20 s, and the T1 was 1.84 ± 0.102 s. Intraclass correlation coefficient was 0.92 (95% confidence interval 0.83-0.97) for f, 0.96 (0.91-0.99) for ATT, and 0.94 (0.88-0.98) for T1 , demonstrating excellent reproducibility. CONCLUSION: A simple, portable 3D-printed perfusion phantom with excellent reproducibility of 2D pseudo-continuous ASL measurements was demonstrated that can serve for quality-controlled and reliable measurements of ASL perfusion.

Comprehensive assessment of nonuniform image quality: Application to imaging near metal.

PURPOSE: Comprehensive assessment of image quality requires accounting for spatial variations in (i) intensity artifact, (ii) geometric distortion, (iii) signal-to-noise ratio (SNR), and (iv) spatial resolution, among other factors. This work presents an ensemble of methods to meet this need, from phantom design to image analysis, and applies it to the scenario of imaging near metal. METHODS: A modular phantom design employing a gyroid lattice is developed to enable the co-registered volumetric quantitation of image quality near a metallic hip implant. A method for measuring spatial resolution by means of local point spread function (PSF) estimation is presented and the relative fitness of gyroid and cubic lattices is examined. Intensity artifact, geometric distortion, and SNR maps are also computed. Results are demonstrated with 2D-FSE and MAVRIC-SL scan protocols on a 3T MRI scanner. RESULTS: The spatial resolution method demonstrates a worst-case error of 0.17 pixels for measuring in-plane blurring up to 3 pixels (full width at half maximum). The gyroid outperforms a cubic lattice design for the local PSF estimation task. The phantom supports four configurations toggling the presence/absence of both metal and structure with good spatial correspondence for co-registered analysis of the four quality factors. The marginal scan time to evaluate one scan protocol amounts to five repetitions. The phantom design can be fabricated in 2 days at negligible material cost. CONCLUSION: The phantom and associated analysis methods can elucidate complex image quality trade-offs involving intensity artifact, geometric distortion, SNR, and spatial resolution. The ensemble of methods is suitable for benchmarking imaging performance near metal.

Effect of particle size on liver MRI R 2 * relaxometry: Monte Carlo simulation and phantom studies.

PURPOSE: To investigate the effect of particle size on liver R 2 * $$ {\mathrm{R}}_2^{\ast } $$ by Monte Carlo simulation and phantom studies at both 1.5 T and 3.0 T. METHODS: Two kinds of particles (i.e., iron sphere and fat droplet) with varying sizes were considered separately in simulation and phantom studies. MRI signals were synthesized and analyzed for predicting R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , based on simulations by incorporating virtual liver model, particle distribution, magnetic field generation, and proton movement into phase accrual. In the phantom study, iron-water and fat-water phantoms were constructed, and each phantom contained 15 separate vials with combinations of five particle concentrations and three particle sizes. R 2 * $$ {\mathrm{R}}_2^{\ast } $$ measurements in the phantom were made at both 1.5 T and 3.0 T. Finally, differences in R 2 * $$ {\mathrm{R}}_2^{\ast } $$ predictions or measurements were evaluated across varying particle sizes. RESULTS: In the simulation study, strong linear and positively correlated relationships were observed between R 2 * $$ {\mathrm{R}}_2^{\ast } $$ predictions and particle concentrations across varying particle sizes and magnetic field strengths ( r ≥ 0.988 $$ r\ge 0.988 $$ ). The relationships were affected by iron sphere size ( p < 0.001 $$ p<0.001 $$ ), where smaller iron sphere size yielded higher predicted R 2 * $$ {\mathrm{R}}_2^{\ast } $$ , whereas fat droplet size had no effect on R 2 * $$ {\mathrm{R}}_2^{\ast } $$ predictions ( p ≥ 0.617 $$ p\ge 0.617 $$ ) for constant total fat concentration. Similarly, the phantom study showed that R 2 * $$ {\mathrm{R}}_2^{\ast } $$ measurements were relatively sensitive to iron sphere size ( p ≤ 0.004 $$ p\le 0.004 $$ ) unlike fat droplet size ( p ≥ 0.223 $$ p\ge 0.223 $$ ). CONCLUSION: Liver R 2 * $$ {\mathrm{R}}_2^{\ast } $$ is affected by iron sphere size, but is relatively unaffected by fat droplet size. These findings may lead to an improved understanding of the underlying mechanisms of R 2 * $$ {\mathrm{R}}_2^{\ast } $$ relaxometry in vivo, and enable improved quantitative MRI phantom design.

Optimizing pseudo-spiral sampling for abdominal DCE MRI using a digital anthropomorphic phantom.

PURPOSE: For reliable DCE MRI parameter estimation, k-space undersampling is essential to meet resolution, coverage, and signal-to-noise requirements. Pseudo-spiral (PS) sampling achieves this by sampling k-space on a Cartesian grid following a spiral trajectory. The goal was to optimize PS k-space sampling patterns for abdomin al DCE MRI. METHODS: The optimal PS k-space sampling pattern was determined using an anthropomorphic digital phantom. Contrast agent inflow was simulated in the liver, spleen, pancreas, and pancreatic ductal adenocarcinoma (PDAC). A total of 704 variable sampling and reconstruction approaches were created using three algorithms using different parametrizations to control sampling density, halfscan and compressed sensing regularization. The sampling patterns were evaluated based on image quality scores and the accuracy and precision of the DCE pharmacokinetic parameters. The best and worst strategies were assessed in vivo in five healthy volunteers without contrast agent administration. The best strategy was tested in a DCE scan of a PDAC patient. RESULTS: The best PS reconstruction was found to be PS-diffuse based, with quadratic distribution of readouts on a spiral, without random shuffling, halfscan factor of 0.8, and total variation regularization of 0.05 in the spatial and temporal domains. The best scoring strategy showed sharper images with less prominent artifacts in healthy volunteers compared to the worst strategy. Our suggested DCE sampling strategy also showed high quality DCE images in the PDAC patient. CONCLUSION: Using an anthropomorphic digital phantom, we identified an optimal PS sampling strategy for abdominal DCE MRI, and demonstrated feasibility in a PDAC patient.

Validation of single reference variable flip angle (SR-VFA) dynamic T1 mapping with T2 * correction using a novel rotating phantom.

PURPOSE: To validate single reference variable flip angle (SR-VFA) dynamic T1 mapping with and without T2 * correction against inversion recovery (IR) T1 measurements. METHODS: A custom cylindrical phantom with three concentric compartments was filled with variably doped agar to produce a smooth spatial gradient of the T1 relaxation rate as a function of angle across each compartment. IR T1 , VFA T1 , and B1 + measurements were made on the phantom before rotation, and multi-echo stack-of-radial dynamic images were acquired during rotation via an MRI-compatible motor. B1 + -corrected SR-VFA and SR-VFA-T2 * T1 maps were computed from the sliding window reconstructed images and compared against rotationally registered IR and VFA T1 maps to determine the percentage error. RESULTS: Both VFA and SR-VFA-T2 * T1 maps fell within 10% of IR T1 measurements for a low rotational speed, with a mean accuracy of 2.3% ± 2.6% and 2.8% ± 2.6%, respectively. Increasing rotational speed was found to decrease the accuracy due to increasing temporal smoothing over ranges where the T1 change had a nonconstant slope. SR-VFA T1 mapping was found to have similar accuracy as the SR-VFA-T2 * and VFA methods at low TEs (˜<2 ms), whereas accuracy degraded strongly with later TEs. T2 * correction of the SR-VFA T1 maps was found to consistently improve accuracy and precision, especially at later TEs. CONCLUSION: SR-VFA-T2 * dynamic T1 mapping was found to be accurate against reference IR T1 measurements within 10% in an agar phantom. Further validation is needed in mixed fat-water phantoms and in vivo.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Effect of Phase Encoding Direction on Image Quality in Single-Shot EPI Diffusion-Weighted Imaging of the Breast.

BACKGROUND: In breast diffusion-weighted imaging (DWI), distortion and physiologic artifacts affect clinical interpretation. Image quality can be optimized by addressing the effect of phase encoding (PE) direction on these artifacts. PURPOSE: To compare distortion artifacts in breast DWI acquired with different PE directions and polarities, and to discuss their clinical implications. STUDY TYPE: Prospective. POPULATION: Eleven healthy volunteers (median age: 47 years old; range: 22-74 years old) and a breast phantom. FIELD STRENGTH/SEQUENCE: Single-shot echo planar DWI and three-dimensional fast gradient echo sequences at 3 T. ASSESSMENT: All DWI data were acquired with left-right, right-left, posterior-anterior, and anterior-posterior PE directions. In phantom data, displacement magnitude was evaluated by comparing the location of landmarks in anatomical and DWI images. Three breast radiologists (5, 17, and 23 years of experience) assessed the presence or absence of physiologic artifacts in volunteers' DWI datasets and indicated their PE-direction preference. STATISTICAL TESTS: Analysis of variance with post-hoc tests were used to assess differences in displacement magnitude across DWI datasets and observers. A binomial test and a chi-squared test were used to evaluate if each in vivo DWI dataset had an equal probability (25%) of being preferred by radiologists. Inter-reader agreement was evaluated using Gwet's AC1 agreement coefficient. A P-value <0.05 was considered statistically significant. RESULTS: In the phantom study, median displacement was the significantly largest in posterior-anterior data. While the displacement in the anterior-posterior and left-right data were equivalent (P = 0.545). In the in vivo data, there were no physiological artifacts observed in any dataset, regardless of PE direction. In the reader study, there was a significant preference for the posterior-anterior datasets which were selected 94% of the time. There was good agreement between readers (0.936). DATA CONCLUSION: This study showed the impact of PE direction on distortion artifacts in breast DWI. In healthy volunteers, the posterior-to-anterior PE direction was preferred by readers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Clutter resilience via auditory stream segregation in echolocating greater mouse-eared bats.

Bats use echolocation to navigate and hunt in darkness, and must in that process segregate target echoes from unwanted clutter echoes. Bats may do this by approaching a target at steep angles relative to the plane of the background, utilizing their directional transmission and receiving systems to minimize clutter from background objects, but it remains unknown how bats negotiate clutter that cannot be spatially avoided. Here, we tested the hypothesis that when movement no longer offers spatial release, echolocating bats mitigate clutter by calling at lower source levels and longer call intervals to ease auditory streaming. We trained five greater mouse-eared bats (Myotis myotis) to land on a spherical loudspeaker with two microphones attached. We used a phantom-echo setup, where the loudspeaker/target transmitted phantom clutter echoes by playing back the bats' own calls at time delays of 1, 3 and 5 ms with a virtual target strength 7 dB higher than the physical target. We show that the bats successfully landed on the target, irrespective of the clutter echo delays. Rather than decreasing their source levels, the bats used similar source level distributions in clutter and control trials. Similarly, the bats did not increase their call intervals, but instead used the same distribution of call intervals across control and clutter trials. These observations reject our hypothesis, leading us to conclude that bats display great resilience to clutter via short auditory integration times and acute auditory stream segregation rather than via biosonar adjustments.

Available and unavailable decoys in capuchin monkeys (Sapajus spp.) decision-making.

Decision-making has been observed to be systematically affected by decoys, i.e., options that should be irrelevant, either because unavailable or because manifestly inferior to other alternatives, and yet shift preferences towards their target. Decoy effects have been extensively studied both in humans and in several other species; however, evidence in non-human primates remains scant and inconclusive. To address this gap, this study investigates how choices in capuchin monkeys (Sapajus spp.) are affected by different types of decoys: asymmetrically dominated decoys, i.e., available and unavailable options that are inferior to only one of the other alternatives, and phantom decoys, i.e., unavailable options that are superior to another available alternative. After controlling for the subjective strength of initial preferences and the distance of each decoy from its target in attribute space, results demonstrate a systematic shift in capuchins' preference towards the target of both asymmetrically dominated decoys (whether they are available or not) and phantom decoys, regardless of what options is being targeted by such decoys. This provides the most comprehensive evidence to date of decoy effects in non-human primates, with important theoretical and methodological implications for future comparative studies on context effects in decision-making.

Potential radiation dose reduction in clinical photon-counting CT by the small pixel effect: ultra-high resolution (UHR) acquisitions reconstructed to standard resolution.

OBJECTIVE: To assess the potential dose reduction achievable with clinical photon-counting CT (PCCT) in ultra-high resolution (UHR) mode compared to acquisitions using the standard resolution detector mode (Std). MATERIALS AND METHODS: With smaller detector pixels, PCCT achieves far higher spatial resolution than energy-integrating (EI) CT systems. The reconstruction of UHR acquisitions to the lower spatial resolution of conventional systems results in an image noise and radiation dose reduction. We quantify this small pixel effect in measurements of semi-anthropomorphic abdominal phantoms of different sizes as well as in a porcine knuckle in the first clinical PCCT system by using the UHR mode (0.2 mm pixel size at isocenter) in comparison to the standard resolution mode (0.4 mm). At different slice thicknesses (0.4 up to 4 mm) and dose levels between 4 and 12 mGy, reconstructions using filtered backprojection were performed to the same target spatial resolution, i.e., same modulation transfer function, using both detector modes. Image noise and the resulting potential dose reduction was quantified as a figure of merit. RESULTS: Images acquired using the UHR mode yield lower noise in comparison to acquisitions using standard pixels at the same resolution and noise level. This holds for sharper convolution kernels at the spatial resolution limit of the standard mode, e.g., up to a factor 3.2 in noise reduction and a resulting potential dose reduction of up to almost 90%. CONCLUSION: Using sharper convolution kernels, UHR acquisitions allow for a significant dose reduction compared to acquisitions using the standard detector mode. CLINICAL RELEVANCE: Acquisitions should always be performed using the ultra-high resolution detector mode, if possible, to benefit from the intrinsic noise and dose reduction. KEY POINTS: • Ionizing radiation used in computed tomography examinations is a concern to public health. • The ultra-high resolution of novel photon-counting systems can be invested towards a noise and dose reduction if only a spatial resolution below the resolution limit of the detector is desired. • Acquisitions should always be performed in ultra-high resolution mode, if possible, to benefit from an intrinsic dose reduction.

Consistency of Monoenergetic Attenuation Measurements for a Clinical Dual-Source Photon-Counting Detector CT System Across Scanning Paradigms: A Phantom Study.

BACKGROUND. Use of virtual monoenergetic images (VMIs) from multienergy CT scans can mitigate inconsistencies in traditional attenuation measurements that result from variation in scan-related factors. Photon-counting detector (PCD) CT systems produce VMIs as standard image output under flexible scanning conditions. OBJECTIVE. The purpose of this article was to evaluate the consistency of monoenergetic attenuation measurements obtained from a clinical PCD CT scanner across a spectrum of scanning paradigms. METHODS. A phantom with 10 tissue-simulating inserts was imaged using a clinical dual-source PCD CT scanner. Nine scanning paradigms were obtained across combinations of tube voltages (90, 120, and 140 kVp) and image quality (IQ) levels (80, 145, and 180). Images were reconstructed at VMI levels of 50, 60, 70, and 80 keV. Consistency of attenuation measurements was assessed, using the 120 kVp with IQ level of 145 scanning paradigm as the reference scan. RESULTS. For all scanning paradigms, attenuation measurements showed intra-class correlation of 0.999 and higher with respect to the reference scan. Across inserts, mean bias relative to the reference scan ranged from -14.9 to 13.6 HU, -2.7 to 1.7 HU, and -3.9 to 3.8 HU at tube voltages of 90, 120, and 140 kVp, respectively; and from -14.9 to 13.6 HU, -6.4 to 3.8 HU, -3.7 to 1.4 HU, and -7.2 to 4.3 HU at VMI levels of 50, 60, 70, and 80 keV, respectively. Thus, mean bias did not exceed 5 HU for any insert at tube potentials of 120 kVp and 140 kVp, nor for any insert at a VMI level of 70 keV. At a VMI level of 50 keV and tube potential of 90 kVp, mean bias exceeded 5 HU for 14 of 30 possible combinations of inserts and scanning paradigms and exceeded 10 HU for four of 30 such combinations. At VMI levels of both 60 and 80 keV, mean bias exceeded 5 HU for only two combinations of inserts and scanning paradigms, all at a tube potential of 90 kVp. CONCLUSION. PCD CT generally provided consistent attenuation measurements across combinations of scanning paradigms and VMI levels. CLINICAL IMPACT. PCD CT may facilitate quantitative applications of CT data in clinical practice.

The prevalence and risk factors for phantom limb pain: a cross-sectional survey.

BACKGROUND: We previously performed a systematic review and meta-analysis which revealed a Phantom Limb Pain (PLP) prevalence estimate of 64% [95% CI: 60.01-68.1]. The prevalence estimates varied significantly between developed and developing countries. Remarkably, there is limited evidence on the prevalence of PLP and associated risk factors in African populations. METHODS: Adults who had undergone limb amputations between January 2018 and October 2022 were recruited from healthcare facilities in the Western and Eastern Cape Provinces. We excluded individuals with auditory or speech impairments that hindered clear communication via telephone. Data on the prevalence and risk factors for PLP were collected telephonically from consenting and eligible participants. The prevalence of PLP was expressed as a percentage with a 95% confidence interval. The associations between PLP and risk factors for PLP were tested using univariate and multivariable logistic regression analyses. The strength of association was calculated using the Odds Ratio where association was confirmed. RESULTS: The overall PLP prevalence was 71.73% [95% CI: 65.45-77.46]. Persistent pre-operative pain, residual limb pain, and non-painful phantom limb sensations were identified as risk factors for PLP. CONCLUSION: This study revealed a high prevalence of PLP. The use of effective treatments targeting pre-amputation pain may yield more effective and targeted pre-amputation care, leading to improved quality of life after amputation.

Is it really on your hand? Spontaneous sensations are not peripheral sensations - Evidence from able-bodied individuals and a phantom limb syndrome patient.

Among other bodily signals, the perception of sensations arising spontaneously on the skin with no external triggers contributes to body awareness. The topic of spontaneous sensations (SPS) being quite recent in the literature, there is still a debate whether this phenomenon is elicited by peripheral cutaneous units' activity underlying tactile perception or originates directly from central mechanisms. In a first experiment, we figured that, if SPS depended on peripheral afferents, their perception on the glabrous hand should relate to the hand tactile sensitivity. On the contrary, we found no relationship at all, which led us to envisage the scenario of SPS in the absence of cutaneous units. In a second experiment, we present the case of Julie, a right-hand amputee that could perceive and report SPS arising on her phantom limb syndrome. We found that SPS distribution on the phantom limb followed the same gradient as that observed in control participants, unlike SPS perceived on the intact left hand. Those findings are crucial to the understanding of neural factors determining body awareness through SPS perception and provide insights into the existence of a precise neural gradient underlying somesthesis.

Pain after combat injury in male UK military personnel deployed to Afghanistan.

BACKGROUND: Chronic pain after injury poses a serious health burden. As a result of advances in medical technology, ever more military personnel survive severe combat injuries, but long-term pain outcomes are unknown. We aimed to assess rates of pain in a representative sample of UK military personnel with and without combat injuries. METHODS: We used data from the ADVANCE cohort study (ISRCTN57285353). Individuals deployed as UK armed forces to Afghanistan were recruited to include those with physical combat injuries, and a frequency-matched uninjured comparison group. Participants completed self-reported questionnaires, including 'overall' pain intensity and self-assessment of post-traumatic stress disorder, anxiety, and depression. RESULTS: A total of 579 participants with combat injury, including 161 with amputations, and 565 uninjured participants were included in the analysis (median 8 yr since injury/deployment). Frequency of moderate or severe pain was 18% (n=202), and was higher in the injured group (n=140, 24%) compared with the uninjured group (n=62, 11%, relative risk: 1.1, 95% confidence interval [CI]: 1.0-1.2, P<0.001), and lower in the amputation injury subgroup (n=31, 19%) compared with the non-amputation injury subgroup (n=109, 26%, relative risk: 0.9, 95% CI: 0.9-1.0, P=0.034). Presence of at least moderate pain was associated with higher rates of post-traumatic stress (RR: 3.7, 95% CI: 2.7-5.0), anxiety (RR: 3.2, 95% CI: 2.4-4.3), and depression (RR: 3.4, 95% CI: 2.7-4.5) after accounting for injury. CONCLUSION: Combat injury, but not amputation, was associated with a higher frequency of moderate to severe pain intensity in this cohort, and pain was associated with adverse mental health outcomes.

Neuropsychiatric drugs and a neurophysiological marker as predictors of health-related quality of life in patients with phantom limb pain.

OBJECTIVE: To explore the relationship between sociodemographic, clinical, and neurophysiological variables and health-related quality of life (HR-QOL) of patients with phantom limb pain. METHODS: This is a cross-sectional analysis of a previous clinical trial. Univariate and multivariate linear and logistic regression analyses were used to model the predictors of HR-QOL. We utilized a sequential modeling approach with increasing adjustment levels, controlling for age and sex, and other relevant clinical variables (time since amputation, level of amputation, and pain). HR-QOL was assessed by the SF-36 Health Survey and its eight subdomains. RESULTS: We analyzed baseline data from 92 patients with lower-limb amputations. They were mostly male (63%), 45.2 ± 15.6 years, with a mean time since amputation of 82.7 ± 122.4 months, and an overall SF-36 score of 55.9 ± 21.5. We found an association between intracortical facilitation in the affected hemisphere (ICF), gabapentin usage, and HR-QOL. ICF is a predictor of better HRQOL, whereas gabapentin usage was associated with a poorer HR-QOL, with the main model explaining 13.4% of the variance in the outcome. For the SF-36 subdomains, ICF was also a positive predictor for social functioning, bodily pain, and vitality, while medication usage was associated with lower scores in mental health, general health perception, bodily pain, and vitality. CONCLUSION: We found firsthand two new independent predictors of HR-QOL in individuals with PLP, namely, the neurophysiological metric ICF and gabapentin usage. These results highlight the role of the motor cortex excitability in the HR-QOL and stress the need for treatments that favor the neuroplastic adaptation after amputation, for which ICF may be used as a possible marker.

Phantom limb syndrome: from pathogenesis to treatment. A narrative review.

Phantom Limb Syndrome (PLS) can be defined as the disabling or painful sensation of the presence of a body part that is no longer present after its amputation. Anatomical changes involved in Phantom Limb Syndrome, occurring at peripheral, spinal and brain levels and include the formation of neuromas and scars, dorsal horn sensitization and plasticity, short-term and long-term modifications at molecular and topographical levels. The molecular reorganization processes of Phantom Limb Syndrome include NMDA receptors hyperactivation in the dorsal horn of the spinal column leading to inflammatory mechanisms both at a peripheral and central level. At the brain level, a central role has been recognized for sodium channels, BDNF and adenosine triphosphate receptors. In the paper we discuss current available pharmacological options with a final overview on non-pharmacological options in the pipeline.

Vertebral Fracture Risk Thresholds from Phantom-Less Quantitative Computed Tomography-Based Finite Element Modeling Correlate to Phantom-Based Outcomes.

INTRODUCTION: Osteoporosis indicates weakened bones and heightened fracture susceptibility due to diminished bone quality. Dual-energy x-ray absorptiometry is unable to assess bone strength. Volumetric bone mineral density (vBMD) from quantitative computed tomography (QCT) has been used to establish guidelines as equivalent measurements for osteoporosis. QCT-based finite element analysis (FEA) has been implemented using calibration phantoms to establish bone strength thresholds based on the established vBMD. The primary aim was to validate vertebral failure load thresholds using a phantom-less approach with previously established thresholds, advancing a phantom-free approach for fracture risk prediction. METHODOLOGY: A controlled cohort of 108 subjects (68 females) was used to validate sex-specific vertebral fracture load thresholds for normal, osteopenic, and osteoporotic subjects, obtained using a QCT/FEA-based phantom-less calibration approach and two material equations. RESULTS: There were strong prediction correlations between the phantom-less and phantom-based methods (R2: 0.95 and 0.97 for males, and R2: 0.96 and 0.98 for females) based on the two equations. Bland Altman plots and paired t-tests showed no significant differences between methods. Predictions for bone strengths and thresholds using the phantom-less method matched those obtained using the phantom calibration and those previously established, with ≤4500 N (fragile) and ≥6000 N (normal) bone strength in females, and ≤6500 N (fragile) and ≥8500 N (normal) bone strength in males. CONCLUSION: Phantom-less QCT-based FEA can allow for prospective and retrospective studies evaluating incidental vertebral fracture risk along the spine and their association with spine curvature and/or fracture etiology. The findings of this study further supported the application of phantom-less QCT-based FEA modeling to predict vertebral strength, aiding in identifying individuals prone to fractures. This reinforces the rationale for adopting this method as a comprehensive approach in predicting and managing fracture risk.