Localization and quantification of intramuscular damage using statistical parametric mapping and skeletal muscle parcellation.
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ABSTRACT:
SUBMITTER: Foure A
PROVIDER: S-EPMC4686971 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE:PET and SPECT voxel kinetics are highly noised. To our knowledge, no study has determined the effect of denoising on the ability to detect differences in binding at the voxel level using Statistical Parametric Mapping (SPM). METHODS:In the present study, groups of subject-images with a 10%- and 20%- difference in binding of [123I]iomazenil (IMZ) were simulated. They were denoised with Factor Analysis (FA). Parametric images of binding potential (BPND) were produced with the simplified reference tissue model (SRTM) and the Logan non-invasive graphical analysis (LNIGA) and analyzed using SPM to detect group differences. FA was also applied to [123I]IMZ and [11C]flumazenil (FMZ) clinical images (n = 4) and the variance of BPND was evaluated. RESULTS:Estimations from FA-denoised simulated images provided a more favorable bias-precision profile in SRTM and LNIGA quantification. Simulated differences were detected in a higher number of voxels when denoised simulated images were used for voxel-wise estimations, compared to quantification on raw simulated images. Variability of voxel-wise binding estimations on denoised clinical SPECT and PET images was also significantly diminished. CONCLUSION:In conclusion, noise removal from dynamic brain SPECT and PET images may optimize voxel-wise BPND estimations and detection of biological differences using SPM.
| S-EPMC6124809 | biostudies-literature
Project description:Alzheimer's disease (AD), the most common cause of dementia, has limited treatment options. Emerging disease modifying therapies are targeted at clearing amyloid-β (Aβ) aggregates and slowing the rate of amyloid deposition. However, amyloid burden is not routinely evaluated quantitatively for purposes of disease progression and treatment response assessment. Statistical Parametric Mapping (SPM) is a technique comparing single-subject Positron Emission Tomography (PET) to a healthy cohort that may improve quantification of amyloid burden and diagnostic performance. While primarily used in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, SPM's utility in amyloid PET for AD diagnosis is less established and uncertainty remains regarding optimal normal database construction. Using commercially available SPM software, we created a database of 34 non-APOE ε4 carriers with normal cognitive testing (MMSE > 25) and negative cerebrospinal fluid (CSF) AD biomarkers. We compared this database to 115 cognitively normal subjects with variable AD risk factors. We hypothesized that SPM based on our database would identify more positive scans in the test cohort than the qualitatively rated [11C]-PiB PET (QR-PiB), that SPM-based interpretation would correlate better with CSF Aβ42 levels than QR-PiB, and that regional z-scores of specific brain regions known to be involved early in AD would be predictive of CSF Aβ42 levels. Fisher's exact test and the kappa coefficient assessed the agreement between SPM, QR-PiB PET, and CSF biomarkers. Logistic regression determined if the regional z-scores predicted CSF Aβ42 levels. An optimal z-score cutoff was calculated using Youden's index. We found SPM identified more positive scans than QR-PiB PET (19.1 vs. 9.6%) and that SPM correlated more closely with CSF Aβ42 levels than QR-PiB PET (kappa 0.13 vs. 0.06) indicating that SPM may have higher sensitivity than standard QR-PiB PET images. Regional analysis demonstrated the z-scores of the precuneus, anterior cingulate and posterior cingulate were predictive of CSF Aβ42 levels [OR (95% CI) 2.4 (1.1, 5.1) p = 0.024; 1.8 (1.1, 2.8) p = 0.020; 1.6 (1.1, 2.5) p = 0.026]. This study demonstrates the utility of using SPM with a "true normal" database and suggests that SPM enhances diagnostic performance in AD in the clinical setting through its quantitative approach, which will be increasingly important with future disease-modifying therapies.
| S-EPMC9083453 | biostudies-literature
Project description:IntroductionFluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) is widely used to help localize the hypometabolic epileptogenic focus for presurgical evaluation of drug-refractory epilepsy patients. Two voxel-based brain mapping methods to interpret 18F-FDG-PET, statistical parametric mapping (SPM) and three-dimensional stereotactic surface projection (3D-SSP), improve the detection rate of seizure foci. This study aimed to compare the consistency of epileptic focus detection between SPM and 3D-SSP for 18F-FDG-PET brain mapping analysis.MethodsWe retrospectively reviewed the clinical, electroecephalographic, and brain imaging results of 35 patients with refractory epilepsy. 18F-FDG-PET studies were revaluated by SPM, 3D-SSP, and visual assessment, and the results were compared to the magnetic resonance imaging (MRI) lesion location and to the presumed epileptogenic zone (PEZ) defined by video-electroencephalogram and other clinical data. A second consistency study compared PET analyses to histopathology and surgical outcomes in the 19 patients who underwent lesion resection surgery.ResultsOf the 35 patients, consistency with the PEZ was 29/35 for SPM, 25/35 for 3D-SSP, 14/35 for visual assessment, and 10/35 for MRI. Concordance rates with the PEZ were significantly higher for SPM and 3D-SSP than for MRI (P?<?0.05) and visual assessment (P?<?0.05). Differences between SPM and 3D-SSP and between visual assessment and MRI were not significant. In the 19 surgical patients, concordance with histopathology/clinical outcome was 14/19 for SPM, 15/19 for 3D-SSP, 14/19 for visual assessment, and 9/19 for MRI (P?>?0.05). A favorable Engel outcome (class I/II) was found in 16 of 19 cases (84%), and failure of seizure control was found in 3 of 19 patients (class III/IV).ConclusionVoxel-based 18F-FDG-PET brain mapping analysis using SPM or 3D-SSP can improve the detection rate of the epileptic focus compared to visual assessment and MRI. Consistency with PEZ was similar between SPM and 3D-SSP; according to their own characteristics, 3D-SSP is recommended for primary evaluation due to greater efficiency and operability of the software, while SPM is recommended for high-accuracy localization of complex lesions. Therefore, joint application of both software packages may be the best solution for FDG-PET analysis of epileptic focus localization.
| S-EPMC5037321 | biostudies-literature
Project description:Clinical gait analysis is an important biomechanics field that is often influenced by subjectivity in time-varying analysis leading to type I and II errors. Statistical Parametric Mapping can operate on all time-varying joint dynamics simultaneously, thereby overcoming subjectivity errors. We present MovementRx, the first gait analysis modelling application that correctly models the deviations of joints kinematics and kinetics both in 3 and 1 degrees of freedom; presented with easy-to-understand color maps for clinicians with limited statistical training. MovementRx is a python-based versatile GUI-enabled movement analysis decision support system, that provides a holistic view of all lower limb joints fundamental to the kinematic/kinetic chain related to functional gait. The user can cascade the view from single 3D multivariate result down to specific single joint individual 1D scalar movement component in a simple, coherent, objective, and visually intuitive manner. We highlight MovementRx benefit by presenting a case-study of a right knee osteoarthritis (OA) patient with otherwise undetected postintervention contralateral OA predisposition. MovementRx detected elevated frontal plane moments of the patient's unaffected knee. The patient also revealed a surprising adverse compensation to the contralateral limb.
| S-EPMC9918450 | biostudies-literature
Project description:Key pointsMuscle infiltration with adipose tissue (IMAT) is common and associated with loss of skeletal muscle strength and physical function across a diverse set of pathologies. Whether the association between IMAT and muscle weakness is causative or simply correlative remains an open question that needs to be addressed to effectively guide muscle strengthening interventions in people with increased IMAT. In the present studies, we demonstrate that IMAT deposition causes decreased muscle strength using mouse models. These findings indicate IMAT is a novel therapeutic target for muscle dysfunction.AbstractIntramuscular adipose tissue (IMAT) is associated with deficits in strength and physical function across a wide array of conditions, from injury to ageing to metabolic disease. Due to the diverse aetiologies of the primary disorders involving IMAT and the strength of the associations, it has long been proposed that IMAT directly contributes to this muscle dysfunction. However, infiltration of IMAT and reduced strength could both be driven by muscle disuse, injury and systemic disease, making IMAT simply an 'innocent bystander.' Here, we utilize novel mouse models to evaluate the direct effect of IMAT on muscle contraction. First, we utilize intramuscular glycerol injection in wild-type mice to evaluate IMAT in the absence of systemic disease. In this model we find that, in isolation from the neuromuscular and circulatory systems, there remains a muscle-intrinsic association between increased IMAT volume and decreased contractile tension (r2 > 0.5, P < 0.01) that cannot be explained by reduction in contractile material. Second, we utilize a lipodystrophic mouse model which cannot generate adipocytes to 'rescue' the deficits. We demonstrate that without IMAT infiltration, glycerol treatment does not reduce contractile force (P > 0.8). Taken together, this indicates that IMAT is not an inert feature of muscle pathology but rather has a direct impact on muscle contraction. This finding suggests that novel strategies targeting IMAT may improve muscle strength and function in a number of populations.
| S-EPMC8767374 | biostudies-literature
Project description:Perturbations in skeletal muscle metabolism have been reported for a variety of neuromuscular diseases. However, the role of metabolism after constriction injury to a nerve and the associated muscle atrophy is unclear. We have analyzed rat tibialis anterior (TA) four weeks after unilateral constriction injury to the sciatic nerve (DMG) and in the contralateral control leg (CTRL) (n = 7) to investigate changes of the metabolome, immunohistochemistry and protein levels. Untargeted metabolomics identified 79 polar metabolites, 27 of which were significantly altered in DMG compared to CTRL. Glucose concentrations were increased 2.6-fold in DMG, while glucose 6-phosphate (G6-P) was unchanged. Intermediates of the polyol pathway were increased in DMG, particularly fructose (1.7-fold). GLUT4 localization was scattered as opposed to clearly at the sarcolemma. Despite the altered localization, we found GLUT4 protein levels to be increased 7.8-fold while GLUT1 was decreased 1.7-fold in nerve damaged TA. PFK1 and GS levels were both decreased 2.1-fold, indicating an inability of glycolysis and glycogen synthesis to process glucose at sufficient rates. In conclusion, chronic nerve constriction causes increased GLUT4 levels in conjunction with decreased glycolytic activity and glycogen storage in skeletal muscle, resulting in accumulation of intramuscular glucose and polyol pathway intermediates.
| S-EPMC7002415 | biostudies-literature
Project description:Recent developments in Statistical Parametric Mapping (SPM) for continuum data (e.g. kinematic time series) have been adopted by the biomechanics research community with great interest. The Python/MATLAB package spm1d developed by T. Pataky has introduced SPM into the biomechanical literature, adapted originally from neuroimaging. The package already allows many of the statistical analyses common in biomechanics from a frequentist perspective. In this paper, we propose an application of Bayesian analogs of SPM based on Bayes factors and posterior probability with default priors using the BayesFactor package in R. Results are provided for two typical designs (two-sample and paired sample t-tests) and compared to classical SPM results, but more complex standard designs are possible in both classical and Bayesian frameworks. The advantages of Bayesian analyses in general and specifically for SPM are discussed. Scripts of the analyses are available as supplementary materials.
| S-EPMC8211129 | biostudies-literature
Project description:Quantitative analyses of plantar pressure images typically occur at the group level and under the assumption that individuals within each group display homogeneous pressure patterns. When this assumption does not hold, a personalized analysis technique is required. Yet, existing personalized plantar pressure analysis techniques work at the image level, leading to results that can be unintuitive and difficult to interpret. To address these limitations, we introduce PAPPI: the Personalized Analysis of Plantar Pressure Images. PAPPI is built around the statistical modelling of the relationship between plantar pressures in healthy controls and their demographic characteristics. This statistical model then serves as the healthy baseline to which an individual's real plantar pressures are compared using statistical parametric mapping. As a proof-of-concept, we evaluated PAPPI on a cohort of 50 hallux valgus patients. PAPPI showed that plantar pressures from hallux valgus patients did not have a single, homogeneous pattern, but instead, 5 abnormal pressure patterns were observed in sections of this population. When comparing these patterns to foot pain scores (i.e. Foot Function Index, Manchester-Oxford Foot Questionnaire) and radiographic hallux angle measurements, we observed that patients with increased pressure under metatarsal 1 reported less foot pain than other patients in the cohort, while patients with abnormal pressures in the heel showed more severe hallux valgus angles and more foot pain. Also, incidences of pes planus were higher in our hallux valgus cohort compared to the modelled healthy controls. PAPPI helped to clarify recent discrepancies in group-level plantar pressure studies and showed its unique ability to produce quantitative, interpretable, and personalized analyses for plantar pressure images.
| S-EPMC7046232 | biostudies-literature
Project description:Changes in movement pattern in low back pain (LBP) groups have been analysed by reporting predefined discrete variables. However, this approach does not consider the full kinematic data waveform and its dynamic information, potentially exposing the analysis to bias. Statistical Parametric Mapping (SPM) has been introduced and applied to 1 dimensional (D) kinematic variables allowing the assessment of data over time. The aims of this study were to assess differences in 3D kinematics patterns in people with and without LBP during functional tasks by using SPM and to investigate if SPM analysis was consistent with standard 3D range of motion (RoM) assessments. 3D joints kinematics of the spine and lower limbs were compared between 20 healthy controls and 20 participants with non-specific LBP during walking, sit-to-stand and lifting. SPM analysis showed significant differences in the 3Dkinematics of the lower thoracic segment, upper and lower lumbar segment and knee joint during walking and lifting mostly observed at the beginning and/or towards the end of the tasks. ROMs differed between groups in the lower thoracic segment (walking/sit-to-stand), upper and lower lumbar segments (walking/sit-to-stand/lifting), hip and knee (sit-to-stand/lifting). Based on these results, the two approaches can yield different data interpretations. SPM analysis allows the identification of differences in movement that occur over time. This adds value to LBP movement analysis as it allows an understanding of the LBP strategies adopted during motion that may not be conveyed by simple discrete parameters such as ROMs.
| S-EPMC7001037 | biostudies-literature
Project description:Skeletal muscle is ideal for passive vaccine administration as it is easily accessible by intramuscular injection. Recombinant adeno-associated virus (rAAV) vectors are in consideration for passive vaccination clinical trials for HIV and influenza. However, greater human skeletal muscle transduction is needed for therapeutic efficacy than is possible with existing serotypes. To bioengineer capsids with therapeutic levels of transduction, we utilized a directed evolution approach to screen libraries of shuffled AAV capsids in pools of surgically resected human skeletal muscle cells from five patients. Six rounds of evolution were performed in various muscle cell types, and evolved variants were validated against existing muscle-tropic serotypes rAAV1, 6, and 8. We found that evolved variants NP22 and NP66 had significantly increased primary human and rhesus skeletal muscle fiber transduction from surgical explants ex vivo and in various primary and immortalized myogenic lines in vitro. Importantly, we demonstrated reduced seroreactivity compared to existing serotypes against normal human serum from 50 adult donors. These capsids represent powerful tools for human skeletal muscle expression and secretion of antibodies from passive vaccines.
| S-EPMC6077147 | biostudies-literature