Biology subjects

Blemker, S. S.

Publications and source records attributed to Blemker, S. S..

5 recordsLinked to original sources

bioRxiv2025

Big Bones Mean Big Muscles: AI Quantifies 71 Individual Muscles Across the Whole Body, Revealing Widespread Links Between Muscle, Bone, and Body Size

Body sizes and shapes vary widely, even among healthy adults, resulting in diverse muscle sizes, strengths, and performance capacities. This study developed a novel AI-driven algorithm to segment and analyze individual muscles and bones from whole-body MRI. Validated via inter- and intra-observer analyses, the algorithm created 3D segmentations of 71 muscles and 13 bones across the upper limbs, trunk, and lower limbs in 48 healthy adults (24 males, 24 females) aged 18-49 years. Muscle volume, asymmetry, length, and fat fraction were quantified. While asymmetry and fat fraction varied across muscles, they did not differ significantly between sexes. Total muscle volume was the strongest predictor of individual muscle volume, followed by bone volume, which correlated with muscle size at whole-body, regional, and individual levels. Muscle-to-body size relationships (e.g., mass, height, BMI) differed between sexes, while bone-to-body size relationships did not. These findings suggest that skeletal size ("frame size") is a key determinant of muscularity. This study provides the most comprehensive in vivo dataset of human skeletal muscle to date, offering a multi-factorial explanation for variation in muscularity and benchmarks for applications ranging from athletic performance to clinical assessments in muscle disorders. SUMMARYUnderstanding how muscle size varies across the body and what influences these differences is key to advancing both health and performance. This study uses cutting-edge AI to analyze individual muscles across the whole body from MRI scans, creating the most detailed dataset of human muscle and bone relationships to date. The findings reveal how skeletal size ("frame size") and body dimensions shape muscularity, providing new insights into why people differ in muscle size and strength. These results have broad implications, from optimizing athletic training to diagnosing and treating muscle disorders. By uncovering the intricate connections between muscles, bones, and body size, this research offers a powerful framework for understanding human movement and variability.

bioengineering↗

bioRxiv2025

Multi-scale machine learning model predicts muscle and functional disease progression in FSHD

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic neuromuscular disorder characterized by progressive muscle degeneration with substantial variability in severity and progression patterns. FSHD is a highly heterogeneous disease; however, current clinical metrics used tracking disease progression lack sensitivity for personalized assessment, which greatly limits the design and execution of clinical trials. This study introduces a multi-scale machine learning framework leveraging whole-body magnetic resonance imaging (MRI) and clinical data to predict regional, muscle, joint, and functional progression in FSHD. The goal this work is to create a digital twin of individual FSHD patients that can be leveraged in clinical trials. Using a combined dataset of over 100 patients from seven studies, MRI-derived metrics--including fat fraction, lean muscle volume, and fat spatial heterogeneity at baseline--were integrated with clinical and functional measures. A three-stage random forest model was developed to predict annualized changes in muscle composition and a functional outcome (timed up-and-go (TUG)). All model stages revealed strong predictive performance in separate holdout datasets. After training, the models predicted fat fraction change with a root mean square error (RMSE) of 2.16% and lean volume change with a RMSE of 8.1ml in a holdout testing dataset. Feature analysis revealed that metrics fat heterogeneity within muscle predicts muscle-level progression. The stage 3 model that combined functional muscle groups and predicted change in TUG with a RMSE of 0.6 seconds, in the holdout testing dataset. This study demonstrates the machine learning models incorporating individual muscle and performance data can effectively predict MRI disease progression and functional performance of complex tasks, addressing the heterogeneity and nonlinearity inherent in FSHD. Further studies incorporating larger longitudinal cohorts as well as comprehensive clinical and functional measures will allow for expanding and refining this model. As many neuromuscular diseases are characterized by varability and heterogeneity similar to FSHD, such approaches have broad applicability.

bioengineering↗

bioRxiv2023

Agent-based model demonstrates the impact of nonlinear, complex interactions between cytokines on muscle regeneration

Muscle regeneration is a complex process due to dynamic and multiscale biochemical and cellular interactions, making it difficult to identify microenvironmental conditions that are beneficial to muscle recovery from injury using experimental approaches alone. To understand the degree to which individual cellular behaviors impact endogenous mechanisms of muscle recovery, we developed an agent-based model (ABM) using the Cellular Potts framework to simulate the dynamic microenvironment of a cross-section of murine skeletal muscle tissue. We referenced more than 100 published studies to define over 100 parameters and rules that dictate the behavior of muscle fibers, satellite stem cells (SSC), fibroblasts, neutrophils, macrophages, microvessels, and lymphatic vessels, as well as their interactions with each other and the microenvironment. We utilized parameter density estimation to calibrate the model to temporal biological datasets describing cross-sectional area (CSA) recovery, SSC, and fibroblast cell counts at multiple time points following injury. The calibrated model was validated by comparison of other model outputs (macrophage, neutrophil, and capillaries counts) to experimental observations. Predictions for eight model perturbations that varied cell or cytokine input conditions were compared to published experimental studies to validate model predictive capabilities. We used Latin hypercube sampling and partial rank correlation coefficient to identify in silico perturbations of cytokine diffusion coefficients and decay rates to enhance CSA recovery. This analysis suggests that combined alterations of specific cytokine decay and diffusion parameters result in greater fibroblast and SSC proliferation compared to individual perturbations with a 13% increase in CSA recovery compared to unaltered regeneration at 28 days. These results enable guided development of therapeutic strategies that similarly alter muscle physiology (i.e. converting ECM-bound cytokines into freely diffusible forms as studied in cancer therapeutics or delivery of exogenous cytokines) during regeneration to enhance muscle recovery after injury.

systems biology↗

bioRxiv2023

Validation of the association between MRI and gene signatures in facioscapulohumeral dystrophy muscle: implications for clinical trial design

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression, but reproducibility across studies needs further validation. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA. Together with moderate-to-strong correlations of gene signatures and MRI characteristics between the TA muscles bilaterally, these results suggest a whole muscle model of disease progression and provide a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design.

molecular biology↗

bioRxiv2021

Diaphragm muscle fibrosis involves changes in collagen organization with mechanical implications in Duchenne Muscular Dystrophy

In Duchenne muscular dystrophy (DMD), diaphragm muscle dysfunction results in respiratory insufficiency, a leading cause of death in patients. Increased muscle stiffness occurs with buildup of fibrotic tissue, characterized by excessive accumulation of extracellular matrix (ECM) components such as collagen. However, changes in mechanical properties are not explained by collagen amount alone and we must consider the complex structure and mechanics of fibrotic tissue. The goals of our study were to (1) determine if and how collagen organization changes with the progression of DMD in diaphragm muscle tissue, and (2) predict how collagen organization influences the mechanical properties of ECM. We first visualized collagen structure with scanning electron microscopy (SEM) images and then developed an analysis framework to quantify collagen organization and generate image-based finite-element models. The image analysis revealed significant age- and disease-dependent increases in collagen fiber straightness and alignment, ranging from 4.7 to 13.4%, but collagen fibers retained a transverse orientation relative to muscle fibers. The mechanical models predicted significant age- and disease-dependent increases in transverse effective stiffness and average stress, ranging from 8.8 to 12.4%. Additionally, both healthy and diseased models revealed an increase in transverse stiffness relative to longitudinal stiffness, with significant age- and disease-dependent increases in the ratio of transverse to longitudinal stiffness, ranging from 19.7 to 24.5%. This study revealed changes in diaphragm ECM structure and mechanics during the progression of disease in the mdx muscular dystrophy mouse phenotype, highlighting the need to consider the role of collagen organization on diaphragm muscle function.

physiology↗