Figure - available from: Physics in Medicine & Biology
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Panel A: isosurfaces of the shortest distance calculated in three muscles, vastus lateralis (blue shade), vastus intermedius (green), and rectus femoris (dark red) starting from the surface of modeled GTV with λ3=10, λ3=20, and λ3=40. The outermost contour corresponds to the largest value of λ3. Panel B: three levels of isosurfaces of shortest distance with λ3=10. The boundary of the fat, femur, and non-involved muscles completes the modeled CTV.
Source publication
Objective:
Soft-tissue sarcoma spreads preferentially along muscle fibers. We explore the utility of deriving muscle fiber orientations from diffusion tensor MRI (DT-MRI) for defining the boundary of the clinical target volume (CTV) in muscle tissue.
Approach:
We recruited eight healthy volunteers to acquire MR images of the left and right thigh...
Citations
... Diffusion-weighted MRI, notably diffusion tensor imaging (DTI), is considered the gold standard technique for assessing the microstructural organization of muscles by detecting the preferential movement of water molecules in tissues (Secondulfo et al 2022, Martín-Noguerol et al 2023. Shusharina et al (2022) showed that it can be feasible to incorporate muscle fiber orientations derived from DTI into the CTV. Despite its potential, DTI is not standard in sarcoma care and its information is not currently available during the treatment planning process. ...
... In our framework, a relationship between metric and structure tensors can be established by noting that small intensity gradients in image space correspond to reduced resistance to tumor infiltration. Accordingly, the structure tensor T (orT ) can be transformed into G by replacing Λ in (2) by a parameterized diagonal matrix diag(ρ, 1, 1) in muscle tissue and defining (Shusharina et al 2022, Buti et al 2024: ...
... Alternatively, diffusion-weighted DTI scans intrinsically measures patient-specific muscle architecture. A recent study showed that with appropriate experimental conditions for DTI scans, the variability of the principal eigenvector in thigh muscles can be reduced, with potential application in the CTV for soft tissue sarcoma of the extremities (Shusharina et al 2022). This could lead to an integrated approach that combines cadaver image texture analysis eigenvectors with MRI-predicted eigenvectors or DTI eigenvectors. ...
Objective. A major challenge in treatment of tumors near skeletal muscle is defining the target volume for suspected tumor invasion into the muscle. This study develops a framework that generates radiation target volumes with muscle fiber orientation directly integrated into their definition. The framework is applied to nineteen sacral tumor patients with suspected infiltration into surrounding muscles. Approach. To compensate for the poor soft-tissue contrast of CT images, muscle fiber orientation is derived from cryo-images of two cadavers from the human visible project (VHP). The approach consists of (a) detecting image gradients in the cadaver images representative of muscle fibers, (b) mapping this information onto the patient image, and (c) embedding the muscle fiber orientation into an expansion method to generate patient-specific clinical target volumes (CTV). The validation tested the consistency of image gradient orientation across VHP subjects for the piriformis, gluteus maximus, paraspinal, gluteus medius, and gluteus minimus muscles. The model robustness was analyzed by comparing CTVs generated using different VHP subjects. The difference in shape between the new CTVs and standard CTV was analyzed for clinical impact. Main results. Good agreement was found between the image gradient orientation across VHP subjects, as the voxel-wise median cosine similarity was at least 0.86 (for the gluteus minimus) and up to 0.98 for the piriformis. The volume and surface similarity between the CTVs generating from different VHP subjects was on average at least 0.95 and 5.13 mm for the Dice Similarity Coefficient and the Hausdorff 95% Percentile Index, showing excellent robustness. Finally, compared to the standard CTV with different margins in muscle and non-muscle tissue, the new CTV margins are reduced in muscle tissue depending on the chosen clinical margins. Significance. This study implements a method to integrate muscle fiber orientation into the target volume without the need for additional imaging.
... With DW-MRI, the extent of microscopic spread can be defined as the distance from the radiographically visible tumor along the muscle fibers. 5 The principal eigenvector of the diffusion tensor derived from DW-MRI data coincides with the fiber directionality. For applications that require precise detection of the fibers, such as models of tumor spread, the consistency of the principal eigenvector is of major importance. ...
Diffusion-weighted MRI (DW-MRI) is used to quantitatively characterize the microscopic structure of soft tissue due to the anisotropic diffusion of water in muscle. Applications such as fiber tractography or modeling of tumor spread in soft tissue require precise detection of muscle fiber orientation, which is derived from the principal eigenvector of the diffusion tensor. For clinical applications, high image quality and high signal-to-noise ratio (SNR) of DW-MRI for fiber orientation must be balanced with an appropriate scan duration. Muscles with known structural heterogeneity, e.g. bipennate muscles such as the thigh rectus femoris, provide a natural quality benchmark to determine fiber orientation at different scan parameters. Here, we analyze DW-MR images of the thigh of a healthy volunteer at different SNRs and use PCA to identify subsets of voxels with different directions of diffusion tensor eigenvectors. We propose to use the mixing index of spatial co-localization of the clustered eigenvectors as a quality metric for fiber orientation detection. Comparing acquisitions at different SNRs, we find that high SNR results in a low mixing index, reflecting a clear separation of the two compartments of the bipennate muscle on either side of the central tendon. Because the mixing index allows joint estimation of spatial and directional noise in DW-MRI as a single parameter, it will allow future quantitative optimization of DW-MRI protocols for soft tissue.
... The first model, referred to as 'dominant direction only' (DDO), emphasizes tumor growth along the dominant direction of the DTI tensors through the white matter (Shusharina et al 2022). According to this model, only the direction with the largest eigenvalue is weighted by ρ and the other two remain unity. ...
Objective. Current radiotherapy guidelines for glioma target volume definition recommend a uniform margin expansion from the gross tumor volume (GTV) to the clinical target volume (CTV), assuming uniform infiltration in the invaded brain tissue. However, glioma cells migrate preferentially along white matter tracts, suggesting that white matter directionality should be considered in anisotropic CTV expansion. We investigate two models of anisotropic CTV expansion and evaluate their clinical feasibility.
Approach. To incorporate white matter directionality into the CTV, a diffusion tensor imaging (DTI) atlas is used. The DTI atlas consists of water diffusion tensors that are first spatially transformed into local tumor resistance tensors, also known as metric tensors, and secondly fed to a CTV expansion algorithm to generate anisotropic CTVs. Two models of spatial transformation are considered in the first step. The first model assumes that tumor cells experience reduced resistance parallel to the white matter fibers. The second model assumes that the anisotropy of tumor cell resistance is proportional to the anisotropy observed in DTI, with an "anisotropy weighting parameter" controlling the proportionality. The models are evaluated in a cohort of ten brain tumor patients.
Main results. To evaluate the sensitivity of the model, a library of model-generated CTVs was computed by varying the resistance and anisotropy parameters. Our results indicate that the resistance coefficient had the most significant effect on the global shape of the CTV expansion by redistributing the target volume from potentially less involved gray matter to white matter tissue. In addition, the anisotropy weighting parameter proved useful in locally increasing CTV expansion in regions characterized by strong tissue directionality, such as near the corpus callosum.
Significance. By incorporating anisotropy into the CTV expansion, this study is a step toward an interactive CTV definition that can assist physicians in incorporating neuroanatomy into a clinically optimized CTV.
... Microscopic studies confirm that tumor cells invade soft tissue along muscle fiber interfaces (Weigelin et al 2012). Based on this, we presented scientific evidence for the utility of DW-MRI in defining the extent of microscopic tumor spread in sarcomas (Shusharina et al 2022). We leveraged the well-established characterization of tissue microstructure with DW-MRI (Budzik et al 2007, Lansdown et al 2007, Rockel and Noseworthy 2016, Damon et al 2017, Berry et al 2018 and derived information on soft tissue directionality based on the anisotropic diffusion of water molecules. ...
... We leveraged the well-established characterization of tissue microstructure with DW-MRI (Budzik et al 2007, Lansdown et al 2007, Rockel and Noseworthy 2016, Damon et al 2017, Berry et al 2018 and derived information on soft tissue directionality based on the anisotropic diffusion of water molecules. We used this information to develop a model for microscopic tumor propagation by calculating the shortest path in anisotropic media directly from the DW-MRI data without mapping muscle fibers with tractography (Shusharina et al 2022). ...
... In muscle, the largest eigenvalue corresponds to the direction along the fibers (Damon et al 2002), and thus the eigenvector associated with the largest eigenvalue is the preferred direction of tumor spread. Therefore, the directional variability of the principal eigenvector has a direct impact on the accuracy of defining the boundary of microscopic tumor spread in models such as Shusharina et al (2022). ...
Objective: Diffusion-weighted MR imaging (DW-MRI) is known to quantify muscle fiber directionality and thus may be useful for radiotherapy target definition in sarcomas. Here, we investigate the variability of tissue anisotropy derived from diffusion tensor in the human thigh to establish the baseline parameters and protocols for DW-MRI acquisition for future studies in sarcoma patients.
Approach: We recruited ten healthy volunteers to acquire diffusion-weighted MR images of the left and right thigh. DW-MRI data were used to reconstruct diffusion tensor eigenvectors within each individual thigh muscle. Deviations of the principal eigenvector from its mean were calculated for different experimental conditions.
Main results: Within the majority of muscles in most subjects, the mode of the histogram of the angular deviation of the principal eigenvector of the water diffusion tensor from its muscle-averaged value did not exceed 20. On average for all subjects, the mode ranged from 15 to 24. Deviations much larger than 20 were observed in muscles far from the RF coil, including cases with significant amounts of subcutaneous fat and muscle deformation under its own weight.
Significance: Our study is a robust characterization of angular deviations of muscle fiber directionality in the thigh as determined by DW-MRI. We show that an appropriate choice of experimental conditions reduces the variability of the observed directionality. Precise determination of tissue directionality will enable reproducible models of microscopic tumor spread, with future application in defining the clinical target volume for soft tissue sarcoma.
