Evaluation of tractogram filtering methods using human-like connectome phantoms.

Tractography algorithms are prone to reconstructing spurious connections. The set of streamlines generated with tractography can be post-processed to retain the streamlines that are most biologically plausible. Several microstructure-informed filtering algorithms are available for this purpose, however, the comparative performance of these methods has not been extensively evaluated. In this study, we aim to evaluate streamline filtering and post-processing algorithms using simulated connectome phantoms. We first establish a framework for generating connectome phantoms featuring brain-like white matter fiber architectures. We then use our phantoms to systematically evaluate the performance of a range of streamline filtering algorithms, including SIFT, COMMIT, and LiFE. We find that all filtering methods successfully improve connectome accuracy, although filter performance depends on the complexity of the underlying white matter fiber architecture. Filtering algorithms can markedly improve tractography accuracy for simple tubular fiber bundles (F-measure deterministic- unfiltered: 0.49 and best filter: 0.72; F-measure probabilistic- unfiltered: 0.37 and best filter: 0.81), but for more complex brain-like fiber architectures, the improvement is modest (F-measure deterministic- unfiltered: 0.53 and best filter: 0.54; F-measure probabilistic- unfiltered: 0.46 and best filter: 0.50). Overall, filtering algorithms have the potential to improve the accuracy of connectome mapping pipelines, particularly for weighted connectomes and pipelines using probabilistic tractography methods. Our results highlight the need for further advances tractography and streamline filtering to improve the accuracy of connectome mapping.

Development and validation of retrospective electronic frailty index using operational data of aged care homes.

BACKGROUND: Although elderly population is generally frail, it is important to closely monitor their health deterioration to improve the care and support in residential aged care homes (RACs). Currently, the best identification approach is through time-consuming regular geriatric assessments. This study aimed to develop and validate a retrospective electronic frailty index (reFI) to track the health status of people staying at RACs using the daily routine operational data records. METHODS: We have access to patient records from the Royal Freemasons Benevolent Institution RACs (Australia) over the age of 65, spanning 2010 to 2021. The reFI was developed using the cumulative deficit frailty model whose value was calculated as the ratio of number of present frailty deficits to the total possible frailty indicators (32). Frailty categories were defined using population quartiles. 1, 3 and 5-year mortality were used for validation. Survival analysis was performed using Kaplan-Meier estimate. Hazard ratios (HRs) were estimated using Cox regression analyses and the association was assessed using receiver operating characteristic (ROC) curves. RESULTS: Two thousand five hundred eighty-eight residents were assessed, with an average length of stay of 1.2 ± 2.2 years. The RAC cohort was generally frail with an average reFI of 0.21 ± 0.11. According to the Kaplan-Meier estimate, survival varied significantly across different frailty categories (p < 0.01). The estimated hazard ratios (HRs) were 1.12 (95% CI 1.09-1.15), 1.11 (95% CI 1.07-1.14), and 1.1 (95% CI 1.04-1.17) at 1, 3 and 5 years. The ROC analysis of the reFI for mortality outcome showed an area under the curve (AUC) of ≥0.60 for 1, 3 and 5-year mortality. CONCLUSION: A novel reFI was developed using the routine data recorded at RACs. reFI can identify changes in the frailty index over time for elderly people, that could potentially help in creating personalised care plans for addressing their health deterioration.

Physical and digital phantoms for validating tractography and assessing artifacts.

Fiber tractography is widely used to non-invasively map white-matter bundles in vivo using diffusion-weighted magnetic resonance imaging (dMRI). As it is the case for all scientific methods, proper validation is a key prerequisite for the successful application of fiber tractography, be it in the area of basic neuroscience or in a clinical setting. It is well-known that the indirect estimation of the fiber tracts from the local diffusion signal is highly ambiguous and extremely challenging. Furthermore, the validation of fiber tractography methods is hampered by the lack of a real ground truth, which is caused by the extremely complex brain microstructure that is not directly observable non-invasively and that is the basis of the huge network of long-range fiber connections in the brain that are the actual target of fiber tractography methods. As a substitute for in vivo data with a real ground truth that could be used for validation, a widely and successfully employed approach is the use of synthetic phantoms. In this work, we are providing an overview of the state-of-the-art in the area of physical and digital phantoms, answering the following guiding questions: "What are dMRI phantoms and what are they good for?", "What would the ideal phantom for validation fiber tractography look like?" and "What phantoms, phantom datasets and tools used for their creation are available to the research community?". We will further discuss the limitations and opportunities that come with the use of dMRI phantoms, and what future direction this field of research might take.

A critical review of connectome validation studies.

Diffusion MRI tractography is the most widely used macroscale method for mapping connectomes in vivo. However, tractography is prone to various errors and biases, and thus tractography-derived connectomes require careful validation. Here, we critically review studies that have developed or utilized phantoms and tracer maps to validate tractography-derived connectomes, either quantitatively or qualitatively. We identify key factors impacting connectome reconstruction accuracy, including streamline seeding, propagation and filtering methods, and consider the strengths and limitations of state-of-the-art connectome phantoms and associated validation studies. These studies demonstrate the inherent limitations of current fiber orientation models and tractography algorithms and their impact on connectome reconstruction accuracy. Reconstructing connectomes with both high sensitivity and high specificity is challenging, given that some tractography methods can generate an abundance of spurious connections, while others can overlook genuine fiber bundles. We argue that streamline filtering can minimize spurious connections and potentially improve the biological plausibility of connectomes derived from tractography. We find that algorithmic choices such as the tractography seeding methodology, angular threshold, and streamline propagation method can substantially impact connectome reconstruction accuracy. Hence, careful application of tractography is necessary to reconstruct accurate connectomes. Improvements in diffusion MRI acquisition techniques will not necessarily overcome current tractography limitations without accompanying modeling and algorithmic advances.

Towards deep learning for connectome mapping: A block decomposition framework.

We propose a new framework to map structural connectomes using deep learning and diffusion MRI. We show that our framework not only enables connectome mapping with a convolutional neural network (CNN), but can also be straightforwardly incorporated into conventional connectome mapping pipelines to enhance accuracy. Our framework involves decomposing the entire brain volume into overlapping blocks. Blocks are sufficiently small to ensure that a CNN can be efficiently trained to predict each block's internal connectivity architecture. We develop a block stitching algorithm to rebuild the full brain volume from these blocks and thereby map end-to-end connectivity matrices. To evaluate our block decomposition and stitching (BDS) framework independent of CNN performance, we first map each block's internal connectivity using conventional streamline tractography. Performance is evaluated using simulated diffusion MRI data generated from numerical connectome phantoms with known ground truth connectivity. Due to the redundancy achieved by allowing blocks to overlap, we find that our block decomposition and stitching steps per se can enhance the accuracy of probabilistic and deterministic tractography algorithms by up to 20-30%. Moreover, we demonstrate that our framework can improve the strength of structure-function coupling between in vivo diffusion and functional MRI data. We find that structural brain networks mapped with deep learning correlate more strongly with functional brain networks (r â€‹= â€‹0.45) than those mapped with conventional tractography (r â€‹= â€‹0.36). In conclusion, our BDS framework not only enables connectome mapping with deep learning, but its two constituent steps can be straightforwardly incorporated as part of conventional connectome mapping pipelines to enhance accuracy.

Mapping connectomes with diffusion MRI: deterministic or probabilistic tractography?

PURPOSE: Human connectomics necessitates high-throughput, whole-brain reconstruction of multiple white matter fiber bundles. Scaling up tractography to meet these high-throughput demands yields new fiber tracking challenges, such as minimizing spurious connections and controlling for gyral biases. The aim of this study is to determine which of the two broadest classes of tractography algorithms-deterministic or probabilistic-is most suited to mapping connectomes. METHODS: This study develops numerical connectome phantoms that feature realistic network topologies and that are matched to the fiber complexity of in vivo diffusion MRI (dMRI) data. The phantoms are utilized to evaluate the performance of tensor-based and multi-fiber implementations of deterministic and probabilistic tractography. RESULTS: For connectome phantoms that are representative of the fiber complexity of in vivo dMRI, multi-fiber deterministic tractography yields the most accurate connectome reconstructions (F-measure = 0.35). Probabilistic algorithms are hampered by an abundance of false-positive connections, leading to lower specificity (F = 0.19). While omitting connections with the fewest number of streamlines (thresholding) improves the performance of probabilistic algorithms (F = 0.38), multi-fiber deterministic tractography remains optimal when it benefits from thresholding (F = 0.42). CONCLUSIONS: Multi-fiber deterministic tractography is well suited to connectome mapping, while connectome thresholding is essential when using probabilistic algorithms.