The Laboratory of Mathematics in Imaging (LMI) is focused on the application of mathematical theory, analysis, modeling, and signal processing to medical imaging. Research projects within the group cover both novel theoretical contributions and translational clinical efforts. The research team combine strengths in computer science and mathematics with radiology, neuroscience, and novel MRI sequence developmentLearn more

Recent Publications

REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer

Koerte IK, Bahr R, Filipcik P, Gooijers J, Leemans A, Lin AP, Tripodis Y, Shenton ME, Sochen N, Swinnen SP, et al. REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer. Brain Imaging Behav. 2021.Abstract
Repetitive head impacts (RHI) are common in youth athletes participating in contact sports. RHI differ from concussions; they are considered hits to the head that usually do not result in acute symptoms and are therefore also referred to as "subconcussive" head impacts. RHI occur e.g., when heading the ball or during contact with another player. Evidence suggests that exposure to RHI may have cumulative effects on brain structure and function. However, little is known about brain alterations associated with RHI, or about the risk factors that may lead to clinical or behavioral sequelae. REPIMPACT is a prospective longitudinal study of competitive youth soccer players and non-contact sport controls aged 14 to 16 years. The study aims to characterize consequences of exposure to RHI with regard to behavior (i.e., cognition, and motor function), clinical sequelae (i.e., psychiatric and neurological symptoms), brain structure, function, diffusion and biochemistry, as well as blood- and saliva-derived measures of molecular processes associated with exposure to RHI (e.g., circulating microRNAs, neuroproteins and cytokines). Here we present the structure of the REPIMPACT Consortium which consists of six teams of clinicians and scientists in six countries. We further provide detailed information on the specific aims and the design of the REPIMPACT study. The manuscript also describes the progress made in the study thus far. Finally, we discuss important challenges and approaches taken to overcome these challenges.
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Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

Schilling KG, Rheault F, Petit L, Hansen CB, Nath V, Yeh F-C, Girard G, Barakovic M, Rafael-Patino J, Yu T, et al. Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?. Neuroimage. 2021;243 :118502.Abstract
White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.
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Harmonization of In-Plane Resolution in CT Using Multiple Reconstructions From Single Acquisitions

Vegas-Sánchez-Ferrero G, Ramos-Llordén G, San José Estépar R. Harmonization of In-Plane Resolution in CT Using Multiple Reconstructions From Single Acquisitions. Med Phys. 2021.Abstract
PURPOSE: To provide a methodology that removes the spatial variability of in-plane resolution by using different CT reconstructions. The methodology does not require any training, sinogram or specific reconstruction method. METHODS: The methodology is formulated as a reconstruction problem. The desired sharp image is modeled as an unobservable variable to be estimated from an arbitrary number of observations with spatially variant resolution. The methodology comprises three steps: 1) Density harmonization, which removes the density variability across reconstructions. 2) PSF estimation, which estimates a spatially variant PSF with arbitrary shape. 3) Deconvolution, which is formulated as a regularized least squares problem. The assessment was performed with CT scans of phantoms acquired with three different Siemens scanners (Definition AS, Definition AS+, Drive). Four low-dose (LD) acquisitions reconstructed with backprojection and iterative methods were used for the resolution harmonization. A sharp, high-dose (HD) reconstruction was used as a validation reference. The different factors affecting the in-plane resolution (radial, angular, and longitudinal) were studied with regression analysis of the edge decay (between 10 and 90 percent of the edge spread function (ESF) amplitude). RESULTS: Results showed that the in-plane resolution improves remarkably and the spatial variability is substantially reduced without compromising the noise characteristics. The modulated transfer function (MTF) also confirmed a pronounced increase in resolution. The resolution improvement was also tested by measuring the wall thickness of tubes simulating airways. In all scanners, the resolution harmonization obtained better performance than the HD, sharp reconstruction used as a reference (up to 50 percent points). The methodology was also evaluated in clinical scans achieving a noise reduction and a clear improvement in thin-layered structures. The estimated ESF and MTF confirmed the resolution improvement. CONCLUSION: We propose a versatile methodology to reduce the spatial variability of in-plane resolution in CT scans by leveraging different reconstructions available in clinical studies. The methodology does not require any sinogram, training or specific reconstruction, and it is not limited to a fixed number of input images. Therefore, it can be easily adopted in multicenter studies and clinical practice. The results obtained with our resolution harmonization methodology evidence its suitability to reduce the spatially variant in-plane resolution in clinical CT scans without compromising the reconstruction's noise characteristics. We believe that the resolution increase achieved by our methodology may contribute in more accurate and reliable measurements of small structures such as vasculature, airways and wall thickness.
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A Simple Assessment of Lung Nodule Location for Reduction in Unnecessary Invasive Procedures

Kinsey MC, Billatos E, Mori V, Tonelli B, Cole BF, Duan F, Marques H, De La Bruere I, Onieva J, San José Estépar R, et al. A Simple Assessment of Lung Nodule Location for Reduction in Unnecessary Invasive Procedures. J Thorac Dis. 2021;13 (7) :4207-16.Abstract
Background: CT screening for lung cancer results in a significant mortality reduction but is complicated by invasive procedures performed for evaluation of the many detected benign nodules. The purpose of this study was to evaluate measures of nodule location within the lung as predictors of malignancy. Methods: We analyzed images and data from 3,483 participants in the National Lung Screening Trial (NLST). All nodules (4-20 mm) were characterized by 3D geospatial location using a Cartesian coordinate system and evaluated in logistic regression analysis. Model development and probability cutpoint selection was performed in the NLST testing set. The Geospatial test was then validated in the NLST testing set, and subsequently replicated in a new cohort of 147 participants from The Detection of Early Lung Cancer Among Military Personnel (DECAMP) Consortium. Results: The Geospatial Test, consisting of the superior-inferior distance (Z distance), nodule diameter, and radial distance (carina to nodule) performed well in both the NLST validation set (AUC 0.85) and the DECAMP replication cohort (AUC 0.75). A negative Geospatial Test resulted in a less than 2% risk of cancer across all nodule diameters. The Geospatial Test correctly reclassified 19.7% of indeterminate nodules with a diameter over 6mm as benign, while only incorrectly classifying 1% of cancerous nodules as benign. In contrast, the parsimonious Brock Model applied to the same group of nodules correctly reclassified 64.5% of indeterminate nodules as benign but resulted in misclassification of a cancer as benign in 18.2% of the cases. Applying the Geospatial test would result in reducing invasive procedures performed for benign lesions by 11.3% with a low rate of misclassification (1.3%). In contrast, the Brock model applied to the same group of patients results in decreasing invasive procedures for benign lesion by 39.0% but misclassifying 21.1% of cancers as benign. Conclusions: Utilizing information about geospatial location within the lung improves risk assessment for indeterminate lung nodules and may reduce unnecessary procedures. Trial Registration: NCT00047385, NCT01785342.
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Combined Diffusion-Relaxometry Microstructure Imaging: Current Status and Future Prospects

Slator PJ, Palombo M, Miller KL, Westin C-F, Laun F, Kim D, Haldar JP, Benjamini D, Lemberskiy G, de Almeida Martins JP, et al. Combined Diffusion-Relaxometry Microstructure Imaging: Current Status and Future Prospects. Magn Reson Med. 2021.Abstract
Microstructure imaging seeks to noninvasively measure and map microscopic tissue features by pairing mathematical modeling with tailored MRI protocols. This article reviews an emerging paradigm that has the potential to provide a more detailed assessment of tissue microstructure-combined diffusion-relaxometry imaging. Combined diffusion-relaxometry acquisitions vary multiple MR contrast encodings-such as b-value, gradient direction, inversion time, and echo time-in a multidimensional acquisition space. When paired with suitable analysis techniques, this enables quantification of correlations and coupling between multiple MR parameters-such as diffusivity, T 1 , T 2 , and T 2 ∗ . This opens the possibility of disentangling multiple tissue compartments (within voxels) that are indistinguishable with single-contrast scans, enabling a new generation of microstructural maps with improved biological sensitivity and specificity.
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Developing Methods to Detect and Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, and Methodology for the DIAGNOSE CTE Research Project

Alosco ML, Mariani ML, Adler CH, Balcer LJ, Bernick C, Au R, Banks SJ, Barr WB, Bouix S, Cantu RC, et al. Developing Methods to Detect and Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, and Methodology for the DIAGNOSE CTE Research Project. Alzheimers Res Ther. 2021;13 (1) :136.Abstract
BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine and validate clinical research diagnostic criteria (i.e., traumatic encephalopathy syndrome [TES]); examine repetitive head impact exposure, genetic, and other risk factors; and provide shared resources of anonymized data and biological samples to the research community. In this paper, we provide a detailed overview of the rationale, design, and methods for the DIAGNOSE CTE Research Project. METHODS: The targeted sample and sample size was 240 male participants, ages 45-74, including 120 former professional football players, 60 former collegiate football players, and 60 asymptomatic participants without a history of head trauma or participation in organized contact sports. Participants were evaluated at one of four U.S. sites and underwent the following baseline procedures: neurological and neuropsychological examinations; tau and amyloid positron emission tomography; magnetic resonance imaging and spectroscopy; lumbar puncture; blood and saliva collection; and standardized self-report measures of neuropsychiatric, cognitive, and daily functioning. Study partners completed similar informant-report measures. Follow-up evaluations were intended to be in-person and at 3 years post-baseline. Multidisciplinary diagnostic consensus conferences are held, and the reliability and validity of TES diagnostic criteria are examined. RESULTS: Participant enrollment and all baseline evaluations were completed in February 2020. Three-year follow-up evaluations began in October 2019. However, in-person evaluation ceased with the COVID-19 pandemic, and resumed as remote, 4-year follow-up evaluations (including telephone-, online-, and videoconference-based cognitive, neuropsychiatric, and neurologic examinations, as well as in-home blood draw) in February 2021. CONCLUSIONS: Findings from the DIAGNOSE CTE Research Project should facilitate detection and diagnosis of CTE during life, and thereby accelerate research on risk factors, mechanisms, epidemiology, treatment, and prevention of CTE. TRIAL REGISTRATION: NCT02798185.
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