MRI radiomics for hamstring strain injury identification and return to sport classification: a pilot study.

OBJECTIVE: To determine if MRI-based radiomics from hamstring muscles are related to injury and if the features could be used to perform a time to return to sport (RTS) classification. We hypothesize that radiomics from hamstring muscles, especially T2-weighted and diffusion tensor imaging-based features, are related to injury and can be used for RTS classification. SUBJECTS AND METHODS: MRI data from 32 athletes at the University of Wisconsin-Madison that sustained a hamstring strain injury were collected. Diffusion tensor imaging and T1- and T2-weighted images were processed, and diffusion maps were calculated. Radiomics features were extracted from the four hamstring muscles in each limb and for each MRI modality, individually. Feature selection was performed and multiple support vector classifiers were cross-validated to differentiate between involved and uninvolved limbs and perform binary (≤ or > 25 days) and multiclass (< 14 vs. 14-42 vs. > 42 days) classification of RTS. RESULT: The combination of radiomics features from all diffusion tensor imaging and T2-weighted images provided the most accurate differentiation between involved and uninvolved limbs (AUC ≈ 0.84 ± 0.16). For the binary RTS classification, the combination of all extracted radiomics offered the most accurate classification (AUC ≈ 0.95 ± 0.15). While for the multiclass RTS classification, the combination of features from all the diffusion tensor imaging maps provided the most accurate classification (weighted one vs. rest AUC ≈ 0.81 ± 0.16). CONCLUSION: This pilot study demonstrated that radiomics features from hamstring muscles are related to injury and have the potential to predict RTS.

Diffusion tensor imaging of hamstring muscles after acute strain injury and throughout recovery in collegiate athletes.

OBJECTIVE: To identify the region of interest (ROI) to represent injury and observe between-limb diffusion tensor imaging (DTI) microstructural differences in muscle following hamstring strain injury. MATERIALS AND METHODS: Participants who sustained a hamstring strain injury prospectively underwent 3T-MRI of bilateral thighs using T1, T2, and diffusion-weighted imaging at time of injury (TOI), return to sport (RTS), and 12 weeks after RTS (12wks). ROIs were using the hyperintense region on a T2-weighted sequence: edema, focused edema, and primary muscle injured excluding edema (no edema). Linear mixed-effects models were used to compare diffusion parameters between ROIs and timepoints and limbs and timepoints. RESULTS: Twenty-four participants (29 injuries) were included. A significant ROI-by-timepoint interaction was detected for all diffusivity measures. The edema and focused edema ROIs demonstrated increased diffusion at TOI compared to RTS for all diffusivity measures (p-values < 0.006), except λ1 (p-values = 0.058-0.12), and compared to 12wks (p-values < 0.02). In the no edema ROI, differences in diffusivity measures were not observed (p-values > 0.82). At TOI, no edema ROI diffusivity measures were lower than the edema ROI (p-values < 0.001) but not at RTS or 12wks (p-values > 0.69). A significant limb-by-timepoint interaction was detected for all diffusivity measures with increased diffusion in the involved limb at TOI (p-values < 0.001) but not at RTS or 12wks (p-values > 0.42). Significant differences in fractional anisotropy over time or between limbs were not detected. CONCLUSION: Hyperintensity on T2-weighted imaging used to define the injured region holds promise in describing muscle microstructure following hamstring strain injury by demonstrating between-limb differences at TOI but not at follow-up timepoints.

Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks.

Inflammation is associated with depressive symptoms and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited N = 46 healthy controls, and N = 83 depressed cases stratified by CRP (> 3 mg/L: N = 33; < 3 mg/L: N = 50). All completed clinical assessment, venous blood sampling for C-reactive protein (CRP) assay, and brain magnetic resonance imaging (MRI). Micro-structural MRI parameters including proton density (PD), a measure of tissue water content, were measured at 360 cortical and 16 subcortical regions. Resting-state fMRI time series were correlated to estimate functional connectivity between individual regions, as well as the sum of connectivity (weighted degree) of each region. Multiple tests for regional analysis were controlled by the false discovery rate (FDR = 5%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC); and with functional connectivity between pC/pCC, mPFC and hippocampus. Depression was associated with reduced weighted degree of pC/pCC, mPFC, and other nodes of the default mode network (DMN). Thus CRP-related increases in proton density-a plausible marker of extracellular oedema-and changes in functional connectivity were anatomically co-localised with DMN nodes that also demonstrated significantly reduced hubness in depression. We suggest that effects of peripheral inflammation on DMN node micro-structure and connectivity may mediate inflammatory effects on depression.

A method to remove the influence of fixative concentration on postmortem T2 maps using a kinetic tensor model.

Formalin fixation has been shown to substantially reduce T2 estimates, primarily driven by the presence of fixative in tissue. Prior to scanning, post-mortem samples are often placed into a fluid that has more favourable imaging properties. This study investigates whether there is evidence for a change in T2 in regions close to the tissue surface due to fixative outflux into this surrounding fluid. Furthermore, we investigate whether a simulated spatial map of fixative concentration can be used as a confound regressor to reduce T2 inhomogeneity. To achieve this, T2 maps and diffusion tensor estimates were obtained in 14 whole, formalin-fixed post-mortem brains placed in Fluorinert approximately 48 hr prior to scanning. Seven brains were fixed with 10% formalin and seven brains were fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a proposed kinetic tensor (KT) model, which incorporates voxelwise diffusion tensor estimates to account for diffusion anisotropy and tissue-specific diffusion coefficients. Brains fixed with 10% NBF revealed a spatial T2 pattern consistent with modelled fixative outflux. Confound regression of fixative concentration reduced T2 inhomogeneity across both white and grey matter, with the greatest reduction attributed to the KT model versus simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin. Correlations between the transverse relaxation rate R2 and ferritin/myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between R2 and PLP for the two fixative types after KT correction.

PET Image Quality Improvement for Simultaneous PET/MRI with a Lightweight MRI Surface Coil.

Background During simultaneous PET/MRI, flexible MRI surface coils that lay on the patient are often omitted from PET attenuation correction processing, leading to quantification bias in PET images. Purpose To identify potential PET image quality improvement by using a recently developed lightweight MRI coil technology for the anterior array (AA) surface coil in both a phantom and in vivo study. Materials and Methods A phantom study and a prospective in vivo study were performed with a PET/CT scanner under three conditions: (a) no MRI surface coil (standard of reference), (b) traditional AA coil, and (c) lightweight AA coil. AA coils were not used in attenuation correction processing to emulate clinical PET/MRI. For the phantom study, PET images were reconstructed with and without time of flight (TOF) to assess quantification accuracy and uniformity. The in vivo study consisted of 10 participants (mean age, 66 years ± 10 [standard deviation]; six men) referred for a PET/CT oncologic examination who had undergone imaging between October 2019 and February 2020. Assessment of image quantification bias (defined as the standard error of the mean values) was conducted by comparing mean liver region of interest standardized uptake values with the no-coil standard of reference. A Wilcoxon signed-rank test was used to establish significance. Results For TOF and non-TOF, respectively, the phantom study revealed a mean PET quantification bias of -9.0% and -8.6% with the traditional AA coil and a mean PET quantification bias of -4.3% and -4.0% with the lightweight AA coil. The coefficients of variation reduced from 4.3% and 6.2% with the traditional AA coil to 2.1% and 2.7% with the lightweight AA coil, which demonstrated a homogeneity benefit from the lightweight coil that was greater with, versus without, TOF reconstruction. For the in vivo study, the mean liver standardized uptake value error was -5.9% with the traditional AA coil (P = .002 vs no coil) and -2.4% with the lightweight AA coil (P = .004 vs no coil). Conclusion The lightweight anterior array coil reduced PET image quantification bias by more than 50% compared with the traditional coil. Using the lightweight coil and performing time of flight-based reconstruction each reduced the variation of error. © RSNA, 2020 Online supplemental material is available for this article.

Changes in Endogenous Dopamine Induced by Methylphenidate Predict Functional Connectivity in Nonhuman Primates.

Dopamine (DA) levels in the striatum are increased by many therapeutic drugs, such as methylphenidate (MPH), which also alters behavioral and cognitive functions thought to be controlled by the PFC dose-dependently. We linked DA changes and functional connectivity (FC) using simultaneous [18F]fallypride PET and resting-state fMRI in awake male rhesus monkeys after oral administration of various doses of MPH. We found a negative correlation between [18F]fallypride nondisplaceable binding potential (BPND) and MPH dose in the head of the caudate (hCd), demonstrating increased extracellular DA resulting from MPH administration. The decreased BPND was negatively correlated with FC between the hCd and the PFC. Subsequent voxelwise analyses revealed negative correlations with FC between the hCd and the dorsolateral PFC, hippocampus, and precuneus. These results, showing that MPH-induced changes in DA levels in the hCd predict resting-state FC, shed light on a mechanism by which changes in striatal DA could influence function in the PFC.SIGNIFICANCE STATEMENT Dopamine transmission is thought to play an essential role in shaping large scale-neural networks that underlie cognitive functions. It is the target of therapeutic drugs, such as methylphenidate (Ritalin), which blocks the dopamine transporter, thereby increasing extracellular dopamine levels. Methylphenidate is used extensively to treat attention deficit hyperactivity disorder, even though its effects on cognitive functions and their underlying neural mechanisms are not well understood. To date, little is known about the link between changes in dopamine levels and changes in functional brain organization. Using simultaneous PET/MR imaging, we show that methylphenidate-induced changes in endogenous dopamine levels in the head of the caudate predict changes in resting-state functional connectivity between this structure and the prefrontal cortex, precuneus, and hippocampus.

Advancing RF pulse design using an open-competition format: Report from the 2015 ISMRM challenge.

PURPOSE: To advance the best solutions to two important RF pulse design problems with an open head-to-head competition. METHODS: Two sub-challenges were formulated in which contestants competed to design the shortest simultaneous multislice (SMS) refocusing pulses and slice-selective parallel transmission (pTx) excitation pulses, subject to realistic hardware and safety constraints. Short refocusing pulses are needed for spin echo SMS imaging at high multiband factors, and short slice-selective pTx pulses are needed for multislice imaging in ultra-high field MRI. Each sub-challenge comprised two phases, in which the first phase posed problems with a low barrier of entry, and the second phase encouraged solutions that performed well in general. The Challenge ran from October 2015 to May 2016. RESULTS: The pTx Challenge winners developed a spokes pulse design method that combined variable-rate selective excitation with an efficient method to enforce SAR constraints, which achieved 10.6 times shorter pulse durations than conventional approaches. The SMS Challenge winners developed a time-optimal control multiband pulse design algorithm that achieved 5.1 times shorter pulse durations than conventional approaches. CONCLUSION: The Challenge led to rapid step improvements in solutions to significant problems in RF excitation for SMS imaging and ultra-high field MRI. Magn Reson Med 78:1352-1361, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Optimal echo time for functional MRI of the infant brain identified in response to noxious stimulation.

PURPOSE: Blood oxygen level dependent (BOLD) brain activity, measured using functional MRI (fMRI), is dependent on the echo time (TE) and the reversible spin-spin relaxation time constant ( T2*) that describes the decay of transverse magnetization. Use of the optimal TE during fMRI experiments allows maximal sensitivity to BOLD to be achieved. Reports that T2* values are longer in infants (due to higher water concentrations and lower lipid content) have led to the use of longer TEs during infant fMRI experiments; however, the optimal TE has not been established. METHODS: In this study, acute experimental mildly noxious stimuli were applied to the heel in 12 term infants (mean gestational age = 40 weeks, mean postnatal age = 3 days); and the percentage change in BOLD activity was calculated across a range of TEs, from 30 to 70 ms, at 3 Tesla. In addition, T2* maps of the whole brain were collected in seven infants. RESULTS: The maximal change in BOLD occurred at a TE of 52 ms, and the average T2* across the whole brain was 99 ms. CONCLUSION: A TE of approximately 50 ms is recommended for use in 3T fMRI investigations in term infants. Magn Reson Med 78:625-631, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Data-driven optimized flip angle selection for T1 estimation from spoiled gradient echo acquisitions.

PURPOSE: Define criteria for selection of optimal flip angle sets for T1 estimation and evaluate effects on T1 mapping. THEORY AND METHODS: Flip angle sets for spoiled gradient echo-based T1 mapping were selected by minimizing T1 estimate variance weighted by the joint density of M0 and T1 in an initial acquisition. The effect of optimized flip angle selection on T1 estimate error was measured using simulations and experimental data in the human and rat brain. RESULTS: For two-point acquisitions, optimized angle sets were similar to those proposed by other groups and, therefore, performed similarly. For multipoint acquisitions, optimal angle sets for T1 mapping in the brain consisted of a repetition of two angles. Implementation of optimal angles reduced T1 estimate variance by 30-40% compared with a multipoint acquisition using a range of angles. Performance of the optimal angle set was equivalent to that of a repetition of the two-angle set selected using criteria proposed by other researchers. CONCLUSION: Repetition of two carefully selected flip angles notably improves the precision of resulting T1 estimates compared with acquisitions using a range of flip angles. This work provides a flexible and widely applicable optimization method of particular use for those who repeatedly perform T1 estimation. Magn Reson Med 76:792-802, 2016. © 2015 Wiley Periodicals, Inc.