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Contrast transport models are widely used to quantify blood flow and transport in dynamic contrast-enhanced magnetic resonance imaging. These models analyze the time course of the contrast agent concentration, providing diagnostic and prognostic value for many biological systems. Thus, ensuring accuracy and repeatability of the model parameter estimation is a fundamental concern. In this work, we analyze the structural and practical identifiability of a class of nested compartment models pervasively used in analysis of MRI data. We combine artificial and real data to study the role of noise in model parameter estimation. We observe that although all the models are structurally identifiable, practical identifiability strongly depends on the data characteristics. We analyze the impact of increasing data noise on parameter identifiability and show how the latter can be recovered with increased data quality. To complete the analysis, we show that the results do not depend on specific tissue characteristics or the type of enhancement patterns of contrast agent signal.

Introduction1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients.MethodsThis was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC).ResultsTwenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV.ConclusionOur study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.

PurposeTo develop an MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE) technique for simultaneous quantification of permeability and leakage-insensitive perfusion with a single-dose contrast injection.MethodsMT-DICE builds on a saturation-recovery prepared multi-echo fast low-angle shot sequence. The k-space is randomly sampled for 7.6 min, with single-dose contrast agent injected 1.5 min into the scan. MR multitasking is used to model the data into six dimensions, including three spatial dimensions for whole-brain coverage, a saturation-recovery time dimension, and a TE dimension for dynamic T1$$ {\mathrm{T}}_1 $$ and T2*$$ {\mathrm{T}}_2^{\ast } $$ quantification, respectively, and a contrast dynamics dimension for capturing contrast kinetics. The derived pixel-wise T1/T2*$$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ time series are converted into contrast concentration-time curves for calculation of kinetic metrics. The technique was assessed for its agreement with reference methods in T1$$ {\mathrm{T}}_1 $$ and T2*$$ {\mathrm{T}}_2^{\ast } $$ measurements in eight healthy subjects and, in three of them, inter-session repeatability of permeability and leakage-insensitive perfusion parameters. Its feasibility was also demonstrated in four patients with brain tumors.ResultsMT-DICE T1/T2*$$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ values of normal gray matter and white matter were in excellent agreement with reference values (intraclass correlation coefficients = 0.860/0.962 for gray matter and 0.925/0.975 for white matter ). Both permeability and perfusion parameters demonstrated good to excellent intersession agreement with the lowest intraclass correlation coefficients at 0.694. Contrast kinetic parameters in all healthy subjects and patients were within the literature range.ConclusionBased on dynamic T1/T2*$$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ mapping, MT-DICE allows for simultaneous quantification of permeability and leakage-insensitive perfusion metrics with a single-dose contrast injection.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P

PurposeTo provide early and localized glioblastoma (GBM) recurrence prediction, we introduce a novel postsurgery multiparametric magnetic resonance-based support vector machine (SVM) method coupling with stem cell niche (SCN) proximity estimation.Methods and materialsThis study used postsurgery magnetic resonance imaging (MRI) scans from 50 patients with recurrent GBM, obtained approximately 2 months before clinically diagnosed recurrence. The main prediction pipeline consisted of a proximity-based estimator to identify regions with high risk of recurrence (HRRs) and an SVM classifier to provide voxelwise prediction in HRRs. The HRRs were estimated using the weighted sum of inverse distances to 2 possible origins of recurrence-the SCN and the tumor cavity. Subsequently, multiparametric voxels (from T1, T1 contrast-enhanced, fluid-attenuated inversion recovery, T2, and apparent diffusion coefficient) within the HRR were grouped into recurrent (warped from the clinical diagnosis) and nonrecurrent subregions and fed into the proximity estimation-coupled SVM classifier (SVMPE). The cohort was randomly divided into 40% and 60% for training and testing, respectively. The trained SVMPE was then extrapolated to an earlier time point for earlier recurrence prediction. As an exploratory analysis, the SVMPE predictive cluster sizes and the image intensities from the 5 magnetic resonance sequences were compared across time to assess the progressive subclinical traces.ResultsOn 2-month prerecurrence MRI scans from 30 test cohort patients, the SVMPE classifier achieved a recall of 0.80, a precision of 0.69, an F1-score of 0.73, and a mean boundary distance of 7.49 mm. Exploratory analysis at early time points showed spatially consistent but significantly smaller subclinical clusters and significantly increased T1 contrast-enhanced and apparent diffusion coefficient values over time.ConclusionsWe demonstrated a novel voxelwise early prediction method, SVMPE, for GBM recurrence based on clinical follow-up MR scans. The SVMPE is promising in localizing subclinical traces of recurrence 2 months ahead of clinical diagnosis and may be used to guide more effective personalized early salvage therapy.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P

BackgroundDynamic contrast-enhanced MRI (DCE-MRI) parameters have been shown to be biomarkers for treatment response in glioblastoma (GBM). However, variations in analysis and measurement methodology complicate determination of biological changes measured via DCE. The aim of this study is to quantify DCE-MRI variations attributable to analysis methodology and image quality in GBM patients.MethodsThe Extended Tofts model (eTM) and Leaky Tracer Kinetic Model (LTKM), with manually and automatically segmented vascular input functions (VIFs), were used to calculate perfusion kinetic parameters from 29 GBM patients with double-baseline DCE-MRI data. DCE-MRI images were acquired 2-5 days apart with no change in treatment. Repeatability of kinetic parameters was quantified with Bland-Altman and percent repeatability coefficient (%RC) analysis.ResultsThe perfusion parameter with the least RC was the plasma volume fraction (v p ), with a %RC of 53%. The extra-cellular extra-vascular volume fraction (v e ) %RC was 82% and 81%, for extended Tofts-Kety Model (eTM) and LTKM respectively. The %RC of the volume transfer rate constant (K trans ) was 72% for the eTM, and 82% for the LTKM, respectively. Using an automatic VIF resulted in smaller %RCs for all model parameters, as compared to manual VIF.ConclusionsAs much as 72% change in K trans (eTM, autoVIF) can be attributable to non-biological changes in the 2-5 days between double-baseline imaging. Poor K trans repeatability may result from inferior temporal resolution and short image acquisition time. This variation suggests DCE-MRI repeatability studies should be performed institutionally, using an automatic VIF method and following quantitative imaging biomarkers alliance guidelines.

Blood-brain barrier (BBB) dysfunction has been implicated in ischemic risk following aneurysmal subarachnoid hemorrhage (aSAH), but never directly imaged. We prospectively examined whether post-bleed day 4 dynamic contrast-enhanced magnetic resonance (DCE-MR) BBB permeability imaging could predict development of delayed cerebral ischemia (DCI). Global MR-derived BBB permeability ( Ktrans) was significantly higher in aSAH patients who subsequently developed DCI (five patients; 2.28 ± 0.09 × 10-3 min-1) compared to those who experienced radiographic vasospasm only (three patients; 1.85 ± 0.12 × 10-3 min-1; p  2 × 10-3 min-1 predicted development of DCI (AUC = 0.98, 95% CI: 0.93-1). Global BBB dysfunction following aSAH is detectable with DCE-MR and predictive of ischemic risk.

Aside from bidimensional measurements from conventional contrast-enhanced MRI, there are no validated or FDA-qualified imaging biomarkers for high-grade gliomas. However, advanced functional MRI techniques, including perfusion- and diffusion-weighted MRI, have demonstrated much potential for determining prognosis, predicting therapeutic response, and assessing early treatment response. They may also prove useful for differentiating pseudoprogression from true progression after temozolomide chemoradiation and pseudoresponse from true response after anti-angiogenic therapy. This review will highlight recent developments using these techniques and emphasize the need for technical standardization and validation in prospective studies in order for these methods to become incorporated into standard-of-care imaging for brain tumor patients.

Thrombi, or clots, often occlude proximal segments of the cerebral arterial circulation in acute ischemic stroke. Thromboembolic occlusion or thrombi superimposed on atherosclerotic plaque are the principal focus of acute stroke therapies such as thrombolysis or thrombectomy. We review the imaging characteristics of thrombi on multimodal computed tomography and magnetic resonance imaging, angiography, and ultrasonography, summarizing recent studies that facilitate therapeutic decision-making from these noninvasive studies. Information about the location, size, and imaging characteristics can be ascertained using these techniques. Imaging findings in relation to occlusive thrombus have been correlated with clot pathology, response to therapeutic interventions, and clinical outcome. Diagnostic evaluation of occlusive thrombi on noninvasive studies now constitutes an integral component of acute stroke management.

The presence of calcification is uncommon in pituitary adenomas, and often lends support to other diagnoses including craniopharyngioma. The majority of calcified pituitary adenomas are prolactin-secreting tumors. We report two patients with calcified macroprolactinomas, one that was treated medically with a biochemical response and partial tumor response, and one that was treated successfully via an endoscopic endonasal transsphenoidal approach. Suspected calcified prolactinomas can be initially managed medically as per standard treatment for typical prolactinomas; however, the presence of diffuse calcification may hinder tumor shrinkage. Tumors that are refractory to medical treatment can be safely managed with surgery. [ABSTRACT FROM AUTHOR]