Alterations in whole muscle quality and physiological cross-sectional area measured with quantitative MRI following ACL injury.

Background: Emerging evidence suggests that there are morphological and physiological changes to the vastus lateralis after an anterior cruciate ligament (ACL) tear. However, it is unclear whether these alterations are limited to just the vastus lateralis or are more representative of widespread changes across the thigh musculature and/or if these changes precede reconstruction. The purpose of this study was to determine T1ρ relaxation time, a measure of extracellular matrix organization in muscle, and physiological cross-sectional area (PCSA) for muscles of the quadriceps and hamstrings of the ACL-deficient and contralateral limbs soon after ACL injury.

Ungated, plug-and-play preclinical cardiac CEST-MRI using radial FLASH with segmented saturation.

Purpose: Electrocardiography (ECG) and respiratory-gated preclinical cardiac CEST-MRI acquisitions are difficult because of variable saturation recovery with T, RF interference in the ECG signal, and offset-to-offset variation in Z-magnetization and cardiac phase introduced by changes in cardiac frequency and trigger delays.

Methods: The proposed method consists of segmented saturation modules with radial FLASH readouts and golden angle progression. The segmented saturation blocks drive the system to steady-state, and because center k-space is sampled repeatedly, steady-state saturation dominates contrast during gridding and reconstruction.

Imaging of adeno-associated viral capsids for purposes of gene editing using CEST NMR/MRI.

Purpose: Gene therapy using adeno-associated virus (AAV) vector-mediated gene delivery has undergone substantial growth in recent years with promising results in both preclinical and clinical studies, as well as emerging regulatory approval. However, the inability to quantify the efficacy of gene therapy from cellular delivery of gene-editing technology to specific functional outcomes is an obstacle for efficient development of gene therapy treatments. Building on prior works that used the CEST reporter gene lysine rich protein, we hypothesized that AAV viral capsids may generate endogenous CEST contrast from an abundance of surface lysine residues.

Individually tailored spatial-spectral pulsed CEST MRI for ratiometric mapping of myocardial energetic species at 3T.

Purpose: CEST MRI has been used to probe changes in cardiac metabolism via assessment of CEST contrast from Cr. However, B variation across the myocardium leads to spatially variable Cr CEST contrast in healthy myocardium.

Methods: We developed a spatial-spectral (SPSP) saturation pulsed CEST protocol to compensate for B variation.

Noninvasively differentiating acute and chronic nephropathies via multiparametric urea-CEST, nuclear Overhauser enhancement-CEST, and quantitative magnetization transfer MRI.

Purpose: Standardized blood tests often lack adequate sensitivity and specificity to capture the gradual progression of renal injuries. We suggest a multiparametric molecular MRI approach as a noninvasive tool for monitoring renal function loss and distinguishing different types of renal injuries.

Methods: CEST and quantitative magnetization transfer (qMT) imaging were performed on cisplatin (n = 16) and aristolochic acid (AA)-induced nephropathy (n = 22) mouse models at 7T with an infusion of either saline or urea.

Cyclical depressurization degranulates platelets in an agonist-free mechanism of platelet activation.

Activation of circulating platelets by receptor binding and subsequent coagulation events are defined by a well characterized physiological response. However, the growing prevalence of chronic kidney disease (CKD) and implication of platelet-released factors in worsening cardiovascular outcomes with hemodialysis warrant further investigation into the mechanobiology of platelet degranulation. The significant drops in pressure caused by high friction across the hemodialysis flow circuit present an overlooked platelet stimulant not involving immobilization as a driver for cytoskeletal rearrangement.

Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors.

Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation.

T1ρ imaging as a non-invasive assessment of collagen remodelling and organization in human skeletal muscle after ligamentous injury.

Dysregulation and fibrosis of the extracellular matrix (ECM) in skeletal muscle is a consequence of injury. Current ECM assessment necessitates muscle biopsies to evaluate alterations to the muscle ECM, which is often not practical in humans. The goal of this study was to evaluate the potential of a magnetic resonance imaging sequence that quantifies T1ρ relaxation time to predict ECM collagen composition and organization.

Accelerated multi-target chemical exchange saturation transfer magnetic resonance imaging of the mouse heart.

Cardiac chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) has been used to probe levels of various metabolites that provide insight into myocardial structure and function. However, imaging of the heart using CEST-MRI is prolonged by the need to repeatedly acquire multiple images for a full Z-spectrum and to perform saturation and acquisition around cardiac and respiratory cycles. Compressed sensing (CS) reconstruction of sparse data enables accelerated acquisition, but reconstruction artifacts may bias subsequently derived measures of CEST contrast.

Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction.

Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation.

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy.

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression.

Delayed urea differential enhancement CEST (dudeCEST)-MRI with T correction for monitoring renal urea handling.

Purpose: We demonstrate a method of delayed urea differential enhancement CEST for probing urea recycling action of the kidney using expanded multi-pool Lorentzian fitting and apparent exchange-dependent relaxation compensation.

Methods: T correction of urea CEST contrast by apparent exchange-dependent relaxation was tested in phantoms. Nine mice were scanned at 7 Tesla following intraperitoneal injection of 2M 150 μL urea, and later saline.

The effects of mild closed head injuries on tauopathy and cognitive deficits in rodents: Primary results in wild type and rTg4510 mice, and a systematic review.

In humans, the majority of sustained traumatic brain injuries (TBIs) are classified as 'mild' and most often a result of a closed head injury (CHI). The effects of a non-penetrating CHI are not benign and may lead to chronic pathology and behavioral dysfunction, which could be worsened by repeated head injury. Clinical-neuropathological correlation studies provide evidence that conversion of tau into abnormally phosphorylated proteotoxic intermediates (p-tau) could be part of the pathophysiology triggered by a single TBI and enhanced by repeated TBIs.

Fractal Analysis of Cardiac Fibrosis Patterns Derived From Magnetization Transfer Contrast MRI in Patients With End-Stage Renal Disease.

The purpose of this study is to use fractal analysis to characterize diffusely fibrotic, focally fibrotic, and healthy myocardium in patients with end-stage renal disease (ESRD) on the basis of previously published magnetization transfer (MT) contrast images. The MT ratio values of patients with ESRD ( = 34) and healthy control subjects ( = 19) were used to construct anatomically faithful 3D left ventricular reconstructions. Established MT ratio threshold values were used to define healthy, diffusely enhanced, focally enhanced, and total enhanced tissue domains.

Noninvasive imaging of renal urea handling by CEST-MRI.

Purpose: Renal function is characterized by concentration of urea for removal in urine. We tested urea as a CEST-MRI contrast agent for measurement of the concentrating capacity of distinct renal anatomical regions.

Methods: The CEST contrast of urea was examined using phantoms with different concentrations and pH levels.

Myocardial native-T1 times are elevated as a function of hypertrophy, HbA1c, and heart rate in diabetic adults without diffuse fibrosis.

Purpose: Cardiac native-T1 times have correlated to extracellular volume fraction in patients with confirmed fibrosis. However, whether other factors that can occur either alongside or independently of fibrosis including increased intracellular water volume, altered magnetization transfer (MT), or glycation of hemoglobin, lengthen T1 times in the absence of fibrosis remains unclear. The current study examined whether native-T1 times are elevated in hypertrophic diabetics with elevated hemoglobin A1C (HbA1c) without diffuse fibrosis.

CEST MRI reveals a correlation between visceral fat mass and reduced myocardial creatine in obese individuals despite preserved ventricular structure and function.

Systolic cardiac function is typically preserved in obese adults, potentially masking underlying declines in cardiomyocyte metabolism that may contribute to heart failure. We used chemical exchange saturation transfer (CEST) MRI, a sensitive method for measurement of myocardial creatine, to examine whether myocardial creatine levels correlate with cardiac structure, contractile function, or visceral fat mass in obese adults. In this study, obese (body mass index, BMI > 30, n = 20) and healthy (BMI < 25, n = 11) adults were examined with dual-energy x-ray absorptiometry to quantify fat masses.

Quantitative Gadolinium-Free Cardiac Fibrosis Imaging in End Stage Renal Disease Patients Reveals A Longitudinal Correlation with Structural and Functional Decline.

Patients with end stage renal disease (ESRD) suffer high mortality from arrhythmias linked to fibrosis, but are contraindicated to late gadolinium enhancement magnetic resonance imaging (MRI). We present a quantitative method for gadolinium-free cardiac fibrosis imaging using magnetization transfer (MT) weighted MRI, and probe correlations with widely used surrogate markers including cardiac structure and contractile function in patients with ESRD. In a sub-group of patients who returned for follow-up imaging after one year, we examine the correlation between changes in fibrosis and ventricular structure/function.

Typical readout durations in spiral cine DENSE yield blurred images and underestimate cardiac strains at both 3.0 T and 1.5 T.

Introduction: Displacement encoding with stimulated echoes (DENSE) is a phase contrast technique that encodes tissue displacement into phase images, which are typically processed into measures of cardiac function such as strains. For improved signal to noise ratio and spatiotemporal resolution, DENSE is often acquired with a spiral readout using an 11.1 ms readout duration.

Non-invasive detection of adeno-associated viral gene transfer using a genetically encoded CEST-MRI reporter gene in the murine heart.

Research into gene therapy for heart failure has gained renewed interest as a result of improved safety and availability of adeno-associated viral vectors (AAV). While magnetic resonance imaging (MRI) is standard for functional assessment of gene therapy outcomes, quantitation of gene transfer/expression relies upon tissue biopsy, fluorescence or nuclear imaging. Imaging of gene expression through the use of genetically encoded chemical exchange saturation transfer (CEST)-MRI reporter genes could be combined with clinical cardiac MRI methods to comprehensively probe therapeutic gene expression and subsequent outcomes.

Influence of longitudinal position on the evolution of steady-state signal in cardiac cine balanced steady-state free precession imaging.

Background: Emerging quantitative cardiac magnetic resonance imaging (CMRI) techniques use cine balanced steady-state free precession (bSSFP) to measure myocardial signal intensity and probe underlying physiological parameters. This correlation assumes that steady-state is maintained uniformly throughout the heart in space and time.

Purpose: To determine the effects of longitudinal cardiac motion and initial slice position on signal deviation in cine bSSFP imaging by comparing two-dimensional (2D) and three-dimensional (3D) acquisitions.

Identification of changes in neuronal function as a consequence of aging and tauopathic neurodegeneration using a novel and sensitive magnetic resonance imaging approach.

Tauopathies, the most common of which is Alzheimer's disease (AD), constitute the most crippling neurodegenerative threat to our aging population. Tauopathic patients have significant cognitive decline accompanied by irreversible and severe brain atrophy, and it is thought that neuronal dysfunction begins years before diagnosis. Our current understanding of tauopathies has yielded promising therapeutic interventions but have all failed in clinical trials.