Systemic amyloidosis is a serious multiorgan disease with reduced life expectancy, irrespective of type. The impact of magnetic resonance imaging (MRI) in managing this condition has been immense. The last decade in particular has seen a surge of interest in the assessment and evaluation of the heart in patients with systemic amyloidosis by cardiovascular magnetic resonance imaging (CMR), with approximately 85% of all publications on this subject arising in the last 10 years. This has been largely driven by the creation of new sequences and their subsequent modernisation and technical development, thereby rendering previously prohibitive methods clinically more relevant and applicable. In turn, this has led to an increased awareness and recognition of the disease. This review demonstrates how MRI has become a pivotal diagnostic tool in the assessment of cardiac amyloidosis over the last 2 decades, with the ability to track disease and predict mortality. Several different pathognomonic patterns of late gadolinium enhancement (LGE) are now recognised and are able to prognosticate. T1 mapping and extracellular volume (ECV) techniques have resulted in even earlier disease detection before LGE is even visible and along with T2 mapping, provide new insights into biology. As newer therapies also evolve and become available, the need for accurate tracking of cardiac disease response to treatment carries increasing importance. All these are examined in this review, mainly focussing on light-chain (AL) and transthyretin (ATTR) amyloidosis.
PURPOSE: The aim of this study is to evaluate the diagnostic efficacy and safety of gadoxetate disodium vs gadobenate dimeglumine in patients with known or suspected focal liver lesions. METHODS: This was a prospective, multicenter, double-blind, randomized. inter-individual Phase III study. The primary target-technical efficacy-was already published. Here, secondary efficacy parameters-sensitivity and specificity-and safety in specific patient populations are presented. Patients with suspected or known focal liver lesions scheduled for contrast-enhanced liver magnetic resonance imaging (MRI) were recruited and categorized in 4 a priori specified subgroups: (1) all patients, (2) patients with liver cancer (hepatocellular carcinoma [HCC]), (3) patients with cirrhosis, and (4) patients with HCC + cirrhosis. Dual multi-detector liver computed tomography (CT) served as standard of reference. RESULTS: A total of 295 patients were included. While the overall increase in sensitivity across all 4 patient groups was comparable for gadoxetate disodium (increase from pre- to post-contrast ranging from 6.2% to 9.9%) and gadobenate dimeglumine (ranging from -2.9% to 10.0%), significant differences were seen for some of the subgroups. There was a significantly higher increase in sensitivity for gadoxetate disodium in patients with HCC (7%) and HCC + cirrhosis (12.8%) in comparison with gadobenate dimeglumine. Specificity decreased for both agents: gadoxetate disodium by -2,8% to -6.3% and gadobenate dimeglumine by -3.3% to -8.7%. Gadoxetate showed a significantly lower loss of specificity in all subgroups. Safety was comparable in both groups. CONCLUSIONS: Gadoxetate disodium proved to be an effective liver-specific MRI contrast agent. Some distinct advantages over gadobenate dimeglumine were demonstrated in patients with HCC and patients with HCC + liver cirrhosis for sensitivity and specificity in liver lesion detection.
There is a complex interaction between cancer and the immune system. Tumor-associated macrophages (TAMs) can be subverted by the cancer to adopt a pro-tumor phenotype to aid tumor growth. These anti-inflammatory, pro-tumor TAMs have been shown to contribute to a worsened outcome in several different types of cancer. Various strategies aimed at combating the pro-tumor TAMs have been developed. Several therapies, such as oncolytic viral therapy and high-intensity focused ultrasound, have been shown to stimulate TAMs and suppress tumor growth. Targeting TAMs is a promising way to combat cancer, but sensitive imaging methods that are capable of detecting these therapeutic responses are needed. A promising idea is to use imaging contrast agents to label TAMs to determine their relative number and location within, and around the tumor. This can provide information about the efficacy of TAM depletion therapies, as well as macrophage-stimulating therapies. In this review, we describe various in vivo MRI methods capable of tracking TAMs, and conclude with a short section on tracking TAMs in patients.
We investigate the relationship between Gray matter's volume vis-a-vis White matter's integrity indices, such Axial diffusivity, Radial diffusivity, Mean diffusivity, and Fractional anisotropy, in individuals undergoing healthy aging. We investigated MRI scans of 177 adults across 20 to 85 years. We used Voxel-based morphometry, and FDT-FSL analysis for estimation of Gray matter volume and White matter's diffusion indices respectively. Across the life span, we observed an inter-relationship between the Gray matter and White matter, namely that both Axial diffusivity and Mean Diffusivity show strong correlation with Gray matter volume, along the aging process. Furthermore, across all ages the Fractional anisotropy and Mean diffusivity are found to be significantly reduced in females when compared to males, but there are no significant gender differences in Axial Diffusivity and Radial diffusivity. We conclude that for both genders across all ages, the Gray matter's Volume is strongly correlated with White matter's Axial Diffusivity and Mean Diffusivity, while being weakly correlated with Fractional Anisotropy. Our study clarifies the multi-scale relationship in brain tissue, by elucidating how the White matter's micro-structural parameters influences the Gray matter's macro-structural characteristics, during healthy aging across the life-span.
Gadobutrol is a gadolinium (Gd)-based contrast agent for magnetic resonance imaging (MRI). In India, gadobutrol is approved for MRI of the central nervous system (CNS), liver, kidneys, breast and for MR angiography for patients 2 years and older. The standard dose for all age groups is 0.1 mmol/kg body weight. The safety profile has been demonstrated in 42 clinical phase 2 to 4 studies (>6800 patients), 7 observational studies, and by assessing pharmacovigilance data of 29 million applications. Furthermore, studies in children, adults, and elderly and in patients with impaired liver or kidney function did not show any increased adverse event rate. Diagnostic efficacy was demonstrated in numerous studies and various indications, such as diseases of the CNS, peripheral and supra-aortic vessels, kidneys, liver, and breast.
Metabolomics is a rapidly growing field with potential applications in various disciplines. In particular, metabolomics has received special attention in the discovery of biomarkers and diagnostics. This is largely due to the fact that metabolomics provides critical information related to the downstream products of many cellular and metabolic processes which could provide a snapshot of the health/ disease status of a particular tissue or organ. Many of these cellular products eventually find their way to urine; hence, analysis of urine via metabolomics has the potential to yield useful diagnostic and prognostic information. Although there are a number of analytical platforms that can be used for this purpose, this review article will focus on nuclear magnetic resonance-based metabolomics. Furthermore, although there have been many studies addressing different diseases and metabolic disorders, the focus of this review article will be in the following specific applications: urinary tract infection, kidney transplant rejection, diabetes, some types of cancer, and inborn errors of metabolism. A number of methodological considerations that need to be taken into account for the development of a clinically useful optimal test are discussed briefly.
Objective: To compare injector-based contrast agent (CA) administration with hand injection in magnetic resonance angiography (MRA). Methods: Gadobutrol was administered in 6 minipigs with 3 protocols: (a) hand injection (one senior technician), (b) hand injection (6 less-experienced technicians), and (c) power injector administration. The arterial bolus shape was quantified by test bolus measurements. A head and neck MRA was performed for quantitative and qualitative comparison of signal enhancement. Results: A significantly shorter time to peak was observed for protocol C, whereas no significant differences between protocols were found for peak height and bolus width. However, for protocol C, these parameters showed a much lower variation. The MRA revealed a significantly higher signal-to-noise ratio for injector-based administration. A superimposed strong contrast of the jugular vein was found in 50% of the hand injections. Conclusions: Injector-based CA administration results in a more standardized bolus shape, a higher vascular contrast, and a more robust visualization of target vessels.
Gadobutrol is a gadolinium (Gd)-based contrast agent for magnetic resonance imaging (MRI). In India, gadobutrol is approved for MRI of the central nervous system (CNS), liver, kidneys, breast and for MR angiography for patients 2 years and older. The standard dose for all age groups is 0.1 mmol/kg body weight. The safety profile has been demonstrated in 42 clinical phase 2 to 4 studies (>6800 patients), 7 observational studies, and by assessing pharmacovigilance data of 29 million applications. Furthermore, studies in children, adults, and elderly and in patients with impaired liver or kidney function did not show any increased adverse event rate. Diagnostic efficacy was demonstrated in numerous studies and various indications, such as diseases of the CNS, peripheral and supraaortic vessels, kidneys, liver, and breast.
Carotid artery atherosclerosis is a major cause of ischemic stroke. For more than 30 years, future stroke risk and carotid stroke etiology have been determined using percent diameter stenosis based on clinical trials in the 1990s. In the past 10 years, magnetic resonance imaging (MRI) sequences have been developed to detect carotid intraplaque hemorrhage. By detecting carotid intraplaque hemorrhage, MRI identifies potential stroke sources that are often overlooked by lumen imaging. In addition, MRI can dramatically improve assessment of future stroke risk beyond lumen stenosis alone. In this review, we discuss the use of heavily T1-weighted MRI sequences used to detect carotid intraplaque hemorrhage. In addition, advances in ciné imaging, motion robust techniques, and specialized neck coils will be reviewed. Finally, the clinical use and future impact of MRI plaque hemorrhage imaging will be discussed.
In this article, the cause, histology, imaging characteristics, clinical presentation, and treatment of these lesions are thoroughly discussed. Bone marrow edema is the generic term classically used to describe the high-signal-intensity alterations detected on magnetic resonance fluid-sensitive sequences. The significance of bone marrow edema for the patient's clinical condition and the prognosis of the affected joint is being increasingly investigated and discussed, and situations characterized by subchondral insufficiency are receiving increasing attention. More recent studies found some important correlations between bone marrow lesions and patient's pain and osteoarthritis progression. Conservative treatment is based on anti-inflammatory and analgesic uses according to the patient's pain, combined with reduced load on the affected limb. Regarding surgical treatment, subchondroplasty is an option still in development, albeit with promising initial results.
Liposomes are interesting nanosystems with a wide range of medical application. One particular application is their ability to enhance contrast in magnetic resonance images; when properly loaded with magnetic/superparamagnetic nanoparticles, this means to act as contrast agents. The design of liposomes loaded with magnetic particles, magnetoliposomes, presents a large number of possibilities depending on the application from image function to metabolism. More interesting is its double function application as theranostics (diagnostics and therapy). The synthesis, characterization, and possible medical applications of two types of magnetoliposomes are reviewed. Their performance will be compared, in particular, their efficiency as contrast agents for magnetic resonance imaging, measured by their relaxivities r1 and r2 relating to their particular composition. One of the magnetoliposomes had 1,2-diacyl-sn-glycero-3-phosphocholine (soy) as the main phospholipid component, with and without cholesterol, varying its phospholipid to cholesterol molar ratios. The other formulation is a long-circulating liposome composed of 1,2-diacyl-sn-glycero-3-phosphocholine (egg), cholesterol, and 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]. Both nanosystems were loaded with superparamagnetic iron oxide nanoparticles with different sizes and coatings.
Manganese-enhanced magnetic resonance imaging (MEMRI) has been suggested to be a useful tool to visualize and map behavior-relevant neural populations at large scale in freely behaving rodents. A primary concern in MEMRI applications is Mn2+ toxicity. Although a few studies have specifically examined toxicity on gross motor behavior, Mn2+ toxicity on skilled motor behavior was not explored. Thus, the objective of this study was to combine manganese as a functional contrast agent with comprehensive behavior evaluation. We evaluated Mn2+ effect on skilled reach-to-eat action, locomotion, and balance using a single pellet reaching task, activity cage, and cylinder test, respectively. The tests used are sensitive to the pathophysiology of many neurological and neurodegenerative disorders of the motor system. The behavioral testing was done in combination with a moderate dose of manganese. Behavior was studied before and after a single, intravenous infusion of MnCl2 (48 mg/kg). The rats were imaged at 1, 3, 5, 7, and 14 days following infusion. The results show that MnCl2 infusion resulted in detectable abnormalities in skilled reaching, locomotion, and balance that recovered within 3 days compared with the infusion of saline. Because some tests and behavioral measures could not detect motor abnormalities of skilled movements, comprehensive evaluation of motor behavior is critical in assessing the effects of MnCl2. The relaxation mapping results suggest that the transport of Mn2+ into the brain is through the choroid plexus-cerebrospinal fluid system with the primary entry point and highest relaxation rates found in the pituitary gland. Relaxation rates in the pituitary gland correlated with measures of motor skill, suggesting that altered motor ability is related to the level of Mn circulating in the brain. Thus, combined MEMRI and behavioral studies that both achieve adequate image enhancement and are also free of motor skills deficits are difficult to achieve using a single systemic dose of MnCl2.
Computer-based assessment of many cognitive processes (eg, anticipatory and response readiness processes) requires the use of invariant stimulus display times (SDT) and intertrial intervals (ITI). Although designs with invariant SDTs and ITIs have been used in functional magnetic resonance imaging (fMRI) research, such designs are problematic for fMRI studies because of collinearity issues. This study examined regressor modulation with trial-level reaction times (RT) as a method for improving signal detection in a go/no-go task with invariant SDTs and ITIs. The effects of modulating the go regressor were evaluated with respect to the detection of BOLD signal-change for the no-go condition. BOLD signal-change to no-go stimuli was examined when the go regressor was based on a (a) canonical hemodynamic response function (HRF), (b) RT-based amplitude-modulated (AM) HRF, and (c) RT-based amplitude and duration modulated (A&DM) HRF. Reaction time-based modulation reduced the collinearity between the go and no-go regressors, with A&DM producing the greatest reductions in correlations between the regressors, and greater reductions in the correlations between regressors were associated with longer mean RTs and greater RT variability. Reaction time-based modulation increased statistical power for detecting group-level no-go BOLD signal-change across a broad set of brain regions. The findings show the efficacy of using regressor modulation to increase power in detecting BOLD signal-change in fMRI studies in which circumstances dictate the use of temporally invariant stimulus presentations.
Partial volume effects have the potential to cause inaccuracies when quantifying metabolites using proton magnetic resonance spectroscopy (MRS). In order to correct for cerebrospinal fluid content, a spectroscopic voxel needs to be segmented according to different tissue contents. This article aims to detail how automated partial volume segmentation can be undertaken and provides a software framework for researchers to develop their own tools. While many studies have detailed the impact of partial volume correction on proton magnetic resonance spectroscopy quantification, there is a paucity of literature explaining how voxel segmentation can be achieved using freely available neuroimaging packages.
With larger data sets and more sophisticated analyses, it is becoming increasingly common for neuroimaging researchers to push (or exceed) the limitations of standalone computer workstations. Nonetheless, although high-performance computing platforms such as clusters, grids and clouds are already in routine use by a small handful of neuroimaging researchers to increase their storage and/or computational power, the adoption of such resources by the broader neuroimaging community remains relatively uncommon. Therefore, the goal of the current manuscript is to: 1) inform prospective users about the similarities and differences between computing clusters, grids and clouds; 2) highlight their main advantages; 3) discuss when it may (and may not) be advisable to use them; 4) review some of their potential problems and barriers to access; and finally 5) give a few practical suggestions for how interested new users can start analyzing their neuroimaging data using cloud resources. Although the aim of cloud computing is to hide most of the complexity of the infrastructure management from end-users, we recognize that this can still be an intimidating area for cognitive neuroscientists, psychologists, neurologists, radiologists, and other neuroimaging researchers lacking a strong computational background. Therefore, with this in mind, we have aimed to provide a basic introduction to cloud computing in general (including some of the basic terminology, computer architectures, infrastructure and service models, etc.), a practical overview of the benefits and drawbacks, and a specific focus on how cloud resources can be used for various neuroimaging applications.
PURPOSE:To assess the safety and efficacy of gadoxetate disodium-enhanced liver MR imaging in pediatric patients.MATERIAL AND METHODS:Retrospective, multicenter study including pediatric patients aged >2 months to <18 years who underwent contrast-enhanced liver MRI due to focal liver lesions. A single intravenous bolus injection of 0.025 to 0.05 mmol/kg body weight of gadoxetate disodium was administered. Adverse events (AEs) up to 24 hours after injection were recorded and a one-year follow-up was conducted for all serious and unexpected AEs. Efficacy was defined based on the additional diagnostic information obtained from the combined (pre- and postcontrast) image sets as compared with the precontrast image sets by blinded reading.RESULTS:A total of 52 patients for safety and 51 patients for efficacy analyses were evaluated. Twenty-two patients (42.3%) reported a total of 51 serious AEs (SAEs) and one AE after one year. No SAE or AE was related to gadoxetate disodium injection. Gadoxetate disodium-related effects on vital signs were not seen. Additional diagnostic information was obtained for 86.3% of patients. The three most improved efficacy variables were lesion-to-background contrast, lesion characterization, and improved border delineation in 78.4%, 76.5%, and 70.6% of patients, respectively.CONCLUSION:Gadoxetate disodium in pediatric patients did not raise any clinically significant safety concern. Contrast enhancement provided additional clinically relevant information.
Fluorine-19 (19F)-based contrast agents for magnetic resonance imaging stand to revolutionize imaging-based research and clinical trials in several fields of medical intervention. First, their use in characterizing in vivo cell behavior may help bring cellular therapy closer to clinical acceptance. Second, their use in lung imaging provides novel noninvasive interrogation of the ventilated airspaces without the need for complicated, hard-to-distribute hardware. This article reviews the current state of 19F-based cell tracking and lung imaging using magnetic resonance imaging and describes the link between the methods across these fields and how they may mutually benefit from solutions to mutual problems encountered when imaging 19F-containing compounds, as well as hardware and software advancements.
OBJECTIVES:Lung cancer is one of the most lethal cancers. Currently, there are no biomarkers for early detection, monitoring treatment response, and detecting recurrent lung cancer. We undertook this study to determine if 1H magnetic resonance spectroscopy (MRS) of sputum and exhaled breath condensate (EBC), as a noninvasive tool, can identify metabolic biomarkers of lung cancer.MATERIALS AND METHODS:Sputum and EBC samples were collected from 20 patients, comprising patients with pathologically confirmed non-small cell lung cancer (n = 10) and patients with benign respiratory conditions (n = 10). Both sputum and EBC samples were collected from 18 patients; 2 patients provided EBC samples only. 1H MR spectra were obtained on a Bruker Avance 400 MHz nuclear magnetic resonance (NMR) spectrometer. Sputum samples were further confirmed cytologically to distinguish between true sputum and saliva.RESULTS:In the EBC samples, median concentrations of propionate, ethanol, acetate, and acetone were higher in lung cancer patients compared to the patients with benign conditions. Median concentration of methanol was lower in lung cancer patients (0.028 mM) than in patients with benign conditions (0.067 mM; P = 0.028). In the combined sputum and saliva and the cytologically confirmed sputum samples, median concentrations of N-acetyl sugars, glycoprotein, propionate, lysine, acetate, and formate were lower in the lung cancer patients than in patients with benign conditions. Glucose was found to be consistently absent in the combined sputum and saliva samples (88%) as well as in the cytologically confirmed sputum samples (86%) of lung cancer patients.CONCLUSION:Absence of glucose in sputum and lower concentrations of methanol in EBC of lung cancer patients discerned by 1H MRS may serve as metabolic biomarkers of lung cancer for early detection, monitoring treatment response, and detecting recurrence.
The aim is to investigate the relationship between microstructural white matter (WM) diffusivity indices and macrostructural WM volume (WMV) among healthy individuals (20–85 years). Whole-brain diffusion measures were calculated from diffusion tensor imaging using FMRIB software library while WMV was estimated through voxel-based morphometry, and voxel-based analysis was carried out using tract-based spatial statistics. Our results revealed that mean diffusivity, axial diffusivity, and radial diffusivity had shown good correlation with WMV but not for fractional anisotropy (FA). Voxel-wise tract-based spatial statistics analysis for FA showed a significant decrease in four regions for middle-aged group compared to young-aged group, in 22 regions for old-aged group compared to middle-aged group, and in 26 regions for old-aged group compared to young-aged group ( P < 0.05). We found significantly lower WMV, FA, and mean diffusivity values in females than males and inverted-U trend for FA in males. We conclude differential age- and gender-related changes for structural WMV and WM diffusion indices.
Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation.
