The Evolving Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Systemic Amyloidosis

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.

Diagnostic Efficacy and Safety of Gadoxetate Disodium vs Gadobenate Dimeglumine in Patients With Known or Suspected Focal Liver Lesions: Results of a Clinical Phase III Study

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.

A Correlational Study between Microstructural White Matter Properties and Macrostructural Gray Matter Volume Across Normal Ageing: Conjoint DTI and VBM Analysis

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.

In Vivo MR Imaging of Tumor-Associated Macrophages: The Next Frontier in Cancer Imaging

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.

Gadobutrol in India—A Comprehensive Review of Safety and Efficacy

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.

Development of New Contrast Agents for Imaging Function and Metabolism by Magnetic Resonance Imaging

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.

The Impact of Injector-Based Contrast Agent Administration on Bolus Shape and Magnetic Resonance Angiography Image Quality

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.

Bone Marrow Lesion: Image, Clinical Presentation, and Treatment

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.

Manganese-Enhanced Magnetic Resonance Imaging and Studies of Rat Behavior: Transient Motor Deficit in Skilled Reaching, Rears, and Activity in Rats After a Single Dose of MnCl2

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.

Diagnostic Applications of Nuclear Magnetic Resonance–Based Urinary Metabolomics

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.